Q1 2023 Jaguar Health Inc Earnings Call

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Greetings and welcome to Jaguar Health Investor Webcast.

At this time, all participants are in listen only mode.

The brief question and answer session will follow the formal presentation.

If anyone should require operator assistance during the conference, please press star zero from your telephone keypad.

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 the future of the company.

products in the development stage which may not achieve scientific objectives or meet stringent regulatory requirements.

Forward-looking statements are subject to risk and uncertainties that could cause actual results to differ materially from those...

are subject to risk 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 view of the 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 this 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 2022, which was filed March 24th, 2023, and its other filings with the SEC, which are available on the Investor Relations section of JAG WARS 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.

Additionally, please note that the company supplements its condensed consolidated financial statements presented on a GAAP basis by providing non-GAAP EBITDA and non-GAAP recurring EBITDA.

Jaguar believes that the disclosure items of these non-GAAP measures provide investors with additional information that reflects the basis upon which company management assesses and operates the business.

These non-GAAP financial measures should not be viewed in isolation or as substitutes for GAAP net sales and GAAP net loss and are not substitutes for or superior to measures of financial performance in conformity with GAAP.

Today's conference is being recorded. At this time, it's my pleasure to turn the call over to Lisa Conti, Jaguar Health's founder, president, and chief executive officer. Lisa, the floor is yours.

Thank you. Thank you for that very comprehensive, forward-looking statement as well. Thank you all for joining our first quarter 2023 earnings webcast, and welcome to you all. And as you just heard, my name is Lisa Conte, and I am the founder, president, and CEO of Jaguar Health. Well, this is an earnings webcast.

Our overreaching theme for this morning's discussion is patient voice.

and its importance in every aspect of drug development, including labeling and regulatory approval, raising awareness of noninfectious diarrhea, preparation for promotion related to the potential introduction of prophyllumur for prophylaxis and mitigation of cancer therapy-related diarrhea, and commercialization to provide comfort, and in depth information on the Aurelian Gap Initiative.

and treatments to a meaningful share of the affected population.

We are prioritizing learning from and listening to patient voice to bridge from the HIV community to the cancer community.

from Jeffrey Moore, if anybody's familiar with that book.

We can do better by co-creating awareness with the patient community through education around clofelamer's potential entry to the cancer market to provide a better solution to the comfort, the dignity, the health, the safety, the well-being of the patient.

and treatment outcomes to cancer patients with chronic diabetes. We believe this will allow us to best serve these important neglected comorbidities. The potential patient reach is much larger for the cancer community than the HIV community, both in terms of the number of patients affected by non-infectious diabetes,

and of emerging relevance with the paradigm shifting cancer care to long-term, targeted treatments.

on this important issue which we will play for you in a moment and I think you will enjoy and find really important.

issue which we will play for you in a moment and I think you will enjoy and find really important. First however,

I want to address our sales performance for the first quarter of 2023. We have to own this and learn from it. After five consecutive quarters of prescription product sales growth, we have now seen in Q1 a decrease in prescription product sales compared to the prior quarter and compared to the first quarter of 2022.

Let me say it again, this is a learning moment for the organization and likely a wake-up call that we have perhaps lost sight of the depth, reach, and importance of patient voice to facilitate expansion of the care clofelamide can provide into the HIV community, the current approved indication. Thank you.

Over the past 18 months or so, as we shifted to a specialty pharmacy distribution model and incorporated other aspects of a patient access program, we facilitated the difficult process of gaining prior authorization for patient reimbursement and we improved gross waterline payment grants to help connect revenues.

significantly by decreasing distribution costs and improving our payer mix.

A trend we have seen over the last two years is a decrease in net sales in the first quarter of the year over the prior quarter due mainly to commercial and Medicare plan deductibles resetting, which results in a much higher out-of-pocket cost to patients during this time period, the first quarter. The Inflation Reductions Act has specific Medicare provisions that start to take effect in 2024 that will reduce prescription abandonment in the first quarter of the year due to significantly lowered out-of-pocket expenses for patients.

We believe the provisions in this legislation should benefit the Mitessi brand and the Q4 to Q1 dip when implemented. We also believe that higher co-pays in Q1 account for about half of the decrease in net sales in the first quarter of this year over the Q4 2022.

To help address the additional shortfall, we at Jaguar are taking diagnostic steps to understand how the voice of the people in the HIV community needs to be incorporated further into our patient access activities.

