Madrigal Pharmaceuticals (MDGL) 10-K 23 Feb 23 2022 FY Annual report Financial data

Cover Page

Cover Page - USD ($)	12 Months Ended
	Dec. 31, 2022	Feb. 20, 2023	Jun. 30, 2022
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	2022
Document Period End Date	Dec. 31, 2022
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			$ 984,861,131
Entity Filer Category	Large Accelerated Filer
Entity Emerging Growth Company	false
Entity Small Business	false
Entity Shell Company	false
Entity Common Stock, Shares Outstanding		18,138,012
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, 2022	Dec. 31, 2021
Current assets:
Cash and cash equivalents	$ 331,549	$ 36,269
Marketable securities	27,225	234,077
Prepaid expenses and other current assets	2,595	1,338
Total current assets	361,369	271,684
Property and equipment, net	601	851
Right-of-use asset	602	797
Total assets	362,572	273,332
Current liabilities:
Accounts payable	23,831	21,380
Accrued expenses	91,461	55,048
Lease liability	602	410
Total current liabilities	115,894	76,838
Long term liabilities:
Loan payable, net of discount	49,289	0
Lease liability	0	387
Total long term liabilities	49,289	387
Total liabilities	165,183	77,225
Stockholders' equity:
Preferred stock, par value $0.0001 per share authorized: 5,000,000 shares at December 31, 2022 and December 31, 2021; 2,369,797 and 1,969,797 shares issued and outstanding at December 31, 2022 and December 31, 2021, respectively
Common stock, par value $0.0001 per share authorized: 200,000,000 at December 31, 2022 and December 31, 2021; 18,102,523 and 17,103,395 shares issued and outstanding at December 31, 2022 and December 31, 2021, respectively	2	2
Additional paid-in-capital	1,160,079	863,495
Accumulated other comprehensive loss	(32)	(80)
Accumulated deficit	(962,660)	(667,310)
Total stockholders' equity	197,389	196,107
Total liabilities and stockholders' equity	$ 362,572	$ 273,332

Consolidated Balance Sheets (Pa

Consolidated Balance Sheets (Parenthetical) - $ / shares	Dec. 31, 2022	Dec. 31, 2021
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	2,369,797	1,969,797
Preferred stock, shares outstanding	2,369,797	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	18,102,523	17,103,395
Common stock, shares outstanding	18,102,523	17,103,395

Consolidated Statements of Oper

Consolidated Statements of Operations - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Revenues:
Total revenues
Operating expenses:
Research and development	245,441	205,164	184,809
General and administrative	48,130	37,318	21,864
Total operating expenses	293,571	242,482	206,673
Loss from operations	(293,571)	(242,482)	(206,673)
Interest income	2,185	363	4,329
Interest expense	(3,964)	0	0
Other income	0	273	100
Net loss	$ (295,350)	$ (241,846)	$ (202,244)
Net loss per common share:
Basic net loss per common share	$ (17.23)	$ (14.63)	$ (13.09)
Diluted net loss per common share	$ (17.23)	$ (14.63)	$ (13.09)
Basic weighted average number of common shares outstanding	17,137,201	16,535,188	15,446,638
Diluted weighted average number of common shares outstanding	17,137,201	16,535,188	15,446,638

Consolidated Statements of Comp

Consolidated Statements of Comprehensive Loss - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Statement of Comprehensive Income [Abstract]
Net Loss	$ (295,350)	$ (241,846)	$ (202,244)
Other comprehensive income (loss):
Unrealized gain (loss) on available-for-sale securities	48	(127)	(169)
Comprehensive loss	$ (295,302)	$ (241,973)	$ (202,413)

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, 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 and preferred shares in equity offerings, excluding to related parties, net of transaction costs	4,421			4,421
Issuance of common and preferred shares in equity offerings, 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 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		1,969,797	15,508,146
Increase (Decrease) in Stockholders' Equity
Issuance of common and preferred shares in equity offerings, excluding to related parties, net of transaction costs	170,207			170,207
Issuance of common and preferred shares in equity offerings, 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 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
Increase (Decrease) in Stockholders' Equity
Issuance of common and preferred shares in equity offerings, excluding to related parties, net of transaction costs	$ 255,382			255,382
Issuance of common and preferred shares in equity offerings, excluding to related parties, net of transaction costs (in shares)		400,000	783,344
Sale of common shares to related parties and exercise of common stock options, net of transaction cost	8,955			8,955
Sale of common shares to related parties and exercise of common stock options, net of transaction cost ( in shares)			215,784
Compensation expense related to stock options for services	31,625			31,625
Unrealized loss on marketable securities	48				48
Hercules warrant	622			622
Net loss	(295,350)					(295,350)
Balance at Dec. 31, 2022	$ 197,389		$ 2	$ 1,160,079	$ (32)	$ (962,660)
Balance (in shares) at Dec. 31, 2022	18,102,523	2,369,797	18,102,523

Consolidated Statements of Cash

Consolidated Statements of Cash Flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Cash flows from operating activities:
Net loss	$ (295,350)	$ (241,846)	$ (202,244)
Adjustments to reconcile net loss to net cash used in operating activities:
Stock-based compensation expense	31,625	26,873	20,730
Depreciation and amortization expense	467	405	471
Amortization of debt issuance costs and discount	797	0	0
Changes in operating assets and liabilities:
Prepaid expenses and other current assets	(1,257)	(325)	138
Accounts payable	2,451	20,363	(161)
Accrued expense	36,413	9,826	21,585
Accrued interest, net of interest received on maturity of investments	(3)	787	1,920
Net cash used in operating activities	(224,857)	(183,917)	(157,561)
Cash flows from investing activities:
Purchases of marketable securities	(143,478)	(394,120)	(329,342)
Sales and maturities of marketable securities	350,381	389,274	489,456
Purchases of property and equipment, net of disposals	(217)	(209)	(334)
Net cash provided by (used in) investing activities	206,686	(5,055)	159,780
Cash flows from financing activities:
Proceeds from issuances of stock, excluding related parties, net of transaction costs	255,382	170,207	4,421
Proceeds from the sale of related party stock and exercise of common stock options, net of transaction costs	8,955	1,030	667
Proceeds from issuance of loan payable	50,000	0	0
Payment of debt issuance costs	(886)	0	0
Net cash provided by financing activities	313,451	171,237	5,088
Net increase (decrease) in cash and cash equivalents	295,280	(17,735)	7,307
Cash and cash equivalents at beginning of period	36,269	54,004	46,697
Cash and cash equivalents at end of period	331,549	36,269	54,004
Supplemental disclosure of cash flow information:
Obtaining a right-of-use asset in exchange for a lease liability	$ 583	$ 376	$ 451

