Jaguar Health (JAGX) 10-Q 10 May 22 2022 Q1 Quarterly report Financial data

Document and Entity Information

Document and Entity Information - shares	3 Months Ended
	Mar. 31, 2022	May 04, 2022
Document Information [Line Items]
Document Type	10-Q
Document Quarterly Report	true
Document Transition Report	false
Document Period End Date	Mar. 31, 2022
Entity File Number	001-36714
Entity Registrant Name	JAGUAR HEALTH, INC.
Entity Incorporation, State or Country Code	DE
Entity Tax Identification Number	46-2956775
Entity Address, Address Line One	200 Pine Street, Suite 400
Entity Address, City or Town	San Francisco
Entity Address, State or Province	CA
Entity Address, Postal Zip Code	94104
City Area Code	415
Local Phone Number	371-8300
Title of 12(b) Security	Common Stock, Par Value $0.0001 Per Share
Trading Symbol	JAGX
Security Exchange Name	NASDAQ
Entity Current Reporting Status	Yes
Entity Interactive Data Current	Yes
Entity Filer Category	Non-accelerated Filer
Entity Small Business	true
Entity Emerging Growth Company	false
Entity Shell Company	false
Current Fiscal Year End Date	--12-31
Document Fiscal Year Focus	2022
Document Fiscal Period Focus	Q1
Entity Central Index Key	0001585608
Amendment Flag	false
Common stock - voting
Document Information [Line Items]
Entity Common Stock, Shares Outstanding		77,858,506
Common stock - non-voting
Document Information [Line Items]
Entity Common Stock, Shares Outstanding		2,120,786

CONDENSED CONSOLIDATED BALANCE

CONDENSED CONSOLIDATED BALANCE SHEETS - USD ($)	Mar. 31, 2022	Dec. 31, 2021
Current assets:
Cash	$ 17,456,000	$ 17,051,000
Accounts receivable	1,795,000	1,709,000
Other receivable	460,000	435,000
Inventory	4,879,000	4,900,000
Prepaid expenses and other current assets	3,884,000	4,339,000
Total current assets	28,474,000	28,434,000
Property and equipment, net	600,000	650,000
Operating lease - right-of-use asset	1,157,000	1,084,000
Intangible assets, net	22,229,000	22,651,000
Other assets	446,000	446,000
Total assets	52,906,000	53,265,000
Current liabilities:
Accounts payable	3,708,000	4,929,000
Accrued liabilities	8,195,000	7,117,000
Warrant liability	1,000	1,000
Operating lease liability, current	299,000	240,000
Notes payable, current	6,890,000	3,184,000
Total current liabilities	19,093,000	15,471,000
Operating lease liability, net of current portion	921,000	919,000
Notes payable, net of discount, net of current portion (includes hybrid instrument designated at Fair Value Option amounting to $8.1 million and $7.8 million as of March 31, 2022 and December 31, 2021, respectively)	24,783,000	25,022,000
Total liabilities	44,797,000	41,412,000
Commitments and contingencies (See Note 7)
Stockholders' equity
Additional paid-in capital	245,517,000	231,100,000
Noncontrolling interest	64,000	242,000
Accumulated deficit	(237,480,000)	(219,494,000)
Total stockholders' equity	8,109,000	11,853,000
Total liabilities and stockholders' equity	52,906,000	53,265,000
Series D perpetual preferred stock
Current liabilities:
Series D perpetual preferred stock: $0.0001 par value; 977,300 shares authorized at March 31, 2022 and December 31, 2021; zero shares issued and outstanding at March 31, 2022 and December 31, 2021
Series B-2 Preferred Stock
Stockholders' equity
Preferred stock value
Series C perpetual preferred stock
Stockholders' equity
Preferred stock value
Common stock - voting
Stockholders' equity
Common stock value	8,000	5,000
Common stock - non-voting
Stockholders' equity
Common stock value

CONDENSED CONSOLIDATED BALANC_2

CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical) - USD ($) $ in Thousands	Mar. 31, 2022	Dec. 31, 2021
Preferred stock, shares authorized	1,021,165
Notes payable, net of current portion (includes hybrid instrument designated at Fair Value Option)	$ 8,051	$ 7,800
Series D perpetual preferred stock
Convertible preferred stock, par value (in dollars per share)	$ 0.0001	$ 0.0001
Convertible preferred stock, shares authorized	977,300	977,300
Convertible preferred stock, shares issued	0	0
Convertible preferred stock, shares outstanding	0	0
Series B-2 Preferred Stock
Convertible preferred stock, par value (in dollars per share)	$ 0.0001	$ 0.0001
Convertible preferred stock, shares authorized	10,165	10,165
Convertible preferred stock, shares issued	0	0
Convertible preferred stock, shares outstanding	0	0
Preferred stock, shares authorized	10,165
Preferred stock, shares outstanding	0	0
Series C perpetual preferred stock
Preferred stock, shares authorized	1,011,000	1,011,000
Preferred stock, shares issued	0	0
Preferred stock, shares outstanding	0	0
Common Stock
Common stock, shares authorized	204,475,074
Common Stock | Common stock - voting
Common stock, par value (in dollars per share)	$ 0.0001	$ 0.0001
Common stock, shares authorized	150,000,000	150,000,000
Common stock, shares issued	77,073,990	48,352,527
Common stock, shares outstanding	77,073,990	48,352,527
Common Stock | Common stock - non-voting
Common stock, par value (in dollars per share)	$ 0.0001	$ 0.0001
Common stock, shares authorized	50,000,000	50,000,000
Common stock, shares issued	2,120,786	2,120,786
Common stock, shares outstanding	2,120,786	2,120,786

CONDENSED CONSOLIDATED STATEMEN

CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($) $ in Thousands	3 Months Ended
	Mar. 31, 2022	Mar. 31, 2021
Operating expenses
Cost of product revenue	$ 455	$ 583
Research and development	4,945	2,414
Sales and marketing	2,835	2,139
General and administrative	6,144	3,409
Series 3 warrants inducement expense		1,462
Total operating expenses	14,379	10,007
Loss from operations	(11,754)	(8,766)
Interest expense	(4,194)	(1,901)
Loss on extinguishment of debt	(2,815)	(753)
Change in fair value of financial instruments and hybrid instrument designated at Fair Value Option	(233)	(599)
Other income, net	832	10
Loss before income tax	(18,164)	(12,009)
Net loss and comprehensive loss	(18,164)	(12,009)
Net income attributable to noncontrolling interest	(178)
Net loss attributable to common shareholders	(17,986)	(12,009)
Net loss attributable to common shareholders, diluted	$ (17,986)	$ (12,009)
Net loss per share, basic	$ (0.40)	$ (0.28)
Net loss per share, diluted	$ (0.40)	$ (0.28)
Weighted-average common shares outstanding, basic	44,711,588	42,635,466
Weighted-average common shares outstanding, Diluted	44,711,588	42,635,466
Product revenue, net
Revenue
Total revenue	$ 2,625	$ 1,241

CONDENSED CONSOLIDATED STATEM_2

CONDENSED CONSOLIDATED STATEMENTS OF CHANGES IN CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS' EQUITY - USD ($) $ in Thousands	Series 1, Series 2 and Bridge warrantCommon StockCommon stock - voting	Series 1, Series 2 and Bridge warrantAdditional paid-in capital	Series 1, Series 2 and Bridge warrant	Series 3 warrantsCommon StockCommon stock - voting	Series 3 warrantsAdditional paid-in capital	Series 3 warrants	Series 1, Series 2, and 2019 Bridge Note warrants June 2020Registered public offeringCommon StockCommon stock - voting	Series 1, Series 2, and 2019 Bridge Note warrants June 2020Registered public offeringAdditional paid-in capital	Series 1, Series 2, and 2019 Bridge Note warrants June 2020Registered public offering	Private Investment in Public EntitiesCommon StockCommon stock - voting	Private Investment in Public EntitiesAdditional paid-in capital	Private Investment in Public Entities	At The Market OfferingCommon StockCommon stock - voting	At The Market OfferingAdditional paid-in capital	At The Market Offering	Common StockCommon stock - voting	Common StockCommon stock - non-voting	Additional paid-in capital	Noncontrolling Interest	Accumulated deficit	Series D perpetual preferred stock	Total
Beginning Balance at Dec. 31, 2020																$ 4		$ 184,097		$ (166,899)		$ 17,202
Beginning Balance (in shares) at Dec. 31, 2020																38,007,420	2,120,786
Increase (decrease) in Stockholders' Equity (Deficit)
Issuance of common stock								$ 13,398	$ 13,398		$ 975	$ 975		$ 5,365	$ 5,365
Issuance of common stock (In shares)							1,479,290			416,664			669,850
Shares issued on conversion of Napo merger common shares (in shares)				601
Shares issued in extinguishment of Exchange Note 2																		2,516				2,516
Shares issued in extinguishment of Exchange Note 2 (in shares)																471,202
Value of shares issued on exercise of warrants		$ 2,034	$ 2,034		$ 1,776	$ 1,776
Shares issued on exercise of warrants	1,383,524			206,915
Stock-based compensation																		634				634
Net loss																				(12,009)		(12,009)
Ending Balance at Mar. 31, 2021																$ 4		210,795		(178,908)		31,891
Ending Balance (in shares) at Mar. 31, 2021																42,635,466	2,120,786
Ending Balance (in shares) at Dec. 31, 2021																					0
Beginning Balance at Dec. 31, 2020																$ 4		184,097		(166,899)		17,202
Beginning Balance (in shares) at Dec. 31, 2020																38,007,420	2,120,786
Ending Balance at Dec. 31, 2021																$ 5		231,100	$ 242	(219,494)		11,853
Ending Balance (in shares) at Dec. 31, 2021																48,352,527	2,120,786
Ending Balance (in shares) at Mar. 31, 2022																					0
Increase (decrease) in Stockholders' Equity (Deficit)
Issuance of common stock													$ 2	$ 9,108	$ 9,110
Issuance of common stock (In shares)													20,046,463
Shares issued to Iliad in exchange of notes payable and accrued interest																$ 1		4,232				4,233
Shares issued to Iliad in exchange of notes payable and accrued interest (in shares)																8,650,000
Shares issued to third party for services																		14				14
Shares issued to third party for services (in shares)																25,000
Stock-based compensation																		1,063				1,063
Net loss																			(178)	(17,986)		(18,164)
Ending Balance at Mar. 31, 2022																$ 8		$ 245,517	$ 64	$ (237,480)		$ 8,109
Ending Balance (in shares) at Mar. 31, 2022																77,073,990	2,120,786

CONDENSED CONSOLIDATED STATEM_3

CONDENSED CONSOLIDATED STATEMENTS OF CHANGES IN CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS' EQUITY (Parenthetical) - USD ($)	Oct. 05, 2020	Mar. 31, 2022	Mar. 31, 2021	Dec. 31, 2021
Series 1, Series 2 and Bridge warrant
Stock Transactions, Parenthetical Disclosures
Issuance costs		$ 486,000
At The Market Offering
Stock Transactions, Parenthetical Disclosures
Issuance costs	$ 40,000	83,000	$ 311,000	$ 465,000
Registered public offering
Stock Transactions, Parenthetical Disclosures
Issuance costs		$ 1,514,000	$ 1,602,000

CONDENSED CONSOLIDATED STATEM_4

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	1 Months Ended	3 Months Ended		12 Months Ended
	Jan. 31, 2021	Mar. 31, 2022	Mar. 31, 2021	Dec. 31, 2021
Cash flows from operating activities
Net loss		$ (18,164)	$ (12,009)
Adjustments to reconcile net loss to net cash used in operating activities:
Amortization of debt issuance costs, debt discount, and non-cash interest expense		3,429	1,198
Stock-based compensation		1,063	634
Change in fair value of financial instruments and hybrid instrument designated at Fair Value Option		233	599
Depreciation and amortization expense		426	431
Series 3 warrants inducement expense			1,462
Loss on extinguishment of debt	$ (753)	2,815	753
Amortization of operating lease - right-of-use-asset		29
Derecognition of debt discount on settlement of receivables secured borrowing			49
Shares issued in exchange for services		14
Changes in assets and liabilities
Accounts receivable		(86)	(1,365)
Other receivable		(117)	(2)
Inventory		22	(39)
Prepaid expenses and other current assets		507	(649)
Other assets		(5)	18
Accounts payable		(1,173)	(113)
Accrued liabilities		3,341	2,325
Operating lease liability		(29)
Total cash used in operating activities		(7,695)	(6,708)
Cash flows from financing activities
Proceeds from issuance of notes payable, net of issuance costs of $50			10,975
Repayment of receivables secured borrowing			(1,822)
Repayment of insurance financing		(335)	(95)
Noncontrolling interest		(178)	(50)
Repayment of notes payable		(447)
Total cash provided by financing activities		8,150	30,868
Effects of foreign exchange rate changes on assets and liabilities		(50)
Net increase in cash		405	24,160
Cash at beginning of period	$ 8,090	17,051	8,090	$ 8,090
Cash at end of period		17,456	32,250	$ 17,051
Supplemental schedule of cash flow information
Cash paid for interest		11	6
Supplemental schedule of non-cash financing and investing activities
Shares issued to Iliad in exchange of notes payable and accrued interest		4,233
Shares issued in extinguishment of Exchange Note 2			2,516
Shares issued on exercise of Series 3 warrants			1,776
Insurance financing			98
Offering costs included in accounts payable and accrued liabilities			88
Purchase of equipment			6
At The Market Offering
Cash flows from financing activities
Proceeds from issuance of shares in At the Market offering, net of issuance and offering costs of $465		9,110	5,365
Registered public offering
Cash flows from financing activities
Proceeds from issuance of shares in registered public offering, net of issuance and offering costs of $1,514			13,486
2019 Bridge Note Warrants
Cash flows from financing activities
Proceeds from issuance of shares on conversion, net of issuance and offering costs			2,034
Private Investment in Public Entities
Cash flows from financing activities
Proceeds from issuance of shares in PIPE financing			$ 975
Series 3 warrants
Supplemental schedule of non-cash financing and investing activities
Recognition of operating lease - right-of-use asset and operating lease liability		$ 90

CONDENSED CONSOLIDATED STATEM_5

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Parenthetical)	3 Months Ended
	Mar. 31, 2022USD ($)
Notes payable
Debt issuance costs	$ 50,000
Registered public offering
Issuance costs	1,514,000
At The Market Offering
Issuance costs	83,000
Series 1, Series 2 and Bridge warrant
Issuance costs	$ 486,000

Organization and Business

Organization and Business	3 Months Ended
	Mar. 31, 2022
Organization and Business
Organization and Business	1. Organization and Business Jaguar Health, Inc. (“Jaguar” or the “Company”) is a San Francisco, California-based commercial stage pharmaceuticals company focused on developing novel, plant-based, non-opioid, and sustainably derived prescription medicines for people and animals with GI distress, including chronic, debilitating diarrhea. Jaguar Animal Health is a tradename of Jaguar Health. Our wholly owned subsidiary, Napo Pharmaceuticals, Inc. (“Napo”), focuses on developing and commercializing proprietary plant-based human pharmaceuticals for the global marketplace from plants or plant products used traditionally in rainforest areas. Napo’s marketed drug Mytesi (crofelemer 125 mg delayed-release tablets) is a first-in-class oral botanical drug product approved by the U.S. Food and Drug Administration (“FDA”) for the symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy. To date, this is the only oral plant-based botanical prescription medicine approved under the FDA’s Botanical Guidance. Jaguar Animal Health’s Canalevia-CA1 (crofelemer delayed-release tablets) drug is the first and only oral plant-based prescription product that is FDA conditionally approved to treat chemotherapy-induced diarrhea (CID) in dogs. Canalevia-CA1 a canine-specific formulation of crofelemer. Napo Therapeutics S.p.A. (f/k/a Napo EU S.p.A.), Napo’s majority owned Italian subsidiary, focuses on expanding crofelemer access in Europe. Jaguar, formerly known as Jaguar Animal Health, Inc., was founded in San Francisco, California as a Delaware corporation on June 6, 2013 (inception). The Company was a majority-owned subsidiary of Napo until the close of the Company's initial public offering on May 18, 2015. The Company was formed to develop and commercialize first-in-class prescription and non-prescription products for companion and production animals and horses. The Company's first non-prescription commercial products, Neonorm Calf and Neonorm Foal, were launched in 2014 and 2016, respectively. On July 31, 2017, Jaguar completed a merger with Napo pursuant to the Agreement and Plan of Merger dated March 31, 2017, by and among Jaguar, Napo, Napo Acquisition Corporation (“Merger Sub”), and Napo's representative (the “Merger Agreement”). In accordance with the terms of the Merger Agreement, upon the completion of the merger, Merger Sub merged with and into Napo, with Napo surviving as the wholly owned subsidiary (the “Merger” or “Napo Merger”). Immediately following the Merger, Jaguar changed its name from “Jaguar Animal Health, Inc.” to “Jaguar Health, Inc.” Napo now operates as a wholly owned subsidiary of Jaguar focused on human health including the ongoing development of crofelemer and commercialization of Mytesi. On March 15, 2021, Jaguar established Napo EU S.p.A (which changed its name in January 2022 to Napo Therapeutics S.p.A. “Napo Therapeutics”) based in Milan, Italy as a subsidiary of Napo. Napo Therapeutics’ core mission is to provide access to crofelemer in Europe to address significant rare/orphan disease indications, including, initially, two key orphan target indications: Short bowel syndrome (SBS) with intestinal failure, and congenital diarrheal disorders (CDD). On November 3, 2021, Napo Therapeutics merged with Dragon SPAC S.p.A. (“Dragon SPAC”). On December 13, 2021, the European Medicines Agency (EMA) granted orphan-drug designation (ODD) for crofelemer for the short bowel syndrome (SBS) indication in the European Union following review of the ODD application Napo submitted to the EMA in September 2021. Following this decision from the EMA, Napo Therapeutics is initiating efforts to commence clinical development of crofelemer in both adult and pediatric SBS patients in support of the company’s key focus on leveraging the EMA’s accelerated conditional marketing authorization pathway in Europe for this rare disease. Napo Therapeutics has also agreed to support investigator-initiated trials (IITs), which are expected to provide proof of concept (POC) support for potential expanded access programs for crofelemer for patients with CDD and/or SBS patients with intestinal failure. The expanded access program will be initiated following completion of these studies and upon publication of POC results, potentially in 2023. Crofelemer previously received ODD in the U.S. from the FDA for SBS. SBS affects approximately 10,000 to 20,000 people in the U.S., according to the Crohn's & Colitis Foundation, and it is estimated that the population of SBS patients in Europe is approximately the same size. Despite limited treatment options, the global SBS market exceeded $568 million in 2019 and is expected to reach $4.6 billion by 2027, according to a report by Vision Research Reports. On December 21, 2021, we received conditional approval from the FDA for Canalevia-CA1 (crofelemer delayed-release tablets), our oral plant-based prescription drug and the only drug for the treatment of CID in dogs. Canalevia-CA1 is being commercialized as a prescription drug product under the Company’s Jaguar Animal Health tradename, and as announced April 27, 2022, Canalevia-CA1 is now available from multiple leading veterinary distributors in the U.S. to veterinarians. Most of the activities of the Company are focused on the commercialization of Mytesi and Canalevia-CA1 and the ongoing clinical development of crofelemer for the prophylaxis of diarrhea in adult patients receiving targeted cancer therapy (CTD). Napo’s pivotal OnTarget Phase 3 clinical trial of crofelemer for prophylaxis of CTD was initiated in October 2020 and is ongoing. In the field of animal health, we are continuing limited activities related to developing and commercializing first-in-class gastrointestinal products for dogs, dairy calves, foals, and high value horses. We believe Jaguar is poised to realize a number of synergistic, value adding benefits—and the above-referenced expanded pipeline of potential blockbuster human indications of crofelemer and lechlemer—upon which to build global partnerships. Jaguar, through Napo, holds global unencumbered rights for crofelemer, Mytesi, and Canalevia-CA1. Additionally, several of the drug product opportunities in Jaguar’s crofelemer pipeline are backed Phase 2 and proof of concept evidence from human clinical trials. Nasdaq Communication and Compliance Minimum Bid Price Requirement On February 17, 2022, the Company received a letter from the Staff of Nasdaq indicating that the bid price of the Company’s common stock for the last 30 consecutive business days had again closed below the minimum $1.00 per share required for the continued listing under Nasdaq Listing Rule 5550(a)(2). ​ Under Nasdaq Listing Rule 5810(c)(3)(A), the Company has been granted a 180 -calendar day grace period, or until August 16, 2022, to regain compliance with the minimum bid price requirement. The continued listing standard will be met if the Company evidences a closing bid price of at least $1.00 per share for a minimum of 10 consecutive business days during the 180 -calendar day grace period. In order for Nasdaq to consider granting the Company additional time beyond August 16, 2022, the Company would be required, among other things, to meet the continued listing requirement for market value of publicly held shares as well as all other standards for initial listing on Nasdaq, with the exception of the minimum bid price requirement. If measured today, the Company would qualify for Nasdaq’s consideration of an extension because the Company currently has stockholders’ equity of at least $5.0 million. In the event the Company does not regain compliance with the $1.00 bid price requirement by August 16, 2022, eligibility for Nasdaq’s consideration of a second 180-day grace period would be determined on the Company’s compliance with the above referenced criteria on August 16, 2022. ​ The Company is diligently working to evidence compliance with the minimum bid price requirement for continued listing on Nasdaq; however, there can be no assurance that the Company will be able to regain compliance or that Nasdaq will grant the Company a further extension of time to regain compliance, if necessary. If the Company fails to regain compliance with the Nasdaq continued listing standards, its common stock will be subject to delisting from Nasdaq. ​ Liquidity and Going Concern The Company, since its inception, has incurred recurring operating losses and negative cash flows from operations and has an accumulated deficit of $237.5 million as of March 31, 2022. The Company expects to incur substantial losses and negative cash flows in future periods. Further, the Company’s future operations, including the operations of substantially owned Italian subsidiary, Napo EU S.p.A., which include the satisfaction of current obligations, are dependent on the success of the Company’s ongoing development and commercialization efforts, as well as securing additional financing and generating positive cash flows from operations. There is no assurance that the Company will have adequate cash balances to maintain its operations. ​ Although the Company plans to refinance its operations and cash flow needs through equity and/or debt financing, collaboration arrangements with either entities, license royalty agreements, as well as revenue from future product sales, the Company does not believe its current cash balances are sufficient to funds its operating plan through one year from the issuance of these unaudited condensed consolidated financial statements. The Company has an immediate need to raise cash. There can be no assurance that additional funding will be available to the Company on acceptable terms, or on a timely basis, if at all, or that the Company will generate sufficient cash from operations to adequately fund operating needs. If the Company is unable to obtain an adequate level of financing needed for the long-term development and commercialization of our products, the Company will need to curtail planned activities and reduce costs. Doing so will likely have an adverse effect on our ability to execute our business plan; accordingly, there is substantial doubt about the ability of the Company to continue in existence as a going concern. The accompanying unaudited condensed consolidated financial statements do not include any adjustments that might result from the outcome of these uncertainties. Reverse Stock Split On September 3, 2021, the Company filed the Certificate of Fifth Amendment to its Third Amended and Restated Certificate of Incorporation with the Secretary of State of Delaware to effect a 1

