Protara Therapeutics (TARA) 10-K 13 Mar 19 2018 FY Annual report Financial data

Document And Entity Information

Document And Entity Information - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2018	Mar. 08, 2019	Jun. 30, 2018
Document Information [Line Items]
Entity Registrant Name	PROTEON THERAPEUTICS INC
Entity Central Index Key	0001359931
Trading Symbol	prto
Current Fiscal Year End Date	--12-31
Entity Filer Category	Non-accelerated Filer
Entity Current Reporting Status	Yes
Entity Voluntary Filers	No
Entity Well-known Seasoned Issuer	No
Entity Emerging Growth Company	true
Entity Small Business	true
Entity Common Stock, Shares Outstanding (in shares)		19,243,651
Entity Public Float			$ 26.2
Document Type	10-K
Document Period End Date	Dec. 31, 2018
Document Fiscal Year Focus	2018
Document Fiscal Period Focus	FY
Amendment Flag	false
Entity Shell Company	false
Entity Ex Transition Period	false

Consolidated Balance Sheets

Consolidated Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Current assets:
Cash and cash equivalents	$ 19,371	$ 21,170
Available-for-sale investments	2,496	20,971
Prepaid expenses and other current assets	1,369	1,339
Total current assets	23,236	43,480
Property and equipment, net	263	259
Restricted cash	22	22
Other non-current assets		218
Total assets	23,521	43,979
Current liabilities:
Accounts payable	441	291
Accrued expenses	2,637	8,949
Total current liabilities	3,078	9,240
Total liabilities	3,078	9,240
Commitments and contingencies (Note 6)
Stockholders’ equity:
Preferred stock
Common stock, $0.001 par value, 100,000,000 shares authorized at December 31, 2018 and 2017; 19,243,651 and 17,674,729 shares issued and outstanding at December 31, 2018 and 2017, respectively	19	18
Additional paid-in capital	209,366	202,953
Accumulated deficit	(210,470)	(189,741)
Accumulated other comprehensive income (loss)	5	(14)
Total stockholders’ equity	20,443	34,739
Total liabilities and stockholders’ equity	23,521	43,979
Series A Convertible Preferred Stock [Member]
Stockholders’ equity:
Preferred stock	$ 21,523	$ 21,523

Consolidated Balance Sheets (Pa

Consolidated Balance Sheets (Parentheticals) - $ / shares	Dec. 31, 2018	Dec. 31, 2017
Preferred stock, par value (in dollars per share)	$ 0.001	$ 0.001
Preferred stock, shares authorized (in shares)	10,000,000	10,000,000
Common stock, par value (in dollars per share)	$ 0.001	$ 0.001
Common stock, shares authorized (in shares)	100,000,000	100,000,000
Common stock, shares issued (in shares)	19,243,651	17,674,729
Common stock, shares outstanding (in shares)	19,243,651	17,674,729
Series A Convertible Preferred Stock [Member]
Preferred stock, par value (in dollars per share)	$ 0.001	$ 0.001
Preferred stock, shares authorized (in shares)	22,000	22,000
Preferred stock, shares issued (in shares)	22,000	22,000
Preferred stock, shares outstanding (in shares)	22,000	22,000

Consolidated Statements of Oper

Consolidated Statements of Operations and Comprehensive Loss - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Operating expenses:
Research and development	$ 11,848	$ 21,686	$ 18,869
General and administrative	9,524	8,676	9,836
Total operating expenses	21,372	30,362	28,705
Loss from operations	(21,372)	(30,362)	(28,705)
Other income:
Investment income	436	259	193
Other income (expense), net	207	139	(14)
Total other income	643	398	179
Net loss	(20,729)	(29,964)	(28,526)
Foreign currency translation adjustment	(1)	6
Unrealized gain (loss) on available-for-sale investments	20	(20)	11
Comprehensive loss	(20,710)	(29,978)	(28,515)
Reconciliation of net loss to net loss attributable to common stockholders:
Net loss	(20,729)	(29,964)	(28,526)
Accretion of convertible preferred stock to redemption value		(6,747)
Net loss attributable to common stockholders	$ (20,729)	$ (36,711)	$ (28,526)
Net loss per share attributable to common stockholders - basic and diluted (in dollars per share)	$ (1.15)	$ (2.13)	$ (1.72)
Weighted-average common shares outstanding used in net loss per share attributable to common stockholders - basic and diluted (in shares)	18,102,219	17,274,326	16,561,799
Included in operating expenses, above, are the following amounts for non-cash stock-based compensation expense:
Allocated share-based compensation	$ 3,429	$ 3,227	$ 3,343
Research and Development Expense [Member]
Included in operating expenses, above, are the following amounts for non-cash stock-based compensation expense:
Allocated share-based compensation	1,142	1,109	1,114
General and Administrative Expense [Member]
Included in operating expenses, above, are the following amounts for non-cash stock-based compensation expense:
Allocated share-based compensation	$ 2,287	$ 2,118	$ 2,229

Statements of Stockholders' Equ

Statements of Stockholders' Equity - USD ($) $ in Thousands	Series A Preferred Stock [Member]Preferred Stock [Member]	Series A Preferred Stock [Member]Additional Paid-in Capital [Member]	Series A Preferred Stock [Member]	Common Stock [Member]	Additional Paid-in Capital [Member]	Retained Earnings [Member]	AOCI Attributable to Parent [Member]	Total
Balance (in shares) at Dec. 31, 2015				16,501,500
Balance at Dec. 31, 2015				$ 16	$ 194,651	$ (131,251)	$ (11)	$ 63,405
Exercise of common stock options (in shares)				97,521
Exercise of common stock options				$ 1	196			197
Issuance of common stock upon ESPP purchase (in shares)				4,538
Issuance of common stock upon ESPP purchase					11			11
Stock-based compensation expense					3,343			3,343
Unrealized gain (loss) on available-for-sale investments							11	11
Net loss						(28,526)		(28,526)
Balance (in shares) at Dec. 31, 2016				16,603,559
Balance at Dec. 31, 2016				$ 17	198,201	(159,777)		38,441
Exercise of common stock options (in shares)				74,001
Exercise of common stock options					108			108
Issuance of common stock upon ESPP purchase (in shares)				100,358
Issuance of common stock upon ESPP purchase					130			130
Stock-based compensation expense					3,227			3,227
Unrealized gain (loss) on available-for-sale investments								(20)
Net loss						(29,964)		(29,964)
Issuance of stock, net of issuance costs (in shares)	22,000			896,811
Issuance of stock, net of issuance costs	$ 14,776	$ 6,747	$ 21,523	$ 1	1,287			1,288
Accretion of Series A Convertible Preferred Stock	$ 6,747				(6,747)
Other comprehensive gain/(loss)							(14)	(14)
Balance (in shares) at Dec. 31, 2017	22,000			17,674,729
Balance at Dec. 31, 2017	$ 21,523			$ 18	202,953	(189,741)	(14)	34,739
Issuance of common stock upon ESPP purchase (in shares)				74,343
Issuance of common stock upon ESPP purchase					132			132
Stock-based compensation expense					3,429			3,429
Unrealized gain (loss) on available-for-sale investments								20
Net loss						(20,729)		(20,729)
Issuance of stock, net of issuance costs (in shares)				1,494,579
Issuance of stock, net of issuance costs				$ 1	2,852			2,853
Other comprehensive gain/(loss)							19	19
Balance (in shares) at Dec. 31, 2018	22,000			19,243,651
Balance at Dec. 31, 2018	$ 21,523			$ 19	$ 209,366	$ (210,470)	$ 5	$ 20,443

Consolidated Statements of Cash

Consolidated Statements of Cash Flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Operating activities
Net loss	$ (20,729)	$ (29,964)	$ (28,526)
Reconciliation of net loss to net cash used in operating activities:
Depreciation	115	148	123
Amortization of premium/discount on available-for-sale securities	(51)	(2)	131
Unrealized loss on forward foreign currency contracts included in net income			(127)
Foreign currency remeasurement (loss)/gain	(25)	(173)	76
Stock-based compensation	3,429	3,227	3,343
Changes in:
Prepaid expenses and other assets	141	297	246
Interest receivable	49	(46)	(26)
Accounts payable and accrued expenses	(6,162)	4,161	1,073
Net cash used in operating activities	(23,233)	(22,352)	(23,687)
Investing activities
Purchases of available-for-sale investments	(15,443)	(32,942)	(39,756)
Proceeds from maturities of available-for-sale investments	31,990	16,878	59,943
Proceeds from sale of available-for-sale investments	1,999
Purchase of property and equipment	(119)	(35)	(271)
Net cash provided by (used in) investing activities	18,427	(16,099)	19,916
Financing activities
Proceeds from issuance of common stock, net of issuance costs	2,853	1,288
Proceeds from the issuance of Series A Convertible Preferred Stock, net of issuance costs		21,523
Proceeds from issuance of common stock under ESPP	132	130	11
Exercise of stock options		108	197
Net cash provided by financing activities	2,985	23,049	208
Effect of exchange rate changes on cash	22	180	(76)
Decrease in cash, cash equivalents and restricted cash	(1,799)	(15,222)	(3,639)
Cash, cash equivalents and restricted cash, beginning of period	21,192	36,414	40,045
Cash, cash equivalents and restricted cash, end of period	19,393	21,192	36,414
Supplemental disclosure of non-cash investing and financing activities
Accretion of convertible preferred stock		$ 6,747

Note 1 - Organization and Opera

Note 1 - Organization and Operations	12 Months Ended
	Dec. 31, 2018
Notes to Financial Statements
Nature of Operations [Text Block]	1. Organization and Operations The Company Proteon Therapeutics, Inc. (the “Company”) is a late-stage biopharmaceutical company focused on the development of novel, first June 2001 March 24, 2006. The Company devotes substantially all of its efforts to product research and development, initial market development and raising capital. The Company has not third Liquidity and Going Concern As of December 31, 2018, $21.9 first 2020. $210.5 December 31, 2018. Based on these available cash resources, the Company does not twelve 10 The Company’s plans to address this condition include pursuing one none • raise additional funding through the possible sale of additional shares of the Company’s common stock, including public or private equity financings, and/or possible debt financings; and • use the worldwide commercial rights to vonapanitase currently held by the Company to establish partnerships for the development and commercialization of vonapanitase in all or parts of Europe and other countries outside of the United States to secure additional funding. There can be no twelve 10 Pursuant to the requirements of Accounting Standards Codification (ASC) 205 40, Disclosure of Uncertainties about an Entity’s Ability to Continue as a Going Concern one not not 1 one 2 one Under ASC 2015 40, none 10 not none one The Company believes that its approximate $21.9 December 31, 2018, first 2020. no no no 2019 If the Company is unable to obtain sufficient capital to continue to advance its programs, the Company would be forced to delay, reduce or eliminate its ongoing development and other activities. The accompanying financial statements have been prepared on a going concern basis, which contemplates the realization of assets and satisfaction of liabilities in the ordinary course of business. The financial statements do not At-The-Market Equity Offering Program On November 12, 2015, 3 $40 January 12, 2016. 3% March 16, 2017 I.B.6 3, may February 7, 2019, 3, No. 333 228865, December 31, 2017, 896,811 $1.4 $0.1 December 31, 2018, 1,494,579 $3.0 December 31, 2018, $46,000, 1,494,579 December 31, 2018 September 25, 2018 Series A Preferred Financing On June 22, 2017, 22,000 $0.001 $1,000 $22.0 August 2, 2017 ( 7 On August 2, 2017, August 3, 2017, 3 August 21, 2017.