Organization, Business and Basi

Organization, Business and Basis of Presentation	12 Months Ended
	Dec. 31, 2022
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 Certain prior period amounts have been reclassified to align with current period presentation.

Summary of Significant Accounti

Summary of Significant Accounting Policies	12 Months Ended
	Dec. 31, 2022
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 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, 2022, 2021 and 2020, 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, 2022 and 2021, 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, 2022, 2021 and 2020, the Company did not have any transfers of financials assets between Levels 1 and 2. As of December 31, 2022 and 2021, 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 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, $0.5 million and $0.4 million for the years ended December 31, 2022, 2021 and 2020, respectively. Stock-Based Compensation The Company recognizes stock-based compensation expense based on the grant date fair value of stock options granted to employees, officers and directors. The Company uses the Black-Scholes option pricing model to determine the grant date fair value as management believes it is the most appropriate valuation method for its option grants. The Black-Scholes model requires inputs for risk-free interest rate, dividend yield, volatility and expected lives of the options. The expected lives for options granted represent the period of time that options granted are expected to be outstanding. The Company uses the simplified method for determining the expected lives of options. Expected volatility is based upon an industry estimate or blended rate including the Company’s historical trading activity. The risk-free rate for periods within the expected life of the option is based on the U.S. Treasury yield curve in effect at the time of the grant. The Company estimates the forfeiture rate based on historical data. This analysis is 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, 2022, 2021 and 2020, diluted net loss per share is the same as basic net loss per share because the inclusion of common stock issuable upon the exercise of stock options or warrants, and common stock issuable upon the conversion of preferred stock 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, 2022 2021 2020 Common stock options 2,857,054 2,301,574 1,837,540 Preferred stock 2,369,797 1,969,797 1,969,797 Warrants 14,899 — — Recent Accounting Pronouncements None.

Liquidity and Uncertainties

Liquidity and Uncertainties	12 Months Ended
	Dec. 31, 2022
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 $295.4 million for the year ended December 31, 2022, resulting in an accumulated deficit of approximately $962.7 million and $667.3 million as of December 31, 2022 and 2021, 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, 2022 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, 2022
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, 2022 Unrealized Unrealized Fair Cost gains losses value Cash and cash equivalents: Cash (Level 1) $ 15,100 $ — $ — $ 15,100 Money market funds (Level 1) 316,449 — — 316,449 Total cash and cash equivalents 331,549 — — 331,549 Marketable securities: Corporate debt securities due within 1 year of date of purchase (Level 2) 27,257 7 (39 ) 27,225 Total cash, cash equivalents and marketable securities $ 358,806 $ 7 $ (39 ) $ 358,774 December 31, 2021 Cost Unrealized Unrealized Fair gains losses 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

Accrued Liabilities

Accrued Liabilities	12 Months Ended
	Dec. 31, 2022
Accrued Liabilities, Current [Abstract]
Accrued Liabilities	5. Accrued Liabilities Accrued liabilities as of December 31, 2022 and 2021 consisted of the following (in thousands): December 31, December 31, 2022 2021 Contract research organization costs $ 53,119 $ 38,349 Other clinical study related costs 6,582 3,957 Manufacturing and drug supply 11,262 3,239 Compensation and benefits 14,864 6,769 Professional fees 4,867 2,455 Other 767 279 Total accrued liabilities $ 91,461 $ 55,048

Long Term Debt

Long Term Debt	12 Months Ended
	Dec. 31, 2022
Debt Disclosure [Abstract]
Long Term Debt	6. Long Term Debt In May 2022 the Company and its wholly-owned subsidiary, Canticle Pharmaceuticals, Inc., entered into the $250.0 million Loan Facility (the “Loan Facility”) with the several banks and other financial institutions or entities party thereto (each, a “Lender” and collectively referred to as the “Lenders”), and Hercules Capital, Inc. (“Hercules”), in its capacity The Loan Facility had a minimum interest rate of 7.45% and adjusted with changes in the prime rate. The Company will pay interest-only monthly payments of accrued interest under the Loan Facility through May 1, 2025, for a period of 36 months, which period may be extended to May 1, 2026 and May 3, 2027, upon the achievement of regulatory approval milestones and future revenue covenants, subject to The Loan Facility includes affirmative and restrictive financial covenants commencing on January 1, 2023, including maintenance of a minimum cash, cash equivalents and liquid funds covenant of $35.0 million, which may decrease in certain circumstances if the Company achieves certain clinical milestones and a revenue milestone, and a revenue-based covenant that could apply commencing at or after the time that financial reporting is due for the quarter ending September 30, 2024. The Loan Facility contains event of default provisions for: the Company’s failure to make required payments or maintain compliance with covenants under the Loan Facility; the Company’s breach of certain representations or default under certain obligations outside the Loan Facility; insolvency, attachment or judgment events affecting the Company; and any circumstance which has occurred or could reasonably be expected to have a material adverse effect on the Company, provided that, any failure to achieve approval or certain other milestones As of December 31, 2022, the outstanding principal under the Loan Facility was $50.0 million. The interest rate as of December 31, 2022 was 11.45%. As of December 31, 2022, the Company was in compliance with all loan covenants and provisions. Future minimum payments, including interest and principal, under the loans payable outstanding as of December 31, 2022 are as follows (in thousands): Period Ending December 31, 2022: Amount 2023 $ 5,795 2024 5,820 2025 34,788 Thereafter 23,272 $ 69,675 Less amount representing interest (17,000 ) Less unamortized discount (3,386 ) Loans payable, net of discount $ 49,289 See Footnote 13 for a description of certain amended terms set forth in the First Amendment to this Loan Facility, which was entered into during the first quarter of 2023.