Summary of Significant Accounti

Summary of Significant Accounting Policies	3 Months Ended
	Mar. 31, 2022
Summary of Significant Accounting Policies
Summary of Significant Accounting Policies	2. Summary of Significant Accounting Policies Basis of Presentation The unaudited condensed consolidated financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America (“U.S. GAAP”) for interim financial information and on a basis consistent with the annual consolidated financial statements, and in the opinion of management, reflect all adjustments, which include only normal recurring adjustments, necessary for a fair presentation of the periods presented. These interim financial results are not necessarily indicative of the results to be expected for the year ending Annual Report on Form 10-K for the year ended December 31, 2021. The condensed consolidated balance sheet at December 31, 2021 has been derived from the audited consolidated financial statements at that date, but does not include all disclosures, including notes, required by U.S. GAAP for complete financial statements. There has been no material change to the Company's significant accounting policies during the three months ended March 31, 2022, as compared to the significant accounting policies described in Note 2 of the “Notes to Consolidated Financial Statements” in the Company's Annual Report on Form 10-K as of and for the year ended December 31, 2021 which was filed to SEC on March 11, 2022. Except as noted above, the unaudited condensed consolidated financial statements have been prepared on the same basis as the audited consolidated financial statements and, in the opinion of management, reflect all adjustments of a normal recurring nature considered necessary to present fairly the financial position as of March 31, 2022, results of operations for the three months ended March 31, 2022 and 2021, changes in convertible preferred stock and stockholders' equity for the three months ended March 31, 2022 and 2021, and cash flows for the three months ended March 31, 2022 and 2021. The interim results are not necessarily indicative of the results for any future interim periods or for the entire year. Principles of Consolidation The unaudited interim condensed consolidated financial statements have been prepared in accordance with U.S. GAAP and applicable rules and regulations of the Securities and Exchange Commission (“SEC”) and include the accounts of the Company and its wholly-owned subsidiary. All inter-company transactions and balances have been eliminated in consolidation. Use of Estimates The preparation of the unaudited condensed consolidated financial statements in conformity with U.S. GAAP requires the Company’s management to make judgments, assumptions and estimates that affect the amounts reported in its unaudited condensed consolidated financial statements and the accompanying notes. The accounting policies that reflect the Company’s more significant estimates and judgments and that the Company believes are the most critical to aid in fully understanding and evaluating its reported financial results are the valuation of stock options, valuation of hybrid instruments designated at fair value option (“FVO”), valuation of warrant liabilities, acquired in-process research and development (“IPR&D”), and useful lives assigned to long-lived assets; valuation adjustments for excess and obsolete inventory; allowance for doubtful accounts; deferred taxes and valuation allowances on deferred tax assets; evaluation and measurement of contingencies; and recognition of revenue, including estimates for product returns. Those estimates could change, and as a result, actual results could differ materially from those estimates. In March 2020, the World Health Organization declared the COVID-19 outbreak to be a pandemic. During the period ended March 31, 2022, the Company’s financial results were not significantly affected by the COVID-19 outbreak. The Company has considered all information available as of the date of issuance of these financial statements and the Company is not aware of any specific events or circumstances that would require an update to its estimates or judgments, or a revision to the carrying value of its assets or liabilities. These estimates may change as new events occur and additional information becomes available. The extent to which the COVID-19 outbreak affects the Company’s future financial results and operations will depend on future developments which are highly uncertain and cannot be predicted, including new information which may emerge concerning the severity of the outbreak, and current or future domestic and international actions to contain and treat it. For a discussion of risks of COVID-19 relating to the Company’s business, see “Item 1A. - Risk Factors- Risks Related to Our Business- The novel coronavirus global pandemic could adversely impact our business, including our supply chain, clinical trials and commercialization of Mytesi and Canalevia.” ​ ​ Cash The Company’s cash on deposit may exceed United States federally insured limits at certain times during the year. The Company maintain cash accounts with certain major financial institutions in the United States. The Company does not have cash equivalents as of March 31, 2022 and December 31, 2021. Accounts Receivable Accounts receivable is recorded net of allowances for discounts for prompt payment and credit losses. The Company estimates an allowance for credit losses by considering factors such as historical experience, credit quality, the age of the accounts receivable balances, and current economic conditions that may affect a customer’s ability to pay. The corresponding expense for the credit loss allowance is reflected in general and administrative expenses. The credit loss allowance was immaterial as of March 31, 2022 and December 31, 2021. Concentrations Cash is the financial instrument that potentially subjects the Company to a concentration of credit risk as cash is deposited with a bank and cash balances are generally in excess of Federal Deposit Insurance Corporation insurance limits. For the three months ended March 31, 2022 and 2021, substantially all of the Company’s revenue was derived from the sale of Mytesi. In looking at sales by the Company to distributors whose net revenue percentage of total net revenue was equal to or greater than 10%, for the three months ended March 31, 2022, the Company earned Mytesi revenue primarily from three pharmaceutical distributors located in the United States. For the three months ended March 31, 2021, the Company earned Mytesi revenue primarily from two pharmaceutical distributors in the United States. Revenue earned from each as a percentage of total revenue is as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ ​ March 31, ​ ​ (unaudited) ​ ​ 2022 2021 Customer 1 ​ — % 86 % Customer 2 ​ 34 % 10 % Customer 3 ​ 49 % — % Customer 4 ​ 10 % — % ​ The Company is subject to credit risk from its accounts receivable related to its sales. The Company generally does not perform evaluations of customers' financial condition and generally does not require collateral. As of ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, December 31, ​ 2022 ​ 2021 ​ ​ ​ (unaudited) ​ ​ ​ Customer 1 ​ — % 16 % Customer 2 ​ 34 % 37 % Customer 3 ​ 52 % 37 % ​ The Company is subject to concentration risk from its suppliers. The Company sources raw material used to produce the active pharmaceutical ingredient (“API”) in Mytesi from two suppliers and is dependent on a single third-party contract manufacturer for the supply of API in Mytesi and a single third-party contract manufacturer as well for the supply of finished products for commercialization. Other Risks and Uncertainties The Company’s future results of operations involve a number of risks and uncertainties. Factors that could affect the Company’s future operating results and cause actual results to vary materially from expectations include, but are not limited to, rapid technological change, obtaining second source suppliers, regulatory approval from the FDA or other regulatory authorities, the results of clinical trials and the achievement of milestones, market acceptance of the Company’s product candidates, competition from other products and larger companies, protection of proprietary technology, strategic relationships and dependence on key individuals. Fair Value The Company’s financial instruments include accounts receivable, accounts payable, accrued liabilities, warrant liabilities, equity-linked financial instruments and debt. The recorded carrying amounts of accounts receivable, accounts payable and accrued liabilities reflect their fair value due to their short-term nature. Other financial liabilities are initially recorded at fair value, and subsequently measured at either fair value or amortized cost using the effective interest method. See Note 4 for the fair value measurements. Fair Value Option ASC 825-10, Financial Instruments Inventory ​ Inventory is stated at the lower of cost or net realizable value. Cost is determined using the first-in, first-out method. Cost is initially recorded at the invoiced amount of raw materials or API, including the sum of qualified expenditures and charges in bringing the inventory to its existing condition and location. The Company calculates inventory valuation adjustments when conditions indicate that net realizable value is less than cost due to physical deterioration, usage, obsolescence, reductions in estimated future demand or reduction in selling price. Inventory write-downs are measured as the difference between the cost of inventory and net realizable value. Property and Equipment Land is stated at cost, reflecting the fair value of the property at July 31, 2017, the date of the Napo merger. Equipment is stated at cost, net of accumulated depreciation. Equipment begins to be depreciated when it is placed into service. Depreciation is calculated using the straight-line method over estimated useful lives ranging between 3 to 10 years. Expenditures for repairs and maintenance of assets are charged to expense as incurred. Costs of major additions and betterments are capitalized and depreciated on a straight-line basis over their estimated useful lives. Upon retirement or sale, the cost and related accumulated depreciation of assets disposed of are removed from the accounts and any resulting gain or loss is included in the unaudited condensed consolidated statements of operations. Long-lived Assets Indefinite-lived Intangible Assets Acquired IPR&D are intangible assets acquired in the July 2017 Napo merger. Under ASC 805, IPR&D are initially recognized at fair value and classified as indefinite-lived assets until the successful completion or abandonment of the associated research and development efforts. During the development period, these assets will not be amortized as charges to earnings; instead, these assets will be tested for impairment on an annual basis or more frequently if impairment indicators are identified. An impairment loss is measured based on the excess of the carrying amount over the asset’s fair value. The Company recorded no impairment in the three months ended March 31, 2022 and 2021. Leases The Company accounts for its leases in accordance with ASC 842, Leases At the inception of an arrangement, the Company determines whether the arrangement is or contains a lease based on the unique facts and circumstances present. Operating lease liabilities and their corresponding right-of-use assets are recorded based on the present value of lease payments over the expected lease term. Because the interest rate implicit in lease contracts is typically not readily determinable, the Company utilizes its incremental borrowing rate, which is the rate incurred to borrow on a collateralized basis over a similar term, an amount equal to the lease payments in a similar economic environment. Certain adjustments to the right-of-use asset may be required for items such as initial direct costs paid or incentives received. Operating Lease The Company entered into a sublease agreement with Peacock Construction Inc. (“Peacock”), a California corporation, for office space located in San Francisco, California. The term of the sublease began on August 31, 2020 and expired on May 31, 2021. The rent under the sublease is $15,000 per month beginning October 1, 2020, which includes operating expenses and taxes. On October 1, 2020, the Company transitioned its operations from its existing premises to the sublease premises, which the Company expects will serve as its principal administrative headquarters. The Company elected not to apply the recognition requirements to short-term leases, and instead recognize the lease payments in profit or loss on a straight-line basis over the lease term. As a result, there was no right-of-use asset and lease liability In April 2021, the Company entered into an office lease agreement with M & E, LLC, a California Limited Liability Company, to lease approximately 10,526 square feet of office space located in San Francisco, California, inclusive of office space currently covered under the sublease agreement with Peacock. The term of the lease began on September 1, 2021 and will expire on August 31, 2024, unless earlier terminated. The base rent under the lease will be $42,000 monthly for the first 12 months, $43,000 monthly for the next 12 months and $45,000 for the last twelve months. ​ In October 2021, the Company entered into an agreement with Copernico Centrale for the lease of office premises from November 1, 2021 to April 30, 2022, subject to automatic renewal for subsequent periods until terminated by either party. Base rent amounted to €10,000. If the contract is not terminated within 12 months, the lease amount will be increased in line with the index of relevant inflation at each annual expiration of the start date of the contract. On January 26, 2022, the lease agreement was amended whereby the term was extended by 20 months from May 1, 2022 to December 31, 2023. All other contract provisions remained the same. In December 2021, the Company entered into an agreement with Arval Service Lease Italia SpA for the lease of two separate vehicles for 48 months expiring on November 30, 2025. Total monthly lease payment amounted to €2,000 payable in advance. The Company elected to include both the lease and non-lease components as a single component and account for it as a lease. The Company also paid a total deposit of €19,000, exclusive of VAT. Early termination of the contracts requires the payment of specified amounts. In December 2021, the Company entered into the first amendment to the lease with M & E, LLC whereby the commencement date of one of the leased premises was modified to March 1, 2022. Accordingly, the expiration of the lease was extended to February 28, 2025. The base rent under the original agreement remained the same but will be due starting March 1, 2022. In addition, the rent for one of the leased premises being occupied by the Company will continue to be $21,000 until the new commencement date. In January 2022, the Company entered into an agreement with Copernico Centrale for the lease of office premises from March 1, 2022 to December 31, 2023, subject to automatic renewal for subsequent periods until terminated by either party. Base rent amounted to €4,000. A similar agreement was entered with the lessor for the lease of premises to be used as office space from November 1, 2022 to December 31, 2023, subject to automatic renewal for subsequent periods until terminated by either party. Base rent amounted to €3,817. If the contracts are not terminated within 12 months, the lease amounts will be increased in line with the index of relevant inflation at each annual expiration of the start date of the contract. Research and Development Expense Research and development expense consists of expenses incurred in performing research and development activities including related salaries, clinical trials and related drug and non-drug product costs, contract services and other outside service expenses. Research and development expense is charged to operating expense in the period incurred. Clinical Trial Accruals Clinical trial costs are a component of research and development expenses. The Company accrues and expenses clinical trial activities performed by third parties based upon actual work completed in accordance with agreements established with clinical research organizations and clinical sites. The Company determines the costs to be recorded based upon validation with the external service providers as to the progress or stage of completion of trials or services and the agreed-upon fee to be paid for such services. Revenue Recognition The Company recognizes revenue in accordance with ASC 606, Revenue from Contracts with Customers The Company’s policy typically permits returns if the product is damaged, defective, or otherwise cannot be used when received by the customer if the product has expired. Returns are accepted for product that will expire within three months or that have expired up to one year after their expiration dates. Estimates for expected returns of expired products are based primarily on an ongoing analysis of our historical return patterns. The Company recognizes revenue in accordance with the core principle of ASC 606 or when there is a transfer of control of promised goods or services to customers in an amount that reflects the consideration that the Company expects to be entitled to in exchange for those goods or services. The Company recognizes the incremental costs of obtaining a contract as an expense when incurred if the amortization period of the asset that the Company otherwise would have recognized is one year or less. The Company does not adjust the amount of consideration for the effects of a significant financing component if, at contract inception, the expected period between the transfer of promised goods or services and customer payment is one year or less. The Company has elected to treat shipping and handling activities as fulfillment costs. Additionally, the Company elected to record revenue net of sales and other similar taxes. Contracts – Cardinal Health Effective January 16, 2019, the Company engaged Cardinal Health as its exclusive third-party logistics distribution agent for commercial sales of the Company’s Mytesi product and to perform certain other services which include, without limitation, storage, distribution, returns, customer support, financial support, Electronic Data Interchange (“EDI”) and system access support (the “Exclusive Distribution Agreement”). On September 3, 2021, the Company ended its engagement with Cardinal Health as its exclusive title model customer for commercial sales and fully implemented its limited distribution Specialty Pharmacy model. Cardinal Health continues to provide third-party logistics services for Mytesi. The Company's Neonorm and botanical extract products are primarily sold to distributors, who then sell the products to the end customers. Since 2014, the Company has entered into several distribution agreements with established distributors such as Animart, Vedco, VPI, RJ Matthews, Covetrus, and Stockmen Supply to distribute the Company's products in the United States, Japan, and China. The distribution agreements and the related purchase order together meet the contract existence criteria under ASC 606-10-25-1. The Company sells directly to its customers without the use of an agent. Performance obligations For animal products sold by the Company, the single performance obligation identified above is the Company’s promise to transfer the Company’s animal products to distributors based on specified payment and shipping terms in the arrangement. Product warranties are assurance-type warranties that do not represent a performance obligation. For the Company’s human product, Mytesi, the single performance obligation identified above is the Company’s promise to transfer Mytesi to Cardinal Health, based on specified payment and shipping terms as outlined in the Exclusive Distribution Agreement. Transaction price For contracts with Cardinal Health, the transaction price is the amount of consideration to which the Company expects to collect in exchange for transferring the promised goods or services. The transaction price of Mytesi and Neonorm is the Wholesaler Acquisition Cost (“WAC”), net of discounts, returns, and price adjustments. Allocate transaction price For contracts with Cardinal Health, the entire transaction price is allocated to the single performance obligation contained in each contract. Revenue recognition For contracts with Cardinal Health, a single performance obligation is satisfied at a point in time, upon the free on board (“FOB”) terms of each contract when control, including title and all risks, has transferred to the customer. Disaggregation of Product Revenue Human Sales of Mytesi are recognized as revenue at a point in time when the products are delivered to the wholesaler. Net revenue from the sale of Mytesi were $438,000 and $1.2 million for the three months ended March 31, 2022 and 2021, respectively. Animal The Company recognized Neonorm revenues of $20,000 and $33,000 for the three months ended March 31, 2022 and 2021, respectively. Revenues are recognized at a point in time upon shipment, which is when title and control is transferred to the buyer. Sales of Neonorm Calf and Foal to distributors are made under agreements that may provide distributor price adjustments and rights of return under certain circumstances. ​ Contracts – Specialty Pharmacies Effective October 1, 2020, the Company engaged a private company as its third-party logistics distribution agent for commercial sales of the Company’s Mytesi product. Under the Specialty Product Distribution Agreement, the Company shall supply the products to the private company’s specialty pharmacies, through a designated wholesaler, in such amounts as may be ordered. There is no minimum purchase or inventory requirement. The specialty pharmacies were authorized distributors of record for all National Drug Codes (“NDCs”) of Mytesi. Effective April 20, 2021, the Company engaged another private company as an authorized specialty pharmacy provider of Mytesi. Under the Specialty Pharmacy Distribution and Services Agreement, the private company shall sell and dispense the Mytesi directly ordered from the Company at the agreed price to patients within the territories identified in the agreement. The two contracts with the two specialty pharmacies were combined into one portfolio of contract as they share similar characteristics. Performance obligations The single performance obligation is the Company’s promise to transfer Mytesi to specialty pharmacies, based on specified payment and shipping terms as outlined in the agreements. Transaction price The transaction price is the amount of consideration to which the Company expects to collect in exchange for transferring the promised goods or services. The transaction price of Mytesi is the WAC, net of estimated discounts, returns, and price adjustments. Allocate transaction price The entire transaction price is allocated to the single performance obligation contained in each contract. Revenue recognition The single performance obligation is satisfied at a point in time, upon the free on board (“FOB”) terms of each contract when control, including title and all risks, has transferred to the customer. Disaggregation of Product Revenue Sales of Mytesi are recognized as revenue at a point in time when products are delivered to the specialty pharmacies. Net revenue from the sale of Mytesi to the specialty pharmacies were $2.2 million and $479,000 for the three months ended March 31, 2022 and 2021, respectively. Collaboration Revenue Revenue recognition for collaboration agreements requires significant judgment. The Company’s assessments and estimates are based on contractual terms, historical experience and general industry practice. Revisions in these values or estimations have the effect of increasing or decreasing collaboration revenue in the period of revision. On September 24, 2018, the Company entered into a Distribution, License and Supply Agreement (“License Agreement”) with Knight Therapeutics ("Knight"). The License Agreement has a term of 15 years (with automatic renewals) and provides Knight with an exclusive right to commercialize current and future Jaguar human health products (including crofelemer, Lechlemer, and any product containing a proanthocyanidin or with an anti-secretory mechanism) in Canada and Israel. Knight forfeited its right of first negotiation for expansion to Latin America. Under the License Agreement, Knight is responsible for applying for and obtaining necessary regulatory approvals in the territory of Canada and Israel, as well as marketing, sales and distribution of the licensed products. Knight will pay a transfer price for all licensed products, and upon achievement of certain regulatory and sales milestones, the Company may receive payments from Knight in an aggregate amount of up to approximately $18 million payable throughout the initial 15-year term of the agreement. The Company did not have any license revenues for the three months ended March 31, 2022 and 2021. Modifications to Liability-classified Instruments In accounting for debt modifications and exchange transactions, it is the Company’s policy to first determine whether it qualifies as a troubled debt restructuring (“TDR”) pursuant to the guidance provided in ASC 470-60. A debt modification or exchange transaction that is not within the scope of the ASC 470-60 is accounted for under ASC 470-50 to determine if the transaction is a mere modification or an extinguishment. ​ In the three months ended March 31, 2022 and 2021, the Company amended the terms of its October 2020 Purchase Agreement and Exchange Note 2, respectively (see Note 8). ​ Modifications to Equity-classified Instruments ​ In accounting for modifications of equity-classified warrants, it is the Company’s policy to determine the impact by analogy to the share-based compensation guidance of ASC 718, Compensation - Stock Compensation ​ The Company did not modify any equity-classified warrants in the three months ended March 31, 2022 and 2021. In accounting for amendments to preferred stock, it is the Company’s policy to measure the impact by analogy to ASC 470-50 in determining if such an amendment is an extinguishment or a modification. If the amendment results in an extinguishment, the Company follows the SEC staff guidance in ASC 260-10-S99-2 and ASC 470-20. If the amendment results in a modification, the Company follows the model in either ASC 718 or ASC 470-50, depending on the nature of the amendment. ​ The Company did not modify any preferred stock in the three months ended March 31, 2022 and 2021. Stock-based Compensation The Company uses the grant date fair market value of its common stock to determine the grant date fair value of options granted to employees, non-employees and directors. The Company measures and recognizes compensation expense for all stock options and restricted stock units (“RSUs”) granted to its employees and directors based on the estimated fair value of the award on the grant date. The Company uses the Black-Scholes valuation model to estimate the fair value of stock option awards. The fair value is recognized as expense, net of estimated forfeitures, over the requisite service period, which is generally the vesting period of the respective award, on a straight-line basis. The Company believes that the fair value of stock options granted to non-employees is more reliably measured than the fair value of the services received. The determination of the grant date fair value of options using an option pricing model is affected by the Company’s estimated Common Stock fair value and requires management to make a number of assumptions including the expected life of the option, the volatility of the underlying stock, the risk-free interest rate and expected dividends. The Company estimates the fair value of stock options using the Black-Scholes option valuation model. The fair value of employee stock options is being amortized on a straight-line basis over the requisite service period of the awards. The fair market value of common stock is based on the closing price of the Company’s common stock as reported on the date of the grant. Income Taxes The Company uses the asset and liability method of accounting for income taxes. Under this method, deferred tax assets and liabilities are determined based on the differences between the financial reporting and the tax bases of assets and liabilities and are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. A valuation allowance is provided when it is more likely than not that some portion or all of a deferred tax asset will not be realized. The Company has adopted the provisions of ASC 740, Income Taxes Related to Uncertain Tax Positions . Under these principals, tax positions are evaluated in a two-step process. The Company first determines whether it is more-likely-than-not that a tax position will be sustained upon examination. If a tax position meets the more-likely-than-not recognition threshold, it is then measured to determine the amount of benefit to be recognized in the financial statements. The tax position is measured as the largest amount of benefit that has a greater than 50 percent likelihood of being realized upon ultimate settlement. Foreign Currency Remeasurement and Translation The functional currency of Napo Therapeutics is Euro. The Company follows ASC 830, Foreign Currency Matters measured using the functional currency of that foreign operation. Exchange gains or losses from remeasuring transactions and monetary accounts in a currency other than the functional currency are included in current earnings. For certain subsidiaries, translation adjustments result from the process of translating the functional currency of subsidiary financial statements into the U.S. Dollar reporting currency. These translation adjustments are reported separately and accumulated in the consolidated balance sheets as a component of accumulated other comprehensive loss. Comprehensive Loss For the three months ended March 31, 2022, the comprehensive loss was equal to the net loss; therefore, a separate statement of comprehensive loss is not included in the accompanying unaudited condensed consolidated financial statements. For the three months ended March 31, 2021, the amount of other comprehensive loss was only de minimis; hence, a separate statement of comprehensive loss was not included in the accompanying unaudited condensed consolidated financial statements. Basic and Diluted Net Loss Per Common Share Basic net loss per common share is computed by dividing net loss attributable to common stockholders for the year by the weighted-average number of common shares outstanding during the year. Diluted net loss per share is computed by dividing the net loss attributable to common stockholders for the year by the weighted-average number of common shares, including potential dilutive shares of common stock assuming the dilutive effect of potential dilutive securities. For periods in which the Company reports a net loss, diluted net loss per common share is the same as basic net loss per common share, because the impact of the potential dilutive shares of common stock would be anti-dilutive to the calculation of net loss per common share. Diluted net loss per common share is the same as basic net loss per common share for the three months ended March 31, 2022 and 2021. Recent Accounting Pronouncements Recently Adopted Accounting Pronouncements In August 2020, the FASB issued ASU 2020-06, Debt – Debt with Conversion and Other Options (Subtopic 470-20) and Derivatives and Hedging – Contracts in Entity’s Own Equity (Subtopic 815-40): Accounting for Convertible Instruments and Contracts in an Entity’s Own Equity ​ In May 2021, the FASB issued ASU 2021-04, Issuer’s Accounting for Certain Modification or Exchanges of Freestanding Equity-Classified Written Call Options In December 2019, the FASB issued ASU 2019-12, Income Taxes (Topic 740): Simplifying the Accounting for Income Taxes ​ ​ ​ Recently Issued Accounting Pronouncements Not Yet Adopted ​ In June 2016, the FASB issued ASU 2016-13, Financial Instruments – Credit Losses (Topic 326): Measurement of Credit Losses on Financial Instruments. Reclassification of Prior Period Presentation

Napo Therapeutics Subsidiary

Napo Therapeutics Subsidiary	3 Months Ended
	Mar. 31, 2022
Napo Therapeutics Subsidiary
Napo Therapeutics Subsidiary	3. Napo Therapeutics Subsidiary

Fair Value Measurements

Fair Value Measurements	3 Months Ended
	Mar. 31, 2022
Fair Value Measurements
Fair Value Measurements	4. Fair Value Measurements ASC 820, Fair Value Measurements ● Level 1 – Observable inputs such as quoted prices (unadjusted) for identical instruments in active markets. ​ ● Level 2 – Observable inputs such as quoted prices for similar instruments in active markets, quoted prices for identical or similar instruments in markets that are not active, or model-derived valuations whose significant inputs are observable. ​ ● Level 3 – Unobservable inputs that reflect the reporting entity’s own assumptions. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ The following tables set forth the fair value of the Company’s financial instruments that were measured at fair value on a recurring basis as of March 31, 2022 and December 31, 2021. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, 2022 (in thousands) Level 1 Level 2 Level 3 Total Warrant liability ​ $ — ​ $ — ​ $ 1 ​ $ 1 Streeterville note ​ ​ — ​ ​ — ​ ​ 8,051 ​ ​ 8,051 Total fair value ​ $ — ​ $ — ​ $ 8,052 ​ $ 8,052 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, 2021 (in thousands) Level 1 Level 2 Level 3 Total Warrant liability ​ $ — ​ $ — ​ $ 1 ​ $ 1 Streeterville note ​ $ — ​ $ — ​ $ 7,117 ​ $ 7,117 Total fair value ​ $ — ​ $ — ​ $ 7,117 ​ $ 7,117 ​ The change in the estimated fair value of Level 3 liabilities is summarized below: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ ​ March 31, 2022 (in thousands) ​ Warrant liability Streeterville note Beginning fair value of Level 3 liability $ 1 $ 7,818 Additions ​ ​ — ​ ​ — Exercises ​ ​ — ​ ​ — Change in fair value — ​ ​ 233 Ending fair value of Level 3 liability $ 1 $ 8,051 ​ Warrant Liability ​ The warrants associated with the Level 3 warrant liability November 2016 Series A Warrants and the October 2018 Underwriter The November 2016 Series A Warrants The Series A warrant valuation of zero at March 31, 2022 was computed using the Black-Scholes-Merton pricing model using a stock price of $0.71, a strike price of $2,363 per share, an expected term of 0.16 years, volatility of 108% and a risk-free discount rate of 0.34%. The Series A warrant valuation of zero at December 31, 2021 was computed using the Black-Scholes-Merton pricing model using a stock price of $1.04, a strike price of $2,363 per share, an expected term of 0.41 years, volatility of 89% and a risk-free discount rate of 0.19%. The change in fair value of the warrants for the three months ended March 31, 2022 was zero. The October 2018 Underwriter Warrants The October 2018 Underwriter Warrants valuation of zero at March 31, 2022 was computed using the Black-Scholes-Merton pricing model using a stock price of $0.71, a strike price of $158 per share, an expected term of 1.51 years, volatility of 175% and a risk-free discount rate of 1.96%. The October 2018 Underwriter Warrants valuation of $1,000 at December 31, 2021 was computed using the Black-Scholes-Merton pricing model using a stock price of $1.04, a strike price of $158 per share, an expected term of 1.75 years, volatility of 180% and a risk-free discount rate of 0.65%. The change in the fair value of the warrants for the three months ended March 31, 2022 was zero. ​ The May 2020 Series 3 Warrants There were no outstanding May 2020 Series 3 Warrants as of March 31, 2022 and December 31, 2021. For the year ended December 31, 2021, certain holders of the Series 3 Warrants agreed to exercise total of 206,915 shares for a 1-for-1 exchange of common shares in an Alternate Cashless Exercise. The aggregate fair value of the common stock issued upon the exercise of the Series 3 Warrants as of the exercise date was $1.8 million. Streeterville Note The fair value of the Streeterville Note at January 13, 2021, date of issuance and as of March 31, 2022 amounting to $6.0 million and $8.1 million, respectively, were based on the weighted average discounted expected future cash flows representing the terms of the note, discounting them to their present value equivalents. This was classified as Level 3 fair values in the fair value hierarchy due to the use of unobservable inputs, including the Company’s own credit risk. ​ The Company determined and performed the valuations of the Streeterville Note with the assistance of an independent valuation service provider. On a quarterly basis, the Company considers the main Level 3 inputs used derived as follows: ​ ● Discount rate for the Streeterville note which was determined using a comparison of various effective yields on bonds as of the valuation date ​ ● Market indications for vouchers, which affect the Return Bonus from the sale of Tropical Disease Priority Review Voucher (“TDPRV”) ​ ● Weighted probability of cash outflows which was estimated based on the entity's knowledge of the business and how the current economic environment is likely to impact the timing of the cash outflows, attributed to the different repayment features of the note ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ The following table summarizes the quantitative information about the significant unobservable inputs used in Level 3 fair value measurement: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Range of Inputs ​ ​ ​ ​ (probability-weighted average) ​ Relationship of unobservable inputs Unobservable Inputs ​ 2022 ​ 2021 ​ to fair value Risk Adjusted Discount Rate ​ 7.29%-21.82% (21.82%) ​ 6.56% - 22% ​ If discount rate is adjusted to total of additional 100 basis points (bps), fair value would have decreased by $367,000. Sales Proceeds: Amount of comparable TDPRV ​ $67.5 million to $350 million ($100 million) ​ $67.5 million to $350.0 million ($100.0 million) ​ If expected cash flows by management considered the lowest amount of market indications for vouchers, FV would have decreased by $1.2 million. Range of Probability for Timing of Cash Flows: ​ 0.39%-41.88% ​ 0.39% - 39.78% ​ If expected cash flows by management considered the scenario with the least amount of indicated value, FV would have decreased by $236,000. ​ Fair Value Option ​ Beginning January 1, 2021, the Company elected to apply the FVO accounting to selected financial instruments to align the measurement attributes of those instruments under U.S. GAAP and to simplify the accounting model applied to those financial instruments. The Company elected to apply FVO accounting to the entire class of hybrid instruments, including structured notes, of which there are assessed embedded derivatives that would be eligible for bifurcation. Changes in the fair value of FVO assets and liabilities as well as the mark-to-market adjustment on the entire class of hybrid instruments, including derivatives and the net realized gains or losses on these instruments are reported in the change in fair value of financial instruments in the unaudited condensed consolidated statements of operations. As of March 31, 2022, the Company did not note any fair value movement on FVO liabilities attributable to any instrument-specific credit risk, which is recorded in other comprehensive income (loss). Hybrid Instruments The Company elected to apply FVO accounting to all of the hybrid instruments issued, including structured notes. The valuation of the hybrid instruments is predominantly driven by the derivative features embedded within the instruments. The Company determined and performed the valuations of the hybrid instruments with the assistance of an independent valuation service provider. The valuation methodology utilized is consistent with the income approach for estimating the fair value of the interest-bearing portion of the instrument and the related derivatives. Cash flows of the hybrid instruments in their entirety, including the embedded derivatives, are discounted at an appropriate rate for the applicable duration of the instrument. Interest on the interest-bearing portion of the instrument that is held to maturity is aggregated as gain (loss) on instruments designated at fair value and related derivatives in the change in fair value of financial instruments and hybrid instruments designated at FVO of the unaudited condensed consolidated statements of operations. The following table summarizes the fair value and unpaid principal balance for items the Company accounts for under FVO: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ (in thousands) ​ Fair value ​ Unpaid Principal Balance ​ Fair Value Over (Under) Unpaid Principal Balance At March 31, 2022 ​ ​ ​ ​ ​ ​ ​ ​ ​ Hybrid Instrument: ​ ​ ​ ​ ​ ​ ​ ​ ​ Streeterville note ​ $ 8,051 ​ $ 6,221 ​ $ 1,830 ​

Balance Sheet Components

Balance Sheet Components	3 Months Ended
	Mar. 31, 2022
Balance Sheet Components
Balance Sheet Components	​ ​ 5. Balance Sheet Components Inventory Inventory at March 31, 2022 and December 31, 2021 consisted of the following: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31, ​ 2022 2021 (in thousands) ​ (unaudited) ​ ​ ​ Raw Material ​ $ 1,562 ​ $ 1,248 Work in Process ​ ​ 2,422 ​ ​ 2,760 Finished Goods ​ ​ 895 ​ ​ 892 Inventory ​ $ 4,879 ​ $ 4,900 ​ Property and Equipment, net Property and equipment at March 31, 2022 and December 31, 2021 consisted of the following: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31, ​ 2022 2021 (in thousands) ​ (unaudited) ​ ​ ​ Land ​ $ 396 ​ $ 396 Lab equipment ​ ​ 478 ​ ​ 403 Clinical equipment ​ 65 ​ 65 Software ​ ​ 63 ​ ​ 63 Furnitures and fixtures ​ ​ 14 ​ ​ 14 Computers and peripherals ​ ​ 7 ​ ​ 7 Total property and equipment at cost ​ 1,023 ​ 948 Accumulated depreciation ​ (423) ​ (298) Property and equipment, net ​ $ 600 ​ $ 650 ​ Depreciation and amortization expense was $8,000 and $9,000 for the three months ended ​ Intangible Assets, net Intangible assets at March 31, 2022 and December 31, 2021 consisted of the following: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31, ​ 2022 2021 (in thousands) ​ (unaudited) ​ ​ ​ Developed technology ​ $ 25,000 ​ $ 25,000 Accumulated developed technology amortization ​ (7,778) ​ (7,361) Developed technology, net ​ 17,222 ​ 17,639 In-process research and development ​ ​ 4,800 ​ ​ 4,800 In process research and development, net ​ 4,800 ​ 4,800 Trademarks ​ 300 ​ 300 Accumulated trademark amortization ​ (93) ​ (88) Trademarks, net ​ 207 ​ 212 Total intangible assets, net ​ $ 22,229 ​ $ 22,651 ​ Amortization expense of finite-lived intangible assets was $418,000 for the three months ended March 31, 2022 and 2021. The following table summarized the Company’s estimated future amortization expense of intangible assets with finite lives as of March 31, 2022: ​ ​ ​ ​ (in thousands) Amounts Remainder of 2022 ​ $ 1,265 2023 ​ ​ 1,687 2024 ​ ​ 1,687 2025 ​ ​ 1,687 2026 ​ ​ 1,687 Thereafter ​ ​ 9,416 ​ ​ $ 17,429 ​

