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What changed in Jaguar Health, Inc.'s 10-K — 2023 vs 2024

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Paragraph-level year-over-year comparison of Jaguar Health, Inc.'s 2023 and 2024 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2024 report.

+590 added−395 removedSource: 10-K (2025-03-31) vs 10-K (2024-04-01)

Top changes in Jaguar Health, Inc.'s 2024 10-K

590 paragraphs added · 395 removed · 361 edited across 6 sections

Item 1. Business

Business — how the company describes what it does

109 edited+36 added−10 removed270 unchanged
Biggest changeIn addition, NP-300 is in development for symptomatic relief and treatment of moderate-to-severe diarrhea, with or without concomitant antimicrobial therapy, from bacterial, viral, and parasitic infections, including Vibrio cholerae , the bacterium that causes cholera. 9 Table of Contents Napo Prescription Drug Product Candidates ​ Product Candidates ​ Indication Completed Milestones Current Phase of Development Anticipated Near-Term Milestones* Mytesi CTD • Initiated pivotal Phase 3 clinical trial in October 2020 ​ Phase 3 • Awaiting unblinding Mytesi IBS-D • Two Phase 2 studies completed Phase 2 • Potential business development opportunities Mytesi Chronic idiopathic diarrhea • Clinical POC study initiated at The University of Texas Health Science Center at Houston (“UTH”) Phase 2 POC study • Top line results expected in 2023 Mytesi Functional diarrhea • Initiated clinical study at Beth Israel Deaconess Medical Center, Harvard Medical School, Boston Phase 2 POC study • Enrollment ongoing Crofelemer powder for oral solution* Rare disease indication: SBS with intestinal failure in adults • ODD for SBS granted by FDA and EMA Clinical POC study • IIT POC study in 2024 Crofelemer powder for oral solution* Rare disease indication: Pediatric MVID, a CDD condition • ODD for MVID granted by FDA and EMA IND stage • Initiating clinical study in 2024 NP-300* Second-generation antidiarrheal drug for infectious diarrhea including from Vibrio cholerae , the bacterium that causes cholera • FDA activated Company’s IND: Q3 2022 Phase I • Initiating Phase 1 trial ​ ​ ​ *Clinical trials are funding dependent Estimated Size of Mytesi Target Markets We believe the medical need for Mytesi is significant, compelling, and unmet, and that doctors are looking for a drug product with a mechanism of action that is distinct from the options currently available to resolve diarrhea.
Biggest changeIn addition, NP-300 is in development for symptomatic relief and treatment of moderate-to-severe diarrhea, with or without concomitant antimicrobial therapy, from bacterial, viral, and parasitic infections, including Vibrio cholerae , the bacterium that causes cholera. 10 Table of Contents Napo Prescription Drug Product Candidates Product Candidates Indication Completed Milestones Current Phase of Development Anticipated Near‑Term Milestones* Mytesi CTD • Initiated pivotal Phase 3 clinical trial in October 2020 • Phase 3 OnTarget study conducted • Statistically significant positive results in breast cancer patients presented at December 2024 San Antonio Brest Cancer Symposium • Q2 2025 meeting with FDA to review the statistically significant positive results in the prespecified subgroup of patients with breast cancer in the Phase 3 OnTarget trial Mytesi IBS‑D • Two Phase 2 studies completed • Phase 2 • Potential business development opportunities Mytesi Chronic idiopathic diarrhea • Clinical POC study initiated at The University of Texas Health Science Center at Houston (“UTH”) • Completed Mytesi Functional diarrhea • Initiated clinical study at Beth Israel Deaconess Medical Center, Harvard Medical School, Boston • Completed Crofelemer powder for oral solution* Rare disease indication: SBS with intestinal failure in adults • ODD for SBS granted by FDA and EMA • Phase 2 POC study • IIT POC study initiated December 2024 Crofelemer powder for oral solution* Rare disease indication: Pediatric MVID, a CDD condition • ODD for MVID granted by FDA and EMA • Phase 2 POC study initiated • IIT POC study in Abu Dhabi initiated January 2025 NP‑300* Second‑generation antidiarrheal drug for infectious diarrhea including from Vibrio cholerae , the bacterium that causes cholera • FDA activated Company’s IND: Q3 2022 • Phase 1 • Initiating Phase 1 trial * Clinical trials are funding dependent 11 Table of Contents Estimated Size of Mytesi Target Markets We believe the medical need for Mytesi is significant, compelling, and unmet, and that doctors are looking for a drug product with a mechanism of action that is distinct from the options currently available to resolve diarrhea.
Crofelemer powder for oral solution is being developed to support orphan or rare disease indications for adults with SBS with intestinal failure and for pediatric microvillus inclusion disease (“MVID”) patients.
Crofelemer powder for oral solution is being developed to support orphan or rare disease indications for adults and pediatric patients with SBS with intestinal failure and for pediatric microvillus inclusion disease (“MVID”) patients.
Jaguar’s exclusive license agreement with Napo Therapeutics provides a perpetual, royalty-bearing license for Europe and includes traditional terms such as royalties on sales in Europe, and a supply agreement, and rights to utilize all data Napo Therapeutics generates for Jaguar development and approval activities globally. Competition Several significantly larger pharmaceutical companies are competing with us in the gastrointestinal segment.
Jaguar’s exclusive license agreement with Napo Therapeutics provides a perpetual, royalty-bearing license for Europe and includes traditional terms such as royalties on sales in Europe, a supply agreement, and rights to utilize all data Napo Therapeutics generates for Jaguar development and approval activities globally. Competition Several significantly larger pharmaceutical companies are competing with us in the gastrointestinal segment.
Other agents’ patients may use include over-the-counter anti-diarrheal remedies such as Mylanta or Kaopectate. Cancer therapy-related diarrhea. We are not aware of any FDA-approved drugs specifically indicated for prophylaxis of cancer therapy-related diarrhea in patients receiving targeted therapies with or without standard chemotherapy. Opioids and over-the-counter drugs are commonly used to treat chemotherapy-induced diarrhea, but these drugs affect motility.
Other agents’ patients may use and include over-the-counter anti-diarrheal remedies such as Mylanta or Kaopectate. Cancer therapy-related diarrhea. We are not aware of any FDA-approved drugs specifically indicated for prophylaxis of cancer therapy-related diarrhea in patients receiving targeted therapies with or without standard chemotherapy. Opioids and over-the-counter drugs are commonly used to treat chemotherapy-induced diarrhea, but these drugs affect motility.
The legal basis is Article 14-a of Regulation (EC) No 726/2004. The provisions for granting a conditional marketing authorization are further elaborated in Regulation (EC) No 507/2006.
The legal basis is Article 14-a of Regulation (EC) No 726/2004. The provisions for granting conditional marketing authorization are further elaborated in Regulation (EC) No 507/2006.
This program is being pursued with the potential targeted incentive from the the US Food and Drug Administration (“FDA”) for a tropical disease priority review voucher. Napo’s marketed drug Mytesi, crofelemer 125 mg delayed-release tablets, is a first-in-class oral botanical drug product approved by the FDA for the symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy.
This program is being pursued with the potential targeted incentive of a tropical disease review voucher from the US Food and Drug Administration (“FDA”). Napo’s marketed drug Mytesi, (crofelemer 125 mg delayed-release tablets), is a first-in-class oral botanical drug product approved by the FDA for the symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy.
For example, in March 2010, the ACA was enacted, which, among other things, increased the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program; introduced a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated 32 Table of Contents for drugs that are inhaled, infused, instilled, implanted or injected; extended the Medicaid Drug Rebate Program to the utilization of prescriptions of individuals enrolled in Medicaid managed care plans; imposed mandatory discounts for certain Medicare Part D beneficiaries as a condition for manufacturers’ outpatient drugs covered under Medicare Part D; subjected drug manufacturers to new annual fees based on pharmaceutical companies’ share of sales to federal healthcare programs; created a new Patient Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research; creation of the Independent Payment Advisory Board, once empaneled, will have authority to recommend certain changes to the Medicare program that could result in reduced payments for prescription drugs; and establishment of a Center for Medicare Innovation at the CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending.
For example, in March 2010, the ACA was enacted, which, among other things, increased the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program; introduced a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected; extended the Medicaid Drug Rebate Program to the utilization of prescriptions of individuals enrolled in Medicaid managed care plans; imposed mandatory discounts for certain Medicare Part D beneficiaries as a condition for manufacturers’ outpatient drugs covered under Medicare Part D; subjected drug manufacturers to new annual fees based on pharmaceutical companies’ share of sales to federal healthcare programs; created a new Patient Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research; creation of the Independent Payment Advisory Board, once empaneled, will have authority to recommend certain changes to the Medicare program that could result in reduced payments for prescription drugs; and establishment of a Center for Medicare Innovation at the CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending.
Even if the FDA agrees to the design, execution, and analyses proposed in protocols reviewed under the SPA process, the FDA may revoke or alter its agreement under the following circumstances: • public health concerns emerge that were unrecognized at the time of the protocol assessment; • the director of the review division determines that a substantial scientific issue essential to determining safety or efficacy has been identified after testing has begun; • a sponsor fails to follow a protocol that was agreed upon with the FDA; or • the relevant data, assumptions, or information provided by the sponsor in a request for SPA change, are found to be false statements or misstatements or are found to omit relevant facts.
Even if the FDA agrees to the design, execution, and analyses proposed in protocols reviewed under the SPA process, the FDA may revoke or alter its agreement under the following circumstances: • public health concerns emerged that were unrecognized at the time of the protocol assessment; • the director of the review division determines that a substantial scientific issue essential to determining safety or efficacy has been identified after testing has begun; • a sponsor fails to follow a protocol that was agreed upon with the FDA; or • the relevant data, assumptions, or information provided by the sponsor in a request for SPA change, are found to be false statements or misstatements or are found to omit relevant facts.
While Napo and Jaguar remain steadfastly focused on the commercial success of Mytesi and on the potential development of crofelemer for CTD and the rare disease indications of SBS with intestinal failure and CDD, the Company believes the same competencies and multi-disciplinary scientific strategy that led to the successful development of Mytesi will support collaborative efforts with potential partners—such as the recently formed joint venture Magdalena Biosciences—to develop novel first-in-class prescription medicines derived from plants.
While Napo and Jaguar remain steadfastly focused on the commercial success of Mytesi and Gelclair on the potential development of crofelemer for CTD and the rare disease indications of SBS with intestinal failure and CDD and MVID, the Company believes the same competencies and multi-disciplinary scientific strategy that led to the successful development of Mytesi will support collaborative efforts with potential partners—such as the recently formed joint venture Magdalena Biosciences—to develop novel first-in-class prescription medicines derived from plants.
Other Regulatory Considerations We believe regulatory rules relating to human food safety, food additives, or drug residues in food will not apply to the products we currently are developing because our animal prescription drug product candidates are not intended for use in production animals, with the exception of horses, which qualify as food animals in Europe and Canada; and our nonprescription products are not regulated by section 201(g) of the Federal Food, Drug, and Cosmetic Act, which the FDA is authorized to administer.
Other Regulatory Considerations We believe regulatory rules relating to human food safety, food additives, or drug residues in food will not apply to the products we currently are developing because our animal prescription drug product candidates are not intended for use in production animals, with the exception of horses, which qualify as food animals in Europe and Canada; and our non-prescription products are not regulated by section 201(g) of the Federal Food, Drug, and Cosmetic Act, which the FDA is authorized to administer.
European Union orphan designation and exclusivity In the EU, the EMA’s Committee for Orphan Medicinal Products grants ODD to promote the development of products that are intended for the diagnosis, prevention, or treatment of life-threatening or chronically debilitating conditions affecting not more than 5 in 10,000 persons in the European Union Community and for which no satisfactory method of diagnosis, prevention, or treatment has been authorized (or the product would be a significant benefit to those affected).
European Union orphan designation and exclusivity In the EU, the EMA’s Committee for Orphan Medicinal Products grants ODD to promote the development of products that are intended for the diagnosis, prevention, or treatment of life-threatening or chronically debilitating conditions affecting not more than five in 10,000 persons in the European Union Community and for which no satisfactory method of diagnosis, prevention, or treatment has been authorized (or the product would be a significant benefit to those affected).
To date, this is the only oral plant-based botanical prescription medicine approved under the FDA’s Botanical Guidance. The Company’s Canalevia-CA, 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. In October 2020, Napo initiated its pivotal OnTarget Phase 3 clinical trial of crofelemer.
To date, this is the only oral plant-based botanical prescription medicine approved under the FDA’s Botanical Guidance. The Company’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. In October 2020, Napo initiated its pivotal OnTarget Phase 3 clinical trial of crofelemer.
In July 2014, BioMarin announced that it had sold a priority review voucher to Sanofi and Regeneron for $67.5 million. (https://investors.biomarin.com/2014-07-30-BioMarin-Sells-Priority-Review-Voucher-for-67-5-Million). ​ 11 Table of Contents The following diagram illustrates the mechanism of action of crofelemer, which normalizes chloride ion secretion and fluid content of the gut to improve stool consistency.
In July 2014, BioMarin announced that it had sold a priority review voucher to Sanofi and 12 Table of Contents Regeneron for $67.5 million. ( https://investors.biomarin.com/2014-07-30-BioMarin-Sells-Priority-Review-Voucher-for-67-5-Million ). The following diagram illustrates the mechanism of action of crofelemer, which normalizes chloride ion secretion and fluid content of the gut to improve stool consistency.
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. 4 Table of Contents MVID is considered an ultra-rare CDD, with likely a couple of hundred patients diagnosed globally.
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. MVID is considered an ultra-rare CDD, with likely a couple of hundred patients diagnosed globally.
In December 2021, we received conditional approval from the FDA to market Canalevia-CA1 (crofelemer delayed-release tablets), our oral plant-based 5 Table of Contents prescription drug and the only available veterinary drug for the treatment of CID in dogs, and Canalevia-CA1 is now available to multiple leading veterinary distributors in the US, including Chewy.
In December 2021, we received conditional 6 Table of Contents approval from the FDA to market Canalevia-CA1 (crofelemer delayed-release tablets), our oral plant-based prescription drug and the only available veterinary drug for the treatment of CID in dogs, and Canalevia-CA1 is now available to multiple leading veterinary distributors in the US, including Chewy.
Certain tyrosine kinase inhibitor chemotherapy agents have diarrhea as a significant side effect. For example, FDA guidance suggests diarrhea prophylaxis prior to initiating adjuvant therapy with neratinib. CDD . We are not aware of any FDA-approved drugs specifically indicated for CDD. 14 Table of Contents SBS with intestinal failure.
Certain tyrosine kinase inhibitor chemotherapy agents have diarrhea as a significant side effect. For example, FDA guidance suggests diarrhea prophylaxis prior to initiating adjuvant therapy with neratinib. CDD . We are not aware of any FDA-approved drugs specifically indicated for CDD. 15 Table of Contents SBS with intestinal failure.
We have learned from discussions with cancer drug manufacturers that the adoption and continued use of targeted cancer therapies is directly related to the ability of patients to tolerate these therapies—highlighting the importance of supportive care drugs like crofelemer to help manage cancer treatment-related diarrhea in this patient population.
We have learned from discussions with cancer drug manufacturers that the adoption and continued use of targeted cancer therapies are directly related to the ability of patients to tolerate these therapies—highlighting the importance of supportive care drugs like crofelemer to help manage cancer treatment-related diarrhea in this patient population.
Napo grants license to Napo Therapeutics In August 2021, Napo signed a license agreement with Napo Therapeutics to study, develop, manufacture, and commercialize Napo’s plant-based crofelemer and NP-300 drug product candidates in the European Union (excluding Russia) and in specified non-EU countries in Europe for specific indications, which rights and obligations were assumed by the combined company formed by the merger of Napo EU S.p.A. with Dragon SPAC (the combined 16 Table of Contents company uses the Napo Therapeutics name).
Napo grants license to Napo Therapeutics In August 2021, Napo signed a license agreement with Napo Therapeutics to study, develop, manufacture, and commercialize Napo’s plant-based crofelemer and NP-300 drug product candidates in the European Union (excluding Russia) and in specified non-EU countries in Europe for specific indications, which rights and obligations were assumed by the combined company formed by the merger of Napo EU S.p.A. with Dragon SPAC (the combined company uses the Napo Therapeutics name).
Recent studies have shown that EGFR inhibitors cause increased chloride secretion into the lumen of the gut and that crofelemer, through its unique and novel mechanism of normalizing the chloride-secretory actions of the cystic fibrosis transmembrane conductance regulator (“CFTR”) and calcium-activated chloride channels (“CaCC"), is 3 Table of Contents considered to be mechanistically- and physiologically-appropriate for reducing the loss of electrolyte and fluid in breast cancer patients receiving this regimen.
Recent studies have shown that EGFR inhibitors cause increased chloride secretion into the lumen of the gut and that crofelemer, through its unique and novel mechanism of normalizing the chloride-secretory actions of the cystic fibrosis transmembrane conductance regulator (“CFTR”) and calcium-activated chloride channels (“CaCC"), is considered to be mechanistically- and physiologically-appropriate for reducing the loss of electrolyte and fluid in breast cancer patients receiving this regimen.
Jaguar Animal Health is a trademark owned by Jaguar. 15 Table of Contents License Agreements Patent Portfolio Napo Napo owns a portfolio of patents and patent applications covering formulations of and treatment methods with proanthocyanidin polymers isolated from Croton spp. or Calophyllum spp., including Mytesi (crofelemer).
Jaguar Animal Health is a trademark owned by Jaguar. 16 Table of Contents License Agreements Patent Portfolio Napo Napo owns a portfolio of patents and patent applications covering formulations of and treatment methods with proanthocyanidin polymers isolated from Croton spp. or Calophyllum spp., including Mytesi (crofelemer).
These include: ● full prescribing information and package leaflet with detailed instructions for safe use and conditions for storage; ● a robust risk-management and safety monitoring plan; ● manufacturing controls, including official batch controls for vaccines, as required; ● legally binding post-approval obligations (i.e., conditions) for the marketing authorization holder and a clear legal framework for the evaluation of emerging efficacy and safety data; ● a pediatric investigation plan.
These include: • full prescribing information and package leaflet with detailed instructions for safe use and conditions for storage; • a robust risk-management and safety monitoring plan; • manufacturing controls, including official batch controls for vaccines, as required; 23 Table of Contents • legally binding post-approval obligations (i.e., conditions) for the marketing authorization holder and a clear legal framework for the evaluation of emerging efficacy and safety data; • a pediatric investigation plan.
To the best of our knowledge, no drugs have been approved in the US or the rest of the world (ROW) to reduce parenteral support with a concomitant reduction in the high stool volume and diarrhea in SBS patients. Diarrhea predominant irritable bowel syndrome .
To the best of our knowledge, no drugs have been approved in the US or the rest of the world (“ROW”) to reduce parenteral support with a concomitant reduction in the high stool volume and diarrhea in SBS patients. Diarrhea predominant irritable bowel syndrome .
The overall ten-year period will be extended to a maximum of 11 years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.
The overall ten-year period will be extended to a maximum of 11 years if, during the first eight years of those ten years, the marketing authorization holder obtains 27 Table of Contents an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.
In general, medicines that are not yet authorized are first made available through clinical trials, and patients should always be considered for inclusion in trials before being offered compassionate use programs. 25 Table of Contents Compassionate use recommendations EMA's recommendations cover how a medicine should be used in compassionate use programs across the EU, and the type of patient who may benefit from treatment.
In general, medicines that are not yet authorized are first made available through clinical trials, and patients should always be considered for inclusion in trials before being offered compassionate use programs. Compassionate use recommendations EMA's recommendations cover how a medicine should be used in compassionate use programs across the EU, and the type of patient who may benefit from treatment.
Violations of fraud and abuse laws, including federal and state Anti-Kickback and false claims laws, may be punishable by criminal and civil sanctions, including fines and civil monetary penalties, the possibility of exclusion from federal healthcare programs (including Medicare and Medicaid), disgorgement and corporate integrity agreements, which impose, among other things, rigorous operational and monitoring requirements on companies.
Violations of fraud and abuse laws, including federal and state Anti-Kickback and false claims laws, may be punishable by criminal and civil sanctions, including fines and civil monetary penalties, the possibility of exclusion from federal healthcare programs (including Medicare and Medicaid), disgorgement and corporate integrity 29 Table of Contents agreements, which impose, among other things, rigorous operational and monitoring requirements on companies.
Novel "targeted cancer therapy" agents, such as epidermal growth factor receptor (“EGFR”) antibodies and tyrosine kinase inhibitors (“TKIs”), with or without cycle chemotherapy agents, may cause increased electrolyte and fluid content in the gut 2 Table of Contents lumen, which results in passage of loose/watery stools (i.e., diarrhea).
Novel "targeted cancer therapy" agents, such as epidermal growth factor receptor (“EGFR”) antibodies and tyrosine kinase inhibitors (“TKIs”), with or without cycle chemotherapy agents, may cause increased electrolyte and fluid content in the gut lumen, which results in passage of loose/watery stools (i.e., diarrhea).
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH”), and their respective implementing regulations, including the Final HIPAA 29 Table of Contents Omnibus Rule, published on January 25, 2013, impose specified requirements relating to privacy, security, and transmission of individually identifiable health information held by covered entities and their business associates.
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH”), and their respective implementing regulations, including the Final HIPAA Omnibus Rule, published on January 25, 2013, impose specified requirements relating to privacy, security, and transmission of individually identifiable health information held by covered entities and their business associates.
The FDCA defines a new animal drug (in part) as any drug intended for use for animals other than man, the composition of which is not generally recognized among experts qualified by scientific training and experience, as safe and effective for use under the conditions prescribed, recommended, or suggested in its labeling.