Stockholders' Equity

Stockholders' Equity	12 Months Ended
	Dec. 31, 2022
Stockholders' Equity Note [Abstract]
Stockholders' Equity	7. 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 and B Preferred Stock have a par value of $0.0001 per share and are convertible into shares of the common stock at a one-to-one winding-up as-if-converted-to-Common-Stock as-converted December 2022 Registered Direct Offering In December 2022, the Company entered into a Securities Purchase Agreement (the “Purchase Agreement”) with a group of institutional accredited investors, who were existing, non-controlling 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 entered into an at-the-market “at-the-market” In December 2022, the Company sold 738,900 shares under the 2021 Sales Agreement for an aggregate of $159.1 million in gross proceeds, with net proceeds to the Company of $155.9 million after deducting commissions and other transaction costs. In total, under the 2021 Sales Agreement the Company sold 1,235,943 shares for an aggregate of $199.9 million in gross proceeds, with net proceeds to the Company of approximately $195.8 million after deducting commissions and other transaction costs. Of those shares sold, 738,900 were sold in 2022, and 497,043 were sold in 2021. All shares were sold pursuant to the Company’s effective shelf registration statement and the prospectus supplement relating thereto. As of December 31, 2022, no amounts remained reserved and available for sale under the 2021 Sales Agreement and the related prospectus supplement.

Stock-based Compensation

Stock-based Compensation	12 Months Ended
	Dec. 31, 2022
Share-based Payment Arrangement [Abstract]
Stock-based Compensation	8. Stock-based Compensation The 2015 Stock Plan, as amended, is our primary plan through which equity based grants are awarded. We ceased making new awards under the 2006 Stock Plan upon adoption of the 2015 Stock Plan. The 2015 Stock Plan provides for the grant of incentive stock options, non-statutory The following table summarizes stock option activity during the twelve months ended December 31, 2022: Shares Weighted Weighted Aggregate Outstanding at January 1, 2022 2,301,574 $ 78.90 Options granted 860,795 81.39 Options exercised (215,784 ) 41.50 Options cancelled (89,531 ) 100.71 Outstanding at December 31, 2022 2,857,054 $ 81.78 6.49 $ 596,279 Exercisable at December 31, 2022 1,610,185 $ 76.31 4.90 $ 345,162 The total cash received by the Company as a result of stock option exercises was $9.0 million, $1.0 million and $0.7 million for the years ended December 31, 2022, 2021, and 2020. The total intrinsic value of options exercised was $47.3 million $0.1 million and $4.1 million for the years ended December 31, 2022, 2021, and 2020. The weighted-average grant date fair values, based on the Black-Scholes option model, of options granted during the year ended December 31, 2022, 2021 and 2020 was $54.68, $73.29, and $68.07, respectively. Stock-Based Compensation Expense Stock-based compensation expense during the years ended December 31, 2022, 2021 and 2020 was as follows (in thousands): Year Ended December 31, 2022 2021 2020 Stock-based compensation expense by type of award: Stock options $ 31,625 $ 26,873 $ 20,730 Total stock-based compensation expense $ 31,625 $ 26,873 $ 20,730 Effect of stock-based compensation expense by line item: Research and development $ 13,876 $ 10,698 $ 8,833 General and administrative 17,749 16,175 11,897 Total stock-based compensation expense included in net loss $ 31,625 $ 26,873 $ 20,730 Unrecognized stock-based compensation expense on stock options as of December 31, 2022 was $58.7 million with a weighted average remaining period of 2.57 years.

Leases

Leases	12 Months Ended
	Dec. 31, 2022
Leases [Abstract]
Leases	9. Leases In 20 19, t 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, 2022 was as follows (in thousand): Operating 2023 622 Thereafter — Total minimum payments $ 622 Less: imputed interest (20 ) Present value of lease liabilities $ 602 As of December 31, 2022, the weighted average remaining operating lease term was 0.7 years and the weighted average discount rate used to determine the operating lease liabilities was 6.72%. Cash paid related to the lease liability was $0.7 and $0.4 million for years ended December 31, 2022 and 2021 respectively. Operating lease costs were $0.8 and $0.4 million for years ended December 31, 2022 and 2021 respectively. Rent, short term and variable leases costs were immaterial during the years ended December 31, 2022, 2021 and 2020.

Commitments and Contingencies

Commitments and Contingencies	12 Months Ended
	Dec. 31, 2022
Commitments and Contingencies Disclosure [Abstract]
Commitments and Contingencies	10. 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 clinical trials.