Related Party Transactions

Related Party Transactions	3 Months Ended
	Mar. 31, 2022
Related Party Transactions
Related Party Transactions	6. Related Party Transactions Management Services Agreement In March 2018, concurrent with the issuance of the Company’s Series A Convertible Preferred Stock to Sagard Capital Partners, L.P. (“Sagard Capital”), the Company entered into a Management Services Agreement with Sagard Capital. Under the agreement, Sagard Capital was to provide consulting and management advisory service to the Company from March 2018 through March 2021. These services include assistance with strategic planning regarding the Company’s commercial strategy, research and due diligence regarding human resource activities, and strategic advice in financial matters. In consideration for such services, the Company paid Sagard Capital an annual fee of $450,000, with total fees over the term of the agreement not to exceed $1.4 million. On September 1, 2020, in concurrence with other transactions by and between the Company, Chicago Venture Partners, L.P. (“CVP” or “Chicago Venture Partners”) and its affiliates, and Sagard Capital, the Company and Iliad Research and Trading, L.P. (“Iliad”), a Utah limited partnership affiliated with CVP, agreed to issue 2,289,474 shares of the Company’s Common Stock to Sagard Capital pursuant to the Stock Plan Agreement for termination of the Management Services Agreement in lieu of payment of $1.1 million in accrued consulting and management fees. For the three months ended March 31, 2022 and 2021, total fees incurred were zero and $225,000, respectively. As of March 31, 2022 and December 31, 2021, the Company had a balance of zero due to Sagard Capital. BOD Cash Compensation ​

Commitments and Contingencies

Commitments and Contingencies	3 Months Ended
	Mar. 31, 2022
Commitments and Contingencies
Commitments and Contingencies	7. Commitments and Contingencies Commitments Leases On August 28, 2018, the Company entered into an office lease extension agreement for approximately 6,311 square feet of office space in San Francisco, CA. The term of the lease began on September 1, 2018 and expired on March 31, 2021. An existing shareholder provided a standby letter of credit in the amount of $475,000 to the lessor as collateral for the full performance by the Company of all of its obligations under the lease. In consideration of the Letter of Credit, the Company issued the shareholder a five-year warrant (see Note 9) to purchase 9,580 shares of the Company’s voting common stock. On August 31, 2020, the Company entered into an office sublease of approximately 5,263 square feet of office space in San Francisco. The term of the sublease expired on May 31, 2021. The rent sublease is $15,000 per month beginning on October 1, 2020, which includes operating expenses and taxes. The Company recognizes rent expense on a straight-line basis over the non-cancelable lease period. Rent expense, included in general and administrative expenses in the unaudited condensed consolidated statements of operations, was zero and $60,000 for the three months ended March 31, 2022, respectively. As of March 31, 2022, there were no remaining commitment under the lease. On April 6, 2021, the Company entered into an office lease agreement of approximately 10,526 square feet of office space in San Francisco, inclusive of office space covered under the previous sublease agreement. The term of the lease began on September 1, 2021 and will expire on August 31, 2024, unless terminated earlier. The lease had an early occupancy provision which entitled the Company to use a portion of the leased premises on June 1, 2021, free of rent obligation. In addition, the Company has the option to extend the lease for one three-year period after the expiration date. This option was not included as part of the lease term as the Company was not reasonably certain to exercise it, hence the lease term only includes the noncancellable period of three years plus the period of early occupancy. The base rent under the lease were $42,000 monthly for the first 12 months, $43,000 monthly for the next 12 months and $45,000 for the last twelve months. The lease agreement only contained one lease component, that is, the lease of the office space. Non-lease components such as payment of building operating costs and share in real property taxes were accounted for separately and were not considered as part of the total lease payments. The lease was classified as an operating lease. On October 7, 2021, the Company entered into an agreement for the lease of office premises from November 1, 2021 to April 30, 2022, subject to automatic renewal for subsequent periods until terminated by either party. Base rent amounted to €10,000. If the contract is not terminated within 12 months, the lease amount will be increased in line with the index of relevant inflation at each annual expiration of the start date of the contract. The lessor has the right to decline the renewal of the contract. Upon the happening of certain specified events, the lessor may immediately withdraw from the contract. The Company is required leave the occupied spaces immediately in the same condition in which they were found in the event of contract termination or expiry. The Company paid deposit of €20,000 to the lessor. On January 26, 2022, the lease agreement was amended whereby the term was extended by 20 months from May 1, 2022 to December 31, 2023. All other contract provisions remained the same. On December 22, 2021, the Company entered into an agreement for the lease of two separate vehicles for 48 months expiring on November 30, 2025. Total monthly lease payment amounted to €2,000 payable in advance. The Company elected to include both the lease and non-lease components as a single component and account for it as a lease. The Company also paid a total deposit of €19,000, exclusive of VAT. Early termination of the contracts requires the payment of specified amounts. On December 24, 2021, the Company entered into the first amendment of the lease of office space in San Francisco. The expiration of the lease was extended to February 28, 2025 due to the change in the commencement date of one of the leased premises to March 1, 2022. The base rent under the lease amendment remained the same but will only be due starting March 1, 2022. The rent in one of the leased premises currently being occupied by the Company was and will still be $21,000 until the new commencement date. The lease amendment constituted a lease modification where the Company remeasured the original lease liability using a discount rate determined at the effective date of the modification and the amount of remeasurement of the lease liability was recognized as an adjustment to the corresponding right-of-use asset without affecting profit or loss. On January 25, 2022, the Company entered into an agreement for the lease of office premises from March 1, 2022 to December 31, 2023, subject to automatic renewal for subsequent periods until terminated by either party. Base rent amounted to €4,000. A similar agreement was entered with the lessor for the lease of premises to be used as office space from November 1, 2022 to December 31, 2023, subject to automatic renewal for subsequent periods until terminated by either party. Base rent amounted to €3,817. If the contracts are not terminated within 12 months, the lease amounts will be increased in line with the index of relevant inflation at each annual expiration of the start date of the contract. The lessor has the right to decline the renewal of the contracts. Upon the happening of certain specified events, the lessor may immediately withdraw from the contracts. The Company is required leave the occupied spaces immediately in the same conditions in which they were found in the event of contract termination or expiry. The Company paid deposit of €9,000 to the Lessor. The table below provided additional details of the office space lease presented in the condensed consolidated balance sheet as of March 31, 2022 and December 31, 2021: ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31 ​ 2022 ​ 2021 (in thousands) (unaudited) ​ ​ ​ Operating lease - right-of-use asset $ 1,157 ​ $ 1,084 ​ ​ ​ ​ ​ ​ Operating lease liability, current ​ 299 ​ ​ 240 Operating lease liability, net of current portion ​ 921 ​ ​ 919 Total $ 1,220 ​ $ 1,159 ​ ​ ​ ​ ​ ​ Weighted-average remaining life (years) ​ 2.96 ​ ​ 3.21 Weighted-average discount rate ​ 21.80% ​ ​ 21.10% ​ Lease cost included in the general and administrative expenses in the unaudited condensed consolidated statements of operations for the three months ended March 31, 2022 and 2021 was approximately $104,000 and zero, respectively. For the year three months ended March 31, 2022 and 2021, cash paid for operating lease liabilities recognized under operating cash flows amounted to $105,260 and zero respectively. ​ The following table summarizes the undiscounted cash payment obligations for the operating lease liability as of March 31, 2022: ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31 ​ 2022 ​ 2021 (in thousands) (unaudited) ​ ​ ​ 2022 ​ 403 ​ ​ 463 2023 ​ 542 ​ ​ 518 2024 ​ 557 ​ ​ 534 2025 ​ 107 ​ ​ 89 Total undiscounted operating lease payments ​ 1,609 ​ ​ 1,604 Imputed interest expenses ​ (389) ​ ​ (445) Total operating lease liability ​ 1,220 ​ ​ 1,159 Less: Operating lease liability, current ​ 299 ​ ​ 240 Operating lease liability, net of current portion $ 921 ​ $ 919 ​ On October 10, 2021, the Company also entered into a short-term office lease in Milan, Italy. The term of the lease began on November 1, 2021 and will expire on April 30, 2022, subject to automatic renewal equal to the present term until terminated by mutual agreement. The Company recognizes rent expense on a straight-line basis over the non-cancellable lease period. Rent expense, included in general and administrative expenses in the unaudited condensed consolidated statements of operations, was $42,000 and zero for the three months ended March 31, 2022 and 2021, respectively. ​ ​ Purchase Commitment ​ On September 3, 2020, the Company entered into a manufacturing and supply agreement (the “Agreement”) with Glenmark Life Sciences Limited (“Glenmark”), pursuant to which Glenmark will continue to serve as the Company’s manufacturer of crofelemer for use in Mytesi, the Company’s human prescription drug product approved by the U.S. Food and Drug Administration, and for other crofelemer-based products manufactured by the Company or its affiliates for human or animal use. The term of the Agreement is approximately 2.5 years (i.e., until March 31, 2023) and may be extended for successive two-year renewal terms upon mutual agreement between the parties thereto. Pursuant to the terms of the Agreement, Glenmark will supply crofelemer to the Company. The Agreement contains provisions regarding the rights and responsibilities of the parties with respect to manufacturing specifications, forecasting and ordering, delivery arrangements, payment terms, confidentiality and indemnification, as well as other customary provisions. The Agreement includes a commitment for the purchase from Glenmark of a minimum quantity of 300 kilograms of crofelemer per year, pro-rated for partial years, where the Company may be obligated to pay any shortfall. Either party may terminate the Agreement for any reason with 12 months prior written notice to the other party. In addition, either party may terminate the Agreement upon written notice as a result of a material breach of the Agreement that remains uncured for a period of 90 days. If the Company terminates the Agreement as a result of a material breach caused by Glenmark, the Company will not be obligated to pay for any minimum quantity shortfall. ​ Master Services Agreement (“MSA”) On June 24, 2019, the Company entered into an MSA for clinical research organization services (the “2019 MSA”) and a service order under such 2019 MSA with Integrium, LLC (“Integrium”). The service order supports the Company’s study to evaluate the effect of Mytesi on gastrointestinal microbiome in people living with HIV. The 2019 MSA will terminate upon the satisfactory performance of all services to be provided thereunder unless earlier terminated by the parties. As of March 31, 2022, there are no remaining commitment under the 2019 MSA. On October 5, 2020, the Company entered into another MSA for clinical research organization services (the “2020 MSA”) and a service order under such 2020 MSA with Integrium. The service order covers the Company’s planned upcoming pivotal Phase 3 clinical trial for cancer-therapy related diarrhea. As consideration for its services, the Company will pay Integrium a total amount of up to approximately $12.4 million that will be paid over the term of the engagement and based on the achievement of certain milestones. The 2020 MSA will terminate upon the satisfactory performance of all services to be provided thereunder unless earlier terminated by the parties . For the three months ended March 31, 2022 and 2021, the Company paid Integrium $275,911 and $770,911 , respectively. Asset Transfer and Transition Commitment On September 25, 2017, the Company entered into the Termination, Asset Transfer and Transition Agreement dated September 22, 2017 with Glenmark. As a result of the agreement, the Company now controls commercial rights for Mytesi for all indications, territories and patient populations globally, and also holds commercial rights to the existing regulatory approvals for crofelemer in Brazil, Ecuador, Zimbabwe and Botswana. In exchange, the Company agrees to pay Glenmark 25% of any payment it receives from a third party to whom the Company grants a license or sublicense or with whom the Company partners in respect of, or sells or otherwise transfers any of the transferred assets, subject to certain exclusions, until Glenmark has received a total of $7.0 million. For the three months ended March 31, 2022 and 2021, the Company paid Glenmark $559,000 million and zero, respectively. Revenue Sharing Commitment Update On December 14, 2017, the Company announced its entry into a collaboration agreement with Seed Mena Businessmen Services LLC (“SEED”) for Equilevia™, the Company's non-prescription, personalized, premium product for total gut health in equine athletes. According to the terms of the Agreement, the Company will pay SEED 15% of total revenue generated from any clients or partners introduced to the Company by SEED in the form of fees, commissions, payments or revenue received by the Company or its business associates or partners, and the agreed-upon revenue percentage increases to 20% after the first million dollars of revenue. In return, SEED will provide the Company access to its existing United Arab Emirates (“UAE”) network and contacts and assist the Company with any legal or financial requirements. The agreement became effective on December 13, 2017 and will continue indefinitely until terminated by either party pursuant to the terms of the Agreement. No payments have been made to date. Legal Proceedings On July 20, 2017, a putative class action complaint was filed in the United States District Court, Northern District of California, Civil Action No. 3:17 cv 04102, by Tony Plant (the “Plaintiff”). The Company answered the complaint on August 2, 2019; the answer denied the material allegations of the second amended complaint. Following the completion of document discovery, the parties engaged in a mediation that resulted in an agreement in principle to settle the litigation on a class-wide basis for $2.6 million. On May 27, 2021, the court gave the final approval to the proposed settlement and the entire settlement consideration will be provided by the Company’s director and officer liability insurance carrier. Under the loss recovery model in ASC 450 and in reference to ASC 410, the ultimate net income effect of the recognized loss and the insurance proceeds directly related to the recognized loss is zero . Settlement of Underwriter Fee ​ In August 2018, the Company entered into an agreement with an underwriter pursuant to which the underwriter would aid the Company in identifying certain financing transactions, in exchange for a percentage fee of any such financing and warrants. In the first quarter of 2020, the Company and the underwriter agreed on a final settlement for the underwriter services comprised of a cash payment, warrants and common stock. The cash payment amount totalled $387,000 , of which $202,000 had been paid in 2019, and $185,000 was paid in 2020. The total warrant issuance payment consisted of the Company issuing 365 equity-classified warrants to the underwriter in 2018 and, in 2020, issuing an additional 33,593 equity-classified warrants (see Note 9) to the underwriter to purchase shares of common stock at an exercise price of $7.50 per share. The common stock issuance payment consisted of the Company issuing 33,333 shares of the Company’s common stock to the underwriter with a value of $45,000 in 2020. The Company classified the cash payments, warrant and common stock issuance payments as issuance costs in the unaudited condensed consolidated statements of changes in convertible preferred stock and stockholders’ equity. Severance Agreements In June 2020, the Company entered into certain agreements relating to the payment of severance and other benefits to executive officers of the Company, the severance agreements provide for compensation and benefits if the executive officer is subject to (a) a termination of employment by the Company without cause or (b) a good reason termination, within three months following a change in control. Contingencies From time to time, the Company maybe a party to various legal actions, both inside and outside the U.S., arising in the ordinary course of its business or otherwise. The Company accrues amounts, to the extent they can be reasonably estimated, that the Company believes will result in a probable loss (including, among other things, probable settlement value), to adequately address any liabilities related to legal proceedings and other loss contingencies. A loss or a range of loss is disclosed when it is reasonably possible that a material loss will incur and can be estimated, or when it is reasonably possible that the amount of a loss, when material, will exceed the recorded provision. The Company did not have any material accruals for any currently active legal action in its consolidated balance sheets as of March 31, 2022, as the Company could not predict the ultimate outcome of these matters, or reasonably estimate the potential exposure.

Debt

Debt	3 Months Ended
	Mar. 31, 2022
Debt
Debt	​ ​ 8. Debt Notes payable at March 31, 2022 and December 31, 2021 consisted of the following: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31, ​ ​ 2022 2021 (in thousands) ​ (unaudited) ​ ​ ​ Royalty Interest ​ $ 34,151 ​ $ 37,000 Streeterville Note ​ ​ 8,051 ​ ​ 7,818 Insurance Financing ​ ​ — ​ ​ 335 Tempesta Note ​ ​ 300 ​ ​ 350 ​ ​ ​ 42,502 ​ 45,503 Less: unamortized discount and debt issuance costs ​ (10,829) (17,297) Note payable, net of discount ​ $ 31,673 $ 28,206 Notes payable - non-current, net ​ $ 24,783 ​ $ 25,022 Notes payable - current, net ​ $ 6,890 ​ $ 3,184 ​ Future maturities of the notes payable not designated at FVO as of March 31, 2022 are as follows: ​ ​ ​ ​ (in thousands) ​ Amounts As of March 31, ​ ​ ​ 2023 ​ $ 6,890 2024 ​ ​ 12,837 2025 ​ ​ 5,016 2026 ​ ​ 8,100 2027 ​ ​ 1,608 ​ ​ ​ 34,451 Less: unamortized discount and debt issuance costs ​ ​ (14,798) Total ​ $ 19,653 ​ Future maturities are based on contractual minimum payments. Timing of maturities may fluctuate based on future revenue. ​ Sale of Future Royalty Interest October 2020 Purchase Agreement On October 8, 2020, the Company entered into another royalty interest purchase agreement (the “October 2020 Purchase Agreement”) with Iliad, pursuant to which the Company sold to Iliad a royalty interest entitling Iliad to receive $12.0 million of future royalties on sales of Mytesi and certain up-front license fees and milestone payments from licensees and/or distributors (the “Royalty Repayment Amount”) for an aggregate purchase price of $6.0 million. Until such time as the Royalty Repayment Amount has been paid in full, the Company will pay Iliad 10% of the Company’s net sales on included products and 10% of worldwide revenues related to upfront licensing fees and milestone payments from licensees and/or distributors, but specifically excluding licensing fees and/or milestone payments that are reimbursements of clinical trial expenses (the “Royalty Payments”). Beginning on the six-month anniversary of the delivery of the October 2020 Purchase Agreement to the Company (the “Purchase Price Date”) and continuing until the 12-month anniversary of the Purchase Price Date, the monthly Royalty Payment shall be the greater of (a) $250,000, and (b) the actual Royalty Payment amount Iliad is entitled to for such month. Beginning on the 12-month anniversary of the Purchase Price Date and continuing until 18-month anniversary of the Purchase Price Date, the monthly Royalty Payment shall be the greater of (a) $400,000 and (b) the actual Royalty Payment amount Iliad is entitled to for such month. Beginning on the 18-month anniversary of the Purchase Price Date and continuing until 24-month anniversary of the Purchase Price Date, the monthly Royalty Payment shall be the greater of (a) $600,000 and (b) the actual Royalty Payment amount Iliad is entitled to for such month. Beginning on the 24-month anniversary of the Purchase Price Date and continuing until the Royalty Repayment Amount has been paid in full, the monthly Royalty Payment shall be the greater of (a) $750,000, and (b) the actual Royalty Payment amount Iliad is entitled to for such month. The Royalty Interest amount of $12.0 million was classified as debt, net of a $6.0 million discount, at initial recognition. Under ASC 470-10-35-3, royalty payments to Iliad will be amortized under the interest method per ASC 835-30. Because there is no set interest rate, and because the royalty payments are variable, the discount rate is variable. After each royalty payment, the Company will use a prospective method to determine a new discount rate based on the revised estimate of remaining cash flows. The new rate is the discount rate that equates the present value of the revised estimate of remaining cash flows with the carrying amount of the debt, and it will be used to recognize interest expense for the remaining periods. At issuance, based on projected cash outflows from future revenue streams, the discount rate was 34.51% . Pursuant to the October 2020 Purchase Agreement, if the weekly volume weighted average price (“VWAP”) of the Company’s common stock is not equal or greater than the minimum VWAP of $0.9105 at least twice during each calendar month during the six-month period beginning on November 1, 2020, then the Royalty Repayment Amount will be automatically increased by $6.0 million at the end of such six-month period. During the observation period starting November 1, 2020, the Company’s weekly VWAP failed to reach the minimum VWAP of $0.9105 and on November 13, 2020, the Company concluded that the contingent clause has been met, warranting an additional $6.0 million Royalty Repayment Amount, to be added to the outstanding balance commencing on May 10, 2021 for the purpose of cash interest calculation. The change in the Royalty Repayment Amount was accounted for as a debt modification and resulted in a new discount rate of 45.42% . ​ On April 13, 2021, the Company entered into an exchange agreement with Iliad, pursuant to which the parties agreed to partition $3.0 million from the original outstanding balance of the royalty interest. The parties further agreed to exchange the partitioned royalty for 588,235 shares of the Company’s common stock. The exchange consisted of Iliad surrendering the partitioned royalty in exchange for the exchange shares. The exchange agreement was accounted for as a modification and resulted in a new discount rate of 77.09% . As of March 31, 2022, the forecasted future revenues changed which resulted to a new discount rate of 74.59% . ​ On February 22, 2022, the Company entered into an exchange agreement with Iliad, pursuant to which the parties agreed to partition $2.4 million from the outstanding balance of the royalty interest. The parties further agreed to exchange the partitioned royalty for 1,733,750 shares of the Company’s common stock. The exchange consisted of Iliad surrendering the partitioned royalty in exchange for the exchange shares. ​ On March 2, 2022, the Company entered into an exchange agreement with Iliad, pursuant to which the parties agreed to partition $1.1 million from the outstanding balance of the royalty interest. The parties further agreed to exchange the partitioned royalty for 2,425,000 shares of the Company’s common stock. The exchange consisted of Iliad surrendering the partitioned royalty in exchange for the exchange shares. ​ On March 4, 2022, the Company entered into an exchange agreement with Iliad, pursuant to which the parties agreed to partition $800,000 from the outstanding balance of the royalty interest. The parties further agreed to exchange the partitioned royalty for 2,000,000 shares of the Company’s common stock. The exchange consisted of Iliad surrendering the partitioned royalty in exchange for the exchange shares. ​ On March 9, 2022, the Company entered into an exchange agreement with Iliad, pursuant to which the parties agreed to partition $700,000 from the outstanding balance of the royalty interest. The parties further agreed to exchange the partitioned royalty for 1,850,000 shares of the Company’s common stock. The exchange consisted of Iliad surrendering the partitioned royalty in exchange for the exchange shares. ​ Because the period between the first and last exchanges occurred within a 12-month period and each was individually assessed as a modification, the debt terms that existed prior to the February 13 exchange was used in the application of the 10% test on the cumulative assessment performed. The exchanges were cumulatively accounted for as an extinguishment and resulted to a loss of $2.8 million. As of March 31, 2022, the forecasted future revenues changed which resulted to a new discount rate of 45.05% . ​ Interest expense for the three months ended March 31, 2022 and 2021 was $3.1 million and $1.9 million, respectively. As of March 31, 2022 and December 31, 2021, the carrying value of the debt is $8.3 million and $6.3 million, respectively. ​ December 2020 Purchase Agreement ​ On December 22, 2020, the Company entered into a royalty interest purchase agreement (the “December 2020 Purchase Agreement”) with Irving Park Capital, LLC (“Irving”), a company affiliated with CVP, pursuant to which the Company sold to Irving a royalty interest entitling Irving to receive $12.0 million of future royalties on sales of Mytesi and certain up-front license fees and milestone payments from licensees and/or distributors (the “Royalty Repayment Amount”) for an aggregate purchase price of $6.0 million. ​ Until such time as the Royalty Repayment Amount has been paid in full, the Company will pay Irving 10% of the Company’s Net Sales on Included Products and 10% of worldwide revenues related to upfront licensing fees and milestone payments from licensees and/or distributors, but specifically excluding licensing fees and/or milestone payments that are reimbursements of clinical trial expenses (the “Royalty Payments”). Beginning on the payment start date of March 8, 2024 and continuing until the 12-month anniversary of the Purchase Price Date, the monthly Royalty Payment shall be the greater of (a) $750,000, and (b) the actual Royalty Payment amount Irving is entitled to for such month. ​ The Royalty Interest amount of $12.0 million is classified as debt, net of a $6.0 million discount, at initial recognition. Under ASC 470-10-35-3, royalty payments to Irving will be amortized under the interest method per ASC 835-30. Because there is no set interest rate, and because the royalty payments are variable, the discount rate is variable. After each royalty payment, the Company will use a prospective method to determine a new discount rate based on the revised estimate of remaining cash flows. The new rate is the discount rate that equates the present value of the revised estimate of remaining cash flows with the carrying amount of the debt, and it will be used to recognize interest expense for the remaining periods. At issuance, based on projected cash outflows from future revenue streams, the discount rate was 23.70% . As of March 31, 2022, the forecasted future revenues changed which resulted to a new discount rate of 23.28% . ​ Interest expense for the three months ended March 31, 2022 and 2021 was $784,000 and $664,000 , respectively. As of March 31, 2022 and December 31, 2021, the carrying value of the debt is $8.0 million and $6.3 million, respectively. ​ March 2021 Purchase Agreement ​ On March 8, 2021, the Company entered into a purchase agreement (the “March 2021 Purchase Agreement”) with Streeterville Capital, LLC (“Streeterville”), a company affiliated with CVP, pursuant to which the Company sold a royalty interest entitling Streeterville to $10.0 million and any interest, fees, and charges as royalty repayment amount for an aggregate purchase price of $5.0 million. Interest will accrue on the royalty repayment amount at a rate of 5% per annum, compounding quarterly, and will increase to 10% per annum, compounding quarterly on the 12-month anniversary of the closing date. ​ The Company will be obligated to make minimum royalty payments on a monthly basis beginning at the earlier of (a) 36 months following the closing date or (b) 30 days following the satisfaction of all existing royalties to Streeterville, and its affiliates namely Iliad and Irving, but not earlier than 18 months following the closing date in an amount equal to the greater of (i) $250,000 beginning on the royalty payment start date and continuing until either the royalty repayment amount has been paid in full or the 6-month anniversary of the royalty payment start date, $400,000 beginning on the 6-month anniversary of the royalty payment start date and continuing until either the royalty repayment amount has been paid in full or the 12-month anniversary of the royalty payment start date, $600,000 beginning on the 12-month anniversary of the royalty payment start date and continuing until either the royalty repayment amount has been paid in full or the 18-month anniversary of the royalty payment start date, $750,000 beginning on the 18-month anniversary of the royalty payment start date and continuing until the royalty repayment amount has been paid in full, and (ii) 10% of the Company’s net sales on included products, 10% of worldwide revenues related to upfront licensing fees and milestone payments from licensees and/or distributors but specifically excluding licensing fees and/or milestone payments that are reimbursements of clinical trial expenses or associated with the license of Included Products from the Company to Napo EU, including but not limited to the upfront fee payable by Napo EU to Napo for included products and Crofelemer for other indications; and 50% of royalties collected from licenses of the included products to third parties. ​ The Royalty Interest amount of $10.0 million is classified as debt, net of a $5.0 million discount, at initial recognition. Under ASC 470-10-35-3, royalty payments to Streeterville will be amortized under the interest method per ASC 835-30. Because there is no set interest rate, and because the royalty payments are variable, the discount rate is variable. After each royalty payment, the Company will use a prospective method to determine a new discount rate based on the revised estimate of remaining cash flows. The new rate is the discount rate that equates the present value of the revised estimate of remaining cash flows with the carrying amount of the debt, and it will be used to recognize interest expense for the remaining periods. At issuance, based on projected cash outflows from future revenue streams, the discount rate was 19.36% . As of March 31, 2022, the forecasted future revenues changed which resulted to a new discount of 19.14% . ​ Interest expense for the three months ended March 31, 2022 and 2021 was $416,000 and $62,000 , respectively. As of March 31, 2022 and December 31, 2022, the carrying value of the debt is $6.1 million and $5.8 million, respectively. ​ Streeterville Note ​ On January 13, 2021, the Company issued a secured promissory note to Streeterville in the original principal amount of $6.2 million for an aggregate purchase price of $6.0 million. The Company will use the proceeds to fund development of the Company’s NP-300 (lechlemer) drug product candidate for the indication of the symptomatic relief of diarrhea from cholera and general corporate purposes, including the Company’s product pipeline activities. The note is due after four years and bears interest at 3.25% per annum. Interest on the note is payable annually in advance by adding the interest charge for each upcoming year to the outstanding balance on the date each such interest charge is accrued. The Company also paid $25,000 to cover legal fees, accounting costs, due diligence, monitoring and other transaction costs incurred in connection with the issuance of the note. The first year of prepaid interest and the transaction expenses are included in the original principal amount. ​ At any time following the occurrence of a trial failure which refers to any of the following: (i) the Company abandons the clinical trial with lechlemer for an indication for the symptomatic relief of infectious diarrhea for cholera; (ii) the Company fails to start the Phase 1 clinical trial of lechlemer for the symptomatic relief of infectious diarrhea for cholera by July 1, 2022; or (iii) the Company fails to meet all primary endpoints in the pivotal trials of Lechlemer for the symptomatic relief if infectious diarrhea for cholera with statistical significance, Streeterville may elect to increase the outstanding balance as of the date of the trial failure by 25% without acceleration (the “Trial Failure Effect”). If Streeterville elects to apply the Trial Failure Effect, it reserves the right to declare the outstanding balance immediately due and payable at any time. As of March 31, 2022, no trial failure occurred. ​ Streeterville is entitled to a maximum of 18% and a minimum of 1% of the gross proceeds received by the Company from the sale of TDPRV (the “Return Bonus”). The Return Bonus percentage is reduced pro rata based on the percentage of the original principal balance of the note that has been repaid as of the date of the sale of the TDPRV. Even if the note has been paid in full at the time of the sale of the TDPRV, the Company is still obliged to pay Streeterville a Return Bonus of 1%. If Streeterville applies the Trial Failure Effect, the Return Bonus will automatically be reduced to 1%. If the TDPRV has not been sold as of the day immediately preceding the maturity date of the note, the Return Bonus percentage will be fixed as of such date. As of March 31, 2022, the Company has not sold any TDPRV. ​ Beginning on the earlier of (a) 6 months after January 2021, and (b) initiation of human trials with lechlemer for symptomatic relief of infectious diarrhea for cholera, the Company may pay all or any portion of the outstanding balance earlier than it is due. In the event the Company elects to prepay all or any portion of the outstanding balance, it shall pay to Streeterville 112.5% of the portion of the outstanding balance the Company elects to prepay. The Company may not prepay the note without the Streeterville’s consent on the date the last patient is enrolled in a pivotal trial. ​ After Streeterville becomes aware of the occurrence of any default, Streeterville may accelerate the note, with the outstanding balance becoming immediately due and payable in cash at the Mandatory Default Amount (i.e., the outstanding balance following the application of the Default Effect). Streeterville reserves the right to declare the outstanding balance immediately due and payable at any time following the default. Default Effect means multiplying the outstanding balance as of the date of default by 5% or 15% for each occurrence of default, capped at an aggregate of 25%, and then adding the resulting product to the outstanding balance. The percentage to be used depends on whether the default is viewed as minor or major as defined in the agreement. Furthermore, interest accrues on the outstanding balance beginning on the date of default at an interest rate equal to the lesser of 18% per annum or the maximum rate permitted under applicable law. As of March 31, 2022, no default has occurred. ​ In connection with the note issuance, the Company has entered into a security agreement with Streeterville, pursuant to which Streeterville will receive a first priority security interest in all existing and future lechlemer technology, and any TDPRV and the sale proceeds therefrom that may be granted to the Company by the FDA in connection with the development of lechlemer for the cholera indication. The Company also agreed, with certain exceptions, not to grant any lien on any of the collateral securing the note and not to grant any license under any of the intellectual property relating to such collateral. The grant of security interest has become effective upon the receipt of the Salix Waiver on April 6, 2021 in observance to the requirement of the settlement agreement previously entered by the Company with Salix Pharmaceuticals, Inc. ​ The Company irrevocably elected to initially and subsequently apply the FVO accounting to the entire note. The fair value at transaction date was equal to the cash proceeds received of $6.0 million. The transaction expense of $25,000 was recognized in profit and loss as incurred. The Company used the valuation report from an independent valuation service provided to measure the reporting date fair value of the note. At March 31, 2022 and December 31, 2021, the fair value was determined to be $8.1 million and $7.8 million, respectively. For the three months ended March 31, 2022, the net increase in the fair value of $233,000 was recorded as loss included in the change in fair value of financial instruments and hybrid instrument designated at FVO in the unaudited condensed consolidated statements of operations. ​ Insurance Financing ​ March 2021 First Insurance Financing ​ In March 2021, the Company entered into a premium finance agreement for $98,000 with First Insurance Funding (“First Insurance”) representing the unpaid balance of the total premiums, taxes, and fees of $115,000 with an annual interest rate of 4.6%. The total finance charge was $2,000. Payment of principal and interest is due in equal monthly installments over ten months. The Company granted and assigned First Insurance a first priority lien on and security interest in the financed policies and any additional premium required under the financed policies. Interest expense for the three months ended March 31, 2022 and 2021 was zero and $207, respectively. The financing balance was zero and $10,000 at March 31, 2022 and December 31, 2021, respectively. ​ May 2021 First Insurance Financing ​ In May 2021, the Company entered into another premium finance agreement for $1.1 million with First Insurance representing the unpaid balance of the total premiums, taxes, and fees of $1.4 million with an annual interest rate of 4.15%. The total finance charge was $21,000. Payment of principal and interest is due in equal monthly installments over ten months. Interest expense for the three months ended March 31, 2022 was $6,000. The financing balance was zero and $326,000 at March 31, 2022 and December 31, 2021, respectively. ​ 2019 Tempesta Note ​ In October 2019, the Company entered into a License Termination and Settlement Agreement with Dr. Michael Tempesta, pursuant to which certain royalty payment disputes between the Company and Tempesta were settled. Per the terms of the Agreement, Tempesta received $50,000 in cash, an unsecured promissory note issued by the Company in the aggregate principal amount of $550,000 and 13,333 shares of the Company’s common stock in exchange for the cessation of all royalty payments by the Company to Dr. Tempesta under the License Agreements. The $550,000 promissory note bears interest at the rate of 2.5% per annum and matures on March 1, 2025. The promissory note provides for the Company to make semi-annual payments equal to $50,000 plus accrued interest beginning on March 1, 2020 until the Note is paid in full. Interest expense for the three months ended March 31, 2022 and 2021 was $2,000 and $3,000, respectively. At March 31, 2022 and December 31, 2021, the net carrying value of the note was $300,000 and $350,000, respectively. ​ Oasis Secured Borrowing ​ The Purchase Agreement ​ In May 2020, the Company, entered into a one-year Accounts Receivable Purchase Agreement (the “Purchase Agreement”) with Oasis Capital (“Oasis”). ​ In December 2020, the Company received cash proceeds of $1.6 million from Oasis (the “Tranche #6 Secured Note”). Oasis purchased accounts receivable with a carrying value of $2.2 million, or gross accounts receivable of $3.8 million net of chargebacks and discounts of $1.6 million. ​ In February 2021, the Company made its final required payment to Oasis under Tranche #6 Secured Note, with total payments equaling the $1.8 million Threshold amount plus the transaction fee, and the Tranche #6 Secured Note was extinguished. ​ Exchange Note 2 ​ In May 2019, CVP and the Company agreed to exchange two Napo convertible notes for a single CVP Note (“Exchange Note 1”). Per agreement, in consideration of the extension of the maturity date of Exchange Note 1 from December 31, 2019 to December 31, 2020, the Company issued a note (“Exchange Note 2”) with a principal balance of $2.3 million. The maturity date of Exchange Note 2 is December 31, 2020, with an interest rate of 10%. Between September 2020 and November 2020, the Company and CVP entered into a series of note exchange agreements pursuant to which the Company made prepayments of principal and related accrued interest of an aggregate amount of $5.0 million, in lieu of making cash payments to CVP on Exchange Note 1, by issuing a total of 6,740,573 shares of the Company’s common stock to CVP. The series of exchanges was accounted for as an extinguishment which resulted in a loss of $560,000. As of December 31, 2020, the carrying value of Exchange Note 1 was zero. ​ In September 2020, the Company and CVP also entered into a global amendment agreement, pursuant to which the maturity date of Exchange Note 2 is extended to December 31, 2021. In consideration of CVP’s grant of extension, together with the related fees and other accommodation set forth, principal debt was increased by 5% of the outstanding balance of Exchange Note 2, which was $2.6 million as of the global amendment date. The global amendment requires redemption of Series D Perpetual Preferred Stock prior to payment of principal of Exchange Note 2. The Company determined the incremental value of cash flows amounting to $228,000 with the assistance of an independent valuation service provider, based on weighted probability assumptions of various settlement conditions and penalties stipulated in the contract therein. The global amendment agreement was accounted for as a modification; hence a new effective rate was determined at the date of modification that equated the revised cash flows to the carrying amount of the note. Pursuant to the global amendment agreement, the Company issued 842,500 shares of Series D Perpetual Preferred Stock. The Series D Perpetual Preferred shares were redeemable upon the option or discretion of the Company. The Series D Perpetual Preferred stockholders were entitled to receive 8% cumulative stock dividends, to be payable in arrears on a monthly basis for 24 be payable through the Company’s issuance of Series D Perpetual Preferred share by delivering to each record holder the calculated number of payment-in-kind (“PIK”) dividend shares. The Series D Perpetual Preferred shares were classified as liability and were measured at fair value using the income approach, which considered the weighted probability of discounted cash flows at various scenarios of redemption and perpetual holding of the shares. The Company determined the fair value of $6.4 million at contract inception date with the assistance of an independent valuation service provider to be based on discounted cash flows representing the settlement value of the shares and cumulative dividends issued using an effective borrowing rate of 12% to 15% adjusted for counterparty and a maturity date of March 31, 2022. In consideration of the global amendment agreement, no principal payment shall be made to the Exchange Note 2 until the redemption of Series D Perpetual Preferred shares. Due to the restrictive nature of the timing of cash outflows in response to the settlement of the Exchange Note 2, Series D Perpetual Preferred shares were implicitly deemed to be mandatorily redeemable upon the ultimate settlement of the outstanding balance of Exchange Note 2. The shares were redeemable at $8.00 per share on or before December 31, 2024, the date in which contractual cash outflows of the Exchange Note 2 require the entire settlement or redemption of the Series D Perpetual Preferred shares. In December 2020, the Company entered into a series of exchange agreements with a stockholder pursuant to which the Company agreed to issue a total of 5,296,623 shares of common stock in exchange for redeeming 859,348 shares of Series D Perpetual Preferred Stock. The series of exchanges was accounted for as an extinguishment which resulted to a loss amounting to $1.3 million. This is included in loss on extinguishment of debt and conversion of Series D Perpetual Preferred Stock on the statement of operations as of December 31, 2020. As of March 31, 2022 and December 31, 2021, there were no Series D Perpetual Preferred shares outstanding. ​ In December 2020, the Company and CVP entered into a note exchange agreement to which the Company made a prepayment of principal amounting to $1.0 million, in lieu of making cash payments to CVP on Exchange Note 2, by issuing 416,666 shares of the Company’s common stock to CVP on December 31, 2020. The exchange agreement was accounted for as a modification. ​ In January 2021, the Company and CVP entered into another note exchange agreement to which the Company made a prepayment of the remaining outstanding balance of Exchange Note 2 amounting to $1.8 million, in lieu of making cash payments to CVP by issuing 471,202 shares of the Company’s common stock to CVP on January 4, 2021. The exchange was accounted for as debt extinguishment which resulted in a loss of $753,000. ​ As of March 31, 2022 and December 31, 2021, the carrying value of Exchange Note 2, net of discount, was zero.

