Q2 2024 Jaguar Health Inc Earnings Call and Business Update

Transcription by CastingWords

Hello, I'm Lisa Conte, I'm Lisa Conte, I'm Lisa

Unknown Executive: Before I turn the call over to the management, I would 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 productive initiatives, including products in the development stage, which may not achieve scientific objectives or meet stringent regulatory requirements.

[inaudible]

Speaker Change: Before I turn the call over to the management, I would like to remind you that the management make forward-looking statements relating to such matters as continued growth prospects for the company.

Speaker Change: Uncertainties regarding market acceptance of products

Speaker Change: The impact of competitive products and pricing, industry trends, and productive initiatives including products in the development stage, which may not achieve scientific objectives or meet stringent regulatory requirements.

Unknown Executive: Forward-looking statements 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 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 Factors section of the company's Form 10-K for the year 2023, which was filed April 1, Accept them as required by the law.

Speaker Change: Forward-looking statements are subject to risk and uncertainties that could cause actual results to differ materially from those contemplated in such forward-looking statements.

Speaker Change: These statements are based on currently available information and management's current assumptions, expectations and projections about future events.

Speaker Change: While management believes its assumptions, expectations, and projections are reasonable in view of currently available information, you are cautioned not to place undue reliance on these forward-looking statements.

Speaker Change: The company's actual result may differ materially from those discussed during this webcast for a variety of reasons, including those described in the forward-looking statements and risk factors section of the company's Form 10-K for the year 2023, which was filed

Speaker Change: April 1, 2024, and its other filings with the SEC, which are available on the investor relation section of the Jaguars website.

Unknown Executive: 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 item of these non-GAAP measures provides investors with additional information that reflects the basis upon which companies' management assesses and operates the business. However, 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.

Speaker Change: Accept as required by the law.

Speaker Change: Jaguar undertakes no obligation to update or revise any forward-looking statements contained in this presentation to reflect new information, future events or otherwise.

Speaker Change: 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.

Speaker Change: Jaguar believes that the disclosure item of these non-GAAP measures provide investors with additional information that reflects the basis upon which companies' management assesses and operates the business.

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

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

Speaker Change: Today's conference is being recorded. At this time, it is now my pleasure to turn the call over to Lisa Conte, Jaguar Health Founder, President and Chief Executive Officer. Lisa, the floor is yours.

Lisa Conte: Thank you. Thank you.

Speaker Change: Thank you. Thank you. Hello and thank you all for joining our investor webcast today. My name as you heard is Lisa Conte.

Lisa Conte: Hello, and thank you all for joining our investor webcast today. My name, as you heard, is Lisa Conte, the founder, president, and CEO of Jaguar Health and our wholly owned subsidiary, NAPO Pharmaceuticals, and I'm also the chairman of our Italian subsidiary, NAPO Therapeutics. As usual, I'm going to use the words Jaguar and NAPO interchangeably when I'm referring to our company and our activities.

Speaker Change: The founder, president and CEO of Jaguar Health and our wholly owned subsidiary, NAPO Pharmaceuticals. And I'm also the chairman of our Italian subsidiary, NAPO Therapeutics. As usual, I may use the words Jaguar and NAPO interchangeably when I'm referring to our company and our activities.

Lisa Conte: As announced, this is an earnings webcast for the second quarter of 2024. I'm going to steal the thunder of our CFO, Carol Lizak, who will be speaking at the end of this webcast, as I am pleased to report our combined net second quarter 2024 revenue of approximately $2.72 million for prescription and non-prescription products increased approximately 16 percent versus next Q1 2024 revenue, which was $2,350,000,000, and it increased approximately 2% versus net Q2 2023 revenue of $2.67 million. We're very pleased with them.

Speaker Change: As announced, this is an earnings webcast for the second quarter of 2024. I'm going to steal the thunder of our CFO, Carol Lizak, who will be speaking at the end of this webcast.

Carol Lizak: As I am pleased to report, our combined net second quarter 2024 revenue of approximately $2.72 million for prescription and non-prescription products increased approximately 16%.

Carol Lizak: versus Nick Q1 2024 revenue, which was $2,350,000,000.

Carol Lizak: and it increased approximately 2% versus net Q2 2023 revenue of $2.67 million.

Lisa Conte: In addition, on this webcast, I will be joined by my colleagues, Dr. Pravin Chaturvedi, our Chief Scientific Officer, and Kathy Collis, our recently appointed Senior Vice President of Growth Strategy, to speak to the robustness of our clinical pipeline and commercial activities. Pravin will further review the data and regulatory strategy for the clinically meaningful results reported on July 23rd, 2024, clinically meaningful results identified in patients in the subgroups of breast and lung cancer.

Carol Lizak: We're very pleased with that.

Speaker Change: In addition, on this webcast, I will be joined by my colleagues, Dr. Pravin Chaturvedi, our Chief Scientific Officer, and Kathy Collis, our recently appointed Senior Vice President of Growth Strategy.

Speaker Change: To speak to the robustness of our clinical pipeline and commercial activities.

Speaker Change: Preven will further review the data and regulatory strategy for the clinically meaningful results reported on July 23rd 2024 clinically meaning results identified in patients in the subgroups of breast and lung cancer.

Lisa Conte: In the initial data from our recently completed Pivotal Phase III on-target trial of prophelomer for the prophylaxis of diarrhea in adult cancer patients with solid tumors, all solid tumors, receiving targeted therapy with or without standard chemotherapy. Again, the signal was seen in the two subgroups of breast and lung cancer. Today, Pravin will also discuss Jaguar's other clinical core focus areas for the development of clofelamur for two targeted rare and orphan disease indications. Microvirus Inclusion Disease, which we refer to as MVID, which is an ultra rare pediatric congenital diarrheal disorder, and also Short Bowel Syndrome with Intestinal Failure, which we'll refer to just as SBS.

Speaker Change: In the initial data from our recently completed Pivotal Phase III on-target trial of prophyllumur,

Speaker Change: for the prophylaxis of diarrhea in adult cancer patients with solid tumors, all solid tumors receiving targeted therapy with or without standard chemotherapy. Again, the signal was seen in the two subgroups of breast and lung cancer.

Speaker Change: Today Pravin will also discuss Jaguar's other clinical core focus areas for the development of clofelamur for two targeted rare and orphan disease indication.

Pravin: Microvirus Inclusion Disease, we refer to as MVID, which is an ultra-rare pediatric congenital diarrheal disorder.

Pravin: And also Short Bowel Syndrome with Intestinal Failure with the acronym SBS-IF or we'll refer to just as SBS.

Lisa Conte: As announced, with Jaguar leadership and participation from the Jaguar family company Napco Therapeutics based in Milan, Italy. We are also supporting independent, investigator-initiated, proof-of-concept studies of clofalamer for MVID and SBAs in the U.S. and the MENA regions, the Middle East and North Africa regions. With results, proof of concept results expected by the end of this year 2024 and throughout the beginning of 2025. Profilometer has already received orphan drug designation in both the United States and EU and for both MVID and SBS indications, which allows us to pursue that strategy and the rare disease business model for these indications. AH-CHOO!

Pravin: As announced, with Jaguar leadership and participation from the Jaguar family company, Napco Therapeutics, based in Milan, Italy.

Pravin: We are also supporting independent investigator-initiated proof-of-concept studies of crofilamer for MVID and SBAs in the U.S. and the MENA regions, Middle East, North Africa regions.

Pravin: With results, proof of concept results expected by the end of this year 2024 and throughout the beginning of 2025.

Pravin: Profilomir has already received orphan drug designation in both the United States and EU and for both MVID and SBS indications and allows us to pursue that strategy and rare disease business model for these indications.