The FDCA defines a new animal drug (in part) as any drug intended for use for animals other than man, the composition of which is not generally recognized among experts qualified by scientific training and 30 Table of Contents experience, as safe and effective for use under the conditions prescribed, recommended, or suggested in its labeling.
Indexing is allowed for drugs for: ● Non-food-producing minor species, such as pet birds, hamsters, and ornamental fish. These animals are typically not eaten by people or by other animals that produce food for people to eat, and ● An early non-food life stage of a food-producing minor species, such as oyster spat (immature oysters).
Indexing is allowed for drugs for: • Non-food-producing minor species, such as pet birds, hamsters, and ornamental fish. These animals are typically not eaten by people or by other animals that produce food for people to eat, and 31 Table of Contents • An early non-food life stage of a food-producing minor species, such as oyster spat (immature oysters).
At the present time, we hold approximately 148 issued worldwide patents, with coverage in many cases that extends until 2031. These issued patents cover multiple indications, including HIV/AIDS diarrhea, irritable bowel syndrome (“IBS”), IBD, manufacturing, and enteric protection from gastric juices, among others.
At the present time, we hold approximately 194 issued patents, with coverage in many cases that extends until 2031. These issued patents cover multiple indications, including HIV/AIDS diarrhea, irritable bowel syndrome (“IBS”), IBD, manufacturing, and enteric protection from gastric juices, among others.
As previously announced, Jaguar has received MUMS designation status from the FDA for Canalevia-CA1 for the indication of CID in dogs. MUMS designation is modeled on the ODD for human drug development and offers possible financial incentives to encourage MUMS drug development, such as the availability of grants to help with the cost of developing the MUMS drug.
As announced in July 2024, Jaguar has received MUMS designation status from the FDA for Canalevia-CA1 for the indication of CID in dogs. MUMS designation is modeled on the ODD for human drug development and offers possible financial incentives to encourage MUMS drug development, such as the availability of grants to help with the cost of developing the MUMS drug.
We will conduct 31 Table of Contents a review of advertising and promotional material for compliance with the local and regional requirements in the markets where we sell our product candidates. Coverage and Reimbursement Significant uncertainty exists as to the coverage and reimbursement status of any pharmaceutical products for which Napo obtains regulatory approval.
We will conduct a review of advertising and promotional material for compliance with the local and regional requirements in the markets where we sell our product candidates. Coverage and Reimbursement Significant uncertainty exists as to the coverage and reimbursement status of any pharmaceutical products for which Napo obtains regulatory approval.
Sponsors must submit an annual report on development to the EMA summarizing the status of the development of the medicine. 24 Table of Contents Sponsors of medicines with orphan designation should also remember to apply for a pediatric investigation plan (“PIP”), deferral, or waiver at the appropriate time, as specified in the Pediatric regulation.
Sponsors must submit an annual report on development to the EMA summarizing the status of the development of the medicine. Sponsors of medicines with orphan designation should also remember to apply for a pediatric investigation plan (“PIP”), deferral, or waiver at the appropriate time, as specified in the Pediatric regulation.
Description of Properties Our corporate headquarters are located in San Francisco, California, where we currently lease 10,526 rentable square feet of office space from M & E, LLC.
Description of Properties Our corporate headquarters are located in San Francisco, California, where we currently lease 10,998 rentable square feet of office space from M & E, LLC.
Jaguar’s and Napo’s portfolio development strategy involves meeting with Key Opinion Leaders (“KOLs”) to identify indications that are potentially high value because they address important medical needs that are significantly or globally unmet, obtain input on protocol practicality and protocol generation, and then strategically 7 Table of Contents sequencing indication development priorities, second-generation product pipeline development, and partnering goals on a global basis.
Jaguar’s and Napo’s portfolio development strategy involves meeting with Key Opinion Leaders (“KOLs”) to identify indications that are potentially high value because they address important medical needs that are significantly or globally unmet, obtain input on protocol practicality and protocol generation, and then strategically sequencing indication development priorities, second-generation product pipeline development, and partnering goals on a global basis.
The federal false claims and civil monetary penalties laws, including the civil False Claims Act, prohibit any person or entity from, among other things, knowingly presenting, or causing to be presented, a false, fictitious, or 28 Table of Contents fraudulent claim for payment to, or approval by, the federal government, knowingly making, using, or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government, or from knowingly making a false statement to avoid, decrease or conceal an obligation to pay money to the US federal government.
The federal false claims and civil monetary penalties laws, including the civil False Claims Act, prohibit any person or entity from, among other things, knowingly presenting, or causing to be presented, a false, fictitious, or fraudulent claim for payment to, or approval by, the federal government, knowingly making, using, or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government, or from knowingly making a false statement to avoid, decrease or conceal an obligation to pay money to the US federal government.
More recently, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which have resulted in several recent Congressional inquiries and proposed bills designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for pharmaceutical products.
More recently, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which have resulted in several recent Congressional inquiries and proposed bills 33 Table of Contents designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for pharmaceutical products.
Crofelemer was evaluated in Phase 2 clinical study called HALT-D, for the effectiveness of crofelemer for the reduction of diarrhea in HER2-positive breast cancer patients receiving trastuzumab, pertuzumab, and chemotherapy agents such as docetaxel or paclitaxel with or without carboplatin.
Crofelemer was evaluated in Phase 2 clinical study called HALT-D, for the effectiveness of crofelemer for the reduction of diarrhea in HER2-positive breast cancer patients receiving trastuzumab, pertuzumab, and 3 Table of Contents chemotherapy agents such as docetaxel or paclitaxel with or without carboplatin.
The EMA encourages sponsors to consider coordinating the timing of protocol assistance from the EMA with the request for scientific advice from the FDA. Parallel scientific advice with the FDA is available. 23 Table of Contents Access to the centralized authorization procedure All designated orphan medicines are assessed for central marketing authorization in the European Union.
The EMA encourages sponsors to consider coordinating the timing of protocol assistance from the EMA with the request for scientific advice from the FDA. Parallel scientific advice with the FDA is available. Access to the centralized authorization procedure All designated orphan medicines are assessed for central marketing authorization in the European Union.
EMA can also take regulatory action if the company does not comply with the imposed obligations. 22 Table of Contents Despite earlier approval, it guarantees that the medicine meets rigorous EU safety, efficacy and quality standards and that comprehensive data is still generated post-approval. It offers a robust post-authorization regulatory framework based on legally binding obligations, safeguards, and controls.
EMA can also take regulatory action if the company does not comply with the imposed obligations. Despite earlier approval, it guarantees that the medicine meets rigorous EU safety, efficacy and quality standards and that comprehensive data is still generated post-approval. It offers a robust post-authorization regulatory framework based on legally binding obligations, safeguards, and controls.
We also have approximately 50 pending patent applications worldwide in the human health areas that are being prosecuted. Mytesi is the first oral drug approved under the FDA’s Botanical Guidance, providing another entry barrier from potential generic competition.
We also currently have approximately 45 pending patent applications worldwide in the human health areas that are being prosecuted. Mytesi is the first oral drug approved under the FDA’s Botanical Guidance, providing another entry barrier from potential generic competition.
This is the case even when the studies' results are negative. For orphan medicines, the incentive is an additional two years of market exclusivity. Scientific advice and protocol assistance at the EMA are free of charge for questions relating to the development of pediatric medicines.
This is the case even when the studies' results are negative. 26 Table of Contents For orphan medicines, the incentive is an additional two years of market exclusivity. Scientific advice and protocol assistance at the EMA are free of charge for questions relating to the development of pediatric medicines.
Transfers of orphan designation from one sponsor to another are possible. Transfers are free of charge. Sponsors can also request removal of an orphan designation. EMA Compassionate Use Program Compassionate use is a treatment option that allows the use of an unauthorized medicine.
Transfers of orphan designation from one sponsor to another are possible. Transfers are free of charge. Sponsors can also request removal of an orphan designation. 25 Table of Contents EMA Compassionate Use Program Compassionate use is a treatment option that allows the use of an unauthorized medicine.
The conditional approval is valid for one year. The drug company can ask the FDA to renew the conditional approval annually for up to four more years, for a total of five years of conditional approval. During the 5-year period, the drug company can legally sell the animal drug while collecting the remaining effectiveness data.
The drug company can ask the FDA to renew the conditional approval annually for up to four more years, for a total of five years of conditional approval. During the 5-year period, the drug company can legally sell the animal drug while collecting the remaining effectiveness data.
We do not believe that our animal nonprescription products are currently subject to regulation in the US. The CVM only regulates those animal supplements that fall within the FDA’s definition of an animal drug, food or feed additive.
We do not believe that our animal non-prescription products are currently subject to regulation in the US. The CVM only regulates those animal supplements that fall within the FDA’s definition of an animal drug, food or feed additive.
Canalevia is also the Company’s drug candidate for the proposed indication of exercise-induced diarrhea (“EID”) in dogs. Crofelemer is extracted and purified from the Croton lechleri tree, which we sustainably harvest and manage through programs that we have been developing over the past 30 years.
Canalevia-CA1 is also the Company’s drug candidate for the proposed indication of exercise-induced diarrhea (“EID”) in dogs. 9 Table of Contents Crofelemer is extracted and purified from the Croton lechleri tree, which we sustainably harvest and manage through programs that we have been developing over the past 30 years.
Our goal is to have de risked the program as much as we believe we possibly can, by the 13 Table of Contents time we start devoting significant funds to a clinical trial, in particular the regulatory pathway. We believe this approach will lead to better long-term outcomes for our products in development.
Our goal is to have de risked the program as much as we believe we possibly can, by the time we start devoting significant funds to a clinical trial, in particular the regulatory pathway. We believe this approach will lead to better long-term outcomes for our products in development.
Accordingly, manufacturers must continue to expend time, money, and effort in production and quality control to maintain cGMP compliance. Once approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.
Accordingly, manufacturers must continue to expend time, money, and effort in production and quality control to maintain cGMP compliance. 21 Table of Contents Once approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.
Feed additives are defined as those articles that are added to an animal’s feed or water, as illustrated by the guidance documents. Our nonprescription products are not added to food, are not ingredients in food, nor are they added to any animal’s drinking water.
Feed additives are defined as those articles that are added to an animal’s feed or water, as illustrated by the guidance documents. Our non-prescription products are not added to food, are not ingredients in food, nor are they added to any animal’s drinking water.
This process has involved working with local and indigenous communities to plant trees, obtain permits for export, and create a supply network that is robust and reliable. 8 Table of Contents Our team continues to have relationships with partners that we began working within the 1990s.
This process has involved working with local and indigenous communities to plant trees, obtain permits for export, and create a supply network that is robust and reliable. Our team continues to have relationships with partners that we began working within the 1990s.
In addition, a NP-300 is in development for symptomatic relief and treatment of moderate-to-severe diarrhea, with or without concomitant antimicrobial therapy, from bacterial, viral and parasitic infections including Vibrio cholerae , the bacterium that causes cholera. Our management team collectively has extensive experience in the development of prescription drugs.
In addition, an NP-300 is in development for symptomatic relief and treatment of moderate-to-severe diarrhea, with or without concomitant antimicrobial therapy, caused by bacterial, viral, and parasitic infections, including Vibrio cholerae , the bacterium that causes cholera. Our management team collectively has extensive experience in the development of prescription drugs.
Jaguar family company Napo Therapeutics, S.p.A is an Italian corporation Jaguar established in Milan, Italy in 2021 focused on expanding crofelemer access in Europe, specifically for orphan and/or rare diseases. Jaguar 1 Table of Contents Animal Health is a Jaguar tradename.
Jaguar family company Napo Therapeutics, S.p.A is an Italian corporation Jaguar established in Milan, Italy in 2021 focused on expanding crofelemer access in Europe, specifically for orphan and/or rare diseases. Jaguar Animal Health is a Jaguar tradename.
The global OnTarget clinical trial is a 24-week (two 12-week stages), randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of crofelemer in diarrhea prophylaxis in adult solid tumor patients receiving targeted therapies with or without standard chemotherapy.
The recently conducted global OnTarget clinical trial was a 24-week (two 12-week stages), randomized, multicenter, placebo-controlled, double-blind study to evaluate the safety and efficacy of crofelemer in diarrhea prophylaxis in adult solid tumor patients receiving targeted therapies with or without standard chemotherapy.
Centralized Procedure is mandatory for certain types of products, such as biotechnology medicinal products, orphan medicinal products, and medicinal products containing a new active substance indicated for the treatment of AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and viral diseases. Conditional marketing authorization The EMA supports the development of medicines that address unmet medical needs.
Centralized Procedure is mandatory for certain types of products, such as biotechnology medicinal products, orphan medicinal products, and medicinal products containing a new active substance indicated for the treatment of AIDS, cancer, neurodegenerative disorders, diabetes, autoimmune and viral diseases. 22 Table of Contents Conditional marketing authorization The EMA supports the development of medicines that address unmet medical needs.
The FDA reviews an NDA to determine, among other things, whether the drug is safe and effective and whether the facility in which it is manufactured, processed, packaged, or held meets standards designed to assure the product’s continued safety, quality, and purity. The FDA may refer an application for a novel drug to an advisory committee.
The FDA reviews an NDA to determine, among other things, whether the drug is safe and effective and whether the facility in which it is manufactured, processed, packaged, or held meets standards designed to ensure the product’s continued safety, quality, and purity. 20 Table of Contents The FDA may refer an application for a novel drug to an advisory committee.
The European Commission is the authorizing body for all centrally authorized product, who takes a legally binding decision based on EMA's recommendation. This decision is issued within 67 days of receipt of EMA’s recommendation.
The European Commission is the authorizing body for all centrally authorized products, which takes a legally binding decision based on EMA's recommendation. This decision is issued within 67 days of receipt of EMA’s recommendation.
There is 33 Table of Contents no intent to make our nonprescription products a component of animal food, either directly or indirectly. We do not believe that our nonprescription products fit the definition of an animal drug, food, or food additive and, therefore are not regulated by the FDA at this time.
There is no intent to make our non-prescription products a component of animal food, either directly or indirectly. We do not believe that our non-prescription products fit the definition of an animal drug, food, or food additive and, therefore are not regulated by the FDA at this time.
Multiple sites may necessitate the involvement of multiple IRBs and submissions for human health products; ● performance of adequate and well-controlled human clinical trials in accordance with good clinical practices (“GCPs”), requirements to establish the safety and efficacy of the proposed drug product for each indication; ● submission to the FDA of an NDA for marketing approval of human prescription drugs; ● satisfactory completion of FDA advisory committees review, if applicable; ● satisfactory completion of an FDA pre-approval inspection (“PAI”) of the manufacturing facility or facilities at which the product is produced to assess compliance with current good manufacturing 17 Table of Contents practices (“cGMPs”), requirements and to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity; and ● FDA review and approval of the NDA.
Multiple sites may necessitate the involvement of multiple IRBs and submissions for human health products; • performance of adequate and well-controlled human clinical trials in accordance with good clinical practices (“GCPs”), requirements to establish the safety and efficacy of the proposed drug product for each indication; • submission to the FDA of an NDA for marketing approval of human prescription drugs; • satisfactory completion of FDA advisory committees review, if applicable; • satisfactory completion of an FDA pre-approval inspection (“PAI”) of the manufacturing facility or facilities at which the product is produced to assess compliance with current good manufacturing practices (“cGMPs”), requirements and to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity; and • FDA review and approval of the NDA. 18 Table of Contents Pre-clinical Studies Pre-clinical studies include laboratory evaluation of the drug product’s chemistry, toxicity, and formulation and animal studies to assess potential safety and effectiveness.
EMA's Committee for Medicinal products for Human Use (“CHMP”) or Committee for Medicinal products for Veterinary Use (“CVMP”) carry out a scientific assessment of the application and give a recommendation on whether the medicine should be marketed or not. However, under EU law EMA has no authority to actually permit 21 Table of Contents marketing in the different EU countries.
EMA's Committee for Medicinal Products for Human Use (“CHMP”) or Committee for Medicinal Products for Veterinary Use (“CVMP”) carries out a scientific assessment of the application and gives a recommendation on whether the medicine should be marketed or not. However, under EU law EMA has no authority to actually permit marketing in the different EU countries.
ODD qualifies the drug's sponsor for various development incentives, including tax credits for qualified clinical testing and relief of filing fees. Additionally, the ODA provides a seven-year period of marketing exclusivity to the first sponsor who obtains marketing approval for a designated orphan drug.
This status is referred to as ODD (or sometimes "orphan status"). ODD qualifies the drug's sponsor for various development incentives, including tax credits for qualified clinical testing and relief of filing fees. Additionally, the ODA provides a seven-year period of marketing exclusivity to the first sponsor who obtains marketing approval for a designated orphan drug.
With support provided by concomitant marketing, promotional activities, patient empowerment programs, including an integrated social digital campaign, and medical education initiatives described below, we expect a proportional response in the number of patients treated with Mytesi. 12 Table of Contents Leverage our relationships with Scientific Advisory Board (SAB) members for crofelemer commercialization and development in follow-on indications The Company has retained several subject matter experts and KOLS as its SAB members across the therapeutic areas of HIV, CTD, gastrointestinal disorders, SBS, and/or CDD. ​ Establish partnerships to support moving pipeline indications to pivotal clinical trials The Company’s goal is to establish partnerships to support moving pipeline indications towards commercialization in the US and/or other geographies.
With support provided by concomitant marketing, promotional activities, patient empowerment programs, including an integrated social digital campaign, and medical education initiatives described below, we expect a proportional response in the number of patients treated with Mytesi. 13 Table of Contents Leverage our relationships with Scientific Advisory Board (SAB) members for crofelemer commercialization and development in follow-on indications The Company has retained several subject matter experts and KOLS as its SAB members across the therapeutic areas of HIV, CTD, gastrointestinal disorders, SBS, and/or CDD.
We believe the novel mechanism of action of crofelemer may have considerable potential to manage the severe secretory loss of electrolytes and fluid resulting in dehydration. There are currently no therapies for MVID except parenteral nutrition. Thus, crofelemer may reduce the associated morbidity and mortality of MVID and lessen the need for parenteral nutrition (“PN”).
We believe the novel mechanism of action of crofelemer may have considerable potential to manage the severe secretory loss of electrolytes and fluid resulting in dehydration. There are currently no therapies for MVID except parenteral nutrition.
Approximately one in ten infected persons will have severe disease characterized by profuse, watery diarrhea, vomiting, and leg cramps. In these people, rapid loss of body fluids leads to dehydration and shock. Without treatment, death can occur within hours.
Approximately one in ten infected persons will have severe disease characterized by profuse, watery diarrhea, vomiting, and leg cramps. In these people, rapid loss of body fluids leads to dehydration and shock. Without treatment, death can occur within hours. Cholera is now endemic in many countries outside the US.
They also have rights to commercialization, for Mytesi for CTD, for which crofelemer is currently in a pivotal Phase 3 clinical trial. In addition, the agreement grants Quadri Pharma exclusive rights to distribute crofelemer in these countries in the immediate future under Named Patient Programs. As announced September 24, 2018, Jaguar and Knight Therapeutics Inc.
They also have rights to commercialization, for Mytesi for CTD. In addition, the agreement grants Quadri Pharma exclusive rights to distribute crofelemer in these countries in the immediate future under Named Patient Programs. As announced September 24, 2018, Jaguar and Knight Therapeutics Inc.
Our voting common stock is listed on the Nasdaq Capital Market and trades under the symbol “JAGX.” On July 31, 2017, we completed the acquisition of Napo pursuant to the Agreement and Plan of Merger, dated March 31, 2017, by and among the Company, Napo, Napo Acquisition Corporation, and Napo’s representative (the “Merger”).
Our voting common stock is listed on the Nasdaq Capital Market and trades under the symbol “JAGX.” On July 31, 2017, we completed the acquisition of Napo pursuant to the Agreement and Plan of Merger, dated March 31, 2017, by and among the Company, Napo, Napo Acquisition Corporation, and Napo’s representative (the “Merger”). 34 Table of Contents Employees As of December 31, 2024, we had forty-nine employees.
Employees As of December 31, 2023, we had forty nine employees. Twelve employees hold M.D., D.V.M and/or Ph.D. degrees. Twenty-three of our employees are in research and development activities, and thirteen are in sales and marketing. We have four employees within Napo Therapeutics in Italy. Our employees are not represented by labor unions or covered by collective bargaining agreements.
Twelve employees hold M.D., D.V.M and/or Ph.D. degrees. Twenty-two of our employees are in research and development activities, and seventeen are in sales and marketing. We have four employees within Napo Therapeutics in Italy. Our employees are not represented by labor unions or covered by collective bargaining agreements.
Magdalena Biosciences, a joint venture formed by Jaguar and Filament Health Corp. with funding from One Small Plant Capital LLC that emerged from Jaguar’s Entheogen Therapeutics Initiative (“ETI”), is focused on developing novel prescription medicines derived from plants for mental health indications. Jaguar was founded in San Francisco, California, as a Delaware corporation on June 6, 2013 (“inception”).
Magdalena Biosciences, a joint venture formed by Jaguar and Filament Health Corp. with funding from One Small Plant Capital LLC that emerged from Jaguar’s Entheogen Therapeutics Initiative (“ETI”), is focused on developing novel prescription medicines derived from plants for mental health indications.
In this population, a novel anti-diarrheal like crofelemer may hold promise for treating secretory diarrhea—and therefore also support long-term cancer treatment adherence.
Diarrhea in this patient population has the potential to cause dehydration, potential infections, and non-adherence to treatment. In this population, a novel anti-diarrheal like crofelemer may hold promise for treating secretory diarrhea—and therefore also support long-term cancer treatment adherence.