Note 2 - Summary of Significant

Note 2 - Summary of Significant Accounting Policies	12 Months Ended
	Dec. 31, 2018
Notes to Financial Statements
Significant Accounting Policies [Text Block]	2. Summary of Significant Accounting Policies Basis of Presentation, Principles of Consolidation and Use of Estimates The accompanying consolidated financial statements include the accounts of the Company and its wholly-owned subsidiaries. All intercompany balances and transactions have been eliminated in consolidation. These consolidated financial statements have been prepared in conformity with accounting principles generally accepted in the United States of America (“GAAP”). Any reference in these notes to applicable guidance is meant to refer to the authoritative United States generally accepted accounting principles as found in the Accounting Standards Codification (“ASC”) and Accounting Standards Update (“ASU”) of the Financial Accounting Standards Board (“FASB”). The preparation of financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the amounts reported in the financial statements and accompanying notes. On an ongoing basis, the Company’s management evaluates its estimates, which include, but are not may Segment Information Operating segments are defined as components of an enterprise about which separate discrete information is available for evaluation by the chief operating decision maker, or decision-making group, in deciding how to allocate resources and in assessing performance. The Company and the Company's chief operating decision maker view the Company's operations and manage its business in one one Fair Value of Financial Instruments The Company’s financial instruments consist of cash and cash equivalents, available-for-sale investments, forward foreign currency contracts (see Note 3 820, Fair Value Measurement and Disclosures not one three Level 1—Valuations Level 2—Valuations not Level 3—Valuations To the extent that valuation is based on models or inputs that are less observable or unobservable in the market, the determination of fair value requires more judgment. Accordingly, the degree of judgment exercised by the Company in determining fair value is greatest for instruments categorized in Level 3. Financial instruments measured at fair value on a recurring basis include cash equivalents, available-for-sale investments and forward foreign currency contracts (see Note 3 no December 31, 2018 2017. no December 31, 2018 2017. Recent Accounting Pronouncements In May 2014, 2014 09, Revenue from Contracts with Customers 2014 09” January 1, 2018, 2017 09 March 31, 2018. not In February 2016, 2016 02, 842 2016 02” January 1, 2019 not In August 2016, 2016 15, Statement of Cash Flows (Topic 230 2016 15” eight December 15, 2017, first 2018 2016 15 March 31, 2018. not In November 2016, 2016 18, Statement of Cash Flows, Restricted Cash December 15, 2017, first 2018. 2016 18 March 31, 2018. $22,000 $14,000 December 31, 2018 2017, $22,000 December 31, 2018 2017. In May 2017, No. 2017 09, Compensation - Stock Compensation (Topic 718 2017 09” 2017 09, not 2017 09 December 15, 2017. 2017 09 March 31, 2018. not In June 2018, No. 2018 07, 718 2018 07” 2018 07 2018 07 December 15, 2018. January 1, 2019. Cash and Cash Equivalents The Company considers all highly liquid investments with maturities of 90 Short-Term Investments The Company classifies its investments as available-for-sale and records such assets at estimated fair value in the consolidated balance sheets, with unrealized gains and losses, if any, reported as a component of other comprehensive income (loss) within the consolidated statements of operations and comprehensive loss and as a separate component of stockholders' equity (deficit). The Company invests its excess cash balances primarily in government debt securities and money market funds with strong credit ratings and maturities of less than one no December 31, 2018, 2017 2016. At each balance sheet date, the Company assesses available-for-sale securities in an unrealized loss position to determine whether the unrealized loss is other-than-temporary. The Company considers factors including: the significance of the decline in value compared to the cost basis, underlying factors contributing to a decline in the prices of securities in a single asset class, the length of time the market value of the security has been less than its cost basis, the security's relative performance versus its peers, sector or asset class, expected market volatility and the market and economy in general. When the Company determines that a decline in the fair value below its cost basis is other-than-temporary, the Company recognizes an impairment loss in the year in which the other-than-temporary decline occurred. There have been no December 31, 2018, 2017 2016, not Concentrations of Credit Risk and Off-Balance Sheet Risk Financial instruments that potentially subject the Company to concentrations of credit risk are primarily cash, cash equivalents and short-term investments. The Company's cash and cash equivalents are held in accounts with financial institutions that management believes are creditworthy. The Company's investment policy includes guidelines on the quality of the institutions and financial instruments and defines allowable investments that the Company believes minimizes the exposure to concentration of credit risk. These amounts at times may not not no Property and Equipment Property and equipment is stated at cost, less accumulated depreciation. Maintenance and repairs that do not not, Asset Estimated Useful Life (in years) Computer equipment and software 3 Furniture, fixtures and other 5 Laboratory equipment 7 Research and Development Costs Research and development costs are charged to expense as incurred in performing research and development activities. The costs include employee compensation costs, facilities and overhead, clinical study and related clinical manufacturing costs, regulatory and other related costs. Nonrefundable advanced payments for goods or services to be received in the future for use in research and development activities are deferred and capitalized. The capitalized amounts are expensed as the related goods are delivered or the services are performed. Stock-Based Compensation Expense The Company accounts for its stock-based compensation awards to employees and directors in accordance with FASB ASC Topic 718, Compensation-Stock Compensation 718” 718 718 505, Equity The Company estimates the fair value of its stock options using the Black-Scholes option pricing model, which requires the input of subjective assumptions, including (a) the expected stock price volatility, (b) the expected term of the award, (c) the risk-free interest rate, (d) expected dividends and (e) the estimated fair value of its Common Stock on the measurement date. Due to the lack of company specific historical and implied volatility data of its Common Stock, the Company has based its estimate of expected volatility on the historical volatility of a group of similar companies that are publicly traded. When selecting these public companies on which it has based its expected stock price volatility, the Company selected companies with comparable characteristics to it, including enterprise value, risk profiles, position within the industry and with historical share price information sufficient to meet the expected term of the stock based awards. The Company computes historical volatility data using the daily closing prices for the selected companies' shares during the equivalent period of the calculated expected term of the stock-based awards. During 2018 not 2, Use of Estimates Income Taxes Income taxes are recorded in accordance with FASB ASC Topic 740, 740” not not may not The Company accounts for uncertain tax positions in accordance with the provisions of ASC 740. not not December 31, 2018 2017, not 10 Net Income (Loss) per Share Attributable to Common Stockholders Basic net income (loss) per share is calculated by dividing net income (loss) attributable to common stockholders by the weighted-average number of common shares outstanding during the period. Diluted net income per share is calculated by dividing the net income attributable to common stockholders by the weighted-average number of common equivalent shares outstanding for the period, including any dilutive effect from outstanding stock options and warrants using the treasury stock method. The Company follows the two two two not Comprehensive Loss Comprehensive loss consists of net income or loss and changes in equity during a period from transactions and other events and circumstances generated from non-owner sources. The Company's net loss equals comprehensive loss, net of any changes in the unrealized gains and losses of the Company's short-term investments, held as available-for-sale, and foreign currency translation for all periods presented. Subsequent Events The Company considers events or transactions that occur after the balance sheet date but prior to the date the consolidated financial statements are available to be issued for potential recognition or disclosure in the financial statements. The Company has completed an evaluation of all subsequent events after the consolidated balance sheet date of December 31, 2018 December 31, 2018 not

Note 3 - Fair Value Measurement

Note 3 - Fair Value Measurements	12 Months Ended
	Dec. 31, 2018
Notes to Financial Statements
Fair Value Disclosures [Text Block]	3. Fair Value Measurements Below is a summary of assets and liabilities measured at fair value (in thousands): As of December 31, 2018 Quoted Prices Significant Significant in Active Observable Unobservable Markets Inputs Inputs (Level 1) (Level 2) (Level 3) Total Assets Cash equivalents $ 18,353 $ - $ - $ 18,353 Government securities 2,496 - - 2,496 Total $ 20,849 $ - $ - $ 20,849 As of December 31, 2017 Quoted Prices Significant Significant in Active Observable Unobservable Markets Inputs Inputs (Level 1) (Level 2) (Level 3) Total Assets Cash equivalents $ 11,662 $ - $ - $ 11,662 Government securities 20,971 - - 20,971 Total $ 32,633 $ - $ - $ 32,633 As of December 31, 2018, 2017, 90 Available-for-sale securities at December 31, 2018 2017 Amortized Cost Unrealized Gains Unrealized Losses Fair Value December 31, 2018 Government securities (Due within 1 year) $ 2,496 $ - $ - $ 2,496 $ 2,496 $ - $ - $ 2,496 December 31, 2017 Government securities (Due within 1 year) $ 20,991 $ - $ (20 ) $ 20,971 $ 20,991 $ - $ (20 ) $ 20,971

