Jaguar Health, Inc. (NASDAQ:JAGX) Special Conference Call July 23, 2024 8:30 AM ET
Company Participants
Lisa Conte - Founder, President & Chief Executive Officer
Pravin Chaturvedi - Chief Scientific Officer & Chairman of Scientific Advisory Board
Stacey Tinianov - Member of Napo's Scientific Advisory Board
Allison Ackerman Shrier - Vice President of Medical Affairs & Clinical Research at Napo Pharmaceuticals
Operator
[Call starts abruptly]
Before I turn the call over to management, I'd like to remind you that management may make forward-looking statements relating to such matters as continued growth prospects for the company, uncertainties regarding market acceptance of products, the impact of competitive products and pricing, industry trends and product initiatives, including products in the development stage which may not achieve scientific objectives or meet stringent regulatory requirements. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those contemplated in such forward-looking statements. These statements are based on currently available information and management's current assumptions, expectations and projections about future events. While management believes its assumptions, expectations and projections are reasonable in the view of currently available information, you are cautioned not to place undue reliance on these forward-looking statements.
The company's actual results may differ materially from those discussed during the webcast for a variety of reasons, including those described in the forward-looking statements and Risk Factor sections of the company's Form 10-K for the year 2023 which was filed on April 1, 2024 and its other filings with the SEC which are available on the Investor Relations section of Jaguar's website. Except as required by law, Jaguar undertakes no obligation to update or revise any forward-looking statements contained in this presentation to reflect new information, future events or otherwise. Today's conference is being recorded.
At this time, it's my pleasure to turn the call over to Lisa Conte, Jaguar Health's Founder, President and Chief Executive Officer. Lisa, the floor is yours.
Lisa Conte
Thank you. Thank you. Hello and thank you for joining our investor webcast today to all who are listening. My name is Lisa Conte. I'm the Founder, President and CEO of Jaguar Health and our wholly owned subsidiary, Napo Pharmaceuticals, and I'm the Chairman of our Italian subsidiary, Napo Therapeutics. As usual, I may use the words Jaguar and Napo interchangeably to refer to the company.
Now let's get right to it. We announced earlier today that the initial results of our unprecedented OnTarget trial, a study that included 10 different solid tumor types, did not meet its primary endpoint across all tumor types. We are, however, pleased that the trial did reveal clinically relevant signals for crofelemer in prespecified subgroups of patients with breast and respiratory cancers, including lung cancer.
I am here with our Chief Scientific Officer and Chair of our Scientific Advisory Board, Dr. Pravin Chaturvedi, the architect of the OnTarget trial design. And also for full reference, Dr. Chaturvedi was also the architect of the successful ADVENT trial that supported the approval of crofelemer under the brand name Mytesi, which is currently commercialized under the current approved indication of HIV-related diarrhea. And he has 7 approved NDAs to his name. He knows his way around the regulatory pathway.
Pravin, I have a few questions for you. So let's -- and by the way, good morning. And let's explore the meaning of this announcement. First, why is this called an unprecedented supportive care trial?
Pravin Chaturvedi
Thank you for the question, Lisa and good morning, everybody. We chose to be patient-centric and designed the trial to include all patients regardless of their tumor type or targeted therapy. We designed a clinical study that was informed by the patients for addressing their bowel control habits regardless of their targeted therapy or cancer.
OnTarget study is unprecedented trial because it's truly the first trial of its kind. It was prophylactic, randomized, double-blind, placebo-controlled study in patients who are receiving targeted therapies which, as you know it, Lisa, are cytostatic and are administered chronically, unlike cytotoxic chemotherapies which are given as a cycle every 3 weeks or so.
And we conducted this prophylactic study in a real-world setting, where the primary endpoint was determined based on patient-reported outcomes of their bowel habits. This trial was truly patient-centric and included all adult solid tumor patients receiving targeted therapies, which are appropriate for their tumors, contributing to the heterogeneity of the patient population and their treatments. We randomized patients across 10 solid tumor types who received 24 different targeted therapies which had deferring mechanisms of action.
Thus, the patients and the therapies that were included in the trial were based on the diversity and heterogeneity and included drugs that cause an incidence of more than 50% all-grade diarrhea. These numbers are not available in the public domain as oncology drugs only report grade 3 and 4 diarrheas. To put it into context, a grade 3 diarrhea is more than 7 loose watery stools per day every day and targeted therapies are taken for prolonged periods, sometimes indefinitely. It is deemed that grade 1 and 2 diarrhea which is between 3 and 6 loose watery stools every day which is 21 to 42 loose watery bowel movements per week, are manageable.
We were unprecedented because we do not believe that this should be acceptable nor should anyone live with that much toxicity every day. Hence, we call it an unprecedented trial.
Lisa Conte
Thank you. And the trial -- the OnTarget trial showed a clinically relevant signal in breast cancer and lung cancer patients. What does clinically relevant mean?
Pravin Chaturvedi
So clinically relevant refers to what is important to the patients. As Dr. Pablo Okhuysen stated in this morning's press release, who is the National PI from MD Anderson Cancer Center, that it is important to note that the prespecified secondary outcomes for this study were based on outcomes that were considered to be meaningful to the patients experiencing diarrhea due to their targeted therapy.
We designed an endpoint for OnTarget study that was based on a patient survey on what was important to the patients. It is clinically relevant because unlike an expectation of no diarrhea which means no loose watery stools per day, cancer patients are remarkably resilient and understand that their treatments will cause adverse events. A majority of the patients, almost 3 out of 4, told us that we can reduce -- if we can reduce their loose watery bowel movements per week to about 14 per week which is about 2 a day, they would be able to tolerate their cancer regimens and take the required medication to treat their cancers.
Based on this input, we designed a trial to assess the proportion of patients that would have achieved their stated clinically meaningful and acceptable bowel control outcomes. Hence, in our prespecified subgroup analysis, we evaluated patients achieving this secondary clinical outcome which makes it relevant to the patients.
Lisa Conte
Okay. Thank you for that. So with regard to the breast cancer and the respiratory, basically, the lung cancer patients where we -- where the study showed a clinically relevant signal, what does a prespecified subgroup mean? And tell me about those patients.
Pravin Chaturvedi
So in that OnTarget study, we had stratified patients based on their tumor types and the various targeted therapies' mechanisms of action. We had prespecified subgroups, including respiratory and breast, as they represent a significant portion of the patients that are eligible for targeted therapies that are quite diarrheagenic.
To be more specific, each of the targeted therapies that were included in this trial, including those for breast and respiratory, were reported to have greater than 50% incidence of diarrhea. For instance, the breast cancer therapy, pertuzumab, has a diarrhea incidence rate up to 71%. Abemaciclib has a diarrhea rate up to 85%. And lung cancer therapy patients that received osimertinib have a diarrhea rate up to 58% of the patients.
Of the 287 patients enrolled in the OnTarget study, 37 patients had respiratory cancers and 180 patients had breast cancer. So combined, these 2 groups alone were about 217 patients that represented 75% of the patients randomized in the OnTarget study. So it was important to have these subgroups analyzed.
Lisa Conte
So Pravin, we've worked together a long time to bring crofelemer to, for example, people living with HIV/AIDS on antiretroviral therapy. What do we do next year in this patient population?
Pravin Chaturvedi
Thank you for asking that. As you know, we've just received the initial results from the analysis of the first 12 weeks of this double-blind placebo-controlled study. We have seen that the prespecified subgroups of breast and respiratory cancer patients have an improvement in the incidence of diarrhea over the first 12 weeks. We appreciate that the majority of subjects also chose to continue on to the stage 2 part of the study which is also blinded and so we have to look at those data.
So what we plan to do is to conduct further analysis of all the data from both stage 1 and stage 2 for the prespecified and exploratory endpoints for various subgroups. Subsequently, we will engage in discussions with the FDA to explore options available to us to bring crofelemer to at least the subgroups in which crofelemer is showing a clinically relevant effect. That's what our plan is at this time.
Lisa Conte
Okay. And as always, I'd love to hear it, can you comment on the paradigm-shifting mechanism of action of crofelemer, why this is important to get this product out?
Pravin Chaturvedi
Thank you for that. So for those of you who don't know, crofelemer is a first-in-class chloride ion channel modulator that does not have any effect on gastrointestinal motility. Furthermore, it is negligibly absorbed orally and acts locally in data from both stage 1 and stage 2 for the prespecified and exploratory gut lumen. It does not belong to the class of opioids and, therefore, does not present the risk of constipation.
It is also unlike any other currently grandfathered anti-diarrheals such as anti-motility drugs, anticholinergic drugs, adsorbent drugs or bile acid sequestrant that are commonly administered to manage the toxicity and -- of diarrhea specifically in oncology patients. Due to its unique mechanism of action and lack of systemic absorption, crofelemer's safety profile over the years when we have studied it and developed and commercialized it has been consistently not different from placebo. So that makes it a paradigm shift in terms of safety and tolerability.
Lisa Conte
Okay. You referred to the trial as a real-world evidence trial. What does that mean?
Pravin Chaturvedi
So as I said a little earlier, we had designed the OnTarget study to be a prophylactic protocol that allows for the inclusion of all solid tumor types and their standard of care treatments that included targeted therapies. We wanted to remain patient-centric and did not want to dictate their cancer treatment based on the OnTarget study protocol.
So what that means is that the patients got whatever drugs were appropriate for their cancer care and then whatever other drugs their providers were administering them for control of their adverse events, including opioids for pain and any other interventions for their diarrhea as deemed appropriate by their health care professional.
This made for a very complicated analysis. It contributed to the heterogeneity as well as the lengthy duration of the time required for the analysis of this study. It's a real-world study because we did not change any other parameter for the patients being treated for their cancer.
Lisa Conte
Thank you for that. And are you expecting to present and/or publish the results from this trial?
Pravin Chaturvedi
Absolutely. Obviously, we have more analysis to conduct for both the stage 1 and stage 2 portions. We intend to collaborate with our clinical and scientific advisers to evaluate the significance of the clinical outcome signals, especially in these prespecified subgroups and we will present that in a setting that will allow peer reviewed presentations and publications. So we are very, very hopeful about that.
Lisa Conte
Thank you very much, Pravin and thank you for all the hard work to the team for implementing this trial and especially the patients who participated in the trial, the health care providers, the nurses, et cetera.
I'd like to let all of you who are listening to us today know that both, Pravin and I, are cancer survivors. In my case, it was breast cancer last year after the trial was already planned and started and included treatment with targeted therapy, the same as the majority of the patients in the OnTarget trial, same patient population where there's a clinically relevant signal. So Pravin and I know first-hand that no cancer therapy-related side effect should ever be viewed as acceptable or tolerable.
The patient perspective and certainly in my case, it was unanticipated and it's extraordinary, this perspective, in driving home the unmet need for supportive care to address patient dignity, patient quality of life, the ability of patients to stay on their life-saving cancer therapy and continue with their life. Not a new normal, continue with their life. And this is all at the heart of Jaguar's mission.
We're now going to play a series of short video clips from 4 important thought leaders. The amazing patient thought leader who is a member of our Scientific Advisory Board, Stacey Tinianov. She's an 11-year cancer survivor who founded the non-profit organization Advocates for Collaborative Education and who serves on our Scientific Advisory Board. Stacey is leading the charge with Napo's Make Cancer Less Shitty patient engagement program which we premiered at Napo's exhibits at the San Antonio Breast Cancer Symposium last December -- we would fully expect to be there this coming December and at the past April's Oncology Nursing Society Congress.
The program is designed to provide a voice to cancer survivors who are no longer willing to accept debilitating side effects of cancer treatments as an acceptable trade-off for survival. Patients don't want to just exists. They want to live.
Following Stacey, Dr. Lee Schwartzberg will discuss the significant unmet medical need of cancer therapy-related diarrhea. He is a leading breast cancer medical oncologist and hematologist who serves as Chief Medical Oncology and Hematology at the Renown Health-William N. Pennington Cancer Institute in Reno, Nevada, also a member of our Scientific Advisory Board involved in the design of the OnTarget study with Dr. Chaturvedi.
We'll then view a short recording from oncologist Dr. Allison Shrier, Napo's Vice President of Clinical Research and Medical Affairs. And after Allison speaks, we're going to hear from Dr. Maged [ph]. He's a well-known radiation oncologist and oral mucositis expert with Northwell Health Cancer Institute, Monter Cancer Center, speaking about oral mucositis.
As a reminder, we recently expanded Jaguar's cancer supportive care portfolio through our in-license of the FDA-approved oral mucositis prescription product Gelclair for the U.S. market and we plan to conduct the commercial launch of Gelclair in the fourth quarter of this year. Another topic near and dear to my heart because one of my side effects in my cancer care was oral mucositis.
And then today's webcast will end after the videos finish. I want to thank you all. Drug development is a long-term process. We are committed. We have brought crofelemer under the trade name Mytesi to people living with HIV/AIDS as a first indication. We are committed to patient-supportive care, not only with crofelemer but as you can see with, Gelclair and there's 21 side effects that are reported in the supportive care world and unmet needs for cancer supportive care. So we're going to start taking them off one at a time.
Dr. Chaturvedi, Pravin, we worked together a long time. Are there any final words you would like to say about the drug development process?
Pravin Chaturvedi
No, I think you summarized it well. I thank also all the patients and all the participants and the investigators for the OnTarget study. Work to be done and it's in the right direction. Thank you so much for the opportunity to speak to the listeners.
Lisa Conte
Thank you. And to those of you who can stay on another 12 minutes or so, there'll be some really informative webcast right -- or videos right now as part of this webcast. Thank you again.
Stacey Tinianov
Good morning. My name is Stacey Tinianov and I'm a member of Napo's Scientific Advisory Board, a patient research and policy advocate in the cancer community and the founder of Advocates for Collaborative Education. Today, speaking as a member of the larger cancer patient advocacy community, I am very excited to share with you updates from the trenches of patient advocacy.
You may recall that nearly a year ago, Napo provided generous support to the Advocate Collaborative with the More Than a Diagnosis survey. Specifically, More Than a Diagnosis with a quality of life survey for individuals with a diagnosis or a history of cancer. The anonymous survey was created by patients and advocates, distributed electronically to the patient and survivor community and it collected over 500 responses in just 5 weeks.
Specific data sets from that survey have since been presented at several key oncology meetings, including the San Antonio Breast Cancer Symposium and ASCO24. After examining not only the published data from that survey but also information gathered by key patient advocates, the Make Cancer Less Shitty campaign has been designed to highlight the harsh realities of cancer treatment and of survivorship and the frequent lack of quality supportive care that address these issues.
Basically, as the pharmaceutical industry expands the availability of anticancer therapeutics, we are, unfortunately, seeing incredibly challenging side effects to go along with those improved survival curves. And I believe all of you present today are likely to agree that survival is vital and yet the dignify and quality of that extended life is paramount. Candidly, as patients and as advocates, we do not believe that any cancer therapy-related side effect, whether it be extreme fatigue, debilitating diarrhea, hair loss, chronic pain or any other should ever be viewed as acceptable or tolerable. I am grateful that the Napo leadership agrees.
With that in mind, the Make Cancer Less Shitty [ph] campaign seeks to broadly acknowledge the rigors of both short-term and perpetual treatment by sharing the voices and stories of individuals with that lived experience. We have now kicked off the campaign's ambassador program with 3 ambassadors from the cancer patient community who, beyond sharing their own stories, will assist in capturing other stories and co-creating goals around what we all might do together to make cancer less [indiscernible]. Thank you.
Unidentified Company Representative
It's at a very interesting juncture in the development of therapies for breast cancer, specifically and for cancers in general. So what we've seen over the last decade is a gradual evolution from using cytotoxic chemotherapy with the spectrum of toxicities that occur with those types of drugs. And we're now in a new era where targeted therapies are becoming more and more important.
Many of the targeted therapies are oral agents. And one thing that many of the targeted therapies have in common, regardless of their mechanism of action, is a profound effect on the GI tract and that leads to diarrhea as a common and, in many cases, the most common and most severe toxicity that many of these agents take -- cause. Because the mode of delivery is different, not only are they oral but they're typically given continuously. And because patients now do much better than they did in years past, particularly patients with advanced cancers, we're now, in many cases, making advanced cancer as a chronic disease. So that means that these patients are exposed to oral agents that can cause toxicities, notably diarrhea, for long periods of time.
And we know from clinical trials of the tyrosine kinase inhibitors, of which there are now many that are used in multiple different diseases and, in my own field, the CDK4/6 inhibitors which have really transformed the treatment of advanced breast cancer and are now just recently approved for abemaciclib but one of them, the one that causes the most diarrhea is now approved in the adjuvant setting, opening up patients who are without cancer, many of which are cured but we don't know who they are and they'll be taking this drug for 2 years. So the implications of toxicity in that group is even more profound.