Warrants

Warrants	3 Months Ended
	Mar. 31, 2022
Warrants
Warrants	8. Warrants The following table summarizes information about warrants outstanding and exercisable into shares of the Company’s common stock as of March 31, 2022 and December 31, 2021: ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31 ​ ​ 2022 ​ 2021 Warrants outstanding, beginning balance ​ 563,451 ​ 2,401,818 Issuances ​ — ​ 168,750 Exercises ​ — ​ (2,007,117) Expirations and cancelations ​ — ​ - Warrants outstanding, ending balance ​ 563,451 ​ 563,451 ​ October 2018 Underwriter Warrants In October 2018, the Company issued warrants to various service providers to purchase an aggregate of 5,713 shares of common stock at an exercise price of $157.50 per common share. The warrants were classified as liabilities pursuant to ASC 815-40 as there was potential cash settlement. April 2020 Underwriter Warrants In April 2020, in consideration of the settlement of a dispute regarding underwriting fees (see Note 7), the Company issued warrants to purchase 33,592 shares of common stock at an exercise price of $7.50 per common share. The warrants were equity classified in the unaudited condensed consolidated statements of changes in convertible preferred stock and stockholders’ equity. March 2019 Ladenburg Warrants In March 2019, the Company issued warrants to purchase an aggregate of 253 shares of common stock at an exercise price of $52.50 per common share. The warrants were equity classified in the unaudited condensed consolidated statements of changes in convertible preferred stock and stockholders’ equity. March 2019 LOC Warrant In March 2019, the Company issued a warrant to purchase warrant shares equal to a fixed principal amount divided by a variable exercise price. On July 23, 2019, upon the exercise price of the warrants becoming fixed, the warrants became exercisable into 15,250 shares of the Company’s common stock and were reclassified to additional paid-in-capital. 2019 Bridge Note Warrants Between March 18, 2019 and June 26, 2019, the Company issued twenty-one warrants to purchase warrant shares equal to a fixed principal amount divided by a variable exercise price. On July 23, 2019, upon the exercise price of the warrants becoming fixed, the warrants became exercisable into 927,083 shares of the Company’s common stock and were reclassified to additional paid-in-capital with a strike price of $6.00 per share. A total of 190,622 2019 Bridge Notes Warrants were outstanding as of March 31, 2022 and December 31, 2021with a strike price of $1.47. July 2019 Series 1 Warrants In July 2019, the Company entered into an underwriting agreement, relating to a public offering, which was comprised of (1) 962,166 Class A Units, priced at $6.00 per unit, with each unit consisting of (i) one share of the Company’s voting common stock, (ii) one Series 1 warrant to purchase one share of common stock, and (iii) one Series 2 warrant to purchase one share of common stock, and (2) 10,787 Class B Units, priced at a price of $1,000 per unit, with each unit consisting of (i) one share of Series B convertible preferred stock, convertible into 166 shares of common stock, (ii) 166 Series 1 Warrants and (iii) 166 Series 2 Warrants. The Series 1 Warrants had an exercise price of $6.00 and expire on the earlier of (a) 5 years from the date of issuance and (b) 30 calendar days following the public announcement of Positive Interim Results related to the diarrhea results from the HALT-D investigator-initiated trial, if and only if certain trading benchmarks are achieved during such 30-calendar day period. In the offering, the Company sold (i) 962,166 Class A Units, which included Series 1 warrants to purchase 962,166 shares of the Company’s common stock and (ii) 10,787 Class B Units, which included Series 1 warrants to purchase 1,797,833 shares of the Company’s common stock. In total, 2,760,000 Series 1 warrants were issued, with a strike price of $6.00. Upon issuance, the Series 1 warrants were classified in additional paid-in-capital. During the three months ended March 31, 2021, an aggregate of 464,058 shares of common stock were issued upon the exercise of the Series 1 Warrants for total proceeds of $682,000. A total of 145,396 Series 1 Warrants were outstanding as of March 31, 2022 and December 31, 2021. July 2019 Series 2 Warrants The Series 2 Warrants have an exercise price of $6.00 and expire on the first date on the earlier of (a) 5 years from the date of issuance and (b) 30 calendar days following the public announcement by the Company that a pivotal phase 3 clinical trial using crofelemer (Mytesi, or the same or similar product with a different name) for the treatment of cancer therapy-related diarrhea in humans has met its primary endpoint in accordance with the protocol, if and only if certain trading benchmarks are achieved during such 30 calendar day period. In addition, each Series 2 Warrant has an embedded call option that allows the Company to redeem any unexercised warrants if certain contingencies are met. In the July 2019 offering, the Company sold (i) 962,166 Class A Units, which included Series 2 warrants to purchase 962,166 shares of the Company’s common stock and (ii) 10,787 Class B Units, which included Series 2 warrants to purchase 1,797,833 shares of the Company’s common stock. In total, 2,760,000 Series 2 warrants were issued, with a strike price of $6.00, and an expected term of 5.0 years. Upon issuance, the Series 2 Warrants were classified in additional paid-in-capital. During the three months ended March 31, 2021, an aggregate of 1,427,175 shares of common stock were issued upon the exercise of the Series 2 Warrants for total proceeds of $700,000. A total of 133,730 Series 2 Warrants were outstanding as of March 31, 2022 and December 31, 2021. April 2021 ELOC Warrants On April 7, 2021, in consideration for Oasis Capital’s entry into the March 2020 ELOC amendment, the Company issued Oasis Capital a common stock purchase warrant (“ELOC Warrants”) exercisable for 33,333 shares of common stock with an exercise price per share equal to $5.61 on the date of the amendment. The warrants were valued at $172,000 using the Black-Scholes option pricing model as follows: exercise price of $5.61 per share, stock price of $5.61 per share, expected life of five years, volatility of 156%, and a risk-free rate of 0.87%. The warrants were classified in additional paid-in-capital.

Preferred Stock

Preferred Stock	3 Months Ended
	Mar. 31, 2022
Preferred Stock.
Preferred Stock	10. Preferred Stock At March 31, 2022 and December 31, 2021, preferred stock consisted of the following: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Liquidation ( in thousands, except share and per share data) ​ Shares Issued and Carrying ​ Preference Series ​ Authorized ​ Outstanding ​ Value ​ per Share B-2 ​ ​ 10,165 ​ ​ — ​ $ — ​ $ — C ​ ​ 1,011,000 ​ ​ — ​ ​ — ​ ​ 8.00 Total ​ ​ 1,021,165 ​ ​ — ​ $ — ​ ​ ​ ​ Series B-2 Convertible Preferred Stock In December 2019, the Company entered into an exchange agreement with Oasis Capital, pursuant to which Oasis Capital gave up (i) its remaining unexercised Prepaid Forward contracts exercisable for 412,074 shares of the Company’s common stock and (ii) 231,709 common shares held as an investment by Oasis Capital, in exchange for 10,165 shares of the Company’s newly authorized Series B-2 Convertible Preferred Stock. Holders of the Series B-2 Convertible Preferred Stock are entitled to receive dividends on shares of Series B-2 Convertible Preferred Stock equal (on an as-if-converted-to-Common-Stock basis) to and in the same form as dividends actually paid on shares of the Common Stock when, as and if such dividends are paid on shares of the Common Stock. No other dividends shall be paid on shares of the Series B-2 Convertible Preferred Stock. The shares of Series B-2 Convertible Preferred Stock have no voting rights. However, as long as any shares of Series B-2 Convertible Preferred Stock remain outstanding, the Company shall not, without the affirmative vote of holders of a majority of the then outstanding shares of Series B-2 Convertible Preferred Stock, (a) alter or change adversely the powers, preferences or rights given to the Series B-2 Convertible Preferred Stock or alter or amend the Series B-2 Certificate of Designation or (b) enter into any agreement with respect to any of the foregoing. Upon any liquidation, dissolution or winding-up of the Company, whether voluntary or involuntary, the Holders of the Series B-2 Convertible Preferred Stock were entitled to receive out of the assets, whether capital or surplus, of the Company the same amount that a holder of common stock would receive if the Series B-2 Convertible Preferred Stock were fully converted to Common Stock which amounts shall be paid pari passu with all holders of common stock. Each share of Series B-2 Convertible Preferred Stock is convertible at any time at the holder’s option into 63 shares of Common Stock, as determined by dividing the $153.90 stated value of each Series B-2 Convertible Preferred Share by the $2.43 conversion price ( $153.90 divided by $2.43 = 63 conversion ratio), and which conversion ratio is subject to adjustment for stock splits, stock dividends, distributions, subdivisions and combinations and other similar transactions as specified in the Series B-2 Certificate of Designation. The Series B-2 Convertible Preferred Stock was classified in stockholders' equity in accordance with authoritative guidance. In January 2020, a holder of the Series B-2 Convertible Preferred Stock converted 2,631 preferred shares into 166,630 shares of common stock. In October 2020, the Company entered into an exchange agreement with Oasis Capital pursuant to which the Company agreed to issue 166,728 shares of common stock in exchange for 975 shares of the Series B-2 Convertible Preferred Stock. The exchange agreement was accounted for as a modification. In December 2020, an investor converted the remaining 6,559 Series B-2 Convertible Preferred Stock into a total of 415,403 shares of the Company’s common stock. As of March 31, 2022 and December 31, 2021, there were no Series B-2 Convertible Preferred shares outstanding. Series C Perpetual Preferred Stock In September 2020, the Company entered into an exchange agreement with Iliad to issue 842,500 shares of the Company's Series C Perpetual Preferred Stock at $0.0001 par value per share, for a non-cash exchange of equity instruments. The exchange agreement was contemporaneously entered with the issuance of Series D Perpetual Preferred shares, in exchange of remaining Series A Convertible Preferred shares totaling 5,524,926 shares, and accreted value of $11.2 million as of the exchange date. An amendment agreement of the Exchange Note 2 was also entered into, with issuance value of $2.3 million and carrying value of $2.6 million as of the exchange date, to extend maturity from December 31, 2020 to December 31, 2021, in consideration of 5% increase in the outstanding balance. ​ Holders of the Series C Perpetual Preferred Stock were not entitled to voting rights. However, as long as any Series C Perpetual Preferred share is outstanding, the Company is restricted to alter, change, or enter into an agreement to alter or change adversely the powers, preferences, or rights given to the shareholders. ​ In the event of any voluntary or involuntary liquidation, dissolution or winding up of the Company or deemed liquidation event, the holders of Series C Perpetual Preferred shares then outstanding would be entitled to be paid in cash out of the assets of the Company before any payment shall be made to the holders of common stock or shares of any series or class of preferred or other capital stock then outstanding that by its terms is junior to the Series C Perpetual Preferred shares in respect of the preferences as to distributions and payments upon such liquidation event by reason of their ownership, an amount per share of Series C equal to one times the Series C original issue price. ​ The Series C Perpetual Preferred shares were redeemable upon the option or discretion of the Company. ​ The Series C Perpetual Preferred shares were entitled to receive 10% cumulative stock dividends, to be payable in arrears on a monthly basis for 24 shall be payable through the Company’s issuance of Series C Perpetual Preferred share by delivering to each record holder the calculated number of PIK dividend shares. ​ The Series C Perpetual Preferred shares were initially measured at fair value using the income approach, which considered the weighted probability of discounted cash flows at various scenarios of redemption by the Company or liquidation event and perpetual holding of the shares. As of the date of exchange, total fair value of the Series C Perpetual Preferred shares amounted to $4.7 million. Subsequently, the carrying amount of Series C Perpetual Preferred shares increased as the PIK dividend shares were recognized. ​ The preferred stock has been classified as permanent stockholders' equity in accordance with authoritative guidance for the classification and measurement of perpetual shares without mandatory redemption period because the redemption option was ultimately in the control of the Company. ​ ​ As of March 31, 2022 and December 31, 2021, there were no Series C Perpetual Preferred shares outstanding.

Stockholders' Equity

Stockholders' Equity	3 Months Ended
	Mar. 31, 2022
Stockholders' Equity
Stockholders' Equity	11. Stockholders' Equity As of March 31, 2022 and December 31, 2021, the Company had reserved shares of common stock, on an as-if converted basis, for issuance as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ ​ 2022 ​ 2021 Options issued and outstanding 2,323,032 2,464,803 Inducement options issued and outstanding ​ 128,072 ​ 38,289 Options available for grant under stock option plans 431,371 631,270 Restricted stock unit awards issued and outstanding 3,462,170 487,456 Warrants issued and outstanding 563,451 563,451 Total 6,908,096 4,185,269 ​ Common Stock The holders of common stock are entitled to one vote for each share of common stock held. The common stockholders are also entitled to receive dividends whenever funds and assets are legally available and when declared by the Board of Directors. The holders of non-voting common stock are not entitled to vote, except on an as converted basis with respect to any change of control of the Company that is submitted to the stockholders of the Company for approval. Shares of the Company's non-voting common stock have the same rights to dividends and other distributions and are convertible into shares of the Company's common stock on a The Company is authorized to issue a total number of 204,475,074 shares, of which 150,000,000 shares are common stock, 50,000,000 are non-voting common stock and 4,475,074 are preferred stock. Reverse Stock Split On September 3, 2021, the reverse stock split of the Company’s issued and outstanding voting common stock at a ratio not less than 1 1 three March 2020 ELOC (Equity Line of Credit) In March 2020, the Company entered into an equity purchase agreement (the “March 2020 ELOC”) with Oasis Capital, which provides that Oasis Capital is committed to purchase up to an aggregate of $2.0 million shares of the Company’s common stock over the 36-month term of the March 2020 ELOC. Pursuant to the terms and conditions of the March 2020 ELOC, on any trading day selected by the Company (such date the “Put Date”), after the SEC has declared effective the registration statement registering the sale of the shares of common stock that may be issued to Oasis Capital under the March 2020 ELOC, the Company has the right, in its sole discretion, to present to Oasis Capital with a purchase notice (each a “Put Notice”), directing Oasis Capital to purchase up to the lesser of (i) 66,666 shares of common stock or (ii) 20% of the average trading volume of common stock in the 10 trading days immediately preceding the date of such Put Notice, at a per share price equal to $1.31 (each an “Option 1 Put”), provided that the aggregate of all Option 1 Puts and Option 2 Puts (described below) does not exceed $2.0 million. In addition, on any date on which Oasis Capital receives shares of common stock in connection with a Put Notice (the “Clearing Date”), the Company also has the right, in its sole discretion, to present to Oasis Capital with a Put Notice (each an “Option 2 Put”) directing Oasis Capital to purchase an amount of common stock equal to the lesser of (i) such amount that equals 10% of the daily trading volume of the common stock on the date of such Put Notice and (ii) $200,000, provided that the aggregate amount of the Option 1 Put and Option 2 Put on any Put Date or Clearing Date does not exceed $500,000 and the aggregate amount of all Option 1 Puts and Option 2 Puts does not exceed $2.0 million. The purchase price per share pursuant to such Option 2 Put is equal to $1.31. The threshold price and the purchase price will be adjusted for any reorganization, recapitalization, non-cash dividend, stock split, reverse stock split or other similar transaction occurring during the period used to compute the threshold price or the purchase price. On April 15, 2020, the SEC declared effective the registration statement registering the sale of the shares of common stock issued to Oasis Capital under the March 2020 ELOC. The Company will control the timing and amount of sales of common stock to Oasis Capital. Oasis Capital has no right to require any sales by the Company but is obligated to make purchases from the Company as directed by the Company in accordance with the March 2020 ELOC. In connection with the equity line, the Company agreed to pay Oasis Capital a commitment fee and in April 2020, in settlement of the commitment fee, the Company issued to Oasis Capital 22,935 shares of common stock. At issuance, the Per the terms of the equity purchase agreement, the Option Put 1 and Option Put 2 may be exercised only at a price that is always above the trading price of the underlying common stock at the exercise date, thereby rendering any exercise by the Company being out-of-the-money. At inception of the equity line on March 24, 2020, the Put Options were classified as derivative assets with a fair value of zero, and upon an effective registration statement on In April 2020, the Company exercised a single Put Option Put 1 under which the Company sold 17,333 common shares to Oasis for gross proceeds of $22,627. As of March 31, 2022 and December 31, 2021, the Company had not exercised any further put options to require Oasis Capital to purchase common stock under the equity purchase agreement. On April 7, 2021, the Company entered into an amendment to the March 2020 ELOC with Oasis Capital, pursuant to which the parties agreed to increase (i) the purchase price from $1.31 to $9.00 and (ii) the threshold price from $1.50 to $10.35. In consideration for Oasis Capital’s entry into the amendment, the Company issued Oasis Capital a common stock purchase warrant (“ELOC Warrants”) exercisable for 33,333 shares of common stock with an exercise price per share equal to $5.61 on the date of the amendment. ​ At the Market Offering (“ATM”) ​ October 2020 ATM Agreement On October 5, 2020, the Company entered into an ATM Agreement with Ladenburg, pursuant to which the Company may offer and sell, from time to time through Ladenburg, shares of common stock, subject to the terms and conditions of the ATM Agreement. The ATM Agreement will terminate upon the earlier of (i) October 5, 2022 and (ii) termination of the ATM Agreement as permitted therein. In 2020, the Company sold 1,271,639 shares of common stock under the ATM Agreement resulting in net proceeds of approximately $1.3 million after commissions and expenses of approximately $40,000 . ​ In 2021, the Company issued an aggregate of 669,850 shares under the ATM Agreement for total net proceeds of $5.4 million after commissions and expenses of approximately $311,000 . ​ As of March 31, 2022 and December 31, 2021, all shares under the ATM Agreement have been issued. ​ December 2021 ATM Agreement On December 10, 2021, the Company entered into another ATM Agreement (“December 2021 ATM Agreement”) with Ladenburg, pursuant to which the Company may offer and sell, from time to time through Ladenburg, shares of common stock having an aggregate offering price of up to $15.0 million, subject to the terms and conditions of the December 2021 ATM Agreement. The offering will terminate upon the earlier of (i) December 10, 2024 and (ii) termination of the December 2021 ATM Agreement as permitted therein. On February 2, 2022, the Company entered into an amendment to the December 2021 ATM Agreement, pursuant to which, the aggregate offering amount of the shares of the Company’s common stock which the Company may sell and issue through Ladenburg, as the sales agent, was increased from $15.0 million to $75.0 million (the “ATM Upsize”). As of December 31, 2021, the Company has issued 2,261,596 shares under the December 2021 ATM Agreement for a total net proceeds of $3.2 million. ​ During the three months ended March 31, 2022, the Company issued an aggregate of 20,046,463 shares under the ATM Agreement for total net proceeds of $9.1 million after commissions and expenses of approximately $83,000 . ​ Securities Purchase Agreement ​ On January 13, 2021, the Company entered into a securities purchase agreement, pursuant to which the Company agreed to issue and sell, in a registered public offering an aggregate of 1,479,290 shares of common stock at an offering price of $10.14 per share for gross proceeds of approximately $15.0 million before deducting $1.6 million placement agent fee and related offering expenses. The offering closed on January 15, 2021. ​ On April 29, 2021, the Company entered into another securities purchase agreement, pursuant to which the Company agreed to issue and sell, in a registered public offering through Ladenburg as the placement agent, an aggregate of 2,549,000 shares of common stock at an offering price of $4.23 per share for gross proceeds of approximately $10.8 million before deducting placement agent fees and related offering expenses of $948,000 . ​ Subscription Agreement On June 1, 2021, the Company entered into a subscription agreement with the SPAC and its sponsor, pursuant to which the SPAC agreed to issue and sell, in a private placement by the SPAC directly to the Company, units of the SPAC, with each unit consisting of one ordinary share of the SPAC and a warrant to purchase a share, for gross proceeds of approximately €8.8 million (corresponding, as at June 1, 2021, to $10.8 million). The SPAC is an Italy special purpose acquisition company formed for the purpose of entering into a business combination with Napo EU, with the aim of developing the pharmaceutical activities of the SPAC/Napo EU combined entity in Europe. Each warrant will entitle the holder thereof to purchase one share at an exercise price of €10 per share at any time prior to the earlier of (i) the 10-year anniversary of the consummation of the business combination and (ii) the five-year anniversary of the listing of the combined entity on a public exchange. ​ On November 3, 2021 and the SPAC issued 883,000 ordinary shares, each reserved to the exercise of warrants pursuant to the warrant agreement approved by the SPAC (see Note 15). As a result, the SPAC became a substantially owned subsidiary, at the same time, the related advances will be converted to investment at a stand-alone level, and will be eliminated at the consolidated level. ​ September 2021 PIPE Financing On September 13, 2021, the Company entered into a securities purchase agreement (the “September 2021 PIPE Financing”) with certain investors, pursuant to which the Company agreed to issue and sell to the investors in a private placement an aggregate of 309,242 unregistered shares of the Company’s common stock for an aggregate purchase price of approximately $776,197 or $2.51 per share. ​ Noncontrolling Interest As a result of the merger last November 3, 2021 between Napo EU and Dragon SPAC, the Company assumed a non-controlling interest amounting to $242,000 as of December 31, 2021 which represents noncontrolling interest held by an investor in Napo Therapeutics. During the three months ended March 31, 2022, noncontrolling interest decreased by $178,000 due to the share in net loss on Napo EU’s financial performance.

