Madrigal Pharmaceuticals (MDGL) 10-K 24 Feb 22 2021 FY Annual report Financial data

Cover Page

Cover Page - USD ($)	12 Months Ended
	Dec. 31, 2021	Feb. 21, 2022	Jun. 30, 2021
Cover [Abstract]
Document Type	10-K
Document Annual Report	true
Document Transition Report	false
Entity Interactive Data Current	Yes
Amendment Flag	false
Document Fiscal Year Focus	2021
Document Period End Date	Dec. 31, 2021
Document Fiscal Period Focus	FY
Entity Registrant Name	MADRIGAL PHARMACEUTICALS, INC.
Entity Central Index Key	0001157601
Entity File Number	001-33277
Current Fiscal Year End Date	--12-31
Entity Tax Identification Number	04-3508648
Entity Incorporation, State or Country Code	DE
Entity Well-known Seasoned Issuer	Yes
Entity Voluntary Filers	No
Entity Current Reporting Status	Yes
Entity Public Float			$ 819,348,240
Entity Filer Category	Large Accelerated Filer
Entity Emerging Growth Company	false
Entity Small Business	false
Entity Shell Company	false
Entity Common Stock, Shares Outstanding		17,103,395
City Area Code	267
Local Phone Number	824-2827
Trading Symbol	MDGL
Security Exchange Name	NASDAQ
Title of 12(b) Security	Common Stock, $0.0001 Par Value Per Share
Entity Address, Address Line One	Four Tower Bridge
Entity Address, Address Line Two	200 Barr Harbor Drive, Suite 200
Entity Address, City or Town	West Conshohocken
Entity Address, Postal Zip Code	19428
Entity Address, State or Province	PA
ICFR Auditor Attestation Flag	true
Auditor Name	PricewaterhouseCoopers LLP
Auditor Firm ID	238
Auditor Location	Philadelphia, Pennsylvania

Consolidated Balance Sheets

Consolidated Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Current assets:
Cash and cash equivalents	$ 36,269	$ 54,004
Marketable securities	234,077	230,145
Prepaid expenses and other current assets	1,338	1,014
Total current assets	271,684	285,163
Property and equipment, net	851	1,047
Right-of-use asset	797	785
Total assets	273,332	286,995
Current liabilities:
Accounts payable	21,380	1,017
Accrued expenses	55,048	45,222
Lease liability	410	318
Total current liabilities	76,838	46,557
Long-term liabilities:
Lease liability	387	468
Total long term liabilities	387	468
Total liabilities	77,225	47,025
Stockholders' equity:
Preferred stock, par value $0.0001 per share authorized: 5,000,000 shares at December 31, 2020 and December 31, 2019; 1,969,797 shares issued and outstanding at December 31, 2020 and December 31, 2019
Common stock, par value $0.0001 per share authorized: 200,000,000 at December 31, 2020 and December 31, 2019; 15,508,146 and 15,429,154 shares issued and outstanding at December 31, 2020 and December 31, 2019, respectively	2	2
Additional paid-in-capital	863,495	665,385
Accumulated other comprehensive gain (loss)	(80)	47
Accumulated deficit	(667,310)	(425,464)
Total stockholders' equity	196,107	239,970
Total liabilities and stockholders' equity	$ 273,332	$ 286,995

Consolidated Balance Sheets (Pa

Consolidated Balance Sheets (Parenthetical) - $ / shares	Dec. 31, 2021	Dec. 31, 2020
Statement of Financial Position [Abstract]
Preferred stock, par value (in dollars per share)	$ 0.0001	$ 0.0001
Preferred stock, shares authorized	5,000,000	5,000,000
Preferred stock, shares issued	1,969,797	1,969,797
Preferred stock, shares outstanding	1,969,797	1,969,797
Common stock, par value (in dollars per share)	$ 0.0001	$ 0.0001
Common stock, shares authorized	200,000,000	200,000,000
Common stock, shares issued	17,103,395	15,508,146
Common stock, shares outstanding	17,103,395	15,508,146

Consolidated Statements of Oper

Consolidated Statements of Operations - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Revenues:
Total revenues	$ 0	$ 0	$ 0
Operating expenses:
Research and development	205,164	184,809	72,324
General and administrative	37,318	21,864	22,648
Total operating expenses	242,482	206,673	94,972
Loss from operations	(242,482)	(206,673)	(94,972)
Interest income	363	4,329	11,024
Other income	273	100	0
Net loss	$ (241,846)	$ (202,244)	$ (83,948)
Net loss per common share:
Basic and diluted net loss per common share (in dollars per share)	$ (14.63)	$ (13.09)	$ (5.45)
Basic and diluted weighted average number of common shares outstanding	16,535,188	15,446,638	15,394,659

Consolidated Statements of Comp

Consolidated Statements of Comprehensive Loss - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Statement of Comprehensive Income [Abstract]
Net Loss	$ (241,846)	$ (202,244)	$ (83,948)
Other comprehensive income (loss):
Unrealized gain (loss) on available-for-sale securities	(127)	(169)	535
Comprehensive loss	$ (241,973)	$ (202,413)	$ (83,413)

Consolidated Statements of Stoc

Consolidated Statements of Stockholders' Equity - USD ($) $ in Thousands	Total	Preferred Stock	Common stock	Additional paid-in Capital	Accumulated other comprehensive income (loss)	Accumulated deficit
Balance at Dec. 31, 2018	$ 476,984		$ 2	$ 616,573	$ (319)	$ (139,272)
Balance (in shares) at Dec. 31, 2018		1,969,797	15,409,023
Increase (Decrease) in Stockholders' Equity
Sale of common shares to related parties and exercise of common stock options, net of transaction cost	235			235
Sale of common shares to related parties and exercise of common stock options, net of transaction cost ( in shares)			20,131
Compensation expense related to stock options for services	22,759			22,759
Unrealized gain (loss) on marketable securities	535				535
Net loss	(83,948)					(83,948)
Balance at Dec. 31, 2019	416,565		$ 2	639,567	216	(223,220)
Balance (in shares) at Dec. 31, 2019		1,969,797	15,429,154
Increase (Decrease) in Stockholders' Equity
Issuance of common shares in equity offering, excluding to related parties, net of transaction costs	4,421		$ 0	4,421
Issuance of common shares in equity offering, excluding to related parties, net of transaction costs (in shares)			39,607
Sale of common shares to related parties and exercise of common stock options, net of transaction cost	667			667
Sale of common shares to related parties and exercise of common stock options, net of transaction cost ( in shares)			39,385
Compensation expense related to stock options for services	20,730			20,730
Unrealized gain (loss) on marketable securities	(169)				(169)
Net loss	(202,244)					(202,244)
Balance at Dec. 31, 2020	$ 239,970		$ 2	665,385	47	(425,464)
Balance (in shares) at Dec. 31, 2020	15,508,146	1,969,797	15,508,146
Increase (Decrease) in Stockholders' Equity
Issuance of common shares in equity offering, excluding to related parties, net of transaction costs	$ 170,207			170,207
Issuance of common shares in equity offering, excluding to related parties, net of transaction costs (in shares)			1,584,169
Sale of common shares to related parties and exercise of common stock options, net of transaction cost	1,030			1,030
Sale of common shares to related parties and exercise of common stock options, net of transaction cost ( in shares)			11,080
Compensation expense related to stock options for services	26,873			26,873
Unrealized gain (loss) on marketable securities	(127)				(127)
Net loss	(241,846)					(241,846)
Balance at Dec. 31, 2021	$ 196,107		$ 2	$ 863,495	$ (80)	$ (667,310)
Balance (in shares) at Dec. 31, 2021	17,103,395	1,969,797	17,103,395

