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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

FORM 10-Q
ýFORM10-Q

QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the quarterly period ended September 29, 2017July 1, 2022
or
¨
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
Commission File Number: 000-30235
exel-20220701_g1.jpg
EXELIXIS, INC.
(Exact name of registrant as specified in its charter)

Delaware04-3257395
(State or other jurisdiction of incorporation or organization)(I.R.S. Employer Identification Number)
210 East Grand Ave.
South San Francisco,1851 Harbor Bay Parkway
Alameda, CA 9408094502
(650) 837-7000
(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)
Securities registered pursuant to Section 12(b) of the Act:
Title of each classTrading Symbol(s)Name of each exchange on which registered
Common Stock $.001 Par Value per ShareEXELThe Nasdaq Stock Market LLC
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 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, a 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 filerýAccelerated filer¨
Non-accelerated filer
¨ (Do not check if a smaller reporting company)
Smaller reporting company¨
Emerging growth company¨
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 7(a)(2)(B)13(a) of the Securities Act. ¨
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 October 24, 2017,August 1, 2022, there were 295,853,210321,831,784 shares of the registrant’s common stock outstanding.



Table of Contents

EXELIXIS, INC.
QUARTERLY REPORT ON FORM 10-Q
INDEX
Page
Item 1.
Item 2.
Item 3.
Item 4.
Item 1.
Item 1A.
Item 2.
Item 3.
Item 4.
Item 5.
Item 6.

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PART I - FINANCIAL INFORMATION
Item 1. Financial Statements
EXELIXIS, INC.
CONDENSED CONSOLIDATED BALANCE SHEETS
(in thousands, except share and per share data)amounts)
(unaudited)
 September 30,
2017
 December 31, 2016*
ASSETS   
Current assets:   
Cash and cash equivalents$149,357
 $151,686
Short-term investments217,741
 268,117
Trade and other receivables90,005
 40,444
Inventory, net5,806
 3,338
Prepaid expenses and other current assets8,012
 5,416
Total current assets470,921
 469,001
Long-term investments50,569
 55,601
Long-term restricted cash and investments4,650
 4,150
Property and equipment, net19,256
 2,071
Goodwill63,684
 63,684
Other long-term assets692
 1,232
Total assets$609,772
 $595,739
LIABILITIES AND STOCKHOLDERS’ EQUITY   
Current liabilities:   
Accounts payable$5,988
 $6,565
Accrued compensation and benefits19,914
 20,334
Accrued clinical trial liabilities16,181
 14,131
Accrued collaboration liabilities9,137
 2,046
Current portion of deferred revenue31,377
 19,665
Convertible notes
 109,122
Term loan payable
 80,000
Other current liabilities26,356
 16,923
Total current liabilities108,953
 268,786
Long-term portion of deferred revenue246,092
 237,094
Other long-term liabilities16,012
 541
Total liabilities371,057
 506,421
Commitments
 
Stockholders’ equity   
Preferred stock, $0.001 par value, 10,000,000 shares authorized and no shares issued
 
Common stock, $0.001 par value; 400,000,000 shares authorized; issued and outstanding: 295,700,576 and 289,923,798 at September 30, 2017 and December 31, 2016, respectively296
 290
Additional paid-in capital2,106,132
 2,072,591
Accumulated other comprehensive loss(52) (416)
Accumulated deficit(1,867,661) (1,983,147)
Total stockholders’ equity238,715
 89,318
Total liabilities and stockholders’ equity$609,772
 $595,739
*The condensed consolidated balance sheet as of December 31, 2016 has been derived from the audited financial statements as of that date.
The accompanying notes are an integral part of these condensed consolidated financial statements.

EXELIXIS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS
(in thousands, except per share data)
(unaudited)
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Revenues:       
Net product revenues$96,416
 $42,742
 $253,297
 $83,459
Collaboration revenues56,094
 19,452
 79,108
 30,414
Total revenues152,510
 62,194
 332,405
 113,873
Operating expenses:       
Cost of goods sold4,658
 2,455
 10,875
 4,700
Research and development28,543
 20,256
 79,967
 72,166
Selling, general and administrative38,129
 32,463
 113,116
 103,143
Restructuring (recovery) charge
 (244) (32) 871
Total operating expenses71,330
 54,930
 203,926
 180,880
Income (loss) from operations81,180
 7,264
 128,479
 (67,007)
Other income (expense), net:       
Interest income and other, net3,408
 3,059
 6,098
 4,010
Interest expense
 (7,834) (8,679) (28,575)
Loss on extinguishment of debt
 (13,773) (6,239) (13,773)
Total other income (expense), net3,408
 (18,548) (8,820) (38,338)
Income (loss) before income taxes84,588
 (11,284) 119,659
 (105,345)
Income tax expense3,206
 
 3,921
 
Net income (loss)$81,382
 $(11,284) $115,738
 $(105,345)
Net income (loss) per share, basic$0.28
 $(0.04) $0.39
 $(0.44)
Net income (loss) per share, diluted$0.26
 $(0.04) $0.37
 $(0.44)
Shares used in computing net income (loss) per share, basic294,269
 256,319
 292,776
 238,024
Shares used in computing net income (loss) per share, diluted312,940
 256,319
 311,555
 238,024
 June 30, 2022December 31, 2021
ASSETS
Current assets:
Cash and cash equivalents$627,000 $647,169 
Short-term investments907,938 819,905 
Trade receivables, net235,400 282,650 
Inventory33,020 27,493 
Prepaid expenses and other current assets48,281 57,530 
Total current assets1,851,639 1,834,747 
Long-term investments463,889 371,112 
Property and equipment, net108,529 104,031 
Deferred tax assets, net113,958 111,663 
Goodwill63,684 63,684 
Other long-term assets279,705 131,002 
Total assets$2,881,404 $2,616,239 
LIABILITIES AND STOCKHOLDERS’ EQUITY
Current liabilities:
Accounts payable$19,978 $24,258 
Accrued compensation and benefits61,450 61,969 
Accrued clinical trial liabilities76,740 77,544 
Rebates and fees due to customers43,795 33,700 
Accrued collaboration liabilities29,990 86,753 
Other current liabilities72,568 53,366 
Total current liabilities304,521 337,590 
Long-term portion of deferred revenues7,209 8,739 
Long-term portion of operating lease liabilities161,019 51,272 
Other long-term liabilities17,395 8,023 
Total liabilities490,144 405,624 
Commitments and contingencies00
Stockholders' equity
Preferred stock, $0.001 par value, 10,000 shares authorized and 0 shares issued— — 
Common stock, $0.001 par value; 400,000 shares authorized; issued and outstanding: 321,800 and 318,842 at June 30, 2022, and December 31, 2021, respectively322 319 
Additional paid-in capital2,477,117 2,427,561 
Accumulated other comprehensive loss(8,917)(758)
Accumulated deficit(77,262)(216,507)
Total stockholders' equity2,391,260 2,210,615 
Total liabilities and stockholders' equity$2,881,404 $2,616,239 
The accompanying notes are an integral part of these condensed consolidated financial statements.Condensed Consolidated Financial Statements.
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EXELIXIS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS)
(in thousands)thousands, except per share amounts)
(unaudited)
 Three Months Ended June 30,Six Months Ended June 30,
 2022202120222021
Revenues:
Net product revenues$347,044 $284,248 $657,342 $511,460 
License revenues57,526 39,640 89,593 67,168 
Collaboration services revenues14,857 61,289 28,472 76,779 
Total revenues419,427 385,177 775,407 655,407 
Operating expenses:
Cost of goods sold13,481 14,884 26,684 28,082 
Research and development199,481 148,790 356,152 308,078 
Selling, general and administrative122,759 98,495 225,622 200,846 
Total operating expenses335,721 262,169 608,458 537,006 
Income from operations83,706 123,008 166,949 118,401 
Interest income4,757 1,891 6,579 4,573 
Other income (expense), net45 (11)209 (101)
Income before income taxes88,508 124,888 173,737 122,873 
Provision for income taxes17,836 28,796 34,492 25,180 
Net income$70,672 $96,092 $139,245 $97,693 
Net income per share:
Basic$0.22 $0.31 $0.43 $0.31 
Diluted$0.22 $0.30 $0.43 $0.30 
Weighted-average common shares outstanding:
Basic321,117 314,117 320,349 313,295 
Diluted324,904 322,941 324,096 322,114 
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Net income (loss)$81,382
 $(11,284) $115,738
 $(105,345)
Other comprehensive income (loss) (1)
67
 (209) 364
 152
Comprehensive income (loss)$81,449
 $(11,493) $116,102
 $(105,193)
____________________
(1)Other comprehensive income (loss) consisted solely of unrealized gains or losses, net, on available-for-sale securities arising during the periods presented. There were nominal or no reclassification adjustments to net income (loss) resulting from realized gains or losses on the sale of securities and there was no income tax expense related to other comprehensive income during those periods.
The accompanying notes are an integral part of these condensed consolidated financial statements.Condensed Consolidated Financial Statements.


EXELIXIS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME
(in thousands)
(unaudited)
Three Months Ended June 30,Six Months Ended June 30,
2022202120222021
Net income$70,672 $96,092 $139,245 $97,693 
Other comprehensive loss:
Net unrealized losses on available-for-sale debt securities, net of tax impact of $639, $257, $2,295 and $756, respectively(2,252)(755)(8,159)(2,491)
Comprehensive income$68,420 $95,337 $131,086 $95,202 
The accompanying notes are an integral part of these Condensed Consolidated Financial Statements.
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EXELIXIS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY
(in thousands)
(unaudited)

Three Months Ended June 30, 2022
Common StockAdditional
Paid-in
Capital
Accumulated Other Comprehensive LossAccumulated DeficitTotal Stockholders' Equity
SharesAmount
Balance at March 31, 2022320,268 $320 $2,448,130 $(6,665)$(147,934)$2,293,851 
Net income— — — — 70,672 70,672 
Other comprehensive loss— — — (2,252)— (2,252)
Issuance of common stock under equity incentive plans and stock purchase plan1,532 10,317 — — 10,319 
Stock transactions associated with taxes withheld on equity awards— — (6,225)— — (6,225)
Stock-based compensation— — 24,895 — — 24,895 
Balance at June 30, 2022321,800 $322 $2,477,117 $(8,917)$(77,262)$2,391,260 
Three Months Ended June 30, 2021
Common StockAdditional
Paid-in
Capital
Accumulated Other Comprehensive IncomeAccumulated DeficitTotal Stockholders' Equity
SharesAmount
Balance at March 31, 2021313,262 $313 $2,354,103 $2,740 $(445,969)$1,911,187 
Net income— — — — 96,092 96,092 
Other comprehensive loss— — — (755)— (755)
Issuance of common stock under equity incentive plans and stock purchase plan1,560 11,283 — — 11,285 
Stock transactions associated with taxes withheld on equity awards— — (2,767)— — (2,767)
Stock-based compensation— — 28,035 — — 28,035 
Balance at June 30, 2021314,822 $315 $2,390,654 $1,985 $(349,877)$2,043,077 

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EXELIXIS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY
(in thousands)
(unaudited)

Six Months Ended June 30, 2022
Common StockAdditional
Paid-in
Capital
Accumulated Other Comprehensive LossAccumulated DeficitTotal Stockholders' Equity
SharesAmount
Balance at December 31, 2021318,842 $319 $2,427,561 $(758)$(216,507)$2,210,615 
Net income— — — — 139,245 139,245 
Other comprehensive loss— — — (8,159)— (8,159)
Issuance of common stock under equity incentive plans and stock purchase plan2,958 15,829 — — 15,832 
Stock transactions associated with taxes withheld on equity awards— — (11,185)— — (11,185)
Stock-based compensation— — 44,912 — — 44,912 
Balance at June 30, 2022321,800 $322 $2,477,117 $(8,917)$(77,262)$2,391,260 
Six Months Ended June 30, 2021
Common StockAdditional
Paid-in
Capital
Accumulated Other Comprehensive IncomeAccumulated DeficitTotal Stockholders' Equity
SharesAmount
Balance at December 31, 2020311,627 $312 $2,321,895 $4,476 $(447,570)$1,879,113 
Net income— — — — 97,693 97,693 
Other comprehensive loss— — — (2,491)— (2,491)
Issuance of common stock under equity incentive plans and stock purchase plan3,195 15,484 — — 15,487 
Stock transactions associated with taxes withheld on equity awards— — (9,413)— — (9,413)
Stock-based compensation— — 62,688 — — 62,688 
Balance at June 30, 2021314,822 $315 $2,390,654 $1,985 $(349,877)$2,043,077 

The accompanying notes are an integral part of these Condensed Consolidated Financial Statements.
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EXELIXIS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(in thousands)
(unaudited)
 Six Months Ended June 30,
 20222021
Net income$139,245 $97,693 
Adjustments to reconcile net income to net cash provided by operating activities:
Depreciation and amortization9,266 6,895 
Stock-based compensation44,381 62,688 
Non-cash lease expense6,443 2,586 
Deferred taxes— 22,800 
Other, net4,359 22,831 
Changes in operating assets and liabilities:
Trade receivables, net46,693 (12,313)
Inventory(8,322)(8,020)
Prepaid expenses and other assets(26,025)(12,296)
Deferred revenue(1,831)9,346 
Accrued collaboration liabilities(53,263)2,972 
Accounts payable and other liabilities17,903 25,863 
Net cash provided by operating activities178,849 221,045 
Cash flows from investing activities:
Purchases of property, equipment and other(17,946)(33,768)
Purchases of investments(692,091)(688,903)
Proceeds from maturities and sales of investments500,356 714,081 
Net cash used in investing activities(209,681)(8,590)
Cash flows from financing activities:
Proceeds from issuance of common stock under equity incentive plans15,791 15,487 
Taxes paid related to net share settlement of equity awards(11,164)(9,413)
Net cash provided by financing activities4,627 6,074 
Net (decrease) increase in cash, cash equivalents, and restricted cash equivalents(26,205)218,529 
Cash, cash equivalents and restricted cash equivalents at beginning of period663,891 320,772 
Cash, cash equivalents and restricted cash equivalents at end of period$637,686 $539,301 
Supplemental cash flow disclosures:
Non-cash operating activities:
Right-of-use assets obtained in exchange for lease obligations$120,363 $4,893 
Non-cash investing activities:
Unpaid liabilities incurred for purchases of property and equipment$3,570 $5,125 
Unpaid liabilities incurred in asset acquisition$500 $9,000 
Unpaid liabilities incurred for unsettled investment purchases$— $7,378 
 Nine Months Ended September 30,
 2017 2016
Net income (loss)$115,738
 $(105,345)
Adjustments to reconcile net income (loss) to net cash provided by operating activities:   
Depreciation and amortization842
 754
Stock-based compensation expense15,029
 18,346
Loss on extinguishment of debt6,239
 13,773
Amortization of debt discounts and debt issuance costs182
 8,295
Interest paid in kind(11,825) 5,939
Gain on other equity investments(2,980) (2,494)
Other1,530
 1,332
Changes in assets and liabilities:   
Trade and other receivables(49,241) (85,026)
Inventory, net(2,468) (676)
Prepaid expenses and other current assets(2,530) (3,342)
Other long-term assets689
 535
Accounts payable(577) (2,436)
Accrued compensation and benefits(420) 12,357
Accrued clinical trial liabilities2,050
 (3,184)
Accrued collaboration liabilities7,091
 7,772
Deferred revenue20,710
 251,512
Other current and long-term liabilities12,199
 7,183
Net cash provided by operating activities112,258
 125,295
Cash flows from investing activities:   
Purchases of property and equipment(3,449) (1,116)
Proceeds from sale of property and equipment14
 92
Purchases of investments(248,046) (258,509)
Proceeds from maturities of investments266,335
 100,635
Proceeds from sale of investments37,294
 2,266
Purchase of restricted cash and investments(11,150) (4,150)
Proceeds from maturities of restricted cash and investments10,650
 2,650
Proceeds from other equity investments2,980
 2,494
Net cash provided by (used in) investing activities54,628
 (155,638)
Cash flows from financing activities:   
Repayment of convertible notes and term loan payable(185,788) 
Payment on conversion of convertible notes

 (7,134)
Proceeds from exercise of stock options16,532
 9,296
Proceeds from employee stock purchase plan3,053
 479
Taxes paid related to net share settlement of equity awards(3,012) (2,713)
Net cash used in financing activities(169,215) (72)
Net decrease in cash and cash equivalents(2,329) (30,415)
Cash and cash equivalents at beginning of period151,686
 141,634
Cash and cash equivalents at end of period$149,357
 $111,219
Supplemental cash flow disclosure - non-cash investing and financing activity:   
Construction-in-progress deemed to have been acquired under build-to-suit lease

$14,530
 $
Issuance of common stock in settlement of convertible notes$
 $285,308

The accompanying notes are an integral part of these condensed consolidated financial statements.Condensed Consolidated Financial Statements.

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EXELIXIS, INC.
NOTES TO CONDENSED CONSOLIDATED FINANCIAL STATEMENTS
(unaudited)
NOTE 1. ORGANIZATION AND SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES
Organization
Exelixis, Inc. (“Exelixis,” “we,” “our”(Exelixis, we, our or “us”)us) is aan oncology-focused biotechnology company committedthat strives to accelerate the discovery, development and commercialization of new medicines for patients with difficult-to-treat cancers. Using our considerable drug discovery, development and commercialization resources and capabilities, we have invented and brought to market innovative therapies that appropriately balance patient benefits and risks; we will continue to build on this foundation as we strive to provide cancer patients with new treatment options that improve care and outcomesupon current standards of care.
Today, 4 products that originated in Exelixis laboratories are available to be prescribed to patients. Sales related to our flagship molecule, cabozantinib, account for people with cancer. Sincethe large majority of our founding in 1994, three products discovered at Exelixis have progressed through clinical development, received regulatory approval, and entered the marketplace. Two are derived from cabozantinib,revenues. Cabozantinib is an inhibitor of multiple tyrosine kinases including VEGF, MET, AXL, VEGF receptors and RET receptors:and has been approved by the U.S. Food and Drug Administration (FDA) and in 62 other countries as: CABOMETYX® (cabozantinib) tablets approved for previously treated advanced renal cell carcinoma (“RCC”)(RCC), both alone and in combination with Bristol-Myers Squibb Company’s (BMS) OPDIVO® (nivolumab), for previously treated hepatocellular carcinoma (HCC) and, currently by the FDA and European Commission (EC), for previously treated, radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC); and COMETRIQ® (cabozantinib) capsules approved for progressive, metastatic medullary thyroid cancer. cancer (MTC). For physicians treating these types of cancer, cabozantinib has become or is becoming an important medicine in their selection of effective therapies.
The third product,other 2 products resulting from our discovery efforts are: COTELLIC® (cobimetinib) tablets, is a reversible, an inhibitor of MEK approved as part of multiple combination regimens to treat specific forms of advanced melanoma and marketed under a collaboration with Genentech, (aInc. a member of the Roche Group)Group (Genentech); and MINNEBRO® (esaxerenone), an oral, non-steroidal, selective blocker of the mineralocorticoid receptor approved for the treatment of hypertension in Japan and is approved as part of a combination regimenlicensed to treat advanced melanoma.Daiichi Sankyo Company, Limited (Daiichi Sankyo).
Basis of ConsolidationPresentation
The condensed consolidated financial statementsaccompanying Condensed Consolidated Financial Statements include the accounts of Exelixis and those of our wholly-ownedwholly owned subsidiaries. These entities’ functional currency is the United States (“U.S.”) dollar. All intercompany balances and transactions have been eliminated.
Basis of Presentation
The accompanying unaudited condensed consolidated financial statementsCondensed Consolidated Financial Statements have been prepared in accordance with accounting principles generally accepted in the U.S. for interim financial information and pursuant to Form 10-Q and Article 10 of Regulation S-X of the Securities and Exchange Commission (“SEC”)(SEC). Accordingly, they do not include all of the information and footnotes required by U.S. generally accepted accounting principles for complete financial statements. In our opinion, all adjustments (consisting only of normal recurring adjustments) considered necessary for a fair presentation of the results of operations and cash flowsour financial statements for the periods presented have been included. Operating results for the six months ended June 30, 2022 are not necessarily indicative of the results that may be expected for the year ending December 31, 2022 or for any future period. The accompanying Condensed Consolidated Financial Statements and Notes thereto should be read in conjunction with our Consolidated Financial Statements and Notes included in Part II, Item 8 of our Annual Report on Form 10-K for the fiscal year ended December 31, 2021, filed with the SEC on February 18, 2022 (Fiscal 2021 Form 10-K).
We have adopted a 52- or 53-week fiscal year policy that generally ends on the Friday closest to December 31st. Fiscal year 20172022, which is a 52-week fiscal year, will end on December 29, 201730, 2022 and fiscal year 20162021, which was a 52-week fiscal year, ended on December 30, 2016.31, 2021. For convenience, references in this report as of and for the fiscal periods ended September 29, 2017July 1, 2022 and September 30, 2016,July 2, 2021, and as of and for the fiscal years ended December 29, 2017 andyear ending December 30, 2016,2022 are indicated as being as of and for the fiscal periods ended SeptemberJune 30, 20172022 and SeptemberJune 30, 2016,2021, and the years ended December 31, 2017 and December 31, 2016, respectively.
Operating results for the nine months ended September 30, 2017 are not necessarily indicative of the results that may be expected for the year ending December 31, 2017 or2022, respectively.
Segment Information
We operate in 1 business segment that focuses on the discovery, development and commercialization of new medicines for anydifficult-to-treat cancers. Our Chief Executive Officer, as the chief operating decision-maker, manages and allocates resources to our operations on a total consolidated basis. Consistent with this decision-making process, our Chief
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Executive Officer uses consolidated, single-segment financial information for purposes of evaluating performance, forecasting future period. Theseperiod financial statementsresults, allocating resources and notes should be readsetting incentive targets.
All of our long-lived assets are located in conjunction with the consolidated financial statementsU.S. See “Note 2. Revenues” for enterprise-wide disclosures about product sales, revenues from major customers and notes thereto for the year ended December 31, 2016, included in our Annual Report on Form 10-K filed with the SEC on February 27, 2017.revenues by geographic region.
Use of Estimates
The preparation of our condensed consolidated financial statementsthe accompanying Condensed Consolidated Financial Statements conforms to accounting principles generally accepted in the U.S., which requires management to make judgments, estimates and assumptions that affect the reported amounts of assets, liabilities, revenueequity, revenues and expenses, and related disclosures. On an ongoing basis, management evaluates its estimates including, but not limited to, those related to revenue recognition, including deductions from revenues (such as rebates, chargebacks, sales returns and sales allowances), the period of performance, identification of deliverables and evaluation of milestones with respect towe evaluate our collaborations, the amounts of revenues and expenses under our profit and loss sharing agreement, recoverability of inventory, certain accrued liabilities including accrued clinical trial liability, and stock-based compensation.significant estimates. We base our estimates on historical experience and on various other market-specific and other relevant assumptions that we believe to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Actual results could differ materially from those estimates.


Reclassifications
Certain prior period amounts in the condensed consolidated financial statementsaccompanying Condensed Consolidated Financial Statements have been reclassified to conform to the current period presentation. We reclassified $1.8 million in payableSuch reclassifications did not impact previously reported total revenues, income from operations, net income, total assets, total liabilities or total stockholders’ equity.
Significant Accounting Policies
There have been no material changes to our customerssignificant accounting policies during the six months ended June 30, 2022, compared to the significant accounting policies disclosed in “Note 1. Organization and Summary of Significant Accounting Policies” of the “Notes to Consolidated Financial Statements” included in Part II, Item 8 of our Fiscal 2021 Form 10-K.
Recently Adopted Accounting Pronouncements
There were no new accounting pronouncements adopted by us since the filing of our Fiscal 2021 Form 10-K, which could have a significant effect on our Condensed Consolidated Financial Statements.
Recent Accounting Pronouncements Not Yet Adopted
There were no new accounting pronouncements issued since the filing of our Fiscal 2021 Form 10-K, which could have a significant effect on our Condensed Consolidated Financial Statements.
NOTE 2. REVENUES
Revenues consisted of the following (in thousands):
Three Months Ended June 30,Six Months Ended June 30,
2022202120222021
Product revenues:
Gross product revenues$483,073 $380,204 $931,310 $694,409 
Discounts and allowances(136,029)(95,956)(273,968)(182,949)
Net product revenues347,044 284,248 657,342 511,460 
Collaboration revenues:
License revenues57,526 39,640 89,593 67,168 
Collaboration services revenues14,857 61,289 28,472 76,779 
Total collaboration revenues72,383 100,929 118,065 143,947 
Total revenues$419,427 $385,177 $775,407 $655,407 
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The percentage of total revenues by customer who individually accounted for 10% or more of our total revenues were as follows:
Three Months Ended June 30,Six Months Ended June 30,
2022202120222021
Affiliates of McKesson Corporation16 %14 %17 %14 %
Affiliates of CVS Health Corporation16 %13 %16 %14 %
Affiliates of AmerisourceBergen Corporation15 %12 %16 %13 %
Ipsen Pharma SAS15 %24 %12 %19 %
Accredo Health, Incorporated10 %%%%
The percentage of trade receivables by customer who individually accounted for 10% or more of our trade receivables were as follows:
June 30, 2022December 31, 2021
Ipsen Pharma SAS30 %50 %
Affiliates of McKesson Corporation17 %10 %
Affiliates of AmerisourceBergen Corporation14 %11 %
Affiliates of CVS Health Corporation14 %%
Cardinal Health10 %%
Revenues by geographic region were as follows (in thousands):
Three Months Ended June 30,Six Months Ended June 30,
2022202120222021
U.S.$349,615 $287,190 $663,680 $517,147 
Europe62,240 90,921 96,767 124,727 
Japan7,572 7,066 14,960 13,533 
Total revenues$419,427 $385,177 $775,407 $655,407 
Total revenues include net product revenues attributed to geographic regions based on the ship-to location and license and collaboration services revenues attributed to geographic regions based on the location of our collaboration partners’ headquarters.
Net product revenues and license revenues are recorded in accordance with ASC Topic 606, Revenue from OtherContracts with Customers (Topic 606). License revenues include the recognition of the portion of milestone payments allocated to the transfer of intellectual property licenses for which it had become probable in the current liabilitiesperiod that the milestone would be achieved and a significant reversal of revenues would not occur, as well as royalty revenues and our share of profits under our collaboration agreement with Genentech. Collaboration services revenues were recorded in accordance with ASU 2018-18, Collaborative Arrangements (Topic 808): Clarifying the Interaction between Topic 808 and Topic 606 and by analogy to TradeTopic 606. Collaboration services revenues include the recognition of deferred revenues for the portion of upfront and milestone payments allocated to our research and development services performance obligations, development cost reimbursements earned under our collaboration agreements, product supply revenues, net of product supply costs, and the royalties we paid on sales of products containing cabozantinib by our collaboration partners.
Net product revenues by product were as follows (in thousands):
Three Months Ended June 30,Six Months Ended June 30,
2022202120222021
CABOMETYX$339,159 $275,614 $641,971 $499,209 
COMETRIQ7,885 8,634 15,371 12,251 
Net product revenues$347,044 $284,248 $657,342 $511,460 
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Product Sales Discounts and Allowances
The activities and ending reserve balances for each significant category of discounts and allowances, which constitute variable consideration, were as follows (in thousands):
Chargebacks, Discounts for Prompt Payment and OtherOther Customer Credits/Fees and Co-pay AssistanceRebatesTotal
Balance at December 31, 2021$14,625 $8,875 $24,825 $48,325 
Provision related to sales made in:
Current period175,564 24,444 72,890 272,898 
Prior periods1,311 (168)(73)1,070 
Payments and customer credits issued(171,534)(22,186)(64,812)(258,532)
Balance at June 30, 2022$19,966 $10,965 $32,830 $63,761 
The allowance for chargebacks, discounts for prompt payment and other are recorded as a reduction of trade receivables, net, and the remaining reserves are recorded as rebates and fees due to customers in the accompanying December 31, 2016 Condensed Consolidated Balance Sheet. Sheets.
Contract Assets and Liabilities
We receive payments from our collaboration partners based on billing schedules established in each contract. Amounts are recorded as accounts receivable when our right to consideration is unconditional. We may also recognize revenue in advance of the contractual billing schedule, and such amounts are recorded as a contract asset when recognized. We may be required to defer recognition of revenue for upfront and milestone payments until we perform our obligations under these arrangements, and such amounts are recorded as deferred revenue upon receipt or when due. For those contracts that have also reclassified the related balances between line items in Changes inmultiple performance obligations, contract assets and liabilities are reported on a net basis at the contract level. Contract assets are primarily related to Ipsen Pharma SAS (Ipsen) and contract liabilities are primarily related to deferred revenues from Takeda Pharmaceutical Company Limited (Takeda).
Contract assets and liabilities were as follows (in thousands):
June 30, 2022December 31, 2021
Contract assets (1)
$394 $1,665 
Contract liabilities:
Current portion (2)
$7,513 $7,814 
Long-term portion (3)
7,209 8,739 
Total contract liabilities$14,722 $16,553 
____________________
(1)    Presented in other long-term assets in the accompanying Condensed Consolidated Balance Sheets.
(2)    Presented in other current liabilities in the accompanying Condensed Consolidated StatementBalance Sheets.
(3)    Presented in the long-term portion of Cash Flows fordeferred revenues in the nine months ended September 30, 2016 to conform the presentation of those line items to the corresponding presentation of assets and liabilities in our accompanying Condensed Consolidated Balance Sheets.Sheets
Segment InformationDuring the six months ended June 30, 2022 and 2021, we recognized $4.5 million and $4.8 million, respectively, in revenues that were included in the beginning deferred revenues balance for those periods.
We operate as a single reportable segment.
Stock-Based Compensation
In January 2017,During the three and six months ended June 30, 2022, we adopted Accounting Standards Update (“ASU”) No. 2016-09, Compensation—Stock Compensation (Topic 718): Improvementsrecognized $59.4 million and $91.1 million, respectively, in revenues for performance obligations satisfied in previous periods. Such revenues were primarily related to Employee Share-Based Payment Accounting, (“ASU 2016-09”). ASU 2016-09 is aimed at the simplification of several aspects of the accounting for employee share-based payment transactions, including accounting for forfeitures, income tax consequences and classification on the statement of cash flows.
Pursuantroyalty payments allocated to the adoption of ASU 2016-09, we have made an election to record forfeitures when they occur. Previously, stock-based compensation was based on the number of awards expected to vest after considering estimated forfeitures. The change in accounting principlelicense performance obligations for our collaborations with regards to forfeitures was adopted using a modified retrospective approach, with a cumulative adjustment of $0.3 million to accumulated deficitIpsen, Takeda, Daiichi Sankyo and additional paid-in-capital as of January 1, 2017. No prior periods were restated as a result of this change in accounting principle.
As a result of the adoption of ASU 2016-09, as of January 1, 2017 we also recorded an increase to the federalGenentech and state net operating losses of $56.9 million for excess tax benefits previously not included. The resulting increase to the deferred tax assets of approximately $21.2 million was offset by a corresponding increase to the valuation allowance, resulting in a net zero impact to both our income tax expense in our Condensed Consolidated Statements of Operations and our deferred tax assets and liabilities in our Condensed Consolidated Balance Sheets.
ASU 2016-09 also requires that cash paid to taxing authorities when directly withholding shares for tax withholding purposes be classified as a financing activity on our Condensed Consolidated Statement of Cash Flows. Previously, we classified such payments as operating cash flows. The change in accounting principle with regards to such cash flows was adopted using a retrospective approach. Accordingly, we recorded a reclassification that resulted in an increase in cash provided by operating activities by $2.7 million along with a corresponding increase in cash used in financing activities in our Condensed Consolidated Statement of Cash Flows for the nine months ended September 30, 2016.
Recent Accounting Pronouncements
In May 2014, the Financial Accounting Standards Board (“FASB”) issued ASU No. 2014-09, Revenue from Contracts with Customers (Topic 606) (“ASU 2014-09”). In August 2015, the FASB issued ASU No. 2015-14, Revenue from Contracts with Customers (Topic 606): Deferral of the Effective Date, which delayed the effective date of ASU 2014-09 by one year. ASU 2014-09, as amended, becomes effective for us in the first quarter of fiscal year 2018, which is when we will adopt the standard. ASU 2014-09 also 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 (the modified retrospective method). We will adopt ASU 2014-09 using the modified retrospective method.
The core principle of ASU 2014-09 is that an entity should recognize revenue when it transfers promised goods or services to customers in an amount that reflects the consideration to which the entity expects to be entitled in exchange for those goods or services. ASU 2014-09 defines a five step process to achieve this core principle and, in doing so, has created the possibility that more judgment and estimates may be required within the revenue recognition process than required under existing U.S. generally accepted accounting pronouncements. We have substantially completed our analysis on the adoption of ASU 2014-09 and have determined the adoption will not have a material impact on the recognition of license revenue from product sales. ASU 2014-09 will impactfor the timingachievement of recognition of revenuemilestones during the three months ended June 30, 2022, allocated to the license performance obligations for our collaboration arrangements with Ipsen.
As of June 30, 2022, $89.3 million of the combined transaction prices for our Ipsen Pharma SAS (“Ipsen”)and Takeda collaborations were allocated to our research and Takeda Pharmaceutical Company Ltd. (“Takeda”). development services performance obligations that had not yet been satisfied. See “Note 3. Collaboration Agreements and Business Development Activities” of the “Notes to Consolidated Financial Statements”
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included in Part II, Item 8 of our Fiscal 2021 Form 10-K for additional information about the expected timing to satisfy these performance obligations.
NOTE 3. COLLABORATION AGREEMENTS AND BUSINESS DEVELOPMENT ACTIVITIES
We expect to reclassify deferred revenue

to accumulated deficit (a concept known as “lost revenue”)have established multiple collaborations with leading pharmaceutical companies for amounts associated with these collaboration arrangements upon recordingthe commercialization and further development of our transition adjustment in the first quarter of 2018, primarily due to the timing of recognition of revenue related to intellectual property licenses thatcabozantinib franchise. Additionally, we have transferredentered into several research collaborations, in-licensing arrangements and other strategic transactions to further enhance our early-stage pipeline and expand our ability to discover, develop and commercialize novel therapies with the goal of providing new treatment options for developmentcancer patients and commercializationtheir physicians. Historically, we also entered into other collaborations with leading pharmaceutical companies pursuant to which we out-licensed other compounds and programs in our portfolio.
See “Note 3. Collaboration Agreements and Business Development Activities” of the “Notes to Consolidated Financial Statements” included in Part II, Item 8 of our products. Additionally,Fiscal 2021 Form 10-K, as further described below, for alladditional information on certain of our collaboration arrangements, the timing of recognition of certain of our developmentagreements and regulatory milestones could change as a result of the variable consideration guidance included in ASU 2014-09. ASU 2014-09 will also require additional disclosures regarding our revenue transactions.in-licensing arrangements.
NOTE 2: COLLABORATION AGREEMENTSCabozantinib Commercial Collaborations
Ipsen Collaboration
In February 2016, we entered into a collaboration and license agreement (the “Ipsen Collaboration Agreement”) with Ipsen for the commercialization and further development of cabozantinib. Pursuant toUnder the terms of the Ipsen Collaboration Agreement,collaboration agreement, as amended, Ipsen received exclusive commercialization rights for current and potential future cabozantinib indications outside of the U.S., Canada and Japan (the “Ipsen Territory”). The Ipsen Collaboration Agreement was subsequently amended in December 2016 (the “Amendment”) to include commercialization rights in Canada in the Ipsen Territory.Japan. We have also agreed to collaborate with Ipsen on the development of cabozantinib for current and potential future indications. The parties’ efforts are governed through a joint steering committee and appropriate subcommittees established to guide and oversee the collaboration’s operation and strategic direction; provided, however, that we retain final decision-making authority with respect to cabozantinib’s ongoing development.
In consideration for the exclusive license and other rights contained in the Ipsen Collaboration Agreement, Ipsen paid us an upfront nonrefundable payment of $200.0 million in March 2016. Additionally, as a result of the Amendment, we received a $10.0 million upfront nonrefundable payment from Ipsen in December 2016 and, as a result of the approval of cabozantinib in second-line RCC by the European Commission (“EC”) in September 2016, we received a $60.0 million milestone in November 2016. We are receiving a 2% royalty on the initial $50.0 million of net sales by Ipsen, and are entitled to receive a 12% royalty on the next $100.0 million of net sales by Ipsen. After the initial $150.0 million of sales, we are entitled to receive a tiered royalty of 22% to 26% on annual net sales by Ipsen; these tiers will reset each calendar year. We are primarily responsible for funding cabozantinib-related development costs for those trials in existence at the time we entered into the Ipsen Collaboration Agreement; global development costs for additional trials are shared between the parties, with Ipsen reimbursing us for 35% of such costs, provided Ipsen opts in to participate in such additional trials. Pursuant to the terms of the Ipsen Collaboration Agreement, we will remain responsible for the manufacture and supply of cabozantinib for all development and commercialization activities. As part ofRevenues under the collaboration agreement we entered into a supply agreement pursuant to which we will supply finished, labeled drug product towith Ipsen for distribution in the Ipsen Territories at our cost,were as defined in the agreement, which excludes the 3% royalty we are required to pay GlaxoSmithKline (“GSK”) on Ipsen’s Net Sales of any product incorporating cabozantinib.follows (in thousands):
The Ipsen Collaboration Agreement contains multiple deliverables consisting of intellectual property licenses, delivery of products and/or materials containing cabozantinib to Ipsen for all development and commercial activities, research and development services, and participation on the joint steering, development and commercialization committees (as defined in the Ipsen Collaboration Agreement). We determined that these deliverables do not have stand-alone value and accordingly, combined these deliverables into a single unit of accounting and allocated the entire arrangement consideration to that combined unit of accounting. As a result, the upfront payment of $200.0 million, received in the first quarter of 2016 and the $10.0 million upfront payment received in December 2016 in consideration for the development and commercialization rights in Canada are being recognized ratably over the term of the Ipsen Collaboration Agreement, through early 2030, which is the current estimated patent expiration of cabozantinib in the European Union. At the time we entered into the Ipsen Collaboration Agreement, we also determined that the $60.0 million milestone we achieved upon the approval of cabozantinib by the EC in second-line RCC was not substantive due to the relatively low degree of uncertainty and relatively low amount of effort required on our part to achieve the milestone as of the date of the collaboration agreement; the $60.0 million was deferred entirely until the date of the European Medicines Agency’s (the “EMA”) approval of cabozantinib in second-line RCC in September 2016 and has been and will continue to be recognized ratably over the remainder of the term of the Ipsen Collaboration Agreement. The two $10.0 million milestones for the first commercial sales of CABOMETYX in Germany and the United Kingdom were determined to be substantive at the time we entered into the Ipsen Collaboration Agreement and were recognized as collaboration revenues in the fourth quarter of 2016. We determined that the remaining development and regulatory milestones are substantive and will be recognized as revenue in the periods in which they are achieved. We consider the contingent payments due to us upon the achievement of specified sales volumes to be similar to royalty payments. Reimbursements for development costs are classified as revenue as the development services represent our ongoing major or central operations.

