Table of Contents

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 10-Q

☒ýQUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the quarterly period ended September 30, 20172021
OR
☐TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from _______ to _______
Commission File Number: 001-37798
Selecta Biosciences, Inc.
(Exact Namename of Registrantregistrant as Specifiedspecified in its Charter)
charter)
Delaware26-1622110
(State or other jurisdiction
of incorporation or organization)
(I.R.S. Employer Identification No.)
65 Grove Street, Watertown, MA02472
(Address of principal executive offices)(Zip Code)
(617) 923-1400
(Registrant’s telephone number, including area code)

Securities registered pursuant to Section 12(b) of the Act:
DelawareTitle of each classTrading Symbol(s)26-1622110Name of each exchange on which registered
(State or Other Jurisdiction of Incorporation or Organization)Common Stock, $0.0001 par value per shareSELB(I.R.S. Employer Identification No.)
480 Arsenal Way
Watertown, MA02472
(Address Of Principal Executive Offices)(Zip Code)The Nasdaq Stock Market LLC
617-923-1400
(Registrant’s Telephone Number, Including Area Code)

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.
Yes ☒ý No ☐

Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Web site, if any, every Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit and post such files). Yes ☒ý No ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filer☐Accelerated filer☐
Non-accelerated filerýSmaller reporting companyý
Large accelerated filer ☐Accelerated filer ☐
Non-accelerated filer ☒Smaller reporting company ☐
Emerging growth company ☒ý
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒ý
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒ý
As of November 3, 20175, 2021, the registrant had 22,336,576116,648,919 shares of common stock, par value $0.0001 per share, outstanding.



TABLE OF CONTENTS
TABLE OF CONTENTS
PART I. FINANCIAL INFORMATION
Part I. FINANCIAL INFORMATION
Item 1. 
34
34
45
56
68
79
Item 2.
3229
Item 3.
4143
Item 4.
4143
Part
PART II. OTHER INFORMATION
Item 1. Legal Proceedings
42
Item 1A. Risk Factors1. 
44
Item 1A. 
44
Item 2.
7946
Item 3.
8046
Item 4.
8046
Item 5.
8046
Item 6.Exhibits
47
SIGNATURES



2

FORWARD-LOOKING STATEMENTS
This Quarterly Report on Form 10-Q, or the Quarterly Report, contains forward-looking statements. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, as amended, or the Securities Act, and Section 21E of the Securities Exchange Act of 1934.1934, as amended, or the Exchange Act. All statements other than statements of historical facts contained in this Quarterly Report, including statements regarding our future results of operations and financial position, business strategy, prospective products, product approvals, research and development costs, timing and likelihood of success, and the plans and objectives of management for future operations and future results of anticipated products,the impact of the COVID-19 pandemic on our business and operations and our future financial results, and the period over which we estimate our existing cash and cash equivalents will be sufficient to fund our future operating expenses and capital expenditure requirements are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements.
In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential”, or “continue” or the negative of these terms or other similar expressions. The forward-looking statements in this Quarterly Report are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition and results of operations. These forward-looking statements speak only as of the date of this Quarterly Report and are subject to a number of important factors that could cause actual results to differ materially from those in the forward-looking statements, including the factors described under the sections in this Quarterly Report titled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” as well as the following:
-    •our status as a development-stage company and our expectation to incur losses in the future;
-    •our future capital needs and our need to raise additional funds;
-    •our ability to build a pipeline of product candidates and develop and commercialize drugs;such pipeline;
-    •our unproven approach to therapeutic intervention;
-our ability to enroll patients in clinical trials, timely and successfully complete those trials and receive necessary regulatory approvals;
-our ability to establish our own manufacturing facilities and to receive or manufacture sufficient quantities of our product candidates;
-    •our ability to enroll patients in clinical trials, timely and successfully complete those trials and receive necessary regulatory approvals;
•our ability to access manufacturing facilities and to receive or manufacture sufficient quantities of our product candidates;
•our ability to maintain our existing or future collaborations or licenses;
-    •the continuing impact of the COVID-19 pandemic on our operations, the continuity of our business, including our preclinical studies and clinical trials, and general economic conditions;
•our ability to protect and enforce our intellectual property rights;
-    •federal, state, and foreign regulatory requirements, including FDA regulation of our product candidates;
-    •our ability to obtain and retain key executives and attract and retain qualified personnel;
•developments relating to our competitors and our industry, including the impact of government regulation; and
-    •our ability to successfully manage our growth.
Moreover, we operate in an evolving environment. New risk factorsrisks and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties.
You should read this Quarterly Report and the documents that we reference in this Quarterly Report completely and with the understanding that our actual future results may be materially different from what we expect. We qualify all of our forward-looking statements by these cautionary statements. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

3

Table of Contents
PART I. FINANCIAL INFORMATION
Item 1. Financial Statements

Selecta Biosciences, Inc. and Subsidiaries
Consolidated Balance Sheets
(Amounts in thousands, except share data and par value)
(Unaudited)
 September 30,December 31,
 20212020
 (Unaudited) 
Assets  
Current assets:  
Cash and cash equivalents$114,645 $138,685 
Marketable securities24,018 — 
Accounts receivable7,324 7,224 
Prepaid expenses and other current assets5,781 5,434 
Total current assets151,768 151,343 
Non-current assets:
Property and equipment, net1,807 1,395 
Right-of-use asset, net10,117 10,948 
Long-term restricted cash1,379 1,379 
Investments2,000 — 
Other assets91 370 
Total assets$167,162 $165,435 
Liabilities and stockholders’ (deficit) equity  
Current liabilities:  
Accounts payable$1,593 $443 
Accrued expenses10,742 8,146 
Loan payable4,125 — 
Lease liability1,013 908 
Income taxes payable15,828 — 
Deferred revenue62,315 72,050 
Total current liabilities95,616 81,547 
Non-current liabilities:
Loan payable, net of current portion21,304 24,793 
Lease liability8,873 9,647 
Deferred revenue20,057 38,746 
Warrant liabilities40,043 28,708 
Total liabilities185,893 183,441 
Commitments and contingencies (Note 17)00
Stockholders’ (deficit) equity:  
Preferred stock, $0.0001 par value; 10,000,000 shares authorized; no shares issued and outstanding at September 30, 2021 and December 31, 2020— — 
Common stock, $0.0001 par value; 200,000,000 shares authorized; 115,443,500 and 108,071,249 shares issued and outstanding as of September 30, 2021 and December 31, 2020, respectively12 11 
Additional paid-in capital428,371 391,175 
Accumulated deficit(442,555)(404,629)
Accumulated other comprehensive loss(4,559)(4,563)
Total stockholders’ (deficit) equity(18,731)(18,006)
Total liabilities and stockholders’ (deficit) equity$167,162 $165,435 
 September 30, December 31,
 2017 2016
 (Unaudited)  
Assets   
Current assets:   
Cash and cash equivalents$72,151
 $58,656
Short-term deposits and investments32,237
 25,485
Restricted cash76
 78
Accounts receivable—
 215
Prepaid expenses and other current assets2,888
 2,382
Total current assets107,352

86,816
Property and equipment, net2,055
 2,047
Restricted cash and other deposits316
 316
Other assets—
 122
Total assets$109,723

$89,301
Liabilities and stockholders’ equity   
Current liabilities:   
Accounts payable$1,519
 $3,882
Accrued expenses6,547
 3,921
Loans payable, current portion—
 4,067
Deferred revenue, current portion3,256
 1,836
Total current liabilities11,322

13,706
Non‑current liabilities:   
Deferred rent and lease incentive168
 222
Loans payable, net of current portion20,954
 7,977
Deferred revenue, net of current portion10,953
 12,439
Other long‑term liabilities1,250
 —
Total liabilities44,647

34,344
Commitments and contingencies (Notes 8 and 13)
 
Stockholders’ equity:   
Preferred stock, $0.0001 par value; 10,000,000 shares authorized; no shares issued and outstanding at September 30, 2017 and December 31, 2016, respectively.—
 —
Common stock, $0.0001 par value; 200,000,000 shares authorized; 22,120,507 and 18,438,742 shares issued and outstanding as of September 30, 2017 and December 31, 2016, respectively.2
 1
Additional paid-in capital266,836
 211,125
Receivable from stock option exercises—
 (75)
Accumulated deficit(197,353) (151,576)
Accumulated other comprehensive loss(4,409) (4,518)
Total stockholders’ equity65,076
 54,957
Total liabilities and stockholders’ equity$109,723

$89,301

The accompanying notes are an integral part of these unaudited consolidated financial statements.

4
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Selecta Biosciences, Inc. and Subsidiaries
Consolidated Statements of Operations and Comprehensive Loss
(Amounts in thousands, except share and per share data)
(Unaudited)

Three Months Ended September 30, Nine Months Ended September 30, Three Months Ended
September 30,		Nine Months Ended
September 30,
2017 2016 2017 2016 2021202020212020
(Unaudited)(Unaudited)
Grant and collaboration revenue$27
 $1,048
 $190
 $5,153
Grant and collaboration revenue$24,427 $4,646 $55,140 $4,646 
Operating expenses:       Operating expenses:
Research and development9,504
 6,021
 31,542
 18,669
Research and development20,951 13,960 48,418 39,414 
General and administrative4,377
 2,495
 13,155
 7,294
General and administrative5,445 4,420 15,397 14,155 
Total operating expenses13,881
 8,516
 44,697
 25,963
Total operating expenses26,396 18,380 63,815 53,569 
Loss from operations(13,854) (7,468) (44,507) (20,810)
Operating lossOperating loss(1,969)(13,734)(8,675)(48,923)
Investment income165
 98
 379
 121
Investment income11 4 35 257 
Loss on extinguishment of debt(673) —
 (673) —
Loss on extinguishment of debt— (461)— (461)
Foreign currency transaction gain (loss), net(30) (51) (113) (429)
Foreign currency transaction, netForeign currency transaction, net2 43 (5)83 
Interest expense(268) (311) (847) (931)Interest expense(711)(365)(2,133)(843)
Other expense, net(16) 4
 (16) (78)
Change in fair value of warrant liabilitiesChange in fair value of warrant liabilities592 4,779 (11,335)(3,606)
Other income, netOther income, net9 5 15 63 
Loss before income taxesLoss before income taxes(2,066)(9,729)(22,098)(53,430)
Income tax expenseIncome tax expense(15,828)— (15,828)— 
Net loss(14,676) (7,728) (45,777) (22,127)Net loss$(17,894)$(9,729)$(37,926)$(53,430)
Other comprehensive loss:       
Other comprehensive income (loss):Other comprehensive income (loss):
Foreign currency translation adjustment(1) 15
 79
 416
Foreign currency translation adjustment(1)(32)5 (61)
Unrealized gain (loss) on securities5
 16
 30
 16
Comprehensive loss$(14,672) $(7,697) $(45,668) $(21,695)
Net loss(14,676) (7,728) (45,777) (22,127)
Accretion of redeemable convertible preferred stock—
 —
 —
 (4,566)
Net loss attributable to common stockholders$(14,676) $(7,728) $(45,777) $(26,693)
Net loss per share attributable to common stockholders       
Unrealized loss on marketable securitiesUnrealized loss on marketable securities(1)— (1)— 
Total comprehensive lossTotal comprehensive loss$(17,896)$(9,761)$(37,922)$(53,491)
Net loss per share:Net loss per share:
Basic and diluted$(0.66) $(0.43) $(2.31) $(3.39)Basic and diluted$(0.16)$(0.09)$(0.34)$(0.54)
Weighted average common shares outstanding       
Weighted average common shares outstanding:Weighted average common shares outstanding:
Basic and diluted22,082,207
 18,108,014
 19,803,551
 7,881,625
Basic and diluted115,169,949 105,325,788 113,161,622 98,968,359 

The accompanying notes are an integral part of these unaudited consolidated financial statements.

5

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Selecta Biosciences, Inc. and Subsidiaries
Consolidated Statements of Changes in Stockholders’ (Deficit) Equity
(Amounts in thousands, except share data)
(Unaudited)

     Accumulated
   Additional otherStockholders’
 Common stockpaid-inAccumulatedcomprehensive(Deficit)
 SharesAmountcapitaldeficitlossEquity
Balance at December 31, 2020108,071,249 $11 $391,175 $(404,629)$(4,563)$(18,006)
Issuance of common stock under Employee Stock Purchase Plan34,696 — 72 — — 72 
Issuance of common stock upon exercise of options153,278 — 244 — — 244 
Issuance of vested restricted stock units10,937 — — — — — 
Issuance of common stock through at-the-market offering, net4,706,844 — 20,943 — — 20,943 
Stock-based compensation expense— — 1,780 — — 1,780 
Currency translation adjustment— — — — (6)(6)
Unrealized (losses) on marketable securities— — — — (1)(1)
Net loss— — — (24,597)— (24,597)
Balance at March 31, 2021112,977,004 $11 $414,214 $(429,226)$(4,570)$(19,571)
Issuance of common stock upon exercise of options242,278 — 425 — — 425 
Issuance of vested restricted stock units10,938 — — — — — 
Issuance of common stock through at-the-market offering, net1,849,072 1 8,562 — — 8,563 
Stock-based compensation expense— — 1,783 — — 1,783 
Currency translation adjustment— — — — 12 12 
Unrealized gain on marketable securities— — — — 1 1 
Net income— — — 4,565 — 4,565 
Balance at June 30, 2021115,079,292 $12 $424,984 $(424,661)$(4,557)$(4,222)
Issuance of common stock under Employee Stock Purchase Plan24,098 — 89 — — 89 
Issuance of common stock upon exercise of options1,936 — 5 — — 5 
Issuance of vested restricted stock units10,937 — — — — — 
Issuance of common stock through at-the-market offering, net327,237 — 1,389 — — 1,389 
Stock-based compensation expense— — 1,904 — — 1,904 
Currency translation adjustment— — — — (1)(1)
Unrealized (losses) on marketable securities— — — — (1)(1)
Net loss— — — (17,894)— (17,894)
Balance at September 30, 2021115,443,500 $12 $428,371 $(442,555)$(4,559)$(18,731)

The accompanying notes are an integral part of these unaudited consolidated financial statements.
6
             
          Accumulated  
    Additional Stock   other  
 Common stock paid‑In option Accumulated comprehensive Stockholders’
 SharesAmount Capital receivable deficit loss Equity
Balance at December 31, 201618,438,742
$1
 $211,125
 $(75) $(151,576) $(4,518) $54,957
Issuance of common stock under Employee Stock Purchase Plan16,263
—
 180
 —
 —
 —
 180
Issuance of common stock upon exercise of options252,349
—
 545
 75
 —
 —
 620
Stock‑based compensation expense—
—
 2,872
 —
 —
 —
 2,872
Issuance of common stock, license agreement324,362
—
 5,000
 —
 —
 —
 5,000
Issuance of common stock, Private placement net of issuance costs3,088,791
1
 47,114
 —
 —
 —
 47,115
Currency translation adjustment—
—
 —
 —
 —
 79
 79
Unrealized gains (losses) on securities—
—
 —
 —
 —
 30
 30
Net loss—
—
 —
 —
 (45,777) —
 (45,777)
Balance at September 30, 201722,120,507
$2
 $266,836
 $—
 $(197,353) $(4,409) $65,076
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Selecta Biosciences, Inc. and Subsidiaries
Consolidated Statements of Changes in Stockholders’ (Deficit) Equity
(Amounts in thousands, except share data)
(Unaudited)
     Accumulated 
   Additional otherStockholders’
 Common stockpaid-inAccumulatedcomprehensive(Deficit)
 SharesAmountcapitaldeficitlossEquity
Balance at December 31, 201986,325,547 $9 $348,664 $(335,753)$(4,523)$8,397 
Issuance of common stock under Employee Stock Purchase Plan78,583 — 114 — — 114 
Issuance of common stock upon exercise of options5,128 — 3 — — 3 
Issuance of vested restricted stock units10,937 — — — — — 
Issuance of common stock through at-the-market offering, net598,977 — 1,141 — — 1,141 
Other financing fees— — (147)— — (147)
Stock-based compensation expense— — 1,409 — — 1,409 
Currency translation adjustment— — — — (60)(60)
Net loss— — — (19,620)— (19,620)
Balance at March 31, 202087,019,172 $9 $351,184 $(355,373)$(4,583)$(8,763)
Issuance of common stock upon exercise of options37,500 — 98 — — 98 
Issuance of vested restricted stock units10,938 — — — — — 
Issuance of common stock through at-the-market offering, net470,509 — 967 — — 967 
Issuance of common stock upon exercise of pre-funded warrants8,342,128 1 — — — 1 
Issuance of common stock upon exercise of common warrants4,967,563 — 17,214 — — 17,214 
Stock-based compensation expense— — 1,481 — — 1,481 
Currency translation adjustment— — — — 31 31 
Net loss— — — (24,081)— (24,081)
Balance at June 30, 2020100,847,810 $10 $370,944 $(379,454)$(4,552)$(13,052)
Issuance of common stock under Employee Stock Purchase Plan31,629 — 70 — — 70 
Issuance of vested restricted stock units60,937 — — — — — 
Issuance of common stock through private placement5,416,390 1 10,268 — — 10,269 
Issuance of common warrants with long-term debt, net— — 444 — — 444 
Issuance of common stock upon exercise of common warrants879,210 — 3,485 — — 3,485 
Other financing fees— — (133)— — (133)
Stock-based compensation expense— — 1,296 — — 1,296 
Currency translation adjustment— — — — (32)(32)
Net loss— — — (9,729)— (9,729)
Balance at September 30, 2020107,235,976 $11 $386,374 $(389,183)$(4,584)$(7,382)

The accompanying notes are an integral part of these unaudited consolidated financial statements.

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Selecta Biosciences, Inc. and Subsidiaries 
Consolidated Statements of Cash Flows
 (Amounts(Amounts in thousands)
(Unaudited)
 Nine Months Ended
September 30,
20212020
(Unaudited)
Cash flows from operating activities
Net loss$(37,926)$(53,430)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization851 490 
Amortization of premiums and discounts on marketable securities37 — 
Non-cash lease expense832 861 
Loss on disposal of property and equipment— (39)
Stock-based compensation expense5,467 4,186 
Non-cash interest expense800 406 
Warrant liabilities revaluation11,335 3,606 
Loss on extinguishment of debt— 461 
Changes in operating assets and liabilities:
Accounts receivable(100)(7,626)
Prepaid expenses, deposits and other assets(510)(6,656)
Accounts payable1,148 (29)
Income taxes payable15,828 — 
Deferred revenue(28,424)99,512 
Accrued expenses and other liabilities1,740 389 
                    Net cash (used in) provided by operating activities(28,922)42,131 
Cash flows from investing activities
Proceeds from maturities of marketable securities6,400 — 
Payment made for investments(2,000)— 
Purchases of marketable securities(30,455)— 
Purchases of property and equipment(807)(625)
Proceeds from the sale of property and equipment— 50 
                    Net cash used in investing activities(26,862)(575)
Cash flows from financing activities
Proceeds from issuance of long-term debt, net of expenses— 24,838 
Repayments of principal on outstanding debt— (19,313)
Net proceeds from issuance of common stock- at-the-market offering30,906 2,137 
Net proceeds from issuance of common stock- private placement— 10,269 
Issuance costs paid for December 2019 financing— (4,381)
Other financing fees— (192)
Proceeds from exercise of pre-funded and common warrants— 978 
Proceeds from exercise of stock options674 101 
Proceeds from issuance of common stock under Employee Stock Purchase Plan161 184 
                    Net cash provided by financing activities31,741 14,621 
Effect of exchange rate changes on cash3 (88)
Net change in cash, cash equivalents, and restricted cash(24,040)56,089 
Cash, cash equivalents, and restricted cash at beginning of period140,064 91,551 
Cash, cash equivalents, and restricted cash at end of period$116,024 $147,640 
Supplement cash flow information
Cash paid for interest$1,503 $519 
Noncash investing and financing activities
Cashless warrant exercise$— $18,228 
Reclassification of warrant liability to equity upon exercise of warrants$— $1,494 
Fair value of warrants issued in connection with issuance of long-term debt$— $444 
Purchase of property and equipment not yet paid$17 $17 
Equity offering costs in accrued liabilities$11 $117 
Unrealized (losses) on marketable securities$(1)$— 
Debt issuance costs in accrued liabilities$— $100 
 Nine Months Ended September 30,
 2017 2016
 (Unaudited)
Operating activities   
Net loss$(45,777) $(22,127)
Adjustments to reconcile net loss to net cash used in operating activities:   
Depreciation567
 545
Amortization of premiums and accretion of discounts on investments200
 113
Loss on disposal of fixed assets16
 —
Stock‑based compensation expense2,872
 1,281
Non‑cash interest expense249
 176
Loss on extinguishment of debt673
 —
Change in fair value of redeemable convertible preferred stock warrant—
 12
Changes in operating assets and liabilities:   
Accounts receivable215
 341
Prepaid expenses and other assets(386) (1,668)
Restricted cash and other deposits703
 507
Accounts payable(2,399) (35)
Deferred revenue(66) 586
Contingently repayable grant funding—
 (207)
Accrued expenses and other liabilities3,768
 (763)
Net cash used in operating activities(39,365) (21,239)
Investing activities   
Maturities of Short-term government obligations41,115
 6,900
Purchase of Short-term investments(48,736) (23,318)
Purchases of property and equipment(584) (478)
Net cash used in investing activities(8,205) (16,896)
Financing activities   
Vesting of restricted stock—
 16
Repayments of long-term debt(12,934) —
Deferred IPO costs paid—
 (4,068)
Proceeds from Initial Public Offering, net of underwriters' discounts and commissions—
 68,871
Proceeds from Private Placement, net of issuance costs ($2.9 million)47,120
 —
Proceeds from issuance of common stock under Employee Stock Purchase Plan180
 —
Issuance of common stock5,000
 —
Issuance of long-term debt, net of expenses20,999
 —
Exercise of stock options620
 48
Net cash provided by financing activities60,985
 64,867
Effect of exchange rate changes on cash80
 419
Net increase in cash and cash equivalents13,495
 27,151
Cash and cash equivalents at beginning of period58,656
 32,337
Cash and cash equivalents at end of period$72,151
 $59,488
Cash paid during the year for:   
Interest660
 729
Supplemental noncash investing and financing activities:   
Purchase of property and equipment not yet paid$8
 $31
Reclassification of deferred IPO costs from non-current assets to additional paid-in capital—
 4,369
Debt issuance costs included in account payable
29
 —
Accrued dividends and accretion of preferred stock to redemption value—
 4,566
Private placement offering costs in accounts payable and accrued liabilities7
 —
Unrealized gain on marketable securities$31
 $16
The accompanying notes are an integral part of these unaudited consolidated financial statements.

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Selecta Biosciences, Inc. and Subsidiaries
Notes to Consolidated Financial Statements (Unaudited)
(Year Ended December 31, 2016 and Unaudited Three Months and Nine Months Ended September 30, 2017 and 2016)

1. Nature of the Business and Basis of Presentation
Selecta Biosciences, Inc. (the “Company”), or the Company, was incorporated in Delaware on December 10, 2007, and is based in Watertown, Massachusetts. The Company is a clinical-stage biopharmaceutical company dedicatedleveraging its ImmTOR™ immune tolerance platform with the goals of amplifying the efficacy of biologics, including enabling the re-dosing of life-saving gene therapies, and restoring self-tolerance in autoimmune diseases. The Company’s ImmTOR platform encapsulates rapamycin, also known as sirolimus, an immunomodulator, in biodegradable nanoparticles and is designed to developinginduce antigen-specific immune tolerance. The Company believes ImmTOR has the first generationpotential to enhance the efficacy without compromising the safety of nanoparticle immunomodulatory drugs for the treatmentbiologic therapies, improve product candidates under development, and prevention of human diseases.enable novel therapeutic modalities. Since inception, the Company has devoted its efforts principally to research and development of its technology and product candidates, recruiting management and technical staff, acquiring operating assets, and raising capital.
The Company is subject to risks common to companies in the biotechnology industry including, but not limited to, new technological innovations, protection of proprietary technology, dependence on key personnel, compliance with government regulations and the need to obtain additional financing. Product candidates currently under development will require significant additional research and development efforts, including extensive pre-clinicalpreclinical and clinical testing and regulatory approval, prior to commercialization. These efforts require significant amounts of additional capital, adequate personnel infrastructure and extensive compliance-reporting capabilities.
The Company’s product candidates are in development. There can be no assurance that the Company’s research and development will be successfully completed, that adequate protection for the Company’s intellectual property will be obtained, or maintained, that any products developed will obtain necessary government regulatory approval or that any approved products will be commercially viable. Even if the Company’s product development efforts are successful, it is uncertain when, if ever, the Company will generate significant revenue from product sales. The Company operates in an environment of rapid change in technology and substantial competition from pharmaceutical and biotechnology companies. In addition, the Company is dependent upon the services of its employees and consultants.
Unaudited Interim Financial Information
The accompanying unaudited consolidated financial statements for the three and nine months ended September 30, 20172021 and 20162020 have been prepared by the Company, pursuant to the rules and regulations of the Securities and Exchange Commission, (the “SEC”)or the SEC, for interim financial statements. Certain information and footnote disclosures normally included in financial statements prepared in accordance with accounting principles generally accepted in the United States of America, (“GAAP”)or U.S. GAAP, have been condensed or omitted pursuant to such rules and regulations. However, the Company believes that the disclosures are adequate to make the information presented not misleading. These consolidated financial statements should be read in conjunction with the Company’s audited consolidated financial statements and the notes thereto for the year ended December 31, 20162020 included in the Company’s Annual Report on Form 10-K that was filed with the SEC on March 28, 2017 (the "Annual Report on Form 10-K").
12, 2021. The unaudited interim financial statements have been prepared on the same basis as the audited consolidated financial statements. In the opinion of management, the accompanying unaudited interim consolidated financial statements contain all adjustments whichthat are necessary for a fair statement of the Company’s financial position as of September 30, 2017 and2021, the consolidated results of operations for the three and nine months ended September 30, 20172021, and cash flows for the nine months ended September 30, 2017.2021. Such adjustments are of a normal and recurring nature. The results of operations for the three and nine months ended September 30, 20172021 are not necessarily indicative of the results of operations that may be expected for the year ending December 31, 2017.2021.
Liquidity and Management’s Plan
The Company has incurred losses since inception and negative cash flows from operating activities. As of September 30, 2017 and December 31, 2016, the Company had an accumulated deficit of $197.4 million and $151.6 million, respectively. The Company’s cash and cash equivalents as of September 30, 2017 and December 31, 2016, includes $1.6 million and $2.4 million of unrestricted cash held by its Russian subsidiary. The future success of the Company is dependent uponon its ability to obtain additional capital through issuances of equity and debt securities and from collaboration and grant agreements in order to further the development ofdevelop its technology and product candidates and ultimately upon its ability to attain and sustain profitable operations. There can be no assurance that theThe Company will be ableis subject to obtain the necessary financinga number of risks similar to successfully develop and marketother early-stage life science companies, including, but not limited to, successful development of its product candidates, or attain profitability. 
Based on the current operating plan,raising additional capital with favorable terms, protection of proprietary technology and market acceptance of any approved future products. The successful development of product candidates requires substantial working capital, which may not be available to the Company expects thaton favorable terms or at all.
To date, the Company has financed its operations primarily through the initial public offering of its common stock, private placements of its common stock, issuances of common and preferred stock, debt, research grants and research collaborations. The Company currently has no source of product revenue, and it does not expect to generate product revenue for the foreseeable future. To date, all of the Company’s revenue has been collaboration and grant revenue. The Company has devoted substantially all of its financial resources and efforts to developing its ImmTOR platform, identifying potential product
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candidates and conducting preclinical studies and clinical trials. The Company is in the early stages of development of its product candidates, and it has not completed development of any ImmTOR-enabled therapies.
As of September 30, 2021, the Company’s cash, cash equivalents, short-term investmentsrestricted cash and short-termmarketable securities were $140.0 million, of which $1.4 million was restricted cash related to lease commitments and $0.3 million was held by its Russian subsidiary designated solely for use in its operations. The Company believes the cash, cash equivalents, restricted cash and marketable securities as of September 30, 2017,2021 will enable it to fund its operating expenses and capital expenditure requirements into mid-2019 based onfor at least twelve months from the latest forecast.issuance of these financial statements. As of September 30, 2021, the Company had an accumulated deficit of $442.6 million. The Company has based this estimate on assumptions that may proveanticipates operating losses to be wrong,continue for the foreseeable future due to, among other things, costs related to research and the Company could use its capital resources sooner than it currently expects. Additionally, the process of testing product candidates in clinical trials is costly, and the timing of progress in these trials is uncertain. Because the Company’s product

candidates are in various stages of clinical and preclinical development and the outcome of these efforts is uncertain, the Company cannot estimate the actual amounts necessary to successfully complete the development and commercialization of its product candidates and its administrative organization. The Company will require substantial additional financing to fund its operations and to continue to execute its strategy, and the Company intends to pursue a range of options to secure additional capital.
At this time, any impact of COVID-19 on the Company’s business, revenues, results of operations and financial condition will largely depend on future developments, which are highly uncertain and cannot be predicted with confidence, such as the duration of the pandemic, travel restrictions and social distancing in the United States and other countries, business closures or whether, or when, it may achieve profitability.business disruptions, supply chain disruptions, the ultimate impact on financial markets and the global economy, and the effectiveness of actions taken in the United States and other countries to contain and treat the disease.
Guarantees and Indemnifications
As permitted under Delaware law, the Company indemnifies its officers, directors, consultants and employees for certain events or occurrences that happen by reason of the relationship with, or position held at, the Company. Through September 30, 2017,2021, the Company had not experienced any losses related to these indemnification obligations, and no claims were outstanding. The Company does not expect significant claims related to these indemnification obligations and, consequently, concluded that the fair value of these obligations is negligible, and no related reserves were established.

2. Summary of Significant Accounting Policies
PrinciplesThe Company disclosed its significant accounting policies in Note 2 – Summary of ConsolidationSignificant Accounting Policies included in the Company’s Annual Report on Form 10-K for the year ended December 31, 2020. There have been no material changes previously disclosed, with the exception of the matters discussed in recent accounting pronouncements.
Recent Accounting Pronouncements
Recently Adopted
In October 2020, the FASB issued ASU 2020-10, Codification Improvements, which updates various codification topics by clarifying or improving disclosure requirements to align with the SEC’s regulations. The Company adopted the new standard effective January 1, 2021, and there was no impact on its consolidated financial statements includestatements.
In December 2019, the accountsFASB issued ASU 2019-12, Income Taxes (Topic 740) – Simplifying the Accounting for Income Taxes. ASU 2019-12 simplifies the accounting for income taxes by removing certain exceptions to the general principles in Topic 740. The Company adopted the new standard effective January 1, 2021, and there was no impact on its consolidated financial statements.
Not Yet Adopted
In May 2021, the FASB issued ASU 2021-04, Earnings Per Share (Topic 260), Debt – Modifications and Extinguishments (Subtopic 470-50), Compensation – Stock Compensation (Topic 718), and Derivatives and Hedging – Contracts in Entity’s Own Equity (Subtopic 815-40): Issuer's Accounting for Certain Modifications or Exchanges of Freestanding Equity-Classified Written Call Options. ASU 2021-04 provides guidance as to how entities should account for a modification of the Company and its wholly owned subsidiaries, Selecta RUS, LLC (“Selecta (RUS)”)terms or conditions or an exchange of a freestanding equity-classified written call option (i.e., a Russian limited liability corporation, and Selecta Biosciences Security Corporation,warrant) that remains equity-classified after modification or exchange as an exchange of the original instrument for a Massachusetts Security Corporation. All significant intercompany accounts and transactionsnew instrument. An entity should apply the guidance provided in ASU 2021-04 prospectively to modifications or exchanges occurring on or after the effective date. This new standard will be effective for us for fiscal years beginning after December 15, 2021 including interim periods within those fiscal years. The adoption of ASU 2021-04 is not expected to have been eliminated.
Foreign Currency
The functional currency of Selecta (RUS) isan impact on the Russian ruble. Assets and liabilities of Selecta (RUS) are translated at period-end exchange rates, while revenues and expenses are translated at average exchange rates for the period. Translation gains and losses are reflected in accumulated other comprehensive loss within stockholders’ deficit. Foreign currency transaction gainsCompany’s financial position or losses are reflected in the consolidated statementsresults of operations upon adoption.
In August 2020, the FASB issued ASU 2020-06, Debt – Debt with Conversion and comprehensive loss. 
UseOther Options (Subtopic 470-20) and Derivatives and Hedging – Contracts in Entity’s Own Equity (Subtopic 815-40). ASU 2020-06 simplifies the accounting for certain financial instruments with characteristics of Estimates
liabilities and equity, including convertible instruments and contracts on an entity’s own equity. This new standard will be effective for us for fiscal years beginning after December 15, 2021, including interim periods within those fiscal years. The preparation of consolidated financial statements in conformity with U.S. GAAP requiresCompany is assessing the Company’s management to make estimates and assumptions that affect the reported amounts of assets and liabilities, the disclosure of contingent assets and liabilities at the date of theimpact this standard will have on its consolidated financial statements and disclosures.
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In June 2016, the reported amountsFASB issued ASU 2016-13, Financial Instruments-Credit Losses (Topic 326), Measurement of revenues and expenses duringCredit Losses on Financial Instruments. Subsequently, in November 2018, the FASB issued ASU 2018-19, Codification Improvements to Topic 326, Financial Instruments-Credit Losses. ASU 2016-13 requires entities to measure all expected credit losses for most financial assets held at the reporting period. The Company’s management considers many factors in selecting appropriate financial accounting policies and controls, and bases its estimatesdate based on an expected loss model which includes historical experience, current conditions, and other market-specific or other relevant assumptions that it believesreasonable and supportable forecasts. ASU 2016-13 also requires enhanced disclosures to be reasonable under the circumstances. In preparing these consolidatedhelp financial statements, management used significant estimates in the following areas, among others: revenue recognition, the fair value of common stock and other equity instruments, accounting for stock-based compensation, income taxes, collectability of accounts receivable, useful lives of long-lived assets, accrued expenses, and accounting for project development. The Company assesses the above estimates on an ongoing basis; however, actual results could materially differ from those estimates.
The Company’s management madestatement users better understand significant estimates and assumptionsjudgments used in determining the fair valueestimating credit losses. This new standard will be effective for us for fiscal years beginning after December 15, 2021. The adoption of its common stock for those periods reported priorASU 2016-13 is not expected to the completion of the initial public offering ofhave an impact on the Company’s common stock (the “IPO”). financial position or results of operations upon adoption.

3. Marketable Securities
The Company utilized various valuation methodologies in accordance withfollowing table summarizes the frameworkmarketable securities held as of the 2004 American InstituteSeptember 30, 2021 (in thousands):
Amortized
cost		Unrealized gainsUnrealized lossesFair
value
September 30, 2021
Corporate bonds$2,035 $— $(1)$2,034 
Commercial paper21,984 — — 21,984 
Total$24,019 $— $(1)$24,018 
All marketable securities held at September 30, 2021 had maturities of Certified Public Accountants’ Technical Practice Aid, Valuation of Privately-Held Company Equity Securities Issuedless than 12 months when purchased and are classified as Compensation, to estimate the fair value of its common stock. Each valuation methodology included estimates and assumptions that require the Company’s judgment. These estimates and assumptions included a number of objective and subjective factors, including external market conditions affecting the biotechnology industry sector, the prices at which the Company sold shares of its preferred stock, the superior rights and preferences ofshort-term marketable securities senior to the Company’s common stock at the time and the likelihood of achieving a liquidity event, such as an initial public offering or sale. Significant changes to the key assumptions used in the valuations could result in different fair values of common stock at each valuation date.
Segment Information
Operating segments are identified as components of an enterprise about which separate discrete financial information is available for evaluation by the chief operating decision maker, the Company’s Chief Executive Officer, in making decisions regarding resource allocation and assessing performance. The Company views its operations and manages its business in one operating segment, the research and development of nanoparticle immunomodulatory drugs for the treatment and prevention of human diseases.
Reverse Stock Split
In connection with the initial public offering, the Company’s Board of Directors and stockholders approved a one-for-3.9 reverse stock split of the Company’s common stock. The reverse stock split became effective June 7, 2016. All share and per share amounts presented have been retroactively adjusted for all periods presented to give effect to this reverse stock split, including reclassifying an amount equal to the reduction in par value of common stock to additional paid-in capital.

Cash Equivalents and Short-term Investments
Cash equivalents include all highly liquid investments maturing within 90 days from the date of purchase. Investments consist of securities with remaining maturities greater than 90 days when purchased. The Company classifies these investments as available‑for‑sale and records them at fair value inon the accompanying consolidated balance sheets. Unrealized gains or losses are included in accumulated other comprehensive income (loss). Premiums or discounts from par value are amortized to investment income over the life of the underlying investment.
The Company, as part of its cash management strategy, may invest in reverse repurchase agreements. All reverse repurchase agreements are tri-party and have maturities of three months or less at the time of investment. These agreements are collateralized by U.S. treasury securities for an amount no less than 102% of their value.
Although available to be sold to meet operating needs or otherwise, securities are generally held through maturity. The cost of securities sold is determined based on the specific identification method for purposes of recording realized gains and losses.sheet. During the reporting periods,nine months ended September 30, 2021, there were no realized gains or losses on sales of investments, and no investments weremarketable securities adjusted for other than temporary declines in fair value.
ConcentrationsAs of Credit Risk and Off‑Balance Sheet Risk
Financial instruments that potentially subjectDecember 31, 2020, the Company to concentration of credit risk consist primarily of cash, cash equivalents, and accounts receivable. Cash and cash equivalents are deposited with federally insured financial institutions in the United States and may, at times, exceed federally insured limits. Management believes that the financial institutions that hold the Company’s deposits are financially credit worthy and, accordingly, minimal risk exists with respect to those balances. Generally, these deposits may be redeemed upon demand and therefore bear minimal interest rate risk. As an integral part of operating its Russian subsidiary, the Company also maintains cash in Russian bank accounts in denominations of both Russian rubles and U.S. dollars. As of September 30, 2017, the Company maintained approximately $1.7 million in Russian bank accounts, of which $1.6 million was held in U.S. dollars.no marketable securities.

4. Net Loss Per Share
The Company has minimal credit riskreported a net loss for the three and nine months ended September 30, 2021 and 2020. The Company used the treasury stock method to determine the number of dilutive shares. The following table sets forth the computation of basic and diluted net loss per share (in thousands, except share and per-share data):
 Three Months Ended
September 30,		Nine Months Ended
September 30,
 2021202020212020
Numerator:
     Net loss$(17,894)$(9,729)$(37,926)$(53,430)
Denominator:
     Weighted-average common shares outstanding - basic and diluted115,169,949 105,325,788 113,161,622 98,968,359 
Net loss per share:
     Basic and diluted$(0.16)$(0.09)$(0.34)$(0.54)

The following table represents the potential dilutive common shares excluded from the computation of the diluted net loss per share for all periods presented, as the majorityeffect would have been anti-dilutive:
 Three Months Ended
September 30,		Nine Months Ended
September 30,
 2021202020212020
Options, RSUs and ESPP shares11,701,844 7,638,839 11,701,844 7,638,839 
Warrants to purchase common stock12,378,016 13,888,525 12,378,016 13,888,525 
Total24,079,860 21,527,364 24,079,860 21,527,364 

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Table of accounts receivable relates to amounts due underContents
5. Fair Value Measurements
The following tables present the Company’s assets and liabilities that are measured at fair value on a government sponsored grant, collaboration with large pharmaceutical companies or grants from well‑known and supported non‑profit organizations. The Company did not have any off balance sheet arrangementsrecurring basis as of September 30, 20172021 and December 31, 2016.2020 (in thousands):
Fair Value of Financial Instruments
September 30, 2021
TotalLevel 1Level 2Level 3
Assets:
     Money market funds (included in cash equivalents)$56,563 $56,563 $— $— 
Marketable securities:
     Corporate bonds2,034 — 2,034 — 
     Commercial paper21,984 — 21,984 — 
Total assets$80,581 $56,563 $24,018 $— 
Liabilities:
     Warrant liabilities$40,043 $— $— $40,043 
Total liabilities$40,043 $— $— $40,043 
The Company’s financial instruments consist mainly of cash equivalents, short‑term investments, restricted cash, accounts receivable, accounts payable, loans payable, and common stock warrants. The carrying amounts of cash equivalents, Short-term investments, restricted cash, accounts receivable, and accounts payable approximate their estimated fair value due to their Short-term maturities.
Accounting standards define fair value as the price that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. A three‑level hierarchy is used to prioritize the inputs to valuation techniques used to measure fair value. The hierarchy gives the highest priority to unadjusted quoted prices in active markets for identical assets or liabilities (Level 1 measurements), and the lowest priority to unobservable inputs (Level 3 measurements). The three levels of the fair value hierarchy are described below:
December 31, 2020
TotalLevel 1Level 2Level 3
Assets:
     Money market funds (included in cash equivalents)$80,576 $80,576 $— $— 
Total assets$80,576 $80,576 $— $— 
Liabilities:
     Warrant liabilities$28,708 $— $— $28,708 
Total liabilities$28,708 $— $— $28,708 
Level 1—Level 1 inputs are quoted prices in active markets for identical assets or liabilities that the reporting entity has the ability to access at the measurement date.
Level 2—Level 2 inputs are inputs other than quoted prices included within Level 1 that are observable for the asset or liability, either directly or indirectly. If the asset or liability has a specified (contractual) term, a Level 2 input must be observable for substantially the full term of the asset or liability.
Level 3—Level 3 inputs are unobservable inputs for the asset or liability in which there is little, if any, market activity for the asset or liability at the measurement date.
To the extent that a valuation is based on models or inputs that are less observable or unobservable in the market, the determination of fair value requires more judgment. Accordingly, the degree of judgment exercised by the Company in determining fair value is greatest for instruments categorized in Level 3. A financial instrument’s level within the fair value hierarchy is based on the lowest level of any input that is significant to the fair value measurement. The fair value of the Company's loan payable was determined using Level 3 inputs.
Fair value is a market‑based measure considered from the perspective of a market participant rather than an entity‑specific measure. Therefore, even when market assumptions are not readily available, the Company’s own assumptions are set to reflect those that market participants would use in pricing the asset or liability at the measurement date. The Company uses prices and inputs that are current as of the measurement date, including during periods of market dislocation. In periods of market

dislocation, the observability of prices and inputs may change for many instruments. This condition could cause an instrument to be reclassified within levels in the fair value hierarchy. There were no transfers within the fair value hierarchy during the nine months ended September 30, 20172021 or the year ended December 31, 2016.2020.

Cash, Cash Equivalents, and Restricted Cash
As of September 30, 2021 and December 31, 2020, the money market funds were classified as cash and cash equivalents on the accompanying consolidated balance sheets as they mature within 90 days from the date of purchase.
As of September 30, 2021, the Company had restricted cash balances relating to a secured letter of credit in connection with its lease for the Company’s headquarters (see Note 8 included elsewhere in this Quarterly Report). The Company’s consolidated statement of cash flows includes the following as of September 30, 2021 and 2020 (in thousands):
September 30,
20212020
Cash and cash equivalents$114,645 $146,261 
Long-term restricted cash1,379 1,379 
Total cash, cash equivalents, and restricted cash$116,024 $147,640 

Marketable Securities
As of September 30, 2021, marketable securities classified as Level 2 within the valuation hierarchy consist of corporate bonds and commercial paper. Marketable securities represent holdings of available-for-sale marketable debt securities in accordance with the Company’s investment policy. The Company estimates the fair value of these marketable securities by taking into consideration valuations that include market pricing based on real-time trade data for the same or similar securities, and other observable inputs. The amortized cost of available-for-sale debt securities is adjusted for amortization of premiums and accretion of discounts to the earliest call date for premiums or to maturity for discounts.
Loans Payable
At September 30, 2021, in light of the recent issuance of the Term A Loan under the 2020 Term Loan, the Company believes the carrying value approximates the fair value of the loan.
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Common Warrants
In December 2019, the Company issued common warrants in connection with a private placement of common shares. Pursuant to the terms of the common warrants, the Company could be required to settle the common warrants in cash in the event of certain acquisitions of the Company and, as a result, the common warrants are required to be measured at fair value and reported as a liability on the balance sheet. The Company recorded the fair value of the common warrants upon issuance using the Black-Scholes valuation model and is required to revalue the common warrants at each reporting date with any changes in fair value recorded in the statement of operations and comprehensive loss. The valuation of the common warrants is considered Level 3 of the fair value hierarchy due to the need to use assumptions in the valuation that are both significant to the fair value measurement and unobservable including the volatility rate and the estimated term of the warrants. Generally, increases (decreases) in the fair value of the underlying stock and estimated term would result in a directionally similar impact to the fair value measurement. The changes in the fair values of the Level 3 warrant liability are reflected in the statement of operations and comprehensive loss for the three and nine months ended September 30, 2021 and 2020.
The estimated fair value of warrants is determined using Level 3 inputs inherent in the Black-Scholes simulation valuation.
Estimated fair value of the underlying stock.The Company estimates the fair value of the common stock based on the closing stock price at the end of each reporting period.
Risk-free interest rate. The risk-free interest rate is based on the U.S. Treasury at the valuation date commensurate with the expected remaining life assumption.
Dividend rate. The dividend rate is based on the historical rate, which the Company anticipates will remain at zero.
Expected life. The expected life of the warrants is assumed to be equivalent to their remaining contractual term which expires on December 23, 2024.
Volatility. The Company estimates stock price volatility based on the Company’s historical volatility and the historical volatility of peer companies for a period of time commensurate with the expected remaining life of the warrants.
A summary of the Black-Scholes pricing model assumptions used to record the fair value of the warrant liability is as follows:
September 30,
2021
Risk-free interest rate0.53 %
Dividend yield— 
Expected life (in years)3.23
Expected volatility98.07 %
Changes in Level 3 Liabilities Measured at Fair Value on a Recurring Basis
The following table reflects a roll-forward of fair value for the Company’s Level 3 warrant liabilities (see Note 10), for the nine months ended September 30, 2021 (in thousands):
Warrant liabilities
Fair value as of December 31, 2020$28,708 
     Change in fair value11,335 
Fair value as of September 30, 2021$40,043 

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6. Property and Equipment
Property and equipment are recorded at cost and depreciated using the straight‑line method over the estimated useful livesconsists of the respective assets, generally seven yearsfollowing (in thousands):
 September 30,December 31,
 20212020
Laboratory equipment$5,095 $4,427 
Computer equipment and software734 532 
Leasehold improvements45 38 
Furniture and fixtures327 327 
Office equipment163 163 
Construction in process93 163 
Total property and equipment6,457 5,650 
Less accumulated depreciation(4,650)(4,255)
Property and equipment, net$1,807 $1,395 

Depreciation expense was $0.1 million and $0.4 million for furniture, five yearsthe three and nine months ended September 30, 2021, respectively. Depreciation expense was $0.1 million and $0.5 million for equipmentthe three and three yearsnine months ended September 30, 2020, respectively.