Consolidated Statements of Cash

Consolidated Statements of Cash Flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Cash flows from operating activities:
Net loss	$ (241,846)	$ (202,244)	$ (83,948)
Adjustments to reconcile net loss to net cash used in operating activities:
Stock-based compensation expense	26,873	20,730	22,759
Depreciation and amortization expense	405	471	112
Changes in operating assets and liabilities:
Prepaid expenses and other current assets	(325)	138	332
Accounts payable	20,363	(161)	(1,309)
Accrued expense	9,826	21,585	16,783
Accrued interest, net of interest received on maturity of investments	787	1,920	3,647
Net cash used in operating activities	(183,917)	(157,561)	(41,624)
Cash flows from investing activities:
Purchases of marketable securities	(394,120)	(329,342)	(619,303)
Sales and maturities of marketable securities	389,274	489,456	650,182
Purchases of property and equipment, net of disposals	(209)	(334)	(172)
Net cash provided by (used in) investing activities	(5,055)	159,780	30,707
Cash flows from financing activities:
Proceeds from issuances of stock, excluding related parties, net of transaction costs	170,207	4,421
Proceeds from the sale of related party stock and exercise of common stock options, net of transaction costs	1,030	667	235
Net cash provided by financing activities	171,237	5,088	235
Net increase (decrease) in cash and cash equivalents	(17,735)	7,307	(10,682)
Cash and cash equivalents at beginning of period	54,004	46,697	57,379
Cash and cash equivalents at end of period	36,269	54,004	46,697
Supplemental disclosure of cash flow information:
Obtaining a right-of-use asset in exchange for a lease liability	$ 376	$ 451	900
Purchases of property and equipment in accounts payable at period end			$ 897

Organization, Business and Basi

Organization, Business and Basis of Presentation	12 Months Ended
	Dec. 31, 2021
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Organization, Business and Basis of Presentation	1. Organization, Business and Basis of Presentation Organization and Business Madrigal Pharmaceuticals, Inc. (the “Company” or “Madrigal”) is a clinical-stage pharmaceutical company developing novel, high-quality, small-molecule drugs addressing major unmet needs in cardiovascular, metabolic, and liver diseases. The Company’s lead compound, resmetirom, is being advanced for non-alcoholic non-alcoholic MAESTRO-NAFLD-1

Summary of Significant Accounti

Summary of Significant Accounting Policies	12 Months Ended
	Dec. 31, 2021
Accounting Policies [Abstract]
Summary of Significant Accounting Policies	2. Summary of Significant Accounting Policies Principle of Consolidation The consolidated financial statements include the financial statements of the Company and its wholly owned subsidiaries. All significant intercompany balances and transactions have been eliminated in consolidation. Use of Estimates The preparation of financial statements in conformity with GAAP requires management to make estimates and assumptions that affect certain reported amounts of assets and liabilities, and the reported amounts of revenues and expenses during the reporting periods. The Company bases its estimates on historical experience and various other assumptions that management believes to be reasonable under the circumstances. Changes in estimates are recorded in the period in which they become known. Actual results could differ from those estimates. Cash and Cash Equivalents The Company considers all highly liquid investments with original maturities of three months or less at the date of purchase to be cash equivalents. The Company maintains its cash in bank accounts, the balance of which, at times, exceeds Federal Deposit Insurance Corporation insured limits. The primary objective of the Company’s investment activities is to preserve its capital for the purpose of funding operations and the Company does not enter into investments for trading or speculative purposes. The Company’s cash is deposited in highly rated financial institutions in the United States. The Company invests in money market funds and high-grade, commercial paper and corporate bonds, which management believes are subject to minimal credit and market risk. Marketable Securities Marketable securities consist of investments in high-grade corporate obligations, and government and government agency obligations that are classified as available-for-sale. The Company adjusts the cost of available-for-sale than-temporary on available-for-sale Marketable securities are stated at fair value, including accrued interest, with their unrealized gains and losses included as a component of accumulated other comprehensive income or loss, which is a separate component of stockholders’ equity. The fair value of these securities is based on quoted prices and observable inputs on a recurring basis. Realized gains and losses are determined on the specific identification method. During the years ended December 31, 2021, 2020 and 2019, the Company did not have any realized gains or losses on marketable securities. Fair Value of Financial Instruments The carrying amounts of the Company’s financial instruments, which include cash equivalents, and marketable securities, approximate their fair values. The fair value of the Company’s financial instruments reflects the amounts that would be received upon sale of an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. The fair value hierarchy has the following three levels: Level 1—quoted prices in active markets for identical assets and liabilities. Level 2—observable inputs other than Level 1 inputs. Examples of Level 2 inputs include quoted prices in active markets for similar assets or liabilities and quoted prices for identical assets or liabilities in markets that are not active. Level 3—unobservable inputs that reflect the Company’s own assumptions about the assumptions market participants would use in pricing the asset or liability. Financial assets and liabilities are classified in their entirety within the fair value hierarchy based on the lowest level of input that is significant to the fair value measurement. The Company measures the fair value of its marketable securities by taking into consideration valuations obtained from third-party pricing sources. The pricing services utilize industry standard valuation models, including both income and market-based approaches, for which all significant inputs are observable, either directly or indirectly, to estimate fair value. These inputs include reported trades of and broker-dealer quotes on the same or similar securities, issuer credit spreads, benchmark securities and other observable inputs. As of December 31, 2021 and 2020, the Company’s financial assets valued based on Level 1 inputs consisted of cash and cash equivalents in a money market fund and its financial assets valued based on Level 2 inputs consisted of high-grade corporate bonds and commercial paper. During the years ended December 31, 2021, 2020 and 2019, the Company did not have any transfers of financials assets between Levels 1 and 2. As of December 31, 2021 and 2020, the Company did not have any financial liabilities that were recorded at fair value on a recurring basis on the balance sheet. Research and Development Costs Research and development costs are expensed as incurred. Research and development costs are comprised of costs incurred in performing research and development activities, including internal costs (including stock-based compensation), costs for consultants, milestone payments under licensing agreements, and other costs associated with the Company’s preclinical and clinical programs. In particular, the Company has conducted safety studies in animals, optimized and implemented the manufacturing of our drug, and conducted Phase 1-3 Patents Costs to secure and defend patents are expensed as incurred and are classified as general and administrative expense in the Company’s statements of operations. Patent expenses were approximately $0.5 million, $0.4 million and $0.4 million for the years ended December 31, 2021, 2020 and 2019, respectively. Stock-Based Compensation The Company recognizes re-evaluated Certain of the employee stock options granted by the Company are structured to qualify as incentive stock options (ISOs). Under current tax regulations, the Company does not receive a tax deduction for the issuance, exercise or disposition of ISOs if the employee meets certain holding requirements. If the employee does not meet the holding requirements, a disqualifying disposition occurs, at which time the Company may receive a tax deduction. The Company does not record tax benefits related to ISOs unless and until a disqualifying disposition is reported. In the event of a disqualifying disposition, the entire tax benefit is recorded as a reduction of income tax expense. The Company has not recognized any income tax benefit for its share-based compensation arrangements due to the fact that the Company does not believe it is more likely than not it will realize the related deferred tax assets. Income Taxes The Company uses the asset and liability method to account for income taxes. Deferred tax assets and liabilities are determined based on the expected future tax consequences of temporary differences between the Company’s financial statement carrying amounts and the tax basis of assets and liabilities using enacted tax rates expected to be in effect in the years in which the differences are expected to reverse. The Company currently maintains a 100% valuation allowance on its deferred tax assets. Comprehensive Loss Comprehensive loss is defined as the change in equity of a business enterprise during a period from transactions and other events and circumstances from non-owner Basic and Diluted Loss Per Common Share Basic net loss per share is computed using the weighted average number of common shares outstanding during the period, excluding restricted stock that has been issued but is not yet vested. Diluted net loss per common share is computed using the weighted average number of common shares outstanding and the weighted average dilutive potential common shares outstanding using the treasury stock method. However, for the years ended December 31, 2021, 2020 and 2019, diluted net loss per share is the same as basic net loss per share as the inclusion of weighted average shares of unvested restricted common stock and common stock issuable upon the exercise of stock options would be anti-dilutive. The following table summarizes outstanding securities not included in the computation of diluted net loss per common share as their inclusion would be anti-dilutive: As of December 31, 2021 2020 2019 Common stock options 2,301,574 1,837,540 1,461,987 Unvested restricted common stock 0 0 0 Preferred stock 1,969,797 1,969,797 1,969,797 Recent Accounting Pronouncements None.