Note 4 - Property and Equipment

Note 4 - Property and Equipment, Net	12 Months Ended
	Dec. 31, 2018
Notes to Financial Statements
Property, Plant and Equipment Disclosure [Text Block]	4. Property and Equipment, net Property and equipment, net consists of the following (in thousands): As of December 31, 2018 2017 Computer equipment and software $ 211 $ 192 Furniture, fixtures, and other 365 302 Laboratory equipment 514 477 1,090 971 Accumulated depreciation (827 ) (712 ) Property and equipment, net $ 263 $ 259 Depreciation expense for the years ended December 31, 2018, 2017 2016 $0.1 $0.1 $0.1

Note 5 - Accrued Expenses

Note 5 - Accrued Expenses	12 Months Ended
	Dec. 31, 2018
Notes to Financial Statements
Accounts Payable and Accrued Liabilities Disclosure [Text Block]	5. Accrued Expenses Accrued expenses consist of the following (in thousands): As of December 31, 2018 2017 Payroll and employee-related costs $ 1,390 $ 1,318 Contracted service costs 968 7,218 Professional fees and other 279 413 Total $ 2,637 $ 8,949

Note 6 - Commitments and Contin

Note 6 - Commitments and Contingencies	12 Months Ended
	Dec. 31, 2018
Notes to Financial Statements
Commitments and Contingencies Disclosure [Text Block]	6. Commitments and Contingencies Significant Contracts and Agreements In February 2002, 2.5% December 31, 2018 not no Operating Leases The Company has various non-cancellable operating leases for facilities and office equipment that expire at various dates through 2019. August 2017, July 13, 2009 ( fifteen 15 June 30, 2018 September 30, 2019 2,552 7,500 200 one six $0.3 $0.2 $0.2 December 31, 2018, 2017 2016, Future minimum payments required under operating leases as of December 31, 2018 Year Ending December 31: Amount 2019 207 Total minimum lease payments $ 207 In addition to the base rent, the Company is also responsible for its share of operating expenses and real estate taxes, in accordance with the terms of the lease agreement. As of December 31, 2018, $22,000 Restricted cash related to facilities leases At December 31, 2018 2017, $22,000 December 31, 2018 2017, $22,000

Note 7 - Series A Preferred Fin

Note 7 - Series A Preferred Financing	12 Months Ended
	Dec. 31, 2018
Notes to Financial Statements
Preferred Stock [Text Block]	7. Series A Preferred Financing On August 2, 2017, 22,000 $0.001 $1,000 $22.0 June 22, 2017. $0.5 1,005 $0.9949 13 9.985% December 31, 2018 2017, 22,000 Upon issuance, each share of Series A Preferred included an embedded beneficial conversion feature as the market price of the Company’s Common Stock on the date of issuance of the Series A Preferred was $1.30 $6.7 not The Company evaluated the Series A Preferred for liability or equity classification in accordance with the provisions of ASC 480, not not not not 480 no not Dividends Holders of the Series A Preferred Stock are entitled to receive dividends, if and when declared by the Board of Directors. Liquidation Preference Holders of the Series A Preferred Stock have preference in the event of a liquidation or dissolution of the Company equal to $0.001 Thereafter, the Holders of the shares of Series A Preferred Stock shall share ratably in any distributions and payments of any remaining assets of the Company, on an as converted basis, with the holders of Common Stock. Voting Rights Except for matters with specific voting rights as provided in the Series A Preferred Stock Purchase Agreement, the Holders of shares of Series A Preferred Stock have no

Note 8 - Common Stock

Note 8 - Common Stock	12 Months Ended
	Dec. 31, 2018
Notes to Financial Statements
Common Stock [Text Block]	8. Common Stock General At December 31, 2018, 100,000,000 $0.001 19,243,651 Reserved for Future Issuance The Company has the following shares of Common Stock reserved for future issuance: December 31, December 31, 2018 2017 Conversion of Series A Preferred Stock 22,112,775 22,112,775 Stock-based compensation awards 5,163,957 3,572,457 Employee Stock Purchase Plan 118,120 192,463 Total 27,394,852 25,877,695

Note 9 - Stock-based Compensati

Note 9 - Stock-based Compensation	12 Months Ended
	Dec. 31, 2018
Notes to Financial Statements
Disclosure of Compensation Related Costs, Share-based Payments [Text Block]	9. Stock-based Compensation On August 21, 2014, 2006 “2006 2014 “2014 2014 “2014 October 3, 2014, 2014 July 31, 2017. The Plans provide for the grant of incentive and non-statutory stock options, stock appreciation rights, restricted stock and stock unit awards, performance units, stock grants and qualified performance-based awards. Under the 2006 no 704,000 2014 2014 2014 January 1, January 1, 2015 four December 31 January 1st. Terms of the stock awards, including vesting requirements, are determined by the Board of Directors, subject to the provisions of the Plans. Options granted by the Company typically vest over three four 2006 ten 2014 Stock-based compensation expense Total stock-based compensation expense is recognized for stock options granted to employees and non-employees and has been reported in the Company’s consolidated statements of operations as follows (in thousands): Year Ended December 31, 2018 2017 2016 Research and development $ 1,142 $ 1,109 $ 1,114 General and administrative 2,287 2,118 2,229 Total $ 3,429 $ 3,227 $ 3,343 The Company estimates the fair value of each employee stock award on the grant date using the Black-Scholes option-pricing model based on the following assumptions regarding the fair value of the underlying Common Stock on each measurement date: Year Ended December 31, 2018 2017 2016 Weighted average expected volatility 93.5 % 94.5 % 84.4 % Expected term (in years) 6.07 6.06 6.05 Risk free interest rate 2.55 % 2.09 % 1.45 % Expected dividend yield 0 % 0 % 0 % Stock options issued to non-employees are accounted for using the fair value method of accounting; they are periodically revalued as the options vest and are recognized as expense over the related service period. The total expense related to all options granted to non-employees was $0 December 31, 2018, 2017 2016. Stock Options The following table summarizes stock option activity for employees and non-employees: Options Weighted- Weighted- Aggregate Outstanding at December 31, 2017 2,681,072 $ 7.18 6.8 $ 121 Granted 2,041,600 $ 2.61 Exercised - Forfeited (83,433 ) $ 5.82 Expired (42,013 ) $ 13.30 Outstanding at December 31, 2018 4,597,226 $ 5.12 7.4 $ 404 Exercisable at December 31, 2018 2,067,356 $ 7.57 5.7 $ 241 Vested or expected to vest at December 31, 2018 (1) 4,597,226 $ 5.12 7.4 $ 404 __________________ ( 1 December 31, 2018 December 31, 2018. During the year ended December 31, 2018, 2,041,600 $2.61. December 31, 2017, 719,337 $1.99. December 31, 2016, 132,495 $7.11 $5.08. The total intrinsic value of options exercised in the years ended December 31, 2018 2017 $0 $27,000 December 31, 2018, 2017 $4.6 $4.2 2.40 Employee Stock Purchase Plan The 2014 140,500 January 1, January 1, 2015 January 1, 2024, one 281,000 January 1st. no January 1, 2018. December 31, 2018, 2014 304,991 seventh 2014 January 1, 2018 June 30, 2018 eight July 1, 2018 December 31, 2018. December 31, 2018 2017, 74,343 100,358 2014 $0.1 2014 December 31, 2018, 2017, 2016.

Note 10 - Income Taxes

Note 10 - Income Taxes	12 Months Ended
	Dec. 31, 2018
Notes to Financial Statements
Income Tax Disclosure [Text Block]	10. Income Taxes The components of loss from operations before income taxes are as follows (in thousands): Year Ended December 31, 2018 2017 2016 Domestic $ (17,855 ) $ (24,803 ) $ (15,860 ) Foreign (2,874 ) (5,161 ) (12,666 ) Total $ (20,729 ) $ (29,964 ) $ (28,526 ) For the years ended December 31, 2018, 2017, 2016, not A reconciliation of income taxes computed using the U.S. federal statutory rate to that reflected in operations is as follows (in thousands): Year Ended December 31, 2018 2017 2016 Income tax benefit computed at federal statutory tax rate $ (4,348 ) $ (10,186 ) $ (9,696 ) Permanent differences 6 4 430 Stock compensation - permanent items 325 689 - R&D credit - permanent items - 1,751 1,437 State income taxes, net of federal benefit (958 ) (853 ) (498 ) Tax credits (1,466 ) (5,495 ) (4,846 ) Change in valuation allowance 5,409 (54,319 ) 8,804 Foreign rate differential 602 1,752 4,304 Rate change - 2,202 - 382 limitation - 64,975 - Other 430 (520 ) 65 Total $ - $ - $ - The significant components of the Company's deferred tax assets are as follows (in thousands): Year Ended December 31, 2018 2017 2016 Deferred tax assets: Net operating loss carryforwards $ 6,742 $ 2,651 $ 37,237 Federal and state tax credits 3,122 2,244 21,223 Accrued expenses 411 399 544 Patents 132 191 360 Stock-based compensation 1,782 1,262 1,353 Other 169 202 321 Total deferred tax assets 12,358 6,949 61,038 Valuation allowance (12,358 ) (6,949 ) (61,038 ) Net deferred assets $ - $ - $ - Management of the Company has evaluated the positive and negative evidence bearing upon the realizability of its deferred tax assets. Based on the Company's history of operating losses, management of the Company has concluded that it is more likely than not not December 31, 2018, 2017, 2016. On December 22, 2017, 34% 21%. $2.2 no not 2017 2018 The Company’s preliminary estimate of the TCJA and the remeasurement of its deferred tax assets and liabilities is subject to the finalization of management’s analysis related to certain matters, such as developing interpretations of the provisions of the TCJA, changes to certain estimates and the filing of our tax returns. U.S. Treasury regulations, administrative interpretations or court decisions interpreting the TJCA may 2017 fourth 2018 no Net operating loss and tax credit carryforwards are subject to review and possible adjustment by the Internal Revenue Service (the "IRS") and may three 50% 382 383 may August 2, 2017, $22.0 §382 §383 August 2, 2017 August 2, 2017 $107.3 $34.1 $23.8 $5.0 $2.1 As a result of current year activity, the valuation allowance increased by approximately $5.4 December 31, 2018. December 31, 2017, $13.1 $65.0 §382 $2.2 $54.1 $8.8 December 31, 2016, Subject to the limitations described below, as of December 31, 2018, 2017, 2016, $25.7 $10.6 $0.0 2018 2037. 2018 December 31, 2018 $14.7 December 31, 2018, 2017, 2016, $21.5 $6.8 $0.0 2037 2038. December 31, 2018, 2017 2016, $3.1 $2.3 $0.0 2037 2038. The Company had no December 31, 2018, 2017, 2016. The Company is subject to U.S. federal income tax and primarily Massachusetts state income tax. The statute of limitations for assessment by the IRS and state tax authorities is open for tax years ending December 31, 2015 2018, 2015 may no

