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Equity Incentive Plans
 12 Months Ended
Dec. 31, 2021
Share-based Payment Arrangement [Abstract]  
Equity Incentive Plans EQUITY INCENTIVE PLANS
2008 Plan
We granted options under its 2008 Stock Incentive Plan (the “2008 Plan”) until June 2014 when it was terminated as to future awards, although it continues to govern the terms of options that remain outstanding under the 2008 Plan. The 2008 Plan provided for the granting of incentive and non-qualified stock options, and stock purchase rights to employees, directors and consultants at the discretion of the Board of Directors. Stock options granted generally vest over a period of four years from the date of grant. In connection with the Board of Directors and stockholders’ approval of the 2014 Plan, all remaining shares available for future award under the 2008 Plan were transferred to 2014 Plan, and the 2008 Plan was terminated.
2014 Plan
The 2014 Equity Incentive Award Plan (the “2014 Plan”) became effective on June 18, 2014. Under the 2014 Plan, 1.4 million shares of common stock were initially reserved for issuance pursuant to a variety of stock-based compensation awards, including stock options, stock appreciation rights ("SARs"), restricted stock awards, service-based restricted stock unit (“RSU”) awards, performance-based restricted stock unit (“PRSU”) awards, deferred stock awards, deferred stock unit awards, dividend equivalent awards, stock payment awards and performance awards. In addition, 35 thousand shares that had been available for future awards under the 2008 Plan as of June 18, 2014, were added to the initial reserve available under the 2014 Plan, bringing the total reserve upon the effective date of the 2014 Plan to 1.5 million shares. The number of shares initially reserved for issuance or transfer pursuant to awards under the 2014 Plan will be increased by (i) the number of shares represented by awards outstanding under 2008 Plan on June 18, 2014, that are either forfeited or lapse unexercised or that are repurchased for the original purchase price thereof, up to a maximum of 1.2 million shares, and (ii) if approved by the Administrator of the 2014 Plan, an annual increase on the first day of each fiscal year ending in 2024 equal to the lesser of (A) four percent (4.0%) of the shares of stock outstanding (on an as converted basis) on the last day of the immediately preceding fiscal year and (B) such smaller number of shares of stock as determined by our board of directors; provided, however, that no more than 10.7 million shares of stock may be issued upon the exercise of incentive stock options.
2016 Plan
In November 2016, our board of directors approved the 2016 Employment Commencement Incentive Plan (the “Inducement Plan”) under which 1.0 million shares were reserved. In January 2021 and 2022, 0.5 million and 2.0 million shares, respectively, were added to the Inducement Plan. As of December 31, 2021, 0.4 million shares of our common stock were subject to inducement grants that were issued pursuant to the Inducement Plan.
Stock Options
The following table summarizes activity under the 2008 Plan and the 2014 Plan, including grants issued to nonemployees, in the year ended December 31, 2021:
Shares Available for GrantOptions Issued and OutstandingWeighted
Average
Remaining
Contractual Term		Aggregate
Intrinsic Value
Number of SharesWeighted-Average
Exercise Price 
per Share
(in Years)(in thousands)
Balance at December 31, 20201,757,058 9,790,049 $6.76 
Options authorized4,201,766 — $— 
Options granted(3,409,719)3,409,719 $6.60 
Options exercised— (331,310)$1.96 
Options canceled2,451,306 (2,451,306)$6.17 
Issuance of common stock for services(25,989)— — 
Balance at December 31, 20214,974,422 10,417,152 $7.00 6.57$— 
Vested and expected to vest at December 31, 202110,417,152 $7.00 6.57$— 
Exercisable at December 31, 20216,772,289 $7.39 5.58$— 
The aggregate intrinsic value represents the difference between the total pre-tax value (i.e., the difference between our stock price and the exercise price) of stock options outstanding as of December 31, 2021, based on our common stock closing
price of $1.10 per share, which would have been received by the option holders had all their in-the-money options been exercised as of that date.
The intrinsic value of options exercised during the years ended December 31, 2021, 2020 and 2019, was $1.7 million, $2.7 million, and $0.4 million, respectively.
The weighted-average grant-date estimated fair value of options granted during the years ended December 31, 2021, 2020 and 2019 was $3.92, $4.82 and $1.79 per share, respectively. The estimated grant date fair value of employee stock options was calculated using the Black-Scholes option-pricing model, based on the following weighted-average assumptions:
Year Ended December 31,
202120202019
Expected term (years)4.976.006.00
Expected volatility77 %83 %81 %
Risk-free interest rate4.69 %1.07 %2.42 %
Dividend yield— %— %— %
Expected Term—We have limited historical information to develop reasonable expectations about future exercise patterns and post-vesting employment termination behavior for its stock-option grants. As such, the expected term has been estimated using the simplified method whereby the expected term equals the arithmetic average of the vesting term and the original contractual term of the option. Beginning in 2021, we estimate the expected term of our options based upon historical exercises and post-vesting termination behavior, which has not resulted in a material difference as compared to using the simplified method.
