In October 2017, the Company entered into the Sales Agreement with SVB Leerink, pursuant to which the Company may sell up to $30 million in shares of its common stock from time to time through SVB Leerink, acting as its sales agent, in one or more at-the-market offerings. In January 2019, the Company raised approximately $25.8 million in gross proceeds through the sale of 3,164,015 shares under the Sales Agreement. Upon completion of this final sale, the Sales Agreement was automatically terminated, SVB Leerink received a commission of 3.0% of the gross proceeds for all shares sold under the Sales Agreement.

In December 2017, the Company completed the Registered Direct Offering, whereby it sold an aggregate of $9.5 million worth of units (“Units”) at a purchase price of $5.325 per Unit with each Unit consisting of (i) one share of the Company’s common stock, and (ii) a Common Warrant at an exercise price equal to $5.25 per share. The Company sold an aggregate of 1,783,587 Units for gross proceeds of approximately $9.5 million and net proceeds of approximately $8.8 million, net of underwriting discounts and offering expenses. Additionally, the Company issued 107,015 Placement Agent Warrants. The Company incurred issuance costs associated with the Units offering of $745,856, which included $81,000 related to issuance of 107,015 Placement Agent Warrants, of which, $583,768 was allocated to the common stock sold and was recorded as a reduction to equity. The remaining amount was allocated to the Common Warrants and was expensed. The Placement Agent Warrants have the same terms as the Common Warrants, except for the exercise price of $6.6562 per share. The Common Warrants priced at $5.25 and Placement Agent Warrants priced at $6.6562 utilized the 2016 Shelf Registration Statement for a total of $9.4 million and $712,313.

On September 27, 2018, the Company entered into a purchase agreement with certain institutional and accredited investors (collectively, the “RDO Investors”) for the sale by the Company directly to the RDO Investors of an aggregate of 2,966,667 shares of the Company’s common stock, at a purchase price of $3.00 per share (the “2018 Registered Direct Offering”), for gross proceeds of approximately $8.9 million. The 2018 Registered Direct Offering closed on October 1, 2018, and the Company received net proceeds of approximately $8.8 million, after deducting transaction expenses. The 2,966,667 shares of common stock sold in the 2018 Registered Direct Offering were offered and sold by the Company directly to the RDO Investors, without a placement agent, underwriter, broker or dealer, pursuant to a prospectus supplement to the 2016 Shelf Registration Statement.

In May 2019, the Company entered into the May 2019 Sales Agreement with SVB Leerink, pursuant to which the Company may sell up to $50 million in shares of the Company’s common stock from time to time through SVB Leerink, acting as the Company’s sales agent, in one or more at-the-market offerings utilizing the 2016 Shelf Registration Statement. SVB Leerink is entitled to receive a commission of 3.0% of the gross proceeds for any shares sold under the May 2019 Sales Agreement. Due to expiration of the 2016 Shelf Registration Statement, at the Company’s option, the shares that were unsold of approximately $29.9 million under the May 2019 Sales Agreement, may be rolled over to the December 2019 Sales Agreement (see below).

In December 2019, the Company entered into the December 2019 Sales Agreement with SVB Leerink, pursuant to which the Company may sell up to $80 million in shares of the Company’s common stock from time to time through SVB Leerink, acting as the Company’s sales agent, in one or more at-the-market offerings utilizing the 2019 Shelf Registration Statement. SVB Leerink is entitled to receive a commission of 3.0% of the gross proceeds for any shares sold under the December 2019 Sales Agreement. For the year ended December 31, 2020, the Company received approximately $14.6 million in gross proceeds through the sale of 167,243 shares, of which net proceeds were approximately $14.1 million. For the year ended December 31, 2019, the Company received approximately $7.3 million in gross proceeds through the sale of 89,390 shares, of which net proceeds were approximately $7.1 million.

In December 2019, the Company completed an underwritten public offering, whereby the Company sold 2,300,000 shares of our common stock at a public offering price of $87.00 per share. The Company received gross proceeds of approximately $200.1 million and net proceeds of approximately $187.1 million, net of underwriting discounts and offering expenses.

The holders of shares of common stock are entitled to one vote for each share of common stock held at all meetings of stockholders and written actions in lieu of meetings. The holders of shares of common stock are entitled to receive dividends, if and when declared by the board of directors.

On December 5, 2019, the Company filed an automatic shelf registration statement (“2019 Shelf Registration”) with the Securities and Exchange Commission (“SEC”) for the issuance of common stock, preferred stock, warrants, rights, debt securities and units. It became effective upon filing with the SEC and is currently the Company’s only active shelf registration. Through the date of this report, the Company has issued common stock of approximately $221.9 million pursuant to such shelf registration statement.

Under SEC rules, the 2019 Shelf Registration Statement allows for the potential future offer and sale by the Company, from time to time, in one or more public offerings, of an indeterminate amount of the Company’s common stock, preferred stock, debt securities, and units at indeterminate prices. At the time any of the securities covered by the 2019 Shelf Registration Statement are offered for sale, a prospectus supplement will be prepared and filed with the SEC containing specific information about the terms of any such offering.