Note 11 - Net Loss Per Share At

Note 11 - Net Loss Per Share Attributable to Common Stockholders	12 Months Ended
	Dec. 31, 2018
Notes to Financial Statements
Earnings Per Share [Text Block]	11. Net Loss per Share Attributable to Common Stockholders As described in Note 2, December 31, 2018, 2017 2016 no two 2017 not $6.7 not The following Common Stock equivalents, presented on an as converted basis, were excluded from the calculation of net loss per share for the periods presented, due to their anti-dilutive effect: Year Ended December 31, 2018 2017 2016 Outstanding stock options 4,597,226 2,681,072 2,166,254 Convertible preferred stock 22,112,775 22,112,775 - 26,710,001 24,793,847 2,166,254

Note 12 - Quarterly Financial I

Note 12 - Quarterly Financial Information (Unaudited, in Thousands, Except Share and Per Share Data)	12 Months Ended
	Dec. 31, 2018
Notes to Financial Statements
Quarterly Financial Information [Text Block]	12. Quarterly Financial Information (unaudited, in thousands, except share and per share data) The following table contains selected quarterly financial information from 2018 2017. not Three Months Ended (a) March 31, June 30, September 30, December 31, 2018 2018 2018 2018 Operating expenses $ 6,365 $ 5,000 $ 4,622 $ 5,385 Net loss attributable to common stockholders (6,081 ) (4,879 ) (4,510 ) (5,259 ) Net loss per share attributable to common stockholders: Basic and Diluted $ (0.34 ) $ (0.28 ) $ (0.25 ) $ (0.27 ) Weighted-average common shares outstanding used in net loss per share attributable to common stockholders: Basic and Diluted 17,674,729 17,674,729 17,824,186 19,221,292 Three Months Ended (a) March 31, June 30, September 30, December 31, 2017 2017 2017 2017 Operating expenses $ 6,480 $ 5,986 $ 12,306 $ 5,590 Net loss attributable to common stockholders (6,498 ) (5,608 ) (19,054 ) (5,551 ) Net loss per share attributable to common stockholders: Basic and Diluted $ (0.39 ) $ (0.33 ) $ (1.08 ) $ (0.33 ) Weighted-average common shares outstanding used in net loss per share attributable to common stockholders: Basic and Diluted 16,636,201 17,207,672 17,619,418 (b) 17,619,418 __________________ (a) The amounts were computed independently for each quarter, and the sum of the quarters may not (b) Adjusted to correct an immaterial error in the weighted-average share calculation in the Company's Form 10 September 30, 2017.

Significant Accounting Policies

Significant Accounting Policies (Policies)	12 Months Ended
	Dec. 31, 2018
Accounting Policies [Abstract]
Basis of Accounting, Policy [Policy Text Block]	Basis of Presentation, Principles of Consolidation and Use of Estimates The accompanying consolidated financial statements include the accounts of the Company and its wholly-owned subsidiaries. All intercompany balances and transactions have been eliminated in consolidation. These consolidated financial statements have been prepared in conformity with accounting principles generally accepted in the United States of America (“GAAP”). Any reference in these notes to applicable guidance is meant to refer to the authoritative United States generally accepted accounting principles as found in the Accounting Standards Codification (“ASC”) and Accounting Standards Update (“ASU”) of the Financial Accounting Standards Board (“FASB”). The preparation of financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the amounts reported in the financial statements and accompanying notes. On an ongoing basis, the Company’s management evaluates its estimates, which include, but are not may
Fair Value Measurement, Policy [Policy Text Block]	Segment Information Operating segments are defined as components of an enterprise about which separate discrete information is available for evaluation by the chief operating decision maker, or decision-making group, in deciding how to allocate resources and in assessing performance. The Company and the Company's chief operating decision maker view the Company's operations and manage its business in one one
Derivatives, Policy [Policy Text Block]	Fair Value of Financial Instruments The Company’s financial instruments consist of cash and cash equivalents, available-for-sale investments, forward foreign currency contracts (see Note 3 820, Fair Value Measurement and Disclosures not one three Level 1—Valuations Level 2—Valuations not Level 3—Valuations To the extent that valuation is based on models or inputs that are less observable or unobservable in the market, the determination of fair value requires more judgment. Accordingly, the degree of judgment exercised by the Company in determining fair value is greatest for instruments categorized in Level 3. Financial instruments measured at fair value on a recurring basis include cash equivalents, available-for-sale investments and forward foreign currency contracts (see Note 3 no December 31, 2018 2017. no December 31, 2018 2017.
New Accounting Pronouncements, Policy [Policy Text Block]	Recent Accounting Pronouncements In May 2014, 2014 09, Revenue from Contracts with Customers 2014 09” January 1, 2018, 2017 09 March 31, 2018. not In February 2016, 2016 02, 842 2016 02” January 1, 2019 not In August 2016, 2016 15, Statement of Cash Flows (Topic 230 2016 15” eight December 15, 2017, first 2018 2016 15 March 31, 2018. not In November 2016, 2016 18, Statement of Cash Flows, Restricted Cash December 15, 2017, first 2018. 2016 18 March 31, 2018. $22,000 $14,000 December 31, 2018 2017, $22,000 December 31, 2018 2017. In May 2017, No. 2017 09, Compensation - Stock Compensation (Topic 718 2017 09” 2017 09, not 2017 09 December 15, 2017. 2017 09 March 31, 2018. not In June 2018, No. 2018 07, 718 2018 07” 2018 07 2018 07 December 15, 2018. January 1, 2019.
Cash and Cash Equivalents, Policy [Policy Text Block]	Cash and Cash Equivalents The Company considers all highly liquid investments with maturities of 90
Investment, Policy [Policy Text Block]	Short-Term Investments The Company classifies its investments as available-for-sale and records such assets at estimated fair value in the consolidated balance sheets, with unrealized gains and losses, if any, reported as a component of other comprehensive income (loss) within the consolidated statements of operations and comprehensive loss and as a separate component of stockholders' equity (deficit). The Company invests its excess cash balances primarily in government debt securities and money market funds with strong credit ratings and maturities of less than one no December 31, 2018, 2017 2016. At each balance sheet date, the Company assesses available-for-sale securities in an unrealized loss position to determine whether the unrealized loss is other-than-temporary. The Company considers factors including: the significance of the decline in value compared to the cost basis, underlying factors contributing to a decline in the prices of securities in a single asset class, the length of time the market value of the security has been less than its cost basis, the security's relative performance versus its peers, sector or asset class, expected market volatility and the market and economy in general. When the Company determines that a decline in the fair value below its cost basis is other-than-temporary, the Company recognizes an impairment loss in the year in which the other-than-temporary decline occurred. There have been no December 31, 2018, 2017 2016, not
Concentration Risk, Credit Risk, Policy [Policy Text Block]	Concentrations of Credit Risk and Off-Balance Sheet Risk Financial instruments that potentially subject the Company to concentrations of credit risk are primarily cash, cash equivalents and short-term investments. The Company's cash and cash equivalents are held in accounts with financial institutions that management believes are creditworthy. The Company's investment policy includes guidelines on the quality of the institutions and financial instruments and defines allowable investments that the Company believes minimizes the exposure to concentration of credit risk. These amounts at times may not not no
Property, Plant and Equipment, Policy [Policy Text Block]	Property and Equipment Property and equipment is stated at cost, less accumulated depreciation. Maintenance and repairs that do not not, Asset Estimated Useful Life (in years) Computer equipment and software 3 Furniture, fixtures and other 5 Laboratory equipment 7
Research and Development Expense, Policy [Policy Text Block]	Research and Development Costs Research and development costs are charged to expense as incurred in performing research and development activities. The costs include employee compensation costs, facilities and overhead, clinical study and related clinical manufacturing costs, regulatory and other related costs. Nonrefundable advanced payments for goods or services to be received in the future for use in research and development activities are deferred and capitalized. The capitalized amounts are expensed as the related goods are delivered or the services are performed.
Share-based Compensation, Option and Incentive Plans Policy [Policy Text Block]	Stock-Based Compensation Expense The Company accounts for its stock-based compensation awards to employees and directors in accordance with FASB ASC Topic 718, Compensation-Stock Compensation 718” 718 718 505, Equity The Company estimates the fair value of its stock options using the Black-Scholes option pricing model, which requires the input of subjective assumptions, including (a) the expected stock price volatility, (b) the expected term of the award, (c) the risk-free interest rate, (d) expected dividends and (e) the estimated fair value of its Common Stock on the measurement date. Due to the lack of company specific historical and implied volatility data of its Common Stock, the Company has based its estimate of expected volatility on the historical volatility of a group of similar companies that are publicly traded. When selecting these public companies on which it has based its expected stock price volatility, the Company selected companies with comparable characteristics to it, including enterprise value, risk profiles, position within the industry and with historical share price information sufficient to meet the expected term of the stock based awards. The Company computes historical volatility data using the daily closing prices for the selected companies' shares during the equivalent period of the calculated expected term of the stock-based awards. During 2018 not 2, Use of Estimates
Income Tax, Policy [Policy Text Block]	Income Taxes Income taxes are recorded in accordance with FASB ASC Topic 740, 740” not not may not The Company accounts for uncertain tax positions in accordance with the provisions of ASC 740. not not December 31, 2018 2017, not 10
Earnings Per Share, Policy [Policy Text Block]	Net Income (Loss) per Share Attributable to Common Stockholders Basic net income (loss) per share is calculated by dividing net income (loss) attributable to common stockholders by the weighted-average number of common shares outstanding during the period. Diluted net income per share is calculated by dividing the net income attributable to common stockholders by the weighted-average number of common equivalent shares outstanding for the period, including any dilutive effect from outstanding stock options and warrants using the treasury stock method. The Company follows the two two two not
Comprehensive Income, Policy [Policy Text Block]	Comprehensive Loss Comprehensive loss consists of net income or loss and changes in equity during a period from transactions and other events and circumstances generated from non-owner sources. The Company's net loss equals comprehensive loss, net of any changes in the unrealized gains and losses of the Company's short-term investments, held as available-for-sale, and foreign currency translation for all periods presented.
Subsequent Events, Policy [Policy Text Block]	Subsequent Events The Company considers events or transactions that occur after the balance sheet date but prior to the date the consolidated financial statements are available to be issued for potential recognition or disclosure in the financial statements. The Company has completed an evaluation of all subsequent events after the consolidated balance sheet date of December 31, 2018 December 31, 2018 not