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 animals.
Jaguar 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 animals.
Most of the activities of the Company are focused on the development and/or commercialization of Mytesi, the ongoing clinical development of crofelemer for the prophylaxis of diarrhea in adult patients receiving targeted cancer therapy, and our prioritized clinical program centered around investigator-initiated POC trials of crofelemer for SBS and MVID.
Thus, crofelemer may reduce the associated morbidity and mortality of MVID and lessen the need for parenteral nutrition (“PN”). 5 Table of Contents Most of the activities of the Company are focused on the development and/or commercialization of Mytesi, the ongoing clinical development of crofelemer for the prophylaxis of diarrhea in adult patients receiving targeted cancer therapy, the ongoing commercial launch of Gelclair, and our prioritized clinical program centered around investigator-initiated POC trials of crofelemer for SBS and MVID.
Once the marketing authorization is obtained in all Member States of the EU and study results are included in the product information, even when negative, the product is eligible for six six-month supplementary protection certificate extension.
Once the marketing authorization is obtained in all Member States of the EU and study results are included in the product information, even when negative, the product is eligible for six six-month supplementary protection certificate extension. For orphan drug-designated medicinal products, the 10-year period of market exclusivity is extended to 12 years.
For orphan drug-designated medicinal products, the 10-year period of market exclusivity is extended to 12 years. 27 Table of Contents Clinical Trials Regulation in Europe In the EU, pursuant to the currently applicable Clinical Trials Directive 2001/20/EC and the Directive 2005/28/EC on GCP, a system for the approval of clinical trials in the EU has been implemented through national legislation of the EU member states.
Clinical Trials Regulation in Europe In the EU, pursuant to the currently applicable Clinical Trials Directive 2001/20/EC and the Directive 2005/28/EC on GCP, a system for the approval of clinical trials in the EU has been implemented through national legislation of the EU member states.
The FDA may also require other information as part of the NDA filing, such as an environmental impact statement.
The FDA may also require other information as part of the NDA filing, such as an environmental impact statement. The FDA can waive some or delay compliance with some of these requirements.
Government Regulation The FDA and comparable regulatory authorities in state and local jurisdictions and in other countries impose substantial and burdensome requirements upon companies involved in the clinical development, manufacture, marketing, and distribution of prescription drugs such as those Napo is that Jaguar and its subsidiaries are commercializing and/or developing.
The license agreement grants Napo Therapeutics the rights for SBS-IF, HIV-related diarrhea, and the symptomatic relief and treatment of IF-related diarrhea in patients with congenital disorders. 17 Table of Contents Government Regulation The FDA and comparable regulatory authorities in state and local jurisdictions and in other countries impose substantial and burdensome requirements upon companies involved in the clinical development, manufacture, marketing, and distribution of prescription drugs such as those that Jaguar and its subsidiaries are commercializing and/or developing.
Some pre-clinical testing may continue even after the IND is submitted. An IND automatically becomes effective 30 days after receipt by the FDA unless, before that time, the FDA raises concerns or questions about one or more proposed clinical trials and places the clinical trial on a clinical hold.
An IND automatically becomes effective 30 days after receipt by the FDA unless, before that time, the FDA raises concerns or questions about one or more proposed clinical trials and places the clinical trial on a clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin.
Review of the market exclusivity period Article 8(2) of the Orphan Regulation establishes the possibility for Member States to request that the market exclusivity be reduced from ten to six years under certain circumstances. 26 Table of Contents Expiry of market exclusivity When the period of market exclusivity for an indication ends, the orphan designation for that indication expires, and the European Commission removes it from the CHMP.
Review of the market exclusivity period Article 8(2) of the Orphan Regulation establishes the possibility for Member States to request that the market exclusivity be reduced from ten to six years under certain circumstances.
Other US Healthcare Laws In addition to FDA restrictions on the marketing of pharmaceutical and biological products, other US federal and state healthcare regulatory laws restrict business practices in the pharmaceutical industry, which include, but are not limited to, state and federal anti-kickback, false claims, data privacy and security and physician payment and drug pricing transparency laws.
For instance, the new Clinical Trials Regulation provides for a streamlined application procedure via a single entry point and strictly defined deadlines for the assessment of clinical trial applications. 28 Table of Contents Other US Healthcare Laws In addition to FDA restrictions on the marketing of pharmaceutical and biological products, other US federal and state healthcare regulatory laws restrict business practices in the pharmaceutical industry, which include, but are not limited to, state and federal anti-kickback, false claims, data privacy and security and physician payment and drug pricing transparency laws.
A conditionally approved animal drug has gone through the FDA's approval process, but the drug has not yet met the effectiveness standard for full approval. FDA’s conditional approval means that when used according to the label, the drug is safe and has a “reasonable expectation of effectiveness.” FDA's conditional approval also means that the drug is properly manufactured.
FDA’s conditional approval means that when used according to the label, the drug is safe and has a “reasonable expectation of effectiveness.” FDA's conditional approval also means that the drug is properly manufactured. The conditional approval is valid for one year.
Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients. 18 Table of Contents Special Protocol Assessment for Human Health Prescription Drugs The special protocol assessment (“SPA”) process is designed to facilitate the FDA’s review and approval of drugs by allowing the FDA to evaluate issues related to the adequacy of certain clinical trials, including Phase 3 clinical trials that can form the primary basis for a drug product’s efficacy claim in an NDA.
Special Protocol Assessment for Human Health Prescription Drugs The special protocol assessment (“SPA”) process is designed to facilitate the FDA’s review and approval of drugs by allowing the FDA to evaluate issues related to the adequacy of certain clinical trials, including Phase 3 clinical trials that can form the primary basis for a drug product’s efficacy claim in an NDA.
ITEM 1. BUSINESS BUSINESS Jaguar Health, Inc. (“Jaguar”) is a commercial-stage pharmaceuticals company focused on developing novel proprietary prescription medicines sustainably derived from plants from rainforest areas for people and animals with gastrointestinal (“GI”) distress. Jaguar family company Napo Pharmaceuticals, Inc.
ITEM 1. BUS INESS BUSINESS Jaguar Health, Inc. (“Jaguar”) is a commercial-stage pharmaceuticals company focused on developing novel proprietary prescription medicines sustainably derived from plants from rainforest areas for people and animals with gastrointestinal (“GI”) distress specifically associated with overactive bowel, which includes symptoms such as chronic debilitating diarrhea, urgency, bowel incontinence, and cramping pain.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

187 edited+113 added−16 removed131 unchanged
Biggest changeThe termination of either of these contracts would result in a disruption to product development and harm our business. ● We are dependent upon third-party contract manufacturers, both for the supply of the active pharmaceutical ingredient in Mytesi and Canalevia-CA1, as well as for the supply of finished products for commercialization. ● If we are unable to establish sales capabilities on our own or through third parties, we may not be able to market and sell our current or future human products and product candidates, if approved, and generate product or other revenue. 35 Table of Contents ● We will need to increase the size of our organization and may not successfully manage such growth. ● Canalevia-CA1 and our animal health prescription drug product candidates may be marketed in the US only in the target animals and for the indications for which they are approved, and if we want to expand the approved animals or indications, it will need to obtain additional approvals, which may not be granted. ● The misuse or extra-label use of Mytesi, Canalevia, and our human or animal prescription drug product candidates, if approved by regulatory authorities, may harm our reputation or result in financial or other damages. ● We may be unable to obtain, or obtain on a timely basis, a renewal of conditional approval for Canalevia-CA1 or to eventually obtain full regulatory approval of Canalevia-CA1, which would harm our operating results. ● We may not maintain the benefits associated with MUMS designation, including market exclusivity. ● The market for our human and animal products, and the gastrointestinal health market as a whole, is uncertain and may be smaller than we anticipate, which could lead to lower revenue and harm our operating results. ● Insurance coverage for Mytesi for its current approved indication could decrease or end, or Mytesi might not receive insurance coverage for any approved follow-on indications, which could lead to lower revenue and harm our operating results. ● We may engage in future acquisitions that increase our capital requirements, dilute our stockholders, cause us to incur debt or assume contingent liabilities, and subject us to other risks. ● Certain of the countries in which we plan to commercialize our products in the future are developing countries, some of which have potentially unstable political and economic climates. ● Fluctuations in the exchange rate of foreign currencies could result in currency transaction losses. ● Laws and regulations governing global trade compliance could adversely impact our business. ● There are other gastrointestinal-focused human pharmaceutical companies, and we face competition in the marketplaces in which we operate or plan to operate. ● Our obligations to Streeterville are secured by a security interest in all of Napo’s NP-300 assets, so if we default on those obligations, Streeterville could foreclose on our assets. ● Our royalty interests require us to make minimum royalty payments, even if we do not sell a sufficient amount of products to cover the amount of such payments, which may strain our cash resources. ● Failure in our information technology systems, including by cyber-attacks or other data security incidents, could significantly disrupt our operations. ● Global macroeconomic conditions may negatively affect us and may magnify certain risks that affect our business. ● Unfavorable global economic conditions could adversely affect our business, financial condition, or results of operations. ● Substantially all of our revenue for recent periods has been received from two customers. ● The Company’s ability to attract and retain qualified members of our board of directors may be impacted due to new state laws, including recently enacted gender quotas. ● Evolving expectations around corporate responsibility practices, specifically related to environmental, social, and governance (“ESG”) matters, may expose us to reputational and other risks. ● The growing use of artificial intelligence (“AI”) systems to automate processes, analyze data, and support decision-making poses inherent risks. ​ Risks Related to Our Intellectual Property ● We cannot be certain that our patent strategy will be effective in protecting against competition. ● Obtaining and maintaining our patent protection depends on compliance with various procedural requirements, document submission, fee payment, and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements. ● Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, which would be costly and time-consuming and, if successfully asserted against us, delay or prevent the development and commercialization of our current or future products and product candidates. 36 Table of Contents ● Our proprietary position depends upon the botanical guidance of our drug approval and patents that are formulation or method-of-use patents, which do not prevent a competitor from using the same human or animal drug for another use. ● We may be involved in lawsuits to protect or enforce our patents, which could be expensive, time-consuming, and unsuccessful, and third parties may challenge the validity or enforceability of our patents, and they may be successful. ● If we are unable to prevent disclosure of our trade secrets or other confidential information to third parties, our competitive position may be impaired. ● Changes in US patent law could diminish the value of patents in general, thereby impairing our ability to protect our products. ● We may not be able to protect our intellectual property rights throughout the world, which could impair our business. ● Our business could be harmed if we fail to obtain certain registered trademarks in the US or in other countries. ● We may be subject to claims that our employees, consultants, or independent contractors have wrongfully used or disclosed confidential third-party information. ● Even if we receive any of the required regulatory approvals for our current or future prescription drug product candidates and non-prescription products, we will be subject to ongoing obligations and continued regulatory review, which may result in significant additional expenses. ● Any of our current or future prescription drug product candidates or non-prescription products may cause or contribute to adverse medical events that we would be required to report to regulatory authorities and if we fail to do so, we could be subject to sanctions that would harm our business. ● Legislative or regulatory reforms with respect to animal health may make it more difficult and costly for us to obtain regulatory clearance or approval for any of our current or future product candidates and to produce, market, and distribute our products after clearance or approval is obtained. ● We believe that our non-prescription products are not subject to regulation by regulatory agencies in the US, but there is a risk that regulatory bodies may disagree with our interpretation or may redefine the scope of their regulatory reach in the future, which would result in additional expense and could delay or prevent the commercialization of these products. ● Even if we receive the required regulatory approvals for our current or future prescription drug product candidates and non-prescription products, we will be subject to ongoing obligations and continued regulatory review, which may result in significant additional expenses. ​ Risks Related to Our Common Stock ● Our failure to meet the continued listing requirements of The Nasdaq Capital Market could result in a delisting of our common stock. ● If our shares become subject to the penny stock rules, it would become more difficult to trade our shares. ● The price of our common stock could be subject to volatility related or unrelated to our operations, and purchasers of our common stock could incur substantial losses. ● A possible “short squeeze” due to a sudden increase in demand for our common stock that largely exceeds supply may lead to further price volatility in our common stock. ● You may be unable to resell our common stock when you wish to sell it or at a price that you consider attractive or satisfactory. ● If securities or industry analysts do not publish research or reports about our company, or if they issue adverse or misleading opinions regarding us or our stock, our stock price and trading volume could decline. ● You may be diluted by conversions of outstanding shares of non-voting common stock, exercises of outstanding options and warrants, and issuances of securities pursuant to our ATM Agreement. ● Provisions in our charter documents and under Delaware law could discourage a takeover that stockholders may consider favorable and may lead to entrenchment of management. ● Our amended and restated bylaws designate the Court of Chancery of the State of Delaware as the sole and exclusive forum for certain actions and proceedings that may be initiated by our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or other employees. 37 Table of Contents ● We do not intend to pay dividends on our common stock, and your ability to achieve a return on your investment will depend on appreciation in the market price of our common stock. ● The requirements of being a public company, including compliance with the reporting requirements of the Exchange Act and the requirements of the Sarbanes-Oxley Act, may strain our resources, increase our costs, and distract management, and we may be unable to comply with these requirements in a timely or cost-effective manner. ● We are a smaller reporting company, and the reduced reporting requirements applicable to smaller reporting companies may make our common stock less attractive to investors. ​ Risks Related to Our Business ​ We have a limited operating history, expect to incur further losses as we grow, and may be unable to achieve or sustain profitability. ​ Since the consummation of our merger with Napo Pharmaceuticals Inc. in 2017, our operations have been primarily focused on research, development, and the ongoing commercialization of our lead prescription drug product, Mytesi, which the FDA approves for the symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy.
Biggest changeThe termination of any of these contracts would result in a disruption to product development and manufacturing and harm our business. • If we are unable to establish sales capabilities on our own or through third parties, we may not be able to market and sell our current or future human products and product candidates, if approved, and generate product or other revenue. • We will need to increase the size of our organization and may not successfully manage such growth. • Canalevia-CA1 and our animal health prescription drug product candidates may be marketed in the US only in the target animals and for the indications for which they are approved, and if we want to expand the approved animals or indications, it will need to obtain additional approvals, which may not be granted. 36 Table of Contents • The misuse or extra-label use of Mytesi, Canalevia, and our human or animal prescription drug product candidates, if approved by regulatory authorities, may harm our reputation or result in financial or other damages. • We may be unable to obtain, or obtain on a timely basis, a renewal of conditional approval for Canalevia-CA1 or to eventually obtain full regulatory approval of Canalevia-CA1, which would harm our operating results. • We may not maintain the benefits associated with MUMS designation, including market exclusivity. • The market for our human and animal products, and the gastrointestinal health market as a whole, is uncertain and may be smaller than we anticipate, which could lead to lower revenue and harm our operating results. • Insurance coverage for Mytesi for its current approved indication could decrease or end, or Mytesi might not receive insurance coverage for any approved follow-on indications, which could lead to lower revenue and harm our operating results. • We may face challenges obtaining favorable reimbursement and insurance coverage for Gelclair, which could limit its market adoption and commercial success. • We may engage in future acquisitions that increase our capital requirements, dilute our stockholders, cause us to incur debt or assume contingent liabilities, and subject us to other risks. • Certain of the countries in which we plan to commercialize our products in the future are developing countries, some of which have potentially unstable political and economic climates. • Changing political environment in the US could adversely affect our business and financial performance. • Fluctuations in the exchange rate of foreign currencies could result in currency transaction losses. • Laws and regulations governing global trade compliance could adversely impact our business. • There are other gastrointestinal-focused human pharmaceutical companies, and we face competition in the marketplaces in which we operate or plan to operate. • Our obligations to Streeterville are secured by a security interest in all of Napo’s NP-300 assets, so if we default on those obligations, Streeterville could foreclose on the NP-300 assets. • Our royalty interests require us to make minimum royalty payments, even if we do not sell a sufficient amount of products to cover the amount of such payments, which may strain our cash resources. • Failure in our information technology systems, through cyber-attacks or other data security incidents, could significantly disrupt our operations. • Global macroeconomic conditions may negatively affect us and may magnify certain risks that affect our business. • Unfavorable global economic conditions could adversely affect our business, financial condition, or results of operations. • Substantially all of our revenue for recent periods has been received from two customers. • The Company’s ability to attract and retain qualified members of our board of directors may be impacted due to new state laws, including recently enacted gender quotas. • Evolving expectations around corporate responsibility practices, specifically related to environmental, social, and governance (“ESG”) matters, may expose us to reputational and other risks. 37 Table of Contents • The growing use of artificial intelligence (“AI”) systems to automate processes, analyze data, and support decision-making poses inherent risks.
If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained, and we may not achieve or sustain profitability, which would harm our business.
If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained, and we may not achieve or sustain profitability, which would harm our business.
Further, even if we are successful in the ongoing commercialization of Mytesi and Canalevia, we may not achieve commercial success. ● Human and animal gastrointestinal health products are subject to unanticipated post-approval safety or efficacy concerns, which may harm our business and reputation. ● Future federal and state legislation may result in increased exposure to product liability claims, which could result in substantial losses. ● If we fail to retain current members of our senior management or to identify, attract, integrate, and retain additional key personnel, our business will be harmed. ● We are dependent on two suppliers for the raw material used to produce the active pharmaceutical ingredients in Mytesi and Canalevia.
Further, even if we are successful in the ongoing commercialization of Mytesi and Canalevia, we may not achieve commercial success. • Human and animal gastrointestinal health products are subject to unanticipated post-approval safety or efficacy concerns, which may harm our business and reputation. • Future federal and state legislation may result in increased exposure to product liability claims, which could result in substantial losses. • If we fail to retain current members of our senior management or to identify, attract, integrate, and retain additional key personnel, our business will be harmed. • We are dependent on two suppliers for the raw material used to produce the active pharmaceutical ingredients in Mytesi and Canalevia-CA1.
We will need to seek additional funds through public or private equity or debt financings or other sources such as strategic collaborations. Any such financings or collaborations may result in dilution to our stockholders, the imposition of debt covenants and repayment obligations, or other restrictions that may harm our business or the value of our common stock.
We will need to seek additional funds through public or private equity or debt financing or other sources such as strategic collaborations. Any such financings or collaborations may result in dilution to our stockholders, the imposition of debt covenants and repayment obligations, or other restrictions that may harm our business or the value of our common stock.
Further, even if we are successful in the ongoing commercialization of Mytesi and Canalevia, we may not achieve commercial success. ​ If we obtain necessary regulatory approvals for planned follow-on indications of crofelemer or our other product candidates, such products may still not achieve market acceptance and may not be commercially successful.
Further, even if we are successful in the ongoing commercialization of Mytesi, Canalevia-CA1 and our other product candidates, we may not achieve commercial success. If we obtain necessary regulatory approvals for planned follow-on indications of crofelemer or our other product candidates, such products may still not achieve market acceptance and may not be commercially successful.
We have issued three US patents, which are listed in the FDA’s Orange Book for Mytesi. We plan to rely on certain of these issued patents as protection for Canalevia. The strength of patents in the field of pharmaceuticals and animal health involves complex legal and scientific questions and can be uncertain.
We have issued three US patents, which are listed in the FDA’s Orange Book for Mytesi. We plan to rely on certain of these issued patents as protection for Canalevia-CA1. The strength of patents in the field of pharmaceuticals and animal health involves complex legal and scientific questions and can be uncertain.
Unanticipated safety or efficacy concerns can subsequently arise with respect to approved prescription drugs products, such as Mytesi, or non-prescription products, such as Neonorm, which may result in product recalls or withdrawals or suspension of sales, as well as product liability and other claims.
Unanticipated safety or efficacy concerns can subsequently arise with respect to approved prescription drugs products, such as Mytesi and Gelclair, or non-prescription products, such as Neonorm, which may result in product recalls or withdrawals or suspension of sales, as well as product liability and other claims.
If any of the foregoing were to occur, regulatory approval, if required, and commercialization of our product candidates may be delayed, and we may be required to expend substantial additional resources. ​ 44 Table of Contents Even if we obtain regulatory approval for planned follow-on indications of crofelemer, Canalevia, or our other product candidates, they may never achieve market acceptance.
If any of the foregoing were to occur, regulatory approval, if required, and commercialization of our product candidates may be delayed, and we may be required to expend substantial additional resources. 46 Table of Contents Even if we obtain regulatory approval for planned follow-on indications of crofelemer, Canalevia, or our other product candidates, they may never achieve market acceptance.
As a result, we have limited meaningful historical operations upon which to evaluate our business and prospects and have not yet demonstrated an ability to broadly commercialize any of our human health products beyond Mytesi for HIV-related diarrhea or animal health products, obtain any required marketing approval for any of our animal prescription drug product candidates or successfully overcome the risks and uncertainties frequently encountered by companies in emerging fields such as the animal health industry or the gastrointestinal health industry in general.
As a result, we have limited meaningful historical operations upon which to evaluate our business and prospects and have not yet demonstrated an ability to broadly commercialize any of our human health products beyond Mytesi for HIV-related diarrhea or animal health products, obtain any required marketing approval for any of our animal prescription drug product candidates or successfully overcome the risks and uncertainties 39 Table of Contents frequently encountered by companies in emerging fields such as the animal health industry or the gastrointestinal health industry in general.
Furthermore, the use of an approved human or animal drug such as Mytesi and Canalevia for indications other than those indications for which such products have been approved may not be effective, which could harm our reputation and lead to an increased risk of litigation.
Furthermore, the use of an approved human or animal drug such as Mytesi, Canalevia-CA1 and Gelclair for indications other than those indications for which such products have been approved may not be effective, which could harm our reputation and lead to an increased risk of litigation.
