Lisa Conte is the founder, president, and CEO of San Francisco-based Jaguar Health, a unique commercial stage pharmaceuticals company that develops and commercializes gastrointestinal pharmaceuticals by working with substances found in plants typically located in rainforest regions and used by Indigenous populations.

Over her 32-year career, Lisa has taken three companies public, raised approximately $500 million, and successfully brought the first and only oral plant-based prescription drug approved under FDA Botanical Guidance to market: Mytesi^®, an antidiarrheal indicated for the symptomatic relief of noninfectious diarrhea in adult human patients with HIV/AIDS on antiretroviral therapy. Crofelemer, the active pharmaceutical ingredient in Mytesi, is sustainably derived from the sap, or latex, of the Amazonian tree species “Croton lechleri” which has a rich history of medicinal use by Indigenous peoples in the Western Amazon rainforests of South America.

Important milestones

In the next year, Jaguar expects to achieve key milestones including Phase 3 pivotal data for crofelemer in cancer therapy-related diarrhea (CTD) and a proof-of-concept clinical result for the orphan designated disease indication of crofelemer for short bowel syndrome.

2022: Jaguar Health's year of the dog

Lisa and Jaguar Health recently achieved another key milestone when the FDA granted conditional approval of Canalevia™-CA1 (crofelemer), the company’s oral plant-based prescription drug for the treatment of chemotherapy-induced diarrhea (CID) in dogs. Canalevia™-CA1is the first and only product indicated for the treatment of CID in dogs to receive any type of approval from the FDA.

Due to the increasing number of chemotherapeutic agents being adopted by veterinarians, chemotherapy is fast becoming the most widely used cancer treatment in veterinary medicine. Studies have found the incidence of CID to be one of the three most prevalent side effects in dogs undergoing cancer treatment, and managing side-effects such as diarrhea can be important to maintain successful cancer treatment. More than half of the U.S. veterinarians who responded to a recent Jaguar Health-sponsored survey reported that CID interferes with their patients' chemotherapy treatment plans, indicating an unmet need for an effective product for the treatment of CID.

A quest that began halfway up Mt. Kilimanjaro

When Lisa founded Jaguar Health’s predecessor company, she was a California venture capitalist on a search for early-stage technologies. During a climb of Mount Kilimanjaro, her hiking partner was beset by altitude sickness. But the mountain came to their aid that day in 1987. A nearby villager offered them a strange elixir at what appeared to be a makeshift pharmacy on the trail. “He held what looked like a bottle of Scotch,” remembers Lisa. “It had green stuff in it that was dripping down the side, and there were plants popping out of it. It looked very mysterious.”

Lisa’s friend drank the green substance and felt relief. The climbers continued to Kilimanjaro’s 19,341-foot summit. The bottle contents, Lisa surmises, may have been khat, a flowering plant native to the Horn of Africa known for its amphetamine-like effects. The experience made Lisa aware that local people had used certain plant-based medicines for millennia. She realized demystifying these traditional medicines and identifying the active ingredients could lead to the development of new prescription drugs. Based on that insight, Jaguar Health’s predecessor company was formed.

Pipeline within a product

Today, more than three decades after that experience on Kilimanjaro, Lisa leads a team of researchers at Jaguar Health dedicated to expanding access to crofelemer to patients in need around the globe. Crofelemer has a first-in-class anti-secretory mechanism of action, acting locally in the gastrointestinal tract to modulate and normalize the patient's waterflow.

The drug’s mechanism of action may have the potential to benefit multiple disorders and is in development for an array of possible gastrointestinal follow-on indications in humans, including IBD, IBS and CTD. OnTarget, Jaguar’s pivotal Phase 3 clinical trial of crofelemer for prophylaxis of diarrhea in adult cancer patients receiving targeted therapy, is actively enrolling patients.

A significant proportion of patients undergoing cancer therapy experience diarrhea, and diarrhea has the potential to cause dehydration, potential infections, and non-adherence to treatment in this population. Novel “targeted cancer therapy” agents, such as epidermal growth factor receptor antibodies and tyrosine kinase inhibitors (TKIs)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 outcome.

A new venture focused on expanding crofelemer access in Europe

In 2021, Jaguar Health formed Napo Therapeutics, a specialty drug development and marketing company in Milan, Italy, based on an exclusive license to crofelemer technology in Europe. Napo Therapeutics' mission is to provide access to crofelemer in Europe to address significant rare/orphan disease indications, including, initially, two key orphan target indications: short bowel syndrome (SBS) with intestinal failure, and congenital diarrheal disorders (CDD).

SBS is a complex condition characterized by severe malabsorption of fluids and nutrients due to surgical resection of bowel segments, congenital anomalies, or disease-associated loss of absorption. For SBS patients who endure the catastrophic loss of their bowel, the resulting excessive intestinal fluid output and lifelong restriction and adjustment of oral intake of food and liquids leads to the requirement to receive intravenous fluids for most of every day. This challenges their ability to carry out activities of daily living and has a significant impact on their quality of life.

CDD is a group of rare, chronic intestinal channel diseases which occur exclusively in early infancy and are characterized by severe, lifelong diarrhea and a lifelong need for nutritional intake either parenterally or with a feeding tube. Infants with CDD experience chronic diarrhea.

Napo Therapeutics expects to generate proof-of-concept clinical data that can support an early patient access program available in certain European countries for this orphan disease indication of crofelemer.

An unwavering commitment to people, plants, and the planet

In addition to focusing on bringing crofelemer to patients in need, Lisa and Jaguar Health are deeply committed to responsible harvesting. Two new “Croton lechleri” trees are planted for every tree harvested, and approximately 800,000 trees have been planted since 2001. “We are also dedicated to maintaining a close, positive relationship with the Indigenous and local communities with which we work,” Lisa said, “and to respecting and conserving the vast body of ancient and powerful plant-based medicinal knowledge of Indigenous peoples and local communities in the Amazon Rainforest.”

Certain statements in this article constitute “forward-looking statements.” These forward-looking statements speak only as of the date of this article and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond Jaguar Health’s control. Some of the factors that could affect Jaguar Health’s actual results are included in the periodic reports on Form 10-K and Form 10-Q that Jaguar Health files with the Securities and Exchange Commission. Except as required by applicable law, Jaguar does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.