It appears we've lost our reach to some of the patients.

The continued learning of how to effectively navigate the HIV market is foundational to our preparations for the potential introduction of prophyllum to the much larger U.S. oncology market.

for our target indication of prophylaxis of cancer therapy related diarrhea.

Much larger here, when I say much larger, oncology market is referring to the estimated 1.8 million patients newly diagnosed with cancer each year in the United States.

Additionally, annually in the United States there are an estimated 1 million cancer patients on targeted therapies chronically.

with an average rate of non-infectious diarrhea of 80%, the most common side effect.

estimated 40% of patients have their therapeutic dose, their cancer therapeutic dose reduced or go off

because of the side effect of diarrhea. With the now fully enrolled phase three on target trial, we are addressing this paradigm shift of prophylactic treatment of cancer therapy related diarrhea with clofelamide. And I do wanna say that again, fully enrolled on target trial, which we're very excited about.

This is analogous to what already occurs in the supportive care cancer world with chemotherapy-induced nausea and vomiting. It's referred to as CINV. Guidelines and protocols that incorporate prophylaxis for CINV typically the first three days of cytotoxic chemotherapy.

That global market is projected to reach $3.9 billion by 2029 according to a report from iHealthcare Analyst, Inc. And there's a good portion of that market that is addressed with generic products.

With targeted cancer therapy, we're talking about chronic diarrhea for several months to several years in both the metastatic and curative scenarios, and nothing tested or approved specifically for cancer therapy-related diarrhea. Diarrhea would be the first entry.

to this market.

We're going to play two short recent videos for you consisting of segments from interviews regarding the neglected comorbidity of cancer treatment related diarrhea with two amazing women, both of whom are members of Jaguar's Scientific Advisory Board.

Dr. Sandy Swain is a professor of medicine at Georgetown University and former president of ASCO, the American Society of Clinical Oncology. She served as the senior investigator of the Investigator Initiated Whole D trial, phase 2 trial, evaluating prothelamine for preventing...

chemotherapy-induced diarrhea in her two positive breast cancer patients, which was published last October in the peer-reviewed journal Breast Cancer Research and Treatment. The other video features Dr. Kelly Shanahan.

a metastatic breast cancer patient who is now a full-time independent patient advocate.

who made a shared decision with her oncologist regarding chronic targeted therapy, specifically to avoid the side effect of chronic diarrhea. And she so eloquently says that she could live, not just exist.

Following the videos, Carol Liza, Jaguar's Chief Financial Officer, who's having a little trouble connecting, so hopefully Carol Liza, Jaguar's Chief Financial Officer, will provide a more detailed recap of key financial results for the first quarter of 2023, and we will review the clinical milestones.

we have coming up in 2023 this year that we feel will be transformative in terms of value and selection for the company.

We'll now move forward with the two videos, and I'll turn it over to Lisa. I'm Lisa Conti. I'm the founder, president, and CEO of Jaguar Health. Hi, I'm Dr. Sandy Swain. I am a breast cancer medical oncologist and professor of medicine at Georgetown.

which is what ASCO is. It's an international organization and really the biggest in the world for oncology. We have now 45,000 members. So what I did in 2013, I started Women Who Conquer Cancer as part of the Conquer Cancer Foundation to raise money for young women investigators. That is quite incredible. Congratulations.

and have a lot of chemotherapy drugs that were that effective. Early on in my career, I just...

of chemotherapy drugs that were that effective. And so early on in my career, I just saw that.

Some of our treatments weren't that effective, especially in patients with metastatic disease, but the toxicities were pretty significant. And so what is that interaction like with a patient? Well I think that, you know, every patient or person coming with the cancer diagnosis is a scare to death. I think it's...

you know, gotten harder for women in many ways. I just see women for the most part because there's so many choices. I think that makes it harder because you want to make the right choice but as a person who's never dealt with cancer before you have no idea what the right choice is so you have to trust that.

person that you're talking to the physician. So I really tried to build up the trust with them so they can feel comfortable and that we are together making the right decision or their treatment.

Fortunately, in breast cancer we've had extraordinary advances for HER2 specifically is something that I work on and patients are surviving. With that being said, it's really important to pick the best treatments for the quality of life. So I've been always interested in that.

interested in the cardiac toxicity. The other big toxicity because I work on HER2 targeted therapy is diarrhea which is a significant problem for many patients on the the standard treatment regimen. So we did a study called HALT-D and we used a drug called Crophelimer to try to decrease.

diarrhea in these patients and we did show that the episodes of diarrhea were decreased. So tell me about chemotherapy-induced nausea and vomiting.