7. Accrued Expenses
Accrued expenses consist of the following (in thousands):
 September 30,December 31,
 20212020
Payroll and employee related expenses$2,552 $3,049 
Collaboration and licensing1,350 1,350 
Accrued patent fees457 534 
Accrued external research and development costs4,551 2,029 
Accrued professional and consulting services1,205 798 
Accrued interest165 170 
Other462 216 
Accrued expenses$10,742 $8,146 

8. Leases
65 Grove Street Lease
In July 2019, the Company entered into a lease for computer25,078 square feet of laboratory and office equipment. Leasehold improvements are amortized over their useful lifespace located at 65 Grove Street, Watertown, Massachusetts, or the lifeHeadquarters Lease. As part of the Headquarters Lease, the Company incurred $0.8 million in non-reimbursable construction costs. The lease whichever is shorter. Major additions and betterments are capitalized. Maintenance and repairs, which do not improve or extendbegan in March 2020, when the lifeCompany took control of the respective assets, are charged to operations as incurred. Costs incurred for construction in progress are recorded as assets and are not amortized until the construction is substantially completeoffice space, and the assets are ready for their intended use.
Impairmentlease term is 8 years. The discount rate of Long‑Lived Assets
The Company periodically evaluates its long‑lived assets for potential impairment. Impairment is assessed when there is evidence that events or changes in circumstances indicate that the carrying amount of an asset may not be recovered. Recoverability of these assets is assessed8.9% was determined based on undiscounted expected futurethe Company’s incremental borrowing rate adjusted for the lease term, including any reasonably certain renewal periods. In connection with the Headquarters Lease, the Company secured a letter of credit from Silicon Valley Bank, or SVB, for $1.4 million, recognized as long-term restricted cash, flows from the assets, considering a number of factors, including past operating results, budgets and economic projections, market trends, and product development cycles. Impairment in the carrying value of each asset is assessed when the undiscounted expected future cash flows derived from the asset are less than their carrying value. The Company did not recognize any impairment charges as of September 30, 20172021 and December 31, 2016.2020, respectively, which automatically renews each year.
Debt Issuance CostsMoscow, Russia Lease
The Company has a month-to-month facility agreement for its Moscow, Russia office. Rent expense is recognized as incurred.
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For the three and nine months ended September 30, 2021 and 2020 the components of lease costs were as follows (in thousands):
Three Months Ended
September 30,		Nine Months Ended
September 30,
2021202020212020
Operating lease cost$457 $506 $1,355 $1,590 
Variable lease cost182 123 652 496 
Short-term lease cost2 3 7 8 
Total lease cost$641 $632 $2,014 $2,094 

The maturity of the Company’s operating lease liabilities as of September 30, 2021 were as follows (in thousands):
September 30,
2021
2021 (remainder)$457 
20221,866 
20231,922 
20241,980 
20252,039 
Thereafter4,945 
     Total future minimum lease payments13,209 
Less imputed interest3,323 
     Total operating lease liabilities$9,886 

The supplemental disclosure for the statement of cash flows related to operating leases were as follows (in thousands):
September 30,
20212020
Cash paid for amounts included in the measurement of lease liabilities:$1,355 $2,079 

Other than the initial recording of the right-of-use asset and lease liability for the Headquarters Lease in 2020, which was non-cash, the changes in the Company’s right-of-use asset and lease liability for the nine months ended September 30, 2021 and 2020 are reflected in the non-cash lease expense and accrued expenses and other liabilities, respectively, in the consolidated statements of cash flows.
The following summarizes additional information related to operating leases:
September 30,
20212020
Weighted-average remaining lease term6.6 years7.7 years
Weighted-average discount rate8.9 %8.9 %

9. Debt
2020 Term Loan
On August 31, 2020, the Company entered into a term loan of up to $35.0 million, or the 2020 Term Loan, consisting of term loans in an aggregate amount of $25.0 million, or the Term A Loan, and term loans in an aggregate amount of $10.0 million, or the Term B Loan, governed by a loan and security agreement, or the Loan Agreement, between the Company and Oxford Finance LLC, or Oxford, as Collateral Agent and a Lender, and SVB, as a Lender. The Term A Loan was funded in full on August 31, 2020, or the Funding Date.
The Term B Loan was to be available, subject to Collateral Agent’s discretion and customary terms and conditions, during the period commencing on the date the Company had delivered to the Collateral Agent and the Lenders evidence: (i) the Company or one of the Company’s collaboration partners has enrolled its first patient for a Phase 1 clinical trial evaluating the treatment of methylmalonic acidemia, or MMA, and (ii) the Company has enrolled the first patient in each of two Phase 3 pivotal trials evaluating SEL-212, or the Second Draw Period Milestone, and ending on the earliest of (i) the date which is 30 days following the date the Second Draw Period Milestone is achieved, (ii) September 30, 2021 and (iii) the occurrence of an event of default, other than an event of default that has been waived in writing by Collateral Agent and the Lenders in their sole
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discretion, with such period referred to as the Second Draw Period. The Second Draw Period expired on September 30, 2021 and the Term B Loan is no longer available to be drawn by the Company in the future.
The 2020 Term Loan will mature on August 1, 2025. Each advance under the Term Loan accrues interest at a floating per annum rate equal to the greater of (a) 7.90%, and (b) the lesser of (x) the sum of (i) the prime rate reported in The Wall Street Journal on the last business day of the month that immediately precedes the month in which the interest will accrue, and (ii) 4.65% and (y) 10.00%. The Term Loan provides for interest-only payments on a monthly basis until April 1, 2022. Thereafter, amortization payments will be payable monthly in equal installments of principal and interest to fully amortize the outstanding principal over the remaining term of the loan, subject to recalculation upon a change in the prime rate. The Company may prepay the Term Loan in full but not in part provided that the Company (i) provides ten days’ prior written notice to Collateral Agent, (ii) pays on the date of such prepayment (A) all outstanding principal plus accrued and unpaid interest, and (B) a prepayment fee of between 3.0% and 1.0% of the aggregate original principal amount advanced by the lender depending on the timing of the prepayment. Amounts outstanding during an event of default are payable upon SVB’s demand and shall accrue interest at an additional rate of 5.0% per annum of the past due amount outstanding. At the end of the loan term (whether at maturity, by prepayment in full or otherwise), the Company shall make a final payment to the lender in the amount of 9.0% of the aggregate original principal amount advanced by the lender. The final payment fee totaling $2.3 million is recorded as a loan discount.
The Term Loan is secured by a lien on substantially all of the assets of the Company, other than intellectual property, provided that such lien on substantially all assets includes any rights to payments and proceeds from the sale, licensing or disposition of intellectual property. The Company has also granted the Collateral Agent a negative pledge with respect to its intellectual property.
The Loan Agreement contains customary covenants and representations, including but not limited to financial reporting obligations and limitations on dividends, indebtedness, collateral, investments, distributions, transfers, mergers or acquisitions, taxes, corporate changes, deposit accounts, and subsidiaries. The Loan Agreement also contains other customary provisions, such as expense reimbursement, non-disclosure obligations as well as indemnification rights for the benefit of the Collateral Agent.
The events of default under the Loan Agreement include, but are not limited to, the Company’s failure to make any payments of principal or interest under the Loan Agreement or other transaction documents, the Company’s breach or default in the performance of any covenant under the Loan Agreement or other transaction documents, the occurrence of a material adverse change, the Company making a false or misleading representation or warranty in any material respect under the Loan Agreement, the Company’s insolvency or bankruptcy, any attachment or judgment on the Company’s assets of at least $0.5 million, or the occurrence of any default under any agreement or obligation of the Company involving indebtedness in excess of $0.5 million. If an event of default occurs, the Collateral Agent is entitled to take enforcement action, including acceleration of amounts due under the Loan Agreement.
The Company incurred $0.4 million in debt issuance costs in connection with the closing of the 2020 Term Loan. Debt issuance costs and fees paid to lenders are classified as a debt discount, and are recordedpresented in the consolidated balance sheet as a direct deduction from the face amount of the related debt. Issuance costs paidassociated liability and amortized to third parties that are the direct result of the debt issuance are capitalized as a direct deduction from the face amount of the related debt. Debt issuance costs are amortizedinterest expense over the term of the related debt usingdebt.
The Company assessed all terms and features of the 2020 Term Loan to identify any potential embedded features that would require bifurcation. As part of this analysis, the Company assessed the economic characteristics and risks of the 2020 Term Loan, including any put, call, and contingent features. The Company determined that the interest methodrate collar and prepayment call option did not require bifurcation; whereas the contingent put option and default (contingent) interest rate feature met bifurcation criteria resulting in immaterial amounts.
Warrants
On August 31, 2020, in connection with the 2020 Term A Loan, the Company issued warrants to the Lenders to purchase an aggregate of 196,850 shares of its common stock at an exercise price equal to $2.54 per share. In accordance with ASC 815-40, these warrants are classified as permanent equity in the accompanying consolidated balance sheets and will expire ten years from the date of issuance. The initial grant date fair value of the warrants was $0.4 million as determined by the Black-Scholes valuation model and recorded to stockholders' equity, with the SVB portion allocated to the reacquisition price of the 2017 Term Loan and the Oxford fair value portion as a loan discount to the Term A Loan.
Additionally, on August 31, 2020, pursuant to the terms of a Warrant Side Letter agreement among the Company and the Lenders, the Company agreed to issue to the Lenders, on the date the Company draws the Term B Loan and in accordance with each party’s respective pro rata share with respect to the Term B Loan, one or more warrants to purchase an aggregate number of shares of its common stock that is equal to $200,000 divided by the average closing price of the Company’s common stock on The Nasdaq Stock Market LLC for the ten consecutive trading days ending the day before such issuance, rounded down to the nearest whole number of shares, and having an exercise price equal to the Term B Warrant Price. As the Company is no
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longer able to draw the Term B Loan due to the expiration of the Second Draw Period, this additional warrant issuance is no longer possible.
Payoff
On the Funding Date, the Company entered into a payoff letter with SVB, pursuant to which the Company utilized $13.7 million of the 2020 Term Loan to pay off all outstanding obligations under the previous term loan, consisting of the principal payment, final prepayment and accrued interest. During the three and nine months ended September 30, 2020, the Company recognized a loss on extinguishment of debt in the amount of $0.5 million determined as the difference between the reacquisition price and carrying value at August 31, 2020.
As of September 30, 2021 and December 31, 2020, the outstanding principal balance under the 2020 Term Loan was $25.0 million.
Future minimum principal and interest expense. Costs and fees paid to third partiespayments on the 2020 Term Loan as of September 30, 2021 are expensed as incurred.
Accumulated Other Comprehensive Income (Loss)
The components of accumulated other comprehensive income (loss), net of tax, were as follows (in thousands):
2021 (remainder)$499 
20227,343 
20238,611 
20248,027 
20257,274 
Total minimum debt payments31,754 
Less: Amount representing interest(4,505)
Less: Debt discount and deferred charges(1,820)
Less: Current portion of loan payable(4,125)
Loan payable, net of current portion$21,304 

10. Equity
Equity Financings
August 2020 Shelf Registration Statement
On August 6, 2020, the Company filed an updated universal shelf registration statement on Form S-3 (Reg. No. 333-241692) with the SEC to sell an aggregate amount of up to $200.0 million of certain of its securities. The shelf registration statement was declared effective by the SEC on August 14, 2020.
“At-the-Market” Offerings
2017 Sales Agreement
In August 2017, the Company entered into a sales agreement, or the 2017 Sales Agreement, with Jefferies LLC, as sales agent, to sell shares of its common stock with an aggregate value of up to $50.0 million in an “at the market offering.” On August 6, 2020, concurrent with the filing of the updated shelf registration statement, the Company entered into a sales agreement, or the 2020 Sales Agreement with Jefferies LLC, as sales agent, pursuant to which the Company may, from time to time, issue and sell common stock with an aggregate value of up to $50.0 million in an “at the market offering.” The 2017 Sales Agreement terminated pursuant to its terms in August 2020.
During the nine months ended September 30, 2021, the Company sold 6,883,153 shares of its common stock pursuant to the 2020 Sales Agreement for aggregate net proceeds of $30.9 million, after deducting commissions and other transaction costs. During the year ended December 31, 2020, the Company sold 1,069,486 shares of its common stock pursuant to the 2020 and 2017 Sales Agreements at an average price of approximately $2.16 per share for aggregate net proceeds of $2.1 million, after deducting commissions and other transaction costs. On October 8, 2021, the Company delivered notice to Jefferies LLC that the Company was terminating the 2017 Sales Agreement, with effect as of October 19, 2021. Refer to Note 18 Subsequent Events.
June 2020 Sobi Stock Purchase
On June 11, 2020, the Company entered into a stock purchase agreement with Sobi, pursuant to which the Company sold an aggregate of 5,416,390 shares of its common stock at a purchase price equal to $4.6156 per share, which represented 120% of the 10-day volume-weighted average price of the Company’s common stock prior to signing, for aggregate gross proceeds of $25.0 million, or the Sobi Private Placement. The closing of the Sobi Private Placement occurred on July 31, 2020. The shares
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 Foreign exchange translation adjustment Unrealized gains (losses) on available-for-sale securities Accumulated other comprehensive income (loss)
Balance at December 31, 2016$(4,482) $(36) $(4,518)
Other comprehensive gain (loss) during the period79
 30
 109
Balance at September 30, 2017$(4,403) $(6) $(4,409)
of common stock acquired in the Sobi Private Placement are subject to a one-year lock-up from closing, during which time Sobi is prohibited from selling or otherwise disposing of such shares.
Comprehensive income (loss)In accordance with ASC 815, this forward sale treatment qualified as equity classification as the shares are not within the scope of ASC 480. The gross proceeds of $25.0 million were determined to include a premium to the fair value of the Company’s shares as of July 28, 2020 of approximately $14.5 million. As a result, such amount was included in the transaction price for revenue recognition of the Sobi License. See Note 12 for details.
Also on June 11, 2020, the Company entered into a registration rights agreement (as amended by that certain letter agreement, dated as of November 4, 2020) with Sobi, pursuant to which the Company agreed to prepare and file a registration statement with respect to the resale of the shares of common stock acquired in the Sobi Private Placement. The Company will be required to file this resale registration statement within 30 days following receipt by the Company of a written request from Sobi to file such resale registration statement, and to have the registration statement declared effective within 10 business days after the SEC informs the Company that no review of such resale registration statement will be made or that the SEC has no further comments on such resale registration statement.
December 2019 Financing
On December 18, 2019, the Company entered into a securities purchase agreement, or the 2019 Purchase Agreement, with a group of institutional investors and certain members of the Board of Directors. Pursuant to the 2019 Purchase Agreement, the Company sold an aggregate of 37,634,883 shares of its common stock at a purchase price of $1.46 per share, warrants to purchase an aggregate of 22,988,501 shares of common stock at a purchase price of $0.125 per share underlying each common warrant, and pre-funded warrants to purchase an aggregate of 8,342,128 shares of common stock at a purchase price of $1.46 per share, all with five year terms, or the 2019 PIPE. The closing of the 2019 PIPE occurred on December 23, 2019. The exercise price of the pre-funded warrants is $0.0001 per share and the exercise price for the common warrants is $1.46 per share. In the event of a certain sale of the Company, the terms of the common warrants require us to make a payment to such common warrant holders based on a Black-Scholes valuation (using variables as specified in the warrants). This provision does not apply to the pre-funded warrants. Therefore, the Company is required to account for the common warrants as liabilities and record them at fair value, while the pre-funded warrants met the criteria to be classified as permanent equity.
The Company recorded the fair value of the common warrants of $40.7 million upon issuance using the Black-Scholes valuation model. Issuance costs were allocated between the equity component with an offset to additional paid-in capital and the liability component recorded as expense on a relative fair value basis. Total net proceeds from the equity offering was $65.6 million, after deducting transaction costs and commissions of $4.4 million which was paid in the three months ended March 31, 2020.
The common warrants were revalued as of September 30, 2021 at $40.0 million. During the three months ended September 30, 2021 and 2020, the Company recorded a decrease in the fair value of the warrants of $0.6 million and $4.8 million, respectively, in the unaudited consolidated statements of operations and comprehensive loss. During the nine months ended September 30, 2021 and 2020, the Company recorded an increase in the fair value of the warrants of $11.3 million and $3.6 million, respectively, in the unaudited consolidated statements of operations and comprehensive loss.

Warrants
During the nine months ended September 30, 2021, there were no warrants issued, exercised, or canceled.
Number of Warrants
Equity
 classified		Liability classifiedTotalWeighted average
exercise price
Outstanding at September 30, 2021292,469 12,085,547 12,378,016 $1.60 

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Reserved Shares
The Company has authorized shares of common stock for future issuance as follows:
 As of
 September 30, 2021December 31, 2020
Exercise of common warrants12,378,016 12,378,016 
Shares available for future stock incentive awards6,049,422 4,916,374 
Unvested restricted stock units561,888 87,500 
Outstanding common stock options11,082,277 7,775,249 
Total30,071,603 25,157,139 
11. Stock Incentive Plans
The Company maintains the 2008 Stock Incentive Plan, or the 2008 Plan, for employees, consultants, advisors, and directors. The 2008 Plan provided for the granting of incentive and non-qualified stock option and restricted stock awards as determined by the Board.
In June 2016, the Company’s stockholders approved the 2016 Incentive Award Plan, or the 2016 Plan, which authorized 1,210,256 shares of common stock for future issuance under the 2016 Plan and the Company ceased granting awards under the 2008 Plan. Upon the effective date of the 2016 Plan, awards issued under the 2008 Plan remain subject to the terms of the 2008 Plan. Awards granted under the 2008 Plan that expire, lapse or terminate become available under the 2016 Plan as shares available for future grants.
Additionally, pursuant to the terms of the 2016 Plan, the Board is authorized to grant awards with respect to common stock, and may delegate to a committee of one or more members of the Board or executive officers of the Company the authority to grant options and restricted stock units. On December 9, 2020, the Board established a Stock Option Committee authorized to grant awards to certain employees and consultants subject to conditions and limitations within the 2016 Plan. In January 2021 and 2020, the number of shares of common stock that may be issued under the 2016 Plan was increased by 4,322,850 and 3,453,022 shares, respectively. As of September 30, 2021, 1,935,395 shares remain available for future issuance under the 2016 Plan.
In September 2018, the Company’s 2018 Employment Inducement Incentive Award Plan, or the 2018 Inducement Incentive Award Plan was adopted by the Board without stockholder approval pursuant to Rule 5635(c)(4) of the Nasdaq Stock Market LLC listing rules, which authorized 1,175,000 shares of its common stock for issuance. In March 2019, the Board approved the amendment and restatement of the 2018 Inducement Incentive Award Plan to reserve an additional 2,000,000 shares of the Company’s common stock for issuance thereunder. As of September 30, 2021, there are 1,591,661 shares available for future grant under the 2018 Inducement Incentive Award Plan.
Stock-based Compensation Expense
Stock-based compensation expense by classification included within the consolidated statements of operations and comprehensive loss was as follows (in thousands):
 Three Months Ended
September 30,		Nine Months Ended
September 30,
 2021202020212020
Research and development$791 $532 $2,331 $1,773 
General and administrative1,113 764 3,136 2,413 
Total stock-based compensation expense$1,904 $1,296 $5,467 $4,186 

Stock Options
Employees
The estimated grant date fair values of employee stock option awards granted under the 2016 Plan and the 2018 Inducement Incentive Award Plan were calculated using the Black-Scholes option pricing model, based on the following weighted-average assumptions:
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Three Months Ended
September 30,		Nine Months Ended
September 30,
 2021202020212020
Risk-free interest rate1.01 %0.24 %0.79 %1.19 %
Dividend yield— — — — 
Expected term6.066.086.036.05
Expected volatility93.55 %94.88 %95.05 %90.19 %
Weighted-average fair value of common stock$4.19 $2.47 $3.58 $2.39 

The weighted average grant date fair value of stock options granted to employees during the three and nine months ended September 30, 2021 and 2020 was $3.17 and $1.88, $2.73 and $1.77 respectively.
As of September 30, 2021, total unrecognized compensation expense related to unvested employee stock options was $12.8 million, which is expected to be recognized over a weighted average period of 2.9 years.

Non-employee consultants
As of September 30, 2021, there was no unrecognized compensation expense related to non-employee consultants’ stock options.
The following table summarizes the stock option activity under the 2008 Plan, 2016 Plan, and 2018 Inducement Incentive Award Plan:
   Weighted-average 
  remainingAggregate
 Number ofWeighted-averagecontractual termintrinsic value
 optionsexercise price ($)(in years)(in thousands)
Employees    
Outstanding at December 31, 20207,302,176 $3.98 8.43$4,456 
Granted4,609,811 $3.58   
Exercised(397,492)$1.72   
Forfeited(905,291)$2.82   
Outstanding at September 30, 202110,609,204 $3.99 8.44$11,080 
Vested at September 30, 20213,583,316 $5.27 7.32$4,133 
Vested and expected to vest at September 30, 20219,775,480 $4.04 8.36$10,400 
Non-employee consultants    
Outstanding at December 31, 2020473,073 $5.89 5.23$86 
Granted— $— 
Exercised— $— 
Forfeited— $— 
Outstanding at September 30, 2021473,073 $5.89 4.48$282 
Vested at September 30, 2021473,073 $5.89 4.48$282 
Vested and expected to vest at September 30, 2021473,073 $5.89 4.48$282 

Restricted Stock Units
In January 2021, the Company granted 369,800 restricted stock awards to employees under the 2016 Plan, which will vest over a four year term. In addition, during the first quarter of 2021, the Company awarded 197,500 restricted stock units to executives under the 2016 Plan, of which 98,750 were determined to be granted as of the award date consistent with ASC 718.
On September 24, 2021, the Compensation Committee of the Board of Directors, under authority duly granted to them by the Board of Directors, determined a definitive performance metric for the second performance condition previously undefined, and therefore granted the previously reserved 98,750 restricted stock units. These restricted stock units will vest in 2 equal installments on the dates an applicable performance condition is achieved, on or prior to December 31, 2021. If the performance conditions are not satisfied on or prior to December 31, 2021, the restricted stock units will be forfeited for no consideration.
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The restricted stock units granted during the first quarter of 2021 had a weighted average fair value of $2.99 per share based on the closing price of the Company’s common stock on the date of grant. The restricted stock units were valued at approximately $1.4 million on their grant date. Forfeitures are estimated at the time of grant and are adjusted, if necessary, in subsequent periods if actual forfeitures differ from those estimates. The Company has estimated a forfeiture rate of 10% for restricted stock awards to employees based on historical attrition trends.
In September 2021, the Company granted 36,300 restricted stock awards to executives under the 2016 Plan which will vest over a four-year term.
Unrecognized compensation expense for all restricted stock units was $1.4 million as of September 30, 2021, which is expected to be recognized over a weighted average period of 2.1 years.
The following table summarizes the Company’s restricted stock units under the 2016 Plan and 2018 Inducement Incentive Award Plan:
 Number of sharesWeighted average
grant date
fair value ($)
Unvested at December 31, 202087,500 $6.03 
Granted603,600 3.24 
Vested(32,812)6.03 
Forfeited(96,400)2.99 
Unvested at September 30, 2021561,888 $3.56 

Employee Stock Purchase Plan
In June 2016, the Company approved the 2016 Employee Stock Purchase Plan, or the ESPP, which authorized 173,076 shares of common stock for future issuance under the ESPP to participating employees. In January 2021 and 2020, the number of shares of common stock authorized for issuance under the ESPP was increased by 1,080,711 shares and 863,254 shares, respectively. During the nine months ended September 30, 2021, the Company issued 58,794 shares of common stock under the ESPP. As of September 30, 2021, 2,522,366 shares remain available for future issuance under the ESPP.
For each of the three and nine months ended September 30, 2021 and 2020, the Company recognized less than $0.1 million and $0.1 million of stock-based compensation expense under the ESPP, respectively.

12. Revenue Arrangements
Swedish Orphan Biovitrum
License and Development Agreement
On June 11, 2020, the Company and Sobi entered into the Sobi License. Pursuant to the Sobi License, the Company has agreed to grant Sobi an exclusive, worldwide (except as to Greater China) license to develop, manufacture and commercialize the Company’s SEL-212 drug candidate, which is currently in development for the treatment of chronic refractory gout. The SEL-212 drug candidate is a pharmaceutical composition containing a combination of SEL-037, or the Compound, and ImmTOR. Pursuant to the Sobi License, in consideration of the license, Sobi agreed to pay the Company a one-time, up-front payment of $75.0 million. Sobi has also agreed to make milestone payments totaling up to $630.0 million to the Company upon the achievement of various development and regulatory milestones and, if commercialized, sales thresholds for annual net sales of SEL-212, and tiered royalty payments ranging from the low double digits on the lowest sales tier to the high teens on the highest sales tier.
Pursuant to the Sobi License, the Company has agreed to supply (at cost) quantities of the Compound and ImmTOR as necessary for completion of the two Phase 3 clinical trials of SEL-212 (DISSOLVE I and DISSOLVE II) and a 6-month placebo extension. The Company is required to supply quantities of the Compound until all rights to the Compound and any materials needed to manufacture the Compound are transferred to Sobi. Sobi has agreed to reimburse the Company for all budgeted costs incurred to complete development of SEL-212, including but not limited to costs incurred while conducting and completing the Phase 3 DISSOLVE trials, except for any costs of additional development activities required that are related to ImmTOR and that are unrelated to SEL-212. Sobi will have control and responsibility over all regulatory filings, including any investigational drug applications (IND), biologics license applications (BLA), and marketing authorization applications (MAA) relating to the licensed product.
The transactions contemplated by the Sobi License were consummated on July 28, 2020 following the expiration or termination of the required waiting periods under the Hart-Scott-Rodino Antitrust Improvements Act of 1976. Sobi may
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terminate the Sobi License for any reason upon 180 days’ written notice to the Company, whereby all rights granted under the Sobi License would revert back to the Company. In addition, if Sobi were to terminate the Sobi License, the Company has the option to obtain a license to all patents and know-how necessary to exploit SEL-212 in existence as of the termination date from Sobi in return for making an equitable royalty payment to Sobi.
Additionally, on June 11, 2020, the Company entered into the Sobi Purchase Agreement in connection with the Sobi License. The closing of the Sobi Private Placement occurred on July 31, 2020, following the closing of the transactions contemplated under the Sobi License. See Note 10 for details.
The Company determined that the Sobi License represents a service arrangement under the scope of ASC 606. In addition, given the Sobi License and Sobi Purchase Agreement were executed contemporaneously and negotiated as a package with a single commercial objective, the Company will account for the two agreements as a single contract. The term of the Sobi License commenced upon the effective date of July 28, 2020 and will continue on a product-by-product basis until the royalty terms for each country have expired. The royalty term for a given product begins upon the first commercial sale of the product in a country and ends at the later of ten years from the first commercial sale, expiration of the last valid patent claim covering the product and expiration of all regulatory exclusivity periods for the product in a country. Given the reversion of the rights under the Sobi License represents a penalty in substance for a termination by Sobi, the contract term would remain the stated term of the Sobi License.
The Company determined that the Sobi License contains 3 distinct performance obligations due to the nature of the promises in the contract, which includes conducting the Phase 3 DISSOLVE trials, Sobi’s option to set-up a second source supplier, and a combined obligation comprised of the delivery of the license to SEL-212, transfer of the know-how and the manufacturing and delivery of SEL-212 supply for development, or the Combined License Obligation. As the set-up of a second source supplier is optional for Sobi and the Company will be reimbursed at cost for its efforts in the subsequent set-up and technology transfer, the option for this future service was determined to be at a significant and incremental discount to its standalone selling price and treated as a material right in the arrangement, namely a distinct performance obligation.
In determining the transaction price, the Company concluded the upfront payment of $75.0 million and the $5.0 million development milestone associated with the dosing of the first patient in the Phase 3 DISSOLVE trials will be included in the transaction price. All other development milestones will be fully constrained and only be included in the transaction price when the respective milestone is deemed probable of achievement. Each of these variable consideration items was evaluated under the most likely amount method to determine whether such amounts were probable of occurrence, or whether such amounts should be constrained until they become probable. As part of the evaluation of the constraint, the Company considered numerous factors, including that receipt of such milestones is outside the control of the Company and probability of success criteria is estimated. The Company will re-evaluate the transaction price in each reporting period, as uncertain events are resolved. In accordance with ASC 606, the Company will only recognize revenue associated with sales-based milestones and royalties when the subsequent sales thresholds are reached and underlying sales occur, respectively. In connection with the Sobi Purchase Agreement, the Company determined that the gross proceeds of $25.0 million from the Sobi Private Placement included a premium to the fair value of the Company’s shares as of July 28, 2020 equal to approximately $14.5 million. The premium amount will be included in the transaction price for revenue recognition. The Company will estimate and include in the transaction price the total net earningsreimbursements to be received from Sobi for both the manufacturing and all other non-owner changes in equity. Except for net incomedelivery of the Compound and unrealized gains and losses on available-for-sale securities and foreign exchange translation adjustments, the Company does not have any transactions or other economic events that qualify as comprehensive income (loss). There were no reclassifications out of accumulated other comprehensive income or lossImmTOR as well as no tax effectconducting the Phase 3 DISSOLVE trials. The Company determined that a significant financing component does not exist in its arrangement with Sobi.
The Company allocated the transaction price based on the relative standalone selling prices of the 3 distinct performance obligations. The Company estimated the standalone selling price of conducting the Phase 3 DISSOLVE trials by forecasting its anticipated costs and applying a margin reflective of the industry. The Company must determine the standalone selling price of the second source supplier option by determining the discount given to Sobi multiplied by the likelihood that Sobi will exercise the option in the future. Similar to the Phase 3 program estimate, the Company estimated the discount of the option by forecasting the set-up costs and applying a margin that is reflective of the industry. As the Company will be providing the set-up and technology transfer services and the future supply at cost, the discount of the option is equal to the margin amount. The Company considered discussions with Sobi as well as probability of regulatory success of SEL-212 in determining the likelihood of exercise. The Company estimated the standalone selling price of the Combined License Obligation by utilizing a discounted cash flow model.
The Company determined that the delivery of the supply to Sobi best represents the pattern of delivery of the Combined License Obligation as the supply is essential to the utility of the license and know-how. The Company will recognize the revenue allocated to the Combined License Obligation by utilizing the output method. The Company estimated the total supply of the Compound and ImmTOR to be required during the clinical trial period and will recognize revenue as this supply is shipped for use in the clinical trials. The Company will recognize the revenue allocated to the conducting of the Phase 3 DISSOLVE trials obligation by utilizing the input method. The Company estimated the total budgeted costs to be incurred over the Phase 3 DISSOLVE trials and will recognize revenue as these costs are incurred. The Company’s costs best represent the pattern of transfer as these will capture all performance of the trials completed to date and can be readily measured. The
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Company will recognize the revenue allocated to the second source supplier option when the future services and goods are transferred.
As of September 30, 2021 and December 31, 2020, the Company recorded $55.9 million and $68.3 million, respectively, as a short-term contract liability and $5.5 million and $24.2 million, respectively, as a long-term contract liability, representing deferred revenue associated with this agreement. In addition, as of September 30, 2021 the Company has recorded $1.0 million of contract assets related to incremental costs that would not have been incurred if the Sobi License had not been obtained, of which $0.9 million is presented in prepaid expenses and other current assets and $0.1 million is presented in other assets in the accompanying unaudited consolidated balance sheets. Amortization of contract assets was $0.4 million for the period presented.nine months ended September 30, 2021.
As of September 30, 2021 and December 31, 2020, the Company recorded a total outstanding receivable of $7.0 million and $6.9 million, respectively, representing billings for the Phase 3 DISSOLVE program that are subject to reimbursement by Sobi. Revenue Recognitionof $24.3 million and $54.8 million related to the Sobi License was recognized during the three and nine months ended September 30, 2021, respectively. Revenue of $4.3 million related to the Sobi License was recognized during the three and nine months ended September 30, 2020.
The Company’s revenue is primarily generated from research grants in bothSarepta Therapeutics, Inc.
Research License and Option Agreement
On June 13, 2020, the United StatesCompany and Russia,Sarepta entered into a Research License and priorOption Agreement, or the Sarepta Agreement. Pursuant to its termination,the Sarepta Agreement, the Company agreed to grant Sarepta a license under the Company’s intellectual property rights covering the Company’s antigen-specific biodegradable nanoparticle encapsulating ImmTOR to research and research collaboration agreementevaluate ImmTOR in combination with Sanofi.Sarepta’s adeno-associated virus gene therapy technology, or gene editing technology, using viral or non-viral delivery, to treat Duchenne Muscular Dystrophy and certain Limb-Girdle Muscular Dystrophy subtypes, or the Indications. Sarepta will have an option term of 24 months during which it can opt-in to obtain an exclusive license to further develop and commercialize the Product to treat at least one Indication, with a potential to extend the option term for an additional fee. The Company recognizeswill supply ImmTOR to Sarepta for clinical supply on a cost-plus basis.
Sarepta paid a $2.0 million up-front payment to the Company upon signing of the Sarepta Agreement, and the Company is eligible to receive additional preclinical payments during the option term. If Sarepta opts-in to an exclusive license agreement, the Company could receive option exercise payments per Indication upon execution of the exclusive license, and the Company would be entitled to significant development and commercial milestone payments and tiered royalties ranging from the mid-to-high single digits based on net sales.
Pursuant to the Sarepta Agreement, the Company determined the Sarepta Agreement represents a service arrangement under the scope of ASC 606, with a 24 month contract duration. Given the reversion of the rights under the Sarepta Agreement represents a penalty in substance for a termination by Sarepta, the contract term would remain the stated term of the Sarepta Agreement.
The Company determined that the Sarepta Agreement and supply obligation including the delivery of the research license, the licensed know-how, the manufactured supply and delivery of materials represent a single promise and performance obligation to be transferred to Sarepta over time due to the nature of the promises in the contract. The delivery of the manufactured supply is the predominant promise within the arrangement, as it is essential to the utility of the licensed intellectual property. As such, consideration in the initial transaction price will be allocated to the single performance obligation based on the contractual price.
In determining the transaction price, the Company concluded the payment associated with all the performance milestones will be fully constrained and only be included in the transaction price when the respective milestone is deemed probable of achievement. Each of these variable consideration items was evaluated under the most likely amount method to determine whether such amounts were probable of occurrence, or whether such amounts should be constrained until they become probable. As part of its evaluation of the constraint, the Company considered numerous factors, including that receipt of such study milestones is outside the control of the Company and probability of success criteria is estimated.
The Company also determined the option to enter into a future commercial license agreement and extend the term of the option does not represent a material right since it was not priced at an incremental discount. Sarepta may terminate the Sarepta Agreement for any reason upon 30 days’ written notice to the Company. The Sarepta Agreement contains other customary terms and conditions, including representations and warranties, covenants, termination, and indemnification obligations in favor of each party. During the year ended December 31, 2020, the Company and Sarepta entered into 2 amendments relating to an additional feasibility study. During the nine months ended September 30, 2021, the Company and Sarepta entered into a third amendment relating to the additional feasibility study.
On April 13, 2021, the Company was notified by Sarepta of the achievement of the milestone event related to the completion of a non-clinical study for Duchenne muscular dystrophy and certain limb-girdle muscular dystrophies under the
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Sarepta Agreement. Accordingly, the Company received a milestone payment of $3.0 million during the three months ended June 30, 2021.
As of September 30, 2021, two milestones remained constrained, and as of December 31, 2020, all milestones were constrained. The Company will re-evaluate the transaction price in each reporting period, as uncertain events are resolved. The Company will recognize the revenue associated with the upfront payment and combined single performance obligation utilizing the output method, over the 24 month term as the manufactured supply is delivered to Sarepta.
As of September 30, 2021 and December 31, 2020, the Company recorded $4.8 million and $2.0 million, respectively, as a short-term contract liability representing deferred revenue associated with this agreement. Revenue of $0.2 million related to the Sarepta Agreement was recognized during each of the three and nine months ended September 30, 2021. Revenue of $0.3 million related to the Sarepta License Agreement was recognized during the three and nine months ended September 30, 2020.
Asklepios Biopharmaceutical, Inc.
License Agreement for Pompe Disease
On December 17, 2019, the Company and AskBio entered into a license agreement, or the AskBio License Agreement. Pursuant to the AskBio License Agreement, AskBio has exercised its option to exclusively license the Company’s intellectual property rights covering the Company’s ImmTOR platform to research, develop, and commercialize certain AAV gene therapy products utilizing ImmTOR, and targeting the GAA gene, or derivatives thereof, to treat Pompe Disease.
Pursuant to the AskBio License Agreement and ancillary documents, AskBio agreed to pay to the Company upfront fees of an aggregate of $7.0 million. Assuming successful development and commercialization, the Company could receive up to an additional $237.0 million in development, regulatory, and sales milestone payments. If commercialized, the Company would be eligible to receive tiered royalties on global net sales at percentages ranging from mid-to-high single digits. Under the terms of the agreement, the Company will be eligible to receive these royalties commencing on the first commercial sale of the licensed product until the expiration of the later of (i) ten years after the first commercial sale and (ii) expiration of the last to expire valid claim on patents covering the licensed product.
Pursuant to the AskBio License Agreement, the Company will supply AskBio with its ImmTOR platform, or the Supply Obligation, and AskBio will be responsible for all preclinical, clinical and commercial manufacture and supply of licensed products (other than ImmTOR) and carry out all other activities related to the research, development, and commercialization of licensed products at its sole expense, including all regulatory activities related thereto.
The Company determined that the AskBio License Agreement and Supply Obligation represent a single promise and performance obligation. This is because AskBio cannot derive benefit from the license without the simultaneous transfer of the patent protected ImmTOR supply. Therefore, the License Obligation and Supply Obligation represent the only promise in the arrangement and are combined as a single performance obligation.
In determining the transaction price, the Company concluded that the future development milestones, regulatory milestones, sales milestones, and sales royalties all represent variable consideration. Each of these variable consideration items was evaluated under the most likely amount method to determine whether such amounts were probable of occurrence, or whether such amounts should be constrained until they become probable. As part of its evaluation of the constraint, the Company considered numerous factors, including that receipt of such milestones is outside the control of the Company. Consideration related to sales-based milestones as well as royalties on net sales upon commercialization by AskBio, will be recognized when the related sales occur, as they were determined to relate predominantly to the intellectual property granted to AskBio and, therefore, have also been excluded from the transaction price in accordance with the royalty recognition constraint. As of September 30, 2021 and December 31, 2020, all milestones were constrained. The Company will re-evaluate the transaction price in each reporting period, as uncertain events are resolved, or as other changes in circumstances occur.
The total initial transaction price of the contract on the effective date was $7.0 million, comprised of a $2.0 million initial up-front payment upon agreement of terms, and a $5.0 million initial up-front execution fee.
At each of September 30, 2021 and December 31, 2020, the Company recorded $1.7 million as short-term contract liability and $5.3 million as a long-term contract liability, representing deferred revenue associated with this agreement. Revenue will be recognized over the period in which the particles are delivered. No revenue related to the AskBio License Agreement was recognized during the three and nine months ended September 30, 2021 and 2020 as no deliveries were made during these periods.
Spark Therapeutics, Inc.
Spark License Agreement
The disclosures relating to the Company’s license and option agreement, or the Spark License Agreement, with Spark pursuant to which the Company and Spark agreed to collaborate on the development of gene therapies for certain targets
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utilizing the ImmTOR platform reported in the Company’s Annual Report on Form 10-K for the year ended December 31, 2020 which was filed with the SEC on March 12, 2021 have not materially changed since the Company filed such report.
Skolkovo Foundation
During the nine months ended September 30, 2021, revenue of $0.1 million related to the remaining contract liability of the Russia-based Development Fund of New Technologies Development and Commercialization Center, or Skolkovo, grant funding was recognized at the expiration of the three-year audit period.
Transaction Price Allocated to Future Performance Obligations
Remaining performance obligations represent the transaction price of contracts for which work has not been performed (or has been partially performed). As of September 30, 2021, the aggregate amount of the transaction price allocated to remaining performance obligations was $82.4 million.
Contract Balances from Contracts with Customers (Sobi, Sarepta, AskBio, Spark and Skolkovo)
The following table presents changes in the Company’s contract liabilities during the nine months ended September 30, 2021 (in thousands):
Balance atBalance at
beginning of periodAdditionsDeductionsend of period
Nine Months Ended September 30, 2021
Contract liabilities:
     Deferred revenue$110,796 $3,000 $(31,424)$82,372 
Total contract liabilities$110,796 $3,000 $(31,424)$82,372 

13. Related-Party Transactions
Consulting Services
The Company incurred expenses for consulting services provided by its founders totaling less than $0.1 million and $0.1 million during the three and nine months ended September 30, 2021 and 2020, respectively. The Company entered into consulting agreements with its founders to serve on its Scientific Advisory Board, effective January 1, 2020 to December 31, 2021, under which they will be paid quarterly for their services.

14. Collaboration and License Agreements
Cyrus Biotechnology, Inc.
Collaboration and License Agreement
On September 7, 2021, the Company and Cyrus Biotechnology, Inc., or Cyrus, entered into a collaboration and license agreement, or the Cyrus Agreement. Pursuant to the Cyrus Agreement, Cyrus agreed to grant the Company an exclusive, worldwide license to certain intellectual property to form a protein engineering collaboration combining the Company’s ImmTOR platform with Cyrus’ ability to redesign protein therapeutics. The lead program is a proprietary interleukin-2, or IL-2, protein agonist designed to selectively promote expansion of regulatory T cells for treatment of patients with autoimmune diseases and other deleterious immune conditions. Cyrus will contribute its expertise to apply its Rosetta-based computational platform to design candidate variants. Cyrus will also experimentally screen and characterize candidate variants for expression, stability, and receptor binding. The Company will experimentally characterize lead candidates for regulatory T cell expansion and activation in vitro and in vivo. In return for the licensed intellectual property, the Company is obligated to make an upfront payment and pay certain discovery, development, and sales-based milestones which could potentially total up to approximately $1.5 billion across multiple programs. The Cyrus Agreement was assessed for collaboration components and was determined not to be within the scope of ASC 808 as the risk is not shared by both parties. The Company will expense costs related to the Cyrus Agreement as incurred until regulatory approval is received in accordance with ASC Topic 605, Revenue Recognition. Accordingly, revenue730. The Company will assess the capitalization of costs incurred after the receipt of regulatory approval and, if applicable, will amortize these payments based on the expected useful life of each asset, typically based on the expected commercial exclusivity period. The Company is recognized when allalso obligated to pay Cyrus tiered royalties ranging from mid-single digit to low-double digit percentages of annual net sales of collaboration products which will be expensed as the commercial sales occur.
Additionally, on September 7, 2021, the Company entered into a stock purchase agreement, or the Series B Preferred Stock Purchase Agreement, in connection with the Cyrus Agreement. Pursuant to the Series B Preferred Stock Purchase Agreement, the Company purchased 2,326,934 shares of Cyrus’ Series B Preferred Stock, par value $0.0001 per share at a purchase price of $0.8595 per share for $2.0 million.
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In accordance with ASC 810, the Company has a variable interest in Cyrus resulting from its equity investment. The Company will share in Cyrus’ expected losses or receive a portion of its expected returns and absorb the variability associated with changes in the entity’s net assets. However, the Company is not the primary beneficiary as it does not have the power to direct the activities most significant to Cyrus, and therefore it is not required to consolidate Cyrus. The Company determined its equity interest to be within the scope of ASC 321 and elected to record the $2.0 million investment of Cyrus’ Series B Preferred Stock at cost on the purchase date.
As of September 30, 2021, no impairment indicators are present and therefore the carrying value of the following criteria are met:
-    Persuasive evidence of an arrangement exists;
-    Delivery has occurred or services have been rendered;
-investment in Cyrus is $2.0 million on the accompanying consolidated balance sheet. The seller’s priceCompany’s maximum exposure to loss related to this variable interest entity is limited to the buyer is fixedcarrying value of the investment. The Company has not provided financing to Cyrus other than the amount contractually required by the Series B Preferred Stock Purchase Agreement.
Asklepios Biopharmaceutical, Inc.
Feasibility Study and License Agreement
In August 2019, the Company entered into a feasibility study and license agreement with AskBio, or determinable;the AskBio Collaboration Agreement. Pursuant to the AskBio Collaboration Agreement, the Company and
-    Collectability is reasonably assured.
Amounts received prior AskBio agreed to satisfying the revenue recognition criteria are recognizedlicense intellectual property rights to each other as deferred revenue inpart of a collaboration to research, develop, and commercialize certain AAV gene therapy products utilizing the Company’s consolidated balance sheets. Amounts expectedImmTOR platform to be recognizedenable re-dosing of such AAV gene therapy products to treat serious rare and orphan genetic diseases for which there is a significant unmet medical need.
Pursuant to the AskBio Collaboration Agreement, the Company and AskBio agreed to conduct proof of concept studies to potentially validate the use of ImmTOR in conjunction with AskBio’s AAV gene therapy, or SEL-302, (previously disclosed as revenue withinMMA-101, in combination with ImmTOR) for the 12 months followingtreatment of MMA, to mitigate the balance sheet date are classified as deferred revenue, current portion. Amounts not expectedformation of neutralizing anti-AAV capsid antibodies, or the POC Studies. On April 29, 2021, the Company was notified by AskBio that it intended to be recognized as revenue withinopt-out of development of the 12 months followingMMA indication. Consequently, the balance sheet date are classified as deferred revenue, netCompany will assume all rights to the MMA program and intends to continue to progress the SEL-302 program through clinical development.
The SEL-399 program combines an empty AAV capsid (EMC-101), which is an AAV capsid containing no transgene, with ImmTOR and is being conducted in partnership with AskBio. Building on the preclinical data the Company has generated showing ImmTOR’s effect on mitigating or reducing the formation of current portion.



