In the accompanying consolidated statement of operations, the Company recognized stock-based compensation expense for its employees and non-employees as follows:

	Year ended December 31,
	2021		2020		2019
	(in thousands)
Research and development	$	7,197	$	4,316	$	3,873
General and administrative		5,693		5,154		1,822
Total stock-based compensation	$	12,890	$	9,470	$	5,695

The estimated grant-date fair value of all the Company’s stock-based awards was calculated using the Black-Scholes option pricing model, based on the following assumptions:

	Year Ended December 31,
	2021			2020			2019
Expected term (in years)	5.3 – 7.0			5.3 – 7.0			5.3 – 6.9
Expected volatility		82 – 85	%		87 – 90	%		89 – 94	%
Risk-free interest rate		0.5 – 1.3	%		0.3 – 1.2	%		1.6 – 2.6	%
Expected dividend rate		—	%		—	%		—	%

The fair value of each stock option grant was determined by the Company on the date of grant using the methods and assumptions discussed below. Each of these inputs is subjective and generally requires significant judgment and estimation by management.

Expected Term—The expected term represents the period that stock-based awards are expected to be outstanding. As the Company’s historical share option exercise is limited due to a lack of sufficient data points, and does not provide a reasonable basis upon which to estimate an expected term, the expected term is derived by using the midpoint between the weighted-average vesting term and the contractual expiration period of the stock-based award.

Expected Volatility—The expected volatility is determined based on stock volatilities over a period equivalent to the expected term of the stock-based award. Expected volatility was derived from the trading history of the Company’s common stock for the year ended December 31, 2021, a weighted volatility using both the Company’s trading history for its common stock and the historical stock volatilities of comparable peer public companies within its industry for the year ended December 31, 2020, a weighted volatility using solely the historical stock volatilities of comparable peer public companies within its industry for the year ended December 31, 2019.

Risk-Free Interest Rate—The risk-free interest rate is based on the U.S. Treasury yield curve in effect at the date of grant for zero-coupon U.S. Treasury notes with maturities approximately equal to the stock-based awards’ expected term.

Expected Dividend Rate—The expected dividend is zero as the Company has not paid nor anticipate paying any dividends on its common stock in the foreseeable future.

In September 2018, the Company’s Compensation Committee approved the 2018 Equity Inducement Plan (2018 Plan). The number of shares available for awards under the 2018 Plan was set to 37,500. In June 2020 and February 2021, amendments to the 2018 Plan were approved by the Company’s Board of Directors and Compensation Committee, respectively, each to increase the authorized number of shares available for issuance by 500,000 shares for an aggregate increase of 1,000,000 shares. As of December 31, 2021, 1,037,500 shares were reserved for issuance under the 2018 Plan. On February 8, 2022, the Company’s Compensation Committee approved an amendment to the 2018 Plan to increase the authorized number of shares available for issuance by 500,000. The exercise price of each stock-based award issued under the 2018 Plan is required to be no less than the fair value of the Company’s common stock. The vesting and exercise provisions of options or restricted awards granted are determined individually with each grant. Stock options have a 10-year life and expire if not exercised within that period or if not exercised within three months of cessation of employment with the Company or such longer period of time as specified in the option agreement.

The 2015 Equity Incentive Plan (2015 Plan) became effective on July 14, 2015. On January 21, 2020, the Company’s stockholders approved the following amendments to the 2015 Plan: (i) increase to the authorized number of shares available for issuance by 4,312,500 shares and proportionately increase the share limit related to incentive stock options, (ii) provide limits on the total value of compensation that may be granted to any non-employee director in each calendar year, and (iii) eliminate the annual individual grant limit to reflect changes to the tax law in 2017 tax legislation.

As of December 31, 2021, 5,123,736 shares were reserved for issuance under the 2015 Plan. The number of shares reserved for issuance under the 2015 Plan will increase automatically on January 1 of each calendar

year 2016 through 2025 by the number of shares equal to 4% of the total outstanding shares of the Company’s common stock as of the immediately preceding December 31. The Company’s Board of Directors or Compensation Committee may reduce the amount of the increase in any particular year. The exercise price of each stock-based award issued under the 2015 Plan is required to be no less than the fair value of the Company’s capital stock. The vesting and exercise provisions of options or restricted awards granted are determined individually with each grant. Stock options have a 10-year life and expire if not exercised within that period or if not exercised within three months of cessation of employment with the Company or such longer period of time as specified in the option agreement, unless modified.