Well, with nausea and vomiting, there are several classes of drugs that have gotten approved over probably the last 20 or 30 years. So we're very aggressive about prophylactically treating for nausea and vomiting. Very, very aggressive. As I mentioned before, the diarrhea is one of the things I've been very interested in because of the research. I've been very interested in the diarrhea.

and they all have different toxicities. The abamacyclib causes diarrhea and that's significant for patients. You can reduce the dose.

But, you know, there's not a whole lot else you can do because the opioids don't, you know, they don't really treat the cause. They're just causing you to have constipation, essentially. So you are remarkable in the approach that you have to hearing the patient's voice in your individual meetings with them and your patient treatment and the research.

Do you find that there's a cultural difference, perhaps Asia, Europe , the US, in the role of, we're going to use the word for now, supportive care, the role of supportive care in oncology care? I think in Japan, for example, they don't like any kind of toxicity. In Europe , my experience, you know, it's not homogeneous.

ever say and I try to strike them out of any paper that I ever write because you know manageable for whom. I think the interaction with the nurses is very helpful because they will tell more to the nurses and the nurses are very nurturing and really do help with some of these side effects.

always being there asking them questions and making sure we were doing the right thing for that patient.

I'm Lisa Conti, I'm the founder, president and CEO of Jaguar Health and I'm sitting here with an amazing patient advocate, Dr. Kelly Shanahan. Hi, I'm Kelly Shanahan, former OBGYN, now not dead yet with metastatic breast cancer since 2013.

I am here with Dr. Kelly Shanahan, amazing woman, mom, wife, leader, physician, who charted just an amazing life for herself. Isn't that good?

Throwing a little got a little wrench into the next year. Thank you Lisa for inviting me here. I Was living my life going about my business in 2008. I had a nine-year-old daughter I was a dinosaur at that time solo practice ob-gyn up in Lake Tahoe

When my office manager scheduled me for a slightly overdue mammogram and much to my surprise Obvious cancer being the primary breadwinner Taking care of my very active very involved daughter. I chose to come down to San Francisco and have a bilateral mastectomy That's gonna be GYN. I was a surgeon. I like surgery and I went about my life

driving my daughter to rehearsals, she was a theater kid, going wine tasting with my husband and traveling as much as we could. When five years later I developed sudden back pain. And I thought, okay Kelly, you're in your 50s now you probably herniated a bit. I'll go have an MRI.

Prove that I have a herniated disc.

I'll have a pet scan while I'm at it because I did have cancer and there was a voicemail on my phone Kelly call me and I went back and I looked at the images with the radiologist and I had metastasis in Every bone in my body and the reason I had back pain. I'd actually broken her brain and this oncologist said to me the national Coalition of cancer networks the MCC and

I was like, let's just keep doing it. Tell us about your life during that time. Are you working? So I went back to work, but I did develop permanent neuropathy, numbness in my hands and in my feet. And I realized that I would never, ever, ever be able to do surgery again.

You don't want somebody, you know, wielding a scalpel if they can't feel their fingers. And that was a huge blow. So I started becoming involved with various advocacy organizations, primarily Medivivor. What are your goals in being a patient advocate? I mean there are selfish goals, and that is the feeling of self-worth. And then as I got involved in the advocacy community.

When you have a disease that will kill you prematurely, there is no time for all the usual things that happen when you develop a friendship. It's like we are, it's instant bonding. In the metastatic community, friendships are like love at first sight. Alright, so tell me about, you educated me on terminology that we should use.

that you are living, not just existing. What does that mean? So with cancer of any type, and often with the treatments for cancer.

The treatments are sometimes I think worse than the disease itself and it's just a matter of just existing, just making it to the next day. But I do get to choose every day how I deal with it. I can wake up with the attitude that not dead yet and do as much as possible. Keep on living.