Income Taxes

Income Taxes	12 Months Ended
	Dec. 31, 2022
Income Tax Disclosure [Abstract]
Income Taxes	11. Income Taxes At December 31, 2022, the Company had federal net operating loss (“NOL”) carryforwards of approximately $275.5 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 $264.2 million, available to reduce future taxable income, which expire between 2031 and 2041. The Company has unused federal research and development carryforwards of approximately $33.1 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 $59.5 million for the year ended December 31, 2022. 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, 2022 there were no uncertain positions. The 2018 through 2022 tax returns are open to review by the IRS and state taxing authorities. Interest and penalties, if any, as they relate to no Temporary differences that give rise to deferred tax assets and liabilities are as follows (in thousands): For the years ended December 31, 2022 2021 2020 Deferred Tax Liabilities Unrealized gains on investments $ — $ — $ 14 Total Deferred Tax Liabilities $ — $ — $ 14 Deferred Tax Assets Charitable contributions $ 45 $ 53 $ 51 Accrued expenses 2,398 1,857 1,318 Intangibles 589 783 883 Stock compensation 27,226 24,335 16,812 Property, plant & equipment 106 80 68 Unrealized loss on investment 8 23 — Net operating losses 68,305 47,864 27,933 Capitalized R&D 137,328 112,848 71,128 R&D credit 35,103 23,799 14,205 Total deferred tax assets before valuation allowance 271,108 211,642 132,398 Valuation allowance (271,108 ) (211,642 ) (132,384 ) Total deferred tax assets — — 14 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, 2022 2021 2020 Tax benefit at U.S. federal statutory rate $ (62,023 ) $ (50,788 ) $ (17,629 ) Stock based compensation (7,844 ) — (47 ) 162M limitation 7,996 22 — Other nondeductible expenses 16 5 14 State income taxes benefit before valuation allowance, net of federal benefit 13,090 (19,622 ) (6,613 ) Increase in domestic valuation allowance 59,466 79,258 26,843 Research and development credit (10,712 ) (9,002 ) (2,636 ) Other adjustments 11 127 68 Income tax expense (benefit) $ — $ — $ —

Quarterly Financial Data (unaud

Quarterly Financial Data (unaudited)	12 Months Ended
	Dec. 31, 2022
Quarterly Financial Information Disclosure [Abstract]
Quarterly Financial Data (unaudited)	12. Quarterly Financial Data (unaudited) The following tables present a summary of quarterly results of operations for 2022 and 2021 (in thousands, except shares and per share data): Three months ended March 31, 2022 June 30, 2022 September 30, December 31, Revenues: Total revenues $ — $ — $ — $ — Operating expenses: Research and development 47,929 58,499 68,271 70,742 General and administrative 9,658 11,774 12,141 14,557 Total operating expenses 57,587 70,273 80,412 85,299 Loss from operations (57,587 ) (70,273 ) (80,412 ) (85,299 ) Interest income 69 323 717 1,076 Interest expense — (780 ) (1,502 ) (1,682 ) Other income — — — — Net loss $ (57,518 ) $ (70,730 ) $ (81,197 ) $ (85,905 ) Net loss per common share: Basic and diluted net loss per common share $ (3.36 ) $ (4.14 ) $ (4.75 ) $ (4.98 ) Basic and diluted weighted average number of common shares outstanding 17,103,395 17,103,395 17,103,395 17,237,517 Three months ended March 31, 2021 June 30, 2021 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 Interest expense — — — — 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

Subsequent Event

Subsequent Event	12 Months Ended
	Dec. 31, 2022
Subsequent Events [Abstract]
Subsequent Event	13. Subsequent Event On February 3, 2023, the Company entered into the First Amendment (the “Amendment”) to the Loan Facility described in Footnote 6 (as amended, the “Amended Loan Facility”). Under the terms of the Loan Facility, the first $50.0 million tranche was drawn at closing in May 2022 . Under the Amended Loan Facility, was drawn a expanded, of following . million remains unchanged by the Amendment, and such borrowings are available subject to the Company obtaining a certain FDA approval for resmetirom. Coincident with the expansion of Tranche 2 borrowing capacity by $ million, the Amendment reduced the fourth tranche under the Loan Facility (“Tranche ”) by $ million to $ million , which amount is available subject to Hercules’ sole discretion. In connection with the $ million drawn under the second tranche at the closing of the Amendment, the Company issued to Hercules and affiliates Tranche Warrants to purchase shares of common stock at an exercise price of $285.31 per share . The Amendment reduced the interest rate under the Amended Loan Facility to the greater of (i) the prime rate as reported in The Wall Street Journal plu s % and (ii) %. The Amendment and the Amended Loan Facility summary terms were disclosed in the Company’s Current Report on Form 8-K filed with the Securities and Exchange Commission on February , .

Summary of Significant Accoun_2

Summary of Significant Accounting Policies (Policies)	12 Months Ended
	Dec. 31, 2022
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 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, 2022, 2021 and 2020, 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, 2022 and 2021, 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, 2022, 2021 and 2020, the Company did not have any transfers of financials assets between Levels 1 and 2. As of December 31, 2022 and 2021, 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 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, $0.5 million and $0.4 million for the years ended December 31, 2022, 2021 and 2020, respectively.
Stock-Based Compensation	Stock-Based Compensation The Company recognizes stock-based compensation expense based on the grant date fair value of stock options granted to employees, officers and directors. The Company uses the Black-Scholes option pricing model to determine the grant date fair value as management believes it is the most appropriate valuation method for its option grants. The Black-Scholes model requires inputs for risk-free interest rate, dividend yield, volatility and expected lives of the options. The expected lives for options granted represent the period of time that options granted are expected to be outstanding. The Company uses the simplified method for determining the expected lives of options. Expected volatility is based upon an industry estimate or blended rate including the Company’s historical trading activity. The risk-free rate for periods within the expected life of the option is based on the U.S. Treasury yield curve in effect at the time of the grant. The Company estimates the forfeiture rate based on historical data. This analysis is 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, 2022, 2021 and 2020, diluted net loss per share is the same as basic net loss per share because the inclusion of common stock issuable upon the exercise of stock options or warrants, and common stock issuable upon the conversion of preferred stock 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, 2022 2021 2020 Common stock options 2,857,054 2,301,574 1,837,540 Preferred stock 2,369,797 1,969,797 1,969,797 Warrants 14,899 — —
Recent Accounting Pronouncements	Recent Accounting Pronouncements None.

