In June 2012, the Company adopted the 2012 Equity Incentive Plan (as amended, the 2012 Plan). The 2012 Plan provides for the granting of incentive stock options, nonstatutory stock options, restricted stock units (RSUs), stock bonuses and rights to acquire restricted stock to employees, officers, directors and consultants. Incentive stock options may be granted with exercise prices of not less than 100% of the estimated fair value of the common stock and nonstatutory stock options may be granted with an exercise price of not less than 85% of the estimated fair value of the common stock on the date of grant. Stock options granted to a stockholder owning more than 10% of the voting stock must have an exercise price of not less than 110% of the estimated fair value of the common stock on the date of grant. The Board of Directors determines the estimated fair value of common stock. Stock options were generally granted with terms of up to ten years and vest over a period of four years. Upon the exercise of options, the Company issues new common stock from its authorized shares. Effective with the Company’s initial public offering in August 2015, the Company no longer issues shares from this plan and all cancelled or forfeited shares are returned to the 2015 Stock Option and Incentive Plan.

In October 2015, the Company’s Board of Directors and stockholders adopted the 2015 Stock Option and Incentive Plan (the 2015 Plan) and the 2015 Employee Stock Purchase Plan (2015 ESPP). Under the 2015 Plan, 1,650,000 shares of common stock were initially reserved for issuance, as of the pricing of the Company’s initial public offering. The number of shares initially reserved for issuance under the 2015 Plan will be increased by (i) the number of shares represented by awards outstanding under the Company’s 2012 Equity Incentive Plan that are forfeited or lapse unexercised and which following the pricing date are not issued under the 2012 Plan, and (ii) an annual increase on January 1 of each year beginning on January 1, 2017. Effective January 1, 2020 and 2019, the Company reserved an additional 1,855,162 and 1,611,557 shares of common stock, respectively, for issuance under the 2015 Plan.

The Company began issuing RSUs to employees under the 2015 Plan during the year ended December 31, 2018. RSUs settle into shares of common stock upon vesting, generally over a four-year period, and the fair value is the market price on the date of grant. During the year ended December 31, 2019, the Company also granted certain key employees performance-based RSUs.

The Company accounts for stock-based compensation arrangements with employees in accordance with ASC 718, Stock Compensation. Stock-based awards granted include stock options with time-based vesting, performance-based stock options, and restricted stock units (RSUs). ASC 718 requires the recognition of compensation expense, using a fair value-based method, for costs related to all stock-based payments. The Company’s determination of the fair value of stock options with time-based vesting on the date of grant utilizes the Black-Scholes option-pricing model, and is impacted by its common stock price as well as other variables including, but not limited to, expected term that options will remain outstanding, expected common stock price volatility over the term of the option awards, risk-free interest rates and expected dividends.

Stock-based compensation expense for performance stock options and RSUs is based on the probability of achieving certain performance criteria, as defined in the individual grant agreement. The Company estimates the number of performance options and RSUs ultimately expected to vest and recognizes stock-based compensation expense for those options and RSUs expected to vest when it becomes probable that the performance criteria will be met.

The fair value of a stock-based award is recognized over the period during which a grantee is required to provide services in exchange for the option or RSU award, known as the requisite service period (usually the vesting period), on a straight-line basis. The Company accounts for forfeitures as they occur.

Equity instruments issued to non-employees are recorded at their fair value on the grant date. The fair value of options granted to consultants is expensed over the non-employees’ vesting period. Non-employee stock-based compensation expense was not material for all periods presented.

Estimating the fair value of equity-settled awards as of the grant date using valuation models, such as the Black-Scholes option pricing model, is affected by assumptions regarding a number of complex variables. Changes in the assumptions can materially affect the fair value and ultimately how much stock-based compensation expense is recognized. These inputs are subjective and generally require significant analysis and judgment to develop.

Expected Term—The expected term assumption represents the weighted-average period that the Company’s stock-based awards are expected to be outstanding. The expected term of the Company’s options exceeds the number of years the Company has been a publicly held corporation; therefore, the Company has opted to use the “simplified method” for estimating the expected term of the options. The simplified method is calculated as average of the vesting term and the original contractual term of the option.

Expected Volatility—For all stock options granted to date, the volatility data was estimated based on a study of the Company’s trading history and that of its publicly traded industry peer companies. For purposes of identifying these peer companies, the Company considered the industry, stage of development, size and financial leverage of potential comparable companies.

Expected Dividend—The Black-Scholes valuation model calls for a single expected dividend yield as an input. The Company currently has no history or expectation of paying cash dividends on its common stock.