Collaboration Revenueneutralizing antibodies to AAV gene therapies, the Company has commenced a clinical trial of SEL-399 in healthy adult volunteers in Belgium. The goal of the SEL-399 clinical trial is to demonstrate the appropriate dose of ImmTOR in humans to mitigate the formation of antibodies to AAV capsids used in gene therapies.
The Company enters into collaborative arrangementsand AskBio will share responsibility for the research, development and commercialization of product candidates utilizingproducts developed under the Company’s Synthetic Vaccine Particles (SVP) technology.SEL-399 program collaboration. The parties will also share research, development, and commercialization costs equally for all collaboration products, but with a right of either party to opt out of certain products, and thereby no longer be required to share costs for such products. Each party will receive a percentage of net profits under the collaboration equal to the percentage of shared costs borne by such party in the development of such product. Pursuant to the AskBio Collaboration Agreement, AskBio is responsible for manufacturing the AAV capsids and AAV vectors and the Company is responsible for manufacturing ImmTOR.
The AskBio Collaboration Agreement is considered to be within the scope of ASC 808, as both parties are active participants and exposed to the risks and rewards of the collaborative activity. The Company evaluated the terms of these agreements contain multiple deliverables which may include (i) licenses, or options to obtain licenses, to its technology platforms, (ii) rights to future technological improvements, (iii)the AskBio Collaboration Agreement and have identified the following promises in the arrangement (1) conducting research and development activities to be performed on behalfdevelop and commercialize products under the collaboration, or the R&D Services, (2) granting a non-exclusive, non-transferable, royalty-free, fully paid up, worldwide license to certain intellectual property of the collaborative partnerCompany, or as partthe IP Rights, for the purpose of performing the POC Studies, or the Research License, (3) granting an exclusive, nontransferable, worldwide license to the IP Rights for use in certain indications, or the Collaboration License, (4) providing manufactured supply of preclinical and clinical ImmTOR, or the Manufactured Supply, (5) participation on identified steering committees responsible for the oversight of the collaboration, (iv)or the manufactureJSC Participation, and (6) granting an exclusive option to obtain a license under the IP Rights to research, develop and commercialize Licensed Products. The Company determined that the R&D Services, Research License, Collaboration License, Manufactured Supply, and JSC Participation were not capable of pre-clinicalbeing distinct, and therefore must be combined into a single performance obligation. Therefore, promises (1) through (5) identified above were combined into a single performance obligation. Furthermore, the Company evaluated the Option Agreement and determined that it does not provide AskBio with a material right under ASC 606 as the option was not priced at a discount (see discussion of the option exercise in Note 12). The Company noted that AskBio did not meet the definition of a customer within the scope of ASC 606 for any distinct performance obligations as the Company concluded that such items were not an output of the Company’s ordinary activities. As such, the Company determined that the entire arrangement would be accounted for within the scope of ASC 808. In accordance with ASC 808, collaboration expenses are recognized within R&D expense and selling, general and administrative expense on the Company’s condensed consolidated statements of operations.
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Under certain collaborative arrangements, the Company is entitled to reimbursement of certain R&D expense. Activities under collaborative arrangements for which the Company is entitled to reimbursement are considered to be collaborative activities under the scope of ASC 808. For these units of account, the Company does not analogize to ASC 606 or clinical materialsrecognize revenue. Rather, the Company analogizes to the guidance in ASC 730, which requires that reimbursements from counterparties be recognized as an offset to the related costs. In accordance with ASC 730, the Company records reimbursement payments received from collaborators as reductions to R&D expense.
For the three and nine months ended September 30, 2021, the Company recognized $0.6 million and $2.3 million, respectively, of collaboration expense under the AskBio Collaboration Agreement in which actual costs incurred by both parties approximate a 50% cost share. For the three and nine months ended September 30, 2020, the Company recognized $0.6 million and $2.6 million, respectively, of collaboration expense under the AskBio Collaboration Agreement.
Massachusetts Institute of Technology
In November 2008, the Company entered into an exclusive patent license agreement, or the MIT License, with the Massachusetts Institute of Technology, or MIT, under which the Company received an exclusive royalty-bearing license to utilize patents held by MIT in exchange for upfront consideration and annual license maintenance fees. Such fees are expensed as incurred and have not been material to any period presented.
In June 2020, the Company entered into a Fifth Amendment, or the MIT Amendment, to the MIT License, which is effective as of May 15, 2020. Pursuant to the MIT Amendment, certain of the Company’s diligence obligations were extended. The extension included the obligation to commence a Phase 3 trial for a licensed product by the second quarter of 2021 or to file an IND (or equivalent) with the FDA or comparable European regulatory agency for a licensed product by the second quarter of 2023. Additionally, certain of the Company’s development and regulatory milestones and payments upon achievement of such milestones were adjusted.
As of September 30, 2021, and in connection with the execution of the Spark License Agreement, the Company has made contractual payments pursuant to the MIT License totaling $2.2 million for the collaborative partner,sublicense granted to Spark, and (v) options to acquire licenses for additional therapeutic areas. Payments$0.4 million relative to the Company under these agreements may include nonrefundable license fees, option fees, exercise fees, payments for research and development activities, paymentscalculated premium paid by Spark for the manufactureequity investments made under the Spark Purchase Agreement. The Company made no additional payments during the nine months ended September 30, 2021.
Shenyang Sunshine Pharmaceutical Co., Ltd
In May 2014, the Company entered into a license agreement, or the 3SBio License, with Shenyang Sunshine Pharmaceutical Co., Ltd., or 3SBio. The Company has paid to 3SBio an aggregate of preclinical or clinical materials,$7.0 million in upfront and milestone-based payments basedunder the 3SBio License as of September 30, 2021. The Company is required to make future payments to 3SBio contingent upon the occurrence of events related to the achievement of certainclinical and regulatory approval milestones and royalties on product sales.of up to an aggregate of $15.0 million for products containing the Company’s ImmTOR platform.
When evaluating multiple element arrangements such as the agreements discussed in Note 13, the Company considers whether the deliverables under the arrangement represent separate units of accounting. This evaluation requires subjective determinations and requires management to make judgments about the individual deliverables and whether such deliverables are separable from the other aspects of the contractual relationship. In determining the units of accounting, management evaluates certain criteria, including whether the deliverables have standalone value, based on the consideration of the relevant facts and circumstances for each arrangement. The consideration received is allocated among the separate units of accounting using the relative selling price method, and the applicable revenue recognition criteria are applied to each of the separate units.
15. Income Taxes
The Company determinesprovides for income taxes under ASC 740. Under ASC 740, the estimated selling price for deliverables within each agreement using vendor‑specific objective evidence (“VSOE”) of selling price, if available, third‑party evidence (“TPE”) of selling price if VSOE is not available, or best estimate of selling price if neither VSOE nor TPE is available. Determining the best estimate of selling price for a deliverable requires significant judgment. Since the Company is a clinical stage company without a marketable product, and currently there is no technologically comparative product on the market, to determine either VSOE or TPE, the Company has used its best estimate of selling price to estimate the selling price for licenses and deliverables related to the Company’s proprietary technology. Under the circumstances, the Company considers market conditions as well as entity‑specific factors, including those factors contemplated in negotiating the agreements, estimated development costs, probability of success and the time needed to commercialize a product candidate pursuant to the license. In validating the Company’s best estimate of selling price, the Company evaluates whether changes in the key assumptions used to determine the best estimate of selling price will have a significant effect on the allocation of arrangement consideration between multiple deliverables.
Options for future deliverables are considered substantive if, at the inception of the arrangement, the Company is at risk as to whether the collaboration partner will choose to exercise the option. Factors that the Company considers in evaluating whether an option is substantive include the overall objective of the arrangement, the benefit the collaborator might obtain from the arrangement without exercising the option, the cost to exercise the option and the likelihood that the option will be exercised. When an option is considered substantive and there is no significant incremental discount, the option is not considered a deliverable in the arrangement and no consideration is allocated to it. Conversely, when an option is not considered substantive or it is considered substantive but is priced at an incremental discount, it would be considered a deliverable at the inception of the arrangement and a corresponding amount would be included in the initial consideration.
The Company may receive upfront payments when licensing its intellectual property in conjunction with a manufacturing or a research and development agreement. When management believes the license to its intellectual property does not have stand‑alone value from the other deliverables to be provided in the arrangement, the Company generally recognizes revenue attributed to the license over the Company’s contractual or estimated performance period. When management believes the license to its intellectual property has stand‑alone value, the Company generally recognizes revenue attributed to the license upon delivery. The periods over which revenue should be recognized are subject to estimates by management and may change over the course of the research and development agreement. Such a change could have a material impact on the amount of revenue the Company records in future periods. Payments or reimbursements resulting from the Company’s deliveries of manufactured products and research and development efforts are recognized as the services are performed.
At the inception of each agreement that includes milestone payments, the Company evaluates whether each milestone is substantive and at risk to both parties based on the contingent nature of the milestone, specifically reviewing factors such as the scientific and other risks that must be overcome to achieve the milestone, whether the milestone consideration is reasonable relative to all deliverables and payment terms, as well as the level of effort and investment required. Revenues from milestones, if they are nonrefundable and deemed substantive, are recognized upon successful accomplishment of the milestones. Milestones that are not considered substantive are accounted for as license payments and recognized over the remaining period of performance.
Grant Agreements
Grant revenue is generally recognized as the related research and development work is performed. Grant arrangements frequently include payment milestones which the Company has judged to be non‑substantive milestones as they are typically

entitled to receive payment regardless of the outcome of the research work. Revenue under such arrangements is recognized using a proportional performance method, but not more than cash received.
Amounts received prior to satisfying the above revenue recognition criteria are recorded as deferred revenue in the accompanying consolidated balance sheets.
Research and Development Costs
Costs incurred in the research and development of the Company’s products are expensed as incurred. Research and development expenses include costs incurred in performing research and development activities, including salaries and benefits, facilities cost, overhead costs, contract services, supplies and other outside costs. Nonrefundable advance payments for goods and services that will be used in future research and development activities are expensed when the activity has been performed or when the goods have been received rather than when the payment is made.
Clinical Trial Costs
Clinical trial costs are a component of research and development expenses. The Company accrues and expenses clinical trial activities performed by third parties based on an evaluation of the progress to completion of specific tasks using data such as patient enrollment, clinical site activation, and other information provided to the Company by its vendors.
Income Taxes
The Company provides deferred tax assets and liabilities for the expected future tax consequences of temporary differences between the Company’s financial statement carrying amounts and the tax basisbases of assets and liabilities using enacted tax rates expected to be in effect in the years in which the differences are expected to reverse. A valuation allowance
On June 11, 2020, the Company entered into the Sobi License (see Note 12). In September 2020, Sobi paid the Company a one-time up-front payment of $75.0 million. Sobi has also agreed to make milestone payments totaling up to $630.0 million to the Company upon the achievement of various development and regulatory milestones and sales thresholds for annual net sales of SEL-212, and tiered royalty payments ranging from the low double digits on the lowest sales tier to the high teens on the highest sales tier.
For income tax purposes, the transfer of trademark and product rights is providedtreated as a sale and the net proceeds from the sale are taxed under the default installment method as cash is received by the Company. During the three months ended September 30, 2021, the Company completed an analysis of future tax obligations under the default installment sale method versus making a timely filed election on its 2020 tax return due October 15, 2021 to elect out of the installment sale method for income tax purposes. As a result, the Company elected out of the default installment sale treatment with the filing of its tax return. In the elect out method, the Company was taxed based upon the estimated fair value of all present and future proceeds from the sale and the Company utilized all of its available net operating losses and income tax credits, which served to reduce the federal and state tax liability. As such, the Company has recognized a total tax expense, inclusive of estimated penalties and interest, of $15.8 million as of September 30, 2021. As the Company recognizes future revenue under the Sobi license for US GAAP purposes, the Company will exclude that revenue from taxable income.
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The Company will maintain its full valuation allowance against its deferred tax assets tofor 2021, as the amountCompany believes that will more‑likely‑than‑not be realized.
The Company determines whether it is more likely than not that athe deferred tax positionassets will not be sustained upon examination. If it is not more-likely-than-not that a position will be sustained, nonerealized.
Utilization of the benefit attributablenet operating loss and research and development credit carryforwards may be subject to the position is recognized. The tax benefit to be recognized for any tax position that meets the more‑likely‑than‑not recognition threshold is calculated as the largest amount that is more than 50% likely of being realized upon resolutiona substantial annual limitation under Section 382 and 383 of the contingency.Internal Revenue Code due to ownership change limitations that have occurred previously, or that could occur in the future. These ownership changes may limit the amount of net operating loss and research and development credit carryforwards that can be utilized annually to offset future taxable income and tax, respectively. As of December 31, 2020, the Company completed both a Section 382 and R&D tax credit study. As a result of using the elect out method described above, the Company utilized all available federal and state net operating losses and income tax credits with the filing of its tax returns for the year ended December 31, 2020.
The statute of limitations for assessment by the United States Internal Revenue Service and Massachusetts tax authorities is open for tax years since inception. The Company accounts for interestfiles income tax returns in the United States and penalties related to uncertain tax positions as part of its provision for income taxes. To date, the Company has not incurred interest and penalties related to uncertain tax positions.Massachusetts. There are currently no federal, state or foreign audits in progress.
Preferred stock
Prior to the completion of the IPO, the Company classified preferred stock as temporary equity and initially records it at the original issuance price, net of issuance costs and discounts. The carrying value was accreted up to the redemption value over the earliest redemption period. The carrying value was also adjusted for dividends expected to be paid upon redemption or liquidation according to the preferred stock terms on each balance sheet date.
Warrants16. Defined Contribution Plan
The Company determines the accounting classification of warrants that are issued, as either liability or equity, by first assessing whether the warrants meet liability classification in accordance with ASC 480-10, Accounting for Certain Financial Instruments with Characteristics of both Liabilities and Equity, and then in accordance with ASC 815-40, Accounting for Derivative Financial Instruments Indexed to, and Potentially Settled in,maintains a Company’s Own Stock. Under ASC 480, warrants are considered liability classified if the warrants are mandatorily redeemable, obligate the issuer to settle the warrantsdefined contribution plan, or the underlying shares401(k) Plan, under Section 401(k) of the Internal Revenue Code. The 401(k) Plan covers all employees who meet defined minimum age and service requirements and allows participants to defer a portion of their annual compensation on a pretax basis. The 401(k) Plan provides for matching contributions on a portion of participant contributions pursuant to the 401(k) Plan’s matching formula. All matching contributions vest ratably over 4 years and participant contributions vest immediately. Contributions by paying cash or other assets, or warrants that must or may require settlement by issuing variable number of shares.
If warrants do not meet liability classification under ASC 480-10, the Company assesses the requirements under ASC 815-40, which states that contracts that require or may require the issuer to settle the contract for cash are liabilities recorded at fair value, irrespectivetotaled less than $0.1 million during each of the likelihoodthree months ended September 30, 2021 and 2020, respectively, and $0.1 million during each of the transaction occurring that triggers the net cash settlement feature. If the warrants do not require liability classification under ASC 815-40, in order to conclude equity classification, the Company assesses whether the warrants are indexed to our common stocknine months ended September 30, 2021 and whether the warrants are classified as equity under ASC 815-40 or other applicable GAAP. After all relevant assessments are made, the Company concludes whether the warrants are classified as liability or equity. Liability classified warrants are required to be accounted for at fair value both on the date of issuance2020.

17. Commitments and on subsequent accounting period ending dates, with all changes in fair value after the issuance date recorded in the statements of operations as a gain or loss.  Equity classified warrants are accounted for at fair value on the issuance date with no changes in fair value recognized after the issuance date.Contingencies
Stock‑Based Compensation
The Company accounts for all stock‑based compensation granted to employees and non‑employees using a fair value method. Stock‑based compensation awarded to employees is measured at the grant date fair value and is recognized over the requisite service period of the awards, usually the vesting period, on a straight‑line basis, net of estimated forfeitures. Stock‑based

compensation awarded to non‑employees are subject to revaluation over their vesting terms. The Company reduces recorded stock‑based compensation for estimated forfeitures. To the extent that actual forfeitures differ from the Company’s estimates, the differences are recorded as a cumulative adjustment in the period the estimates were adjusted. Stock‑based compensation expense recognized in the financial statements is based on awards that are ultimately expected to vest.
Comprehensive Loss
Comprehensive loss is defined as the change in the equity of a business entity during a period from transactions and other events and circumstances from non‑owner sources. It includes all changes in equity during a period except those resulting from investments by owners and distributions to owners. Comprehensive loss consists of both: (i) all components of net loss and (ii) all components of comprehensive loss other than net loss, referred to as other comprehensive loss. For all periods presented, other comprehensive loss is comprised of foreign currency translation adjustments and the unrealized gains and losses on investments.
Net Loss Per Share
The Company has reported losses since inception and has computed basic net loss per share attributable to common stockholders by dividing net loss attributable to common stockholders by the weighted average number of common shares outstanding for the period. The Company has computed diluted net loss per common share after considering all potentially dilutive common shares, including stock options, convertible preferred stock, and warrants outstanding during the period except where the effect of including such securities would be antidilutive. Because the Company has reported net losses since inception, these potential common shares have been anti‑dilutive and basic and diluted loss per share have been the same.
Deferred Rent
Rent expense and lease incentives from operating leases are recognized on a straight‑line basis over the lease term. The difference between rent expense recognized and rental payments is recorded as deferred rent in the accompanying consolidated balance sheets.
Contingent Liabilities
The Company accounts for its contingent liabilities in accordance with ASC No. 450, Contingencies. A provision is recorded when it is both probable that a liability has been incurred and the amount of the loss can be reasonably estimated. With respect to legal matters, provisions are reviewed and adjusted to reflect the impact of negotiations, estimated settlements, legal rulings, advice of legal counsel and other information and events pertaining to a particular matter. As of September 30, 2017 and December 31, 2016,2021, the Company was not a party to any litigation that could have a material adverse effect on the Company’s business, financial position, results of operations or cash flows.
Recent Accounting Pronouncements
From timeOn August 4, 2020, a putative stockholder of Selecta filed a stockholder derivative action, purportedly on behalf of Selecta and against certain current and former members of the Company’s Board of Directors, as well as one affiliated company owned by a current board member, in the Court of Chancery of the State of Delaware, namely Franchi v. Barabe, et al. The complaint alleges that the individual defendants breached their fiduciary duties and committed corporate waste when they authorized a private placement transaction, announced on December 19, 2019, at a price allegedly below fair value. The complaint further alleges that the four defendant directors who participated in the private placement were unjustly enriched in connection with the transaction. On September 25, 2020, the defendants filed a motion to time, new accounting pronouncements are issueddismiss the lawsuit. On November 6, 2020, the plaintiff filed an amended complaint, and the defendants filed a second motion to dismiss on January 8, 2021. On December 31, 2020, the Company received a litigation demand letter from two other putative stockholders relating to the same private placement transaction. On April 12, 2021, the Court of Chancery in the State of Delaware granted a motion to stay the litigation pending a review by a Special Committee appointed by the Financial Accounting StandardsCompany’s Board (“FASB”) or other standard setting bodies that the Company adopts as of the specified effective date.
In May 2014, the FASB issued ASU No. 2014-09, Revenue from Contracts with Customers (“ASU 2014-09”), which amends the guidance for revenue recognition to replace numerous industry- specific requirements. ASU 2014-09 implements a five-step process for customer contract revenue recognition that focuses on transfer of control, as opposed to transfer of risk and rewards. ASU 2014-09 also requires enhanced disclosures regarding the nature, amount, timing, and uncertainty of revenues and cash flows from contracts with customers. Other major provisions include ensuring theDirectors. At this time, value of money is considered in the transaction price, and allowing estimates of variable consideration to be recognized before contingencies are resolved in certain circumstances. The guidance permits two methods of adoption: retrospectively to each prior reporting period presented (full retrospective method), or retrospectively with the cumulative effect of initially applying the guidance recognized at the date of initial application (modified retrospective method). The amendments in ASU 2014-09 are effective for reporting periods beginning after December 15, 2017. Early adoption is permitted, but not before December 15, 2016. The new standard will be effective for us beginning January 1, 2018.
The Company initiated an assessment of the potential changes from adopting ASU 2014-09. The assessment includes identifying and analyzing the impact of the standard by reviewing the Company's current accounting policies and practices to identify potential differences that would result from applying the requirements of the new standard to each revenue contract associated with all of the Company's revenue streams. As of September 30, 2017, the Company had two revenue contracts that would require assessment under ASU 2014-09. The Company plans to adopt the new standard effective January 1, 2018 using the modified retrospective method. The Company continues to monitor additional changes, modifications, clarifications or interpretations being undertaken by the FASB, which may impact the Company’s current conclusions. The Company is still evaluating aspects of ASU 2014-09 and has not determined how it may impact its financial position, results of operations or related disclosures.

In August 2014, the FASB issued ASU No. 2014-15, Presentation of Financial Statements-Going Concern (“ASU 2014-15”). ASU 2014-15 requires management to assess an entity’s ability to continue as a going concern and to provide related disclosures in certain circumstances. The requirement of ASU 2014-15 became effective for the annual financial statement period ending after December 15, 2016. We adopted ASU 2014-15 for the year ended December 31, 2016, and the adoption did not have a material effect on the Company's consolidated financial statements.
In January 2016, the FASB issued ASU No. 2016-01, Recognition and Measurement of Financial Assets and Financial Liabilities (Topic 825) (“ASU 2016-01”). The amendments in this Update supersede the guidance to classify equity securities with readily determinable fair values into different categories (that is, trading or available-for-sale) and require equity securities (including other ownership interests, such as partnerships, unincorporated joint ventures, and limited liability companies) to be measured at fair value with changes in the fair value recognized through net income. The amendments allow equity investments that do not have readily determinable fair values to be remeasured at fair value either upon the occurrence of an observable price change or upon identification of an impairment. The amendments also require enhanced disclosures about those investments. This guidance is effective for annual reporting beginning after December 15, 2017, including interim periods within the year of adoption, and calls for prospective application, with early application permitted. Accordingly, the standard is effective for the Company on January 1, 2018. The Company is currently evaluating the effect of the adoption of this guidance on its consolidated financial statements.
In February 2016, FASB issued ASU No. 2016-02, Leases (“ASU 2016-02”). ASU 2016-02 requires a lessee to separate the lease components from the non-lease components in a contract and recognize in the statement of financial position a liability to make lease payments (the lease liability) and a right-of-use asset representing its right to use the underlying asset for the lease term. It also aligns lease accounting for lessors with the revenue recognition guidance in ASU 2014-09. ASU 2016-02 is effective for fiscal years beginning after December 15, 2018, including interim periods within those fiscal years. The Company is currently evaluating the effect of the adoption of this guidance on its consolidated financial statements.
In March 2016, the FASB issued ASU No. 2016-9, Improvements to Employee Share-Based Payment Accounting (“ASU 2016-9”), which simplifies several aspects of accounting for share-based payment transactions including the income tax consequences, classification of awards as either equity or liabilities, the estimation of forfeitures, shares withheld for taxes and classification on the statement of cash flows. This guidance is effective for the Company on January 1, 2017 and early adoption was permitted. The Company adopted ASU 2016-09 during the first fiscal quarter ended on March 31, 2017. As part of the adoption of this guidance the Company will continue to use estimated forfeitures in its calculation of stock-based compensation expense.
The excess tax benefits and tax deficiencies from stock-based compensation awards accounted for under ASC 718 are recognized as income tax benefit or expense, respectively, in the statements of operations. The income tax related items had no effect on the current period presentation as the Company maintains a full valuation allowance against its deferred tax assets. In addition, excess tax benefits for share-based payments are presented as an operating activity in the statements of cash flows rather than financing activity. The changes have been applied prospectively in accordance with the ASU and prior periods have not been adjusted. As a result of the adoption on January 1, 2017, the net operating losses deferred tax assets were increased by $0.3 million, which was offset by a corresponding increase in the valuation allowance. 
In August 2016, the FASB issued ASU No. 2016-15, Statements of Cash Flows - Classifications of Certain Cash Receipts and Cash Payments ("ASU 2016-15"), to clarify how companies present and classify certain cash receipts and cash payments in the statement of cash flows. This guidance is effective for annual reporting periods beginning after December 15, 2017, including interim periods within that reporting period, with early adoption permitted. The Company is currently evaluating the effect of the adoption of this guidance on its consolidated financial statements.
In November 2016, the FASB issued ASU No. 2016-18, Statement of Cash Flows, Restricted Cash ("ASU 2016-18"). This guidance requires that a statement of cash flows explain the total change during the period of cash, cash equivalents, and amounts generally described as restricted cash or restricted cash equivalents. Amounts described as restricted cash and restricted cash equivalents should be included with cash and cash equivalents when reconciling the beginning of period and end of period to total amounts shown on the statement of cash flows. This guidance is effective for annual reporting periods beginning after December 15, 2017, including interim periods within that reporting period, with early adoption permitted. Upon implementation of ASU 2016-18 the Company will present $0.4 million in the Consolidated Statements of Cash Flows in the "Cash and cash equivalents at beginning of period".
3. Available-for-Sale Marketable Securities
As of September 30, 2017 and December 31, 2016, the Company’s available-for-sale marketable securities consisted of debt securities issued by the U.S. government and corporate debt securities.

The following tables summarize the Company’s available-for-sale marketable securities by major type of security as of September 30, 2017 and December 31, 2016 (in thousands):
 September 30, 2017
 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Estimated Fair Value
Corporate bonds32,241
     —

(4)
32,237
Total available-for-sale marketable securities$32,241
 $—
 $(4) $32,237
 December 31, 2016
 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Estimated Fair Value
Corporate bonds24,821
     17
     (53)     24,785
Total available-for-sale marketable securities$24,821
 $17
 $(53) $24,785
All available-for-sale marketable securities are classified in the Company’s Condensed Balance Sheets as Short-term deposits and investments.
The Company classifies its marketable debt securities based on their contractual maturity dates. As of September 30, 2017, the Company’s marketable debt securities mature at various dates through March 2018. The fair values and amortized cost of marketable debt securities by contractual maturity were as follows (in thousands):
 September 30, 2017 December 31, 2016
 Fair Value Amortized Cost Fair Value Amortized Cost
Less than one year$32,237
 $32,241
 $24,785
 $24,821
As of September 30, 2017 the Company held a total of 25 positions, 22 of which were in an unrealized loss position, none of which had been in an unrealized loss position for 12 months or greater. The aggregate fair value of the investments in an unrealized loss position is $28.0 million. Based on the Company’s review of these securities, the Company believes that the cost basis of its available-for-sale marketable securities is recoverable and it hadno other-than-temporary impairments on these securities as of September 30, 2017. The Company does not intend to sell these debt securities and the Company believes it is not more-likely-than-not that it will be required to sell these securities before the recovery of their amortized cost basis, which may be at maturity.
4. Net Loss Per Share
Because the Company has reportednot accrued a net loss attributableliability for this matter, as any liability has been determined to common stockholders for all periods presented, basic and diluted net loss per share attributable to common stockholders are the same for those periods. The following table sets forth the computation of basic and diluted net loss per share (in thousands, except share and per‑share data):
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
 (unaudited) (unaudited)
Numerator:       
Net (loss)$(14,676) $(7,728) $(45,777) $(22,127)
Less: accretion on preferred stock—
 —
 —
 (4,566)
Net loss attributable to common stockholders$(14,676) $(7,728) $(45,777) $(26,693)
Denominator:       
Weighted‑average common shares outstanding—basic and diluted22,082,207
 18,108,014
 19,803,551
 7,881,625
Net loss per share attributable to common stockholders—basic and diluted$(0.66) $(0.43) $(2.31) $(3.39)
Potential common shares issuable upon conversion of warrants to purchase common stock and stock options that are excluded from the computation of diluted weighted average shares outstanding are as follows:

 September 30,
 2017 2016
 (unaudited)
Stock options to purchase common stock2,419,540
 2,140,295
Stock warrants to purchase common stock176,432
 113,795
Total2,595,972
 2,254,090
5. Fair Value Measurements
The tables below present information about the Company’s financial assets and liabilities that are measured and carried at fair value as of September 30, 2017 and December 31, 2016, and indicate the level within the fair value hierarchy where each measurement is classified. Below is a summary of assets measured at fair value on a recurring basis (in thousands):
 September 30, 2017
 (level 1) (level 2) (level 3) Total
Money market funds, included in cash equivalents$10,062
 $—
 $—
 $10,062
Corporate bonds, included in investments$32,237
 $—
 $—
 $32,237
 December 31, 2016
 (level 1) (level 2) (level 3) Total
Money market funds, included in cash equivalents$183
     $—
     $—
 $183
Tri-party repurchase agreements, included in cash equivalents$—
 $27,000
 $—
 $27,000
Corporate bonds, included in investments$24,785
 $—
 $—
 $24,785
At September 30, 2017, all cash and cash equivalent investments where held in money market funds. At December 31, 2016, all cash and cash equivalent investments where held in money market funds and tri-party repurchase agreements. The tri-party repurchase agreements are collateralized by government securities for an amountbe either not less than 102% of their value. All tri-party repurchase agreements have maturities of three monthsestimable or less at the time of investment.
The average maturity date for Corporate Bonds, included in investments at September 30, 2017 and December 31, 2016 was 152 days and 297 days, respectively. Fair value of Corporate Bonds approximates amortized value.
6. Property and Equipment
Property and equipment consists of the following (in thousands):
 September 30, December 31,
 2017 2016
 (unaudited)  
Laboratory equipment$5,117
 $4,713
Computer equipment and software453
 562
Leasehold improvements268
 222
Furniture and fixtures232
 226
Office equipment64
 64
Total property and equipment6,134

5,787
Less accumulated depreciation(4,079) (3,740)
Property and equipment, net$2,055

$2,047
Depreciation expense was $0.2 million and $0.1 million for the three months ended September 30, 2017 and 2016, respectively, and $0.6 million and $0.5 million for the nine months ended September 30, 2017 and 2016, respectively.






7. Accrued Expenses
Accrued expenses consist of the following (in thousands):
 September 30, December 31,
 2017 2016
 (unaudited)  
Payroll and employee related expenses$1,976
 $1,551
Current portion of deferred rent and lease incentive67
 29
Collaboration and licensing1,239
 170
Accrued patent fees284
 245
Accrued external research and development costs2,054
 794
Accrued professional fees204
 420
Accrued grant refund175
 152
Accrued interest47
 81
Other501
 479
Accrued expenses$6,547

$3,921
8. Commitments and Contingencies
Operating Leases
The Company has a non‑cancellable operating lease for its laboratory and office space located at 480 Arsenal Way, Watertown, Massachusetts ("Headquarters Lease"). As part of the Headquarters Lease agreement, the landlord provided the Company a tenant improvement allowance of up to $0.7 million, which the Company fully utilized during 2012. The tenant improvement allowance is accounted for as a lease incentive obligation and is being amortized as a reduction to rent expense over the lease term. The leasehold improvements are capitalized as a component of property and equipment.
In connection with the Headquarters Lease, the Company secured a letter of credit for $0.3 million which renews automatically each year and is classified in restricted cash and other deposits in the accompanying consolidated balance sheets.
In August 2016, the Company signed an amendment to the Headquarters Lease, which extends the term through March 31, 2020. The Headquarters Lease includes a rent escalation clause, and accordingly, rent expense is being recognized on a straight-line basis over the term.
Deferred rent and lease incentive liability totaled $0.2 million and $0.3 million as of September 30, 2017 and December 31, 2016, respectively. Included in that amount, the current portion of deferred rent and lease incentive liability is classified as accrued expenses and was less than $0.1 million at September 30, 2017 and December 31, 2016, respectively.
The Company has a month‑to‑month facility agreement for its Moscow, Russia facility. Rent expense is recognized as incurred.
Rent expense for the three months ended September 30, 2017 and 2016 was $0.5 million and $0.4 million, respectively. For the nine months ended September 30, 2017 and 2016, the rent expense was 1.4 million and $1.1 million, respectively.
As of December 31, 2016, the future minimum lease payments under the Headquarters Lease, as amended are as follows (in thousands):
Year ended December 31, 
2017$1,244
20181,291
20191,330
2020335
Total minimum lease payments$4,200
not probable.
Other
As permitted under Delaware law, the Company indemnifies its directors for certain events or occurrences while the director is, or was, serving at the Company’s request in such capacity. The term of the indemnification is for the director’s lifetime. The maximum potential amount of future payments the Company could be required to make is unlimited; however, the Company has directors’ insurance coverage that limits its exposure and enables it to recover a portion of any future amounts paid. The Company also has indemnification arrangements under certain of its facility leases that require it to indemnify the landlord against certain costs, expenses, fines, suits, claims, demands, liabilities, and actions directly resulting from certain breaches,

violations, or non‑performancenon-performance of any covenant or condition of the Company’s lease. The term of the indemnification is for the term of the related lease agreement. The maximum potential amount of future payments the Company could be required to make under these indemnification agreements is unlimited. To date, the Company had not experienced any material losses related to any of its indemnification obligations, and no material claims with respect thereto were outstanding.
The Company is a party in various other contractual disputes and potential claims arising in the ordinary course of business. The Company does not believe that the resolution of these matters will have a material adverse effect the Company'sCompany’s business, financial position, results of operations or cash flows.

9. Debt
28
2015 Term Loan
Table of Contents
18. Subsequent Events
Licenses and Collaborations
On August 9, 2013,October 25, 2021, the Company entered into a loanCollaboration and security agreementLicense Agreement, or the Ginkgo Agreement, with Oxford Finance LLC (“Oxford”)Ginkgo Bioworks Holdings, Inc., or Ginkgo. Under the Ginkgo Agreement, the Company will engage with Ginkgo to design novel and Square 1 Bank (“Square 1”)improved enzymes with transformative therapeutic potential to borrowadvance treatments for orphan and rare diseases. In return, Ginkgo is eligible to earn both upfront research and development fees and milestone payments, including certain milestone payments in the form of Selecta common stock, clinical and commercial milestone payments of up to $7.5 million. The Company initially borrowed $3.0$85.0 million in August 2013 and subsequently borrowed an additional $4.5 millioncash, as well as downstream value in July 2014. In December 2015,the form of royalties on sales.
On October 21, 2021, the Company refinanced this debt facilityentered into an Exclusive License Agreement, or the Genovis Agreement, with Genovis AB (publ.), or Genovis, a Swedish corporation. Under the Genovis Agreement, the Company paid to increase the amountGenovis an upfront payment in exchange for an exclusive license to Genovis’ Xork IgG Protease enzyme technology across all therapeutic uses in humans, excluding research, preclinical, diagnostic and other potential non-therapeutic applications of the borrowingenzyme. Additionally, Genovis is eligible to $12.0 millionearn development and to extendsales-based milestones, as well as tiered royalties on worldwide sales in the repayment term. The amounts borrowed are collectively referred to as the “2015 Term Loan”. The lenders for the refinanced debt facility are Oxford and Pacific Western Bank (“Pacific Western”). Pacific Western had acquired Squarelow double digits.
On October 1, since the time of the original loan. Such a change in lender does not constitute third party financing on its own, and does not require extinguishment accounting. As a result of the refinancing, the stated interest rate was also adjusted to reflect the current market borrowing rate.
Prior to the extinguishment of the 2015 Term Loan debt in September 2017 that is discussed in greater detail below, the 2015 Term Loan was collateralized by substantially all of the assets of2021, the Company and bore interest at 8.1% per annum. The monthly payments forentered into a License Agreement, or the 2015 Term Loan were initially interest only through January 2017. Principal repayments forTakeda Agreement, with Takeda Pharmaceuticals USA, Inc., or Takeda. Under the 2015 Term Loan were due over 30 monthly installments beginning on February 1, 2017.
The 2015 Term Loan could be prepaid at the Company’s option at any time prior to maturity subject to a prepayment fee of 2% if prepaid after the first anniversary but before the second anniversaries, and 1% if prepaid after the second anniversary. The 2015 Term Loan did not include any financial covenants. The 2015 Term Loan required a final payment fee of 6.0% on the aggregate principal amounts borrowed upon repayment at maturity, on a prepayment date, or upon default. The final payment fee totaling $0.7 million was recorded as a loan discount.
In connection with the 2015 Term Loan,Takeda Agreement, the Company granted Takeda an exclusive license to the lenders warrants in August 2013Company’s ImmTOR technology initially for two specified disease indications within the field of lysosomal storage disorders. Under the terms of the Takeda Agreement, the Company is entitled to purchasereceive an upfront payment and up to 26,668 shares$1.124 billion in future additional payments over the course of the Company’s Series D Preferred and additional warrants in July 2014partnership that are contingent on the achievement of development or commercial milestones or Takeda’s election to purchase upcontinue its activities at specified development stages. The Company is also eligible for tiered royalties on future commercial sales of any licensed products.
“At-the-Market” Offerings
2021 Sales Agreement
On October 25, 2021, the Company entered into a Sales Agreement, or the 2021 Sales Agreement, with SVB Leerink LLC to 40,000 shares of the Company’s Series D Preferred. As of the IPO, the warrants to purchase up to 66,668 shares of the Company’s Series D Preferred were converted to warrants to purchase up to 17,888sell shares of the Company’s common stock, atfrom time to time, through an exercise price of $16.77 per share. These warrants are classified“at the market” equity offering program under which SVB Leerink will act as permanent equity in the accompanying consolidated balance sheets and will expire ten years from the date of issuance.
Additionally, with the refinancing of the 2015 Term Loan at December 31, 2015, the Company granted the lenders 37,978 shares of the Company’s Series E Preferred which also was converted at the IPO to warrants to purchase up to 15,094 shares of Company’s common stock at an exercise price of $11.32 per share.  These warrants are classified as permanent equity in the accompanying consolidated balance sheets and will expire ten years from the date of issuance.
sales agent. The initial grant date fair value of the Series D Preferred and Series E Preferred warrants was $0.1 million and $0.1 million for each issuance respectively, and was recorded as a loan discount.
In December 2016, a total of 16,493 warrants to purchase common stock were exercised under a cashless exercise, resulting in a net issuance of 4,697 shares of common stock. The warrant exercise price had been established at the time that the warrants were converted.
2017 Term Loan
On September 12, 2017, the Company entered into a term loan facility of up to $21.0 million (the “2017 Term Loan”) with Silicon Valley Bank, a California corporation (“SVB”), the proceeds of which were used to repay the 2015 Term Loan and for general corporate and working capital purposes. The Company refersstock sold pursuant to the 2015 Term Loan and the 2017 Term Loan, collectively, as the “Term Loans.” The 2017 Term Loan is governed by a loan and security agreement, dated September 12, 2017, between the Company and SVB (the “Loan Agreement”). The 2017 Term Loan was funded in full on September 13, 2017 (the “Funding Date”).
On the Funding Date, the Company entered into a payoff letter with SVB,2021 Sales Agreement will be issued pursuant to which SVB utilized $10.0 million of the 2017 Term Loan to pay off all outstanding obligations under the 2015 Term Loan. The Company recognized a loss on extinguishment of debt of $0.7 million during the nine months ended September 30, 2017, which is reflected in the consolidated statements of operations and comprehensive loss under the header “Loss on extinguishment of debt”.

The Company incurred less than $0.1 million in debt issuance costs in connection with the closing of the 2017 Term Loan. Debt issuance costs are presented in the consolidated balance sheet as a direct deduction from the associated liability and amortized to interest expense over the term of the related debt.
The 2017 Term Loan will mature on February 1, 2022. Each advance under the 2017 Term Loan accrues interest at a floating per annum rate equal to one-half of one percent above the prime rate (as published in the money rates section of The Wall Street Journal). The 2017 Term Loan provides for interest-only payments monthly until August 31, 2019. Thereafter, amortization payments will be payable monthly in equal installments of principal and variable interest to fully amortize the outstanding principal over the remaining term of the loan. The monthly interest is subject to recalculation upon a change in the prime rate. The Company may prepay the 2017 Term Loan in full but not in part provided that the Company (i) provides five business days’ prior written notice to SVB, (ii) pays on the date of such prepayment (A) all outstanding principal plus accrued and unpaid interest, and (B) a prepayment premium of 3% if prepaid before the first anniversary, 2% if prepaid after the first anniversary but before the second anniversaries, and 1% if prepaid after the second anniversary.
Amounts outstanding during an event of default are payable upon SVB’s demand and shall accrue interest at an additional rate of 4.0% per annum of the past due amount outstanding. The events of default under the Loan Agreement include, but are not limited to, the Company’s failure to make any payments of principal or interest under the Loan Agreement or other transaction documents, the Company’s breach or default in the performance of any covenant under the Loan Agreement or other transaction documents, the occurrence of a material adverse effect, the Company making a false or misleading representation or warranty in any material respect under the Loan Agreement, the Company’s insolvency or bankruptcy, any attachment or judgment on the Company’s assets in excess of approximately $0.3 million, or the occurrence of any default under any agreement or obligation of the Company involving indebtedness in excess of approximately $0.3 million. If an event of default occurs, SVB is entitled to take enforcement action, including acceleration of amounts due under the Loan Agreement.
The 2017 Term Loan is secured by a lien on substantially all of the assets of the Company, other than intellectual property, provided that such lien on substantially all assets includes any rights to payments and proceeds from the sale, licensing or disposition of intellectual property. The Company has also granted SVB a negative pledge with respect to its intellectual property.
The 2017 Term Loan does not include any financial covenants. The 2017 Term Loan requires a final payment fee of 5% on the aggregate principal amounts borrowed upon repayment at maturity, on a prepayment date, or upon default. The final payment fee totaling $1.1 million is recorded as a loan discount. Under the 2017 Term Loan, the Company is not required to maintain a minimum cash balance. In addition, the 2017 Term Loan contains a subjective acceleration clause whereby in an event of default, an immediate acceleration of repayment occurs if there is a material impairment of the lenders’ lien or the value of the collateral, a material adverse change in the business condition or operations, or a material uncertainty exists that any portion of the loan may not be repaid. To date, there have been no such events and the lender has not exercised its right under this clause.
The Company assessed all terms and features of the 2017 Term Loan in order to identify any potential embedded features that would require bifurcation. As part of this analysis, the Company assessed the economic characteristics and risks of the 2017 Term Loan, including any put and call features. The Company determined that all features of the 2017 Term Loan were clearly and closely associated with the debt host and did not require bifurcation as a derivative liability, or the fair value of the embedded feature was immaterial to the Company's financial statements. The Company reassesses the identified features on a quarterly basis to determine if they require bifurcation.
As of September 30, 2017 and December 31, 2016, the outstanding principal balances under the Term Loans were $21.0 million and $12.0 million, respectively.
Future minimum payments on the 2017 Term Loan as of September 30, 2017 are as follows (in thousands):
Remaining for 2017$296
2018998
20194,470
20209,048
20218,649
20221,753
Total minimum debt payments25,214
Less: Amount representing interest(3,164)
Less: Debt discount and deferred charges(1,096)
Less: Current portion of loans payable—
Loans payable, net of current portion$20,954

During the three months ended September 30, 2017 and 2016, the Company recognized $0.3 million, respectively, of interest expense related to the Term Loans. A total of $0.9 million was recorded as interest expense related to the Term Loans for the nine months ended September 30, 2017 and 2016, respectively.
10. Preferred Stock
Prior to the completion of its IPO, the Company had 37,835,623 and 28,804,969 authorized shares of preferred stock, par value $0.0001 per share (the "Preferred Stock") as of December 31, 2015 and 2014, respectively. The Company issued Preferred Stock to investors for cash or as settlement for outstanding debt under convertible notes.
The Company had issued and outstanding Preferred Stock of (i) 2,589,868 shares of Series A redeemable convertible preferred stock (“Series A Preferred”), (ii) 7,437,325 shares of Series B redeemable convertible preferred stock (“Series B Preferred”), (iii) 5,000,002 shares of Series C redeemable convertible preferred stock (“Series C Preferred”), (iv) 8,099,994 shares of Series D Preferred, (v) 2,111,109 shares of Series SRN Redeemable Convertible Preferred Stock (“Series SRN Preferred”) and (vi) 8,888,888 shares of Series E Preferred. All outstanding shares of the Company’s convertible preferred stock automatically converted into 10,126,118 shares of the Company’s common stock upon the closing of the IPO on June 27, 2016.

11. Common Stock
2017 Shelf Registration Statement
On August 10, 2017, the Company filed a universal shelf registration statement on Form S-3 with the SEC to sell up to $200 million of equity and/or debt securities and entered into a sales agreement with Jefferies LLC, as sales agent, pursuant to which the Company may, from time to time, issue and sell common stock with an aggregate value of up to $50 million in an at-the-market, or ATM, offering. The shelf registration statement was declared effective by the SEC(File No. 333-241692), filed on August 28, 2017. As of September 30, 3017, no securities have been issued from this shelf registration statement.
PIPE Financing
On June 26, 2017, the Company entered into a securities purchase agreement (the "Institutional Purchase Agreement") with a select group of institutional investors (the “Institutional Investors”) and a securities purchase agreement with Timothy Springer, Ph.D., a member of the board of directors (the "Springer Purchase Agreement") for a private placement of the Company's securities (the "2017 PIPE"). The closing of the 2017 PIPE occurred on June 27, 2017.
Pursuant to the Institutional Purchase Agreement, the Company agreed to sell an aggregate of 2,750,000 shares of its common stock, par value $0.0001 per share, at a purchase price equal to $16.00 per share. Pursuant to the Springer Purchase Agreement, the Company agreed to sell to Dr. Springer an aggregate of 338,791 shares of common stock at a purchase price equal to $17.71 per share, which was equal to the most recent consolidated closing bid price on the Nasdaq Global Market on June 23, 2017, and warrants to purchase up to 79,130 shares of common stock (“Warrant Shares”), exercisable at $17.71 per Warrant Share, and with a term of five years. The purchase price for each warrant was equal to $0.125 for each Warrant Share, consistent with Nasdaq Global Market requirements for an “at the market” offering. Under the terms of the Common Stock Purchase Warrant, the warrants can be settled in unregistered shares. The Warrant Shares qualify for equity classification. The fair value of the allocated proceeds was determined on the relative fair value basis.
After deducting for placement agent fees and offering expenses, the aggregate net proceeds from the 2017 PIPE was approximately $47.2 million. The Company expects to use the proceeds from the 2017 PIPE towards working capital requirements and general corporate purposes.
On June 27, 2017, in connection with the 2017 PIPE, the Company entered into a Registration Rights Agreement (the “Registration Rights Agreement”) with the Institutional Investors and Dr. Springer (together, the “Investors”). Pursuant to the Registration Rights Agreement, the Company agreed to prepare and file a registration statement6, 2020 with the Securities and Exchange Commission (the “SEC”) within 20 days afterand related prospectus supplement, filed on October 25, 2021 with the closingSecurities and Exchange Commission, for aggregate gross sales proceeds of up to $75.0 million.
Under the 2021 Sales Agreement, the Company will set the parameters for the sale of shares, including the number of shares to be issued, the time period during which sales are requested to be made, limitations on the number of shares that may be sold in any one trading day and any minimum price below which sales may not be made. Subject to the terms and conditions of the 2017 PIPE for purposesSales Agreement, SVB Leerink may sell the shares by methods deemed to be an “at the market offering” as defined in Rule 415(a)(4) promulgated under the Securities Act, in negotiated transactions at market prices prevailing at the time of registeringsale or at prices related to such prevailing market prices and/or any other method permitted by law. If the resaleCompany and SVB Leerink so agree, SVB Leerink may act as principal in connection with the sale of shares under the 2021 Sales Agreement. The Company will pay SVB Leerink a commission of up to 3.0% of the sharesgross sales proceeds of common stock issued and sold in the 2017 PIPE (the “Shares”), the Warrant Shares, and any shares of common stock issued as a dividend or other distribution with respect to the Shares or Warrant Shares. The registration statement was declared effective by the SEC on July 21, 2017.
The Company agreed to indemnify the Investors, their officers, directors, members, employees and agents, successors and assignssold through SVB Leerink under the registration statement from certain liabilities and to pay all fees and expenses (excluding any legal fees of the selling holder(s), and any underwriting discounts and selling commissions) incident to the Company’s obligations under the Registration Rights Agreement.



Initial Public Offering
On June 21, 2016 the Company completed the IPO and issued and sold 5,000,000 shares of common stock at a price to the public of $14.00 per share for net proceeds of $60.8 million after deducting underwriting discounts and commissions and offering expenses.  On July 25, 2016, 289,633 additional shares of the Company’s common stock were sold to the underwriters pursuant to the exercise of their option to purchase additional shares of common stock at a price to the public of $14.00 per share resulting in additional net proceeds of approximately $3.7 million after deducting underwriting discounts, commissions and offering expenses, bringing the total IPO net proceeds to $64.5 million. Upon the closing of the IPO on June 27, 2016, all outstanding shares of the Company’s convertible preferred stock automatically converted into 10,126,118 shares of the Company’s common stock. In addition, at this time, the warrants to purchase shares of the Company’s Series D and Series E convertible preferred stock were converted into warrants to purchase shares of the Company’s common stock.
As of September 30, 2017, the Company has 200,000,000 shares of common stock authorized for issuance, $0.0001 par value per share, with 22,120,507 shares issued and outstanding. The voting, dividend and liquidation rights of the common stockholders are subject to and qualified by the rights, powers and preferences of the preferred stock. The common stock has the following characteristics:
Voting
The common stockholders are entitled to one vote for each share of common stock held with respect to all matters voted on by the stockholders of the Company.
Dividends
The common stockholders are entitled to receive dividends, if and when declared by the Board of Directors. Through September 30, 2017, no dividends have been declared or paid on common stock.
Liquidation
Upon the liquidation of the Company, the common stockholders are entitled to receive all assets of the Company available for distribution to such stockholders.
Reserved Shares
The Company has authorized shares of common stock for future issuance as follows:
 Periods ending
 September 30, 2017 December 31, 2016
 (unaudited)  
Exercise of common warrants176,432
 97,302
Shares available for future stock incentive awards1,309,243
 939,317
Outstanding common stock options2,419,540
 2,128,346
Total3,905,215

3,164,965
12. Stock Incentive Plans
Stock Options
The Company maintained the 2008 Stock Incentive Plan (the “2008 Plan”) for employees, consultants, advisors, and directors. The 2008 Plan provided for the granting of incentive and non‑qualified stock option and restricted stock awards as determined by the Board. As of September 30, 2017, a total of 2,213,412 shares of common stock were authorized for grants under the 2008 Plan with 18,947 shares available for future grants. Stock options that are granted under the 2008 Plan, and subject to cancellation become available under the 2016 Plan as shares available for future grants. All unvested stock options granted under the 2008 Plan may be exercised into restricted stock subject to forfeiture provisions upon termination.
The 2008 Plan provided that the exercise price of incentive stock options cannot be less than 100% of the fair market value of the common stock on the grant date for participants who own 10% or less of the total combined voting power of the Company, and not less than 110% for participants who own more than 10% of the Company’s voting power. Options and restricted stock granted under the 2008 Plan vest over periods as determined by the Board, which are generally four years and, for options, with terms that generally expire ten years from the grant date. The fair value of each option award was estimated on the grant date using Black‑Scholes. Expected volatilities were based on historical volatilities from guideline companies, since there was no active market for the Company’s common stock. The Company used the “simplified” method to estimate the expected life of options granted and are expected to be outstanding. The risk‑free interest rate used is the rate for a U.S. Treasury zero coupon issue with a remaining life consistent with the options expected life on the grant date. The Company has not paid, and does not expect to pay, any cash dividends in the foreseeable future. Forfeitures were estimated at the time of grant and were adjusted, if

necessary, in subsequent periods if actual forfeitures differed from those estimates. The Company had estimated a forfeitures rate of 10% based on historical attrition trends. The Company records stock‑based compensation expense only on the awards that are expected to vest.
As of the effective date of our Registration Statement on Form S-1 relating to the initial public offering of our common stock on June 21, 2016, the Company ceased granting awards under the 2008 Plan; however, awards issued under the 2008 Plan remain subject to the terms of the 2008 Plan and the applicable 2008 Plan agreement.
On June 7, 2016, the Company’s stockholders approved the 2016 Incentive Award Plan (the “2016 Plan”), which became effective June 21, 2016.  The 2016 Plan provides for the granting of incentive and non‑qualified stock option, restricted stock and other stock and cash based awards as determined by the Board. As of September 30, 2017, a total of 1,947,779 shares of common stock are authorized for grants under the 2016 Plan with 949,103 shares available for future grant.
The 2016 Plan provides that the exercise price of incentive stock options cannot be less than 100% of the fair market value of the common stock on the grant date for participants who own 10% or less of the total combined voting power of the Company, and not less than 110% for participants who own more than 10% of the Company’s voting power. Options and restricted stock granted under the 2016 Plan vest over periods as determined by the Board, which are generally four years and, for options, with terms that generally expire ten years from the grant date.
The weighted average assumptions used for employee stock option grants issued during the nine months ended September 30, 2017 and 2016 are as follows:
 Nine Months Ended September 30,
 2017 2016
Risk-free interest rate1.98% 1.39%
Expected dividend yield—
 —
Expected life5.95
 6.05
Expected volatility84.40% 95.62%
Weighted-average fair value of common stock$18.25
 $9.79
The resulting weighted average grant date fair value of stock options granted to employees during the nine months ended September 30, 2017 and 2016 was $13.04 and $9.79, respectively. The aggregate intrinsic value of stock options exercised during the nine months ended September 30, 2017 and 2016 was $2.0 million and $0.1 million, respectively.
Employee stock-based compensation for the three and nine months ended September 30, 2017 was $1.2 million and $2.5 million, respectively, as compared to $0.5 million and $1.1 million, respectively, for the comparable 2016 periods.
As of September 30, 2017 and 2016, total unrecognized compensation expense related to unvested employee stock options was $9.7 million and $5.5 million, respectively, which is expected to be recognized over a weighted average period of 2.9 years and 3.2 years, respectively.
During the nine months ended September 30, 2017, there were no options granted to non-employees. The weighted average assumptions used for unvested non‑employee stock options that were granted during the nine months ended September 30, 2016 are as follows:
Nine Months Ended September 30,
2016
Risk‑free interest rate1.58%
Expected dividend yield—
Expected life (in years)9.41
Expected volatility87.75%
The unvested options held by non‑employees are revalued using the Company’s estimate of fair value on each vesting and reporting date through the remaining vesting period. Non-employee stock-based compensation for the three and nine months ended September 30, 2017 were $0.1 million and $0.3 million, respectively, as compared to $0.1 million and $0.2 million, respectively, for the comparable 2016 periods.
As of September 30, 2017 and 2016, total unrecognized compensation expense related to unvested non‑employee stock options was $0.6 million and $1.0 million, respectively.