So a lot of people say they call themselves survivors, they call themselves thrivers. I like to say it like it is, I am living with metastatic breast cancer. Okay, so you wake up every day, you make choices, you've made choices also about your treatment. At that point, the only thing that mattered to me was living long enough, even existing long enough.

to get my daughter through high school. But my goals have changed now. And so now I am all about quality of life. Most people might get 18 months to 24 months, but I got six years. It did not fail you for a long time. Right. Surprisingly long time. I was on it for six years. And I had my very first progression of my cancer in 2021. And I see a incredibly brilliant, results

world-renowned metastatic breast cancer expert here in San Francisco that you may know as well. I think everybody knows her. Yes. I'm Dr. Hope Rugo. I went to see her and she said I want to put you on a CDK-46 inhibitor.

We want to change that aromatase inhibitor. You've developed a mutation that makes aromatase inhibitors not effective anymore. And we're going to put you on this injection called Fulvestrin. What kind of side effects are you having? How are you feeling? So on just my aromatase inhibitor, I had arthritis type symptoms, stiffness in my joints. I walked like a hundred year old person when I got up. But if I kept active, if I kept moving...

that side effect. I'm like, oh, but that causes constipation.

And I don't want to take a medication to deal with a side effect and then sometimes another medication to deal with the side effect of the side effect medication. I could be put on a drug that would make me bald. I don't care. I could be on a drug that makes my skin turn purple. And I say I wouldn't care, although if I was purple maybe I really would. That doesn't bother me.

I cannot stand vomiting and I really cannot stand diarrhea. But let's talk about what, let's talk about diarrhea. The anti-mutility drugs. The holy grail for patients is a highly effective treatment that does not have...

unwanted side effects. If there's a medication to mitigate a side effect that itself does not have side effects, that need additional mitigation, then yeah, that would be acceptable to me. Quality of life is so much more important to me as I've gotten my daughter into young adulthood. What do you want to achieve as a patient advocate at this time?

I want to make the path easier for the people who follow me. I attend scientific conferences and I tweet, usually, about the findings so that other people can understand it. And I can spread that information to people who...

don't have the ability to go to these big cancer conferences and sit in a room with thousands of oncologists and researchers. Either because they can't financially, or they can't because they're too ill to travel, or it's just not their thing. I also am on the board of directors of MetaViber, which raises funds for metastatic breast cancer research.

And what advice would you have for other patients? You have to find the right care team. You know, here's what my goals are. You're advocating for yourself. If you're that, you know, PTA parent who always was raising money for your kids' school, you'd be great at fundraising for various organizations.

Okay, so tell me about the growing metastatic voice. Yeah. Are you unique? Is this a growing population? What's important to this voice? So I think my friend Elaine Shatner has recently written a book called From Whispers to Shouts about cancer advocacy. People never talked about cancer.

And I think that's really important. Breast cancer doesn't just affect women. Men get breast cancer. Men die at a higher rate. Blacks die at a higher rate than whites. And I think we all have to use our voices and I think we are doing that. Do you find a difference when you're at meetings in Europe , meetings in Asia? I think there is a difference. I haven't been to any meetings in Asia.

and that is, in the US at least, that is absolutely changing. That's it, I'm going to ask you a true or false question. Supportive care is cancer care. Absolutely. ASCO has a position paper out a guideline that every patient with advanced and metastatic cancer should be offered supportive care.

a.k.a. palliative care, although I like the term supportive care better. How prevalent is that in the treatment community? It's not offered.

anywhere close to what it should be, partly because of a lack of enough providers of supportive care services. And in some institutions, they reserve referring patients to palliative care because their resources are limited. Now, I would really like to say thank you for the opportunity to spread some of that information.

knowledge and awareness about metastatic breast cancer that yes it is a life shortening disease but it is not an immediate death sentence. What percentage of dollars go to metastatic research versus preventative and early treatment? Not nearly enough. Supportive care, quality of life, softer issues and research into metastatic breast cancer.

only comprises about 10% of research dollars. And that's up from 3 to 5% about 3 to 5 years ago. All right, thank you so much. Thank you, Lisa.

Thank you, Peter, for showing those videos. I hope everybody had an opportunity to see those. It's impossible to overstate how inspirational and powerful these women are and all the advocates in the healthcare profession as well as patient advocacy.

in the cancer community.

in part learn some patient advocacy in the HIV community and now back full circle from the cancer community back to the HIV community. So we're so honored to have them on our Scientific Advising Board.

patient advocacy in the HIV community and now back full circle from the cancer community back to the HIV community. So we're so honored to have them on our Scientific Advisory Board. As a company HIV, as a company HIV. They're Cro TEST.