Three Months Ended June 30,Six Months Ended June 30,
2022202120222021
License revenues$51,168 $33,656 $75,782 $56,107 
Collaboration services revenues11,072 57,265 20,985 68,620 
Total$62,240 $90,921 $96,767 $124,727 
During the three months ended March 31, 2017, we reclassified $9.0 million of deferred revenue to Accrued collaboration liabilities and Other long-term liabilities, and accordingly adjusted our amortization of the upfront payment of $200.0 million as a result of a change in operational responsibilities for certain clinical programs in the Ipsen Territory. As of SeptemberJune 30, 2017, we had paid $2.1 million toward the $9.0 million of reimbursements due to Ipsen for these clinical programs.
In September 2017,2022, we recognized two milestones totaling $45.0$25.7 million resulting from Ipsen’s receipt of the validation from the EMA for the application for variation to the CABOMETYX marketing authorization for the addition of a new indication in first-line treatment of advanced RCC in adults. The two milestones were determined to be substantive at the time we entered into the Ipsen Collaboration Agreement and were recognized as collaboration revenues in the third quarter of 2017. Payment for the first milestone of $20.0 million is due in the fourth quarter of 2017 and payment for the second milestone of $25.0 million is due in the first quarter of 2018.
See “Note 2 - Collaboration Agreements” to our Consolidated Financial Statements included in our Annual Report on Form 10-K for the year ended December 31, 2016 filed with the SEC on February 27, 2017 for additional description of our collaboration agreement with Ipsen.
During the three and nine months ended September 30, 2017 and 2016, collaboration revenues under the Ipsen Collaboration Agreement were as follows (in thousands):
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Milestones achieved$45,000
 $
 $45,000
 $
Amortization of upfront payments and deferred milestone4,742
 3,780
 13,788
 8,570
Royalty revenue371
 
 814
 
Development cost reimbursements1,123
 
 2,322
 
Product supply agreement revenue1,681
 
 3,483
 
Cost of supplied product(1,681) 
 (3,483) 
Royalty payable to GSK on net sales by Ipsen(557) 
 (1,221) 
Collaboration revenues under the Ipsen Collaboration Agreement$50,679
 $3,780
 $60,703
 $8,570
As of September 30, 2017, short-term and long-term deferred revenue relating to the Ipsen Collaboration Agreement was $19.0 million and $215.0 million, respectively.
Genentech Collaboration
In December 2006, we out-licensed the further development and commercialization of cobimetinib to Genentech pursuant to a worldwide collaboration agreement (the “Genentech Collaboration Agreement”). Under the terms of the Genentech Collaboration Agreement for cobimetinib, we are entitled to a share of profits and losses received in connection with cobimetinib’s commercialization intwo regulatory milestones totaling $27.0 million upon approval by the U.S. This profitEuropean Commission and loss share has multiple tiers: we are entitledHealth Canada of cabozantinib as monotherapy for the treatment of adult patients with locally advanced or metastatic differentiated thyroid carcinoma (DTC), refractory or not eligible to 50%radioactive iodine (RAI) who have progressed during or after prior systemic therapy.
As of profits and losses from the first $200.0June 30, 2022, $51.9 million of U.S. actual sales, decreasingthe transaction price for this collaboration was allocated to 30% of profitsour research and losses from U.S. actual sales in excess of $400.0 million. Separately, we are entitled to low double-digit royalties on net sales outside the U.S. In November 2013, we exercised an option under the Genentech Collaboration Agreement to co-promote COTELLIC in the U.S., which allows for us to provide up to 25% of the total sales force for approved cobimetinib indications in the U.S. In 2015, we began fielding 25% of the sales force promoting COTELLIC in combination with Zelboraf® as a treatment for patients with BRAF mutation-positive advanced melanoma.
On June 3, 2016, we filed a Demand for Arbitration before JAMS in San Francisco, California asserting claims against Genentech related to its clinical development pricing and commercialization of COTELLIC, and cost and revenue allocations arising from COTELLIC’s commercialization in the U.S. Our arbitration demand assertedservices performance obligations that Genentech breached the Genentech Collaboration Agreement by, amongst other breaches, failing to meet its diligence and good faith obligations.
On July 13, 2016, Genentech asserted a counterclaim for breach of contract seeking monetary damages and interest related to the cost allocations under the Genentech Collaboration Agreement. On December 29, 2016, however, Genentech withdrew its counterclaim against us and stated that it would unilaterally change its approach to the allocation

of promotional expenses arising from commercialization of the COTELLIC plus Zelboraf combination therapy, both retrospectively and prospectively. The revised allocation approach substantially reduced our exposure to costs associated with promotion of the COTELLIC plus Zelboraf combination in the U.S. However, other significant issues remained in dispute between the parties. Genentech’s action didhave not address the claims in our demand for arbitration related to Genentech’s clinical development of cobimetinib, or pricing or promotional costs for COTELLIC in the U.S. and it did not fully resolve claims over revenue allocation. In addition, Genentech’s unilateral action did not clarify how it intended to allocate promotional costs incurred with respect to the promotion of other combination therapies that include COTELLIC for other indications that may be developed or are in development and may be approved. As a result, we continued to press our position before the arbitral panel to obtain a just resolution of these claims.
On June 8, 2017, the parties settled the arbitration, which was dismissed with prejudice. The settlement was memorialized in a settlement agreement dated July 19, 2017, that included a mutual release of all claims arising out of or related in any way to the causes of actions and/or claims that were asserted or could haveyet been asserted based on the facts alleged in the arbitration. The settlement does not provide for payments in settlement of the asserted claims; as part of the settlement, on July 19, 2017, the parties entered into an amendment to the Genentech Collaboration Agreement. Pursuant to the terms of the amendment, we continue to be entitled to a share of U.S. profits and losses received in connection with the commercialization of COTELLIC in accordance with the profit share tiers as originally set forth in the collaboration agreement, which share continues to decrease as sales of COTELLIC increase. However, effective as of July 1, 2017, the revenue for each sale of COTELLIC applied to the profit and loss statement for the collaboration agreement (the “Collaboration P&L”) is being calculated using the average of the quarterly net selling prices of COTELLIC and any additional branded Genentech product(s) prescribed with COTELLIC in such sale. While we also continue to share U.S. commercialization costs for COTELLIC, the amendment expressly sets forth that the amount of commercialization costs Genentech is entitled to allocate to the Collaboration P&L is to be reduced based on the number of Genentech products in any given combination including COTELLIC. In addition, the amendment also sets forth the parties’ confirmation and agreement that we have exercised our co-promotion option and that, as such, we have the option to co-promote current and future Genentech combinations that include COTELLIC in the U.S.
During the three and nine months ended September 30, 2017 and 2016, ex-U.S. royalty revenues and U.S. losses under the Genentech Collaboration Agreement were as follows (in thousands):
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Royalty revenues on ex-U.S. sales of COTELLIC included in Collaboration revenues$1,392
 $672
 $5,057
 $1,844
U.S. losses included in Selling, general and administrative expenses (1)
$(891) $(2,922) $(2,298) $(14,845)
____________________
(1)A portion of the accrual for losses for the three and nine months ended September 30, 2016 were reversed in December 2016 when we were relieved of our obligation to pay certain disputed costs as a result of Genentech’s unilateral change to its approach to the allocation of promotional expenses arising from commercialization of the COTELLIC plus Zelboraf combination therapy.
The U.S. losses under the Genentech Collaboration Agreement include our share of the net loss from the collaboration, as well as personnel and other costs we have incurred to co-promote COTELLIC plus Zelboraf in the U.S.
Royalty revenues from the Genentech Collaboration Agreement are based on amounts reported to us by Genentech and are recorded when such information becomes available to us. For prior periods, from the launch of COTELLIC through December 31, 2016, such information was not available until the following quarter, meaning that historically we recorded royalty revenues on a one quarter lag. Beginning in 2017, such information became available to us in the current quarter. As a result of this change, during the nine months ended September 30, 2017, in addition to the royalties reported to us for that period we also recorded $1.1 million in royalties for the sales activity related to the three months ended December 31, 2016.satisfied.
Takeda Collaboration
OnIn January 30, 2017, we entered into a collaboration and license agreement (the “Takeda Collaboration Agreement”) with Takeda for the commercialization and further clinical development of cabozantinib in Japan.cabozantinib. Pursuant to the terms of thethis collaboration and license agreement, as amended, Takeda Collaboration Agreement, Takeda will havehas exclusive commercialization rights for current and potential future cabozantinib indications in Japan. The companiesJapan, and the parties have also agreed to collaborate on the clinical

development of cabozantinib in Japan. The operation and strategic direction of the parties’ collaboration is governed through a joint executive committee and appropriate subcommittees.
In consideration for the exclusive license and other rights contained in the Takeda Collaboration Agreement, Takeda paid us an upfront nonrefundable payment
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Table of $50.0 million in February 2017. We will be eligible to receive development, regulatory and first-sales milestones of up to $95.0 million related to second-line RCC, first-line RCC and second-line hepatocellular carcinoma (“HCC”), as well as additional development, regulatory and first-sale milestone payments for potential future indications. The Takeda Collaboration Agreement also provides that we will be eligible to receive pre-specified payments of up to $83.0 million associated with potential sales milestones. We will also receive royalties on net sales of cabozantinib in Japan at an initial tiered rate of 15% to 24% on net sales for the first $300.0 million of cumulative net sales. Thereafter, the royalty rate will be adjusted to 20% to 30% on annual net sales.Contents
Takeda will be responsible for 20% of the costs associated with the global cabozantinib development plan’s current and future trials, provided Takeda opts to participate in such future trials, and 100% of costs associated with cabozantinib development activities that are exclusively for the benefit of Japan. Pursuant to the terms of the Takeda Collaboration Agreement, we will remain responsible for the manufacture and supply of cabozantinib for all development and commercialization activitiesRevenues under the collaboration. As part of the collaboration the parties will enter into appropriate supply agreements for the manufacture and supply of cabozantinib for Takeda’s territory.
During the three and nine months ended September 30, 2017, collaboration revenues under theagreement with Takeda Collaboration Agreement were as follows (in thousands):
Three Months Ended June 30,Six Months Ended June 30,
2022202120222021
License revenues$2,700 $2,097 $5,065 $3,398 
Collaboration services revenues3,785 4,024 7,487 8,159 
Total$6,485 $6,121 $12,552 $11,557 
 Three Months Ended September 30, Nine Months Ended September 30,
Amortization of upfront payment$2,830
 $7,547
Development cost reimbursements1,193
 3,301
Collaboration revenues under the Takeda Collaboration Agreement$4,023
 $10,848
There was no such revenue during the comparable periods in 2016. As of SeptemberJune 30, 2017, short-term and long-term deferred revenue relating to the Takeda Collaboration Agreement was $11.32022, $37.5 million and $31.1 million, respectively.
The Takeda Collaboration Agreement may be terminated for cause by either party based on uncured material breach by the other party, bankruptcy of the other party ortransaction price for safety reasons. For clarity, Takeda’s failurethis collaboration was allocated to achieve specified levels of commercial performance, based upon sales volume and/or promotional effort, during the first six years following the first commercial sale of cabozantinib in Japan shall constitute a material breach of the Takeda Collaboration Agreement. We may terminate the agreement if Takeda challenges or opposes any patent covered by the Takeda Collaboration Agreement. At any time prior to August 1, 2023, the parties may mutually agree to terminate the Takeda Collaboration Agreement if Japan’s Pharmaceuticals and Medical Devices Agency is unlikely to grant approval of the marketing authorization application in any cancer indication in Japan. After the commercial launch of cabozantinib in Japan, Takeda may terminate the Takeda Collaboration Agreement upon twelve months’ prior written notice following the third anniversary of the first commercial sale of cabozantinib in Japan. Upon termination by either party, all licenses granted by us to Takeda will automatically terminate, and the licenses granted by Takeda to us shall survive such termination and shall automatically become worldwide.
The Takeda Collaboration Agreement contains multiple deliverables consisting of intellectual property licenses, delivery of products and/or materials containing cabozantinib to Takeda for all development and commercial activities,our research and development services and participation on the joint executive, development and commercialization committees (as defined in the Takeda Collaboration Agreement). We determinedperformance obligations that these deliverables, other than the commercial supply and joint commercialization committee participation, are non-contingent in nature. The commercial supply deliverable was deemed contingent, primarily due to the fact that there is uncertainty around approval in Japan, which is dependent on successful clinical trial results from a study in Japanese patients. We also determined that the non-contingent deliverables dohave not have stand-alone value, because each one of them has value only if we meet our obligation as a whole to provide Takeda with research and development services, including clinical supply of cabozantinib under the Takeda Collaboration Agreement. Accordingly, we combined the non-contingent deliverables into a single unit of accounting and allocated the $50.0 million upfront fee to that combined unit of accounting. We also determined that the level of effort required of us to meet our obligations under the Takeda Collaboration Agreement is not expected to vary significantly overyet been satisfied.

Royalty Pharma
the development period of the Takeda Collaboration Agreement. As a result, the upfront payment of $50.0 million, received in the first quarter of 2017, will be recognized ratably over the development period of the Takeda Collaboration Agreement of approximately four years. We determined that the development and regulatory milestones are substantive and will be recognized as revenue in the periods in which they are achieved. We consider the contingent payments due to us upon the achievement of specified sales volumes to be similar to royalty payments. We will record reimbursements for development costs as revenue as the development services represent a part of our ongoing major or central operations.
Bristol-Myers Squibb Collaboration - First-Line Advanced RCC, Bladder Cancer and HCC Combination Studies
In February 2017, we entered into a clinical trial collaboration agreement with Bristol-Myers Squibb Company(the “BMS Collaboration Agreement”) for the purpose of evaluating the combination of cabozantinib and nivolumab with or without ipilimumab in various tumor types, including, in RCC, HCC and bladder cancer. To date, a phase 3 trial in first-line advanced RCC and a phase 2 trial in HCC evaluating these combinations has been initiated. Pursuant to the terms of the BMS Collaboration Agreement, each party will grant to the other a non-exclusive, worldwide (within the collaboration territory as defined in the BMS Collaboration Agreement), non-transferable, royalty-free license to use the other party’s compounds in the conduct of each clinical trial. The parties’ efforts are governed through a joint development committee established to guide and oversee the collaboration’s operation. Each trial will be conducted under a combination Investigational New Drug Application, unless otherwise required by a regulatory authority. Each party will be responsible for supplying drug product for the applicable clinical trial in accordance with the terms of the supply agreement entered into between the parties in April 2017, and costs for each such trial will be shared equally between the parties, unless two Bristol-Myers Squibb Company (“BMS”) compounds will be utilized in such trial, in which case BMS will bear two-thirds of the costs and we will bear one-third of the costs for such study treatment arms. Unless earlier terminated, the BMS Collaboration Agreement will remain in effect until the completion of all clinical trials under the collaboration, all related trial data has been delivered to both parties and the completion of any then agreed upon analysis. Ipsen has opted in to participate in the phase 3 pivotal trial in first-line advanced RCC and will have access to the results to support potential future regulatory submissions. Ipsen may also participate in future studies at its choosing.
The Roche Group Collaboration
In February 2017, we established a clinical trial collaboration with The Roche Group (“Roche”) for the purpose of evaluating the safety and tolerability of cabozantinib in combination with Roche’s atezolizumab in patients with locally advanced or metastatic solid tumors. Each party is responsible for supplying drug product for the applicable clinical trial in accordance with the terms of the clinical supply agreement entered into by the parties in February 2017. Based on the dose-escalation results, the trial has the potential to enroll up to four expansion cohorts, including a cohort of patients with previously untreated advanced clear cell RCC and three cohorts of urothelial carcinoma, namely platinum eligible first-line patients, first or second-line platinum ineligible patients and patients previously treated with platinum-containing chemotherapy. The trial was initiated in June 2017 and is open for enrollment. We are the sponsor of the trial, and Roche is responsible for supplying atezolizumab to us. Ipsen has opted to participate in the study and will have access to the results to support potential future development in its territories.
GlaxoSmithKline Collaboration
In October 2002, we established a collaboration with GSK to discover and develop novel therapeutics in the areas of vascular biology, inflammatory disease and oncology. Under the terms of the product development and commercialization collaboration agreement GSK had the rightwith GlaxoSmithKline (GSK), that required us to choose cabozantinib for further development and commercialization, but notified us in October 2008 that it had waived its right to select the compound for such activities. As a result, we retained the rights to develop, commercialize, and license cabozantinib, subject to payment to GSK ofpay a 3% royalty to GSK on the worldwide net sales of any product incorporating cabozantinib. Thecabozantinib sold by us and our collaboration partners. Effective January 1, 2021, Royalty Pharma plc (Royalty Pharma) acquired from GSK all rights, title and interest in royalties on net product sales containing cabozantinib for non-U.S. markets for the full term of the royalty and for U.S. market through September 2026, after which time U.S. royalties will revert back to GSK. Royalties earned by Royalty Pharma in connection with our sales of cabozantinib are included in cost of goods sold and in connection with sales by our collaboration partners are included as a reduction of collaboration services revenues. Such royalties were $14.6 million and $27.7 million during the three and six months ended June 30, 2022, respectively, as compared to $12.1 million and $22.2 million in the corresponding periods in 2021.

Other Commercial Collaborations
Genentech Collaboration
In December 2006, we out-licensed the development and commercialization of cobimetinib to Genentech under a worldwide collaboration agreement. In November 2015, the FDA approved cobimetinib, under the brand name COTELLIC, in combination with Genentech’s ZELBORAF® (vemurafenib) for the treatment of patients with BRAF V600E or V600K mutation-positive advanced melanoma. COTELLIC in combination with ZELBORAF has also been approved in the European Union and multiple additional countries for use in the same indication. In July 2020, the FDA also approved COTELLIC for use in combination with ZELBORAF and TECENTRIQ® (atezolizumab) for the treatment of patients with BRAF V600 mutation-positive advanced melanoma in previously untreated patients.
License revenues under the collaboration agreement was terminated during 2014, although GSK will continue to be entitled to a 3% royalty on net sales by us or our collaboration partners of any product incorporating cabozantinib, including COMETRIQ and CABOMETYX.
During the three and nine months ended September 30, 2017 and 2016, royalties owed to GSK in connection with the sales of COMETRIQ and CABOMETYXGenentech were as follows (in thousands):
 Three Months Ended June 30,Six Months Ended June 30,
 2022202120222021
Profits on U.S. commercialization$1,682 $2,160 $3,821 $3,954 
Royalty revenues on ex-U.S. sales$889 $782 $2,517 $1,733 
Research Collaborations, In-Licensing Arrangements and Other Business Development Activities
Our research collaborations, in-licensing arrangements and other strategic transactions include upfront payments, development, regulatory, commercial milestone payments and royalty payments, contingent upon the occurrence of certain future events linked to the success of the asset in development. Certain of our research collaborations provide us exclusive options that give us the right to license programs developed under the research collaborations for further discovery and development. When we decide to exercise the options, we are required to pay an exercise fee and then, in most instances we will assume the responsibilities for all subsequent clinical development, manufacturing and commercialization. In conjunction with each of these collaborative in-licensing arrangements, we were subject to upfront payments and will make payments for potential future development, regulatory, and commercial milestones as well as royalties on future net product sales.
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 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Royalties owed to GSK$3,446
 $1,277
 $8,809
 $2,495
In June 2022, we entered into an exclusive option and license agreement with BioInvent International AB (BioInvent), upon which we paid BioInvent an upfront payment of $25.0 million. Upon option exercise, we will pay BioInvent an option exercise fee, and BioInvent will be eligible for additional payments from us for future development and commercial milestones, as well as royalties on future net product sales.

Royalties owedAs of June 30, 2022, in conjunction with each of our collaborative in-licensing arrangements, and an asset purchase agreement entered in 2021, we will make payments for potential future development milestones of up to GSK are included in Cost$321.8 million, regulatory milestones of goods sold for sales by usup to $453.7 million and as a reductioncommercial milestones of Collaboration revenues for sales by Ipsenup to $2,070.7 million, each in the accompanying Condensed Consolidated Statements of Operations.aggregate per product or target, as well as royalties on future net product sales.
Other Collaborations
During the nine months ended September 30, 2017, we recognized $2.5 million in contract revenues from a milestone payment received from BMS related to its ROR gamma program.
During the three and nine months ended September 30, 2016, we recognized $15.0 million in contract revenues from a milestone payment earned from Daiichi Sankyo Company, Limited (“Daiichi Sankyo”) related to its worldwide license of our compounds that modulate the mineralocorticoid receptor (“MR”), including CS-3150 (an isomer of XL550). During the nine months ended September 30, 2016, we also recognized $5.0 million in contract revenues from a milestone payment earned from Merck related to its worldwide license of our phosphoinositide-3 kinase-delta program.
See “Note 2 - Collaboration Agreements” to our Consolidated Financial Statements included in our Annual Report on Form 10-K for the year ended December 31, 2016 filed with the SEC on February 27, 2017 for a description of our existing collaboration agreements.
NOTE 3:4. CASH AND INVESTMENTS
AllCash, Cash Equivalents and Restricted Cash Equivalents
A reconciliation of cash, cash equivalents, and restricted cash equivalents reported in the accompanying Condensed Consolidated Balance Sheets to the amount reported within the accompanying Condensed Consolidated Statements of Cash Flows was as follows (in thousands):
 June 30, 2022December 31, 2021
Cash and cash equivalents$627,000 $647,169 
Restricted cash equivalents included in other long-term assets10,686 16,722 
Cash, cash equivalents, and restricted cash equivalents as reported in the accompanying Condensed Consolidated Statements of Cash Flows$637,686 $663,891 
Restricted cash equivalents are used to collateralize letters of credit and consist of money-market funds and certificates of deposit with original maturities of 90 days or less. The restricted cash equivalents are classified as other long-term assets based upon the remaining term of the underlying restriction. As of June 30, 2022, restricted cash equivalents included $9.2 million of short-term investments, which is collateral under our January 2021 standby letter of credit to guarantee our obligation to fund a portion of the total tenant improvements related to our build-to-suit lease at our corporate campus. As we fund these tenant improvements, our restricted cash becomes available for operations. Our January 2021 standby letter of credit will remain effective through August 31, 2022.
Cash, Cash Equivalents, Restricted Cash Equivalents and Investments
Cash, cash equivalents, restricted cash equivalents and investments are classified as available-for-sale. Theconsisted of the following tables summarize cash(in thousands):
June 30, 2022
Amortized CostGross Unrealized GainsGross Unrealized LossesFair Value
Debt securities available-for-sale:
Commercial paper$880,593 $— $(107)$880,486 
Corporate bonds573,343 117 (9,059)564,401 
U.S. Treasury and government-sponsored enterprises255,407 58 (2,057)253,408 
Municipal bonds12,350 — (202)12,148 
Total debt securities available-for-sale1,721,693 175 (11,425)1,710,443 
Cash80,747 — — 80,747 
Money market funds87,821 — — 87,821 
Certificates of deposit130,502 — — 130,502 
Total cash, cash equivalents, restricted cash equivalents and investments$2,020,763 $175 $(11,425)$2,009,513 

14

December 31, 2021
Amortized CostGross Unrealized GainsGross Unrealized LossesFair Value
Debt securities available-for-sale:
Commercial paper$945,801 $42 $(2)$945,841 
Corporate bonds541,774 876 (1,672)540,978 
U.S. Treasury and government-sponsored enterprises33,965 (21)33,945 
Municipal bonds12,924 15 (35)12,904 
Total debt securities available-for-sale1,534,464 934 (1,730)1,533,668 
Cash135,653 — — 135,653 
Money market funds66,531 — — 66,531 
Certificates of deposit119,056 — — 119,056 
Total cash, cash equivalents, restricted cash equivalents and investments$1,855,704 $934 $(1,730)$1,854,908 
Interest receivable was $3.6 million and cash equivalents, investments, and restricted cash and investments by balance sheet line item$2.9 million as of SeptemberJune 30, 20172022 and December 31, 2016 (in thousands):
 September 30, 2017
 
Amortized
Cost
 
Gross
Unrealized
Gains
 
Gross
Unrealized
Losses
 Fair Value
Cash and cash equivalents$149,357
 $
 $
 $149,357
Short-term investments217,805
 17
 (81) 217,741
Long-term investments50,557
 41
 (29) 50,569
Long-term restricted cash and investments4,650
 
 
 4,650
Total cash and investments$422,369
 $58
 $(110) $422,317
 December 31, 2016
 
Amortized
Cost
 
Gross
Unrealized
Gains
 
Gross
Unrealized
Losses
 Fair Value
Cash and cash equivalents$151,686
 $
 $
 $151,686
Short-term investments268,234
 13
 (130) 268,117
Long-term investments55,792
 1
 (192) 55,601
Long-term restricted cash and investments4,150
 
 
 4,150
Total cash and investments$479,862
 $14
 $(322) $479,554
Under our loan2021, respectively, and security agreement with Silicon Valley Bank, we were required to maintain compensating balances on depositis included in one or more investment accounts with Silicon Valley Bank or one of its affiliates. The total collateral balance of $81.6 million as of December 31, 2016 is reflectedprepaid expenses and other current assets in ourthe accompanying Condensed Consolidated Balance Sheet in short-term investments; as a result of our repayment of the term loan with Silicon Valley Bank, the compensating balance requirement was terminated as of March 29, 2017. See “Note 7 - Debt” to our Consolidated Financial Statements included in our Annual Report on Form 10-K for the year ended December 31, 2016 filed with the SEC on February 27, 2017 for more information regarding the collateral balance requirements under our Silicon Valley Bank loan and security agreement.Sheets.

The following tables summarize our cash equivalents and investments by security type as of September 30, 2017 and December 31, 2016. The amounts presented exclude cash, but include investments classified as cash equivalents (in thousands):
 September 30, 2017
 
Amortized
Cost
 
Gross
Unrealized
Gains
 
Gross
Unrealized
Losses
 Fair Value
Money market funds$42,797
 $
 $
 $42,797
Commercial paper168,738
 
 
 168,738
Corporate bonds187,197
 58
 (95) 187,160
U.S. Treasury and government sponsored enterprises14,659
 
 (15) 14,644
Total investments$413,391
 $58
 $(110) $413,339
 December 31, 2016
 
Amortized
Cost
 
Gross
Unrealized
Gains
 
Gross
Unrealized
Losses
 Fair Value
Money market funds$71,457
 $
 $
 $71,457
Commercial paper165,375
 
 
 165,375
Corporate bonds152,712
 3
 (308) 152,407
U.S. Treasury and government sponsored enterprises70,730
 11
 (14) 70,727
Total investments$460,274
 $14
 $(322) $459,966
GainsRealized gains and losses on the sales of investments available-for-sale were nominal or zeroinsignificant during the three and ninesix months ended SeptemberJune 30, 20172022, and 2016.2021.
AllWe manage credit risk associated with our investment portfolio through our investment policy, which limits purchases to high-quality issuers and limits the amount of our investments are subject toportfolio that can be invested in a quarterly impairment review. During the nine months ended September 30, 2017single issuer. The fair value and 2016 we did not record any other-than-temporary impairment chargesgross unrealized losses on ourdebt securities available-for-sale securities. As of September 30, 2017, therein an unrealized loss position were 84as follows (in thousands):
June 30, 2022
Fair ValueGross Unrealized Losses
Corporate bonds$540,226 $(9,059)
U.S. Treasury and government-sponsored enterprises237,680 (2,057)
Commercial paper14,000 (107)
Municipal bonds12,148 (202)
Total$804,054 $(11,425)
December 31, 2021
Fair ValueGross Unrealized Losses
Corporate bonds$385,053 $(1,672)
Commercial paper43,290 (2)
U.S. Treasury and government-sponsored enterprises18,962 (21)
Municipal bonds7,475 (35)
Total$454,780 $(1,730)
There were 237 and 133 investments in an unrealized loss position with gross unrealized lossesas of $0.1 millionJune 30, 2022 and an aggregate fair value of $134.9 million. The investmentsDecember 31, 2021, respectively. All securities presented above have been in an unrealized loss position comprisefor less than twelve months except for six corporate bondsbond securities with an aggregate fair value of $124.9$18.1 million and securities issued by U.S. Treasury and government sponsored enterprises with an aggregate fair valueimmaterial unrealized loss as of $10.0 million. TheJune 30, 2022. During the six months ended June 30, 2022, and 2021, we did not record an allowance for credit losses or other impairment charges on our investment securities. Based upon our quarterly impairment review, we determined that the unrealized losses were not attributed to credit risk but ratherwere primarily associated with the changes in interest rates.rates and
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market liquidity. Based on the scheduled maturities of our investments, we concludeddetermined that the unrealized losses in our investment securities are not other-than-temporary, as it iswas more likely than not that we will hold these investments for a period of time sufficient for a recovery of our cost basis.
The following table summarizes the fair value of debt securities classified as available-for-sale by contractual maturity was as of September 30, 2017follows (in thousands):
 June 30, 2022December 31, 2021
Maturing in one year or less$1,253,553 $1,168,256 
Maturing after one year through five years456,890 365,412 
Total debt securities available-for-sale$1,710,443 $1,533,668 
NOTE 5. FAIR VALUE MEASUREMENTS
Fair value reflects the amounts that would be received upon sale of an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. The fair value hierarchy has the following three levels:
Level 1 - quoted prices (unadjusted) in active markets for identical assets and liabilities;
Level 2 - inputs other than level 1 that are observable either directly or indirectly, such as quoted prices in active markets for similar instruments or on industry models using data inputs, such as interest rates and prices that can be directly observed or corroborated in active markets; and
Level 3 - unobservable inputs that are supported by little or no market activity that are significant to the fair value measurement.
The classifications within the fair value hierarchy of our financial assets that were measured and recorded at fair value on a recurring basis were as follows (in thousands):
June 30, 2022
Level 1Level 2Total
Commercial paper$— $880,486 $880,486 
Corporate bonds— 564,401 564,401 
U.S. Treasury and government-sponsored enterprises— 253,408 253,408 
Municipal bonds— 12,148 12,148 
Total debt securities available-for-sale— 1,710,443 1,710,443 
Money market funds87,821 — 87,821 
Certificates of deposit— 130,502 130,502 
Total financial assets carried at fair value$87,821 $1,840,945 $1,928,766 
December 31, 2021
Level 1Level 2Total
Commercial paper$— $945,841 $945,841 
Corporate bonds— 540,978 540,978 
U.S. Treasury and government-sponsored enterprises— 33,945 33,945 
Municipal bonds— 12,904 12,904 
Total debt securities available-for-sale— 1,533,668 1,533,668 
Money market funds66,531 — 66,531 
Certificates of deposit— 119,056 119,056 
Total financial assets carried at fair value$66,531 $1,652,724 $1,719,255 
When available, we value investments based on quoted prices for those financial instruments, which is a Level 1 input. Our remaining investments are valued using third-party pricing sources, which use observable market prices, interest
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 Mature within One Year After One Year through Five Years Fair Value
Money market funds$42,797
 $
 $42,797
Commercial paper168,738
 
 168,738
Corporate bonds136,592
 50,568
 187,160
U.S. Treasury and government sponsored enterprises14,644
 
 14,644
Total investments$362,771
 $50,568
 $413,339
rates and yield curves observable at commonly quoted intervals for similar assets as observable inputs for pricing, which is a Level 2 input.
CashThe carrying amount of our remaining financial assets and liabilities, which include cash, receivables and payables, approximate their fair values due to their short-term nature.

Forward Foreign Currency Contracts
We have entered into forward contracts to hedge certain operational exposures for the changes in foreign currency exchanges rates associated with assets or liabilities denominated in foreign currencies, primarily the Euro.
As of June 30, 2022, we had 1 forward contract outstanding to sell €9.3 million. The forward contract with a maturity of three months is excluded fromrecorded at fair value and is included in prepaid expenses and other current assets in the table above.Condensed Consolidated Balance Sheets. The classificationforward contract is considered a Level 2 in the fair value hierarchy of certain restricted investments is dependent uponour fair value measurements. For the termsix months ended June 30, 2022, and 2021, we recognized $0.7 million and $0.3 million, respectively, of the underlying restrictionnet gains on the asset and not the maturity date of the investment. Therefore, certain long-term restricted cash and investments have contractual maturities within one year.our forward contracts, which is included in other income (expense), net on our Condensed Consolidated Statements of Income.

NOTE 4.6. INVENTORY
Inventory consistsconsisted of the following (in thousands):
 June 30, 2022December 31, 2021
Raw materials$9,760 $8,867 
Work in process35,233 27,717 
Finished goods13,371 12,927 
Total$58,364 $49,511 
Balance Sheet classification:
Current portion included in inventory$33,020 $27,493 
Long-term portion included in other long-term assets25,344 22,018 
Total$58,364 $49,511 
 September 30,
2017
 December 31,
2016
Raw materials$378
 $863
Work in process2,951
 2,343
Finished goods2,856
 738
Total6,185
 3,944
Less: non-current portion included in Other long-term assets(379) (606)
Inventory, net$5,806
 $3,338
We generally relieve inventory on a first-expiry, first-out basis. A portion of the manufacturing costs for inventory was incurred prior to regulatory approval of CABOMETYX and COMETRIQ and therefore was expensed as research and development costs when those costs were incurred, rather than capitalized as inventory. Write-downs related to excess and expiring inventory are charged to either Cost of goods sold or the cost of supplied product included in Collaboration revenues. Such write-downs were $1.2 million for the nine months ended September 30, 2017 and $0.4 million for the comparable period in 2016. The non-current portion of inventory is expected to be used or sold in future periods more than 12 months from the date presented. As of September 30, 2017, the non-current portion of inventory consists of finished goods. As of December 31, 2016, the non-current portion of inventory consists of raw materials and a portion of the active pharmaceutical ingredient that is included in work in process inventories.
NOTE 5. PROPERTY AND EQUIPMENT
Property and equipment consisted of the following (in thousands): 
 September 30,
2017
 December 31,
2016
Computer equipment and software$14,242
 $13,738
Leasehold improvements4,715
 6,646
Laboratory equipment5,836
 4,310
Furniture and fixtures1,954
 2,240
Construction-in-progress15,627
 19
 42,374
 26,953
Less: accumulated depreciation and amortization(23,118) (24,882)
Property and equipment, net$19,256
 $2,071
Depreciation expense was $0.8 million during both the nine months ended September 30, 2017 and 2016.
Build-to-Suit Lease
On May 2, 2017, we entered into a Lease Agreement (the “Lease”) with Ascentris 105, LLC (“Ascentris”), to lease 110,783 square feet of space in office and research facilities located at 1851, 1801, and 1751 Harbor Bay Parkway, Alameda, California (the “Premises”). On October 16, 2017, we executed an amendment to the Lease for 19,778 square feet of additional space located at the Premises with terms consistent with the original Lease. See “Note 12. Commitments” for a description of the Lease.
In connection with the Lease, we received a tenant improvement allowance of $6.7 million from Ascentris, for the costs associated with the design, development and construction of tenant improvements for the Premises. We are obligated to fund all costs incurred in excess of the tenant improvement allowance and to certain indemnification obligations related to the construction activities. We evaluated our involvement during the construction period and determined the scope of the tenant improvements on portions of the Premises including the building shells did not qualify as “normal tenant improvements” under Accounting Standards Codification topic 840, Leases. Accordingly, for accounting purposes, we are the deemed owner of such portions of the Premises during the construction period. As such, we will capitalize the construction costs as a build-to-suit property within property and equipment, net, including the estimated fair value of the

building shells that we are deemed to own at the lease inception date, as determined using a third-party appraisal. The capitalized construction costs will also include the estimated tenant improvements incurred by Ascentris. Accordingly, we capitalized $14.5 million of costs related to the Lease in construction-in-progress as of May 2, 2017, with a corresponding build-to-suit lease obligation in Other long-term liabilities. As of September 30, 2017, we have capitalized an additional $0.5 million to construction in progress for improvements to the Premises.
Once the construction is complete, we will consider the requirements for sale-leaseback accounting treatment, including evaluating whether all risks of ownership have been transferred back to Ascentris, as evidenced by a lack of continuing involvement in the leased property. If the arrangement does not qualify for sale-leaseback accounting treatment, the building assets will remain on our consolidated balance sheets at their historical cost.
NOTE 6. DEBT
The amortized carrying amount of our debt consists of the following (in thousands):
 September 30,
2017
 December 31,
2016
Secured Convertible Notes due 2018 (“Deerfield Notes”)$
 $109,122
Term loan payable
 80,000
Total debt$
 $189,122
See “Note 7 - Debt” to our Consolidated Financial Statements included in our Annual Report on Form 10-K for the year ended December 31, 2016 filed with the SEC on February 27, 2017 for additional information on the terms of our debt, including a description of the material features of the Deerfield Notes.
Deerfield Notes
On June 28, 2017, we repaid all amounts outstanding under the Deerfield Notes. The repayment amount totaled $123.8 million which comprised $113.9 million in principal, including $13.9 million of interest paid in kind paid through the repayment date, a $5.8 million prepayment penalty associated with the early repayment of the notes and $4.2 million in accrued and unpaid interest. As a result of the early repayment, there was a $6.2 million loss on the extinguishment of the debt which comprised the prepayment penalty and the unamortized fees and costs on the date of the repayment.
Prior to our early repayment of the notes, the outstanding principal amount of the Deerfield Notes bore interest at the rate of 7.5% per annum to be paid in cash, quarterly in arrears, and 7.5% per annum to be paid in kind, quarterly in arrears, for a total interest rate of 15% per annum. The following is a summary of interest expense for the Deerfield Notes (in thousands):
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Stated coupon interest$
 $2,031
 $4,151
 $5,939
Interest paid in kind
 2,031
 4,151
 5,939
Amortization of debt discount and debt issuance costs
 121
 182
 327
Total interest expense$
 $4,183
 $8,484
 $12,205
The balance of unamortized fees and costs was $0.4 million as of December 31, 2016, which was recorded as a reduction of the carrying amount of the Deerfield Notes on the accompanying Condensed Consolidated Balance Sheet.
Silicon Valley Bank Loan and Security Agreement
On March 29, 2017, we repaid all amounts outstanding under our term loan with Silicon Valley Bank. The repayment included $80.0 million in principal plus $0.1 million in accrued and unpaid interest. There was no gain or loss on the extinguishment of debt as a result of the repayment of the term loan. Prior to our early repayment of the term loan, the principal amount outstanding under the term loan had accrued interest at 1.0% per annum, which was due and payable monthly.
In accordance with the terms of the loan and security agreement, we were required to maintain an amount equal to at least 100%, but not to exceed 107%, of the outstanding principal balance of the term loan on deposit in one or more

investment accounts with Silicon Valley Bank or one of its affiliates as support for our obligations under the loan and security agreement. We were entitled to retain income earned on the amounts maintained in such accounts. The total collateral balance as of December 31, 2016 was $81.6 million and was reflected in our Condensed Consolidated Balance Sheet in Short-term investments as the amounts were not restricted as to withdrawal. As a result of our repayment of the term loan, the compensating balance requirement was terminated as of March 29, 2017.
NOTE 7. 2014 WARRANTS
In connection with an amendment to the note purchase agreement for the Secured Convertible Notes due 2015, (the “Original Deerfield Notes”), in January 2014 we issued two-year warrants to purchase an aggregate of 1,000,000 shares of our common stock at an exercise price of $9.70 per share (the “2014 Warrants”). Subsequent to our March 2015 notification of our election to extend the maturity date of the Deerfield Notes, the exercise price of the 2014 Warrants was reset to $3.445 per share, the term was extended by two years to January 22, 2018, and the 2014 Warrants were transferred to Additional paid-in capital as of that date at their then estimated fair value of $1.5 million as their terms had become fixed.
On September 11, 2017, we issued an aggregate of 877,451 shares of common stock pursuant to the cashless exercises of the 2014 Warrants issued to an accredited investor transferee. The number of shares issued upon exercise was net of 122,549 shares withheld to effect the cashless exercise of the 2014 Warrants in accordance with their terms.
NOTE 8. STOCK-BASED COMPENSATION
We recorded and allocated employee stock-based compensation expense for our equity incentive plans and our 2000 Employee Stock Purchase Plan (“ESPP”) as follows (in thousands):
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Research and development expense$1,663
 $1,165
 $4,741
 $7,894
Selling, general and administrative expense3,626
 2,438
 10,288
 10,452
Total stock-based compensation expense$5,289
 $3,603
 $15,029
 $18,346
We use the Black-Scholes Merton option pricing model to value our stock options and ESPP purchases. The weighted average grant-date fair value per share of our stock options and ESPP purchases was as follows:
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Stock options$11.75
 $8.59
 $10.32
 $4.31
ESPP$6.85
 $1.51
 $5.29
 $1.65
The fair value of stock options and ESPP purchases was estimated using the following assumptions:
 Stock Options
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Risk-free interest rate1.70% 1.07% 1.68% 1.09%
Dividend yield% % % %
Expected volatility58% 76% 61% 76%
Expected life4.0 years
 4.5 years
 4.1 years
 4.4 years

 ESPP
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Risk-free interest rate1.14% 0.37% 0.88% 0.39%
Dividend yield% % % %
Expected volatility55% 63% 61% 66%
Expected life6 months
 6 months
 6 months
 6 months
We considered implied volatility as well as our historical volatility in developing our estimate of expected volatility. The expected life computation is based on historical exercise patterns and post-vesting termination behavior.
A summary of stock option activity for the nine months endedSeptember 30, 2017 is presented below (dollars in thousands, except per share amounts):
 Shares 
Weighted
Average
Exercise Price Per Share
 
Weighted
Average
Remaining Contractual
Term
 
Aggregate
Intrinsic
Value
Options outstanding at December 31, 201624,999,665
 $4.91
    
Granted821,260
 $21.60
    
Exercised(4,282,847) $3.94
    
Forfeited(204,525) $8.14
    
Options outstanding at September 30, 201721,333,553
 $5.72
 4.08 years $395,212
Exercisable at September 30, 201715,961,685
 $4.41
 3.59 years $316,415
As of September 30, 2017, a total of 24,037,291 shares were available for grant under our stock option plans.
A summary of restricted stock unit (“RSU”) activity for the nine months endedSeptember 30, 2017 is presented below (dollars in thousands, except per share amounts):
 Shares 
Weighted
Average
Grant Date
Fair Value Per Share
 
Weighted
Average
Remaining
Contractual
Term
 
Aggregate
Intrinsic
Value
RSUs outstanding at December 31, 20162,469,791
 $8.69
    
Awarded331,847
 $22.03
    
Vested and released(348,294) $4.63
    
Forfeited(111,603) $10.89
    
RSUs outstanding at September 30, 20172,341,741
 $11.08
 1.55 years $56,740
NOTE 9. INCOME TAXES
Income tax expense consists of the following (in thousands):
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Income tax expense$3,206
 $
 $3,921
 $
During the nine months ended September 30, 2017, we recorded income tax expense of $3.9 million, which primarily comprises our computed income tax expense of $5.2 million reduced by $1.2 million of excess benefits associated with equity compensation. The income tax expense for the three and nine months ended September 30, 2017 primarily relates to state taxes in jurisdictions outside of California, for which we do not have net operating loss carry-forwards due to a limited operating history.