The following table summarizes the activity under the 2008 Plan and the 2016 Plan during the nine months ended September 30, 2017:
     Weighted‑average  
   Weighted‑average remaining Aggregate
 Number of exercise contractual term intrinsic value
 options price (in years) (in thousands)
Employee       
Outstanding at December 31, 20161,809,945
 $7.57
 7.26 $17,459
Granted560,100
 $18.25
    
Exercised(189,617) $2.42
    
Forfeited(15,684) $11.29
    
Outstanding at September 30, 20172,164,744
 $10.73
 7.60 $16,791
Vested at September 30, 20171,017,735
 $6.30
 6.01 $12,180
Vested and expected to vest at September 30, 20172,010,425
 $10.36
 7.48 $16,302
Non‑Employee       
Outstanding at December 31, 2016318,342
 $4.55
 5.96 $4,044
Granted—
 $—
    
Exercised(63,546) $3.72
    
Forfeited—
 $—
    
Outstanding at September 30, 2017254,796
 $4.76
 5.35 $3,465
Vested at September 30, 2017211,542
 $4.30
 4.72 $2,980
Vested and expected to vest at September 30, 2017254,796
 $4.76
 5.35 $3,465
Employee Stock Purchase Plan
On June 7, 2016, the Company’s stockholders approved the 2016 Employee Stock Purchase Plan (the “ESPP”), which became effective June 21, 2016. The ESPP is intended to qualify as an "employee stock purchase plan" under Section 423 of the Internal Revenue Code of 1986 with the purpose of providing employees with an opportunity to purchase the Company's common stock through accumulated payroll deductions.
Under the ESPP, the Company has set two six-month offering periods during each calendar year, one beginning March 1st and the other beginning September 1st of each calendar year, during which employees may elect to have up to 25% of their eligible compensation deducted on each payday on an after-tax basis for use in purchasing the Company's common stock on the last trading day of each offering period, subject to limits imposed by the Internal Revenue Code. The purchase price of the shares may not be less than 85% of the fair market value on the first or last trading day of the offering period, whichever is lower.
A total of 357,456 shares of common stock are authorized and reserved for future issuance under the ESPP. The number of shares of common stock that may be issued under the ESPP will automatically increase on the first day of each calendar year, beginning in 2017 and ending in and including 2026, by an amount equal to the lesser of: (i) 1% of the number of shares of the Company’s common stock outstanding on the last day of the applicable preceding calendar year and (ii) such smaller number of shares as is determined by the Company’s Board of Directors. During the three and nine months ended September 30, 2017, the Company issued 16,263 shares of common stock under the ESPP. As of September 30, 2017, there were 341,193 shares of common stock available for future issuance under the ESPP.
The fair value of the purchase rights granted under the ESPP for each of the six month offering periods beginning March 1, 2017 and September 1, 2017 were estimated by applying the Black-Scholes option-pricing model using the following range of assumptions:
 Nine Months Ended September 30, 2017
Fair value of common stock$13.08-$18.02
Risk-free interest rate0.79%-1.19%
Expected volatility46.73%-75.78%
Expected life (years)0.1-0.5
Expected dividend yield—%
For the three and nine months ended September 30, 2017, the Company recorded less than $0.1 million and $0.1 million, respectively, of stock-based compensation expense under the ESPP. There was no stock-based compensation expense related to the ESPP recorded for the three and nine months ended September 30, 2016.

The Company recorded stock-based compensation expense related to stock options, the ESPP and restricted common stock in the following expense categories of its consolidated statements of operations and comprehensive loss (in thousands):
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Research and development$532
     $353
     $1,271
 $747
General and administrative782
 280
 1,601
 534
Total$1,314
 $633
 $2,872
 $1,281
13. Revenue Arrangements
Spark License Agreement
In December 2016, the Company entered into a License and Option Agreement (“Spark License Agreement”) with Spark Therapeutics, Inc. (“Spark”) pursuant to which the Company and Spark agreed to collaborate on the development of gene therapies for certain targets utilizing the SVP™ technology. The Spark License Agreement provides Spark with certain exclusive, worldwide, royalty bearing licenses to the Company’s intellectual property, allowing Spark to develop and commercialize gene therapies for an initial identified target.
In addition to an upfront cash payment of $10.0 million under the Spark License Agreement, additional payments of an aggregate of $5.0 million in two payments of $2.5 million each were paid within twelve months of December 2, 2016 (“Contract Date”). The first of the two additional payments was scheduled to be made on or before May 31, 2017 (the “May 2017 License Payment”) (see “Spark Letter Agreement” below) and the second was made on October 31, 2017. Spark may also exercise options to research, develop and commercialize gene therapies utilizing the SVP technology for up to four additional targets. The Company is eligible to receive a variable fee up to $2.0 million for each additional target option elected, dependent on the incidence of the applicable indication. As per the agreement, the election period in which Spark can exercise additional targets is a term of three years from the Contract Date, or December 1, 2019.
Assuming successful development and commercialization, the Company could receive up to an additional $65.0 million in development and regulatory milestone payments and $365.0 million in commercialization milestone payments for each indication. If commercialized, the Company would be eligible to receive tiered royalties on global net sales at percentages ranging from mid-single to low-double digits, all of which apply on a target-by-target basis. Under the terms of the agreement, the Company will be eligible to receive these royalties commencing on the first commercial sale of the licensed product and terminating upon the later of (i) ten years after the first commercial sale, (ii) expiration of the last to expire valid claim on patents covering the jointly invented field specific improvements, or (iii) the expiration of regulatory exclusivity in the applicable country for the licensed product.
The License Agreement may be terminated by Spark for convenience upon ninety days’ notice. Either party may terminate the License Agreement on a target-by-target basis for material breach with respect to such target.
In December 2016, the Company also entered into a Share Purchase Agreement (the “Spark Purchase Agreement”) with Spark. Pursuant to the Spark Purchase Agreement, the Company sold 197,238 shares of the Company’s common stock to Spark for gross proceeds of $5.0 million, or $25.35 per share of common stock, at an initial closing (the “Initial Closing”). The purchase price per share represents an amount equal to 115% of the average daily volume weighted average price (“VWAP”) of the common stock during the thirty consecutive calendar days leading up to and ending on the day prior to the Contract Date. Under the Spark Purchase Agreement, Spark has agreed not to dispose of any of the Initial Closing Shares or any Acquisition Right Shares that it may acquire until January 1, 2018 and, thereafter, transfers will be contractually subject to volume limitations applicable to an “affiliate” under Rule 144 of the Securities Act. Closings under the Spark Purchase Agreement are subject to customary conditions.
Beyond the Initial Closing, the Spark Purchase Agreement contemplated potential future sales of shares by the Company to Spark as follows:
First Acquisition Right. During the period beginning on May 1, 2017 and ending on June 1, 2017, Spark had the right (the “First Acquisition Right”) to purchase a number of shares of common stock equal to an aggregate price of $5.0 million. See "Spark letter agreement" below.
Second Acquisition Right. During the period beginning on October 1, 2017 and ending on November 1, 2017, Spark had the right (the “Second Acquisition Right”) to purchase a number of shares of common stock equal to an aggregate price of $5.0 million. On October 31, 2017 Spark exercised this right and purchased 205,254 shares of common stock from the Company for $5.0 million, or $24.36 per share of common stock. The purchase price per share represents an

amount equal to 115.0% of the average daily VWAP of the common stock during the thirty consecutive calendar days leading up to and ending on the day prior to the Second Acquisition Right notification date.
The First Acquisition Rights and Second Acquisition Rights are collectively referred to herein as the “Acquisition Rights”. The aggregate number of shares that the Company may issue pursuant to the Stock Purchase Agreement may not exceed the lesser of (i) 2,758,112 shares and (ii) such number of shares that would require the Company to obtain prior shareholder approval under the Nasdaq Marketplace Rules.
In connection with the Spark License2021 Sales Agreement, and Spark Purchase Agreement, the Companyalso has made contractual payments defined in the MIT license agreement (Note 15) totaling $1.9 million for the MIT sub-license provided to Spark, and $0.3 million relative to the calculated premium paid by Spark for the equity investment made under the First Acquisition Right outlined in the Spark Purchase Agreement.
Accounting Analysis
SVB Leerink with customary indemnification rights. The Spark License Agreement contains the following deliverables: (1) certain exclusive, worldwide, royalty bearing licenses to the Company’s intellectual property and a license to conduct certain research activities under the collaboration, or the License Deliverable, (2) options to research, develop and commercialize gene therapies utilizing the SVP technology for up to four additional target therapy options, or the Option Deliverable, and (3) manufactured supplyoffering of pre-clinical and clinical SVP, or the Supply Deliverable. The Company considered the provisions of the multiple-element arrangement guidance in determining how to recognize the revenue associated with the identified deliverables. The Company has accounted for access to certain of the Company's technology through the various licenses and rights to use under the license deliverables listed above and the delivery of the manufactured supply as a single unit of accounting. The deliverables are not considered to have standalone value from one another and amounts allocated to these obligations will be recognized throughout the estimated period of delivery of the supply.
The Option Deliverable is determined to be substantive at the outset of the agreement, and therefore will not be considered an element of the arrangement when allocating the consideration as there is considerable uncertainty that the options would be exercised. Although the options are not considered a deliverable at inception, it was determined that there is a significant and incremental discount that requires inclusion as an element of the initial allocation of contract consideration.
In addition, the Company evaluated the Spark Purchase Agreement and the Spark License agreement as one arrangement and determined that the initial purchase of common stock combined with the embedded future stock Acquisition Rights had a fair value of $2.7 million and this amount was recorded in equity.
The Company evaluated and determined that the Acquisition Rights under the Spark Purchase Agreement are not freestanding instruments as these rights are not legally detachable from the Company’s common stock. In addition, the Company has further assessed that the Acquisition Rights were clearly and closely related to the economic characteristic and risk of the common stock. The Company determined that the Acquisition Rights are embedded and inseparable from the initial stock purchase and no subsequent remeasurement is necessary.
Allocable arrangement consideration at inception consisted of the total non-contingent payments aggregating to $15 million. The Company allocated $2.7 million to equity (representing the fair value of the initial purchase of common stock combined with the embedded future stock Acquisition Rights), $7.1 million to the License and Supply Deliverable combined unit of accounting and $5.2 million to the discount on the Option Deliverable. The total arrangement consideration for the License and Supply deliverable and the Option deliverable was allocated using the relative best estimate of selling price method to each deliverable. The best estimate of selling price for the License and Supply deliverable was determined using a discounted cash flow model that includes Level 3 fair value measurements. The best estimate of selling price for the Option Deliverable was determined based on the fair value of the license minus the strike price of the option. The consideration allocated to the combined unit of accounting for the License and Supply Deliverable, totaling $7.1 million, will be recognized based on the expected deliveries over an initial term which is estimated to be approximately four years. The discount associated with the Option Deliverable, totaling $5.2 million, will be recognized, if the options are exercised, over the related expected deliveries of supply. If the options expire without exercise, the related deferred revenue will be recognized upon expiration (December 1, 2019).
The Company recognized less than $0.1 million in revenues related to the Spark License Agreement during the three and nine months ended September 30, 2017. There were no revenues recognized for the three and nine months ended September 30, 2016.
The Company determined that each potential future clinical and regulatory milestone was non-substantive, therefore, any consideration received will be allocated to the License and Supply Deliverable and Option Deliverable using the relative selling price.
Sales-based milestones and royalty payments are expected to be recognized when earned.

As of September 30, 2017, there was $12.2 million of deferred revenue related to this agreement. A total of $3.2 million was recorded as a current liability and $9.0 million was classified as a long term liability in the accompanying consolidated balance sheet.
Spark Letter Agreement
On June 6, 2017, the Company and Spark entered into a letter agreement (the “Letter Agreement”), pursuant to which the parties agreed that Spark would make the May 2017 License Payment by June 6, 2017. The May 2017 License Payment was received, and recorded as a liability as of June 30, 2017, of which some or all may potentially constitute the reimbursement described below. The parties also agreed that Spark would be deemed to have delivered notice on May 31, 2017 exercising its right to purchase the shares pursuant to the First Acquisition Right. The Letter Agreement further outlines a cost reimbursement arrangement, pursuant to which the Company agreed to reimburse Spark for all costs and expenses, including the cost of materials provided by the Company, associated with the preclinical research and toxicology studies being performed by Spark for any licensed products for a specified amount of time (the “Reimbursement Period”), up to an agreed upon cap.
Consistent with the First Acquisition Right, Spark purchased 324,362 shares of common stock pursuant to the Spark Purchase2021 Sales Agreement as amended by the Letter Agreement, for an aggregate purchase price of $5.0 million, or $15.41 per share of common stock. The purchase price per share represents an amount equal to 115.0% of the average daily volume weighted average price (“VWAP”) of the common stock during the thirty consecutive calendar days leading up to and ending on the day prior to the First Acquisition Right notification date. At the initial contract assessment, the Company allocated $2.7 million to equity (representing the fair value of the initial purchase of common stock combined with the embedded future stock Acquisition Rights). Upon exercise of the First Acquisition Right, the Company recorded the purchase amount to stockholders’ equity.
Sanofi Collaboration Agreement
On November 27, 2012, the Company and Sanofi entered into a license and research collaboration agreement focused on the identification and development of vaccines against food allergies (the “Sanofi Agreement”). Under the arrangement, the Company agreed to perform research to identify an initial vaccine candidate for development and commercialization by Sanofi under an exclusive license.
Pursuant to the Sanofi Agreement, the Company received an upfront payment of $2.0 million for the initial indication in November 2012 and an additional payment of $3.0 million in August 2013. In November 2014, Sanofi exercised the option to include celiac disease as an additional indication, and in May 2015, the Sanofi Agreement was amended to add terms specific to the celiac disease indication and towill terminate Sanofi's right to exercise its option for any additional indications. Sanofi paid the Company an additional $2.0 million upon the exerciseearlier of (i) the option in May 2015 and an additional $1.0 million in July 2016 upon attaining the first milestone for the celiac disease indication. To date, Sanofi has paid the Company $8.0 million in the aggregate under the Sanofi Agreement.
Except as authorized by Sanofi or permitted under the Sanofi Agreement, during the termsale of the Sanofi Agreement, exclusivity obligations prevent the Company from researching, developing, or commercializing products in these indications or granting third party licenses under the intellectual property rights and technologies licensed to Sanofi for use in these indications.
As per the agreement, the research term expired for the first indication on the third anniversary (November 27, 2015) of the agreement. The Company completed its research obligations within the initial three year period and is not obligated to perform any further research on the specific indication under the agreement. A vaccine candidate for development and commercialization was not selected by Sanofi by the end of the research plan, and therefore no further milestone payments have been received.
The Company identified the deliverables under the arrangement as the license, the research necessary to identify the development candidate, and participation of the Joint Research Committee (“JRC”). The Company determined that the exclusive license granted to Sanofi did not have standalone value from the research to be performed to identify the vaccine development candidate. As a result, each upfront and milestone consideration was allocated to the combined unit of account comprising the license and research services, and is being recognized over the estimated development period using a proportional performance method. The consideration allocated to participation on the JRC was not material. The Company recognized no revenue for the three and nine months ended September 30, 2017, and $0.2 million and $0.6 million for the three and nine months ended September 30, 2016, respectively.
Termination of the Sanofi Collaboration Agreement
On November 9, 2016, the Company received written notice from Sanofi that Sanofi had elected to terminate in its entirety the Sanofi Agreement. The termination of the Sanofi Agreement was effective on May 8, 2017, or the Termination Date, which was six months from the date of the notice.

As discussed above, Sanofi has paid the Company $8.0 million in the aggregate under the Sanofi Agreement to date. The Company would have been eligible to receive additional development-based, regulatory-based and sales-based milestone payments and tiered royalties on net sales of any approved product generated by the collaboration had the Sanofi Agreement not been terminated. As of December 31, 2016, the Company recognized the remaining $2.2 million in revenue associated with the Sanofi Agreement, as the Company has no further performance obligation under the contact.
All rights granted to Sanofi terminated and reverted to the Company effective on the Termination Date, and Sanofi is required to grant to the Company a royalty bearing, exclusive license, with the right to grant sublicenses, under certain Sanofi intellectual property solely to the extent necessary to research, develop, make, have made, use, offer for sale, import, export and otherwise commercialize the vaccine candidates developed under the Sanofi Agreement. The exclusivity obligations discussed above also expired on the Termination Date.
The Company has exercised its right to acquire the development programs under the Sanofi Agreement. The Company is solely responsible for performing and funding any development and clinical trial activities relating to further development of vaccine candidates that it chooses to undertake after the Termination Date.
Other Research and Collaboration Agreements
The Company has not entered into other research and collaboration agreements in 2017 and the Company recognized no revenue with respect to other research and collaboration agreements for the three and nine months ended September 30, 2017. For any other research or collaboration agreements that the Company was part of during 2016, no revenue was recognized in the three months ended September 30, 2016 and less than $0.1 million was recognized for the nine months ended September 30, 2016.
Grant Agreements
The Company receives funding in the form of grants from the National Institutes of Health (“NIH”), the Juvenile Diabetes Research Foundation (“JDRF”), the Bill and Melinda Gates Foundation, the Russian Ministry of Industry and Trade (“Minpromtorg”), and the Russia based Development Fund of New Technologies Development and Commercialization Center (“Skolkovo”).
NIH
The Company has two grants through the NIH. The first grant, for an aggregate amount of $8.1 million, was awarded in May 2014 to support research in the development of a next generation vaccine for smoking cessation and relapse prevention. The Company recognized no revenue for the three and nine months ended September 30, 2017. For the three and nine months ended September 30, 2016, the Company recognized revenue of $0.7 million and $3.7 million, respectively.
The second grant is for an aggregate amount of $0.2 million, which was awarded in September 2015 for the development of nanoparticles for immune tolerance to factor VIII. The Company recognized no revenue and less than $0.1 million for the three months ended September 30, 2017 and 2016, respectively, and less than $0.1 million for each of the nine months ended September 30, 2017 and 2016, related to this grant.
JDRF
The Company, together with Sanofi, entered into a joint grant with JDRF in September 2014 for $0.4 million to conduct Type 1 Diabetes research. The Company recognized no revenue for the three months ended September 30, 2017 and less than $0.1 million for the three months ended September 30, 2016. During the nine months ended September 30, 2017 and 2016 the Company recognized less than $0.1 million and $0.1 million related to this grant, respectively.
Bill and Melinda Gates Foundation
The Company received a grant in 2013 from the Bill and Melinda Gates Foundation for $1.2 million to fund the Company’s immunology research on malaria antigens. During 2014, the grant amount was increased to a total of $1.6 million and the term was extended to a three-year research term. Revenue is recognized on a proportional performance basis as it relates to employee time expended on the research, along with reimbursement for external costs directly related to, and approved, by the grant terms.  For the three months ended September 30, 2017 and 2016, the Company recognized revenue of less than $0.1 million and $0.1 million, respectively. Total revenue recognized for the nine months ended September 30, 2017 and 2016 was $0.1 million and $0.4 million, respectively.
Minpromtorg
The Company had a contract awarded from Minpromtorg for approximately $4.6 million to fund the Company’s nicotine cessation vaccine clinical trial to be conducted in Russia. The grant covered a term from July 9, 2013 through December 31, 2015, and provided for reimbursement of expenses incurred by the Company from the clinical trial. Under the agreement term, the Company was subject to a penalty in the event that the clinical trial was delayed or terminated prior to completion. As a

result of the penalty provision, the Company concluded the amounts received under the agreement were not fixed or determinable.  In 2014, the Company terminated its plan to conduct the clinical trial in Russia subjecting the Company to the penalty obligation.
In February 2015, the Company received an executed final settlement agreement from Minpromtorg that included the repayment of funds previously received by the Company totaling $0.2 million, and a penalty fee that equaled to 10% of the contract value, or $0.2 million. The Company paid the settlement payment in March 2015 and all mutual claims under the contract were terminated. According to the terms of the agreement, Minpromtorg has the right to audit the expenditure incurred under the agreement for a period up to three years from each research milestone date. All grant funding received in excess of the penalty settlement will remain as a liability on the balance sheet until such time the audit period has expired and at which time, the amount will be recognized as revenue. Through September 30, 2017, the Company received payments totaling approximately $1.4 million. No additional payments are expected to be received under the terms of the contract.
The first audit period expired on December 31, 2015, and as a result $0.4 million of revenue was recognized for the year ended December 31, 2015.  The second and third audit periods expired during the twelve months ended December 31, 2016, and as a result $0.5 million of revenue was recognized for the year ended December 31, 2016. The third audit period, is the final audit to be conducted under the contract. As of December 31, 2016, the deferred revenue associated with Minpromtorg contract has been fully recognized. There was no revenue recognized during the three and nine months ended September 30, 2017, and a total of less than $0.1 million and $0.2 million of revenue recognized during the three and nine months ended September 30, 2016, respectively.
Skolkovo
On November 28, 2014, the Company executed a grant awarded by Skolkovo for the development of a therapeutic vaccine using nanoparticles to treat chronic infection caused by human papillomavirus (HPV) and diseases associated with this infection. The grant covers a period from August 1, 2014 through July 21, 2017. The grant provides for up to $2.7 million that covers 48.5% of the estimated total cost of the research plan with the remaining 51.5% of estimated costs to be contributed by the Company. The Company has received from Skolkovo $1.8 million through the nine months ended September 30, 2017.
At any time during the term of the grant agreement, but not more than once per quarter, Skolkovo has the right to request information related to the project and to conduct an audit of the expenses incurred by the Company. In the event the project or the expenses do not meet predefined requirements, the Company may be required to reimburse the funds received up to three years after the completion of the project. As a result, the Company has determined that the grant funding is not fixed or determinable and all amounts received to date are recorded as deferred revenue in the consolidated balance sheet until the completion of the Skolkovo audit or the expiration of the audit term.
14. Related‑Party Transactions
As part of the Series B Preferred and Series D Preferred financings (as described in Note 11), the Company’s landlord (the “Landlord”) purchased 49,254 shares of Series B Preferred at $2.03 per share for total proceeds of $0.1 million and 488,888 shares of Series D Preferred at $4.50 per share for total proceeds of $2.2 million. Additionally, in April 2015, the Landlord participated in the Company’s bridge loan in the amount of $0.2 million, which converted into Series E Preferred (see Note 11). The Landlord paid the same price as the price paid by other investors in each of these Preferred Stock purchases.  At the IPO, all preferred stock was converted to common stock.
In connection with the 2017 PIPE, the Company sold to Timothy Springer, Ph.D., a member of its Board of Directors, an aggregate of 338,791 shares of common stock at a purchase price equal to $17.71 per share, which was equalsubject to the most recent consolidated closing bid price2021 Sales Agreement and (ii) the termination of the 2021 Sales Agreement as permitted therein.
Warrants
During October 2021, warrant holders exercised 1,642,036 common warrants on the Nasdaq Global Market on June 23, 2017. In addition, the Company sold warrants to Dr. Springer to purchase up to 79,130a cashless basis and received 1,076,669 shares of common stock (“Warrant Shares”), exercisable at $17.71 per Warrant Share, and with a term of five years. The purchase price for each warrant was equal to $0.125 for each Warrant Share, consistent with Nasdaq Global Market requirements for an “at the market” offering.stock.
The Company incurred expenses for consulting services provided by its founders totaling less than $0.1 million and $0.1 million during the three months ended September 30, 2017 and 2016, respectively, and $0.2 million for each of the nine months ended September 30, 2017 and 2016.

15. Technology License Agreements
MIT
On November 25, 2008, the Company entered into an Exclusive Patent License agreement with the Massachusetts Institute of Technology (“MIT”), which is referred to as the Exclusive Patent License. The Company received an exclusive royalty‑bearing license to utilize patents held by MIT in exchange for upfront consideration and annual license maintenance fees. Such fees are expensed as incurred and have not been material to any period presented. In the event the Company sublicenses the MIT

patents to a third party, it will be required to remit to MIT a percentage (ranging from 10% to 30%) of sublicense income. In addition, the Company is obligated to pay MIT a certain amount upon the achievement of defined clinical milestones, up to a total of $1.5 million. On December 18, 2008, the Company entered into a patent‑cross‑license agreement with BIND Therapeutics, Inc. whereby each party receives a license for the use of the other patents in their respective fields of use. In exchange for this license, the Company paid a one‑time expense in 2008.
As of September 30, 2017, and in connection with the execution of the Spark License Agreement, the Company has made contractual payments pursuant to the Exclusive Patent License totaling $1.9 million for the sublicense granted to Spark, and $0.3 million relative to the calculated premium paid by Spark for the initial equity investment and the First Acquisition Right made under the Spark Purchase Agreement.
Shenyang Sunshine Pharmaceutical Co., Ltd
In May 2014, the Company entered into a license agreement with Shenyang Sunshine Pharmaceutical Co., Ltd. (“3SBio”), which is referred to as the 3SBio License. Pursuant to the 3SBio License, which was amended and restated in May 2017, the Company was granted an exclusive license to certain pegsiticase‑related patents and related “know‑how” owned or in‑licensed by 3SBio for the worldwide (except for Greater China and Japan) development and commercialization of products based thereupon for human therapeutic, diagnostic and prophylactic use. The Company was also granted a worldwide (except for Greater China) exclusive license to develop, commercialize and manufacture or have manufactured products combining the Company’s proprietary SVP technology with pegsiticase or related compounds supplied by 3SBio (or otherwise supplied if the Company’s rights to manufacture are in effect) for human therapeutic, diagnostic and prophylactic use. The Company was also granted a co‑exclusive license to manufacture and have manufactured pegsiticase and related compounds for preclinical and clinical use or, if the 3SBio License is terminated for 3SBio’s material breach, for any use under the 3SBio License. Otherwise, the Company is obligated to obtain all of its supply of such compounds for Phase 3 clinical trials and commercial use from 3SBio under the terms of supply agreements to be negotiated.
Pursuant to the 3SBio License, the Company is required to use commercially reasonable efforts to develop and commercialize a product containing pegsiticase or a related compound. If the Company does not commercialize any such product in a particular country in Asia, Africa or South America within 48 months after approval of any such product in the United States or a major European country, then 3SBio will have the right to do so, but only until the Company commercializes a product combining the Company’s SVP technology with any such compound in such country. The Company has paid to 3SBio an aggregate of $1.0 million in upfront and milestone‑based payments under the 3SBio License. An additional liability totaling $2.0 million for milestone payments was expensed in 2016, and is included with Accounts Payable on the balance sheet as of December 31, 2016. The Company is required to make future payments to 3SBio contingent upon the occurrence of events related to the achievement of clinical and regulatory approval milestones of up to an aggregate of $21.0 million for products containing the Company’s SVP technology, and up to an aggregate of $41.5 million for products without the Company’s SVP technology. The Company is also required to pay 3SBio tiered royalties on annual worldwide net sales (on a country‑by‑country and product‑by‑product basis) related to the pegsiticase component of products at percentages ranging from the low‑to‑mid single digits for products containing the Company’s SVP technology, and a range of no more than ten percent points from the mid‑single digits to low double‑digits for products without the Company’s SVP technology. The Company will pay these royalties to 3SBio, subject to specified reductions, on a country‑by‑country and product‑by‑product basis until the later of (i) the date that all of the patent rights for that product have expired in that country, or (ii) a specified number of years from the first commercial sale of such product in such country.
The 3SBio License expires on the date of expiration of all of the Company’s royalty payment obligations unless earlier terminated by either party for an uncured material default or for the other party’s bankruptcy. Any such termination by 3SBio for material default may be on a country‑by‑country or product‑by‑product basis in certain circumstances. The Company may also terminate the 3SBio License on a country‑by‑country or product‑by‑product basis for any reason effective upon 60 days’ prior written notice to 3SBio or, with respect to a given product, immediately upon written notice to 3SBio if the Company identifies a safety or efficacy concern related to such product.
Massachusetts Eye and Ear Infirmary and The Schepens Eye Research Institute, Inc.
In May 2016, the Company entered into a license agreement with the Massachusetts Eye and Ear Infirmary and The Schepens Eye Research Institute, Inc. (collectively, “MEE”), which is referred to as the MEE License. Under the MEE License, the Company was granted an exclusive commercial worldwide license, with the right to grant sublicenses through multiple tiers, to make, have made, use, offer to sell, sell and import certain products and to practice certain processes, the sale, use or practice of which are covered by patents and proprietary know‑how owned or controlled by MEE, for use of Anc80 gene therapy vectors for gene augmentation therapies expressing certain target sequences.
MEE also granted the Company exclusive options to exclusively license certain of their intellectual property rights relating to several additional target sequences and variations thereof each linked to a specified disease. During a defined option period, the

Company may exercise this right for up to a designated number of target sequences. If the Company exercises its options, under certain circumstances, the Company may substitute alternative target sequences for previously selected target sequences.
The Company agreed to use commercially reasonable efforts to develop and commercialize licensed products pursuant to a development plan, and to market and sell at least one product for each target sequence for which the Company exercised its option as soon as reasonably practicable. Subject to certain exceptions, following commercial launch, the Company must use commercially reasonable efforts to market, sell, and maintain public availability of licensed products in a certain number of specified major markets.
Pursuant to the MEE License, the Company agreed to pay MEE a license fee in the low six figures, annual license maintenance fees ranging from the mid‑twenty thousands to mid‑seventy thousands and an option maintenance fee in the low five figures for each exercisable option. The Company also agreed to reimburse MEE for a specified percentage of the past patent expenses for the patents licensed to the Company. The Company also agreed to pay development milestones on a licensed product‑by‑licensed product basis, totaling up to an aggregate of between $4.2 million to $37.0 million and sales milestones on a licensed product‑by‑licensed product basis, totaling up to an aggregate of between $50.0 million to $70.0 million; tiered royalties on a licensed product‑by‑licensed product and country‑by‑country basis equal to a percentage of net sales ranging from mid‑single digits to mid‑teens, subject to the prevalence of the targeted disease and certain reductions; and a percentage, in a range expected to be in the mid‑teens depending on timing, of any sublicense income the Company receives from sublicensing its rights granted thereunder, subject to certain reductions and exclusions. Upon exercise of each option, the Company agreed to pay MEE an option exercise fee ranging from low‑six figures to mid‑six figures, depending on the prevalence of the targeted disease.
The MEE License will continue until the expiration of the last to expire of the patent rights licensed thereunder. The Company may terminate the MEE License in whole or in part upon prior written notice. MEE may terminate the MEE License on a target sequence‑by‑target sequence basis if the Company fails to make any scheduled payments in respect of such target sequence or if the Company materially breaches a diligence obligation in respect of such target sequence, in each case if the Company fails to cure within a specified time period. MEE may terminate the MEE License in its entirety if the Company materially breaches certain of its obligations related to diligence, representations and warranties, and maintenance of insurance; if the Company challenges the validity or enforceability of any patents licensed thereunder; if any of the Company’s executive officers are convicted of a felony relating to manufacture, use, sale or importation of licensed products; or upon the Company’s insolvency or bankruptcy.
As of June 30, 2016, the Company had paid a total of $0.1 million in license fees due under the MEE License. No additional license fees are due under the MEE License as of September 30, 2017.
16. Income Taxes
The Company did not provide for any income taxes in any of the three or nine month periods ended September 30, 2017 or 2016.
In 2014, the Company's Russian subsidiary was granted a 10 year tax holiday in Russia. The Company's foreign operations continue to benefit from the tax holiday, which is set to expire December 31, 2023.
The Company has evaluated the positive and negative evidence bearing upon the realizability of its U.S. net deferred tax assets. As required by the provisions of ASC 740, Income Taxes, management has determined that it is more-likely-than-not that the Company will not utilize the benefits of federal and state U.S. net deferred tax assets for financial reporting purposes. Accordingly, the net deferred tax assets are subject to a full valuation allowance at September 30, 2017 and December 31, 2016.

17. 401(k) Savings Plan
The Company maintains a defined‑contribution savings plan under Section 401(k) of the Internal Revenue Code (the “401(k) Plan”). The 401(k) Plan covers all employees who meet defined minimum age and service requirements, and allows participants to defer a portion of their annual compensation on a pretax basis. The 401 (k) Plan provides for matching contributions on a portion of participant contributions pursuant to the 401(k) Plan’s matching formula. All matching contributions vest ratably over 4 years and participant contributions vest immediately.
Contributions by the Company totaling less than $0.1 million for the three months ended September 30, 2017 and 2016, and $0.2 million and $0.1 million for the nine months ended September 30, 2017 and 2016, respectively, have been recorded in the consolidated statements of operations and comprehensive loss.


18. Subsequent Events
On October 26, 2017, the Company appointed John H. Leaman, M.D. as Chief Financial Officer, Head of Corporate Strategy and Treasurer of the Company. Dr. Leaman was also designated as the Company’s principal accounting officer, and succeeds David Siewers as Chief Financial Officer, Treasurer and principal accounting officer.
On October 31, 2017 Spark paid the Company a $2.5 million milestone payment pursuant to the license agreement with Spark. In addition, Spark exercised the Second Acquisition Right set forth in Section 2.4 of the Spark Purchase Agreement and purchased 205,254 shares of common stock from the Company for $5.0 million, or $24.36 per share of common stock. The purchase price per share represents an amount equal to 115.0% of the average daily VWAP of the common stock during the thirty consecutive calendar days leading up to and ending on the day prior to the Second Acquisition Right notification date.




Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations
The following discussion and analysis of our financial condition and results of operations should be read in conjunction with our unaudited consolidated financial statements and related notes appearing elsewhere in this Quarterly Report on Form 10-Q. Some ofand with our audited financial statements and the information containednotes thereto included in this discussion and analysis or set forth elsewhere in this Quarterlyour Annual Report on Form 10-Q, including information10-K for the year ended December 31, 2020, which we filed with respect to our plansthe SEC on March 12, 2021. In addition, you should read the “Risk Factors” and strategy for our business, includes forward-looking statements that involve risks and uncertainties. As a result of many factors, including those factors set forth in the ‘‘Risk Factors’’ section“Information Regarding Forward-Looking Statements” sections of this Quarterly Report and our Annual Report on Form 10-Q, our10-K
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for the year ended December 31, 2020 for a discussion of important factors that could cause actual results couldto differ materially from the results described in or implied by thesethe forward-looking statements.statements contained in the following discussion and analysis.


OVERVIEWOverview
We are a clinical‑stageclinical-stage biopharmaceutical company usingleveraging our proprietary synthetic vaccine particle, or SVP, technology to discoverImmTOR™ immune tolerance platform with the goals of amplifying the efficacy of biologics, including enabling the re-dosing of life-saving gene therapies, and develop targeted therapies that are designed to modulate the immune system to effectively and safely treat rare and seriousrestoring self-tolerance in autoimmune diseases. Many such diseases are treated with biologic therapies that are foreign to the patient’s immune system and, therefore, elicit an undesired immune response.
Our proprietary SVP technologyImmTOR platform encapsulates rapamycin, also known as sirolimus, an immunomodulator, in biodegradable nanoparticles and is designed to induce antigen‑specificantigen-specific immune tolerance.
We believe ImmTOR has the potential to enhance the efficacy without compromising the safety of biologic therapies, improve product candidates under development, and enable novel therapeutic modalities. We have developed a portfolio of proprietary and collaboration-driven applications of ImmTOR, and we plan to continue to develop proprietary compounds and pursue collaboration-driven development in certain disease areas, which could include strategic collaborations, out-licensing, and in-licensing transactions.
We believe our ImmTOR platform has a broad range of potential applications.
Enzyme therapies. Enzyme therapies are a class of biologic drugs frequently used to treat rare diseases. Through our analysis of biologic drugs, including in our preclinical studies, we have observed that enzymes are especially prone to causing undesired immune responses. Our product candidate, SEL-212, which is currently in Phase 3 clinical development, includes pegadricase, a pegylated uricase enzyme, which is an example of an immunogenic enzyme for which we are applying ImmTOR with the intention of improving the enzyme’s efficacy and safety. We are also combining ImmTOR with an immunoglobulin A, or IgA, protease for the treatment of IgA nephropathy. We intend to seek, if appropriate, licenses to other enzymes that we would evaluate in combination with ImmTOR.
Gene therapies. We believe gene therapies have the potential to address key unmet medical needs for many rare genetic diseases, but undesired immune responses to the viral vectors used for gene replacement, augmentation and editing may be restricting their broader use. Through our analysis of genetic diseases, we have identified applications and patient segments that we believe would benefit from our ImmTOR platform. We intend to develop ImmTOR-enabled non-immunogenic gene therapy candidates which are designed to be utilized with adeno-associated virus, or AAV, vectors. We believe our product candidates have the potential to increase transgene expression and to prevent undesired immune responses to the vector and transgene product that can occur with the first dose of gene therapy by using our ImmTOR platform. Our initial area of focus is on genetic metabolic diseases and genetic muscular diseases. We believe we are the first company to systematically pursue the development of AAV gene therapy product candidates with the goal of enabling repeat administration. We have engaged third parties with experience in gene therapy and rare diseases to support the development of our products. We also have licensed our ImmTOR platform to AskBio, Sarepta, Takeda, and Spark for certain pre-specified targets.
Restoring self-tolerance to auto-antigens. We believe that ImmTOR has the potential to restore self-tolerance in autoimmune diseases. Our first program in autoimmune diseases is in primary biliary cholangitis, or PBC. PBC has a significant unmet medical need and a well-defined target antigen, known as PDC-E2. In a strategic collaboration with leading protein design company Cyrus Biotechnology, Inc., or Cyrus, we are developing ImmTOR in connection with a proprietary interleukin-2 (IL-2) protein agonist designed to selectively promote expansion of regulatory T cells for the potential treatment of patients with autoimmune diseases and other deleterious immune conditions.
Other products and product candidates affected by undesired immune responses. We have generated preclinical data which we believe suggests a broad potential benefit of ImmTOR for immune tolerance. For many biologic drugs, undesired immune responses limit efficacy and cause safety concerns. We intend to strategically out-license ImmTOR for use with other products that are outside our focus to larger biopharmaceutical companies. We believe our ImmTOR platform may also be of interest to biopharmaceutical companies with novel biologic development concepts or product candidates in clinical development that have demonstrated initial efficacy but are experiencing issues with safety or sustained efficacy due to inhibitory ADAs.
Our Current Programs
Amplifying the Efficacy of Biologics: Enzyme therapy – Chronic Refractory Gout
SEL-212 is designed to be a monthly treatment for chronic refractory gout, a debilitating rare disease with an unmet medical need. SEL-212 consists of a combination of our ImmTOR platform co-administered with pegadricase. Pegadricase is an investigational recombinant pegylated uricase (urate oxidase), an enzyme not naturally found in humans, and is therefore highly immunogenic. This enzyme is designed to treat patients with symptomatic gout, refractory to standard uric acid lowering treatment, by breaking down the excess uric acid to the more soluble allantoin. In preclinical studies, we observed that ImmTOR, when co-administered with pegadricase, induced antigen-specific immune tolerance to mitigatepegadricase and substantially
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reduced the formation of anti‑drug antibodies, or ADAs, in response to life‑sustaining biologic drugs. Weassociated ADAs. Based on our clinical data, we believe our SVP technologythat SEL-212 has the potential for broad application to both enhance existing biologic drugs and enable novel therapies. Our lead product candidate, SEL‑212, is a combination of a therapeutic enzyme and our SVP technology designed to be the first biologic treatment for gout that durably controlscontrol serum uric acid, in refractory gout and dissolves and removes harmful deposits of uric acid crystals in chronic tophaceous gout, each a painful and debilitating disease with unmet medical need. SEL‑212 is currently in a comprehensive Phase 1/2 clinical program. The Phase 1/2 clinical program is designed to evaluate the ability of SEL 212 to control uric acidor SUA levels and mitigate the formation of ADAs. It is comprisedADAs in response to the therapeutic enzyme. Additionally, we believe that SEL-212 serves as proof of concept for the ImmTOR platform in ameliorating the unwanted immune response to an immunogenic biologic. SEL-212 has been licensed (except as to Greater China) to Sobi, pursuant to our license and development agreement dated June 11, 2020 with Sobi, or the Sobi License.
We and Sobi commenced the Phase 3 DISSOLVE clinical program of SEL-212 in September 2020. The Phase 3 clinical program consists of two double blinded, placebo-controlled trials of SEL-212, DISSOLVE I and DISSOLVE II. Each trial is expected to enroll 105 patients, with 35 patients receiving 0.1 mg/kg of ImmTOR and 0.2 mg/kg of pegadricase, 35 patients receiving 0.15 mg/kg of ImmTOR and 0.2 mg/kg of pegadricase, and 35 patients receiving placebo. DISSOLVE I and DISSOLVE II both have a six-month primary endpoint with a six-month safety extension for DISSOLVE I. The primary endpoint of the DISSOLVE program is the maintenance of SUA levels below 6 mg/dL at six months. Secondary endpoints include tender and swollen joint counts, tophus burden, patient reported outcomes of activity limitation and quality of life and gout flare incidence. Topline data from the Phase 13 DISSOLVE clinical trials, which have been completed, and a Phase 2 clinical trial, which commenced in October 2016 and that we expect to hold our end-of-phase 3 meeting with the FDAprogram is expected in the firstsecond half of 2018.2022. The Phase 3 DISSOLVE clinical program is being conducted by Selecta and funded by Sobi.
Amplifying the Efficacy of Biologics: Enzyme therapy – IgA Nephropathy
The second indication in our enzyme therapy program is IgA nephropathy, an autoimmune kidney disease that occurs when immune complexes of a subclass of antibodies called immunoglobulin A1, or IgA1, accumulates in the kidneys.
In additionOctober 2020, we entered into an Option and License Agreement, or the IGAN Agreement, with IGAN Biosciences, Inc., or IGAN. Pursuant to SEL-212, we have two other product candidatesthe IGAN Agreement, IGAN has granted us an exclusive license to research, evaluate, and conduct pre-clinical development activities on IGAN’s proprietary IgA proteases. Previous studies in animal models conducted at independent laboratories demonstrated that IgA protease removed injurious IgA immune complexes from kidneys and reduced inflammation, fibrosis, and hematuria. These results suggest that it is an excellent candidate to potentially decrease the rate of disease progression and possibly even reverse the disease. The barrier to IgA protease commercialization is the bacterial origin of the protease, which makes it immunogenic. Our ImmTOR platform has shown in clinical development: SEL-403 and SELA-070.studies the ability to mitigate the formation of ADAs to immunogenic enzymes, which has been observed with SEL-212. We are developing SEL-403, which isintend to combine IgA protease with our ImmTOR platform to develop a novel combination of LMB-100 and SVP-Rapamycin,product candidate for the treatment of pancreatic cancerIgA nephropathy and mesothelioma. LMB-100IgA-mediated diseases. We will have an option term of 24 months, during which we can elect to obtain an exclusive license to further develop and commercialize the product candidate to treat all IgA-mediated diseases, including IgA nephropathy, Linear IgA bullous dermatitis, IgA pemphigus, and Henoch-Schonlein purpura (also known as IgA vasculitis).
We expect to file an Investigational New Drug, or IND, application, for this program in 2022.
Amplifying the Efficacy of Biologics: Gene Therapies
When used in combination with AAV gene therapy vectors, ImmTOR has been observed to inhibit the immune response to the vector and enable successful redosing in mice and non-human primates, or NHPs. Currently, the ability to re-administer systemic AAV gene therapy is limited by the development of neutralizing antibodies. The ability to safely re-dose AAV may help achieve therapeutic benefit in patients who are under-dosed; it may also help restore transgene expression in patients, particularly pediatric patients, who may lose gene expression over time as they grow. In addition, a next-generation immunotoxinstudy conducted in NHPs showed that co-administration of AAV vector and ImmTOR in NHPs enabled higher and more durable transgene expression after the first dose of gene therapy as well as robust inhibition of anti-AAV8 immunoglobulin G, or IgG, and neutralizing antibodies. The observation that co-administration of AAV vector and ImmTOR leads to higher transgene expression demonstrates the potential for dosing lower levels of AAV gene therapies when combined with ImmTOR. Thus, integrating ImmTOR into a gene therapy protocol has the potential to provide a first dose benefit by enhancing liver-directed transgene expression and durability, as well as the potential for enabling re-dosing.
Our lead therapeutic gene therapy program is in methylmalonic acidemia, or MMA, an inherited disorder in which the body is unable to process certain proteins and fats (lipids) properly. This program was previously being conducted under our collaboration with AskBio. In April 2021, we were notified by AskBio that it intended to opt-out of development of the MMA indication. The feasibility study and license agreement with AskBio, or AskBio Collaboration Agreement, otherwise remains in effect. The previously disclosed MMA-101 manufacturing issue was resolved. Manufacturing of a new lot has been completed and is currently inundergoing final release testing. We filed an IND to conduct a Phase 11/2 clinical development at the Center for Cancer Research at the National Cancer Institute. We are also developing SELA-070, a nicotine vaccinetrial of our SEL-302 product candidate in pediatric patients with methylmalonic acidemia in the third quarter of 2021. As of the filing of this quarterly report, the FDA’s 30-day review period for smoking cessationthis IND has expired. However, we have been informed orally by FDA that they are still considering certain aspects of our filing related to chemistry, manufacturing and relapse prevention. In May 2017, we commenced dosing of SELA-070 in acontrol (CMC). We intend to wait for formal clearance from FDA before initiating the proposed Phase 11/2 clinical trial assessing safety, tolerability and pharmacodynamic profile.to work with FDA to resolve any concerns they may have with our submission. If we are unable to do so we expect FDA may impose a clinical hold on this trial. ImmTOR manufacturing, controlled by us, continues to proceed in accordance with our expectations, and we have not observed any impact to any of our ImmTOR programs. In October and November 2020, we and AskBio received rare pediatric disease
We are also developing two
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designation and orphan drug designation, respectively, from the FDA for MMA-101, for the treatment of MMA due to methylmalonyl-CoA mutase, or MMUT gene therapy product candidates in preclinical development for rare inborn errors of metabolism. SEL-302, our lead gene therapy product candidate, is a potential treatment for methylmalonic acidemia. mutations.
Our secondproprietary gene therapy product candidate, SEL-313, is being developed to treat ornithine transcarbamylase, deficiency.
We were incorporatedor OTC deficiency, and is currently in 2007 underpreclinical development. OTC deficiency is a rare genetic disorder that causes ammonia to accumulate in the lawsblood due to mutations in the OTC gene, which is critical for proper function of the Stateurea cycle. The most severe form of Delawarethe disorder presents within the first few days of life. Severe symptoms include inability to control body temperature and breathing rate, seizures, coma, developmental delays and intellectual disability. Less severe forms of the disorder are characterized by delirium, erratic behavior, aversion to high protein foods, vomiting and seizures. We expect to file an IND and/or Clinical Trial Application for SEL-313 in 2022.
SEL-399 combines an empty AAV capsid (EMC-101), which is an AAV capsid containing no transgene, with ImmTOR and is being conducted in partnership with AskBio. Building on the preclinical data we have generated showing ImmTOR’s effect on mitigating or reducing the formation of neutralizing antibodies to AAV gene therapies, we have commenced a clinical trial of SEL-399 in healthy adult volunteers in Belgium. The goal of the SEL-399 clinical trial is to demonstrate the appropriate dose of ImmTOR in humans to mitigate the formation of antibodies to AAV capsids used in gene therapies. An initial control cohort of healthy volunteers received a single dose of EMC-101 in December 2020 and dose escalating cohorts of EMC-101 plus ImmTOR were initiated in February 2021. On November 8, 2021, we announced the top-line data from the Phase 1 clinical trial evaluating the potential of the ImmTOR platform in mitigating the formation of neutralizing antibodies against adeno-associated viral serotype 8 (AAV8) capsids used in gene therapies. Top-line results indicated that AAV8 empty capsids elicited peak median anti-AA8 neutralizing antibody (NAb) titers of 1:6875. Median day 30 NAb titers were 1:25 and 1:5 in the 0.15 mg/kg and 0.3 mg/kg ImmTOR cohorts, respectively, representing a 50-fold and 250-fold difference, respectively, compared to the median of control subjects dosed with AAV8 empty capsid alone. Further, we observed that at Day 30, 6 of 6 or 100% of subjects that received 0.3 mg/kg exhibited NAb titers of 1:25 or less, and 4 of 6 or 67% of those subjects at this dose exhibited NAb titers of 1:5 or less. We observed at Day 30 that 6 of 9 or 67% of subjects that received 0.15 mg/kg of ImmTOR exhibited NAb titers of 1:25 or less, and 2 of 9 or 22% of subjects at this dose had a titer of 1:5 or less. At Day 90, 2 of 6 subjects in the 0.3 mg/kg cohort were observed to have sustained control of neutralizing antibodies with titers of 1:25 or less. Consistent with preclinical data, we observed that the single dose ImmTOR cohorts saw delayed formation of neutralizing antibodies eventually reaching similar median levels of neutralizing antibodies to the control group by Day 90. ImmTOR showed safety results consistent with prior human studies and was well tolerated. No serious adverse events were reported. The most common treatment-related adverse events included mild-to-moderate stomatitis and rash.
In a strategic collaboration with Genovis, an enzyme technology company, we are leveraging Genovis’ proprietary immunoglobulin G (IgG) protease, IdeXork, or Xork, and our corporate headquartersImmTOR platform to enable the dosing of transformative gene therapies in patients with preexisting adeno-associated virus (AAV) immunity and to treat certain IgG-mediated autoimmune diseases.
Restoring Self-tolerance inAutoimmune Diseases
Our lead autoimmune diseases indication is PBC, a T-cell driven autoimmune disease that causes progressive destruction of the bile ducts. Patients with PBC are in Watertown, Massachusetts. need of a highly targeted, liver-directed approach to treating the root cause of the disorder. We believe PBC has a well-defined target antigen, significant unmet medical need, and is well suited to the application of our ImmTOR immune tolerance platform, as preclinical data suggest that ImmTOR has the potential to enhance the tolerogenic environment in the liver and provide a hepatoprotective benefit. We expect to file an IND for our PBC program in the second half of 2022.
Our operationscollaboration with Cyrus is a proprietary interleukin-2 (IL-2) protein in combination with ImmTOR to date have been limitedpotentially mitigate unwanted immune responses by reducing the inherent immunogenicity of the protein while also promoting immune tolerance. The IL-2 pathway influences critical aspects of both immune stimulation and immune regulation, through the development and expansion of Treg cells. These Treg cells are a specialized subpopulation of T cells involved in suppressing certain immune responses and maintaining the body’s self-tolerance. Early preclinical data investigating the effects of ImmTOR in combination with a Treg-selective IL-2 mutant protein, or IL-2 mutein, demonstrate substantial synergistic activity in increasing the percentage and durability of Treg expansion in the spleen.
Licenses and Collaborations
Ginkgo Bioworks Holdings, Inc.
On October 25, 2021, Selecta Biosciences, Inc. entered into a Collaboration and License Agreement, or the Ginkgo Agreement, with Ginkgo Bioworks Holdings, Inc., or Ginkgo. Under the Ginkgo Agreement, the Company will engage with Ginkgo to organizingdesign novel and staffing our company, business planning, acquiring operating assets, raising capital, developing our technology, identifyingimproved enzymes with potentially transformative therapeutic potential nanoparticle immunomodulatory product candidates,to advance treatments for orphan and rare diseases. In return, Ginkgo is eligible to earn both upfront research and development undertakingfees and milestone payments, including certain milestone payments in the form of Selecta common stock, clinical and commercial milestone payments of up to $85 million in cash, as well as downstream value in the form of royalties on sales.
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Genovis
On October 21, 2021, we entered into a strategic licensing agreement with Genovis, or the Genovis Agreement. Under the Genovis Agreement, we paid to Genovis an upfront payment in exchange for an exclusive license to Genovis’ Xork IgG Protease enzyme technology across all therapeutic uses in humans, excluding research, preclinical, diagnostic and other potential non-therapeutic applications of the enzyme. Additionally, Genovis is eligible to earn development and sales-based milestones, as well as tiered royalties on worldwide sales in the low double digits.
Takeda Pharmaceutical Company Limited
On October 1, 2021, we entered into a strategic licensing agreement with Takeda Pharmaceutical Company Limited, or the Takeda Agreement. Under the Takeda Agreement, we granted Takeda an exclusive license to the Company’s ImmTOR technology initially for two specified disease indications within the field of lysosomal storage disorders. Under the terms of the Takeda Agreement, we are entitled to receive an upfront payment and up to $1.124 billion in future additional payments over the course of the partnership that are contingent on the achievement of development or commercial milestones or Takeda’s election to continue its activities at specified development stages. We are also eligible for tiered royalties on future commercial sales of any licensed products.
Cyrus Biotechnology, Inc.
On September 7, 2021, we entered into a Collaboration and License Agreement with Cyrus, or the Cyrus Agreement, pursuant to which Cyrus agreed to grant us an exclusive, worldwide license to certain intellectual property in order to form a protein engineering collaboration combining the ImmTOR platform with Cyrus’ ability to redesign protein therapeutics. We expect that novel engineered protein therapeutic candidates from the partnership will be used to expand our proprietary pipeline and further bolster the ImmTOR platform. In return for the licensed intellectual property, we are obligated to make an upfront payment and pay certain discovery, development, and sales-based milestones which could potentially total up to approximately $1.5 billion across multiple programs.
Swedish Orphan Biovitrum
In June 2020, we announced that we had entered into the Sobi License, pursuant to which we agreed to grant Sobi an exclusive, worldwide (except as to Greater China) license to develop, manufacture and commercialize SEL-212, which is currently in development for the treatment of chronic refractory gout. In September 2020, pursuant to the Sobi License, Sobi paid us a one-time, up-front payment of $75 million. Sobi has also agreed to make milestone payments totaling up to $630 million to us upon the achievement of various development and regulatory milestones and sales thresholds for annual net sales of SEL-212, and tiered royalty payments ranging from the low double digits on the lowest sales tier to the high teens on the highest sales tier.
Additionally, Sobi purchased an aggregate of 5,416,390 shares of our common stock at $4.6156 for aggregate gross proceeds of $25 million, which we refer to as the Sobi Private Placement. The closing of the Sobi Private Placement occurred on July 31, 2020.
Under the Sobi License, we will have operational oversight of the Phase 3 DISSOLVE clinical program of SEL-212 (DISSOLVE I and DISSOLVE II) that commenced in September 2020, at Sobi’s expense.
IGAN Biosciences
In October 2020, we entered into the IGAN Agreement. Pursuant to the IGAN Agreement, IGAN granted us an exclusive license to research, evaluate, and conduct pre-clinical development activities on IGAN’s proprietary IgA proteases. We have an option term of 24 months, during which we can elect to obtain an exclusive license to further develop and commercialize the product to treat all IgA-mediated diseases, including IgA nephropathy, Linear IgA bullous dermatitis, IgA pemphigus, and Henoch-Schonlein purpura (also known as IgA vasculitis).
Sarepta Therapeutics
In June 2020, we entered into a research license and option agreement with Sarepta, or the Sarepta Agreement. Pursuant to the agreement, we granted Sarepta a license to research and evaluate ImmTOR in combination with Sarepta’s AAV gene therapy or gene editing technology, using viral or non-viral delivery, or the Sarepta Product, to treat Duchenne Muscular Dystrophy and certain Limb-Girdle Muscular Dystrophy subtypes, or the Sarepta Indications. Sarepta will have an option term of 24 months during which it can opt-in to obtain an exclusive license to further develop and commercialize the Sarepta Product to treat at least one Sarepta Indication, with a potential to extend the option term if Sarepta pays an additional fee to us. Sarepta made an up-front payment to us upon signing of the agreement, and we are eligible to receive additional payments under the option term. During the nine months ending September 30, 2021, we received a $3.0 million milestone payment from Sarepta. If Sarepta opts-in to an exclusive license agreement, we could receive option exercise payments per indication, we would be entitled to significant development and commercial milestone payments and tiered royalties ranging from the mid-to-high single digits based on net sales.
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AskBio
In August 2019, we entered into the AskBio Collaboration Agreement. The initial proof-of-concept study being conducted under this collaboration is in SEL-399, which combines an empty AAV capsid (EMC-101), an AAV capsid containing no transgene, with ImmTOR, and is being conducted in partnership with AskBio. Building on the preclinical data we have generated showing ImmTOR’s effect on mitigating or reducing the formation of neutralizing antibodies to AAV gene therapies, we have commenced a clinical trial of SEL-399 in healthy adult volunteers in Belgium. The goal of the SEL-399 clinical trial is to demonstrate the appropriate dose of ImmTOR in humans to mitigate the formation of antibodies to AAV capsids used in gene therapies, which currently precludes re-dosing. An initial control cohort of healthy volunteers received a single dose of EMC-101 in December 2020 and dose escalating cohorts of EMC-101 plus ImmTOR were initiated in February 2021. On November 8, 2021, we announced the top-line data from the Phase 1 clinical trial evaluating the potential of the ImmTOR platform in mitigating the formation of neutralizing antibodies against adeno-associated viral serotype 8 (AAV8) capsids used in gene therapies. Top-line results indicated that AAV8 empty capsids elicited peak median anti-AA8 neutralizing antibody (NAb) titers of 1:6875. Median day 30 NAb titers were 1:25 and 1:5 in the 0.15 mg/kg and 0.3 mg/kg ImmTOR cohorts, respectively, representing a 50-fold and 250-fold difference, respectively, compared to the median of control subjects dosed with AAV8 empty capsid alone. Further, we observed that at Day 30, 6 of 6 or 100% of subjects that received 0.3 mg/kg exhibited NAb titers of 1:25 or less, and 4 of 6 or 67% of those subjects at this dose exhibited NAb titers of 1:5 or less. We observed at Day 30 that 6 of 9 or 67% of subjects that received 0.15 mg/kg of ImmTOR exhibited NAb titers of 1:25 or less, and 2 of 9 or 22% of subjects at this dose had a titer of 1:5 or less. At Day 90, 2 of 6 subjects in the 0.3 mg/kg cohort were observed to have sustained control of neutralizing antibodies with titers of 1:25 or less. Consistent with preclinical data, we observed that the single dose ImmTOR cohorts saw delayed formation of neutralizing antibodies eventually reaching similar median levels of neutralizing antibodies to the control group by Day 90. ImmTOR showed safety results consistent with prior human studies and was well tolerated. No serious adverse events were reported. The most common treatment-related adverse events included mild-to-moderate stomatitis and rash.
Previously, we and AskBio were developing a gene therapy for MMA, which can cause severe developmental defects and premature death as a result of an accumulation of toxic metabolites. We conducted preclinical studies for this product candidate and will leverage that work within the collaboration. In April 2021, we were notified by AskBio that it intended to opt-out of development of the MMA indication. The AskBio Collaboration Agreement otherwise remains in effect and we intend to continue to develop SEL-302 through clinical development.
Additionally, in December 2019, we entered into a License Agreement with AskBio, or the AskBio License Agreement, which provides AskBio with exclusive worldwide rights to our ImmTOR platform to research, develop and commercialize certain AAV-gene therapy products targeting the GAA gene, or derivatives thereof, to treat Pompe Disease.
Spark Therapeutics
In December 2016, we entered into a license and option agreement with Spark Therapeutics, or the Spark License Agreement, which provides Spark with exclusive worldwide rights to our ImmTOR platform to research, develop and commercialize gene therapies for Factor VIII, an essential blood clotting protein relevant to the treatment of hemophilia A.
Impact of COVID-19
We are closely monitoring how COVID-19 is affecting our employees, business, preclinical studies and conducting clinical trials. In response to the spread of COVID-19, we have continued to have our administrative employees work outside of our offices and limited the number of staff in any given research and development laboratory. Disruptions caused by the COVID-19 pandemic may result in difficulties or delays in initiating, enrolling, conducting or completing our planned and ongoing clinical trials, and the incurrence of unforeseen costs as a result of preclinical study or clinical trial delays.
While the COVID-19 pandemic has not had a material impact on our clinical programs as of the date of this Quarterly Report, it could have an impact on our ability to complete the Phase 3 DISSOLVE clinical program of SEL-212, our ability to commence preclinical studies and clinical trials of our IgA nephropathy, gene therapy, and autoimmune disease programs, and our ability to obtain supply of both active drug substances and finished drug product as well as efficient execution of the overall supply chain for SEL-212 and our other programs. We have been proactively working with our CRO, clinical sites, and principal investigators to provide patients with more convenient locations to have their SUA measured for the primary endpoint of the study, such as at local laboratories or their homes, as well as alternative sites to receive infusions of study drug. We are also working with our primary and back-up suppliers for SEL-037 (pegadricase) and SEL-110 (ImmTOR) to ensure that we have adequate supply of our materials for both our clinical and preclinical programs. We believe we will have adequate supply of all material necessary to conduct our Phase 3 DISSOLVE clinical program of SEL-212 in chronic refractory gout.
At this time, any impact of COVID-19 on the Company’s business, revenues, results of operations and financial condition will largely depend on future developments, which are highly uncertain and cannot be predicted with confidence, such as the duration of the pandemic, travel restrictions and social distancing in the United States and other countries, business closures or
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business disruptions, supply chain disruptions, the ultimate impact on financial markets and the global economy, and the effectiveness of actions taken in the United States and other countries to contain and treat the disease.