Note 2 - Summary of Significa_2

Note 2 - Summary of Significant Accounting Policies (Tables)	12 Months Ended
	Dec. 31, 2018
Notes Tables
Property Plant and Equipment Useful Lives [Table Text Block]	Asset Estimated Useful Life (in years) Computer equipment and software 3 Furniture, fixtures and other 5 Laboratory equipment 7

Note 3 - Fair Value Measureme_2

Note 3 - Fair Value Measurements (Tables)	12 Months Ended
	Dec. 31, 2018
Notes Tables
Fair Value, Assets Measured on Recurring Basis [Table Text Block]	As of December 31, 2018 Quoted Prices Significant Significant in Active Observable Unobservable Markets Inputs Inputs (Level 1) (Level 2) (Level 3) Total Assets Cash equivalents $ 18,353 $ - $ - $ 18,353 Government securities 2,496 - - 2,496 Total $ 20,849 $ - $ - $ 20,849 As of December 31, 2017 Quoted Prices Significant Significant in Active Observable Unobservable Markets Inputs Inputs (Level 1) (Level 2) (Level 3) Total Assets Cash equivalents $ 11,662 $ - $ - $ 11,662 Government securities 20,971 - - 20,971 Total $ 32,633 $ - $ - $ 32,633
Available-for-sale Securities [Table Text Block]	Amortized Cost Unrealized Gains Unrealized Losses Fair Value December 31, 2018 Government securities (Due within 1 year) $ 2,496 $ - $ - $ 2,496 $ 2,496 $ - $ - $ 2,496 December 31, 2017 Government securities (Due within 1 year) $ 20,991 $ - $ (20 ) $ 20,971 $ 20,991 $ - $ (20 ) $ 20,971

Note 4 - Property and Equipme_2

Note 4 - Property and Equipment, Net (Tables)	12 Months Ended
	Dec. 31, 2018
Notes Tables
Property, Plant and Equipment [Table Text Block]	As of December 31, 2018 2017 Computer equipment and software $ 211 $ 192 Furniture, fixtures, and other 365 302 Laboratory equipment 514 477 1,090 971 Accumulated depreciation (827 ) (712 ) Property and equipment, net $ 263 $ 259

Note 5 - Accrued Expenses (Tabl

Note 5 - Accrued Expenses (Tables)	12 Months Ended
	Dec. 31, 2018
Notes Tables
Schedule of Accrued Liabilities [Table Text Block]	As of December 31, 2018 2017 Payroll and employee-related costs $ 1,390 $ 1,318 Contracted service costs 968 7,218 Professional fees and other 279 413 Total $ 2,637 $ 8,949

Note 6 - Commitments and Cont_2

Note 6 - Commitments and Contingencies (Tables)	12 Months Ended
	Dec. 31, 2018
Notes Tables
Schedule of Future Minimum Rental Payments for Operating Leases [Table Text Block]	Year Ending December 31: Amount 2019 207 Total minimum lease payments $ 207

Note 8 - Common Stock (Tables)

Note 8 - Common Stock (Tables)	12 Months Ended
	Dec. 31, 2018
Notes Tables
Common Stock Reserved for Future Issuance [Table Text Block]	<table cellpadding="0" cellspacing="0" style="border-collapse: collapse; min-; min-width: 700px;"> <tr style="vertical-align: bottom"> <td style="font-size: 10pt"> </td> <td style="font-size: 10pt; font-weight: bold; padding-bottom: 1pt"> </td> <td colspan="3" style="font-size: 10pt; font-weight: bold; text-align: center; border-bottom: Black 1pt solid">December 31,</td> <td style="font-size: 10pt; font-weight: bold; padding-bottom: 1pt"> </td> <td colspan="3" style="font-size: 10pt; font-weight: bold; text-align: center; border-bottom: Black 1pt solid">December 31,</td> </tr> <tr style="vertical-align: bottom"> <td style="font-size: 10pt"> </td> <td style="font-size: 10pt; font-weight: bold; padding-bottom: 1pt"> </td> <td colspan="3" style="font-size: 10pt; font-weight: bold; text-align: center; border-bottom: Black 1pt solid">2018</td> <td style="font-size: 10pt; font-weight: bold; padding-bottom: 1pt"> </td> <td colspan="3" style="font-size: 10pt; font-weight: bold; text-align: center; border-bottom: Black 1pt solid">2017</td> </tr> <tr style="vertical-align: bottom"> <td style="font-size: 10pt"> </td> <td style="font-size: 10pt"> </td> <td colspan="3" style="font-size: 10pt; text-align: center"> </td> <td> </td> <td colspan="3"> </td> </tr> <tr style="vertical-align: bottom; background-color: rgb(204,238,255)"> <td style="width: 74%; font-size: 10pt; text-align: left">Conversion of Series A Preferred Stock</td> <td style="width: 1%; font-size: 10pt"> </td> <td style="width: 1%; font-size: 10pt; text-align: left"> </td> <td style="width: 10%; font-size: 10pt; text-align: right"><div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">22,112,775</div></td> <td style="width: 1%; font-size: 10pt; text-align: left"> </td> <td style="width: 1%; font-size: 10pt"> </td> <td style="width: 1%; font-size: 10pt; text-align: left"> </td> <td style="width: 10%; font-size: 10pt; text-align: right"><div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">22,112,775</div></td> <td style="width: 1%; font-size: 10pt; text-align: left"> </td> </tr> <tr style="vertical-align: bottom; background-color: White"> <td style="font-size: 10pt; text-align: left">Stock-based compensation awards</td> <td style="font-size: 10pt"> </td> <td style="font-size: 10pt; text-align: left"> </td> <td style="font-size: 10pt; text-align: right"><div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">5,163,957</div></td> <td style="font-size: 10pt; text-align: left"> </td> <td style="font-size: 10pt"> </td> <td style="font-size: 10pt; text-align: left"> </td> <td style="font-size: 10pt; text-align: right"><div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">3,572,457</div></td> <td style="font-size: 10pt; text-align: left"> </td> </tr> <tr style="vertical-align: bottom; background-color: rgb(204,238,255)"> <td style="font-size: 10pt; text-align: left; padding-bottom: 1pt">Employee Stock Purchase Plan</td> <td style="font-size: 10pt; padding-bottom: 1pt"> </td> <td style="border-bottom: Black 1pt solid; font-size: 10pt; text-align: left"> </td> <td style="border-bottom: Black 1pt solid; font-size: 10pt; text-align: right"><div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">118,120</div></td> <td style="border-bottom: Black 1pt solid; font-size: 10pt; text-align: left"> </td> <td style="font-size: 10pt; padding-bottom: 1pt"> </td> <td style="border-bottom: Black 1pt solid; font-size: 10pt; text-align: left"> </td> <td style="border-bottom: Black 1pt solid; font-size: 10pt; text-align: right"><div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">192,463</div></td> <td style="border-bottom: Black 1pt solid; font-size: 10pt; text-align: left"> </td> </tr> <tr style="vertical-align: bottom; background-color: White"> <td style="font-size: 10pt; padding-bottom: 2.5pt">Total</td> <td style="font-size: 10pt; padding-bottom: 2.5pt"> </td> <td style="border-bottom: Black 2.5pt double; font-size: 10pt; text-align: left"> </td> <td style="border-bottom: Black 2.5pt double; font-size: 10pt; text-align: right"><div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">27,394,852</div></td> <td style="border-bottom: Black 2.5pt double; font-size: 10pt; text-align: left"> </td> <td style="font-size: 10pt; padding-bottom: 2.5pt"> </td> <td style="border-bottom: Black 2.5pt double; font-size: 10pt; text-align: left"> </td> <td style="border-bottom: Black 2.5pt double; font-size: 10pt; text-align: right"><div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">25,877,695</div></td> <td style="border-bottom: Black 2.5pt double; font-size: 10pt; text-align: left"> </td> </tr> </table></div>" id="sjs-B4">&lt;div style="display: inline; font-family: times new roman; font-size: 10pt">&lt;table cellpadding="0" cellspacing="0" style="border-collapse: collapse; min-; min-width: 700px;"> &lt;tr style="vertical-align: bottom"> &lt;td style="font-size: 10pt">&nbsp;&lt;/td> &lt;td style="font-size: 10pt; font-weight: bold; padding-bottom: 1pt">&nbsp;&lt;/td> &lt;td colspan="3" style="font-size: 10pt; font-weight: bold; text-align: center; border-bottom: Black 1pt solid">December 31,&lt;/td> &lt;td style="font-size: 10pt; font-weight: bold; padding-bottom: 1pt">&nbsp;&lt;/td> &lt;td colspan="3" style="font-size: 10pt; font-weight: bold; text-align: center; border-bottom: Black 1pt solid">December 31,&lt;/td> &lt;/tr> &lt;tr style="vertical-align: bottom"> &lt;td style="font-size: 10pt">&nbsp;&lt;/td> &lt;td style="font-size: 10pt; font-weight: bold; padding-bottom: 1pt">&nbsp;&lt;/td> &lt;td colspan="3" style="font-size: 10pt; font-weight: bold; text-align: center; border-bottom: Black 1pt solid">2018&lt;/td> &lt;td style="font-size: 10pt; font-weight: bold; padding-bottom: 1pt">&nbsp;&lt;/td> &lt;td colspan="3" style="font-size: 10pt; font-weight: bold; text-align: center; border-bottom: Black 1pt solid">2017&lt;/td> &lt;/tr> &lt;tr style="vertical-align: bottom"> &lt;td style="font-size: 10pt">&nbsp;&lt;/td> &lt;td style="font-size: 10pt">&nbsp;&lt;/td> &lt;td colspan="3" style="font-size: 10pt; text-align: center">&nbsp;&lt;/td> &lt;td>&nbsp;&lt;/td> &lt;td colspan="3">&nbsp;&lt;/td> &lt;/tr> &lt;tr style="vertical-align: bottom; background-color: rgb(204,238,255)"> &lt;td style="width: 74%; font-size: 10pt; text-align: left">Conversion of Series A Preferred Stock&lt;/td> &lt;td style="width: 1%; font-size: 10pt">&nbsp;&lt;/td> &lt;td style="width: 1%; font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;td style="width: 10%; font-size: 10pt; text-align: right">&lt;div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">22,112,775&lt;/div>&lt;/td> &lt;td style="width: 1%; font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;td style="width: 1%; font-size: 10pt">&nbsp;&lt;/td> &lt;td style="width: 1%; font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;td style="width: 10%; font-size: 10pt; text-align: right">&lt;div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">22,112,775&lt;/div>&lt;/td> &lt;td style="width: 1%; font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;/tr> &lt;tr style="vertical-align: bottom; background-color: White"> &lt;td style="font-size: 10pt; text-align: left">Stock-based compensation awards&lt;/td> &lt;td style="font-size: 10pt">&nbsp;&lt;/td> &lt;td style="font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;td style="font-size: 10pt; text-align: right">&lt;div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">5,163,957&lt;/div>&lt;/td> &lt;td style="font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;td style="font-size: 10pt">&nbsp;&lt;/td> &lt;td style="font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;td style="font-size: 10pt; text-align: right">&lt;div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">3,572,457&lt;/div>&lt;/td> &lt;td style="font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;/tr> &lt;tr style="vertical-align: bottom; background-color: rgb(204,238,255)"> &lt;td style="font-size: 10pt; text-align: left; padding-bottom: 1pt">Employee Stock Purchase Plan&lt;/td> &lt;td style="font-size: 10pt; padding-bottom: 1pt">&nbsp;&lt;/td> &lt;td style="border-bottom: Black 1pt solid; font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;td style="border-bottom: Black 1pt solid; font-size: 10pt; text-align: right">&lt;div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">118,120&lt;/div>&lt;/td> &lt;td style="border-bottom: Black 1pt solid; font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;td style="font-size: 10pt; padding-bottom: 1pt">&nbsp;&lt;/td> &lt;td style="border-bottom: Black 1pt solid; font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;td style="border-bottom: Black 1pt solid; font-size: 10pt; text-align: right">&lt;div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">192,463&lt;/div>&lt;/td> &lt;td style="border-bottom: Black 1pt solid; font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;/tr> &lt;tr style="vertical-align: bottom; background-color: White"> &lt;td style="font-size: 10pt; padding-bottom: 2.5pt">Total&lt;/td> &lt;td style="font-size: 10pt; padding-bottom: 2.5pt">&nbsp;&lt;/td> &lt;td style="border-bottom: Black 2.5pt double; font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;td style="border-bottom: Black 2.5pt double; font-size: 10pt; text-align: right">&lt;div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">27,394,852&lt;/div>&lt;/td> &lt;td style="border-bottom: Black 2.5pt double; font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;td style="font-size: 10pt; padding-bottom: 2.5pt">&nbsp;&lt;/td> &lt;td style="border-bottom: Black 2.5pt double; font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;td style="border-bottom: Black 2.5pt double; font-size: 10pt; text-align: right">&lt;div style="display: inline; font-style: italic; font-weight: inherit; font-style: normal;">25,877,695&lt;/div>&lt;/td> &lt;td style="border-bottom: Black 2.5pt double; font-size: 10pt; text-align: left">&nbsp;&lt;/td> &lt;/tr> &lt;/table>&lt;/div>