Lisa Conte: We are very pleased to announce last week that the required import permit for profilomerase has been granted in Abu Dhabi in the UAE, United Arab Aramid, for the planned investigator-initiated proof of concept trial in pediatric patients for MVID and SVS, which is an important and critical regulatory event that we have worked on for some time and have known the principal investigator there for many years who is excited to treat patients. After Pravin speaks, Kathy will provide a brief overview of our plans for October 2024.

Speaker Change: Good to meet you!

Speaker Change: We're very pleased to announce last week that the required import permit for Crofilamir has been granted in Abu Dhabi in the UAE, United Arab Emirates, for the planned investigator-initiated proof-of-concept trial in pediatric patients for MVID and SVS.

Speaker Change: which is an important and critical regulatory event that we worked on for some time and have known the principal investigator there for many years, who's excited to treat patients after proven speaks.

Lisa Conte: This year, we launched the FDA-approved oral mucositis prescription product GelClear for the U.S. market. This is our third prescription product launch; oral mucositis, also called chemo mouth, has emerged as the most significant adverse event in ecology, according to the National Comprehensive Cancer Network Task Force. Kathy was instrumental in executing Jaguar's in-license agreement for Gelcler.

Speaker Change: Kathy will provide a brief overview of our plans October 2024. This year commercial launch of the FDA approved oral mucositis prescription product gelclair for the US market. This is our third prescription product launch.

Kathy: Oral mucositis, also called chemo mouth, has emerged as the most significant adverse event in ecology, according to the National Comprehensive Cancer Network Task Force.

Kathy: Kathy was instrumental in executing Jaguar's in-license agreement for Gelclair.

Lisa Conte: She is results-oriented. She's a commercial leader with more than 25 years of experience in the biopharmaceutical industry. We're thrilled she has joined Jaguar's team in this important role as head of growth strategy. And we're very excited about this important product launch with a side effect that is so devastating to cancer patients.

Speaker Change: She is results oriented.

Speaker Change: She's commercial leader with more than 25 years of experience in the bio-pharmaceutical industry, where's thrilled she has joined Jaguar's team in this important role as head of growth strategy.

Speaker Change: and we're very excited about this important product launch with a side effect that is so devastating to cancer patients.

Lisa Conte: Towards the end of the webcast, our CFO, Carol Lizak, will provide a recap of the financial highlights for the second quarter of 2024. So before I introduce Pravin, just a reminder that our ambitious Phase 3 on-target trial broadly and boldly studied the prophylaxis of diarrhea in adult cancer patients with 10 distinct types of solid tumors, receiving any of 24 different targeted therapy drugs, all of which have a reported rate of diarrhea of more than 50 percent, and with or without standard chemotherapy.

Carol Lizak: For the end of the webcast, our CFO finally, Carol Lizak will provide a recap of the financial highlights for the second quarter of 2024.

Speaker Change: So, before I introduce PREVIM, just a reminder that our ambitious Phase III on-target trial broadly and boldly studied the prophylaxis of diarrhea in adult cancer patients with ten distinct types of solid tumors.

Speaker Change: Receiving any of 24 different targeted therapy drugs, all of which have a reported rate of diarrhea of more than 50% and with or without standard chemotherapy.

Lisa Conte: So quite a heterogeneous population, quite important that we were looking to understand how we could mitigate diarrhea with the broadest potential label. We observed the meaningful clinical signals in breast and lung cancer patients, two of the most common cancer diagnoses. We are collaborating with our clinical and scientific advisors to elevate the significance of these clinical outcome signals in order to prepare for potential scientific publications, as well as submissions to support clinical and regulatory meetings as we seek to explore potential pathways of FDA approval to make profilomer which is our novel oral plant-based prescription medicine, which is already available for people living with HIV, AIDS, and diarrhea, available to patient populations of breast and or lung cancer patients for cancer therapy-related diarrhea, so looking for an opportunity to expand the label.

Speaker Change: So quite a heterogeneous population, quite important that we were looking to understand how we could mitigate diarrhea with the broadest potential label.

Speaker Change: We observed the meaningful clinical signals in breast and lung cancer patients, two of the most common cancer diagnoses.

Speaker Change: We are collaborating with our clinical and scientific advisers to elevate the significance of these clinical outcome signals in order to prepare for potential scientific publications.

Speaker Change: As well as submissions to support clinical and regulatory meetings as we seek to explore potential pathways of FDA approval to make profilomer

Speaker Change: which is our novel oral plant-based prescription medicine.

Speaker Change: which is already available for people living with HIV, AIDS, and diarrhea, available to patient populations of breast and or lung cancer patients for cancer therapy-related diarrhea. So looking for an opportunity to expand the label.

Lisa Conte: It is important to emphasize that the standard of care and treatment policy for cancer patients in the on target trial was patient-centric, including, though not limited to, the full journey of their treatment, rescue therapies, reductions, changes, or holidays to the cancer agents causing side effects, many side effects, including diarrhea, and other supportive care interventions which impact gut function at different times in different patient populations. Because of this, and given the rich and extensive database from OnTarget, there is a great deal of work still ahead to analyze data for numerous pre-specified and non-pre-specified subgroups from the trial.

Speaker Change: It is important to emphasize that standard of care and treatment policy for cancer patients in the on target trial was patient centric.

Speaker Change: including the not limited to the full journey of their treatment. Rescue therapies, reductions changes or holidays to the cancer agent's causing side effects, many side effects including diarrhea.

Speaker Change: and other supportive care interventions, which impact gut function at different times in different patient populations.

Speaker Change: Because of this, and given the rich and extensive database from OnTarget, there is a great deal of work still ahead to analyze data for numerous pre-specified and non-pre-specified subgroups from the trial.

Lisa Conte: Transcription by Transquinho beacon. Transcription by CastingWords, is necessary to address statistical rules for censoring data, for handling missing data points, addressing intercurrent events, and data imputations, among others. We are absolutely encouraged by the results we've seen thus far in what are relatively small sample sizes represented by the aforementioned subgroups, because they are subgroups of patients with breast and lung cancer, and we are energized with anticipation as the analyses continue to reveal important insights and signals to achieve our clinical and regulatory goals. So with that, good morning, Pravin.

Speaker Change: Complex programming is necessary to address statistical rules for censoring data, for handling missing data points, addressing intercurrent events and data imputations, among others.

Speaker Change: We are absolutely encouraged by the results, we've seen thus far in what are relatively small sample sizes represented by the aforementioned subgroup.

Speaker Change: because they are subgroups of patients with breast and lung cancer. And we are energized with anticipation as the analyses continue to reveal important insights and signals to achieve our clinical and regulatory goals.

Pravin Chaturvedi: Good morning, Lisa. Good morning, all. And thank you for joining today's Investor Web Crisis.

Prevent: So, with that, good morning, Prevent.

Prevent: Good morning Lisa, good morning all and thank you for joining today's Investor Webcast.

Lisa Conte: Okay, Pravin, it's been two weeks since we announced clinically meaningful signals in the subpopulations of breast and lung cancer patients in the ONTARGET trial. I know this has been a focus of yours for many years now, since then.

Lisa Conte: Okay, it's been two weeks since we announced the clinically meaningful signals in the subpopulations of breast and lung cancer patients in the OnTarget trial. I know this has been a focus of yours for many years now. Since that time,

Lisa Conte: We also, excuse me, we also announced significant positive results with clofelamer benefiting subgroups of diarrhea-predominant irritable bowel syndrome, and that's an acronym IBSD, irritable bowel syndrome patients with chronic refractory diarrhea. And by the way, each of those studies and results have been accepted for poster presentations at the American College of Gastroenterology Annual Scientific Meeting, ACG, which is also in Pravin will begin by explaining the relevance of those study results and analyses, which have come out since we released the preliminary results on OnTarget, so the relevance of those study results and analyses to the OnTarget results.