The Company granted options under the 2008 Stock Plan (2008 Plan) until July 2015 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 Stock Options (ISO), nonqualified stock options and stock purchase rights. In connection with the Board of Director’s approval of the 2015 Plan, all remaining shares available for future award under the 2008 Plan were transferred to the 2015 Plan, and the 2008 Plan was terminated.

A summary of activity under the 2008 Plan, 2015 Plan and 2018 Plan and related information is as follows:

				Options Outstanding
	Shares Available for Grant			Number of Shares Outstanding			Weighted- Average Exercise Price Per Share		Weighted- Average Remaining Contractual Term (Years)		Aggregate Intrinsic Value of Outstanding Options (in thousands)
Outstanding — December 31, 2020		1,117,796			4,146,928		$	19.45		8.84	$	12,227
Awards authorized		945,139
Options granted		(1,134,860	)		1,134,860			17.78
Options exercised		—			(64,847	)		13.06
Options forfeited/cancelled		279,752			(279,752	)		17.99
Outstanding — December 31, 2021		1,207,827			4,937,189		$	19.23	8.14		$	36,080
Exercisable — December 31, 2021					1,421,885		$	30.98		6.56	$	9,682
Vested and expected to vest — December 31, 2021					4,422,699		$	20.06	8.07		$	31,146

The weighted-average grant date fair values of options granted during the years ended December 31, 2021, 2020 and 2019 was $12.54, $8.81 and $50.40 per share. The aggregate intrinsic value of options exercised was $0.5 million and $0.1 million for the years ended December 31, 2021 and 2019. There were no options exercised for the year ended December 31, 2020. The total grant date fair value of options vested for the years ended December 31, 2021, 2020 and 2019 was $11.3 million, $5.2 million and $6.0 million.

In August 2020, the Company granted executives and employees stock options with performance-based conditions. Vesting is achieved based upon the satisfaction of pre-determined milestones. There were 1,029,000 and 1,104,500 of the performance-based options outstanding and unvested as of December 31, 2021 and 2020. In January 2022, the first performance-based milestone was met, and accordingly 257,255 of the performance-based options vested. For the years ended December 31, 2021 and 2020, the Company recognized $3.0 million and $0.9 million in stock-based compensation expense related to the options with performance-based criteria.

In May 2020, the Company entered into a separation agreement with the Company’s former President and Chief Executive Officer, in connection with his resignation. Pursuant to the separation agreement, the former executive’s unvested options that would have vested during the one-year period from the date of separation accelerated and vested immediately. The vesting date of all remaining unvested options accelerated by one year and vested in accordance with the accelerated vesting schedule through December 31, 2020. All unvested

options were cancelled on December 31, 2020. Furthermore, the former executive received an extension of the expiration date of his vested stock options to 75 days following the Company’s announcement of the top-line data results from its MOMENTUM clinical trial, which was announced by the Company on January 25, 2022, setting the expiration to April 10, 2022. Compensation costs relating to the vesting acceleration and the modifications to option terms was $2.2 million for the year ended December 31, 2020.

As of December 31, 2021, total unrecognized stock-based compensation related to unvested stock options was $25.3 million, which the Company expects to recognize over a remaining weighted-average period of 2.7 years. In addition, as of December 31, 2021, total unrecognized stock-based compensation related to unvested stock options with performance-based conditions was $5.3 million.

The Company adopted the 2015 Employee Stock Purchase Plan (ESPP) and initially reserved 17,500 shares of common stock as of its effective date of July 15, 2015. The aggregate number of shares issued over the term of the 2015 Employee Stock Purchase Plan will not exceed 85,000 shares of common stock. The ESPP will not become effective until such time as the Compensation Committee determines in the future, and as of December 31, 2021, the initial offering periods had not commenced. As of December 31, 2021, no shares of common stock have been issued to employees participating in the ESPP and 17,500 shares were available for issuance under the ESPP.