NOTE 10. NET INCOME (LOSS) PER SHARE
The following table sets forth a reconciliation of basic and diluted net income (loss) per share (in thousands, except per share amounts):
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Net income (loss)$81,382
 $(11,284) $115,738
 $(105,345)
Net income allocated to participating securities(221) 
 (368) 
Net income allocable to common stock for basic net income (loss) per share81,161
 (11,284) 115,370
 (105,345)
Adjustment to net income allocated to participating securities14
 
 23
 
Net income allocable to common stock for diluted net income (loss) per share$81,175
 $(11,284) $115,393
 $(105,345)
        
Weighted-average shares of common stock outstanding294,269
 256,319
 292,776
 238,024
Dilutive securities:       
Outstanding stock options, unvested RSUs and ESPP contributions18,671
 
 18,779
 
Weighted-average shares of common stock outstanding and dilutive securities312,940
 256,319
 311,555
 238,024
        
Net income (loss) per share, basic$0.28
 $(0.04) $0.39
 $(0.44)
Net income (loss) per share, diluted$0.26
 $(0.04) $0.37
 $(0.44)
The 2014 Warrants were participating securities and the warrant holders did not have a contractual obligation to share in our losses. See “Note 7 - 2014 Warrants” for a description of the 2014 Warrants.
The following table sets forth potentially dilutive shares of common stock that are not included in the computation of diluted net income (loss) per share because to do so would be anti-dilutive (in thousands): 
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Outstanding stock options, unvested RSUs and ESPP contributions583
 30,474
 1,108
 30,474
Deerfield Notes
 33,890
 
 33,890
4.25% convertible senior subordinated notes due 2019 (the “2019 Notes”)
 413
 
 413
2014 Warrants
 1,000
 
 1,000
Total potentially dilutive shares583
 65,777
 1,108
 65,777
The 2014 Warrants were exercised in September 2017. The Deerfield Notes were repaid in June 2017. The 2019 Notes were converted and redeemed between August and November 2016.


NOTE 11. FAIR VALUE MEASUREMENTS7. STOCK-BASED COMPENSATION
We allocated the stock-based compensation expense for our equity incentive plans and our Employee Stock Purchase Plan (ESPP) as follows (in thousands):
Three Months Ended June 30,Six Months Ended June 30,
2022202120222021
Research and development$9,549 $13,667 $18,448 $26,063 
Selling, general and administrative15,073 14,368 25,933 36,625 
Total stock-based compensation expense$24,622 $28,035 $44,381 $62,688 
17

Stock-based compensation for each type of award under our equity incentive plans and ESPP were as follows (in thousands):
Three Months Ended June 30,Six Months Ended June 30,
2022202120222021
Stock options$3,493 $5,902 $7,171 $10,596 
Restricted stock units18,928 15,412 32,001 27,081 
Performance stock units1,581 4,698 3,290 22,645 
ESPP620 2,023 1,919 2,366 
Total stock-based compensation expense$24,622 $28,035 $44,381 $62,688 
On May 25, 2022, at the 2022 Annual Meeting of Stockholders, our stockholders approved the amendment and restatement of Exelixis, Inc. 2017 Equity Incentive Plan (as amended and restated, the 2017 Plan). The following table sets forthamendment and restatement increased the classificationshare reserve under the 2017 Plan by 28,500,000 shares. As of our financial assets withinJune 30, 2022, 31,687,133 shares were available for grant under the Exelixis, Inc. 2017 Equity Incentive Plan. The share reserve is reduced by 1 share for each share issued pursuant to a stock option and 2 shares for full value awards, including restricted stock units (RSUs). 
During the six months ended June 30, 2022, we granted 587,762 stock options with a weighted average exercise price of $19.99 per share and a weighted average grant date fair value hierarchy that were measured and recorded at fair value on a recurring basis as of September$8.36 per share. As of June 30, 2017 and December 31, 2016. We did not have any financial liabilities measured and recorded at fair value on a recurring basis as of those dates. The amounts presented exclude cash, but include investments classified as cash equivalents (in thousands):
 September 30, 2017
 Level 1 Level 2 Total
Money market funds$42,797
 $
 $42,797
Commercial paper
 168,738
 168,738
Corporate bonds
 187,160
 187,160
U.S. Treasury and government sponsored enterprises
 14,644
 14,644
Total financial assets$42,797
 $370,542
 $413,339
 December 31, 2016
 Level 1 Level 2 Total
Money market funds$71,457
 $
 $71,457
Commercial paper
 165,375
 165,375
Corporate bonds
 152,407
 152,407
U.S. Treasury and government sponsored enterprises
 70,727
 70,727
Total financial assets$71,457
 $388,509
 $459,966
We did not have any financial assets or liabilities classified as Level 3 in the fair value hierarchy as of September 30, 2017 or December 31, 2016 and2022, there were no transfers12,307,775 stock options outstanding and $23.6 million of financial assets or liabilities classified as Level 3 during the nine months ended September 30, 2017 or the year ended December 31, 2016.related unrecognized compensation expense.
The carrying amounts of cash, trade and other receivables, accounts payable, accrued clinical trial liabilities, accrued compensation and benefits, and other liabilities approximate their fair values and are excluded from the tables above.
When available,In March 2022, we value investments based on quoted prices for those financial instruments, which is a Level 1 input. Our remaining investments are valued using third-party pricing sources, which use observable market prices, interest rates and yield curves observable at commonly quoted intervals of similar assets as observable inputs for pricing, which are Level 2 inputs.
NOTE 12. COMMITMENTS
Leases
On May 2, 2017, we entered into the Lease with Ascentris forawarded to certain employees an aggregate of 110,783 square feet of space in office and research facilities located at the Premises in Alameda, California. We also have the right to make certain tenant improvements to the space leased on the Premises. The Lease has an initial term of 10 years with a1,003,482 (the target commencement date of February 1, 2018, and,amount) RSUs that are subject to a partial twelve-month rent abatementtotal shareholder return (TSR) market condition (the TSR-based RSUs). The TSR market condition is based on our relative TSR percentile rank compared to companies in the NASDAQ Biotechnology Index during the performance period, rent payments will begin uponwhich is January 1, 2022 through January 3, 2025. Depending on the results relative to the TSR market condition, the holders of the TSR-based RSUs may earn up to 175% of the target commencement date. amount of shares. 50% of the shares earned pursuant to the TSR-based RSU awards will vest at the end of the performance period, and the remainder will vest approximately one year later, subject to employee’s continuous service. These TSR-based RSUs will be forfeited if the market condition at or above a threshold level is not achieved at the end of the performance period on January 3, 2025.
We used a Monte Carlo simulation model and the following assumptions to determine the grant date fair value of $33.17 per share for the TSR-based RSUs:
Fair value of the Company’s common stock on grant date$20.70 
Expected volatility46.85 %
Risk-free interest rate1.59 %
Dividend yield— %
The Monte Carlo simulation model also assumed correlations of returns of the stock prices of the Company’s common stock and the common stock of a peer group of companies and historical stock price volatility of the peer group of companies. The valuation model also used terms based on the length of the performance period and compound annual growth rate goals for total stockholder return based on the provisions of the award.
During the six months ended June 30, 2022, we granted 4,585,618 service-based RSUs with a weighted average grant date fair value of $20.64 per share. As of June 30, 2022, there were 11,496,162 RSUs outstanding, including the TSR-based RSUs, and $207.2 million of related unrecognized compensation expense.
Stock options and service-based RSUs granted to employees during the six months ended June 30, 2022 have twovesting conditions and contractual lives of a similar nature to those described in “Note 8. Employee Benefit Plans” of the “Notes to Consolidated Financial Statements” included in Part II, Item 8 of our Fiscal 2021 Form 10-K.
As of June 30, 2022, there were 5,662,157 performance-based restricted stock units (PSUs) outstanding and $113.5 million of related unrecognized stock-based compensation expense. Expense recognition for PSUs commences when it is determined that achievement of the performance target is probable. For more information about our PSUs, see “Note 8. Employee Benefit Plans” of the “Notes to Consolidated Financial Statements” included in Part II, Item 8 of our Fiscal 2021 Form 10-K.
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NOTE 8. PROVISION FOR INCOME TAXES
The effective tax rate for the three and six months ended June 30, 2022 were 20.2% and 19.9% respectively, as compared to 23.1% and 20.5% for the corresponding periods 2021. The effective tax rate for the three and six months ended June 30, 2022 and June 30, 2021 differed from the U.S. federal statutory tax rate of 21% primarily due to excess tax benefits related to the exercise of certain stock options during the periods and the generation of federal tax credits, which were partially offset by state taxes.
NOTE 9. NET INCOME PER SHARE
Net income per share - basic and diluted, were computed as follows (in thousands, except per share amounts):
Three Months Ended June 30,Six Months Ended June 30,
2022202120222021
Numerator:
Net income$70,672 $96,092 $139,245 $97,693 
Denominator:
Weighted-average common shares outstanding — basic321,117 314,117 320,349 313,295 
Dilutive securities3,787 8,824 3,747 8,819 
Weighted-average common shares outstanding — diluted324,904 322,941 324,096 322,114 
Net income per share — basic$0.22 $0.31 $0.43 $0.31 
Net income per share — diluted$0.22 $0.30 $0.43 $0.30 
Dilutive securities included outstanding stock options, unvested RSUs, including TSR-based RSUs, PSUs and ESPP contributions.
Certain potential common shares were excluded from our calculation of weighted-average common shares outstanding - diluted because either they would have had an anti-dilutive effect on net income per share or they were related to shares from PSUs that were contingently issuable and the contingency had not been satisfied at the end of the reporting period. The weighted-average potential common shares excluded from our calculation were as follows (in thousands):
Three Months Ended June 30,Six Months Ended June 30,
2022202120222021
Anti-dilutive securities and contingently issuable shares excluded14,350 12,285 15,436 11,146 
NOTE 10. COMMITMENTS AND CONTINGENCIES
Build-to-Suit Lease and Headquarters Lease
In April 2022, the office building (New Premises) associated with our October 2019 build-to-suit lease agreement (Build-to-Suit Lease) was substantially completed. The New Premises is 220,517 square feet and is in Alameda, California, adjacent to our existing corporate headquarters. The Build-to-Suit Lease term is 242 months, includes 2 five-year options to extend the Leaseterm of the lease and a one-time option to terminate the Lease without cause onlease after 180 months. In addition to the last daymonthly lease payments, currently estimated at $0.7 million, subject to an annual increase of 3% during the Term, we are also responsible for paying operating expenses related to the New Premises. On April 15, 2022, the lease commenced for the New Premises. We determined the classification of the 8th yearlease was an operating lease. Upon commencement of the initial term. We are obligated to make lease, payments totaling $24.1we recognized a right-of-use asset of $160.9 million overinclusive of $44.9 million for the Lease term. The Lease further provides that we are obligated to pay to Ascentris certain costs, including taxes and operating expenses. We also have a right of first offer to lease certain additional space, in the aggregate of approximately 170,000 square feet of space, as that additional space becomes available over the remaindercost of the initial term at 1601, 1701, 1751,tenant improvements in excess of the allowance provided by the lessor and 1801an operating lease liability of $116.0 million discounted over 180 months using our estimated incremental borrowing rate of 4.9%.
19

In May 2022, we entered into the seventh amendment to the lease for our corporate headquarters located on Harbor Bay Parkway, Alameda, California at a market rate determined according(the Alameda Lease). The May 2022 amendment to the Lease.
We are deemed,Alameda Lease (the Seventh Lease Amendment) provides, among other things, for accounting purposes only, to be the owner of portionsexpansion of the Premises, including two building shells, even though we are notpremises under the legal owner. See “Note 5. Property and Equipment - Build-to-Suit Lease” for a further description of the accounting for that portion of the Premises.

On May 2, 2017, we also entered into an Agreement for Conditional Option to AmendAlameda Lease (the “Optional Amendment Agreement”) with Ascentris. Under the terms of the Optional Amendment Agreement, a current tenant (the “Tenant”) occupying approximately 16,343by 34,745 square feet of the facilityoffice facilities located at 18011751 Harbor Bay Parkway, was givenAlameda, California (the 1751 Expansion Space). The term for the option to relocate to another building on1751 Expansion Space will run coterminous with the premises or terminate their current lease early, requiring them to relocate within six months from the termination date. Under the termsterm of the Optional Amendment Agreement, we would reimburse AscentrisAlameda Lease for the first $1.5 millionexisting space. In connection with the Seventh Lease Amendment, we remeasured our lease components under the Alameda Lease relating to the existing premises using an incremental borrowing rate of costs incurred to induce the Tenant to relocate. In August 2017, the Tenant communicated to Ascentris that they were terminating their lease early.5.0%. As of September 30, 2017,June 1, 2022, we have accrued $1.4 milliontaken possession of the 1751 Expansion Space, and accordingly we have adjusted our right-of-use asset and liability by $4.3 million.

For more information about our Leases, see “Note 11. Commitments and Contingencies—Leases” of the “Notes to Consolidated Financial Statements” included in Part II, Item 8 of our Fiscal 2021 Form 10-K.
Legal Proceedings
In September 2019, we received a notice letter regarding an Abbreviated New Drug Application (ANDA) submitted to the FDA by MSN Pharmaceuticals, Inc. (MSN), requesting approval to market a generic version of CABOMETYX tablets. MSN’s initial notice letter included a Paragraph IV certification with respect to our U.S. Patents No. 8,877,776 (salt and polymorphic forms), 9,724,342 (formulations), 10,034,873 (methods of treatment) and 10,039,757 (methods of treatment), which are listed in the Approved Drug Products with Therapeutic Equivalence Evaluations, also referred to as the Orange Book, for our anticipated reimbursementCABOMETYX. MSN’s initial notice letter did not provide a Paragraph IV certification against U.S. Patents No. 7,579,473 (composition of costs to Ascentrismatter) or 8,497,284 (methods of treatment), each of which is listed in the Orange Book. On October 29, 2019, we filed a complaint in the United States District Court for the Tenant’s relocation. District of Delaware (the Delaware District Court) for patent infringement against MSN asserting infringement of U.S. Patent No. 8,877,776 arising from MSN’s ANDA filing with the FDA. On November 20, 2019, MSN filed its response to the complaint, alleging that the asserted claims of U.S. Patent No. 8,877,776 are invalid and not infringed. On May 5, 2020, we received notice from MSN that it had amended its ANDA to include additional Paragraph IV certifications. In particular, the May 5, 2020 amended ANDA requested approval to market a generic version of CABOMETYX tablets prior to expiration of two previously unasserted CABOMETYX patents: U.S. Patents No. 7,579,473 and 8,497,284. On May 11, 2020, we filed a complaint in the Delaware District Court for patent infringement against MSN asserting infringement of U.S. Patents No. 7,579,473 and 8,497,284 arising from MSN’s amended ANDA filing with the FDA. Neither of our complaints have alleged infringement of U.S. Patents No. 9,724,342, 10,034,873 and 10,039,757. On May 22, 2020, MSN filed its response to the complaint, alleging that the asserted claims of U.S. Patents No. 7,579,473 and 8,497,284 are invalid and not infringed. On March 23, 2021, MSN filed its First Amended Answer and Counterclaims (amending its prior filing from May 22, 2020), seeking, among other things, a declaratory judgment that U.S. Patent No. 9,809,549 (salt and polymorphic forms) is invalid and would not be infringed by MSN if its generic version of CABOMETYX tablets were approved by the FDA. U.S. Patent No. 9,809,549 is not listed in the Orange Book. On April 7, 2021, we filed our response to MSN’s First Amended Answer and Counterclaims, denying, among other things, that U.S. Patent No. 9,809,549 is invalid or would not be infringed. These 2 lawsuits, numbered Civil Action Nos. 19-02017 and 20-00633, were consolidated in April 2021.
On October 16, 2017, we executed1, 2021, pursuant to a stipulation between us and MSN, the Delaware District Court entered an amendmentorder that (i) MSN’s submission of its ANDA constitutes infringement of certain claims relating to U.S. Patents No. 7,579,473 and 8,497,284, if those claims are not found to be invalid, and (ii) upon approval, MSN’s commercial manufacture, use, sale or offer for sale within the U.S., and importation into the U.S., of MSN’s ANDA product prior to the Lease forexpiration of U.S. Patents No. 7,579,473 and 8,497,284 would also infringe certain claims of each patent, if those claims are not found to be invalid. Then, on October 12, 2021, pursuant to a separate stipulation between us and MSN, the Delaware District Court entered an additional 19,778 square feetorder dismissing MSN’s counterclaims with respect to U.S. Patent No. 9,809,549. In our complaints, we are seeking, among other relief, an order that the effective date of space located onany FDA approval of MSN’s ANDA be a date no earlier than the Premises, which includes the space vacated by the Tenant, with terms consistent with the original Lease.
Asexpiration of September 30, 2017, the aggregate future minimum lease payments under our leases are as follows (in thousands): 
 Operating leases 
Other financing obligations (1)
Remainder of 2017$1,006
 $
Year Ending December 31,   
20182,802
 566
2019605
 1,477
2020630
 1,685
2021637
 1,745
2022646
 1,814
Thereafter3,465
 10,441
 $9,791
 $17,728
____________________
(1)Other financing obligations includes payments related to our build-to-suit lease.
Rent expense and sublease income were as follows for the periods presented (in thousands):
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Gross rental expense$1,215
 $1,972
 $4,986
 $7,424
less: Sublease income
 (908) (1,225) (2,637)
Net rental expense$1,215
 $1,064
 $3,761
 $4,787
Letter of Credit
We obtained a standby letter of credit in May 2017 in the amount of $0.5 million, which may be drawn down by Ascentris in the event we fail to fully and faithfully perform all of our obligations underU.S. Patents No. 7,579,473, 8,497,284 and 8,877,776, the Leaselatest of which expires on October 8, 2030, and equitable relief enjoining MSN from infringing these patents. In an effort to compensate Ascentris for all lossesstreamline the case, the parties have narrowed their assertions. On April 8, 2022, MSN withdrew its validity challenge to U.S. Patent No. 8,877,776. On April 14, 2022, we agreed not to assert U.S. Patent No. 8,497,284 at trial and damages Ascentris may sufferMSN has, correspondingly, agreed to withdraw its validity challenges to U.S. Patent No. 8,497,284, as well as claims 1-4 and 6-7 of U.S. Patent No. 7,579,473. As a result of this narrowing, the occurrencetrial addressed two issues: (1) infringement of claims 1 and 2 of the U.S. Patent No. 8,877,776; and (2) validity of claim 5 of the U.S. Patent No. 7,579,473. A bench trial occurred in May 2022, and a judgment is expected during the third or fourth quarter of 2022.
On January 11, 2022, we received notice from MSN that it had further amended its ANDA to assert additional Paragraph IV certifications. In particular, the January 11, 2022 amended ANDA requested approval to market a generic
20

Table of Contents
version of CABOMETYX tablets prior to expiration of three previously-unasserted CABOMETYX patents that are now listed in the Orange Book: U.S. Patents No. 11,091,439 (crystalline salt forms), 11,091,440 (pharmaceutical composition) and 11,098,015 (methods of treatment). On February 23, 2022, we filed a complaint in the Delaware District Court for patent infringement against MSN asserting infringement of U.S. Patents No. 11,091,439, 11,091,440 and 11,098,015 (the February 2022 MSN ANDA Complaint) arising from MSN’s further amendment of its ANDA filing with the FDA. In the February 2022 MSN ANDA Complaint, we are seeking, among other remedies, equitable relief enjoining MSN from infringing these patents, as well as an order that the effective date of any defaultFDA approval of MSN’s ANDA would be a date no earlier than the expiration of the patents identified in the February 2022 MSN ANDA Complaint, the latest of which expires on our partJanuary 15, 2030. The February 2022 MSN ANDA Complaint is a new case, numbered Civil Action No. 22-00228, against MSN involving Exelixis patents that are different from those asserted in the consolidated Civil Action Nos. 19-02017 and 20-00633 described above. On February 25, 2022, MSN filed its response to the complaint, alleging that the asserted claims of U.S. Patents No. 11,091,439, 11,091,440 and 11,098,015 are invalid and not curedinfringed.
On June 21, 2022, pursuant to a stipulation between us and MSN, the Delaware District Court entered an order that (i) MSN’s submission of its ANDA constitutes infringement of certain claims relating to U.S. Patents No. 11,091,439, 11,091,440 and 11,098,015, if those claims are not found to be invalid, and (ii) upon approval, MSN’s commercial manufacture, use, sale or offer for sale within the applicable cure period.U.S., and importation into the U.S., of MSN’s ANDA product prior to the expiration of U.S. Patents No. 11,091,439, 11,091,440 and 11,098,015 would also infringe certain claims of each patent, if those claims are not found to be invalid. A bench trial in connection with the February 2022 MSN ANDA Complaint has been scheduled for May 2023.
On June 6, 2022, we received notice from MSN that it had further amended its ANDA to assert an additional Paragraph IV certification. As currently amended, MSN’s ANDA now requests approval to market a generic version of September 30, 2017, noneCABOMETYX tablets prior to expiration of a previously-unasserted CABOMETYX patent that is now listed in the Orange Book: U.S. Patent No. 11,298,349 (pharmaceutical composition). On July 18, 2022, we filed a complaint in the Delaware District Court for patent infringement against MSN asserting infringement of U.S. Patent No. 11,298,349 (the July 2022 MSN ANDA Complaint) arising from MSN’s further amendment of its ANDA Filing with the FDA. In the July 2022 MSN ANDA Complaint, we are seeking, among other remedies, equitable relief enjoining MSN from infringing this patent, as well as an order that the effective date of any FDA approval of MSN’s ANDA would be a date no earlier than the expiration of the standby letterpatent identified in the July 2022 MSN ANDA Complaint, which expires on February 10, 2032. The July 2022 MSN ANDA Complaint is a new case against MSN involving an Exelixis patent that is different from those asserted in the consolidated Civil Action Nos. 19-02017, 20-00633 and 22-00228 described above. MSN’s response to the complaint is due on August 9, 2022. A trial has not yet been scheduled in connection with the July 2022 MSN ANDA Complaint.
In May 2021, we received notice letters from Teva Pharmaceuticals Development, Inc. and Teva Pharmaceuticals USA, Inc. (individually and collectively referred to as Teva) regarding an ANDA Teva submitted to the FDA, requesting approval to market a generic version of credit amount has been used.
See “Note 13 - Commitments”CABOMETYX tablets. Teva’s notice letters included a Paragraph IV certification with respect to our Consolidated Financial Statements includedU.S. Patents No. 9,724,342 (formulations), 10,034,873 (methods of treatment) and 10,039,757 (methods of treatment), which are listed in our Annual Report on Form 10-Kthe Orange Book and expire in 2033, 2031 and 2031, respectively. Teva’s notice letters did not provide a Paragraph IV certification against any additional CABOMETYX patents. On June 17, 2021, we filed a complaint in the Delaware District Court for the year ended December 31, 2016 filedpatent infringement against Teva, along with Teva Pharmaceutical Industries Limited (Teva Parent), asserting infringement of U.S. Patents No. 9,724,342, 10,034,873 and 10,039,757 arising from Teva’s ANDA filing with the SECFDA. On August 27, 2021, Teva filed its answer and counterclaims to the complaint, alleging that the asserted claims of U.S. Patents No. 9,724,342, 10,034,873 and 10,039,757 are invalid and not infringed, and on August 23, 2021, we and Teva entered into a stipulation wherein Teva Parent was dismissed without prejudice from this lawsuit and agreed to be bound by any stipulation, judgment, order or decision rendered as to Teva, including any appeals and any order granting preliminary or permanent injunctive relief against Teva. On September 17, 2021, we filed an answer to Teva’s counterclaims. We are seeking, among other relief, an order that the effective date of any FDA approval of Teva’s ANDA be a date no earlier than the expiration of all of U.S. Patents No. 9,724,342, 10,034,873 and 10,039,757, the latest of which expires on July 9, 2033, and equitable relief enjoining Tevafrom infringing these patents. On February 8, 2022, the parties filed a stipulation to stay all proceedings, which was granted by the Delaware District Court on February 27, 2017 for9, 2022. On February 11, 2022, this case was administratively closed.
On July 29, 2022, we received notice from Teva that it had amended its ANDA to assert an additional Paragraph IV certification. As amended, Teva’s ANDA now requests approval to market a descriptiongeneric version of additional letters of credits that were entered intoCABOMETYX tablets prior to December 31, 2016.
NOTE 13. CONCENTRATIONS OF CREDIT RISK
Financial instrumentsexpiration of a previously-unasserted CABOMETYX patent that potentially subject us to concentrations of credit risk are primarily trade and other receivables and investments. Investments consist of money market funds, commercial paper, corporate bonds with high credit quality, and securities issued by the U.S. Treasury and other government sponsored enterprises. All investments are maintained with financial institutions that management believes are creditworthy.
Trade and other receivables are unsecured and are concentratedis now listed in the Orange Book: U.S. Patent No. 11,298,349 (pharmaceutical and biotechnology industries. Accordingly, we may be exposed to credit risk generally associated with pharmaceutical and biotechnology

companies.composition). We have incurred no bad debt expense since inception. As of September 30, 2017, 55% of our trade receivables are with Ipsen, which include45 days from the amounts due from two milestones totaling $45.0 million resulting from Ipsen’s receipt of the validationJuly 29, 2022 notice to file a patent infringement claim against Teva relating to the newly challenged patent.
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The sale of any generic version of CABOMETYX earlier than its patent expiration could significantly decrease our revenues derived from the EMA forU.S. sales of CABOMETYX and thereby materially harm our business, financial condition and results of operations. It is not possible at this time to determine the application for variationlikelihood of an unfavorable outcome or estimate of the amount or range of any potential loss.
We may also from time to the CABOMETYX marketing authorization for the addition oftime become a new indication in first-line treatment of advanced RCC in adults. Payment for the first milestone of $20.0 million is dueparty or subject to various other legal proceedings and claims, either asserted or unasserted, which arise in the fourth quarterordinary course of 2017business. Some of these proceedings have involved, and payment for the second milestone of $25.0 million is duemay involve in the first quarter of 2018. Ipsen historically has paid promptly.future, claims that are subject to substantial uncertainties and unascertainable damages.
The percentage of total revenues recognized by customer that represent 10% or more of total revenues was as follows:

 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Diplomat Specialty Pharmacy13% 31% 19% 41%
Ipsen33% 6% 18% 8%
Caremark L.L.C.13% 9% 16% 8%
Affiliates of McKesson Corporation10% 6% 12% 5%
Accredo Health, Incorporated9% 9% 11% 7%
Daiichi Sankyo% 24% % 13%
All of our long-lived assets are located in the U.S. We have operations solely in the U.S., while some of our collaboration partners have headquarters outside of the U.S. and some of our clinical trials for cabozantinib are also conducted outside of the U.S.
The following table shows the revenues earned by geographic region. Net product revenues are attributed to regions based on the delivery location. Collaboration revenues are attributed to regions based on the location of our collaboration partner's headquarters (in thousands):
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
U.S.$97,807
 $41,971
 $260,853
 $87,757
Europe50,680
 5,223
 60,704
 11,116
Japan4,023
 15,000
 10,848
 15,000
We recorded losses of $0.2 million relating to foreign exchange fluctuations for both the nine months ended September 30, 2017 and 2016.

Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations.
The following discussion and analysisThis Quarterly Report on Form 10-Q contains forward-looking statements. These statements are based on Exelixis, Inc.’s (“Exelixis,” “we,” “our”(Exelixis, we, our or “us”)us) current expectations, assumptions, estimates and projections about our business and our industry and involve known and unknown risks, uncertainties and other factors that may cause our company’s or our industry’s results, levels of activity, performance or achievements to be materially different from any future results, levels of activity, performance or achievements expressed or implied in, or contemplated by, the forward-looking statements. Words such as “expect,” “potential,” “will,” “goal,” “would,” “intend,” “continues,” “objective,” “anticipate,” “initiate,” “believe,” “could,” “plan,” “trend,” or the negative of such terms or other similar expressions identify forward-looking statements. Our actual results and the timing of events may differ significantly from the results discussed in the forward-looking statements. Factors that might cause such a difference include those discussed in “Risk Factors” in Part II, Item 1A of this Quarterly Report on Form 10-Q, as well as those discussed elsewhere in this report. These and many other factors could affect our future financial and operating results. We undertake no obligation to update any forward-looking statement to reflect events after the date of this report.
This discussion and analysis should be read in conjunction with our condensed consolidated financial statements and accompanying notes included in this report and the consolidated financial statements and accompanying notes thereto included in our Annual Report on Form 10-K for the fiscal year ended December 31, 2016,2021, filed with the Securities and Exchange Commission or SEC,(SEC) on February 27, 2017. Operating results are not necessarily indicative of results that may occur in future periods. We undertake no obligation to update any forward-looking statement to reflect events after the date of this report.18, 2022 (Fiscal 2021 Form 10-K).
Overview
We are aan oncology-focused biotechnology company committedthat strives to accelerate the discovery, development and commercialization of new medicines for patients with difficult-to-treat cancers. Using our considerable drug discovery, development and commercialization resources and capabilities, we have invented and brought to market innovative therapies that appropriately balance patient benefits and risks; we will continue to build on this foundation as we strive to provide cancer patients with new treatment options that improve care and outcomesupon current standards of care.
Today, four products that originated in Exelixis laboratories are available to be prescribed to patients. Sales related to our flagship molecule, cabozantinib, account for people with cancer. Sincethe large majority of our founding in 1994, three products discovered at Exelixis have progressed through clinical development, received regulatory approval, and entered the marketplace. Two are derived from cabozantinib,revenues. Cabozantinib is an inhibitor of multiple tyrosine kinases including VEGF, MET, AXL, VEGF receptors and RET receptors:and has been approved by the U.S. Food and Drug Administration (FDA) and in 62 other countries as: CABOMETYX® (cabozantinib) tablets approved for previously treated advanced renal cell carcinoma or RCC,(RCC), both alone and in combination with Bristol-Myers Squibb Company’s (BMS) OPDIVO® (nivolumab), for previously treated hepatocellular carcinoma (HCC) and, currently by the FDA and European Commission (EC), for previously treated, radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC); and COMETRIQ® (cabozantinib) capsules approved for progressive, metastatic medullary thyroid cancer (MTC). For physicians treating these types of cancer, cabozantinib has become or MTC. is becoming an important medicine in their selection of effective therapies.
The third product,other two products resulting from our discovery efforts are: COTELLIC® (cobimetinib) tablets, is a reversible, an inhibitor of MEK, approved as part of multiple combination regimens to treat specific forms of advanced melanoma and marketed under a collaboration with Genentech, (aInc., a member of the Roche Group)Group (Genentech); and MINNEBRO® (esaxerenone), an oral, non-steroidal, selective blocker of the mineralocorticoid receptor, approved for the treatment of hypertension in Japan and licensed to Daiichi Sankyo, Company, Limited (Daiichi Sankyo).
Our plan is to utilize our operating cash flows and cash and investments to expand the cabozantinib franchise by potentially adding new indications in areas of unmet medical need. We will also leverage our operating cash flows to continue advancing our diverse small molecule and biotherapeutics programs, exploring multiple modalities and mechanisms of action to discover new oncology drugs. So far, these drug discovery and preclinical activities have resulted in four clinical-stage compounds: XL092, a next-generation oral tyrosine kinase inhibitor (TKI); XB002, an antibody drug
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conjugate (ADC) that targets tissue factor (TF); XL102, a potent, selective and orally bioavailable covalent inhibitor of cyclin-dependent kinase 7 (CDK7); and XL114, a novel anti-cancer compound that inhibits the CARD11-BCL10-MALT1 (CBM) complex.
Cabozantinib Franchise
The FDA first approved CABOMETYX as parta monotherapy for previously treated patients with advanced RCC in April 2016, and then for previously untreated patients with advanced RCC in December 2017. In January 2021, the CABOMETYX label was expanded to include first-line advanced RCC in combination with OPDIVO, which was the first CABOMETYX regimen approved for treatment in combination with an immune checkpoint inhibitor (ICI). In addition to RCC, in January 2019, the FDA approved CABOMETYX for the treatment of a combination regimen to treatpatients with HCC previously treated with sorafenib, and then in September 2021, the FDA approved CABOMETYX for the treatment of adult and pediatric patients 12 years of age and older with locally advanced melanoma. Both cabozantinibor metastatic DTC that has progressed following prior VEGF receptor-targeted therapy and cobimetinib have shown potential in a variety of forms of cancerwho are RAI-refractory or ineligible.
To develop and are the subject of broad clinical development programs for multiple oncology indications.
While our commercialization efforts forcommercialize CABOMETYX and COMETRIQ are focused inoutside the United States, or U.S., we have licensed developmententered into license agreements with Ipsen and commercializationTakeda. We granted to Ipsen the rights to cabozantinib outside of the U.S. to Ipsen Pharma SAS, or Ipsen,develop and Takeda Pharmaceutical Company Ltd., or Takeda. Ipsen has been granted rights tocommercialize cabozantinib outside of the U.S. and Japan, and to Takeda has beenwe granted the rights to develop and commercialize cabozantinib in Japan. Both Ipsen and Takeda also contribute financially and operationally to the further global development and commercialization of the cabozantinib franchise in other potential indications, and we are workingwork closely with them on these activities. Utilizing its regulatory expertise and established international oncology marketing network, Ipsen has continued to execute on its commercialization plans for CABOMETYX, having received regulatory approvals and launched in multiple territories outside of the U.S., including in the European Union (EU), the United Kingdom (U.K.) and Canada, as a treatment for advanced RCC and for HCC in adults who have previously been treated with sorafenib. In addition, in March 2021, Ipsen and BMS received regulatory approval from the EC for CABOMETYX in combination with OPDIVO as a first-line treatment for patients with advanced RCC, followed by additional regulatory approvals for the combination in other territories beyond the EU. Most recently, in May 2022, we announced that Ipsen received regulatory approval from the EC for CABOMETYX as a monotherapy for the treatment of adult patients with locally advanced or metastatic, RAI-refractory or ineligible DTC and who have progressed during or after prior systemic therapy. With respect to the Japanese market, Takeda received Manufacturing and Marketing Approvals in 2020 from the Japanese Ministry of Health, Labour and Welfare (MHLW) of CABOMETYX as a treatment of patients with curatively unresectable or metastatic RCC and as a treatment of patients with unresectable HCC who progressed after cancer chemotherapy. In August 2021, Takeda and Ono Pharmaceutical Co., Ltd. (Ono), BMS’ development and commercialization partner in Japan, received Manufacturing and Marketing Approval from the Japanese MHLW of CABOMETYX in combination with OPDIVO as a treatment for unresectable or metastatic RCC.
BeyondIn addition to our currently approvedregulatory and commercialization efforts in the U.S. and the support provided to our collaboration partners for rest-of-world regulatory and commercialization activities, we are also pursuing other indications for RCC and MTC, we are pursuing other indicationscabozantinib that have the potential to expandincrease the number of cancer patients thatwho could potentially benefit from cabozantinib. Most advancedthis medicine. We continue to evaluate cabozantinib, both as a single agent and in the cabozantinibcombination with ICIs, in a broad development program iscomprising over 100 ongoing or planned clinical trials across multiple tumor types. We, along with our evaluationcollaboration partners, sponsor some of CABOMETYX as a treatment for patients with previously untreated advanced RCC. On August 15, 2017, we submitted a supplemental New Drug Application, or sNDA, for cabozantinib in this indication to the U.S. Foodtrials, and Drug Administration, or FDA, and on October 16, 2017, we announced thatindependent investigators conduct the FDA had accepted this filing and granted it Priority Review, assigning a Prescription Drug User Fee Act, or PDUFA, action date of February 15, 2018. The data in support of this filing are derived from CABOSUN, a randomized phase 2 trial comparing cabozantinib to sunitinib in the first-line treatment of patients with intermediate- or poor-risk RCC that was conducted by The Alliance for Clinical Trials in Oncology, or The Alliance,remaining trials through our Cooperative Research and Development Agreement or CRADA,(CRADA) with the National Cancer Institute’s Cancer Therapy Evaluation Program or NCI-CTEP. In May 2016, The Alliance informed us that CABOSUN met its primary endpoint demonstrating a statistically significant and clinically meaningful improvement of progression-free survival, or PFS, compared with sunitinib. The CABOSUN primary efficacy endpoint results were later confirmed by a blinded independent radiology review committee, or IRRC, in June 2017.
Closely behind our FDA filing for first-line RCC is our investigation of CABOMETYX as a treatment for patients with advanced hepatocellular carcinoma, or HCC, who have previously been treated with sorafenib. On October 16, 2017, we announced that, at the time of the second planned interim analysis, the study’s independent data monitoring committee had recommended that CELESTIAL, our company-sponsored, global phase 3 trial of cabozantinib versus placebo in patients with advanced HCC who have been previously treated with sorafenib, be stopped because it had met its primary endpoint, with cabozantinib providing a statistically significant and clinically meaningful improvement in overall survival, or OS, compared to placebo. Safety data from the study were consistent with the established profile of cabozantinib. Based on the results of CELESTIAL, we plan to submit an sNDA to the FDA in the first quarter of 2018, for cabozantinib as a second-line treatment for patients with advanced HCC. We will discuss the trial results with regulatory authorities and determine next steps for the trial, including offering patients currently receiving placebo the opportunity to cross over to cabozantinib.
We believe that the available clinical data demonstrate that cabozantinib has the potential to be a broadly active anti-cancer agent that can make a meaningful difference in the lives of patients. Accordingly, we are engaged in a broad development program composed of over 50 ongoing or planned clinical trials to explore the clinical potential of cabozantinib in additional tumor types. This program includes Exelixis sponsored trials and trials conducted through our CRADA with NCI-CTEP(NCI-CTEP) or our investigator sponsored trial (IST) program. We are particularly interestedThe data from these third-party clinical trials have helped advance our development program for the cabozantinib franchise by informing subsequent label-enabling trials, including COSMIC-311, our phase 3 pivotal trial evaluating cabozantinib in examining cabozantinib’s potential in combinationpreviously treated patients with immunotherapies to determine if such combinations further improve outcomesRAI-refractory DTC, from which positive results served as the basis for patients. the FDA’s and EC’s approvals of CABOMETYX for DTC.
Building on preclinical and clinical observations that cabozantinib createsin combination with ICIs may promote a more immune-permissive tumor environment, potentially resultingwe initiated numerous pivotal studies to further explore these combination regimens. The first of these studies to deliver results was CheckMate -9ER, a phase 3 pivotal trial evaluating the combination of CABOMETYX and OPDIVO compared to sunitinib in previously untreated, advanced or metastatic RCC, and positive results from CheckMate -9ER served as the cooperative activitybasis for the FDA’s, EC’s and MHLW’s approvals of cabozantinibCABOMETYX in combination with these products,OPDIVO as a first-line treatment of patients with advanced RCC in January 2021, March 2021 and August 2021, respectively. We are also collaborating with BMS on COSMIC-313, a phase 3 pivotal trial evaluating the triplet combination of cabozantinib, nivolumab and ipilimumab versus the combination of nivolumab and ipilimumab in patients with previously untreated advanced intermediate- or poor-risk RCC. In July 2022, we areannounced results from COSMIC-313. The trial met its primary endpoint, demonstrating significant improvement in blinded independent radiology committee (BIRC) assessed progression free survival (PFS) at the primary analysis for the triplet combination, reducing the risk of
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disease progression or death compared with the doublet combination of nivolumab and ipilimumab (hazard ratio: 0.73; 95% confidence internal: 0.57-0.94; P=0.01). At a prespecified interim analysis for the secondary endpoint of overall survival (OS), the triplet combination did not demonstrate a significant benefit, and therefore, the trial will continue to the next analysis of OS. The safety profile observed in the trial was reflective of the known safety profiles for each single agent, as well as the combination regimens used in this study, and no new safety signals were identified. We intend to discuss the results with the FDA to determine next steps toward a potential regulatory submission for the combination regimen for patients with previously untreated, advanced intermediate- or poor-risk RCC, and detailed findings will be presented at a future medical meeting.
To expand our exploration of combinations with ICIs, we also initiated multiple trials evaluating cabozantinib in combination with F. Hoffmann-La Roche Ltd.’s (Roche) ICI, atezolizumab, beginning in 2017 with COSMIC-021, a variety of immune checkpoint inhibitors in multiple clinical trials. The most advanced of these combination studies includes a phase 3 trial evaluating cabozantinib with nivolumab (Opdivo®) or with nivolumab and ipilimumab (Yervoy®) in first-line advanced RCC and a phase 2 evaluation of the same combinations in HCC, each in collaboration with Bristol-Myers Squibb Company, or BMS. As a further part of our clinical collaboration with BMS, we also plan to evaluate cabozantinib and nivolumab with or without ipilimumab in various other tumor types, including in bladder cancer. Diversifying our exploration of immunotherapy combinations, we have also initiated abroad phase 1b dose escalation study evaluating the safety and tolerability of cabozantinib in combination with The Roche Group’s, or Roche’s, atezolizumab (Tecentriq®) in patients with a wide variety of locally advanced or metastatic solid tumors.
Significant progress also continues to be made under The data from COSMIC-021 have been instrumental in guiding our December 2006 worldwide collaboration agreementclinical development strategy for cabozantinib in combination with Genentech, orICIs, including supporting the Genentech Collaboration Agreement, with respect to theinitiation of COSMIC-312, a phase 3 clinical development program for our second approved cancer agent, cobimetinib. Genentech is now conductingpivotal trial evaluating cabozantinib in combination with atezolizumab versus sorafenib in previously untreated advanced HCC, and three phase 3 pivotal trials exploringin collaboration with Roche, CONTACT-01, CONTACT-02 and CONTACT-03, evaluating the combination of cobimetinibcabozantinib with atezolizumab in colorectal carcinoma (IMblaze370)patients with metastatic non-small cell lung cancer (NSCLC), metastatic castration-resistant prostate cancer (mCRPC) and BRAF wild type melanoma population (IMspire170),advanced RCC, respectively. CONTACT-01 and CONTACT-03 are sponsored by Roche and co-funded by us, and we announced the combinationcompletion of cobimetinibenrollment for the two trials in November 2021 and January 2022, respectively, with atezolizumab and vemurafenib in BRAF V600 mutant melanoma (IMspire150 TRILOGY). Enrollment for IMblaze370 was completedresults from both trials expected in the first quartersecond half of 2017,2022. CONTACT-02 is sponsored by us and Genentech has announced that top line results for the trial are expected duringco-funded by Roche, and we anticipate completing enrollment in the first half of 2018. Should2023.
Pipeline Activities
Our small molecule discovery programs are supported by a robust and expanding infrastructure, including a library of 4.6 million compounds. We have extensive experience in the identification and optimization of drug candidates against multiple target classes for oncology, inflammation and metabolic diseases. The first compound to enter the clinic following our re-initiation of drug discovery activities in 2017 was XL092, a next-generation oral TKI that targets VEGF receptors, MET, AXL, MER and other kinases implicated in cancer’s growth and spread. In designing XL092, we sought to build upon our experience with cabozantinib, retaining a similar target profile while improving key characteristics, including the pharmacokinetic half-life. To date, we have initiated two large phase 1b clinical trials studying XL092: STELLAR-001 and STELLAR-002. STELLAR-001 is a phase 1b clinical trial evaluating XL092, both as a monotherapy and in combination with either atezolizumab or avelumab, an ICI developed by Merck KGaA Damstadt, Germany and Pfizer Inc. We have established recommended doses for single-agent XL092 and XL092 in combination with atezolizumab and have begun enrolling expansion cohorts for patients with clear cell RCC, non-clear cell RCC, hormone-receptor positive breast cancer, mCRPC and colorectal cancer (CRC); the dose-escalation phase for XL092 in combination with avelumab is ongoing. STELLAR-002 is a phase 1b clinical trial evaluating XL092 in combination with either nivolumab or nivolumab and ipilimumab. We are enrolling patients with advanced solid tumors in dose-escalation cohorts, and depending on the dose-escalation results, STELLAR-002 may enroll expansion cohorts for patients with clear cell and non-clear cell RCC, mCRPC and urothelial carcinoma (UC). To better understand the individual contribution of the therapies, treatment arms in the expansion cohorts may include XL092 as a single-agent in addition to the ICI combination regimens. We also initiated STELLAR-303, the first global phase 3 pivotal trial for XL092, in June 2022, and other phase 3 pivotal trials may follow in late 2022 and early 2023. STELLAR-303 is evaluating XL092 in combination with atezolizumab versus regorafenib in patients with metastatic non-microsatellite instability-high or non-mismatch repair-deficient CRC who have progressed after or are intolerant to the current standard of care, and the trial aims to enroll approximately 600 patients worldwide with documented RAS status. The primary objective of STELLAR-303 is to evaluate the efficacy of the combination in patients with RAS wild-type disease, and outcomes in patients with RAS-mutated disease will also be evaluated. The primary endpoint of STELLAR-303 is OS, and additional efficacy endpoints include PFS, objective response rate (ORR) and duration response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1. as assessed by the investigator.
We augment our small molecule discovery activities through research collaborations and in-licensing arrangements with other companies. The most advanced compounds to emerge from these arrangements are XL102 , the lead program targeting CDK7 under our collaboration with Aurigene Discovery Technologies Limited (Aurigene), and XL114, Aurigene’s novel anti-cancer compound that inhibits the CBM complex. Based on encouraging preclinical data, we exercised our exclusive options to license XL102 and XL114 from Aurigene and initiated phase 1 clinical trials prove positive,evaluating XL102 and XL114 in January 2021 and April 2022, respectively, and we believeexpect to provide clinical updates from the phase 1 study of XL102 in the second half of 2022.
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Beyond small molecules, we have also launched rigorous efforts to discover and advance various biotherapeutics that cobimetinib will have the potential to become anti-cancer therapies, such as bispecific antibodies, ADCs and other innovative treatments. ADCs in particular present a unique opportunity for new cancer treatments, given their capabilities to deliver anti-cancer payload drugs to targets with increased precision while minimizing impact on healthy tissues, and this biotherapeutic approach has been validated by multiple regulatory approvals for the commercial sale of ADCs in the past several years. To facilitate the growth of these programs, we have established multiple research collaborations and in-licensing arrangements and entered into other strategic transactions that provide us with access to antibodies, binders, payloads and conjugation technologies, which are the components employed to generate next-generation ADCs or multispecific antibodies. We have already made significant progress under these arrangements and expect we will continue to advance our biotherapeutics programs throughout the remainder of 2022 and in future years:

Ryvu. We entered into a collaboration with Ryvu Therapeutics S.A. (Ryvu) in July 2022, focused on the development of novel targeted therapies utilizing Ryvu’s STING (STimulator of INterferon Genes) technology. The collaboration is intended to expand our portfolio of biotherapeutics by combining our tumor-specific targeting approaches with Ryvu’s proprietary small molecule STING agonists and STING biology know-how.
BioInvent. We entered into a collaboration with BioInvent International AB (BioInvent) in June 2022, focused on the identification and development of novel antibodies for use as oncology therapeutics. The collaboration is intended to expand our portfolio of antibody-based therapies and will utilize BioInvent’s proprietary n-CoDeR® antibody library and patient-centric F.I.R.S.TTM screening platform, which together are designed to allow for parallel target and antibody discovery.
GamaMabs. We completed an asset purchase from GamaMabs Pharma SA (GamaMabs) in May 2022. In the transaction, we acquired all rights, title and interest in GamaMabs’ antibody program directed at anti-Müllerian hormone receptor 2 (AMHR2), a novel oncology target with relevance in multiple forms of cancer.
Iconic. We in-licensed XB002, our lead TF-targeting ADC program, from Iconic, Inc. (Iconic) in December 2020 and then initiated a phase 1 clinical trial in June 2021. We expect to provide clinical updates from the trial in the second meaningful sourcehalf of revenue. With respect2022. In December 2021, we amended our exclusive option and license agreement with Iconic to COTELLIC commercializationacquire broad rights to use the anti-TF antibody used in XB002 for any application, including conjugated to other payloads, as well as rights within oncology to a number of other anti-TF antibodies developed by Iconic, including for use in ADCs and multispecific biotherapeutics.
Invenra. We have expanded our collaboration with Invenra, Inc. (Invenra) several times since our first engagement in 2018, most recently in August 2021 to include an additional 20 oncology targets.
WuXi Bio. We expanded our access to antibodies through arrangements with WuXi Biologics Ireland Limited, a wholly owned subsidiary of WuXi Biologics (Cayman) Inc. (individually and collectively referred to as WuXi Bio) in March 2021. We are focused on leveraging WuXi Bio’s panel of monoclonal antibodies (mAbs) against an undisclosed target for the development of ADC, bispecific and certain other novel tumor-targeting biotherapeutics.
Adagene. We entered into a collaboration with Adagene Inc. (Adagene) in February 2021, focused on using Adagene’s SAFEbody® technology to develop novel masked ADCs or other innovative biotherapeutics, with the potential to develop ADCs or other biotherapeutics with improved therapeutic index.
NBE and Catalent. We entered into collaborations with NBE-Therapeutics AG (NBE) and Catalent, Inc.’s wholly owned subsidiaries Redwood Bioscience, Inc., R.P. Scherer Technologies, LLC and Catalent Pharma Solutions, Inc. (individually and collectively referred to as Catalent) in September 2020. These platform collaborations allow us to utilize their site-specific conjugation technologies and payloads to construct ADCs using the antibodies we have sourced from our arrangements with WuXi Bio, GamaMabs and Invenra.
These arrangements have led directly to the advancement of two biotherapeutics development candidates, XB010 and XB014. XB010, our first ADC advanced internally, targets the tumor antigen 5T4 and incorporates antibodies sourced from Invenra. It was constructed using Catalent’s SMARTag® site-specific bioconjugation platform. XB014 is our first bispecific antibody, which combines a PD-L1 targeting arm with a CD47 targeting arm to block a macrophage checkpoint, and was developed through our collaboration with Invenra.
As of the date of this Quarterly Report, we are currently advancing more than 10 discovery programs and expect to progress up to five new development candidates into preclinical development during 2022. We will continue to engage in business development initiatives with the goal of acquiring and in-licensing promising oncology platforms and assets and then further characterize and develop them utilizing our established preclinical and clinical development infrastructure.
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COVID-19 Update
As of the date of this Quarterly Report on Form 10-Q, the COVID-19 pandemic continues to have a modest impact on our business operations. While the pandemic has created operational difficulties and complexities, we have thus far been successful at devising solutions designed to mitigate its impact. We will continue to monitor new developments that could pose additional risks for us, including the spread of the Omicron variant and its subvariants in the U.S. underand other countries, and the Genentech Collaboration Agreement,potential emergence of new SARS-CoV-2 variants that may prove especially contagious or virulent. Despite our COVID-19 pandemic mitigation efforts, we have been fielding 25%may experience delays or an inability to execute on our clinical and preclinical development plans, reduced revenues or other adverse impacts to our business as described in more detail in “Risk Factors” in Part II, Item 1A of this Quarterly Report on Form 10-Q. We recognize that this pandemic will continue to present unique challenges for us throughout 2022, and potentially into 2023.

Second Quarter 2022 Business Updates and Financial Highlights
During the sales force promoting COTELLIC in combination with Zelboraf® as a treatment for patients with BRAF mutation-positive advanced melanoma. However, following a recent commercial review, commencing in January 2018, second quarter of 2022, we continued to execute on our business objectives, generating significant revenues from operations and Genentech will scale back the personal promotion of COTELLIC in combination with Zelboraf as a treatment for patients with BRAF mutation-positive advanced melanoma in the U.S. This decision is not indicative of any change in our intentionenabling us to promote COTELLIC for other therapeutic indications for which it may be approved in the future.
As we continue to seek to maximize the clinical therapeutic and commercial potential of cabozantinibour products and cobimetinib, we remain steadfast inexpand our commitment to discover and develop new cancer therapies for patients. In this regard, we have resumed internal drug discovery efforts with the goal of identifying new product candidates to advance into clinical trials. Notably, these efforts are led by some of the same experienced scientists responsible for the discovery of cabozantinib and cobimetinib, which have been approved for commercialization by regulatory authorities, as well as other promising Exelixis compounds that are in earlier stages of clinical and regulatory development pursuant to our collaborations with Daiichi Sankyo Company, Limited, or Daiichi Sankyo, Merck and BMS.
Third Quarter 2017 Business Development Updates and Financial Highlights
During the third quarter of 2017, we continued to build infrastructure intended to support our anticipated growth and evolution beyond our current product pipeline. Significant business development updates and financial highlights for the quarter and subsequent to quarter-end include:
Business Development Updates
In July 2017, BMS initiatedApril 2022, we announced the initiation of a phase 1 clinical trial evaluating XL114 as a monotherapy in patients with non-Hodgkin’s Lymphoma.
In May 2022, we announced that Ipsen received regulatory approvals from the EC and Health Canada for CABOMETYX as a monotherapy for patients with previously treated, RAI-refractory DTC.
In June 2022, cabozantinib was the subject of multiple data presentations in NSCLC, UC, RCC, head and neck squamous cell carcinoma, and DTC at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
In June 2022, we announced an exclusive option and license agreement with BioInvent to identify and develop novel antibodies for use in immuno-oncology therapeutics utilizing BioInvent’s n-CoDeR antibody library and patient-centric F.I.R.S.T screening platform.
In June 2022, we announced the initiation of STELLAR-303, a global phase 3 pivotal trial CheckMate 9ER, to evaluate cabozantinibevaluating XL092 in combination with atezolizumab in patients with metastatic non-microsatellite instability-high or non-mismatch repair-deficient CRC who have progressed after or are intolerant to the current standard of care. The primary endpoint of the trial is OS, and additional efficacy endpoints include PFS, ORR and DOR per RECIST v. 1.1.
In July 2022, we announced an exclusive license agreement with Ryvu to develop novel targeted therapies utilizing Ryvu’s STING technology.
In July 2022, we announced results from the phase 3 COSMIC-313 trial, in which the triplet combination of cabozantinib, nivolumab and ipilimumab met its primary endpoint, demonstrating significant improvement in PFS versus the doublet combination of nivolumab and ipilimumab at the primary analysis. At a prespecified interim analysis for the secondary endpoint of OS, the triplet combination did not demonstrate a significant benefit, and therefore the trial will continue to the next analysis of OS. We intend to discuss the results with or without ipilimumab, versus sunitinib in the FDA to determine next steps toward a potential regulatory submission for the combination regimen for patients with previously untreated, advanced intermediate- or metastatic RCC. The primary endpointpoor-risk RCC, and detailed findings will be presented at a future medical meeting.
In July 2022, we filed a patent lawsuit in the United States District Court for the trial is PFS.
In July 2017, we entered into anDistrict of Delaware (the Delaware District Court) against MSN Pharmaceuticals, Inc. (MSN) asserting infringement of U.S. Patent No. 11,298,349 arising from MSN’s further amendment to our collaboration agreement with Genentech in connection with the settlement of our arbitration concerning claims asserted by us against Genentech related to the development, pricing and commercialization of COTELLIC. The amendment resolves our concerns outlined in the arbitration demand and provides for a favorably revised revenue and cost-sharing arrangement, effective as of July 1, 2017, that is applicable to current and potential future commercial uses of COTELLIC.
In August 2017, we completed the submission of an sNDAits Abbreviated New Drug Application (ANDA), originally filed with the FDA for cabozantinib as a treatment for patients with previously untreated advanced RCC.
Inin September 2017, Ipsen received validation from the European Medicines Agency, or EMA, for the application for variation to the CABOMETYX marketing authorization for the addition of a new indication in first-line treatment of advanced RCC in adults.
In September 2017, at the 2017 European Society for Medical Oncology Congress, we announced updated results from CABOSUN, including the IRRC analysis that confirmed the primary efficacy endpoint results of investigator-assessed PFS. Per the IRRC analysis, cabozantinib demonstrated a clinically meaningful and statistically significant 52% reduction in the rate of disease progression or death (HR 0.48, 95% CI 0.31-0.74, two-sided P=0.0008). The median PFS for cabozantinib was 8.6 months versus 5.3 months for sunitinib, corresponding to a 3.3 month (62%) improvement favoring cabozantinib over sunitinib.
In September 2017, we announced that our partner Daiichi Sankyo reported positive top-line results from ESAX-HTN, a phase 3 pivotal trial of esaxerenone, a product of the companies’ prior research collaboration, in patients with essential hypertension in Japan. With the trial achieving its primary endpoint, Daiichi Sankyo communicated its intention to submit a Japanese regulatory application for esaxerenone for2019. We are seeking, among other relief, an essential hypertension indication in the first quarter of 2018.
In October 2017, we announced that BMS filed a Clinical Trial Authorization in Europe for a first-in-human study of a RORγt inverse agonist, which will trigger a $10.0 million milestone payment to us in the fourth quarter of 2017 under the terms of the parties’ worldwide collaboration for compounds targeting retinoic acid-related orphan receptor, a family of nuclear hormone receptors implicated in inflammatory conditions.
In October 2017, we announcedorder that the FDA determined that our sNDA for cabozantinib for patients with previously untreated advanced RCC was sufficiently complete to permit a substantive review. The FDA granted Priority Review of the filing and assigned a PDUFA actioneffective date of any FDA approval of MSN’s ANDA would be a date no earlier than the expiration of U.S. Patent No. 11,298,349 on February 15, 2018.
In October 2017,10, 2032. This is our fourth case against MSN and involves an Exelixis patent that is different from those asserted previously in consolidated patent lawsuits that we announced that CELESTIAL met its primary endpointfiled in 2019 and 2020 and the separate lawsuit filed in February 2022. For a more detailed discussion of OS, with cabozantinib providing a statistically significant and clinically meaningful improvementthis litigation matter, see “Legal Proceedings” in OS compared to placebo in patients with advanced HCC. BasedPart II, Item 1 of this Quarterly Report on these results, we plan to submit an sNDA to the FDA in the first quarter of 2018.Form 10-Q.
Financial Highlights
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Net incomeproduct revenues for the thirdsecond quarter of 2017 was $81.42022 were $347.0 million,, or $0.28 per share, basic and $0.26 per share, diluted, compared to a net loss of $(11.3)$284.2 million, or $(0.04) per share, basic and fully diluted, for the thirdsecond quarter of 2016.
2021.
Total revenues for the thirdsecond quarter of 2017 increased to $152.52022 were $419.4 million,, compared to $62.2$385.2 million for the thirdsecond quarter of 2016.
2021.
Cost of goods sold for the third quarter of 2017 increased to $4.7 million, compared to $2.5 million for the third quarter of 2016.
Research and development expenses for the thirdsecond quarter of 2017 increased to $28.52022 were $199.5 million,, compared to $20.3$148.8 million for the thirdsecond quarter of 2016.
2021.
Selling, general and administrative expenses for the thirdsecond quarter of 2017 increased to $38.12022 were $122.8 million,, compared to $32.5$98.5 million for the thirdsecond quarter of 2016.
2021.
Total otherProvision for income (expense), nettaxes for the thirdsecond quarter of 2017 increased to $3.42022 was $17.8 million,, compared to $(18.5)$28.8 million for the thirdsecond quarter of 2016.
2021.
CashNet income for the second quarter of 2022 was $70.7 million, or $0.22 per share, basic and investments decreased to $422.3 million at September 30, 2017,diluted, compared to $479.6net income of $96.1 million, at December 31, 2016.
or $0.31 per share, basic and $0.30 per share, diluted, for the second quarter of 2021.
See “Results of Operations” below for a discussion of the detailed components and analysis of the amounts above.
Although we reported net income of $115.7 million for the nine months ended September 30, 2017, we may not be able to maintain or increase profitability on a quarterly or annual basis and we are unable to accurately predict the extent of long-range future profits or losses. We expect to continue to spend significant additional amounts to fund the continued development and commercialization of cabozantinib. In addition, we intend to expand our product pipeline through the measured resumption of drug discovery and the evaluation of in-licensing and acquisition opportunities that align with our oncology drug expertise, which efforts could involve substantial costs. As a result, we are unable to predict the extent of any future profits or losses because we expect to continue to incur substantial operating expenses and, consequently, we will need to generate substantial revenues to maintain or increase profitability.
Outlook, Challenges and Risks
We anticipate that we will continue to face a number ofnumerous challenges and risks to our business that may impact our ability to execute on our 2022 business objectives. In particular, we anticipate that for the foreseeable future, we expect our ability to generate meaningful revenuesufficient cash flow to fund our commercialbusiness operations and our development and discovery programs is dependentgrowth will depend upon the successful commercializationcontinued commercial success of CABOMETYX, both alone and in combination with other therapies, as a treatment for the treatment of advanced RCChighly competitive indications for which it is approved, and possibly for other indications for which cabozantinib is currently being evaluated in territoriespotentially label-enabling clinical trials, if warranted by the data generated from these trials. However, we cannot be certain that the clinical trials we and our collaboration partners are conducting will demonstrate adequate safety and efficacy in these additional indications to receive regulatory approval in the major commercial markets where it has been or may be approved. The commercial potential of CABOMETYX for the treatment of advanced RCC remains subject to a variety of factors, most importantly, CABOMETYX’s perceived benefit/risk profile as compared to the benefit/risk profiles of other treatments available or currently in development for the treatment of advanced RCC. Our ability to generate meaningful product revenue from CABOMETYX is also affected by a number of other factors, includingapproved. Even if the extentrequired regulatory approvals to whichmarket cabozantinib for additional indications are achieved, we and our collaboration partners may not be able to commercialize CABOMETYX effectively and successfully in these additional indications. In addition, CABOMETYX will only continue to be commercially successful if private third-party and government payers continue to provide coverage and reimbursement. As is the case for all innovative pharmaceutical therapies, obtaining and maintaining coverage and reimbursement for CABOMETYX is available from government and other third-party payers. Obtaining and maintaining appropriate coverage and reimbursement for CABOMETYX isbecoming increasingly challenging due to, among other things, efforts by payors to contain and slow increases in healthcare costs indifficult, both within the U.S. and worldwide. It is also potentially threatened by increasing interest amongin foreign markets. In addition, healthcare policymakers in the U.S. with respectare increasingly expressing concern over healthcare costs, and corresponding legislative and policy initiatives and activities have been launched, aimed at increasing the healthcare cost burdens borne by pharmaceutical manufacturers, as well as expanding access to, controlling pharmaceutical drug pricing practices. Our ability to fulfilland restricting the fullest commercial potentialprices and growth in prices of, cabozantinib also ultimately depends on our ability to expand the compound’s use by generating data in clinical development that will support regulatory approval of cabozantinib in additional indications. Our immediate focus in this regard is the potential regulatory approval of our sNDA for cabozantinib as a treatment for patients with previously untreated advanced RCC based upon data from CABOSUN. Obtaining this approval represents a significant challenge because CABOSUN was not originally designed as a registration enabling trial. However, given the positive nature of CABOSUN results, combined with the confirming analysis of such results by the IRRC, we submitted an sNDA to the FDA on August 15, 2017, which, as we announced on October 16, 2017, was deemed by the FDA as sufficiently complete to permit a substantive review. The FDA granted the file Priority Review and assigned a PDUFA action date of February 15, 2018.pharmaceuticals.
Achievement of our 2022 business objectives will also depend on our ability to adapt our development and commercialization strategy to navigate the increasing prevalence of immunotherapy, which is bothmaintain a competitive threat and a potential opportunity due to interestposition in the useshifting landscape of combination therapy to treat cancer.
In addition totherapeutic strategies for the challenges we encounter while working toward the achievementtreatment of our development and commercial objectives, we also face significant challenges in our efforts to expand our pipeline through the measured resumption of internal drug discovery activities and the evaluation of in-licensing and acquisition opportunities. Internal discovery efforts require substantial technical, financial and human resources and may fail to yield product candidates for clinical development. Furthermore, we continue to operate in an environment with significant market competition for relevant product candidates, and, even if we are able to identify an attractive and available product candidate,cancer, which we may not be able to in-licensedo. On an ongoing basis, we assess the constantly evolving landscape of other approved and investigational cancer therapies that could be competitive, or acquirecomplementary in combination, with our products, and then we adapt our development strategies for the cabozantinib franchise and our pipeline product candidates accordingly, such as by modifying our clinical trials to include evaluation of our therapies with ICIs and other targeted agents. Even if our current and future clinical trials, including those evaluating cabozantinib in combination with an ICI in NSCLC and mCRPC or evaluating XL092 in combination with an ICI in CRC, produce positive results sufficient to obtain marketing approval by the FDA and other global regulatory authorities, it is uncertain whether physicians will choose to prescribe regimens containing our products instead of competing products and product combinations in approved indications.
In the longer term, we may eventually face competition from potential manufacturers of generic versions of our marketed products, including the proposed generic versions of CABOMETYX tablets that are the subject of ANDAs submitted to the FDA by MSN and Teva Pharmaceuticals Development, Inc. and Teva Pharmaceuticals USA, Inc. (individually and collectively referred to as Teva). The approval of either MSN’s or Teva’s ANDA and subsequent launch of any generic version of CABOMETYX could significantly decrease our revenues derived from the U.S. sales of CABOMETYX and thereby materially harm our business, financial condition and results of operations.
Separately, our research and development objectives may be impeded by the challenges of scaling our organization to meet the demands of expanded drug development, unanticipated delays in clinical testing and the inherent
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risks and uncertainties associated with drug discovery operations, especially on acceptable terms that would enablethe global level. In connection with efforts to expand our continued growth as an organization.product pipeline, we may be unsuccessful in discovering new drug candidates or identifying appropriate candidates for in-licensing or acquisition.
Some of these challenges and risks are specific to our business, and others are common to companies in the pharmaceuticalbiopharmaceutical industry with development and commercial operations.operations, and an additional category are macroeconomic, affecting all companies. For a completemore detailed discussion of challenges and risks we face, see “Risk Factors” in Part II, Item 1A of this Quarterly Report on Form 10-Q.
Fiscal Year Convention
We have adopted a 52- or 53-week fiscal year policy that generally ends on the Friday closest to December 31st. Fiscal year 20172022, which is a 52-week fiscal year, will end on December 29, 201730, 2022 and fiscal year 20162021, which was a 52-week fiscal year, ended on December 30, 2016.31, 2021. For convenience, references in this report as of and for the fiscal periods ended September 29, 2017July 1, 2022 and September 30, 2016,July 2, 2021, and as of and for the fiscal years ended December 29, 2017 andyear ending December 30, 2016,2022 are indicated as being as of and for the fiscal periods ended SeptemberJune 30, 20172022 and SeptemberJune 30, 2016,2021, and the years endedyear ending December 31, 2017 and December 31, 2016,2022, respectively.

Results of Operations
Revenues
Revenues by category were as follows (dollars in thousands):
 Three Months Ended June 30,Percent ChangeSix Months Ended June 30,Percent Change
 2022202120222021
Net product revenues$347,044 $284,248 22 %$657,342 $511,460 29 %
License revenues57,526 39,640 45 %89,593 67,168 33 %
Collaboration services revenues14,857 61,289 -76 %28,472 76,779 -63 %
Total revenues$419,427 $385,177 %$775,407 $655,407 18 %
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Product revenues:       
Gross product revenues$111,148
 $46,720
 $289,365
 $92,383
Discounts and allowances(14,732) (3,978) (36,068) (8,924)
Net product revenues96,416
 42,742
 253,297
 83,459
Collaboration revenues:       
Contract revenues (1)
45,000
 15,000
 47,500
 20,000
License revenues (2)
7,572
 3,780
 21,335
 8,570
Development cost reimbursements2,316
 
 5,623
 
Royalty and product supply revenues, net1,206
 672
 4,650
 1,844
Total collaboration revenues56,094
 19,452
 79,108
 30,414
Total revenues$152,510
 $62,194
 $332,405
 $113,873
Dollar change$90,316
   $218,532
 

Percentage change145%   192% 

Net Product Revenues
____________________Gross product revenues, discounts and allowances, and net product revenues were as follows (dollars in thousands):
(1)Includes milestone payments.
(2)Includes amortization of upfront payments.
 Three Months Ended June 30,Percent ChangeSix Months Ended June 30,Percent Change
 2022202120222021
Gross product revenues$483,073 $380,204 27 %$931,310 $694,409 34 %
Discounts and allowances(136,029)(95,956)42 %(273,968)(182,949)50 %
Net product revenues$347,044 $284,248 22 %$657,342 $511,460 29 %
Net product revenues by product were as follows (dollars in thousands):
 Three Months Ended June 30,Percent ChangeSix Months Ended June 30,Percent Change
 2022202120222021
CABOMETYX$339,159 $275,614 23 %$641,971 $499,209 29 %
COMETRIQ7,885 8,634 -9 %15,371 12,251 25 %
Net product revenues$347,044 $284,248 22 %$657,342 $511,460 29 %
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
CABOMETYX$90,362
 $31,238
 $233,582
 $48,812
COMETRIQ6,054
 11,504
 19,715
 34,647
Net product revenues$96,416
 $42,742
 $253,297

$83,459
Dollar change$53,674
   $169,838
  
Percentage change126%   203%  
For the three and nine months ended September 30, 2017, net product revenues increased 126% and 203%, respectively, as compared to the comparable periods in 2016. For the three and nine months ended September 30, 2017, the 189% and 379% increaseThe increases in net product revenues for CABOMETYXthe three and six months ended June 30, 2022, as compared to the comparable period in 2016, wascorresponding prior year periods, were primarily duerelated to a 174%increases of 19% and 353% increase,25%, respectively, in the number of CABOMETYX units sold, as well as anand to a lesser extent a 3% increase in the average net selling price of the product. CABOMETYX was approved by the FDA on April 25, 2016 as a treatment for patients with advanced RCC who have received prior anti-angiogenic therapy. The increase in CABOMETYX sales volume was due to an increase in market share. Forboth the three and ninesix months ended SeptemberJune 30, 2017,2022, as compared to the 47% and 43% decrease incorresponding prior year periods.
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We project that our net product revenues for COMETRIQthe remainder of 2022 may increase, as compared to the comparable periods in 2016, was primarily due to a 77% and 65% decrease, respectively, in the number of COMETRIQ units sold; the decrease in units sold was partially offset by an increase in the average selling price of the product. The decrease in COMETRIQ sales volume was primarily driven by the adoption of CABOMETYX by our customers.
Contract revenuescorresponding prior year period, for the three and nine months ended September 30, 2017 reflects recognition of two milestones totaling $45.0 million resulting from Ipsen’s receipt of the validation from the EMA for the application for variation to the CABOMETYX marketing authorization for the addition of a new indication in first-line treatment of advanced RCC in adults. Payment of the first milestone of $20.0 million is due in the fourth quarter of 2017 and payment of the second milestone of $25.0 million is due in the first quarter of 2018. Contract revenues for the nine months ended September 30, 2017 also reflects recognition of a $2.5 million milestone earned from BMS related to the RORγ program. Contract revenues for the three and nine months ended September 30, 2016 reflect recognition of $15.0 million from a milestone payment earned in

September 2016 from Daiichi Sankyo related to its worldwide license of our compounds that modulate mineralocorticoid receptor, or MR, including CS-3150 (an isomer of XL550). Contract revenues for the nine months ended September 30, 2016 also reflects recognition of a $5.0 million from a milestone payment earned from Merck related to its worldwide license of our phosphoinositide-3 kinase-delta program.
License revenues consists of the recognition of the upfront payments and non-substantive milestone received in connection with our February 2016 collaboration agreement with Ipsen, or the Ipsen Collaboration Agreement, and the upfront payment received in connection with our January 2017 collaboration agreement with Takeda, or the Takeda Collaboration Agreement. For the three and nine months ended September 30, 2017, we recognized $4.7 million and $13.8 million, respectively, of such revenue in connection with the Ipsen Collaboration Agreement, as compared to $3.8 million and $8.6 million, respectively, during the comparable periods in 2016. For the three and nine months ended September 30, 2017, we recognized $2.8 million and $7.5 million, respectively, of such revenue in connection with the Takeda Collaboration Agreement. No such revenue was recognized for Takeda during the comparable periods in 2016. The increase in such revenues is due to the timing of the execution of those agreements.
Development cost reimbursements for the three and nine months ended September 30, 2017 consisted of reimbursements pursuant to our collaboration and license agreements, including $1.1 million and $2.3 million, respectively, under the Ipsen Collaboration Agreement and $1.2 million and $3.3 million, respectively, under the Takeda Collaboration Agreement. There were no such development cost reimbursements during the comparable periods in 2016.
Royalty and product supply revenues, net, primarily consisted of royalties on ex-U.S. net sales of COTELLIC under our collaboration agreement with Genentech for cobimetinib.
Total revenues by significant customer were as follows (in thousands): 
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Diplomat Specialty Pharmacy$20,460
 $19,392
 $62,909
 $46,770
Ipsen50,680
 3,873
 60,704
2,000
8,663
Caremark L.L.C.20,272
 5,591
 52,526
 8,728
Affiliates of McKesson Corporation14,575
 3,683
 38,699
 5,764
Accredo Health, Incorporated13,445
 5,880
 36,504
 8,340
Daiichi Sankyo
 15,000
 
 15,000
Others, individually less than 10% of total revenues for all periods presented33,078
 8,775
 81,063
 20,608
Total revenues$152,510
 $62,194
 $332,405
 $113,873
similar reasons noted above.
We recognize product revenuerevenues net of discounts and allowances that are further described in “Note 1. Organization and Summary of Significant Accounting Policies” to our “Notes to Consolidated Financial Statements” containedincluded in Part II, Item 8 of our Annual Report onFiscal 2021 Form 10-K filed with10-K.
The increases in discounts and allowances for the SEC on February 27, 2017. The activitiesthree and ending reserve balances for each significant category of discountsix months ended June 30, 2022, as compared to the corresponding prior year periods, were primarily from higher utilization in the 340B Drug Pricing Program.
Discounts and allowance were as follows (in thousands):
 Chargebacks and discounts for prompt payment Other customer credits and co-pay assistance Rebates Returns Total
Balance at December 31, 2016$1,802
 $794
 $2,627
 $351
 $5,574
Provision related to sales made in:        
Current period22,823
 5,135
 8,389
 
 36,347
Prior periods(864) 
 584
 
 (280)
Payments and customer credits issued(22,221) (4,501) (7,533) (351) (34,606)
Balance at September 30, 2017$1,540
 $1,428
 $4,067
 $
 $7,035
Chargebacks and discounts for prompt payment are recordedallowances as a reductionpercentage of trade receivablesgross revenues have increased over time as the number of patients participating in government programs, as well as the discounts given and the remaining reserve balances are classified as Other current liabilities in the accompanying Condensed Consolidated Balance Sheets. Balances as of December 31, 2016 have been reclassified to reflect that presentation.

The increase in the reserve balance at September 30, 2017 was the result of an increase in product sales volume and a shift in payer mixrebates paid to government programs, which was offset by payments, the issuance of customer creditspayers, has also increased. We project this trend will continue and the prior period adjustments for chargebacks and certain rebates. We expectthat our discounts and allowances as a percentage of gross product revenue torevenues may increase during the remainder of 20172022, as compared to the corresponding prior year period.
License Revenues
License revenues generally include: (a) the recognition of the portion of milestone payments allocated to the transfer of intellectual property licenses for which it had become probable in the related period that the milestone would be achieved and a significant reversal of revenues would not occur; (b) royalty revenues; and (c) the profit on the U.S. commercialization of COTELLIC from Genentech.
Milestone revenues, which are allocated between license revenues and collaboration services revenues, were $26.2 million and $26.9 million for the three and six months ended June 30, 2022, respectively, as compared to $12.9 million and $13.5 million for the corresponding prior year periods. Milestone revenues by period included the following:
For the three and six months ended June 30, 2022, $25.7 million in revenues recognized in connection with two regulatory milestones totaling $27.0 million upon the approval by the European Commission and Health Canada of cabozantinib as a monotherapy for the treatment of adult patients with locally advanced or metastatic DTC, refractory or not eligible to radioactive iodine who have progressed during or after prior systemic therapy.
For the three and six months ended June 30, 2021, $11.8 million in revenues recognized in connection with a $12.5 million regulatory milestone we determined was probable of achievement.
Royalty revenues increased primarily as a result of increases in Ipsen’s net sales of cabozantinib outside of the U.S. and Japan. Ipsen royalties were $27.5 million and $52.1 million for the three and six months ended June 30, 2022, respectively, as compared to $22.8 million and $45.3 million for the corresponding prior year period. Ipsen’s net sales of cabozantinib have continued to grow since Ipsen’s commercial sale of CABOMETYX in the fourth quarter of 2016, primarily due to regulatory approval in new territories, including regulatory approval in the EU for the combination therapy of CABOMETYX and OPDIVO received in March 2021. Royalty revenues for the three and six months ended June 30, 2022 also included $2.7 million and $5.1 million, respectively, related to Takeda’s net sales of CABOMETYX, as compared to $2.1 million and $3.4 million for the corresponding prior year periods. Takeda royalty revenues have continued to grow since Takeda’s first commercial sale of CABOMETYX in Japan in 2020. As of June 30, 2022, CABOMETYX is approved and is commercially available in 62 countries outside the U.S.
Our share of profits on the U.S. commercialization of COTELLIC under our business evolvescollaboration agreement with Genentech was $1.7 million and $3.8 million for the three and six months ended June 30, 2022, respectively, as compared to $2.2 million and $4.0 million for the corresponding prior year periods. We also earned royalties on ex-U.S. net sales of COTELLIC by Genentech of $0.9 million and $2.5 million for the three and six months ended June 30, 2022, respectively, as compared to $0.8 million and $1.7 million for the corresponding prior year periods.
Due to uncertainties surrounding the timing and achievement of regulatory and development milestones, it is difficult to predict future milestone revenues and milestones can vary significantly from period to period.
Collaboration Services Revenues
Collaboration services revenues include the recognition of deferred revenues for the portion of upfront and milestone payments that have been allocated to research and development services performance obligations, development cost reimbursements earned under our collaboration agreements, and product supply revenues, which are net of product supply costs and the numberroyalties we pay on sales by Ipsen and Takeda of patients participatingproducts containing cabozantinib.
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Development cost reimbursements of $17.3 million and $34.5 million for the three and six months ended June 30, 2022, respectively, as compared to $62.5 million and $80.9 million for the corresponding prior year periods decreased primarily due to Ipsen’s decision to opt in government programs increases,and co-fund COSMIC-311 development costs in the discounts or rebatessecond quarter of 2021, which included a cumulative catch up for Ipsen’s share of global development costs incurred since the beginning of the study and through the end of the period.
Collaboration services revenues, for the 3% royalty we are required to government payers increase,pay on the net sales by Ipsen and Takeda of any product incorporating cabozantinib, were reduced by $4.2 million and $8.0 million for the three and six months ended June 30, 2022, respectively, as compared to $3.5 million and $6.9 million for the corresponding prior year periods. As royalty generating sales of cabozantinib by Ipsen and Takeda have increased as described above, our royalty payments have also increased.
We project our collaboration services revenues may decrease for the remainder of 2022, as compared to the corresponding prior year period, primarily as a result of decreased development cost reimbursements related to Ipsen’s opt-in and co-funding of COSMIC-311 and the engagementrelated cumulative catch-up in commercial contractingdevelopment cost reimbursements recognized in 2021 for which may resultno similar event is projected to occur in additional discounts or rebates.2022.
Cost of Goods Sold
The cost of goods sold and our gross marginsmargin were as follows (dollars in thousands):
 Three Months Ended June 30,Percent ChangeSix Months Ended June 30,Percent Change
 2022202120222021
Cost of goods sold$13,481$14,884-9 %$26,684$28,082-5 %
Gross margin96 %95 %96 %95 %
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Cost of goods sold$4,658
 $2,455
 $10,875
 $4,700
Gross margin95% 94% 96% 94%
Cost of goods sold is related to our product revenues and consists primarily of a 3% royalty payable to GlaxoSmithKline on U.S. net sales of any product incorporating cabozantinib, indirect labor costs,as well as the cost of manufacturing,inventory sold, indirect labor costs, write-downs related to expiring, excess and excessobsolete inventory, and other third partythird-party logistics costs. Portions of the manufacturing costs for inventory were incurred prior to the regulatory approval of CABOMETYX and COMETRIQ and, therefore, were expensed as research and development costs when incurred, rather than capitalized as inventory. The sale of products containing previously expensed materials resulted in a 1% and 6% reduction in the Cost of goods sold during the three and nine months ended September 30, 2017, respectively, as compared to a 6% and 5% reduction during the comparable periods in 2016. As of September 30, 2017 and December 31, 2016, our inventory includes approximately $0.5 million and $1.2 million, respectively, of materials that were previously expensed, are not capitalized, and will not be charged to Costs of goods sold in future periods. Write-downs related to excess and expiring inventory were $1.1 million for the three and ninesix months ended SeptemberJune 30, 2017 as compared to $0.4 million for the comparable periods in 2016.
The increase in Cost of goods sold was primarily related to the growth in sales of CABOMETYX due to an increase in market share.
Gross margin is net product revenues less cost of goods sold, divided by net product revenues. The increase in gross margin for the three and nine months ended September 30, 2017,2022, as compared to the comparablecorresponding prior year periods, in 2016, was related to the change in product mix as CABOMETYX sales volumes have increased while COMETRIQ volumes have decreased, and CABOMETYX tablets having a lower manufacturing cost than COMETRIQ capsules which have additional packaging requirements and are made in smaller batchesprimarily due to limited demand.lower period costs, partially offset by an increase in royalties as a result of increased U.S. CABOMETYX sales. We project our gross margin will not change significantly during the remainder of 2022.
Research and Development Expenses
Total research and development expenses were as follows (dollars in thousands): 
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Research and development expenses$28,543
 $20,256
 $79,967
 $72,166
Dollar change$8,287
   $7,801
  
Percentage change41%   11%  
Research and development expenses consist primarily of clinical trial costs, personnel expenses, consulting and outside services, an allocation for general corporate costs, stock-based compensation, and expenses for temporary personnel.
The increase in research and development expenses for the three months ended September 30, 2017, as compared to the comparable period in 2016, was primarily related to increases in personnel expenses, clinical trial costs and consulting and outside services. The increase in personnel expenses was $2.5 million for the three months ended September 30, 2017, as compared to the comparable period in 2016, and was primarily a result of an increase in headcount associated with the re-launch of our internal discovery program and the build-out of our medical affairs organization. The increase in clinical trial costs, which includes services performed by third-party contract research organizations and other vendors who support our clinical trials, was $2.5 million for the three months ended September 30, 2017, as compared to

the comparable period in 2016. The increase in clinical trial costs was predominantly due to start-up costs associated with CheckMate 9ER and the phase 1b trial of cabozantinib and atezolizumab in locally advanced or metastatic solid tumors; those increases were partially offset by decreases in costs related to METEOR, our completed phase 3 pivotal trial comparing CABOMETYX to everolimus in patients with advanced RCC. The increase in consulting and outside services was $1.1 million for the three months ended September 30, 2017, as compared to the comparable period in 2016, and was primarily in support of our medical affairs organization. The increase in research and development expenses also reflects a $1.0 million filing fee for the submission of our sNDA to the FDA in August 2017 for cabozantinib as a treatment for patients with previously untreated advanced RCC.
The increase in research and development expenses for the nine months ended September 30, 2017, as compared to the comparable period in 2016, was primarily related to an increase in personnel expenses and consulting and outside services that were partially offset by a decrease in stock-based compensation. The increase in personnel expenses of $6.7 million for the nine months ended September 30, 2017, as compared to the comparable period in 2016, was primarily a result of an increase in headcount associated with the re-launch of our internal discovery program and the build-out of our medical affairs organization. The increase in consulting and outside services was $1.2 million for the three months ended September 30, 2017, as compared to the comparable period in 2016, and was primarily in support of our medical affairs organization. The increase in research and development expenses also reflects a $1.0 million filing fee for the submission of our sNDA to the FDA. These increases were partially offset by a decrease in stock-based compensation of $3.2 million for the nine months ended September 30, 2017, as compared to the comparable period in 2016, primarily due to the 2016 recognition of stock-based compensation expense pertaining to the performance-based stock-options tied to the acceptance and anticipated approval of our CABOMETYX New Drug Application, or NDA, submission to the FDA and a 2016 bonus to our employees in the form of fully-vested restricted stock units.
We do not track fully-burdenedfully burdened research and development expenses on a project-by-project basis. We group our research and development expenses into three categories: development,(1) development; (2) drug discoverydiscovery; and (3) other. Our development group leads the development and implementation of our clinical and regulatory strategies and prioritizes disease indications in which our compounds are being or may be studied in clinical trials. Our drug discovery group utilizes a variety of technologies, including in-licensed technologies, to enable the rapid discovery, optimization and extensive characterization of lead compounds such that we are ableand biologics in order to select development candidates with the best potential for further evaluation and advancement into clinical development. Drug discovery expenses relate primarily to personnel expenses, consulting and outside services, and laboratory supplies. The “Other” category includes stock-based compensation and the allocation
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Table of general corporate costs to research and development. The expenditures for researchContents
Research and development expenses by category were as follows (in thousands):
Three Months Ended June 30,PercentSix Months Ended June 30,Percent
20222021Change20222021Change
Research and development expenses:
Development:
Clinical trial costs$59,788 $49,568 21 %$119,786 $110,259 %
Personnel expenses37,313 29,175 28 %71,579 58,059 23 %
Consulting and outside services8,910 6,646 34 %15,346 11,935 29 %
Other development costs11,703 7,534 55 %21,072 14,818 42 %
Total development117,714 92,923 27 %227,783 195,071 17 %
Drug discovery:
License and other collaboration costs(1)
33,158 23,466 41 %42,809 51,904 -18 %
Other drug discovery (2)
21,609 11,724 84 %39,440 23,011 71 %
Total drug discovery54,767 35,190 56 %82,249 74,915 10 %
Stock-based compensation9,549 13,667 -30 %18,448 26,063 -29 %
Other research and development(3)
17,451 7,010 149 %27,672 12,029 130 %
Total research and development expenses$199,481 $148,790 34 %$356,152 $308,078 16 %
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Development:       
Clinical trial costs$9,754
 $7,279
 $27,966
 $27,504
Personnel expenses7,437
 5,661
 21,649
 16,168
Consulting and outside services2,464
 1,938
 6,370
 6,453
Other development costs3,771
 2,228
 10,318
 8,273
Total development23,426
 17,106
 66,303
 58,398
Drug discovery1,743
 213
 3,986
 723
Other3,374
 2,937
 9,678
 13,045
Total$28,543
 $20,256
 $79,967
 $72,166
____________________
(1)    Primarily includes upfront license fees, development milestone payments, program initiation fees, and research funding commitments associated with programs in preclinical development stage.
(2)    Primarily includes personnel expenses, consulting and outside services and laboratory supplies.
(3)    Includes the allocation of general corporate costs to research and development services, and development cost reimbursements in connection with our collaboration arrangement with Roche executed in December 2019.

