			Gross Unrealized
					Losses
	Amortized				Less than			Greater than			Estimated
December 31, 2022	Cost		Gains		One Year			One Year			Fair Value
Short-term investments:
Available-for-sale securities:
Corporate debt securities	$	145,421	$	—	$	(432	)	$	(2,054	)	$	142,935
U.S. government and agency debt securities		143,710		16		(266	)		(1,289	)		142,171
Non-U.S. government debt securities		31,452		—		(20	)		(546	)		30,886
Total short-term investments		320,583		16		(718	)		(3,889	)		315,992
Long-term investments:
Available-for-sale securities:
Corporate debt securities		68,229		—		(1,550	)		(676	)		66,003
U.S. government and agency debt securities		62,220		—		(917	)		(1,424	)		59,879
Non-U.S. government debt securities		4,099		—		—			(191	)		3,908
		134,548		—		(2,467	)		(2,291	)		129,790
Held-to-maturity securities:
Certificates of deposit		1,820		—		—			—			1,820
Total long-term investments		136,368		—		(2,467	)		(2,291	)		131,610
Total investments	$	456,951	$	16	$	(3,185	)	$	(6,180	)	$	447,602

December 31, 2021
Short-term investments:
Available-for-sale securities:
Corporate debt securities	$	85,201	$	177	$	(39	)	$	—		$	85,339
U.S. government and agency debt securities		45,349		35		(24	)		—			45,360
Non-U.S. government debt securities		68,046		75		(53	)		—			68,068
Total short-term investments		198,596		287		(116	)		—			198,767
Long-term investments:
Available-for-sale securities:
Corporate debt securities		111,793		—		(654	)		—			111,139
U.S. government and agency debt securities		81,296		—		(517	)		—			80,779
Non-U.S. government debt securities		35,902		—		(210	)		—			35,692
		228,991		—		(1,381	)		—			227,610
Held-to-maturity securities:
Certificates of deposit		1,820		—		—			—			1,820
Total long-term investments		230,811		—		(1,381	)		—			229,430
Total investments	$	429,407	$	287	$	(1,497	)	$	—		$	428,197

At December 31, 2022, the Company reviewed its investment portfolio to assess whether the unrealized losses on its available-for-sale investments were temporary. Investments with unrealized losses consisted primarily of corporate debt securities and debt securities issued by non-U.S. agencies and backed by non-U.S. governments. At December 31, 2022, 280 of the Company’s 289 investment securities were in an unrealized loss position and had an aggregate estimated fair value of $422.7 million. Approximately 47% and 45% of the Company’s investment securities at December 31, 2022 are in corporate debt securities, with a minimum rating of A2 (Moody’s)/A (Standard and Poor’s), and debt securities issued by the U.S. government or its agencies, respectively. In a rising interest rate environment, the Company expects its fixed-rate investment securities will carry unrealized losses. In making the determination whether the decline in fair value of these securities was other-than-temporary, the Company evaluated whether it intended to sell the security and whether it was more likely than not that the Company would be required to sell the security before recovering its amortized cost basis. The Company has the intent and ability to hold these investments until recovery, which may be at maturity.

In September 2019, the Company purchased $1.9 million of convertible promissory notes from Synchronicity Pharma, Inc. (“Synchronicity”), a related party. The notes were due to mature on the earlier of June 30, 2021, the closing of a preferred equity financing, the closing of a merger, business combination or sale of stock resulting in Synchronicity’s stockholders owning less than 50% of the surviving entity, or an event of default. During the years ended December 31, 2021 and 2020, the Company recorded an other-than-temporary credit loss of $0.9 million and $1.0 million, respectively, against the value of this investment and at December

31, 2021, this investment was fully impaired. The losses were recorded within “Other income, net” in the accompanying consolidated statements of operations and comprehensive loss.

In January 2022, the Company purchased $0.5 million of convertible promissory notes from Synchronicity that matured on the earlier of September 30, 2022, the closing of a preferred equity financing, the closing of a merger, business combination or sale of stock resulting in Synchronicity’s stockholders owning less than 50% of the surviving entity, or an event of default. During the year ended December 31, 2022, the Company determined there was an other-than-temporary loss related to this investment in Synchronicity and the $0.5 million was recorded within “Other income, net” in the accompanying consolidated statements of operations and comprehensive loss.

In May 2014, the Company entered into an agreement whereby it is committed to provide up to €7.4 million to a partnership, Fountain Healthcare Partners II, L.P. of Ireland (“Fountain”), which was created to carry on the business of investing exclusively in companies and businesses engaged in the healthcare, pharmaceutical and life sciences sectors. As of December 31, 2022, the Company’s total contribution in Fountain was equal to €7.4 million, and its commitment represented approximately 7% of the partnership’s total funding. The Company is accounting for its investment in Fountain under the equity method.

During the year ended December 31, 2020, two of the companies within the Fountain portfolio were acquired by third parties. The Company’s proportional share of the proceeds from these transactions was $11.1 million, of which $10.4 million was received during the year ended December 31, 2020 and the remaining $0.7 million was received during the year ended December 31, 2021. The transactions were accounted for under the cumulative earnings approach whereby the return on investment of $8.3 million was recorded as a gain within “Other income, net” in the accompanying consolidated statements of operations and comprehensive loss and the return of investment of $2.8 million was recorded as a reduction in the Company’s net investment in Fountain.

During the three months ended March 31, 2022, one of the companies within the Fountain portfolio was acquired by a third party. The Company’s proportional share of the proceeds from this transaction was $1.1 million, of which $1.0 million was received during the three months ended March 31, 2022 and the remaining $0.1 million is being held in escrow until May 2023. The transaction was accounted for under the cumulative earnings approach whereby the return on investment of $0.6 million was recorded as a gain within “Other income, net” in the accompanying consolidated statements of operations and comprehensive loss and the return of investment of $0.5 million was recorded as a reduction in the Company’s net investment in Fountain. The Company’s net investment in Fountain was $7.9 million and $6.1 million at December 31, 2022 and 2021, respectively, and was included within “Other assets” in the accompanying consolidated balance sheets.

During the years ended December 31, 2022, 2021 and 2020, the Company recorded an increase in its investment in Fountain of $1.8 million, a decrease of $0.4 million and an increase of $0.3 million, respectively, which represented the Company’s proportional share of Fountain’s net gains or losses for such periods.

Realized gains and losses on the sales and maturities of investments, which were identified using the specific identification method, were as follows:

The Company’s available‑for‑sale and held‑to‑maturity securities at December 31, 2022 had contractual maturities in the following periods: