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Jaguar Health CEO And Lead Ethnobotanical Researcher Explain The Decades Of Research That Made It A Leader In Plant-Based Drug Treatment

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Jaguar Health CEO And Lead Ethnobotanical Researcher Explain The Decades Of Research That Made It A Leader In Plant-Based Drug Treatment

The following post is sponsored by Jaguar Health, Inc. It is for informational purposes only and not intended to be investing advice.

With more than 30 years of ethnobotanical field research and ethnopharmacological compound analysis encompassing plant species and medical traditions from indigenous communities throughout the world’s rainforest and tropical biomes, the management team at Jaguar Health (NASDAQ: JAGX) has garnered a unique reservoir of knowledge and expertise within the biotech industry.

The first fruits of this knowledge catalog yielded the company’s lead drug compound, crofelemer, which is marketed under the trade name Mytesi as a first-in-class, botanically-derived, antisecretory agent indicated for the symptomatic relief of non-infectious diarrhea in adults with HIV/AIDS on antiretroviral therapy. As the only oral plant-based prescription medicine approved under FDA botanical guidance, crofelemer represents a new paradigm in refining and applying traditional medical practices into contemporary Western healthcare.

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Man holding tree. Illias Gualinga, a Shaman of the Quichua village of Molino, on the Bobanaza River in the Ecuador Amazon, examining a young tree in the primary forest that is used as part of his traditional medicine practice.  
(Photo Courtesy of Steven R. King)

In a recent interview with Benzinga, Jaguar Health founder and CEO Lisa Conte described the many years of exploration and research that went into identifying, purifying and manufacturing crofelemer and why crofelemer stood out as the most promising compound from the team’s three-decade-long research mission.

“We worked with the healers seven or eight times over several years, and they would talk to our team of researchers about the plants they've been using for the symptoms that we were interested in,” explained Conte. “From that came crofelemer, which kept landing on the top of the stack of our prioritization process for safety, for efficacy, for sustainability, for exclusivity, for formulation, and so forth.”

Raising awareness of these factors among investors and partners within the biotech space remains a key focus for Jaguar Health. A recent virtual event from the company, Diarrhea Dialogues: Why Bowel Control is Critical to Supportive Care in Cancer, highlights the need for supportive care for people experiencing conditions related to chronic lower gastrointestinal tract distress — specifically, cancer therapy-related diarrhea, which can have debilitating effects on patients and can interfere with the efficacy of treatment.

However, as Jaguar Health continues to define its unique place in the pharmaceutical market, Conte sees the company’s reservoir of knowledge in sourcing and refining traditional plant-based medicines as a key driver of future growth in developing treatments with novel mechanisms of action for patients for whom existing drugs are either ineffective or not tolerable. 

Recovering From Timothy Leary

Conte explained that her team’s years of field research generated a massive library of 2,300 proprietary plants with medicinal properties and 3,200 extracts, many of which were discovered in a period in the 1990s when ethnopharmacological research was an overlooked aspect of pharmaceutical science. 

Focus areas for potential indications include diabetes management and anti-infective treatment, as well as central nervous system (CNS) and mental health disorders. In particular, Conte indicated that plant-based medicines that elicit psychoactive effects were observed and recorded by her research team in the past but not pursued due to the fraught legacy these kinds of treatments carried in the West at the time.

“Anything that had a psychoactive or psychedelic effect, we deprioritized – because 30 years ago, even 10 years ago, there really was no regulatory pathway to take these findings forward. The field was still recovering from Timothy Leary and the restrictions that were put on psychoactive and psychedelic plants.”

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Picralima nitida plant, a species of West African plant of the genus Picralima in the family Apocynaceae, and the source of the active ingredient alstonine 
(Picralima nitida image copyrighted by Hiobson and licensed under the Creative Commons Attribution-Share Alike 4.0 International license)

While Conte made clear that Jaguar Health’s primary focus continues to be on novel gastrointestinal non-opioid plant based medicines, she did speak to the emerging interest and potential novel ways to treat mental health and mood disorders, particularly as a corollary to nascent research that other companies are now conducting in psilocybin, DMT and ketamine. 

Already, Jaguar has identified one psychoactive compound, alstonine, which derived from a species of a West African plant from its library as a potential treatment for schizophrenia, for which Jaguar is looking to partner with larger biotech firms to aid in designing clinical trials and navigating the regulatory landscape.

A Global Research Effort

Providing more insight into the firm’s research legacy, Conte put Benzinga in touch with Jaguar Health’s chief sustainable supply, ethnobotanical research and IP officer, Steven King, Ph.D, who managed the original scientific strategy team that contributed to the development of Jaguar's plant library.