When you add up all of these patients who are getting these therapies, we are left with a cancer treatment-related diarrhea as an unsolved problem for us. And despite the many advances in supportive care, we do not have an advance in a CRD. And it's really very troubling because the only thing that we can do for these patients is give them anti-motility agents which may stop the diarrhea and cause constipation and cause discomfort, or we have to hold the drug or reduce the dose of the drug and we may compromise efficacy there.
So we're in a critical juncture. We desperately need medications that will reduce diarrhea in the growing number of patients that are getting agents that cause diarrhea.
Allison Ackerman Shrier
Good morning, everyone. My name is Dr. Allison Ackerman Shrier, Vice President of Medical Affairs and Clinical Research at Napo Pharmaceuticals. As a medical oncologist, I'm here to discuss the broadening scope of oral mucositis, a devastating and common side effect of not only head and neck cancer radiation but also traditional chemotherapy and emerging therapies.
Oral mucositis affects approximately 40% of patients undergoing traditional chemo, with the prevalence varying dependent on agent and dose. The incidents can soar as high as 80% in patients treated with methotrexate, fluorouracil and combinations of doxorubicin and taxanes in breast cancer. For patients undergoing bone marrow transplant, the prevalence is even higher. Nearly all patients undergoing chemotherapy with total body irradiation and over 85% with other types of intense conditioning regimens will develop mucositis. In this population, oral mucositis is associated not only with pain and swallowing difficulties but also increased mortality.
The growth of targeted therapies has introduced new challenges. Drugs like tyrosine kinase inhibitors and mTOR inhibitors affect normal cells as well as targeting cancer cells. Their oral mucositis prevalence varies, with up to 2/3 of patients having various experience in oral mucositis.
In the emerging space of antibody drug conjugates, antibodies deliver the chemo payload using targeted cancer antigens that are also present on normal tissues. For example, the investigational antibody drug conjugate, datopotamab deruxtecan, where the recent positive data in breast cancer at ASCO revealed a rate of oral mucositis of 90% in some populations in the TROPION-PanTumor01 study.
Overall, oral mucositis remains a common and debilitating side effect across various modalities. And despite its clinical consequences, patients have limited options for management. Patients need better management strategies to mitigate its impact on their quality of life and treatment outcomes. We want to improve the lives of those affected by this challenging condition. Thank you.
Unidentified Company Representative
My name is Maged [ph]. I'm a radiation oncologist specialized in head and neck cancer. My practice at Northwell Health in New York City. And I've been practicing in my field for the last 20 years. Head and neck cancer are often a curable disease. However, oral mucositis, it's one of the common debilitating adverse side effect happen to the patient during the treatment with chemotherapy-radiation medicine. Up to 60% of the patients will experience some oral discomfort and mucositis throughout their treatment with radiation oncology.
Oral mucositis, it's inflammation and ulceration of the mucosal lining or oral cavity on your throat. It will cause pain. And as it progress, it affect your ability to talk, to speak and to eat and in progressive cases, you will have to increase the opioid dependency, maybe end up with hospital admission and a feeding tube. But the most important concern from the oncology, it will interrupt the treatment paradigm which might affect the result -- the clinical results and outcome of the disease.
Oral mucositis can be managed by different modalities, including good oral hygiene which will help to decrease the risk severity of the mucositis. Also dental intervention before the treatment starts, including removing the compromised tooth or filling the cavities, will decrease the severity of the mucositis up to 25% of the patient.
One of the most new technology is the invention of the gel -- topical gels such as Gelclair which we'll provide it in a viscous mouthwash. Patient will use it before they start radiation therapy. And how the Gelclair works, so you have this thin film which lining the mucosa of your oral cavity on your throat. It will protect it from the threat of radiation, where the new data shows that it decrease the severity of the reaction as well as it delay the onset of toxicity of such a patient. Well, my experience using the topical gels, it will help to delay the onset of and the severity of the treatment and allow the patient to proceed with the treatment and complete radiation with an excellent curable results. Thank you.
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Question-and-Answer Session