Financial Operations
To date, we have financed our operations primarily through our initial public offering, or IPO, of common stock in June 2016,offerings and private placements of our preferred stock, common stock and debt securities, funding received from research grants and collaboration arrangements and our credit facility. We do not have any products approved for sale and have not generated any product sales. All of our revenue to date has been generated from research grantscollaboration and contracts.grant revenue.
Since inception, we have incurred significant operating losses. We incurred net losses of $45.8$37.9 million and $22.1$53.4 million for the nine months ended September 30, 20172021 and 2016,2020, respectively. As of September 30, 2017,2021, we had an accumulated deficit of $197.4$442.6 million. We expect to continue incurringto incur significant expenses and operating losses for at least the next several years as we:
-    conduct and expand clinical trials for SEL‑212, our lead product candidate;
-    conduct clinical trials for other product candidates including SEL-403;
-    •continue the research and development of our other product candidates;candidates as well as product candidates that we may be developing jointly with collaboration partners;
-    •seek to enhance our ImmTOR platform and discover and develop additional product candidates;
•seek to enter into collaboration, licensing and other agreements, including, but not limited to research and development, and/or commercialization agreements;
•seek regulatory approvalapprovals for any product candidates that successfully complete clinical trials;
-potentially establish a sales, marketing and distribution infrastructure and scale‑up external manufacturing capabilities to commercialize any products for which we may obtain regulatory approval;

-    •potentially establish a sales, marketing and distribution infrastructure and scales-up external manufacturing capabilities to commercialize any products for which we may obtain regulatory approval;
•maintain, expand and protect our intellectual property portfolio;portfolio, including through licensing arrangements; and
-hire additional staff, including clinical, scientific, operational and financial personnel, to execute our business plan; and
-add personnel and clinical, scientific, operational, financial and management information systems to support our product development and potential future commercialization efforts, and to enable us to operate as a public company.
•add clinical, scientific, operational, financial and management information systems and personnel, including personnel to support our product development and potential future commercialization efforts and to support our operations as a public company.
Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of equity offerings, debt financings, license and collaboration agreements, with partners, and research grants. We may be unable to raise capital when needed or on reasonable terms, if at all, which would force us to delay, limit, reduce or terminate our product development or future commercialization efforts. We will need to generate significant revenues to achieve profitability, and we may never do so.
We believe that our existing cash, cash equivalents, restricted cash, and marketable securities as of September 30, 2021 will enable us to fund our operating expenses and capital expenditure requirements into the second quarter of 2023. We have based this estimate on assumptions that may prove to be wrong, and we could use our capital resources sooner than we currently expect.
The consolidated financial information presented below includes the accounts of Selecta Biosciences, Inc. and our wholly owned subsidiaries, Selecta (RUS) LLC, a Russian limited liability company, or Selecta RUS,(RUS), and Selecta Biosciences Security Corporation, a Massachusetts securities corporation. All intercompany accounts and transactions have been eliminated.
We expect that our existing cash, cash equivalents, short-term investmentsCollaboration and restricted cash as of September 30, 2017, will enable us to fund our operating expenses and capital expenditure requirements into mid-2019. For additional information, see “-Liquidity and Capital Resources.”

FINANCIAL OPERATIONS OVERVIEW
Grant and collaborationgrant revenue
To date, we have not generated any revenue from product sales. Our revenue consists of grantcollaboration and collaborationgrant revenue, which includes amounts recognized related to upfront and milestone payments for research and development funding under collaboration and license agreements. In addition, we earn revenue under the terms of government contracts or grants, which require the performance of certain research and development activities. We expect that any revenue we generate will fluctuate from quarter to quarter because of the timing and amount of fees, research and development reimbursements and other payments from collaborators. We do not expect to generate revenue from product sales for at least the next several years. If we or our collaborators fail to complete the development of our product candidates in a timely manner or fail to obtain regulatory approval as needed, our ability to generate future revenue will be harmed, and will affect the results of our operations and financial position. For a further description of the agreements underlying our collaboration and grant‑basedgrant-based revenue, see Notes 2 and 1312 to our unaudited consolidated financial statements included elsewhere in this Quarterly Report on Form 10-Q.Report.
Research and development
Our research and development expenses consist of external research and development costs, which we track on a program‑by‑programprogram-by-program basis and primarily include contract manufacturing organization, or CMO, relatedCMO-related costs, fees paid to contract research organizations, or CROs and internal research and development costs, which are primarily compensation expenses for our research and development employees, lab supplies, analytical testing,
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allocated overhead costs and other related expenses. Our internal research and development costs are often devoted to expanding our programs and are not necessarily allocable to a specific target.
We have incurred a total of $136.7$343.8 million in research and development expenses from inception through September 30, 2017,2021, with a majority of the expenses being spent on the development of SEL‑212SEL-212 and a prior nicotine vaccine candidate, and the remainder being spent on our various discovery and preclinical stage product candidate programs and the general expansion of our technology.
As we expand the clinical development of SEL‑212, we expect our research and development expenses to increase. In addition, as a result of the termination of the Sanofi Agreement, which was effective on May 8, 2017, we exercised our right to acquire the development programs under the Sanofi Agreement. The exercise itself did not require the payment of any consideration to Sanofi. We are solely responsible for performing and funding any development and clinical trial activities relating to further development of vaccine candidates that we choose to undertake after the termination date of the Sanofi Agreement.
We expense research and development costs as incurred. Conducting a significant amount of research and development is central to our business model. Product candidates in clinical development generally have higher development costs than those in earlier stages of development, primarily due to the size, duration and durationcost of clinical trials. We plan to increase our research and development expenses for the foreseeable future as we seek to complete development of SEL‑212, and to further advance our preclinical and earlier stage research and development projects. The successful development of our clinical and preclinical product candidates is highly uncertain. At this time, we cannot reasonably estimate the nature, timing or costs of the efforts that

will be necessary to complete the development of SEL‑212 or any of our preclinical programs or the period, if any, in which material net cash inflows from these product candidates may commence. Clinical development timelines, the probability of success and development costs can differ materially from our expectations. For example, if the FDA or another regulatory authority were to require us to conduct clinical trials beyond those which we currently expect will be required for the completion of clinical development of a product candidate, or if we experience significant delays in enrollment in any of our clinical trials, we could be required to expend significant additional financial resources and time to complete any clinical development.
On June 11, 2020, we and Sobi entered into the Sobi License. Pursuant to the Sobi License, clinical trial costs incurred to complete development of SEL-212, including but not limited to costs incurred while conducting and completing the Phase 3 DISSOLVE trials, will be reimbursed by Sobi. These costs, when reimbursed, will be recognized as revenue consistent with the revenue recognition methodology disclosed in Note 12 to our unaudited consolidated financial statements included elsewhere in this Quarterly Report. The following table sets forth the componentsreimbursable costs exclude any costs of our researchadditional development activities required that are related to ImmTOR and development expenses during the periods indicated (in thousands, except percentages):
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
External research and development expenses:(unaudited)
SEL-212$4,162
 $1,489
 $13,491
 $5,322
SELA-070471
 680
 1,004
 3,067
Discovery and preclinical stage product candidate programs, collectively1,919
 458
 4,041
 1,173
Internal research and development expenses2,952
 3,394
 13,006
 9,107
Total research and development expenses$9,504

$6,021

$31,542
 $18,669
that are unrelated to SEL-212.
General and administrative
General and administrative expenses consist primarily of salaries and related benefits, including stock‑basedstock-based compensation, related to our executive, finance, business development and support functions. Other general and administrative expenses include facility‑relatedfacility-related costs not otherwise allocated to research and development expenses, travel expenses for our general and administrative personnel and professional fees for auditing, tax and corporate legal services, including intellectual property‑relatedproperty-related legal services. We expect that our general and administrative expenses will increase in future periods, reflecting an expanding infrastructure and increased professional fees associated with being a public reporting company and maintaining and expanding our intellectual property portfolio.
Investment income
Investment income consists primarily of interest income earned on our cash, and cash equivalents and Short-term investments.
Loss on Extinguishment of Debt
The Company recognized a loss on extinguishment of debt of $0.7 million for the three and nine months ended September 30, 2017. The loss on extinguishment of debt consists of a final payment fee, a loan prepayment fee, the write-off of unamortized debt issuance costs, unamortized warrant valuation discount and miscellaneous costs incurred as a result of our repayment of the 2015 Term Loan totaling $10.0 million.marketable securities.
Interest expense
Interest expense consists of interest expense on amounts borrowed under our credit facility.facilities.
Other expenseincome (expense)
Other expense forincome was de minimis during the three and nine months ended September 30, 20172021 and 2016 was de minimis.2020.
Change in fair value of warrant liabilities
Common warrants classified as liabilities are remeasured at fair value, utilizing a Black-Scholes valuation methodology, quarterly with the change in fair value recognized as a component of earnings.
Foreign currency transaction gain (loss)
The functional currency of our Russian subsidiary is the Russian ruble. In addition to holding cash denominated in Russian rubles, our Russian bank accounts also hold cash balances denominated in U.S. dollars to facilitate payments to be settled in U.S. dollars or other currencies. AtAs of September 30, 20172021 and December 31, 2016,2020, we maintained cash of $1.7$0.3 million and $2.5 million, respectively, in Russian banks, all of which $1.6 million and $1.6 million was denominated in U.S. dollars for the periods ended September 30, 2017 and December 31, 2016, respectively.dollars. The amounts denominated in U.S. dollars and used in transacting the day to dayday-to-day operations of our Russian subsidiary are subject to transaction gains and losses, which are reported as incurred.
Income taxes
As
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Table of December 31, 2016, we had net operating loss carryforwards, or NOLs, for federal and state income tax purposesContents
Results of $102.1 million and $95.6 million, respectively, which expire at various times through 2036. In 2014, our wholly owned subsidiary, Selecta RUS, was granted a “Skolkovo designated” resident status in Russia. As a result, the subsidiary operates as a corporate tax-exempt entity, with lower employee and employment taxes. All foreign net operating loss carryforwards have been eliminated. The state NOLs began expiring in 2015 and will continue to expire through 2036. At December 31, 2016, weOperations

had available federal and state research and development income tax credits of approximately $2.1 million and $1.5 million respectively, which may be available to reduce future income taxes, if any, at various times through 2036.
Utilization of the NOLs and credits may be subject to a substantial annual limitation due to ownership change limitations provided by Section 382 of the Internal Revenue Code of 1986, as amended. The annual limitation may result in the expiration of our NOLs and credits before we can use them. We have recorded a valuation allowance on our deferred tax assets, including our deferred tax assets related to our NOLs and research and development tax credit carryforwards. We commissioned a study to analyze and determine if any historical ownership changes have occurred to determine if there are any permanent limitations on our ability to utilize NOLs and other tax attributes in the future. However, we may experience ownership changes as a result of subsequent shifts in our stock ownership. As a result, we are unable to estimate the effect of these limitations, if any, on our ability to utilize NOLs and other tax attributes in the future.

RESULTS OF OPERATIONS
Comparison of the Three Months Ended September 30, 20172021 and 20162020
Revenue
The following is a comparison of revenue for the three months ended September 30, 20172021 and 20162020 (in thousands, except percentages):
 Three Months Ended September 30, Increase
 2017 2016 (decrease)
 (unaudited)    
Grant revenue$4
     $891
     $(887)     (100)%
Collaboration revenue23
 157
 (134) (85)%
Total revenue$27
 $1,048
 $(1,021) (97)%
 Three Months Ended
September 30,		Increase
 20212020(decrease)
Collaboration revenue$24,427 $4,646 $19,781 426 %
During the three months ended September 30, 2017, total2021, collaboration revenue decreased by $1.0was $24.4 million, or 97%, as compared to $4.6 million of revenue recognition in 2020. During the three months ended September 30, 2016.2021 and 2020, we recognized $24.3 million and $4.4 million, respectively, under the license agreement with Sobi resulting from both the shipment of clinical supply and the reimbursement of costs incurred for the Phase 3 DISSOLVE clinical program. The decrease wassignificant revenue increase is the result of reduced revenue from the Company's NIDA grant, resultingcontinued enrollment of the Phase 3 DISSOLVE clinical program that was initiated in a $0.7 million reduction year over year, as well as athe third quarter of 2020.
Additionally, we recognized $0.2 million decrease in other grant revenues, all resulting from the wind downfor each of the grant terms. Collaboration revenues decreased by $0.1 million as a result ofthree months ended September 30, 2021 and 2020, for shipments under the termination of the Sanofi collaboration in November 2016.license agreement with Sarepta.

Research and development
The following is a comparison of research and development expenses for the three months ended September 30, 20172021 and 20162020 (in thousands, except percentages):
 Three Months Ended September 30, Increase
 2017 2016 (decrease)
 (unaudited)    
Research and development$9,504
     $6,021
     $3,483
 58%
 Three Months Ended
September 30,		Increase
 20212020(decrease)
SEL-212$10,231 $9,059 $1,172 13 %
AskBio collaboration1,705 445 1,260 283 %
Preclinical stage product candidate programs2,997 204 2,793 1,369 %
Other internal research and development expenses6,018 4,252 1,766 42 %
Total research and development expenses$20,951 $13,960 $6,991 50 %
During the three months ended September 30, 2017,2021, our research and development expenses increased by $3.5$7.0 million, or 58%50%, as comparedcompared to 2020. The increase in cost was primarily the comparable period in 2016, reflectingresult of expenses incurred for the incremental costs forpreclinical programs, salaries, headcount consulting and clinical activities to continue and expand the Phase 2 stage of our Phase 1/2 clinical program for our lead product candidate SEL-212 and consulting, licensing, supplies and testing activities to initiate or expand research on our other pipeline indications.AskBio collaboration costs.

General and administrative
The following is a comparison of general and administrative expenses for the three months ended September 30, 20172021 and 20162020 (in thousands, except percentages):
 Three Months Ended September 30, Increase
 2017 2016 (decrease)
 (unaudited)    
General and administrative$4,377
     $2,495
     $1,882
 75%
For
 Three Months Ended
September 30,		Increase
 20212020(decrease)
General and administrative$5,445 $4,420 $1,025 23 %
During the three months ended September 30, 2017,2021, our general and administrative expenses increased $1.9by $1.0 million, or 75%23%, as compared to the same period in 2016, primarily due to (i) $0.7 million related to growth in headcount to support public company filings and control processes, (ii) a $0.4 million2020. The increase in costs was primarily the result of salaries, professional fees related to the universal shelf registration

filing, (iii) $0.5 million ofand stock compensation expense, (iv) $0.4 million relating to the continued increase in our patent inventory and reimbursement of expenses for our patent in-licensing activities and (v) $0.1 million of office and facilities expense resulting from increased headcount, offset by a $0.2 million reduction in licensing fees associated with collaborations.expenses.
Investment income
Investment income increased by $0.1 million duringwas de minimis for each of the three months ended September 30, 2017 as compared to the comparable period in 2016. This increase was due to an increase of $12.4 million of investments held by us as of September 30, 2017 as compared to the holdings as of September 30, 2016.
Loss on Extinguishment of Debt
The Company recognized a loss on extinguishment of debt of $0.7 million for the three2021 and nine months ended September 30, 2017. There was no extinguishment of debt during the three or nine months ended September 30, 2016. The loss on extinguishment of debt consists of the unamortized portion of the final fee payment, a loan prepayment fee, the write-off of unamortized debt issuance costs, unamortized warrant valuation discount and miscellaneous costs incurred as a result of our repayment of the 2015 Term Loan totaling $10.0 million.2020.
Foreign currency transaction gain (loss)
We recognized aminimal foreign currency loss of less than $0.1 millionfluctuations during each of the three months ended September 30, 20172021 and 2016, reflecting the fluctuation2020.
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Table of the U.S. dollar to the Russian ruble from the beginning to the end of each period.Contents
Interest expense
Interest expense was $0.3$0.7 million and $0.4 million for each of the three months ended September 30, 20172021 and 2016,2020, respectively, representing interest expense and amortization of the carrying costs of our credit facilities.
Change in fair value of warrant liabilities
For the three months ended September 30, 2021, we recognized $0.6 million of income from the change in the fair value of warrant liabilities utilizing the Black-Scholes valuation methodology. The decrease in value was primarily driven by a decrease in the Company’s share price. For the three months ended September 30, 2020, we recognized $4.8 million change in the fair value of warrant liabilities primarily driven by a decrease in the Company’s share price and volatility, and a decreased discount rate this quarter.
Other income (expense)
Other income (expense) was de minimis for each of the three months ended September 30, 2021 and 2020.
Income taxes
For the three months ended September 30, 2021, we recognized $15.8 million of expense for the income taxes primarily related to the license agreement with Sobi upon the Company’s election to opt out of the installment sale method of taxation. As a result of this election, the Company has prepaid all taxes related to future Sobi License revenue streams.
Net loss
Net loss for the three months ended September 30, 2017 and 2016.2021 was $17.9 million compared to a net loss of $9.7 million for the three months ended September 30, 2020.


Comparison of the Nine Months Ended September 30, 20172021 and 20162020
Revenue
The following is a comparison of revenue for the nine months ended September 30, 20172021 and 20162020 (in thousands, except percentages):
 Nine Months Ended September 30, Increase
 2017 2016 (decrease)
 (unaudited)    
Grant revenue$152
     $4,492
     $(4,340)     (97)%
Collaboration revenue38
 661
 (623) (94)%
Total revenue$190
 $5,153
 $(4,963) (96)%
 Nine Months Ended
September 30,		Increase
 20212020(decrease)
Collaboration revenue$55,140 $4,646 $50,494 1,087 %
During the nine months ended September 30, 2017, total revenue decreased by $5.02021, we recognized $54.8 million or 96%, as compared tounder the license agreement with Sobi resulting from the shipment of clinical supply and the reimbursement of costs incurred for the Phase 3 DISSOLVE clinical program, all of which began in July 2020, $0.2 million for shipments under the license agreement with Sarepta, and $0.1 million resulting from the expiration of the contractual audit term under the Skolkovo Foundation grant. During the nine months ended September 30, 2016. The decrease in grant revenue was2020, we recognized $4.3 million under the result of reduced revenue from our NIDA grant, resulting in a $3.7 million reduction year over year, as well as a $0.6 million decrease in other grant revenueslicense agreement with Sobi resulting from the wind downshipment of grant terms. Collaboration revenues decreased $0.6clinical supply and the reimbursement of costs incurred for the Phase 3 DISSOLVE clinical program and $0.3 million as a result offor shipments under the termination of the Sanofi collaboration in November 2016.agreement with Sarepta.
Research and development
The following is a comparison of research and development expenses for the nine months ended September 30, 20172021 and 20162020 (in thousands, except percentages):
 Nine Months Ended September 30, Increase
 2017 2016 (decrease)
 (unaudited)    
Research and development$31,542
     $18,669
     $12,873
 69%
 Nine Months Ended
September 30,		Increase
 20212020(decrease)
SEL-212$22,911 $23,992 $(1,081)(5)%
AskBio collaboration2,882 2,019 863 43 %
Preclinical stage product candidate programs6,389 684 5,705 834 %
Other internal research and development expenses16,236 12,719 3,517 28 %
Total research and development expenses$48,418 $39,414 $9,004 23 %
During the nine months ended September 30, 2017,2021, our research and development expenses increased by $12.9$9.0 million, or 69%23%, as comparedcompared to 2020. The increase in cost was primarily the comparable period in 2016, reflectingresult of expenses incurred for the incrementalOTC and gene therapy preclinical programs, salaries, and AskBio collaboration costs for headcount, consulting andSEL-399, offset by a decrease of clinical supply expense for the SEL-212 clinical programs.

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costs to continue and expand the Phase 2 stage
Table of our Phase 1/2 clinical program for our lead product candidate SEL-212 and consulting, licensing, supplies and testing activities to initiate or expand research on our other pipeline programs.Contents
General and administrative
The following is a comparison of general and administrative expenses for the nine months ended September 30, 20172021 and 20162020 (in thousands, except percentages):
 Nine Months Ended September 30, Increase
 2017 2016 (decrease)
 (unaudited)    
General and administrative$13,155
     $7,294
     $5,861
 80%
For
 Nine Months Ended
September 30,		Increase
 20212020(decrease)
General and administrative$15,397 $14,155 $1,242 9 %
During the nine months ended September 30, 2017,2021, our general and administrative expenses increased $5.9by $1.2 million, or 80%9%, as compared to the comparable 2016 period, primarily due to (i) $2.0 million related to growth in headcount to support public company filings and control processes, (ii) a $0.2 million2020. The increase in costs was the result of expenses incurred for consulting and professional fees for market research and investor relations, (iii) $1.1 million of stock compensation expense, (iv) $0.1 million of licensing fees associated with collaborations, (v) $1.3 million relating to the continued increase in ouroffset by decreased patent inventorycosts and reimbursement of expenses for our patent in-licensing activities, (vi) $0.4 million of office and facilities expense resulting from increased headcount (vii) a $0.6 million increase in professional fees related to the universal shelf registration filing and (viii) $0.2 million of other expenses.less travel expense.
Investment income
Investment income increased bywas less than $0.1 million and $0.3 million, respectively during the nine months ended September 30, 20172021 as compared to the comparable period in 2016. This increase was due to an increase of $12.4 million of investments held by the Company as of September 30, 2017 compared to the holdings as of September 30, 2016.
Loss on Extinguishment of Debt
2020. The Company recognized a loss on extinguishment of debt of $0.7 million for the three and nine months ended September 30, 2017. There was no extinguishment of debt during the three or nine months ended September 30, 2016. The loss on extinguishment of debt consists of the unamortized portion of the final fee payment, a loan prepayment fee, the write-off of unamortized debt issuance costs, unamortized warrant valuation discount and miscellaneous costs incurred as a result of our repayment of the 2015 Term Loan totaling $10.0 million.decrease reflects reduced interest rates.
Foreign currency transaction gain (loss)
We recognized aminimal foreign currency lossfluctuations during each of $0.1 million and $0.4 million during the nine months ended September 30, 20172021 and 2016, respectively, reflecting the fluctuation of the U.S. dollar to the Russian ruble from the beginning to the end of each period.2020.
Interest expense
Interest expense was $0.8$2.1 million and $0.9$0.8 million for the nine months ended September 30, 20172021 and 2016,2020, respectively, representing interest expense and amortization of the carrying costs of our credit facilities.
Change in fair value of warrant liabilities
For the nine months ended September 30, 2021, we recognized a $11.3 million charge for the increase in the fair value of warrant liabilities utilizing a Black-Scholes valuation methodology. The increase in value was primarily driven by an increase in the Company’s share price and a small increase in the discount rate this quarter. For the nine months ended September 30, 2020, we recognized $3.6 million charge for the increase in the fair value of warrant liabilities primarily driven by an increase in the Company’s share price and volatility, offset by a decreased discount rate this quarter.
Other income (expense)
Other income (expense) was de minimis for each of the nine months ended September 30, 2021 and 2020.
Income taxes
For the nine months ended September 30, 2021, we recognized $15.8 million of expense for the income taxes primarily related to the license agreement with Sobi upon the Company’s election to opt out of the installment sale method of taxation. As a result of this election, the Company has prepaid all taxes related to future Sobi License revenue streams.
Net loss
Net loss for the nine months ended September 30, 20172021 was $37.9 million compared to $53.4 million for the nine months ended September 30, 2020.

Liquidity and 2016.

LIQUIDITY AND CAPITAL RESOURCESCapital Resources
Since our inception, we have incurred recurring net losses. We expect that we will continue to incur losses and that such losses will increase for the foreseeable future. We expect that our research and development and general and administrative expenses will continue to increase and, as a result, we will need additional capital to fund our operations, which we may raise through a combination of equity offerings, debt financings, third‑partythird-party funding and other collaborations and strategic alliances.
From our inception through September 30, 2017,2021, we hadhave raised an aggregate of $302.2$606.4 million to fund our operations, of which includes $118.5 million was from the sale of preferred stock, $9.9$11.1 million was fromin government grants, $25.3grant funding, $36.7 million was from borrowings under our credit facility, $36.8facilities past and present, $192.3 million was throughfrom our collaborations and license agreements, $64.5 million in combined net proceeds was raised from our initial public offering, in June 2016 and the underwriters' exercise in part of their option to purchase additional shares of our common stock in July 2016, and $47.2$149.3 million in combined net proceeds was raised from our private placement of common stock in June 2017, or the 2017 PIPE.

On June 26, 2017, we entered into a Securities Purchase Agreement, or the Institutional Purchase Agreement, with the purchasers named therein, or the Institutional Investors,placements and a Securities Purchase Agreement, or the Springer Purchase Agreement, with Timothy Springer, Ph.D., a member of our board of directors.
Pursuant to the Institutional Purchase Agreement, we agreed to sell an aggregate of 2,750,000 sharesfollow-on offerings of our common stock, to the Institutional Investors for aggregate gross proceeds of $44.0 million, at a purchase price equal to $16.00 per share. Pursuant to the Springer Purchase Agreement, we agreed to sell to Dr. Springer an aggregate of 338,791 shares of common stock at a purchase price equal to $17.71 per share, which was equal to the most recent consolidated closing bid price on the Nasdaq Global Market on June 23, 2017, and, warrants to purchase up to 79,130 shares of common stock, or the Warrant Shares, exercisable at $17.71 per Warrant Share. The purchase price for each warrant was equal to $0.125 for each Warrant Share, consistent with Nasdaq Global Market requirements for an “at the market” offering. The Springer Offering resulted in additional aggregate gross proceeds to us of approximately $6.0 million for total aggregate gross proceeds to us of $50.0 million. On June 27, 2017, in connection with issuance of the Warrant Shares, we entered into a Common Stock Purchase Warrant with Dr. Springer, or the Warrant. The Warrant has a term of five years. We closed under the Institutional Purchase Agreement and the Springer Purchase Agreement on June 27, 2017.
On August 10, 2017, we entered into a sales agreement with Jefferies LLC, as sales agent, or the Sales Agreement, pursuant to which we may, from time to time, issue and sell common stock with an aggregate value of up to $50through September 30, 2021, $34.0 million in an at-the-market, or ATM, offering. During the third quarteraggregate net proceeds from “at-the-market” offerings of 2017, there were no sales ofour common stock pursuant to the Sales Agreement.stock.
As of September 30, 2017,2021, our cash, cash equivalents, Short-term depositsrestricted cash, and Short-term investmentsmarketable securities were $104.4$140.0 million, of which $1.7$1.4 million was restricted cash related to lease commitments and $0.3 million was held by our Russian subsidiary designated solely for use in its operations including $0.1 million of restricted cash.operations. Our Russian subsidiary cash is consolidated for financial reporting purposes.
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In addition to our existing cash equivalents, and Short-term investments, we receive research and development funding pursuant to our research grants and collaboration agreements. In November 2016, we received written notice from Sanofi that Sanofi had elected to terminate in its entirety the Sanofi Agreement. The termination of the Sanofi Agreement was effective on May 8, 2017. Currently, funding from research grants and payments under our remaining collaboration agreements represent our only source of committed external funds.
Indebtedness
On September 12, 2017,August 31, 2020, we entered into a term loan facility of up to $21.0$35.0 million, withconsisting of term loans in an aggregate amount of $25.0 million, or the Term A Loan, and term loans in an aggregate amount of $10.0 million, or the Term B Loan, governed by a loan and security agreement among us and Oxford Finance LLC, or Oxford, as collateral agent and a lender, and Silicon Valley Bank, or SVB, as a California corporation (“SVB”),lender. The Term A Loan was funded in full on August 31, 2020, the proceeds of which were used to repay our previously existing term loan facility with Oxford Finance LLC and Pacific Western Bank, as successor in interest to Square 1 Bank,2017 Term Loan and for general corporate and working capital purposes. The term loan facility is governed by a loanTerm B Loan was to be available, subject to the collateral agent’s discretion and security agreement, dated September 12, 2017, between uscustomary terms and conditions, during the period commencing on the date we have delivered to Oxford and SVB evidence: (i) we or one of the our collaboration partners has enrolled its first patient for a Phase 1 clinical trial evaluating the treatment of MMA, and (ii) we have enrolled the first patient in each of two Phase 3 pivotal trials evaluating SEL-212, or the Second Draw Period Milestone, and ending on the earliest of (i) the date which was fundedis 30 days following the date the Second Draw Period Milestone is achieved, (ii) September 30, 2021 (iii) and the occurrence of an event of default, other than an event of default that has been waived in fullwriting by Oxford and SVB in their sole discretion. The Second Draw Period expired on September 13, 2017. 30, 2021 and the Term B Loan is no longer available to be drawn in the future.
The term loan facility with SVB2020 Term Loan is secured by a lien on substantially all of our assets, other than intellectual property, provided that such lien on substantially all assets includes any rights to payments and proceeds from the sale, licensing or disposition of intellectual property. We also granted SVBOxford a negative pledge with respect to our intellectual property.
The term loan facility2020 Term Loan contains customary covenants and representations, including but not limited to financial reporting obligations and limitations on dividends, indebtedness, collateral, investments, distributions, transfers, mergers or acquisitions, taxes, corporate changes, deposit accounts, and subsidiaries. The term loan facility2020 Term Loan also contains other customary provisions, such as expense reimbursement, non-disclosure obligations as well as indemnification rights for the benefit of SVB.rights.
The events of default under the term loan facility2020 Term Loan include, but are not limited to, our failure to make any payments of principal or interest under the term loan facility2020 Term Loan or other transaction documents, our breach or default in the performance of any covenant under the term loan facility2020 Term Loan or other transaction documents, the occurrence of a material adverse effect,event, making a false or misleading representation or warranty in any material respect under the term loan facility,2020 Term Loan, our insolvency or bankruptcy, any attachment or judgment on our assets in excess of at least approximately $0.3$0.5 million, or the occurrence of any default under any of our agreements or obligations involving indebtedness in excess of approximately $0.3$0.5 million. If an event of default occurs, Oxford and SVB isare entitled to take enforcement action, including acceleration of amounts due under the term loan facility.2020 Term Loan. If we raise any additional debt financing, the terms of such additional debt could further restrict our operating and financial flexibility.
For a further description of the 2020 Term Loan, see Note 9 to our unaudited consolidated financial statements included elsewhere in this Quarterly Report.
Plan of operations and future funding requirements
As of the date of this Quarterly Report, on Form 10-Q, we have not generated any revenue from product sales. We do not know when, or if, we will generate revenue from product sales. We will not generate significant revenue from product sales unless and until we obtain regulatory approval and commercialize one of our current or future product candidates. Our primary uses of capital are, and we expect will continue to be, compensation and related expenses, third-party clinical research and development services, laboratory and related supplies, clinical costs, legal and other regulatory expenses, and general overhead costs. Moreover, as a result of the termination of the Sanofi Agreement, which was effective on May 8, 2017, we exercised our right to acquire the

development programs under the Sanofi Agreement. This exercise itself did not require the payment of any consideration to Sanofi. We are solely responsible for performing and funding any development and clinical trial activities relating to further development of vaccine candidates that we choose to undertake after the termination date of the agreement. We expect that we will continue to generate losses for the foreseeable future, and we expect the losses to increase as we continue the development of, and seek regulatory approvals for, our product candidates, and begin to commercialize any approved products. We are subject to risks in the development of our products, and we may encounter unforeseen expenses, difficulties, complications, delays and other unknown factors that may adversely affect our business. We expect that we will need substantial additional funding to support our continuing operations.
BasedAs of September 30, 2021, we had an accumulated deficit of $442.6 million. We anticipate operating losses to continue for the foreseeable future due to, among other things, costs related to research, development of our product candidates, conducting preclinical studies and clinical trials, and our administrative organization. We will require substantial additional financing to fund our operations and to continue to execute our strategy, and we will pursue a range of options to secure additional capital.
We are continually evaluating various potential sources of additional funding such as strategic collaborations and the issuance of equity to fund our operations. If we raise additional funds through strategic collaborations and alliances, which may include existing collaboration partners, we may have to relinquish valuable rights to our technologies or product candidates, or grant licenses on terms that are not favorable to us. To the current operating plan,extent that we expectraise additional capital through the sale of equity, the ownership interest of our existing shareholders will be diluted, and other preferences may be necessary that adversely affect the rights of existing shareholders.
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We believe that our existing cash, cash equivalents, short-term investmentsrestricted cash, and restricted cashmarketable securities as of September 30, 2017,2021 will enable us to fund our operating expenses and capital expenditure requirements into mid-2019.the second quarter of 2023. Additionally, while the potential economic impact brought by and the duration of the COVID-19 pandemic may be difficult to assess or predict, the widespread pandemic has resulted in, and may continue to result in, significant disruption of global financial markets, reducing our ability to access capital as and when needed. We have based this estimate on assumptions that may prove to be wrong, and we could use our capital resources sooner than we currently expect. Additionally, the process of testing product candidates in clinical trials is costly, and the timing of progress in these trials is uncertain. Because our product candidates are in various stages of clinical and preclinical development and the outcome of these efforts is uncertain, we cannot estimate the actual amounts necessary to successfully complete the development and commercialization of our product candidates or whether, or when, we may achieve profitability.
Our future capital requirements will depend on many factors, including:
-    the progress and results of our clinical trials of SEL-212;
-the progress and results of our clinical trials with our other product candidates, including SEL-403;
-our collaboration agreements remaining in effect, our ability to enter into additional collaboration agreements and our ability to achieve milestones under these agreements;
-the scope, progress, results and costs of preclinical development, laboratory testing and clinical trials for our other product candidates;
-    •the number and development requirements of other product candidates that we pursue;
-    •our collaboration agreements remaining in effect, our entering into additional collaboration agreements and our ability to achieve milestones under these agreements;
•the cost of manufacturing clinical supplies of our product candidates;
•our headcount growth and associated costs;
•the scope, progress, results and costs of preclinical development, laboratory testing and clinical trials for our other product candidates;
•the costs, timing and outcome of regulatory review of our product candidates;
-the costs and timing of future commercialization activities, including manufacturing, marketing, sales and distribution, for any of our product candidates for which we receive marketing approval;
-the revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval;
-the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims; and
-    •the costs and timing of future commercialization activities, including manufacturing, marketing, sales and distribution, for any of our product candidates for which we receive marketing approval;
•the revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval;
•the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims;
•the effect of competing technological and market developments; and
•the extent to which we acquire or in-license otherinvest in businesses, products and technologies.
Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of equity offerings, debt financings and revenue from license and collaboration arrangements. Except for any obligations of our collaborators to reimburse us for research and development expensestechnologies, including entering into licensing or to make milestone payments under our agreements with them, we do not have any committed external source of liquidity. To the extent that we raise additional capital through the future sale of equity or debt, the ownership interest of our stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our existing common stockholders. If we raise additional funds through collaboration arrangements infor product candidates.
As noted above, the future, we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to developmagnitude and market product candidates that we would otherwise prefer to develop and market ourselves.









Cash flows
Comparisonduration of the Nine Months Ended September 30, 2017COVID-19 pandemic and 2016its impact on our liquidity future funding requirements is uncertain as of the filing date of this Quarterly Report as this continues to evolve globally.
The following is a summary
Summary of cash flows for the nine months ended September 30, 2017 and 2016 (in thousands):
Cash Flows
 Nine Months Ended September 30,
 2017 2016
Beginning of the period$58,656
 $32,337
Net cash used in operating activities(39,365) (21,239)
Net cash used in investing activities(8,205) (16,896)
Net cash provided by financing activities60,985
 64,867
Effect of exchange rate changes on cash80
 419
End of the period$72,151
 $59,488
 Nine Months Ended
September 30,
(In thousands)20212020
Cash (used in) and provided by:
Operating activities$(28,922)$42,131 
Investing activities(26,862)(575)
Financing activities31,741 14,621 
Effect of exchange rate changes on cash3 (88)
Net change in cash, cash equivalents, and restricted cash$(24,040)$56,089 
Net cash
Operating activities
Cash used in operating activities
Net cash used in operating activities was $39.4 of $28.9 million for the nine months ended September 30, 2017 as compared to $21.22021 included approximately $18.6 million of net losses, adjusted for non-cash items, and uses of cash of approximately $10.3 million for changes in operating assets and liabilities.
Cash provided by operating activities of $42.1 million for the nine months ended September 30, 2016. The increase in2020 included $43.5 million of net losses, adjusted for non-cash items, partially offset by cash usedgenerated from changes in operating activities of $18.1 million reflects a $23.6 million increase in recorded net loss associated with the increased researchassets and development expenses as we advanced from Phase 1 to Phase 2 clinical trials coupled with (i) $2.4 million in net cash used to pay outstanding accounts payable associated with operations and (ii) a decrease in recorded deferred revenues of $0.4 million offset by (i) an increase in recorded accrued expenses and other liabilities of $4.5$85.6 million, (ii) a $1.5 million reductionprincipally related to changes in restricted cashaccounts receivable and other assets (iii) an increase in (non-cash) stock-based compensation expense of $1.6 million and (iv) a $0.7 million loss on early extinguishment of debt.deferred revenue.
Net cash used in investingInvesting activities
Net cash used in investing activities was $8.2 million for the nine months ended September 30, 2017, as compared to $16.9 million of net cash used in investing activities for the nine months ended September 30, 2016.2021 was $26.9 million compared to net cash used in investing activities of $0.6 million in the same period in 2020. The net change in cash of $8.7 million used in investing activities in 2021 was
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primarily to purchase marketable securities and to invest in Cyrus Biotechnology, offset by proceeds from the maturities of marketable securities. The net cash used in investing activities in 2020 was to purchase property and equipment.
Financing activities
Net cash provided by financing activities for the nine months ended September 30, 2017 resulted from the purchase of additional Short-term investments totaling $25.42021 was $31.7 million combined with additional equipment purchases of $0.1 million offset by maturities of Short-term investments of $34.2 million.
Netcompared to net cash provided by financing activities
Net of $14.6 million in the same period in 2020. The net cash provided by financing activities in 2021 was $61.0 million forprimarily the nine months ended September 30, 2017 as compared to $64.9 million for the nine months ended September 30, 2016. The decrease of $3.9 million resulted from (i) $47.1 millionresult of net cash derivedproceeds from the 2017 PIPE, (ii) $21.0 million from the issuance of the 2017 Term Loan, (iii) $5.0 million received in connection with the issuance of common stock to Spark pursuant to contractual equity acquisition rights, (iv) $0.6 million“at-the-market” offerings and from the exercise of employee stock optionsoptions.
The net cash provided by financing activities in 2020 was the result of $10.3 million from the Sobi Private Placement, $24.8 million from the Term A Loan, and (v) $0.1$2.1 million innet proceeds from the issuancesales of common stock under the ESPP,in “at-the-market” offerings, offset by $12.9$4.4 million of loan repayments made during the nine months ended September 30, 2017 as opposedissuance costs paid for December 2019 financing and $19.3 million principal payment on outstanding debt.
Recent Accounting Pronouncements
For a discussion of recently adopted or issued accounting pronouncements please see Note 2 to the net cash of $64.8 million received in connection with our IPO related activities in 2016.
The functional currency of our Russian subsidiary is the Russian ruble. The statement of cash flows for our Russian subsidiary is translated using the average translation rate applicable during the period except that all cash and cash equivalents, Short-term investments and restricted cash at the beginning of the period is translated using the exchange rate as of the beginning balance sheet date, and cash and cash equivalents, Short-term investments and restricted cash at the end of the period is translated using the exchange rate as of the ending balance sheet date.
Contractual obligations and contingent liabilities
In September 2017, we repaid $10.0 million in outstanding debt for the 2015 Term Loan and also entered into a $21.0 million Term Loan. See Note 9 to ourunaudited consolidated financial statements for information about the 2015 Term Loan repayment and the terms of the 2017 Term Loan agreement. Other than the item previously discussed, there have been no material changes, outside of the ordinary course of business, to our contractual obligations and commitments as previously disclosedincluded elsewhere in our 2016 Annual Report on Form 10-K for the year ended December 31, 2016.this Quarterly Report.
OFF-BALANCE SHEET ARRANGEMENTSOff-Balance Sheet Arrangements
As of September 30, 2017,2021, we did not have any off-balance sheet arrangements as defined in the rules and regulations of the Securities and Exchange Commission.