Note 9 - Stock-based Compensa_2

Note 9 - Stock-based Compensation (Tables)	12 Months Ended
	Dec. 31, 2018
Notes Tables
Schedule of Employee Service Share-based Compensation, Allocation of Recognized Period Costs [Table Text Block]	Year Ended December 31, 2018 2017 2016 Research and development $ 1,142 $ 1,109 $ 1,114 General and administrative 2,287 2,118 2,229 Total $ 3,429 $ 3,227 $ 3,343
Schedule of Share-based Payment Award, Stock Options, Valuation Assumptions [Table Text Block]	Year Ended December 31, 2018 2017 2016 Weighted average expected volatility 93.5 % 94.5 % 84.4 % Expected term (in years) 6.07 6.06 6.05 Risk free interest rate 2.55 % 2.09 % 1.45 % Expected dividend yield 0 % 0 % 0 %
Share-based Compensation, Stock Options, Activity [Table Text Block]	Options Weighted- Weighted- Aggregate Outstanding at December 31, 2017 2,681,072 $ 7.18 6.8 $ 121 Granted 2,041,600 $ 2.61 Exercised - Forfeited (83,433 ) $ 5.82 Expired (42,013 ) $ 13.30 Outstanding at December 31, 2018 4,597,226 $ 5.12 7.4 $ 404 Exercisable at December 31, 2018 2,067,356 $ 7.57 5.7 $ 241 Vested or expected to vest at December 31, 2018 (1) 4,597,226 $ 5.12 7.4 $ 404

Note 10 - Income Taxes (Tables)

Note 10 - Income Taxes (Tables)	12 Months Ended
	Dec. 31, 2018
Notes Tables
Schedule of Income before Income Tax, Domestic and Foreign [Table Text Block]	Year Ended December 31, 2018 2017 2016 Domestic $ (17,855 ) $ (24,803 ) $ (15,860 ) Foreign (2,874 ) (5,161 ) (12,666 ) Total $ (20,729 ) $ (29,964 ) $ (28,526 )
Schedule of Effective Income Tax Rate Reconciliation [Table Text Block]	Year Ended December 31, 2018 2017 2016 Income tax benefit computed at federal statutory tax rate $ (4,348 ) $ (10,186 ) $ (9,696 ) Permanent differences 6 4 430 Stock compensation - permanent items 325 689 - R&D credit - permanent items - 1,751 1,437 State income taxes, net of federal benefit (958 ) (853 ) (498 ) Tax credits (1,466 ) (5,495 ) (4,846 ) Change in valuation allowance 5,409 (54,319 ) 8,804 Foreign rate differential 602 1,752 4,304 Rate change - 2,202 - 382 limitation - 64,975 - Other 430 (520 ) 65 Total $ - $ - $ -
Schedule of Deferred Tax Assets and Liabilities [Table Text Block]	Year Ended December 31, 2018 2017 2016 Deferred tax assets: Net operating loss carryforwards $ 6,742 $ 2,651 $ 37,237 Federal and state tax credits 3,122 2,244 21,223 Accrued expenses 411 399 544 Patents 132 191 360 Stock-based compensation 1,782 1,262 1,353 Other 169 202 321 Total deferred tax assets 12,358 6,949 61,038 Valuation allowance (12,358 ) (6,949 ) (61,038 ) Net deferred assets $ - $ - $ -

Note 11 - Net Loss Per Share _2

Note 11 - Net Loss Per Share Attributable to Common Stockholders (Tables)	12 Months Ended
	Dec. 31, 2018
Notes Tables
Schedule of Antidilutive Securities Excluded from Computation of Earnings Per Share [Table Text Block]	Year Ended December 31, 2018 2017 2016 Outstanding stock options 4,597,226 2,681,072 2,166,254 Convertible preferred stock 22,112,775 22,112,775 - 26,710,001 24,793,847 2,166,254

Note 12 - Quarterly Financial_2

Note 12 - Quarterly Financial Information (Unaudited, in Thousands, Except Share and Per Share Data) (Tables)	12 Months Ended
	Dec. 31, 2018
Notes Tables
Quarterly Financial Information [Table Text Block]	Three Months Ended (a) March 31, June 30, September 30, December 31, 2018 2018 2018 2018 Operating expenses $ 6,365 $ 5,000 $ 4,622 $ 5,385 Net loss attributable to common stockholders (6,081 ) (4,879 ) (4,510 ) (5,259 ) Net loss per share attributable to common stockholders: Basic and Diluted $ (0.34 ) $ (0.28 ) $ (0.25 ) $ (0.27 ) Weighted-average common shares outstanding used in net loss per share attributable to common stockholders: Basic and Diluted 17,674,729 17,674,729 17,824,186 19,221,292 Three Months Ended (a) March 31, June 30, September 30, December 31, 2017 2017 2017 2017 Operating expenses $ 6,480 $ 5,986 $ 12,306 $ 5,590 Net loss attributable to common stockholders (6,498 ) (5,608 ) (19,054 ) (5,551 ) Net loss per share attributable to common stockholders: Basic and Diluted $ (0.39 ) $ (0.33 ) $ (1.08 ) $ (0.33 ) Weighted-average common shares outstanding used in net loss per share attributable to common stockholders: Basic and Diluted 16,636,201 17,207,672 17,619,418 (b) 17,619,418

Note 1 - Organization and Ope_2

Note 1 - Organization and Operations (Details Textual) - USD ($)	Aug. 02, 2017	Nov. 12, 2015	Dec. 31, 2018	Dec. 31, 2017
Cash, Cash Equivalents, and Short-term Investments, Total			$ 21,900,000
Retained Earnings (Accumulated Deficit), Ending Balance			$ (210,470,000)	$ (189,741,000)
Preferred Stock, Par or Stated Value Per Share			$ 0.001	$ 0.001
Series A Convertible Preferred Stock [Member]
Stock Issued During Period, Shares, New Issues	22,000
Payments of Stock Issuance Costs	$ 500,000
Preferred Stock, Par or Stated Value Per Share	$ 0.001		$ 0.001	$ 0.001
Shares Issued, Price Per Share	$ 1,000
Proceeds from Issuance of Convertible Preferred Stock	$ 22,000,000
Common Stock [Member]
Stock Issued During Period, Shares, New Issues			1,494,579	896,811
Sales Agreement [Member] | Cowen and Company, LLC [Member] | Common Stock [Member]
Sale of Stock, Maximum Value of Stock Offered		$ 40,000,000
Sale of Stock, Commission to Sales Agent, Percentage			3.00%
Stock Issued During Period, Shares, New Issues				896,811
Proceeds from Issuance of Common Stock				$ 1,400,000
Payments of Stock Issuance Costs				$ 100,000
Sales Agreement [Member] | New Leaf Venture Partners LLC [Member] | Common Stock [Member]
Stock Issued During Period, Shares, New Issues			1,494,579
Proceeds from Issuance of Common Stock			$ 3,000,000
Payments of Stock Issuance Costs			$ 46,000