Risk-Free Interest Rate—The risk-free interest rate is based on the yield available on U.S. Treasury zero-coupon issues similar in duration to the expected term of the equity-settled award.

In October 2015, the Company adopted the 2015 ESPP, which provides eligible employees with the opportunity to acquire an ownership interest in the Company through periodic payroll deductions, based on a six-month look-back period, at a price equal to the lesser of 85% of the fair market value of the common stock at either the first business day or last business day of the relevant offering period, provided that no more than 2,500 shares of common stock may be purchased by any one employee during each offering period. The 2015 ESPP is intended to constitute an “employee stock purchase plan” under Section 423(b) of the Internal Revenue Code of 1986, as amended. The 2015 ESPP may be terminated by the Company’s board of directors at any time. A total of 255,000 shares of common stock were initially reserved for issuance under the 2015 ESPP, subject to an annual increase on January 1 of each year beginning on January 1, 2017. Effective January 1, 2020 and 2019, the Company reserved an additional 463,790 and 402,889 shares of common stock, respectively, for issuance under the 2015 ESPP.

The following table summarizes stock option activity and related information for the periods presented below:

	Shares Subject to Outstanding Options			Weighted Average Exercise Price Per Option		Weighted Average Remaining Contractual Term (in years)		Aggregate Intrinsic Value (in thousands)
Balance at December 31, 2018		3,701,461		$	26.40
Options granted		1,371,130			43.27
Options exercised		(337,846	)		15.78
Options canceled		(160,587	)		38.75
Balance at December 31, 2019		4,574,158		$	31.81		7.7	$	187,879
Exercisable at December 31, 2019		2,380,560		$	23.21		7.0	$	118,246
Vested and expected to vest at December 31, 2019		4,574,158		$	31.81		7.7	$	187,879

The aggregate intrinsic value of options was calculated as the difference between the exercise price of the options and the estimated fair value of common stock. The aggregate intrinsic value of options exercised was $14.3 million, $21.1 million and $9.8 million for the years ended December 31, 2019, 2018 and 2017, respectively. The weighted‑average grant date fair value of options granted under the Company’s stock plans in the years ended December 31, 2019, 2018 and 2017 was $27.02, $34.70 and $9.92 per share, respectively. As of December 31, 2019, total unamortized stock-based compensation relating to options was $55.3 million, which is expected to be recognized over the average remaining vesting period of 2.4 years. The following table illustrates the assumptions for the Black-Scholes option-pricing model used in determining the fair value of time-based and performance-based options granted to employees:

	Year Ended December 31,
	2019	2018	2017
Risk-free interest rate	1.59% - 2.54%	2.54% - 2.98%	1.92% - 2.27%
Expected life (in years)	6.1%	5.3 - 6.1	5.3 - 6.1
Volatility	65% - 69%	69% - 75%	71% - 75%
Dividend yield	0%	0%	0%

The following table summarizes RSU activity and related information for the period presented below:

	Shares Subject to Outstanding Awards			Weighted Average Grant Date Fair Value		Weighted Average Remaining Contractual Term (in years)		Aggregate Intrinsic Value (in thousands)
Balance at December 31, 2018		162,946		$	53.37
RSUs awarded		643,814			45.36
RSUs released		(42,214	)		53.08
RSUs forfeited		(23,450	)		48.23
Balance at December 31, 2019		741,096		$	46.59		2.2	$	54,015

The weighted -average grant-date fair value of RSUs granted during the years ended December 31, 2019 and 2018 was $45.36 and $53.27, respectively. The total fair value of RSUs vested during the years ended December 31, 2019, 2018 and 2017 was $2.0 million, $167,000 and zero, respectively. As of December 31, 2019, total unamortized stock-based compensation relating to RSUs was $27.9 million, which is expected to be recognized over the average remaining vesting period of 3.1 years.

Stock-based compensation expense, net of forfeitures, as applicable for the years ended December 31, 2019, 2018 and 2017, is reflected in the statements of operations and comprehensive loss as follows (in thousands):

	Year Ended December 31,
	2019		2018		2017
Research and development	$	14,673	$	8,144	$	2,752
Selling, general and administrative	$	18,321		11,197		3,386
Total stock-based compensation	$	32,994	$	19,341	$	6,138

During the years ended December 31, 2018, 2017, and 2016, the Company recognized $340,000, $248,000 and $174,000 in stock-based compensation expense relating to stock options issued with performance-based vesting criteria, including the achievement of certain clinical and regulatory development milestones related to product candidates as well as commercial milestones. Recognition of stock-based compensation expense associated with these 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 activities described by the milestones.