The Company had granted stock options under its 2013 Equity Compensation Plan (the “2013 Plan”), which was adopted for employees and consultants for the purpose of advancing the interests of the Company's stockholders by enhancing its ability to attract, retain and motivate persons who are expected to make important contributions to the Company. In November 2015, the 2015 Omnibus Incentive Compensation Plan (the “2015 Plan”) was adopted by the Company’s stockholders. The 2015 Plan is the successor to the Company's 2013 Plan. In conjunction with the adoption of the 2015 Plan, no additional grants were made from the 2013 Plan and options from the 2013 Plan remain outstanding. As of December 31, 2020, there were 4,149,112 shares available for future grant under the 2015 Plan.

In June 2020, in connection with the decision not to stand for re-election by a member of the Company’s Board of Director’s, the vesting of stock options covering 21,666 shares of common stock was accelerated. As a result of this modification, the Company recorded incremental stock-based compensation expense of approximately $1.3 million for the year ended December 31, 2020.

In November 2020, certain employee Stock Options and Restricted Stock Units were cancelled. Stock options to purchase an aggregate of 38,267 shares of common stock were cancelled, and the Company recognized non-cash stock-based compensation expense of $2.1 million related to this cancellation for the year ended December 31, 2020. Restricted Stock Units for an aggregate of 11,735 shares of common stock were cancelled, and the Company recognized non-cash stock-based compensation expense of $0.5 million related to this cancellation for the year ended December 31, 2020.

						Weighted
				Weighted		average		Aggregate
	Number			average		contractual		intrinsic
	of shares			exercise price		term		value
Outstanding at December 31, 2019		3,458,447			10.19
Granted		649,142			54.50
Exercised		(127,778	)		8.22
Forfeited		(207,628	)		35.85
Cancelled		(38,267	)		58.98
Outstanding at December 31, 2020		3,733,916			16.03		7.2		243,556,917
Vested and expected to vest at December 31, 2020		3,727,747			16.36		7.2		243,062,340
Exercisable at December 31, 2020		2,479,110			10.66		6.0		175,575,360

The fair value of each stock option grant is estimated on the date of grant using the Black‑Scholes option pricing model. The expected term of the Company’s stock options has been determined utilizing the “simplified” method as described in the SEC’s Staff Accounting Bulletin No. 107 relating to stock‑based compensation. The simplified method was chosen because the Company has limited historical option exercise experience due to its short operating history. The risk‑free interest rate is based on the U.S. Treasury yield in effect at the time of grant for a period approximately equal to the expected term of the award. Expected dividend yield is based on the fact that the Company has never paid cash dividends and does not expect to pay any cash dividends in the foreseeable future. Expected volatility is based on historical volatilities of similar entities within the Company’s industry which were commensurate with the Company’s expected term assumption. The relevant data used to determine the value of the stock option grants for the years ended December 31, 2020, 2019, and 2018 is as follows:

Black-Scholes option valuation assumptions	2020		2019		2018
Risk-free interest rates	0.3 - 1.7%		1.4 - 2.7%		2.0 - 3.1%
Dividend yield		—		—		—
Volatility	67 - 99%		87 - 91 %		74 - 87%
Weighted average expected term	3.51 - 6.14 years		5.00 - 6.13 years		3.66 - 6.13 years

The weighted average grant date fair value of options granted was $36.77, $12.49, and $1.99 per option for the years ended December 31, 2020, 2019 and 2018, respectively. As of December 31, 2020, there was $20.9 million of total unrecognized compensation cost related to non‑vested stock options which is expected to be recognized over a weighted average period of 2.8 years. These amounts do not include 10,716 options outstanding as of December 31, 2020, which are performance‑based and vest upon the achievement of certain corporate milestones. Stock‑based compensation will be measured and recorded if and when it is probable that the milestone will occur. The intrinsic value of stock options exercised during the years ended December 31, 2020, 2019 and 2018 was $9.4 million, $4.5 million and $0.5 million, respectively.

In 2020, the Company began granting RSUs covering an equal number of its shares of common stock to employees. The fair value of RSUs is determined on the date of the grant based on the market price of its shares of common stock as of that date. The fair value of the RSUs is recognized as an expense ratably over the vesting period of four years. As of December 31, 2020, total compensation cost not yet recognized related to unvested RSUs was $4.1 million, which is expected to be recognized over a weighted-average period of 3.3 years.

The following table sets forth the RSU activity for the year ended December 31, 2020:

				Weighted
				average
	Number			grant date
	of shares			fair value
Outstanding at December 31, 2019		—		$	—
Granted		161,268			37.42
Released		—			—
Forfeited		(13,466	)		86.88
Cancelled		(11,735	)		45.14
Outstanding at December 31, 2020		136,067		$	35.76

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

	2020		2019		2018
Research and development	$	3,953,939	$	1,584,165	$	391,946
General and administrative		10,802,267		4,530,995		1,363,028
Total	$	14,756,206	$	6,115,160	$	1,754,974