On July 2, 2014, the stockholders of the Company approved the 2014 Stock Option and Incentive Plan (the “2014 Plan”), which became effective immediately prior to the completion of the Company’s IPO. The 2014 Plan provides for the grant of restricted stock awards, restricted stock units, incentive stock options and non-statutory stock options. The 2014 Plan replaced the Company’s 2011 Stock Option and Grant Plan (the “2011 Plan”). The Company no longer grants stock options or other awards under its 2011 Plan, but any stock options outstanding under the 2011 Plan remain outstanding and effective in accordance with their terms.

The 2014 Plan provides for an annual increase, to be added on the first day of each fiscal year, by up to 4% of the Company’s outstanding shares of common stock as of the last day of the prior year. On January 1, 2022, 2,357,482 shares of common stock, representing 4% of the Company’s outstanding shares of common stock as of December 31, 2021, were added to the 2014 Plan.

On December 15, 2016, the Board of Directors of the Company (the “Board”) approved the 2016 Inducement Equity Plan (as amended and restated, the “2016 Plan”). The 2016 Plan provides for the grant of equity awards to individuals who have not previously been an employee or a non-employee director of the Company to induce them to accept employment and to provide them with a proprietary interest in the Company. On September 20, 2018, the Board amended the 2016 Plan to increase the total number of shares reserved for issuance by 1,200,000 shares.

Terms of equity grants, including vesting requirements, are determined by the Board or the Compensation Committee of the Board, subject to the provisions of the applicable plan. Stock options granted by the Company that are not performance-based are considered time-based because they vest based on the continued service of the grantee with the Company during a specified period following grant. These awards, when granted to employees, generally vest ratably over four years, with 25% vesting at the one-year anniversary. All stock option awards expire 10 years after the date of grant.

As of March 31, 2022, the total number of shares underlying outstanding awards under all equity plans was 9,239,206 and the total number of shares available for future issuance under all equity plans was 7,201,589 shares.

The table below summarizes activity relating to time-based restricted stock units and performance restricted stock units:

	Shares
Outstanding as of December 31, 2021		1,256,098
Granted		415,565
Vested		—
Forfeited		(47,659	)
Outstanding as of March 31, 2022		1,624,004

During the three months ended March 31, 2022 and 2021, the Company granted no time-based restricted stock units.

During the three months ended March 31, 2022 and 2021, the Company granted to its employees and consultants 415,565 and 341,721 performance restricted stock units, respectively. The performance restricted stock units granted during the three months ended March 31, 2022 are related to the achievement of certain clinical and regulatory development milestones related to product candidates and commercial milestones.

Recognition of stock-based compensation expense associated with performance restricted stock units commences when the performance condition is considered probable of achievement, using management’s best estimates, which consider the inherent risk and uncertainty regarding the future outcomes of the milestones.

As of March 31, 2022 and 2021, for performance-based restricted stock units that were outstanding, the achievement of the milestones that had not been met was considered not probable, and therefore no expense has been recognized related to these awards in the three months ended March 31, 2022 and 2021, respectively.

During the three months ended March 31, 2022 and 2021, no time-based restricted stock units or performance restricted stock units vested.

At March 31, 2022, 541,913 time-based restricted stock units were both outstanding and unvested, and the total unrecognized stock-based compensation expense related to these awards was $9.5 million.

At March 31, 2022, 1,082,091 performance restricted stock units were both outstanding and unvested, and the total unrecognized stock-based compensation expense related to these awards was $65.9 million.

The table below summarizes activity related to time-based and performance-based stock options:

	Shares			Weighted Average Exercise Price		Weighted Average Remaining Life (in years)		Aggregate Intrinsic Value (in thousands)
Outstanding as of December 31, 2021		7,283,439		$	84.17		6.74	$	16,590
Granted		662,208		$	42.71
Exercised		(105,474	)	$	6.13
Forfeited		(224,971	)	$	78.31
Outstanding as of March 31, 2022		7,615,202		$	81.82		6.86	$	4,532
Exercisable as of March 31, 2022		4,476,344		$	88.64		5.51	$	4,529

At March 31, 2022, the Company had unrecognized stock-based compensation expense related to its unvested time-based stock option awards of $84.6 million, which is expected to be recognized over the remaining weighted average vesting period of 2.77 years.

The intrinsic value of stock options exercised during the three months ended March 31, 2022 and 2021 was $3.2 million and $2.2 million, respectively.

Recognition of stock-based compensation expense associated with performance-based stock options commences when the performance condition is considered probable of achievement, using management’s best estimates, which consider the inherent risk and uncertainty regarding the future outcomes of the milestones.

As of March 31, 2022 and 2021, for performance-based stock option grants that were outstanding, the achievement of the milestones that had not been met was considered not probable, and therefore no expense has been recognized related to these awards in the three months ended March 31, 2022 and 2021, respectively.

During the three months ended March 31, 2021, in connection with the hiring of its chief executive officer, the Company granted to its chief executive officer 650,000 stock options to purchase shares of common stock that contain performance-based vesting criteria, such that the shares underlying such stock options which will vest upon the achievement of certain regulatory and commercial milestones.

During the three months ended March 31, 2022, the Company granted no stock options to employees to purchase shares of common stock that contain performance-based vesting criteria.

During the three months ended March 31, 2022 and 2021, no milestones were achieved under performance-based stock options granted to employees.

As of March 31, 2022, 682,764 performance-based stock options were both outstanding and unvested, the total unrecognized stock-based compensation expense related to these awards was $11.0 million and the timing of recognition of this stock-based compensation expense is subject to judgment of the Company as to when the performance conditions are considered probable of being achieved.

Stock-based compensation expense recognized during the three months ended March 31, 2022 and 2021 was as follows:

	Three Months Ended March 31,
	2022		2021
	(in thousands)
Research and development	$	8,615	$	9,281
Selling, general and administrative		9,938		12,695
	$	18,553	$	21,976

Stock-based compensation expense recognized during the three months ended March 31, 2022 and 2021 by award type was as follows:

	Three Months Ended March 31,
	2022		2021
	(in thousands)
Stock options	$	15,465	$	19,679
Restricted stock units		2,803		2,055
Employee stock purchase plan		285		242
	$	18,553	$	21,976

The weighted average grant date fair value per share of stock options granted under the Company’s stock option plans during the three months ended March 31, 2022 and 2021 was $27.93 and $54.93, respectively.