Expected Volatility—Since January 1, 2017, we use the historic volatility of our own stock over the retrospective period corresponding to the expected remaining term of the options, or the period since our shares were first quoted on The Nasdaq Global Market, if that is shorter, to compute our expected stock price volatility.
Risk-Free Interest Rate—The risk-free interest rate assumption is based on the zero-coupon U.S. treasury instruments on the date of grant with a maturity date consistent with the expected term of our stock option grants.
Dividend Yield—To date, we have not declared or paid any cash dividends and does not have any plans to do so in the future. Therefore, we use an expected dividend yield of zero.
Restricted Stock Units
The following table summarizes restricted stock unit activity under the 2014 Plan in the year ended December 31, 2021, and includes restricted stock units with time or service-based vesting and those restricted stock units with performance-based vesting:
Number of
RSUs		Weighted-Average
Grant Date Fair
Value Per Share
Non-vested restricted stock units at December 31, 2020158,626 $5.64 
Granted4,144,051 $2.71 
Vested(193,147)$6.39 
Forfeited(580,848)$6.38 
Non-vested restricted stock units at December 31, 20213,528,682 $2.04 
In July 2018, we granted 0.9 million PRSUs to our employees that vested upon the achievement of certain performance conditions, subject to the employees’ continued service relationship with us through the achievement date. During 2020, we granted an additional 30 thousand PRSUs subject to the same performance conditions. All 0.9 million of these PRSUs vested in September 2020. None of these PRSUs vested during the years ended December 31, 2019 or 2018. We recognized zero and $1.2 million of related expense during the years ended December 31, 2021 and 2020, respectively.
The total estimated fair value of RSUs vested during the years ended December 31, 2021, 2020 and 2019 was $0.8 million, zero and $0.2 million, respectively.
Issuance of Common Stock for Services
During the years ended December 31, 2021, 2020 and 2019, we issued approximately 26 thousand, 42 thousand and 113 thousand shares, respectively, of common stock to members of the board of directors who elected to receive stock in lieu of their cash fees under our Non-Employee Director Compensation Program. The shares issued during the years ended December 31, 2021, 2020 and 2019 were valued at $0.2 million, $0.3 million and $0.3 million for each year, respectively, based on the fair value of the common stock on the date of grant.
Employee Stock Purchase Plan
We adopted the 2014 Employee Stock Purchase Plan (“ESPP”) and initially reserved approximately 0.2 million shares of common stock as of its effective date of June 18, 2014. If approved by the Administrator of the ESPP, on the first day of each calendar year, ending in 2024, the number of shares in the reserve will increase by an amount equal to the lesser of (i) one percent (1.0%) of the shares of common stock outstanding on the last day of the immediately preceding fiscal year and (ii) such number of shares of common stock as determined by the board of directors; provided, however, no more than $2.2 million shares of our common stock may be issued under the ESPP.
The following table summarizes our ESPP activity during the year ended December 31, 2021:
Shares Available
for Grant		Number of Shares
Purchased		Average Purchase Price
per Share		Gross Proceeds
(in thousands)
Balance at December 31, 2020349,647 661,611 
Shares purchased(386,664)386,664 $2.12 $819 
Balance at December 31, 2021898,982 1,048,275 
The following table illustrates the weighted-average assumptions for the Black-Scholes option-pricing model used in determining the fair value of ESPP purchase rights granted to our employees:

Year Ended December 31,
202120202019
Expected term (years)0.500.500.50
Expected volatility123 %79 %69 %
Risk-free interest rate0.65 %0.48 %2.00 %
Dividend yield— %— %— %
Stock-based Compensation Expense
Total stock-based compensation recognized was as follows (in thousands):
Year Ended December 31,
202120202019
Research and development$4,116 $4,061 $4,104 
General and administrative7,923 6,522 5,832 
Total$12,039 $10,583 $9,936 
At December 31, 2021, the Company had total unrecognized stock-based compensation expense, net of estimated forfeitures, of the following (dollars in thousands):
December 31, 2021
Unrecognized Compensation ExpenseAverage Remaining Vesting Period (Years)
Stock options grant$14,506 2.4
RSU grants$2,262 0.8
ESPP$44 0.1