Note 2 - Summary of Significa_3

Note 2 - Summary of Significant Accounting Policies (Details Textual)	12 Months Ended
	Dec. 31, 2018USD ($)	Dec. 31, 2017USD ($)	Dec. 31, 2016USD ($)
Number of Operating Segments	1
Number of Reportable Segments	1
Cash, Cash Equivalents, Restricted Cash and Restricted Cash Equivalents, Period Increase (Decrease), Including Exchange Rate Effect, Total	$ (1,799,000)	$ (15,222,000)	$ (3,639,000)
Restricted Cash and Cash Equivalents, Total	22,000	22,000
Available-for-sale Securities, Gross Realized Gain (Loss), Total	0	0	0
Other than Temporary Impairment Losses, Investments, Available-for-sale Securities, Total	0	0	$ 0
Liability for Uncertainty in Income Taxes, Current	0	0
Accounting Standards Update 2016-18 [Member]
Cash, Cash Equivalents, Restricted Cash and Restricted Cash Equivalents, Period Increase (Decrease), Including Exchange Rate Effect, Total	$ 22,000	$ 14,000

Note 2 - Summary of Significa_4

Note 2 - Summary of Significant Accounting Policies - Property and Equipment Useful Lives (Details)	12 Months Ended
	Dec. 31, 2018
Computer Equipment and Software [Member]
Property and equipment, useful life (Year)	3 years
Furniture and Fixtures [Member]
Property and equipment, useful life (Year)	5 years
Laboratory Equipment [Member]
Property and equipment, useful life (Year)	7 years

Note 3 - Fair Value Measureme_3

Note 3 - Fair Value Measurements - Summary of Assets and Liabilities Measured at Fair Value (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Total	$ 20,849	$ 32,633
Cash Equivalents [Member]
Cash equivalents	18,353	11,662
US Government Agencies Debt Securities [Member]
Government securities	2,496	20,971
Fair Value, Inputs, Level 1 [Member]
Total	20,849	32,633
Fair Value, Inputs, Level 1 [Member] | Cash Equivalents [Member]
Cash equivalents	18,353	11,662
Fair Value, Inputs, Level 1 [Member] | US Government Agencies Debt Securities [Member]
Government securities	2,496	20,971
Fair Value, Inputs, Level 2 [Member]
Total
Fair Value, Inputs, Level 2 [Member] | Cash Equivalents [Member]
Cash equivalents
Fair Value, Inputs, Level 2 [Member] | US Government Agencies Debt Securities [Member]
Government securities
Fair Value, Inputs, Level 3 [Member]
Total
Fair Value, Inputs, Level 3 [Member] | Cash Equivalents [Member]
Cash equivalents
Fair Value, Inputs, Level 3 [Member] | US Government Agencies Debt Securities [Member]
Government securities

Note 3 - Fair Value Measureme_4

Note 3 - Fair Value Measurements - Available-for-sale Securities (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Amortized Cost	$ 2,496	$ 20,991
Unrealized Gains
Unrealized Losses		(20)
Fair Value	2,496	20,971
US Government Agencies Debt Securities [Member]
Amortized Cost	2,496	20,991
Unrealized Gains
Unrealized Losses		(20)
Fair Value	$ 2,496	$ 20,971

Note 4 - Property and Equipme_3

Note 4 - Property and Equipment, Net (Details Textual) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Depreciation, Total	$ 115	$ 148	$ 123

Note 4 - Property and Equipme_4

Note 4 - Property and Equipment, Net - Summary of Property and Equipment (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Property and equipment	$ 1,090	$ 971
Accumulated depreciation	(827)	(712)
Property and equipment, net	263	259
Computer Equipment and Software [Member]
Property and equipment	211	192
Furniture and Fixtures [Member]
Property and equipment	365	302
Laboratory Equipment [Member]
Property and equipment	$ 514	$ 477

Note 5 - Accrued Expenses - Acc

Note 5 - Accrued Expenses - Accrued Expenses (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Payroll and employee-related costs	$ 1,390	$ 1,318
Contracted service costs	968	7,218
Professional fees and other	279	413
Total	$ 2,637	$ 8,949

Note 6 - Commitments and Cont_3

Note 6 - Commitments and Contingencies (Details Textual)	1 Months Ended		12 Months Ended
	Aug. 31, 2017ft²	Feb. 28, 2002	Dec. 31, 2018USD ($)	Dec. 31, 2017USD ($)	Dec. 31, 2016USD ($)
Royalty Payment, Percentage of Net Sales		2.50%
Lessee, Operating Lease, Term of Contract	1 year 90 days
Operating Leases, Increase in Office Space | ft²	2,552
Area of Real Estate Property | ft²	7,500
Lessee, Operating Lease, Renewal Term	1 year
Operating Leases, Notice Required to Extend Term	180 days
Operating Leases, Rent Expense, Total			$ 300,000	$ 200,000	$ 200,000
Security Deposit			22,000
Letters of Credit Outstanding, Amount			22,000	22,000
Loans Pledged as Collateral			$ 22,000	$ 22,000

Note 6 - Commitments and Cont_4

Note 6 - Commitments and Contingencies - Future Minimum Payments for Operating Leases (Details) $ in Thousands	Dec. 31, 2018USD ($)
2019	$ 207
Total minimum lease payments	$ 207

Note 7 - Series A Preferred F_2

Note 7 - Series A Preferred Financing (Details Textual) - USD ($)	Aug. 02, 2017	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Preferred Stock, Par or Stated Value Per Share		$ 0.001	$ 0.001
Preferred Stock, Shares Authorized		10,000,000	10,000,000
Accretion of Redeemable Convertible Preferred Stock to Redemption Value			$ 6,747,000
Series A Convertible Preferred Stock [Member]
Stock Issued During Period, Shares, New Issues	22,000
Preferred Stock, Par or Stated Value Per Share	$ 0.001	$ 0.001	$ 0.001
Shares Issued, Price Per Share	$ 1,000
Proceeds from Issuance of Convertible Preferred Stock	$ 22,000,000
Payments of Stock Issuance Costs	$ 500,000
Convertible Preferred Stock, Shares Issued upon Conversion	1,005
Convertible Preferred Stock, Conversion Price of Shares Issued upon Conversion	$ 0.9949
Convertible Preferred Stock, Maximum Ownership Percentage Allowed after Conversion of Stock	9.985%
Preferred Stock, Shares Authorized		22,000	22,000
Preferred Stock, Redemption Price Per Share	$ 1.30
Accretion of Redeemable Convertible Preferred Stock to Redemption Value	$ 6,700,000
Preferred Stock, Liquidation Preference Per Share		$ 0.001

Note 8 - Common Stock (Details

Note 8 - Common Stock (Details Textual) - $ / shares	Dec. 31, 2018	Dec. 31, 2017
Common Stock, Shares Authorized	100,000,000	100,000,000
Common Stock, Par or Stated Value Per Share	$ 0.001	$ 0.001
Common Stock, Shares, Issued, Total	19,243,651	17,674,729
Common Stock, Shares, Outstanding, Ending Balance	19,243,651	17,674,729

Note 8 - Common Stock - Common

Note 8 - Common Stock - Common Stock Reserved for Future Issuance (Details) - shares	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2014
Reserved for future issuance (in shares)	27,394,852	25,877,695
The 2014 Employee Stock Purchase Plan [Member]
Reserved for future issuance (in shares)	118,120	192,463	140,500
Performance Shares [Member]
Reserved for future issuance (in shares)	5,163,957	3,572,457
Conversion of Series A Preferred Stock to Common Stock [Member]
Reserved for future issuance (in shares)	22,112,775	22,112,775

Note 9 - Stock-based Compensa_3

Note 9 - Stock-based Compensation (Details Textual) - USD ($)	Jan. 01, 2018	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2014
Share-based Compensation Arrangement by Share-based Payment Award, Options, Exercisable, Weighted Average Remaining Contractual Term		5 years 255 days
Allocated Share-based Compensation Expense, Total		$ 3,429,000	$ 3,227,000	$ 3,343,000
Share-based Compensation Arrangement by Share-based Payment Award, Options, Grants in Period, Gross		2,041,600	719,337	132,495
Share-based Compensation Arrangement by Share-based Payment Award, Options, Grants in Period, Weighted Average Grant Date Fair Value		$ 2.61	$ 1.99	$ 5.08
Share-based Compensation Arrangements by Share-based Payment Award, Options, Grants in Period, Weighted Average Exercise Price		$ 2.61		$ 7.11
Share-based Compensation Arrangement by Share-based Payment Award, Options, Exercises in Period, Intrinsic Value		$ 0	$ 27,000
Employee Service Share-based Compensation, Nonvested Awards, Compensation Not yet Recognized, Stock Options		$ 4,600,000	$ 4,200,000
Employee Service Share-based Compensation, Nonvested Awards, Compensation Cost Not yet Recognized, Period for Recognition		2 years 146 days	2 years 146 days
Common Stock, Capital Shares Reserved for Future Issuance		27,394,852	25,877,695
Employee Stock Option [Member] | Non-Employees [Member]
Allocated Share-based Compensation Expense, Total		$ 0	$ 0	$ 0
The 2014 Plan [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Number of Shares Authorized		704,000
Share-based Compensation Arrangement by Share-based Payment Award, Number of Annual Additional Shares, Percentage		4.00%
The 2014 Plan [Member] | Minimum [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Award Vesting Period		3 years
The 2014 Plan [Member] | Maximum [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Award Vesting Period		4 years
The 2006 Plan [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Options, Exercisable, Weighted Average Remaining Contractual Term		10 years
The 2014 Employee Stock Purchase Plan [Member]
Share-based Compensation Arrangement by Share-based Payment Award, Number of Shares Authorized		304,991
Share-based Compensation Arrangement by Share-based Payment Award, Number of Annual Additional Shares, Percentage		1.00%
Allocated Share-based Compensation Expense, Total		$ 100,000	$ 100,000	$ 100,000
Common Stock, Capital Shares Reserved for Future Issuance		118,120	192,463		140,500
Share-based Compensation Arrangement by Share-based Payment Award, Maximum Number of Additional Shares Authorizable	281,000
Share-based Compensation Arrangement by Share-based Payment Award, Number of Additional Shares Authorized	0
Share-based Compensation Arrangement by Share-based Payment Award, Shares Issued in Period		74,343	100,358

