We have three stock-based compensation plans – the Amended and Restated 2017 Inducement Equity Plan, or the 2017 Inducement Plan, the Amended and Restated 2015 Stock Option and Incentive Plan, or 2015 Plan, and the 2012 Stock Option and Grant Plan, or 2012 Plan. As of June 30, 2022, there were 2,329,397 shares reserved under the 2017 Inducement Plan and 5,396,563 shares reserved under the 2015 Plan for the future issuance of equity awards. Upon adoption of the 2015 Plan in July 2015, no new awards or grants are permitted under the 2012 Plan. See Note 11 to the Consolidated Financial Statements included in our Annual Report on Form 10-K for the year ended December 31, 2021, for additional information related to these stock-based compensation plans.

The following summarizes stock option activity under the 2017 Inducement Plan, 2015 Plan and 2012 Plan:


	Number of Options			Weighted-Average Exercise Price
Outstanding—December 31, 2021		3,553,763		$	42.00
Options granted		671,701			29.32
Options exercised		(36,668	)		14.73
Options canceled		(150,247	)		50.13
Outstanding—June 30, 2022		4,038,549		$	39.84

The fair values of stock options granted to employees were calculated using the following assumptions:


	Three Months Ended June 30,		Six Months Ended June 30,
	2022	2021	2022	2021
Expected term (in years)	5.3	5.3-6.1	5.3-6.1	5.3-6.1
Volatility	65.50%	68.1%-72.2%	65.5%-70.5%	68.1%-72.7%
Risk-free interest rate	3.6%	1.0%-1.1%	1.4%-3.6%	0.9%-1.1%
Dividend yield	—	—	—	—

The following table summarizes activity of restricted stock units, or RSUs, granted to employees with service-based vesting under the 2017 Inducement Plan and 2015 Plan and related information:



				Weighted-
				Average
	Number			Grant Date
	of RSUs			Fair Value
Non-vested units — December 31, 2021		2,986,269		$	45.37
RSUs granted		1,886,774			29.83
RSUs vested		(482,023	)		51.13
RSUs forfeited		(300,044	)		40.03
Non-vested units — June 30, 2022		4,090,976		$	37.92

Beginning in June 2020, the Compensation Committee of our Board of Directors has granted awards of performance-based RSUs to certain of our senior management, including our executive officers, under the 2015 Plan, the vesting of which is contingent upon the achievement of three escalating stock price targets, which we refer to as the 2020 Market-Condition RSU Awards. Since June 1, 2020, certain awards have been forfeited in connection with employee terminations and new awards have been granted in connection with new appointments, with awards for up to an aggregate of 450,800 RSUs outstanding as of June 30, 2022. Upon the achievement of the respective stock price targets, 50% of the RSUs allotted to that tranche will vest, while the remaining 50% will vest on the first anniversary of the date the stock price target was achieved, subject to the employee’s continued employment or other service relationship with us through such vesting date. Under the terms of the awards, if the stock price targets are not achieved for all or some of the tranches on or before June 30, 2024, the unvested awards will be automatically terminated and forfeited. The compensation cost for the RSUs with a market condition is not reversed when the market condition is not satisfied. The target prices and vesting tranches are set forth in the following table:

The grant date fair value of the 2020 Market-Condition RSU Awards was estimated using a Monte Carlo simulation model, which includes variables such as the expected volatility of our share price and interest rates to generate potential future outcomes. We recognize the related compensation expense on a straight-line basis over the applicable derived service periods, which are the estimated periods of time that would be required to satisfy the market conditions.

The following table summarizes the 2020 Market-Condition RSU Awards granted and forfeited during the six months ended June 30, 2022:


					Weighted-
			Weighted-		Average
			Average		Remaining		Aggregate
	Number		Grant Date		Vesting		Intrinsic
	of RSUs		Fair Value		Period (years)		Value
Non-vested market-condition awards — December 31, 2021		450,800	$	43.17		0.30	$	13,195
Granted		—		—		—
Vested		—		—		—
Forfeited		—		—		—
Non-vested market condition awards — June 30, 2022		450,800	$	43.15		0.21	$	14,403

At June 30, 2022, total unrecognized compensation expense related to non-vested 2020 Market-Condition RSU Awards was $1.6 million, which is expected to be recognized over their respective remaining derived service periods. The weighted average remaining derived service period is 0.21 years. For the three and six months ended June 30, 2022, and 2021, we recognized $0.9 million, $2.0 million, $1.5 million, and $4.6 million, respectively, in stock-based compensation expense related to the 2020 Market-Condition RSU Awards.