CRITICAL ACCOUNTING POLICIES AND USE OF ESTIMATESCritical Accounting Policies and Use of Estimates
ThisOur management’s discussion and analysis of our financial condition and results of operations is based on our consolidated financial statements, which we have been prepared in accordance with United States generally accepted accounting principles. We believe that several accounting policies are important to understanding our historical and future performance. We refer toU.S. GAAP. The preparation of these policies as critical because these specific areas generally requireconsolidated financial statements requires us to make judgmentsestimates and estimates about mattersassumptions that are uncertainaffect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the time we makedate of the estimate,consolidated financial statements, as well as the reported revenues and different estimates—which also would have been reasonable—could have been used. On an ongoing basis, we evaluateexpenses incurred during the reporting periods. Our estimates are based on our estimates and judgments. We base our estimates on historical experience and on various other market-specific or other relevant assumptionsfactors that we believe to beare reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions.
During the three and nine months ended September 30, 2017,2021, there were no material changes to our critical accounting policies as reportedfrom those described in our 2016 Annual Report on Form 10-K.10-K for the year ended December 31, 2020.

Emerging Growth Company Status
The Jumpstart Our Business Startups Act of 2012, or the JOBS Act, permits an ‘‘emerging growth company’’ such as us to take advantage of an extended transition period to comply with new or revised accounting standards applicable to public companies until those standards would otherwise apply to private companies. We have irrevocably elected not to avail ourselves of this exemption and, therefore, we will be subject to the same new or revised accounting standards as other public companies that are not emerging growth companies. We will remain an emerging growth company until December 31, 2021, the last day of the fiscal year following the fifth anniversary of the closing of the initial public offering of our common stock. However, if certain events occur prior to December 31, 2021, including if we become a “large accelerated filer,” our annual gross revenues exceed $1.07 billion or we issue more than $1.07 billion of non-convertible debt in any three-year period, we will cease to be an emerging growth company prior to December 31, 2021.
Smaller Reporting Company
We qualify as a “smaller reporting company” under the rules of the Securities Act and the Exchange Act. As a result, in addition to the exemptions available to us as an “emerging growth company,” we may choose to take advantage of certain scaled disclosure requirements available specifically to smaller reporting companies. Additionally, even if we cease to be an emerging growth company as noted above, as long as we continue to be a smaller reporting company, we may continue to rely on the reduced executive compensation disclosure obligations available to emerging growth companies. We will remain a smaller reporting company until the last day of the fiscal year in which the aggregate market value of our common stock held by non-affiliated persons and entities, or our public float, is more than $700 million as of the last business day of our most recently completed second fiscal quarter, or the last day of the fiscal year in which we have at least $100 million in revenue and at least $250 million in public float as of the last business day of our most recently completed second fiscal quarter.

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Item 3.Quantitative and Qualitative Disclosures About Market Risk
The market risk inherent in our financial instruments and in our financial position represents the potential loss arising from adverse changes in interest rates. As of September 30, 20172021 and December 31, 2016,2020, we had cash, cash equivalents, Short-term depositsrestricted cash and Short-term investmentsmarketable securities of $104.4$140.0 million and $84.1$140.1 million, respectively, consisting of non‑interestnon-interest and interest‑bearinginterest-bearing money market accounts, repurchase agreements, short-term investments of treasuries and government obligations.accounts. Our primary exposure to market risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates. Due to the short‑termshort-term and the low risk profile of our money market accounts and investments,marketable securities, and our current plan to hold investmentsmarketable securities to maturity, an immediate 100 basis point change in interest rates would not have a material effect on the fair market value of our cash equivalents or short-term investments.marketable securities.
In addition, we are subject to currency risk for balances held in Russian rubles in our foreign subsidiary. We hold portions of our funds in both U.S. dollars and Russian rubles. The exchange rate between the U.S. dollar and Russian ruble changes from period to period. AtAs of September 30, 2017,2021, we held $1.7cash and cash equivalents totaling $0.3 million of total cash in Russian banks to support our Russian subsidiary, which includes $1.6 millionall of cash and cash equivalents and $0.1 million of restricted cash, of which $1.6 million of cash and cash equivalents were denominated in U.S. dollars. We do not hedge against foreign currency risks. We do not believe that inflation and changing prices had a significant impact on our results of operations for any periods presented herein.


Item 4. Controls and Procedures
Limitations on effectiveness of controls and procedures
In designing and evaluating our disclosure controls and procedures, management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving the desired control objectives. In addition, the design of disclosure controls and procedures must reflect the fact that there are resource constraints and that management is required to apply judgment in evaluating the benefits of possible controls and procedures relative to their costs.
Evaluation of disclosure controls and procedures
Our management, with the participation of our Chief Executive Officer and Chief Financial Officer, evaluated, as of the end of the period covered by this Quarterly Report, on Form 10-Q, the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended (the “Exchange Act”))Act). Based on that evaluation, our Chief Executive Officer and Chief Financial Officer concluded that our disclosure controls and procedures were effective at the reasonable assurance level as of September 30, 2017.2021.
Changes in internal control over financial reporting
There were no changes in our internal control over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act) during the three months ended September 30, 20172021 that have materially affected, or isare reasonably likely to materially affect, our internal control over financial reporting.

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PART II. OTHER INFORMATION
Item 1. Legal Proceedings.Proceedings
We are not partyOn August 4, 2020, a putative stockholder of Selecta filed a stockholder derivative action, purportedly on behalf of Selecta and against certain current and former members of the Company’s Board of Directors, as well as one affiliated company owned by a current board member, in the Court of Chancery of the State of Delaware, namely Franchi v. Barabe, et al. The complaint alleges that the individual defendants breached their fiduciary duties and committed corporate waste when they authorized a private placement transaction, announced on December 19, 2019, at a price allegedly below fair value. The complaint further alleges that the four defendant directors who participated in the private placement were unjustly enriched in connection with the transaction. On September 25, 2020, the defendants filed a motion to any material legal proceedings.dismiss the lawsuit. On November 6, 2020, the plaintiff filed an amended complaint, and the defendants filed a second motion to dismiss on January 8, 2021. On December 31, 2020, we received a litigation demand letter from two other putative stockholders relating to the same private placement transaction. On April 12, 2021, the Court of Chancery in the State of Delaware granted a motion to stay the litigation pending a review by a Special Committee appointed by the Company’s Board of Directors.

Item 1A. Risk Factors
InvestingOur risk factors are disclosed in Item 1A of our common stock involves a high degree of risk. You should consider carefully the risks described below, together with the other information included or incorporated by reference in this QuarterlyAnnual Report on Form 10-Q. If any of the following risks occur, our business, financial condition, results of operations and future growth prospects could be materially and adversely affected. In these circumstances, the market price of our common stock could decline. Other events that we do not currently anticipate or that we currently deem immaterial may also affect our business, prospects, financial condition and results of operations.
RISKS RELATED TO OUR FINANCIAL POSITION AND NEED FOR ADDITIONAL CAPITAL
We are a development‑stage company and have incurred significant losses since our inception. We expect to incur losses10-K for the foreseeable future and may never achieve or maintain profitability.
Since inception, we have incurred significant operating losses in every year. Our net loss was $45.8 million for the nine months ended September 30, 2017 and $36.2 million and $25.2 million for the yearsyear ended December 31, 2016 and 2015, respectively. As of September 30, 2017, we had an accumulated deficit of $197.4 million. To date, we2020. Except as set forth below, there have financed our operations primarily through our initial public offering of our common stock, a private placement of our common stock, issuances of preferred stock, debt, research grants and research collaborations. We currently havebeen no source of product revenue, and we do not expect to generate product revenue for the foreseeable future. All of our revenue to date has been collaboration and grant revenue. In November 2016, we received written notice from Sanofi that Sanofi had elected to terminate in its entirety our license and research collaboration agreement with Sanofi, or the Sanofi Agreement. As a result of the termination of the Sanofi Agreement, which was effective on May 8, 2017, we will not receive any future payments related to the Sanofi Agreement. We have devoted substantially all of our financial resources and efforts to developing our SVP technology, identifying potential product candidates and conducting preclinical studies and our clinical trials. We are in the early stages of development of our product candidates, and we have not completed development of any SVP-enabled therapies. We expect to continue to incur significant expenses and operating losses for the foreseeable future. We expect that our expenses will increase substantially as we:
-    conduct additional clinical trials of SEL‑212, our lead product candidate;
-    conduct clinical trials for our other product candidates, including SEL-403;
-continue the research and development of our other product candidates;
-    seek to enhance our SVP technology and discover and develop additional product candidates;
-    seek regulatory approvals for any product candidates that successfully complete clinical trials;
-potentially establish a sales, marketing and distribution infrastructure and scale up external manufacturing capabilities to commercialize any products for which we may obtain regulatory approval;
-scale up external manufacturing capabilities to commercialize any products for which we may obtain regulatory approval;
-    maintain, expand and protect our intellectual property portfolio, including through licensing arrangements;
-add clinical, scientific, operational, financial and management information systems and personnel, including personnel to support our product development and potential future commercialization efforts and to support our operations as a public company; and
-experience any delays or encounter any issues with any of the above, including, but not limited to, failed studies, complex results, safety issues or other regulatory challenges.
To become and remain profitable, we must succeed in developing and eventually commercializing products that generate significant revenue. This will require us to be successful in a range of challenging activities, including completing preclinical testing and clinical trials of our product candidates, discovering additional product candidates, obtaining regulatory approval and securing reimbursement for these product candidates, manufacturing, marketing and selling any products for which we may obtain regulatory approval, and establishing and managing our collaborations at various stages of a product candidate’s development. We are only in the preliminary stages of most of these activities. We may never succeed in these activities and, even if we do, may never generate revenues that are significant enough to achieve profitability.

Because of the numerous risks and uncertainties associated with pharmaceutical and biological product development, we are unable to accurately predict the timing or amount of increased expenses or when, or if, we will be able to achieve profitability. If we are required by the U.S. Food and Drug Administration, or FDA, or other regulatory authorities to perform studies in addition to those currently expected, or if there are any delays in completing our clinical trials or the development of any of our product candidates, our expenses could increase and revenue could be further delayed.
Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to become and remain profitable would depress our value and could impair our ability to raise capital, expand our business, maintain our research and development efforts, diversify our product offerings or continue our operations.
In addition, we have recurring losses and negative cash flows from operations and will require additional capital to fund planned operations. There can be no assurance that we will be able to raise additional capital on reasonable terms, if at all, which could prevent us from continuing our operations.
We will need substantial additional funding in order to complete development of our product candidates and commercialize our products, if approved. If we are unable to raise capital when needed, we could be forced to delay, reduce or eliminate our product development programs or commercialization efforts.
We expect our expenses to increase in connection with our ongoing activities, particularly as we conduct our clinical trials of SEL‑212, SEL-403 and SELA-070, and continue research and development for our other product candidates. In addition, if we obtain regulatory approval for any of our product candidates, we expect to incur significant commercialization expenses related to product manufacturing, marketing, sales and distribution. Accordingly, we will need to obtain substantial additional funding to continue operations. If we are unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our research and development programs or any future commercialization efforts.
We believe that our existing cash, cash equivalents and investments, and restricted cash as of September 30, 2017 will enable us to fund our operating expenses and capital expenditure requirements into mid-2019. We have based this estimate on assumptions that may prove to be wrong, and we could use our capital resources sooner than we currently expect. Our future capital requirements will depend on many factors, including:
-    the progress and results of our clinical trials of SEL‑212 and SEL-403;
-    the number of product candidates that we pursue;
-our collaboration agreements remaining in effect, our entering into additional collaboration agreements and our ability to achieve milestones under these agreements;
-    the cost of manufacturing clinical supplies of our product candidates;
-    our headcount growth and associated costs;
-the scope, progress, results and costs of preclinical development, laboratory testing and clinical trials for our other product candidates;
-    the costs, timing and outcome of regulatory review of our product candidates;
-the costs and timing of future commercialization activities, including manufacturing, marketing, sales and distribution, for any of our product candidates for which we receive marketing approval;
-    the revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval;
-the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property‑related claims;
-    the effect of competing technological and market developments; and
-the extent to which we acquire or invest in businesses, products and technologies, including entering into licensing or collaboration arrangements for product candidates.
Any additional fundraising efforts may divert our management from their day‑to‑day activities, which may adversely affect our ability to develop and commercialize our product candidates. In addition, we cannot guarantee that future financing will be available in sufficient amounts or on terms acceptable to us, if at all. Moreover, the terms of any financing may adversely affect the holdings or the rights of our stockholders, and the issuance of additional securities, whether equity or debt, by us, or the possibility of such issuance, may cause the market price of our shares to decline. The sale of additional equity or convertible securities would dilute all of our stockholders. The incurrence of indebtedness could result in increased fixed payment obligations and we may be required to agree to certain restrictive covenants, such as limitations on our ability to incur additional debt, limitations on our ability to acquire, sell or license intellectual property rights and other operating restrictions that could adversely impact our ability to conduct our business. We could also be required to seek funds through arrangements

with collaborators or others at an earlier stage than otherwise would be desirable and we may be required to relinquish rights to some of our technologies or product candidates or otherwise agree to terms unfavorable to us, any of which may have a material adverse effect on our business, operating results and prospects.
If we are unable to obtain funding on a timely basis, we may be required to significantly curtail, delay or discontinue one or more of our research or development programs or the commercialization of any product candidates, or be unable to expand our operations or otherwise capitalize on our business opportunities, as desired, which could materially affect our business, financial condition and results of operations.
Revenues from research and development activities in collaboration with Sanofi represented a significant portion of our revenues and the loss of these revenues may adversely affect our business and our liquidity.
Revenues from research and development activities under the Sanofi Agreement were a significant source of revenues in 2016. In November 2016, we received written notice from Sanofi that Sanofi had elected to terminate in its entirety the Sanofi Agreement. The termination of the Sanofi Agreement was effective on May 8, 2017, which was six monthschanges from the date of the notice. The loss of revenue derived from research and development activities under the Sanofi Agreement may adversely affect our business and our liquidity. In addition, Sanofi's termination of this agreement could adversely affect our reputation.
Our limited operating history may make it difficult for you to evaluate the success of our business to date and to assess our future viability.
We commenced active operationsrisk factors previously disclosed in 2007, and our operations to date have been limited to developing and researching our SVP technology and related products and programs, building our intellectual property portfolio, developing our supply chain, planning our business, raising capital and providing general and administrative support for these operations. Other than SEL-212, our lead product candidate, SEL-403, our product candidate utilizing LMB-100 in combination with SVP-Rapamycin, and SELA-070, our nicotine vaccine product candidate for smoking cessation and relapse prevention, our product candidates are still in preclinical development. While we have completed our Phase 1 clinical trial for SEL‑212, we have not yet completed any other clinical trials for SEL‑212 or any other product candidate. We initiated our Phase 2 clinical trial of SEL‑212 in October 2016, but have not yet demonstrated our ability to successfully complete any Phase 3 or other pivotal clinical trials, obtain regulatory approvals, manufacture a commercial scale product, or arrange for a third party to do so on our behalf, or conduct sales and marketing activities necessary for successful product commercialization. Additionally, we expect our financial condition and operating results to continue to fluctuate significantly from quarter‑to‑quarter and year‑to‑year due to a variety of factors, many of which are beyond our control. Consequently, any predictions you make about our future success or viability may not be as accurate as they could be if we had a longer operating history.
The terms of our credit facility and subsidiary’s charter place restrictions on our operating and financial flexibility. If we raise additional capital through debt financing, the terms of any new debt could further restrict our ability to operate our business.
On September 12, 2017, we entered into a term loan facility of up to $21.0 million with Silicon Valley Bank, a California corporation (“SVB”), the proceeds of which were used to repay our existing term loan facility with Oxford Finance LLC and Pacific Western Bank, as successor in interest to Square 1 Bank, and for general corporate and working capital purposes. The term loan facility is governed by a loan and security agreement, dated September 12, 2017, between us and SVB, which was funded in full on September 13, 2017. The term loan facility with SVB is secured by a lien on substantially all of our assets, other than intellectual property, provided that such lien on substantially all assets includes any rights to payments and proceeds from the sale, licensing or disposition of intellectual property. We also granted SVB a negative pledge with respect to our intellectual property.
The term loan facility contains customary covenants and representations, including but not limited to financial reporting obligations and limitations on dividends, indebtedness, collateral, investments, distributions, transfers, mergers or acquisitions, taxes, corporate changes, deposit accounts, and subsidiaries. The term loan facility also contains other customary provisions, such as expense reimbursement, non-disclosure obligations as well as indemnification rights for the benefit of SVB. The events of default under the term loan facility include, but are not limited to, our failure to make any payments of principal or interest under the term loan facility or other transaction documents, our breach or default in the performance of any covenant under the term loan facility or other transaction documents, the occurrence of a material adverse effect, making a false or misleading representation or warranty in any material respect under the term loan facility, our insolvency or bankruptcy, any attachment or judgment on our assets of at least approximately $0.3 million, or the occurrence of any default under any of our agreements or obligations involving indebtedness in excess of approximately $0.3 million. If an event of default occurs, SVB is entitled to take enforcement action, including acceleration of amounts due under the term loan facility. If we raise any additional debt financing, the terms of such additional debt could further restrict our operating and financial flexibility.
In addition, the charter of our subsidiary, Selecta RUS, prohibits distributions to us in violation of Russian law or if, as a result of such distribution, Selecta RUS would be insolvent or its net assets would be less than its charter capital and statutory

reserves. Selecta RUS held $1.7 million of total cash in Russian banks as of September 30, 2017, including $1.6 million of cash and cash equivalents and $0.1 million of restricted cash.
Our ability to use our net operating loss and research and development tax credit carryforwards to offset future taxable income may be subject to certain limitations.
We have net operating loss carryforwards, or NOLs, for federal and state income tax purposes which may be available to offset our future taxable income, if any. In general, under Sections 382 and 383 of the U.S. Internal Revenue Code of 1986, as amended, or the Code, a corporation that undergoes an “ownership change” is subject to limitations on its ability to use its pre‑change NOLs to offset future taxable income. If the U.S. Internal Revenue Service challenges our analysis that existing NOLs will not expire before utilization due to previous ownership changes, or if we undergo an ownership change in connection with or after this public offering, our ability to use our NOLs could be limited by Section 382 of the Code. Future changes in our stock ownership, some of which are outside of our control, could result in an ownership change under Sections 382 and 383 of the Code. Furthermore, our ability to use NOLs of companies that we may acquire in the future may be subject to limitations. As a result, we may not be able to use a material portion of the NOLs reflected on our balance sheet, even if we attain profitability.

RISKS RELATED TO THE DISCOVERY, DEVELOPMENT AND REGULATORY APPROVAL OF OUR PRODUCT CANDIDATES
We are very early in our clinical development efforts and may not be successful in our efforts to use our SVP technology to build a pipeline of product candidates and develop marketable drugs.
We are primarily using our SVP technology to improve and enable biologics that treat rare and serious diseases, with an initial focus on developing SEL‑212 for the treatment of chronic severe gout. We are also leveraging our SVP platform to pursue programs in additional therapeutic areas such as oncology and gene therapy.
For instance, in May 2017 we licensed LMB-100, a potent anti-bacterial toxin, and are currently planning a Phase 1b trial of our product candidate SEL-403 to evaluate LMB-100 in combination with our SVP technology in patients with rare, serious and aggressive forms of cancer, including pancreatic cancer and mesothelioma. In addition, we are developing two gene therapy product candidates for rare inborn errors of metabolism. Our lead gene therapy program is a potential treatment for methylmalonic acidemia. This product candidate is known as SEL-302. Our second gene therapy product candidate, or SEL-313, is intended to treat ornithine transcarbamylase deficiency.
While we believe our preclinical and clinical data to date have validated our technology to a degree, we are at an early stage of development and our technology has not yet led to, and may never lead to, approvable or marketable drugs. We are developing additional product candidates to address the problem of anti‑drug antibodies, and immunogenicity in biologic therapy and other areas. We may have problems identifying new product candidates and applying our technologies to these other areas. Even if we are successful in identifying additional product candidates, they may not be suitable for clinical development, including as a result of harmful side effects, limited efficacy or other characteristics that indicate that they are unlikely to be products that will receive marketing approval and achieve market acceptance. The success of our product candidates will depend on several factors, including the following:
-    completion of preclinical studies and clinical trials with positive results;
-    receipt of marketing approvals from applicable regulatory authorities;
-    obtaining and maintaining patent and trade secret protection and regulatory exclusivity for our product candidates;
-making arrangements with third-party manufacturers for, or establishing, commercial manufacturing capabilities, or --establishing such capabilities ourselves;
-    launching commercial sales of our products, if and when approved, whether alone or in collaboration with others;
-our existing collaboration agreements remaining in effect and our ability to enter into new collaborations throughout the development process as appropriate, from preclinical studies through to commercialization;
-    acceptance of our products, if and when approved, by patients and the medical community;
-    effectively competing with other therapies;
-obtaining and maintaining coverage and adequate reimbursement by third‑party payors, including government payors, for our products, if approved;
-    protecting our rights in our intellectual property portfolio;

-    operating without infringing or violating the valid and enforceable patents or other intellectual property of third parties;
-    maintaining an acceptable safety profile of our products following approval; and
-maintaining and growing an organization of scientists and business people who can develop and commercialize our product candidates and technology.
If we do not successfully develop and commercialize product candidates based upon our technological approach, we will not be able to obtain future revenues, which would result in significant harm to our financial position and adversely affect our stock price.
Our product candidates are based on our SVP technology, which is an unproven approach designed to induce antigen‑specific immune tolerance to biologic drugs or stimulate the immune system.
All of our product candidates are derived from our SVP technology, which is an unproven approach to inducing antigen‑specific tolerance or stimulating the immune system. In addition, SEL‑212, our lead product candidate, uses pegsiticase, a biologic, which we source primarily from Shenyang Sunshine Pharmaceutical Co., Ltd., or 3SBio, in China. We have not, nor to our knowledge has any other company, received FDA approval for a therapeutic based on SVP or for a biologic product manufactured in China. In addition, we may use biologics other than pegsiticase with our SVP technology.
As a result, we cannot be certain that our approach, or our development of SEL‑212, will lead to the development or approval of marketable products. In addition:
-due to the unproven nature of our SVP therapeutics, they may have different efficacy and safety rates in various indications;
-the FDA or other regulatory agencies may lack experience in evaluating the efficacy and safety of products based on SVP or a biologic sourced from China or other jurisdictions, which could result in a longer‑than‑expected regulatory review process, increase our expected development costs or delay or prevent commercialization of our product candidates; and
-in the event of a biologics license application for SEL‑212 or another product and a pre‑approval inspection by the FDA of the facilities of 3SBio or any other manufacturer of biologics we may use, the FDA may not approve the facility for production or may make observations that will take significant time for 3SBio or such other provider to address.
The occurrence of any of the foregoing, would effectively prevent or delay approval of our lead and other product candidates.
We are applying our SVP technology to antigen-specific immune tolerance for gene therapy involving gene augmentation, replacement or editing. So far no gene therapy product has been approved for a genetic disease in the United States and only two such products have been approved in the European Union.
Our future success depends in part on our successful development of viable gene therapy product candidates utilizing SVP technology. We may experience problems or delays in developing such product candidates and any such problems or delays (i) may result in unanticipated costs and time to develop our product candidates and/or (ii) may not be resolved in a satisfactory manner.
The requirements of the FDA, the European Medicines Agency, or EMA, and other regulatory authorities, and the criteria these regulators use to determine the safety and efficacy of a product candidate, vary substantially according to the type, complexity, novelty and intended use and market of such product candidates. The regulatory approval process and clinical trial requirements for novel product candidates can be more expensive and take longer than for other, better known or more extensively studied product candidates.
Sponsors of certain clinical studies of cells containing recombinant or synthetic nucleic acid molecules, including human gene transfer studies, must comply with the National Institutes of Health’s, or NIH’s, Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules, or (“NIH Guidelines”). The NIH Guidelines set forth the principles and requirements for NIH and institutional oversight of research with recombinant or synthetic nucleic acid molecules, including the standards for investigators and institutions to follow to ensure the safe handling and containment of such molecules. In April 2016, modifications to the NIH Guidelines went into effect, pursuant to which only a subset of human gene transfer protocols are subject to review by the NIH Recombinant DNA Advisory Committee, or RAC, a federal advisory committee that provides recommendations regarding research involving recombinant or synthetic nucleic acid molecules. Specifically, under the modified NIH Guidelines, RAC review of the protocol will be required only in exceptional cases where (a) an oversight body such as an Institutional Biosafety Committee, or IBC, which provides local review and oversight of research utilizing recombinant or synthetic nucleic acid molecules, or an IRB determines that the protocol would significantly benefit from RAC review, and (b) the protocol (i) uses a new vector, genetic material, or delivery methodology that represents a first-in-human experience and thus presents an unknown risk, and/or (ii) relies on preclinical safety data that were obtained using a new preclinical model system of unknown and unconfirmed value, and/or (iii) involves a proposed vector, gene construct, or method of delivery associated with possible toxicities that are not widely known and that may render it difficult for oversight bodies to

evaluate the protocol rigorously. The RAC review proceedings are public, and reports are posted publicly to the website for the NIH’s Office of Biotechnology Activities. Although compliance with the NIH Guidelines is mandatory for research conducted at or sponsored by institutions receiving NIH funding of recombinant or synthetic nucleic acid molecule research, many companies and other institutions not otherwise subject to the NIH Guidelines voluntarily follow them. Independent of RAC review, the NIH Guidelines also require all human gene transfer protocols subject to the NIH Guidelines to be registered with NIH, with limited exemptions. A study subject to the NIH Guidelines may not begin until the IBC approves the protocol, and the IBC cannot approve the protocol until confirmation from the NIH that such registration is complete. In the event that RAC review is warranted, the protocol registration process cannot be completed until RAC review has taken place.
Although the FDA decides whether individual gene therapy protocols may proceed, the RAC public review process, if undertaken, can delay the initiation of a clinical trial. Conversely, the FDA can delay or prevent the initiation of a clinical study even if the RAC has provided a favorable review the study is not subject to in-depth, public RAC review. In addition, clinical trials involving a gene therapy product candidate must be authorized by an applicable IRB and an IBC, which provides oversight of recombinant DNA research.
In 2012, the European Medicines Agency approved a gene therapy product called Glybera, which is the first gene therapy product approved by regulatory authorities anywhere in the Western world. GlaxoSmithKline plc’s Strimvelis and uniQure N.V.’s Glybera, are the only two gene therapy products for a genetic disease that have received marketing authorization from the European Commission. In October 2017 UniQure let its marketing authorization for Glybera in Europe expire after deciding not to pursue a renewal for commercial reasons. We cannot predict how long it will take or how much it will cost to obtain regulatory approvals for a gene therapy product candidate in either the United States or the European Union or how long it will take to commercialize a gene therapy product candidate. Regulatory requirements governing gene therapy products have changed frequently and may continue to change in the future. Adverse developments in clinical trials of gene therapy products conducted by others may cause the FDA or other oversight bodies to modify the requirements for testing or approval of any of our product candidates. Similarly, the EMA may issue new guidelines concerning the development and marketing authorization for gene therapy medicinal products and require that we comply with these new guidelines.
As we advance any gene therapy product candidates, we will be required to consult with various regulatory authorities, and we must comply with applicable laws, rules, and regulations, which may change from time to time including during the course of development of our product candidates. If we fail to do so, we may be required to delay or discontinue development of certain of our product candidates. These additional processes may result in a review and approval process that is longer than we otherwise would have expected. Even if we comply with applicable laws, rules, and regulations, and even if we maintain close coordination with the applicable regulatory authorities with oversight over our product candidates, our development programs may fail to succeed. Delay or failure to obtain, or unexpected costs in obtaining, the regulatory approval necessary to bring a potential product to market would materially and adversely affect our business, financial condition, results of operations and prospects.
We may expend our limited resources to pursue a particular product candidate or indication and fail to capitalize on other product candidates or indications that may be more profitable or for which there is a greater likelihood of success.
Because we have limited financial and management resources, we focus on a limited number of research programs and product candidates and are currently principally focused on SEL‑212. As a result, we may forego or delay our pursuit of opportunities with other product candidates or for other indications that later prove to have greater commercial potential. Our resource‑allocation decisions may cause us to fail to capitalize on viable commercial drugs or profitable market opportunities. Our spending on current and future research and development programs and product candidates for specific indications may not yield any commercially viable drugs. If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may not pursue such product candidate, or we may relinquish valuable rights to that product candidate through future collaboration, licensing or other arrangements, in cases in which it would have been more advantageous for us to retain sole development and commercialization rights.filing.
Clinical drug development involves a lengthy and expensive process, with an uncertain outcome. We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of our product candidates.
Our lead product candidate, SEL-212, is currently being evaluated in a Phase 2 clinical program that we initiated in October 2016 and that we expect to hold our end-of-phase 2 meeting with the FDA in the first half of 2018. In May 2017, we announced we in-licensed LMB-100, a next-generation immunotoxin that is currently in a Phase 1 clinical program at the Center for Cancer Research at the NCI, for pancreatic cancer, mesothelioma and other cancers. For this product candidate, known as SEL-403, we plan to co-administer LMB-100 with SVP-Rapamycin. In May 2017, we commenced dosing for a Phase 1 clinical trial for SELA-070, a nicotine vaccine candidate in development for smoking cessation and relapse prevention, to assess its safety, tolerability and pharmacodynamic profile. Aside from these programs,SEL-212, our other product candidates are in preclinical development. It is impossible to predict when or if any of our product candidates will prove effective and safe in

humans or will receive regulatory approval, and the risk of failure through the development process is high. Before obtaining marketing approval from regulatory authorities for the sale of any product candidate, we must complete preclinical development and then conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidates in humans. Preclinical development is costly and inherently uncertain. Early preclinical results may not be predictive of future results, however, if our technology proves to be ineffective or unsafe as a result of, among other things, adverse side effects, pre-existing anti-drug antibodies that can neutralize the viral vector and block gene transfer, or cellular immune response to the transduced cells, we may incur additional costs or experience delays in completing, or ultimately be unable to complete, the clinical development and commercialization of our product candidates.
Before obtaining marketing approval from regulatory authorities for the sale of our product candidates, we must conduct extensive clinical trials to demonstrate the safety and efficacy of the product candidate for its intended indications. Clinical testing is expensive, difficult to design and implement, can take many years to complete and its outcome is inherently uncertain. A failed clinical trial can occur at any stage of testing. Moreover, the outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results.
We had a prior SVP-nicotine product candidate, which entered clinical development after a promising preclinical program. However, results from a Phase 1 For example, the topline clinical trial conducted in smokers and non-smokers with this product candidate showed that nicotine-specific antibodies were induced at sub-therapeutic levels. In this regard, manyresults we reported from our Phase 2 head-to-head COMPARE study of SEL-212 may not be predictive of future results. Moreover, we may not be able to complete, or may be required to deviate from the current clinical trial protocol for a variety of reasons.
Many companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in clinical trials after achieving positive results in preclinical development or early-stage clinical trials, and we cannot be certain that we will not face similar setbacks. These setbacks have been caused by, among other things, preclinical findings made while clinical trials were underway or safety or efficacy observations made in clinical trials, including adverse events. For example, multiple seriousSerious adverse events, or SAEs, havecaused by, or other unexpected properties of, any product candidates that we may choose to develop could cause us, an institutional review board or regulatory authority to interrupt, delay or halt clinical trials of one or more of such product candidates and could result in a more restrictive label or the delay or denial of marketing approval by the FDA or comparable non-U.S. regulatory authorities. If any product candidate that we may choose to develop is associated with SAEs or other unexpected properties, we may need to abandon development or limit development of that product candidate to certain uses or subpopulations in which those undesirable characteristics would be expected to be less prevalent, less severe or more tolerable from a risk-benefit perspective. For example, in the SEL-403 Phase 1 clinical trial, a Grade 5 SAE (patient death) occurred in connection with SEL-212’sthat was deemed by the trial investigator to be probably related to SVP-Rapamycin and possibly related to the patient's pleural mesothelioma condition which led us to abandon development of SEL-403. In the SEL-212 Phase 1/2 clinical program, multiple SAEs have occurred, and future SAEs may occur causing us to incur additional SAEscosts or similar events could occur duringexperience delays in completing, or causing us to ultimately be unable to complete, the coursedevelopment and commercialization of our development of SEL-212 or other product candidates, which could be materially adverseand delay or prevent our ability to the success of these programs.obtain FDA approval. Moreover, preclinical and clinical data is often susceptible to varying interpretations and analyses, and many companies that believed their product candidates performed satisfactorily in preclinical studies and clinical trials nonetheless failed to obtain FDA or other regulatory authority approval. If we fail to produce positive results in our clinical trials of our product candidates, the development timeline
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and regulatory approval and commercialization prospects for our product candidates, and, correspondingly, our business and financial prospects, would be negatively impacted.
In addition, we cannot be certain as to what type and how many clinical trials the FDA will require us to conduct before we may successfully gain regulatory approval to market SEL-212 or any of our other product candidates in the United States or other countries.countries, if any. Prior to approving a new therapeutic product, the FDA generally requires that safety and efficacy be demonstrated in two adequate and well-controlled clinical trials. In some situations, evidence from a Phase 2 trialWe expect that we and a Phase 3 trial or from a single Phase 3 trial can be sufficient for FDA approval, such as in cases where the trial or trials provide highly reliable and statistically strong evidence of an important clinical benefit. We expectSobi will need to conduct more than one Phase 3 trial for SEL-212 in thefor a chronic refractory gout indication in order to gain approval. Additional clinical trials could cause us to incur significant development costs,approval from the FDA. Even if we and Sobi conduct more than one Phase 3 trial for SEL-212, the FDA may not accept the data, and may delay, limit or prevent the commercializationdeny approval of SEL-212, or otherwise adversely affect our business.which could have an impact on the timing of development milestone payments owed to us by Sobi.
We may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent our ability to receive marketing approval for, or commercialize, our product candidates, including:
-clinical trials of our product candidates may produce unfavorable, incomplete or inconclusive results;
-regulators or institutional review boards may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site;
-we may experience delays in reaching, or fail to reach, agreement on acceptable terms with CROs, or clinical trial sites;
-we may be unable to recruit suitable patients to participate in a clinical trial, the number of patients required for clinical trials of our product candidates may be larger than we expect, enrollment in these clinical trials may be slower than we expect or participants may drop out of these clinical trials at a higher rate than we expect;
-the number of clinical trial sites required for clinical trials of our product candidates may be larger than we expect;
-our third‑party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all;
-we may have to suspend or terminate clinical trials of our product candidates for various reasons, including a finding that the participants are being exposed to unacceptable health risks;
-investigators, regulators, data safety monitoring boards or institutional review boards may require that we or our investigators suspend or terminate clinical research, or we may decide to do so ourselves, for various reasons including noncompliance with regulatory requirements, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues such as a finding that the participants are being exposed to unacceptable health risks, undesirable side effects or other unexpected characteristics, failure to demonstrate a benefit from using a drug, changes in governmental regulations or administrative actions;
-investigators may deviate from the trial protocol, fail to conduct the trial in accordance with regulatory requirements or misreport study data;
-the cost of clinical trials of our product candidates may be greater than we expect;

•clinical trials of our product candidates may produce unfavorable, incomplete or inconclusive results;
-the supply or quality of raw materials or manufactured product candidates (whether provided by us or third parties) or other materials necessary to conduct clinical trials of our product candidates may be insufficient, inadequate or not available at an acceptable cost, or we may experience interruptions in supply;
-regulators may revise the requirements for approving our product candidates, or such requirements may not be as we expect;
-the FDA or comparable foreign regulatory authorities may disagree with our clinical trial design or our interpretation of data from preclinical studies and clinical trials, or may change the requirements for approval even after it has reviewed and commented on the design of our clinical trials; and
-regarding trials managed by our existing or any future collaborators, our collaborators may face any of the above issues, and may conduct clinical trials in ways they view as advantageous to them but potentially suboptimal for us.
•regulators or institutional review boards may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site;
•we may experience delays in reaching, or fail to reach, agreement on acceptable terms with contract research organizations, or CROs, or clinical trial sites;
•we may be unable to recruit suitable patients to participate in a clinical trial, the number of patients required for clinical trials of our product candidates may be larger than we expect, enrollment in these clinical trials may be slower than we expect or participants may drop out of these clinical trials at a higher rate than we expect;
•the number of clinical trial sites required for clinical trials of our product candidates may be larger than we expect;
•our third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all;
•we may have to suspend or terminate clinical trials of our product candidates for various reasons, including a finding that the participants are being exposed to unacceptable health risks;
•investigators, regulators, data safety monitoring boards or institutional review boards may require that we or our investigators suspend or terminate clinical research, or we may decide to do so ourselves;
•investigators may deviate from the trial protocol, fail to conduct the trial in accordance with regulatory requirements or misreport study data;
•the cost of clinical trials of our product candidates may be greater than we expect or we may have insufficient resources to pursue or complete certain aspects of our clinical trial programs or to do so within the timeframe we planned;
•the supply or quality of raw materials or manufactured product candidates (whether provided by us or third parties) or other materials necessary to conduct clinical trials of our product candidates may be insufficient, inadequate or not available at an acceptable cost, or in a timely manner, or we may experience interruptions in supply;
•regulators may revise the requirements for approving our product candidates, or such requirements may not be as we expect;
•the FDA or comparable foreign regulatory authorities may disagree with our clinical trial design or our interpretation of data from preclinical studies and clinical trials, or may change the requirements for approval even after it has reviewed and commented on the design of our clinical trials; and
•regarding trials managed by our existing or any future collaborators, our collaborators may face any of the above issues, and may conduct clinical trials in ways they view as advantageous to them but potentially suboptimal for us.
If we are required to conduct additional clinical trials or other testing of our product candidates beyond those that we currently contemplate, if we are unable to successfully complete clinical trials of our product candidates or other testing, if the results of these trials or tests are not positive or are only modestly positive or if there are safety concerns, or if we are forced to delay or abandon certain clinical trials or other testing in order to conserve capital resources, we may:
-be delayed in obtaining marketing approval for our product candidates, if at all;
-lose the support of collaborators, requiring us to bear more of the burden of research and development;
-not obtain marketing approval at all;
-obtain marketing approval in some countries and not in others;
-obtain approval for indications or patient populations that are not as broad as intended or desired;
-obtain approval with labeling that includes significant use or distribution restrictions or safety warnings;
-be subject to additional post‑marketing testing requirements; or
-have a product removed from the market after obtaining marketing approval.
•be delayed in obtaining marketing approval for our product candidates, if at all;
•lose the support of collaborators, requiring us to bear more of the burden of research and development;
•obtain marketing approval in some countries and not in others;
•obtain approval for indications or patient populations that are not as broad as intended or desired;
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•obtain approval with labeling that includes significant use or distribution restrictions or safety warnings;
•be subject to additional post-marketing testing requirements; or
•have a product removed from the market after obtaining marketing approval.
In addition, disruptions caused by the COVID-19 pandemic may increase the likelihood that we encounter such difficulties or delays in initiating, enrolling, conducting or completing our planned and ongoing clinical trials. We could also encounter delays if a clinical trial is suspended or terminated by us, by the IRBs of the institutions in which such trials are being conducted, by a data safety monitoring board for such trial or by the FDA or comparable foreign regulatory authorities. Such authorities may impose such a suspension or termination due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or comparable foreign regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a drug, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial. In addition, changes in regulatory requirements and policies may occur, and we may need to amend clinical trial protocols to comply with these changes. Amendments may require us to resubmit our clinical trial protocols to IRBs for reexamination, which may impact the costs, timing or successful completion of a clinical trial.
We filed an IND to conduct a Phase 1/2 clinical trial of our SEL-302 product candidate in pediatric patients with methylmalonic acidemia in the third quarter of 2021. As of the filing of this quarterly report, the FDA’s 30-day review period for this IND has expired. However, we have been informed orally by FDA that they are still considering certain aspects of our filing related to chemistry, manufacturing and control, or CMC. We intend to wait for formal clearance from FDA before initiating the proposed Phase 1/2 clinical trial and to work with FDA to resolve any concerns they may have with our submission. If we are unable to do so we expect FDA may impose a clinical hold on this trial.
Our product development costs will increase if we experience delays in clinical testing or in obtaining marketing approvals. We do not know whether any of our preclinical studies or clinical trials will begin as planned, will need to be restructured or will be completed on schedule, or at all. Significant preclinical or clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize our product candidates or allow our competitors to bring products to market before we do, potentially impairing our ability to successfully commercialize our product candidates and harming our business and results of operations.
If we experience delays or difficulties in the enrollment of patients in clinical trials, our receipt of necessary regulatory approvals could be delayed or prevented.
We may not be able to initiate or continue clinical trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials as required by the FDA or similar regulatory authorities outside the United States. In addition, from time to time our competitors have ongoing clinical trials for product candidates that treat the same indications as our product candidates, and patients who would otherwise be eligible for our clinical trials may instead enroll in clinical trials of our competitors’ product candidates.
We are initially developing our lead product candidate, SEL‑212, for the treatment of chronic refractory gout, which affects approximately 50,000 patients in the United States. Accordingly, there is a limited number of patients who could enroll in our clinical studies.
In addition to the size of the patient population, patient enrollment is also affected by other factors including:
-the severity of the disease under investigation;
-the patient eligibility criteria for the study in question;
-the perceived risks and benefits of the product candidate under study;
-the availability of other treatments for the disease under investigation;
-the existence of competing clinical trials;
-our efforts to facilitate timely enrollment in clinical trials;
-investigators engagement with, or enthusiasm about, the trial;
-our payments for participating in clinical trials;

-the patient referral practices of physicians;
-the design of the trial;
-the ability to monitor patients adequately during and after treatment; and
-the proximity and availability of clinical trial sites for prospective patients.
Our inability to enroll a sufficient number of patients for our clinical trials would result in significant delays and could require us to abandon one or more clinical trials altogether. Enrollment delays in our clinical trials may result in increased development costs for our product candidates, which could cause the value of our common stock to decline and limit our ability to obtain additional financing.
If we are not able to obtain, or if there are delays in obtaining, required regulatory approvals, we will not be able to commercialize our product candidates, and our ability to generate revenue will be materially impaired.
Our product candidates and the activities associated with their development and commercialization, including their design, testing, manufacture, safety, efficacy, recordkeeping, labeling, packaging, storage, approval, advertising, promotion, adverse event reporting, sale and distribution, are subject to comprehensive regulation by the FDA and other regulatory agencies in the United States, and by the EMA and similar regulatory authorities outside the United States. Failure to obtain marketing approval for a product candidate will prevent us from commercializing that product candidate. We have not received approval to market any of our product candidates from regulatory authorities in any jurisdiction. We have only limited experience in filing and supporting the applications necessary to gain marketing approvals and expect to rely on third parties to assist us in this process. Securing marketing approval requires the submission of extensive preclinical and clinical data and supporting information to regulatory authorities for each therapeutic indication to establish the product candidate’s safety and efficacy. Securing marketing approval also requires the submission of information about the product manufacturing process to, and inspection of manufacturing facilities by, the regulatory authorities. Our product candidates may not be effective, may be only moderately effective or may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude our obtaining marketing approval for, or prevent or limit the commercial use of, such product candidates.
The process of obtaining marketing approvals, both in the United States and abroad, is expensive and may take many years. If additional clinical trials are required for certain jurisdictions, these trials can vary substantially based upon a variety of factors, including the type, complexity and novelty of the product candidates involved, and may ultimately be unsuccessful. Changes in marketing approval policies during the development period, changes in or the enactment or promulgation of additional statutes or regulations, respectively, or changes in the regulatory review process for each submitted product application, may cause delays in the review and approval of an application. Regulatory authorities have substantial discretion in the approval process and may refuse to accept a marketing application as deficient or may decide that our data is insufficient for approval and require additional preclinical, clinical or other studies. In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent marketing approval of a product candidate. Any marketing approval we ultimately obtain may be limited or subject to restrictions or post‑approval commitments that render the approved product not commercially viable.
Although the FDA and other regulatory authorities have approved nanotechnology‑based therapeutics in the past, they are monitoring whether nanotechnology‑based therapeutics pose any specific health and human safety risks. While they have not issued any regulations to date, it is possible that the FDA and other regulatory authorities could issue regulations in the future regarding nanotechnology‑based therapeutics that could adversely affect our product candidates.
If we experience delays in obtaining approval or if we fail to obtain approval of our product candidates, the commercial prospects for our product candidates may be harmed and our ability to generate revenues will be materially impaired.
We may not be able to obtain orphan drug designation for our product candidates, and even if we do, we may be unable to maintain the benefits associated with orphan drug designation, including the potential for market exclusivity.
Regulatory authorities in some jurisdictions, including the United States and Europe, may designate drugs for relatively small patient populations as orphan drugs. We expect to seek orphan drug designation for several of our product candidates. Under the Orphan Drug Act of 1983, the FDA may designate a product as an orphan product if it is intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 individuals annually in the United States, or a patient population of greater than 200,000 individuals in the United States, but for which there is no reasonable expectation that the cost of developing the drug or biologic will be recovered from sales in the United States.
In the United States, orphan designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user‑fee waivers. In addition, if a product candidate that has orphan designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications, including a full biologics license application, or BLA, or full new drug application, or NDA, to market the same biologic or drug for the same indication for

seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or where the manufacturer is unable to assure sufficient product quantity. Our competitors, including Horizon Pharma plc, may seek orphan drug status for the same biologic or drug for the same indication as our product candidates. In this regard, Krystexxa® (pegloticase) previously obtained orphan drug status for chronic refractory gout, although the exclusivity period has lapsed. However, Krystexxa could in the future obtain orphan drug status for chronic tophaceous gout, an indication we plan to pursue.
The applicable exclusivity period is ten years in the European Union, but such exclusivity period can be reduced to six years if a product no longer meets the criteria for orphan designation or if the product is sufficiently profitable so that market exclusivity is no longer justified.
Even if we obtain orphan drug exclusivity for a product, that exclusivity may not effectively protect the product from competition because different drugs can be approved for the same condition. Even after an orphan drug is approved, the FDA can subsequently approve the same drug for the same condition if the FDA concludes that the later drug is clinically superior if it is shown to be safer, more effective or makes a major contribution to patient care.
Any breakthrough therapy designation that we may receive from the FDA for our product candidates may not lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing approval.
We may in the future seek breakthrough therapy designation for some of our product candidates. A breakthrough therapy is defined as a drug that is intended, alone or in combination with one or more other drugs, to treat a serious or life‑threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. For drugs that have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens. Drugs designated as breakthrough therapies by the FDA are also eligible for accelerated approval.
Designation as a breakthrough therapy is within the discretion of the FDA. Accordingly, even if we believe one of our product candidates meets the criteria for designation as a breakthrough therapy, the FDA may disagree and instead determine not to make such designation. The availability of breakthrough therapy designation was established recently with the passage of the Food and Drug Administration Safety and Innovation Act of 2012. We cannot be sure that any evaluation we may make of our product candidates as qualifying for breakthrough therapy designation will meet the FDA’s expectations. In any event, the receipt of a breakthrough therapy designation for a product candidate may not result in a faster development process, review or approval compared to drugs considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA. In addition, even if one or more of our product candidates qualify as breakthrough therapies, the FDA may later decide that such product candidates no longer meet the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.
Our product candidates may cause undesirable side effects or have other properties that could delay or prevent their regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any.
Undesirable side effects caused by our product candidates could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA or other comparable foreign authorities. Further, therapies such as those we are developing involve unique side effects that could be exacerbated compared to side effects from other types of therapies with singular components. Results of our clinical trials could reveal a high and unacceptable severity and prevalence of side effects. In such an event, our trials could be suspended or terminated and the FDA or comparable foreign regulatory authorities could order us to cease further development of or deny approval of our product candidates for any or all targeted indications. The drug‑related side effects could affect patient enrollment in our clinical trials or the ability of any enrolled patients to complete such trials or result in potential product liability claims. Any of these occurrences may harm our business, financial condition and prospects significantly.
Additionally, if one or more of our product candidates receives marketing approval, and we or others later identify undesirable side effects caused by such products, a number of potentially significant negative consequences could result, including:
-regulatory authorities may withdraw approvals of such product;
-regulatory authorities may require the addition of labeling statements, such as a “black box” warning or a contraindication;
-regulatory authorities may impose additional restrictions on the marketing of, or the manufacturing processes for, the particular product;
-we may be required to create a medication guide outlining the risks of such side effects for distribution to patients;

-we could be sued and held liable for harm caused to patients, or become subject to fines, injunctions or the imposition of civil or criminal penalties; and
-our reputation may suffer.
Any of these events could prevent us from achieving or maintaining market acceptance of the particular product candidate, if approved, and could significantly harm our business, results of operations and prospects.
In addition, if our product candidates are associated with undesirable side effects in certain patient populations, such as pediatric patients or the elderly, we may need to abandon their development or limit development to more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk‑benefit perspective, any of which would harm our business.