If this occurs, our competitors may take advantage of our investment in development and trials by referencing our clinical and preclinical data and launching their product earlier than might otherwise be the case. ​ Even where laws provide protection, or we are able to obtain patents, costly and time-consuming litigation may be necessary to enforce and determine the scope of our proprietary rights, and the outcome of such litigation would be uncertain.
If this occurs, our competitors may take advantage of our investment in development and trials by referencing our clinical and preclinical data and launching their product earlier than might otherwise be the case. 57 Table of Contents Even where laws provide protection, or we are able to obtain patents, costly and time-consuming litigation may be necessary to enforce and determine the scope of our proprietary rights, and the outcome of such litigation would be uncertain.
In addition, third parties may obtain patents in the future and claim that the use of our technologies infringes upon these patents. ​ To the extent we become subject to future third-party claims against us or our collaborators, we could incur substantial expenses, and if any such claims are successful, we could be liable to pay substantial damages, including treble damages and attorney’s fees if we or our collaborators are found to be willfully infringing a third-party’s patents.
In addition, third parties may obtain patents in the future and claim that the use of our technologies infringes upon these patents. 56 Table of Contents To the extent we become subject to future third-party claims against us or our collaborators, we could incur substantial expenses, and if any such claims are successful, we could be liable to pay substantial damages, including treble damages and attorney’s fees if we or our collaborators are found to be willfully infringing a third-party’s patents.
Failure to gain agreement from the FDA on a timely basis could adversely affect our commercial supply of products. ​ Lastly, if we obtain conditional approval for our current or future drug product candidates, this conditional approval is renewable annually for five years and may be withdrawn or terminated under certain circumstances either during or at the end of the five-year period.
Failure to gain agreement from the FDA on a timely basis could adversely affect our commercial supply of products. 60 Table of Contents Lastly, if we obtain conditional approval for our current or future drug product candidates, this conditional approval is renewable annually for five years and may be withdrawn or terminated under certain circumstances either during or at the end of the five-year period.
If adequate funds are not available to us on a timely basis, we may be required to delay, limit, reduce, or terminate one or more of our product development programs or future commercialization efforts. ​ We are substantially dependent on the success of Mytesi, our current lead prescription drug product, and Canalevia-CA1, our conditionally approved prescription drug product for CID in dogs.
If adequate funds are not available to us on a timely basis, we may be required to delay, limit, reduce, or terminate one or more of our product development programs or future commercialization efforts. 41 Table of Contents We are substantially dependent on the success of Mytesi, our current lead prescription drug product, and Canalevia-CA1, our conditionally approved prescription drug product for CID in dogs.
We will remain an SRC so long as (a) the aggregate market value of our outstanding common stock held by non-affiliates as of the last business day our most recently completed second fiscal quarter is less than $250 million or (b) (1) we have less than $100 million in annual revenues and (2) the aggregate market value of our outstanding common stock held by non-affiliates as of the last business day our most recently completed second fiscal quarter is less than $700 million.
We will remain an SRC so long as (a) the aggregate market value of our outstanding common stock held by non-affiliates as of the last business day our most recently completed second fiscal quarter is less than $250 million or (b) (1) we have less than $100 million in annual revenues and (2) the 68 Table of Contents aggregate market value of our outstanding common stock held by non-affiliates as of the last business day our most recently completed second fiscal quarter is less than $700 million.
Any failure or delay in the development of our internal sales, marketing, and distribution capabilities and entry into adequate arrangements with distributors or other partners would adversely impact the commercialization of Mytesi and Canalevia-CA1.
Any failure or delay in the development of our internal sales, marketing, and distribution capabilities and entry into adequate arrangements with distributors or other partners would adversely impact the commercialization of Mytesi, Canalevia-CA1, Gelclair, and/or any of our other products.
If the FDA objects to any of our proposed proprietary product names, we may be required to expend significant additional resources in an effort to identify a suitable substitute name that would qualify under applicable trademark laws, not infringe the existing rights of third parties and be acceptable to the FDA. ​ 58 Table of Contents We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties. ​ We have received confidential and proprietary information from third parties.
If the FDA objects to any of our proposed proprietary product names, we may be required to expend significant additional resources in an effort to identify a suitable substitute name that would qualify under applicable trademark laws, not infringe the existing rights of third parties and be acceptable to the FDA. 59 Table of Contents We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties.
As a result of or in order to avoid potential patent infringement claims, we or our collaborators may be compelled to seek a license from a third party for which we would be required to pay license 55 Table of Contents fees, royalties, or both. Moreover, these licenses may not be available on acceptable terms or at all.
As a result of or in order to avoid potential patent infringement claims, we or our collaborators may be compelled to seek a license from a third party for which we would be required to pay license fees, royalties, or both. Moreover, these licenses may not be available on acceptable terms or at all.
If our financial relationships with veterinarians are found to be in violation of such laws that apply to us, we may be subject to penalties. ​ 59 Table of Contents Further, our commercial supply is regulated by the FDA, which requires regular filings of annual reports and may include modifications by the Company to our approvals.
If our financial relationships with veterinarians are found to be in violation of such laws that apply to us, we may be subject to penalties. Further, our commercial supply is regulated by the FDA, which requires regular filings of annual reports and may include modifications by the Company to our approvals.
If our contract manufacturer cannot manufacture sufficient quantities of the API in a timely manner, we could suffer losses due to lost sales opportunities. We currently have sufficient quantities of the botanical extract used in Neonorm and Equilevia to support planned commercialization efforts for Neonorm and Equilevia.
If our contract manufacturer cannot manufacture sufficient quantities of the API in a timely manner, we could suffer losses due to lost sales opportunities. We currently have sufficient quantities of the botanical extract used in Neonorm and Equilevia to support planned 48 Table of Contents commercialization efforts for Neonorm and Equilevia.
Delisting from Nasdaq could adversely affect our ability to raise additional financing through the public or private sale of equity securities, 62 Table of Contents and we would incur additional costs under requirements of state “blue sky” laws in connection with any sales of our securities.
Delisting from Nasdaq could adversely affect our ability to raise additional financing through the public or private sale of equity securities, and we would incur additional costs under requirements of state “blue sky” laws in connection with any sales of our securities.
On April 22, 1996, the FDA published a statement in the Federal Register, 61 FR 17706, that it believes that the Dietary Supplement and Health Education Act (“DSHEA”) does not apply to animal health supplement products, such as our non-prescription products.
On April 22, 1996, the FDA published a statement 61 Table of Contents in the Federal Register, 61 FR 17706, that it believes that the Dietary Supplement and Health Education Act (“DSHEA”) does not apply to animal health supplement products, such as our non-prescription products.
The USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment, and other similar provisions during the patent application process.
The USPTO and various foreign governmental patent agencies require compliance with a number of procedurals, documentary, fee payment, and other similar provisions during the patent application process.
ITEM 1A. RISK FACTORS The business, financial condition, and operating results of the Company may be affected by a number of factors, whether currently known or unknown, including but not limited to those described below.
ITEM 1A. R ISK FACTORS The business, financial condition, and operating results of the Company may be affected by a number of factors, whether currently known or unknown, including but not limited to those described below.
We currently have sufficient quantities of the API used in Mytesi and Canalevia to support our projected sales efforts. We are working with our contract manufacturers to increase the API manufacturing capacity of the API to support the sales forecast for 2024 and beyond.
We currently have sufficient quantities of the API used in Mytesi and Canalevia-CA1 to support our projected sales efforts. We are working with our contract manufacturers to increase the API manufacturing capacity of the API to support the sales forecast for 2025 and beyond.
We cannot be certain that pending applications will be issued as patents. For those patents that are already issued and even if other patents are successfully issued, third parties may challenge their validity, enforceability, or scope, which may result in such patents being narrowed, invalidated, or held unenforceable.
We cannot be 55 Table of Contents certain that pending applications will be issued as patents. For those patents that are already issued and even if other patents are successfully issued, third parties may challenge their validity, enforceability, or scope, which may result in such patents being narrowed, invalidated, or held unenforceable.
When our independent registered 67 Table of Contents public accounting firm is required to undertake an assessment of our internal control over financial reporting, the cost of our compliance with Section 404 will correspondingly increase.
When our independent registered public accounting firm is required to undertake an assessment of our internal control over financial reporting, the cost of our compliance with Section 404 will correspondingly increase.
Because the 51 Table of Contents techniques used to obtain unauthorized access or sabotage systems change frequently, become more sophisticated, and often are not recognized until launched against a target, we may be unable to anticipate these techniques or implement adequate preventative measures.
Because the techniques used to obtain unauthorized access or sabotage systems change frequently, become more sophisticated, and often are not recognized until launched against a target, we may be unable to anticipate these techniques or implement adequate preventative measures.
If we are not successful in the development and commercialization of Mytesi, our business, and our prospects will be harmed. ​ The successful development and commercialization of Mytesi and Canalevia-CA1 will depend on a number of factors, including the following: ​ ● our ability to demonstrate, to the satisfaction of the FDA and any other regulatory bodies, the safety and efficacy of Canalevia; ​ ● our ability and that of our contract manufacturers to manufacture supplies of Mytesi and Canalevia-CA1 and to develop, validate, and maintain viable commercial manufacturing processes that are compliant with current good manufacturing practices, or cGMPs if required; ​ ● our ability to successfully market Mytesi and Canalevia-CA1, whether alone or in collaboration with others; ​ ● the availability, perceived advantages, relative cost, relative safety, and relative efficacy of our prescription drug product candidates compared to alternative and competing treatments; ​ ● the acceptance of our prescription drug product candidates and non-prescription products as safe and effective by physicians, veterinarians, patients, animal owners, and the human and animal health community, as applicable; ​ ● our ability to achieve and maintain compliance with all regulatory requirements applicable to our business; and ​ ● our ability to obtain and enforce our intellectual property rights and marketing exclusivity for our prescription drug product candidates and non-prescription products, and avoid or prevail in any third-party patent interference, patent infringement claims, or administrative patent proceedings initiated by third parties or the US Patent and Trademark Office (“USPTO”). ​ Many of these factors are beyond our control.
The successful development and commercialization of Mytesi, Canalevia-CA1 and Gelclair will depend on a number of factors, including the following: • our ability to demonstrate, to the satisfaction of the FDA and any other regulatory bodies, the safety and efficacy of Canalevia; • our ability and that of our contract manufacturers to manufacture supplies of Mytesi, Canalevia-CA1 and Gelclair, and to develop, validate, and maintain viable commercial manufacturing processes that are compliant with current good manufacturing practices, or cGMPs if required; • our ability to successfully market Mytesi, Canalevia-CA1 and Gelclair, whether alone or in collaboration with others; • the availability, perceived advantages, relative cost, relative safety, and relative efficacy of our prescription drug product candidates compared to alternative and competing treatments; • the acceptance of our prescription drug product candidates and non-prescription products as safe and effective by physicians, veterinarians, patients, animal owners, and the human and animal health community, as applicable; 42 Table of Contents • our ability to achieve and maintain compliance with all regulatory requirements applicable to our business; and • our ability to obtain and enforce our intellectual property rights and marketing exclusivity for our prescription drug product candidates and non-prescription products, and avoid or prevail in any third-party patent interference, patent infringement claims, or administrative patent proceedings initiated by third parties or the US Patent and Trademark Office (“USPTO”).
We also depend on our third-party contractors to comply with cGMPs. If our third-party contractors do not maintain compliance with these strict regulatory requirements, they and we will not be able to secure or maintain regulatory approval for their facilities, which would have an adverse effect on our operations.
If our third-party contractors do not maintain compliance with these strict regulatory requirements, they and we will not be able to secure or maintain regulatory approval for their facilities, which would have an adverse effect on our operations.
Factors that may have contributed to such volatility include but are not limited to, those discussed previously in this “Risk Factors” section of this report and others, such as: ​ ● delays in the commercialization of Mytesi, Canalevia-CA1, or our other current or future prescription drug product candidates and non-prescription products; ​ ● any delays in, or suspension or failure of, our current and future studies; ​ 63 Table of Contents ● announcements of regulatory approval or disapproval of any of our current or future product candidates or of regulatory actions affecting our company or our industry; ​ ● manufacturing and supply issues that affect product candidate or product supply for our studies or commercialization efforts; ​ ● quarterly variations in our results of operations or those of our competitors; ​ ● changes in our earnings estimates or recommendations by securities analysts; ​ ● the payment of licensing fees or royalties in shares of our common stock; ​ ● announcements by us or our competitors of new prescription drug products or product candidates or non-prescription products, significant contracts, commercial relationships, acquisitions or capital commitments; ​ ● announcements relating to future development or license agreements including termination of such agreements; ​ ● adverse developments with respect to our intellectual property rights or those of our principal collaborators; ​ ● commencement of litigation involving us or our competitors; ​ ● any major changes in our board of directors or management; ​ ● new legislation in the US relating to the prescription, sale, distribution or pricing of gastrointestinal health products; ​ ● product liability claims, other litigation or public concern about the safety of our prescription drug product or product candidates and non-prescription products or any such future products; ​ ● market conditions in the human or animal industry, in general, or in the gastrointestinal health sector, in particular, including performance of our competitors; ​ ● future issuances of shares of common stock or other securities; ​ ● uncertainties related to COVID-19; ​ ● general economic conditions in the US and abroad; and ​ ● market speculation regarding ​ In addition, the stock market, in general, or the market for stocks in our industry, in particular, may experience broad market fluctuations, which may adversely affect the market price or liquidity of our common stock.
Factors that may have contributed to such volatility include but are not limited to, those discussed previously in this “Risk Factors” section of this report and others, such as: • delays in the commercialization of Mytesi, Canalevia-CA1, or our other current or future prescription drug product candidates and non-prescription products; • any delays in, or suspension or failure of, our current and future studies; • announcements of regulatory approval or disapproval of any of our current or future product candidates or of regulatory actions affecting our company or our industry; • manufacturing and supply issues that affect product candidate or product supply for our studies or commercialization efforts; 64 Table of Contents • quarterly variations in our results of operations or those of our competitors; • changes in our earnings estimates or recommendations by securities analysts; • the payment of licensing fees or royalties in shares of our common stock; • announcements by us or our competitors of new prescription drug products or product candidates or non-prescription products, significant contracts, commercial relationships, acquisitions or capital commitments; • announcements relating to future development or license agreements including termination of such agreements; • adverse developments with respect to our intellectual property rights or those of our principal collaborators; • commencement of litigation involving us or our competitors; • any major changes in our board of directors or management; • new legislation in the US relating to the prescription, sale, distribution or pricing of gastrointestinal health products; • product liability claims, other litigation or public concern about the safety of our prescription drug product or product candidates and non-prescription products or any such future products; • market conditions in the human or animal industry, in general, or in the gastrointestinal health sector, in particular, including performance of our competitors; • future issuances of shares of common stock or other securities; • general economic conditions in the US and abroad; and • market speculation regarding any of the foregoing.
A severe or prolonged economic downturn, including as a result of the COVID-19 pandemic, the ongoing war in Ukraine, interest rate fluctuations, rising inflation, recession, or other global financial or geopolitical crises, could result in a variety of risks to our business, including weakened demand for our product candidates, if approved, or our ability to raise additional capital when needed on acceptable terms, if at all.
A severe or prolonged economic downturn, 54 Table of Contents including as a result of the ongoing war in Ukraine, interest rate fluctuations, rising inflation, recession, or other global financial or geopolitical crises, could result in a variety of risks to our business, including weakened demand for our product candidates, if approved, or our ability to raise additional capital when needed on acceptable terms, if at all.
If new legislation is passed to allow recovery for such non-economic damages, or if precedents are set allowing for such recovery, we could be exposed to increased product liability claims that could result in substantial 45 Table of Contents losses to us if successful.
If new legislation is passed to allow recovery for such non-economic damages, or if precedents are set allowing for such recovery, we could be exposed to increased product liability claims that could result in substantial losses to us if successful.
We also may contract with additional third parties for the formulation and supply of finished products, which we will use in our planned studies and commercialization efforts. 46 Table of Contents ​ We are dependent upon our contract manufacturers for the supply of the API in Mytesi and Canalevia-CA1.
We also may contract with additional third parties for the formulation and supply of finished products, which we will use in our planned studies and commercialization efforts. We are dependent upon our contract manufacturers for the supply of the API in Mytesi, Canalevia-CA1 and our other products.
These disclosure requirements may have the effect of reducing the trading activity in the secondary market for our common stock, and therefore, stockholders may have difficulty selling their shares. ​ The price of our common stock could be subject to volatility related or unrelated to our operations, and purchasers of our common stock could incur substantial losses. ​ We have experienced and may continue to experience significant volatility in the price of our common stock.
These disclosure requirements may have the effect of reducing the trading activity in the secondary market for our common stock, and therefore, stockholders may have difficulty selling their shares. The price of our common stock could be subject to volatility related or unrelated to our operations, and purchasers of our common stock could incur substantial losses.
The basis for a lost designation can include but is not limited to, our failure to engage with due diligence in moving forward with a non-conditional approval.
The basis for a lost designation can include but is not limited to, our failure to engage with due diligence in moving forward with a nonconditional approval.
To counter infringement or unauthorized use of any patents we may 56 Table of Contents obtain, we may be required to file infringement claims, which can be expensive and time-consuming to litigate.
To counter infringement or unauthorized use of any patents we may obtain, we may be required to file infringement claims, which can be expensive and time-consuming to litigate.
Such a loss of patent protection could harm our business. We cannot be certain that there is no invalidating prior art, of which we and the patent examiner were unaware during prosecution or other basis for a finding of invalidity. Litigation proceedings may fail and, even if successful, may result in substantial costs and distract our management and other employees.
We cannot be certain that there is no invalidating prior art, of which we and the patent examiner were unaware during prosecution or other basis for a finding of invalidity. Litigation proceedings may fail and, even if successful, may result in substantial costs and distract our management and other employees.
In addition to our 42 Table of Contents internal activities, we will partially rely on contract research organizations (“CROs”) and other third parties to conduct our toxicology studies, biostatistical analysis, and certain other product development activities.
In addition to our internal activities, we will partially rely on contract research organizations (“CROs”) and other third parties to conduct our toxicology studies, biostatistical analysis, and certain other product development activities.
Additionally, cyber-attacks could also compromise trade secrets and other sensitive information and result in such information being disclosed to others and becoming less valuable, which could negatively affect our business.
Additionally, cyber-attacks could also compromise trade secrets and other sensitive information and result in such information being disclosed to others and becoming less valuable, which could 53 Table of Contents negatively affect our business.
These provisions include the following: ​ ● a classified board of directors with three-year staggered terms, which may delay the ability of stockholders to change the membership of a majority of our board of directors; ​ ● no cumulative voting in the election of directors, which limits the ability of minority stockholders to elect director candidates; ​ ● the exclusive right of our board of directors to elect a director to fill a vacancy created by the expansion of the board of directors or the resignation, death or removal of a director, which prevents stockholders from being able to fill vacancies on our board of directors; ​ ● the ability of our board of directors to authorize the issuance of shares of preferred stock and to determine the terms of those shares, including preferences and voting rights, without stockholder approval, which could adversely affect the rights of our common stockholders or be used to deter a possible acquisition of our company; ​ ● the ability of our board of directors to alter our bylaws without obtaining stockholder approval; ​ ● the required approval of the holders of at least 75% of the shares entitled to vote at an election of directors to adopt, amend, or repeal our bylaws or repeal the provisions of our third amended and restated certificate of incorporation regarding the election and removal of directors; ​ ● a prohibition on stockholder action by written consent, which forces stockholder action to be taken at an annual or special meeting of our stockholders; ​ ● the requirement that a special meeting of stockholders may be called only by the chairman of the board of directors, the chief executive officer, the president, or the board of directors, which may delay the ability of our stockholders to force consideration of a proposal or to take action, including the removal of directors; and ​ ● advance notice procedures that stockholders must comply with in order to nominate candidates to our board of directors or to propose matters to be acted upon at a stockholders’ meeting, which may discourage or deter a potential acquirer from conducting a solicitation of proxies to elect the acquirer’s own slate of directors or otherwise attempting to obtain control of us. ​ These provisions could inhibit or prevent possible transactions that some stockholders may consider attractive. ​ We are also subject to the anti-takeover provisions contained in Section 203 of the Delaware General Corporation Law.
These provisions include the following: • a classified board of directors with three-year staggered terms, which may delay the ability of stockholders to change the membership of a majority of our board of directors; • no cumulative voting in the election of directors, which limits the ability of minority stockholders to elect director candidates; 66 Table of Contents • the exclusive right of our board of directors to elect a director to fill a vacancy created by the expansion of the board of directors or the resignation, death or removal of a director, which prevents stockholders from being able to fill vacancies on our board of directors; • the ability of our board of directors to authorize the issuance of shares of preferred stock and to determine the terms of those shares, including preferences and voting rights, without stockholder approval, which could adversely affect the rights of our common stockholders or be used to deter a possible acquisition of our company; • the ability of our board of directors to alter our bylaws without obtaining stockholder approval; • the required approval of the holders of at least 75% of the shares entitled to vote at an election of directors to adopt, amend, or repeal our bylaws or repeal the provisions of our third amended and restated certificate of incorporation regarding the election and removal of directors; • a prohibition on stockholder action by written consent, which forces stockholder action to be taken at an annual or special meeting of our stockholders; • the requirement that a special meeting of stockholders may be called only by the chairman of the board of directors, the chief executive officer, the president, or the board of directors, which may delay the ability of our stockholders to force consideration of a proposal or to take action, including the removal of directors; and • advance notice procedures that stockholders must comply with in order to nominate candidates to our board of directors or to propose matters to be acted upon at a stockholders’ meeting, which may discourage or deter a potential acquirer from conducting a solicitation of proxies to elect the acquirer’s own slate of directors or otherwise attempting to obtain control of us.