Lisa Conte: We also, excuse me, we also announced significant positive results.

Lisa Conte: with Crofelmer benefiting subgroups of diarrhea predominant irritable bowel syndrome and that's an acronym IBSD.

Lisa Conte: Irritable Bowel Syndrome patients with chronic refractory diarrhea and by the way each of those studies and results have been accepted for poster presentations at the American College of Gastroenterology annual scientific meeting ACG which is also in October of this year.

Previn: Previn will begin by explaining the relevance of those study results and analyses which have come out since we preliminary results and on target so the relevance of those study results and analyses to the on target results

Pravin Chaturvedi: Thank you, Lisa. I think I'll go into some specific details. As you stated last week, we were very excited about the fact that Grafoma continues to demonstrate clinical robustness in the Responder Analysis for Multiple Gastroenterology Conditions, including functional diarrhea and chronic idiopathic diarrhea in the subgroups of diarrhea-predominant irritable bowel syndrome patients. These analyses are done by what is called responder analysis, and that's the key word. Simply put, a responder analysis is a preponderance of weeks of improvement in loose water stool frequency and other bowel endpoints, depending on the indication, within a chronic, multi-month study. That's what these two recent diarrhea-predominant IPS studies showed.

Previn: Thank you, Lisa. I think I'll go into some specific details.

Speaker Change: As you stated last week, we were very excited about the fact that Profilma continues to demonstrate clinical robustness.

Speaker Change: in the Responder Analysis for Multiple Gastroenterology Conditions.

Speaker Change: including functional diarrhea and chronic idiopathic diarrhea in the subgroups of diarrhea predominant irritable bowel syndrome patients.

Speaker Change: These analyses are done by what is called responder analysis, and that's the key word. Simply put, a responder analysis is a preponderance of weeks of improvement.

Speaker Change: in Lose Watery Stool Frequency, Lose Watery Stool Consistency, and Other Bowel Endpoints, depending on the indication, within a chronic multi-month study.

Speaker Change: That's what these two recent diary predominant IPS studies showed.

Pravin Chaturvedi: Just to remind you, similarly, we analyzed a pivotal trial for the currently approved indication of Grofelma for HIV-related diarrhea, which was based on the proportion of patients with an acceptable number of loose watery stools per week for 50% of the time. Responder analysis is where we saw the initially clinically important signals in patients with breast and lung cancer.

Speaker Change: Just to remind, similarly we analyzed a pivotal trial for the currently approved indication of grafelma for HIV-related diarrhea, which was based on the proportion of patients with an acceptable number of loose, watery stools per week for 50% of the time.

Speaker Change: A responder analysis is where we saw the initially clinically important signals in patients with breast and lung cancer.

Pravin Chaturvedi: Although it is not a pre-specified primary endpoint in the on-target study, it's clinically important. Clinical importance is defined as a greater than 10 percentage point difference in the proportion of subjects with less than or equal to less than 7 watery stools per week compared to placebo. That was seen in the breast and lung cancer patients in months 2 and 3 of the 3-month treatment period of the on-target study. Clinical relevance for this analysis has been informed by a cancer patient survey that we conducted prior to the start of the on-target study that indicated that the patients wanted to get to less than or equal to two watery stools per day, i.e.

Speaker Change: And.

Speaker Change: Although it is not a pre-specified primary endpoint in the on-target study, it's clinically important. Clinical importance is defined as a greater than 10 percentage point difference.

Speaker Change: In the proportion of subjects with less than or equal to less than 7 watery stools per week compared to placebo, that was seen in the breast and lung cancer patients in months 2 and 3 of the 3-month treatment period of the on-target study.

Speaker Change: Clinical relevance for this analysis has been informed by a cancer patient survey that we conducted prior to the start of the on-target study that indicated.

Speaker Change: that the patients wanted to get to less than or equal to two watery stools per day, i.e. less than or equal to 14 watery stools per week, which would be clinically meaningful to the patients, which would reflect an improvement in their bowel control habits, presumably leading to more comfort and improved quality of life.

Pravin Chaturvedi: Less than or equal to 14 watery stools per week would be clinically meaningful to the patients and would reflect an improvement in their bowel control habits, presumably leading to more comfort and an improved quality of life.

Pravin Chaturvedi: And I'll provide some more technical details about the responder analysis in the on-target trial subgroups. Since these are exploratory analyses in subgroups of breast and lung cancer patients receiving targeted therapies, the sample size for each of these subgroups is smaller, as we had designed the trial to be all-inclusive for adult solid tumor patients that were eligible to receive diuregenic targeted therapies in at least 50% of the patients receiving those therapies. It was a multi-center, double-blind, placebo-controlled study that included U.S. and ex-U.S. sites, and it used patient-reported outcomes (PROs) as the primary determinant of their clinical responses.

Speaker Change: And I'll provide some more technical details about the responder analysis in the on-target trial subgroups. Since these are exploratory analyses in subgroups of breast and lung cancer patients receiving targeted therapies, the sample size for each of these subgroups is smaller.

Speaker Change: As we had designed the trial to be all-inclusive for adult solid tumor patients that were eligible to receive diuregenic targeted therapies in at least 50% of the patients receiving those therapies.

Speaker Change: And it was a multi-center, double-blind, placebo-controlled study that included U.S. and ex-U.S. sites, and it used patient-reported outcomes, PROs, as the primary determinant of their clinical responses.

Pravin Chaturvedi: When we combined all the breast and lung cancer patients receiving different targeted therapies that achieved the monthly responder status in months two and three, defined as those patients having less than or equal to seven watery stools per week at least 50% of the time, it showed that 79% of the patients in the Crofelma group had achieved the threshold compared to 68% of the placebo group patients. As a reminder for our audience, this was a prophylactic trial, which means the patients did not come in with diarrhea.

Speaker Change: When we combined all the breast and lung cancer patients receiving different targeted therapies that achieved the monthly responder status in months 2 and 3, defined as those patients having less than or equal to 7 watery stools per week at least 50% of the time.

Speaker Change: It showed that 79% of the patients in crofelma group

Speaker Change: had achieved a threshold compared to 68%.

Speaker Change: in the placebo group patients. As a reminder for our audience, it was a prophylactic trial, which means the patients not come in with diarrhea.

Pravin Chaturvedi: The one-sided t-value was 0.027, which is nearly statistically significant as the hurdle for on-target study design is less than 0.025, and the difference was clinically important. However, as the subgroup sample size gets smaller, the p-value is further impaired as the study was not powered to detect these signals at a statistically significant ratio.

Speaker Change: The one-sided p-value was 0.027.

Speaker Change: which is nearly statistically significant as the hurdle for on-target study design is less than 0.025.

Speaker Change: and the difference was clinically important. As the subgroup sample size gets smaller, the p-value is further impaired, as the study was not powered to detect these signals at a statistically significant ratio.

Pravin Chaturvedi: Unknown Speaker 1-1-1, We are also looking at odds or hazard ratios. For sake of clarity, an odds ratio analysis is similar to a hazard ratio assessment, which measures the frequency of an event in two groups over time, and a ratio being greater than one is deemed favorable for profile models, when we evaluated all the breast cancer patients receiving three different types of targeted therapies, the proportion of monthly responders for months two and three that achieved less than, 7 watery stools per week, at least 50% of the time, Karaselma group had 78% responders, compared to 68% in the placebo group, for Breast Cancer Patients Receiving Abema Ceclib.