Summary of Significant Accoun_3

Summary of Significant Accounting Policies (Tables)	12 Months Ended
	Dec. 31, 2022
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, 2022 2021 2020 Common stock options 2,857,054 2,301,574 1,837,540 Preferred stock 2,369,797 1,969,797 1,969,797 Warrants 14,899 — —

Cash, Cash Equivalents and Ma_2

Cash, Cash Equivalents and Marketable Securities (Tables)	12 Months Ended
	Dec. 31, 2022
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, 2022 Unrealized Unrealized Fair Cost gains losses value Cash and cash equivalents: Cash (Level 1) $ 15,100 $ — $ — $ 15,100 Money market funds (Level 1) 316,449 — — 316,449 Total cash and cash equivalents 331,549 — — 331,549 Marketable securities: Corporate debt securities due within 1 year of date of purchase (Level 2) 27,257 7 (39 ) 27,225 Total cash, cash equivalents and marketable securities $ 358,806 $ 7 $ (39 ) $ 358,774 December 31, 2021 Cost Unrealized Unrealized Fair gains losses 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

Accrued Liabilities (Tables)

Accrued Liabilities (Tables)	12 Months Ended
	Dec. 31, 2022
Accrued Liabilities, Current [Abstract]
Schedule of Accrued Liabilities	Accrued liabilities as of December 31, 2022 and 2021 consisted of the following (in thousands): December 31, December 31, 2022 2021 Contract research organization costs $ 53,119 $ 38,349 Other clinical study related costs 6,582 3,957 Manufacturing and drug supply 11,262 3,239 Compensation and benefits 14,864 6,769 Professional fees 4,867 2,455 Other 767 279 Total accrued liabilities $ 91,461 $ 55,048

Long Term Debt (Tables)

Long Term Debt (Tables)	12 Months Ended
	Dec. 31, 2022
Debt Disclosure [Abstract]
Schedule of Maturities of Long-Term Debt [Table Text Block]	Future minimum payments, including interest and principal, under the loans payable outstanding as of December 31, 2022 are as follows (in thousands): Period Ending December 31, 2022: Amount 2023 $ 5,795 2024 5,820 2025 34,788 Thereafter 23,272 $ 69,675 Less amount representing interest (17,000 ) Less unamortized discount (3,386 ) Loans payable, net of discount $ 49,289

Stock-based Compensation (Table

Stock-based Compensation (Tables)	12 Months Ended
	Dec. 31, 2022
Share-based Payment Arrangement [Abstract]
Summary of stock option activity	The following table summarizes stock option activity during the twelve months ended December 31, 2022: Shares Weighted Weighted Aggregate Outstanding at January 1, 2022 2,301,574 $ 78.90 Options granted 860,795 81.39 Options exercised (215,784 ) 41.50 Options cancelled (89,531 ) 100.71 Outstanding at December 31, 2022 2,857,054 $ 81.78 6.49 $ 596,279 Exercisable at December 31, 2022 1,610,185 $ 76.31 4.90 $ 345,162
Schedule of stock-based compensation expense	Stock-based compensation expense during the years ended December 31, 2022, 2021 and 2020 was as follows (in thousands): Year Ended December 31, 2022 2021 2020 Stock-based compensation expense by type of award: Stock options $ 31,625 $ 26,873 $ 20,730 Total stock-based compensation expense $ 31,625 $ 26,873 $ 20,730 Effect of stock-based compensation expense by line item: Research and development $ 13,876 $ 10,698 $ 8,833 General and administrative 17,749 16,175 11,897 Total stock-based compensation expense included in net loss $ 31,625 $ 26,873 $ 20,730

Leases (Tables)

Leases (Tables)	12 Months Ended
	Dec. 31, 2022
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, 2022 was as follows (in thousand): Operating 2023 622 Thereafter — Total minimum payments $ 622 Less: imputed interest (20 ) Present value of lease liabilities $ 602

Income Taxes (Tables)

Income Taxes (Tables)	12 Months Ended
	Dec. 31, 2022
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, 2022 2021 2020 Deferred Tax Liabilities Unrealized gains on investments $ — $ — $ 14 Total Deferred Tax Liabilities $ — $ — $ 14 Deferred Tax Assets Charitable contributions $ 45 $ 53 $ 51 Accrued expenses 2,398 1,857 1,318 Intangibles 589 783 883 Stock compensation 27,226 24,335 16,812 Property, plant & equipment 106 80 68 Unrealized loss on investment 8 23 — Net operating losses 68,305 47,864 27,933 Capitalized R&D 137,328 112,848 71,128 R&D credit 35,103 23,799 14,205 Total deferred tax assets before valuation allowance 271,108 211,642 132,398 Valuation allowance (271,108 ) (211,642 ) (132,384 ) Total deferred tax assets — — 14 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, 2022 2021 2020 Tax benefit at U.S. federal statutory rate $ (62,023 ) $ (50,788 ) $ (17,629 ) Stock based compensation (7,844 ) — (47 ) 162M limitation 7,996 22 — Other nondeductible expenses 16 5 14 State income taxes benefit before valuation allowance, net of federal benefit 13,090 (19,622 ) (6,613 ) Increase in domestic valuation allowance 59,466 79,258 26,843 Research and development credit (10,712 ) (9,002 ) (2,636 ) Other adjustments 11 127 68 Income tax expense (benefit) $ — $ — $ —

Quarterly Financial Data (una_2

Quarterly Financial Data (unaudited) (Tables)	12 Months Ended
	Dec. 31, 2022
Quarterly Financial Information Disclosure [Abstract]
Schedule of quarterly results of operations	The following tables present a summary of quarterly results of operations for 2022 and 2021 (in thousands, except shares and per share data): Three months ended March 31, 2022 June 30, 2022 September 30, December 31, Revenues: Total revenues $ — $ — $ — $ — Operating expenses: Research and development 47,929 58,499 68,271 70,742 General and administrative 9,658 11,774 12,141 14,557 Total operating expenses 57,587 70,273 80,412 85,299 Loss from operations (57,587 ) (70,273 ) (80,412 ) (85,299 ) Interest income 69 323 717 1,076 Interest expense — (780 ) (1,502 ) (1,682 ) Other income — — — — Net loss $ (57,518 ) $ (70,730 ) $ (81,197 ) $ (85,905 ) Net loss per common share: Basic and diluted net loss per common share $ (3.36 ) $ (4.14 ) $ (4.75 ) $ (4.98 ) Basic and diluted weighted average number of common shares outstanding 17,103,395 17,103,395 17,103,395 17,237,517 Three months ended March 31, 2021 June 30, 2021 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 Interest expense — — — — 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

