In May 2013 the Company’s Board of Directors adopted the 2013 Equity Incentive Plan (the “2013 Plan”). The Company’s Board of Directors and stockholders approved an amendment to the 2013 Plan in 2021 to, among other things, increase the aggregate number of shares of common stock authorized for issuance under the 2013 Plan by 2.5 million shares. In May 2022, the 2022 Equity Incentive Plan (the “2022 Plan”) was approved by the Company’s Board of Directors and stockholders as the successor to the 2013 Plan. All shares available under the 2013 Plan were transferred to the 2022 Plan and the aggregate number of shares of common stock authorized for issuance under the 2022 Plan was increased by 3.5 million shares. As of December 31, 2022, there were approximately 4.1 million shares available to be granted from the 2022 Plan.

In December 2019, the Company’s Board of Directors adopted the Inducement Plan, reserving shares of the Company’s common stock for issuance of stock options and other equity-based awards to new employees who satisfy the standards for inducement grants in accordance with the Nasdaq Stock Market LLC listing rules. In July 2022, the Company's Board of Directors approved an amendment to the Inducement Plan to increase the aggregate number of shares of common stock authorized for issuance by 1.0 million shares. As of December 31, 2022, there were 0.4 million shares available to be issued from the Inducement Plan.

As of December 31, 2022, share-based compensation awards consist of incentive and non-qualified stock options, restricted stock units, and performance stock units. Stock options granted under each of the plans must have an exercise price equal to at least 100% of the fair market value of the Company’s common stock on the date of grant and generally vest over four years. Stock options granted under the 2013 Plan, the 2022 Plan and the Inducement Plan have a contractual term of ten years.


	Number of Options	Weighted Average Exercise Price		Weighted-Average Remaining Contractual Term (years)	Aggregate Intrinsic Value (millions)
Balance outstanding as of December 31, 2021	4,532,252	$	85.38
Granted	1,690,707	$	94.43
Exercised	(272,434)	$	36.43
Forfeited and expired	(412,734)	$	132.27
Balance outstanding as of December 31, 2022	5,537,791	$	87.05	6.7	$	33.0
Options exercisable at December 31, 2022	3,187,936	$	68.49	5.1	$	32.4

The total intrinsic value of stock options exercised was $15.5 million, $91.1 million and $121.5 million for the years ended December 31, 2022, 2021 and 2020, respectively. The Company received total cash of $9.9 million, $28.0 million and $45.9 million for the exercise of options for the years ended December 31, 2022, 2021 and 2020, respectively. The total fair value of options vested during the years ended December 31, 2022, 2021 and 2020 was $73.9 million, $58.3 million and $52.1 million, respectively.

The fair value of options granted is estimated at the date of grant using the Black-Scholes option pricing model. Forfeitures are accounted for as incurred as a reversal of any share-based compensation expense related to options that will not vest. The assumptions used for the specified reporting periods and the resulting estimates of weighted-average estimated fair value per share of options granted during those periods are as follows:


	Year Ended December 31,
	2022	2021	2020
Risk-free interest rate	2.4%	0.8%	1.1%
Dividend yield	—%	—%	—%
Volatility factor	74.5%	76.9%	81.5%
Expected term (in years)	5.1	5.1	5.6
Weighted-average estimated fair value per share	$58.11	$110.43	$77.92

Dividend Yield - The dividend yield is based on the Company’s history and expectation of dividend payouts. The Company has not paid, and does not intend to pay dividends.

The total compensation cost not yet recognized as of December 31, 2022 related to non-vested option awards was $79.0 million which will be recognized over a weighted-average period of 1.3 years.

The Company began issuing RSUs during 2020. RSUs generally vest annually over four years and are subject to continued service. A summary of the Company’s RSU activity for the year ended December 31, 2022 is as follows:


	Number of RSUs	Weighted Average Grant Date Fair Value		Aggregate Intrinsic Value (millions)
Balance outstanding as of December 31, 2021	720,567	$	156.55
Granted	1,571,697	$	83.78
Released	(217,542)	$	152.95
Canceled/forfeited	(193,048)	$	124.21
Balance outstanding as of December 31, 2022	1,881,674	$	99.51	$	85.3

The total fair value of RSUs that vested during the year ended December 31, 2022 was $33.3 million. The total compensation cost not yet recognized as of December 31, 2022 related to non-vested RSUs was $99.8 million, which will be recognized over a weighted-average period of 1.5 years.

The Company began issuing PSUs during 2020. PSUs generally begin to vest upon achievement of certain performance goals and are subject to continued service. A summary of the Company’s PSU activity for the year ended December 31, 2022 is as follows:


	Number of PSUs	Weighted Average Grant Date Fair Value		Aggregate Intrinsic Value (millions)
Balance outstanding as of December 31, 2021	281,611	$	157.58
Granted	99,050	$	35.57
Released	(67,850)	$	158.89
Canceled/forfeited	(32,720)	$	150.31
Balance outstanding as of December 31, 2022	280,091	$	114.96	$	12.7

The total fair value of PSUs that vested during the year ended December 31, 2022 was $10.8 million. The total compensation cost not yet recognized as of December 31, 2022 related to non-vested PSUs was $15.8 million, which will be recognized over a weighted-average period of 1.3 years.


	Year ended December 31,
	2022		2021		2020
Research and development expense	$	113,544	$	68,496	$	48,044
Selling, general and administrative expense	72,644		45,006		37,803
	$	186,188	$	113,502	$	85,847

For the years ended December 31, 2022, 2021 and 2020, no share-based compensation expense was capitalized and there were no recognized tax benefits associated with the share-based compensation charge.

In May 2013, the Company’s Board of Directors adopted and the stockholders approved the 2013 Employee Stock Purchase Plan (the “ESPP”). In December 2014, the ESPP became effective and the first purchase period began. The ESPP permits eligible employees to make payroll deductions to purchase up to $25,000 of the Company’s common stock on regularly scheduled purchase dates at a discount. Offering periods under the ESPP are not more than six months in duration and shares are purchased at 85% of the lower of the closing price for the Company’s common stock on the first day of the offering period or the date of purchase. The ESPP initially authorized the issuance of 300,000 shares of the Company’s common stock pursuant