Speaker Change: Value.

Speaker Change: We are also looking at odds or hazard ratios.

Speaker Change: For sake of clarity, an odds ratio analysis is similar to a hazard ratio assessment.

Speaker Change: which measures the frequency of an event in two groups over time.

Speaker Change: and a ratio being greater than one is deemed favorable for Crofalmer.

Speaker Change: When we evaluated all the breast cancer patients receiving three different types of targeted therapies, the proportion of monthly responders for months two and three that achieved less than

Speaker Change: 7 water stools per week, at least 50% of the time. Crofilma group had 78% responders, compared to 68% in the placebo group.

Pravin Chaturvedi: The monthly responder rate, for having less than 7 water use tools for months 2 and 3, was 69% for the Crofilma group versus 58% for the placebo group. And the odds ratio for this group, this subgroup, was 1.796 over the 3-month period. Continuing with breast cancer patients, those patients that received pertuzumab, that were monthly responders in months two and three, having at least less than seven water use tools per week for 50% of the time.

Speaker Change: For breast cancer patients receiving abimaciclib.

Speaker Change: The monthly responder rate was, for having less than 7 water stools for months 2 and 3, was 69% for the grafelma group versus 58% for the placebo group. And the odds ratio for this group, this subgroup, was 1.796 over the 3-month period.

Speaker Change: Continuing with breast cancer patients, those patients that received Protuzumab that were monthly responders in months two and three, having at least less than seven water use tools per week for 50% of the time. It was 87% of patients in the Crofilmer arm compared to 75% in the placebo arm.

Pravin Chaturvedi: It was 87% of patients in the Profilomer arm, compared to 75% in the placebo arm, and the odds ratio was 1.44. Similarly, lung cancer patients receiving kinase inhibitors, achieving a monthly responder status for months 2 and 3 with less than 7 watery stools per week, was 81% in the profelmar arm compared to 64% in the placebo group, had the sample sizes been larger. In these subgroups, the same differences that we observed would have reached statistical significance. These exploratory odds ratio analyses for each subgroup are also being evaluated using non-parametric rank sum tests due to the skewness of the data in both groups, but especially in the placebo group. To be more specific,

Speaker Change: and the odds ratio was 1.44.

Speaker Change: Similarly, lung cancer patients receiving kinase inhibitors, achieving a monthly responder status for months 2 and 3 with less than 7 watery stools per week, was 81% in the profilomar arm, compared to 64% in the placebo group.

Speaker Change: Had the sample sizes been larger, in these subgroups, the same differences that we observed would have reached statistical significance.

Speaker Change: These exploratory odds ratio analysis for each subgroup are also being evaluated using non-parametric rank sum tests due to the skewness of the data in both groups but especially in the placebo group. To be more specific.

Pravin Chaturvedi: The range of average number of weekly loose watery stools for the Crofilma group was 0 to 30, compared to 0 to 42 for the placebo group across all tumor types and targeted therapies in the on-target study. The wide variation in the average number of weekly loose-watery stools contributes to the skewness of the data. We are very encouraged by the signals we are seeing in these small subgroups.

Speaker Change: The range of average number of weekly loose watery stools for the Crofilma group was 0 to 30.

Speaker Change: compared N0 to 42 for the placebo group across all tumor types and targeted therapies in the on-target study.

Speaker Change: The wide variation in the average number of weekly loose water use tools contributes to the skewness of the data.

Speaker Change: We are very encouraged by the signals we are seeing in these small subgroups.

Pravin Chaturvedi: While different tumor types, different treatment regimens, and complex handling of data for various intercurrent events in each individual patient's journey have limited the subgroup patient sizes, we are grateful for the consistency of the signals and the benefit we are able to discern in breast and lung cancer patients. We have seen Crofoma benefit patients in multiple studies and in multiple patient populations. I will underline your comment, Lisa.

Speaker Change: While different tumor types, different treatment regimens, and complex handling of data for various intercurrent events in each individual patient's journey have limited the subgroup patient sizes, we are grateful for the consistency of the signals and the benefit we are able to discern in breast and lung cancer patients.

Speaker Change: We've seen proforma benefit patients in multiple studies and in multiple patient populations. I will underscore your comment, Lisa. We are energized and hopeful as we undertake more analyses and potentially further reveal important and potentially statistically significant results in these complex data sets.

Pravin Chaturvedi: We are energized and hopeful as we undertake more analyses and potentially further reveal important and potentially statistically significant results in these complex data sets. As an important example, we have not yet evaluated the responder analysis for patients who continued into the extension phase of the on-target study called Stage 2, which is, for the whole study. We know about two-thirds of the patients continued to receive the treatment for another three months, and we plan to analyze those as well. In addition, these clinically important signals are seen in breast and lung cancer patients receiving targeted therapies.

Speaker Change: As an important example, we have not yet evaluated the responder analysis for patients who continued into the extension phase of the on-target study called Stage 2.

Speaker Change: Which is, for the whole study, we know about two-thirds of the patients continued to receive the treatment for another three months, and we plan to analyze those as well.

Speaker Change: In addition to these clinically important signals in breast and lung cancer patients receiving targeted therapies, I'd like to add that CREFELMA continues to show improvement in various gastrointestinal indications due to its novel paradigm-shifting mechanism of action, physiologic mechanism of action.

Pravin Chaturvedi: I'd like to add that Crofilma continues to show improvement in various gastrointestinal indications due to its novel paradigm-shifting mechanism of action, the physiologic mechanism of action. We had previously conducted two diarrhea-predominant IBSD clinical trials, and profilema showed improvement in abdominal pain and discomfort and stool consistency in those studies. The change in stool consistency, together with improvement in abdominal pain and discomfort, are now regulatory and clinically specified primary endpoints for drugs being developed for diarrhea-predominant irritable bowel syndrome patients.

Speaker Change: We had previously conducted two diarrhea-predominant IBSD clinical trials, and Crofelma showed improvement in abdominal pain and discomfort and stool consistency in those studies.

Speaker Change: The Change in Stool Consistency, together with Improvement in Abdominal Pain and Discomfort.

Speaker Change: Are now regulatory and clinically specified primary endpoints for drugs being developed for diarrhea predominant irritable bowel syndrome patients

Pravin Chaturvedi: Two independent scientific and clinical thought leaders in gastroenterology at the Beth Israel Deaconess Hospital at Harvard Medical School and at the University of Texas in Houston studied Crofelmer in refractory diarrhea subgroups of diarrhea-predominant IBS patients with functional and chronic idiopathic diarrhea, respectively, and they submitted their abstracts that were accepted for poster presentations at the American College of Gastroenterology meeting later this year. Any questions now, Well,

Speaker Change: Two independent scientific and clinical thought leaders in gastroenterology at the Beth Israel Deaconess Hospital at Harvard Medical School.

Speaker Change: and at the University of Texas in Houston studied Crofelmer in refractory diarrhea subgroups of diarrhea predominant IBS patients with functional and chronic idiopathic diarrhea respectively.

Speaker Change: And they submitted their abstracts that were accepted for poster presentations at the American College of Gastroenterology meeting later this year.

Lisa Conte: Well, thank you for that detailed response, Pravin, and it's a snapshot of just how rich this database is and how complex this trial was, the on-target trial. But I know, Pravin, that you have personally designed many of the successful trials with clofelamer in different patient populations, so I definitely appreciate that detailed explanation. Pravin, I'd like you to please explain the plan with the responder analysis in the on-target trial and the plan specifically related to our goal of meeting with the FDA, which is the gating item, to get Crofelamer, Mitesi, to people living with cancer therapy-related diarrhea.