Liquidity and Uncertainties

Liquidity and Uncertainties	12 Months Ended
	Dec. 31, 2021
Liquidity and Uncertainties
Liquidity and Uncertainties	3. Liquidity and Uncertainties The Company is subject to risks common to development stage companies in the biopharmaceutical industry including, but not limited to, uncertainty of product development and commercialization, dependence on key personnel, uncertainty of market acceptance of products and product reimbursement, product liability, uncertain protection of proprietary technology, potential inability to raise additional financing necessary for development and commercialization, and compliance with the U.S. Food and Drug Administration and other government regulations. The Company has incurred losses since inception, including approximately $241.8 million for the year ended December 31, 2021, resulting in an accumulated deficit of approximately $667.3 million and $425.5 million as of December 31, 2021 and 2020, respectively. Management expects to incur losses for the foreseeable future. To date, the Company has funded its operations primarily through proceeds from sales of the Company’s capital stock. The Company believes that its cash, cash equivalents and marketable securities at December 31, 2021 will be sufficient to fund operations past one year from the issuance of these financial statements. To meet its future capital needs, the Company intends to raise additional capital through debt or equity financings, collaborations, partnerships or other strategic transactions. However, there can be no assurance that the Company will be able to complete any such transactions on acceptable terms or otherwise. The inability of the Company to obtain sufficient funds on acceptable terms when needed could have a material adverse effect on the Company’s business, results of operations and financial condition. The Company has the ability to delay certain research activities and related clinical expenses if necessary due to liquidity concerns until a date when those concerns are relieved.

Cash, Cash Equivalents and Mark

Cash, Cash Equivalents and Marketable Securities	12 Months Ended
	Dec. 31, 2021
Cash and Cash Equivalents [Abstract]
Cash, Cash Equivalents and Marketable Securities	4. Cash, Cash Equivalents and Marketable Securities A summary of cash, cash equivalents and available-for-sale December 31, 2021 Cost Unrealized Unrealized Fair value Cash and cash equivalents: Cash (Level 1) $ 18,877 $ — $ — $ 18,877 Money market funds (Level 1) 17,392 — — 17,392 Total cash and cash equivalents 36,269 — — 36,269 Marketable securities: Corporate debt securities due within 1 year of date of purchase (Level 2) 228,348 6 (66 ) 228,288 Corporate debt securities due within 1 to 2 years of date of purchase (Level 2) 5,809 — (20 ) 5,789 Total cash, cash equivalents and marketable securities $ 270,426 $ 6 $ (86 ) $ 270,346 December 31, 2020 Cost Unrealized Unrealized Fair value Cash and cash equivalents: Cash (Level 1) $ 716 $ — $ — $ 716 Money market funds (Level 1) 53,288 — — 53,288 Total cash and cash equivalents 54,004 — — 54,004 Marketable securities: Corporate debt securities due within 1 year of date of purchase (Level 2) 227,172 80 (36 ) 227,216 Corporate debt securities due within 1 to 2 years of date of purchase (Level 2) 2,926 4 (1 ) 2,929 Total cash, cash equivalents and marketable securities $ 284,102 $ 84 $ (37) $ 284,149

Accrued Liabilities

Accrued Liabilities	12 Months Ended
	Dec. 31, 2021
Accrued Liabilities, Current [Abstract]
Accrued Liabilities	5. Accrued Liabilities Accrued liabilities as of December 31, 2021 and 2020 consisted of the following (in thousands): December 31, December 31, Contract research organization costs $ 38,349 $ 31,646 Other clinical study related costs 3,957 3,901 Compensation and benefits 6,769 4,686 Professional fees 2,455 830 Other 3,518 4,159 Total accrued liabilities $ 55,048 $ 45,222

Stockholders' Equity

Stockholders' Equity	12 Months Ended
	Dec. 31, 2021
Stockholders' Equity Note [Abstract]
Stockholders' Equity	6. Stockholders’ Equity Common Stock Each common stockholder is entitled to one vote for each share of common stock held. The common stock will vote together with all other classes and series of stock of the Company as a single class on all actions to be taken by the Company’s stockholders. Each share of common stock is entitled to receive dividends, as and when declared by the Company’s board of directors. The Company has never declared cash dividends on its common stock and does not expect to do so in the foreseeable future. Preferred Stock The Series A Preferred Stock has a par value of $0.0001 per share and is convertible into shares of the common stock at a one-to-one winding-up as-if-converted-to-Common-Stock as-converted At-The-Market In November 2020, the Company entered into an at-the-market “at-the-market” Under the 2020 Sales Agreement the Company sold 1,126,733 shares for an aggregate of approximately $137.4 million in gross proceeds, with net proceeds to the Company of approximately $134.8 million after deducting commissions and other transaction costs. Of those shares sold, 1,087,126 were sold in 2021, and 39,607 were sold in 2020. In June 2021, the Company filed with the SEC and had declared effective a new shelf registration statement on Form S-3 at-the-market As of December 31, 2021, 497,043 shares had been sold under the 2021 Sales Agreement for an aggregate of approximately $40.8 million in gross proceeds, with net proceeds to the Company of approximately $39.8 million after deducting commissions and other transaction costs. As of December 31, 2021, $159.2 million remained reserved and available for sale under the 2021 Sales Agreement and the Company’s related prospectus supplement.

Stock-based Compensation

Stock-based Compensation	12 Months Ended
	Dec. 31, 2021
Share-based Payment Arrangement [Abstract]
Stock-based Compensation	7. Stock-based Compensation The 2015 Stock Plan, as amended, is our primary plan through which non-statutory The following table summarizes stock option activity during the twelve months ended December 31, 2021: Shares Weighted Weighted Aggregate Outstanding at January 1, 2021 1,837,540 $ 71.80 Options granted 687,059 109.03 Options exercised (11,080 ) 92.96 Options cancelled (211,945 ) 114.34 Outstanding at December 31, 2021 2,301,574 $ 78.89 6.51 $ 62,566 Exercisable at December 31, 2021 1,432,144 $ 62.66 5.38 $ 60,932 The total cash received by the Company as a result of stock option exercises was $1.0 million, $0.7 million and $0.2 million for the years ended December 31, 2021, 2020, and 2019. The total intrinsic value of options exercised was $0.1 million $4.1 million and $2.2 million for the years ended December 31, 2021, 2020, and 2019. The weighted-average grant date fair values, based on the Black-Scholes option model, of options granted during the year ended December 31, 2021, 2020 and 2019 was $ 73.29, $68.07, and $91.19, respectively. Restricted Common Stock The Company’s share-based compensation plan provides for awards of restricted shares of common stock to employees, officers, directors and consultants to the Company. Restricted stock awards are subject to forfeiture if employment or service terminates during the prescribed retention period. Restricted shares vest over the service period. There were no outstanding restricted shares or activity in 2021. Stock-Based Compensation Expense Stock-based compensation expense during the years ended December 31, 2021, 2020 and 2019 was as follows (in thousands): Years Ended December 31, 2021 2020 2019 Stock-based compensation expense by type of award: Stock options $ 26,873 $ 20,730 $ 22,487 Restricted stock — — 272 Total stock-based compensation expense $ 26,873 $ 20,730 $ 22,759 Effect of stock-based compensation expense by line item: Research and development $ 10,698 $ 8,833 $ 8,277 General and administrative 16,175 11,897 14,482 Total stock-based compensation expense included in net loss $ 26,873 $ 20,730 $ 22,759 Unrecognized stock-based compensation expense on stock options as of December 31, 2021 was $48.9 million with a weighted average remaining period of 2.79 years.