Summary of Significant Accoun_4

Summary of Significant Accounting Policies - Patents (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Accounting Policies [Abstract]
Patent expenses	$ 0.5	$ 0.5	$ 0.4

Summary of Significant Accoun_5

Summary of Significant Accounting Policies - Income Taxes (Details)	12 Months Ended
	Dec. 31, 2022
Income Taxes
Valuation allowance on deferred tax assets (as a percent)	100%

Summary of Significant Accoun_6

Summary of Significant Accounting Policies - Basic and Diluted Loss Per Common Share (Details) - shares	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
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)	2,857,054	2,301,574	1,837,540
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)	2,369,797	1,969,797	1,969,797
Warrants
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)	14,899	0	0

Liquidity and Uncertainties (De

Liquidity and Uncertainties (Details) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2022	Sep. 30, 2022	Jun. 30, 2022	Mar. 31, 2022	Dec. 31, 2021	Sep. 30, 2021	Jun. 30, 2021	Mar. 31, 2021	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Liquidity and Uncertainties
Net loss	$ (85,905)	$ (81,197)	$ (70,730)	$ (57,518)	$ (64,549)	$ (63,100)	$ (61,651)	$ (52,546)	$ (295,350)	$ (241,846)	$ (202,244)
Accumulated deficit	$ (962,660)				$ (667,310)				$ (962,660)	$ (667,310)

Cash, Cash Equivalents and Ma_3

Cash, Cash Equivalents and Marketable Securities (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Cash, Cash Equivalents and Marketable Securities
Total cash, cash equivalents and marketable securities, Unrealized gains	$ 7	$ 6
Total cash, cash equivalents and marketable securities, Unrealized losses	(39)	(86)
Carrying value
Cash, Cash Equivalents and Marketable Securities
Cash and cash equivalents	331,549	36,269
Total cash, cash equivalents and marketable securities, Cost	358,806	270,426
Fair value
Cash, Cash Equivalents and Marketable Securities
Cash and cash equivalents	331,549	36,269
Total cash, cash equivalents and marketable securities, Fair value	$ 358,774	$ 270,346
Corporate debt securities due within 1 year of date of purchase
Cash, Cash Equivalents and Marketable Securities
Corporate debt securities due within 1 year of date of purchase (Level 2)	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	$ 7	$ 6
Marketable securities, unrealized losses	(39)	(66)
Corporate debt securities due within 1 year of date of purchase | Carrying value | Level 2
Cash, Cash Equivalents and Marketable Securities
Marketable securities, cost	27,257	228,348
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	27,225	$ 228,288
Corporate debt securities due within 1 to 2 years of date of purchase | Maximum [Member]
Cash, Cash Equivalents and Marketable Securities
Corporate debt securities due within 1 year of date of purchase (Level 2)		2 years
Corporate debt securities due within 1 to 2 years of date of purchase | Minimum [Member]
Cash, Cash Equivalents and Marketable Securities
Corporate debt securities due within 1 year of date of purchase (Level 2)		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 losses		$ (20)
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
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
Cash | Carrying value | Level 1
Cash, Cash Equivalents and Marketable Securities
Cash and cash equivalents	15,100	18,877
Cash | Fair value | Level 1
Cash, Cash Equivalents and Marketable Securities
Cash and cash equivalents	15,100	18,877
Money market funds | Carrying value | Level 1
Cash, Cash Equivalents and Marketable Securities
Cash and cash equivalents	316,449	17,392
Money market funds | Fair value | Level 1
Cash, Cash Equivalents and Marketable Securities
Cash and cash equivalents	$ 316,449	$ 17,392

Accrued Liabilities (Details)

Accrued Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Accrued Liabilities, Current [Abstract]
Contract research organization costs	$ 53,119	$ 38,349
Other clinical study related costs	6,582	3,957
Manufacturing and drug supply	11,262	3,239
Compensation and benefits	14,864	6,769
Professional fees	4,867	2,455
Other	767	279
Total accrued liabilities	$ 91,461	$ 55,048

Long Term Debt - Schedule of M

Long Term Debt - Schedule of Maturities of Long-Term Debt (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2022 USD ($)
Long-Term Debt, Fiscal Year Maturity [Abstract]
2023	$ 5,795
2024	5,820
2025	34,788
Thereafter	23,272
Long-Term Debt	69,675
Less amount representing interest	(17,000)
Less unamortized discount	(3,386)
Loans payable, net of discount	$ 49,289

Long Term Debt (Details)

Long Term Debt (Details) - USD ($) $ in Millions				1 Months Ended
	Jan. 01, 2023	May 09, 2022	May 01, 2022	May 31, 2022	Dec. 31, 2022
Debt instrument, Face amount					$ 50
Interest rate					11.45%
Percenatge of Term charges on aggregate principal amount				5.35%
Debt conversion, converted instrument, warrants or options issued			14,899
Debt conversion, converted instrument, amount		$ 0.6
Loan Facility [Member] | Subsequent Event [Member]
Line of credit facility, maximum borrowing capacity	$ 35
Line of credit facility, expiration date	Sep. 30, 2024
Drawn In Two Separate Tranches Upon Achievement of Resmetirom Clinical And Regulatory Milestone
Unused borrowing capacity that can be drawn				$ 125
Term Loan [Member]
Debt instrument, Face amount				250
Proceeds from issuance of debt				$ 50
Long term debt floor interest rate percentage				7.45%
Debt Instrument Interest Payments Terms				The Company will pay interest-only monthly payments of accrued interest under the Loan Facility through May 1, 2025, for a period of 36 months, which period may be extended to May 1, 2026 and May 3, 2027, upon the achievement of regulatory approval milestones
Term Loan [Member] | Drawn In Two Separate Tranches Upon Achievement of Resmetirom Clinical And Regulatory Milestone
Unused borrowing capacity that can be drawn				$ 75