Stock Based Compensation

Stock Based Compensation	3 Months Ended
	Mar. 31, 2022
Stock Based Compensation
Stock Based Compensation	12. Stock-based Compensation 2013 Equity Incentive Plan Effective November 1, 2013, the Company's BOD and sole stockholder adopted the Jaguar Health, Inc. 2013 Equity Incentive Plan (the “2013 Plan”). The 2013 Plan allows the Company's BOD to grant stock options, restricted stock awards and restricted stock unit awards to employees, officers, directors and consultants of the Company. Following the effective date of the IPO and after effectiveness of any grants under the 2013 Plan that were contingent on the IPO, no additional stock awards will be granted under the 2013 Plan. Outstanding grants continue to be exercisable; however, any unissued shares under the plan and any forfeitures of outstanding options do not rollover to the 2014 Stock Incentive Plan. There were 123 option shares outstanding at March 31, 2022 and December 31, 2021. 2014 Stock Incentive Plan Effective May 12, 2015, the Company adopted the Jaguar Health, Inc. 2014 Stock Incentive Plan (“2014 Plan”). The 2014 Plan provides for the grant of options, restricted stock and restricted stock units to eligible employees, directors and consultants to purchase the Company's common stock. The term of an incentive stock option may not exceed 10 years, except that with respect to any participant who owns more than 10% of the voting power of all classes or our outstanding stock, the term must not exceed 5 years. The 2014 Plan that provides for automatic share increases on the first day of each fiscal year in the amount of 2% of the outstanding number of shares of the Company's common stock on the last day of the preceding calendar year. The 2014 Plan replaced the 2013 Plan except that all outstanding options under the 2013 Plan remain outstanding until exercised, canceled or expired. As of March 31, 2022, there were 2,323,032 options outstanding and 87,470 options available for grant. As of December 31, 2021, there were 2,348,076 options outstanding and 619,480 options available for grant. 2020 New Employee Inducement Award Plan Effective June 16, 2020, the Company adopted the Jaguar Health, Inc. New Employee Inducement Award Plan (“2020 Inducement Award Plan”) and, subject to the adjustment provisions of the Inducement Award Plan, reserved 166,666 shares of the Company’s common stock for issuance pursuant to equity awards granted under the Inducement Award Plan. The term of an incentive stock option may not exceed 10 years , except that with respect to any participant who owns more than 10% of the voting power of all classes or our outstanding stock, the term must not exceed 5 years . The 2020 Inducement Award Plan provides for the grant of nonstatutory stock options, restricted stock units, restricted stock, and performance shares. The 2020 Inducement Award Plan was adopted without stockholder approval pursuant to Rule 5635(c)(4) of the Nasdaq Listing Rules. The terms and conditions of the 2020 Inducement Award Plan are substantially similar to the Company’s 2014 Stock Incentive Plan, but with such other terms and conditions intended to comply with the Nasdaq inducement award rules. In accordance with Rule 5635(c)(4) of the Nasdaq Listing Rules, the only persons eligible to receive grants of equity awards under the Inducement Award Plan are individuals who were not previously an employee or director of the Company, or following a bona fide period of non-employment, as an inducement material to such persons entering into employment with the Company. As of March 31, 2022, there were 127,932 options outstanding and 343,901 options available for grant. As of December 31, 2021, there were 154,876 options outstanding and 11,790 options available for grant. Stock Options and Restricted Stock Units (“RSUs”) The following table summarizes incentive plan activity for the three months ended March 31, 2022 (unaudited) ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Weighted ​ Weighted Average ​ ​ ​ ​ ​ Shares ​ Stock ​ ​ ​ Average ​ Remaining ​ Aggregate ​ ​ Available ​ Options ​ RSUs ​ Stock Option ​ Contractual Life ​ Intrinsic (in thousands, except share and per share data) for Grant Outstanding Outstanding Exercise Price (Years) Value* Outstanding at December 31, 2021 ​ 631,270 ​ 2,503,075 ​ 487,456 ​ $ 9.44 ​ 8.35 ​ $ 3 Additional shares authorized ​ 2,722,827 ​ — ​ — ​ ​ — ​ ​ ​ ​ — Options granted ​ — ​ — ​ — ​ ​ — ​ ​ ​ ​ — Options exercised ​ — ​ — ​ — ​ ​ — ​ ​ ​ ​ — Options canceled ​ 51,988 ​ (51,988) ​ — ​ ​ 4.01 ​ ​ ​ ​ — RSUs granted ​ (2,974,714) ​ — ​ 2,974,714 ​ ​ — ​ ​ ​ ​ — Outstanding at March 31, 2022 ​ 431,371 ​ 2,451,087 ​ 3,462,170 ​ $ 9.55 ​ 8.07 ​ $ — Exercisable at March 31, 2022 ​ ​ 1,611,407 ​ ​ ​ $ 12.02 7.64 ​ $ — Vested and expected to vest at ​ ​ 2,349,585 ​ ​ ​ $ 9.74 8.03 ​ $ — ​ *Fair market value of JAGX common stock on March 31, 2022 was $0.71 per share. The intrinsic value is calculated as the difference between the exercise price of the underlying options and the fair market value of the Company's common stock for options that were in-the-money. The number of options exercised during the three months ended March 31, 2022 and 2021 was zero. The weighted average grant date fair value of stock options granted was zero and $5.28 per share during the three months ended March 31, 2022 and 2021, respectively. The number of options that vested in the three months ended March 31, 2022 and 2021 was 188,924 and 127,806, respectively. The grant date weighted average fair value of options that vested in the three months ended March 31, 2022 and 2021 was $4.45 and $4.95, respectively. Stock-Based Compensation The following table summarizes stock-based compensation expense related to stock options, inducement stock options and RSUs for the three months ended March 31, 2022 and 2021, and are included in the unaudited condensed consolidated statements of operations as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ ​ ​ March 31, ​ (in thousands) 2022 2021 ​ Research and development expense ​ $ 348 ​ $ 164 ​ Sales and marketing expense ​ 82 ​ 52 ​ General and administrative expense ​ 633 ​ 418 ​ Total ​ $ 1,063 ​ $ 634 ​ ​ As of March 31, 2022, the Company had $3.1 million of unrecognized stock-based compensation expense for options, inducement options and restricted stock units outstanding, which is expected to be recognized over a weighted-average period of 1.79 years. ​ The fair value of options granted during the three months ended March 31, 2022 and 2021, respectively, were calculated using the range of assumptions set forth below: ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ ​ March 31, ​ 2022 2021 Volatility ​ — ​ 163.8 - 164.0 % Expected term (years) ​ — 5.0 Risk-free interest rate ​ — 0.5 - 0.9 % Expected dividend yield ​ — ​ — ​ 401(k) Plan The Company sponsors a 401(k) defined contribution plan covering all employees. There were no employer contributions to the plan from plan inception through March 31, 2022.

Net Loss Per Share

Net Loss Per Share	3 Months Ended
	Mar. 31, 2022
Net Loss Per Share
Net Loss Per Share Attributable to Common Stockholders	13. Net Loss Per Share The following table presents the calculation of basic and diluted net loss per share of common stock for the periods indicated: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended March 31, (In thousands, except share and per share data) 2022 2021 ​ ​ ​ Net loss attributable to common shareholders (basic and diluted) ​ $ (17,986) ​ $ (12,009) Shares used to compute net loss per common share, basic and diluted ​ ​ 44,711,588 ​ ​ 42,635,466 Net loss per share attributable to common shareholders, basic and diluted ​ $ (0.40) ​ $ (0.28) ​ Basic net loss per share is calculated by dividing net loss by the weighted-average number of common shares outstanding during the period. Diluted net loss per share is computed by dividing net loss by the weighted-average number of common shares and common share equivalents outstanding for the period. Common stock equivalents are only included when their effect is dilutive. The Company's potentially dilutive securities which include stock options, convertible preferred stock, RSUs and common stock warrants have been excluded from the computation of diluted net loss per share as they would be anti-dilutive. For all periods presented, there is no difference in the number of shares used to compute basic and diluted shares outstanding due to the Company's net loss position. The following outstanding common stock equivalents have been excluded from diluted net loss per common share for the three months ended March 31, 2022 and 2021 because their inclusion would be anti-dilutive. ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31, ​ 2022 ​ 2021 Options issued and outstanding ​ 2,323,032 ​ 2,464,803 Inducement options issued and outstanding ​ 128,072 ​ 38,289 Restricted stock units issued and outstanding ​ 3,462,170 ​ 487,456 Warrants issued and outstanding ​ 563,451 ​ 563,451 Total ​ 6,476,725 ​ 3,553,999 ​ ​ As of May 4, 2022, there were 784,516 shares of common stock issued after the balance sheet date. Including these shares will have a material effect on the diluted net loss per common share in future periods.

Segment Information

Segment Information	3 Months Ended
	Mar. 31, 2022
Segment Information
Segment Information	14. Segment Information The Company has two reportable segments-human health and animal health. The animal health segment is focused on developing and commercializing prescription and non-prescription products for companion and production animals. The human health segment is focused on developing and commercializing of human products and the ongoing commercialization of Mytesi, which is approved by the U.S. FDA for the symptomatic relief of non-infectious diarrhea in adults with HIV/AIDS on antiretroviral therapy. The accounting policies of the segments are the same as those described in the summary of significant accounting policies. The Company's reportable segments net revenues and net loss for the three months ended March 31, 2022 and 2021 consisted of the following: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ ​ March 31, (in thousands) 2022 2021 Revenue from external customers ​ ​ Human Health ​ $ 2,605 ​ $ 1,208 Animal Health ​ 20 ​ 33 Consolidated Totals ​ $ 2,625 ​ $ 1,241 ​ ​ ​ ​ ​ ​ ​ Segment net loss ​ ​ Human Health ​ $ (9,967) ​ $ (3,941) Animal Health ​ (8,197) ​ (8,068) Consolidated Totals ​ $ (18,164) ​ $ (12,009) ​ The Company's reportable segments assets consisted of the following: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31, (in thousands) 2022 2021 Segment assets ​ ​ Human Health ​ $ 38,880 ​ $ 42,250 Animal Health ​ 121,467 ​ 115,580 Total ​ $ 160,347 ​ $ 157,830 ​ The reconciliation of segments assets to the consolidated assets is as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31, (in thousands) 2022 2021 Total assets for reportable segments ​ $ 160,347 ​ $ 157,830 Less: Investment in subsidiary ​ (29,232) ​ (29,232) Less: Intercompany loan ​ (78,209) ​ (75,333) Consolidated Totals ​ $ 52,906 ​ $ 53,265 ​

Subsequent Events

Subsequent Events	3 Months Ended
	Mar. 31, 2022
Subsequent Events
Subsequent Events	15. Subsequent Events Royalty Interest Amendment On April 14, 2022, the Company entered into amendments (the “Royalty Interest Global Amendments”) to (i) the royalty interest in the original principal amount of $12 million (the “October 2020 Royalty Interest”) with Iliad Research and Trading, L.P., (ii) the royalty interest in the original principal amount of $12 million (the “December 2020 Royalty Interest”) with Uptown Capital, LLC (f/k/a Irving Park Capital, LLC) and (iii) the royalty interest in the original principal amount of $10 million (the “March 2021 Royalty Interest” and, together with the October 2020 Royalty Interest and the December 2020 Royalty Interest, the “Royalty Interests”) with Streeterville Capital, LLC (“Streeterville”), pursuant to which the Company was granted the right to exchange from time to time at the Company’s sole discretion, all or any portion of the Royalty Interests for shares of the Company’s common stock at a price per share equal to the Minimum Price (as defined in Nasdaq Listing Rule 5635(d)) as of the date of the applicable exchange (the “Exchange Price”). Under the Royalty Interest Global Amendments, the Company’s ability to exchange the Royalty Interests for shares of the Company’s common stock is subject to certain limitations, including no exchange transaction to the extent the issuance of shares in such exchange would result in the total cumulative number of shares of the Company’s common stock issued pursuant to the Royalty Interests would exceed the requirements of The Nasdaq Capital Market (including the rules related to the aggregation of offerings under Nasdaq Listing Rule 5635(d) if applicable) (the “Exchange Cap”), unless stockholder approval is obtained to issue more than the Exchange Cap. Debt Amendment On April 14, 2022, the Company and Napo Pharmaceuticals, Inc., the Company’s wholly-owned subsidiary (“Napo” and together with the Company, the “Borrower”), entered into an amendment (the “Note Global Amendment”) to the secured promissory note in the original principal amount of $6.2 million (the “Note”) with Streeterville, pursuant to which the Borrower was granted the right to exchange from time to time at Borrower’s sole discretion, all or any portion of the Note for shares of the Company’s common stock at a price per share equal to the Exchange Price. Under the Note Global Amendment, the Borrower’s ability to exchange the Note for shares of the Company’s common stock is subject to certain limitations, including no exchange transaction to the extent the issuance of shares in such exchange would result in the total cumulative number of shares of the Company’s common stock issued pursuant to the Note would exceed the Exchange Cap, unless stockholder approval is obtained to issue more than the Exchange Cap. Plan Amendment On April 13, 2022, the Board of Directors of the Company approved an amendment (the “Plan Amendment”) to the New Employee Inducement Award Plan (the “Inducement Award Plan”) to reserve an additional 471,833 shares of the Company’s common stock for issuance pursuant to equity awards granted under the Inducement Award Plan, thereby increasing the number of shares of the Company’s common stock issuable thereunder from 500,000 shares to 971,833 shares. The Inducement Award Plan was adopted on June 16, 2020 without stockholder approval pursuant to Rule 5635(c)(4) of the Nasdaq Listing Rules. ​

Summary of Significant Accoun_2

Summary of Significant Accounting Policies (Policies)	3 Months Ended
	Mar. 31, 2022
Summary of Significant Accounting Policies
Basis of Presentation	Basis of Presentation The unaudited condensed consolidated financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America (“U.S. GAAP”) for interim financial information and on a basis consistent with the annual consolidated financial statements, and in the opinion of management, reflect all adjustments, which include only normal recurring adjustments, necessary for a fair presentation of the periods presented. These interim financial results are not necessarily indicative of the results to be expected for the year ending Annual Report on Form 10-K for the year ended December 31, 2021. The condensed consolidated balance sheet at December 31, 2021 has been derived from the audited consolidated financial statements at that date, but does not include all disclosures, including notes, required by U.S. GAAP for complete financial statements. There has been no material change to the Company's significant accounting policies during the three months ended March 31, 2022, as compared to the significant accounting policies described in Note 2 of the “Notes to Consolidated Financial Statements” in the Company's Annual Report on Form 10-K as of and for the year ended December 31, 2021 which was filed to SEC on March 11, 2022. Except as noted above, the unaudited condensed consolidated financial statements have been prepared on the same basis as the audited consolidated financial statements and, in the opinion of management, reflect all adjustments of a normal recurring nature considered necessary to present fairly the financial position as of March 31, 2022, results of operations for the three months ended March 31, 2022 and 2021, changes in convertible preferred stock and stockholders' equity for the three months ended March 31, 2022 and 2021, and cash flows for the three months ended March 31, 2022 and 2021. The interim results are not necessarily indicative of the results for any future interim periods or for the entire year.
Principles of Consolidation	Principles of Consolidation The unaudited interim condensed consolidated financial statements have been prepared in accordance with U.S. GAAP and applicable rules and regulations of the Securities and Exchange Commission (“SEC”) and include the accounts of the Company and its wholly-owned subsidiary. All inter-company transactions and balances have been eliminated in consolidation.
Use of Estimates	Use of Estimates The preparation of the unaudited condensed consolidated financial statements in conformity with U.S. GAAP requires the Company’s management to make judgments, assumptions and estimates that affect the amounts reported in its unaudited condensed consolidated financial statements and the accompanying notes. The accounting policies that reflect the Company’s more significant estimates and judgments and that the Company believes are the most critical to aid in fully understanding and evaluating its reported financial results are the valuation of stock options, valuation of hybrid instruments designated at fair value option (“FVO”), valuation of warrant liabilities, acquired in-process research and development (“IPR&D”), and useful lives assigned to long-lived assets; valuation adjustments for excess and obsolete inventory; allowance for doubtful accounts; deferred taxes and valuation allowances on deferred tax assets; evaluation and measurement of contingencies; and recognition of revenue, including estimates for product returns. Those estimates could change, and as a result, actual results could differ materially from those estimates. In March 2020, the World Health Organization declared the COVID-19 outbreak to be a pandemic. During the period ended March 31, 2022, the Company’s financial results were not significantly affected by the COVID-19 outbreak. The Company has considered all information available as of the date of issuance of these financial statements and the Company is not aware of any specific events or circumstances that would require an update to its estimates or judgments, or a revision to the carrying value of its assets or liabilities. These estimates may change as new events occur and additional information becomes available. The extent to which the COVID-19 outbreak affects the Company’s future financial results and operations will depend on future developments which are highly uncertain and cannot be predicted, including new information which may emerge concerning the severity of the outbreak, and current or future domestic and international actions to contain and treat it. For a discussion of risks of COVID-19 relating to the Company’s business, see “Item 1A. - Risk Factors- Risks Related to Our Business- The novel coronavirus global pandemic could adversely impact our business, including our supply chain, clinical trials and commercialization of Mytesi and Canalevia.” ​
Cash	Cash The Company’s cash on deposit may exceed United States federally insured limits at certain times during the year. The Company maintain cash accounts with certain major financial institutions in the United States. The Company does not have cash equivalents as of March 31, 2022 and December 31, 2021.
Accounts Receivable	Accounts Receivable Accounts receivable is recorded net of allowances for discounts for prompt payment and credit losses. The Company estimates an allowance for credit losses by considering factors such as historical experience, credit quality, the age of the accounts receivable balances, and current economic conditions that may affect a customer’s ability to pay. The corresponding expense for the credit loss allowance is reflected in general and administrative expenses. The credit loss allowance was immaterial as of March 31, 2022 and December 31, 2021.
Concentrations	Concentrations Cash is the financial instrument that potentially subjects the Company to a concentration of credit risk as cash is deposited with a bank and cash balances are generally in excess of Federal Deposit Insurance Corporation insurance limits. For the three months ended March 31, 2022 and 2021, substantially all of the Company’s revenue was derived from the sale of Mytesi. In looking at sales by the Company to distributors whose net revenue percentage of total net revenue was equal to or greater than 10%, for the three months ended March 31, 2022, the Company earned Mytesi revenue primarily from three pharmaceutical distributors located in the United States. For the three months ended March 31, 2021, the Company earned Mytesi revenue primarily from two pharmaceutical distributors in the United States. Revenue earned from each as a percentage of total revenue is as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ ​ March 31, ​ ​ (unaudited) ​ ​ 2022 2021 Customer 1 ​ — % 86 % Customer 2 ​ 34 % 10 % Customer 3 ​ 49 % — % Customer 4 ​ 10 % — % ​ The Company is subject to credit risk from its accounts receivable related to its sales. The Company generally does not perform evaluations of customers' financial condition and generally does not require collateral. As of ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, December 31, ​ 2022 ​ 2021 ​ ​ ​ (unaudited) ​ ​ ​ Customer 1 ​ — % 16 % Customer 2 ​ 34 % 37 % Customer 3 ​ 52 % 37 % ​ The Company is subject to concentration risk from its suppliers. The Company sources raw material used to produce the active pharmaceutical ingredient (“API”) in Mytesi from two suppliers and is dependent on a single third-party contract manufacturer for the supply of API in Mytesi and a single third-party contract manufacturer as well for the supply of finished products for commercialization.
Other Risks and Uncertainties	Other Risks and Uncertainties The Company’s future results of operations involve a number of risks and uncertainties. Factors that could affect the Company’s future operating results and cause actual results to vary materially from expectations include, but are not limited to, rapid technological change, obtaining second source suppliers, regulatory approval from the FDA or other regulatory authorities, the results of clinical trials and the achievement of milestones, market acceptance of the Company’s product candidates, competition from other products and larger companies, protection of proprietary technology, strategic relationships and dependence on key individuals.
Fair Value	Fair Value The Company’s financial instruments include accounts receivable, accounts payable, accrued liabilities, warrant liabilities, equity-linked financial instruments and debt. The recorded carrying amounts of accounts receivable, accounts payable and accrued liabilities reflect their fair value due to their short-term nature. Other financial liabilities are initially recorded at fair value, and subsequently measured at either fair value or amortized cost using the effective interest method. See Note 4 for the fair value measurements.
Fair Value Option	Fair Value Option ASC 825-10, Financial Instruments
Inventory	Inventory ​ Inventory is stated at the lower of cost or net realizable value. Cost is determined using the first-in, first-out method. Cost is initially recorded at the invoiced amount of raw materials or API, including the sum of qualified expenditures and charges in bringing the inventory to its existing condition and location. The Company calculates inventory valuation adjustments when conditions indicate that net realizable value is less than cost due to physical deterioration, usage, obsolescence, reductions in estimated future demand or reduction in selling price. Inventory write-downs are measured as the difference between the cost of inventory and net realizable value.
Property and Equipment	Property and Equipment Land is stated at cost, reflecting the fair value of the property at July 31, 2017, the date of the Napo merger. Equipment is stated at cost, net of accumulated depreciation. Equipment begins to be depreciated when it is placed into service. Depreciation is calculated using the straight-line method over estimated useful lives ranging between 3 to 10 years. Expenditures for repairs and maintenance of assets are charged to expense as incurred. Costs of major additions and betterments are capitalized and depreciated on a straight-line basis over their estimated useful lives. Upon retirement or sale, the cost and related accumulated depreciation of assets disposed of are removed from the accounts and any resulting gain or loss is included in the unaudited condensed consolidated statements of operations.
Long-Lived Assets	Long-lived Assets
Indefinite-lived Intangible Assets	Indefinite-lived Intangible Assets Acquired IPR&D are intangible assets acquired in the July 2017 Napo merger. Under ASC 805, IPR&D are initially recognized at fair value and classified as indefinite-lived assets until the successful completion or abandonment of the associated research and development efforts. During the development period, these assets will not be amortized as charges to earnings; instead, these assets will be tested for impairment on an annual basis or more frequently if impairment indicators are identified. An impairment loss is measured based on the excess of the carrying amount over the asset’s fair value. The Company recorded no impairment in the three months ended March 31, 2022 and 2021.
Leases	Leases The Company accounts for its leases in accordance with ASC 842, Leases At the inception of an arrangement, the Company determines whether the arrangement is or contains a lease based on the unique facts and circumstances present. Operating lease liabilities and their corresponding right-of-use assets are recorded based on the present value of lease payments over the expected lease term. Because the interest rate implicit in lease contracts is typically not readily determinable, the Company utilizes its incremental borrowing rate, which is the rate incurred to borrow on a collateralized basis over a similar term, an amount equal to the lease payments in a similar economic environment. Certain adjustments to the right-of-use asset may be required for items such as initial direct costs paid or incentives received. Operating Lease The Company entered into a sublease agreement with Peacock Construction Inc. (“Peacock”), a California corporation, for office space located in San Francisco, California. The term of the sublease began on August 31, 2020 and expired on May 31, 2021. The rent under the sublease is $15,000 per month beginning October 1, 2020, which includes operating expenses and taxes. On October 1, 2020, the Company transitioned its operations from its existing premises to the sublease premises, which the Company expects will serve as its principal administrative headquarters. The Company elected not to apply the recognition requirements to short-term leases, and instead recognize the lease payments in profit or loss on a straight-line basis over the lease term. As a result, there was no right-of-use asset and lease liability In April 2021, the Company entered into an office lease agreement with M & E, LLC, a California Limited Liability Company, to lease approximately 10,526 square feet of office space located in San Francisco, California, inclusive of office space currently covered under the sublease agreement with Peacock. The term of the lease began on September 1, 2021 and will expire on August 31, 2024, unless earlier terminated. The base rent under the lease will be $42,000 monthly for the first 12 months, $43,000 monthly for the next 12 months and $45,000 for the last twelve months. ​ In October 2021, the Company entered into an agreement with Copernico Centrale for the lease of office premises from November 1, 2021 to April 30, 2022, subject to automatic renewal for subsequent periods until terminated by either party. Base rent amounted to €10,000. If the contract is not terminated within 12 months, the lease amount will be increased in line with the index of relevant inflation at each annual expiration of the start date of the contract. On January 26, 2022, the lease agreement was amended whereby the term was extended by 20 months from May 1, 2022 to December 31, 2023. All other contract provisions remained the same. In December 2021, the Company entered into an agreement with Arval Service Lease Italia SpA for the lease of two separate vehicles for 48 months expiring on November 30, 2025. Total monthly lease payment amounted to €2,000 payable in advance. The Company elected to include both the lease and non-lease components as a single component and account for it as a lease. The Company also paid a total deposit of €19,000, exclusive of VAT. Early termination of the contracts requires the payment of specified amounts. In December 2021, the Company entered into the first amendment to the lease with M & E, LLC whereby the commencement date of one of the leased premises was modified to March 1, 2022. Accordingly, the expiration of the lease was extended to February 28, 2025. The base rent under the original agreement remained the same but will be due starting March 1, 2022. In addition, the rent for one of the leased premises being occupied by the Company will continue to be $21,000 until the new commencement date. In January 2022, the Company entered into an agreement with Copernico Centrale for the lease of office premises from March 1, 2022 to December 31, 2023, subject to automatic renewal for subsequent periods until terminated by either party. Base rent amounted to €4,000. A similar agreement was entered with the lessor for the lease of premises to be used as office space from November 1, 2022 to December 31, 2023, subject to automatic renewal for subsequent periods until terminated by either party. Base rent amounted to €3,817. If the contracts are not terminated within 12 months, the lease amounts will be increased in line with the index of relevant inflation at each annual expiration of the start date of the contract.
Research and Development Expense	Research and Development Expense Research and development expense consists of expenses incurred in performing research and development activities including related salaries, clinical trials and related drug and non-drug product costs, contract services and other outside service expenses. Research and development expense is charged to operating expense in the period incurred.
Clinical Trial Accruals	Clinical Trial Accruals Clinical trial costs are a component of research and development expenses. The Company accrues and expenses clinical trial activities performed by third parties based upon actual work completed in accordance with agreements established with clinical research organizations and clinical sites. The Company determines the costs to be recorded based upon validation with the external service providers as to the progress or stage of completion of trials or services and the agreed-upon fee to be paid for such services.
Revenue Recognition	Revenue Recognition The Company recognizes revenue in accordance with ASC 606, Revenue from Contracts with Customers The Company’s policy typically permits returns if the product is damaged, defective, or otherwise cannot be used when received by the customer if the product has expired. Returns are accepted for product that will expire within three months or that have expired up to one year after their expiration dates. Estimates for expected returns of expired products are based primarily on an ongoing analysis of our historical return patterns. The Company recognizes revenue in accordance with the core principle of ASC 606 or when there is a transfer of control of promised goods or services to customers in an amount that reflects the consideration that the Company expects to be entitled to in exchange for those goods or services. The Company recognizes the incremental costs of obtaining a contract as an expense when incurred if the amortization period of the asset that the Company otherwise would have recognized is one year or less. The Company does not adjust the amount of consideration for the effects of a significant financing component if, at contract inception, the expected period between the transfer of promised goods or services and customer payment is one year or less. The Company has elected to treat shipping and handling activities as fulfillment costs. Additionally, the Company elected to record revenue net of sales and other similar taxes. Contracts – Cardinal Health Effective January 16, 2019, the Company engaged Cardinal Health as its exclusive third-party logistics distribution agent for commercial sales of the Company’s Mytesi product and to perform certain other services which include, without limitation, storage, distribution, returns, customer support, financial support, Electronic Data Interchange (“EDI”) and system access support (the “Exclusive Distribution Agreement”). On September 3, 2021, the Company ended its engagement with Cardinal Health as its exclusive title model customer for commercial sales and fully implemented its limited distribution Specialty Pharmacy model. Cardinal Health continues to provide third-party logistics services for Mytesi. The Company's Neonorm and botanical extract products are primarily sold to distributors, who then sell the products to the end customers. Since 2014, the Company has entered into several distribution agreements with established distributors such as Animart, Vedco, VPI, RJ Matthews, Covetrus, and Stockmen Supply to distribute the Company's products in the United States, Japan, and China. The distribution agreements and the related purchase order together meet the contract existence criteria under ASC 606-10-25-1. The Company sells directly to its customers without the use of an agent. Performance obligations For animal products sold by the Company, the single performance obligation identified above is the Company’s promise to transfer the Company’s animal products to distributors based on specified payment and shipping terms in the arrangement. Product warranties are assurance-type warranties that do not represent a performance obligation. For the Company’s human product, Mytesi, the single performance obligation identified above is the Company’s promise to transfer Mytesi to Cardinal Health, based on specified payment and shipping terms as outlined in the Exclusive Distribution Agreement. Transaction price For contracts with Cardinal Health, the transaction price is the amount of consideration to which the Company expects to collect in exchange for transferring the promised goods or services. The transaction price of Mytesi and Neonorm is the Wholesaler Acquisition Cost (“WAC”), net of discounts, returns, and price adjustments. Allocate transaction price For contracts with Cardinal Health, the entire transaction price is allocated to the single performance obligation contained in each contract. Revenue recognition For contracts with Cardinal Health, a single performance obligation is satisfied at a point in time, upon the free on board (“FOB”) terms of each contract when control, including title and all risks, has transferred to the customer. Disaggregation of Product Revenue Human Sales of Mytesi are recognized as revenue at a point in time when the products are delivered to the wholesaler. Net revenue from the sale of Mytesi were $438,000 and $1.2 million for the three months ended March 31, 2022 and 2021, respectively. Animal The Company recognized Neonorm revenues of $20,000 and $33,000 for the three months ended March 31, 2022 and 2021, respectively. Revenues are recognized at a point in time upon shipment, which is when title and control is transferred to the buyer. Sales of Neonorm Calf and Foal to distributors are made under agreements that may provide distributor price adjustments and rights of return under certain circumstances. ​ Contracts – Specialty Pharmacies Effective October 1, 2020, the Company engaged a private company as its third-party logistics distribution agent for commercial sales of the Company’s Mytesi product. Under the Specialty Product Distribution Agreement, the Company shall supply the products to the private company’s specialty pharmacies, through a designated wholesaler, in such amounts as may be ordered. There is no minimum purchase or inventory requirement. The specialty pharmacies were authorized distributors of record for all National Drug Codes (“NDCs”) of Mytesi. Effective April 20, 2021, the Company engaged another private company as an authorized specialty pharmacy provider of Mytesi. Under the Specialty Pharmacy Distribution and Services Agreement, the private company shall sell and dispense the Mytesi directly ordered from the Company at the agreed price to patients within the territories identified in the agreement. The two contracts with the two specialty pharmacies were combined into one portfolio of contract as they share similar characteristics. Performance obligations The single performance obligation is the Company’s promise to transfer Mytesi to specialty pharmacies, based on specified payment and shipping terms as outlined in the agreements. Transaction price The transaction price is the amount of consideration to which the Company expects to collect in exchange for transferring the promised goods or services. The transaction price of Mytesi is the WAC, net of estimated discounts, returns, and price adjustments. Allocate transaction price The entire transaction price is allocated to the single performance obligation contained in each contract. Revenue recognition The single performance obligation is satisfied at a point in time, upon the free on board (“FOB”) terms of each contract when control, including title and all risks, has transferred to the customer. Disaggregation of Product Revenue Sales of Mytesi are recognized as revenue at a point in time when products are delivered to the specialty pharmacies. Net revenue from the sale of Mytesi to the specialty pharmacies were $2.2 million and $479,000 for the three months ended March 31, 2022 and 2021, respectively.
Collaboration Revenue	Collaboration Revenue Revenue recognition for collaboration agreements requires significant judgment. The Company’s assessments and estimates are based on contractual terms, historical experience and general industry practice. Revisions in these values or estimations have the effect of increasing or decreasing collaboration revenue in the period of revision. On September 24, 2018, the Company entered into a Distribution, License and Supply Agreement (“License Agreement”) with Knight Therapeutics ("Knight"). The License Agreement has a term of 15 years (with automatic renewals) and provides Knight with an exclusive right to commercialize current and future Jaguar human health products (including crofelemer, Lechlemer, and any product containing a proanthocyanidin or with an anti-secretory mechanism) in Canada and Israel. Knight forfeited its right of first negotiation for expansion to Latin America. Under the License Agreement, Knight is responsible for applying for and obtaining necessary regulatory approvals in the territory of Canada and Israel, as well as marketing, sales and distribution of the licensed products. Knight will pay a transfer price for all licensed products, and upon achievement of certain regulatory and sales milestones, the Company may receive payments from Knight in an aggregate amount of up to approximately $18 million payable throughout the initial 15-year term of the agreement. The Company did not have any license revenues for the three months ended March 31, 2022 and 2021.
Modifications to Liability-classified Instruments	Modifications to Liability-classified Instruments In accounting for debt modifications and exchange transactions, it is the Company’s policy to first determine whether it qualifies as a troubled debt restructuring (“TDR”) pursuant to the guidance provided in ASC 470-60. A debt modification or exchange transaction that is not within the scope of the ASC 470-60 is accounted for under ASC 470-50 to determine if the transaction is a mere modification or an extinguishment. ​ In the three months ended March 31, 2022 and 2021, the Company amended the terms of its October 2020 Purchase Agreement and Exchange Note 2, respectively (see Note 8). ​
Modifications to Equity-classified Instruments	Modifications to Equity-classified Instruments ​ In accounting for modifications of equity-classified warrants, it is the Company’s policy to determine the impact by analogy to the share-based compensation guidance of ASC 718, Compensation - Stock Compensation ​ The Company did not modify any equity-classified warrants in the three months ended March 31, 2022 and 2021. In accounting for amendments to preferred stock, it is the Company’s policy to measure the impact by analogy to ASC 470-50 in determining if such an amendment is an extinguishment or a modification. If the amendment results in an extinguishment, the Company follows the SEC staff guidance in ASC 260-10-S99-2 and ASC 470-20. If the amendment results in a modification, the Company follows the model in either ASC 718 or ASC 470-50, depending on the nature of the amendment. ​ The Company did not modify any preferred stock in the three months ended March 31, 2022 and 2021.
Stock-Based Compensation	Stock-based Compensation The Company uses the grant date fair market value of its common stock to determine the grant date fair value of options granted to employees, non-employees and directors. The Company measures and recognizes compensation expense for all stock options and restricted stock units (“RSUs”) granted to its employees and directors based on the estimated fair value of the award on the grant date. The Company uses the Black-Scholes valuation model to estimate the fair value of stock option awards. The fair value is recognized as expense, net of estimated forfeitures, over the requisite service period, which is generally the vesting period of the respective award, on a straight-line basis. The Company believes that the fair value of stock options granted to non-employees is more reliably measured than the fair value of the services received. The determination of the grant date fair value of options using an option pricing model is affected by the Company’s estimated Common Stock fair value and requires management to make a number of assumptions including the expected life of the option, the volatility of the underlying stock, the risk-free interest rate and expected dividends. The Company estimates the fair value of stock options using the Black-Scholes option valuation model. The fair value of employee stock options is being amortized on a straight-line basis over the requisite service period of the awards. The fair market value of common stock is based on the closing price of the Company’s common stock as reported on the date of the grant.
Income Taxes	Income Taxes The Company uses the asset and liability method of accounting for income taxes. Under this method, deferred tax assets and liabilities are determined based on the differences between the financial reporting and the tax bases of assets and liabilities and are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. A valuation allowance is provided when it is more likely than not that some portion or all of a deferred tax asset will not be realized. The Company has adopted the provisions of ASC 740, Income Taxes Related to Uncertain Tax Positions . Under these principals, tax positions are evaluated in a two-step process. The Company first determines whether it is more-likely-than-not that a tax position will be sustained upon examination. If a tax position meets the more-likely-than-not recognition threshold, it is then measured to determine the amount of benefit to be recognized in the financial statements. The tax position is measured as the largest amount of benefit that has a greater than 50 percent likelihood of being realized upon ultimate settlement.
Foreign Currency Remeasurement and Translation	Foreign Currency Remeasurement and Translation The functional currency of Napo Therapeutics is Euro. The Company follows ASC 830, Foreign Currency Matters measured using the functional currency of that foreign operation. Exchange gains or losses from remeasuring transactions and monetary accounts in a currency other than the functional currency are included in current earnings. For certain subsidiaries, translation adjustments result from the process of translating the functional currency of subsidiary financial statements into the U.S. Dollar reporting currency. These translation adjustments are reported separately and accumulated in the consolidated balance sheets as a component of accumulated other comprehensive loss.
Comprehensive Loss	Comprehensive Loss For the three months ended March 31, 2022, the comprehensive loss was equal to the net loss; therefore, a separate statement of comprehensive loss is not included in the accompanying unaudited condensed consolidated financial statements. For the three months ended March 31, 2021, the amount of other comprehensive loss was only de minimis; hence, a separate statement of comprehensive loss was not included in the accompanying unaudited condensed consolidated financial statements.
Basic and Diluted Net Loss Per Common Share	Basic and Diluted Net Loss Per Common Share Basic net loss per common share is computed by dividing net loss attributable to common stockholders for the year by the weighted-average number of common shares outstanding during the year. Diluted net loss per share is computed by dividing the net loss attributable to common stockholders for the year by the weighted-average number of common shares, including potential dilutive shares of common stock assuming the dilutive effect of potential dilutive securities. For periods in which the Company reports a net loss, diluted net loss per common share is the same as basic net loss per common share, because the impact of the potential dilutive shares of common stock would be anti-dilutive to the calculation of net loss per common share. Diluted net loss per common share is the same as basic net loss per common share for the three months ended March 31, 2022 and 2021.
Recent Accounting Pronouncements	Recent Accounting Pronouncements Recently Adopted Accounting Pronouncements In August 2020, the FASB issued ASU 2020-06, Debt – Debt with Conversion and Other Options (Subtopic 470-20) and Derivatives and Hedging – Contracts in Entity’s Own Equity (Subtopic 815-40): Accounting for Convertible Instruments and Contracts in an Entity’s Own Equity ​ In May 2021, the FASB issued ASU 2021-04, Issuer’s Accounting for Certain Modification or Exchanges of Freestanding Equity-Classified Written Call Options In December 2019, the FASB issued ASU 2019-12, Income Taxes (Topic 740): Simplifying the Accounting for Income Taxes ​ ​ ​ Recently Issued Accounting Pronouncements Not Yet Adopted ​ In June 2016, the FASB issued ASU 2016-13, Financial Instruments – Credit Losses (Topic 326): Measurement of Credit Losses on Financial Instruments.
Reclassification of Prior Year Presentation	Reclassification of Prior Period Presentation