Leases

Leases	12 Months Ended
	Dec. 31, 2021
Leases [Abstract]
Leases	8. Leases In 2019, the Company entered into an operating lease for office space, which was renewed and extended in 2020. We adopted ASU 2016-02, right-of-use non-cancelable Future minimum payments under the Company’s operating leases related to the ROU asset and lease liability as of December 31, 2021 was as follows (in thousand): Operating 2022 436 2023 400 Thereafter — Total minimum payments $ 836 Less: imputed interest 39 Present value of lease liabilities $ 797 As of December 31, 2021, the weighted average remaining operating lease term was 1.92 years and the weighted average discount rate used to determine the operating lease liabilities was 3.25%. Cash paid related to the lease liability was $0.4 and $0.3 million for years ended December 31, 2021 and 2020 respectively. Operating lease costs were $0.4 and $0.3 million for years ended December 31, 2021 and 2020 respectively. Rent, short term and variable leases costs were immaterial during the years ended December 31, 2021, 2020 and 2019.

Commitments and Contingencies

Commitments and Contingencies	12 Months Ended
	Dec. 31, 2021
Commitments and Contingencies Disclosure [Abstract]
Commitments and Contingencies	9. Commitments and Contingencies The Company has a Research, Development and Commercialization Agreement with Hoffmann-La The agreement requires future milestone payments to Roche. In 2019, the Company commenced a Phase 3 study in Non-Alcoholic The Company has entered into customary contractual arrangements and letters of intent in preparation for and in support of the Phase 3 clinical trials.

Income Taxes

Income Taxes	12 Months Ended
	Dec. 31, 2021
Income Tax Disclosure [Abstract]
Income Taxes	10. Income Taxes At December 31, 2021, the Company had federal net operating loss (“NOL”) carryforwards of approximately $168.8 million available to reduce future taxable income, of which $40.4 million will expire between 2031 and 2037. The Company also has state operating loss carryforwards of approximately $157.5 million, available to reduce future taxable income, which expire between 2031 and 2041. The Company has unused federal research and development carryforwards of approximately $22.4 million which will begin to expire in 2031. The Internal Revenue Code (“IRC”) limits the amounts of NOL carryforwards that a Company may use in any one year in the event of certain cumulative changes in ownership over a three-year period as described in Section 382 of the IRC. Such change in ownership could limit the Company’s utilization of the NOL, and could be triggered by subsequent sales of securities by the Company or stockholders. The deferred tax asset related to the NOL reflected on the financial statements could be affected by this limitation. Although a formal analysis has not been completed, the Company has determined that an ownership change likely occurred for Madrigal during the year ended December 31, 2017. In assessing the realizability of deferred tax assets, management considers whether it is more likely than not that some portion of the deferred tax assets will not be realized. The ultimate realization of deferred tax assets is dependent upon the generation of future taxable income during the periods in which those temporary differences become deductible. As there is no assurance of future taxable income, a full valuation allowance has been established to offset the deferred tax assets. The valuation allowance increased $79.3 million for the year ended December 31, 2021. Changes in the deferred tax asset will be recorded as an income tax benefit or expense on the accompanying consolidated statements of operations. Entities are also required to evaluate, measure, recognize and disclose any uncertain income tax provisions taken on their income tax returns. The Company has analyzed its tax positions and has concluded that as of December 31, 2021 there were no uncertain positions. The 2017 through 2021 tax returns are open to review by the IRS and state taxing authorities. Interest and penalties, if any, as they relate to income taxes assessed, are included in the income tax provision. There was no income tax related interest and penalties included in the income tax provision for 2021. Temporary differences that give rise to deferred tax assets and liabilities are as follows (in thousands): For the years ended December 31, 2021 2020 2019 Deferred Tax Liabilities Unrealized gains on investments $ — $ 14 $ 62 Total Deferred Tax Liabilities $ — $ 14 $ 62 Deferred Tax Assets Charitable contributions $ 53 $ 51 $ 15 Accrued expenses 1,857 1,318 759 Intangibles 783 883 983 Stock compensation 24,335 16,812 10,943 Property, plant & equipment 80 68 13 Unrealized loss on investment 23 — — Net operating losses 47,864 27,933 17,635 Capitalized R&D 112,848 71,128 29,364 R&D credit 23,799 14,205 6,141 Total deferred tax assets before valuation allowance 211,642 132,398 65,853 Valuation allowance (211,642 ) (132,384 ) (65,791 ) Total deferred tax assets — 14 62 Net deferred tax assets $ — $ — $ — Differences between the effective income tax rate and the US statutory rate were as follows (in thousands): For the years ended December 31, 2021 2020 2019 Tax benefit at U.S. federal statutory rate $ (50,788 ) $ (42,471 ) $ (17,629 ) Stock based compensation — (68 ) (47 ) Other nondeductible expenses 5 1 14 State income taxes benefit before valuation allowance, net of federal benefit (19,622 ) (16,580 ) (6,613 ) Increase in domestic valuation allowance 79,258 66,593 26,843 Research and development credit (9,002 ) (7,472 ) (2,636 ) Other adjustments 149 (3 ) 68 Income tax expense (benefit) $ — $ — $ —

Quarterly Financial Data (unaud

Quarterly Financial Data (unaudited)	12 Months Ended
	Dec. 31, 2021
Quarterly Financial Information Disclosure [Abstract]
Quarterly Financial Data (unaudited)	11. Quarterly Financial Data (unaudited) The following tables present a summary of quarterly results of operations for 2021 and 2020 (in thousands, except shares and per share data): Three months ended March 31, June 30, September 30, December 31, Revenues: Total revenues $ — $ — $ — $ — Operating expenses: Research and development 45,770 51,632 54,873 52,889 General and administrative 7,209 10,110 8,287 11,712 Total operating expenses 52,979 61,742 63,160 64,601 Loss from operations (52,979 ) (61,742 ) (63,160 ) (64,601 ) Interest income 160 91 60 52 Other income 273 — — — Net loss $ (52,546) $ (61,651) $ (63,100) $ (64,549) Net loss per common share: Basic and diluted net loss per common share $ (3.32) $ (3.72) $ (3.79) $ (3.78) Basic and diluted weighted average number of common shares outstanding 15,840,401 16,571,322 16,639,776 17,074,543 Three months ended March 31, June 30, September 30, December 31, Revenues: Total revenues $ — $ — $ — $ — Operating expenses: Research and development 33,400 44,688 53,292 53,429 General and administrative 4,605 5,639 5,494 6,126 Total operating expenses 38,005 50,327 58,786 59,555 Loss from operations (38,005 ) (50,327 ) (58,786 ) (59,555 ) Interest income 1,870 1,204 823 432 Other income — 100 — — Net loss $ (36,135) $ (49,023) $ (57,963) $ (59,123) Net loss per common share: Basic and diluted net loss per common share $ (2.34) $ (3.18) $ (3.75) $ (3.82) Basic and diluted weighted average number of common shares outstanding 15,429,154 15,433,348 15,448,425 15,475,291