Note 9 - Stock-based Compensa_4

Note 9 - Stock-based Compensation - Stock-based Compensation Expense Recognized for Stock Options Granted (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Allocated share-based compensation	$ 3,429	$ 3,227	$ 3,343
Research and Development Expense [Member]
Allocated share-based compensation	1,142	1,109	1,114
General and Administrative Expense [Member]
Allocated share-based compensation	$ 2,287	$ 2,118	$ 2,229

Note 9 - Stock-based Compensa_5

Note 9 - Stock-based Compensation - Black-scholes Valuation Assumptions (Details)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Weighted average expected volatility	93.50%	94.50%	84.40%
Expected term (in years) (Year)	6 years 25 days	6 years 21 days	6 years 18 days
Risk free interest rate	2.55%	2.09%	1.45%
Expected dividend yield	0.00%	0.00%	0.00%

Note 9 - Stock-based Compensa_6

Note 9 - Stock-based Compensation - Stock Option Activity for Employees and Non-employees (Details) - USD ($) $ / shares in Units, $ in Thousands		12 Months Ended
		Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Options Outstanding, Beginning Balance (in shares)		2,681,072
Options Outstanding, Weighted Average Exercise Price, Beginning Balance (in dollars per share)		$ 7.18
Options Outstanding, Weighted-average Remaining Contractual Term (Year)		7 years 146 days	6 years 292 days
Options Outstanding, Aggregate Intrinsic Value		$ 404	$ 121
Options Granted (in shares)		2,041,600	719,337	132,495
Options Granted, Weighted Average Exercise Price (in dollars per share)		$ 2.61		$ 7.11
Options Exercised, Weighted Average Exercise Price (in dollars per share)
Options Forfeited (in shares)		(83,433)
Options Forfeited, Weighted Average Exercise Price (in dollars per share)		$ 5.82
Options Expired (in shares)		(42,013)
Options Expired, Weighted Average Exercise Price (in dollars per share)		$ 13.30
Options Outstanding, Ending Balance (in shares)		4,597,226	2,681,072
Options Outstanding, Weighted Average Exercise Price, Ending Balance (in dollars per share)		$ 5.12	$ 7.18
Options Exercisable (in shares)		2,067,356
Options Exercisable, Weighted Average Exercise Price (in dollars per share)		$ 7.57
Options Exercisable, Weighted-average Remaining Contractual Term (Year)		5 years 255 days
Options Exercisable, Aggregate Intrinsic Value		$ 241
Options Vested or Expected to Vest (in shares)	[1]	4,597,226
Options Vested or Expected to Vest, Weighted Average Exercise Price (in dollars per share)	[1]	$ 5.12
Options Vested or Expected to Vest, Weighted-average Remaining Contractual Term (Year)	[1]	7 years 146 days
Options Vested or Expected to Vest, Aggregate Intrinsic Value	[1]	$ 404
[1]	Represents the number of vested options at December 31, 2018 plus the number of unvested options expected to vest based on the unvested options outstanding at December 31, 2018.

Note 10 - Income Taxes (Details

Note 10 - Income Taxes (Details Textual) - USD ($)	Aug. 02, 2017	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Income Tax Expense (Benefit), Total
Effective Income Tax Rate Reconciliation, at Federal Statutory Income Tax Rate, Percent		21.00%	34.00%
Deferred Tax Assets, Increase (Decrease) from Revaluation Due to Tax Rate Change			$ (2,200,000)
Income Tax Expense (Benefit), Continuing Operations, Adjustment of Deferred Tax (Asset) Liability			0
Valuation Allowance, Deferred Tax Asset, Increase (Decrease), Amount			(54,100,000)	8,800,000
Operating Loss Carryforwards, Net, Indefinite Lived		$ 14,700,000
Tax Credit Carryforward, Amount		3,100,000	2,300,000	0
Unrecognized Tax Benefits, Ending Balance		0	0	0
Current Year Deferred Tax Assets Activity [Member]
Valuation Allowance, Deferred Tax Asset, Increase (Decrease), Amount		5,400,000	13,100,000
Effect on Deferred Tax Assets of Section 382 Limitation [Member]
Valuation Allowance, Deferred Tax Asset, Increase (Decrease), Amount			(65,000,000)
Effect of Tax Rate Change on Deferred Tax Assets [Member]
Valuation Allowance, Deferred Tax Asset, Increase (Decrease), Amount			(2,200,000)
Series A Preferred Stock [Member]
Proceeds from Issuance of Convertible Preferred Stock	$ 22,000,000
Domestic Tax Authority [Member]
Income Tax Expense (Benefit), Total		0	0	0
Operating Loss Carryforwards, Total		25,700,000	10,600,000	0
Domestic Tax Authority [Member] | Internal Revenue Service (IRS) [Member]
Decrease in Net Operating Loss Carryforwards from Section 382 Limitation	107,300,000
Decrease in Net Operating Loss Carryforwards from Section 382 Limitation, Tax Affected	34,100,000
Decrease in Tax Credit Carryforward Amount from Section 382 Limitation	23,800,000
State and Local Jurisdiction [Member]
Income Tax Expense (Benefit), Total		0	0	0
Decrease in Net Operating Loss Carryforwards from Section 382 Limitation	5,000,000
Decrease in Tax Credit Carryforward Amount from Section 382 Limitation	$ 2,100,000
Operating Loss Carryforwards, Total		$ 21,500,000	$ 6,800,000	$ 0

Note 10 - Income Taxes - Domest

Note 10 - Income Taxes - Domestic and Foreign Loss Before Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Domestic	$ (17,855)	$ (24,803)	$ (15,860)
Foreign	(2,874)	(5,161)	(12,666)
Total	$ (20,729)	$ (29,964)	$ (28,526)

Note 10 - Income Taxes - Reconc

Note 10 - Income Taxes - Reconciliation of Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Income tax benefit computed at federal statutory tax rate	$ (4,348)	$ (10,186)	$ (9,696)
Permanent differences	6	4	430
Stock compensation - permanent items	325	689
R&D credit - permanent items		1,751	1,437
State income taxes, net of federal benefit	(958)	(853)	(498)
Tax credits	(1,466)	(5,495)	(4,846)
Change in valuation allowance	5,409	(54,319)	8,804
Foreign rate differential	602	1,752	4,304
Rate change		2,202
382 limitation		64,975
Other	430	(520)	65
Total

Note 10 - Income Taxes - Summar

Note 10 - Income Taxes - Summary of Deferred Tax Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Net operating loss carryforwards	$ 6,742	$ 2,651	$ 37,237
Federal and state tax credits	3,122	2,244	21,223
Accrued expenses	411	399	544
Patents	132	191	360
Stock-based compensation	1,782	1,262	1,353
Other	169	202	321
Total deferred tax assets	12,358	6,949	61,038
Valuation allowance	(12,358)	(6,949)	(61,038)
Net deferred assets

Note 11 - Net Loss Per Share _3

Note 11 - Net Loss Per Share Attributable to Common Stockholders (Details Textual) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Accretion of Redeemable Convertible Preferred Stock to Redemption Value		$ 6,747

Note 11 - Net Loss Per Share _4

Note 11 - Net Loss Per Share Attributable to Common Stockholders - Common Stock Equivalents Excluded From Calculation of Net Loss Per Share (Details) - shares	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Antidilutive Securities (in shares)	26,710,001	24,793,847	2,166,254
Convertible Preferred Stock [Member]
Antidilutive Securities (in shares)	22,112,775	22,112,775
Employee Stock Option [Member]
Antidilutive Securities (in shares)	4,597,226	2,681,072	2,166,254

Note 12 - Quarterly Financial_3

Note 12 - Quarterly Financial Information (Unaudited, in Thousands, Except Share and Per Share Data) - Quarterly Financial Information (Details) - USD ($) $ / shares in Units, $ in Thousands		3 Months Ended																12 Months Ended
		Dec. 31, 2018		Sep. 30, 2018		Jun. 30, 2018		Mar. 31, 2018		Dec. 31, 2017		Sep. 30, 2017		Jun. 30, 2017		Mar. 31, 2017		Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Total operating expenses		$ 5,385	[1]	$ 4,622	[1]	$ 5,000	[1]	$ 6,365	[1]	$ 5,590	[1]	$ 12,306	[1]	$ 5,986	[1]	$ 6,480	[1]	$ 21,372	$ 30,362	$ 28,705
Net loss attributable to common stockholders	[1]	$ (5,259)		$ (4,510)		$ (4,879)		$ (6,081)		$ (5,551)		$ (19,054)		$ (5,608)		$ (6,498)
Net loss per share attributable to common stockholders - basic and diluted (in dollars per share)		$ (0.27)	[1]	$ (0.25)	[1]	$ (0.28)	[1]	$ (0.34)	[1]	$ (0.33)	[1]	$ (1.08)	[1]	$ (0.33)	[1]	$ (0.39)	[1]	$ (1.15)	$ (2.13)	$ (1.72)
Weighted-average common shares outstanding used in net loss per share attributable to common stockholders - basic and diluted (in shares)		19,221,292	[1]	17,824,186	[1]	17,674,729	[1]	17,674,729	[1]	17,619,418	[1]	17,619,418	[1],[2]	17,207,672	[1]	16,636,201	[1]	18,102,219	17,274,326	16,561,799
[1]	The amounts were computed independently for each quarter, and the sum of the quarters may not total the annual amounts.
[2]	Adjusted to correct an immaterial error in the weighted-average share calculation in the Company's Form 10-Q as of September 30, 2017.