Summary of Significant Accoun_3

Summary of Significant Accounting Policies (Tables) - Customer risk	3 Months Ended
	Mar. 31, 2022
Total net revenue
Schedule of concentration risk	​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ ​ March 31, ​ ​ (unaudited) ​ ​ 2022 2021 Customer 1 ​ — % 86 % Customer 2 ​ 34 % 10 % Customer 3 ​ 49 % — % Customer 4 ​ 10 % — %
Total accounts receivable
Schedule of concentration risk	​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, December 31, ​ 2022 ​ 2021 ​ ​ ​ (unaudited) ​ ​ ​ Customer 1 ​ — % 16 % Customer 2 ​ 34 % 37 % Customer 3 ​ 52 % 37 %

Fair Value Measurements (Tables

Fair Value Measurements (Tables)	3 Months Ended
	Mar. 31, 2022
Fair Value Measurements
Summary of information about the company's financial instruments that were measured at fair value on a recurring basis	​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, 2022 (in thousands) Level 1 Level 2 Level 3 Total Warrant liability ​ $ — ​ $ — ​ $ 1 ​ $ 1 Streeterville note ​ ​ — ​ ​ — ​ ​ 8,051 ​ ​ 8,051 Total fair value ​ $ — ​ $ — ​ $ 8,052 ​ $ 8,052 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ December 31, 2021 (in thousands) Level 1 Level 2 Level 3 Total Warrant liability ​ $ — ​ $ — ​ $ 1 ​ $ 1 Streeterville note ​ $ — ​ $ — ​ $ 7,117 ​ $ 7,117 Total fair value ​ $ — ​ $ — ​ $ 7,117 ​ $ 7,117
Summary of change in the estimated fair value of level 3 liabilities	​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ ​ March 31, 2022 (in thousands) ​ Warrant liability Streeterville note Beginning fair value of Level 3 liability $ 1 $ 7,818 Additions ​ ​ — ​ ​ — Exercises ​ ​ — ​ ​ — Change in fair value — ​ ​ 233 Ending fair value of Level 3 liability $ 1 $ 8,051
Summary of information about the significant unobservable inputs used in level 3 fair value measurements	​ ​ ​ ​ ​ ​ ​ ​ ​ Range of Inputs ​ ​ ​ ​ (probability-weighted average) ​ Relationship of unobservable inputs Unobservable Inputs ​ 2022 ​ 2021 ​ to fair value Risk Adjusted Discount Rate ​ 7.29%-21.82% (21.82%) ​ 6.56% - 22% ​ If discount rate is adjusted to total of additional 100 basis points (bps), fair value would have decreased by $367,000. Sales Proceeds: Amount of comparable TDPRV ​ $67.5 million to $350 million ($100 million) ​ $67.5 million to $350.0 million ($100.0 million) ​ If expected cash flows by management considered the lowest amount of market indications for vouchers, FV would have decreased by $1.2 million. Range of Probability for Timing of Cash Flows: ​ 0.39%-41.88% ​ 0.39% - 39.78% ​ If expected cash flows by management considered the scenario with the least amount of indicated value, FV would have decreased by $236,000.
Summary of the fair value and unpaid principal balance for items the Company accounts for under FVO	​ ​ ​ ​ ​ ​ ​ ​ ​ ​ (in thousands) ​ Fair value ​ Unpaid Principal Balance ​ Fair Value Over (Under) Unpaid Principal Balance At March 31, 2022 ​ ​ ​ ​ ​ ​ ​ ​ ​ Hybrid Instrument: ​ ​ ​ ​ ​ ​ ​ ​ ​ Streeterville note ​ $ 8,051 ​ $ 6,221 ​ $ 1,830

Balance Sheet Components (Table

Balance Sheet Components (Tables)	3 Months Ended
	Mar. 31, 2022
Balance Sheet Components
Schedule of inventory	​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31, ​ 2022 2021 (in thousands) ​ (unaudited) ​ ​ ​ Raw Material ​ $ 1,562 ​ $ 1,248 Work in Process ​ ​ 2,422 ​ ​ 2,760 Finished Goods ​ ​ 895 ​ ​ 892 Inventory ​ $ 4,879 ​ $ 4,900
Schedule of property and equipment	​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31, ​ 2022 2021 (in thousands) ​ (unaudited) ​ ​ ​ Land ​ $ 396 ​ $ 396 Lab equipment ​ ​ 478 ​ ​ 403 Clinical equipment ​ 65 ​ 65 Software ​ ​ 63 ​ ​ 63 Furnitures and fixtures ​ ​ 14 ​ ​ 14 Computers and peripherals ​ ​ 7 ​ ​ 7 Total property and equipment at cost ​ 1,023 ​ 948 Accumulated depreciation ​ (423) ​ (298) Property and equipment, net ​ $ 600 ​ $ 650
Schedule of intangible assets	​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31, ​ 2022 2021 (in thousands) ​ (unaudited) ​ ​ ​ Developed technology ​ $ 25,000 ​ $ 25,000 Accumulated developed technology amortization ​ (7,778) ​ (7,361) Developed technology, net ​ 17,222 ​ 17,639 In-process research and development ​ ​ 4,800 ​ ​ 4,800 In process research and development, net ​ 4,800 ​ 4,800 Trademarks ​ 300 ​ 300 Accumulated trademark amortization ​ (93) ​ (88) Trademarks, net ​ 207 ​ 212 Total intangible assets, net ​ $ 22,229 ​ $ 22,651
Schedule of estimated future amortization expense of intangible assets with finite lives	The following table summarized the Company’s estimated future amortization expense of intangible assets with finite lives as of March 31, 2022: ​ ​ ​ ​ (in thousands) Amounts Remainder of 2022 ​ $ 1,265 2023 ​ ​ 1,687 2024 ​ ​ 1,687 2025 ​ ​ 1,687 2026 ​ ​ 1,687 Thereafter ​ ​ 9,416 ​ ​ $ 17,429

Commitments and Contingencies (

Commitments and Contingencies (Tables)	3 Months Ended
	Mar. 31, 2022
Commitments and Contingencies
Schedule of additional details of office space lease	​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31 ​ 2022 ​ 2021 (in thousands) (unaudited) ​ ​ ​ Operating lease - right-of-use asset $ 1,157 ​ $ 1,084 ​ ​ ​ ​ ​ ​ Operating lease liability, current ​ 299 ​ ​ 240 Operating lease liability, net of current portion ​ 921 ​ ​ 919 Total $ 1,220 ​ $ 1,159 ​ ​ ​ ​ ​ ​ Weighted-average remaining life (years) ​ 2.96 ​ ​ 3.21 Weighted-average discount rate ​ 21.80% ​ ​ 21.10%
Schedule of undiscounted cash payment obligations	The following table summarizes the undiscounted cash payment obligations for the operating lease liability as of March 31, 2022: ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31 ​ 2022 ​ 2021 (in thousands) (unaudited) ​ ​ ​ 2022 ​ 403 ​ ​ 463 2023 ​ 542 ​ ​ 518 2024 ​ 557 ​ ​ 534 2025 ​ 107 ​ ​ 89 Total undiscounted operating lease payments ​ 1,609 ​ ​ 1,604 Imputed interest expenses ​ (389) ​ ​ (445) Total operating lease liability ​ 1,220 ​ ​ 1,159 Less: Operating lease liability, current ​ 299 ​ ​ 240 Operating lease liability, net of current portion $ 921 ​ $ 919

Debt (Tables)

Debt (Tables)	3 Months Ended
	Mar. 31, 2022
Debt
Schedule of notes payable	​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31, ​ ​ 2022 2021 (in thousands) ​ (unaudited) ​ ​ ​ Royalty Interest ​ $ 34,151 ​ $ 37,000 Streeterville Note ​ ​ 8,051 ​ ​ 7,818 Insurance Financing ​ ​ — ​ ​ 335 Tempesta Note ​ ​ 300 ​ ​ 350 ​ ​ ​ 42,502 ​ 45,503 Less: unamortized discount and debt issuance costs ​ (10,829) (17,297) Note payable, net of discount ​ $ 31,673 $ 28,206 Notes payable - non-current, net ​ $ 24,783 ​ $ 25,022 Notes payable - current, net ​ $ 6,890 ​ $ 3,184
Schedule of future maturities of notes payable	Future maturities of the notes payable not designated at FVO as of March 31, 2022 are as follows: ​ ​ ​ ​ (in thousands) ​ Amounts As of March 31, ​ ​ ​ 2023 ​ $ 6,890 2024 ​ ​ 12,837 2025 ​ ​ 5,016 2026 ​ ​ 8,100 2027 ​ ​ 1,608 ​ ​ ​ 34,451 Less: unamortized discount and debt issuance costs ​ ​ (14,798) Total ​ $ 19,653

Warrants (Tables)

Warrants (Tables)	3 Months Ended
	Mar. 31, 2022
Warrants
Summary of warrant activity	​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31 ​ ​ 2022 ​ 2021 Warrants outstanding, beginning balance ​ 563,451 ​ 2,401,818 Issuances ​ — ​ 168,750 Exercises ​ — ​ (2,007,117) Expirations and cancelations ​ — ​ - Warrants outstanding, ending balance ​ 563,451 ​ 563,451

Preferred Stock (Tables)

Preferred Stock (Tables)	3 Months Ended
	Mar. 31, 2022
Preferred Stock.
Schedule of convertible preferred stock	At March 31, 2022 and December 31, 2021, preferred stock consisted of the following: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Liquidation ( in thousands, except share and per share data) ​ Shares Issued and Carrying ​ Preference Series ​ Authorized ​ Outstanding ​ Value ​ per Share B-2 ​ ​ 10,165 ​ ​ — ​ $ — ​ $ — C ​ ​ 1,011,000 ​ ​ — ​ ​ — ​ ​ 8.00 Total ​ ​ 1,021,165 ​ ​ — ​ $ — ​ ​ ​

Stockholders' Equity (Tables)

Stockholders' Equity (Tables)	3 Months Ended
	Mar. 31, 2022
Stockholders' Equity
Schedule of common reserved shares of common stock for issuance	​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ ​ 2022 ​ 2021 Options issued and outstanding 2,323,032 2,464,803 Inducement options issued and outstanding ​ 128,072 ​ 38,289 Options available for grant under stock option plans 431,371 631,270 Restricted stock unit awards issued and outstanding 3,462,170 487,456 Warrants issued and outstanding 563,451 563,451 Total 6,908,096 4,185,269

Stock Based Compensation (Table

Stock Based Compensation (Tables)	3 Months Ended
	Mar. 31, 2022
Stock Based Compensation
Summary of incentive plan activity	​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Weighted ​ Weighted Average ​ ​ ​ ​ ​ Shares ​ Stock ​ ​ ​ Average ​ Remaining ​ Aggregate ​ ​ Available ​ Options ​ RSUs ​ Stock Option ​ Contractual Life ​ Intrinsic (in thousands, except share and per share data) for Grant Outstanding Outstanding Exercise Price (Years) Value* Outstanding at December 31, 2021 ​ 631,270 ​ 2,503,075 ​ 487,456 ​ $ 9.44 ​ 8.35 ​ $ 3 Additional shares authorized ​ 2,722,827 ​ — ​ — ​ ​ — ​ ​ ​ ​ — Options granted ​ — ​ — ​ — ​ ​ — ​ ​ ​ ​ — Options exercised ​ — ​ — ​ — ​ ​ — ​ ​ ​ ​ — Options canceled ​ 51,988 ​ (51,988) ​ — ​ ​ 4.01 ​ ​ ​ ​ — RSUs granted ​ (2,974,714) ​ — ​ 2,974,714 ​ ​ — ​ ​ ​ ​ — Outstanding at March 31, 2022 ​ 431,371 ​ 2,451,087 ​ 3,462,170 ​ $ 9.55 ​ 8.07 ​ $ — Exercisable at March 31, 2022 ​ ​ 1,611,407 ​ ​ ​ $ 12.02 7.64 ​ $ — Vested and expected to vest at ​ ​ 2,349,585 ​ ​ ​ $ 9.74 8.03 ​ $ — ​ *Fair market value of JAGX common stock on March 31, 2022 was $0.71 per share.
Summary of stock-based compensation expense	​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ ​ ​ March 31, ​ (in thousands) 2022 2021 ​ Research and development expense ​ $ 348 ​ $ 164 ​ Sales and marketing expense ​ 82 ​ 52 ​ General and administrative expense ​ 633 ​ 418 ​ Total ​ $ 1,063 ​ $ 634 ​
Employee stock options
Stock Based Compensation
Schedule of estimated grant-date fair value of stock options calculated using the Black-Scholes option-pricing model	​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ ​ March 31, ​ 2022 2021 Volatility ​ — ​ 163.8 - 164.0 % Expected term (years) ​ — 5.0 Risk-free interest rate ​ — 0.5 - 0.9 % Expected dividend yield ​ — ​ —

Net Loss Per Share (Tables)

Net Loss Per Share (Tables)	3 Months Ended
	Mar. 31, 2022
Net Loss Per Share
Schedule of calculation of basic and diluted net loss per common share	​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended March 31, (In thousands, except share and per share data) 2022 2021 ​ ​ ​ Net loss attributable to common shareholders (basic and diluted) ​ $ (17,986) ​ $ (12,009) Shares used to compute net loss per common share, basic and diluted ​ ​ 44,711,588 ​ ​ 42,635,466 Net loss per share attributable to common shareholders, basic and diluted ​ $ (0.40) ​ $ (0.28)
Schedule of common stock equivalents excluded from the calculation of diluted net loss per common share	​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31, ​ 2022 ​ 2021 Options issued and outstanding ​ 2,323,032 ​ 2,464,803 Inducement options issued and outstanding ​ 128,072 ​ 38,289 Restricted stock units issued and outstanding ​ 3,462,170 ​ 487,456 Warrants issued and outstanding ​ 563,451 ​ 563,451 Total ​ 6,476,725 ​ 3,553,999

Segment Information (Tables)

Segment Information (Tables)	3 Months Ended
	Mar. 31, 2022
Segment Information
Schedule of reportable segments net revenue and net loss	​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended ​ ​ March 31, (in thousands) 2022 2021 Revenue from external customers ​ ​ Human Health ​ $ 2,605 ​ $ 1,208 Animal Health ​ 20 ​ 33 Consolidated Totals ​ $ 2,625 ​ $ 1,241 ​ ​ ​ ​ ​ ​ ​ Segment net loss ​ ​ Human Health ​ $ (9,967) ​ $ (3,941) Animal Health ​ (8,197) ​ (8,068) Consolidated Totals ​ $ (18,164) ​ $ (12,009)
Schedule of reportable segments assets	​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31, (in thousands) 2022 2021 Segment assets ​ ​ Human Health ​ $ 38,880 ​ $ 42,250 Animal Health ​ 121,467 ​ 115,580 Total ​ $ 160,347 ​ $ 157,830
Schedule of reconciliation of segments assets to the consolidated assets	​ ​ ​ ​ ​ ​ ​ ​ ​ ​ March 31, ​ December 31, (in thousands) 2022 2021 Total assets for reportable segments ​ $ 160,347 ​ $ 157,830 Less: Investment in subsidiary ​ (29,232) ​ (29,232) Less: Intercompany loan ​ (78,209) ​ (75,333) Consolidated Totals ​ $ 52,906 ​ $ 53,265

Organization and Business - Nas

Organization and Business - Nasdaq Communication and Compliance (Details) $ / shares in Units, $ in Millions	Feb. 17, 2022USD ($)$ / shares
Consecutive business days	30 days
Share issue price (in dollars per share)	$ 1
Grace period	180 days
Second grace period	180 days
Minimum
Consecutive business days	10 days
Share issue price (in dollars per share)	$ 1
Consideration of an extension | $	$ 5
Maximum
Share issue price (in dollars per share)	$ 1

Organization and Business - Liq

Organization and Business - Liquidity and Going Concern (Details) - USD ($) $ in Thousands	Mar. 31, 2022	Dec. 31, 2021
Organization and Business
Accumulated deficit	$ (237,480)	$ (219,494)

Organization and Business - Rev

Organization and Business - Reverse Stock Split (Details)	Sep. 03, 2021
Organization and Business
Reverse stock split ratio	33.33