Summary of Significant Accoun_2

Summary of Significant Accounting Policies (Policies)	12 Months Ended
	Dec. 31, 2021
Accounting Policies [Abstract]
Principle of Consolidation	Principle of Consolidation The consolidated financial statements include the financial statements of the Company and its wholly owned subsidiaries. All significant intercompany balances and transactions have been eliminated in consolidation.
Use of Estimates	Use of Estimates The preparation of financial statements in conformity with GAAP requires management to make estimates and assumptions that affect certain reported amounts of assets and liabilities, and the reported amounts of revenues and expenses during the reporting periods. The Company bases its estimates on historical experience and various other assumptions that management believes to be reasonable under the circumstances. Changes in estimates are recorded in the period in which they become known. Actual results could differ from those estimates.
Cash and Cash Equivalents	Cash and Cash Equivalents The Company considers all highly liquid investments with original maturities of three months or less at the date of purchase to be cash equivalents. The Company maintains its cash in bank accounts, the balance of which, at times, exceeds Federal Deposit Insurance Corporation insured limits. The primary objective of the Company’s investment activities is to preserve its capital for the purpose of funding operations and the Company does not enter into investments for trading or speculative purposes. The Company’s cash is deposited in highly rated financial institutions in the United States. The Company invests in money market funds and high-grade, commercial paper and corporate bonds, which management believes are subject to minimal credit and market risk.
Marketable Securities	Marketable Securities Marketable securities consist of investments in high-grade corporate obligations, and government and government agency obligations that are classified as available-for-sale. The Company adjusts the cost of available-for-sale than-temporary on available-for-sale Marketable securities are stated at fair value, including accrued interest, with their unrealized gains and losses included as a component of accumulated other comprehensive income or loss, which is a separate component of stockholders’ equity. The fair value of these securities is based on quoted prices and observable inputs on a recurring basis. Realized gains and losses are determined on the specific identification method. During the years ended December 31, 2021, 2020 and 2019, the Company did not have any realized gains or losses on marketable securities.
Fair Value of Financial Instruments	Fair Value of Financial Instruments The carrying amounts of the Company’s financial instruments, which include cash equivalents, and marketable securities, approximate their fair values. The fair value of the Company’s financial instruments reflects the amounts that would be received upon sale of an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. The fair value hierarchy has the following three levels: Level 1—quoted prices in active markets for identical assets and liabilities. Level 2—observable inputs other than Level 1 inputs. Examples of Level 2 inputs include quoted prices in active markets for similar assets or liabilities and quoted prices for identical assets or liabilities in markets that are not active. Level 3—unobservable inputs that reflect the Company’s own assumptions about the assumptions market participants would use in pricing the asset or liability. Financial assets and liabilities are classified in their entirety within the fair value hierarchy based on the lowest level of input that is significant to the fair value measurement. The Company measures the fair value of its marketable securities by taking into consideration valuations obtained from third-party pricing sources. The pricing services utilize industry standard valuation models, including both income and market-based approaches, for which all significant inputs are observable, either directly or indirectly, to estimate fair value. These inputs include reported trades of and broker-dealer quotes on the same or similar securities, issuer credit spreads, benchmark securities and other observable inputs. As of December 31, 2021 and 2020, the Company’s financial assets valued based on Level 1 inputs consisted of cash and cash equivalents in a money market fund and its financial assets valued based on Level 2 inputs consisted of high-grade corporate bonds and commercial paper. During the years ended December 31, 2021, 2020 and 2019, the Company did not have any transfers of financials assets between Levels 1 and 2. As of December 31, 2021 and 2020, the Company did not have any financial liabilities that were recorded at fair value on a recurring basis on the balance sheet.
Research and Development Costs	Research and Development Costs Research and development costs are expensed as incurred. Research and development costs are comprised of costs incurred in performing research and development activities, including internal costs (including stock-based compensation), costs for consultants, milestone payments under licensing agreements, and other costs associated with the Company’s preclinical and clinical programs. In particular, the Company has conducted safety studies in animals, optimized and implemented the manufacturing of our drug, and conducted Phase 1-3
Patents	Patents Costs to secure and defend patents are expensed as incurred and are classified as general and administrative expense in the Company’s statements of operations. Patent expenses were approximately $0.5 million, $0.4 million and $0.4 million for the years ended December 31, 2021, 2020 and 2019, respectively.
Stock-Based Compensation	Stock-Based Compensation The Company recognizes re-evaluated Certain of the employee stock options granted by the Company are structured to qualify as incentive stock options (ISOs). Under current tax regulations, the Company does not receive a tax deduction for the issuance, exercise or disposition of ISOs if the employee meets certain holding requirements. If the employee does not meet the holding requirements, a disqualifying disposition occurs, at which time the Company may receive a tax deduction. The Company does not record tax benefits related to ISOs unless and until a disqualifying disposition is reported. In the event of a disqualifying disposition, the entire tax benefit is recorded as a reduction of income tax expense. The Company has not recognized any income tax benefit for its share-based compensation arrangements due to the fact that the Company does not believe it is more likely than not it will realize the related deferred tax assets.
Income Taxes	Income Taxes The Company uses the asset and liability method to account for income taxes. Deferred tax assets and liabilities are determined based on the expected future tax consequences of temporary differences between the Company’s financial statement carrying amounts and the tax basis of assets and liabilities using enacted tax rates expected to be in effect in the years in which the differences are expected to reverse. The Company currently maintains a 100% valuation allowance on its deferred tax assets.
Comprehensive Loss	Comprehensive Loss Comprehensive loss is defined as the change in equity of a business enterprise during a period from transactions and other events and circumstances from non-owner
Basic and Diluted Loss Per Common Share	Basic and Diluted Loss Per Common Share Basic net loss per share is computed using the weighted average number of common shares outstanding during the period, excluding restricted stock that has been issued but is not yet vested. Diluted net loss per common share is computed using the weighted average number of common shares outstanding and the weighted average dilutive potential common shares outstanding using the treasury stock method. However, for the years ended December 31, 2021, 2020 and 2019, diluted net loss per share is the same as basic net loss per share as the inclusion of weighted average shares of unvested restricted common stock and common stock issuable upon the exercise of stock options would be anti-dilutive. The following table summarizes outstanding securities not included in the computation of diluted net loss per common share as their inclusion would be anti-dilutive: As of December 31, 2021 2020 2019 Common stock options 2,301,574 1,837,540 1,461,987 Unvested restricted common stock 0 0 0 Preferred stock 1,969,797 1,969,797 1,969,797
Recent Accounting Pronouncements	Recent Accounting Pronouncements None.