The increases in research and development expenses for the three and six months ended June 30, 2022, as compared to the corresponding prior year periods, were primarily related to increases in personnel expenses, clinical trial costs, and consulting and outside services, which were partially offset by decreases in stock-based compensation. Personnel expenses increased primarily due to increases in headcount to support our expanding discovery and development organization. Clinical trial costs, which include services performed by third-party contract research organizations and other vendors who support our clinical trials, increased as compared to the corresponding prior year periods primarily due to higher costs associated with the XL092, CONTACT-02 and CONTACT-03 studies which were partially offset by decreases in costs associated with COSMIC-313, COSMIC-021, and COSMIC-312 studies. Consulting and outside services expenses increased primarily as a result of the continued growth in our discovery and research activities. Stock-based compensation expense decreased as compared to the corresponding prior year periods, primarily due to lower compensation expense associated with the completion of expense amortization for certain performance-based restricted stock units (PSUs) granted in prior years, fewer stock options granted and higher forfeiture amounts. License and other collaboration costs increased for the three months ended June 30, 2022 as compared to the corresponding prior year period, primarily due to an increase in upfront license fees related to a new in-licensing collaboration arrangement in the second quarter of 2022. License and other collaboration costs decreased during the six months ended June 30, 2022, as compared to the corresponding prior period, primarily due to lower upfront license fees from business development activities.
In addition to reviewing the three categories of research and development expenses described above, we principally consider qualitative factors in making decisions regarding our research and development programs. SuchThese factors include enrollment in clinical trials for our drug candidates, thepreliminary data and final results of and data from clinical trials, the potential indications, for our drug candidates, theand clinical and commercial potential for our drug candidates, and competitive dynamics. We also make our research and development decisions in the context of our overall business strategy, which includes the pursuit of commercial collaborations with major pharmaceutical and biotechnology companies for the development of our drug candidates.strategy.
We are focusing a significant amount of our development and commercialization efforts primarily on cabozantinib to maximize the therapeutic and commercial potential of this compound and, as a result, we expectproject that a substantial portion of our near-term research and

development expenses to primarilywill relate to the continuing clinical development program of cabozantinib. We expect to continue to incur significant development costs for cabozantinib, in future periods as we evaluate its potential in a broad development program comprising approximately 50which includes over 100 ongoing or planned clinical trials across multiple indications. The most notableNotable ongoing company-sponsored studies resulting from
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this program are CELESTIAL, our company-sponsored phase 3 trial of cabozantinib in advanced HCC, our phase 3 study in collaboration withinclude: COSMIC-313, for which BMS evaluating cabozantinib in combination with nivolumab oris providing nivolumab and ipilimumab as compared to sunitinib in previously untreated patientsfree of charge; and CONTACT-02, for which Roche is sharing the development costs and providing atezolizumab free of charge.
We are expanding our oncology product pipeline through drug discovery efforts, which encompass both small molecule and biologics programs with advanced RCC,multiple modalities and our phase 2 study, in collaboration with BMS, evaluating cabozantinib and nivolumab or nivolumab and ipilimumab in advanced HCC, as well as our phase 1b study, in collaboration with Roche, evaluating cabozantinib in combination with atezolizumab in patients with advanced malignancies. In addition, post-marketing commitments in connectionmechanisms of action, with the approvalgoal of COMETRIQidentifying new product candidates to advance into clinical trials. We also continue to engage in progressive, metastatic MTC dictate that we conduct an additional study in that indication. As a result, we expectbusiness development initiatives aimed at acquiring and in-licensing promising oncology platforms and assets, with the goal of utilizing our established preclinical and clinical development infrastructure to further characterize and develop such acquisitions.
We project our research and development expenses may increase for the remainder of 2022, as compared to increase as we continue to developthe corresponding prior year period, primarily driven by our ongoing clinical evaluation of cabozantinib, and our pipeline.
The lengththe initiation of time required for clinical development of a particular product candidate and our development costs for that product candidate may be impacted by the scope and timing of enrollment innew clinical trials for theand expansion of ongoing clinical trials evaluating other product candidate,candidates in our decisions to develop a product candidate for additional indications, and whether we pursue development of the product candidate or a particular indication with a collaborator or independently. For example, cabozantinib is being developed in multiple indications, and we do not yet know how many of those indications we will ultimately pursue regulatory approval for. In this regard, our decisions to pursue regulatory approval of cabozantinib for additional indications depend on several variables outside of our control,pipeline including the strengthJune 2022 initiation of the data generated inSTELLAR-303, our prior, ongoingfirst global phase 3 pivotal trial for XL092 and potential future clinical trials. Furthermore, the scopecurrent early-stage trials evaluating XL092, XB002, XL102 and number of clinical trials required to obtain regulatory approval for each pursued indication is subject to the input of the applicable regulatory authorities, and we have not yet sought such input for all potential indications that we may elect to pursue, and even after having given such input, applicable regulatory authorities may subsequently require additional clinical studies prior to granting regulatory approval based on new data generated by us or other companies, or for other reasons outside of our control. As a condition to any regulatory approval, we may also be subject to post-marketingXL114, as well as anticipated business development commitments, including additional clinical trial requirements. As a result of the uncertainties discussed above, we are unable to determine the duration of or complete costs associated with the development of cabozantinib or any other research and development projects.activities.
In any event, our potential therapeutic products are subject to a lengthy and uncertain regulatory process that may not result in receipt of the necessary regulatory approvals. Failure to receive the necessary regulatory approvals would prevent us from commercializing the product candidates affected, including cabozantinib in any additional indications. In addition, clinical trials of our potential product candidates may fail to demonstrate safety and efficacy, which could prevent or significantly delay regulatory approval. A discussion of the risks and uncertainties with respect to our research and development activities including completing the development of our product candidates, and the consequences to our business, financial position and growth prospects can be found in “Risk Factors” in Part II, Item 1A of this Quarterly Report on Form 10-Q.
Selling, General and Administrative Expenses
Total selling,Selling, general and administrative expenses were as follows (dollars in thousands):
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Selling, general and administrative expenses$38,129
 $32,463
 $113,116
 $103,143
Dollar change$5,666
   $9,973
  
Percentage change17%   10%  
Three Months Ended June 30,Percent ChangeSix Months Ended June 30,Percent Change
2022202120222021
Selling, general and administrative expenses$107,686 $84,127 28 %$199,689 $164,221 22 %
Stock-based compensation15,073 14,368 %25,933 $36,625 -29 %
Total selling, general and administrative expenses$122,759 $98,495 25 %$225,622 $200,846 12 %
Selling, general and administrative expenses consist primarily of personnel expenses, consulting and outside services, stock-based compensation, marketing legal and accounting costs, facility costs and travel and entertainment.certain other administrative costs.
The increaseincreases in selling, general and administrative expenses for the three and ninesix months ended SeptemberJune 30, 2017,2022, as compared to the comparablecorresponding prior year periods, in 2016, waswere primarily related to increases in personnel expenses, consultingmarketing costs, business technology initiatives and outside services, and for the nine months ended September 30, 2017, legal and accounting costs; those increases were partially offset by a decrease in marketing costs. Personnel expenses increased by $2.0 million and $11.8 million for the three and nine months ended September 30, 2017, respectively, as compared to the comparablecorresponding prior year periods, in 2016, primarily due to an increaseincreases in general and administrative headcount to support our commercial and research and development organizations, incentive compensation and the accrual for bonuses. Consulting and outside servicesorganizations. Marketing costs increased by $4.3

million and $6.0 million for the three and nine months ended September 30, 2017, respectively, as compared to the comparablecorresponding prior year periods, in 2016, primarily due to increasesincreased spending in consulting for marketing activities. Legalsupport of the commercialization of the combination therapy of CABOMETYX and accounting expenses increased by $3.8 millionOPDIVO for the ninetreatment of advanced RCC. The decrease in stock-based compensation expense for the six months ended SeptemberJune 30, 20172022, as compared to the comparablecorresponding prior year period, in 2016,was primarily due to increaseslower compensation expense associated with the completion of expense amortization for certain PSUs granted in costs relatedprior years, fewer stock options granted and higher forfeiture amounts.
We project our selling, general and administrative expenses may continue to our dispute with Genentech. Marketing costs decreased by $3.3 million and $14.6 millionincrease for the three and nine months ended September 30, 2017, respectively,remainder of 2022, as compared to the comparable periods in 2016,corresponding prior year period primarily due to a decrease in losses recognized under our collaboration agreement with Genentech driven by Genentech’s changeour continuing commercial investment in cost allocation approach in December 2016.CABOMETYX and the growth of the broader organization.
Other
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Non-operating Income (Expense), Net
OtherNon-operating income (expense), net, was as follows (dollars in thousands):
Three Months Ended June 30,Percent ChangeSix Months Ended June 30,Percent Change
2022202120222021
Interest income$4,757 $1,891 152 %$6,579 $4,573 44 %
Other income (expense), net45 (11)n/a209 (101)n/a
Non-operating income$4,802 $1,880 155 %$6,788 $4,472 52 %
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Interest income and other, net$3,408
 $3,059
 $6,098
 $4,010
Interest expense
 (7,834) (8,679) (28,575)
Loss on extinguishment of debt
 (13,773) (6,239) (13,773)
Total other income (expense), net$3,408
 $(18,548) $(8,820) $(38,338)
Dollar change$21,956
   $29,518
  
Percentage change(118)%   (77)%  
Interest expense decreased by $7.8 million and $19.9 millionThe increases in non-operating income for the three and ninesix months ended SeptemberJune 30, 2017, respectively,2022, as compared to the comparablecorresponding prior year periods, in 2016,were primarily due to conversions and the redemptionresult of the 4.25% convertible senior subordinated notes due 2019, or the 2019 Notes, during the third and fourth quarters of 2016, the repayment of the Silicon Valley Bank term loan in March 2017 and the repayment of the Secured Convertible Notes due 2018, or the Deerfield Notes, in June 2017.
During the nine months ended September 30, 2017, we recognized a $6.2 million loss on extinguishment of debt resulting primarily from the prepayment penalty associated with the early the repayment of the Deerfield Notes. During the three and nine months ended September 30, 2016, we recognized a $13.8 million loss on extinguishment of debt associated with the conversion of $285.3 million in aggregate principal amount of the 2019 Notes for 53,704,911 shares of our Common Stock. See “Note 6 - Debt” in our “Notes to Condensed Consolidated Financial Statements” for more information on the repayment of our debt during 2017.
The increaseincreases in interest income due to higher interest rates and other, nethigher investment balances.
Provision for Income Taxes
The provision for income taxes were as follows (dollars in thousands):
Three Months Ended June 30,Percent ChangeSix Months Ended June 30,Percent Change
2022202120222021
Provision for income taxes$17,836 $28,796 -38 %$34,492 $25,180 37 %
Effective tax rate20.2 %23.1 %19.9 %20.5 %
The effective tax rates for the three and ninesix months ended SeptemberJune 30, 2017, as compared to2022, differed from the comparable periods in 2016, wasU.S. federal statutory rate of 21% primarily related to increases in interest income. Interest income increased by $0.4 million and $1.8 million for the three and nine months ended September 30, 2017, respectively, as compared to the comparable periods in 2016, due to both an increase in our investment balances and an increase in the yield earned on those investments. Interest income and other, net also included the recognition of a $2.3 million and $3.0 million gain during the three and nine months ended September 30, 2017, respectively,excess tax benefits related to the saleexercise of our 9% interest in Akarna Therapeutics, Ltd. to Allergan Holdco UK Limited in August 2016. We acquired our interest in Akarna in 2015, in exchange for intellectual property rights related tocertain stock options during the Exelixis discovered compound XL335.periods and the generation of federal tax credits, which were partially offset by state taxes.
Income Tax Expense
Income tax expense was as follows (in thousands): 
 Three Months Ended September 30, Nine Months Ended September 30,
 2017 2016 2017 2016
Income tax expense$3,206
 $
 $3,921
 $
Income tax expense for the three and nine months ended September 30, 2017 primarily relates to state taxes in jurisdictions outside of California, for which we do not have net operating loss carry-forwards due to a limited operating history. Our historical losses are sufficient to fully offset any federal taxable income.

Liquidity and Capital Resources
We have incurred net lossesAs of June 30, 2022, we had $2.0 billion in every fiscal year since our inception, with the exception of the 2011 fiscal year,cash, cash equivalents, restricted cash equivalents and investments, compared to $1.9 billion as of September 30, 2017, we had an accumulated deficit of $1.9 billion. Although we reported net income of $115.7 million for the nine months ended September 30, 2017, we may not be able to maintain or increase profitability on a quarterly or annual basis and we are unable to accurately predict the extent of long-range future profits or losses. We expect to continue to spend significant additional amounts to fund the continued development and commercialization of cabozantinib. In addition, we intend to expand our product pipeline through the measured resumption of drug discovery and the evaluation of in-licensing and acquisition opportunities that align with our oncology drug expertise, which efforts could involve substantial costs. As a result, we are unable to predict the extent of any future profits or losses because we expect to continue to incur substantial operating expenses and, consequently, we will need to generate substantial revenues to maintain or increase profitability.
Since the launch of our first commercial product in January 2013, through September 30, 2017, we have generated an aggregate of $463.0 million in net product revenues, including $253.3 million for the nine months ended September 30, 2017. Other than sales of CABOMETYX and COMETRIQ, we have derived substantially all of our revenues since inception from collaborative arrangements, including upfront and milestone payments and research funding we earn from any products developed from the collaborative research. The amount of our net profits or losses will depend, in part, on: the level of sales of CABOMETYX and COMETRIQ in the U.S. (which may be impacted by our ability to obtain FDA approval for cabozantinib for additional indications); achievement of clinical, regulatory and commercial milestones and the amount of royalties, if any, from sales of CABOMETYX and COMETRIQ under the Ipsen Collaboration Agreement; our share of the net profits and losses for the commercialization of COTELLIC in the U.S. under our collaboration with Genentech; the amount of royalties from COTELLIC sales outside the U.S. under our collaboration with Genentech; other license and contract revenues; and the level of our expenses, including commercialization activities for cabozantinib and any pipeline expansion efforts.
As of September 30, 2017, we had $422.3 million in cash and investments, which included $417.6 million available for operations and $4.7 million of long-term restricted investments.December 31, 2021. We anticipate that the aggregate of our current cash and cash equivalents, and short-term investments available for operations, net product revenues and collaboration revenues will enable us to maintain our operations for a period of at least 12 months following the filing date of this report. The sufficiency
Our primary cash requirements for operating activities, which we project will increase for the remainder of 2022, as compared to the corresponding period in 2021, are for: employee related expenditures; costs related to our development and discovery programs; income tax payments; cash payments for inventory; royalty payments on our net product sales; and our leased facilities. Our primary sources of operating cash are: cash collections from customers related to net product sales, which we project will increase for the remainder of 2022, as compared to the corresponding period in 2021; cash collections related to royalties earned from our commercial collaboration arrangements with Ipsen, Takeda and others and the achievement of certain development, regulatory and commercial milestones; and cash collections for cost reimbursements under certain of our development programs. The timing of cash resources depends on numerous assumptions, including assumptionsgenerated from commercial collaborations and cash payments required for in-licensing collaborations relative to upfront payments, initiation fees, milestone payments and cost reimbursements may vary from period to period.
We also have cash requirements related to product sales and operating expenses, as well ascapital expenditures to support the other factors set forth in “Risk Factors” under the headings “Risks Related to our Capital Requirements and Financial Results,” in Part II, Item 1Aplanned growth of this Quarterly Report on Form 10-Q. Our assumptions may prove to be wrong or other factors may adversely affect our business including investments in laboratory facilities and as a resultequipment. We project that we may notcontinue to spend significant amounts of cash to fund the continued development and commercialization of cabozantinib. In addition, we intend to continue to expand our oncology product pipeline through our drug discovery efforts, including additional research collaborations, in-licensing arrangements and other strategic transactions that align with our oncology drug development, regulatory and commercial expertise. Financing these activities could materially impact our liquidity and capital resources and may require us to incur debt or raise additional funds through the issuance of equity. Furthermore, even though we believe we have the cash resources to fundsufficient funds for our current and future operating plans. This in turn could require us to raise additional funds, whichplans, we may be unablechoose to do, which could have a material adverse effect on our business. We may also choose toincur debt or raise additional funds through the issuance of equity based on market conditions or debtstrategic considerations.
Letters of Credit
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We have obtained standby letters of credit related to meet our business objectives.lease obligations and certain other obligations with combined credit limits of $10.7 million and $16.7 million as of June 30, 2022 and December 31, 2021, respectively.
In January 2021, we entered into a standby letter of credit as a guarantee of our obligation to fund our portion of the tenant improvements related to our build-to-suit lease at our corporate campus. The letter of credit is secured by our short-term investments, which are recorded as restricted cash equivalents and presented in other long-term assets in our Condensed Consolidated Balance Sheets and will be reduced as we fund our portion of the tenant improvements. As of June 30, 2022, restricted cash equivalents included $9.2 million of short-term investments as collateral under our standby letter of credit for our portion of the tenant improvements.
Sources and Uses of Cash
 June 30, 2022December 31, 2021Percent Change
Working capital$1,547,118 $1,497,157 %
Cash, cash equivalents, restricted cash equivalents, and investments$2,009,513 $1,854,908 %
Working capital: The following table summarizesincrease in working capital as of June 30, 2022, as compared to December 31, 2021, was primarily due to the favorable impacts to our net current assets resulting from our net income during the six months ended June 30, 2022, which was partially offset by purchases of long-term investments and estimated tax payments made that are classified as long-term. In the future, our working capital may be impacted by one of these factors or other factors, the amounts and timing of which are variable.
Cash, cash equivalents, restricted cash equivalents and investments: Cash and cash equivalents primarily consist of cash deposits held at major banks, commercial paper and other securities with original maturities 90 days or less. Restricted cash equivalents and investments relate to our letter of credit agreements and are invested in short-term marketable securities. For additional information regarding our cash, cash equivalents, restricted cash equivalents and investments, see “Note 4. Cash and Investments,” in our “Notes to Condensed Consolidated Financial Statements” included in Part I, Item 1 of this Quarterly Report on Form 10-Q. The increase in cash, cash equivalents, restricted cash equivalent and investments at June 30, 2022, as compared to December 31, 2021, was primarily due to cash inflows generated by our operations, including collections of amounts due from customers, and collection of a $100.0 million milestone payment from Ipsen, partially offset by operating cash payments for employee-related expenditures, our development and discovery programs, and capital expenditures.
Cash flow activities were as follows (in thousands):
 Nine Months Ended September 30,
 2017 2016
Net cash provided by operating activities:   
Net income (loss)$115,738
 $(105,345)
Adjustments to reconcile net income (loss) to net cash provided by operating activities9,017
 45,945
Changes in operating assets and liabilities(12,497) 184,695
Net cash provided by operating activities112,258
 125,295
Net cash provided by (used in) investing activities54,628
 (155,638)
Net cash used in financing activities(169,215) (72)
Net decrease in cash and cash equivalents(2,329) (30,415)
Cash and cash equivalents at beginning of period151,686
 141,634
Cash and cash equivalents at end of period$149,357
 $111,219

 Six Months Ended June 30,
 20222021
Net cash provided by operating activities$178,849 $221,045 
Net cash used in investing activities$(209,681)$(8,590)
Net cash provided by financing activities$4,627 $6,074 
Operating Activities
Cash flows provided by operating activities represent the cash receipts and disbursements related to all of our activities other than investing and financing activities. Cash provided by operating activities is derived by adjusting our net income (loss) for:for non-cash operating items such as deferred taxes, stock-based compensation, depreciation, and amortization, non-cash interestlease expense and share-based compensation charges; and changes in operating assets and liabilities, which reflect timing differences between the receipt and payment of cash associated with transactions and when they are recognized in our Condensed Consolidated ResultsStatements of Operations. Our operating activities provided cash of $112.3 million for the nine months ended September 30, 2017, as compared to $125.3 million for the same period in 2016. The decrease inIncome.
Net cash provided by operating activities wasfor the six months ended June 30, 2022 decreased as compared to the corresponding prior year period, primarily due to the upfront nonrefundablean increase in cash paid for certain operating expenses resulting in net unfavorable changes in operating assets and liabilities, which was partially offset by an increase in cash received on sales of our products and from our commercial collaboration arrangements, including collection of a $100.0 million milestone payment of $200.0 million received from Ipsen.
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Investing Activities
The changes in cash flows from investing activities primarily relates to the ninetiming of marketable securities investment activity and capital expenditures. Our capital expenditures primarily consist of investments to expand our operations and acquire assets that further our research and development.
Net cash used in investing activities for the six months ended SeptemberJune 30, 20162022 increased as compared to the corresponding prior year period, primarily due to a decrease in consideration for the exclusive licensecash proceeds from maturities and other rights containedsales of investments, and an increase in our collaboration and license agreement with Ipsen along with increasing operating expenses. That decreasepurchases of investments, which was partially offset by a $169.8 million increasedecrease in net product revenues and the upfront nonrefundable payment of $50.0 million received from Takeda in the nine months ended September 30, 2017 in consideration for the exclusive license and other rights contained in the Takeda Collaboration Agreement.
Investing Activities
Our investing activities provided cash of $54.6 million for the nine months ended September 30, 2017, as compared to $155.6 million of cash used during the same period in 2016.
Cash provided by investing activities for the nine months endedSeptember 30, 2017 was primarily due to cash provided by the maturity of investments of $277.0 million and the sale of investments of $37.3 million, less cash used for investment purchases of $259.2 million.
Cash used by investing activities for the nine months ended September 30, 2016 was primarily due to investment purchases of $262.7 million, less cash from the maturity of unrestricted and restricted investments of $103.3 million.capital expenditures.
Financing Activities
Cash usedThe changes in cash flows from financing activities was $169.2 million for the nine months ended September 30, 2017, as comparedprimarily relate to $0.1 million during the same period in 2016.proceeds from employee stock programs and taxes paid related to net share settlement of equity awards.
Cash used inNet cash provided by financing activities for the ninesix months ended September June 30, 2017 was2022 decreased as compared to the corresponding prior year period, primarily a resultdue to an increase in withholding taxes remitted to the government related to net share settlements of $185.8 million paid for all amounts outstanding under the Deerfield Notes and our term loan with Silicon Valley Bank.
Cash used in financing activities for the nine months ended September 30, 2016 was primarily a result of payments on conversion of convertible notes and employees’ tax withholding paid to taxing authorities from shares withheld on stockequity awards, which was almost completelypartially offset by an increase in proceeds received from the issuance of common stock under our equity incentive plans.
Contractual Obligations
As of SeptemberDuring the three months ended June 30, 2017, we have contractual obligations in the form of capital and operating leases, purchase obligations and other long-term liabilities.
On June 28, 2017, we repaid all amounts outstanding under the Deerfield Notes. On March 29, 2017, we repaid all amounts outstanding under our term loan with Silicon Valley Bank. See “Note 6 - Debt” in the accompanying Notes to the Condensed Consolidated Financial Statements for more information on the Deerfield Notes and our loan and security agreement with Silicon Valley Bank.
On May 2, 2017,2022, we entered into a Lease Agreement, or the Lease, with Ascentris 105, LLC, or Ascentris,seventh amendment to the lease for an aggregateour corporate headquarters located on Harbor Bay Parkway, Alameda, California (the Alameda Lease) for the expansion of 110,783the premises by 34,745 square feet of space in office and research facilities located at 1851, 1801 and 1751 Harbor Bay Parkway, Alameda, California. We are obligatedCalifornia (the 1751 Expansion Space). The term of the 1751 Expansion Space is coterminous with the term of the Alameda Lease for the existing space.
In April 2022, the office building (New Premises) associated with our October 2019 build-to-suit lease agreement (Build-to-Suit Lease) was substantially completed. The New Premises is 220,517 square feet and is in Alameda, California, adjacent to makeour existing corporate headquarters. The Build-to-Suit Lease term is 242 months, includes two five-year options to extend the term of the lease and a one-time option to terminate the lease after 180 months. In addition to the lease payments, totaling $24.1 million over the Lease term. The Lease further provides that we are obligated to pay to Ascentris certain costs, including taxes andalso responsible for paying operating expenses. See “Note 12. Commitments” in the accompanying Notesexpenses related to the Condensed Consolidated Financial Statements for a description of the Lease.New Premises.
There were no other material changes outside of the ordinary course of business in our contractual obligations as of June 30, 2022 from those asdisclosed in our Fiscal 2021 Form 10-K. For more information about our Build-to-Suit Lease, and our other contractual obligations see “Note 10. Commitments and contingencies” in “Notes to Condensed Consolidated Financial Statements” included in Part I, Item I of December 31, 2016.this Quarterly Report on Form 10-Q and see “Note 11. Commitments and contingencies” of the “Notes to Consolidated Financial Statements included in Part II, Item 8 of our Fiscal 2021 Form 10-K.

Off-Balance Sheet Arrangements
As of September 30, 2017, we did not have any material off-balance-sheet arrangements, as defined by applicable SEC regulations.
Critical Accounting Policies and Estimates
The preparation of our Condensed Consolidated Financial Statements conforms to accounting principles generally accepted in the U.S. which requires management to make judgments, estimates and assumptions that affect the reported amounts of assets, liabilities, revenueequity, revenues and expenses, and related disclosures. An accounting policy is considered to be critical if it requires an accounting estimate to be made based on assumptions about matters that are highly uncertain at the time the estimate is made, and if different estimates that reasonably could have been used, or changes in the accounting estimates that are reasonably likely to occur periodically, could materially impact our Condensed Consolidated Financial Statements. On an ongoing basis, management evaluates its estimates including, but not limited to,to: those related to revenue recognition, including deductions from revenues (suchdetermining the nature and timing of satisfaction of performance obligations, and determining the standalone selling price of performance obligations, and variable consideration such as rebates, chargebacks, sales returns and sales allowances), the period of performance, identification of deliverables and evaluation ofallowances as well as milestones with respect to our collaborations,included in collaboration arrangements; the amounts of revenues and expenses under our profit and loss sharing agreement,agreement; recoverability of inventory,inventory; the accrual for certain accrued liabilities including accrued clinical trial liability,liabilities; valuations of equity awards used to determine stock-based compensation, including certain awards with vesting subject to market and/or performance conditions; and stock-based compensation.the amounts of deferred tax assets and liabilities including the related valuation allowance. We base our estimates on historical experience and on various other market-specific and other relevant assumptions that we believe to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily
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apparent from other sources. Our senior management has discussed the development, selection and disclosure of these estimates with the Audit Committee of our Board of Directors. Actual results could differ materially from those estimates.
We believe our critical accounting policies relating to revenue recognition, inventory, clinical trial accruals, inventorystock-based compensation and share based compensationincome taxes reflect the moremost significant estimates and assumptions used in the preparation of our Condensed Consolidated Financial Statements.
There have been no significant changes in our critical accounting policies and estimates during the ninesix months endedSeptember June 30, 2017, as2022, compared to the critical accounting policies and estimates disclosed in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” included in Part II, Item 7 of our Annual Report onFiscal 2021 Form 10-K for the year ended December 31, 2016 filed with the SEC on February 27, 2017.
10-K.

Recent Accounting Pronouncements
For a description of the expected impact of recent accounting pronouncements, see “Note 1 -1. Organization and Summary of Significant Accounting Policies” in the “Notes to Condensed Consolidated Financial Statements” included in Part I, Item 1 of this Quarterly Report on Form 10-Q and “Note 1 - Organization and Summary of Significant Accounting Policies” in the “Notes to Consolidated Financial Statements” included in our Annual Report on Form 10-K filed with the SEC on February 27, 2017.10-Q.
Item 3. Quantitative and Qualitative Disclosures About Market Risk
Our market risks at Septemberas of June 30, 20172022 have not changed significantly from those discusseddescribed in Item 7A of our Annual Report onFiscal 2021 Form 10-K for the year ended December 31, 2016, filed with the SEC on February 27, 2017.10-K.
Our exposure to market risk for changes in interest rates relates to our investment portfolio, and for prior periods, our debt. As of September 30, 2017, an increase in the interest rates of one percentage point would have had a net adverse change in the fair value of interest rate sensitive assets and liabilities of $(1.5) million as compared to a net positive change in the fair value of $0.3 million as of December 31, 2016.
In addition, we have exposure to fluctuations in certain foreign currencies in countries in which we conduct clinical trials. As of September 30, 2017, and December 31, 2016, approximately $1.7 million and $2.2 million, respectively, of our accrued clinical trial liability was owed in foreign currencies. An adverse change of one percentage point in the foreign currency exchange rates would not have resulted in a material impact as of either of the dates presented. We recorded losses of $0.2 million relating to foreign exchange fluctuations for both the nine months ended September 30, 2017 and 2016.

Item 4. Controls and Procedures.Procedures
Evaluation of disclosure controls and procedures. Based on the evaluation of our disclosure controls and procedures (as defined in Rules 13a-15(e) or 15d-15(e) of the Securities Exchange Act of 1934, as amended, or the Exchange Act) required by Rules 13a-15(b) or 15d-15(b) of the Exchange Act, our Chief Executive Officer and Chief Financial Officer have concluded that as of the end of the period covered by this report, our disclosure controls and procedures were effective at the reasonable assurance level.
Limitations on the effectiveness of controls. A control system, no matter how well conceivedwell-conceived and operated, can provide only reasonable, not absolute, assurance that the objectives of the control system are met. Because of inherent limitations in all control systems, no evaluation of controls can provide absolute assurance that all control issues, if any, within an organization have been detected. Accordingly, our disclosure controls and procedures are designed to provide reasonable, not absolute, assurance that the objectives of our disclosure control system are met and, as set forth above, our principal executive officer and principal financial officer have concluded, based on their evaluation as of the end of the period covered by this report, that our disclosure controls and procedures were effective to provide reasonable assurance that the objectives of our disclosure control system were met.
Changes in internal control over financial reporting. There were no changes in our internal control over financial reporting that occurred during our most recent fiscal quarter that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