Summary of Significant Accoun_4

Summary of Significant Accounting Policies - Accounts receivable and Concentrations (Details) - item	3 Months Ended		12 Months Ended
	Mar. 31, 2022	Mar. 31, 2021	Dec. 31, 2021
Supplier risk
Concentrations
Number of suppliers	2
Total net revenue | Customer risk | Customer 1
Concentrations
Concentration risk (as a percentage)		86.00%
Total net revenue | Customer risk | Customer 2
Concentrations
Concentration risk (as a percentage)	34.00%	10.00%
Total net revenue | Customer risk | Customer 3
Concentrations
Concentration risk (as a percentage)	49.00%
Total net revenue | Customer risk | Two major pharmaceutical distributors
Concentrations
Number of major distributors		2
Total net revenue | Customer risk | Three major pharmaceutical distributors
Concentrations
Number of major distributors	3
Total net revenue | Customer risk | Customer 4
Concentrations
Concentration risk (as a percentage)	10.00%
Total net revenue | Customer risk | Minimum | Customer 1
Concentrations
Concentration risk (as a percentage)	10.00%
Total accounts receivable | Credit risk | Customer 1
Concentrations
Concentration risk (as a percentage)			16.00%
Total accounts receivable | Credit risk | Customer 2
Concentrations
Concentration risk (as a percentage)	34.00%		37.00%
Total accounts receivable | Credit risk | Customer 3
Concentrations
Concentration risk (as a percentage)	52.00%		37.00%

Summary of Significant Accoun_5

Summary of Significant Accounting Policies - Property and Equipment and Indefinite-lived Intangible Assets (Details) - USD ($) $ in Thousands	3 Months Ended
	Mar. 31, 2022	Mar. 31, 2021
Goodwill impairment charges
Impairment of long-lived assets	$ 0	$ 0
Impairment of indefinite-lived intangible assets	$ 0	$ 0
Napo Member | Equipment | Minimum
Goodwill
Estimated useful lives	3 years
Napo Member | Equipment | Maximum
Goodwill
Estimated useful lives	10 years

Summary of Significant Accoun_6

Summary of Significant Accounting Policies - Leases (Details)	Jan. 25, 2022EUR (€)	Dec. 24, 2021USD ($)	Dec. 22, 2021EUR (€)	Oct. 07, 2021EUR (€)	Apr. 06, 2021USD ($)ft²	Aug. 31, 2020USD ($)ft²	Mar. 31, 2022USD ($)	Dec. 31, 2021USD ($)
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Operating lease - right-of-use asset							$ 1,157,000	$ 1,084,000
Lease liabilities							1,220,000	$ 1,159,000
Monthly base rents	€ 4,000	$ 21,000
Total deposit paid | €	9,000
If contracts are terminated within 12 months
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Monthly base rents | €	€ 3,817
Office space sub lease
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Sub lease rent						$ 15,000
Operating lease - right-of-use asset							0
Lease liabilities							$ 0
Area (in square feet) | ft²					10,526	5,263
Monthly base rent for first twelve months					$ 42,000
Monthly base rent for subsequent twelve months					43,000
Monthly base rent for final months					$ 45,000
Extension period					3 years
Lease term					3 years
Leased office premises | Copernico Centrale agreement
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Monthly base rents | €				€ 10,000
Extension period				20 months
Total deposit paid | €				€ 20,000
Leased vehicle | Arval Service Lease Italia Spa agreement
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Monthly base rents | €			€ 2,000
Lease term			48 months
Total deposit paid | €			€ 19,000

Summary of Significant Accoun_7

Summary of Significant Accounting Policies - Revenue Recognition (Details)	3 Months Ended
	Mar. 31, 2022USD ($)contractitem	Mar. 31, 2021USD ($)
Disaggregation of Product Revenue
Number of contracts | contract	2
Number of specialty pharmacies. | item	2
Number of portfolio of contract | contract	1
Mytesi
Disaggregation of Product Revenue
Product revenue	$ 438,000	$ 1,200,000
Mytesi | Specialty Pharmacies
Disaggregation of Product Revenue
Product revenue	2,200,000	479,000
Neonorm
Disaggregation of Product Revenue
Product revenue	$ 20,000	$ 33,000

Summary of Significant Accoun_8

Summary of Significant Accounting Policies - Revenue Recognition - Collaboration Revenue (Details) - USD ($) $ in Thousands	Sep. 03, 2020	Sep. 24, 2018	Mar. 31, 2022	Mar. 31, 2021
Stockholders' Equity
License agreement term (in years)	2 years 6 months
Collaboration revenue			$ 0	$ 0
Knight
Stockholders' Equity
License agreement term (in years)		15 years
Transfer price receivable upon achievement of certain regulatory and sales milestones		$ 18,000

Napo Therapeutics Subsidiary (D

Napo Therapeutics Subsidiary (Details)	Nov. 03, 2021
Napo Therapeutics Subsidiary
Percentage of equity owned by parent	99.00%

Fair Value Measurements - Fair

Fair Value Measurements - Fair Value of Liabilities Measured on a Recurring Basis (Details) - USD ($) $ in Thousands	Mar. 31, 2022	Dec. 31, 2021	Jan. 13, 2021
Fair value of liabilities measured on a recurring basis
Warrant liability	$ 1	$ 1
Fair value	8,051	7,800
Total fair value	8,052	7,117
Level 3
Fair value of liabilities measured on a recurring basis
Warrant liability	1	1
Total fair value	8,052	7,117
Streeterville Note
Fair value of liabilities measured on a recurring basis
Fair value	8,051	7,117	$ 6,000
Streeterville Note | Level 3
Fair value of liabilities measured on a recurring basis
Fair value	$ 8,051	$ 7,117

Fair Value Measurements - Estim

Fair Value Measurements - Estimated fair value of Level 3 (Details) - Level 3 - Recurring $ in Thousands	3 Months Ended
	Mar. 31, 2022USD ($)
Warrant liability
Fair Value, Liabilities Measured on Recurring Basis, Unobservable Input Reconciliation, Calculation [Roll Forward]
Beginning fair value of Level 3 liability	$ 1
Ending fair value of level 3 liability	1
Streeterville Note
Fair Value, Liabilities Measured on Recurring Basis, Unobservable Input Reconciliation, Calculation [Roll Forward]
Beginning fair value of Level 3 liability	7,818
Change in fair value	233
Ending fair value of level 3 liability	$ 8,051

Fair Value Measurements - Est_2

Fair Value Measurements - Estimated Fair Value of Warrant Liability (Details)	3 Months Ended
	Mar. 31, 2022USD ($)$ / sharesshares	Dec. 31, 2021USD ($)$ / shares	Jul. 23, 2019$ / shares
Series A Warrants | Stock price
Fair Value Assumptions and Methodology for Assets and Liabilities
Warrant liability | $ / shares	0.71	1.04
Series A Warrants | Strike price
Fair Value Assumptions and Methodology for Assets and Liabilities
Warrant liability | $ / shares	2,363	2,363
Series A Warrants | Expected life
Fair Value Assumptions and Methodology for Assets and Liabilities
Weighted-average expected term (years)	1 month 28 days	4 months 28 days
Series A Warrants | Volatility
Fair Value Assumptions and Methodology for Assets and Liabilities
Warrant liability	108	89
Series A Warrants | Risk free rate
Fair Value Assumptions and Methodology for Assets and Liabilities
Warrant liability	0.34	0.19
Underwriter Warrants
Fair Value Assumptions and Methodology for Assets and Liabilities
Fair value of warrant	$ 0	$ 1,000
Underwriter Warrants | Stock price
Fair Value Assumptions and Methodology for Assets and Liabilities
Warrant liability | $ / shares	0.71	1.04
Underwriter Warrants | Strike price
Fair Value Assumptions and Methodology for Assets and Liabilities
Warrant liability | $ / shares	158	158
Underwriter Warrants | Expected life
Fair Value Assumptions and Methodology for Assets and Liabilities
Weighted-average expected term (years)	1 year 6 months 3 days	1 year 9 months
Underwriter Warrants | Volatility
Fair Value Assumptions and Methodology for Assets and Liabilities
Warrant liability	175	180
Underwriter Warrants | Risk free rate
Fair Value Assumptions and Methodology for Assets and Liabilities
Warrant liability	1.96	0.65
2019 Bridge Note Warrants | Strike price
Fair Value Assumptions and Methodology for Assets and Liabilities
Warrant liability | $ / shares	1.47	1.47	6
Warrant liability | Recurring | Level 3
Fair Value Assumptions and Methodology for Assets and Liabilities
Fair value of warrant	$ 1,000	$ 1,000
Warrant liability | Series A Warrants
Fair Value Assumptions and Methodology for Assets and Liabilities
Fair value of warrant	0	0
Change in fair value	0
Warrant liability | Series 3 warrants
Fair Value Assumptions and Methodology for Assets and Liabilities
Fair value of warrant	$ 0	0
Warrants exercised | shares	206,915
Warrants conversion | shares	1
Aggregate fair value of the common stocks issued by the exercise of Warrants	$ 1,800,000
Warrant liability | Underwriter Warrants
Fair Value Assumptions and Methodology for Assets and Liabilities
Fair value of warrant	0	$ 1,000
Change in fair value	$ 0

Fair Value Measurements - Stree

Fair Value Measurements - Streeterville Note (Details) - USD ($) $ in Thousands	Mar. 31, 2022	Dec. 31, 2021	Jan. 13, 2021
Fair value of liabilities measured on a recurring basis
Fair value	$ 8,051	$ 7,800
Streeterville Note
Fair value of liabilities measured on a recurring basis
Fair value	$ 8,051	$ 7,117	$ 6,000

Fair Value Measurements - Quant

Fair Value Measurements - Quantitative information about the significant unobservable inputs (Details) - Level 3	3 Months Ended	12 Months Ended
	Mar. 31, 2022USD ($)	Dec. 31, 2021USD ($)
Discount rate | Minimum
Fair Value Measurement Inputs and Valuation Techniques [Line Items]
Probability (as a percent)	7.29	6.56
Basis point for adjustment of discount rate	1
Fair value increase (decrease)	$ (367,000)
Discount rate | Maximum
Fair Value Measurement Inputs and Valuation Techniques [Line Items]
Probability (as a percent)	21.82	22
Basis point for adjustment of discount rate	1
Fair value increase (decrease)	$ 367,000
Discount rate | Weighted average
Fair Value Measurement Inputs and Valuation Techniques [Line Items]
Probability (as a percent)	21.82	21.09
Sale Proceeds | Minimum
Fair Value Measurement Inputs and Valuation Techniques [Line Items]
Amount of comparable TDPRV	$ 67,500,000	$ 67,500,000
Fair value increase (decrease)	(1,200,000)
Sale Proceeds | Maximum
Fair Value Measurement Inputs and Valuation Techniques [Line Items]
Amount of comparable TDPRV	350,000,000	350,000,000
Fair value increase (decrease)	9,500,000
Sale Proceeds | Weighted average
Fair Value Measurement Inputs and Valuation Techniques [Line Items]
Amount of comparable TDPRV	$ 100,000,000	$ 100,000,000
Timing of Cash Flows | Minimum
Fair Value Measurement Inputs and Valuation Techniques [Line Items]
Probability (as a percent)	0.39	0.39
Fair value increase (decrease)	$ (236,000)
Timing of Cash Flows | Maximum
Fair Value Measurement Inputs and Valuation Techniques [Line Items]
Probability (as a percent)	41.88	39.78
Fair value increase (decrease)	$ 2,300,000

Fair Value Measurements - Fai_2

Fair Value Measurements - Fair Value Option - Hybrid Instruments (Details) - USD ($) $ in Thousands	Mar. 31, 2022	Dec. 31, 2021
Fair Value Measurements
Notes payable, net of current portion (includes hybrid instrument designated at Fair Value Option)	$ 8,051	$ 7,800
Unpaid Principal Balance	6,221
Fair Value Over (Under) Unpaid Prepaid Balance	$ 1,830

Balance Sheet Components - Inve

Balance Sheet Components - Inventory (Details) - USD ($) $ in Thousands	Mar. 31, 2022	Dec. 31, 2021
Inventory, Gross [Abstract]
Raw Material	$ 1,562	$ 1,248
Work in Process	2,422	2,760
Finished Goods	895	892
Inventory	$ 4,879	$ 4,900

Balance Sheet Components - Prop

Balance Sheet Components - Property and Equipment (Details) - USD ($)	3 Months Ended
	Mar. 31, 2022	Mar. 31, 2021	Dec. 31, 2021
Land, Property and Equipment
Total property and equipment at cost	$ 1,023,000		$ 948,000
Accumulated depreciation	(423,000)		(298,000)
Property and equipment, net	600,000		650,000
Depreciation and amortization expense	8,000	$ 9,000
Land
Land, Property and Equipment
Total property and equipment at cost	396,000		396,000
Lab equipment
Land, Property and Equipment
Total property and equipment at cost	478,000		403,000
Clinical equipment
Land, Property and Equipment
Total property and equipment at cost	65,000		65,000
Software
Land, Property and Equipment
Total property and equipment at cost	63,000		63,000
Furniture and fixtures
Land, Property and Equipment
Total property and equipment at cost	14,000		14,000
Computers and peripherals
Land, Property and Equipment
Total property and equipment at cost	$ 7,000		$ 7,000

Balance Sheet Components - Inta

Balance Sheet Components - Intangible assets (Details) - USD ($)	3 Months Ended
	Mar. 31, 2022	Dec. 31, 2021
Intangible assets
Finite-lived intangible assets, net	$ 17,429,000
Total intangible assets, net	22,229,000	$ 22,651,000
Amortization expense	418,000
Developed technology
Intangible assets
Total intangible assets	25,000,000	25,000,000
Accumulated amortization	(7,778,000)	(7,361,000)
Finite-lived intangible assets, net	17,222,000	17,639,000
In process research and development
Intangible assets
Total intangible assets	4,800,000	4,800,000
Finite-lived intangible assets, net	4,800,000	4,800,000
Trademarks
Intangible assets
Total intangible assets	300,000	300,000
Accumulated amortization	(93,000)	(88,000)
Finite-lived intangible assets, net	$ 207,000	$ 212,000

Balance Sheet Components - Esti

Balance Sheet Components - Estimated future amortization expense (Details) $ in Thousands	Mar. 31, 2022USD ($)
Balance Sheet Components
Remainder of 2022	$ 1,265
2023	1,687
2024	1,687
2025	1,687
2026	1,687
Thereafter	9,416
Finite-lived intangible assets, net	$ 17,429

Related Party Transactions - Ma

Related Party Transactions - Management Services Agreement (Details) - Sagard Capital Partners, L.P. - USD ($)	Sep. 01, 2020	Mar. 31, 2018	Mar. 31, 2022	Mar. 31, 2021	Dec. 31, 2021
Related Party Transaction [Line Items]
Consulting and management advisory services fees		$ 450,000
Maximum aggregate payments for consulting and management advisory services received		$ 1,400,000
Issuance of common stock in exchange for services (in shares)	2,289,474
Accrued consulting and management fees	$ 1,100,000
Management fee incurred			$ 0	$ 225,000
Payable amount			$ 0		$ 0

Related Party Transactions - Le

Related Party Transactions - Letter of Credit (Details)	3 Months Ended
	Mar. 31, 2022USD ($)
Board of directors
Related party Transactions
Payment of compensation	$ 35,000

Commitments and Contingencies -

Commitments and Contingencies - Commitments (Details)	Jan. 25, 2022EUR (€)	Dec. 24, 2021USD ($)	Dec. 22, 2021EUR (€)	Oct. 07, 2021EUR (€)	Apr. 06, 2021USD ($)ft²	Aug. 31, 2020USD ($)ft²	Aug. 28, 2018USD ($)ft²shares	Mar. 31, 2022USD ($)	Mar. 31, 2021USD ($)
Commitments and Contingencies
Standby letter of credit received as collateral							$ 475,000
Term							5 years
Warrants to purchase (in shares) | shares							9,580
Lease expense under non-cancelable operating lease	€ 4,000	$ 21,000
Cash paid for operating lease liabilities recognized under operating cash flows								$ 105,260	$ 0
Total deposit paid | €	9,000
General and administrative expense
Commitments and Contingencies
Lease expense under non-cancelable operating lease								0	60,000
Lease cost								104,000	0
If contracts are terminated within 12 months
Commitments and Contingencies
Lease expense under non-cancelable operating lease | €	€ 3,817
Office lease extension agreement
Commitments and Contingencies
Area (in square feet) | ft²							6,311
Office space sub lease
Commitments and Contingencies
Area (in square feet) | ft²					10,526	5,263
Sub lease rent						$ 15,000
Remaining commitment								0
Extension period					3 years
Lease term					3 years
Monthly base rent for first twelve months					$ 42,000
Monthly base rent for subsequent twelve months					43,000
Monthly base rent for final months					$ 45,000
Short-term office lease in Milan, Italy | General and administrative expense
Commitments and Contingencies
Lease expense under non-cancelable operating lease								$ 42,000	$ 0
Copernico Centrale agreement | Leased office premises
Commitments and Contingencies
Lease expense under non-cancelable operating lease | €				€ 10,000
Extension period				20 months
Total deposit paid | €				€ 20,000
Arval Service Lease Italia Spa agreement | Leased vehicle
Commitments and Contingencies
Lease expense under non-cancelable operating lease | €			€ 2,000
Lease term			48 months
Total deposit paid | €			€ 19,000

Commitments and Contingencies_2

Commitments and Contingencies - Additional details of office space lease (Details) - USD ($) $ in Thousands	Mar. 31, 2022	Dec. 31, 2021
Commitments and Contingencies
Operating lease - right-of-use asset	$ 1,157	$ 1,084
Operating lease liability, current	299	240
Operating lease liability, net of current portion	921	919
Total	$ 1,220	$ 1,159
Weighted-average remaining life (years)	2 years 11 months 15 days	3 years 2 months 15 days
Weighted-average discount rate	21.80%	21.10%

Commitments and Contingencies_3

Commitments and Contingencies - Undiscounted cash payment obligation (Details) - USD ($) $ in Thousands	Mar. 31, 2022	Dec. 31, 2021
Commitments and Contingencies
Remainder of 2022	$ 403	$ 463
2023	542	518
2024	557	534
2025	107	89
Total undiscounted operating lease payments	1,609	1,604
Imputed interest expenses	(389)	(445)
Total	1,220	1,159
Operating lease liability, current	299	240
Operating lease liability, net of current portion	$ 921	$ 919

Commitments and Contingencies_4

Commitments and Contingencies - Purchase Commitment (Details)	Sep. 03, 2020kg
Purchase Commitment
License agreement term (in years)	2 years 6 months
Agreement extension term	2 years
Manufacturing and Supply Agreement with Glenmark Life Sciences Limited [Member]
Purchase Commitment
License termination term option	12 months
License termination activated upon written notice of material breach of Agreement	90 days
Manufacturing and Supply Agreement with Glenmark Life Sciences Limited [Member] | Minimum
Purchase Commitment
Number of kilograms of crofelemer per year per agreement	300

Commitments and Contingencies_5

Commitments and Contingencies - Master Services Agreement (Details) - USD ($)	Mar. 31, 2022	Dec. 31, 2021	Mar. 31, 2021	Oct. 05, 2020
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Lease liabilities	$ 1,220,000	$ 1,159,000
Master Services Agreement With Integrium LLC, 2019
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Lease liabilities	0
Master Services Agreement With Integrium LLC, 2020
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Lease liabilities	$ 275,911		$ 770,911
Master Services Agreement With Integrium LLC, 2020 | Maximum
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Consideration payable on achievement of milestones				$ 12,400,000

Commitments and Contingencies_6

Commitments and Contingencies - Asset Transfer and Transition Commitment Update (Details) - USD ($)	Sep. 25, 2017	Mar. 31, 2022	Mar. 31, 2021
Commitments and Contingencies
Percentage of amount received to be paid to Glenmark	25.00%
Maximum amount to be received by Glenmark	$ 7,000,000
Payments to Glenmark		$ 559,000	$ 0

Commitments and Contingencies_7

Commitments and Contingencies - Revenue Sharing Commitment Update and Legal Proceedings (Details) - USD ($)	May 27, 2021	Aug. 02, 2019	Dec. 14, 2017	Mar. 31, 2022
Long-term Purchase Commitment [Line Items]
Damages awarded		$ 2,600,000
Insurance proceeds directly related to the recognized loss	$ 0
SEED
Long-term Purchase Commitment [Line Items]
Percentage of revenue sharing commitment			15.00%
Percentage of revenue sharing commitment after first million dollars of revenue			20.00%
Payments made to date to SEED				$ 0

Commitments and Contingencies_8

Commitments and Contingencies - Settlement of Underwriter Fee (Details) - USD ($)	1 Months Ended	12 Months Ended
	Aug. 31, 2018	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018	Aug. 28, 2018
Number of pre-funded warrants issued		168,750
Convertible preferred stock						9,580
Underwriters' over-allotment option
Underwriters settlement fee	$ 387,000
Payments of underwriters settlement fee			$ 185,000	$ 202,000
Number of pre-funded warrants issued					365
Convertible preferred stock			33,593
Exercise price (in dollars per share)			$ 7.50
Issuance of common stock (In shares)			33,333
Amount of shares issued			$ 45,000

Debt - Notes Payable (Details)

Debt - Notes Payable (Details) - USD ($)	Mar. 31, 2022	Dec. 31, 2021	Oct. 31, 2019
Notes payable
Notes payable - non-current, net	$ 24,783,000	$ 25,022,000
Notes payable - current, net	6,890,000	3,184,000
Notes payable
Notes payable
Principal amount of debt	42,502,000	45,503,000
Less: unamortized discount and debt issuance costs	(10,829,000)	(17,297,000)
Notes payable, net of discount	31,673,000	28,206,000
Notes payable - non-current, net	24,783,000	25,022,000
Notes payable - current, net	6,890,000	3,184,000
Royalty Interest | Notes payable
Notes payable
Principal amount of debt	34,151,000	37,000,000
Streeterville Note | Notes payable
Notes payable
Principal amount of debt	8,051,000	7,818,000
Insurance Premium Financing | Notes payable
Notes payable
Principal amount of debt		335,000
Tempesta Note
Notes payable
Principal amount of debt			$ 550,000
Tempesta Note | Notes payable
Notes payable
Principal amount of debt	$ 300,000	$ 350,000

Debt - Notes Payable - Future M

Debt - Notes Payable - Future Maturities (Details) - USD ($) $ in Thousands	Mar. 31, 2022	Dec. 31, 2021
Notes payable
Years ended March 31,
Less: unamortized discount and debt issuance costs	$ (10,829)	$ (17,297)
Notes payable, net of discount	31,673	$ 28,206
Future maturities of the notes payable not designated at FVO
Years ended March 31,
2023	6,890
2024	12,837
2025	5,016
2026	8,100
2027	1,608
Total	34,451
Less: unamortized discount and debt issuance costs	(14,798)
Notes payable, net of discount	$ 19,653

Debt - Sale of Future Royalty I

Debt - Sale of Future Royalty Interest (Details) - USD ($)	Mar. 09, 2022	Mar. 04, 2022	Mar. 02, 2022	Feb. 22, 2022	Apr. 13, 2021	Mar. 08, 2021	Dec. 22, 2020	Nov. 13, 2020	Oct. 31, 2020	Oct. 08, 2020	Jan. 31, 2021	Mar. 31, 2022	Mar. 31, 2021	Dec. 31, 2021	Jan. 13, 2021	Dec. 31, 2020	Nov. 01, 2020	Oct. 31, 2019
Debt Instrument [Line Items]
Gain (Loss) on extinguishment of debt											$ 753,000	$ (2,815,000)	$ (753,000)
Iliad
Debt Instrument [Line Items]
Royalty Expense	$ 700,000	$ 800,000	$ 1,100,000	$ 2,400,000	$ 3,000,000
Issuance of common stock (In shares)	1,850,000	2,000,000	2,425,000	1,733,750	588,235
Tempesta Note
Debt Instrument [Line Items]
Principal amount																		$ 550,000
Principal amount of debt																		$ 550,000
Carrying value of notes												300,000		$ 350,000
Streeterville Note
Debt Instrument [Line Items]
Principal amount															$ 6,200,000
Aggregate purchase price															$ 6,000,000
October 2020 Purchase Agreement
Debt Instrument [Line Items]
Royalty interest										$ 12,000,000
Payments for Royalties										12,000,000
Royalty payments due									$ 6,000,000
Aggregate purchase price										$ 6,000,000
Percentage of net sales										10.00%
Percentage of worldwide revenues										10.00%
Minimum Volume Weighted Average Price									$ 0.9105								$ 0.9105
Additional Royalty Financings Committed								$ 6,000,000
Carrying value of notes												$ 8,300,000		6,300,000
Gain (Loss) on extinguishment of debt	$ (2,800,000)
Discount rate												45.05%
Interest expense												$ 3,100,000	1,900,000
Royalty discount										$ 6,000,000
Royalty discount rate					77.09%			45.42%		34.51%		74.59%
October 2020 Purchase Agreement | Beginning On April 2021
Debt Instrument [Line Items]
Minimum monthly royalty repayment amount										$ 250,000
October 2020 Purchase Agreement | Beginning On October 2021
Debt Instrument [Line Items]
Minimum monthly royalty repayment amount										400,000
October 2020 Purchase Agreement | Beginning On April 2022
Debt Instrument [Line Items]
Minimum monthly royalty repayment amount										600,000
October 2020 Purchase Agreement | Beginning On October 2022
Debt Instrument [Line Items]
Minimum monthly royalty repayment amount										$ 750,000
December 2020 Purchase Agreement
Debt Instrument [Line Items]
Principal amount																$ 1,000,000
Royalty interest							$ 12,000,000
Aggregate purchase price							$ 6,000,000
Percentage of net sales							10.00%
Percentage of worldwide revenues							10.00%
Minimum monthly royalty repayment amount							$ 750,000
Carrying value of notes												$ 8,000,000		6,300,000
Interest expense												$ 784,000	664,000
Royalty discount							$ 6,000,000
Royalty discount rate							23.70%					23.28%
March 2021 Purchase Agreement [Member]
Debt Instrument [Line Items]
Aggregate purchase price						$ 5,000,000
Percentage of net sales						10.00%
Percentage of worldwide revenues						10.00%
Carrying value of notes												$ 6,100,000		$ 5,800,000
Interest expense												$ 416,000	$ 62,000
Percentage of royalties collected from licenses						50.00%
Threshold price						$ 10,000,000
March 2021 Purchase Agreement [Member] | Beginning on March 2021
Debt Instrument [Line Items]
Royalty interest						10,000,000
Royalty discount						$ 5,000,000
Royalty discount rate						19.36%						19.14%
March 2021 Purchase Agreement [Member] | Beginning On April 2021
Debt Instrument [Line Items]
Minimum monthly royalty repayment amount						$ 250,000
Increase in Royalty Repayment, Percent						5.00%
March 2021 Purchase Agreement [Member] | Beginning On October 2021
Debt Instrument [Line Items]
Minimum monthly royalty repayment amount						$ 400,000
March 2021 Purchase Agreement [Member] | Beginning On April 2022
Debt Instrument [Line Items]
Increase in Royalty Repayment, Percent						10.00%
Royalty Instrument, Debt Instrument Carrying Value						$ 600,000
March 2021 Purchase Agreement [Member] | Beginning On October 2022
Debt Instrument [Line Items]
Minimum monthly royalty repayment amount						$ 750,000

Debt - Streeterville Note (Deta

Debt - Streeterville Note (Details)	Jan. 13, 2021USD ($)	Jul. 01, 2020	Jan. 31, 2021USD ($)	Mar. 31, 2022USD ($)	Mar. 31, 2021USD ($)	Dec. 31, 2021USD ($)
Debt
Proceeds from issuance of notes payable, net of issuance costs of $50					$ 10,975,000
Long-term Debt, Gross				$ 6,221,000
Loss on extinguishment of debt			$ (753,000)	2,815,000	753,000
Cash proceeds					$ 10,975,000
Fair value				8,051,000		$ 7,800,000
Streeterville Note
Debt
Principal amount	$ 6,200,000
Aggregate purchase price	$ 6,000,000
Proceeds from issuance of notes payable, net of issuance costs of $50				$ 6,000,000
Debt Instrument, Term	4 years
Percentage of Return Bonus Payable		1
Percentage of Reduction in Return Bonus			1
Interest rate (as a percent)	3.25%
Term for Initiation of Human Trials			6 months
Percentage of Outstanding Balance Payable the Company Elects to Prepay				112.5
Capped percentage of aggregate default	25.00%
Cash proceeds				$ 6,000,000
Transaction expense				25,000
Fair value				8,100,000		$ 7,800,000
Net increase in the Fair value recorded as loss				$ 233,000
Streeterville Note | Maximum
Debt
Percentage of Gross Proceeds Received from Return Bonus				18
Interest rate (as a percent)	18.00%
Percentage of default effect	15.00%
Streeterville Note | Minimum
Debt
Interest rate (as a percent)				1.00%
Percentage of default effect	5.00%
Accounts Receivable Purchase Agreement | Streeterville Note
Debt
Interest rate (as a percent)	25.00%
Payment Of Transaction Fee	$ 25,000