Summary of Significant Accoun_3

Summary of Significant Accounting Policies (Tables)	12 Months Ended
	Dec. 31, 2021
Accounting Policies [Abstract]
Summary of the outstanding securities not included in the computation of diluted net loss per common share as their inclusion would be anti-dilutive	The following table summarizes outstanding securities not included in the computation of diluted net loss per common share as their inclusion would be anti-dilutive: As of December 31, 2021 2020 2019 Common stock options 2,301,574 1,837,540 1,461,987 Unvested restricted common stock 0 0 0 Preferred stock 1,969,797 1,969,797 1,969,797

Cash, Cash Equivalents and Ma_2

Cash, Cash Equivalents and Marketable Securities (Tables)	12 Months Ended
	Dec. 31, 2021
Cash and Cash Equivalents [Abstract]
Summary of cash, cash equivalents and available-for-sale marketable securities	A summary of cash, cash equivalents and available-for-sale December 31, 2021 Cost Unrealized Unrealized Fair value Cash and cash equivalents: Cash (Level 1) $ 18,877 $ — $ — $ 18,877 Money market funds (Level 1) 17,392 — — 17,392 Total cash and cash equivalents 36,269 — — 36,269 Marketable securities: Corporate debt securities due within 1 year of date of purchase (Level 2) 228,348 6 (66 ) 228,288 Corporate debt securities due within 1 to 2 years of date of purchase (Level 2) 5,809 — (20 ) 5,789 Total cash, cash equivalents and marketable securities $ 270,426 $ 6 $ (86 ) $ 270,346 December 31, 2020 Cost Unrealized Unrealized Fair value Cash and cash equivalents: Cash (Level 1) $ 716 $ — $ — $ 716 Money market funds (Level 1) 53,288 — — 53,288 Total cash and cash equivalents 54,004 — — 54,004 Marketable securities: Corporate debt securities due within 1 year of date of purchase (Level 2) 227,172 80 (36 ) 227,216 Corporate debt securities due within 1 to 2 years of date of purchase (Level 2) 2,926 4 (1 ) 2,929 Total cash, cash equivalents and marketable securities $ 284,102 $ 84 $ (37) $ 284,149

Accrued Liabilities (Tables)

Accrued Liabilities (Tables)	12 Months Ended
	Dec. 31, 2021
Accrued Liabilities, Current [Abstract]
Schedule of Accrued Liabilities	Accrued liabilities as of December 31, 2021 and 2020 consisted of the following (in thousands): December 31, December 31, Contract research organization costs $ 38,349 $ 31,646 Other clinical study related costs 3,957 3,901 Compensation and benefits 6,769 4,686 Professional fees 2,455 830 Other 3,518 4,159 Total accrued liabilities $ 55,048 $ 45,222

Stock-based Compensation (Table

Stock-based Compensation (Tables)	12 Months Ended
	Dec. 31, 2021
Share-based Payment Arrangement [Abstract]
Summary of stock option activity	The following table summarizes stock option activity during the twelve months ended December 31, 2021: Shares Weighted Weighted Aggregate Outstanding at January 1, 2021 1,837,540 $ 71.80 Options granted 687,059 109.03 Options exercised (11,080 ) 92.96 Options cancelled (211,945 ) 114.34 Outstanding at December 31, 2021 2,301,574 $ 78.89 6.51 $ 62,566 Exercisable at December 31, 2021 1,432,144 $ 62.66 5.38 $ 60,932
Schedule of stock-based compensation expense	Stock-based compensation expense during the years ended December 31, 2021, 2020 and 2019 was as follows (in thousands): Years Ended December 31, 2021 2020 2019 Stock-based compensation expense by type of award: Stock options $ 26,873 $ 20,730 $ 22,487 Restricted stock — — 272 Total stock-based compensation expense $ 26,873 $ 20,730 $ 22,759 Effect of stock-based compensation expense by line item: Research and development $ 10,698 $ 8,833 $ 8,277 General and administrative 16,175 11,897 14,482 Total stock-based compensation expense included in net loss $ 26,873 $ 20,730 $ 22,759

Leases (Tables)

Leases (Tables)	12 Months Ended
	Dec. 31, 2021
Leases [Abstract]
Schedule of future minimum payments for operating leases	Future minimum payments under the Company’s operating leases related to the ROU asset and lease liability as of December 31, 2021 was as follows (in thousand): Operating 2022 436 2023 400 Thereafter — Total minimum payments $ 836 Less: imputed interest 39 Present value of lease liabilities $ 797

Income Taxes (Tables)

Income Taxes (Tables)	12 Months Ended
	Dec. 31, 2021
Income Tax Disclosure [Abstract]
Schedule of temporary differences that give rise to deferred tax assets and liabilities	Temporary differences that give rise to deferred tax assets and liabilities are as follows (in thousands): For the years ended December 31, 2021 2020 2019 Deferred Tax Liabilities Unrealized gains on investments $ — $ 14 $ 62 Total Deferred Tax Liabilities $ — $ 14 $ 62 Deferred Tax Assets Charitable contributions $ 53 $ 51 $ 15 Accrued expenses 1,857 1,318 759 Intangibles 783 883 983 Stock compensation 24,335 16,812 10,943 Property, plant & equipment 80 68 13 Unrealized loss on investment 23 — — Net operating losses 47,864 27,933 17,635 Capitalized R&D 112,848 71,128 29,364 R&D credit 23,799 14,205 6,141 Total deferred tax assets before valuation allowance 211,642 132,398 65,853 Valuation allowance (211,642 ) (132,384 ) (65,791 ) Total deferred tax assets — 14 62 Net deferred tax assets $ — $ — $ —
Schedule of differences between the effective income tax rate and the US statutory rate	Differences between the effective income tax rate and the US statutory rate were as follows (in thousands): For the years ended December 31, 2021 2020 2019 Tax benefit at U.S. federal statutory rate $ (50,788 ) $ (42,471 ) $ (17,629 ) Stock based compensation — (68 ) (47 ) Other nondeductible expenses 5 1 14 State income taxes benefit before valuation allowance, net of federal benefit (19,622 ) (16,580 ) (6,613 ) Increase in domestic valuation allowance 79,258 66,593 26,843 Research and development credit (9,002 ) (7,472 ) (2,636 ) Other adjustments 149 (3 ) 68 Income tax expense (benefit) $ — $ — $ —

Quarterly Financial Data (una_2

Quarterly Financial Data (unaudited) (Tables)	12 Months Ended
	Dec. 31, 2021
Quarterly Financial Information Disclosure [Abstract]
Schedule of quarterly results of operations	The following tables present a summary of quarterly results of operations for 2021 and 2020 (in thousands, except shares and per share data): Three months ended March 31, June 30, September 30, December 31, Revenues: Total revenues $ — $ — $ — $ — Operating expenses: Research and development 45,770 51,632 54,873 52,889 General and administrative 7,209 10,110 8,287 11,712 Total operating expenses 52,979 61,742 63,160 64,601 Loss from operations (52,979 ) (61,742 ) (63,160 ) (64,601 ) Interest income 160 91 60 52 Other income 273 — — — Net loss $ (52,546) $ (61,651) $ (63,100) $ (64,549) Net loss per common share: Basic and diluted net loss per common share $ (3.32) $ (3.72) $ (3.79) $ (3.78) Basic and diluted weighted average number of common shares outstanding 15,840,401 16,571,322 16,639,776 17,074,543 Three months ended March 31, June 30, September 30, December 31, Revenues: Total revenues $ — $ — $ — $ — Operating expenses: Research and development 33,400 44,688 53,292 53,429 General and administrative 4,605 5,639 5,494 6,126 Total operating expenses 38,005 50,327 58,786 59,555 Loss from operations (38,005 ) (50,327 ) (58,786 ) (59,555 ) Interest income 1,870 1,204 823 432 Other income — 100 — — Net loss $ (36,135) $ (49,023) $ (57,963) $ (59,123) Net loss per common share: Basic and diluted net loss per common share $ (2.34) $ (3.18) $ (3.75) $ (3.82) Basic and diluted weighted average number of common shares outstanding 15,429,154 15,433,348 15,448,425 15,475,291