Lisa Conte: Any questions now, Lisa?

Lisa Conte: Well, thank you for that detailed response, and it's a snapshot of just how rich this database is and how complex this trial was, the on-target trial. But I know, Pravin, that you have...

Pravin: personally designed many of the successful trials with cofelamor in different patient populations so definitely appreciate that that detailed explanation.

Vin: For Vin, I'd like you to please now explain the plan with the responder analysis in the on-target trial.

Vin: And the plan specifically related to our goal of meeting with the FDA, which is the gating item to get profile America, my testy to people living with cancer therapy related diarrhea.

Pravin Chaturvedi: The plan is to continue with the responder analysis and show the robustness of our findings, particularly in the subgroups of breast and lung cancer patients in the on-target trial. We will discuss the findings of our exploratory analysis with our clinical and regulatory key opinion leaders and evaluate other gastrointestinal endpoints from a very rich and extensive patient-reported outcomes database, which will better inform us about the preponderance of evidence for the clinical meaningfulness of what we are saying with Krafalny.

Vin: Thanks, Lisa.

Speaker Change: That's a good question. The plan is to continue with the responder analysis and show the robustness of our findings, particularly in the subgroups of breast and lung cancer patients in the on-target trial.

Speaker Change: We will discuss the findings of our exploratory analysis with our clinical and regulatory key opinion leaders.

Speaker Change: and evaluate other gastrointestinal endpoints from a very rich and extensive patient-reported outcomes database.

Speaker Change: which will better inform us about the preponderance of evidence for the clinical meaningfulness of what we are seeing.

Pravin Chaturvedi: Since OnTarget is a pivotal Phase III trial, we will prepare a briefing document for the FDA after our meetings with our internal KOLs on the obligatory pre-specified statistical analysis. We will also prepare a report on the additional exploratory responder analysis and provide the FDA with the findings and the results of our findings in these subgroups of breast and lung cancer. By providing more information on the incidence, severity, and duration of diarrhea from the on-target trial, which we'll particularly see in the placebo group, we will also have a more informed discussion with the FDA about patient impact and the appropriate clinical endpoints and analyses to be able to provide them with an assessment of the benefit-risk ratio of Grafalmar.

Speaker Change: Withufelmar.

Speaker Change: Since OnTarget is a Pivotal Phase 3 trial, we will prepare a briefing document for the FDA after our meetings with our internal KOLs on the obligatory pre-specified statistical analyses.

Speaker Change: We will also prepare a report on the additional exploratory responder analysis and provide the FDA the findings, the results of our findings in these subgroups of breast and lung cancer.

Speaker Change: By providing more information on the incidence, severity, and duration of diarrhea from the on-target trial, which we'll particularly see in the placebo group, we will also have more informed discussion with the FDA about patient impact.

Speaker Change: and the appropriate clinical endpoints and analyses to be able to provide them with an assessment of the benefit-risk ratio of Cro-Palmer.

Pravin Chaturvedi: Since Grofelma delayed release tablets are already approved by the FDA under the brand name Mitessi for HIV-related diarrhea, and the drug acts locally in the gut without any food or drug interactions, and we have seen no profiler related serious adverse events in the 10 plus years of commercialization history. The assessment of benefit-risk ratio adds to the totality of evidence to support Crofelma's value for the cancer therapy-related diarrhea (CTD) indication, in at least the subgroups of breast and lung cancer patients.

Speaker Change: Since Crofelmo delayed-release tablets are already approved by the FDA under the brand name Mitesi for HIV-related diarrhea.

Speaker Change: and the drug acts locally in the gut without any food or drug interactions and we have seen no Grofelmer related serious adverse events in the 10 plus year of commercialization history.

Speaker Change: The assessment of benefit-risk ratio adds to the totality of evidence to support Grafelma's value for the cancer therapy related diarrhea CTD indication in at least the subgroups of breast and lung cancer patients.

Lisa Conte: A very important point, that benefit-risk ratio, and it's interesting to see if there are any analogous situations out there with a drug that has been on the market for such a long period of time with this safety record. Pravin, let's also just remind everybody of the previous work that has been done in cancer patients, in particular in breast cancer patients. The on-target trial added more clinical evidence, or did it, in fact, add more clinical evidence than the previous phase 2 study that was conducted in breast cancer patients?

Speaker Change: a very important point that benefit risk ratio and it's interesting to see if there's any analogous situations out there with a drug that has been on the market for such a long period of time with this safety record

Speaker Change: Prevent

Speaker Change: Let's also just remind everybody of the previous work that has been done in cancer patients in particular.

Speaker Change: In breast cancer patients, the on target trial added more clinical evidence or did they in fact add more clinical evidence than the previous phase to study that was conducted in breast cancer patients.

Pravin Chaturvedi: Thanks for bringing that up, Lisa. I think you're referring to the HALT-D Phase 2 trial that was conducted in breast cancer patients receiving pertuzumab with standard chemotherapy. The HALT-E study, which was a prophylactic study, helped inform us about conducting a longer duration study, and hence the on-target study was designed to have an overall period of treatment of 24 weeks, with the initial analysis being conducted at 12 weeks. The on-target study also identified that Crofilmer, in addition to its effects in breast cancer patients receiving targeted therapies, is also beneficial to lung cancer patients receiving targeted therapy with a kinase That's a feature of having this all-inclusive solid tumor trial, the on-target study. So it was useful. Yeah,

Lisa Conte: Thanks for bringing that up, Lisa. I think you're referring to the HALT-D Phase 2 trial that was conducted in breast cancer patients receiving pertuzumab with standard chemotherapy.

Speaker Change: The HALT-E study, which was a prophylactic study, helped inform us about conducting a longer duration study, and hence the on-target study was designed to have an overall period of treatment of 24 weeks, with the initial analysis being conducted at 12 weeks.

Speaker Change: The On-Target Study also identified

Speaker Change: That profilmer, in addition to its effects in breast cancer patients receiving targeted therapies, is also beneficial to lung cancer patients receiving target therapy with kinase inhibitor. That's a feature of having this all-inclusive solid tumor trial, the on-target study. So it was useful.

Lisa Conte: Which I agree is a gift of this trial design that we were able to find this benefit in lung cancer patients as well. I know a lot of work has to be done to understand the significance of the rich and extensive database from OnTarget, and I hope everybody got a feeling for that from your presentation here. And I know this work will take some time.

Speaker Change: Which I agree is a gift of that of this trial design that we were able to find this benefit in lung cancer patients as well

Speaker Change: I know a lot of work has to be done to understand the significance of the rich and extensive database from OnTarget. And I hope everybody got a feeling for that from your presentation here. And I know this work will take some time. I like to call it, you know, leaving no...

Lisa Conte: I like to call it, you know, leaving no statistical analysis stone unturned here, and it's likely going to go into 2025. So we have the most comprehensive briefing package prepared for the FDA. I'd like to just address the robust... of the profelomer mechanism of action, you called it paradigm shifting, and other nearer-term pipeline opportunities for data reveal. With this in mind, Pravin, please now tell us about the targeted rare disease indications for clofelamur for SPS short bowel syndrome and MVID for clofelamur, which have both received, of course, as I mentioned, orphan drug designation in the U And describe how we expect Profilomer to work in these patient populations. What is the disease progression like for these patients, and what is their standard of care?

Speaker Change: Statistical Analysis Stone unturned here and it's likely going to go into 2025 so we have the most comprehensive briefing package prepared for the FDA.

Speaker Change: I'd like to just address the robustness.