We went to great lengths to incorporate this patient voice and to design a first-of-its-kind patient-centric clinical trial for the investigation of the prophylactic use of crofelomer in cancer therapy-related diarrhea. And this is the on-target trial, which has now completed enrollment. Thank you for your patience in centerlifting.

patient reported outcomes as the primary endpoint.

In support of our goal of obtaining FDA approval for a paradigm shifting first oral anti-diarrheal drug for the management of CTD, OnTarget is the first trial of its kind to include participation of adult cancer patients with a diversity of solid tumor types. It's also the first clinical trial to include multiple targeted therapies.

Our goal and the reality is the enrollment of a diverse population of cancer patients. The trial includes clinical trial sites not only in the United States, but also Georgia, the country, Serbia, Argentina, and Taiwan.

This phase 3 on-target trial is conducted with the same dose and formulation of Crophelimer as our MyTessie product.

Cofellimer has a GMP supply chain in place from the rainforest to our distribution network of specialty pharmacies across the United States.

As a reminder, safety and manufacturing are the two most common reasons that new drug applications fail. These activities are completed for a crofelomer from a regulatory perspective with the commercial approved product we already have on the market, which is being utilized in the Phase III clinical trial. A new near-term development goal

for the company, focuses on something called microvialist inclusion disease. I'll refer to it as MVID. This is an ultra rare pediatric congenital diarrheal disorder often referred to as CDD, congenital diarrheal disorder. MVID in short bowel syndrome is a rare disease

with intestinal failure are our two prioritized rare disease investigative indications for a novel formulation of clopidolumvirate.

MVID is a catastrophic medical situation for pediatric patients, and there are currently no approved drug treatments. We are planning to submit an investigational new drug application to the FDA for MVID in the second quarter of 2023.

literally right around the corner. We're in the second quarter of 2023. For the European market, MVID and other CDD patients could potentially participate in revenue generating early access programs.

targeted for 2024. In accordance with the guidelines of specific European Union countries, publications of data from proof-of-concept trials could support participation in early patient access programs for pro-felonur for these patients.

Participation in early access programs which do not exist in the United States provides an opportunity for reimbursement while impacting the morbidity and the high cost of care for these chronic unmet needs.

So to recap, in 2023, we expect to have top this year, we expect to have top line results from our phase 3 trial for prophylaxis of cancer therapy related diarrhea, our on-target trial.

and the initial proof of concept evidence for patients with either short bowel syndrome with intestinal failure and or for CDD, which may include MVID, in support of potential early access program participation.

in certain European countries with reimbursement. These programs are sufficiently resourced from Jaguar. We are prioritizing for 2023 these late stage clinical development programs and we are prioritizing the learning and listening to patient voice to bridge the chasm from the HIV community.

how we need to do better there and prepare to co-create the education around co-felomers potential entry to the cancer market to provide a better solution to the support that comforts the dignity and the treatment outcomes the cancer treatment outcomes of cancer patients with chronic diarrhea

Before I hand the discussion over to our CFO , Carol Lizak, who was able to connect, I'd like to tell all of you participating today to please stand for the recording. Thank you.

We're going to have a brief Q&A segment at the end of the webcast to address if there's any questions submitted in writing. Ian Wendt, Jaguars Chief Commercial Officer, is also on today's call as well as Dr. Pravin Ceraveli, Jaguars Chief Commercial Officer, is on today's call as Dr. Pravin Ceraveli,

chair of the scientific advisory board and chief scientific officer and they can respond to any submitted questions that may be relevant for their functions. Questions can be submitted via the webcast link for today's event that appears in the events and presentations page of the investor relations section of Jaguar website.

The URL for Jaguar's website is jaguar.health. We'll now move along to the key financial results for the first quarter of 2023. Carol, are you on? Yes, I am. Thank you, Lisa. And thank you all. Thank you. Thank you for joining us.

Yes, thank you all for joining our webcast today. I'll begin my review of our financials for the first quarter of 2023. Our current product net revenue was approximately $2 million in the first quarter of 2023.

representing a decrease of 40% compared to prescription product net revenue in the fourth quarter of 2022 which totaled approximately 3.3 million.

and a decrease of approximately 25% over prescription product net revenue in the first quarter of 2022.

decreased by $2 million from $11.8 million in the quarter ended March 31, 2022 to about $9.8 million during the same period in 2023. non-GAAP recurring EBITDA for the first quarter of 2023 and the first quarter of 2022 were a net loss of $9 million and $9.4 million respectively. Finally, net loss attributable to common shareholders decreased by approximately $6 million from $18 million in the quarter ended March 31, 2022

to 12 million in the same period in 2023. That concludes my recap of high-level financials for the first quarter of 2023. I will now hand the discussion back to Lisa Conte.