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PART II. OTHER INFORMATION
Item 1. Legal Proceedings
In September 2019, we received a notice letter regarding an ANDA submitted to the FDA by MSN, requesting approval to market a generic version of CABOMETYX tablets. MSN’s initial notice letter included a Paragraph IV certification with respect to our U.S. Patents No. 8,877,776 (salt and polymorphic forms), 9,724,342 (formulations), 10,034,873 (methods of treatment) and 10,039,757 (methods of treatment), which are listed in the Approved Drug Products with Therapeutic Equivalence Evaluations, also referred to as the Orange Book, for CABOMETYX. MSN’s initial notice letter did not provide a Paragraph IV certification against U.S. Patents No. 7,579,473 (composition of matter) or 8,497,284 (methods of treatment), each of which is listed in the Orange Book. On June 3, 2016,October 29, 2019, we filed a Demandcomplaint in the Delaware District Court for Arbitration before JAMSpatent infringement against MSN asserting infringement of U.S. Patent No. 8,877,776 arising from MSN’s ANDA filing with the FDA. On November 20, 2019, MSN filed its response to the complaint, alleging that the asserted claims of U.S. Patent No. 8,877,776 are invalid and not infringed. On May 5, 2020, we received notice from MSN that it had amended its ANDA to include additional Paragraph IV certifications. In particular, the May 5, 2020 amended ANDA requested approval to market a generic version of CABOMETYX tablets prior to expiration of two previously unasserted CABOMETYX patents: U.S. Patents No. 7,579,473 and 8,497,284. On May 11, 2020, we filed a complaint in San Francisco, Californiathe Delaware District Court for patent infringement against MSN asserting infringement of U.S. Patents No. 7,579,473 and 8,497,284 arising from MSN’s amended ANDA filing with the FDA. Neither of our complaints have alleged infringement of U.S. Patents No. 9,724,342, 10,034,873 and 10,039,757. On May 22, 2020, MSN filed its response to the complaint, alleging that the asserted claims against Genentech (a memberof U.S. Patents No. 7,579,473 and 8,497,284 are invalid and not infringed. On March 23, 2021, MSN filed its First Amended Answer and Counterclaims (amending its prior filing from May 22, 2020), seeking, among other things, a declaratory judgment that U.S. Patent No. 9,809,549 (salt and polymorphic forms) is invalid and would not be infringed by MSN if its generic version of CABOMETYX tablets were approved by the FDA. U.S. Patent No. 9,809,549 is not listed in the Orange Book. On April 7, 2021, we filed our response to MSN’s First Amended Answer and Counterclaims, denying, among other things, that U.S. Patent No. 9,809,549 is invalid or would not be infringed. These two lawsuits, numbered Civil Action Nos. 19-02017 and 20-00633, were consolidated in April 2021.
On October 1, 2021, pursuant to a stipulation between us and MSN, the Delaware District Court entered an order that (i) MSN’s submission of its ANDA constitutes infringement of certain claims relating to U.S. Patents No. 7,579,473 and 8,497,284, if those claims are not found to be invalid, and (ii) upon approval, MSN’s commercial manufacture, use, sale or offer for sale within the U.S., and importation into the U.S., of MSN’s ANDA product prior to the expiration of U.S. Patents No. 7,579,473 and 8,497,284 would also infringe certain claims of each patent, if those claims are not found to be invalid. Then, on October 12, 2021, pursuant to a separate stipulation between us and MSN, the Delaware District Court entered an order dismissing MSN’s counterclaims with respect to U.S. Patent No. 9,809,549. In our complaints, we are seeking, among other relief, an order that the effective date of any FDA approval of MSN’s ANDA be a date no earlier than the expiration of all of U.S. Patents No. 7,579,473, 8,497,284 and 8,877,776, the latest of which expires on October 8, 2030, and equitable relief enjoining MSN from infringing these patents. In an effort to streamline the case, the parties have narrowed their assertions. On April 8, 2022, MSN withdrew its validity challenge to U.S. Patent No. 8,877,776. On April 14, 2022, we agreed not to assert U.S. Patent No. 8,497,284 at trial and MSN has, correspondingly, agreed to withdraw its validity challenges to U.S. Patent No. 8,497,284, as well as claims 1-4 and 6-7 of U.S. Patent No. 7,579,473. As a result of this narrowing, the trial addressed two issues: (1) infringement of claims 1 and 2 of the Roche Group) relatedU.S. Patent No. 8,877,776; and (2) validity of claim 5 of the U.S. Patent No. 7,579,473. A bench trial occurred in May 2022, and a judgment is expected during the third or fourth quarter of 2022.
On January 11, 2022, we received notice from MSN that it had further amended its ANDA to its clinical development, pricingassert additional Paragraph IV certifications. In particular, the January 11, 2022 amended ANDA requested approval to market a generic version of CABOMETYX tablets prior to expiration of three previously-unasserted CABOMETYX patents that are now listed in the Orange Book: U.S. Patents No. 11,091,439 (crystalline salt forms), 11,091,440 (pharmaceutical composition) and commercialization11,098,015 (methods of COTELLIC,treatment). On February 23, 2022, we filed a complaint in the Delaware District Court for patent infringement against MSN asserting infringement of U.S. Patents No. 11,091,439, 11,091,440 and cost and revenue allocations11,098,015 (the February 2022 MSN ANDA Complaint) arising from COTELLIC’s commercializationMSN’s further amendment of its ANDA filing with the FDA. In the February 2022 MSN ANDA Complaint, we are seeking, among other remedies, equitable relief enjoining MSN from infringing these patents, as well as an order that the effective date of any FDA approval of MSN’s ANDA would be a date no earlier than the expiration of the patents identified in the U.S. Our arbitration demandFebruary 2022 MSN ANDA Complaint, the latest of which expires on January 15, 2030. The February 2022 MSN ANDA Complaint is a new case, numbered Civil Action No. 22-00228, against MSN involving Exelixis patents that are different from those asserted that Genentech breachedin the parties’ December 2006 collaboration agreement for the developmentconsolidated Civil Action Nos. 19-02017 and commercialization20-00633
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Table of COTELLIC, by, amongst other breaches, failing to meetContents
described above. On February 25, 2022, MSN filed its diligence and good faith obligations.
On July 13, 2016, Genentech asserted a counterclaim for breach of contract seeking monetary damages and interest relatedresponse to the cost allocations undercomplaint, alleging that the collaboration agreement. asserted claims of U.S. Patents No. 11,091,439, 11,091,440 and 11,098,015 are invalid and not infringed.
On December 29, 2016, however, Genentech withdrew its counterclaim againstJune 21, 2022, pursuant to a stipulation between us and statedMSN, the Delaware District Court entered an order that it would unilaterally change(i) MSN’s submission of its approachANDA constitutes infringement of certain claims relating to U.S. Patents No. 11,091,439, 11,091,440 and 11,098,015, if those claims are not found to be invalid, and (ii) upon approval, MSN’s commercial manufacture, use, sale or offer for sale within the U.S., and importation into the U.S., of MSN’s ANDA product prior to the allocationexpiration of promotional expenses arising from commercializationU.S. Patents No. 11,091,439, 11,091,440 and 11,098,015 would also infringe certain claims of the COTELLIC plus Zelboraf® combination therapy, both retrospectively and prospectively. The revised allocation approach substantially reduced our exposure to costs associated with promotion of the COTELLIC plus Zelboraf combination in the U.S.
On June 8, 2017, the parties settled the arbitration, which was dismissed with prejudice. The settlement was memorialized in a settlement agreement dated July 19, 2017, that included a mutual release of alleach patent, if those claims arising out of or related in any way to the causes of actions and/or claims that were asserted or could have been asserted based on the facts alleged in the arbitration. The settlement doesare not provide for payments in settlement of the asserted claims; as part of the settlement, on July 19, 2017, the parties entered into an amendment to the Genentech Collaboration Agreement. Pursuant to the terms of the amendment, we continuefound to be entitled to a share of U.S. profits and losses receivedinvalid. A bench trial in connection with the commercializationFebruary 2022 MSN ANDA Complaint has been scheduled for May 2023.
On June 6, 2022, we received notice from MSN that it had further amended its ANDA to assert an additional Paragraph IV certification. As currently amended, MSN’s ANDA now requests approval to market a generic version of COTELLICCABOMETYX tablets prior to expiration of a previously-unasserted CABOMETYX patent that is now listed in accordancethe Orange Book: U.S. Patent No. 11,298,349 (pharmaceutical composition). On July 18, 2022, we filed a complaint in the Delaware District Court for patent infringement against MSN asserting infringement of U.S. Patent No. 11,298,349 (the July 2022 MSN ANDA Complaint) arising from MSN’s further amendment of its ANDA Filing with the profit share tiersFDA. In the July 2022 MSN ANDA Complaint, we are seeking, among other remedies, equitable relief enjoining MSN from infringing this patent, as originally set forthwell as an order that the effective date of any FDA approval of MSN’s ANDA would be a date no earlier than the expiration of the patent identified in the collaboration agreement,July 2022 MSN ANDA Complaint, which share continues to decrease as sales of COTELLIC increase. However, effective as ofexpires on February 10, 2032. The July 1, 2017,2022 MSN ANDA Complaint is a new case against MSN involving an Exelixis patent that is different from those asserted in the revenue for each sale of COTELLIC appliedconsolidated Civil Action Nos. 19-02017, 20-00633 and 22-00228 described above. MSN’s response to the profitcomplaint is due on August 9, 2022. A trial has not yet been scheduled in connection with the July 2022 MSN ANDA Complaint.
In May 2021, we received notice letters from Teva regarding an ANDA Teva submitted to the FDA, requesting approval to market a generic version of CABOMETYX tablets. Teva’s notice letters included a Paragraph IV certification with respect to our U.S. Patents No. 9,724,342 (formulations), 10,034,873 (methods of treatment) and loss statement10,039,757 (methods of treatment), which are listed in the Orange Book and expire in 2033, 2031 and 2031, respectively. Teva’s notice letters did not provide a Paragraph IV certification against any additional CABOMETYX patents. On June 17, 2021, we filed a complaint in the Delaware District Court for patent infringement against Teva, along with Teva Pharmaceutical Industries Limited (Teva Parent), asserting infringement of U.S. Patents No. 9,724,342, 10,034,873 and 10,039,757 arising from Teva’s ANDA filing with the collaboration agreement,FDA. On August 27, 2021, Teva filed its answer and counterclaims to the complaint, alleging that the asserted claims of U.S. Patents No. 9,724,342, 10,034,873 and 10,039,757 are invalid and not infringed, and on August 23, 2021, we and Teva entered into a stipulation wherein Teva Parent was dismissed without prejudice from this lawsuit and agreed to be bound by any stipulation, judgment, order or decision rendered as to Teva, including any appeals and any order granting preliminary or permanent injunctive relief against Teva. On September 17, 2021, we filed an answer to Teva’s counterclaims. We are seeking, among other relief, an order that the Collaboration P&L,effective date of any FDA approval of Teva’s ANDA be a date no earlier than the expiration of all of U.S. Patents No. 9,724,342, 10,034,873 and 10,039,757, the latest of which expires on July 9, 2033, and equitable relief enjoining Tevafrom infringing these patents. On February 8, 2022, the parties filed a stipulation to stay all proceedings, which was granted by the Delaware District Court on February 9, 2022. On February 11, 2022, this case was administratively closed.
On July 29, 2022, we received notice from Teva that it had amended its ANDA to assert an additional Paragraph IV certification. As amended, Teva’s ANDA now requests approval to market a generic version of CABOMETYX tablets prior to expiration of a previously-unasserted CABOMETYX patent that is being calculated usingnow listed in the averageOrange Book: U.S. Patent No. 11,298,349 (pharmaceutical composition). We have 45 days from the receipt of the quarterly net selling prices of COTELLIC and any additional branded Genentech product(s) prescribed with COTELLIC in such sale. While we also continueJuly 29, 2022 notice to share U.S. commercialization costs for COTELLIC, the amendment expressly sets forth that the amount of commercialization costs Genentech is entitled to allocatefile a patent infringement claim against Teva relating to the Collaboration P&L is to be reduced based on the number of Genentech products in any given combination including COTELLIC. In addition, the amendment also sets forth the parties’ confirmation and agreement that we have exercised our co-promotion option and that, as such, we have the option to co-promote current and future Genentech combinations that include COTELLIC in the U.S.newly challenged patent.
We may also from time to time become a party or subject to various other legal proceedings arisingand claims, either asserted or unasserted, which arise in the ordinary course of business. Some of these proceedings have involved, and may involve in the future, claims that are subject to substantial uncertainties and unascertainable damages.
Item 1A. Risk Factors
In addition to the factorsrisks discussed elsewhere in this report, and our other reports filed with the SEC, the following are important factors that make an investment in our securities speculative or risky, and that could cause actual results or events to differ materially from those contained in any forward-looking statements made by us or on our behalf. The risks and uncertainties described below are not the only ones we face. Additional risks and uncertainties not currently known to us or that we deem immaterial also may
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impair our business operations. If any of the following risks or such other risks actually occurs,occur, our business and the value of your investment in our company could be harmed.
We have marked with an asterisk (*) those risk factors below that reflect substantive changes in risks facing us from the risk factors included inRisk Factor Summary
Our ability to grow our Annual Report on Form 10-K for the fiscal year ended December 30, 2016 filed with the Securities and Exchange Commission on February 27, 2017.
Risks Related to Our Business and Industry
Our future prospects are criticallycompany is dependent upon the commercial success of CABOMETYX for advanced RCCin its approved indications and the furthercontinued clinical development, regulatory approval, clinical acceptance and commercial success of the cabozantinib franchise in additional indications.
If we are unable to obtain or maintain coverage and reimbursement for our products from third-party payers, our business will suffer.
Pricing for pharmaceutical products, both in the U.S. and in foreign countries, has come under increasing attention and scrutiny by federal, state and foreign national governments, legislative bodies and enforcement agencies. Initiatives arising from this scrutiny may result in changes that have the effect of reducing our revenue or harming our business or reputation.
The timing of the entrance of generic competitors to CABOMETYX and legislative and regulatory action designed to reduce the barriers to the development, approval and adoption of generic drugs in the U.S. could limit the revenue we derive from our products, most notably CABOMETYX, which could have a material adverse impact on our business, financial condition and results of operations.
We are subject to healthcare laws, regulations and enforcement, as well as laws and regulations relating to privacy, data collection and processing of personal data; our failure to comply with those laws could have a material adverse impact on our business, financial condition and results of operations.
Clinical testing of cabozantinib for new indications, or of new product candidates, is a lengthy, costly, complex and uncertain process that may fail ultimately to demonstrate safety and efficacy data for those products sufficiently differentiated to compete in our highly competitive market environment.
The regulatory approval processes of the U.S. Food and Drug Administration and comparable foreign regulatory authorities are lengthy, uncertain and subject to change, and may not result in regulatory approvals for additional cabozantinib indications or for our other product candidates, which could have a material adverse impact on our business, financial condition and results of operations.
We may be unable to expand our discovery and development pipeline, which could limit our growth and revenue potential.
Our profitability could be negatively impacted if expenses associated with our extensive clinical development, business development and commercialization activities, both for the cabozantinib franchise and our other product candidates, grow more quickly than the revenues we generate.
Our clinical, regulatory and commercial collaborations with major companies make us reliant on those companies for their continued performance and investments, which subjects us to a number of risks. For example, we rely on Ipsen and Takeda for the commercial success of CABOMETYX in its approved indications outside of the U.S., and we are unable to control the amount or timing of resources expended by these collaboration partners in the commercialization of CABOMETYX in its approved indications outside of the U.S. In addition, our growth potential is dependent in part upon companies with which we have entered into research collaborations, in-licensing arrangements and similar business development relationships.
Data breaches, cyber attacks and other failures in our information technology operations and infrastructure could compromise our intellectual property or other sensitive information, damage our operations and cause significant harm to our business and reputation.
If we are unable to adequately protect our intellectual property, third parties may be able to use our technology, which could adversely affect our ability to compete in the market.
If the COVID-19 pandemic is further prolonged or becomes more severe, our business operations and corresponding financial results could suffer, which could have a material adverse impact on our financial condition and prospects for growth.
The loss of key personnel or the inability to retain and, where necessary, attract additional personnel could impair our ability to operate and expand our operations.

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Risks Related to the Commercialization of Our Products
Our ability to grow our company is dependent upon the commercial success of CABOMETYX in its approved indications and the continued clinical development, regulatory approval, clinical acceptance and commercial success of the cabozantinib franchise in additional indications.
Our mission is to maximize the clinical and commercial potential of cabozantinib and cobimetinib and position Exelixis for future growth through the resumption of our discovery efforts and expansion of our development pipeline. We anticipate that for the foreseeable future, our ability to generate meaningful revenuemaintain or meaningfully increase cash flow to fund our commercial operations and our development and discovery programs will be dependent upon the successful commercialization of CABOMETYX for the treatment of advanced RCC in territories where it has been or may soon be approved. The commercial potential of

CABOMETYX for the treatment of advanced RCC remains subject to a variety of factors, most importantly, CABOMETYX’s perceived benefit/risk profile as compared to the benefit/risk profiles of other treatments available or currently in development for the treatment of advanced RCC. If revenue from CABOMETYX decreases, we may need to reduce our operating expenses or raise additional funds to execute our business plan, which would have a material adverse effect on our business and financial condition, results of operations and growth prospects. Furthermore,will depend upon the continued commercial success of CABOMETYX, both alone and in combination with other therapies, as a consequence of the Ipsen Collaboration Agreement, we rely heavily upon Ipsen’s regulatory, commercial, medical affairs, and other expertise and resources for commercialization of CABOMETYX in territories outside of the U.S. and Japan. If Ipsen is unable to, or does not invest the resources necessary to successfully commercialize CABOMETYXtreatment for the treatmenthighly competitive indications for which it is approved, and possibly for other indications for which cabozantinib is currently being evaluated in potentially label-enabling clinical trials, if warranted by the data generated from these trials. In this regard, part of advanced RCC in the European Union and other international territories where it may be approved, this could reduce the amount of revenue we are dueour strategy is to receive under Ipsen Collaboration Agreement, thus resulting in harm to our business and operations.
We also believe that there are commercial opportunities for cabozantinib in therapeutic indications beyond advanced RCC, and we are dedicating substantial proprietary resources to developing cabozantinib into a potentially broad and significant oncology franchise. Even following the approval of CABOMETYX for the treatment of advanced RCC in the U.S. and European Union, our success remains contingent upon, among other things, successful clinical development, regulatory approval and market acceptance of cabozantinib inpursue additional indications such as previously untreated advanced RCC, advanced HCC, non-small cell lungfor CABOMETYX and increase the number of cancer and other forms of cancer. Wepatients who could potentially benefit from this medicine. However, we cannot be certain that that the clinical trials we and our collaboration partners are currently conducting or may conduct in the future, will demonstrate adequate safety and efficacy in clinical testingthese additional indications to receive regulatory approval. Should we prove unsuccessful in advancing the further clinical development and commercialization of cabozantinib beyond MTC or advanced RCC, we may be unable to execute our business plan and our revenues and financial condition would be materially adversely affected.
We are heavily dependent on our partner, Genentech (a member of the Roche group), for the successful development, regulatory approval and commercialization of cobimetinib.*
The terms of our collaboration agreement provide Genentech with exclusive authority over the global development and commercialization plans for cobimetinib and the execution of those plans. We have limited effective influence over those plans and are heavily dependent on Genentech’s decision making. Any significant changes to Genentech’s business strategy and priorities, over which we have no control, could adversely affect Genentech’s willingness or ability to complete their obligations under our collaboration agreement and result in harm to our business and operations. Subject to contractual diligence obligations, Genentech has complete control over and financial responsibility for cobimetinib’s development program, regulatory and commercial strategy and execution, and we are not able to control the amount or timing of resources that Genentech will devote to the product. Of particular significance are Genentech’s development efforts with respect to the combination of cobimetinib with immuno-oncology agents, a promising and competitive area of clinical research. Regardless of Genentech’s efforts and expenditures for the further development of cobimetinib, the results of such additional clinical investigation may not prove positive and may not produce label expansions or approval in additional indications.
Thethe major commercial success ofmarkets where CABOMETYX is approved. Even if the required regulatory approvals to market cabozantinib as CABOMETYX tablets for advanced RCC and as COMETRIQ capsules for MTC, and if approved for additional indications will dependare achieved, we and our collaboration partners may not be able to commercialize CABOMETYX effectively and successfully in these additional indications. If revenue from CABOMETYX decreases or remains flat, or if we are unable to expand the number of labeled indications for which CABOMETYX is approved, or if we or our collaboration partners fail to achieve anticipated product royalties and collaboration milestones, we may need to reduce our operating expenses, access other sources of cash or otherwise modify our business plans, which could have a material adverse impact on our business, financial condition and results of operations.
Our ability to grow revenues from sales of CABOMETYX depends upon the degree of market acceptance among physicians, patients, health carehealthcare payers, and the medical community.
Our ability to successfully commercialize cabozantinib, asincrease or maintain revenues from sales of CABOMETYX tablets for advanced RCC and COMETRIQ capsules for MTCits approved indications is, and if approved for additional indications will be, highly dependent upon the extent to which cabozantinib gainsof market acceptance of CABOMETYX among physicians, patients, health careforeign and U.S. government healthcare payers such as Medicare and Medicaid, and commercial healthcare plans and the medical community. If cabozantinib does not achieve an adequate level ofMarket acceptance we may not generate significant future product revenues. The degree of market acceptancefor CABOMETYX could be impacted by numerous factors, including the effectiveness and safety profile, or the perceived effectiveness and safety profile, of CABOMETYX and COMETRIQ will depend upon a number of factors, including:
the effectiveness, or perceived effectiveness, of cabozantinib in comparisoncompared to competing products;
the safety of cabozantinib, including the existence of serious side effects of cabozantinib and their severity in comparison to those of any competing products;
cabozantinib’s relative convenience and ease of administration;
unexpected results connected with analysis of data from future or ongoing clinical trials;
the timing of cabozantinib label expansions for additional indications, if any, relative to competitive treatments;

the price of cabozantinib relative to competitive therapies and any new government initiatives affecting pharmaceutical pricing;
products, the strength of CABOMETYX sales and marketing efforts marketing, medical affairs and distribution support;changes in pricing and reimbursement for CABOMETYX. If CABOMETYX does not continue to be prescribed broadly for the treatment of patients in its approved indications, our product revenues could flatten or decrease, which could have a material adverse impact on our business, financial condition and results of operations.
Our competitors may develop products and technologies that impair the sufficiencyrelative value of our marketed products and any current and future product candidates.
The biopharmaceutical industry is competitive and characterized by constant technological change and diverse offerings of products, particularly in the area of oncology therapies. Many of our competitors have greater capital resources, larger research and development staff and facilities, deeper regulatory expertise and more extensive product manufacturing and commercial capabilities than we do, which may afford them a competitive advantage. Further, our competitors may be more effective at in-licensing and developing new commercial products that could render our products, and those of our collaboration partners, obsolete and noncompetitive. We face, and will continue to face, intense competition from biopharmaceutical companies, as well as academic research institutions, clinical reference laboratories and government insurance coverageagencies that are pursuing scientific and reimbursement;clinical research activities similar to ours.
Furthermore, the specific indications for which CABOMETYX is currently or may be approved, based on the results from clinical trials currently evaluating cabozantinib, are highly competitive. Several novel therapies and combinations of therapies have been approved, are in advanced stages of clinical development or are under expedited regulatory review in these indications, and these other therapies are currently competing or are expected to compete with CABOMETYX. Even if our current and future clinical trials, including those evaluating cabozantinib in combination with an ICI in NSCLC and mCRPC or evaluating XL092 in combination with an ICI in CRC, produce positive results sufficient to obtain marketing approval by the FDA and other global regulatory authorities, it is uncertain whether physicians will choose to prescribe regimens containing our products instead of competing products and product combinations in approved indications.
our ability to enforce our intellectual property rights with respect to cabozantinib.
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If we are unable to maintain or scale adequateincrease our sales, marketing, market access and product distribution capabilities or enter into or maintain agreements with third parties to do so,for our products, we may be unable to maximize product revenues, andwhich could have a material adverse impact on our business, financial condition and results of operations and prospects may be adversely affected.*operations.
Maintaining our sales, marketing, market access medical affairs and product distribution capabilities requires significant resources. If we cannot maintainresources, and there are numerous risks involved with maintaining and continuously improving our commercial organization, including our potential inability to successfully recruit, train, retain and incentivize adequate numbers of qualified and effective sales and marketing market access, medical affairspersonnel. We are competing for talent with numerous commercial- and product distribution capabilities,precommercial-stage, oncology-focused biopharmaceutical companies seeking to build out and maintain their commercial organizations, as well as larger biopharmaceutical organizations that have extensive, well-funded and more experienced sales and marketing operations, and we may be unable to maximize themaintain or adequately scale our commercial potentialorganization as a result of cabozantinib in its approved indications.such competition. Also, to the extent that the commercial opportunities for cabozantinibCABOMETYX grow over time, we may not properly judgescale the requisite size and experience of theour commercialization teams or the scale of distribution necessary to market and sell cabozantinib successfully.CABOMETYX successfully in an expanded number of indications. If we are unable to maintain or scale our organizationcommercial function appropriately, we may not be able to maximize product revenues, and our business, financial condition, results of operations and prospects may be adversely affected.
We currently rely on third-party providers to handle storage and distribution for our commercial supply of both CABOMETYX and COMETRIQ in the U.S. While we have expanded our U.S. distribution and pharmacy channels in connection with the approval of CABOMETYX by the FDA for the treatment of patients with advanced RCC in the U.S., we still rely on a relatively limited distribution network to dispense COMETRIQ in fulfillment of prescriptions in the U.S. Furthermore, we rely on our collaboration partners for the commercialization and distribution of CABOMETYX and COMETRIQ in territories outside of the U.S., as well as for access and distribution activities for the approved products under the Named Patient Use program or a similar program with the effect of introducing earlier patient access to COMETRIQ and CABOMETYX.
Our current and anticipated future dependence upon the activities, support, and legal and regulatory compliance, of third parties, may adversely affect our ability to supply cabozantinib to the marketplace on a timely and competitive basis. These third parties may not provide services in the time required to meet our commercial timelines and objectives or to meet regulatory requirements. We may not be able to maintain or renew our arrangements with third parties, or enter into new arrangements, on acceptable terms, or at all. Third parties could terminate or decline to renew our arrangements based on their own business priorities. If we are unable to contract for these third-party services related to the distribution of cabozantinib on acceptable terms, our commercialization efforts and those of our collaboration partners may be delayed or otherwise adversely affected, which could have a material adverse impact on our business, financial condition and results of operations and prospects.
We are subject to certain healthcare laws, regulation and enforcement; our failure to comply with those laws could have a material adverse effect on our results of operations and financial condition.*
We are subject to certain healthcare laws and regulations and enforcement by the federal government and the states in which we conduct our business. Should our compliance controls prove ineffective at preventing or mitigating the risk and impact of improper conduct, the laws that may affect our ability to operate include, without limitation:
the federal Anti-Kickback Statute, or AKS, which governs our business activities, including our marketing practices, educational programs, pricing policies, and relationships with healthcare providers or other entities. The AKS prohibits, among other things, persons and entities from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, in exchange for or to induce 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 federal healthcare programs such as the Medicare and Medicaid programs. Remuneration is not defined in the AKS and has been broadly interpreted to include anything of value, including for example, gifts, discounts, coupons, the furnishing of supplies or equipment, credit arrangements, payments of cash, waivers of payments, ownership interests and providing anything at less than its fair market value. The AKS has been broadly interpreted to apply to manufacturer arrangements with prescribers, purchasers and formulary managers, among others;
the Federal Food, Drug, and Cosmetic Act, or FDCA, and its regulations, which prohibit, among other things, the introduction or delivery for introduction into interstate commerce of any food, drug, device, or cosmetic that is adulterated or misbranded;

federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payers that are false or fraudulent, or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;
federal criminal laws that prohibit executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;
the Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and their implementing regulations, which impose certain requirements relating to the privacy, security and transmission of individually identifiable health information;
state law equivalents of each of the above federal laws, such as anti-kickback and false claims laws, which may apply to items or services reimbursed by any third-party payer, including commercial insurers, and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts;
the Foreign Corrupt Practices Act, a U.S. law which regulates certain financial relationships with foreign government officials (which could include, for example, certain medical professionals);
federal and state consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers;
federal and state government price reporting laws that require us to calculate and report complex pricing metrics to government programs, where such reported prices may be used in the calculation of reimbursement and/or discounts on our marketed drugs, as well as certain state and municipal government price reporting laws that require us to provide justifications where drug prices exceed a certain price increase threshold (and participation in these programs and compliance with the applicable requirements may subject us to potentially significant discounts on our products, increased infrastructure costs, and could potentially affect our ability to offer certain marketplace discounts);
federal and state financial transparency laws, which generally require certain types of expenditures in the U.S. to be tracked and reported (and compliance with such requirements may require investment in infrastructure to ensure that tracking is performed properly, and some of these laws result in the public disclosure of various types of payments and relationships with healthcare providers and healthcare entities, which could potentially have a negative effect on our business and/or increase enforcement scrutiny of our activities);
proposals by state legislatures and regulators to impose caps on the amount that pharmaceutical manufacturers may compensate healthcare providers for certain services (which could potentially restrict, or increase enforcement scrutiny with respect to, certain of our activities); and
federal and state healthcare fraud and abuse laws, FDA rules and regulations, as well as false claims laws, including the civil False Claims Act, which govern certain marketing practices, including off-label promotion.
If our operations are found to be in violation of any of the laws described above or any other governmental regulations that apply to us, we, or our officers or employees, may be subject to penalties, including administrative civil and criminal penalties, damages, fines, regulatory penalties, the curtailment or restructuring of our operations, exclusion from participation in Medicare, Medicaid and other federal and state healthcare programs, reputational harm, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement, any of which would adversely affect our ability to sell our products and operate our business and also adversely affect our financial results. Of particular concern are suits filed under the civil False Claims Act, known as “qui tam” actions, which can be brought by any individual on behalf of the government. Such individuals, commonly known as “whistleblowers,” may potentially then share in amounts paid by the entity to the government in fines or settlement. The filing of qui tam actions has caused a number of pharmaceutical, medical device and other healthcare companies to have to defend civil False Claims Act actions. When an entity is determined to have violated the civil False Claims Act, it may be required to pay up to three times the actual damages sustained by the government, plus civil penalties for each separate false claim. Defending against any such actions can be costly, time-consuming and may require significant financial and personnel resources. Therefore, even if we are successful in defending against any such actions that may be brought against us, our business may be impaired.
The legislative and regulatory landscape for privacy and data protection continues to evolve, and there has been an increasing amount of focus on privacy and data protection issues with the potential to affect our business, including state security breach notification laws, state health information privacy laws and federal and state consumer protection laws,

govern the collection, use and disclosure of personal information. In addition, most healthcare providers who are expected to prescribe our products and from whom we obtain patient health information are subject to privacy and security requirements under HIPAA. Although we are not directly subject to HIPAA, we could be subject to criminal penalties if we knowingly obtain individually identifiable health information from a HIPAA-covered entity in a manner that is not authorized or permitted by HIPAA. Other countries also have, or are developing, laws governing the collection, use and transmission of personal information. For example, the EU Data Privacy Directive (95/46/EC), which will be replaced on May 28, 2018 by the more restrictive General Data Protection Regulation (Regulation (EU) 2016/679) and the Swiss Federal Act on Data Protection, regulate the processing of personal data within the European Union and between countries in the European Union and countries outside of the European Union, including the U.S. Failure to provide adequate privacy protections and maintain compliance with the new EU-U.S. Privacy Shield framework, which will replace the previous safe harbor mechanisms, could jeopardize business transactions across borders and result in significant penalties, These laws could create liability for us or increase our cost of doing business.operations.
If we are unable to obtain both adequateor maintain coverage and adequate reimbursement for our products from third-party payers, for CABOMETYX or COMETRIQ, our revenues and prospects for profitabilitybusiness will suffer.
Our ability to commercialize CABOMETYX or COMETRIQour products successfully is highly dependent on the extent to which health insurance coverage and reimbursement is, and will be, available from third-party payers, including foreign and U.S. governmental payers, such as Medicare and Medicaid, and private health insurers. Third-party payers continue to scrutinize and manage access to pharmaceutical products and services and may limit reimbursement for newly approved products and indications. Patients mayare generally not be capable of paying for CABOMETYX or COMETRIQ themselves and may rely on third-party payers to pay for, or subsidize, the costs of their medications, among other medical costs. Accordingly, market acceptance of CABOMETYX and COMETRIQ is dependent on the extent to which coverage and reimbursement is available from third-party payers. These entities could refuse, limit or condition coverage for our products, such as by using tiered reimbursement or pressing for new forms of contracting, or alternatively for patients who rely on our co-pay assistance program, implement co-pay accumulators or maximizers that exempt such co-pay assistance from patient deductibles, which has increased and could further increase the costs of our co-pay assistance program or cause patients to abandon CABOMETYX or COMETRIQ therapy due to higher out-of-pocket costs. If third-party payers do not provide or increase limitations on coverage or reimbursement for CABOMETYX or COMETRIQ, our revenues and prospects for profitability willresults of operations may suffer. In addition, even if third-party payers provide some coverage or reimbursement for CABOMETYX or COMETRIQ, the availability of such coverage or reimbursement for prescription drugs under private health insurance and managed care plans, which often varies based on the type of contract or plan purchased, may not be sufficient for patients to afford cabozantinib. There has been negative publicity regarding,CABOMETYX or COMETRIQ.
Current healthcare laws and increasing legislative and enforcement interestregulations in the U.S. with respectand future legislative or regulatory reforms to drug pricing and the use of specialty pharmacies, whichU.S. healthcare system may result in physicians being less willing to participate in our patient access programs and thereby limitaffect our ability to increasecommercialize our marketed products profitably.
Federal and state governments in the U.S. are considering legislative and regulatory proposals to change the U.S. healthcare system in ways that could affect our ability to continue to commercialize CABOMETYX and COMETRIQ profitably. Similarly, among policy makers and payers, there is significant interest in promoting such changes with the stated goals of containing healthcare costs and expanding patient accessaccess. The life sciences industry and adoptionspecifically the market for the sale, insurance coverage and distribution of cabozantinib. Specifically, therepharmaceuticals has been a particular focus of these efforts and would likely be significantly affected by any major legislative or regulatory initiatives.
For instance, efforts to repeal, substantially modify or invalidate some or all of the provisions of the Patient Protection and Affordable Care Act of 2010, as amended (PPACA), some of which have been several recent U.S. Congressional inquiries and proposed bills designedsuccessful, create considerable uncertainties for all businesses involved in healthcare, including our own. Although such efforts have not significantly impacted our business to among other things, bring more transparencydate, it is possible that the PPACA will be subject to drug pricing, reviewadditional judicial or legislative challenges in the relationship between pricing and manufacturer patient programs, reduce the price of drugs under Medicare, and reform government program reimbursement methodologies for drugs. If future, legislation were to impose direct governmental price controls and access restrictions, it couldwhich may have a significantmaterial adverse impact on our business, financial condition and financial results.results of operations, and we cannot predict how future healthcare reform measures of the Biden Administration and federal or state legislative or administrative changes relating to healthcare reform will affect our business.
In addition, there are pending federal and state-level legislative proposals that would significantly expand government-provided health insurance coverage, ranging from establishing a single-payer, national health insurance system to more limited “buy-in” options to existing public health insurance programs, each of which could have a significant impact
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on the healthcare industry. It is also possible that additional governmental actions will be taken in response to the ongoing COVID-19 pandemic, and that such actions would have a significant impact on these public health insurance programs. While we cannot predict how future legislation (or enacted legislation that has yet to be implemented) will affect our business, such proposals could have the potential to impact access to and sales of our products. Furthermore, the expansion of the 340B Drug Pricing Program through the PPACA (the 340B Program) has increased the number of purchasers who are eligible for significant discounts on branded drugs, including our marketed products. Because we participate in the 340B Program to sell a portion of our marketed products, changes in the administration of the program could have a material adverse impact on our revenues, including the implementation or revision of the program’s Administrative Dispute Resolution Process, which is in part intended to resolve claims by covered entities that manufacturers have overcharged them for covered outpatient drugs. A federal court has preliminarily enjoined the 340B Administrative Dispute Resolution Process with respect to the plaintiff manufacturer in that specific challenge, and other legal challenges are ongoing. The Office of Management and Budget initiated review of a new proposed rule titled “340B Drug Pricing Program; Administrative Dispute Resolution” in November 2021.
Some manufacturers are currently involved in ongoing litigation regarding the legality of contract pharmacy arrangements under the 340B Program, which may affect the way in which manufacturers are required to extend discounts to covered entities through contract pharmacies. Effective July 2022, we implemented a 340B Program “integrity initiative,” pursuant to which we will request all hospital covered entities (i.e., hospitals that participate in the 340B Program) to provide claims-level data for CABOMETYX and COMETRIQ dispensed by contract pharmacies. A covered entity that elects not to provide this limited claims data and that does not have an in-house pharmacy may designate a single contract pharmacy location within our authorized specialty pharmacy network. We believe this initiative will provide much-needed transparency and promote compliance with program requirements, and at the same time, should not restrict patient access to our medicines. The U.S. Department of Health and Human Services (HHS) has notified us that it is reviewing our policy, and we have responded to HHS’ request for information. Since 2021, at least nine manufacturers that previously implemented similar contract pharmacy integrity programs have received enforcement letters from HHS stating that those manufacturers’ actions restricted contract pharmacy transactions in violation of the 340B Program statute, which may subject them to repayment of overcharges and civil monetary penalties. As mentioned above, certain of these manufacturers are now in litigation with the government over the legality of these programs, and depending on the outcome of such litigation, we may be required to modify or suspend our 340B Program integrity initiative program. Further, it is possible that HHS could seek to implement administrative proceedings to recover overcharges and/or impose civil monetary penalties against us regarding our 340B Program integrity initiative. If such proceedings were implemented against us, a negative ruling could have a material adverse effect on our business, financial condition and results of operations. Due to general uncertainty with respect to this litigation and in the current regulatory and healthcare policy environment, and specifically regarding positions that the Biden Administration may take with respect to these issues, we are unable to predict the impact of any legislative, regulatory, third-party payer or policy actions, including potential cost containment and healthcare reform measures. If enacted, we and any third parties we may engage may be unable to adapt to any changes implemented as a result of such measures, and we may have difficulties in sustaining profitability or otherwise experience a material adverse impact on our business, financial condition and results of operations.
Pricing for pharmaceutical products in the U.S. has come under increasing attention and scrutiny by federal and state governments, legislative bodies and enforcement agencies. Initiatives arising from this scrutiny may result in changes that have the effect of reducing our revenue or harming our business or reputation.
There continue to be U.S. Congressional inquiries, hearings and proposed and enacted federal legislation and rules, as well as executive orders, designed to, among other things: reduce or limit the prices of drugs and make them more affordable for patients (including, for example, by tying drug prices to the prices of drugs in other countries); reform the structure and financing of Medicare Part D pharmaceutical benefits; implement additional data collection and transparency reporting regarding drug pricing, rebates, fees and other remuneration provided by drug manufacturers; enable the government to negotiate prices under Medicare; revise rules associated with the calculation of average manufacturer price and best price under Medicaid; eliminate the Anti-Kickback Statute (AKS) discount safe harbor protection for manufacturer rebate arrangements with Medicare Part D plan sponsors; create new AKS safe harbors applicable to certain point-of-sale discounts to patients and fixed fee administrative fee payment arrangements with pharmacy benefit managers; and revise the rebate methodology under the Medicaid Drug Rebate Program. For instance, President Biden issued an executive order in July 2021 supporting legislation to enact some of these drug pricing reforms, and in response, HHS released a Comprehensive Plan for Addressing High Drug Prices in September 2021 with specific legislative and administrative policies that Congress could enact to help improve affordability of and access to prescription drugs. While we cannot know the final form or timing of any such legislative, regulatory and/or administrative measures, some of the pending and enacted
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legislative proposals or executive rulemaking if implemented without successful legal challenges, would likely have a significant and far-reaching impact on the biopharmaceutical industry and therefore also likely have a material adverse impact on our business, financial condition and results of operations.
At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biotherapeutic product pricing, including restrictions on pricing or reimbursement at the state government level, limitations on discounts to patients, marketing cost disclosure and transparency measures, and, in some foreigncases, policies to encourage importation from other countries particularly(subject to federal approval) and bulk purchasing, including the National Medicaid Pooling Initiative. In particular, the obligation to provide notices of price increases to purchasers under laws such as California’s SB-17 may influence customer ordering patterns for CABOMETYX and COMETRIQ, which in turn may increase the volatility of our revenues as a reflection of changes in inventory volumes. Furthermore, adoption of these drug pricing transparency regulations, and our associated compliance obligations, may increase our general and administrative costs and/or diminish our revenues. Implementation of these federal and/or state cost-containment measures or other healthcare reforms may limit our ability to generate product revenue or commercialize our products, and in the European Union,case of drug pricing transparency regulations, may result in fluctuations in our results of operations.
Lengthy regulatory pricing and reimbursement procedures and cost control initiatives imposed by governments outside the U.S. could delay the marketing of and/or result in downward pressure on the price of our approved products, resulting in a decrease in revenue.
Outside the U.S., including major markets in the EU and Japan, the pricing and reimbursement of prescription pharmaceuticals is generally subject to governmental control under the respective national health system.control. In these countries, pricepricing and reimbursement negotiations with governmental authorities or payers can take six to twelve12 months or longer after the initial marketing authorization is granted for a product, which hasor after the potential tomarketing authorization for a new indication is granted. This can substantially delay broad availability of the product in some of those countries.product. To obtain reimbursement and/or pricing approval in some countries, we and our collaboration partner,partners Ipsen and Takeda may also be required to conduct a study or otherwise provide data that seeks to establish the cost effectiveness of CABOMETYX compared with other available established therapies to support health technology appraisal.therapies. The conduct of such a study could be expensive andalso result in delays in the commercialization of CABOMETYX. Third-party payers are challenging
Additionally, cost-control initiatives, increasingly based on affordability and accessibility, as well as post-marketing assessments of the added value of CABOMETYX and COMETRIQ as compared to existing treatments, could influence the prices chargedpaid for medicinal products and services,net revenues we realize from CABOMETYX and many third-party payers limit reimbursement for newly-approved health care products. In particular, third-party payers may limitCOMETRIQ, or the indications for which they will reimburse patients who use CABOMETYX or COMETRIQ. Cost-control initiatives could decrease the price we and our collaboration partner, Ipsen, might establish for CABOMETYX,are able to obtain reimbursement, which would result in lower license revenues to us.
Current healthcare laws and regulations and future legislative or regulatory reforms to the healthcare system may affect our ability to sell CABOMETYX and COMETRIQ profitably.*
The U.S. and some foreign jurisdictions are considering or have enacted a number of Upcoming legislative and regulatory proposals to change the healthcare system in ways that could affect our ability to sell CABOMETYX and COMETRIQ profitably. Among policy makers and payerschanges in the U.S. and elsewhere, there is significant interestEU are aimed at increasing cooperation between the EU Member States. Such initiatives, particularly the Regulation on Health Technology Assessment adopted in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access. In the U.S., the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives.
Since its enactment, there have been judicial and Congressional challenges to numerous provisions of the Affordable Care Act,as well as recent efforts by the Trump administration to repeal or replace certain aspects of the

Affordable Care Act. Since January 2017, President Trump has signed two Executive Orders designed to delay the implementation of any certain provisions of the Affordable Care Act or otherwise circumvent some of the requirements for health insurance mandated by the Affordable Care Act. The Trump administration has also announced that it will discontinue the payment of cost-sharing reduction (CSR) payments to insurance companies until Congress approves the appropriation of funds for the CSR payments. The loss of the CSR payments is expected to increase premiums on certain policies issued by qualified health plans under the Affordable Care Act. A bipartisan bill to appropriate funds for CSR payments has been introduced in the Senate, but the future of that bill is uncertain. Further, each chamber of Congress has put forth multiple bills this year designed to repeal or repeal and replace portions of the Affordable Care Act. Although none of these measures has been enacted by Congress to date, CongressDecember 2021, may consider other legislation to repeal and replace elements of the Affordable Care Act. Moreover, certain politicians, including the President, have announced plans to regulate the prices of pharmaceutical products. Congress has also signaled an intent to address pharmaceutical pricing, with Senate hearings to examine the cost of prescription drugs held on June 13 and October 17, 2017. Federal legislators have proposed legislation that would require pharmaceutical manufacturers to report price increases and provide a public justification for increases that exceed given benchmarks and authorize the U.S. Department of Health and Human Services to negotiatefurther impact the price of Part D prescription drugs. Other proposals would allow drug importation from Canada and potentially other countries. We cannot know what form any such measures may take or the market’s perception of how such proposals and provisions would affect us. Any reduction in reimbursement from government programs may result in a similar reduction in payments from private payers. The implementation of cost containment measures or other healthcare reforms may limit our ability to generate revenue or commercialize our current products and/or those for which we may receive regulatory approval in the future.
In August 2017, President Trump signed the FDA Reauthorization Act of 2017, which will reauthorize the FDA user fee programs for prescription drugs, generic drugs, medical devices, and biosimilars, under which manufacturers of such products partially pay for the FDA’s pre-market review of their product candidates. The legislation includes, inter alia, measures to expedite the development and approval of generic products, where generic competition is lacking even in the absence of exclusivities or listed patents. The FDA has also released a Drug Competition Action Plan, which proposes actions to broaden access to generic drugs and lower consumers’ health care costs by, among other things, improving the efficiency of the generic drug approval process and supporting the development of complex generic drugs. We cannot predict what form such regulatory actions may take and how they could affect us.
As a result of the overall trend towards cost-effectiveness criteria and managed healthcare in the U.S., third-party payers are increasingly attempting to contain healthcare costs by limiting both coverage and the level of reimbursement of new drugs. These entities could refuse or limit coverage for CABOMETYX and COMETRIQ, such as by using tiered reimbursement, which would adversely affect demand for CABOMETYX and COMETRIQ. They may also refuse to provide coverage for usesstatus of CABOMETYX and COMETRIQ for medical indications other than those for whichin the FDA has granted market approval. As a result, significant uncertainty exists asfuture.
The timing of the entrance of generic competitors to whetherCABOMETYX and how much third-party payers will cover newly approved drugs, which in turn will put pressure on the pricing of drugs. Duelegislative and regulatory action designed to reduce barriers to the volatilitydevelopment, approval and adoption of generic drugs in the current economic and market dynamics,U.S. could limit the revenue we are unable to predict the impact of any unforeseen or unknown legislative, regulatory, third-party payer or policy actions,derive from our products, most notably CABOMETYX, which may include cost containment and healthcare reform measures. Such policy actions could have a material adverse impact on our revenuesbusiness, financial condition and prospects for profitability.
Pricing for pharmaceutical products has come under increasing scrutiny by governments, legislative bodies and enforcement agencies. These activities may result in actions that have the effectresults of reducing our revenue or harming our business or reputation.*
Many companies in our industry have received a governmental request for documents and information relating to drug pricing and patient support programs. We could receive a similar request, which would require us to incur significant expense and result in distraction for our management team. Additionally, to the extent there are findings, or even allegations, of improper conduct on the part of the company, such findings could further harm our business, reputation and/or prospects. It is possible that such inquiries could result in negative publicity or other negative actions that could harm our reputation; changes in our product pricing and distribution strategies; reduced demand for our approved products and/or reduced reimbursement of approved products, including by federal health care programs such as Medicare and Medicaid and state health care programs.
In addition, the Trump Administration has indicated interest in taking measures pertaining to drug pricing, including potential proposals relating to Medicare price negotiations, importation of drugs from other countries and facilitating value-based arrangements between manufacturers and payers. At this time, it is unclear whether any of these proposals will be pursued and how they would impact our products or our future product candidates.