These products may compete with our products in jurisdictions where we do not have any issued or licensed patents and any future patent claims or other intellectual property rights may not be effective or sufficient to prevent them from so competing. ​ Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions.
These products may compete with our products in jurisdictions where we do not have any issued or licensed patents and any future patent claims or other intellectual property rights may not be effective or sufficient to prevent such competition. Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions.
Alternatively, if a court were to find this provision of our amended and restated bylaws inapplicable or unenforceable with respect to one or more of the specified types of actions or proceedings, we may incur additional costs associated with resolving such matters in other jurisdictions, which could harm our business and financial condition. ​ We do not intend to pay dividends on our common stock, and your ability to achieve a return on your investment will depend on appreciation in the market price of our common stock. ​ We currently intend to invest our future earnings, if any, to fund our growth and not to pay any cash dividends on our common stock.
Alternatively, if a court were to find this provision of our amended and restated bylaws inapplicable or unenforceable with respect to one or more of the specified types of actions or proceedings, we may incur additional costs associated with resolving such matters in other jurisdictions, which could harm our business and financial condition. 67 Table of Contents We do not intend to pay dividends on our common stock, and your ability to achieve a return on your investment will depend on appreciation in the market price of our common stock.
However, in many instances, the Federal Trade Commission will exercise primary or concurrent jurisdiction with the FDA on non-prescription products as to post-marketing claims made regarding the product.
The FDA retains jurisdiction over all animal prescription drug products. However, in many instances, the Federal Trade Commission will exercise primary or concurrent jurisdiction with the FDA on non-prescription products as to post-marketing claims made regarding the product.
Though we endeavor to give reasonable estimates of future revenues and earnings at the time we give such guidance, based on then-current conditions, there is a significant risk that such guidance or outlook will turn out to be, or to have been, incorrect. 52 Table of Contents Unfavorable global economic conditions could adversely affect our business, financial condition, or results of operations. ​ Our business, financial condition, results of operations, or prospects could be adversely affected by general conditions in the global economy and in the global financial markets.
Though we endeavor to give reasonable estimates of future revenues and earnings at the time we give such guidance, based on then-current conditions, there is a significant risk that such guidance or outlook will turn out to be, or to have been, incorrect. Unfavorable global economic conditions could adversely affect our business, financial condition, or results of operations.
We do not influence or control the reporting of these analysts. If one or more of the analysts who do cover us downgrade or provide a negative outlook on our company, our industry, or the stock of any of our competitors, the price of our common stock could decline.
If one or more of the analysts who do cover us downgrade or provide a negative outlook on our company, our industry, or the stock of any of our competitors, the price of our common stock could decline.
If we are unable to continue as a viable entity, our stockholders may lose their investment. ​ We expect to incur significant additional costs as we continue commercialization efforts for current prescription drug candidates or other product candidates and undertake the clinical trials necessary to obtain any necessary regulatory approvals, which will increase our losses. ​ Napo commenced sales of Mytesi for adults with HIV/AIDS on antiretroviral therapy in September 2016.
We expect to incur significant additional costs as we continue commercialization efforts for current prescription drug candidates or other product candidates and undertake the clinical trials necessary to obtain any necessary regulatory approvals, which will increase our losses. Napo commenced sales of Mytesi for adults with HIV/AIDS on antiretroviral therapy in September 2016.
These expenditures will include costs associated with: ​ ● identifying additional potential prescription drug product candidates and non-prescription products; ​ 38 Table of Contents ● formulation studies; ​ ● conducting pilot, pivotal, and toxicology studies; ​ ● completing other research and development activities; ​ ● payments to technology licensors; ​ ● maintaining our intellectual property; ​ ● obtaining necessary regulatory approvals; ​ ● establishing commercial supply capabilities and ​ ● sales, marketing and distribution of our commercialized products. ​ We may also incur unanticipated costs in developing and commercializing our products.
These expenditures will include costs associated with: • identifying additional potential prescription drug product candidates and non-prescription products; • formulation studies; • conducting pilot, pivotal, and toxicology studies; • completing other research and development activities; • payments to technology licensors; • maintaining our intellectual property; • obtaining necessary regulatory approvals; • establishing commercial supply capabilities; and • sales, marketing and distribution of our commercialized products.
Our revenues to date have been insufficient to offset our expenses, and we expect to continue to incur significant research and development and other expenses. Our net comprehensive losses for the years ended December 31, 2023, and 2022 were $41.9 million and $49.1 million, respectively. As of December 31, 2023, we had a total stockholder equity of $4.9 million.
Our revenues to date have been insufficient to offset our expenses, and we expect to continue to incur significant research and development and other expenses. Our net comprehensive losses for the years ended December 31, 2024 and 2023, were $39.0 million and $41.9 million, respectively. As of December 31, 2024, we had a total stockholder equity of $6.5 million.
The composition-of-matter patents for crofelemer, the API in Mytesi and Canalevia-CA1 have expired, and the issued patents and applications relevant to our products and product candidates cover methods of use for crofelemer and the botanical extract in Neonorm and Equilevia. ​ Method-of-use patents protect the use of a product for the specified method, and formulation patents cover formulations of the API or botanical extract.
The composition-of-matter patents for crofelemer, the API in Mytesi and Canalevia-CA1 have expired, and the issued patents and applications relevant to our products and product candidates cover methods of use for crofelemer and the botanical extract in Neonorm and Equilevia.
Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with our contract manufacturers or manufacturing processes, or failure to comply with regulatory requirements, are reportable events to the FDA and may result in, among other things: ​ ● restrictions on the marketing or manufacturing of the product, withdrawal of the product from the market, revised labeling, or voluntary or involuntary product recalls; ​ ● additional clinical studies, fines, warning letters or holds on target animal studies; ​ ● refusal by the FDA, or other regulators to approve pending applications or supplements to approved applications filed by us or our strategic collaborators related to the unknown problems, or suspension or revocation of the problematic product’s license approvals; ​ ● product seizure or detention, or refusal to permit the import or export of products; and ​ ● injunctions and/or the imposition of civil or criminal penalties. ​ The FDA or other regulatory agency’s policies may change, and additional government regulations may be enacted that could prevent, limit, or delay regulatory approval of our product candidates or require certain changes to the labeling or additional clinical work concerning the safety and efficacy of the product candidates.
Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with our contract manufacturers or manufacturing processes, or failure to comply with regulatory requirements, are reportable events to the FDA and may result in, among other things: • restrictions on the marketing or manufacturing of the product, withdrawal of the product from the market, revised labeling, or voluntary or involuntary product recalls; • additional clinical studies, fines, warning letters or holds on target animal studies; • refusal by the FDA, or other regulators to approve pending applications or supplements to approved applications filed by us or our strategic collaborators related to the unknown problems, or suspension or revocation of the problematic product’s license approvals; • product seizure or detention, or refusal to permit the import or export of products; and • injunctions and/or the imposition of civil or criminal penalties.
Speculation on the price of our common stock may involve long and short exposures. To the extent aggregate short exposure exceeds the number of shares of our common stock available for purchase in the open market, investors with short exposure may have to pay a premium to repurchase our common stock for delivery to lenders of our common stock.
To the extent aggregate short exposure exceeds the number of shares of our common stock available for purchase in the open market, investors with short exposure may have to pay a premium to repurchase our common stock for delivery to lenders of our common stock.
Even if we successfully identify potential products, we may still fail to yield products for development and commercialization for many reasons, including the following: ​ ● competitors may develop alternatives that render our potential products obsolete; ​ ● an outside party may develop a cure for any disease state that is the target indication for any of our planned or approved drug products; ​ 41 Table of Contents ● potential products we seek to develop may be covered by third-party patents or other exclusive rights; ​ ● a potential product may, on further study, be shown to have harmful side effects or other characteristics that indicate it is unlikely to be effective or otherwise does not meet applicable regulatory criteria; ​ ● a potential product may not be capable of being produced in commercial quantities at an acceptable cost or at all; and ​ ● a potential product may not be accepted as safe and effective by physicians, veterinarians, patients, animal owners, key opinion leaders, and other decision-makers in the gastrointestinal health market, as applicable. ​ While we are developing specific formulations, including flavors, methods of administration, new patents, and other strategies with respect to our current potential products, we may be unable to prevent competitors from developing substantially similar products and bringing those products to market earlier than we can.
Even if we successfully identify potential products, we may still fail to yield products for development and commercialization for many reasons, including the following: • competitors may develop alternatives that render our potential products obsolete; • an outside party may develop a cure for any disease state that is the target indication for any of our planned or approved drug products; • potential products we seek to develop may be covered by third-party patents or other exclusive rights; • a potential product may, on further study, be shown to have harmful side effects or other characteristics that indicate it is unlikely to be effective or otherwise does not meet applicable regulatory criteria; • a potential product may not be capable of being produced in commercial quantities at an acceptable cost or at all; and 43 Table of Contents • a potential product may not be accepted as safe and effective by physicians, veterinarians, patients, animal owners, key opinion leaders, and other decision-makers in the gastrointestinal health market, as applicable.
Conte founded Napo in 2001 and was Napo's interim chief executive officer and a member of its board of directors prior to the merger. While at Napo, certain members of our management team, including Ms. Conte and Dr. King, continued the development of crofelemer.
Conte founded Napo in 2001 and was Napo's interim chief executive officer and a member of its board of directors prior to the merger. While at Napo, certain members of our management team, including Ms. Conte and Dr. King, continued the development of crofelemer. Following the merger of Jaguar and Napo in July 2017, Napo became Jaguar’s wholly owned subsidiary.
We do not know whether our current or planned pivotal trials for any of our product candidates will begin or conclude on time, and they may be delayed or discontinued for a variety of reasons, including if we are unable to: ​ ● address any safety concerns that arise during the course of the studies; ​ ● complete the studies due to deviations from the study protocols or the occurrence of adverse events; ​ ● add new study sites; ​ ● address any conflicts with new or existing laws or regulations; or ​ ● reach agreement on acceptable terms with study sites, which can be subject to extensive negotiation and may vary significantly among different sites. ​ Further, we may not be successful in developing new indications for Mytesi and Canalevia-CA1, and Neonorm may be subject to the same regulatory regime as prescription drug products in jurisdictions outside the US.
We do not know whether our current or planned pivotal trials for any of our product candidates will begin or conclude on time, and they may be delayed or discontinued for a variety of reasons, including if we are unable to: • address any safety concerns that arise during the course of the studies; • complete the studies due to deviations from the study protocols or the occurrence of adverse events; • add new study sites; • address any conflicts with new or existing laws or regulations; or • reach agreement on acceptable terms with study sites, which can be subject to extensive negotiation and may vary significantly among different sites.
If we are not successful in developing and successfully commercializing these line extension products, we may not be able to grow our revenue, and our business may be harmed. ​ 43 Table of Contents Development of prescription drug products is inherently expensive, time-consuming and uncertain, and any delay or discontinuance of our current or future pivotal trials would harm our business and prospects. ​ Development of prescription drug products for human and animal gastrointestinal health remains an inherently lengthy, expensive, and uncertain process, and our development activities may not be successful.
If we are not successful in developing and successfully commercializing these line extension products, we may not be able to grow our revenue, and our business may be harmed. 45 Table of Contents Development of prescription drug products is inherently expensive, time-consuming and uncertain, and any delay or discontinuance of our current or future pivotal trials would harm our business and prospects.
Either outcome could lead to significantly lower revenue and significantly harm our operating results. ​ We may engage in future acquisitions that increase our capital requirements, dilute our stockholders, cause us to incur debt or assume contingent liabilities and subject us to other risks. ​ We may evaluate various strategic transactions, including licensing or acquiring complementary products, technologies, or businesses.
We may engage in future acquisitions that increase our capital requirements, dilute our stockholders, cause us to incur debt or assume contingent liabilities and subject us to other risks. We may evaluate various strategic transactions, including licensing or acquiring complementary products, technologies, or businesses.
If Nasdaq delists our common stock, the price of our common stock may decline, and our common stock may be eligible to trade on the OTC Bulletin Board, another over-the-counter quotation system, or on the pink sheets, which would negatively affect the liquidity of our common stock and an investor may find it more difficult to dispose of their common stock or obtain accurate quotations as to the market value of our common stock. ​ On January 23, 2023, we effected a 1-for-75 reverse stock split of our outstanding voting common stock.
If Nasdaq delists our common stock, the price of our common stock may decline, and our common stock may be eligible to trade on the OTC Bulletin Board, another over-the-counter quotation system, or on the pink sheets, which would negatively affect the liquidity of our common stock and an investor may find it more difficult to dispose of their common stock or obtain accurate quotations as to the market value of our common stock.
Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with our contract manufacturers or manufacturing processes, or failure to comply with regulatory requirements, are reportable events to the FDA and may result in, among other things: ​ ● restrictions on the marketing or manufacturing of the product, withdrawal of the product from the market, revised labeling, or voluntary or involuntary product recalls; ​ ● additional clinical studies fines, warning letters or holds on studies; ​ ● refusal by the FDA, or other regulators to approve pending applications or supplements to approved applications filed by Napo or Napo’s strategic collaborators related to the unknown problems or suspension or revocation of the problematic product’s license approvals; ​ ● product seizure or detention, or refusal to permit the import or export of products; and ​ ● injunctions or the imposition of civil or criminal penalties. ​ The FDA or other regulatory agency’s policies may change, and additional government regulations may be enacted that could prevent, limit, or delay regulatory approval of our product candidates, require certain labeling changes, or require additional clinical work concerning the safety and efficacy of the product candidates.
Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with 62 Table of Contents our contract manufacturers or manufacturing processes, or failure to comply with regulatory requirements, are reportable events to the FDA and may result in, among other things: • restrictions on the marketing or manufacturing of the product, withdrawal of the product from the market, revised labeling, or voluntary or involuntary product recalls; • additional clinical studies fines, warning letters or holds on studies; • refusal by the FDA, or other regulators to approve pending applications or supplements to approved applications filed by Napo or Napo’s strategic collaborators related to the unknown problems or suspension or revocation of the problematic product’s license approvals; • product seizure or detention, or refusal to permit the import or export of products; and • injunctions or the imposition of civil or criminal penalties.
There can be no assurance that we will be able to maintain compliance or, if we fall out of compliance, regain compliance with any deficiency, or if we implement an option that regains our compliance, maintain compliance thereafter. ​ If our shares become subject to the penny stock rules, it would become more difficult to trade our shares. ​ The SEC has adopted rules that regulate broker-dealer practices in connection with transactions in penny stocks.
There can be no assurance that we will be able to maintain compliance or, if we fall out of compliance, regain compliance with any deficiency, or if we implement an option that regains our compliance, maintain compliance thereafter. If our shares become subject to the penny stock rules, it would become more difficult to trade our shares.
Because we do not intend to pay dividends, your ability to receive a return on your investment will depend on any future appreciation in the market price of our common stock.
We currently intend to invest our future earnings, if any, to fund our growth and not to pay any cash dividends on our common stock. Because we do not intend to pay dividends, your ability to receive a return on your investment will depend on any future appreciation in the market price of our common stock.
These royalty interests require us to make minimum royalty payments beginning in 2021, even if we do not sell a sufficient amount of product to cover such payments, which may strain our cash resources.
These royalty interests require us to make minimum royalty payments beginning in 2021, even if we do not sell a sufficient amount of product to cover such payments, which may strain our cash resources. The total minimum royalty payments will be approximately $27.0 million in 2026.
While we currently have product liability insurance, such insurance may not be sufficient to cover any future product liability claims against us. ​ If we fail to retain current members of our senior management or to identify, attract, integrate, and retain additional key personnel, our business will be harmed. ​ Our success depends on our continued ability to attract, retain, and motivate highly qualified management and scientific personnel.
While we currently have product liability insurance, such insurance may not be sufficient to cover any future product liability claims against us. 47 Table of Contents If we fail to retain current members of our senior management or to identify, attract, integrate, and retain additional key personnel, our business will be harmed.
Even if we or our collaborators were able to obtain such a license, the rights may be nonexclusive, which could allow our competitors access to the same intellectual property.
Even if we or our collaborators were able to obtain such a license, the rights may be nonexclusive, which could allow our competitors access to the same intellectual property. Any of these events could harm our business and prospects.
In addition, failure to comply with these regulatory requirements could result in significant penalties and delays. ​ In addition, from time to time, we may enter into consulting and other financial arrangements with physicians or veterinarians, who prescribe or recommend our products once approved.
In addition, failure to comply with these regulatory requirements could result in significant penalties and delays. In addition, from time to time, we may enter into consulting and other financial arrangements with physicians or veterinarians, who prescribe or recommend our products once approved. As a result, we may be subject to state, federal, and foreign healthcare and/or veterinary medicine laws.
The FDA and foreign regulatory authorities also require us and our CROs to comply with regulations and standards, GCPs or GLPs, for conducting, monitoring, recording, and reporting the results of our studies to ensure that the data and results are scientifically valid and accurate. ​ Agreements with CROs generally allow the CROs to terminate in certain circumstances with little or no advance notice.
The FDA and foreign regulatory authorities also require us and our CROs to comply with regulations and standards, GCPs or GLPs, for conducting, monitoring, recording, and reporting the results of our studies to ensure that the data and results are scientifically valid and accurate.
This designation does not allow us to commercialize a product until such time as we obtain approval or conditional approval of the product. ​ Because Canalevia-CA1 has received MUMS designation for the identified particular intended use, we are eligible to obtain seven years of exclusive marketing rights upon approval (or conditional approval) of Canalevia-CA1 for that intended use and become eligible for grants to defray the cost of our clinical work.
Because Canalevia-CA1 has received MUMS designation for the identified particular intended use, we are eligible to obtain seven years of exclusive marketing rights upon approval (or conditional approval) of Canalevia-CA1 for that intended use and become eligible for grants to defray the cost of our clinical work.
Such changes could, among other things, require: ​ ● changes to manufacturing methods; ​ ● additional clinical trials or testing; ​ ● new requirements related to approval to enter the market; ​ ● recall, replacement, or discontinuance of certain products; and ​ ● additional record keeping or the development of certain regulatory-required hazard identification plans. ​ Each of these would likely entail substantial time and cost and could harm our financial results.
Such changes could, among other things, require: • changes to manufacturing methods; • additional clinical trials or testing; • new requirements related to approval to enter the market; • recall, replacement, or discontinuance of certain products; and • additional record keeping or the development of certain regulatory-required hazard identification plans.
The outcome following legal assertions of invalidity and unenforceability is unpredictable. If a defendant were to prevail on a legal assertion of invalidity or unenforceability, we would lose at least part, and perhaps all, of any future patent protection on one or more of our products or our current or future product candidates.
If a defendant were to prevail on a legal assertion of invalidity or unenforceability, we would lose at least part, and perhaps all, of any future patent protection on one or more of our products or our current or future product candidates. Such a loss of patent protection could harm our business.
If we are not successful in commercializing Mytesi and/or Canalevia-CA1, for their respective currently approved or conditionally approved indications or for any potential follow-on indications, either on our own or through one or more distributors, or in generating upfront licensing or other fees, including through the previously announced licensing arrangement between Napo Pharmaceuticals, Inc. and Napo Therapeutics S.p.A., we may never generate significant revenue and may continue to incur significant losses, which would harm our financial condition and results of operations. ​ ​ 47 Table of Contents We will need to increase the size of our organization and may not successfully manage such growth. ​ As of December 31, 2023, we had forty-nine employees.
If we are not successful in commercializing Mytesi Canalevia-CA1, Gelclair, and/or any of our other products, for their respective currently approved or conditionally approved indications or for any potential follow-on indications, either on our own or through one or more distributors, or in generating upfront licensing or other fees, including through the previously announced licensing arrangement between Napo Pharmaceuticals, Inc. and Napo Therapeutics S.p.A., we may never generate significant revenue and may continue to incur significant losses, which would harm our financial condition and results of operations.
If the market potential for our human or animal products is less than we anticipate due to one or more of these factors, it could negatively impact our business, financial condition and results of operations.
If the market potential for our human or animal products is less than we anticipate due to one or more of these factors, it could negatively impact our business, financial condition and results of operations. Further, the willingness of patients to pay for our products may be less than we anticipate, and may be negatively affected by overall economic conditions.
Accordingly, we may not be successful in developing or commercializing Mytesi, Neonorm, Equilevia, Canalevia, or any of our other potential products.
Many of these factors are beyond our control. Accordingly, we may not be successful in developing or commercializing Mytesi, Gelclair, Neonorm, Equilevia, Canalevia, or any of our other potential products.
Mytesi is currently covered by Medicaid in all 50 states. However, the nature or extent of coverage for Mytesi by any of these plans or programs could change or be terminated, or Mytesi might not receive insurance coverage for any approved follow-on indications.
Mytesi is currently covered by Medicaid in all 50 states. However, the nature or extent of coverage for Mytesi by any of these plans or programs could change or be terminated, or Mytesi might not receive insurance coverage for any approved follow-on indications. Either outcome could lead to significantly lower revenue and significantly harm our operating results.