Speaker Change: of the Profelomer Mechanism of Action, you called it paradigm shifting.

Pravin: and other nearer-term pipeline opportunities for data reveal. With this in mind, Pravin, please now tell us about the targeted rare disease indications for clofelamur of SPS short bowel syndrome and MVID for clofelamur.

Pravin: which have both received, of course, as I mentioned, orphan drug designation in the U.S. and Europe. And describe how we expect profilomer to work in these patient populations. What is the disease progression like for these patients and their standard of care?

Pravin Chaturvedi: Thanks Lisa. Continuing this discussion into the Orphan and Rare Disease Indications for Grafelmar is very important to me. We have made significant progress in achieving clinical and regulatory milestones for the rare and often disease indications of short bowel syndrome with intestinal failure, SPSIF, as well as Microvillous Inclusion Disease, MPID, Ocrophelma.

Pravin: Thanks, Lisa. Continuing this discussion into the orphan and rare disease indication for profelma is very important to me.

Speaker Change: We have made significant progress in achieving clinical and regulatory milestones.

Speaker Change: for the Rare and Orphan Disease Indications of Short Bowel Syndrome with Intestinal Failure.

Speaker Change: SPSIF, as well as Microbial Inclusion Disease, MPID, Okra Felmer.

Pravin Chaturvedi: As I mentioned earlier, Crofelma shows consistency in symptomatic management of diarrhea and other gastrointestinal symptoms in various clinical indications. Adult or pediatric patients with short bowel syndrome with intestinal failure are unable to absorb adequate calories from their oral intake due to intestinal failure, which can be due to either anatomic or functional reasons for their intestinal failure, which basically means that they have lost a part of their intestine tract. Hence these patients require their daily caloric and nutritional requirements to be supplemented using total parenteral nutrition, potentially up to 20 hours a day and up to seven days a week in some cases. Obviously, this is a catastrophic situation for the patients and their families.

Speaker Change: As I mentioned earlier, profelma shows a consistency in symptomatic management of diarrhea and other gastrointestinal symptoms in various clinical indications.

Speaker Change: Adult or pediatric patients with short bowel syndrome with intestinal failure are unable to absorb adequate calories from their oral intake due to intestinal failure.

Speaker Change: which can be due to either anatomic or functional reasons for their intestinal failure, which basically means that they have lost a part of their intestinal tract.

Speaker Change: Hence, these patients require their daily caloric and nutritional requirements to be supplemented.

Speaker Change: To using

Speaker Change: Total parenteral nutrition, potentially up to 20 hours a day and up to seven days a week in some cases.

Speaker Change: Obviously, this is a catastrophic situation for the patients and their families.

Pravin Chaturvedi: In addition, some patients require TPN, total parenteral nutrition, with more supplemental IV fluids, intravenous fluids, as they are at risk for dehydration due to severe diarrhea. We are initiating a clinical trial in 2024 in the European Union, in adult SBS IF short bowel syndrome with interstitial failure patients requiring TPN, with regulatory clearance from the European Medicines Agency, EMA, which is the European counterpart of the In addition, we are supporting a couple of investigator-initiated exploratory studies in adult and pediatric SPS-IF patients.

Speaker Change: In addition, some patients require TPN, Total Parenteral Nutrition, with more supplemental IV fluids, intravenous fluids, as they are at risk for dehydration due to severe diarrhea.

Speaker Change: We are initiating a clinical trial in 2024 in the European Union.

Speaker Change: in adult SBS IF short bowel syndrome with interstitial failure patients requiring TPN

Speaker Change: With regulatory clearance from the European Medicines Agency, EMA, which is the European counterpart of the US FDA.

Speaker Change: In addition, we are supporting a couple of investigator-initiated exploratory studies in adult and pediatric SPS-IF patients.

Pravin Chaturvedi: Adult being at Cleveland Clinic and Pediatric being at the Sheikh Khalifa Medical City in Abu Dhabi for evaluating Crofoma's benefits in SBSIS patients. It is important for everyone to understand that these SBSIS patients are monitored very closely. And due to the shortened length of the intestine tract, an oral delayed-release tablet formulation of grafelma currently on the market here in the U.S. is not viable for these patients. Our team developed a novel, proprietary, highly-concentrated, lifelike part of an oral solution which can be administered orally to these patients in very small volumes to evaluate the effects of profelmer on various clinical symptoms of SPSIF patients, including reductions in their stool volume output and the need for reduced parenteral support as a result of profelmer's effect.

Speaker Change: Adult being at Cleveland Clinic and Pediatric being at the Sheikh Khalifa Medical City in Abu Dhabi.

Speaker Change: for evaluating Crofoma's benefits in SBSIS patients.

Speaker Change: It is important for everyone to understand that these SBSIS patients are monitored very closely.

Speaker Change: Due to the shortened length of the intestinal tract, an oral delayed release template formulation of grafelma currently on the market here in the U.S. is not viable for these patients.

Speaker Change: Our team developed a novel, proprietary, highly concentrated lyophilized powder for oral solution which can be administered orally to these patients in very small volumes to evaluate the effects of profelmer.

Speaker Change: on various clinical symptoms of SPSIF patients, including reductions in their stool volume output and the need for reduced parenteral support as a result of Crofelmer's effects.

Pravin Chaturvedi: The collateral benefit of the novel lyophilized oral powder for solution grafelma formulation is that we can also administer that orally to pediatric patients that have the ultra-rare congenital diarrheal disorder called microvillous inclusion disease. MVID patients do have a full-length cut, but they do not have what is called a brush border membrane in their intestines, and therefore, they cannot absorb their required daily intake of nutrients or electroly Hence, these patients also require lifelong total parenteral nutrition support to support their nutritional and caloric needs, and these patients fail to thrive, which means they don't grow as a normal child would.

Speaker Change: The collateral benefit of the novel lyophilized oral powder for solution grafoma formulation is that we can also administer that orally to pediatric patients that have the ultra-rare congenital diarrheal disorder called microvillous inclusion disease.

Speaker Change: MVID patients do have a full length cut, but they do not have what is called a brush border membrane in their intestines, and therefore they cannot absorb their required daily intake of nutrients or electrolytes.

Speaker Change: Hence, these patients also require lifelong total parenteral nutrition support to support their nutritional and caloric needs. And these patients fail to thrive, which means they don't grow as a normal child would.

Pravin Chaturvedi: Thus MVID is associated with significant morbidity and mortality. We have an active U.S. IND for MVID, and we are initiating a pioneering clinical study to evaluate the benefit of Crofilmer in pediatric MVID patients receiving TPN with or without supplemental IV fluids in 2024. We're also adding clinical sites in the European Union and in the Middle East, North Africa (MENA) region, as the incidence of MVID in those geographies is higher than in the United States due to consanguineous marriages.

Speaker Change: Thus, MVID is associated with significant morbidity and mortality.

Speaker Change: We have an active US IND for MVID and we are initiating a pioneering clinical study.

Speaker Change: To evaluate the benefit of crofilmer in pediatric MVID patients receiving TPN with or without supplemental IV fluids in 2024.

Speaker Change: We are also adding clinical sites in the European Union and in the Middle East, North Africa, MENA region, as the incidence of MVID in those geographies is higher than the United States due to consanguineous marriages.

Pravin Chaturvedi: An important near-term milestone for us will be the support we are providing for an investigator-initiated trial with one of our key opinion leaders and a member of my scientific advisory board in the MENA region, Dr. Mohamed Migdadi, who is evaluating the effects of grafelmer in his pediatric patients with either microbial inclusion disease or short bowel syndrome with intestinal failure. As you mentioned at the beginning of this webcast, we just received clearance for an import permit for shipping Crofilma to our SAB member in Abu Dhabi. And we are looking forward to its first patient being dosed there and proof of concept results as early as potentially in Q4 of this year.