State and local governments continue to consider prescription drug pricing transparency proposals. In October 2017, California Governor Jerry Brown signed legislation requiring pharmaceutical manufacturers to report certain price increases. We will review the specific provisions of this new law to assess how it will impact public perception or how it might otherwise affect us. Additionally, Ohio voters will consider a ballot initiative on November 7, 2017, which would require state agencies to pay no more for prescription drugs than the price paid by the U.S. Department of Veterans Affairs. We cannot predict the outcome of this ballot initiative, the market’s perception or the potential impact on us.
Our competitors may develop products and technologies that impair the value of cabozantinib, cobimetinib and any future product candidates.
The pharmaceutical, biopharmaceutical and biotechnology industries are highly diversified and are characterized by rapid technological change. In particular, the area of novel oncology therapies is a rapidly evolving and competitive field. Specifically, the indication of advanced RCC is highly competitive and several novel therapies and combinations of therapies are in advanced stages of clinical development in this indication, and may compete with or displace cabozantinib. We face, and will continue to face, intense competition from biotechnology, biopharmaceutical and pharmaceutical companies, as well as academic research institutions, clinical reference laboratories and government agencies that are pursuing research activities similar to ours. Some of our competitors have entered into collaborations with leading companies within our target markets, including some of our existing collaborators. Some of our competitors are further along in the development of their products than we are. Delays in the development of cabozantinib or cobimetinib for the treatment of additional tumor types, for example, could allow our competitors to bring products to market before us. Our future success will depend upon our ability to maintain a competitive position with respect to technological advances and the shifting landscape of therapeutic strategy following the advent of immunotherapy. Our products may become less marketable if we are unable to successfully adapt our development strategy to address the likelihood that this new approach to treating cancer with immuno-oncology agents will become prevalent in indications for which our products are approved, most notably advanced RCC, and in additional indications where we may seek regulatory approval. Furthermore, the complexities of such a strategy has and may continue to require collaboration with some of our competitors.
The markets for which we intend to pursue regulatory approval of cabozantinib and for which Roche and Genentech intend to pursue regulatory approval for cobimetinib are highly competitive. Further, our competitors may be more effective at using their technologies to develop commercial products. Many of the organizations competing with us have greater capital resources, larger research and development staff and facilities, more experience in obtaining regulatory approvals and more extensive product manufacturing and commercial capabilities than we do. As a result, our competitors may be able to more easily develop technologies and products that would render our technologies and products, and those of our collaborators, obsolete and noncompetitive. There may also be drug candidates of which we are not aware at an earlier stage of development that may compete with cabozantinib, cobimetinib, and our other product candidates.
If competitors use litigation and regulatory means to obtain approval for generic versions of cabozantinib, our business will suffer.operations.
Under the FDCA,Federal Food, Drug and Cosmetic Act (FDCA), the FDA can approve an Abbreviated New Drug Application, or ANDA for a generic version of a branded drug without the applicant undertaking the human clinical testing necessary to obtain approval to market a new drug. The FDA can also approve a New Drug Application (NDA) under section 505(b)(2) NDAof the FDCA that relies in part on the agency’s findings of safety and/or effectiveness for a previously approved drug. The filingdrug, where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use. Both the ANDA and 505(b)(2) NDA processes are discussed in more detail in “Item 1. Business—Government Regulation—FDA Review and Approval—Abbreviated FDA Approval Pathways and Generic Products” in our Fiscal 2021 Form 10-K. In either case, if an ANDA or 505(b)(2) NDA applicant submits an application referencing one of our marketed products prior to the expiry of one or more our Orange Book-listed patents for the applicable product, we may litigate with respectthe potential generic competitor to cabozantinibprotect our patent rights, which would result in substantial costs, divert the attention of management, and could have an adverse impact on our stock price. Moreover, if any suchFor example, MSN and Teva have separately submitted ANDAs to the FDA requesting approval to market their respective generic versions of CABOMETYX tablets, and we have subsequently filed patent lawsuits against both companies. For a more detailed discussion of these litigation matters, see “Legal Proceedings” in Part II, Item 1 of this Quarterly Report on Form 10-Q. It is possible that MSN, Teva or other companies, following FDA approval of an ANDA or 505(b)(2) NDAs were to be approved and theNDA, could introduce generic or otherwise competitor versions of our marketed products before our patents covering cabozantinib wereexpire if they do not upheld in litigation,infringe our
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patents or if it is determined that our patents are invalid or unenforceable, and we expect that generic cabozantinib products would be offered at a significantly lower price compared to our marketed cabozantinib products. Therefore, regardless of the regulatory approach, the introduction of a generic competitor is found not to infringe these patents,version of cabozantinib would likely decrease our revenues derived from the resulting generic competition would negatively affectU.S. sales of CABOMETYX and thereby materially harm our business, financial condition and results of operations. There are also equivalent procedures in the EU permitting authorization of generic versions and biosimilars of medicinal products authorized in the EU once related data and market exclusivity periods have expired.
The U.S. federal government has also taken numerous legislative and regulatory actions to expedite the development and approval of generic drugs and biosimilars. Both Congress and the FDA are considering, and have enacted, various legislative and regulatory proposals focused on drug competition, including legislation focused on drug patenting and provision of drug to generic applicants for testing. For example, the Ensuring Innovation Act, enacted in April 2021, amended the FDA’s statutory authority for granting new chemical entity (NCE) exclusivity to reflect the agency’s existing regulations and longstanding interpretation that award NCE exclusivity based on a drug’s active moiety, as opposed to its active ingredient, which is intended to limit the applicability of NCE exclusivity, thereby potentially facilitating generic competition. The FDA has also released a Drug Competition Action Plan, which proposes actions to broaden access to generic drugs and lower consumers’ healthcare costs by, among other things, improving the efficiency of the generic drug approval process and supporting the development of complex generic drugs. In addition, the Further Consolidated Appropriations Act, 2020, which incorporated the framework from the Creating and Restoring Equal Access To Equivalent Samples (CREATES) legislation, purports to promote competition in the market for drugs and biotherapeutic products by facilitating the timely entry of lower-cost generic and biosimilar versions of those drugs and biotherapeutic products, including by allowing ANDA, 505(b)(2) NDA or biosimilar developers to obtain access to branded drug and biotherapeutic product samples. While the full impact of these provisions is unclear at this regard,time, its provisions do have the potential to facilitate the development and future approval of generic versions of our products, introducing generic competition that could have a material adverse impact on our business, financial condition and results of operations.
Risks Related to Healthcare Regulatory and Other Legal Compliance Matters
We are subject to healthcare laws, regulations and enforcement; our failure to comply with those laws could have a material adverse impact on our business, financial condition and results of operations.
We are subject to federal and state healthcare laws and regulations, which laws and regulations are enforced by the federal government and the states in which we conduct our business. Should our compliance controls prove ineffective at preventing or mitigating the risk and impact of improper business conduct or inaccurate reporting, we could be subject to enforcement of the following, including, without limitation:
the federal AKS;
the FDCA and its implementing regulations;
federal civil and criminal false claims laws, including the civil False Claims Act, and the Civil Monetary Penalties Law;
federal criminal laws that prohibit executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;
the Health Insurance Portability and Accountability Act of 1996 (HIPAA) and its implementing regulations, as amended;
state law equivalents of each of the above federal laws;
the Open Payments program of the PPACA;
state and local laws and regulations that require drug manufacturers to file reports relating to marketing activities, payments and other remuneration and items of value provided to healthcare professionals and entities; and
state and federal pharmaceutical price and price reporting laws and regulations.
In addition, we may be subject to the Foreign Corrupt Practices Act, a U.S. law which mustregulates certain financial relationships with foreign government officials (which could include, for example, medical professionals employed by national healthcare programs) and its foreign equivalents, as well as federal and state consumer protection and unfair competition laws.
These federal and state healthcare laws and regulations govern drug marketing practices, including off-label promotion, and also impact our current and future business arrangements with third parties, including various healthcare entities. If our operations are found, or even alleged, to be in violation of the laws described above or other governmental
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regulations that apply to us, we, or our officers or employees, may be subject to significant penalties, including administrative civil and criminal penalties, damages, fines, regulatory penalties, the curtailment or restructuring of our operations, exclusion from participation in Medicare, Medicaid and other federal and state healthcare programs, imprisonment, reputational harm, additional reporting requirements and oversight through a Corporate Integrity Agreement or other monitoring agreement, any of which would adversely affect our ability to sell our products and operate our business and also adversely affect our financial results. Furthermore, responding to any such allegation or investigation and/or defending against any such enforcement actions can be time-consuming and would require significant financial and personnel resources. Therefore, if any state or the federal government initiates an enforcement action against us, our business may be impaired, and even if we are ultimately successful in our defense, litigating these actions could result in substantial costs and divert the attention of management.
Enhanced governmental and private scrutiny over, or investigations or litigation involving, pharmaceutical manufacturer patient assistance programs and donations to patient assistance foundations created by charitable organizations could negatively impact our business practices, harm our reputation, divert the attention of management and increase our expenses.
To help patients afford our products, we have a patient assistance program and also occasionally make donations to independent charitable foundations that help financially needy patients. These types of programs designed to assist patients with affording pharmaceuticals have become the subject of Congressional interest and enhanced government scrutiny. The HHS Office of Inspector General established guidelines permitting pharmaceutical manufacturers to make donations to charitable organizations that provide co-pay assistance to Medicare patients, provided that manufacturers meet certain specified compliance requirements. In the same quality standards asevent we make such donations but are found not to have complied with these guidelines and other laws or regulations respecting the branded drugs,operation of these programs, we could be subject to significant damages, fines, penalties or other criminal, civil or administrative sanctions or enforcement actions. Moreover, in December 2020, the Centers for Medicare and Medicaid Services (CMS) finalized changes to Medicaid Drug Rebate Program pricing calculations regarding the provision of co-payment assistance to patients that may be impacted by private insurer accumulator programs. Although the portion of this rule dealing with manufacturer co-payment assistance (and related support programs) was struck down by the U.S. District Court for the District of Columbia in May 2022, this ruling is subject to appeal, and it also is possible that CMS could issue new rulemaking or guidance that would be significantly less costly than oursaffect the amount of rebates owed under the Medicaid program or otherwise limit our ability to bringsupport our patient co-pay assistance program. We also rely on a third-party hub provider and exercise oversight to market. Companies that produce generic equivalentsmonitor patient assistance program activities. Hub providers are generally ablehired by manufacturers to offerassist patients with insurance coverage, financial assistance and treatment support after the patients receive a prescription from their products at lower prices. Thus,healthcare professional. For manufacturers of specialty pharmaceuticals (including our marketed products), the ability to have a single point of contact for their therapies helps ensure efficient medication distribution to patients. Accordingly, our hub activities are also subject to scrutiny and may create risk for us if not conducted appropriately. A variety of entities, including independent charitable foundations and pharmaceutical manufacturers, but not including our company, have received subpoenas from the U.S. Department of Justice (DOJ) and other enforcement authorities seeking information related to their patient assistance programs and support, and certain of these entities have entered into costly civil settlement agreements with DOJ and other enforcement authorities that include requirements to maintain complex corporate integrity agreements that impose significant reporting and other requirements. Should we or our hub providers receive a subpoena or other process, regardless of whether we are ultimately found to have complied with the regulations governing patient assistance programs, this type of government investigation could negatively impact our business practices, harm our reputation, divert the attention of management and increase our expenses.
We are subject to laws and regulations relating to privacy, data protection and the collection and processing of personal data. Failure to maintain compliance with these regulations could create additional liabilities for us.
The legislative and regulatory approval pathway, afterlandscape for privacy and data protection continues to evolve in the introductionU.S. and other jurisdictions around the world. For example, the California Consumer Privacy Act of 2018 (CCPA) went into operation in 2020 and affords California residents expanded privacy rights and protections, including civil penalties for violations and statutory damages under a generic competitor,private right of action for data security breaches. These protections will be expanded by the California Privacy Rights Act (CPRA), which will be operational in most key respects on January 1, 2023. Similar legislative proposals have passed or are being advanced in other states, and Congress is also considering additional federal privacy legislation. In addition, most healthcare professionals and facilities are subject to privacy and security requirements under HIPAA with respect to our clinical and commercial activities. Although we are not considered to be a significant percentagecovered entity or business associate under HIPAA, we could be subject to penalties if we use or disclose individually identifiable health information in a manner not authorized or permitted by HIPAA. Other countries also have, or are developing, laws
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governing the collection, use and transmission of personal information. For example, in the EU, the EU General Data Protection Regulation 2016/679 (GDPR) regulates the processing of personal data of individuals within the EU, even if, under certain circumstances, that processing occurs outside the EU, and also places restrictions on transfers of such data to countries outside of the salesEU, including the U.S. Should we fail to provide adequate privacy or data security protections or maintain compliance with these laws and regulations, including the CCPA, CPRA and GDPR, we could be subject to sanctions or other penalties, litigation, an increase in our cost of any branded product are typically lostdoing business and questions concerning the validity of our data processing activities, including clinical trials.
Risks Related to the generic product.Growth of Our Product Portfolio and Research and Development
Clinical testing of cabozantinib for new indications, or of new product candidates, is a lengthy, costly, complex and uncertain process andthat may fail ultimately to demonstrate safety and efficacy.*efficacy data for those products sufficiently differentiated to compete in our highly competitive market environment.
Clinical trials are inherently risky and may reveal that cabozantinib, despite its approval for certain indications, or a new product candidate, even if it is approved for other indications, is ineffective or has an unacceptable safety profile thatwith respect to an intended use. Such results may significantly decrease the likelihood of regulatory approval inof a product candidate or of an approved product for a new indication. For example, COMET-1 and COMET-2, our two phase 3 pivotal trials of cabozantinib in metastatic castration-resistant prostate cancer, or mCRPC, failed to meet their respective primary endpoints of

demonstrating a statistically significant increase in OS for patients treated with cabozantinib as compared to prednisone and to demonstrate improvement in pain response for patients treated with cabozantinib as compared to mitoxantrone/prednisone. Based onMoreover, the outcome of the COMET trials, we deprioritized the clinical development of cabozantinib in mCRPC.
The results of preliminary studies do not necessarily predict clinical or commercial success, and later-stagelate-stage or other potentially label-enabling clinical trials may fail to confirm the results observed in earlier-stageearly-stage trials or preliminary studies. Although we have established timelines for manufacturing and clinical development of cabozantinib and our other product candidates based on existing knowledge of our compounds in development and industry metrics, we may not be able to meet those timelines.
We may experience numerous unforeseen events, during or as a result of clinical testing,investigations, that could delay or prevent commercialization of ourcabozantinib in new indications or of XL092 or other new product candidates, including:candidates. These events may include:
lack of acceptable efficacy or harmful side effects;a tolerable safety profile;
negative or inconclusive clinical trial results maythat require us to conduct further testing or to abandon projects that we had expected to be promising;projects;
discovery or commercialization by our competitors may discover or commercializeof other compounds or therapies that show significantly improved safety or efficacy compared to cabozantinib or our other product candidates;
our inability to identify and maintain a sufficient number of trial sites, many of which may already be engaged in other clinical trial programs;sites;
lower-than-anticipated patient registration or enrollment in our clinical testing may be lower than we anticipate, resultingtesting;
additional complexities posed by clinical trials evaluating cabozantinib, XL092 or our other product candidates in combination with other therapies, including extended timelines to provide for collaboration on clinical development planning, the delay or cancellation of clinical testing;
failure by our collaboratorscollaboration partners to provide us with an adequate and timely supply us on a timely basisof product that complies with the product requiredapplicable quality and regulatory requirements for a combination trial;trial
reduced staffing or shortages in laboratory supplies and other resources necessary to complete the trials;
failure of our third-party contract research organizationorganizations or investigators to satisfy their contractual obligations, including deviating from any trial protocol;protocols; and
withholding of authorization from regulators or institutional review boards may withhold authorization to commence or conduct clinical trials of a product candidate, or delay, suspenddelays, variations, suspensions or terminateterminations of clinical research for various reasons, including noncompliance with regulatory requirements or theira determination by these regulators and institutional review boards that participating patients are being exposed to unacceptable health risks.
The ongoing Russo-Ukrainian War has had a modest impact on our clinical development operations, particularly with respect to patient recruitment, potentially delaying our ability to complete enrollment in a timely manner. In addition, this conflict has had and may continue to have an adverse impact on the ability of clinical sites and their patients to adhere to trial protocols for in-office clinical visits and other procedures, our ability to supply clinical sites with cabozantinib or other study drugs and to pay clinical sites and investigators for work performed, as well as our ability to collect data and conduct site monitoring visits, all of which could undermine the data quality for patients enrolled at these clinical sites. The need to shift enrollment of patients away from these clinical sites or close certain sites entirely, or to replace patients in affected territories should investigators be unable to continue treating and monitoring them, could further impact our anticipated timelines for completing the trials and achieving clinical endpoints, as well as increase our clinical development expenses.
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If we were to have significantthere are further delays in or termination of ourthe clinical testing of cabozantinib, XL092 or our other product candidates as a result ofdue to any of the events described above or otherwise, our expenses could increase and our ability to generate revenues could be impaired, either of which could adversely impact our financial results. Furthermore, we rely on our collaboration partners to fund a significant portion of our clinical development programs. Should one or all of our collaboration partners decline to support future planned clinical trials, we will be entirely responsible for financing the further development of the cabozantinib franchise, XL092 or our other product candidates and, as a result, we may be unable to execute our current business plans, which could have a material adverse impact on our business, financial condition and results of operations.
We may not be able to rapidly or effectively continuepursue the further development of the cabozantinib franchise, XL092 or our other product candidates or meet current or future requirements of the FDA or regulatory authorities in other jurisdictions including those identified based onin accordance with our discussions with the FDAstated timelines or such other regulatory authorities.at all. Our planned clinical trials may not begin on time, or at all, may not be completed on schedule, or at all, may not be sufficient for registration of our product candidates or otherwise may not result in an approvable product.
Completion of clinical trials may take several years or more, but the length of time generally varies substantially according to the type, complexity, novelty and intended use of the product candidate. The duration and the cost of clinical trials may vary significantly over the life of a project as a result of factors relating to thea particular clinical trial, including, among others:
the characteristics of the product candidate under investigation; the number of patients who ultimately participate in the clinical trial;
the duration of patient follow-up that is appropriate in view of the results or required by regulatory authorities;
follow-up; the number of clinical sites included in the trials;trial; and
the length of time required to enroll suitable patient subjects.
eligible patients. Any delay could limit our ability to generate revenues, cause us to incur additional expense and cause the market price of our common stock to decline significantly. Our partners under our collaboration agreements may experience similar risks with respect to the compounds we have out-licensed to them. If any of the events described above were to occur with such programs or compounds, the likelihood of receipt of milestones and royalties under such collaboration agreements could decrease.

The regulatory approval processes of the FDA and comparable foreign regulatory authorities are lengthy, uncertain and uncertain,subject to change, and may not result in regulatory approvals for additional cabozantinib indications or for our other product candidates, which could adversely affecthave a material adverse impact on our business.business, financial condition and results of operations.
The activities associated with the research, development and commercialization of the cabozantinib franchise, XL092 and our products andother product candidates are subject to extensive regulation by the FDA and other regulatory agencies in the U.S. and, as well as by comparable regulatory authorities in other countries. We have only limited experience in preparing and filing the applications necessary to gain regulatory approvals.territories. The processprocesses of obtaining regulatory approvals in the U.S. and other foreign jurisdictions is expensive and often takes many years, if approval is obtained at all, and they can vary substantially based upon the type, complexity and novelty of the product candidates involved. For example, before an NDA or sNDAsupplemental New Drug Application (sNDA) can be submitted to the FDA, or a marketing authorization application to the European Medicines AgencyEMA or any application or submission to comparable regulatory authorities in other jurisdictions, the product candidate must undergo extensive clinical trials, which can take many years and require substantial expenditures.
Any clinical trial may fail to produce results satisfactory to the FDA or regulatory authorities in other jurisdictions. For example, the FDA could determine that the design of a clinical trial is inadequate to produce reliable results. The regulatory process also requires preclinical testing, and data obtained from preclinical and clinical activities are susceptible to varying interpretations. The FDA has substantial discretion in the approval process and may refuse to approve any NDA or sNDA or decide that our data is insufficient for approval and require additional preclinical, clinical or other studies. For example, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent regulatory approval of cabozantinib for any individual, additional indications.
In addition, we may encounter delays or rejections may be encountered based upon changes in regulatory policy, for product approval during the period of product development and regulatory agency review, which maycould cause delays in the approval or rejection of an application for cabozantinib or for XL092 or our other product candidates. For example, the FDA launched Project Optimus in 2021 as an initiative to reform the dose optimization and dose selection paradigm in oncology drug development, which was driven by the FDA’s concerns that the current paradigm for dose selection may result in doses and schedules of molecularly targeted therapies that are inadequately characterized before initiating pivotal trials. Through collaboration with the biopharmaceutical industry, academia and other stakeholders, the FDA’s goal for this initiative is to advance an oncology dose-finding and dose optimization paradigm that emphasizes dose selections that maximize efficacy as well as safety and tolerability. In support of this initiative, the FDA may request sponsors of oncology product candidates to conduct dose optimization studies pre- or post-approval, and the FDA also continues to develop and finalize guidance documents and implement initiatives regarding the development and clinical research of oncology product candidates. Recently, in part due to questions raised by the process underlying the approval of the Alzheimer’s disease drug Aduhelm®,government authorities and other stakeholders have been scrutinizing the accelerated approval pathway, with some stakeholders advocating for reforms. Even prior to the Aduhelm approval, FDA has held Oncologic Drugs Advisory Committee meetings to discuss accelerated approvals for which confirmatory trials have not verified clinical benefit. Such scrutiny, among other factors, has resulted in voluntary withdrawals of certain products and indications approved on an accelerated basis. Moreover, also spurred by the Aduhelm controversy, the HHS Office of Inspector General has initiated an assessment of how the FDA implements the accelerated approval pathway. In addition, members of Congress have introduced proposed legislation to revise the statutory accelerated approval pathway, including with respect to the FDA’s ability to rapidly withdraw products and indications for which effectiveness is not confirmed in post-marketing studies. At this time, it is not clear what impact, if any, these developments may have on the statutory accelerated approval pathway or our business, financial condition and results of operations.
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Even if the FDA or a comparable authority in another jurisdiction approves cabozantinib for one or more new indications beyond advanced RCC and MTC, or approves one of our other product candidates, theincluding XL092, for use, such approval may be limited, imposing significant restrictions on the indicated uses, conditions for use, labeling, distribution, advertising, promotion, marketing and/or production of the product and could impose ongoing requirements for post-approvalpost-marketing studies, including additional research and developmentclinical trials, all of which may result in significant expense and clinical trials. For example,limit our and our collaboration partners’ ability to commercialize cabozantinib, XL092 or our other product candidates in any new indications. Failure to complete post-marketing requirements of the FDA in connection with the FDA’sa specific approval of COMETRIQ for the treatment of progressive, metastatic MTC, we are subject to post-marketing requirement to conduct a clinical study comparing a lower dose of cabozantinib to the approved dose of 140 mg daily cabozantinib in progressive, metastatic MTC. Failure to complete any post-marketing requirements in accordance with the timelines and conditions set forth by the FDA could significantly increase costs or delay, limit or eliminateultimately restrict the commercialization of cabozantinib. Further, thesecabozantinib, XL092 or another product candidate in the approved indication. Regulatory agencies maycould also impose various administrative, civil or criminal sanctions for failure to comply with regulatory requirements, including withdrawal of product approval. Further, current or any future laws or executive orders governing FDA or foreign regulatory approval processes that may be enacted or executed could have a material adverse impact on our business, financial condition and results of operations.
We may be unable to expand our discovery and development pipeline, which could limit our growth and revenue potential.
We are committed toOur business is focused on the discovery, development and promotioncommercialization of new medicines with the potential to improve care and outcomes for people with cancer.difficult-to-treat cancers. In this regard, we have resumed internalinvested in substantial technical, financial and human resources toward drug discovery effortsactivities with the goal of identifying new product candidates to advance into clinical trials. Internal discovery efforts to identify new product candidates require substantial technical, financial and human resources. These internal discovery efforts mayNotwithstanding this investment, many programs that initially show promise in identifying potential product candidates, yetwill ultimately fail to yield product candidates for clinical development for a number of reasons, including where the research methodology used may not be successful in identifying potential product candidates, or where potentialmultiple reasons. For example, product candidates may, on further study, be shown to have inadequate efficacy, harmful side effects, suboptimal pharmaceutical profileprofiles or other characteristics suggesting that they are unlikely to be effectivecommercially viable products.
Apart from our internaldrug discovery efforts, our strategy to expand our development pipeline is also dependent on our ability to successfully identify and acquire or in-license relevant product candidates.candidates and technologies. However, the in-licensing and acquisition of product candidates and technologies is a highly competitive area, and many other companies are pursuing the same or similar product candidates and technologies to those that we may consider attractive. EstablishedIn particular, larger companies in particular, may have a competitive advantage over us due to their size, financialwith more capital resources and more extensive clinical development and commercialization capabilities.capabilities may have a competitive advantage over us. Furthermore, companies that perceive us to be a competitor may be unwilling to assign or license rights to us. We may also be unable to in-license or acquire a relevantadditional product candidatecandidates and technologies on acceptable terms that would allow us to realize an appropriate return on our investment. If we are unable to develop suitable product candidates through internal discovery effort or if we are unable to successfully obtain rights to suitable product candidates, our business, financial

condition and prospects for growth could suffer. Even if we succeed in our efforts to obtain rights to suitable product candidates and technologies, the competitive business environment may result in higher acquisition or licensing costs. costs, and our investment in these potential products and technologies will remain subject to the inherent risks associated with the development and commercialization of new medicines. In certain circumstances, we may also be reliant on the licensor for the continued development of the in-licensed technology and their efforts to safeguard their underlying intellectual property.
With respect to acquisitions, we may not be able to integrate the target company successfully into our existing business, maintain the key business relationships of the target company, or retain key personnel of anthe acquired business. Furthermore, we could assume unknown or contingent liabilities or otherwise incur unanticipated expenses. Any acquisitions or investments made by us also could result in our spending significant amounts, issuing dilutive securities, assuming or incurring significant debt obligations and contingent liabilities, incurring large one-time expenses and acquiring intangible assets that could result in significant future amortization expense and significant write-offs, any of which could harm our operating results.financial condition and results of operations. If our drug discovery efforts, including research collaborations, in-licensing arrangements and other business development activities, do not result in suitable product candidates, our business and prospects for growth could suffer.
Risks Related to OurFinancial Matters and Capital Requirements
Our profitability could be negatively impacted if expenses associated with our extensive clinical development, business development and Financial Resultscommercialization activities, both for the cabozantinib franchise and our other product candidates, grow more quickly than the revenues we generate.
Although we reported net income of $70.7 million and $139.2 million for the three and six months ended June 30, 2022 and $231.1 million for the fiscal year ended December 31, 2021, we may not be able to maintain or increase profitability on a quarterly or annual basis, and we are unable to predict the extent of future profits or losses. The amount of our net profits or losses will depend, in part, on: the level of sales of CABOMETYX and COMETRIQ in the U.S.; our
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achievement of development, regulatory and commercial milestones, if any, under our collaboration agreements; the amount of royalties from sales of CABOMETYX and COMETRIQ outside of the U.S. under our collaboration agreements; other collaboration revenues; and the level of our expenses, including those associated with our extensive drug discovery, clinical development and business development activities, both for the cabozantinib franchise and our other product candidates, as well as our general business expansion plans. Our expected future expenses in particular may also be increased by inflationary pressures, whether resulting from the effects of the ongoing Russo-Ukrainian War or the COVID-19 pandemic or otherwise, which could increase the costs of outside services, labor, raw materials and finished drug product. We expect to continue to spend substantial amounts to fund the continued development of the cabozantinib franchise for additional indications and of our other product candidates, as well as the commercialization of our approved products. In addition, we intend to continue to expand our oncology product pipeline through our drug discovery efforts, including research collaborations, in-licensing arrangements and other strategic transactions that align with our oncology drug development, regulatory and commercial expertise, which efforts could involve substantial costs. To offset these costs in the future, we will need to generate substantial revenues. If these costs exceed our current expectations, or we fail to achieve anticipated revenue targets, the market value of our common stock may decline.
If additional capital is not available to us when we need it, we may be forcedunable to limit the expansion ofexpand our product development programs or commercialization efforts.*
As of September 30, 2017, we had $422.3 million in cashofferings and investments, which included $417.6 million available for operations and $4.7 million of long-term restricted investments. Our business operations grew substantially during 2016 and experienced further development during the nine months ended September 30, 2017. In order to maintain business growth and maximize the clinical and commercial opportunities for cabozantinib and cobimetinib, we plan to continue to execute on the U.S. commercialization plans for CABOMETYX, while reinvesting in our product pipeline through the continued development of cabozantinib, research and development activities, as well as through in-licensing and acquisition efforts. Our ability to execute on these business objectives will depend on many factors including but not limited to:
the commercial success of both CABOMETYX and COMETRIQ and the revenues we generate from those approved products;
costs associated with maintaining our expanded sales, marketing, medical affairs and distribution capabilities for CABOMETYX in advanced RCC and COMETRIQ in the approved MTC indications;
the achievement of stated regulatory and commercial milestones under the Ipsen Collaboration Agreement;
the commercial success of COTELLIC and the revenues generated through our share of related profits and losses for the commercialization of COTELLIC in the U.S. and royalties from COTELLIC sales outside the U.S. under our collaboration with Genentech;
the potential regulatory approval of cabozantinib as a treatment for patients with previously untreated advanced RCC, and in other indications, both in the U.S. and abroad;
our ability to timely prepare and submit an sNDA for cabozantinib as a treatment for patients with advanced HCC;
future clinical trial results;
our future investments in the expansion of our pipeline through drug discovery and corporate development activities;
our ability to control costs;
the cost of clinical drug supply for our clinical trials;
trends and developments in the pricing of oncologic therapeutics in the U.S. and abroad, especially in the European Union;
scientific developments in the market for oncologic therapeutics and the timing of regulatory approvals for competing oncologic therapies; and
the filing, maintenance, prosecution, defense and enforcement of patent claims and other intellectual property rights.growth.
Our commitment of cash resources to CABOMETYX and the reinvestment in our product pipeline through the continued development of the cabozantinib continued researchfranchise and developmentour other product candidates, and increasing drug discovery activities, as well as through in-licensing and acquisition efforts,the execution of business development transactions, could require us to obtain additional capital. We may seek such additional capital through some or all of the following methods: corporate collaborations,collaborations; licensing arrangements,arrangements; and public or private debt or equity financings. Our ability to obtain additional capital may depend on prevailing macroeconomic conditions and financial, business and other factors beyond our control. We do not know whether additional capital will be available when needed, or that, if available, we will obtain additional capital on terms favorable to us or our stockholders. If we are unable to raise additional funds when we need them, we may

be requiredunable to limit the expansion ofexpand our product development programs or commercialization efforts,offerings and maintain business growth, which could have a material adverse effectimpact on our business, and growth prospects.
We have a history of net losses and may incur net losses in the future, and may be unable to maintain profitability.*
We have incurred net losses in every fiscal year since our inception, with the exception of the 2011 fiscal year, and as of September 30, 2017, we had an accumulated deficit of $1.9 billion. Although we reported net income of $115.7 million for the nine months ended September 30, 2017, we may not be able to maintain or increase profitability on a quarterly or annual basis and we are unable to accurately predict the extent of long-range future profits or losses. We expect to continue to spend significant additional amounts to fund the continued development and commercialization of cabozantinib. In addition, we intend to expand our product pipeline through the measured resumption of drug discovery and the evaluation of in-licensing and acquisition opportunities that align with our oncology drug expertise, which efforts could involve substantial costs. As a result, we are unable to predict the extent of any future profits or losses because we expect to continue to incur substantial operating expenses and, consequently, we will need to generate substantial revenues to maintain or increase profitability.
Since the launch of our first commercial product in January 2013, through September 30, 2017, we have generated an aggregate of $463.0 million in net product revenues, including $253.3 million for the nine months ended September 30, 2017. Other than sales of CABOMETYX and COMETRIQ, we have derived substantially all of our revenues since inception from collaborative arrangements, including upfront and milestone payments and research funding we earn from any products developed from the collaborative research. The amount of our net profits or losses will depend, in part, on: the level of sales of CABOMETYX and COMETRIQ in the U.S.; achievement of clinical, regulatory and commercial milestones and the amount of royalties, if any, from sales of CABOMETYX and COMETRIQ under the Ipsen Collaboration Agreement; our share of the net profits and losses for the commercialization of COTELLIC in the U.S. under our collaboration with Genentech; the amount of royalties from COTELLIC sales outside the U.S. under our collaboration with Genentech; other license and contract revenues; and the level of our expenses, including commercialization activities for cabozantinib and any pipeline expansion efforts.
We are exposed to risks related to foreign currency exchange rates.
Most of our foreign expenses incurred are associated with establishing and conducting clinical trials for cabozantinib. The amount of these expenses will be impacted by fluctuations in the currencies of those countries in which we conduct clinical trials. Our agreements with the foreign sites that conduct such clinical trials generally provide that payments for the services provided will be calculated in the currency of that country, and converted into U.S. dollars using various exchange rates based upon when services are rendered or the timing of invoices. When the U.S. dollar weakens against foreign currencies, the U.S. dollar value of the foreign-currency denominated expense increases, and when the U.S. dollar strengthens against these currencies, the U.S. dollar value of the foreign-currency denominated expense decreases. Consequently, changes in exchange rates may affect our financial position and results of operations.
Global credit and financial market conditions could negatively impact the value of our current portfolio of cash equivalents, short-term investments or long-term investments and our ability to meet our financing objectives.
Our cash and cash equivalents are maintained in highly liquid investments with remaining maturities of 90 days or less at the time of purchase. Our short-term and long-term investments consist primarily of readily marketable debt securities with remaining maturities of more than 90 days at the time of purchase. While as of the date of this report we are not aware of any downgrades, material losses, or other significant deterioration in the fair value of our cash equivalents, short-term investments or long-term investments since September 30, 2017, no assurance can be given that a deterioration in conditions of the global credit and financial markets would not negatively impact our current portfolio of cash equivalents or investments or our ability to meet our financing objectives.
Our financial results are impacted by management’s selection of accounting methods and certain assumptions and estimates.*
Our accounting policies and methods are fundamental to how we record and report our financial condition and results of operations. Our management must exercise judgment in selecting and applying many of these accounting policies and methods so they comply with generally accepted accounting principles and reflect management’s judgment of the most appropriate manner to report our financial condition and results of operations. In some cases, management must select the accounting policy or method to apply from two or more alternatives, any of which may be reasonable under the

circumstances, yet may result in our reporting materially different results than would have been reported under a different alternative.
Certain accounting policies are critical to the presentation of our financial condition and results of operations. The preparation of our financial statements requires us to make significant estimates, assumptions and judgments that affect the amounts of assets, liabilities, revenues and expenses and related disclosures. Significant estimates that may be made by us include assumptions used in the determination of revenue recognition, discounts and allowances from gross revenue, inventory and stock-based compensation. Although we base our estimates and judgments on historical experience, our interpretation of existing accounting literature and on various other assumptions that we believe to be reasonable under the circumstances, if our assumptions prove to be materially incorrect, actual results may differ materially from these estimates.
In addition, future changes in financial accounting standards may cause adverse, unexpected revenue fluctuations and affect our financial position or results of operations. New pronouncements and varying interpretations of pronouncements have occurred with frequency in the past and are expected to occur again in the future and as a result we may be required to make changes in our accounting policies. Those changes could adversely affect our reported revenues and expenses, prospects for profitability or financial position. For example, in May 2014, the Financial Accounting Standards Board issued an Accounting Standards Update entitled Accounting Standards Update No. 2014-09, Revenue from Contracts with Customers (Topic 606), or ASU 2014-09, which will replace existing revenue recognition guidance in U.S. generally accepted accounting pronouncements when it becomes effective for us in the first quarter of fiscal year 2018. ASU 2014-09 will not have a material impact on the recognition of revenue from product sales. ASU 2014-09 will impact the timing of recognition of revenue for our Ipsen and Takeda collaboration arrangements. We expect to reclassify deferred revenue to accumulated deficit (a concept known as “lost revenue”) for amounts associated with these collaboration arrangements upon recording our transition adjustment in the first quarter of 2018, primarily due to the timing of recognition of revenue related to intellectual property licenses that we have transferred for development and commercialization of our products. Additionally, for all of our collaboration arrangements, the timing of recognition of certain of our development and regulatory milestones could change as a result of the variable consideration guidance included in ASU 2014-09. In any event, we will continue to evaluate the impact of the new standard on all of our revenues, including those mentioned above, and our preliminary assessments may change in the future based on our continuing evaluation. The application of existing or future financial accounting standards, particularly those relating to the way we account for revenues and costs, could have a significant impact on our reported results.
Risks Related to Our Relationships with Third Parties
We rely on Ipsen and Takeda for the commercial success of CABOMETYX in its approved indications outside of the U.S., and we are dependentunable to control the amount or timing of resources expended by these collaboration partners in the commercialization of CABOMETYX in its approved indications outside of the U.S.
We rely upon the regulatory, commercial, medical affairs, market access and other expertise and resources of our collaboration partners, Ipsen and Takeda, for commercialization of CABOMETYX in their respective territories outside of the U.S. We cannot control the amount and timing of resources that our collaboration partners dedicate to the commercialization of CABOMETYX, or to its marketing and distribution, and our ability to generate revenues from the commercialization of CABOMETYX by our collaboration partners depends on their ability to obtain and maintain regulatory approvals for, achieve market acceptance of, and to otherwise effectively market, CABOMETYX in its approved indications in their respective territories. Further, the operations of our collaboration partners, and ultimately their sales of CABOMETYX in their respective territories outside of the U.S., could be adversely affected by the degree and effectiveness of their respective corporate responses to the COVID-19 pandemic, as well as by the imposition of governmental price or other controls, political and macroeconomic instability, trade restrictions or barriers and changes in tariffs, escalating global trade and political tensions, or other factors. If our collaboration partners are unable or unwilling to invest the resources necessary to commercialize CABOMETYX successfully in the EU, Japan and other international territories where it has been approved, this could reduce the amount of revenue we are due to receive under these collaboration agreements, thus resulting in harm to our business and operations.
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Our clinical, regulatory and commercial collaborations with major companies make us reliant on those companies for their continued performance and investments, which subjects us to a number of risks.*
We have established clinical and commercial collaborations with leading pharmaceutical and biotechnologybiopharmaceutical companies including, Ipsen, Takeda, Genentech, Daiichi Sankyo, Merck (known as MSD outside of the U.S. and Canada), BMS and Sanofi for the development and ultimate commercialization of certain compounds generated from our research and development efforts. Our dependence on our relationships with existing collaborators for the development and commercialization of compounds under the collaborations subjects us to,our products, and our dependence on future collaborators for development and commercialization of additional compounds will subjectthese collaboration partners subjects us to a number of risks, including:including, but not limited to:
we are not ableour collaboration partners’ decision to terminate our collaboration, or their failure to comply with the terms of our collaboration agreements and related ancillary agreements, either intentionally or as a result of negligence or other insufficient performance;
our inability to control the amount and timing of resources that our collaborators or potential future collaborators willcollaboration partners devote to the development or commercialization of drug candidates or to their marketing and distribution;our products;
we are not able to control the U.S. commercial resourcing decisions made and resulting costs incurred by Genentech for cobimetinib, which costs we are obligated to share, in part, underpossibility that our collaboration agreement with Genentech;
collaboratorspartners may stop or delay clinical trials, fail to supply us on a timely basis with the product required for a combination trial, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a drug candidate, repeat or conduct new clinical trials or require a new formulation of a drug candidate for clinical testing;deliver product that fails to meet appropriate quality and regulatory standards;
disputes that may arise between us and our collaboratorscollaboration partners that result in the delay or termination of the research, development or commercialization of our drug candidates, or that diminish or delay receipt of the economic benefits we are entitled to receive under the collaboration, or that result in costly litigation or arbitrationarbitration;
the possibility that diverts management’s attention and resources;