Summary of Significant Accoun_4

Summary of Significant Accounting Policies - Patents (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Accounting Policies [Abstract]
Patent expenses	$ 0.5	$ 0.4	$ 0.4

Summary of Significant Accoun_5

Summary of Significant Accounting Policies - Income Taxes (Details)	12 Months Ended
	Dec. 31, 2021
Income Taxes
Valuation allowance on deferred tax assets (as a percent)	100.00%

Summary of Significant Accoun_6

Summary of Significant Accounting Policies - Basic and Diluted Loss Per Common Share (Details) - shares	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Stock options
Anti-dilutive securities
Outstanding securities not included in the computation of diluted net loss per common share as their inclusion would be anti-dilutive (in shares)	2,301,574	1,837,540	1,461,987
Unvested restricted common stock
Anti-dilutive securities
Outstanding securities not included in the computation of diluted net loss per common share as their inclusion would be anti-dilutive (in shares)	0	0	0
Preferred Stock
Anti-dilutive securities
Outstanding securities not included in the computation of diluted net loss per common share as their inclusion would be anti-dilutive (in shares)	1,969,797	1,969,797	1,969,797

Liquidity and Uncertainties (De

Liquidity and Uncertainties (Details) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2021	Sep. 30, 2021	Jun. 30, 2021	Mar. 31, 2021	Dec. 31, 2020	Sep. 30, 2020	Jun. 30, 2020	Mar. 31, 2020	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Liquidity and Uncertainties
Net loss	$ (64,549)	$ (63,100)	$ (61,651)	$ (52,546)	$ (59,123)	$ (57,963)	$ (49,023)	$ (36,135)	$ (241,846)	$ (202,244)	$ (83,948)
Accumulated deficit	$ (667,310)				$ (425,464)				$ (667,310)	$ (425,464)

Cash, Cash Equivalents and Ma_3

Cash, Cash Equivalents and Marketable Securities (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Cash, Cash Equivalents and Marketable Securities
Total cash, cash equivalents and marketable securities, Unrealized gains	$ 6	$ 84
Total cash, cash equivalents and marketable securities, Unrealized losses	(86)	(37)
Carrying value
Cash, Cash Equivalents and Marketable Securities
Cash and cash equivalents	36,269	54,004
Total cash, cash equivalents and marketable securities, Cost	270,426	284,102
Fair value
Cash, Cash Equivalents and Marketable Securities
Cash and cash equivalents	36,269	54,004
Total cash, cash equivalents and marketable securities, Fair value	$ 270,346	$ 284,149
Corporate debt securities due within 1 year of date of purchase
Cash, Cash Equivalents and Marketable Securities
Maturity period from date of purchase to classify an investment as marketable securities	1 year	1 year
Corporate debt securities due within 1 year of date of purchase | Level 2
Cash, Cash Equivalents and Marketable Securities
Marketable securities, unrealized gains	$ 6	$ 80
Marketable securities, unrealized losses	(66)	(36)
Corporate debt securities due within 1 year of date of purchase | Carrying value | Level 2
Cash, Cash Equivalents and Marketable Securities
Marketable securities, cost	228,348	227,172
Corporate debt securities due within 1 year of date of purchase | Fair value | Level 2
Cash, Cash Equivalents and Marketable Securities
Marketable securities, fair value	$ 228,288	$ 227,216
Corporate debt securities due within 1 to 2 years of date of purchase | Maximum [Member]
Cash, Cash Equivalents and Marketable Securities
Maturity period from date of purchase to classify an investment as marketable securities	2 years	2 years
Corporate debt securities due within 1 to 2 years of date of purchase | Minimum [Member]
Cash, Cash Equivalents and Marketable Securities
Maturity period from date of purchase to classify an investment as marketable securities	1 year	1 year
Corporate debt securities due within 1 to 2 years of date of purchase | Level 2
Cash, Cash Equivalents and Marketable Securities
Marketable securities, unrealized gains		$ 4
Marketable securities, unrealized losses	$ (20)	(1)
Corporate debt securities due within 1 to 2 years of date of purchase | Carrying value | Level 2
Cash, Cash Equivalents and Marketable Securities
Marketable securities, cost	5,809	2,926
Corporate debt securities due within 1 to 2 years of date of purchase | Fair value | Level 2
Cash, Cash Equivalents and Marketable Securities
Marketable securities, fair value	5,789	2,929
Cash | Carrying value | Level 1
Cash, Cash Equivalents and Marketable Securities
Cash and cash equivalents	18,877	716
Cash | Fair value | Level 1
Cash, Cash Equivalents and Marketable Securities
Cash and cash equivalents	18,877	716
Money market funds | Carrying value | Level 1
Cash, Cash Equivalents and Marketable Securities
Cash and cash equivalents	17,392	53,288
Money market funds | Fair value | Level 1
Cash, Cash Equivalents and Marketable Securities
Cash and cash equivalents	$ 17,392	$ 53,288

Accrued Liabilities (Details)

Accrued Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Accrued Liabilities, Current [Abstract]
Contract research organization costs	$ 38,349	$ 31,646
Other clinical study related costs	3,957	3,901
Compensation and benefits	6,769	4,686
Professional fees	2,455	830
Other	3,518	4,159
Total accrued liabilities	$ 55,048	$ 45,222

Stockholders' Equity (Deficit)

Stockholders' Equity (Deficit) - Common Stock (Details)	12 Months Ended
	Dec. 31, 2021Vote
Stockholders' Equity Note [Abstract]
Number of votes per share that common stockholders are entitled to receive	1

Stockholders' Equity (Deficit_2

Stockholders' Equity (Deficit) - Preferred Stock (Details)	1 Months Ended
	Jun. 30, 2017Vote$ / sharesshares	Dec. 31, 2021$ / shares	Dec. 31, 2020$ / shares
Stockholders' Equity (Deficit)
Preferred stock, par value (in dollars per share)		$ 0.0001	$ 0.0001
Series A Convertible Preferred Stock
Stockholders' Equity (Deficit)
Preferred stock, par value (in dollars per share)	$ 0.0001
Preferred stock conversion ratio | shares	1
Preferred shares number voting rights | Vote	0

Stockholders' Equity (Deficit_3

Stockholders' Equity (Deficit) - At The Market Issuances (Details) - USD ($) $ in Millions	1 Months Ended	12 Months Ended
	Nov. 30, 2020	Dec. 31, 2021	Dec. 31, 2020
Stockholders' Equity (Deficit)
Number of shares sold by the entity			39,607
At-The-Market Issuance Sales Agreement
Stockholders' Equity (Deficit)
Number of shares sold by the entity		1,087,126	1,126,733
Value of shares sold by the entity		$ 137.4
Net proceeds after deducting commissions and other transactions costs		$ 134.8
At-The-Market Issuance Sales Agreement | 2021 Sales Agreement [Member]
Stockholders' Equity (Deficit)
Number of shares sold by the entity		497,043
Value of shares sold by the entity		$ 40.8
Net proceeds after deducting commissions and other transactions costs		39.8
Remaining reserved amount under shelf registration		159.2
Cowen & Co. LLC | Maximum | At-The-Market Issuance Sales Agreement
Stockholders' Equity (Deficit)
Maximum aggregate offering price	$ 200	$ 200