Speaker Change: An important near-term milestone for us will be the support we are providing for an investigator-initiated trial with one of our key opinion leaders and a member of my scientific advisory board in the MENA region, Dr. Mohammad Migdadi.

Speaker Change: who is evaluating the effects of grafelmer in his pediatric patients with either microvillous inclusion disease or short bowel syndrome with intestinal failure.

Speaker Change: As you mentioned at the beginning of this webcast, we just received clearance for an import permit for shipping crofilma to our SAB member in Abu Dhabi, and we are looking forward to his first patient being dosed there and proof of concept results as early as potentially in Q4 of this year.

Lisa Conte: Thank you, Pravin, for that. I do want to mention I've known Dr. McDaddy for about six years, and I met him several times in Abu Dhabi and the fortitude and the Transcription by CastingWords, other than TPN. And key members of the Jaguar-NAPO team, including myself and Pravin, have visited many KOLs on three different continents.

Speaker Change: [inaudible]

Speaker Change: Thank you for Ben for that and I do want to mention I've known Dr. McDaddy for about six years and I've met him several times in Abu Dhabi and the fortitude and the

Speaker Change: persistence he showed in going through all the regulatory paperwork to bring the product to his patients and the care that he has for these patients and the lack of alternative treatments again with pediatric MVID, congenital diarrheal disorders, nothing else.

Speaker Change: Other than TPN

Speaker Change: and key members of the Jaguar NAPO team, including myself and Pravin have visited many KOLs on three different continents.

Lisa Conte: And what we hear is that two of the most devastating toxic things that you administer to patients for their situation in both cancer and intestinal failure are chemotherapy and TPN, respectively. So it is remarkable the commitment and the care that these physicians have to not only treating the patient's disorders but also focus on supportive care, quality of life, patient comfort, and patient dignity. So also, Pravin, I've asked you to describe some of the key learnings from these meetings that inform protocol development.

Speaker Change: And what we hear is two of the most devastating toxic things that you administer to patients for their situation in both cancer and intestinal failure are chemotherapy and TPN respectively.

Speaker Change: So it is remarkable, the commitment and the care that these physicians have to not only treating the patient's disorders, but also the focus on supportive care, quality of life, patient comfort, patient dignity.

Pravin: Also, Pravin, I have asked you to describe some of the key learnings from these meetings that inform the protocol development.

Pravin Chaturvedi: Thanks, Lisa. As you know, both MVID and SVSIF are malabsorptive syndromes, and much of the focus of clinicians has been on improving absorption of nutritional and caloric intake in these patients. Both FDA and EMA have approved a drug called tetraglutide, which is a growth hormone called GLP-2, for the management of adult and pediatric SPSI patients. It's given parenterally by injection. Since the approval of tetraglutide, several additional biosimilars have also been under clinical development, and their clinical effects are very similar to tetraglutide, and their only differentiating feature relies on ease or convenience of administration to these patients, such as instead of giving it daily, you give it once or twice a week.

Pravin: Thanks Lisa. As you know both MVID and SBSIF are malabsorptive syndromes and much of the focus of clinicians

Pravin: have been on improving absorbing of nutritional and caloric intake in these patients.

Pravin: Both FDA and EMA have approved a drug called tetraglutide, which is a growth hormone, GLP-2, for the management of adult and pediatric SPSIF patients. It's given parenterally by injection.

Pravin: Since the approval of tetraglutide, several additional biosimilars are also under clinical development, and their clinical effects are very similar to tetraglutide, and their only differentiating feature relies on ease or convenience of administration to these patients.

Speaker Change: Such as instead of giving daily, you give it once or twice a week.

Pravin Chaturvedi: It is important for the audience to understand that a standard of care for short bowel syndrome intestinal failure patients, is Total Parenteral Nutrition, TPN. And teriglutide or any of the biosimilars and other growth hormones cannot be used in cancer patients that have short bowel syndrome, because it's a growth hormone, and Taduglutide, is not approved, for pediatric and VID patients, and it cannot be expected to provide benefit in these patients, in MVID patients, that is, because they don't even have a brush for the membrane and they have limited ability to grow any absorptive villi in the intestine with a growth hormone mechanism of action. So in our travels and discussions with KOLs.

Speaker Change: It is important for the audience to understand that a standard of care for short bowel syndrome intestinal failure patients is total parenteral nutrition, TPN.

Speaker Change: Enteroglutide or any of the biosimilars and other growth hormones cannot be used in cancer patients that have short bowel syndrome.

Speaker Change: Because it's a growth hormone.

Speaker Change: and Total Glutide.

Speaker Change: is not approved for pediatric MVID patients.

Speaker Change: And it cannot be expected to provide benefit in these patients.

Speaker Change: in MVAD patients, that is, because they don't even have a brush for the membrane and they have limited ability to grow any absorptive villi in the intestine with a growth hormone mechanism of action.

Pravin Chaturvedi: Profelmer not having any such limitations of a growth hormone because it acts locally in the gut lumens without significant oral absorption and provides the ability to reduce chloride secretion in the gut, along with the accompanying gut fluid accumulation, thus reducing diarrhea, are clinical investigators across the U.S., the EU, and the MENA region. They welcome the opportunity to evaluate Grofoma because of its truly novel and well-tolerated therapy for their adult SPSIF and pediatric MVAD patients. I couldn't be more grateful to all these clinical investigators who are going to study the patients because they are looking forward to giving a new therapy to their patients with Crofalma.

Speaker Change: So in our travels and discussions with KOLs.

Speaker Change: Profelmer not having any such limitations of a growth hormone.

Speaker Change: because it acts locally in the gut lumen without significant oral absorption.

Speaker Change: and provides the ability to reduce chloride secretion in the gut, along with the accompanying gut fluid accumulation, thus reducing diarrhea.

Speaker Change: are clinical investigators across the US, the EU, and the MENA region.

Speaker Change: They welcome the opportunity to evaluate Grafelma because of its truly novel and well-tolerated therapy for their adult SPSI, FN Pediatrics, and VID patients.

Speaker Change: I couldn't be more grateful to all these clinical investigators who are going to study the patients because they are looking forward to giving a new therapy to their patients with Crofalmer.

Lisa Conte: Thank you, Pravin, and I could not be more grateful to the Jaguar NAPO team.

Speaker Change: Thank you.

Speaker Change: And thank you Pravin, and I could not be more grateful to the Jaguar NAPO team. This is truly

Lisa Conte: This is truly a pipeline within a product with Crofilamer and no other mechanism of action out there like that. And there's a lot going on in a small company. And you get a snapshot here of just how complex clinical trial planning, execution, implementation, and analysis is. And we are committed to getting Crofilamer to all the patient populations that can benefit in the most efficient way possible. So, Pravin, I think we should let you get back to work now because, clearly, you have a lot to do.

Speaker Change: a pipeline within a product with crofellum or no other mechanism of action out there like that and it's a lot

Speaker Change: Going on in a small company and you've got a snapshot here of just how complex clinical trial planning execution implementation and analysis is

Speaker Change: And we are committed to get profile memory to all the patient populations that can benefit in the most efficient way possible. So prevent, I think we should let you get back to work now because clearly you have a lot to do.

Lisa Conte: And we are now going to move the discussion over to the expansion of our commercial pipeline. Kathy Collis is going to leave and talk about our planned October 2024 commercial launch of Joclair, which is FDA-approved for mucositis. And I will just bring up a personal point. We had a mucositis experience in our family. And I can tell you when that side effect occurs, all the focus is on eliminating the side effect and not on the treatment of the cancer or the underlying cause because it is so devastating.