RISKS RELATED TO OUR DEPENDENCE ON THIRD PARTIES AND MANUFACTURING
We rely on 3SBio in China as our primary supplier of pegsiticase and on other third parties for the manufacture of our product candidates for preclinical and clinical testing, and expect to continue to do so for the foreseeable future. Our reliance on third parties increases the risk that we will not have sufficient quantities of our product candidates or that such quantities may not be available at an acceptable cost, which could delay, prevent or impair our development or commercialization efforts.
We obtain the biologic pegsiticase, a component of SEL‑212, our lead product candidate, primarily from 3SBio in China. Under our license agreement with 3SBio, we have limited rights to manufacture pegsiticase and, while we have entered into a contract with a back-up supplier located outside of China, we expect to continue to rely on 3SBio as the primary supplier of pegsiticase for the foreseeable future. .
Any disruption in production or inability of 3SBio in China to produce adequate quantities of pegsiticase to meet our needs, whether as a result of a natural disaster or other causes, could impair our ability to operate our business on a day‑to‑day basis and to continue our research and development of our future product candidates. Furthermore, since 3SBio is located in China, we are exposed to the possibility of product supply disruption and increased costs in the event of changes in the policies of the Chinese government, political unrest or unstable economic conditions in China. Any of these matters could materially and adversely affect our business and results of operations. Any issues related to the manufacturing lots or similar action regarding pegsiticase used in preclinical studies or clinical trials could delay the studies or trials or detract from the integrity of the trial data and its potential use in future regulatory filings. In addition, manufacturing interruptions or failure to comply with regulatory requirements by 3SBio could significantly delay our clinical development of potential products and reduce third‑party or clinical researcher interest and support of our proposed trials. These interruptions or failures could also impede commercialization of our future product candidates and impair our competitive position. Further, we may be exposed to fluctuations in the value of the local currency in China. Future appreciation of the local currency could increase our costs. In addition, our labor costs could continue to rise as wage rates increase due to increased demand for skilled laborers and the availability of skilled labor declines in China.
In addition to 3SBio, we rely, and expect to continue to rely, on other third parties for the manufacture of our product candidates for preclinical and clinical testing, as well as for commercial manufacture if any of our product candidates receive marketing approval. Our reliance on such third parties increases the risk that we will not have sufficient quantities of our product candidates on a timely basis or at all, or that such quantities will be available at an acceptable cost or quality, which could delay, prevent or impair our development or commercialization efforts.
We may be unable to establish any agreements with third‑party manufacturers on acceptable terms or at all. Even if we are able to establish agreements with third‑party manufacturers, reliance on third‑party manufacturers entails additional risks, including the:
-inability, failure or unwillingness of third‑party manufacturers to comply with regulatory requirements, maintain quality assurance, meet our needs, specifications or schedules or continue to supply products to us;
-reduced control we have over product development, including with respect to our lead product candidate, due to our reliance on such third‑party manufacturers,
-breach of manufacturing agreements by the third‑party manufacturers;
-misappropriation or disclosure of our proprietary information, including our trade secrets and know‑how;
-relationships that the third party manufacturer may have with others, some of which may be our competitors, and, if it does not successfully carry out its contractual duties, does not meet expectations, experiences work stoppages, or needs to be replaced, we may need to enter into alternative arrangements, which may not be available, desirable or cost‑effective; and

-termination or nonrenewal of agreements by third‑party manufacturers at times that are costly or inconvenient for us.
Third‑party manufacturers may not be able to comply with current Good Manufacturing Practices, or cGMP, regulations or similar regulatory requirements outside the United States. Our failure, or the failure of our third‑party manufacturers, to comply with applicable regulations could result in sanctions being imposed on us, including clinical holds, fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocations, seizures or recalls of product candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our products. If our CMOs are is unable to comply with cGMP regulations or if the FDA does not approve their facilities upon a pre‑approval inspection, our product candidate may not be approved or may be delayed in obtaining approval. In addition, there are a limited number of manufacturers that operate under cGMP regulations and that might be capable of manufacturing our products. Therefore, our product candidates and any future products that we may develop may compete with other products for access to manufacturing facilities. Any failure to gain access to these limited manufacturing facilities could severely impact the clinical development, marketing approval and commercialization of our product candidates.
Any performance failure on the part of our existing or future manufacturers could delay clinical development or marketing approval. We do not currently have arrangements in place for redundant supply or a second source for required raw materials used in the manufacture of our product candidates or for the manufacture of finished product. Moreover, we often rely on one CMO to produce multiple product components. For instance, one of our CMOs produces several polymers used in our SVP technology. If our current CMOs cannot perform as agreed, we may be required to replace such manufacturers and we may be unable to replace them on a timely basis or at all. Our current and expected future dependence upon others for the manufacture of our product candidates or products could delay, prevent or impair our development and commercialization efforts.
Our existing collaborations are important to our business, and future licenses may also be important to us. If we are unable to maintain any of these collaborations, or if these arrangements are not successful, our business could be adversely affected.
We have entered into collaborations with other parties, including pharmaceutical companies and universities, to develop products based on our SVP technology, and such collaborations and licensing arrangements currently represent a significant portion of our product pipeline. Certain of our collaborations also provide us with important funding for some of our development programs and we expect to receive additional funding under collaborations in the future. Our existing collaborations, and any future collaborations we enter into, may pose a number of risks, including the following:
-collaborators have significant discretion in determining the efforts and resources that they will apply to these -collaborations;
-collaborators may not perform their obligations as expected;
-collaborators may not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs based on preclinical or clinical trial results, changes in the collaborators’ strategic focus or available funding, or external factors, such as an acquisition, that divert resources or create competing priorities;
-collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing;
-collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours, which may cause collaborators to cease to devote resources to the commercialization of our product candidates;
-a collaborator with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval may not commit sufficient resources to the marketing and distribution of such product or products;
-disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development, might cause delays or termination of the research, development or commercialization of product candidates, might lead to additional responsibilities for us with respect to product candidates, or might result in litigation or arbitration, any of which would be time‑consuming and expensive;
-collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation;
-collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability;

-collaborations may be terminated for the convenience of the collaborator and, if terminated, we would potentially lose the right to pursue further development or commercialization of the applicable product candidates;
-collaborators may learn about our technology and use this knowledge to compete with us in the future;
-there may be conflicts between different collaborators that could negatively affect those collaborations and potentially others;
-the number and type of our collaborations could adversely affect our attractiveness to future collaborators or acquirers; and
-we currently have, and in the future may have, a limited number of collaborations and the loss of, or a disruption in our relationship with, any one or more of such collaborators may could harm our business.
If our collaborations do not result in the successful development and commercialization of products or if one of our collaborators terminates its agreement with us, we may not receive any future research and development funding or milestone or royalty payments under such collaborations. For example, in November 2016, we received written notice from Sanofi that Sanofi had elected to terminate in its entirety the Sanofi Agreement, which was effective on May 8, 2017, and as a result we will not receive any future payments related in the Sanofi Agreement.
In addition, in June 2017 we notified Spark Therapeutics, Inc., or Spark, that our license agreement with Spark would automatically terminate because Spark had not made a required milestone payment by May 31, 2017, unless the payment was made within five days. While we subsequently entered into a letter agreement with Spark, pursuant to which the parties agreed that Spark would make the milestone payment by June 6, 2017 and we revoked our notice of termination, there can be no assurance that our license agreement with Spark will not be terminated in the future. If we do not receive the funding we expect under these agreements, our continued development of our SVP technology and product candidates could be delayed and we may need additional resources to develop additional product candidates. All of the risks relating to product development, regulatory approval and commercialization described in this Quarterly Report also apply to the activities of our therapeutic program collaborators and there can be no assurance that our collaborations will produce positive results or successful products on a timely basis or at all.
Additionally, subject to its contractual obligations to us, if one of our collaborators is involved in a business combination or otherwise changes its business priorities, the collaborator might deemphasize or terminate the development or commercialization of any product candidate licensed to it by us. If one of our collaborators terminates its agreement with us, we may find it more difficult to attract new collaborators and the perception of our business in the business and financial communities, and our stock price, could be adversely affected. In addition, we have a limited number of collaborations and if our relationship with any one or more of such collaborators were to cease, our business would be harmed as a result.
We may in the future collaborate with additional pharmaceutical and biotechnology companies for development and potential commercialization of therapeutic products. We face significant competition in seeking appropriate collaborators. Our ability to reach a definitive agreement for a collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors. If we are unable to reach agreements with suitable collaborators on a timely basis, on acceptable terms, or at all, we may not be able to access specific antigens that would be suitable to development with our technology, have to curtail the development of a product candidate, reduce or delay its development program or one or more of our other development programs, delay its potential commercialization or reduce the scope of any sales or marketing activities, or increase our expenditures and undertake development or commercialization activities at our own expense. If we elect to fund and undertake development or commercialization activities on our own, we may need to obtain additional expertise and additional capital, which may not be available to us on acceptable terms or at all. If we fail to enter into collaborations and do not have sufficient funds or expertise to undertake the necessary development and commercialization activities, we may not be able to further develop our product candidates or bring them to market or continue to develop our programs, and our business may be materially and adversely affected.
We rely, and expect to continue to rely, on third parties to conduct our clinical trials, and those third parties may not perform satisfactorily, including by failing to meet deadlines for the completion of such trials.
We expect to continue to rely on third parties, such as CROs, clinical data management organizations, medical institutions and clinical investigators, to conduct and manage our clinical trials, including our Phase 2 clinical trial of SEL‑212.
Our reliance on these third parties for research and development activities will reduce our control over these activities but does not relieve us of our responsibilities. For example, we remain responsible for ensuring that each of our clinical trials is conducted in accordance with the general investigational plan and protocols for the trial. Moreover, the FDA requires us to comply with regulatory standards, commonly referred to as good clinical practice, or GCP, regulations, for conducting, recording and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, safety and welfare of trial participants are protected. Other countries’ regulatory agencies also have requirements for

clinical trials. We also are required to register ongoing clinical trials and post the results of completed clinical trials on a government‑sponsored database, ClinicalTrials.gov, within specified timeframes. Failure to do so can result in fines, adverse publicity and civil and criminal sanctions.
Furthermore, these third parties may also have relationships with other entities, some of which may be our competitors. If these third parties do not successfully carry out their contractual duties, do not meet expected deadlines, experience work stoppages, terminate their agreements with us or need to be replaced, or do not conduct our clinical trials in accordance with regulatory requirements or our stated protocols, we may need to enter into new arrangements with alternative third parties, which could be difficult, costly or impossible, and our clinical trials may be extended, delayed or terminated, or may need to be repeated. If any of the foregoing occur, we may not be able to obtain, or may be delayed in obtaining, marketing approvals for our product candidates or in commercializing our product candidates.
We also expect to rely on other third parties to store and distribute drug supplies for our clinical trials. Any performance failure on the part of our distributors could delay clinical development or marketing approval of our product candidates or commercialization of such product candidates, producing additional losses and depriving us of potential product revenue.
We have no experience manufacturing our product candidates at commercial scale, and if we decide to establish our own manufacturing facility, we cannot assure you that we can manufacture our product candidates in compliance with regulations at a cost or in quantities necessary to make them commercially viable.
We have a pilot manufacturing facility at our Watertown, Massachusetts location where we conduct process development, scale‑up activities and the manufacture of SVP product candidates for preclinical use. We rely on the scale equipment at our CMOs for the manufacture of the clinical supply of all of our product candidates. If our facility, or our CMOs’ facilities, were damaged or destroyed, or otherwise subject to disruption, it would require substantial lead‑time to replace our manufacturing capabilities. In such event, we would be forced to identify and rely entirely on alternative third‑party contract manufacturers for an indefinite period of time. Any disruptions or delays at our facility or its failure to meet regulatory compliance would impair our ability to develop and commercialize our product candidates, which would adversely affect our business and results of operations.
In addition, the FDA and other comparable foreign regulatory agencies must, pursuant to inspections that are conducted after submitting a BLA or relevant foreign marketing submission, confirm that the manufacturing processes for the product candidate meet cGMP regulations. We do not currently have any of our own manufacturing facilities that meet the FDA’s cGMP requirements for the production of any product candidates used in humans, and rely on our CMOs for clinical production.
We may choose to establish a manufacturing facility for our product candidates for production at a commercial scale. However, we have no experience in commercial‑scale manufacturing of our product candidates. We currently intend to develop our manufacturing capacity in part by expanding our current facility or building additional facilities. This activity will require substantial additional funds and we would need to hire and train significant numbers of qualified employees to staff these facilities. We may not be able to develop commercial‑scale manufacturing facilities that are adequate to produce materials for additional later‑stage clinical trials or commercial use.
The equipment and facilities employed in the manufacture of pharmaceuticals are subject to stringent qualification requirements by regulatory agencies, including validation of such facilities, equipment, systems, processes and analytics. We may be subject to lengthy delays and expense in conducting validation studies, if we can meet the requirements at all.

RISKS RELATED TO COMMERCIALIZATION OF OUR PRODUCT CANDIDATES AND OTHER LEGAL COMPLIANCE MATTERS
Even if any of our product candidates receives marketing approval, it may fail to achieve the degree of market acceptance by physicians, patients, third‑party payors and others in the medical community necessary for commercial success.
If any of our product candidates receives marketing approval, it may nonetheless fail to gain sufficient market acceptance by physicians, patients, third‑party payors and others in the medical community. If our product candidates do not achieve an adequate level of acceptance, we may not generate significant product revenues and we may not become profitable. The degree of market acceptance of our product candidates, if any, will depend on a number of factors, including:
-their efficacy, safety and other potential advantages compared to alternative treatments;
-the clinical indications for which our product candidates are approved;
-our ability to offer them for sale at competitive prices;
-their convenience and ease of administration compared to alternative treatments;

-the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;
-the strength of marketing and distribution support;
-the availability of third‑party coverage and adequate reimbursement for our product candidates;
-the prevalence and severity of their side effects and their overall safety profiles;
-any restrictions on the use of our product candidates together with other medications;
-interactions of our product candidates with other medicines patients are taking;
-our ability to create awareness with patients and physicians about the harmful effects of uric acid deposits;
-the timing of market introduction of any approved product candidates as well as competitive products and other therapies;
-inability of certain types of patients to take our product candidates;
-their ability to remain attractive in the event of changing treatment guidelines;
-adverse publicity about the product or favorable publicity about competitive products; and
-potential product liability claims.
The research, development and commercialization of our product candidates depends upon our maintaining strong working relationships with the medical community. We rely on these professionals to provide us with considerable knowledge and experience regarding the development, marketing and commercialization of our product candidates. If we are unable to maintain our strong relationships with these professionals and continue to receive their advice and input, our products and product candidates may not be developed and marketed in line with such professionals’ needs and expectations. Accordingly, the development and commercialization of our products and product candidates could suffer, which could have a material adverse effect on our business and results of operations.
We currently have no sales organization. If we are unable to establish effective sales, marketing and distribution capabilities, or enter into agreements with third parties with such capabilities, we may not be successful in commercializing our product candidates if and when they are approved.
We do not have a sales or marketing infrastructure and have no experience in the sale, marketing or distribution of pharmaceutical products. To achieve commercial success for any product candidate for which we obtain marketing approval, we will need to establish a sales and marketing organization or make arrangements with third parties to perform sales and marketing functions and we may not be successful in doing so.
In the future, we expect to build a focused sales and marketing infrastructure to market or co‑promote our product candidates in the United States and potentially elsewhere, if and when they are approved. There are risks involved with establishing our own sales, marketing and distribution capabilities. For example, recruiting and training a sales force is expensive and time‑consuming and could delay any product launch. If the commercial launch of a product candidate for which we recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses. This may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.
Factors that may inhibit our efforts to commercialize our product candidates on our own include:
-our inability to recruit, train and retain adequate numbers of effective sales and marketing personnel;
-the inability of sales personnel to obtain access to or educate physicians on the benefits of our products;
-the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines;
-unforeseen costs and expenses associated with creating an independent sales and marketing organization; and
-inability to obtain sufficient coverage and reimbursement from third‑party payors and governmental agencies for our product candidates.
Outside the United States, we may rely on third parties to sell, market and distribute our product candidates. We may not be successful in entering into arrangements with such third parties or may be unable to do so on terms that are favorable to us. In addition, our product revenue and our profitability, if any, may be lower if we rely on third parties for these functions than if we were to market, sell and distribute any products that we develop ourselves. We likely will have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our products effectively. If we do not establish sales, marketing and distribution capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing our product candidates.

Our product candidates, if approved, may fail to offer material commercial advantages over other treatments.
The therapeutic advantages that we believe may be offered by our product candidates, if approved, may fail to materialize, or may not be recognized by physicians, hospital administrators, patients, caregivers, healthcare payors and others in the medical community. For example, physicians may be skeptical to use SEL‑212 for the treatment of chronic severe gout. Patients may also be skeptical of using a product based on our SVP technology. The therapeutic advantages of our product candidates may not be sufficient to either move market share to us or expand the population of patients using our treatments.
We face substantial competition, which may result in others discovering, developing or commercializing competing products before or more successfully than we do.
The development and commercialization of new drug and biologic products and technologies is highly competitive and is characterized by rapid and substantial technological development and product innovations. We protect our products and technologies by filing patent applications in major pharmaceutical markets as well as leading emerging growth markets. We have either been granted patents or filed patent applications covering our SVP technology, our immune tolerance programs and our SEL-212 product candidate. To the extent that our product candidates and technologies are protected by such intellectual property rights, they will be protected from competition for the life of the applicable patents. However, we are aware of a number of large pharmaceutical and biotechnology companies, including Sanofi, Horizon Pharma plc, Pfizer Inc., and Merck & Co., Inc., as well as smaller, early-stage companies, that offer or are pursuing the development of pharmaceutical products or technologies that may address one or more indications that our product candidates target. We face competition with respect to our current product candidates, and will face competition with respect to any product candidates that we may seek to develop or commercialize in the future, from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies worldwide.
Many of the companies against which we are competing or against which we may compete in the future have significantly greater financial resources, established presence in the market and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and reimbursement for product candidates and in marketing approved products than we do. Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors.
These third parties compete with us in recruiting and retaining qualified scientific, sales and marketing and management personnel, establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.
Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market, especially for any competitor developing a microbiome therapeutic which will likely share our same regulatory approval requirements. In addition, our ability to compete may be affected in many cases by insurers or other third‑party payors seeking to encourage the use of generic or biosimilar products.
Even if we are able to commercialize any product candidates, the products may become subject to unfavorable pricing regulations or third‑party coverage or reimbursement policies, any of which would harm our business.
Significant uncertainty exists as to the coverage and reimbursement status of any product candidates for which we obtain regulatory approval. Our ability to commercialize any product candidates successfully will depend, in part, on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations. Government authorities and third‑party payors, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels.
Obtaining and maintaining adequate reimbursement for our products may be difficult. The process for determining whether a third‑party payor will provide coverage for a product may be separate from the process for setting the price of a product or for establishing the reimbursement rate that such a payor will pay for the product. Further, one payor’s determination to provide coverage for a product does not assure that other payors will also provide coverage and adequate reimbursement for the product. We cannot be certain if and when we will obtain an adequate level of reimbursement for our products by third‑party payors. Even if we do obtain adequate levels of reimbursement, third‑party payors, such as government or private healthcare insurers, carefully review and increasingly question the coverage of, and challenge the prices charged for, products. Reimbursement rates from private health insurance companies vary depending on the company, the insurance plan and other factors. A primary trend in the U.S. healthcare industry and elsewhere is cost containment. Government authorities and third‑party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications. Increasingly, third‑party payors are requiring that pharmaceutical companies provide them with predetermined

discounts from list prices and are challenging the prices charged for products. We may also be required to conduct expensive pharmacoeconomic studies to justify coverage and reimbursement or the level of reimbursement relative to other therapies. If coverage and reimbursement are not available or reimbursement is available only to limited levels, we may not be able to successfully commercialize any product candidate for which we obtain marketing approval.
There may be significant delays in obtaining reimbursement for newly approved products, and coverage may be more limited than the purposes for which the product is approved by the FDA or similar regulatory authorities outside of the United States. Moreover, eligibility for reimbursement does not imply that a product will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution. Interim reimbursement levels for new products, if applicable, may also not be sufficient to cover our costs and may not be made permanent. Reimbursement rates may vary according to the use of the product and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost products and may be incorporated into existing payments for other services. Net prices for products may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of products from countries where they may be sold at lower prices than in the United States. Our inability to promptly obtain coverage and adequate reimbursement rates from both government‑funded and private payors for any approved products that we develop could have a material adverse effect on our operating results, our ability to raise capital needed to commercialize products and our overall financial condition.
The regulations that govern marketing approvals, pricing, coverage and reimbursement for new products vary widely from country to country. Current and future legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtaining approvals. Some countries require approval of the sale price of a product before it can be marketed. In many countries, the pricing review period begins after marketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control, including possible price reductions, even after initial approval is granted. As a result, we might obtain marketing approval for a product in a particular country, but then be subject to price regulations that delay our commercial launch of the product, possibly for lengthy time periods, and negatively impact the revenues we are able to generate from the sale of the product in that country. Adverse pricing limitations may hinder our ability to recoup our investment in one or more product candidates, even if our product candidates obtain marketing approval. There can be no assurance that our product candidates, if they are approved for sale in the United States or in other countries, will be considered medically necessary for a specific indication or cost‑effective, or that coverage or an adequate level of reimbursement will be available.
Product liability lawsuits against us could cause us to incur substantial liabilities and limit commercialization of any products that we may develop.
We face an inherent risk of product liability exposure related to the testing of our product candidates in clinical trials and will face an even greater risk if we commercially sell any products that we may develop. If we cannot successfully defend ourselves against claims that our product candidates or products caused injuries, we will incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:
-regulatory investigations, product recalls or withdrawals, or labeling, marketing or promotional restrictions;
-decreased demand for any product candidates or products that we may develop;
-injury to our reputation and significant negative media attention;
-loss of clinical trial participants or increased difficulty in enrolling future participants;
-significant costs to defend the related litigation or to reach a settlement;
-substantial payments to trial participants or patients;
-loss of revenue;
-reduced resources of our management to pursue our business strategy; and
-the inability to commercialize any products that we may develop.
We maintain general liability, product liability and umbrella liability insurance. Our existing insurance coverage may not fully cover potential liabilities that we may incur. The cost of any product liability litigation or other proceeding, even if resolved in our favor, could be substantial. We will need to increase our insurance coverage as our risks of exposure increase, which, for example, would happen if and when we begin selling any product candidate that receives marketing approval. In addition, certain types of insurance coverage are becoming increasingly expensive. If we are unable to obtain or maintain sufficient insurance coverage at an acceptable cost or to otherwise protect against potential product liability claims, it could prevent or inhibit the development and commercial production and sale of any approved product candidates, which could adversely affect our business, financial condition, results of operations and prospects.

Failure to obtain marketing approval in international jurisdictions would prevent our product candidates from being marketed abroad.
Although we do not have any current plans to market and sell our products in other jurisdictions outside of the United States, we may decide to do so in the future and either we or our collaborators would need to obtain separate marketing approvals and comply with numerous and varying regulatory requirements. The approval procedure varies among countries and can involve additional testing. The time required to obtain approval in foreign countries may differ substantially from that required to obtain FDA approval. Clinical trials conducted in one country may not be accepted by regulatory authorities in other countries. The regulatory approval process outside the United States generally includes all of the risks associated with obtaining FDA approval. In addition, in many countries outside the United States, it is required that the product candidate be approved for reimbursement before the product candidate can be approved for sale in that country. We or our collaborators may not obtain approvals for our product candidates from regulatory authorities outside the United States on a timely basis, if at all. Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside the United States does not ensure approval by regulatory authorities in other countries or jurisdictions, or by the FDA. However, a failure or delay in obtaining regulatory approval in one country may have a negative effect on the regulatory process in others. We may not be able to file for marketing approvals and may not receive necessary approvals to commercialize our product candidates in any market.
Although we are not currently marketing our product candidates, including to healthcare providers, if and when we do, our relationships with healthcare providers, customers and third‑party payors may be subject to applicable anti‑kickback, fraud and abuse and other healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, exclusion from government healthcare programs, contractual damages, reputational harm and diminished profits and future earnings.
Healthcare providers, customers and third‑party payors will play a primary role in the recommendation and prescription of any product candidates for which we may obtain marketing approval. Our future arrangements with third-party payors and customers may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell and distribute any products for which we obtain marketing approval. Restrictions under applicable federal and state healthcare laws and regulations may include the following:
-the federal Anti‑Kickback Statute, which prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service for which payment may be made under a federal healthcare program such as Medicare and Medicaid. A person or entity does not need to have actual knowledge of the federal Anti‑Kickback Statute or specific intent to violate it to have committed a violation; in addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti‑Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act);
-the federal false claims and civil monetary penalties laws, including the civil False Claims Act, which impose criminal and civil penalties, through civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;
-the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal and civil liability for, among other things, executing or attempting to execute a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters. Similar to the federal Anti‑Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation;
-HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and its implementing regulations, which also imposes obligations, including mandatory contractual terms, on certain types of people and entities with respect to safeguarding the privacy, security and transmission of individually identifiable health information;
-the federal Physician Payments Sunshine Act, which requires manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to the government information related to certain payments or other “transfers of value” made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, and requires applicable manufacturers to report annually to the government ownership and investment interests held by the physicians described above and their immediate family members and payments or other “transfers of value” to such physician owners; and

-analogous state and foreign laws and regulations, such as state anti‑kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by third‑party payors, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures and pricing information; and state and foreign laws governing the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
Efforts to ensure that our business arrangements with third parties comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other governmental laws and regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, disgorgement, contractual damages, reputational harm, diminished profits and the curtailment or restructuring of our operations. If any of the physicians or other healthcare providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs. The risk of our being found in violation of these laws is increased by the fact that many of them have not been fully interpreted by the regulatory authorities or the courts, and their provisions are open to a variety of interpretations. Because of the breadth of these laws and the narrowness of the statutory exceptions and safe harbors available under such laws, it is possible that some of our business activities, including our relationships with physicians and other healthcare providers, some of whom will recommend, purchase and/or prescribe our product candidates, if approved, could be subject to challenge under one or more of such laws.
Recently enacted and future legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and affect the prices we may obtain.
In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of our product candidates, restrict or regulate post‑approval activities and affect our ability to profitably sell any product candidates for which we obtain marketing approval.
For example, in the United States, in 2010, President Obama signed into law the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively the ACA, a sweeping law intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add new transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.
Among the provisions of the ACA of importance to our potential product candidates are the following:
-an annual, nondeductible fee payable by any entity that manufactures or imports specified branded prescription drugs and biologic agents;
-an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program;
-a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected;
-a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 50% point‑of‑sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries under their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D;
-extension of manufacturers’ Medicaid rebate liability to individuals enrolled in Medicaid managed care organizations
-expansion of eligibility criteria for Medicaid programs;
-expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing program;
-a new requirement to annually report drug samples that manufacturers and distributors provide to physicians; and
-a new Patient‑Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research.
Since its enactment, there have been judicial and Congressional challenges to certain aspects of the ACA. As a result, there have been delays in the implementation of, and action taken to repeal or replace, certain aspects of the ACA. We expect that the

new presidential administration and U.S. Congress will continue to seek to modify, repeal, or otherwise invalidate all, or certain provisions of, the ACA. There is uncertainty with respect to the impact the current presidential administration and the U.S. Congress may have, if any, and any changes, which could have an impact on coverage and reimbursement for healthcare items and services covered by plans that were authorized by the ACA, will likely take time to unfold. We cannot predict the ultimate content, timing or effect of any healthcare reform legislation or the impact of potential legislation on us.
In addition, other legislative changes have been proposed and adopted since the ACA was enacted. These changes included aggregate reductions to Medicare payments to providers of 2% per fiscal year, which went into effect in April 2013 and, due to subsequent legislative amendments to the statute, will remain in effect through 2025 unless additional Congressional action is taken. In January 2013, President Obama signed into law the American Taxpayer Relief Act of 2012, which, among other things, further reduced Medicare payments to several types of providers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. These new laws may result in additional reductions in Medicare and other healthcare funding.
We expect that the ACA, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, new payment methodologies and in additional downward pressure on the price that we receive for any approved product. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability or commercialize our products.
Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed bills designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products. For example, the 21st Century Cures Act changed the reimbursement methodology for infusion drugs and biologics furnished through durable medical equipment in an attempt to remedy over- and underpayment of certain products. Individual states in the United States have become increasingly aggressive in implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. Legally mandated price controls on payment amounts by third party payors or other restrictions could harm our business, results of operations, financial condition and prospects. In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs. This could reduce the ultimate demand for our product candidates, if approved, or put pressure on our product pricing, which could negatively affect our business, results of operations, financial condition and prospects.
Legislative and regulatory proposals have been made to expand post‑approval requirements and restrict sales and promotional activities for pharmaceutical products. We cannot be sure whether additional legislative changes will be enacted, or whether the FDA’s regulations, guidance or interpretations will be changed, or what the impact of such changes on the marketing approvals of our product candidates, if any, may be. In addition, increased scrutiny by the U.S. Congress of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject us to more stringent product labeling and post‑marketing testing and other requirements.
Any product candidate for which we obtain marketing approval could be subject to post‑marketing restrictions or withdrawal from the market, and we may be subject to penalties if we fail to comply with regulatory requirements or if we experience unexpected problems with our products, when and if any of them are approved.
Any product candidate for which we obtain marketing approval, along with the manufacturing processes, post‑approval clinical data, labeling, advertising and promotional activities for such product, will be subject to the continual requirements of and review by the FDA and other regulatory authorities. These requirements include submissions of safety and other post‑marketing information and reports, registration and listing requirements, cGMP requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and documents, requirements regarding the distribution of samples to physicians and recordkeeping. We and our contract manufacturers will also be subject to continual review and periodic inspections to assess compliance with cGMP. Accordingly, we and others with whom we work must continue to expend time, money and effort in all areas of regulatory compliance, including manufacturing, production and quality control.
Even if marketing approval of a product candidate is granted, the approval may be subject to limitations on the indicated uses for which the product may be marketed or to the conditions of approval, including the requirement to implement a risk evaluation and mitigation strategy, or REMS, which could include requirements for a medication guide, physician communication plans or additional elements to ensure safe use, such as restricted distribution methods, patient registries and

other risk mitigation tools. If any of our product candidates receives marketing approval, the accompanying label may limit the approved use of our product, which could limit sales of the product.
The FDA may also impose requirements for costly post‑marketing studies or clinical trials and surveillance to monitor the safety or efficacy of our approved products. The FDA closely regulates the post‑approval marketing and promotion of drugs and biologics to ensure they are marketed only for the approved indications and in accordance with the provisions of the approved labeling. The FDA imposes stringent restrictions on manufacturers’ communications regarding off‑label use, and if we market our products outside of their approved indications, we may be subject to enforcement action for off‑label marketing. Violations of the FDA’s restrictions relating to the promotion of prescription products may also lead to investigations alleging violations of federal and state health care fraud and abuse laws, as well as state consumer protection laws.
In addition, if a regulatory agency or we later discover previously unknown problems with our products, such as adverse events of unexpected severity or frequency, problems with manufacturers or manufacturing processes, or failure to comply with regulatory requirements, the regulatory agency may impose restrictions on the products or us, including requiring withdrawal of the product from the market. Any failure to comply with applicable regulatory requirements may yield various results, including:
-litigation involving patients taking our products;
-restrictions on such products, manufacturers or manufacturing processes;
-restrictions on the labeling or marketing of a product;
-restrictions on product distribution or use;
-requirements to conduct post‑marketing studies or clinical trials;
-warning letters;
-withdrawal of products from the market;
-suspension or termination of ongoing clinical trials;
-refusal to approve pending applications or supplements to approved applications that we submit;
-recall of products;
-fines, restitution or disgorgement of profits or revenues;
-suspension or withdrawal of marketing approvals;
-damage to relationships with existing and potential collaborators;
-unfavorable press coverage and damage to our reputation;
-refusal to permit the import or export of our products;
-product seizure or detention;
-injunctions; or
-imposition of civil or criminal penalties.
Noncompliance with other requirements in foreign jurisdictions regarding safety monitoring or pharmacovigilance can also result in significant financial penalties. Similarly, failure to comply with U.S. and foreign regulatory requirements regarding the development of products for pediatric populations and the protection of personal health information can also lead to significant penalties and sanctions.
Any government investigation of alleged violations of law could require us to expend significant time and resources in response, and could generate negative publicity. Any failure to comply with ongoing regulatory requirements may significantly and adversely affect our ability to commercialize and generate revenues. If regulatory sanctions are applied or if regulatory approval is withheld or withdrawn, the value of our company and our operating results will be adversely affected.
The FDA’s and other regulatory authorities’ policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our product candidates. For example, in December 2016, the 21st Century Cures Act, or Cures Act, was signed into law. The Cures Act, among other things, is intended to modernize the regulation of drugs and spur innovation, but its ultimate implementation is unclear. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained and we may not achieve or sustain profitability, which would adversely affect our business, prospects, financial condition and results of operations.

We also cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative or executive action, either in the United States or abroad. For example, certain policies of the current presidential administration may impact our business and industry. Namely, the current presidential administration has taken several executive actions, including the issuance of a number of Executive Orders, that could impose significant burdens on, or otherwise materially delay, FDA’s ability to engage in routine regulatory and oversight activities such as implementing statutes through rulemaking, issuance of guidance, and review and approval of marketing applications. If these executive actions impose constraints on FDA’s ability to engage in oversight and implementation activities in the normal course, our business may be negatively impacted.
We are subject to U.S. and certain foreign export and import controls, sanctions, embargoes, anti‑corruption laws, and anti‑money laundering laws and regulations. Compliance with these legal standards could impair our ability to compete in domestic and international markets. We can face criminal liability and other serious consequences for violations, which can harm our business.
We are subject to export control and import laws and regulations, including the U.S. Export Administration Regulations, U.S. Customs regulations, various economic and trade sanctions regulations administered by the U.S. Treasury Department’s Office of Foreign Assets Controls, the U.S. Foreign Corrupt Practices Act of 1977, as amended, the U.S. domestic bribery statute contained in 18 U.S.C. § 201, the U.S. Travel Act, the USA PATRIOT Act, and other state and national anti‑bribery and anti‑money laundering laws in the countries in which we conduct activities. Anti‑corruption laws are interpreted broadly and prohibit companies and their employees, agents, contractors and other partners from authorizing, promising, offering or providing, directly or indirectly, improper payments or anything else of value to recipients in the public or private sector. We may engage third parties for clinical trials outside of the United States, to sell our product candidates abroad once we enter a commercialization phase, and/or to obtain necessary permits, licenses, patent registrations, and other regulatory approvals. We have direct or indirect interactions with officials and employees of government agencies or government‑affiliated hospitals, universities and other organizations. We can be held liable for the corrupt or other illegal activities of our employees, agents, contractors and other partners, even if we do not explicitly authorize or have actual knowledge of such activities. Our violations of the laws and regulations described above may result in substantial civil and criminal fines and penalties, imprisonment, the loss of export or import privileges, debarment, tax reassessments, breach of contract and fraud litigation, reputational harm and other consequences.
Governments outside the United States tend to impose strict price controls, which may adversely affect our revenues, if any.
In some countries, the pricing of prescription pharmaceuticals is subject to governmental control. In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product candidates. In addition, there can be considerable pressure by governments and other stakeholders on prices and reimbursement levels, including as part of cost containment measures. Political, economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after coverage and reimbursement have been obtained. Reference pricing used by various countries and parallel distribution or arbitrage between low‑priced and high‑priced countries, can further reduce prices. To obtain reimbursement or pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost‑effectiveness of our product candidate to other available therapies, which is time‑consuming and costly. If coverage and reimbursement of our product candidates are unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our business could be harmed, possibly materially.
If we or our contract manufacturers or other third parties fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could harm our business.
We and our contract manufacturers and other third parties with whom we do business are subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. Our operations involve the use of hazardous and flammable materials, including biological materials and chemicals, such as trichloroethylene. Our operations also produce hazardous waste products. We generally contract with third parties for the disposal of these materials and wastes. We cannot eliminate the risk of contamination or injury from these materials. In the event of contamination or injury resulting from our use of hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with such laws and regulations.
Although we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage against potential liabilities. We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous or radioactive materials.
In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. These current or future laws and regulations may impair our research, development or production efforts. The failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions.

Negative public opinion and increased regulatory scrutiny of gene therapy and genetic research may damage public perception of our product candidates or compromise our ability to conduct our business or obtain regulatory approvals for our product candidates.
Gene therapy remains a novel technology. Public perception may be influenced by claims that gene therapy is unsafe, and gene therapy may not gain the acceptance of the public or the medical community. In particular, our success will depend upon physicians specializing in the treatment of those diseases that our product candidates target and prescribing treatments that involve the use of our product candidates in lieu of, or in addition to, existing treatments they are already familiar with and for which greater clinical data may be available. More restrictive government regulations or negative public opinion would have a negative effect on our business or financial condition and may delay or impair the development and commercialization of our product candidates or demand for any products we may develop. Our product candidates, including our products that utilize viral delivery systems, could produce adverse events. Adverse events in our clinical trials or following approval of any of our product candidates, even if not ultimately attributable to our product candidates, could result in increased governmental regulation, unfavorable public perception, potential regulatory delays in the testing or approval of our product candidates, stricter labeling requirements for those product candidates that are approved and a decrease in demand for any such product candidates.

RISKS RELATED TO OUR INTELLECTUAL PROPERTY
If we are unable to adequately protect our proprietary technology, or obtain and maintain issued patents which are sufficient to protect our product candidates, others could compete against us more directly, which would negatively impact our business.
Our success depends in large part on our ability to obtain and maintain patent and other intellectual property protection in the United States and other countries with respect to our proprietary technology and products. We seek to protect our proprietary position by filing patent applications in the United States and abroad related to our novel technologies and product candidates. We also rely on trade secrets to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection.
The patent prosecution process is expensive and time‑consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost, in a timely manner or in all jurisdictions. Prosecution of our patent portfolio is at a very early stage, and we are just beginning to reach the statutory deadlines for deciding whether and where to initiate prosecution in specific foreign jurisdictions by filing national stage applications based on our Patent Cooperation Treaty, or PCT, applications. As those deadlines come due, we will have to decide whether and where to pursue patent protection for the various inventions claimed in our patent portfolio, and we will only have the opportunity to obtain patents in those jurisdictions where we pursue protection. It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection. It is possible that defects of form in the preparation or filing of our patents or patent applications may exist, or may arise in the future, such as, with respect to proper priority claims, inventorship, claim scope or patent term adjustments. If there are material defects in the form or preparation of our patents or patent applications, such patents or applications may be invalid and unenforceable. Moreover, our competitors may independently develop equivalent knowledge, methods and know‑how. Any of these outcomes could impair our ability to prevent competition from third parties, which may have an adverse impact on our business.
In some circumstances, we may not have the right to control the preparation, filing and prosecution of patent applications, or to maintain the patents covering technology that we license from third parties. We may also require the cooperation of our licensors to enforce any licensed patent rights, and such cooperation may not be provided. Therefore, these patents and applications may not be prosecuted and enforced in a manner consistent with the best interests of our business. Moreover, we have obligations under our licenses, and any failure to satisfy those obligations could give our licensor the right to terminate the license. Termination of a necessary license could have a material adverse impact on our business.
We currently own ten issued U.S. patents. Although we have patent applications pending, we cannot provide any assurances that any of these pending patent applications will mature into issued patents and, if they do, that such patents or our current patents will include claims with a scope sufficient to protect our product candidates or otherwise provide any competitive advantage. Further, it is possible that a patent claim may provide coverage for some but not all parts of a product candidate or third‑party product. These and other factors may provide opportunities for our competitors to design around our patents, should they issue.
Moreover, other parties may have developed technologies that may be related or competitive to our approach, and may have filed or may file patent applications, and may have received or may receive patents that may overlap or conflict with our patent applications, either by claiming similar methods or by claiming subject matter that could dominate our patent position. In

addition, given the early stage of prosecution of our portfolio, it may be some time before we understand how patent offices react to our patent claims and whether they identify prior art of relevance that we have not already considered.
Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all. Therefore, we cannot know with certainty whether we were the first to make the inventions claimed in any owned patents or pending patent applications, or that we were the first to file for patent protection of such inventions, nor can we know whether those from whom we may license patents were the first to make the inventions claimed or were the first to file. For these and other reasons, the issuance, scope, validity, enforceability and commercial value of our patent rights are subject to a level of uncertainty. Our pending and future patent applications may not result in patents being issued that protect our technology or products, in whole or in part, or which effectively prevent others from commercializing competitive technologies and products. Changes in either the patent laws or interpretation of the patent laws in the United States and other countries may diminish the value of our patents or narrow the scope of our patent protection.
We may be subject to a third‑party preissuance submission of prior art to the U.S. Patent and Trademark Office, or USPTO, or become involved in opposition, derivation, reexamination, inter partes review, post‑grant review or interference proceedings challenging our patent rights or the patent rights of others. An adverse determination in any such submission, proceeding or litigation could reduce the scope of, or invalidate, our patent rights, allow third parties to commercialize our technology or products and compete directly with us, without payment to us, or result in our inability to manufacture or commercialize product candidates without infringing third‑party patent rights. In addition, if the breadth or strength of protection provided by our patents and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidates. Furthermore, an adverse decision in an interference proceeding can result in a third party receiving the patent right sought by us, which in turn could affect our ability to develop, market or otherwise commercialize our product candidates. The issuance, scope, validity, enforceability and commercial value of our patents are subject to a level of uncertainty.
The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions and has in recent years been the subject of much litigation. Due to legal standards relating to patentability, validity, enforceability and claim scope of patents covering biotechnological and pharmaceutical inventions, our ability to obtain, maintain and enforce patents is uncertain and involves complex legal and factual questions. Even if issued, a patent’s validity, inventorship, ownership or enforceability is not conclusive. Accordingly, rights under any existing patent or any patents we might obtain or license may not cover our product candidates, or may not provide us with sufficient protection for our product candidates to afford a commercial advantage against competitive products or processes, including those from branded and generic pharmaceutical companies.
In addition to the protection afforded by patents, we rely on trade secret protection and confidentiality agreements to protect proprietary know‑how, information, or technology that is not covered by our patents. Although our agreements require all of our employees to assign their inventions to us, and we require all of our employees, consultants, advisors and any other third parties who have access to our trade secrets, proprietary know‑how and other confidential information and technology to enter into appropriate confidentiality agreements, we cannot be certain that our trade secrets, proprietary know‑how, and other confidential information and technology will not be subject to unauthorized disclosure or that our competitors will not otherwise gain access to or independently develop substantially equivalent trade secrets, proprietary know‑how, and other information and technology. Furthermore, the laws of some foreign countries do not protect proprietary rights to the same extent or in the same manner as the laws of the United States As a result, we may encounter significant problems in protecting and defending our intellectual property globally. If we are unable to prevent unauthorized disclosure of our intellectual property related to our product candidates and technology to third parties, we may not be able to establish or maintain a competitive advantage in our market, which could adversely affect our business and operations.
Intellectual property rights do not prevent all potential threats to competitive advantages we may have.
The degree of future protection afforded by our intellectual property rights is uncertain because intellectual property rights have limitations, and intellectual property rights may not adequately protect our business or permit us to maintain our competitive advantage.
The following examples are illustrative:
-others may be able to make compounds that are the same as or similar to our current or future product candidates but that are not covered by the claims of the patents that we own or have exclusively licensed;
-we or any of our licensors or collaborators might not have been the first to make the inventions covered by the patents or pending patent applications that we own or have exclusively licensed;
-we or any of our licensors or collaborators might not have been the first to file patent applications covering certain of our inventions;

-others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights;
-the prosecution of our pending patent applications may not result in granted patents;
-granted patents that we own or have licensed may not cover our products or may be held not infringed, invalid or unenforceable, as a result of legal challenges by our competitors;
-with respect to granted patents that we own or have licensed, especially patents that we either acquire or in‑license, if certain information was withheld from or misrepresented to the patent examiner, such patents might be held to be unenforceable;
-patent protection on our product candidates may expire before we are able to develop and commercialize the product, or before we are able to recover our investment in the product candidates;
-our competitors might conduct research and development activities in the United States and other countries that provide a safe harbor from patent infringement claims for such activities, as well as in countries in which we do not have patent rights, and may then use the information learned from such activities to develop competitive products for sale in markets where we intend to market our product candidates;
-we may not develop additional proprietary technologies that are patentable;
-the patents of others may have an adverse effect on our business; and
-we may choose not to file a patent application for certain technologies, trade secrets or know‑how, and a third party may subsequently file a patent covering such intellectual property.
We may not identify relevant patents or may incorrectly interpret the relevance, scope or expiration of a patent, which might adversely affect our ability to develop and market our product candidates.
We cannot guarantee that any of our patent searches or analyses, including but not limited to the identification of relevant patents, the scope of patent claims or the expiration of relevant patents, are complete and thorough, nor can we be certain that we have identified each and every patent and pending application in the United States and abroad that is relevant to or necessary for the commercialization of our product candidates in any jurisdiction.
The scope of a patent claim is determined by an interpretation of the law, the written disclosure in a patent and the patent’s prosecution history. Our interpretation of the relevance or the scope of a patent or a pending application may be incorrect, which may negatively impact our ability to market our products or pipeline molecules. We may incorrectly determine that our product candidates are not covered by a third‑party patent.
Many patents may cover a marketed product, including but not limited to the composition of the product, methods of use, formulations, cell line constructs, vectors, growth media, production processes and purification processes. The identification of all patents and their expiration dates relevant to the production and sale of an originator product is extraordinarily complex and requires sophisticated legal knowledge in the relevant jurisdiction. It may be impossible to identify all patents in all jurisdictions relevant to a marketed product. Our determination of the expiration date of any patent in the United States or abroad that we consider relevant may be incorrect which may negatively impact our ability to develop and market our product candidates.
Our failure to identify and correctly interpret relevant patents may negatively impact our ability to develop and market our product candidates.
If we are unable to protect the confidentiality of our trade secrets and know‑how, our business and competitive position would be harmed.
In addition to seeking patents for some of our technology and product candidates, we also rely on trade secrets, including unpatented know‑how, technology and other proprietary information, to maintain our competitive position. We seek to protect these trade secrets, in part, by entering into non‑disclosure and confidentiality agreements with parties who have access to them, such as our employees, corporate collaborators, outside scientific collaborators, contract manufacturers, consultants, advisors and other third parties. We also seek to enter into confidentiality and invention or patent assignment agreements with our employees, advisors and consultants. Despite these efforts, any of these parties may breach the agreements and disclose our proprietary information, including our trade secrets, and we may not be able to obtain adequate remedies for such breaches. Our trade secrets may also be obtained by third parties by other means, such as breaches of our physical or computer security systems. Enforcing a claim that a party illegally disclosed or misappropriated a trade secret is difficult, expensive and time‑consuming, and the outcome is unpredictable. In addition, some courts inside and outside the United States are less willing or unwilling to protect trade secrets. Moreover, if any of our trade secrets were to be lawfully obtained or independently developed by a competitor, we would have no right to prevent them, or those to whom they communicate it, from using that

technology or information to compete with us. If any of our trade secrets were to be disclosed to, or independently developed by, a competitor, our competitive position would be harmed.
Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our product candidates.
As is the case with other biotechnology companies, our success is heavily dependent on intellectual property, particularly patents. Obtaining and enforcing patents in the biotechnology industry involves both technological and legal complexity, and is therefore costly, time‑consuming and inherently uncertain. In addition, recent patent reform legislation could further increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents. On September 16, 2011, the Leahy‑Smith America Invents Act, or the Leahy‑Smith Act, was signed into law. The Leahy‑Smith Act includes a number of significant changes to U.S. patent law. These include provisions that affect the way patent applications are prosecuted and may also affect patent litigation. The USPTO recently developed new regulations and procedures to govern administration of the Leahy‑Smith Act, and many of the substantive changes to patent law associated with the Leahy‑Smith Act, in particular the first to file provisions, became effective on March 16, 2013. A third party that files a patent application in the USPTO after that date but before us could therefore be awarded a patent covering an invention of ours even if we had made the invention before it was made by the third party. This requires us to be cognizant of the time from invention to filing of a patent application. Thus, for our U.S. patent applications containing a priority claim after March 16, 2013, there is a greater level of uncertainty in the patent law. Moreover, some of the patent applications in our portfolio will be subject to examination under the pre‑Leahy‑Smith Act law and regulations, while other patents applications in our portfolio will be subject to examination under the law and regulations, as amended by the Leahy‑Smith Act. This introduces additional complexities into the prosecution and management of our portfolio.
In addition, the Leahy‑Smith Act limits where a patentee may file a patent infringement suit and provides opportunities for third parties to challenge any issued patent in the USPTO. These provisions apply to all of our U.S. patents, even those issued before March 16, 2013. Because of a lower evidentiary standard in USPTO proceedings compared to the evidentiary standard in U.S. federal court necessary to invalidate a patent claim, a third party could potentially provide evidence in a USPTO proceeding sufficient for the USPTO to hold a claim invalid even though the same evidence would be insufficient to invalidate the claim if first presented in a federal court action.
Accordingly, a third party may attempt to use the USPTO procedures to invalidate our patent claims because it may be easier for them to do so relative to challenging the patent in a federal court action. It is not clear what, if any, impact the Leahy‑Smith Act will have on the operation of our business. However, the Leahy‑Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our business and financial condition.
In addition, recent U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain situations. From time to time, the U.S. Supreme Court, other federal courts, the U.S. Congress or the USPTO may change the standards of patentability, and any such changes could have a negative impact on our business.
Depending on these and other decisions by the U.S. Congress, the federal courts and the USPTO, the laws and regulations governing patents could change or be interpreted in unpredictable ways that would weaken our ability to obtain new patents or to enforce any patents that may issue to us in the future. In addition, these events may adversely affect our ability to defend any patents that may issue in procedures in the USPTO or in courts.
We may become involved in lawsuits to protect or enforce our patents or other intellectual property, which could be expensive, time‑consuming and ultimately unsuccessful.
Competitors may infringe our issued patents or other intellectual property. To counter infringement or unauthorized use, we may be required to file infringement claims, which can be expensive and time‑consuming. Any claims we assert against perceived infringers could provoke these parties to assert counterclaims against us alleging that we infringe their patents. In addition, in a patent infringement proceeding, a court may decide that one of our patents is invalid or unenforceable, in whole or in part, construe the patent’s claims narrowly or refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology in question. An adverse result in any litigation proceeding could put one or more of our patents at risk of being invalidated or interpreted narrowly, which could materially and adversely affect us and our collaborators.
Any litigation to enforce or defend our patent rights, even if we were to prevail, could be costly and time‑consuming and would divert the attention of our management and key personnel from our business operations. We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded if we were to prevail may not be commercially meaningful. Even if we are successful, domestic or foreign litigation, or USPTO or foreign patent office proceedings, may result in substantial costs and distraction to our management. We may not be able, alone or with our licensors or potential

collaborators, to prevent misappropriation of our proprietary rights, particularly in countries where the laws may not protect such rights as fully as in the United States. Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation or other proceedings, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation or other proceedings. In addition, during the course of this kind of litigation or proceedings, there could be public announcements of the results of hearings, motions or other interim proceedings or developments or public access to related documents. If investors perceive these results to be negative, the market price for our common stock could be significantly harmed.
Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on the success of our business.
Our commercial success depends upon our ability, and the ability of our collaborators, to develop, manufacture, market and sell our product candidates and use our proprietary technologies without infringing the proprietary rights of third parties. There is considerable intellectual property litigation in the biotechnology and pharmaceutical industries. While no such litigation has been brought against us and we have not been held by any court to have infringed a third party’s intellectual property rights, we cannot guarantee that our technology, product candidates or use of our product candidates do not infringe third‑party patents.
We are aware of numerous patents and pending applications owned by third parties, and we monitor patents and patent applications in the fields in which we are developing product candidates, both in the United States and elsewhere. However, we may have failed to identify relevant third‑party patents or applications. For example, applications filed before November 29, 2000 and certain applications filed after that date that will not be filed outside the United States remain confidential until patents issue. Moreover, it is difficult for industry participants, including us, to identify all third‑party patent rights that may be relevant to our product candidates and technologies because patent searching is imperfect due to differences in terminology among patents, incomplete databases and the difficulty in assessing the meaning of patent claims. We may fail to identify relevant patents or patent applications or may identify pending patent applications of potential interest but incorrectly predict the likelihood that such patent applications may issue with claims of relevance to our technology. In addition, we may be unaware of one or more issued patents that would be infringed by the manufacture, sale or use of a current or future product candidate, or we may incorrectly conclude that a third‑party patent is invalid, unenforceable or not infringed by our activities. Additionally, pending patent applications that have been published can, subject to certain limitations, be later amended in a manner that could cover our technologies, our product candidates or the use of our product candidates.
The biotechnology and pharmaceutical industries are characterized by extensive litigation regarding patents and other intellectual property rights. Other parties may allege that our product candidates or the use of our technologies infringes patent claims or other intellectual property rights held by them or that we are employing their proprietary technology without authorization. We may become party to, or threatened with, future adversarial proceedings or litigation regarding intellectual property rights with respect to our product candidates and technology, including interference or derivation proceedings before the USPTO and similar bodies in other countries. Third parties may assert infringement claims against us based on existing intellectual property rights and intellectual property rights that may be granted in the future. If we were to challenge the validity of an issued U.S. patent in court, such as an issued U.S. patent of potential relevance to some of our product candidates or methods of use, we would need to overcome a statutory presumption of validity that attaches to every U.S. patent. This means that in order to prevail, we would have to present clear and convincing evidence as to the invalidity of the patent’s claims. There is no assurance that a court would find in our favor on questions of infringement or validity.
Patent and other types of intellectual property litigation can involve complex factual and legal questions, and their outcome is uncertain. If we are found, or believe there is a risk we may be found, to infringe a third party’s intellectual property rights, we could be required or may choose to obtain a license from such third party to continue developing and marketing our product candidates and technology. However, we may not be able to obtain any such license on commercially reasonable terms or at all. Even if we were able to obtain a license, it could be non‑exclusive, thereby giving our competitors access to the same technologies licensed to us. We could be forced, including by court order, to cease commercializing the infringing technology or product. In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees if we are found to have willfully infringed a patent. A finding of infringement could prevent us from commercializing our product candidates or force us to cease some of our business operations, which could materially harm our business. Claims that we have misappropriated the confidential information or trade secrets of third parties could have a similar negative impact on our business.
Even if we are successful in such proceedings, we may incur substantial costs and divert management time and attention in pursuing these proceedings, which could have a material adverse effect on us. If we are unable to avoid infringing the patent rights of others, we may be required to seek a license, defend an infringement action or challenge the validity of the patents in court, or redesign our product candidates. Patent litigation is costly and time‑consuming. We may not have sufficient resources to bring these actions to a successful conclusion. There could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock.