Market acceptance of Mytesi, Canalevia, and any of our other products depends on a number of factors, including: ​ ● the safety of our products as demonstrated in our target animal studies; ​ ● the indications for which our products are approved or marketed; ​ ● the potential and perceived advantages over alternative treatments or products, including generic medicines and competing products currently prescribed by physicians or veterinarians, as applicable, and, in the case of animal products, products approved for use in humans that are used extra-label in animals; ​ ● the acceptance by physicians, veterinarians, and companion animal owners, as applicable, of our products as safe and effective; ​ ● the cost in relation to alternative treatments and willingness on the part of physicians, veterinarians, patients, and animal owners, as applicable, to pay for our products; ​ ● the prevalence and severity of any adverse side effects of our products; ​ ● the relative convenience and ease of administration of our products; and ​ ● the effectiveness of our sales, marketing, and distribution efforts. ​ Any failure by Mytesi or Canalevia to achieve market acceptance or commercial success would harm our financial condition and the results of operations. ​ Human and animal gastrointestinal health products are subject to unanticipated post-approval safety or efficacy concerns, which may harm our business and reputation. ​ The success of our commercialization efforts will depend upon the perceived safety and effectiveness of human and animal gastrointestinal health products, in general, and of our products, in particular.
Market acceptance of Mytesi, Canalevia, and any of our other products depends on a number of factors, including: • the safety of our products as demonstrated in our target animal studies; • the indications for which our products are approved or marketed; • the potential and perceived advantages over alternative treatments or products, including generic medicines and competing products currently prescribed by physicians or veterinarians, as applicable, and, in the case of animal products, products approved for use in humans that are used extra-label in animals; • the acceptance by physicians, veterinarians, and companion animal owners, as applicable, of our products as safe and effective; • the cost in relation to alternative treatments and willingness on the part of physicians, veterinarians, patients, and animal owners, as applicable, to pay for our products; • the prevalence and severity of any adverse side effects of our products; • the relative convenience and ease of administration of our products; and • the effectiveness of our sales, marketing, and distribution efforts.
We also could be subject to damages claims if we were found to be at fault in connection with a decline in our stock price. ​ 64 Table of Contents A possible “short squeeze” due to a sudden increase in demand for our common stock that largely exceeds supply may lead to further price volatility in our common stock. ​ Investors may purchase shares of our common stock to hedge existing exposure in our common stock or to speculate on the price of our common stock.
We also could be subject to damages claims if we were found to be at fault in connection with a decline in our stock price. A possible “short squeeze” due to a sudden increase in demand for our common stock that largely exceeds supply may lead to further price volatility in our common stock.
We intend to develop, promote, and commercialize approved products for new animal treatment indications in the future, but we cannot be certain whether or at what additional time and expense we will be able to do so.
We intend to develop, promote, and commercialize approved products for new animal treatment indications in the future, but we cannot be certain whether or at what additional time and expense we will be able to do so. If we do not obtain marketing approvals for new indications, our ability to expand our animal health business may be harmed.
Proceedings to enforce our future patent rights, if any, in foreign jurisdictions could result in substantial cost and divert our efforts and attention from other aspects of our business. ​ Our business could be harmed if we fail to obtain certain registered trademarks in the US or in other countries. ​ Our registered and pending US trademarks include MYTESI®, JAGUAR HEALTH®, the Jaguar Health Logo®, NAPO®, Napo Logo®, Napo Therapeutics, CANALEVIA, CANALEVIA-CA1, CANALEVIA-CA2, EQUILEVIA, NEONORM®, JAGUAR ANIMAL HEALTH®, and the Jaguar Animal Health Logo®.
Proceedings to enforce our future patent rights, if any, in foreign jurisdictions could result in substantial cost and divert our efforts and attention from other aspects of our business. Our business could be harmed if we fail to obtain certain registered trademarks in the US or in other countries.
Additionally, an allegation or perception that we have not taken sufficient action in these areas could negatively harm our reputation. ​ The growing use of AI systems to automate processes, analyze data, and support decision-making poses inherent risks. ​ Flaws, biases, or malfunctions in systems powered by AI could lead to operational disruptions, data loss, or erroneous decision-making, that may impact business operations, financial condition, and reputation.
The growing use of AI systems to automate processes, analyze data, and support decision-making poses inherent risks. Flaws, biases, or malfunctions in systems powered by AI could lead to operational disruptions, data loss, or erroneous decision-making, that may impact business operations, financial condition, and reputation.
If we fail to achieve or maintain profitability, then we may be unable to continue our operations at planned levels and be forced to reduce or cease operations. ​ As more fully discussed in Note 1 to our consolidated financial statements, we believe there is substantial doubt about our ability to continue as a going concern as we do not currently have sufficient cash resources to fund our operations through March 2025, or one year from the filing date of our Form 10-K.
As more fully discussed in Note 1 to our consolidated financial statements, we believe there is substantial doubt about our ability to continue as a going concern as we do not currently have sufficient cash resources to fund our operations through March 2026, or one year from the filing date of our Form 10-K.
Although our common stock is listed on The Nasdaq Capital Market, its trading volume has been limited, and an active trading market for our shares may never develop or be sustained.
The listing of our common stock on The Nasdaq Capital Market does not assure that a meaningful, consistent, and liquid trading market exists. Although our common stock is listed on The Nasdaq Capital Market, its trading volume has been limited, and an active trading market for our shares may never develop or be sustained.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeOur board of directors administers its cybersecurity risk oversight function directly as a whole, as well as through the audit committee. Our Chief Financial Officer and Chief Compliance Officer are primarily responsible for assessing and managing our material risks from cybersecurity threats with assistance from third-party service providers.
Biggest changeOur board of directors administers its cybersecurity risk oversight function directly as a whole, as well as through the audit committee.
Personnel at all levels and departments are made aware of our cybersecurity policies through training sessions. We engage consultants or other third parties in connection with our risk assessment processes. These service providers assist us in designing and implementing our cybersecurity policies and procedures and monitor and test our safeguards.
Personnel at all levels and departments are made aware of our cybersecurity policies through training. We engage consultants or other third parties in connection with our risk assessment processes. These service providers assist us in designing and implementing our cybersecurity policies and procedures and monitor and test our safeguards.
Primary responsibility for assessing, monitoring, and managing our cybersecurity risks rests with an IT consultant who reports to our Chief Compliance Officer to manage the risk assessment and mitigation process. 68 Table of Contents As part of our overall risk management system, we monitor and test our safeguards and train our employees on these safeguards in collaboration with IT and management.
Primary responsibility for assessing, monitoring, and managing our cybersecurity risks rests with an IT consultant who reports to our Chief Compliance Officer to manage the risk assessment and mitigation process. As part of our overall risk management system, we monitor and test our safeguards and train our employees on these safeguards in collaboration with IT and management.
ITEM 1C. CYBERSECURITY ​ Risk management and strategy We have established policies and processes for assessing, identifying, and managing material risk from cybersecurity threats and have integrated these processes into our overall risk management systems and processes.
ITEM 1C. CYB ERSECURITY Risk management and strategy We have established policies and processes for assessing, identifying, and managing material risk from cybersecurity threats and have integrated these processes into our overall risk management systems and processes.
PROPERTIES Our corporate headquarters are located at 200 Pine Street, Suite 400, San Francisco, California. ​
PR OPERTIES Our corporate headquarters are located at 200 Pine Street, Suite 400, San Francisco, California.
Our Chief Financial Officer and Chief Compliance Officer oversee our cybersecurity policies and processes, including those described in “Risk Management and Strategy” above. The cybersecurity risk management program includes tools and activities to prevent, detect, and analyze current and emerging cybersecurity threats and plans and strategies to address threats and incidents.
The cybersecurity risk management program includes tools and activities to prevent, detect, and analyze current and emerging cybersecurity threats and plans and strategies to address threats and incidents.
Removed
We require each third-party service provider to certify that it has the ability to implement and maintain appropriate security measures, consistent with all applicable laws, to implement and maintain reasonable security measures in connection with their work with us, and to promptly report any suspected breach of its security measures that may affect our company.
Added
Our Chief Financial Officer and Chief Compliance Officer are primarily responsible for assessing and managing our material risks from cybersecurity threats with assistance from third-party service providers. 69 Table of Contents Our Chief Financial Officer and Chief Compliance Officer oversee our cybersecurity policies and processes, including those described in “Risk Management and Strategy” above.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeWe are not currently subject to any material legal proceedings. ​ ITEM 4. MINE SAFETY DISCLOSURE Not applicable. ​ 69 Table of Contents PART II
Biggest changeWe are not currently subject to any material legal proceedings. ITEM 4. MI NE SAFETY DISCLOSURE Not applicable. 70 Table of Contents P ART II
ITEM 3. LEGAL PROCEEDINGS From time to time, we may be subject to various legal proceedings and claims that arise in the ordinary course of our business activities. Regardless of the outcome, litigation can have a material adverse effect on us due to defense and settlement costs, diversion of our management resources, and other factors.
ITEM 3. LE GAL PROCEEDINGS From time to time, we may be subject to various legal proceedings and claims that arise in the ordinary course of our business activities. Regardless of the outcome, litigation can have a material adverse effect on us due to defense and settlement costs, diversion of our management resources, and other factors.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeRecent Sales of Unregistered Securities On December 28, 2023, pursuant to that certain exchange agreement dated December 28, 2023, the Company issued 4,875,000 shares of the Company’s common stock to Iliad Research and Trading, L.P. in exchange for a $785,362.50 reduction in the outstanding balance of the royalty interest held by Iliad Research and Trading, L.P.
Biggest changeRecent Sales of Unregistered Securities On January 29, 2024, the Company entered into a privately negotiated exchange agreement with Streeterville pursuant to which the Company issued 1,058 shares of the Company’s common stock, par value $0.0001 to Streeterville in exchange for a $165,000 reduction in the outstanding balance of the royalty interest dated August 24, 2022.
ITEM 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES Market Information Our common stock trades on The Nasdaq Capital Market under the symbol “JAGX.” Holders As of April 1, 2025, there were approximately 22 stockholders of record of our common stock.
ITEM 5. MARKET FOR REGISTRANT’S CO MMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES Market Information Our common stock trades on The Nasdaq Capital Market under the symbol “JAGX.” Holders As of March 31, 2025, there were approximately seventeen stockholders of record of our common stock.
Each of the recipients of securities in these transactions was an accredited or sophisticated person and had adequate access, through employment, business, or other relationships, to information about us. ​ ITEM 6. SELECTED FINANCIAL DATA Not Applicable. ​
Each of the recipients of securities in these transactions was an accredited or sophisticated person and had adequate access, through employment, business, or other relationships, to information about us.
Other than equity securities issued in transactions disclosed above and on our Current Report on Form 8-K filed with the SEC on October 5, 2023, there were no unregistered sales of equity securities during the period. Refer to Item 15. Subsequent Events for subsequent sales of unregistered securities.
Other than equity securities issued in transactions disclosed above and on our Current Report on Form 8-K filed with the SEC on March 1, 2024, March 8, 2024, March 21, 2024, June 10, 2024, and July 16, 2024, there were no unregistered sales of equity securities during the period. Refer to Item 15.
Added
On January 29, 2024, the Company entered into a privately negotiated exchange agreement with Iliad pursuant to which the Company issued an aggregate of 5,333 shares of the Company’s common stock to Iliad in exchange for a $836,000 reduction in the outstanding balance of the royalty interest dated October 8, 2020, Royalty Interest.
Added
The effect of the exchange was accounted for as a debt modification. On February 27, 2024, pursuant to the PIPE Purchase Agreement, each of the PIPE investors entered into an exchange agreement with the Company (each, a “PIPE Warrant Exchange Agreement” and collectively, the “PIPE Warrant Exchange Agreements”).
Added
Pursuant to the PIPE Warrant Exchange Agreements, the Company agreed to exchange the PIPE Warrants for shares of common stock at an exchange ratio of 1-for-2.5 (“PIPE Warrant Exchange Transaction”).
Added
Upon completion of the PIPE Warrant Exchange Transaction, the Company exchanged the PIPE Warrants to purchase up to 5,023 shares of Common Stock for 12,558 shares of Common Stock (the “PIPE Exchange Shares”), and the PIPE Warrants were terminated.
Added
The PIPE Exchange Shares would be subject to a twelve-month lock-up, and any other equity security of the Company other than the PIPE Exchange Shares owned by the PIPE investors as of the date of the PIPE Warrant Exchange Agreement would be subject to a six-month lock-up.
Added
On March 1, 2024, the Company entered into a privately negotiated exchange agreement with Streeterville, pursuant to which the Company issued an aggregate of 179 shares of Series J Preferred Stock to Streeterville in exchange for the surrender of the March 2021 Royalty Interest by Streeterville.
Added
Upon completion of the CVP Exchange Transaction, all outstanding balance of the March 2021 Royalty Interest was fully paid, and the March 2021 Royalty Interest was terminated.
Added
On March 5, 2024, the Company entered into a privately negotiated exchange agreement with Streeterville, pursuant to which the Company issued 6,667 shares of the Company’s common stock in exchange for the surrender and cancellation of 40 shares of Series J Perpetual Preferred Stock.
Added
On March 18, 2024, the Company entered into a privately negotiated securities purchase agreement with Gen Ilac Ve Saglik Urunleri Sanayi Ve Ticaret, A.S., ("Gen") pursuant to which the Company issued 11,111 shares of the Company’s common stock at $3.00 per share for gross proceeds of approximately $2.0 million.
Added
The sale of the 71 Table of Contents securities was consummated in connection with the licensing transaction covering the exclusive license and commercialization agreement for the Company's FDA-approved prescription drug Crofelemer with purchasers in certain Eastern European countries.
Added
On March 19, 2024, the Company entered into a privately negotiated exchange agreement with Streeterville, pursuant to which the Company issued 5,556 shares of the Company’s common stock in exchange for the surrender and cancellation of 40 shares of Series J Perpetual Preferred Stock based on an effective exchange price of $180.00 per share of common stock.
Added
On June 7, 2024, the Company entered into an exchange agreement with Iliad, pursuant to which the parties agreed to partition $1,500,000 from the outstanding balance of the royalty interest dated October 8, 2020. This reduced the outstanding balance of the original royalty interest. The partitioned royalty was exchanged for 262 shares of the Company’s common stock.
Added
On July 15, 2024, the Company entered into a privately negotiated exchange agreement with Iliad pursuant to which the Company issued an aggregate of 18,200 shares of the Company's common stock to Iliad in exchange for a $1.9 million reduction in the outstanding balance of the original royalty interest.
Added
The effect of the exchange was accounted for as a debt modification. On July 18, 2024, the Company entered into a privately negotiated exchange agreement with Iliad pursuant to which the Company issued an aggregate of 8,000 shares of the Company's common stock to Iliad in exchange for $819,000 reduction in the outstanding balance of the original royalty interest.
Added
The effect of the exchange was accounted for as a debt modification.
Added
Subsequent Events for subsequent sales of unregistered securities.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

53 edited+63 added−7 removed17 unchanged
Biggest changeResults of Operations Comparison of the Years Ended December 31, 2023 and 2022 The following table summarizes the Company’s results of operations with respect to the items set forth in such table for the years ended December 31, 2023 and 2022 together with the change in such items in dollars and as a percentage. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ ​ ​ ​ ​ ​ ​ December 31, ​ ​ ​ ​ ​ ​ (in thousands) 2023 2022 Variance Variance % ​ Product revenue, net ​ $ 9,761 ​ $ 11,956 ​ $ (2,195) (18.4) % Operating Expenses ​ ​ ​ ​ ​ Cost of product revenue ​ 2,037 ​ 2,019 ​ 18 0.9 % Research and development ​ 18,596 ​ 17,647 ​ 949 5.4 % Sales and marketing ​ 6,460 ​ 8,837 ​ (2,377) (26.9) % General and administrative ​ 16,588 ​ 17,868 ​ (1,280) (7.2) % Impairment loss on intangible assets ​ ​ 371 ​ ​ — ​ ​ 371 ​ 100.0 % Total operating expenses ​ 44,052 ​ 46,371 ​ (2,319) (5.0) % Loss from operations ​ (34,291) ​ (34,415) ​ 124 (0.4) % Interest expense ​ (6,382) ​ (12,723) ​ 6,341 (49.8) % Change in fair value of freestanding and hybrid financial instruments designated at Fair Value Option ​ (5,125) ​ (20) ​ (5,105) 25,525.0 % Gain (loss) on extinguishment of debt ​ 3,697 ​ (2,187) ​ 5,884 (269.0) % Other income ​ 200 ​ 950 ​ (750) (78.9) % Loss before income tax ​ (41,901) ​ (48,395) ​ 6,494 (13.4) % Income tax expense ​ ​ — ​ ​ — ​ ​ — ​ 100.0 % Net loss ​ $ (41,901) ​ $ (48,395) ​ $ 6,494 ​ (13.4) % Net loss attributable to noncontrolling interest ​ $ (601) ​ $ (941) ​ $ 340 ​ (36.1) % Net loss attributable to common stockholders ​ $ (41,300) ​ $ (47,454) ​ $ 6,154 ​ (13.0) % ​ 75 Table of Contents Revenue Product revenue Sales discounts were $1.4 million and $1.2 million for the years ended December 31, 2023, and 2022, respectively, an increase of $267,000. ​ Medicaid and AIDS Drug Assistance Program (“ADAP”) rebates accounted for $2.0 million and $1.8 million for the years ended December 31, 2023 and 2022, respectively, an increase of $205,000. ​ Due to the Company’s arrangements, including elements of variable consideration, gross product sales are reduced in order to reflect the expected consideration to arrive at net product sales.
Biggest changeYear Ended December 31, (in thousands) 2024 2023 Variance Variance % Product revenue, net $ 11,560 $ 9,761 $ 1,799 18.4 % License revenue 129 — 129 100.0 % Total revenue 11,689 9,761 1,928 19.8 % Operating expenses Cost of product revenue 1,955 2,037 (82 ) (4.0 ) % Research and development 16,542 18,596 (2,054 ) (11.0 ) % Sales and marketing 7,692 6,460 1,232 19.1 % General and administrative 16,331 16,588 (257 ) (1.5 ) % Impairment loss on intangible assets — 371 (371 ) (100.0 ) % Total operating expenses 42,520 44,052 (1,532 ) (3.5 ) % Loss from operations (30,831 ) (34,291 ) 3,460 (10.1 ) % Interest expense (231 ) (6,382 ) 6,151 (96.4 ) % Changes in fair value of freestanding and hybrid financial instruments designated at Fair Value Option (9,485 ) (5,125 ) (4,360 ) 85.1 % Gain on extinguishment of debt 1,245 3,697 (2,452 ) (66.3 ) % Other income 51 200 (149 ) (74.5 ) % Loss before income tax expense (39,251 ) (41,901 ) 2,650 (6.3 ) % Income tax expense — — — — % Net loss $ (39,251 ) $ (41,901 ) $ 2,650 (6.3 ) % Net loss attributable to noncontrolling interest $ (759 ) $ (601 ) $ (158 ) 26.3 % Net loss attributable to common stockholders $ (38,492 ) $ (41,300 ) $ 2,808 (6.8 ) % 79 Table of Contents Revenue License revenue License revenues increased by $129,000 from $0 for the year ended December 31, 2023 to $129,000 in the same period in 2024, due to license agreement entered by the Company with GEN on March 18, 2024.
The small number threshold is currently 80,000 for dogs, representing the largest number of dogs that can be affected by a disease or condition over the course of a year and still have the use qualify as a minor use.
The small number threshold is currently 80,000 for dogs, representing the largest number of dogs that can be affected by a disease or condition over a year and still have the use qualify as a minor use.
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 and foals. 71 Table of Contents Crofelemer is a novel, first-in-class anti-secretory antidiarrheal drug which has a normalizing effect on electrolyte and fluid balance in the gut, and this mechanism of action has the potential to benefit multiple disorders that cause gastrointestinal distress, including diarrhea and abdominal discomfort.
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 and foals. 74 Table of Contents Crofelemer is a novel, first-in-class anti-secretory antidiarrheal drug that has a normalizing effect on electrolyte and fluid balance in the gut, and this mechanism of action has the potential to benefit multiple disorders that cause GI distress, including diarrhea and abdominal discomfort.
The timing and amount of our research and development expenses will depend largely upon the outcomes of current and future trials for our prescription drug product candidates as well as the related regulatory requirements, the outcomes of current and future species-specific formulation studies for our non-prescription products, manufacturing 73 Table of Contents costs and any costs associated with the advancement of our line extension programs.
The timing and amount of our research and development expenses will depend largely upon the outcomes of current and future trials for our prescription drug product candidates, as well as the related regulatory requirements, the outcomes of current and future species-specific formulation studies for our non-prescription products, manufacturing costs and any costs associated with the advancement of our line extension programs.
In December 2021 we received conditional approval from the FDA to market Canalevia-CA1 (crofelemer delayed-release tablets), our oral plant-based prescription drug and the only available veterinary drug for the treatment of chemotherapy-induced diarrhea (“CID”) in dogs, and Canalevia-CA1 is now available to multiple leading veterinary distributors in the US Canalevia-CA1 is a tablet that is given orally and can be prescribed for home treatment of CID.
In December 2021, we received conditional approval from the FDA to market Canalevia-CA1 (crofelemer delayed-release tablets), our oral plant-based prescription drug and the only available veterinary drug for the treatment of CID in dogs, and Canalevia-CA1 is now available to multiple leading veterinary distributors in the US Canalevia-CA1 is a tablet that is given orally and can be prescribed for home treatment of CID.
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.
Immediately following the Merger, Jaguar changed its name from 73 Table of Contents “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.
Canalevia-CA1 is conditionally approved by the FDA under application number 141-552. Conditional approval allows for commercialization of the product while Jaguar Animal Health continues to collect the substantial evidence of effectiveness required for full approval. We have received Minor Use in a Major Species (“MUMS”) designation from the FDA for Canalevia-CA1 to treat CID in dogs.
