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, 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 (the “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, 2019 and 2018, the Company reserved an additional 1,611,557 and 1,432,511 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.

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, 2019 and 2018, the Company reserved an additional 402,889 and 358,127 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, 2016		2,141,868		$	6.42		8.4	$	14,963
Options granted		1,735,875			15.41
Options exercised		(333,822	)		4.81
Options canceled		(579,372	)		8.11
Balance at December 31, 2017		2,964,549			11.54		8.3		90,780
Options granted		1,370,381			52.53
Options exercised		(489,153	)		10.61
Options canceled		(144,316	)		22.67
Balance at December 31, 2018		3,701,461			26.40		8.0		88,524
Options outstanding and exercisable as of December 31, 2018		1,519,637			14.35		7.3		52,979

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 $21.1 million, $9.8 million and $337,000 for the years ended December 31, 2018, 2017 and 2016, respectively. The total estimated grant date fair value of options vested during the years ended December 31, 2018, 2017 and 2016 was $13.4 million, $4.8 million and $2.1 million, respectively.

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, 2017		—		$	—		—	$	—
RSUs awarded		171,766			53.27
RSUs released		(3,250	)		48.93
RSUs forfeited		(5,570	)		52.83
Balance at December 31, 2018		162,946			53.37		2.0		7,962

The aggregate intrinsic value of RSUs was calculated using the estimated fair value of common stock times the number of RSUs. The total grant date fair value of RSUs vested during the years ended December 31, 2018, 2017 and 2016 was $159,000, nil and nil, respectively.

Stock-based compensation expense, net of forfeitures, as applicable for the years ended December 31, 2018, 2017 and 2016, is reflected in the statements of operations and comprehensive loss as follows (in thousands):

	Year Ended December 31,
	2018		2017		2016
Research and development	$	8,144	$	2,752	$	1,252
General and administrative		11,197		3,386		1,561
Total stock-based compensation	$	19,341	$	6,138	$	2,813

As of December 31, 2018, total unamortized stock-based compensation relating to options was $45.9 million, which is expected to be recognized over the average remaining vesting period of 3.1 years. As of December 31, 2017, total unamortized stock-based compensation was $16.9 million, which was expected to be recognized over the average remaining vesting period of 1.7 years. As of December 31, 2016, total unamortized stock-based compensation was $7.5 million, which was expected to be recognized over the remaining vesting period of 2.7 years.

As of December 31, 2018, total unamortized stock-based compensation relating to RSUs was $7.0 million, which is expected to be recognized over the average remaining vesting period of 3.2 years.

In relation to stock options and awards that vest upon the achievement of performance criteria, $248,000, $174,000 and $180,000 in stock-based compensation expense was recorded for the years ended December 31, 2018, 2017 and 2016, respectively. The Company begins to recognize expenses related to these options and awards during the period upon concluding that certain performance criteria are considered probable.

The weighted‑average grant date fair value of options granted under the Company’s stock plans in the years ended December 31, 2018, 2017 and 2016 was $34.70, $9.92 and $7.59 per share, respectively. 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,
	2018	2017	2016
Risk-free interest rate	2.54%-2.98%	1.92%-2.27%	1.05%-2.10%
Expected life (in years)	5.3-6.1	5.3-6.1	5.3-6.1
Volatility	69%-75%	71%-75%	71%-73%
Dividend yield	0%	0%	0%

In relation to stock options that vest upon the achievement of market-based stock price target, the Company estimated the fair value on the original grant date using a Monte-Carlo simulation model. Since its IPO, the Company has recognized the stock-based compensation expense on a straight-line basis over the implicit service period as derived under that simulation model.

As of December 31, 2018 and 2017, there were 9,790 and 81,373, respectively, of unvested common shares outstanding that were issued upon the early exercise of stock options prior to the vesting of the underlying shares and subject to repurchase by the Company at the original issuance price upon termination of the stockholders’ services. The right to repurchase these shares generally lapses with respect to 25% of the shares underlying the option after one year of service to the Company and 1/48 of the shares underlying the original grant per month for 36 months thereafter. The shares purchased by the employees pursuant to the early exercise of stock options are not deemed, for accounting purposes, to be issued until those shares vest. The cash received in exchange for exercised and unvested shares related to stock options granted is recorded as a liability for the early exercise of stock options on the consolidated balance sheets and will be reclassified to common stock and additional paid-in capital as the shares vest. As of December 31, 2018, and 2017, the Company recorded $15,000 and $68,000, respectively, within accrued liabilities and other long-term liabilities associated with shares issued subject to repurchase rights.

The Company repurchased 997 and 41,961 shares of unvested early exercised stock in the years ended December 31, 2018 and 2017, for $1,000 and $45,000, respectively.