In addition, intellectual property litigation or claims could force us to do one or more of the following:
-cease developing, selling or otherwise commercializing our product candidates;
-pay substantial damages for past use of the asserted intellectual property;
-obtain a license from the holder of the asserted intellectual property, which license may not be available on reasonable terms, if at all; and
-in the case of trademark claims, redesign or rename some or all of our product candidates, or other brands to avoid infringing the intellectual property rights of third parties, which may not be possible and, even if possible, could be costly and time‑consuming.
We may not have sufficient financial or other resources to conduct such litigation or proceedings adequately. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could compromise our ability to compete in the marketplace.
Any of these risks coming to fruition could harm our business.
Issued patents covering our product candidates could be found invalid or unenforceable or could be interpreted narrowly if challenged in court.
Competitors may infringe our intellectual property, including our patents or the patents of our licensors. As a result, we may be required to file infringement claims to stop third‑party infringement or unauthorized use. This can be expensive, particularly for a company of our size, and time‑consuming. If we initiated legal proceedings against a third party to enforce a patent, if and when issued, covering one of our product candidates, the defendant could counterclaim that the patent covering our product candidate is invalid and/or unenforceable. In patent litigation in the United States, defendant counterclaims alleging invalidity and/or unenforceability are commonplace. Grounds for a validity challenge include alleged failures to meet any of several statutory requirements, including lack of novelty, obviousness or non‑enablement, or failure to claim patent‑eligible subject matter. Grounds for unenforceability assertions include allegations that someone connected with the prosecution of the patent withheld relevant information from the USPTO, or made a misleading statement, during prosecution. Third parties may also raise similar claims before administrative bodies in the United States or abroad, even outside the context of litigation. Such mechanisms include re‑examination, post‑grant review, inter partes review, interference proceedings and equivalent proceedings in foreign jurisdictions, such as opposition proceedings. Such proceedings could result in revocation or amendment of our patents in such a way that they no longer cover our product candidates or competitive products. The outcome following legal assertions of invalidity and unenforceability is unpredictable. With respect to validity, for example, we cannot be certain that there is no invalidating prior art, of which we and the patent examiner were unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity and/or unenforceability, we would lose at least part, and perhaps all, of the patent protection on our product candidates. Moreover, even if not found invalid or unenforceable, the claims of our patents could be construed narrowly or in a manner that does not cover the allegedly infringing technology in question. Such a loss of patent protection would have a material adverse impact on our business.
Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for noncompliance with these requirements.
Periodic maintenance fees on any issued patent are due to be paid to the USPTO and foreign patent agencies in several stages over the lifetime of the patent and, in some jurisdictions, during the pendency of a patent application. The USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. While an inadvertent lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. Noncompliance events that could result in abandonment or lapse of a patent or patent application include, but are not limited to, failure to respond to official actions within prescribed time limits, non‑payment of fees and failure to properly legalize and submit formal documents. In such an event, our competitors might be able to enter the market, which would have an adverse effect on our business.
We may be subject to claims challenging the inventorship or ownership of our patents and other intellectual property.
It is our policy to enter into confidentiality and intellectual property assignment agreements with our employees, consultants, contractors and advisors. These agreements generally provide that inventions conceived by the party in the course of rendering services to us will be our exclusive property. However, these agreements may not be honored and may not effectively assign intellectual property rights to us. For example, even if we have a consulting agreement in place with an academic advisor pursuant to which such academic advisor is required to assign any inventions developed in connection with providing services

to us, such academic advisor may not have the right to assign such inventions to us, as it may conflict with his or her obligations to assign all such intellectual property to his or her employing institution.
Litigation may be necessary to defend against these and other claims challenging inventorship or ownership. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, valuable intellectual property. Such an outcome could have a material adverse effect on our business. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees.
If we fail to comply with our obligations in our intellectual property licenses and funding arrangements with third parties, we could lose rights that are important to our business.
We are party to multiple license agreements that impose, and we may enter into additional licensing and funding arrangements with third parties that may impose, diligence, development and commercialization timelines, milestone payment, royalty, insurance and other obligations on us. Under our existing licensing agreements, we are obligated to pay royalties on net product sales of product candidates or related technologies to the extent they are covered by the agreement. Our results of operations will be affected by the level of royalty payments that we are required to pay to third parties. We cannot precisely predict the amount, if any, of royalties that we will be required to pay to third parties in the future. Any disagreements with the counterparty over the amount of royalties owed could lead to litigation, which is costly. In addition, if we fail to comply with our obligations under current or future license agreements, our counterparties may have the right to terminate these agreements, in which event we might not be able to develop, manufacture or market any product candidate that is covered by these agreements, or may face other penalties under the agreements. Such an occurrence could materially adversely affect the value of product candidates being developed using rights licensed to us under any such agreement. Termination of these agreements or reduction or elimination of our rights under these agreements may result in our having to negotiate new or reinstated agreements with less favorable terms, or cause us to lose our rights under these agreements, including our rights to important intellectual property or technology. Furthermore, our counterparties may allege that we are operating outside the scope of the licenses granted and terminate our license or otherwise require us to alter development, manufacturing or marketing activities.
We may not be successful in obtaining or maintaining necessary rights to our product candidates through acquisitions and in-licenses.
We currently have rights to certain intellectual property, through licenses from third parties and under patents and patent applications that we own, to develop our product candidates. Because we may find that our programs require the use of proprietary rights held by third parties, the growth of our business may depend in part on our ability to acquire, in‑license or use these proprietary rights. We may be unable to acquire or in‑license compositions, methods of use, processes or other third‑party intellectual property rights from third parties that we identify as necessary for our product candidates. The licensing and acquisition of third‑party intellectual property rights is a competitive area, and a number of more established companies are also pursuing strategies to license or acquire third‑party intellectual property rights that we may consider attractive. These established companies may have a competitive advantage over us due to their size, financial resources and greater clinical development and commercialization capabilities. In addition, companies that perceive us to be a competitor may be unwilling to assign or license rights to us. We also may be unable to license or acquire third‑party intellectual property rights on terms that would allow us to make an appropriate return on our investment.
If we are unable to successfully obtain rights to required third‑party intellectual property rights or maintain the existing intellectual property rights we have, we may have to abandon development of that program and our business and financial condition could suffer.
We may be subject to claims by third parties asserting that our employees or we have misappropriated their intellectual property, or claiming ownership of what we regard as our own intellectual property.
Many of our employees were previously employed at universities or other biotechnology or pharmaceutical companies, including our competitors or potential competitors. We may also engage advisors and consultants who are concurrently employed at universities or other organizations or who perform services for other entities. Although we try to ensure that our employees, advisors and consultants do not use the proprietary information or know‑how of others in their work for us, we may be subject to claims that we or our employees, advisors or consultants have used or disclosed intellectual property, including trade secrets or other proprietary information, of any such party’s former or current employer or in violation of an agreement with another party. Although we have no knowledge of any such claims being alleged to date, if such claims were to arise, litigation may be necessary to defend against any such claims.
In addition, while it is our policy to require our employees, consultants, advisors and contractors who may be involved in the development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who in fact develops intellectual property that we regard as our own. Our and their assignment agreements may not be self‑executing or may be breached, and we may be forced to bring claims against third

parties, or defend claims they may bring against us, to determine the ownership of what we regard as our intellectual property. Similarly, we may be subject to claims that an employee, advisor or consultant performed work for us that conflicts with that person’s obligations to a third party, such as an employer, and thus, that the third party has an ownership interest in the intellectual property arising out of work performed for us. Litigation may be necessary to defend against these claims. Although we have no knowledge of any such claims being alleged to date, if such claims were to arise, litigation may be necessary to defend against any such claims.
If we fail in prosecuting or defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel. Even if we are successful in prosecuting or defending against such claims, litigation could result in substantial costs and be a distraction to management.
If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our markets of interest and our business may be adversely affected.
Our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks. We may not be able to protect our rights to these trademarks and trade names, which we need to build name recognition among potential collaborators or customers in our markets of interest. At times, competitors may adopt trade names or trademarks similar to ours, thereby impeding our ability to build brand identity and possibly leading to market confusion. In addition, there could be potential trade name or trademark infringement claims brought by owners of other registered trademarks or trademarks that incorporate variations of our registered or unregistered trademarks or trade names. Over the long term, if we are unable to establish name recognition based on our trademarks and trade names, then we may not be able to compete effectively and our business may be adversely affected. Our efforts to enforce or protect our proprietary rights related to trademarks, trade secrets, domain names, copyrights or other intellectual property may be ineffective and could result in substantial costs and diversion of resources, and could adversely impact our financial condition or results of operations.
We will need to obtain FDA approval for any proposed product names, and any failure or delay associated with such approval may adversely affect our business.
Any proprietary name or trademark we intend to use for our product candidates will require approval from the FDA regardless of whether we have secured a formal trademark registration from the USPTO. The FDA typically conducts a review of proposed product names, including an evaluation of the potential for confusion with other product names. The FDA may also object to a product name if it believes the name inappropriately implies certain medical claims or contributes to an overstatement of efficacy. If the FDA objects to any product names we propose, we may be required to adopt an alternative name for our product candidates. If we adopt an alternative name, we would lose the benefit of any existing trademark applications for such product candidate and may be required to expend significant additional resources in an effort to identify a suitable product name that would qualify under applicable trademark laws, not infringe the existing rights of third parties and be acceptable to the FDA. We may be unable to build a successful brand identity for a new trademark in a timely manner or at all, which would limit our ability to commercialize our product candidates.
We will not seek to protect our intellectual property rights in all jurisdictions throughout the world and we may not be able to adequately enforce our intellectual property rights even in the jurisdictions where we seek protection.
Filing, prosecuting and defending patents on product candidates in all countries and jurisdictions throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States could be less extensive than in the United States, assuming that rights are obtained in the United States and assuming that rights are pursued outside the United States. In this regard, in addition to the United States, we also seek to protect our intellectual property rights in other countries, including Russia. The statutory deadlines for pursuing patent protection in individual foreign jurisdictions are based on the priority date of each of our patent applications. For all of the patent families in our portfolio, including the families that may provide coverage for our lead product candidate, the relevant statutory deadlines have not yet expired. Therefore, for each of the patent families that we believe provide coverage for our lead product candidate, we will need to decide whether and where to pursue additional protection outside the United States or Russia. In addition, the laws of some foreign countries, do not protect intellectual property rights to the same extent as federal and state laws in the United States. Consequently, for our existing patent rights outside the United States and any foreign patent rights we may decide to pursue in the future, we may not be able to obtain relevant claims and/or we may not be able to prevent third parties from practicing our inventions in all countries outside the United States, or from selling or importing products made using our inventions in and into the United States or other jurisdictions.
Competitors may use our technologies in jurisdictions where we do not pursue and obtain patent protection to develop their own products and further, may export otherwise infringing products to territories where we have patent protection, but enforcement is not as strong as in the United States. These products may compete with our product candidates and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing. Even if we pursue and

obtain issued patents in particular jurisdictions, our patent claims or other intellectual property rights may not be effective or sufficient to prevent third parties from so competing.
The laws of some foreign countries do not protect intellectual property rights to the same extent as the laws of the United States. Many companies have encountered significant problems in protecting and defending intellectual property rights in certain foreign jurisdictions. The legal systems of some countries, particularly developing countries, do not favor the enforcement of patents and other intellectual property protection, especially those relating to biotechnology. This could make it difficult for us to stop the infringement of our patents, if obtained, or the misappropriation of our other intellectual property rights. For example, many foreign countries have compulsory licensing laws under which a patent owner must grant licenses to third parties. In addition, many countries limit the enforceability of patents against third parties, including government agencies or government contractors. In these countries, patents may provide limited or no benefit. Patent protection must ultimately be sought on a country‑by‑country basis, which is an expensive and time‑consuming process with uncertain outcomes. Accordingly, we may choose not to seek patent protection in certain countries, and we will not have the benefit of patent protection in such countries.
If our ability to obtain and, if obtained, enforce our patents to stop infringing activities is inadequate, third parties may compete with our product candidates, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing. Accordingly, our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property we develop or license.
If we do not obtain additional protection under the Hatch‑Waxman Act and similar foreign legislation extending the terms of our patents for our product candidates, our business may be harmed.
Depending upon the timing, duration and specifics of FDA regulatory approval for our product candidates, one or more of our U.S. patents may be eligible for limited patent term restoration under the Hatch‑Waxman Act. The Hatch‑Waxman Act permits a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process. Patent term restorations, however, are limited to a maximum of five years and cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval by the FDA.
The application for patent term extension is subject to approval by the USPTO, in conjunction with the FDA. It takes at least six months to obtain approval of the application for patent term extension. We may not be granted an extension because of, for example, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements. Moreover, the applicable time period or the scope of patent protection afforded could be less than we request. If we are unable to obtain patent term extension or restoration or the term of any such extension is less than we request, the period during which we will have the right to exclusively market our product will be shortened, our competitors may obtain earlier approval of competing products and our ability to generate revenues could be materially adversely affected.
We may face competition from biosimilars, which may have a material adverse effect on the future commercial prospects of our product candidates.
Even if we are successful in achieving regulatory approval to commercialize a product candidate faster than our competitors, we may face competition from biosimilars. In the United States, the Biologics Price Competition and Innovation Act of 2009 created an abbreviated approval pathway for biological products that are demonstrated to be “highly similar,” or biosimilar, to or “interchangeable” with an FDA‑approved biological product. This new pathway could allow competitors to reference data from innovative biological products 12 years after the time of approval of the innovative biological product. This data exclusivity does not prevent another company from developing a product that is highly similar to the innovative product, generating its own data, and seeking approval. Data exclusivity only assures that another company cannot rely upon the data within the innovator’s application to support the biosimilar product’s approval. It is possible that Congress may take measures to reduce or eliminate these periods of exclusivity. The Biologics Price Competition and Innovation Act of 2009 is complex and only beginning to be interpreted and implemented by the FDA. As a result, its ultimate impact, implementation and meaning is subject to uncertainty. Although it is uncertain when any such processes may be fully adopted by the FDA, any such processes could have a material adverse effect on the future commercial prospects for our product candidates.

RISKS RELATED TO EMPLOYEE MATTERS AND MANAGING GROWTH AND OTHER RISKS RELATED TO OUR BUSINESS
Our future success depends on our ability to retain key executives and to attract, retain and motivate qualified personnel.
We are highly dependent on Werner Cautreels, Ph.D., our President and Chief Executive Officer, as well as the other principal members of our management, scientific and clinical team. Although we have entered into employment agreements or offer letters with Dr. Cautreels and certain of our executive officers, each of them may terminate their employment with us at any time. We do not maintain “key person” insurance for any of our executives or other employees.

Recruiting and retaining qualified scientific, clinical, manufacturing and sales and marketing personnel will also be critical to our success. The loss of the services of our executive officers or other key employees could impede the achievement of our research, development and commercialization objectives and seriously harm our ability to successfully implement our business strategy. Furthermore, replacing executive officers and key employees may be difficult and may take an extended period of time because of the limited number of individuals in our industry with the breadth of skills and experience required to successfully develop, gain regulatory approval of and commercialize product candidates. Competition to hire from this limited pool is intense, and we may be unable to hire, train, retain or motivate these key personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similar personnel. We also experience competition for the hiring of scientific and clinical personnel from universities and research institutions. In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development and commercialization strategy. Our consultants and advisors may be employed by employers other than us and may have commitments under consulting or advisory contracts with other entities that may limit their availability to us. If we are unable to continue to attract and retain high quality personnel, our ability to pursue our growth strategy will be limited.
We expect to expand our development and regulatory capabilities and potentially implement sales, marketing and distribution capabilities, and as a result, we may encounter difficulties in managing our growth, which could disrupt our operations.
We expect to experience significant growth in the number of our employees and the scope of our operations, particularly in the areas of lead discovery and product development, regulatory affairs, clinical affairs and manufacturing and, if any of our product candidates receives marketing approval, sales, marketing and distribution. To manage our expected future growth, we must continue to implement and improve our managerial, operational and financial systems, expand our facilities and continue to recruit and train additional qualified personnel. Due to our limited financial resources and the limited experience of our management team in managing a company with such expected growth, we may not be able to effectively manage the expansion of our operations or recruit and train additional qualified personnel. The expansion of our operations may lead to significant costs and may divert our management and business development resources. Any inability to manage growth could delay the execution of our business plans or disrupt our operations.
A variety of risks associated with operating in Russia and internationally could adversely affect our business.
In addition to our U.S. operations, we have operations in Russia through our wholly owned subsidiary, Selecta RUS, and may expand international operations in the future, including by conducting clinical trials of our product candidates in countries outside the United States, including Russia and Belgium. We face risks associated with our operations in Russia, including possible unfavorable regulatory, pricing and reimbursement, legal, political, tax and labor conditions, which could harm our business.
We may also rely on collaborators to commercialize any approved product candidates outside of the United States. Doing business in Russia and internationally involves a number of risks, including but not limited to:
-multiple, conflicting and changing laws and regulations, such as privacy regulations, tax laws, export and import restrictions, employment laws, regulatory requirements and other governmental approvals, permits and licenses;
-failure by us to obtain and maintain regulatory approvals for the use of our product candidates in various countries;
-additional potentially relevant third‑party patent rights;
-complexities and difficulties in obtaining protection of and enforcing our intellectual property rights;
-difficulties in staffing and managing foreign operations;
-complexities associated with managing multiple‑payor reimbursement regimes, government payors or patient self‑pay systems;
-limits on our ability to penetrate international markets;
-financial risks, such as longer payment cycles, difficulty collecting accounts receivable, the impact of local and regional financial crises on demand and payment for our product candidates and exposure to foreign currency exchange rate fluctuations, which could result in increased operating expenses and reduced revenues;
-natural disasters, political and economic instability, including wars, events of terrorism and political unrest, outbreak of disease, boycotts, curtailment of trade and other business restrictions and economic weakness, including inflation;
-changes in diplomatic and trade relationships;
-challenges in enforcing our contractual and intellectual property rights, especially in those foreign countries that do not respect and protect intellectual property rights to the same extent as the United States;

-certain expenses including, among others, expenses for travel, translation and insurance;
-legal risks, including use of the legal system by the government to benefit itself or affiliated entities at our expense, including expropriation of property; and
-regulatory and compliance risks that relate to maintaining accurate information and control over sales and activities that may fall within the purview of the FCPA its books and records provisions, or its anti‑bribery provisions.
Any of these factors could significantly harm our future international expansion and operations and, consequently, our results of operations.
Sanctions relating to Russia, and Russia’s response to those sanctions, could adversely affect our business.
In response to the events in Crimea and other factors, the United States and the European Union have imposed sanctions on certain individuals, companies and financial institutions in Russia and additional sanctions could be forthcoming. In response, Russia has imposed entry bans on certain U.S. lawmakers and officials, and Russia has also announced that it is prepared to take additional retaliatory action in response to further Russia-related sanctions imposed by the United States in August 2017. If the United States and European Union were to impose additional sanctions on Russian businesses, or if Russia were to take retaliatory action against U.S. companies operating in Russia, our research and development activities with respect to our program for HPV‑associated cancers currently conducted by Selecta RUS, or any other research and development activities with respect to our other immune stimulation programs conducted by Selecta RUS in the future, could be adversely affected.
Our business and operations would suffer in the event of system failures.
Despite the implementation of security measures, our internal computer systems and those of our current and future contractors and consultants are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. While we are not aware of any such material system failure, accident or security breach to date, if such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our development programs and our business operations. For example, the loss of clinical trial data from completed or future clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. Likewise, we rely on third parties to manufacture our product candidates and conduct clinical trials, and similar events relating to their computer systems could also have a material adverse effect on our business. To the extent that any disruption or security breach were to result in a loss of, or damage to, our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability and the further development and commercialization of our product candidates could be delayed.
Our employees, independent contractors, principal investigators, CROs, consultants, commercial partners and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could expose us to liability and hurt our reputation.
We are exposed to the risk that our employees, independent contractors, principal investigators, CROs, consultants, commercial partners and vendors may engage in fraudulent conduct or other illegal activity. Misconduct by these parties could include intentional, reckless and/or negligent conduct or disclosure of unauthorized activities to us that violates: (1) FDA laws and regulations, including those laws that require the reporting of true, complete and accurate information to the FDA, (2) manufacturing standards, (3) healthcare fraud and abuse laws, or (4) laws that require the true, complete and accurate reporting of financial information or data. Activities subject to these laws also involve the improper use or misrepresentation of information obtained in the course of clinical trials, creating fraudulent data in our preclinical studies or clinical trials or illegal misappropriation of drug product, which could result in regulatory sanctions and cause serious harm to our reputation. It is not always possible to identify and deter misconduct by employees and third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations. Additionally, we are subject to the risk that a person or government could allege such fraud or other misconduct, even if none occurred. If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and financial results, including, without limitation, the imposition of significant civil, criminal and administrative penalties, damages, monetary fines, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, reputational harm, diminished profits and future earnings, and curtailment of our operations, any of which could adversely affect our ability to operate our business and our results of operations.
Acquisitions or joint ventures could disrupt our business, cause dilution to our stockholders and otherwise harm our business.
We may acquire other businesses, product candidates or technologies as well as pursue strategic alliances, joint ventures, technology licenses or investments in complementary businesses. We have not made any acquisitions to date, and our ability to

do so successfully is unproven. Any of these transactions could be material to our financial condition and operating results and expose us to many risks, including:
-disruption in our relationships with future customers or with current or future distributors or suppliers as a result of such a transaction;
-unexpected liabilities related to acquired companies;
-difficulties integrating acquired personnel, technologies and operations into our existing business;
-diversion of management time and focus from operating our business to acquisition integration challenges;
-increases in our expenses and reductions in our cash available for operations and other uses;
-possible write‑offs or impairment charges relating to acquired businesses; and
-inability to develop a sales force for any additional product candidates.
Foreign acquisitions involve unique risks in addition to those mentioned above, including those related to integration of operations across different cultures and languages, currency risks and the particular economic, political and regulatory risks associated with specific countries.
Also, the expected benefit of any acquisition may not materialize. Future acquisitions or dispositions could result in potentially dilutive issuances of our equity securities, the incurrence of debt, contingent liabilities or amortization expenses or write‑offs of goodwill, any of which could harm our financial condition. We cannot predict the number, timing or size of future joint ventures or acquisitions, or the effect that any such transactions might have on our operating results.

RISKS RELATED TO OUR COMMON STOCK
The market price of our common stock may be volatile and fluctuate substantially, which could result in substantial losses for purchasers of our common stock.
The trading price of our common stock is likely to be volatile and could be subject to wide fluctuations in response to various factors, some of which are beyond our control. The stock market in general and the market for smaller biopharmaceutical companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies. As a result of this volatility, you may not be able to sell your common stock at or above the price at which you purchased. The market price for our common stock may be influenced by many factors, including:
-the success of competitive products or technologies;
-results of clinical trials of our product candidates or those of our competitors;
-failure or discontinuation of any of our development programs;
-commencement of, termination of, or any development related to any collaboration or licensing arrangement;
-regulatory or legal developments in the United States and other countries;
-development of new product candidates that may address our markets and make our product candidates less attractive;
-changes in physician, hospital or healthcare provider practices that may make our product candidates less useful;
-announcements by us, our partners or our competitors of significant acquisitions, strategic partnerships, joint ventures, collaborations or capital commitments;
-announcement or market expectation of additional financing efforts;
-developments or disputes concerning patent applications, issued patents or other proprietary rights;
-the recruitment or departure of key personnel;
-the level of expenses related to any of our product candidates or clinical development programs;
-failure to meet or exceed financial estimates, projections or development timelines of the investment community or that we provide to the public;
-the results of our efforts to discover, develop, acquire or in‑license additional product candidates or products;
-actual or expected changes in estimates as to financial results, development timelines or recommendations by securities analysts;

-variations in our financial results or those of companies that are perceived to be similar to us;
-changes in the structure of healthcare payment systems;
-sale of common stock by us or our stockholders in the future as well as the overall trading volume of our common stock;
-market conditions in the pharmaceutical and biotechnology sectors;
-general economic, industry and market conditions; and
-the other factors described in this “Risk factors” section
Our executive officers, directors and principal stockholders, if they choose to act together, will continue to have the ability to control or significantly influence all matters submitted to stockholders for approval.
Our executive officers, directors and stockholders who own more than 5% of our outstanding common stock and their respective affiliates, in the aggregate, hold shares representing approximately 17% of our outstanding voting stock as of September 30, 2017. As a result, if these stockholders choose to act together, they would be able to control or significantly influence all matters submitted to our stockholders for approval, as well as our management and affairs. For example, these persons, if they choose to act together, would control or significantly influence the election of directors, the composition of our management and approval of any merger, consolidation or sale of all or substantially all of our assets.
A significant portion of our total outstanding shares are eligible to be sold into the market, which could cause the market price of our common stock to drop significantly, even if our business is doing well.
Sales of a substantial number of shares of our common stock in the public market, or the perception in the market that the holders of a large number of shares intend to sell shares, could reduce the market price of our common stock. Approximately 12.9 million shares of our common stock became eligible to be sold into the market on December 19, 2016, unless held by one of our affiliates, in which case the resale of those securities is subject to volume limitations under Rule 144 of the Securities Act of 1933, as amended, or Rule 144. Moreover, holders of an aggregate of approximately 12.3 million shares of our common stock as of the completion of the initial public offering of our common stock on June 27, 2016 have rights, subject to specified conditions, to require us to file registration statements covering their shares or to include their shares in registration statements that we may file for ourselves or other stockholders, until such shares can otherwise be sold without restriction under Rule 144 or until the rights terminate pursuant to the terms of the investors’ rights agreement between us and such holders. We have also registered and intend to continue to register all shares of common stock that we may issue under our equity compensation plans. Once we register these shares, they can be freely sold in the public market upon issuance, subject to volume limitations applicable to affiliates. In addition, on June 27, 2017, we issued and sold in a private placement 3,088,791 shares of our common stock and a warrant to purchase 79,130 shares of our common stock. Pursuant to a registration rights agreement entered into with the investors in the private placement, on July 13, 2017, we filed a Registration Statement on Form S-3 to register the shares of common stock sold in the private placement and the shares of common stock issuable upon exercise of the warrant. As a result, these shares can be freely sold in the public market.
We are an “emerging growth company,” and the reduced disclosure requirements applicable to emerging growth companies may make our common stock less attractive to investors.
We are an “emerging growth company,” as defined in the Jumpstart Our Business Startups Act of 2012, or the JOBS Act, and may remain an emerging growth company until the last day of the fiscal year following the fifth anniversary of the closing of the initial public offering of our common stock. However, if certain events occur prior to the end of such five‑year period, including if we become a “large accelerated filer,” our annual gross revenues exceed $1.07 billion or we issue more than $1.07 billion of non‑convertible debt in any three‑year period, we will cease to be an emerging growth company prior to the end of such five‑year period. For so long as we remain an emerging growth company, we are permitted and intend to rely on exemptions from certain disclosure requirements that are applicable to other public companies that are not emerging growth companies. These exemptions include:
-being permitted to provide only two years of audited financial statements, in addition to any required unaudited interim financial statements, with correspondingly reduced “Management’s discussion and analysis of financial condition and results of operations”;
-not being required to comply with the auditor attestation requirements in the assessment of our internal control over financial reporting;
-not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements;
-reduced disclosure obligations regarding executive compensation; and

-exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and shareholder approval of any golden parachute payments not previously approved.
We cannot predict whether investors will find our common stock less attractive if we rely on these exemptions. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stock price may be reduced or more volatile. In addition, the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards. This allows an emerging growth company to delay the adoption of these accounting standards until they would otherwise apply to private companies. We have irrevocably elected not to avail ourselves of this exemption and, therefore, we will be subject to the same new or revised accounting standards as other public companies that are not emerging growth companies.
If we sell shares of our common stock in future financings, stockholders may experience immediate dilution and, as a result, our stock price may decline.
We may from time to time issue additional shares of common stock at a discount from the current trading price of our common stock. As a result, our stockholders would experience immediate dilution upon the sale of any shares of our common stock at such discount. In addition, as opportunities present themselves, we may enter into financing or similar arrangements in the future, including the issuance of debt securities, preferred stock or common stock. If we issue common stock or securities exercisable for or convertible into common stock, our common stockholders would experience additional dilution and, as a result, our stock price may decline.
For instance, we recently completed a private placement that resulted in approximately $50.0 million in aggregate gross proceeds. On June 26, 2017 we entered into a securities purchase agreement, or the Institutional SPA, with the purchasers named therein, or the Institutional Investors, and a securities purchase agreement, or the Springer SPA, with Timothy Springer, Ph.D., a member of our board of directors.
Pursuant to the Institutional SPA, we agreed to sell an aggregate of 2,750,000 shares of our common stock to the Institutional Investors for aggregate gross proceeds of $44.0 million, at a purchase price equal to $16.00 per share. Pursuant to the Springer SPA, we agreed to sell to Dr. Springer an aggregate of 338,791 shares of our common stock at a purchase price equal to $17.71 per share, which was equal to the most recent consolidated closing bid price on the Nasdaq Global Market on June 23, 2017, and warrants to purchase 79,130 shares of common stock, exercisable at $17.71 per share. The closing of the Springer SPA resulted in additional aggregate gross proceeds to us of approximately $6.0 million for a total of $50.0 million. The closing of these transactions occurred on June 27, 2017. Pursuant to a registration rights agreement entered into with the investors in the private placement, on July 13, 2017, we filed a Registration Statement on Form S-3 to register the shares of common stock sold in the private placement and the shares of common stock issuable upon exercise of the warrant. As a result, these shares can be freely sold in the public market.
In addition, on December 2, 2016 we entered into a stock purchase agreement, or the Spark SPA, with Spark in conjunction with our license agreement with Spark. Pursuant to the Spark SPA, we issued and sold 197,238 shares of our common stock to Spark for gross proceeds of $5.0 million, which purchase price per share represented a 115.0% premium to the average of the daily volume-weighted average price, or VWAP, of the common stock during the thirty consecutive calendar days ending on, and including, December 1, 2016. Spark has since made two additional investments of $5.0 million in our common stock, in each case at a 115.0% premium, pursuant to the terms and conditions of the Spark SPA. The first additional investment was consummated on June 8, 2017 when Spark purchased 324,362 shares of common stock pursuant to the Spark SPA, as amended by a letter agreement between Spark and us dated June 6, 2017, for an aggregate purchase price of $5.0 million. The second additional investment was consummated on October 31, 2017 when Spark purchased 205,254 shares of common stock for an aggregate purchase price of $5.0 million.
We have incurred increased costs as a result of operating as a public company, and our management will be required to devote substantial time to new compliance initiatives and corporate governance practices.
As a public company, and particularly after we are no longer an emerging growth company, we have incurred and expect to continue to incur significant legal, accounting and other expenses that we did not incur as a private company. The Sarbanes‑Oxley Act of 2002, the Dodd‑Frank Wall Street Reform and Consumer Protection Act, the listing requirements of The Nasdaq Global Market and other applicable securities rules and regulations impose various requirements on public companies, including establishment and maintenance of effective disclosure and financial controls and corporate governance practices. Our management and other personnel need to devote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations have increased our legal and financial compliance costs and made some activities more time‑consuming and costly.
These rules and regulations are often subject to varying interpretations, in many cases due to their lack of specificity, and, as a result, their application in practice may evolve over time as new guidance is provided by regulatory and governing bodies. This

could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to disclosure and governance practices.
Pursuant to Section 404 of the Sarbanes‑Oxley Act of 2002, or Section 404, we will be required to furnish a report by our management on our internal control over financial reporting. However, while we remain an emerging growth company, we will not be required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm. To achieve compliance with Section 404 within the prescribed period, we are engaged in a process to document and evaluate our internal control over financial reporting, which is both costly and challenging. In this regard, we continue to dedicate internal resources, engage outside consultants, developed a detailed work plan to assess and document the adequacy of internal control over financial reporting, continue steps to improve control processes as appropriate, validate through testing whether such controls are functioning as documented, and implement a continuous reporting and improvement process for internal control over financial reporting. Despite our efforts, there is a risk that we will not be able to conclude, within the prescribed timeframe or at all, that our internal control over financial reporting is effective as required by Section 404. If we identify one or more material weaknesses, it could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our financial statements.
If securities or industry analysts do not publish research or reports about our business, or if they issue an adverse or misleading opinion regarding our stock, our stock price and trading volume could decline.
The trading market for our common stock will be influenced by the research and reports that industry or securities analysts publish about us or our business. If any of the analysts who cover us issue an adverse or misleading opinion regarding us, our business model, our intellectual property or our stock performance, or if our target animal studies and operating results fail to meet the expectations of analysts, our stock price would likely decline. If one or more of these analysts ceases coverage of us or fails to publish reports on us regularly, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline.
Provisions in our restated certificate of incorporation and restated bylaws and under Delaware law could make an acquisition of our company, which may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove our current management.
Provisions in our restated certificate of incorporation and our restated bylaws, which became effective upon the closing of the initial public offering of our common stock may discourage, delay or prevent a merger, acquisition or other change in control of our company that stockholders may consider favorable, including transactions in which you might otherwise receive a premium for your shares. These provisions could also limit the price that investors might be willing to pay in the future for shares of our common stock, thereby depressing the market price of our common stock. In addition, because our board of directors is responsible for appointing the members of our management team, these provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace members of our board of directors. Among other things, these provisions include those establishing:
–a classified board of directors with three‑year staggered terms, which may delay the ability of stockholders to change the membership of a majority of our board of directors;
–no cumulative voting in the election of directors, which limits the ability of minority stockholders to elect director candidates;
–the exclusive right of our board of directors to elect a director to fill a vacancy created by the expansion of the board of directors or the resignation, death or removal of a director, which prevents stockholders from filling vacancies on our board of directors;
–the ability of our board of directors to authorize the issuance of shares of preferred stock and to determine the terms of those shares, including preferences and voting rights, without stockholder approval, which could be used to significantly dilute the ownership of a hostile acquirer;
–the ability of our board of directors to alter our bylaws without obtaining stockholder approval;
–the required approval of the holders of at least two‑thirds of the shares entitled to vote at an election of directors to adopt, amend or repeal our bylaws or repeal the provisions of our restated certificate of incorporation regarding the election and removal of directors;
–a prohibition on stockholder action by written consent, which forces stockholder action to be taken at an annual or special meeting of our stockholders;
–the requirement that a special meeting of stockholders may be called only by the chairman of the board of directors, the chief executive officer, the president or the board of directors, which may delay the ability of our stockholders to force consideration of a proposal or to take action, including the removal of directors; and

–advance notice procedures that stockholders must comply with in order to nominate candidates to our board of directors or to propose matters to be acted upon at a stockholders’ meeting, which may discourage or deter a potential acquirer from conducting a solicitation of proxies to elect the acquirer’s own slate of directors or otherwise attempting to obtain control of us.
Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the General Corporation Law of the State of Delaware, which prohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three years after the date of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribed manner.
Our restated certificate of incorporation provides that, unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for most legal actions between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers, employees or agents.
Our restated certificate of incorporation specifies that, unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for most legal actions involving claims brought against us by stockholders. Any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock shall be deemed to have notice of and to have consented to the provisions of our restated certificate of incorporation described above.
We believe this provision benefits us by providing increased consistency in the application of Delaware law by chancellors particularly experienced in resolving corporate disputes, efficient administration of cases on a more expedited schedule relative to other forums and protection against the burdens of multi‑forum litigation. However, the provision may have the effect of discouraging lawsuits against our directors, officers, employees and agents as it may limit any stockholder’s ability to bring a claim in a judicial forum that such stockholder finds favorable for disputes with us or our directors, officers, employees or agents. The enforceability of similar choice of forum provisions in other companies’ certificates of incorporation has been challenged in legal proceedings, and it is possible that, in connection with any applicable action brought against us, a court could find the choice of forum provisions contained in our restated certificate of incorporation to be inapplicable or unenforceable in such action. If a court were to find the choice of forum provision contained in our restated certificate of incorporation to be inapplicable or unenforceable in an action, we may incur additional costs associated with resolving such action in other jurisdictions, which could adversely affect our business, financial condition or results of operations.
Because we do not expect paying any cash dividends on our capital stock in the foreseeable future, capital appreciation, if any, will be your sole source of gain.
We have never declared or paid cash dividends on our capital stock. We currently intend to retain all of our future earnings, if any, to finance the growth and development of our business. In addition, our credit facility with SVB currently prohibits us from paying cash dividends on our equity securities, and any future debt agreements may likewise preclude us from paying dividends. As a result, capital appreciation, if any, of our common stock will be your sole source of gain for the foreseeable future.
We could be subject to securities class action litigation.
In the past, securities class action litigation has often been brought against a company following a decline in the market price of its securities. This risk is especially relevant for us because biopharmaceutical companies have experienced significant stock price volatility in recent years. If we face such litigation, it could result in substantial costs and a diversion of management’s attention and resources, which could harm our business.

Item 2. Unregistered Sales of Equity Securities and Use of Proceeds
Unregistered Sales of Equity Securities
None.
Use of Proceeds from Registered Securities
On June 21, 2016, we completed the initial public offering of our common stock and issued and sold 5,000,000 shares of our common stock at a public offering price of $14.00 per share.
The offer and sale of all of the shares in the offering were registered under the Securities Act pursuant to a Registration Statement on Form S-1 (File No. 333-211555), as amended, which was declared effective by the Securities and Exchange Commission, or the SEC, on June 21, 2016, and a Registration Statement on Form S-1MEF (File No. 333-212162), which was automatically

effective upon filing with the SEC on June 21, 2016. On July 25, 2016, we closed the underwriters’ over-allotment option in part, and we sold 289,633 shares at a price to the public of $14.00 per share.
The net proceeds of approximately $64.5 million from our initial public offering have been invested in short-term, investment-grade, interest-bearing instruments and U.S. government securities.  There has been no material change in the expected use of the net proceeds from our initial public offering as described in our final prospectus, dated June 21, 2016, filed with the SEC pursuant to Rule 424(b) relating to our Registration Statement on Form S-1. 
Item 3. Defaults uponUpon Senior Securities
None.

Item 4. Mine Safety Disclosures.Disclosures
None.

Item 5. Other Information.Information
None.

46
Table of Contents

Item 6.  Exhibits.Exhibits
The exhibits filed as part
EXHIBIT INDEX
  Incorporated by Reference
Exhibit
Number		Exhibit DescriptionFormFile No.ExhibitFiling
Date
3.1
8-K001-377983.16/29/2016
3.2
8-K001-377983.29/30/2021
10.1#
---Filed herewith
10.2#
---Filed herewith
10.3
---Filed herewith
31.1
---Filed herewith
31.2
---Filed herewith
32.1
---Furnished herewith
101.INSInline XBRL Instance Document (the Instance Document does not appear in the interactive data file because its XBRL tags are embedded within the Inline XBRL document)---Filed herewith
101.SCHInline XBRL Taxonomy Extension Schema Document---Filed herewith
101.CALInline XBRL Taxonomy Extension Calculation Linkbase Document---Filed herewith
101.DEFInline XBRL Taxonomy Extension Definition Linkbase Document---Filed herewith
101.LABInline XBRL Taxonomy Extension Label Linkbase Document---Filed herewith
101.PREInline XBRL Taxonomy Extension Presentation Linkbase Document---Filed herewith
104Cover Page Interactive Data File (formatted as Inline XBRL and contained in Exhibit 101)---Filed herewith
#Indicates management contract or compensatory plan.

47
Table of this Quarterly Report on Form 10-Q are set forth on the Exhibit Index, which Exhibit Index is incorporated herein by reference.Contents

SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed by the following persons on behalf of the registrant in the capacities and on the dates indicated.


SELECTA BIOSCIENCES, INC.
Date: November 9, 2021By:/s/ Carsten Brunn, Ph.D.
Carsten Brunn, Ph.D.
President and Chief Executive Officer, and Director
(Principal Executive Officer)
SELECTA BIOSCIENCES, INC.
Date: November 9, 2021By:/s/ Kevin Tan
Date: November 7, 2017By:/s/ Werner Cautreels, Ph.D.Kevin Tan
Werner Cautreels, Ph.D.
President and Chief Executive Officer, and Director
(Principal Executive Officer)
Date: November 7, 2017By:/s/ John Leaman, M.D.
John Leaman, M.D.
Chief Financial Officer Head of Corporate Strategy, and Treasurer
(Principal Financial and Accounting Officer)


EXHIBIT INDEX
48
    Incorporated by Reference  
Exhibit
Number		 Exhibit Description Form File No. Exhibit Filing
Date		 Filed
Herewith
3.1
 
Restated Certificate of Incorporation of Selecta Biosciences, Inc.
 8-K 001-37798 3.1 6/29/2016  
3.2
 
Amended and Restated By-laws of Selecta Biosciences, Inc.
 8-K 001-37798 3.2 6/29/2016  
10.1
 
Loan and Security Agreement, dated September 12, 2017, by and between the Registrant and Silicon Valley Bank
 8-K 001-37798 10.1 9/13/2017  
10.2
 
Employment Agreement, dated October 26, 2017, by and between the Registrant and John Leaman, M.D.
 8-K 001-37798 10.1 10/26/2017 *
10.3
 
Employment Agreement, dated October 26, 2017, by and between the Registrant and Stephen Smolinski
         *
31.1
 
Rule 13a-14(a) / 15d-14(a) Certification of Chief Executive Officer
         *
31.2
 
Rule 13a-14(a) / 15d-14(a) Certification of Chief Financial Officer
         *
32.1
 
Section 1350 Certification of Chief Executive Officer
         **
32.2
 
Section 1350 Certification of Chief Financial Officer
         **
101.INS XBRL Instance Document         *
101.SCH XBRL Taxonomy Extension Schema Document         *
101.CAL XBRL Taxonomy Extension Calculation Linkbase Document         *
101.DEF XBRL Taxonomy Extension Definition Linkbase Document         *
101.LAB XBRL Taxonomy Extension Label Linkbase Document         *
101.PRE XBRL Taxonomy Extension Presentation Linkbase Document         *
*    Filed herewith.
**  Furnished herewith.
† Certain information in this exhibit has been omitted and filed separately with the Securities and Exchange Commission pursuant to a confidential treatment request under 17 C.F.R. Sections 200.80(b)(4) and 24b-2.
†† Confidential treatment granted as to portions of this exhibit. Certain information in this exhibit has been omitted and filed separately with the Securities and Exchange Commission.