Thank you. Thanks, Carol. Okay, we at Jaguar, NAPO, NAPO Therapeutics, we're energized about all the important initiatives underway in 2023 and beyond. And as you can see from the numbers, working very efficiently with these.

very important, near-term, late-stage clinical activities.

The company's current cash position, the last reported cash at the end of the first quarter, is approximately $14.3 million. And the current cash position also includes gross proceeds from a pipe transaction concluded in the second quarter of approximately $1.86 million.

This financing involved a small group of dedicated long-term Jaguar investors.

Pursuant to the terms of the PIPE purchase agreement, each participating investor agreed not to sell or transfer any JAVAUR equity securities for a period commencing on the signing of the agreement, which was very recent last week, and ending six months after the PIPE closing. For more information on the informs, see flow FL Chancellor MeHAHA programming Glock Cancer Institute

There is no anti-dilution, no resets, no variable pricing rights, nothing toxic associated with the securities issued in this pipe. We believe this financing illustrates the confidence that the participating and well-educated investors have in the company and the expectation that both the on-target trial

and our focus on development of proof of concept data.

for cofelomer for the rare disease indications previously discussed will prove transformational in 2023 for Jaguar value inflection and recognition. So we'll now open the floor for written questions that have come in. I'll repeat the questions.

porcofelomer for the rare disease indications previously discussed will prove transformational in 2023 for Jaguar value inflection and recognition. So we'll now open the floor for written questions that have come in. I'll repeat the questions. Ok

Well, here's a very detailed question. How many shares are currently outstanding? How much cash is on the balance sheet? What is the monthly net burn? So just to recap some of the numbers that we just went through, the last reported cash at the end of the first quarter is approximately 14.3 million. Oh, and the last part of this question, I'm sorry.

What is the expected date of readout from the on-target trial? Okay, last reported cash, $14.3 million. The PIPE, which closed in the second quarter, approximately $1.9 million. If you look at the first quarter average monthly burn, don't we meet the whoever- stereotypesAn fifteen-minute minute in-depth look Make a list- That's a whole lot to see

is about three million per month, and that's pretty heavily into phase three clinical trial operations. The expected reported date for top line results from the on-target trial is in October of this year. So we're talking,

probably a little less than six months away. So we're confident, as I said, about our resource stability to get there. And we have about 19 million shares outstanding right now. I have another question about

the Chewy deal that we just announced and this is for, we did not talk, I didn't talk in my comments about it just to be efficient, we have a small business, a very important business in animal health, we have a conditionally approved product for chemotherapy induced diarrhea in dogs.

called cannellivia conditional approval is how you work with the center of veterinary medicine of the FDA to get a product out there for important and that medical need and Ian if you are on the line, would you mind speaking a little bit about how chewy can expand the opportunity for

parents to be able to get access to canalidia?

Yes, you're happy too. Thank you, Lisa. Yeah, Chewy, you know, is a major retailer including, you know, a lot of different pet related products, but including prescription products and supplements. And this just gives another very convenient option for oncologists or any vets who prescribe cannulivia CA1.

to be able to utilize their services. And it makes it more convenient for the vet, but also more convenient for the pet owner. And so if the vet doesn't have stock in on hand of cantilever, they can e-prescribe to Chewy very easily.

or even the pet owner can initiate the prescription and Chewie will reach out to their vets to fulfill the prescription. So it just gives additional options, additional channels of distribution just to make the lives more convenient as I said of the pet owners and the vet.

We're really happy with this relationship that we have with CHUI. We're already getting good feedback from both pet owners and vets about this. At the end of the day, it makes the product more broadly available and more easily available for all the stakeholders that we believe are so important. Thank you, Ian. You know what? While you're talking, there's a question here.

and government paid programs and how that is likely to change in 2024.