The FDA conditionally approves Canalevia-CA1 under application number 141-552. Conditional approval allows for product commercialization while Jaguar Animal Health continues to collect the substantial evidence of effectiveness required for full approval. We have received a Minor Use in a Major Species (“MUMS”) designation from the FDA for Canalevia-CA1 to treat CID in dogs.
In January 2023, Jaguar and Filament Health (“Filament”), with funding from One Small Planet, formed the US-based joint venture Magdalena Biosciences, Inc. (“Magdalena”). Magdalena’s focus is on the development of novel, natural prescription medicines derived from plants for mental health indications including, initially, attention-deficit/hyperactivity disorder (“ADHD”) in adults.
In January 2023, Jaguar and Filament, with funding from One Small Planet, formed the US-based joint venture Magdalena. Magdalena’s focus is on the development of novel, natural prescription medicines derived from plants for mental health indications, including, initially, attention-deficit/hyperactivity disorder (“ADHD”) in adults.
ITEM 7. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS The following discussion and analysis should be read together with our financial statements and the related notes appearing elsewhere in this report. Overview Jaguar Health, Inc.
ITEM 7. MANAG EMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS The following discussion and analysis should be read together with our financial statements and the related notes appearing elsewhere in this report. Overview Jaguar Health, Inc.
Cash Provided by Financing Activities During the year ended December 31, 2023, net cash provided by financing activities of $34.2 million consisted of $32.1 million in net proceeds from shares issued in an At the Market offering, $1.2 million net proceeds from issuance of warrants in PIPE financing, investment from non-controlling interest of $1.2 million and $611,000 net proceeds from issuance of preferred shares in PIPE financing, offset by $853,000 repayment of insurance financing, and $100,000 in principal payments of Tampesta Note.
During the year ended December 31, 2023, net cash provided by financing activities of $34.2 million consisted of $32.1 million in net proceeds from shares issued in an At the Market offering, $1.2 million net proceeds from issuance of warrants in PIPE financing, investment from non-controlling interest of $1.2 million and $611,000 net proceeds from issuance of preferred shares in PIPE financing, offset by $853,000 repayment of insurance financing, and $100,000 in principal payments of Tempesta Note. 86 Table of Contents
However, there can be no assurance that additional funding will be available to us on acceptable terms on a 80 Table of Contents timely basis, if at all, or that we will generate sufficient cash from operations to adequately fund operating needs or ultimately achieve profitability.
However, there can be no assurance that additional funding will be available to us on acceptable terms on a timely basis, if at all, or that we will generate sufficient cash from operations to adequately fund operating needs or ultimately achieve profitability.
Sales and Marketing Expense Sales and marketing expenses consist of personnel and related benefit expense, stock- based compensation expense, direct sales and marketing expense, employee travel expense, and management consulting expense. We currently incur sales and marketing expenses to promote Mytesi.
Sales and Marketing Expense Sales and marketing expenses consist of personnel and related benefits, stock-based compensation, direct sales and marketing, employee travel, and management consulting expenses. We currently incur sales and marketing expenses to promote Mytesi and Gelclair.
We expect to continue to incur losses and experience increased expenditures for the foreseeable future as we expand our product development activities, seek necessary approvals for our product candidates, conduct species-specific formulation studies for our non-prescription products, establish active pharmaceutical ingredient (“API”) manufacturing capabilities and begin additional commercialization activities.
We expect to continue to incur losses, and experience increased expenditures for the foreseeable future as we expand our product development activities, seek necessary approvals for our product candidates, conduct species-specific formulation studies for our non-prescription products, establish API manufacturing capabilities and begin additional commercialization activities.
Additionally, several of the drug product opportunities in Jaguar’s crofelemer pipeline are backed by Phase 2 and proof of concept evidence from human clinical trials. ​ 72 Table of Contents Financial Operations Overview On a consolidated basis, we have not yet generated enough revenue to date to achieve break-even or positive cash flow, and we expect to continue to incur significant research and development and other expenses.
Additionally, several drug product opportunities in Jaguar’s crofelemer pipeline are backed by Phase 2 and POC evidence from human clinical trials. Financial Operations Overview On a consolidated basis, we have not yet generated enough revenue to date to achieve break-even or positive cash flow, and we expect to continue to incur significant research and development and other expenses.
Magdalena holds an exclusive license to plants and plant extracts in Jaguar's library, not including any sources of crofelemer or NP-300, for specific indications and is in the process of identifying plant candidates in the library that may prove beneficial for addressing indications such as ADHD.
Magdalena holds an exclusive license to plants and plant extracts in Jaguar's library, not including any sources of crofelemer or NP-300, for specific indications and is in the process of identifying plant candidates in the library that may prove beneficial for addressing indications such as ADHD. Magdalena is currently approximately 40-percent owned by Jaguar.
Napo Therapeutics’ core mission is to provide access to crofelemer in Europe to address significant rare/orphan disease indications, including, initially, two key rare disease target indications: Short bowel syndrome (“SBS”) with intestinal failure, rare disease indications of microvillus inclusion disease (“MVID”) and/or congenital diarrheal disorders (“CDD”). Jaguar Animal Health is a tradename of Jaguar Health.
Napo Therapeutics’ core mission is to provide access to crofelemer in Europe to address significant rare/orphan disease indications, including, initially, two key rare disease target indications: Short bowel syndrome (“SBS”) with intestinal failure and microvillus inclusion disease (“MVID”) an ultrarare congenital diarrheal disorder (“CDD"”). Jaguar Animal Health is a tradename of Jaguar Health. Magdalena Biosciences Inc.
Most of the activities of the Company are focused on the development and/or commercialization of Mytesi, including the ongoing clinical development of crofelemer for the prophylaxis of diarrhea in adult patients receiving targeted cancer therapy, and our prioritized clinical program centered around the approved investigator-initiated POC trial of crofelemer for SBS and CDD.
Most of the activities of the Company are focused on the development and commercialization of Mytesi, the ongoing clinical development of crofelemer for the prophylaxis of diarrhea in adult patients receiving targeted cancer therapy, the ongoing commercial launch of Gelclair, and our prioritized clinical program centered around investigator-initiated POC trials of crofelemer for SBS and MVID.
Mytesi is in development for multiple possible follow-on indications, including prophylaxis of diarrhea related to targeted therapy with or without standard chemotherapy. Crofelemer delayed-release tablets are also being evaluated in diarrhea-predominant irritable bowel syndrome (“IBS-D”) and idiopathic/functional diarrhea.
Crofelemer is in development for multiple possible follow-on indications, including for our lead Phase 3 program in CTD, investigating prophylaxis of diarrhea related to targeted therapy with or without standard chemotherapy. Crofelemer delayed-release tablets are also being evaluated in diarrhea-predominant irritable bowel syndrome (“IBS-D”) and being evaluated for chronic idiopathic/functional diarrhea in investigator-initiated trials.
This new venture aligns with Jaguar's mental health Entheogen Therapeutics Initiative (“ETI”) and Filament's corporate mission to develop novel, natural prescription medicines from plants. Magdalena will leverage Jaguar's proprietary medicinal plant library and Filament's proprietary drug development technology.
This venture aligns with Jaguar's ETI program and Filament's corporate mission to develop novel, natural prescription medicines from plants. Magdalena will leverage Jaguar's proprietary medicinal plant library and Filament's proprietary drug development technology.
Jaguar 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 animals.
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 animals.
FDA has established a "small number" threshold for minor use in each of the seven major species covered by the MUMS act.
FDA has established a “small number” threshold for minor use in each of the seven major species covered by 75 Table of Contents the MUMS Act.
Cash Flows for Year Ended December 31, 2023 compared to the Year Ended December 31, 2022 The following table shows a summary of cash flows for the years ended December 31, 2023 and 2022: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ (in thousands) 2023 2022 Total cash used in operating activities ​ $ (33,242) ​ $ (33,104) ​ Total cash used in investing activities ​ ​ — ​ ​ (1,675) ​ Total cash provided by financing activities ​ 34,227 ​ 23,181 ​ Effects of foreign exchange rate changes on assets and liabilities ​ 15 ​ 16 ​ Net increase (decrease) in cash ​ $ 1,000 ​ $ (11,582) ​ ​ ​ 81 Table of Contents Cash Used in Operating Activities During the year ended December 31, 2023, net cash used in operating activities of $33.2 million resulted from our net comprehensive loss of $41.9 million adjusted by amortization of debt issuance costs, debt discount, and non-cash interest expense of $13.2 million, Change in fair value of freestanding and hybrid financial instruments designated at FVO of $5.1 million, stock-based compensation of $2.1 million, depreciation and amortization expenses of $2.0 million, amortization of operating lease right-of-use assets of $375,000, impairment loss on intangible asset of $371,000, shares issued in exchange for services of $171,000, share in joint venture’s loss of $51,000, gain on extinguishment of debt $3.7 million, and net changes in operating assets and liabilities of $11.1 million.
During the year ended December 31, 2023, net cash used in operating activities of $33.2 million resulted from our net comprehensive loss of $41.9 million adjusted by amortization of debt issuance costs, debt discount, and non-cash interest expense of $13.2 million, change in fair value of freestanding and hybrid financial instruments designated at FVO of $5.1 million, stock-based compensation of $2.1 million, depreciation and amortization expenses of $2.0 million, amortization of operating lease right-of-use assets of $375,000, impairment loss on intangible asset of $371,000, shares issued in exchange for services of $171,000, share in joint venture’s loss of $51,000, gain on extinguishment of debt $3.7 million, and net changes in operating assets and liabilities of $11.1 million.
Our net comprehensive losses were $41.9 million and $49.1 million for the years ended December 31, 2023 and 2022, respectively. As of December 31, 2023, we had total stockholders' equity of $4.9 million, an accumulated deficit of $308.2 million, an accumulated other comprehensive loss of $652,000 and cash of $6.5 million.
Our net comprehensive losses were $39.0 million and $41.9 million for the years ended December 31, 2024 and 2023, respectively. As of December 31, 2024, we had total stockholders' equity of $6.5 million, an accumulated deficit of $346.5 million, an accumulated other comprehensive loss of $467,000 and cash of $8.0 million.
Gain or Loss on Extinguishment of Debt Gain on extinguishment of debt increased by $5.9 million from a loss of $2.2 million for the year ended December 31, 2022 to a gain of $3.7 million for the same period in 2023 due to significant modifications resulting to extinguishment recognition.
Gain or Loss on Extinguishment of Debt Gain on extinguishment of debt decreased by $2.5 million from a gain of $3.7 million gain for the year ended December 31, 2023 to a gain of $1.2 million for the same period in 2024 primarily due to significant modifications of royalty interest agreements resulting to extinguishment accounting.
A change in the outcome of any of these variables with respect to the development of a prescription drug product candidate or non-prescription product could mean a significant change in the costs and timing associated with our development activities. We expect research and development expense to increase due to the start-up costs associated with our clinical trials for other indications.
A change in the outcome of any of these variables with respect to the development of a prescription drug product candidate or non‑prescription product could mean a significant change in the costs and timing associated with our development activities.
Change in Fair Value of Financial Instruments and Hybrid Instrument Designated at Fair Value Option Change in fair value of freestanding and hybrid financial instruments designated at Fair Value Option consists of gain or loss recognized related to fair values changes of our instruments designated at FVO. ​ ​ ​ 74 Table of Contents Gain (Loss) on Debt Extinguishment Gain (loss) on debt extinguishment consists of gain or loss incurred related to the exchanges resulting from the extinguishment of our borrowings.
Change in Fair Value of Financial Instruments and Hybrid Instrument Designated at Fair Value Option Change in fair value of freestanding and hybrid financial instruments designated at Fair Value Option consists of gain or loss recognized related to fair values changes of our instruments designated at FVO.
(“Jaguar” or the “Company”) is a commercial stage pharmaceuticals company focused on developing novel, plant-based, sustainably derived prescription medicines for people and animals with gastrointestinal (“GI”) distress, including chronic, debilitating diarrhea. Jaguar Health's wholly owned subsidiary, Napo 70 Table of Contents Pharmaceuticals, Inc. (“Napo”), focuses on developing and commercializing proprietary plant-based human pharmaceuticals from plants harvested responsibly from rainforest areas.
(“Jaguar” or the “Company”) is a commercial-stage pharmaceuticals company focused on developing novel, plant-based, sustainably derived prescription medicines for people and animals with gastrointestinal (“GI”) distress, including chronic, debilitating diarrhea. Jaguar's wholly owned subsidiary, Napo Pharmaceuticals, Inc.
Change in Fair Value of Freestanding and Hybrid Financial Instruments Designated at FVO Change in fair value of freestanding and hybrid financial instruments designated at FVO increased by $5.1 million from a loss of $20,000 for the year ended December 31, 2022, to a loss of $5.1 million for the same period in 2023 primarily due to additional freestanding instruments measured at FVO.
Change in Fair Value of Freestanding and Hybrid Financial Instruments Designated at FVO The fair value of financial instrument and hybrid instrument designated at FVO increased by $4.4 million, from a loss of $5.1 million in year ended December 31, 2023, to a loss of $9.5 million in the same period in 2024 primarily due to fair value adjustments in liability classified warrants and notes payable designated at FVO.
Crofelemer powder for oral solution is being developed to support orphan or rare disease indications for infants and/or children with SBS and/or CDD, such as MVID.
Crofelemer powder for oral solution is being developed to support orphan or rare disease indications for adults with SBS with intestinal failure and for pediatric MVID patients.
The Company’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. Crofelemer was granted ODD by the FDA in February 2023 for MVID, an ultrarare CDD condition, and granted ODD for MVID by the European Medicines Agency (“EMA”) in October 2022.
The Company’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.
During the year ended December 31, 2022, net cash provided by financing activities of $23.2 million consisted of $20.5 million in net proceeds from shares issued in an At the Market offering, $4.0 million in net proceeds from notes payable with Streeterville, offset by $1.2 million repayment of insurance financing and $100,000 payment of Tempesta Note. ​
Cash Provided by Financing Activities During the year ended December 31, 2024, net cash provided by financing activities of $31.2 million consisted of $30.8 million in net proceeds from shares issued in an At the Market offering, $1.2 million proceeds from the issuance of common shares in exchange of License Agreement, offset by $608,000 repayment of insurance financing, and $100,000 in principal payments of the notes payable.
In August 2023 the FDA activated Napo’s Investigational New Drug (“IND”) application for a new crofelemer powder for oral solution formulation for the treatment of MVID. SBS affects approximately 10,000 to 20,000 people in the US, according to the Crohn's & Colitis Foundation, and it is estimated that the population of SBS patients in Europe is approximately the same size.
SBS affects approximately 10,000 to 20,000 people in the US, according to the Crohn's & Colitis Foundation, and it is estimated that the population of SBS patients in Europe is approximately the same size.
Deductions to reduce gross product sales to net product sales for the years ended December 31, 2023 and 2022 are as follows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ ​ ​ December 31, ​ ​ (in thousands) 2023 2022 Variance Variance % Gross product sales ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Mytesi $ 13,435 ​ $ 14,804 ​ $ (1,369) (9.2) % Canalevia ​ 130 ​ ​ 167 ​ (37) (22.2) % Neonorm ​ 42 ​ ​ 48 ​ (6) (12.5) % Total gross product sales ​ 13,607 ​ ​ 15,019 ​ (1,412) (9.4) % Medicaid rebates ​ (2,041) ​ ​ (1,836) ​ (205) 11.2 % Sales discounts ​ (1,449) ​ ​ (1,182) ​ ​ (267) ​ 22.6 % Sales returns ​ (356) ​ ​ (45) ​ ​ (311) ​ 691.1 % Net product sales $ 9,761 ​ $ 11,956 ​ $ (2,195) (18.4) % ​ Our gross product revenues were $13.6 million and $15.0 million for the years ended December 31, 2023 and 2022, respectively.
Deductions to reduce gross product sales to net product sales for the years ended December 31, 2024 and 2023 are as follows: Year Ended December 31, (in thousands) 2024 2023 Variance Variance % Gross product sales Mytesi $ 15,218 $ 13,435 $ 1,783 13.3 % Canalevia 160 130 30 23.1 % Gelclair 49 — 49 100.0 % Neonorm 28 42 (14 ) (33.3 ) % Total gross product sales 15,455 13,607 1,848 13.6 % Medicaid rebates (2,564 ) (2,041 ) (523 ) 25.6 % Sales discounts (1,149 ) (1,449 ) 300 (20.7 ) % Sales returns (182 ) (356 ) 174 (48.9 ) % Product revenue, net $ 11,560 $ 9,761 $ 1,799 18.4 % Product revenue Our gross product revenues were $15.5 million and $13.6 million for the years ended December 31, 2024 and 2023, respectively.
We still plan to finance our operations and capital funding needs through equity and/or debt financing as well as revenue from future product sales.
If we do not generate upfront fees from any anticipated arrangements, it would have a negative effect on our operating plan. We still plan to finance our operations and capital funding needs through equity and/or debt financing as well as revenue from future product sales.
This will include efforts to grow the business. Interest Expense Interest expense consists primarily of non-cash and cash interest costs related to our borrowings.
In the near term, we expect general and administrative expense to remain flat as we focus on our pipeline development and market access expansion. This will include efforts to grow the business. Interest Expense Interest expense consists primarily of non-cash and cash interest costs related to our borrowings.
General and Administrative Expense General and administrative expenses consist of personnel and related benefit expense, stock-based compensation expense, employee travel expense, legal and accounting fees, rent and facilities expense, and management consulting expense. In the near term, we expect general and administrative expense to remain flat as we focus on our pipeline development and market access expansion.
We expect sales and marketing expenses to increase going forward as we focus on expanding our market access activities and commercial partnerships to develop follow-on indications of Mytesi, Gelclair and crofelemer. 77 Table of Contents General and Administrative Expense General and administrative expenses consist of personnel and related benefit expense, stock‑based compensation expense, employee travel expense, legal and accounting fees, rent and facilities expense, and management consulting expense.
Our crofelemer drug product candidate is the subject of the OnTarget study, a pivotal Phase 3 clinical trial for prophylaxis of diarrhea in adult cancer patients receiving targeted therapy. Jaguar is the majority stockholder of Napo Therapeutics S.p.A. (“Napo Therapeutics”), an Italian corporation established by Jaguar in Milan, Italy, in 2021 that focuses on expanding crofelemer access in Europe.
Jaguar is the majority stockholder of Napo Therapeutics S.p.A. (“Napo Therapeutics”), an Italian corporation established by Jaguar in Milan, Italy, in 2021, focusing on expanding crofelemer access in Europe.
These figures reflect revenue from the sale of our human drug Mytesi, our animal products branded as Neonorm Calf and Neonorm Foal. ​ Our Mytesi product revenues were $13.4 million and $14.8 million for the years ended December 31, 2023 and 2022, respectively.
These figures reflect revenue from the sale of our human drug Mytesi, our animal products branded as Neonorm Calf and Neonorm Foal and exclusive distribution agreement for the sale of Gelclair.
Research and Development Expense ​ Research and development expenses consist primarily of clinical and contract manufacturing expense, personnel and related benefit expense, stock-based compensation expense, employee travel expense and reforestation expenses. Clinical and contract manufacturing expense consists primarily of costs to conduct stability, safety and efficacy studies, and manufacturing startup expenses at an outsourced API provider in Italy.
Research and Development Expense Research and development expenses consist primarily of clinical and contract manufacturing expense, personnel and related benefit expense, stock‑based compensation expense, employee travel expense and reforestation 76 Table of Contents expenses.
During the year ended December 31, 2022, net cash used in operating activities of $33.1 million resulted from our net comprehensive loss of $49.1 million adjusted by amortization of debt issuance costs, debt discount, and non-cash interest expense of $11.8 million, stock-based compensation of $3.3 million, loss on extinguishment of debt of $2.2 million, depreciation and amortization expenses of $2.0 million, shares issued in exchange for services of $823,000, amortization of operating lease right-of-use assets of $311,000, change in fair value of hybrid instruments designated at FVO of $21,000, and net changes in operating assets and liabilities of $4.4 million.
We will actively monitor these factors as part of our financial strategy. 85 Table of Contents Cash Flows for Year Ended December 31, 2024 compared to the Year Ended December 31, 2023 The following table shows a summary of cash flows for the years ended December 31, 2024 and 2023: Year Ended December 31, (in thousands) 2024 2023 Total cash used in operating activities $ (29,384 ) $ (33,242 ) Total cash used in investing activities (231 ) — Total cash provided by financing activities 31,202 34,227 Effects of foreign exchange rate changes on assets and liabilities (54 ) 15 Net increase in cash $ 1,533 $ 1,000 Cash Used in Operating Activities During the year ended December 31, 2024, net cash used in operating activities of $29.4 million resulted from our net comprehensive loss of $39.0 million adjusted by the change in fair value of freestanding and hybrid financial instruments designated at FVO of $9.5 million, depreciation and amortization expenses of $1.9 million, stock-based compensation of $1.6 million, amortization of operating lease right-of-use assets of $458,000, amortization of debt issuance costs, debt discount, and non-cash interest expense of $274,000, share in joint venture’s loss of $138,000, shares issued in exchange for services of $9,000, gain on extinguishment of debt $1.2 million, and net changes in operating assets and liabilities of $3.0 million.
We may also not be successful in entering into partnerships that include payment of upfront licensing fees for our products and product candidates for markets outside the US, where appropriate. If we do not generate upfront fees from any anticipated arrangements, it would have a negative effect on our operating plan.
We may seek additional capital due to favorable market conditions or strategic considerations even if we believe we have sufficient funds for our current or future operating plans. We may also not be successful in entering into partnerships that include payment of upfront licensing fees for our products and product candidates for markets outside the US, where appropriate.
For additional information relating to these and other accounting policies, see Note 2 to the consolidated financial statements, appearing elsewhere in this report.
