We primarily use the Black-Scholes option pricing model to value stock options granted to employees and non-employees, including stock options granted to members of our Board of Directors. However, the fair value of stock option market-based awards is calculated based on a Monte Carlo simulation as of the date of issuance. All stock options have 10-year terms and generally vest ratably over a 3 or 4-year period.

A summary of option activity for the nine months ended September 30, 2021 is presented below:

	Options			Weighted Average Exercise Price		Weighted Average Remaining Contractual Term (in years)		Aggregate Intrinsic Value
Outstanding at December 31, 2020		28,966,901		$	3.70
Granted		8,447,864			3.52
Exercised		(2,414,403	)		3.39
Forfeited		(1,343,995	)		3.22
Expired		(846,601	)		5.18
Outstanding at September 30, 2021		32,809,766		$	3.65		7.54	$	54,322,145
Vested or expected to vest at September 30, 2021		32,809,766		$	3.65		7.54	$	54,322,145
Exercisable at September 30, 2021		14,386,054		$	3.89		5.99	$	21,107,993

The weighted average grant-date fair values of stock options granted during the nine months ended September 30, 2021 and 2020 were $2.83 and $1.51, respectively.

As of September 30, 2021, there was approximately $37.0 million of total unrecognized share-based compensation expense related to these stock options and stock options granted under a subsidiary plan which, if all milestones are achieved, will be recognized over a weighted average period of 2.6 years.

Certain employees and consultants have been granted non-vested stock. The fair value of non-vested market-based awards is calculated based on a Monte Carlo simulation as of the date of issuance. The fair value of other non-vested stock is calculated based on the closing sale price of our common stock on the date of issuance.

A summary of non-vested stock activity for the nine months ended September 30, 2021 is presented below:

	Non-vested Shares			Weighted Average Grant Date Fair Value
Outstanding at December 31, 2020		886,816		$	2.14
Granted		1,960,701			3.24
Vested		(1,771,967	)		3.13
Forfeited		(30,000	)		3.23
Outstanding at September 30, 2021		1,045,550		$	2.38

As of September 30, 2021, there was approximately $3.3 million of unrecognized share-based compensation expense related to these non-vested shares and non-vested shares granted under a subsidiary plan which will be recognized over a period of 1.9 years.

During the nine months ended September 30, 2021, 241,507 shares were issued under the 2019 Employee Stock Purchase Plan, 2,414,403 shares were issued as a result of stock option exercises and 192,316 shares were issued as a result of the vesting of non-vested stock. Additionally, 1,579,651 shares were issued as payment for certain employee bonuses, with 550,087 of those shares being withheld to cover taxes, resulting in a net share issuance of 1,029,564.

The impact on our results of operations from share-based compensation for the three and nine months ended September 30, 2021 and 2020, was as follows (in thousands):

	Three Months Ended September 30,				Nine Months Ended September 30,
	2021		2020		2021		2020
Research and development	$	1,185	$	902	$	3,349	$	2,944
General and administrative		3,591		1,718		10,790		4,537
Total share-based compensation expense	$	4,776	$	2,620	$	14,139	$	7,481