Yeah, yeah, happy to. So yeah, every Q1 for my testy, and this is common among most prescription brands, there are some challenges that are seasonal and a little bit unique to Q1 each year. And the main reason that occurs, it really impacts mostly.

and can cause a little bit of disruption. So for those individuals that are on a chronic medication and through the end of Q4, so the proceeding quarter, they may have met their deductibles and what the result there is often that their co-pays are very low or maybe zero for their medications at that time, there's very few cost barriers to fulfilling and getting your medication.

And then in Q1, all of that resets, and we all have to meet our deductibles again, which can present challenges for patients. Now on the commercially insured side, we have a great copay program in place to really assist those patients. It's a very generous program, and very few patients have significant out-of-pocket if they take advantage of that program. So we really work hard to make sure that...

All those commercially insured patients know the program exists so they can take advantage of it and most commercially insured patients are going to pay zero dollars in out-of-pocket, even in Q1, although there are some exceptions with some patients that have catastrophic insurance plans and things like that.

The bigger challenge is with the Medicare Part D patients. So federal law prohibits us from offsetting the out-of-pocket costs for those patients. This is true for every branded product. Manufacturers would love to help those patients, but we're just not allowed to do that. And for those patients, this is a pretty big impact. And this is something that occurs every year.

prescriptions pick back up again because their deductibles are now lower or more manageable. The other positive news here though is the Inflation Reduction Act has some provisions in it specific to Medicare Part D and there's a lot of complexity in there but the main thing that we focus on and that we're excited about...

cap out at $2,000. So this is good news for all of our Mytesi patients, current and future Mytesi patients, because if you think about CTD and our potential future indication there, about 65% of those patients are Medicare Part D. So the timing couldn't be better from our perspective in having this legislation take effect right around the time we'll be launching into that therapeutic area.

Thank you, Ian. We all learned something about Medicare today. Previn, are you on the line?

Yes, I am. Okay. There is a question about, we had mentioned at some point in the past, about COVID-related diarrhea, long-hauler diarrhea, and that is a program that we are not going forward with. It's still not defined well enough for us to...

be sure we have a mechanistic match. Also, as I mentioned, we are focused very much with this year

financial environment in general and specifically about small cap, medium cap biotech companies on those events that we feel can be transformed this year late-stage clinical events that lead to near-term revenue generation. Perhaps you could talk a bit about the

in efficiently the mechanistic rationale for Crocell and MIRV for cancer therapy related diarrhea and how that links to mechanistic rationale that for the current approved indication of HIV related diarrhea.

Oh, absolutely. Happy to. Thanks Lisa. So the thing that CRIFELMA does mechanistically is it regulates the secretory function of ion channels. So if you just want to know what we're talking about right now, the thing that CRIFELMA

And ion channels in general are responsible for brain activity, heart activity, gut activity. And so those of us who experience epilepsy or have family members or friends who have that, they have to have exact balance of ion channel regulation because it's a constitutive function.

in the body that's necessary for normal homeostasis and function of the body. So just like the heart or the brain, you don't wanna have a full stoppage of either of those organs because that would be very detrimental.

So, Crofilma does the same thing for the CFTR chloride channels, which exist in the gut, and it regulates it and slows it down to the appropriate level so that we have forms tools. Diarrhea is like a manifestation, like epilepsy is, of ion channel 5.

levels that lead to dysregulation of the chloride ion channel. And the second factor is the type of antiretroviral therapy that they get. The approved package inserts for all the drugs now a days only list grade 3 and grade 4 diarrhea.

and other AEs at those events. And so we, when we think about what is grade one is going to be great too, just like you heard

Grade 1 diarrhea is three watery stools every day. Imagine having that every day for the rest of your life. While it's not considered bad, it is absolutely impactful on the activities of daily living. And that's because of the inflammation that's caused by HIV as well as a combination of the drugs. In cancer therapy related diarrhea, you get the same inflammation in the gut.

because cancer is a reflection of inflammation. It's a disease of inflammation and aging.

you have dysregulation of your cytokines, and therefore you also have from cancer you have diarrhea. And then if you get targeted therapies, some of them actually are more impactful in the EGFR, Epidermal Growth Factor Regulation, which has a direct effect on another channel that paid down these

and same way it dysregulates, it causes secretory diarrhea. So exactly analogous to the HIV indication is the cancer therapy related indication. And Crofelmer has been around for centuries. The shamans were using it in a different form. And so we were able to draw the analogy and work with the FDA and our clinical advisors and

and impacts them. So we have a lot of interest in this trial as well. I'm very excited that we finished our enrollment and are moving towards the filing with the FDA later this year. Back to you, Lisa.