For additional information relating to these and other accounting policies, see Note 2 to the consolidated financial statements, appearing elsewhere in this report. Potential Material Effects of Trends, Events, and Uncertainties Inflation Reduction Act The Inflation Reduction Act, effective January 1, 2023, introduces several provisions that may impact the Company's operations and financial results.
We track outsourced development costs by prescription drug product candidate and non-prescription product but do not allocate personnel or other internal costs related to development to specific programs or development compounds.
We typically use our employee and infrastructure resources across multiple development programs. We track outsourced development costs by prescription drug product candidate and non‑prescription product but do not allocate personnel or other internal costs related to development to specific programs or development compounds. As of December 31, 2024, the Company has incurred approximately $6.1 million on its primary R&D projects.
Our Canalevia-CA1, Neonorm and botanical extract products are primarily sold to distributors, who then sell the products to the end customers. ● Our 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.
Our Canalevia-CA1, Neonorm and botanical extract products are primarily sold to distributors, who then sell the products to the end customers. • Revenues from the license agreement made with Gen Ilac Ve Saglik Urunleri Sanayi Ve Ticaret, A.S., ("Gen") ("Licensee") from which all finished Mytesi are sold in the licensed territory. • Revenues from a 5-year in-license agreement with United Kingdom-based Venture Life, from which the Company was granted the exclusive rights to market Venture Life's FDA-approved oral mucositis prescription product, Gelclair , within the US market. • Our 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.
We do not currently have any marketing or promotional expenses related to Canalevia-CA1, Neonorm Calf or Neonorm Foal for the years ended December 31, 2023 and 2022. We expect sales and marketing expense to increase going forward as we focus on expanding our market access activities and commercial partnerships for the development of follow-on indications of Mytesi and crofelemer.
We do not have significant marketing or promotional expenses related to Canalevia-CA1 and Neonorm Calf or Neonorm Foal for the years ended December 31, 2024 and 2023.
Interest Expense, net Interest expense decreased $6.3 million from $12.7 million for the year ended December 31, 2022 to $6.4 million in 2023 primarily due to the election of certain freestanding instruments to be valued at Fair Value Option (“FVO”) upon extinguishment.
Interest Expense, net Interest expense decreased by $6.2 million from $6.4 million for the year ended December 31, 2023 to $231,000 in 2024 primarily due to changes in accounting of certain debt instruments to FVO. The lower interest expense was offset by a higher loss in change in fair value of freestanding and hybrid financial instruments designated at FVO.
Sales and marketing expenses are not significant during 2023 and during the same period in 2022. ​ Cost of Product Revenue ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ ​ ​ ​ ​ ​ ​ December 31, ​ ​ ​ ​ ​ (in thousands) 2023 2022 Variance Variance % Cost of Product Revenue ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Direct labor ​ $ 1,152 ​ $ 755 ​ $ 397 52.6 % Material cost ​ 885 ​ 1,011 ​ (126) (12.5) % Royalties ​ — ​ 54 ​ (54) (100.0) % Distribution fees ​ (49) ​ 15 ​ (64) (426.7) % Other ​ 49 ​ 184 ​ (135) (73.4) % Total $ 2,037 $ 2,019 $ 18 0.9 % ​ The change in cost of product revenue of $18,000 for the year ended December 31, 2023 compared to 2022 was primarily due to: 76 Table of Contents ● Direct labor increased $397,000 from $755,000 for the year ended December 31, 2022 to $1.2 million in 2023, due to increased resources in testing and manufacturing. ● Material cost decreased by $126,000 from $1.0 million for the year ended December 31, 2022, to $885,000 in 2023 relative to the decrease in net sales. ● Other costs which includes royalties and APIs decreased $135,000 from $184,000 for the year ended December 31, 2022 to $49,000 in 2023 relative to the decrease in net sales.
Sales returns were $182,000 and $356,000 for the years ended December 31, 2024 and 2023, respectively, a decrease of $174,000, relatively due to enhanced manufacturing process as compared to year 2023. 80 Table of Contents Cost of Product Revenue Year Ended December 31, (in thousands) 2024 2023 Variance Variance % Cost of Product Revenue Direct labor $ 896 $ 1,152 $ (256 ) (22.2 ) % Material cost 796 885 (89 ) (10.1 ) % Distribution fees 186 (49 ) 235 (479.6 ) % Other 77 49 28 57.1 % Total $ 1,955 $ 2,037 $ (82 ) (4.0 ) % The change in cost of product revenue of $82,000 for the year ended December 31, 2024 compared to 2023 was primarily due to: • Direct labor decreased by $256,000 from $1.2 million for the year ended December 31, 2023 to $896,000 in the same period in 2024, due to decrease in resources spent in testing and manufacturing of inventory. • Distribution fees increased by $235,000 from negative $49,000 for the year ended December 31, 2023, to $186,000 in the same period in 2024, due to the increase in warehouse fees driven by the increase in sales volume for Mytesi. • Other costs increased by $28,000 from $49,000 for the year ended December 31, 2023 to $77,000 in the same period in 2024 due to increase in royalties for Mytesi and Gelclair products, which are directly related to the increase in sales.
For the years ended December 31, 2023 and 2022, we had net losses of $41.9 million and $48.4 million, respectively, and expect to incur additional losses in the near-term future. At December 31, 2023, we had an accumulated deficit of $308.2 million and accumulated comprehensive loss of $652,000.
Liquidity and Capital Resources Sources of Liquidity We have incurred net losses since our inception. For the years ended December 31, 2024 and 2023, we had net losses of $39.3 million and $41.9 million, respectively, and expect to incur additional losses in the near-term future due to significant expenses incurred related to the research and development phase.
Cash provided by financing activities for the year ended December 31, 2023, were generated from the issuance of an aggregate of 54,283,779 shares of common stock under the ATM Agreement for total net proceeds of approximately $32.1 million, issuance of an aggregate 6,850,000 warrants and 137 Series G Convertible Preferred Stock in PIPE financing for a total net proceeds of $1.8 million, and investment from non-controlling interest for a total net proceeds of $1.2 million.
Cash provided by financing activities for the year ended December 31, 2024, were generated from the issuance of an aggregate of 388,634 shares of common stock under the ATM Agreement for total net proceeds of approximately $30.8 million, and issuance of an aggregate 11,111 common stock in exchange of License Agreement for total net proceeds of $1.2 million. 84 Table of Contents We expect our expenditures will continue to increase as we continue our efforts to develop our products and continue the development of our pipeline in the near term.
It also includes expenses with a third-party provider for the transfer of the Mytesi manufacturing process, and the related feasibility and validation activities. We typically use our employee and infrastructure resources across multiple development programs.
Clinical and contract manufacturing expense consists primarily of costs to conduct stability, safety and efficacy studies, and manufacturing startup expenses at an outsourced API provider in Italy. It also includes expenses with a third-party provider for the transfer of the Mytesi manufacturing process, and the related feasibility and validation activities.
Cash Used in Investing Activities There are no cash used in investing activities during the year ended December 31, 2023. During the year ended December 31, 2022, cash used in investing activities was $1.7 million which consisted of cash used in software development activities of $1.6 million and cash used to purchase property and equipment of $77,000.
There is no cash used in investing activities during the year ended December 31, 2023.
We cannot determine with certainty the duration and completion costs of the current or future development activities.
We cannot determine with certainty the duration and completion costs of the current or future development activities. The total project costs remain uncertain due to regulatory and clinical trial complexities. Management continues to monitor timelines closely to address any risks that could impact timely project completion and future operations.
We have funded our operations primarily through the issuance of debt and equity securities, in addition to sales of our commercial products.
While we are actively exploring various strategies to optimize our cash flows, we recognize that our current capital resources will not be sufficient to fund our operating plan for at least one year from the issuance of these consolidated financial statements. We have funded our operations primarily through issuing debt and equity securities, in addition to selling our commercial products.
Removed
Crofelemer was granted ODD for SBS by the EMA in December 2021 and by the FDA in August 2017. In 2024 Jaguar expects results from 5 proof-of-concept studies of crofelemer conducted at least 8 clinical sites, including Cleveland Clinic, on three continents for the rare disease indications of MVID – an ultrarare CDD and SBS.
Added
(“Napo”), focuses on developing and commercializing proprietary plant-based human prescriptions from plants for essential supportive care and management of neglected GI symptoms across multiple complicated disease states. Our crofelemer drug product candidate is the subject of the OnTarget study, a recently conducted pivotal Phase 3 clinical trial for prophylaxis of diarrhea in adult cancer patients receiving targeted therapy.
Removed
Napo’s pivotal OnTarget Phase 3 clinical trial of crofelemer for prophylaxis of cancer therapy-related diarrhea (“CTD”) was initiated in October 2020.
Added
The recently completed analysis of the prespecified subgroup of adult patients with breast cancer from OnTarget indicates that crofelemer achieved statistical significance in this subgroup. Patients with breast cancer accounted for 183 of the 287 participants in this unprecedented prophylactic clinical trial in adult patients with solid tumors receiving targeted therapy with or without standard chemotherapy.
Removed
Our Canalevia product revenues were $130,000 and $167,000 for the years ended December 31, 2023 and 2022, respectively. Our Neonorm product revenues were $42,000 and $48,000 for the years ended December 31, 2023 and 2022, respectively.
Added
The OnTarget results in breast cancer were the subject of a poster presentation conducted December 11, 2024 at the San Antonio Breast Cancer Symposium ("SABCS"). Overall, crofelemer was significantly more effective than placebo in providing sustained response in breast cancer patients in OnTarget, potentially helping them stay on their cancer therapies.
Removed
Research and Development Expense The following table presents the components of research and development (“R&D”) expense for the years ended December 31, 2023 and 2022: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ ​ ​ ​ ​ ​ ​ December 31, ​ ​ ​ ​ ​ (in thousands) 2023 2022 Variance Variance % Research and Development: ​ ​ ​ ​ Clinical and contract manufacturing ​ $ 8,155 ​ $ 8,326 ​ $ (171) (2.1) % Personnel and related benefits ​ ​ 5,815 ​ ​ 5,543 ​ ​ 272 4.9 % Stock-based compensation ​ 1,044 ​ 1,263 ​ ​ (219) (17.3) % Materials expense and tree planting ​ 367 ​ 309 ​ ​ 58 18.8 % Travel and other expenses ​ 326 ​ 122 ​ ​ 204 167.2 % Other ​ 2,889 ​ 2,084 ​ ​ 805 38.6 % Total ​ $ 18,596 ​ $ 17,647 ​ $ 949 5.4 % ​ The change in R&D expense of $949,000 for the year ended December 31, 2023 compared to 2022 was primarily due to: ● Clinical and contract manufacturing expenses decreased $171,000 from $8.3 million for the year ended December 31, 2022 to $8.2 million in 2023 largely due to lower clinical trial activities related to start-up of CTD and other indications, additional CMC manufacturing, consulting and contractors’ expenses, and cholera/lechlemer research expenses. ● Personnel and related benefits increased $272,000 from $5.5 million for the year ended December 31, 2022 to $5.8 million in 2023 largely due an increase in headcount. ● Stock-based compensation expense decreased $219,000 from $1.3 million for the year ended December 31, 2022 to $1.0 million in 2023 primarily due to lower options and RSUs granted during the period as compared to 2022. ● Travel, and other expenses increased by $204 ,000 from $122,000 for the year ended December 31, 2022 to $326,000 in 2023 primarily due to more travel activities associated with the clinical trials. ● Other expenses consisting of consulting, formulation and regulatory fees increased $805,000 from $2.1 million for the year ended December 31, 2022, to $2.9 million in 2023 mainly due to increased CTD activities. ​ 77 Table of Contents Sales and Marketing Expense The following table presents the components of sales and marketing (“S&M”) expense for the years ended December 31, 2023 and 2022: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ ​ ​ ​ ​ ​ ​ December 31, ​ ​ ​ ​ ​ (in thousands) 2023 2022 Variance Variance % Sales and Marketing: ​ ​ ​ ​ Personnel and related benefits ​ $ 3,025 ​ $ 3,415 ​ $ (390) (11.4) % Direct marketing fees and expense ​ ​ 1,903 ​ ​ 3,596 ​ ​ (1,693) (47.1) % Stock-based compensation ​ 152 ​ 267 ​ (115) (43.1) % Other ​ 1,380 ​ 1,559 ​ (179) (11.5) % Total ​ $ 6,460 ​ $ 8,837 ​ $ (2,377) (26.9) % ​ The change in S&M expense of $2.4 million for the year ended December 31, 2023 compared to 2022 was primarily due to: ​ ● Personnel and related benefits decreased $390,000 from $3.4 million for the year ended December 31, 2022 to $3.0 million in 2023 due to decreased sales commission and reduced headcount. ● Direct marketing fees and expense decreased $1.7 million from $3.6 million for the year ended December 31, 2022 to $1.9 million in 2023 due to savings associated with the utilization of a more cost-effective patient support services and other Mytesi marketing initiatives. ● Stock-based compensation benefits decreased $115,000 from $267,000 for the year ended December 31, 2022 to $152,000 in 2023 primarily due to lower options and RSUs granted during the period as compared to 2022. ​ ● Other expenses decreased $179,000 from $1.6 million for the year ended December 31, 2022 to $1.4 million 2023 largely due to lower consulting and contractor services but slightly offset by increased travels for sales and marketing personnel. 78 Table of Contents General and Administrative Expense The following table presents the components of general and administrative (“G&A”) expense for the years ended December 31, 2023 and 2022: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended ​ ​ ​ ​ ​ ​ ​ December 31, ​ ​ ​ ​ ​ (in thousands) 2023 2022 Variance Variance % General and Administrative: ​ ​ ​ ​ Personnel and related benefits ​ $ 5,135 ​ $ 5,582 ​ $ (447) (8.0) % Legal services ​ 2,009 ​ 1,225 ​ 784 64.0 % Public company expense ​ 1,789 ​ 2,692 ​ (903) (33.5) % Stock-based compensation ​ 916 ​ 1,788 ​ (872) (48.8) % Lease expense ​ 877 ​ 629 ​ 248 39.4 % Third-party consulting services ​ ​ 679 ​ ​ 507 ​ ​ 172 ​ 33.9 % Audit, tax and accounting services ​ 537 ​ 454 ​ 83 18.3 % Travel and other expenses ​ 435 ​ 378 ​ 57 15.1 % Other ​ 4,211 ​ 4,613 ​ (402) (8.7) % Total ​ $ 16,588 ​ $ 17,868 ​ $ (1,280) (7.2) % ​ The change in G&A expenses of $1.3 million for the year ended December 31, 2023 compared to 2022 was due primarily to: ● Personnel and related benefits decreased $447,000 from $5.6 million for the year ended December 31, 2022 to $5.1 million in 2023 due to lower headcount and no bonus in 2023. ● Legal services increased $784,000 from $1.2 million for the year ended December 31, 2022 to $2.0 million in 2023 primarily due to increased legal consultations for contracts and agreements and other regulatory filings. ● Public company expenses decreased $903,000 from $2.7 million for the year ended December 31, 2022 to $1.8 million in 2023 due to less investor relations and communications consulting expenses, and decreased expenses related to the annual shareholder meetings. ● Stock-based compensation expense decreased $872,000 from $1.8 million for the year ended December 31, 2022 to $916,000 in 2023 primarily due to lower general and administrative expense incurred for options granted with immediate vesting to existing employees. ● Lease expense increased $248,000 from $629,000 for the year ended December 31, 2022 to $877,000 in 2023, primarily due to additional lease space and increase in fees. ● Third-party consulting services increased $172,000 from $507,000 for the year ended December 31, 2022 to $679,000 in 2023, mostly due to the increase in outsourced accounting transactions. ● Audit, tax and accounting services fees increased $83,000 from $454,000 for the year ended December 31, 2022 to $537,000 in 2023, mostly due to the additional financing and complex accounting transactions for the year. ● Other general and administrative expenses decreased $402,000 from $4.6 million for the year ended December 31, 2022 to $4.2 million in 2023 largely due to lower depreciation and amortization of fixed assets and intangible assets, insurance expenses and other support services. 79 Table of Contents Impairment Loss on Intangible Asset The Company recognized an impairment loss on intangible assets amounting to $371,000 as a result of impairment evaluation to its internal use software costs – registry triggered by experiencing lower-than-anticipated sales growth for Canalevia and Neonorm, its two primary animal health products.
Added
This research underscores the potential of crofelemer for prophylaxis of cancer therapy-related diarrhea (“CTD”). A full study report for the breast cancer results is expected to be submitted to a peer-reviewed journal.
Removed
The lower interest expense was offset by a higher loss in change in fair value of financial instruments and hybrid instrument designated at FVO. Liquidity and Capital Resources Sources of Liquidity We have incurred net losses since our inception.
Added
As part of our strategy to expand our commercial footprint beyond HIV-related supportive care to include cancer-related supportive care, on April 12, 2024, we entered into an exclusive 5-year in-license agreement with United Kingdom-based Venture Life Group PLC (“Venture Life”), an international consumer health company focused on the global self-care market, for Venture Life's 510(k) cleared oral mucositis prescription product, Gelclair, for the US market.
Removed
To date, we have generated only limited revenue, and we may never achieve revenue sufficient to offset our expenses. We had cash of $6.5 million as of December 31, 2023 to fund our operating plan through one year from the issuance of these consolidated financial statements.
Added
Gelclair is a 510(k) cleared prescription product and can be commercialized without any clinical development costs for Jaguar. We initiated the commercial launch in October 2024 for Gelclair. Oral mucositis is among the most common, painful, and debilitating cancer treatment-related side effects.
Removed
We expect our expenditures will continue to increase as we continue our efforts to develop our products and continue the development of our pipeline in the near term. We may seek additional capital due to favorable market conditions or strategic considerations even if we believe we have sufficient funds for our current or future operating plans.
Added
Gelclair is a protective gel with a mechanical action indicated for the management of pain and relief of pain by adhering to the mucosal surface of the mouth, soothing oral lesions of various etiologies, including oral mucositis/stomatitis. Unlike other products for oral mucositis, it is not a numbing agent and does not sting the mouth.
Added
(“Magdalena”), a joint venture formed by Jaguar and Filament Health Corp. (“Filament”) that emerged from Jaguar’s Entheogen Therapeutics Initiative (“ETI”), is focused on identifying the next generation of plant-based first-in-class agents for treatment of mental health conditions. Jaguar was founded in San Francisco, California as a Delaware corporation on June 6, 2013 (inception).
Added
Jaguar is currently supporting three proof-of-concept (POC) investigator-initiated trials (IIT), and conducting two Phase 2 studies, of crofelemer for the rare diseases short bowel syndrome (SBS) with intestinal failure and/or MVID in the US, EU, and/or Middle East/North Africa regions.
Added
The Company’s Phase 2 study to evaluate the efficacy of crofelemer for MVID in pediatric patients has been initiated, as has the Company’s Phase 2 study to evaluate the efficacy of crofelemer for SBS with intestinal failure (SBS-IF) in adults, the independent IIT of crofelemer in pediatric patients with SBS-IF or MVID in Abu Dhabi in the United Arab Emirates, and the independent IIT in the US to evaluate crofelemer for SBS-IF in adults.
Added
The additional IIT is expected to initiate in Q2 2025, with the availability of the first POC IIT result potentially in H1 2025, and with additional POC IIT results expected throughout 2025.
Added
Participation in early access programs, which do not exist in the US, provides an opportunity for reimbursement while impacting the morbidity and high cost of care for these chronic unmet needs.
Added
Additionally, the Company expects that if even just a very small number of MVID patients show benefit with crofelemer, this may potentially allow pathways for regulatory approval in the US and other regions and qualify crofelemer for participation in PRIME, a European Medicines Agency (EMA) program providing enhanced interaction and early dialogue with drug developers of novel medicines targeting unmet medical needs, and in the FDA’s Breakthrough Therapies program.
Added
If a drug is designated as breakthrough therapy, the FDA will expedite the development and review of the drug. Crofelemer was granted Orphan Drug Designation (“ODD”) by the FDA in February 2023 for MVID and granted ODD for MVID by the European Medicines Agency (“EMA”) in October 2022.
Added
Crofelemer was granted ODD for SBS by the EMA in December 2021 and by the FDA in August 2017. In August 2023, Napo’s Investigational New Drug (“IND”) application was activated by the FDA for a new crofelemer powder for oral solution formulation for treating MVID. Our global MVID Phase 2 trial for Jaguar is being conducted under this IND.
Added
The global phase 2 trial of crofelemer in adults with SBS-IF is taking place under a Clinical Trial Application ("CTA") approved by European health authorities. We expect that enrollment will continue in 2025 for the MVID phase 2 trial and the phase 2 trial for SBS with intestinal failure, with data expected in the beginning of 2026 for both trials.
Added
Napo Therapeutics is initiating efforts to commence clinical development of crofelemer in SBS patients in support of the Company’s key focus on leveraging the EMA’s accelerated conditional marketing authorization pathway in Europe for these rare diseases.
Added
This program is being pursued with the potential targeted incentive from the FDA for a tropical disease priority review voucher.
Added
As announced, Jaguar is seeking a partner to fund and execute the development and commercialization of NP-300 for the treatment of general, non-infectious diarrhea in dogs, in exchange for commercial rights to the product in the US Diarrhea is one of the most common reasons for veterinary office visits for dogs and is the second most common reason for visits to the veterinary emergency room, yet there are currently no FDA-approved drug to treat canine diarrhea.
Added
According to the American Veterinary Medical Association, there were an estimated 89.7 million dogs in the United States in 2024, with nearly half (45.5%) of US households owning a dog in 2024.

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