Stockholders' Equity (Deficit)

Stockholders' Equity (Deficit) - Common Stock (Details)	12 Months Ended
	Dec. 31, 2022 Vote
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, 2017 Vote $ / shares shares	Dec. 31, 2022 $ / shares	Dec. 31, 2021 $ / shares
Stockholders' Equity (Deficit)
Preferred stock, par value (in dollars per share)		$ 0.0001	$ 0.0001
Convertible Series A and B 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) - Registered Offering (Details) - USD ($) $ / shares in Units, $ in Millions	1 Months Ended	12 Months Ended
	Dec. 23, 2022	Dec. 31, 2020
Stockholders' Equity (Deficit)
Stock Issued During Period, Shares, New Issues		39,607
2022 Registered Direct Offering | Purchase Agreement
Stockholders' Equity (Deficit)
Proceeds from issuance or sale of equity, Gross	$ 100
Proceeds from issuance or sale of equity	$ 99.5
2022 Registered Direct Offering | Common stock | Purchase Agreement
Stockholders' Equity (Deficit)
Stock Issued During Period, Shares, New Issues	44,444
Shares issued, Price per share	$ 225
2022 Registered Direct Offering | Series B Preferred Stock | Purchase Agreement
Stockholders' Equity (Deficit)
Stock Issued During Period, Shares, New Issues	400,000
Shares issued, Price per share	$ 225

Stockholders' Equity (Deficit_4

Stockholders' Equity (Deficit) - At The Market Issuances (Details) - USD ($) $ in Millions	1 Months Ended	12 Months Ended			24 Months Ended
	Nov. 30, 2020	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2022
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		1,126,733	1,087,126
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
Stockholders' Equity (Deficit)
Number of shares sold by the entity		738,900	497,043		1,235,943
Value of shares sold by the entity		$ 159.1			$ 199.9
Net proceeds after deducting commissions and other transactions costs		155.9			195.8
Remaining reserved amount under shelf registration		0			$ 0
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, 2022	Dec. 31, 2021	Dec. 31, 2020
Maximum
Stock-based compensation expense
Expiration period	10 years
Stock options
Stock-based compensation expense
Options outstanding to purchase of common stock	2,857,054	2,301,574
Shares available for future issuance	890,029
Shares
Outstanding at the beginning of the year (in shares)	2,301,574
Options granted (in shares)	860,795
Options exercised (in shares)	(215,784)
Options cancelled (in shares)	(89,531)
Outstanding at the end of the year (in shares)	2,857,054	2,301,574
Exercisable at the end of the year (in shares)	1,610,185
Weighted average exercise price
Outstanding at the beginning of the year (in dollars per share)	$ 78.9
Options granted (in dollars per share)	81.39
Options exercised (in dollars per share)	41.5
Options cancelled (in dollars per share)	100.71
Outstanding at the end of the year (in dollars per share)	81.78	$ 78.9
Exercisable at the end of the year (in dollars per share)	$ 76.31
Weighted average remaining contractual life (years)
Outstanding at the end of the year	6 years 5 months 26 days
Exercisable at the end of the year	4 years 10 months 24 days
Aggregate intrinsic value
Outstanding at the end of the year	$ 596,279
Exercisable at the end of the year	345,162
Additional disclosures
Total intrinsic value of options exercised	47,300	$ 100	$ 4,100
Proceeds resulting from exercise of stock options	$ 9,000	$ 1,000	$ 700
Weighted-average grant date fair value of options (in dollars per share)	$ 54.68	$ 73.29	$ 68.07

Stock-based Compensation - Expe

Stock-based Compensation - Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Stock-based compensation expense
Stock-based compensation expense	$ 31,625	$ 26,873	$ 20,730
Research and development
Stock-based compensation expense
Stock-based compensation expense	13,876	10,698	8,833
General and administrative
Stock-based compensation expense
Stock-based compensation expense	17,749	16,175	11,897
Stock options
Stock-based compensation expense
Stock-based compensation expense	$ 31,625	$ 26,873	$ 20,730

Stock-based Compensation - Unre

Stock-based Compensation - Unrecognized Expense (Details) - Stock options $ in Millions	12 Months Ended
	Dec. 31, 2022 USD ($)
Unrecognized stock-based compensation expense
Unrecognized stock compensation expense	$ 58.7
Weighted average remaining period (in years)	2 years 6 months 25 days

Leases (Details)

Leases (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Operating Leases, Future Minimum Payments Due, Fiscal Year Maturity [Abstract]
2023	$ 622
Total minimum payments	622
Less: imputed interest	(20)
Present value of lease liabilities	$ 602
Weighted average, operating lease term	8 months 12 days
Weighted average, operating discount rate	6.72%
Lease Liability paid in cash	$ 700	$ 400
Operating lease costs	$ 800	$ 400

Commitments and Contingencies (

Commitments and Contingencies (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	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
Milestone payment				$ 2

Income Taxes - Net Operating Lo

Income Taxes - Net Operating Loss Carryforwards (Details) $ in Millions	Dec. 31, 2022 USD ($)
Federal
Income Taxes
Net operating loss	$ 275.5
Federal | Expire In 2037 [Member]
Income Taxes
Net operating loss	40.4
State
Income Taxes
Net operating loss	$ 264.2

Income Taxes - Research and Dev

Income Taxes - Research and Development Carryforward (Details) $ in Millions	Dec. 31, 2022 USD ($)
Federal | Research and development carryforward
Income Taxes
Research and development tax credit carryforwards	$ 33.1