Debt - Insurance Premium Financ

Debt - Insurance Premium Financing (Details) - USD ($)	1 Months Ended		3 Months Ended
	May 31, 2021	Mar. 31, 2021	Mar. 31, 2022	Mar. 31, 2021	Dec. 31, 2021
Short-term Debt [Line Items]
Interest expense			$ 4,194,000	$ 1,901,000
Financing balance			6,221,000
March 2021 First Insurance Financing
Short-term Debt [Line Items]
Principal amount		$ 98,000		98,000
Unpaid balance		$ 115,000		$ 115,000
Debt term		10 months
Interest rate (as a percent)		4.60%		4.60%
Financing balance			0		$ 10,000
Interest expense		$ 2,000	0	$ 207,000
May 2021 First Insurance Financing
Short-term Debt [Line Items]
Principal amount	$ 1,100,000
Unpaid balance	$ 1,400,000
Interest expense			6,000
Debt term	10 months
Interest rate (as a percent)	4.15%
Financing balance		$ 326,000	$ 0	$ 326,000
Interest expense	$ 21,000

Debt - 2019 Tempesta Notes (Det

Debt - 2019 Tempesta Notes (Details) - USD ($)	1 Months Ended	3 Months Ended
	Oct. 31, 2019	Mar. 31, 2022	Mar. 31, 2021	Dec. 31, 2021
Debt Instrument [Line Items]
Interest expense		$ 4,194,000	$ 1,901,000
Tempesta Note
Debt Instrument [Line Items]
Cash received in the settlement	$ 50,000
Principal amount	$ 550,000
Common stock issued in exchange of debt	13,333
Interest rate (as a percent)	2.50%
Semi-annual principal and interest payments	$ 50,000
Principal amount of debt	$ 550,000
Interest expense		2,000	$ 3,000
Carrying value of notes		$ 300,000		$ 350,000

Debt - Oasis Secured Borrowing

Debt - Oasis Secured Borrowing (Details) - USD ($) $ in Thousands	Mar. 08, 2021	Dec. 31, 2020	May 31, 2020	Mar. 31, 2022	Dec. 31, 2021
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Accounts Receivable, Net, Current				$ 1,795	$ 1,709
Oasis Capital | Oasis Secured Note Tranche 6
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Proceeds from receivables, Gross		$ 1,600
Accounts Receivable, Net, Current		2,200
Accounts receivable gross		3,800
Accumulated chargebacks and discounts on accounts receivable		1,600
Threshold price		$ 1,800
Beginning on March 2021
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Shortfall restoration period	30 days
Accounts Receivable Purchase Agreement | Oasis Capital
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Agreement term			1 year

Debt - 2019 Exchange Notes (Det

Debt - 2019 Exchange Notes (Details)	1 Months Ended				3 Months Ended
	Jan. 31, 2021USD ($)shares	Dec. 31, 2020USD ($)shares	Sep. 30, 2020USD ($)$ / sharesshares	May 31, 2019USD ($)item	Mar. 31, 2022USD ($)shares	Mar. 31, 2021USD ($)	Dec. 31, 2021shares
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Gains (Losses) on Extinguishment of Debt	$ 753,000				$ (2,815,000)	$ (753,000)
Global amendment agreement
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Increase in principal debt (in percent)			5.00%
Increase in principal debt			$ 2,600,000
Incremental value of cash flows			$ 228,000
Global amendment agreement | Series D perpetual preferred stock
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Gains (Losses) on Extinguishment of Debt		$ (1,300,000)
Shares issued (in shares) | shares			842,500
Preferred stock dividend rate (as a percent)			8.00%
Preferred stock dividend payable in arrears			24 months
Fair Value of Stock, Inception			$ 6,400,000
Preferred Stock Redemption Price | $ / shares			$ 8
Shares issued on conversion | shares		5,296,623
Shares converted | shares		859,348
Outstanding | shares					0		0
Global amendment agreement | Series D perpetual preferred stock | Minimum
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Effective interest rate			12.00%
Global amendment agreement | Series D perpetual preferred stock | Maximum
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Effective interest rate			15.00%
December 2020 Purchase Agreement
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Principal amount		$ 1,000,000
Exchange Notes
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Number of Napo convertible notes | item				2
2019 Exchange Note 1
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Common stock issued in exchange of debt | shares		6,740,573
Convertible debt payable		$ 0
Debt Conversion, Converted Instrument, Shares Issued | shares		6,740,573
Gains (Losses) on Extinguishment of Debt		$ (560,000)
Share issued for principal and interest payment | shares		6,740,573
Exchange Note 2
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Principal amount	$ 1,800,000	$ 1,000,000		$ 2,300,000
Interest rate (as a percent)		10.00%
Common stock issued in exchange of debt | shares	471,202	416,666
Convertible debt payable					$ 0
Principal amount of exchange note		$ 5,000,000
Debt Conversion, Converted Instrument, Shares Issued | shares	471,202	416,666
Share issued for principal and interest payment | shares	471,202	416,666
Exchange Note 2 | Global amendment agreement | Series D perpetual preferred stock
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Convertible debt payable			$ 0

Warrants - Warrants outstanding

Warrants - Warrants outstanding and exercisable (Details)	12 Months Ended
	Dec. 31, 2021shares
Warrants
Warrants outstanding, beginning balance	2,401,818
Issuances	168,750
Exercises	(2,007,117)
Warrants outstanding, ending balance	563,451

Warrants - Ladenburg Warrants (

Warrants - Ladenburg Warrants (Details) - $ / shares	Jul. 23, 2019	Mar. 31, 2019	Apr. 30, 2020	Oct. 31, 2018	Aug. 28, 2018
Warrants
Warrants exercisable	927,083
Warrants to purchase (in shares)					9,580
Underwriter Warrants
Warrants
Warrants to purchase (in shares)			33,592	5,713
Exercise price (in dollars per share)			$ 7.50	$ 157.50
March 2019 LOC Warrants
Warrants
Warrants exercisable		15,250
Securities purchase agreement | March 2019 Ladenburg Warrants
Warrants
Warrants to purchase (in shares)		253
Exercise price (in dollars per share)		$ 52.50

Warrants - 2019 Bridge Note War

Warrants - 2019 Bridge Note Warrants (Details)	Jul. 23, 2019$ / sharesshares	Mar. 18, 2019USD ($)	Jul. 31, 2019USD ($)$ / sharesshares	Mar. 31, 2022USD ($)$ / sharesshares	Mar. 31, 2021USD ($)shares	Dec. 31, 2021$ / sharesshares	Dec. 31, 2020shares
Debt
Number Of Promissory Notes Issued | $		21
Warrants exercisable	927,083
Warrants outstanding				563,451		563,451	2,401,818
Class A units | Underwritten Public Offering
Debt
Units issued			962,166
Unit Price | $ / shares			$ 6
Number of warrants converted for each share			1
Class B units | Underwritten Public Offering
Debt
Units issued			10,787
Unit Price | $ / shares			$ 1,000
Class B units | Underwritten Public Offering | Series B convertible preferred stock
Debt
Number of shares in exchange for each unit			1
Number of warrants converted for each share			166
2019 Bridge Note Warrants
Debt
Warrants outstanding				190,622		190,622
2019 Bridge Note Warrants | Strike price
Debt
Warrant liability | $ / shares	6			1.47		1.47
Series 1 warrants
Debt
Warrants issued				2,760,000
Warrants outstanding				145,396		145,396
Number of warrants converted for each share				464,058
Term of warrant			5 years
Exercise price (in dollars per share) | $ / shares			$ 6
Proceeds from issuance of warrants | $				$ 682,000
Series 1 warrants | Strike price
Debt
Warrant liability | $ / shares			6
Series 1 warrants | Class A units
Debt
Common stock issued and issuable			962,166
Warrants issued			962,166
Series 1 warrants | Class A units | Underwritten Public Offering
Debt
Number of shares in exchange for each unit			1
Number of warrants converted for each share			1
Series 1 warrants | Class B units
Debt
Units issued			10,787
Common stock issued and issuable			1,797,833
Series 1 warrants | Class B units | Underwritten Public Offering
Debt
Number of shares issued for preferred stock converted			166
Series 2 warrants
Debt
Warrants issued			2,760,000
Number of warrants converted for each share					1,427,175
Term of warrant			5 years
Exercise price (in dollars per share) | $ / shares			$ 6
Proceeds from issuance of warrants | $					$ 700,000
Series 2 warrants | Strike price
Debt
Warrant liability | $ / shares			6
Series 2 warrants | Expected life
Debt
Warrant liability | $			5
Series 2 warrants | Class A units
Debt
Common stock issued and issuable			962,166
Warrants issued			962,166
Series 2 warrants | Class A units | Underwritten Public Offering
Debt
Number of shares in exchange for each unit			1
Number of warrants converted for each share			1
Series 2 warrants | Class B units
Debt
Units issued			10,787
Common stock issued and issuable			1,797,833
Series 2 warrants | Class B units | Underwritten Public Offering
Debt
Number of shares issued for preferred stock converted			166
May 2020 Modification of the July 2019 Series 2 Warrants and Inducement Offer
Debt
Number of warrants converted for each share				133,730		133,730

Warrants - PIPE Financing Warra

Warrants - PIPE Financing Warrants (Details) - USD ($)	Mar. 31, 2022	Dec. 31, 2021	Apr. 07, 2021	Aug. 28, 2018
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Warrants to purchase (in shares)				9,580
Aggregate purchase price of warrants	$ 1,000	$ 1,000
ELOC Warrants
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Warrants to purchase (in shares)			33,333
Aggregate purchase price of warrants			$ 172,000
Exercise price (in dollars per share)			$ 5.61
Stock price | ELOC Warrants
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Exercise price (in dollars per share)			5.61
Strike price | ELOC Warrants
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Exercise price (in dollars per share)			$ 5.61
Expected life | ELOC Warrants
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Term of warrant			5 years
Volatility | ELOC Warrants
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Warrant liability			156
Risk free rate | ELOC Warrants
Convertible Promissory Notes and Common Stock Warrants [Line Items]
Warrant liability			0.87

Preferred Stock (Details)

Preferred Stock (Details) - $ / shares	Mar. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Class of Stock [Line Items]
Shares Authorized	1,021,165
Series B-2 Preferred Stock
Class of Stock [Line Items]
Shares Authorized	10,165
Outstanding	0	0
Series C perpetual preferred stock
Class of Stock [Line Items]
Shares Authorized	1,011,000	1,011,000	1,011,000
Issued	0	0
Outstanding	0	0
Liquidation Preference per Share	$ 8

Preferred Stock - Series B-2 Co

Preferred Stock - Series B-2 Convertible Preferred Stock (Details) - Series B-2 Preferred Stock	1 Months Ended				12 Months Ended
	Dec. 31, 2020shares	Oct. 31, 2020shares	Jan. 31, 2020shares	Dec. 31, 2019USD ($)$ / sharesshares	Dec. 31, 2019USD ($)$ / sharesshares	Mar. 31, 2022shares	Dec. 31, 2021shares
Number of shares for which unexercised prepaid forward contracts are exercisable				412,074
Shares issued in exchange of convertible preferred stock				231,709
Shares Authorized				10,165	10,165	10,165	10,165
Deemed dividend understatement amount | $				$ 0
Conversion ratio				63	63
Value of shares issued on conversion | $					$ 153.90
Conversion Price (in dollars per share) | $ / shares				$ 2.43	$ 2.43
Shares converted	6,559	975	2,631
Shares issued on conversion	415,403	166,728	166,630
Preferred stock, shares outstanding						0	0

Preferred Stock - Series C Conv

Preferred Stock - Series C Convertible Preferred Stock (Details) - USD ($)	1 Months Ended		3 Months Ended	12 Months Ended
	Oct. 31, 2020	Sep. 30, 2020	Mar. 31, 2022	Dec. 31, 2020	Dec. 31, 2021	Aug. 28, 2018
Number of securities issued on conversion						9,580
Carrying amount in excess of fair value amount				$ 2,500,000
Warrants and Rights Outstanding			$ 1,000		$ 1,000
Series A
Preferred stock, shares outstanding		5,524,926
Series C perpetual preferred stock
Preferred stock, shares outstanding			0		0
Carrying value
Percentage of cumulative stock dividends eligible to receive			10.00%
Number of consecutive months			24 months
Fair value of preferred stock			$ 4,700,000
Iliad | Series C perpetual preferred stock
Number of shares issued for each convertible preferred stock		842,500
Preferred stock, par value (in dollars per share)	$ 0.0003	$ 0.0001
Accreted value		$ 11,200,000
Gross proceeds from the issuance of common stock		2,300,000
Carrying value		$ 2,600,000
Percentage increase in the outstanding balance		5.00%
Exchange Agreement with Iliad
Shares issued on conversion	83,333			2,734,626
Exchange Agreement with Iliad | Series C perpetual preferred stock
Shares converted	285,000			573,810
Pre-funded Warrants | Exchange Agreement with Iliad
Number of securities issued on conversion	2,352,563
Pre-funded Warrants | Exchange Agreement with Iliad | Series C perpetual preferred stock
Warrants and Rights Outstanding				$ 1,000

Stockholders' Equity (Details)

Stockholders' Equity (Details)	Sep. 03, 2021	Mar. 31, 2022Voteshares	Dec. 31, 2021shares	Mar. 31, 2021shares
Shares of common stock reserved for issuance
Options issued and outstanding		2,323,032		2,464,803
Options available for grant under stock option plans		431,371		631,270
RSUs awards issued and outstanding		3,462,170		487,456
Warrants issued and outstanding		563,451		563,451
Total		6,908,096		4,185,269
Number of voting rights entitled for each share of common stock held | Vote		1
Reverse stock split ratio	33.33
2014 Plan
Shares of common stock reserved for issuance
Options issued and outstanding		2,323,032	2,348,076
Options available for grant under stock option plans		87,470	619,480
Minimum
Shares of common stock reserved for issuance
Reverse stock split ratio	0.5
Maximum
Shares of common stock reserved for issuance
Reverse stock split ratio	0.05
Inducement options issued and outstanding
Shares of common stock reserved for issuance
Options issued and outstanding		128,072		38,289
Blank check preferred stock
Shares of common stock reserved for issuance
Common stock, shares authorized		4,475,074
Common Stock
Shares of common stock reserved for issuance
Common stock, shares authorized		204,475,074
Common Stock | Common stock - voting
Shares of common stock reserved for issuance
Common stock, shares authorized		150,000,000	150,000,000
Common Stock | Common stock - non-voting
Shares of common stock reserved for issuance
Common stock, shares authorized		50,000,000	50,000,000
Convertible non-voting common stock
Shares of common stock reserved for issuance
Reverse stock split ratio		1

Stockholders' Equity - Transact

Stockholders' Equity - Transactions with Oasis Capital and Underwritten Public Offering (Details)	Feb. 02, 2022USD ($)	Dec. 10, 2021shares	Apr. 29, 2021USD ($)$ / sharesshares	Jan. 13, 2021USD ($)$ / sharesshares	Oct. 05, 2020USD ($)shares	Apr. 30, 2020USD ($)shares	Mar. 31, 2020USD ($)D$ / sharesshares	Feb. 28, 2021USD ($)	Mar. 31, 2022USD ($)shares	Mar. 31, 2021USD ($)	Dec. 31, 2021USD ($)shares	Feb. 28, 2021shares	May 04, 2022shares	Feb. 17, 2022$ / shares	Apr. 07, 2021$ / sharesshares	Dec. 31, 2020USD ($)	Apr. 15, 2020USD ($)	Mar. 24, 2020USD ($)	Jul. 31, 2019$ / shares	Aug. 28, 2018shares
Stockholders' equity									$ 8,109,000	$ 31,891,000	$ 11,853,000					$ 17,202,000
Number of securities issued on conversion | shares																				9,580
Common stock, shares issued | shares													784,516
Proceeds from exercise of warrants										1,776,000
Share Price | $ / shares														$ 1
Maximum
Share Price | $ / shares														1
Minimum
Share Price | $ / shares														$ 1
Registered Direct Offering
Number of shares offered | shares			2,549,000
Gross proceeds from the issuance of common stock			$ 10.8
Share Price | $ / shares			$ 4.23
Issuance costs			$ 948,000
At The Market Offering
Amount of shares issued									9,110,000	5,365,000
Issuance costs					$ 40,000				83,000	311,000	465,000
October 2020 ATM Agreement
Issuance of common stock (In shares) | shares					1,271,639							669,850
Issuance costs								$ 311,000
Sale of worth of shares					$ 1,300,000			$ 5,400,000
December 2021 ATM Agreement
Gross proceeds from issuance									$ 9,100,000		$ 3,200,000
Issuance of common stock (In shares) | shares									20,046,463		2,261,596
Issuance costs									$ 83,000
December 2021 ATM Agreement | Maximum
Number of shares offered | shares		15,000,000
Amount of shares issued	$ 75,000,000
December 2021 ATM Agreement | Minimum
Amount of shares issued	$ 15,000,000
Series 1 warrants
Exercise price (in dollars per share) | $ / shares																			$ 6
Proceeds from issuance of warrants									$ 682,000
Series 2 warrants
Exercise price (in dollars per share) | $ / shares																			$ 6
Proceeds from issuance of warrants										$ 700,000
Securities purchase agreement | Registered Direct Offering
Issuance of common stock (In shares) | shares				1,479,290
Share Price | $ / shares				$ 10.14
Net proceeds				$ 1,600,000
Proceeds from issuance of warrants				$ 15,000,000
Equity Line of Credit
Gross proceeds from issuance						$ 22,627
Number of securities issued on conversion | shares															33,333
Exercise price (in dollars per share) | $ / shares															$ 5.61
Amount of shares issued							$ 200,000
Term of equity purchase agreement							36 months
Shares issued in settlement of commitment fee | shares						22,935
Fair value of equity issued						$ 33,027
Equity Line of Credit | Maximum
Price per share | $ / shares															9
Par value (per share) | $ / shares															10.35
Aggregate amount of put option on any put date or clearing date							$ 500,000
Aggregate amount of equity purchase agreement							$ 2,000,000
Equity Line of Credit | Minimum
Price per share | $ / shares															1.31
Par value (per share) | $ / shares															$ 1.50
Option 1 Put | Equity Line of Credit
Issuance of common stock (In shares) | shares						17,333	66,666
Percentage of average trading volume							20.00%
Trading days | D							10
Share Price | $ / shares							$ 1.31
Option 2 Puts | Equity Line of Credit
Percentage of average trading volume							10.00%
Share Price | $ / shares							$ 1.31
Option 1 and Option 2 Puts | Equity Line of Credit
Stockholders' equity																	$ 0
Derivative Asset, Noncurrent																		$ 0

Stockholders' Equity - Subscrip

Stockholders' Equity - Subscription Agreement (Details) - Subscription Agreement with SPAC € / shares in Units, € in Millions	Nov. 03, 2021shares	Jun. 01, 2021USD ($)	Jun. 01, 2021EUR (€)USD ($)€ / sharesshares
Stockholders' Equity
Number of ordinary shares | $			1
Proceeds from issuance of warrants | €			€ 8.8
Proceeds from Issuance of Common Stock | $		$ 10,800,000
Number of warrants converted for each share | shares			1
Exercise price (in dollars per share) | € / shares			€ 10
Term of anniversary of consummation of business combination		10 years	10 years
Term of anniversary of listing		5 years	5 years
Issuance of common stock (In shares) | shares	883,000

Stockholders' Equity- September

Stockholders' Equity- September 2021 PIPE Financing (Details) - USD ($)	3 Months Ended
	Mar. 31, 2022	Dec. 31, 2021
Stockholders' Equity
Noncontrolling interest	$ 64,000	$ 242,000
Decrease in noncontrolling interest	$ 178,000
September 2021 PIPE Financing
Stockholders' Equity
Stock Issued During Period, Shares, New Issues	309,242
Proceeds from Issuance of Private Placement	$ 776,197
Shares Issued, Price Per Share	$ 2.51

Stock Based Compensation - Summ

Stock Based Compensation - Summary of Stock Incentive Plans (Details) - USD ($)	Jun. 16, 2020	May 12, 2015	Mar. 31, 2022	Mar. 31, 2021	Dec. 31, 2021	Feb. 17, 2022
Stock Based Compensation
Incentive stock option term		10 years
Option outstanding			2,323,032	2,464,803
Options available for grant under stock option plans			431,371	631,270
Shares Available for Grant
Ending balance (in shares)			431,371	631,270
Stock Options Outstanding
Options cancelled (in shares)			(2,974,714)
Ending balance (in shares)			2,323,032	2,464,803
RSUs Outstanding
Ending balance (in shares)			3,462,170	487,456
Options vested, exercisable and expected to vest
Share Price						$ 1
Weighted average grant date fair value of stock options granted (in dollars per share)			$ 0	$ 5.28
Number of options vested (in shares)			188,924	127,806
Weighted average fair value of options vested on grant date			$ 4.45	$ 4.95
Common Stock, Capital Shares Reserved for Future Issuance			6,908,096	4,185,269
Stock options
Stock Based Compensation
Option outstanding			2,451,087		2,503,075
Stock Options Outstanding
Beginning balance (in shares)			2,503,075
Options exercised (in shares)			0	0
Options cancelled (in shares)			(51,988)
Ending balance (in shares)			2,451,087		2,503,075
Weighted Average Stock Option Exercise Price
Beginning balance (in dollars per share)			$ 9.44
Options cancelled (in dollars per share)			4.01
Ending balance (in dollars per share)			$ 9.55		$ 9.44
Weighted Average Remaining Contractual Life (Years)
Weighted Average Remaining Contractual Life (Years)			8 years 25 days		8 years 4 months 6 days
Options vested, exercisable and expected to vest
Options vested and exercisable (in shares)			1,611,407
Options vested and exercisable (in dollars per share)			$ 12.02
Options vested and exercisable (in years)			7 years 7 months 20 days
Options vested and expected to vest (in shares)			2,349,585
Options vested and expected to vest (in dollars per share)			$ 9.74
Options vested and expected to vest (in years)			8 years 10 days
Options exercised (in shares)			0	0
Aggregate Intrinsic Value ,outstanding					$ 3,000
Stock options and RSUs
Stock Based Compensation
Options available for grant under stock option plans			431,371		631,270
Shares Available for Grant
Beginning balance (in shares)			631,270
Additional shares authorized (in shares)			2,722,827
Options cancelled (in shares)			51,988
Ending balance (in shares)			431,371		631,270
Restricted stock units issued and outstanding
RSUs Outstanding
Beginning balance (in shares)			487,456
RSUs Granted (in shares)			2,974,714
Ending balance (in shares)			3,462,170		487,456
2013 Plan
Stock Based Compensation
Option shares outstanding			123		123
2013 Plan | Stock options
Stock Options Outstanding
Options granted (in shares)			0
2014 Plan
Stock Based Compensation
Option outstanding			2,323,032		2,348,076
Options available for grant under stock option plans			87,470		619,480
Shares Available for Grant
Beginning balance (in shares)			619,480
Ending balance (in shares)			87,470		619,480
Stock Options Outstanding
Beginning balance (in shares)			2,348,076
Ending balance (in shares)			2,323,032		2,348,076
2014 Plan | Stock options
Stock Based Compensation
Increase in share reserve based on outstanding number of shares (as a percent)		2.00%
2020 New Employee Inducement Award Plan
Stock Based Compensation
Incentive stock option term	10 years
Option outstanding			127,932		154,876
Options available for grant under stock option plans	166,666		343,901		11,790
Shares Available for Grant
Beginning balance (in shares)			11,790
Ending balance (in shares)	166,666		343,901		11,790
Stock Options Outstanding
Beginning balance (in shares)			154,876
Ending balance (in shares)			127,932		154,876
Common Stock
Options vested, exercisable and expected to vest
Share Price			$ 0.71
Participants Voting Power More than Ten Percent | 2014 Plan
Stock Based Compensation
Incentive stock option term		5 years
Participants Voting Power More than Ten Percent | 2020 New Employee Inducement Award Plan
Stock Based Compensation
Incentive stock option term	5 years

Stock Based Compensation - Stoc

Stock Based Compensation - Stock-Based Compensation (Details) - USD ($) $ in Thousands	3 Months Ended
	Mar. 31, 2022	Mar. 31, 2021
Stock Based Compensation
Total stock-based compensation expense	$ 1,063	$ 634
Research and development expense
Stock Based Compensation
Total stock-based compensation expense	348	164
Sales and marketing expense
Stock Based Compensation
Total stock-based compensation expense	82	52
General and administrative expense
Stock Based Compensation
Total stock-based compensation expense	633	$ 418
Stock options and RSUs
Stock Based Compensation
Unrecognized stock-based compensation expense	$ 3,100
Expected weighted average period to be recognized	1 year 9 months 14 days
Employee stock options
Estimated grant-date fair value of stock options calculated using the Black-Scholes option-pricing model
Expected term (years)		5 years
Minimum | Employee stock options
Estimated grant-date fair value of stock options calculated using the Black-Scholes option-pricing model
Volatility (as a percent)		163.80%
Risk-free interest rate (as a percent)		0.50%
Maximum | Employee stock options
Estimated grant-date fair value of stock options calculated using the Black-Scholes option-pricing model
Volatility (as a percent)		164.00%
Risk-free interest rate (as a percent)		0.90%

Stock Based Compensation - 401(

Stock Based Compensation - 401(k) Plan (Details)	3 Months Ended
	Mar. 31, 2022USD ($)
Stock Based Compensation
Employer contributions to the plan	$ 0

Net Loss Per Share (Details)

Net Loss Per Share (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended
	Mar. 31, 2022	Mar. 31, 2021
Calculation of basic and diluted net loss per common share
Net loss attributable to common stockholders (basic)	$ (17,986)	$ (12,009)
Net loss attributable to common shareholders, diluted	$ (17,986)	$ (12,009)
Shares used to compute net loss per common share, basic	44,711,588	42,635,466
Shares used to compute net loss per common share, diluted	44,711,588	42,635,466
Net loss per share attributable to common shareholders, basic	$ (0.40)	$ (0.28)
Net loss per share attributable to common shareholders, diluted	$ (0.40)	$ (0.28)

Net Loss Per Share - Excluded F

Net Loss Per Share - Excluded From Calculation (Details) - shares	3 Months Ended
	Mar. 31, 2022	Mar. 31, 2021	May 04, 2022
Outstanding common stock equivalents have been excluded from diluted net loss per common share
Total (in shares)	6,476,725	3,553,999
Common stock, shares issued			784,516
Options issued and outstanding
Outstanding common stock equivalents have been excluded from diluted net loss per common share
Total (in shares)	2,323,032	2,464,803
Inducement options issued and outstanding
Outstanding common stock equivalents have been excluded from diluted net loss per common share
Total (in shares)	128,072	38,289
Restricted stock units issued and outstanding
Outstanding common stock equivalents have been excluded from diluted net loss per common share
Total (in shares)	3,462,170	487,456
Warrants issued and outstanding
Outstanding common stock equivalents have been excluded from diluted net loss per common share
Total (in shares)	563,451	563,451

Segment Information (Details)

Segment Information (Details) $ in Thousands	3 Months Ended
	Mar. 31, 2022USD ($)segment	Mar. 31, 2021USD ($)	Dec. 31, 2021USD ($)
Segment Information
Number of reportable segments | segment	2
Segment net loss	$ (18,164)	$ (12,009)
Segment assets	52,906		$ 53,265
Less: investment in subsidiary	(29,232)		(29,232)
Less: Intercompany loan	(78,209)		(75,333)
Human Health
Segment Information
Segment net loss	(9,967)	(3,941)
Segment assets	38,880		42,250
Animal Health
Segment Information
Segment net loss	(8,197)	(8,068)
Segment assets	121,467		115,580
Product revenue, net
Segment Information
Revenue from external customers	2,625	1,241
Product revenue, net | Human Health
Segment Information
Revenue from external customers	2,605	1,208
Product revenue, net | Animal Health
Segment Information
Revenue from external customers	20	$ 33
Operating Segments
Segment Information
Segment assets	$ 160,347		$ 157,830

Subsequent Events (Details)

Subsequent Events (Details) - USD ($) $ in Millions	Apr. 14, 2022	Apr. 13, 2022	Apr. 12, 2022	Mar. 31, 2022	Mar. 31, 2021
Subsequent Events.
Common stock reserved				6,908,096	4,185,269
Subsequent event | Inducement Award Plan
Subsequent Events.
Common stock reserved		471,833
Number of shares reserved for issuance		971,833	500,000
Subsequent event | Secured promissory note | Note global amendment
Subsequent Events.
Principal amount	$ 6.2
Subsequent event | Iliad | October 2020 Purchase Agreement
Royalty Transaction
Principal amount	12
Subsequent event | Uptown Capital, Llc | December 2020 royalty interest agreements
Royalty Transaction
Principal amount	12
Subsequent event | Streeterville Capital, Llc | March 2021 royalty interest agreements
Royalty Transaction
Principal amount	$ 10