Stock-based Compensation - Stoc

Stock-based Compensation - Stock Option (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Maximum
Stock-based compensation expense
Expiration period	10 years
Stock options
Stock-based compensation expense
Options outstanding to purchase of common stock	2,301,574	1,837,540
Shares available for future issuance	1,661,293
Shares
Outstanding at the beginning of the year (in shares)	1,837,540
Options granted (in shares)	687,059
Options exercised (in shares)	(11,080)
Options cancelled (in shares)	(211,945)
Outstanding at the end of the year (in shares)	2,301,574	1,837,540
Exercisable at the end of the year (in shares)	1,432,144
Weighted average exercise price
Outstanding at the beginning of the year (in dollars per share)	$ 71.80
Options granted (in dollars per share)	109.03
Options exercised (in dollars per share)	92.96
Options cancelled (in dollars per share)	114.34
Outstanding at the end of the year (in dollars per share)	78.89	$ 71.80
Exercisable at the end of the year (in dollars per share)	$ 62.66
Weighted average remaining contractual life (years)
Outstanding at the end of the year	6 years 6 months 3 days
Exercisable at the end of the year	5 years 4 months 17 days
Aggregate intrinsic value
Outstanding at the end of the year	$ 62,566
Exercisable at the end of the year	60,932
Additional disclosures
Total intrinsic value of options exercised	100	$ 4,100	$ 2,200
Proceeds resulting from exercise of stock options	$ 1,000	$ 700	$ 200
Weighted-average grant date fair value of options (in dollars per share)	$ 73.29	$ 68.07	$ 91.19

Stock-based Compensation - Rest

Stock-based Compensation - Restricted Common Stock (Details)	Dec. 31, 2021shares
Unvested restricted common stock
Shares
Outstanding restricted shares	0

Stock-based Compensation - Expe

Stock-based Compensation - Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Stock-based compensation expense
Stock-based compensation expense	$ 26,873	$ 20,730	$ 22,759
Research and development
Stock-based compensation expense
Stock-based compensation expense	10,698	8,833	8,277
General and administrative
Stock-based compensation expense
Stock-based compensation expense	16,175	11,897	14,482
Stock options
Stock-based compensation expense
Stock-based compensation expense	26,873	20,730	22,487
Unvested restricted common stock
Stock-based compensation expense
Stock-based compensation expense	$ 0	$ 0	$ 272

Stock-based Compensation - Unre

Stock-based Compensation - Unrecognized Expense (Details) - Stock options $ in Millions	12 Months Ended
	Dec. 31, 2021USD ($)
Unrecognized stock-based compensation expense
Unrecognized stock compensation expense	$ 48.9
Weighted average remaining period (in years)	2 years 9 months 14 days

Leases (Details)

Leases (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Operating Leases, Future Minimum Payments Due, Fiscal Year Maturity [Abstract]
2022	$ 436
2023	400
Total minimum payments	836
Less: imputed interest	39
Present value of lease liabilities	$ 797
Weighted average, operating lease term	1 year 11 months 1 day
Weighted average, operating discount rate	3.25%
Lease Liability paid in cash	$ 400	$ 300
Operating lease costs	$ 400	$ 300

Commitments and Contingencies (

Commitments and Contingencies (Details) - USD ($)	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Commitments and Contingencies
Licensed product sales	$ 0	$ 0	$ 0
Research, Development and Commercialization Agreement | Hoffmann-La Roche ("Roche")
Commitments and Contingencies
Remainder of future milestone payments			8,000,000
Milestone payment			$ 2,000,000

Income Taxes - Net Operating Lo

Income Taxes - Net Operating Loss Carryforwards (Details) $ in Millions	Dec. 31, 2021USD ($)
Federal
Income Taxes
Net operating loss	$ 168.8
Federal | Expire In 2037 [Member]
Income Taxes
Net operating loss	40.4
State
Income Taxes
Net operating loss	$ 157.5

Income Taxes - Research and Dev

Income Taxes - Research and Development Carryforward (Details) $ in Millions	Dec. 31, 2021USD ($)
Federal | Research and development carryforward
Income Taxes
Research and development tax credit carryforwards	$ 22.4

Income Taxes - Valuation Allowa

Income Taxes - Valuation Allowance and Uncertain Tax Position (Details) $ in Millions	12 Months Ended
	Dec. 31, 2021USD ($)
Income Tax Disclosure [Abstract]
Increase in valuation allowance	$ 79.3
Liability for uncertain tax positions	0
Income tax related interest and penalties	$ 0

Income Taxes - Deferred Tax Ass

Income Taxes - Deferred Tax Assets and Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Deferred Tax Liabilities
Unrealized gains on investments		$ 14	$ 62
Total Deferred Tax Liabilities		14	62
Deferred Tax Assets
Charitable Contributions	$ 53	51	15
Accrued Expenses	1,857	1,318	759
Intangibles	783	883	983
Stock Compensation	24,335	16,812	10,943
Property, Plant & Equipment	80	68	13
Unrealized Loss on Investment	23
Net Operating Losses	47,864	27,933	17,635
Capitalized R&D	112,848	71,128	29,364
R&D Credit	23,799	14,205	6,141
Total deferred tax assets before valuation allowance	211,642	132,398	65,853
Valuation Allowance	(211,642)	(132,384)	(65,791)
Total deferred tax assets		$ 14	$ 62
Net deferred tax assets	$ 0

Income Taxes - Effective Income

Income Taxes - Effective Income Tax Rate (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Effective income tax rate reconciliation
Tax benefit at U.S. federal statutory rate	$ (50,788)	$ (42,471)	$ (17,629)
Stock based compensation		(68)	(47)
Other nondeductible expenses	5	1	14
State income taxes benefit before valuation allowance, net of federal benefit	(19,622)	(16,580)	(6,613)
Increase in domestic valuation allowance	79,258	66,593	26,843
Research and development credit	(9,002)	(7,472)	(2,636)
Other adjustments	149	(3)	68
Income tax expense (benefit)		$ 0	$ 0

Quarterly Financial Data (una_3

Quarterly Financial Data (unaudited) (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2021	Sep. 30, 2021	Jun. 30, 2021	Mar. 31, 2021	Dec. 31, 2020	Sep. 30, 2020	Jun. 30, 2020	Mar. 31, 2020	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Operating expenses:
Research and development	$ 52,889	$ 54,873	$ 51,632	$ 45,770	$ 53,429	$ 53,292	$ 44,688	$ 33,400	$ 205,164	$ 184,809	$ 72,324
General and administrative	11,712	8,287	10,110	7,209	6,126	5,494	5,639	4,605	37,318	21,864	22,648
Total operating expenses	64,601	63,160	61,742	52,979	59,555	58,786	50,327	38,005	242,482	206,673	94,972
Loss from operations	(64,601)	(63,160)	(61,742)	(52,979)	(59,555)	(58,786)	(50,327)	(38,005)	(242,482)	(206,673)	(94,972)
Interest income	52	60	91	160	432	823	1,204	1,870
Other income	0	0	0	273	0	0	100	0	273	100	0
Net loss	$ (64,549)	$ (63,100)	$ (61,651)	$ (52,546)	$ (59,123)	$ (57,963)	$ (49,023)	$ (36,135)	$ (241,846)	$ (202,244)	$ (83,948)
Basic and diluted net loss per common share (in dollars per share)	$ (3.78)	$ (3.79)	$ (3.72)	$ (3.32)	$ (3.82)	$ (3.75)	$ (3.18)	$ (2.34)	$ (14.63)	$ (13.09)	$ (5.45)
Basic and diluted weighted average number of common shares outstanding	17,074,543	16,639,776	16,571,322	15,840,401	15,475,291	15,448,425	15,433,348	15,429,154	16,535,188	15,446,638	15,394,659