King described how the research teams collaborated with healers and shamans within these local and Indigenous communities to uncover how the application of each culture’s care practices aligned with the symptoms of the individuals these traditional healers were treating.

“It was a process of respectfully having conversations, spending time with people, discussing our goals and objectives,” said King. “We would ask a healer, ‘do you recognize these symptoms?,’ both in photographs and verbally in the appropriate language. Healers would ponder the question and then begin to discuss with us, ‘Well, here's a patient that sounds like that. Here's what I do to treat that kind of patient.’ We would then collect the plants with the healer or watch them make the treatment. We would bring those materials back, shipping them back to a laboratory where we would conduct extraction of those materials [...] to seek novel compounds that may be responsible for the activity that was presented to us.”

At the time, King echoed Conte’s descriptions of the deprioritization of plants and compounds that carried psychoactive or hallucinogenic effects. 

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Steven King meeting with Awajun indigenous community members to discuss the long term sustainable management of Croton lechleri, in the Northern Peruvian rainforest region.
(Photo courtesy of Kodix Garcia Valles)

However, he also indicated the surprising and illuminating effects of these traditional medicines as described by the research teams. In particular, he pointed to one research episode around the compound Jaguar Health is exploring for a potential schizophrenia indication.

“Our key ethnopharmacologist was working in West Africa when the research team was introduced to this very exciting compound. She was particularly taken when she observed patients getting up off their seats, walking over, shaking hands, introducing themselves to her,” King elaborated. “When she noticed that these people who were being treated with this plant for a certain psychosis were able to actually conduct themselves in a fairly standard and socially acceptable manner, she was especially interested.  Alstonine appears to offer a mechanism of action that is distinct from existing antipsychotic therapies such as clozapine and haloperidol, and it may therefore prove beneficial in the management of some mental health diseases.”

And while these observational and anecdotal data were intriguing, they were also, unfortunately, beyond the accepted norms of pharmacological research at the time.

Leaders In Their Fields

However, thanks to the recent expansion of CNS and psychosis treatment research to again include psychedelic and hallucinogenic agents, the catalog of ethnopharmacological research generated by King and his colleagues have been given new life and potential significance.

“We're going back through this database of world-wide research that we generated over this decade-long period and looking at the data sheets where we had side effects that mentioned psychoactive plants, psychosis and the like. We have the opportunity to resurrect them to a higher level and explore the chemistry, biology, botany and everything related as secondary candidates,” King explained.

Among that wealth of research are studies and observations made by some of the preeminent botanists, doctors and pharmacological researchers who study traditional medicine, including ethnobotanist Michael J. Balick, Ph.D., Brazilian ethnopharmacologist Elaine Elisabetsky, Ph.D., and ethnobotanist, writer, and professor of anthropology at University of British Columbia Wade Davis, Ph.D., as well as many others.

A Foundation Of Knowledge

Both King and Conte view this deep well of research and the library of plants and compounds it helped produce as the foundation of Jaguar Health’s current success in bringing crofelemer to market as a first-in-class, FDA-approved drug. 

Conte explained, “Our recently launched initiative focusing on psychoactive and psychedelic plants is based on the same process that led to the successful identification and development of crofelemer, Mytesi. It is an interdisciplinary approach, a prioritization process focused on the knowledge of local and Indigenous healers, looking at how they treat different symptoms, and then having the integrity on the botany and the ethnobotany side that supports our drug development activities.”

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Chief Cosmas Ozonnamalu, a member of the Nigerian Union of Medical Herbal Practitioners and the Ninth Mile Traditional Healers Association in Engu, Nigeria describing the preparation and utilization of a plant used to treat head injuries.
(photo courtesy of Steven R. King)

This catalog of knowledge supports the core strategy that, according to Conte, will continue to drive Jaguar Health’s research and development of plants and natural compounds that may offer new and overlooked biological pathways for treating patients. With support from partners in the biotech and investment world, she hopes Jaguar Health’s ongoing efforts to identify novel, first-in-class treatment options will lead to the development of additional plant-based drugs to address mental health conditions and improve quality-of-life results among patients.

“While Jaguar remains steadfastly focused on the commercial success of our FDA-approved drug product, Mytesi, and on the development of crofelemer’s follow-on indications in the area of GI health, we're thrilled to be leading this effort to potentially uncover a pipeline of novel psychoactive plant-based compounds, engage with recognized leaders in this space, and share our findings with potential corporate partners with the goal of developing plant-based compounds into possible medical breakthroughs," said Conte. "For decades, our team has recognized the unique and powerful knowledge traditional and Indigenous peoples have about plants, ecosystems, interrelationships, and healing compounds, and we continue to be extremely grateful to the traditional healers who have taught our team of field research scientists about medical applications of plants to treat and heal people in their communities and the world."

 

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