In March 2022, the Compensation Committee of our Board of Directors granted two types of performance-based RSU awards to our executive officers under the 2015 Plan that are milestone based, with 50% of the awards earned based on relative total stockholder return, or TSR (which we refer to as the TSR RSU Awards), and 50% of the awards earned based on patient market share (which we refer to as the Patient Share RSU Awards). Each of these awards are measured over a three-year performance period beginning on January 1, 2022.

The vesting of the TSR RSU Awards is contingent upon our TSR percentile ranking relative to the companies within the NASDAQ Biotechnology Index over the three-year cumulative performance period of January 1, 2022 through December 31, 2024. Vesting is also subject to continued service requirements through the date that the Compensation Committee of our Board of Directors determines achievement of the applicable performance condition following the end of the performance period. The number of shares of common stock that could be distributed at the end of the three-year performance period may range from 0% to 200% of the target

number of shares granted. The TSR percentile rankings and performance multipliers for the TSR RSU Awards are set forth in the following table:

The grant date fair value of the TSR RSU Awards was estimated using a Monte Carlo simulation model, which includes variables such as the expected volatility of our share price and interest rates to generate potential future outcomes. We recognize the related compensation expense on a straight-line basis over the applicable derived service periods, which are the estimated periods of time that would be required to satisfy the market conditions.

The following table summarizes the TSR RSU Awards granted during the six months ended June 30, 2022:


					Weighted-
			Weighted-		Average
			Average		Remaining		Aggregate
	Number		Grant Date		Vesting		Intrinsic
	of RSUs		Fair Value		Period (years)		Value
Total Shareholder Return awards — December 31, 2021		—	$	—		—	$	—
Granted		98,276		47.34		2.59
Vested		—		—		—
Forfeited		—		—		—
Total Shareholder Return awards— June 30, 2022		98,276	$	47.34		2.59	$	3,140

At June 30, 2022, total unrecognized compensation expense related to TSR RSU Awards was $4.1 million, which is expected to be recognized over their respective remaining derived service periods. The weighted average remaining derived service period is 2.59 years. For the three and six months ended June 30, 2022, we recognized $0.4 million and $0.5 million in stock-based compensation expense related to the TSR RSU Awards.

The vesting of the Patient Share RSU Awards is contingent upon our percentage of patient share within a comparator group consisting of all U.S.-based SCD patients (including pediatric patients) during a three-year cumulative performance period of January 1, 2022 through December 31, 2024. Vesting is also subject to continued service requirements through the date that the Compensation Committee of our Board of Directors determines achievement of the applicable performance condition following the end of the performance period. The number of shares of common stock that could be distributed at the end of the three-year performance period may range from 0% to 200% of the target number of shares granted. The patient share percentages and performance multipliers for the Patient Share RSU Awards are set forth in the following table:

The following table summarizes the Patient Share RSU Awards granted during the six months ended June 30, 2022:


					Weighted-
			Weighted-		Average
			Average		Remaining		Aggregate
	Number		Grant Date		Vesting		Intrinsic
	of RSUs		Fair Value		Period (years)		Value
Performance-based awards — December 31, 2021		—	$	—		—	$	—
Granted		98,277		29.87		2.59
Vested		—		—		—
Forfeited		—		—		—
Performance-based awards— June 30, 2022		98,277	$	29.87		2.59	$	3,140

Expense for these grants is based on the fair value on the date of the grant and will be recognized over the period from the date the performance condition is determined to be probable of occurring through the date the applicable condition is expected to be met. If the performance condition is not considered probable of being achieved, no stock-based compensation expense is recognized until such time as the performance condition is considered probable of being met, if at all. As of June 30, 2022, the performance conditions were not deemed probable of achievement, and as a result no stock compensation expense was recognized for these awards. The total unrecognized compensation expense related to unvested Patient Share RSU Awards was $2.9 million.

Total stock-based compensation recognized by function included in the condensed consolidated statements of operations and comprehensive loss was as follows (in thousands):


	Three Months Ended June 30,				Six Months Ended June 30,
	2022		2021		2022		2021
Research and development	$	5,926	$	4,906	$	11,457	$	10,216
Selling, general and administrative		13,917		15,064		27,527		30,134
Total stock-based compensation expense	$	19,843	$	19,970	$	38,984	$	40,350