Jaguar Health Profile
Jaguar Health, Inc. (Jaguar or Jaguar Health) operates as a commercial stage pharmaceutical company.
The company focuses 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 Pharmaceuticals, Inc. (‘Napo’), focuses on developing and commercializing proprietary plant-based human pharmaceuticals from plants harvested responsibly from rainforest areas. The company’s crofelemer drug product candidate is the subject of the OnTarget study, an ongoing pivotal Phase 3 clinical trial for prophylaxis of diarrhea in adult cancer patients receiving targeted therapy. As announced, patient enrollment in OnTarget reached approximately 75% in February 2023, and target trial enrollment of 256 patients is expected to complete in the second quarter of 2023. Jaguar is the majority shareholder 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. 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 congenital diarrheal disorders (‘CDD’). Jaguar Animal Health is a tradename of Jaguar Health.
Napo’s marketed drug Mytesi (crofelemer 125 mg delayed-release tablets) is a first-in-class oral botanical drug product approved by the U.S. Food and Drug Administration (‘FDA’) for the symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy. As of December 31, 2022, 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.
Crofelemer was granted orphan drug designation (‘ODD’) by the FDA in August 2017 and by the European Medicines Agency (‘EMA’) in December 2021. Crofelemer was granted ODD by the FDA in February 2023 for microvillus inclusion disease (‘MVID’), a rare CDD condition, and granted ODD for MVID by the EMA in October 2022. The company is supporting investigator-initiated proof-of-concept (‘POC’) studies of crofelemer in patients with SBS with intestinal failure or CDD, focused on obtaining POC of reduction of requirements of parenteral support, including parenteral nutrition and/or intravenous fluids, throughout 2023. In accordance with the guidelines of specific European Union countries, publications of POC data from these trials could support early patient access to crofelemer for SBS with intestinal failure or CDD through programs in Europe. Early access programs are revenue generating, and reimbursable for participating patients.
Napo Therapeutics is initiating efforts to commence clinical development of crofelemer in SBS patients in the support of the company’s key focus on leveraging the EMA’s accelerated conditional marketing authorization pathway in Europe for these rare diseases.
In February 2022, Napo announced the completion of an investigator-initiated preclinical enterocyte (intestinal cell) in vitro study to evaluate the effects of crofelemer on cells with certain genetic defects that result in specific forms of CDD. The data from this study is expected to support the rare disease business model that Napo Therapeutics is pursuing in Europe under its exclusive license for crofelemer from Jaguar and Napo. 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 no therapies for CDD except parenteral nutrition. Thus, crofelemer may reduce the associated morbidity and mortality of CDD and lessen the need for parenteral nutrition (‘PN’).
Most of the activities of the company is 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. Napo’s pivotal OnTarget Phase 3 clinical trial of crofelemer for prophylaxis of cancer therapy-related diarrhea (‘CTD’) was initiated in October 2020 and is expected to complete enrolment in 2nd quarter of 2023. The company also supports the prioritized clinical program at Napo Therapeutics centered around the POC investigator-initiated trials of Crofelemer for SBS and CDD. In the field of animal health, the company is continuing limited activities related to developing and commercializing gastrointestinal products for dogs, dairy calves and foals.
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. Mytesi is in development for multiple possible follow-on indications, including for the 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 idiopathic/functional diarrhea in investigator-initiated trials.
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.
In addition, a second-generation proprietary anti-secretory antidiarrheal drug (‘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. This program is being pursued with the targeted incentive from the FDA of tropical disease priority review voucher.
In January 2023, Jaguar and Filament Health (‘Filament’), with Funding from One Small Planet, formed the U.S.-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. The goal of the collaboration is to extend the botanical drug development capabilities of Jaguar and Filament in order to develop pharmaceutical-grade, standardized drug candidates for mental health disorders, and to partner with a potential future licensee to develop and commercialize these novel plant-based drugs. 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. Jaguar’s library of 2,300 highly characterized medicinal plants and 3,500 plant extracts, all from firsthand ethnobotanical investigation by Jaguar and members of the ETI Scientific Strategy Team, is a key asset the company has generated over 30 years that bridges the knowledge of traditional healers and Western medicine. 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.
In December 2021, the company received conditional approval from the FDA to market Canalevia-CA1 (crofelemer delayed-release tablets), the company’s 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 available to multiple leading veterinary distributors in the U.S. Canalevia-CA1 is a tablet that is given orally and can be prescribed for home treatment of CID. 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. The company has received Minor Use in a Major Species (‘MUMS’) designation from the FDA for Canalevia-CA1 to treat CID in dogs.
Jaguar is poised to realize a number of synergistic, value adding benefits—an expanded pipeline of potential blockbuster human follow-on indications of crofelemer, and a second-generation anti-secretory agent—upon which to build global partnerships. Jaguar, through Napo, holds global unencumbered rights for crofelemer, Mytesi, and Canalevia-CA1. Additionally, several of the drug product opportunities in Jaguar’s crofelemer pipeline are backed by Phase 2 and proof of concept evidence from human clinical trials.
Napo has a direct sales force of 8 sales representatives and a national sales director covering the U.S. geographies with the highest commercial potential.
A key component of the company’s marketing strategies for Mytesi in 2022 was the company’s focus on the transition of Mytesi distribution to a closed network of specialty pharmacies rather than to wholesalers that resell the product to retail pharmacies. This transition was intended to help remove access barriers for patients receiving Mytesi and includes services, such as a higher level of support for prior authorizations, appeals, adherence counseling, and home delivery options.
Napo expanded the NapoCares Patient Support Program for Mytesi in April 2020 as part of the company’s enhanced market access strategy. The expansion meaningfully increased co-pay support for commercially insured patients, which also includes allowing the co-pay amount to remain the same whether a patient fills a 30-day or a 90-day prescription of Mytesi. The expansion also increased the income ceiling from two times the Federal poverty limit to five times the Federal poverty limit for the company’s patient assistance program, which will allow more low-income patients to receive Mytesi at no cost. The co-pay program and patient assistance program are components of a comprehensive suite of patient support services Napo rolled out in the second quarter of 2020 with the support of AssistRx, a specialty therapy initiation and patient support company.
Napo has actively ensured that its intellectual property (‘IP’) filings in the support of the development of crofelemer for various proposed indications are protected appropriately. The IP portfolio for crofelemer includes the relief and treatment of HIV-associated diarrhea and CID as well as planned indications for inflammatory diarrhea, IBS-D, CDD and SBS, with all indications, Napo prioritizes IP protection. Napo holds approximately 145 patents, the majority of which do not expire until 2027-2031, and approximately 53 patents pending.
In October 2020, Napo initiated its pivotal OnTarget Phase 3 clinical trial of crofelemer for prophylaxis of diarrhea in adult cancer patients receiving targeted therapy with or without chemotherapy. As announced, patient enrollment in OnTarget reached approximately 75% in February 2023, and target trial enrollment of 256 patients is expected to complete in the second quarter of 2023. The company’s efforts over the past year were focused on expanding the trial to new U.S. and international sites – with trial sites now active in Georgia, the Republic of Serbia, Argentina, and Taiwan—which has significantly accelerated enrollment. The OnTarget trial is evaluating crofelemer's effectiveness in prophylaxis of diarrhea in adult solid tumor patients that receive targeted therapies with or without standard chemotherapy. Such prophylaxis would potentially impact the patient's ability to remain on their cancer therapy regimens at approved doses for better cancer treatment outcomes, with less required medical intervention and cost.
The 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 the prophylaxis of diarrhea in adult cancer patients with solid tumors receiving targeted cancer therapy-containing treatment regimens. Patients are randomized to receive either crofelemer or matching placebo treatment that starts concurrently with the initiation of targeted cancer therapy regimen. The primary endpoint will be assessed at the end of the initial (Stage I) 12-week double-blind placebo-controlled primary treatment phase after the last patient has completed 12 weeks of treatment. After completing the Stage I treatment phase, the subjects will have the option to remain on their assigned blinded treatment arm and reconsent to enter into the Stage II 12-week extension phase. The assessment of prophylactic effects on diarrhea will be measured by the average number of weekly loose and/or watery stools for the active (crofelemer) or placebo arms over 12-week Stage I treatment period.
A significant proportion of patients undergoing cancer therapy experience diarrhea, which has the potential to cause dehydration, potential hospitalization, and non-adherence to treatment in this population. 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). Diarrhea has been reported as one of the most common side effects of TKIs and may result in cancer therapy drug holidays or reductions from therapeutic dose, potentially impacting patient outcomes. Diarrhea is also a common side effect of some approved CDK 4/6 inhibitors.
Due to the chronic dosing and toxicity associated with targeted therapies, many cancer patients on targeted therapy require drug holidays or dose reductions in their therapy, including those due to diarrhea. By improving stool consistency and reducing the frequency of loose/watery stools, crofelemer is expected to provide improved adherence to the therapeutic dosing of any targeted therapies, potentially leading to better clinical outcomes. The company has 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.
Crofelemer was evaluated in a Phase 2 clinical study (called HALT-D), for the effectiveness of crofelemer for reduction of diarrhea in HER2 positive breast cancer patients receiving trastuzumab, pertuzumab, and chemotherapy agents, such as docetaxel or pacilitaxel with or without carboplatin. The results of the study were published in October 2022 and showed that prophylaxis with crofelemer resulted in substantial reduction of higher grade diarrhea compared to the standard-of-care control group patients.
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.
As announced October 26, 2022, the results of the HALT-D trial were published in the peer reviewed journal Breast Cancer Research and Treatment.
This HALT-D study evaluated 51 breast cancer patients who were eligible to receive at least three cycles of pertuzumab-containing regimen with chemotherapy that were randomly assigned to either crofelemer in cycles 1 and 2 or the control group, in which patients received standard of care. Breakthrough anti-diarrheal medicines (‘BAM’) were permitted but not given prophylactically. Findings showed that the primary endpoint, the incidence of diarrhea for at least two consecutive days, was not statistically different for the two groups. However, crofelemer patients demonstrated significantly better outcomes compared to control group patients across a number of key secondary endpoints, including reductions in the incidence and severity of diarrhea in cycle 2 based on Investigator and Patient Reported Outcomes (see Jaguar Health's November 19, 2021 press release). The study also showed that CID occurred significantly lesser (by 23%) in the crofelemer group during cycle 1 and crofelemer patients were 1.8 times more likely than control patients to have their diarrhea resolved. These data provide POC support to the primary endpoint in Napo’s ongoing phase 3 OnTarget clinical study.
Napo completed its requisite preclinical and formulation activities to support the Investigational New Drug (IND) application for its second-generation, plant-based oral prescription drug product, NP-300, for its clinical development for the 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. As announced in September 2022, the FDA has activated the company’s Investigational New Drug (IND) application for NP-300and the FDA concluded that Napo may proceed with its proposed phase 1 clinical trial for NP-300. Following the completion of the phase 1 trial, the company will be positioned to initiate the next stage of the company’s clinical development program for cholera-related diarrhea when the company’s development team has the requisite resources and bandwidth to initiate the additional required trials.
Cholera produces a devastating loss of electrolytes and fluid in patients and without appropriate reduction in loss of fluid and electrolytes, patients experience significant hospitalization and mortality. NP-300 provides the opportunity to treat cholera patients in combination with oral rehydration salts (‘ORS’) and the recommended guidelines from the World Health Organization (‘WHO’) for the use of appropriate antibiotics to reduce the burden of the pathogen. Appropriate preclinical toxicity studies and formulation development activities are ongoing to support the conduct of clinical studies with NP-300.
Napo received partial financial support for preclinical services from the National Institute of Allergy and Infectious Diseases (‘NIAID’) of the National Institutes of Health, and Napo is grateful for their support of NP-300’s development.
The company expects that NP-300 will be significantly less expensive and would support development efforts to receive a tropical disease priority review voucher from the FDA for an indication for the symptomatic treatment of diarrhea from acute infections, such as cholera. Priority review vouchers are granted by the FDA as an incentive to develop treatments for neglected diseases and rare pediatric diseases. Additionally, NP-300 may provide a long-term pipeline opportunity as a second-generation anti-secretory agent for multiple gastrointestinal diseases—especially in resource-constrained countries.
The NP-300 program is paired with funding from a promissory note related to the potential future sale of a possible TDPRV.
As previously announced, the company also launched the Entheogen Therapeutics (‘ETI’) initiative to support the discovery and development of novel, natural medicines derived from psychoactive and psychedelic plant compounds for the treatment of mood disorders, neuro-degenerative diseases, addiction, and other mental health disorders. The initiative is initially focused on plants with the potential to treat depression and leverages Napo’s proprietary library of approximately 2,300 plants with medicinal properties.
Field research collaborations have been conducted in the past by members of the scientific strategy team (‘SST’) of Jaguar’s predecessor company Shaman Pharmaceuticals, who are also members of the ETI SST, yielded possible applications for a compound called alstonine. Alstonine is derived from a plant used by traditional healers in Nigeria, and has demonstrated a potential novel mechanism of action for the treatment of difficult to manage conditions, such as schizophrenia.
The ETI SST consists of leading and globally renowned ethnobotanists, physicians, and pharmacologists, as well as experts in the fields of natural product chemistry and neuropharmacology. The wealth of expertise, experience, and commitment of the ETI SST—consisted of multiple members of the original SST that contributed to development of Jaguar's proprietary library of plants—will play an instrumental role in advancing the company’s shared initial goal of identifying plants in the company’s library that may have the potential to treat mood disorders and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic sclerosis. Mood disorders and neurodegenerative diseases affect hundreds of millions of people around the globe and represent classic unmet medical needs.
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 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.
Pipeline Development Opportunities for Crofelemer
Crofelemer is being evaluated for the prophylaxis of CTD in adult solid tumor patients receiving targeted therapy with or without standard chemotherapy. A significant proportion of patients undergoing cancer therapy experience diarrhea. Novel targeted cancer therapy agents, such as epidermal growth factor receptor and tyrosine kinase inhibitors, may activate intestinal chloride secretory pathways leading to increased chloride secretion into the gut lumen, coupled with significant loss of water that would result in secretory diarrhea.
Crofelemer was granted ODD for SBS by the FDA in August 2017 and by the EMA in December 2021. Crofelemer was granted ODD by the U.S. FDA in February 2023 for MVID, a rare CDD condition, and crofelemer received ODD for MVID from the EMA in October 2022. The company is supporting investigator-initiated POC studies of crofelemer in patients with SBS with intestinal failure or CDD, focused on obtaining POC of reduction of requirements of parenteral support, including parenteral nutrition and/or intravenous fluids, throughout 2023. In accordance with the guidelines of specific European Union countries, publications of POC data from these trials could support early patient access to crofelemer for SBS with intestinal failure or CDD in 2023 through programs in Europe. Early access programs are revenue generating, and reimbursable for participating patients.
The Orphan Drug Act (‘ODA’) in the U.S. provides for granting special status to a small molecule drug or biological product to treat a rare disease or condition upon request of a sponsor.
Crofelemer is also being evaluated in another investigator-initiated trial for the management of functional diarrhea in non-HIV patients. This study is being conducted at the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. This clinical study is a randomized double-blind, placebo-controlled study in adult subjects with functional diarrhea.
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.
Mytesi is the only antidiarrheal drug that has been approved by the U.S. FDA for the treatment of chronic, noninfectious diarrhea in adult HIV/AIDS patients receiving ART. This approval was on the basis of the drug’s safety and efficacy in reducing the number of weekly and daily watery stools in patients and improvement of stool consistency, from unformed to formed stools, over a 24-week treatment period.
Unlike other available diarrhea remedies, crofelemer does not act by inhibiting intestinal motility. It has minimal oral absorption and does not have any clinically significant food or drug interactions, thereby allowing patients to maintain their appropriate dosing of treatment to suppress their viral load and maintain adequate CD4 levels in PLWHA. Crofelemer is also the only approved antidiarrheal drug that is approved for chronic use. Moreover, it is not an opioid, like other traditionally used treatments, thus avoiding both the acute side effect of constipation and the potential for abuse.
There are significant barriers to entry for generic competition for Mytesi (crofelemer). Napo holds an extensive global patent portfolio. At the present time, the company holds approximately 145 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, enteric protection from gastric juices, among others. The company also has approximately 55 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, which provides another barrier to entry from potential generic competition. The FDA requires that the manufacturer of crofelemer use a validated proprietary bioassay to release the drug substance and drug product of Mytesi. While most generic products are fashioned to meet chemical release specifications that are in the public domain, the specifics of this assay are not publicly available. There is no pathway by which a generic product can be developed for a drug approved under botanical guidance. In addition, Mytesi is minimally absorbed systemically, so the classic approach of creating a generic drug by matching pharmacokinetic blood levels is not possible. A generic player would have to conduct costly and risky clinical trials.
While Jaguar’s commercial and development efforts have evolved to focus primarily on Mytesi and human pipeline indications since its merger with Napo, the company commenced launch initiatives related to Canalevia-CA1, the company’s drug product, which received conditional approval in December 2021 for the treatment of CID in dogs. CID in dogs is typically caused by the same mechanism of action as in humans, and hence the work in dogs serves as a preclinical proof of concept for the diarrhea in humans that is related to targeted cancer therapy.
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.
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 the company sustainably harvest and manage through programs that the company has been developing over the past 30 years. This process has involved working with local and indigenous communities to plant trees, obtaining permits for export, and creating a supply network that is robust and reliable.
Product Pipeline
In addition to the company’s Mytesi (crofelemer) product that is approved by the U.S. FDA for the symptomatic relief of noninfectious diarrhea in adults with HIV/AIDS on antiretroviral therapy, the company is developing a pipeline of prescription drug product candidates to address unmet needs in gastrointestinal health through Napo. Mytesi (crofelemer) is a novel, first-in-class anti-secretory antidiarrheal drug which has a normalizing effect to restore the electrolyte and fluid balance in the gut and lumen, and this mechanism of action has the potential to benefit multiple disorders. Clinical trials demonstrated that nearly 80% of Mytesi users experienced an improvement in their diarrhea over a four-week period.
The company’s Mytesi pipeline includes prescription drug product candidates for multiple follow-on indications, several of which are backed by Phase 2 evidence from clinical trials. In 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.
Business Strategy
The company’s strategies are to expand Mytesi by leveraging the company’s significant gastrointestinal product knowledge, experience and intellectual property portfolio; maintain commercial capabilities in Mytesi sales and marketing efforts; leverage the company’s relationships with Scientific Advisory Board (SAB) members for crofelemer commercialization and development in follow-on indications; establish partnerships to support moving pipeline indications to pivotal clinical trials; strategically sequence the development of follow-on indications of Mytesi and seek geographically focused licensing opportunities; and reduce risks relating to product development.
Napo Therapeutics Provides New Opportunities to Treat Orphan Indications Like SBS
Jaguar is strategically pursuing multiple important shots on goal for its drug development pipeline: Crofelemer for CTD, led by Napo, and crofelemer for SBS and CDD, led by Napo Therapeutics. 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.
Manufacturing
Napo’s collaborating suppliers obtain CPL and arrange for the shipment of CPL to Napo’s third party contract manufacturer.
Napo’s third party contract manufacturer, India based Glenmark Life Sciences Ltd. (‘Glenmark’), a research driven, global, integrated pharmaceutical company, is Napo’s manufacturer of crofelemer, the active pharmaceutical ingredient in Mytesi. Glenmark processes CPL into crofelemer utilizing a proprietary manufacturing process. The processing occurs at an FDA approved Glenmark facility. Additionally, Napo is establishing a second processing site, which will be operated by Indena S.p.A. (‘Indena’), a Milan, Italy based contract manufacturer dedicated to the identification, development and production of high-quality active principles derived from plants, for use in the pharmaceutical, health food and personal care industries. Indena has completed the required validation activities to gain approval as a manufacturer of crofelemer drug substance.
As announced January 25, 2023, the required procedure of registering the source of the API of crofelemer with the Agenzia Italiana Del Farmaco (‘AIFA’), the Italian Medicines Agency, has been successfully completed. Resultingly, batches of crofelemer API manufactured by Indena can now be used by Jaguar for further development work.
Proprietary Library of Medicinal Plants
The company possess a proprietary library of more than 2,300 medicinal plants.
Intellectual Property
Trademarks
Mytesi is a registered trademark owned by Napo. Jaguar Animal Health is a trademark owned by Jaguar.
License Agreements
Patent Portfolio
Napo
Napo owns a portfolio of patents and patent applications covering formulations of and methods of treatment with proanthocyanidin polymers isolated from Croton spp. or Calophyllum spp., including Mytesi (crofelemer).
Napo owns a family of patents arising from International Patent Application Publication WO2012/058664 that cover methods of treating HIV associated diarrhea and HAART associated diarrhea with proanthocyanidin polymers isolated from Croton spp. or Calophyllum spp., including crofelemer. In the U.S., there are two issued patents, US 8,962,680 and US 9,585,868, both of which expire October 31, 2031. Outside the U.S., patent protection for methods of treating HIV associated diarrhea has been obtained in Australia, Europe, Hong Kong, Japan, Kenya, Mexico, Russia, Ukraine, South Africa, and Zimbabwe, with expiration dates of October 31, 2031, and applications are pending in Brazil, Hong Kong, and China. Napo also has patent families related to methods of treating diarrhea predominant irritable bowel syndrome, methods of treating constipation predominant irritable bowel syndrome, and methods of treating inflammatory bowel disease, familial adenomatous polyposis and colon cancer, with proanthocyanidin polymers isolated from Croton spp. or Calophyllum spp., including crofelemer. In particular, for diarrhea predominant irritable bowel syndrome, Napo has two issued U.S. patents, US 8,846,113 and US 9,980,938, which expire on February 9, 2027, as well as issued patents in Australia, Canada, Europe, Gulf States, Hong Kong, Japan, South Korea, Mexico, New Zealand, Singapore, Thailand, and Taiwan; and pending applications in Bangladesh, and Venezuela, all of which are estimated to expire April 30, 2027; for constipation predominant irritable bowel syndrome, Napo has three issued U.S. patents, with terms to at least April 30, 2027, patents in Australia, Canada, Europe, Hong Kong, Mexico, New Zealand, and Singapore, all of which are estimated to expire April 30, 2027; and for inflammatory bowel disease, familial adenomatous polyposis and/or colon cancer, Napo has two issued U.S. patents, US 8,852,649 and US 9,987,250 with terms until at least January 4, 2028, as well as issued patents in Australia, Hong Kong, and Europe and Canada, which have estimated expiration dates of April 30, 2027. Napo has a U.S. patent for the treatment of CID caused by neratinib with crofelemer and a related continuation application also directed to treating CID effectively filed on March 9, 2018, as well as multiple pending national stage applications outside the U.S. also directed to treating CID with crofelemer effectively filed June 19, 2020. In addition, Napo has two patent families each with pending applications in United States, Australia, Canada, China, Europe, Israel, Jordan, Japan and the Gulf States directed to the treatments of SBS and CDD, respectively, and each filed on May 31, 2018. Napo also has pending International applications to ‘Methods and Compositions For Treating Post-Acute Infection Gastrointestinal Disorders’ filed November 23, 2021.
For methods of manufacturing proanthocyanidin polymers isolated from Croton spp. or Calophyllum spp., including crofelemer, Napo owns issued patents in India, South Africa, and Eurasia with terms at least until August 26, 2029. Napo also owns issued patents in Brazil, India, and Russia, and a pending application in Venezuela that also cover methods of manufacturing proanthocyanidin polymers isolated from Croton spp. or Calophyllum spp., including crofelemer, with terms at least until January 17, 2032. Lastly, Napo owns two U.S. patents covering a formulation of NP 500 (nordihydroguiaretic acid (‘NDGA’)) and its use in treating a metabolic disorder that have terms until April 23, 2031.
Napo also has two international applications pending directed to alstonine derivatives and salts thereof and uses thereof for treating psychotic disorders which were filed on June 14, 2022, and October 26, 2022, respectively.
Napo grants license to Napo Therapeutics
On 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). 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.
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.
History
Jaguar Health, Inc. was founded in 2013.