collaboratorsour collaboration partners may experience financial difficulties;difficulties that prevent them from fulfilling their obligations under our agreements;
collaborators may not be successful in their effortsour collaboration partners’ inability to obtain regulatory approvals in a timely manner, or at all;
collaborators may notour collaboration partners’ failure to comply with legal and regulatory requirements relevant to the authorization, marketing, distribution and supply of our marketed products in the territories outside the U.S. where they are approved; and
our collaboration partners’ failure to properly maintain or defend our intellectual property rights or maytheir use of our intellectual property rights or proprietary information in such a way as to invite litigation that could jeopardize or invalidate our proprietary informationintellectual property rights or expose us to potential litigation;
collaborators may not comply with applicable healthcare regulatory laws;
business combinations or significant changes in a collaborator’s business strategy may adversely affect a collaborator’s willingness or ability to complete its obligations under any arrangement;
a collaborator could independently move forward with a competing drug candidate developed either independently or in collaboration with others, including our competitors;
we may be precluded from entering into additional collaboration arrangements with other parties in an area or field of exclusivity;
future collaborators may require us to relinquish some important rights, such as marketing and distribution rights; and
collaborations may be terminated or allowed to expire, which would delay, and may increase the cost of development of our drug candidates.litigation.
If any of these risks materialize, we may not receive collaboration revenuerevenues or otherwise realize anticipated benefits from such collaborations, and our product development efforts and prospects for growth could be delayed or disrupted, all of which could have a material adverse impact on our business, financial condition and results of operations.
Our growth potential is dependent in part upon companies with which we have entered into research collaborations, in-licensing arrangements and similar business development relationships.
To expand our early-stage product pipeline, we have augmented our drug discovery activities with multiple research collaborations and in-licensing arrangements with other companies. Our dependence on our relationships with these research and in-licensing partners subjects us to numerous risks, including, but not limited to:
our research and in-licensing partners’ decision to terminate our relationship, or their failure to comply with the terms of our agreements, either intentionally or as a result of negligent performance;
disputes that may arise between us and our business, operating resultsresearch and in-licensing partners that result in the delay or termination of research activities with respect to any in-licensed assets or supporting technology platforms;
the possibility that our research and in-licensing partners may experience financial difficulties that prevent them from fulfilling their obligations under our agreements;
our research and in-licensing partners’ failure to properly maintain or defend their intellectual property rights or their use of third-party intellectual property rights or proprietary information in such a way as to invite litigation that could jeopardize or invalidate our license to develop these assets or utilize technology platforms;
laws, regulations or practices imposed by countries outside the U.S. that could impact or inhibit scientific research or the development of healthcare products by foreign competitors or otherwise disadvantage healthcare products made by foreign competitors, as well as general political or economic instability in those countries, any of which could complicate, interfere with or impede our relationships with our ex-U.S. research, development and in-licensing partners; and
our research and in-licensing partners’ failure to comply with applicable healthcare laws, as well as established guidelines, laws and regulations related to Good Manufacturing Practice and Good Laboratory Practice.
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If any of these risks materialize, we may not be able to expand our product pipeline or otherwise realize a return on the resources we will have invested to develop these early-stage assets, which could have a material adverse impact on our financial condition could be adversely affected.and prospects for growth.
If third parties upon which we rely to perform clinical trials for cabozantinib in new indications or for new product candidates do not perform as contractually required or expected, we may not be able to obtain regulatory approval for or commercialize cabozantinib for the treatment of additional indicationsor other product candidates beyond advanced RCC and MTC.currently approved indications.
We do not have the ability to conduct clinical trials for cabozantinib or for new potential product candidates independently, including our post-marketing commitments in connection with the approval of COMETRIQ in progressive, metastatic MTC, so we rely on independent third parties for the performance of these trials, such as the U.S. federal government, (including NCI-CTEP, a department of the National Institutes of Health, with whom we have our CRADA), third-party contract research organizations, medical institutions, clinical investigators and contract laboratories to conduct our clinical trials. If these third parties do not successfully carry out their contractual duties or regulatory obligations or meet expected deadlines, or if the third parties must be replaced or if the quality or accuracy of the data they generate or provide is compromised due to their failure to adhere to our clinical trial or data security protocols or regulatory requirements or for other reasons, our preclinical development activities or clinical trials may be extended, delayed, suspended or terminated, and we may not be able to obtain regulatory approval for or commercialize cabozantinib beyond currently approved indications or obtain regulatory approval for additional indications beyondXL092 or our other product candidates. In addition, due to the advanced RCCcomplexity of our research initiatives, we may be unable to engage with third-party contract research organizations that have the necessary experience and MTC.sophistication to help advance our drug discovery efforts, which would impede our ability to identify, develop and commercialize our potential product candidates.
We lack theour own manufacturing and distribution capabilities necessary for us to produce cabozantinibmaterials required for certain preclinical activities and to produce and distribute our products for clinical development or for commercial sale, and relyour reliance on third parties to do so, whichfor these services subjects us to various risks.*
We do not own or operate manufacturing or distribution facilities for chemistry, manufacturing and control development activities, preclinical, clinical or commercial production and distribution of CABOMETYXfor our current products and COMETRIQ.new product candidates. Instead, we have multiple contractual agreements in place withrely on various third-party contract manufacturing organizations who,to conduct these operations on our behalf, manufacture clinical and commercial supplies of CABOMETYX and COMETRIQ, and willbehalf. As our operations continue to do so for the foreseeable future.grow in these areas, we continue to expand our supply chain through secondary third-party contract manufacturers, distributors and suppliers. To establish and manage thisour supply chain requires a significant financial commitment, the creation of numerous third-party contractual relationships and continued oversight of these third parties.parties to fulfill compliance with applicable regulatory requirements. Although we maintain significant resources to directly and effectively oversee the activities and relationships with the companies in our supply chain, effectively, we do not have direct control over their operations.
Our third-party contract manufacturers may not be able to produce or deliver material on a timely basis or manufacture material with the required quality standards, or in the quantity required to meet our preclinical, clinical development and commercial needs and applicable regulatory requirements. Although we have not yet experienced significant production delays or seen significant impairment to our supply chain as a result of the COVID-19 pandemic or the ongoing Russo-Ukrainian War, our third-party contract manufacturers, distributors and suppliers could experience operational delays due to lack of capacity or resources, facility closures and other hardships as a result of these types of global events, which could impact our supply chain by potentially causing delays to or disruptions in the supply of our preclinical, clinical or commercial products. If our third-party contract manufacturers, distributors and suppliers do not continue to supply us with our products or product candidates in a timely fashion and in compliance with applicable quality and regulatory requirements, or if they otherwise fail or refuse to comply with their obligations to us under our supplymanufacturing, distribution and manufacturingsupply arrangements, we may not have adequate remedies for any breach, andbreach. Furthermore, their failure to supply us could impair or preclude our ability to meet ourmeeting commercial or clinical product supply requirements or our supply needs for clinical trials, including those being conducted in collaboration withus or our partners, which could delay product development and future commercialization efforts and have a material adverse impact on our business, financial condition and results of operations. In addition, through our third-party contract manufacturers and data service providers, we continue to provide serialized commercial products as required to comply with the Drug Supply Chain Security Act (DSCSA). If our third-party contract manufacturers or data service providers fail to support our efforts to continue to comply with DSCSA and any future federal or state electronic pedigree requirements, we may face legal penalties or be restricted from selling our products.
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If third-party scientific advisors and contractors we rely on to assist with our drug discovery efforts do not perform as expected, the expansion of our product pipeline may be delayed.
We work with scientific advisors at academic and other institutions, as well as third-party contractors in various locations throughout the world, that assist us in our research and development efforts, including in drug discovery and preclinical development strategy. These third parties are not our business, operating resultsemployees and financial condition couldmay have other commitments or contractual obligations that limit their availability to us. Although these third-party scientific advisors and contractors generally agree not to do competing work, if a conflict of interest between their work for us and their work for another entity arises, we may lose their services. There has also been increased scrutiny surrounding the disclosures of payments made to medical researchers from companies in the pharmaceutical industry, and it is possible that the academic and other institutions that employ these medical researchers may prevent us from engaging them as scientific advisors and contractors or otherwise limit our access to these experts, or that the scientific advisors themselves may now be more reluctant to work with industry partners. Even if these scientific advisors and contractors with whom we have engaged intend to meet their contractual obligations, their ability to perform services may be impacted by increased demand for such services from other companies or by other external factors, such as reduced capacity to perform services, as we experienced in the early stages of the COVID-19 pandemic. If we experience additional delays in the receipt of services, lose work performed by these scientific advisors and contractors or are unable to engage them in the first place, our discovery and development efforts with respect to the matters on which they were working or would work in the future may be significantly delayed or otherwise adversely affected. Additionally, as part of the Ipsen Collaboration Agreement, we are responsible for the manufacturing and supply of finished, labeled cabozantinib products. Failure to meet our supply obligations under the

collaboration could impair Ipsen’s ability to successfully commercialize cabozantinib and generate revenues to which we are entitled under the collaboration.
Risks Related to Our Information Technology and Intellectual Property
Data breaches, cyber-attacks and cyber-attacksother failures in our information technology operations and infrastructure could compromise our intellectual property or other sensitive information, damage our operations and cause significant damageharm to our business and reputation.
In the ordinary course of our business, we and our third-party service providers, such as contract research organizations, collect, maintain and transmit sensitive data on our networks and systems, including our intellectual property and proprietary or confidential business information (such as research data and personal information) and confidential information with respect to our customers, clinical trial patients and our businesscollaboration partners. We have also outsourced significant elements of our information technology infrastructure to third parties and, as a result, such third parties may or could have access to our confidential information. The secure maintenance of this information is critical to our business and reputation. We believe that companiesreputation, and while we have been increasingly subjectenhanced and are continuing to a wide varietyenhance our cybersecurity efforts commensurate with the growth and complexity of security incidents, cyber-attacks and other attempts to gain unauthorized access. These threats can come from a variety of sources, ranging in sophistication from an individual hacker to a state-sponsored attack and motive (including corporate espionage). Cyber threats may be generic, or they may be custom-crafted against our information systems. Cyber-attacks continue to become more prevalent and much harder to detect and defend against. Our network and storage applicationsbusiness, our systems and those of our vendorsthird-party service providers may be subjectvulnerable to unauthorizeda cyber-attack. In addition, we are heavily dependent on the functioning of our information technology infrastructure to carry out our business processes, such as external and internal communications or access by hackersto clinical data and other key business information. Accordingly, both inadvertent disruptions to this infrastructure and cyber-attacks could cause us to incur significant remediation or breached duelitigation costs, result in product development delays, disrupt critical business operations, expend key information technology resources and divert the attention of management.
Although the aggregate impact of cyber-attacks on our operations and financial condition has not been material to operator error, malfeasance or other system disruptions. It is often difficultdate, we and our third-party service providers have frequently been the target of threats of this nature and expect them to anticipate or immediately detect such incidents and the damage caused by such incidents. Thesecontinue. Any future data breaches and anybreach and/or unauthorized access or disclosure of our information or intellectual property could compromise our intellectual property and expose our sensitive business information.information or sensitive business information of our collaboration partners, which may lead to significant liability for us. A data security breach could also lead to public exposure of personal information of our clinical trial patients, customersemployees or others and others. Cyber-attacks could causeresult in harm to our reputation and business, compel us to incur significant remediation costs,comply with federal and/or state breach notification laws and foreign law equivalents including the GDPR, subject us to investigations and mandatory corrective action, or otherwise subject us to liability under laws and regulations that protect the privacy and security of personal information, which could disrupt our business, result in product development delays, disrupt key businessincreased costs or loss of revenue, and/or result in significant financial exposure. Furthermore, the costs of maintaining or upgrading our cybersecurity systems (including the recruitment and retention of experienced information technology professionals, who are in high demand) at the level necessary to keep up with our expanding operations and divert attention of managementprevent against potential attacks are increasing, and key information technology resources. Ourdespite our best efforts, our network security and data recovery measures and those of our vendorsthird-party service providers may still not be adequate to protect against such security breaches and disruptions. These incidentsdisruptions, which could also subject us to liability, expose us to significant expense and cause significantmaterial harm to our reputationbusiness, financial condition and business.results of operations.
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If we are unable to adequately protect our intellectual property, third parties may be able to use our technology, which could adversely affect our ability to compete in the market.
Our success will depend in part upon our ability to obtain patents and maintain adequate protection of the intellectual property related to our technologies and products. The patent positions of biopharmaceutical companies, including our patent position, are generally uncertain and involve complex legal and factual questions. We will be able to protect our intellectual property rights from unauthorized use by third parties only to the extent that our technologies are covered by valid and enforceable patents or are effectively maintained as trade secrets. We will continue to apply for patents covering our technologies and products as, where and when we deem lawful and appropriate. However, these applications may be challenged or may fail to result in issued patents. Our issued patents have been and may in the future be challenged by third parties as invalid or unenforceable under U.S. or foreign laws, or they may be infringed by third parties. As a result,parties, and we are from time to time involved in the defense and enforcement of our patents or other intellectual property rights in a court of law, U.S. Patent and Trademark Office inter partes review or reexamination proceeding, foreign opposition proceeding or related legal and administrative proceeding in the U.S. and elsewhere. The costs of defending our patents or enforcing our proprietary rights in post-issuance administrative proceedings and litigation maycan be substantial and the outcome can be uncertain. An adverse outcome may allow third parties to use our intellectual property without a license and/or allow third parties to introduce generic and other competing products, any of which would negatively impact our business. Third parties may also attempt to invalidate or design around our patents, or assert that they are invalid or otherwise unenforceable, and seek to introduce generic versions of cabozantinib. For example, we received Paragraph IV certification notice letters from MSN and Teva concerning the respective ANDAs that each had filed with the FDA seeking approval to market their respective generic versions of CABOMETYX tablets. Should MSN, Teva or any other third parties receive FDA approval of an ANDA or a 505(b)(2) NDA with respect to cabozantinib, it is possible that such company or companies could introduce generic versions of our marketed products before our patents expire if they do not infringe our patents or if it is determined that our patents are invalid or unenforceable, and the resulting generic competition could have a material adverse impact on our business, financial condition and results of operations.
In addition, because patent applications can take many years to issue, third parties may have pending applications, unknown to us, which may later result in issued patents that cover the production, manufacture, commercialization or use of our product candidates. Our existing patents and any future patents we obtain may not be sufficiently broad to prevent others from practicing our technologies or from developing competing products. They may also be negatively impacted by the decisions of foreign courts, which could limit the protection contemplated by the original regulatory approval and our ability to thwart the development of competing products that might otherwise have been determined to infringe our intellectual property rights. Furthermore, others may independently develop similar or alternative technologies or design around our patents. In addition, our patents may be challenged or invalidated or may fail to provide us with any competitive advantages, if, for example, others were the first to invent or to file patent applications for closely related inventions.
The laws of some foreign countries do not protect intellectual property rights to the same extent as the laws of the U.S., and many companies have encountered significant problems in protecting and defending such rights in foreign jurisdictions. Many countries, including certain countries in Europe,the EU, have compulsory licensing laws based on related EU rules, under which a patent owner may be compelled to grant licenses to third parties (for example, the patent owner has failed to “work” the invention

in that country or the third party has patented improvements). In addition, many countries limit the enforceability of patents against government agencies or government contractors. In these countries, the patent owner may have limited remedies, which could materially diminish the value of the patent. CompulsoryInitiatives seeking compulsory licensing of life-saving drugs isare also becoming increasingly popularprevalent in developing countries either through direct legislation or international initiatives. SuchGovernments in those developing countries could require that we grant compulsory licenses could be extended to includeallow competitors to manufacture and sell their own versions of our products or product candidates, which couldthereby reducing our product sales. Moreover, the Russian Federation has and may further limit our potential revenue opportunities. Moreover,protections on patents originating from “unfriendly countries” (including the U.S.) in response to sanctions relating to the ongoing Russo-Ukrainian War, and in general, the legal systems of certain countries, particularly certain developing countries, do not favor the aggressive enforcement of patent and other intellectual property protection, which makes it difficult to stop infringement. We also rely on trade secret protection for some of our confidential and proprietary information. We have takeninformation, and we are taking security measures to protect our proprietary information and trade secrets, butparticularly in light of recent instances of data loss and misappropriation of intellectual property in the biopharmaceutical industry. However, these measures may not provide adequate protection. Whileprotection, and while we seek to protect our proprietary information by entering into confidentiality agreements with employees, collaboratorspartners and consultants, as well as maintain cybersecurity protocols within our information technology infrastructure, we cannot assure youprovide assurance that our proprietary information will not be disclosed, or that we can
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meaningfully protect our trade secrets. In addition, our competitors may independently develop substantially equivalent proprietary information or may otherwise gain access to our trade secrets.
Litigation or third-party claims of intellectual property infringement could require us to spend substantial time and money and adversely affect our ability to develop and commercialize products.
Our commercial success depends in part upon our ability to avoid infringing patents and proprietary rights of third parties and not to breach any licenses that we have entered into with regard to our technologies and the technologies of third parties. Other parties have filed, and in the future are likely to file, patent applications covering products and technologies that we have developed or intend to develop. If patents covering technologies required by our operations are issued to others, we may have to obtain licenses from third parties, which may not be available on commercially reasonable terms, or at all, and may require us to pay substantial royalties, grant a cross-license to some of our patents to another patent holder or redesign the formulation of a product candidate so that we do not infringe third-party patents, which may be impossible to obtainaccomplish or could require substantial time and expense. Third partiesIn addition, we may accuse usbe subject to claims that our employees or independent contractors have inadvertently or otherwise used or disclosed trade secrets or other proprietary information of employing their proprietary technology without authorization. In addition,former employers, or that they used or sought to use patent inventions belonging to their former employers. Furthermore, third parties may obtain patents that relate to our technologies and claim that use of such technologies infringes on their patents.patents or otherwise employs their proprietary technology without authorization. Regardless of their merit, such claims could require us to incur substantial costs includingand divert the diversionattention of management and key technical personnel in defending ourselves against any such claims or enforcing our own patents. In the event that aof any third party’s successful claim of patent infringement is brought against us,or misappropriation of trade secrets, we may lose valuable intellectual property rights or personnel, which could impede or prevent the achievement of our product development goals, or we may be required to pay damages and obtain one or more licenses from these third parties.parties, subjecting us to substantial royalty payment obligations. We may not be able to obtain these licenses at aon commercially reasonable cost,terms, or at all. Defense of any lawsuit or failure to obtain any of these licenses could adversely affect our ability to develop and commercialize products.
We may be subjectRisks Related to damages resulting from claimsOur Operations, Managing Our Growth and Employee Matters
If the COVID-19 pandemic is further prolonged or becomes more severe, our business operations and corresponding financial results could suffer, which could have a material adverse impact on our financial condition and prospects for growth.
To date, the COVID-19 pandemic has had a modest impact on our business operations, in particular with respect to our clinical trial, drug discovery and commercial activities. For example, to varying degrees and at different rates across our clinical trials, we experienced declines in screening and enrollment activity during the early days of the COVID-19 pandemic, as well as delays in new site activations and restrictions on the access to treatment sites that we, our employees or independent contractors have wrongfully used or disclosed alleged trade secrets of their former employers.
Many of our employees and independent contractors were previously employed at universities or other biotechnology, biopharmaceutical or pharmaceutical companies, including our competitors or potential competitors. We may be subject to claims that these employees, independent contractors or we have inadvertently or otherwise used or disclosed trade secrets or other proprietary information of their former employers, or used or sought to use patent inventions belonging to their former employers. Litigation may beis necessary to defend against these claims. Even if we are successfulmonitor clinical study progress and administration. As the COVID-19 pandemic continues to have a significant presence in defending against these claims, litigationvarious parts of the world, particularly with the potential emergence of new variants that may prove especially contagious or virulent, the impact on our clinical development operations could result in substantial costs and divert management’s attention. If we fail in defending such claims, in addition to paying money claims, we may lose valuable intellectual property rightscontinue or personnel. A loss of key research personnel and/grow more severe. We anticipate that a further prolonged, or their work productmore severe, global public health crisis could hamper or preventlimit our ability to commercializeidentify and work with clinical investigators at clinical trial sites globally to enroll, initiate and maintain treatment per protocol of patients for our ongoing clinical trials. Disruptions to medical and administrative operations at clinical trial sites, including staffing and materials shortages and the implementation of crisis management initiatives, have and may continue to reduce personnel and other resources necessary to conduct our clinical trials, which could further delay some of our clinical trial plans or may require certain trials to be temporarily suspended. In addition, increased costs connected with our efforts to mitigate the adverse impacts resulting from the COVID-19 pandemic on our clinical trials could cause the expenses we incur in conducting those clinical trials to increase considerably. Depending upon the duration and severity of the COVID-19 pandemic, we could also experience delays in planning and conducting new clinical trials of the investigative product candidates entering and advancing through our development pipeline, which could severely harmincrease the operating expenses associated with these trials and adversely affect their timelines for completion and ultimately our business.ability to obtain regulatory approvals.
Risks RelatedBoth drug discovery work in our laboratories and outsourced drug discovery activities have fully resumed following temporary suspensions during the early days of the COVID-19 pandemic; however, we may be unable to Employeesmaximize the potential of these programs due to the imposition of increased safety protocols, and Locationshould the effects of the COVID-19 pandemic become more severe, we may have to again scale back or suspend activities in the future. We are also reliant on laboratory materials manufactured and distributed from areas impacted by both the COVID-19 pandemic and other natural disasters, for which supply has become limited. If we are unable to obtain the requisite materials to conduct our planned
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drug discovery activities, we may be required to redirect the focus of, or even suspend, such activities. Should the COVID-19 pandemic be further prolonged or grow in severity, we may ultimately be unable to achieve our drug discovery and preclinical development objectives within the previously disclosed timelines, which could have a material adverse impact on our prospects for growth.
In addition, it remains possible that the evolving dynamics of the COVID-19 pandemic may require further modifications to our standard sales and marketing practices, including shifts from in-person back to primarily telephonic and virtual interactions with healthcare professionals. Such changes in our commercial operations could negatively impact the flow of important information regarding our medicines, which along with obstacles to patient access to healthcare professionals, could diminish sales of our marketed products.
These continuing or future effects of the COVID-19 pandemic could materially and adversely affect our business, financial condition, results of operations and growth prospects, and exacerbate the other risks and uncertainties described elsewhere in this ‘‘Risk Factors’’ section.
If we are unable to manage our growth, there could be a material adverse impact on our business, financial condition and results of operations, and our prospects may be adversely affected.
We have experienced and expect to continue to experience growth in the number of our employees and in the scope of our operations.operations, in particular as we continue to expand the cabozantinib franchise into new indications and grow our pipeline of product candidates. This growth places significant demands on our management operational and financial resources, and our current and planned personnel systems, procedures and controlsoperating practices may not be adequate to support our growth. To effectively manage our growth, we must continue to improve existing, and implement new, facilities, operational and financial systems, and procedures and controls, and mustas well as expand, train and manage our growing employee base, and there can be no assurance that we will effectively manage our growth without experiencing operating inefficiencies or control deficiencies. We expect that we may needcontinue to increase our management personnel to oversee our expanding operations, and recruiting

and retaining qualified individuals is difficult. In addition, the physical expansion of our operations may lead to significant costs and may divert our management and capital resources. If we are unable to manage our growth effectively, including as a result of the COVID-19 pandemic or otherwise, or we are unsuccessful in recruiting qualified management personnel, there could be a material adverse impact on our business, financial condition and results of operations and prospects may be adversely affected.operations.
The loss of key personnel or the inability to retain and, where necessary, attract additional personnel could impair our ability to operate and expand our operations.
We are highly dependent upon the principal members of our management, as well as clinical, commercial and scientific staff, the loss of whose services might adversely impact the achievement of our objectives. Also, we may not have sufficient personnel to execute our business plan.plans. Retaining and, where necessary, recruiting qualified clinical, commercial, scientific and scientificpharmaceutical operations personnel will be critical to support activities related to advancing the development programprograms for the cabozantinib franchise and our other compounds,product candidates, successfully executing upon our commercialization plan for the cabozantinib franchise and our internal proprietary research and development efforts. Competition is intense for experienced clinical, commercial, scientific and scientificpharmaceutical operations personnel, and we may be unable to retain or recruit such personnel with the expertise or experience necessary to allow us to successfully develop and commercialize our products. Further, all of our employees are employed “at will” and, therefore, may leave our employment at any time.
Our collaborations with outside scientists may be subject to restriction and change.
We work with scientific and clinical advisors and collaborators at academic and other institutions that assist us in our research and development efforts. These advisors and collaborators are not our employees and may have other commitments that limit their availability to us. Although these advisors and collaborators generally agree not to do competing work, if a conflict of interest between their work for us and their work for another entity arises, we may lose their services. In such a circumstance, we may lose work performed by them, and our development efforts with respect to the matters on which they were working may be significantly delayed or otherwise adversely affected. In addition, although our advisors and collaborators sign agreements not to disclose our confidential information, it is possible that valuable proprietary knowledge may become publicly known through them.
Our headquarters are located near known earthquake fault zones, and the occurrence of an earthquake or other disaster could damage our facilities and equipment, which could harm our operations.
Our headquarters are located in the San Francisco Bay Area, California and, therefore our facilities are vulnerable to damage from earthquakes. We do not carry earthquake insurance. We are also vulnerable to damage from other types of disasters, including fire, floods, power loss, communications failures, terrorism and similar events since any insurance we may maintain may not be adequate to cover our losses. If any disaster were to occur, our ability to operate our business at our facilities could be seriously, or potentially completely, impaired. In addition, the unique nature of our research activities could cause significant delays in our programs and make it difficult for us to recover from a disaster. Accordingly, an earthquake or other disaster could materially and adversely harm our ability to conduct business.
We plan to move our headquarters and may face disruption and turnover of employees.*
In 2018, we plan to move our corporate headquarters from South San Francisco, California to Alameda, California. As a result, we expect to incur additional expenses, including those related to tenant improvements to and furniture for the new corporate headquarters, as well as moving and exit costs, and may encounter disruption of operations related to the move, all of which could have an adverse effect on our financial condition and results of operations. In addition, relocation of our corporate headquarters may make it more difficult to retain certain of our employees, and any resulting need to recruit and train new employees could be disruptive to our business.
Facility security breaches may disrupt our operations, subject us to liability and harm our operating results.
Any break-in or trespass at our facilities that results in the misappropriation, theft, sabotage or any other type of security breach with respect to our proprietary and confidential information, including research or clinical data, or that results in damage to our research and development equipment and assets, could subject us to liability and have a material adverse impact on our business, operating results and financial condition.
Risks Related to Environmental and Product Liability
We use hazardous chemicals and radioactive and biological materials in our business. Any claims relating to improper handling, storage or disposal of these materials could be time consuming and costly.

Our research and development processes involve the controlled use of hazardous materials, including chemicals and radioactivebiological materials, and biological materials. Ourour operations can produce hazardous waste products. We cannot eliminate the risk of accidental contamination or discharge, andor any resultant injury from these materials. Federal, statematerials, and local laws and regulations govern the use, manufacture, storage, handling and disposal of hazardous materials. Wewe may face liability under applicable laws for any injury or contamination that results from our use or the use by our collaboration partners or other third parties of these materials, and suchmaterials. Such liability may exceed our insurance coverage and our total assets. Complianceassets, and in addition, we may be required to indemnify our collaboration partners against all damages and other liabilities arising out of our development activities or products produced in connection with our collaborations with them. Moreover, our continued compliance with environmental laws and regulations may be expensive, and current or future environmental regulations may impair our research, development and production efforts.
In addition, our collaborators may use hazardous materials in connection with our collaborative efforts. In the event
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Table of a lawsuit or investigation, we could be held responsible for any injury caused to persons or property by exposure to, or release of, these hazardous materials used by these parties. Further, we may be required to indemnify our collaborators against all damages and other liabilities arising out of our development activities or products produced in connection with these collaborations.Contents
We face potential product liability exposure far in excess of our limited insurance coverage.
We may be held liable if any product we or our collaboratorscollaboration partners develop or commercialize causes injury or is found otherwise unsuitable during product testing, manufacturing, marketing or sale. Regardless of merit or eventual outcome, product liability claims could result in decreased demand for our products and product candidates, injury to our reputation, withdrawal of patients from our clinical trials, product recall, substantial monetary awards to third parties and the inability to commercialize any products that we may develop. These claims might be made directly by consumers, health care providers, pharmaceutical companies or others selling or testing our products.develop in the future. We have obtainedmaintain limited product liability insurance coverage for our clinical trials and commercial activities for cabozantinib in the amount of $20.0 million per occurrence and $20.0 million in the aggregate.cabozantinib. However, our insurance may not reimburse us or may not be sufficient to reimburse us for expenses or losses we may suffer. Moreover, if insurance coverage becomes more expensive, we may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses due to liability. On occasion, juries have awarded large judgments in class action lawsuits for claims based on drugs that had unanticipated side effects. In addition, the pharmaceutical, biopharmaceutical and biotechnology industries, in general, have been subject to significant medical malpractice litigation. A successful product liability claim or series of claims brought against us could harm our reputation and business and would decrease our cash reserves.
Risks Related to Our Common Stock
We expect that our quarterly results of operations will fluctuate, and this fluctuation could cause our stock price to decline, causing investor losses.*
Our quarterly operating results have fluctuated in the past and are likely to fluctuate in the future. A number of factors, many of which we cannot control, could subject our operating results to volatility, including:
the commercial success of both CABOMETYX and COMETRIQ and the revenues we generate from those approved products;
customer ordering patterns for CABOMETYX and COMETRIQ, which may vary significantly from period to period;
the overall level of demand for CABOMETYX and COMETRIQ, including the impact of any competitive products and the duration of therapy for patients receiving CABOMETYX or COMETRIQ;
the commercial success of COTELLIC and the revenues generated through our share of related profits and losses for the commercialization of COTELLIC in the U.S. and royalties from COTELLIC sales outside the U.S. under our collaboration with Genentech;
costs associated with maintaining our sales, marketing, medical affairs and distribution capabilities for CABOMETYX, COMETRIQ and COTELLIC;
our ability to obtain regulatory approval for cabozantinib as a treatment for patients with previously untreated advanced RCC;
our ability to timely prepare and submit an sNDA for cabozantinib as a treatment for patients with advanced HCC;
the achievement of stated regulatory and commercial milestones, under our collaboration agreements;

the progress and scope of other development and commercialization activities for cabozantinib and our other compounds;
future clinical trial results;
our future investments in the expansion of our pipeline through drug discovery and corporate development activities;
the inability to obtain adequate product supply for any approved drug product or inability to do so at acceptable prices;
recognition of upfront licensing or other fees or revenues;
payments of non-refundable upfront or licensing fees, or payment for cost-sharing expenses, to third parties;
the introduction of new technologies or products by our competitors;
the timing and willingness of collaborators to further develop or, if approved, commercialize our product candidates out-licensed to them;
the termination or non-renewal of existing collaborations or third-party vendor relationships;
regulatory actions with respect to our product candidates and any approved products or our competitors’ products;
disputes or other developments relating to proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies;
the timing and amount of expenses incurred for clinical development and manufacturing of cabozantinib;
adjustments to expenses accrued in prior periods based on management’s estimates after the actual level of activity relating to such expenses becomes more certain;
the impairment of acquired goodwill and other assets;
additions and departures of key personnel;
general and industry-specific economic conditions that may affect our or our collaborators’ research and development expenditures; and
other factors described in this “Risk Factors” section.
Due to the possibility of fluctuations in our revenues and expenses, we believe that quarter-to-quarter comparisons of our operating results are not a good indication of our future performance. As a result, in some future quarters, our operating results may not meet the expectations of securities analysts and investors, which could result in a decline in the price of our common stock.
Our stock price has been and may in the future be extremelyhighly volatile.*
The trading price of our common stock has been highly volatile, and we believe the trading price of our common stock willit may remain highly volatile and mayor fluctuate substantially due to factors such as the following, many of which we cannot control:
adverse results or delays in our or our collaborators’ clinical trials;
the announcement of FDA or other regulatory approval or non-approval, or delays in the FDA or other regulatory review process ofwith respect to cabozantinib, XL092 or our collaborators’other product candidates, our collaboration partners’ product candidates being developed in combination with either cabozantinib, XL092 or our other product candidates, or those of our competitors or actions taken by regulatory agencies with respect to our, our collaborators’ or our competitors’ clinical trials;product candidates;
the commercial successperformance of both CABOMETYX and COMETRIQ and the revenues we generate from those approved products;products, including royalties paid under our collaboration and license agreements;
adverse or inconclusive results or announcements related to our or our collaboration partners’ clinical trials or delays in those clinical trials;
the timing of achievement of our clinical, regulatory, partnering, commercial and other milestones such asfor the commencement of clinical development, the completion of a clinical trial, the filing for regulatory approval or the establishment of collaborative arrangements for cabozantinib franchise, XL092 or any of our other programsproduct candidates or compounds;programs;
our ability to make future investments in the expansion of our pipeline through drug discovery, including future research collaborations, in-licensing arrangements and other strategic transactions;
our ability to obtain the materials and services, including an adequate product supply for any approved drug product, from our third-party vendors or do so at acceptable prices;
the timing and amount of expenses incurred for clinical development and manufacturing of cabozantinib, XL092 and our other product candidates;
actions taken by regulatory agencies, both in the U.S. and abroad, with respect to cabozantinib or our clinical trials for cabozantinib;cabozantinib, XL092 or our other product candidates;
unanticipated regulatory actions taken by the FDA as a result of changing FDA standards and practices concerning the review of product candidates, including approvals at earlier stages of clinical development or with lesser developed data sets and expedited reviews;
the announcement of new products or clinical trial data by our competitors;
the announcement of regulatory applications, such as MSN’s and Teva’s respective ANDAs, seeking approval of generic versions of our marketed products;
quarterly variations in our or our competitors’ results of operations;
developmentschanges in our relationships with our collaborators,collaboration partners, including the termination or modification of our agreements;agreements, or other events or conflicts that may affect our collaboration partners’ timing and willingness to develop, or if approved, commercialize our products and product candidates out-licensed to them;
the announcement of an in-licensed product candidate or strategic acquisition;

conflicts or litigation with our collaborators;
litigation, including intellectual property infringement and product liability lawsuits, involving us;
failure to achieve operating results projected by securities analysts;
changes in earnings estimates or recommendations by securities analysts;analysts, or financial guidance from our management team, and any failure to achieve the operating results projected by securities analysts or by our management team;
the entry into new financing arrangements;
developments in the biotechnology, biopharmaceutical or pharmaceutical industry;
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sales of large blocks of our common stock or sales of our common stock by our executive officers, directors and significant stockholders;
additions and departures of key personnel or board members;
FDA or international regulatory actions;
third-party coverage and reimbursement policies;
the disposition of any of our technologies or compounds; and
general market, economicmacroeconomic and political conditions and other factors, including factors unrelated to our operating performance or the operating performance of our competitors.
These and other factors as well as general economic, political and market conditions, may materially adversely affectcould have material adverse impact on the market price of our common stock. In addition, the stock markets in general, and the markets for biotechnology and pharmaceutical stocks in particular, have historically experienced significant volatility that has often been unrelated or disproportionate to the operating performance of particular companies. For example, negative publicity regarding drug pricing and price increases by pharmaceutical companies has negatively impacted, and may continue to negatively impact, the markets for biotechnology and pharmaceutical stocks. Likewise, as a result of the United Kingdom’s pending withdrawal from the European Union and/or significant changes in U.S. social,or global political regulatory and economicmacroeconomic conditions, or in laws andincluding historically high inflation, as well as policies governing foreign trade and health carehealthcare spending and delivery, includingor the potential repeal and/or replacement of all or portions of the Patient Protection and Affordable Care Act, as amended by the Health Care Education Reconciliation Act, or greater restrictions on free trade stemming from Trump Administration policies,ongoing Russo-Ukrainian War, the financial markets could continue to experience significant volatility that could also continue to negatively impact the markets for biotechnology and pharmaceutical stocks. These broad market fluctuations have adversely affected and may in the future adversely affect the trading price of our common stock. Excessive volatility may continue for an extended period of time following the date of this report.
In the past, following periods of volatility in the market price of a company’s securities, securities class action litigation has often been instituted.initiated. A securities class action suit against us could result in substantial costs and divert management’sthe attention and resources,of management, which could have a material and adverse effectimpact on our business.
Future salesbusiness, financial condition and results of our common stock or the perception that such sales or conversions may occur, may depress our stock price.
A substantial number of shares of our common stock are reserved for issuance upon the exercise of stock options, upon vesting of restricted stock unit awards, upon a purchase under our employee stock purchase plan and upon exercise of certain outstanding warrants. The issuance and sale of substantial amounts of our common stock or the perception that such issuances and sales may occur, could adversely affect the market price of our common stock and impair our ability to raise capital through the sale of additional equity or equity-related securities in the future at a time and price that we deem appropriate.operations.
Anti-takeover provisions in our charter documents and under Delaware law could make an acquisition of us, which may be beneficial to our stockholders, more difficult and may prevent or deter attempts by our stockholders to replace or remove our current management, which could cause the market price of our common stock to decline.
Provisions in our corporate charter and bylaws may discourage, delay or prevent an acquisition of us, a change in control, or attempts by our stockholders to replace or remove members of our current Board of Directors. Because our Board of Directors is responsible for appointing the members of our management team, these provisions could in turn affect any attempt by our stockholders to replace current members of our management team. These provisions include:
a classified Board of Directors;
a prohibition on actions by our stockholders by written consent;
the inability of our stockholders to call special meetings of stockholders;

the ability of our Board of Directors to issue preferred stock without stockholder approval, which could be used to institute a “poison pill” that would work to dilute the stock ownership of a potential hostile acquirer, effectively preventing acquisitions that have not been approved by our Board of Directors; and
limitations on the removal of directors; and
advance notice requirements for director nominations and stockholder proposals.
Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, 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 ability to use net operating losses to offset future taxable income may be subject to limitations.
Under the Internal Revenue Code, or the Code, and similar state provisions, certain substantial changes in our ownership could result in an annual limitation on the amount of net operating loss carry-forwards that can be utilized in future years to offset future taxable income. The annual limitation may result in the expiration of net operating losses and credit carry-forwards before utilization. We concluded, as of December 31, 2016, that an ownership change, as defined under Section 382, had not occurred. However, if there is an ownership change under Section 382 of the Code in the future, we may not be able to utilize a material portion of our net operating losses, or NOLs. Furthermore, our ability to utilize our NOLs, other than the NOLs expected to be utilized to offset income in 2017, is conditioned upon our attaining profitability and generating U.S. federal taxable income. We have incurred significant cumulative operating losses since our inception; thus, we do not know whether or when we will generate the U.S. federal taxable income necessary to utilize our remaining NOLs. A full valuation allowance has been provided for the entire amount of our remaining NOLs.
Item 2. Unregistered Sales of Equity Securities and Use of Proceeds    
On September 11, 2017, we issued an aggregate of 877,451 shares of common stock pursuant to the cashless exercises of warrants issued to an accredited investor transferee that were originally issued to Deerfield Partners, L.P. and Deerfield International Master Fund, L.P. in January 2014 in connection with a financing arrangement. The warrants were exercisable for an aggregate of 1,000,000 shares of common stock and had an exercise price of $3.445 per share. The number of shares issued upon exercise was net of 122,549 shares withheld to effect the cashless exercise of such warrants in accordance with their terms.Not applicable.
All of the shares of common stock identified above were issued pursuant to the exemption from the registration requirements of the Securities Act of 1933, as amended, or the Securities Act, afforded by Section 3(a)(9) of the Securities Act. We received no cash proceeds from such issuances of common stock.
Item 3. Defaults Upon Senior Securities
Not applicable.
Item 4. Mine Safety Disclosures
Not applicable.
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Item 5. Other Information
Not applicable.
Item 6. Exhibits
Exhibit
Number
Exhibit DescriptionIncorporation by Reference
Filed
Herewith
FormFile Number
Exhibit/
Appendix
Reference
Filing Date
3.110-Q000-302353.18/5/2021
3.28-K000-302353.13/3/2021
10.1X
10.2X
10.3X
31.1X
31.2X
32.1‡X
101.INSXBRL Instance DocumentThe XBRL instance document does not appear in the Interactive Data File because its XBRL tags are embedded within the Inline XBRL document.
101.SCHInline XBRL Taxonomy Extension Schema DocumentX
101.CALInline XBRL Taxonomy Extension Calculation Linkbase DocumentX
101.DEFInline XBRL Taxonomy Extension Definition Linkbase DocumentX
101.LABInline XBRL Taxonomy Extension Labels Linkbase DocumentX
101.PREInline XBRL Taxonomy Extension Presentation Linkbase DocumentX
This certification accompanies this Quarterly Report on Form 10-Q, is not deemed filed with the SEC and is not to be incorporated by reference into any filing of Exelixis, Inc. under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended (whether made before or after the date of this Quarterly Report on Form 10-Q), irrespective of any general incorporation language contained in such filing.

58
Exhibit
Number
 Exhibit Description Incorporation by Reference 
Filed
Herewith
Form File Number 
Exhibit/
Appendix
Reference
 Filing Date 
3.1  10-K 000-30235 3.1 3/10/2010  


Table of Contents
Exhibit
Number
 Exhibit Description Incorporation by Reference 
Filed
Herewith
Form File Number 
Exhibit/
Appendix
Reference
 Filing Date 
3.2  10-K 000-30235 3.2 3/10/2010  
3.3  8-K 000-30235 3.1 5/25/2012  
3.4  8-K 000-30235 3.1 10/15/2014  
3.5  8-K 000-30235 3.2 10/15/2014  
3.6  8-K 000-30235 3.1 12/5/2011  
4.1  
S-1,
as amended
 333-96335 4.1 4/7/2000  
10.1*  10-Q 000-30235 10.5 8/2/2017  
10.2**          X
10.3          X
10.4          X
12.1          X
31.1          X
31.2          X
32.1‡          X
101.INS XBRL Instance Document         X
101.SCH XBRL Taxonomy Extension Schema Document         X
101.CAL XBRL Taxonomy Extension Calculation Linkbase Document         X
101.DEF XBRL Taxonomy Extension Definition Linkbase Document         X
101.LAB XBRL Taxonomy Extension Labels Linkbase Document         X
101.PRE XBRL Taxonomy Extension Presentation Linkbase Document         X

*Confidential treatment granted for certain portions of this exhibit.
**Confidential treatment requested for certain portions of this exhibit.
This certification accompanies this Quarterly Report on Form 10-Q, is not deemed filed with the SEC and is not to be incorporated by reference into any filing of Exelixis, Inc. under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended (whether made before or after the date of this Quarterly Report on Form 10-Q), irrespective of any general incorporation language contained in such filing.


SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized. 
EXELIXIS, INC.
August 9, 2022
EXELIXIS, INC.
By:
November 1, 2017By:
/s/ CHRISTOPHER J. SENNER
DateChristopher J. Senner
DateChristopher J. Senner
Executive Vice President and Chief Financial Officer
(Duly Authorized Officer and Principal Financial and Accounting Officer)

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