(12) Stock‑Based Compensation

The Company has the following stock-based compensation plans: the 2004 Employee Stock Purchase Plan (the “2004 ESPP Plan”) and the 2008 Stock Option and Incentive Plan (the “2008 Plan”).

Employee Stock Purchase Plan

At December 31, 2020, a total of 276,666 shares of common stock are reserved for issuance under the 2004 ESPP Plan. Under the 2004 ESPP Plan, each participating employee may purchase shares of common stock through payroll deductions at a purchase price equal to 85% of the lower of the fair market value of the common stock at either the beginning of the offering period or the applicable exercise date. During the years ended December 31, 2020, 2019 and 2018, the Company issued 39,817, 3,507 and 9,524 shares under the 2004 ESPP Plan, respectively. At December 31, 2020, 210,342 shares were available for issuance under the 2004 ESPP Plan.

Employee Stock Option and Incentive Plan

The 2008 Plan permits the granting of incentive stock options (intended to qualify as such under Section 422A of the Internal Revenue Code of 1986, as amended), non‑qualified stock options, stock appreciation rights, performance share units, restricted stock and other awards of restricted stock in lieu of cash bonuses to employees, consultants and non‑employee directors.

At December 31, 2020, the 2008 Plan allowed for a maximum of 4,133,333 shares of common stock to be issued for grants of new awards until June 9, 2025 and grants of incentive stock options until April 16, 2025. The Company’s Board of Directors determines the term of each option, option price, and number of shares for which each option is granted and the rate at which each option vests. Options generally vest over a period not to exceed four years. The term of each option cannot exceed ten years (five years for options granted to holders of more than 10% of the voting stock of the Company), and the exercise price of stock options cannot be less than the fair market value of the common stock at the date of grant (110% of fair market value for incentive stock options granted to holders of more than 10% of the voting stock of the Company). Vesting of all employee and non‑employee director stock option awards may accelerate upon a change in control as defined in the 2008 Plan.

A summary of stock option activity for the year ended December 31, 2020 is as follows:


		Weighted		Weighted
		Average		Average
		Exercise		Remaining
		Price		Contractual
	Shares	Per Share		Term (In Years)
Options outstanding at December 31, 2019	1,699,202	$	44.87	8.0
Granted	1,512,675	$	10.53
Exercised	(78,259)	$	4.57
Canceled	(91,389)	$	41.86
Options outstanding at December 31, 2020	3,042,229	$	28.93	8.2
Options vested and expected to vest at December 31, 2020	2,881,532	$	30.04	8.2
Options exercisable at December 31, 2020	907,982	$	76.39	6.2
Shares available for grant under the 2008 Plan	898,977

The total intrinsic value of stock options exercised during the years ended December 31, 2020, 2019 and 2018 was $0.8 million, $0.0 million and $0.0 million, respectively. The weighted average grant‑date fair value of stock options granted during the years ended December 31, 2020, 2019 and 2018 was $8.08, $2.08 and $6.60, respectively. The total fair value of stock options vested during the years ended December 31, 2020, 2019 and 2018 was $2.4 million, $4.9 million and $8.0 million, respectively.

The aggregate intrinsic value of stock options outstanding at December 31, 2020 was $24.7 million. The aggregate intrinsic value of stock options vested and expected to vest at December 31, 2020 was $23.3 million. As of December 31, 2020, total compensation cost related to non‑vested employee and non‑employee director stock options not yet recognized was approximately $11.3 million, net of estimated forfeitures, which is expected to be recognized as expense over a weighted average period of 3.0 years.

Restricted Stock

A summary of restricted stock activity under the 2008 Plan for the year ended December 31, 2020 is as follows:


		Weighted
		Average
		Grant Date
		Fair Value
	Shares	(per share)
Outstanding and unvested at December 31, 2019	1,110	$	34.83
Granted	—	$	—
Vested	(1,110)	$	34.83
Canceled	—	$	—
Outstanding and unvested at December 31, 2020	—	$	—

Valuation and Expenses Information

Stock‑based compensation expense for the years ended December 31, 2020, 2019 and 2018 was recorded as follows:


	2020		2019		2018
	(In thousands)
Research and development	$	1,933	$	2,053	$	3,874
General and administrative		1,982		2,498		4,207
Total stock-based compensation expense	$	3,915	$	4,551	$	8,081

The fair values of employee and director stock options granted during the years ended December 31, 2020, 2019 and 2018 were valued using the Black‑Scholes option pricing model with the following assumptions:


	2020	2019	2018
Expected stock price volatility	91 - 98%	90 - 91%	73 - 85%
Expected option term	6.0 Years	6.0 Years	6.0 Years
Risk-free interest rate	0.5 - 0.7%	1.6 - 2.5%	2.8 - 3.1%
Expected dividend yield	None	None	None

The Company estimates expected term based on historical exercise patterns. The Company uses its historical stock price volatility consistent with the expected term of grant as the basis for its expected volatility assumption. The risk‑free interest rate is based upon the yield of U.S. Treasury securities consistent with the expected term of the option. The dividend yield assumption is based on the Company’s history of zero dividend payouts and expectation that no dividends will be paid in the foreseeable future.