Income Taxes - Valuation Allowa

Income Taxes - Valuation Allowance and Uncertain Tax Position (Details) $ in Millions	12 Months Ended
	Dec. 31, 2022 USD ($)
Income Tax Disclosure [Abstract]
Increase in valuation allowance	$ 59.5
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, 2022	Dec. 31, 2021	Dec. 31, 2020
Deferred Tax Liabilities
Unrealized gains on investments			$ 14
Total Deferred Tax Liabilities			14
Deferred Tax Assets
Charitable contributions	$ 45	$ 53	51
Accrued expenses	2,398	1,857	1,318
Intangibles	589	783	883
Stock compensation	27,226	24,335	16,812
Property, plant & equipment	106	80	68
Unrealized loss on investment	8	23
Net operating losses	68,305	47,864	27,933
Capitalized R&D	137,328	112,848	71,128
R&D Credit	35,103	23,799	14,205
Total deferred tax assets before valuation allowance	271,108	211,642	132,398
Valuation allowance	(271,108)	$ (211,642)	(132,384)
Total deferred tax assets			$ 14
Net deferred tax assets	$ 0

Income Taxes - Effective Income

Income Taxes - Effective Income Tax Rate (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Effective income tax rate reconciliation
Tax benefit at U.S. federal statutory rate	$ (62,023)	$ (50,788)	$ (17,629)
Stock based compensation	(7,844)		(47)
162M limitation	7,996	22
Other nondeductible expenses	16	5	14
State income taxes benefit before valuation allowance, net of federal benefit	13,090	(19,622)	(6,613)
Increase in domestic valuation allowance	59,466	79,258	26,843
Research and development credit	(10,712)	(9,002)	(2,636)
Other adjustments	11	127	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, 2022	Sep. 30, 2022	Jun. 30, 2022	Mar. 31, 2022	Dec. 31, 2021	Sep. 30, 2021	Jun. 30, 2021	Mar. 31, 2021	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Operating expenses:
Research and development	$ 70,742	$ 68,271	$ 58,499	$ 47,929	$ 52,889	$ 54,873	$ 51,632	$ 45,770	$ 245,441	$ 205,164	$ 184,809
General and administrative	14,557	12,141	11,774	9,658	11,712	8,287	10,110	7,209	48,130	37,318	21,864
Total operating expenses	85,299	80,412	70,273	57,587	64,601	63,160	61,742	52,979	293,571	242,482	206,673
Loss from operations	(85,299)	(80,412)	(70,273)	(57,587)	(64,601)	(63,160)	(61,742)	(52,979)	(293,571)	(242,482)	(206,673)
Interest income	1,076	717	323	69	52	60	91	160
Interest expense	(1,682)	(1,502)	(780)	0	0	0	0	0	(3,964)	0	0
Other income	0	0	0	0	0	0	0	273	0	273	100
Net loss	$ (85,905)	$ (81,197)	$ (70,730)	$ (57,518)	$ (64,549)	$ (63,100)	$ (61,651)	$ (52,546)	$ (295,350)	$ (241,846)	$ (202,244)
Net loss per common share, Basic	$ (4.98)	$ (4.75)	$ (4.14)	$ (3.36)	$ (3.78)	$ (3.79)	$ (3.72)	$ (3.32)	$ (17.23)	$ (14.63)	$ (13.09)
Net loss per common share, Diluted	$ (4.98)	$ (4.75)	$ (4.14)	$ (3.36)	$ (3.78)	$ (3.79)	$ (3.72)	$ (3.32)	$ (17.23)	$ (14.63)	$ (13.09)
Weighted average number of common shares outstanding, Basic	17,237,517	17,103,395	17,103,395	17,103,395	17,074,543	16,639,776	16,571,322	15,840,401	17,137,201	16,535,188	15,446,638
Weighted average number of common shares outstanding, Diluted	17,237,517	17,103,395	17,103,395	17,103,395	17,074,543	16,639,776	16,571,322	15,840,401	17,137,201	16,535,188	15,446,638

Subsequent Event (Details)

Subsequent Event (Details) - USD ($)			1 Months Ended
	Feb. 03, 2023	May 01, 2022	May 31, 2022	Sep. 30, 2023	Jun. 19, 2023
Subsequent Event [Line Items]
Debt Conversion, Converted Instrument, Warrants or Options Issued		14,899
Loan Facility And Amended Loan Facility
Subsequent Event [Line Items]
Proceeds from issuance of debt			$ 50,000,000
Term Loan [Member]
Subsequent Event [Line Items]
Proceeds from issuance of debt			$ 50,000,000
Long term debt floor interest rate percentage			7.45%
Subsequent Event | Loan Facility And Amended Loan Facility
Subsequent Event [Line Items]
Long term debt floor interest rate percentage	8.25%
Subsequent Event | Loan Facility And Amended Loan Facility | Prime Rate
Subsequent Event [Line Items]
Long term debt floor interest rate percentage	2.45%
Subsequent Event | Loan Facility And Amended Loan Facility | Tranche Two
Subsequent Event [Line Items]
Proceeds from issuance of debt	$ 35,000,000
Additional Drawn	$ 65,000,000			$ 15,000,000	$ 15,000,000
Line of Credit Facility, Remaining Borrowing Capacity				$ 30,000,000
Debt Conversion, Converted Instrument, Warrants or Options Issued	2,453
Class of Warrant or Right, Exercise Price of Warrants or Rights	$ 285.31
Line of Credit Facility, Current Borrowing Capacity	$ 15,000,000
Subsequent Event | Loan Facility And Amended Loan Facility | Tranche three
Subsequent Event [Line Items]
Line of Credit Facility, Remaining Borrowing Capacity	75,000,000
Subsequent Event | Loan Facility And Amended Loan Facility | Tranche fouth
Subsequent Event [Line Items]
Line of Credit Facility, Remaining Borrowing Capacity	15,000,000
Subsequent Event | Loan Facility And Amended Loan Facility One | Tranche fouth
Subsequent Event [Line Items]
Line of Credit Facility, Remaining Borrowing Capacity	60,000,000
Subsequent Event | Term Loan [Member] | Loan Facility And Amended Loan Facility
Subsequent Event [Line Items]
Proceeds from issuance of debt	$ 35,000