Thank you. Okay, and here's a related question I'm going to let you comment on from the medical perspective proven. How do you feel the approval when we finish the trial and if we're able to get pro-felomer or my testing introduced to the cancer therapy related diarrhea market, how would that impact the ability to utilize cancer?

the AE is particularly related to GI and lower bowel movement, which is diarrhea, and is by actually reducing the dose of the cancer therapies. So what they do is they either give a drug holiday, and we used to do that for HIV drugs as well back in the 90s and early 2000s and or

discontinue or switch their regimen. And since cancer is like running a marathon, you got to have the right shoes on and basically have enough runway to go through one regimen and then to another because you might be progression free or you may be in remission for a few years. And if you're lucky for several years, but then when the cancer comes back, you need to go to a new regimen.

And so in terms of using your regimens well and at the right dose, by not having so much diarrhea, as I said, even grade one is three watery stools every day, you are able to stay on your regimen and not have to suffer dose reductions and or dose discontinuations. We're gonna analyze that data as well in the ongoing phase three studies, so we will have more information on that.

Hope that answers the question. It does and I hope this answers the question that was posed here about and we're focused on the impact to the patient care all aspects of it including as you just heard from prevent the outcome on the Cancer outcome for these patients the question was about the revenue impact for these cancer therapeutic manufacturers and therefore the

data released from the OnTOGET trial expected in mid-October of this year, that would further those business conversations.

There is a question about the C-Agen Therapeutics Initiative program that we have that is a program, an early stage program within Jaguar that is focused on psychoactive and psychedelic plans for the treatment of, novel treatment of mental health disorders, mood disorders. Ok so let me know...

filicide and NDMA, LSD, a lot of these psychoactive and psychedelic products to look at new ways of treating and potentially curing mental health disorders. Most of the companies that are very well financed, a lot of resources are chasing after these seven.

same compounds and products and approaches. We're looking at the next generation. What can we do like we did with Profel? And we're finding new mechanisms of action, focusing on plant-based...

botanical products that have some more efficient opportunities to get into clinical trials quickly. And so the way that we're pursuing that is in a joint venture with a company called Filament Health and the joint venture which is funded with outside dollars is called Magdalena Biosciences named after the beautiful river flowing through the...

working with healers, working with shamans, bringing our expertise on botanical drug development, natural products, sustainable supply, novel mechanisms of action, everything that we did successfully with Crophelimer is what we're bringing to bear to Magdalena. Magdalena has a post money valuation from its venture funding.

of $5 million, we own approximately 40% of that joint venture. The goal here is to bring the first plant-based product, likely in ADHD, might be in depression or schizophrenia, bring it into clinical development, and then bring on a partner that is really focused with the resources and the expertise on the regulatory and the clinical development.

As I said, we're very well resourced to focus on our 2023 late stage clinical activities of bringing more value and more diversity into the company. And the last question that I'll conclude with, there was a question about ATM and the announcement that we made on ATM utilization. ATM is an at the market facility. I have one more question.

probably one of the most according to investment bankers these days the most efficient and and least costly way to raise money for the company. We have agreed with the investment that we just did the PICE investment that we just did not to utilize the ATM, not to put additional shares into the market.

without certain extraordinary circumstances. And as I said, if we look at our last cash position, the funds that we brought in from the PIPE, the historical burn rate, the target that we have, certainly for the on-target trial of top-line results in mid October .

We feel that we are resourced to get to that as well as likely the proof of concept data for MVID, the Rare Disease Initiative.

So with that I will conclude. Thank you very much for your participation. Thank you all from Jaguar who participated on this call. I will now starts.—

I do want to say that it was International Day of Plant Health as proclaimed by the Food and Agriculture Organization in the United Nations. It was last Friday.

So I do want to take this moment to express our deep dedication as a company to protecting and celebrating all of the world's plant life. Healthy plants constitute the foundation of all life on earth as well as core ecosystem functions, food security and nutrition. According to the U.S. Forest Service, a full 40 percent of all plants are

40% of the drugs behind the pharmacist counter in the Western world are derived from plants that people have used for centuries, including the top 20 best-selling prescription drugs in the United States today.

And we at JAGVAR understand that plants are precious and irreplaceable resource and that humanity's health is inextricably linked to their health.