Speaker Change: and we are now going to move the discussion over to the expansion of our commercial pipeline.

Speaker Change: with the discussion.

Speaker Change: Kathy Collis is going to leave and.

Speaker Change: Talk about our planned October 2024 commercial launch of Gelclair, which is FDA approved for mucositis. And I will just bring on a personal point. We had a mucositis experience in our family, and I can tell you when that side effect

Speaker Change: occurs, all the focus is on eliminating the side effect.

Lisa Conte: So I'm so pleased that we have a commercial launch and a product opportunity in this area to again address patient comfort, their ability to stay on their cancer care, which affects the outcome, and also the dignity of the patient. So Kathy, over to you.

Speaker Change: and not on the treatment of the cancer or the underlying cause because it is so devastating. I'm so pleased

Speaker Change: that we have a commercial launch and a product opportunity in this area to again address patient comfort, their ability to stay on their cancer care, which affects the outcome, and also the dignity of the patient. So, Kathy, over to you.

Kathy Collis: Good morning Lisa and good morning to all of you joining us today. As Lisa alluded to and many of you are aware, oral mucositis is among the most common, painful, and debilitating cancer treatment-related side effects. Jalclair is a protective gel with a mechanical action indicated for the management of pain and relief of pain by adhering to the mucosal surface of the mouth, soothing oral lesions of various etiologies, including oral mucositis slash stomatitis.

Kathy Collis: Good morning, Lisa, and good morning to all of you joining us today. As Lisa's alluded and many of you are aware, oral mucositis is among the most common, painful, and debilitating cancer treatment related side effects.

Jill Clare: Jill Clare is a protective drill with a mechanical action indicated for the management of pain and relief of pain by adhering to the mucosal surface of the mouth

Jill Clare: Soothing oral lesions of various etiologies, including oral mucositis slash stomatitis.

Kathy Collis: It is a clinically proven FDA-approved, convenient, and easy to use product that provides rapid and long-lasting pain relief and improves the ability of oral mucositis patients to eat, drink, swallow, speak, and sleep. Unlike other products for oral mucositis, it is not a numbing agent and does not sting the mouth.

Speaker Change: It is a clinically proven, FDA-approved, convenient, and easy-to-use product that provides rapid and long-lasting pain relief and improves the ability of oral mucositis patients to eat, drink, swallow, speak, and sleep.

Speaker Change: Unlike other products for oral mucositis, it is not a numbing agent and does not sting the mouth.

Kathy Collis: We all know cancer is chaotic because patients feel a loss of control over their lives, their treatment, and their supportive care needs. Jaguar's mission is to change patients' lives for the better, especially in the area of supportive care for complex disease states like cancer. We are excited about our planned commercial launch of GelClaire in October 2024 because we believe we can help cancer patients by giving them a supportive care product for oral mucositis that provides soothing pain relief without numbing and which is effective and safe.

Speaker Change: We all know cancer is chaotic because patients feel a loss of control over their life, their treatment, and their supportive care needs.

Jaguar: Jaguar's mission is to change patients' lives for the better, especially in the area of supportive care for complex disease states like cancer.

Jaguar: We are excited about our planned commercial launch of gel clear in October 2024 because we believe we can help cancer patients by giving them a supportive care product for oral mucositis that provides soothing pain relief without numbing and which is effective and safe.

Kathy Collis: Our focus for the GelClaire launch will be patients with head and neck cancer. Head and neck cancers account for nearly 4% of all cancers in the United States, according to the National Cancer Institute. Counting cancers of the oral cavity, pharynx, and larynx, the NCI, the National Cancer Institute, estimates that about 71,110 cases will occur in the United States this year. While up to 40% of all patients treated with chemotherapy develop oral mucositis, this percentage rises to approximately 90% for patients with cancers treated with chemotherapy and radiotherapy.

Jaguar: Our focus for the GelClaire launch will be patients with head and neck cancer.

Kathy Collis: Of the latter, 19% may end up being hospitalized, experiencing a delay in their cancer treatment for high-grade mucositis management, resulting in a reduction of the quality of life, a worse prognosis, and an increase in patient management costs. Those of us working in the oncology field know the impact that side effect-related delays or cessation of cancer treatment can have on the overall survival and the efficacy of treatment, of patients with head and neck cancers treated with chemotherapy and radiotherapy who develop oral mucositis, half the cases are typically considered severe, meaning oral mucositis of grade three or four, which typically puts a patient in the hospital requiring parental nutrition and IV hydration, and of course, the morbidity and expense associated with those treatments.

Jaguar: Head and neck cancers account for nearly 4% of all cancers in the United States, according to the National Cancer Institute.

Jaguar: Counting cancers of the oral cavity, Cernyx and Larynx, the NCI, National Cancer Institute, estimates that about 71,110 cases will occur in the United States this year.

Jaguar: While up to 40% of all patients treated with chemotherapy develop oral mucositis, this percentage rises to approximately 90% for patients with cancers treated with chemotherapy and radiotherapy.

Jaguar: Of the latter, 19% may end up being hospitalized.

Jaguar: Experiencing a delay in their cancer treatment for high-grade mucositis management, resulting in a reduction of the quality of life, a worse prognosis, and an increase in patient management costs.

Speaker Change: Those of us working in the oncology field know the impact that side effect related delays or cessation of cancer treatment can have on the overall survival and the efficacy of treatment.

Speaker Change: of patients with head and neck cancers treated with chemotherapy and radiotherapy who develop oral mucositis.

Speaker Change: Transcript by Transcription Outsourcing, LLC.

Kathy Collis: We're dedicating a great deal of effort to ensuring that our commercial launch plan for GelClear is executed with sharp strategic focus. We're enhancing our educational, promotional, and sales representative team to include cancer-related supportive care specialists. This positions us well as we anticipate future commitments in the cancer supportive care space. To kick off the GelClaire launch, we plan to exhibit at several key oncology conferences in Q4 of this year. There will also be a strong digital component to our launch, providing information and education for patients to self-advocate. With that, I'll hand the conversation back to Lisa.

Speaker Change: We're dedicating a great deal of effort to ensuring that our commercial launch plan for GelClear is executed with sharp strategic focus. We're enhancing our educational, promotional, and sales representative team to cover

Speaker Change: Cancer Related Supportive Care Specialist. This positions us well as we anticipate future commitments in the cancer supportive care space.

Speaker Change: To kick off the GelClear® launch, we plan to exhibit at several key oncology conferences in Q4 of this year. There will also be a strong digital component to our launch, providing information and education for patients to self-advocate.

Speaker Change: With that, I'll hand the conversation back to Lisa.

Lisa Conte: Thank you. Thank you so much, Kathy.

Lisa Conte: Lisa Conte, Unknown Executive

Lisa Conte: Thank you, thank you so much Kathy and I'm so pleased about that last point of the opportunity to educate, inform patients for their ability to self advocate. Jaguar's mission clearly is to change patients lives for the better.

Lisa Conte: especially.

Speaker Change: in the area of supportive care for complex disease states like cancer. We do not believe that any cancer therapy related side effect, whether it's oral mucositis, debilitating diarrhea, extreme fatigue, neuropathy, chronic pain, I mean the list goes on and on and on.

Lisa Conte: And I'm so pleased about that last point of the opportunity to educate and inform patients about their ability to self-advocate. Jaguar's mission clearly is to change patients' lives for the better, especially in the area of supportive care for complex disease states like cancer. We do not believe that any cancer therapy-related side effect, whether it's oral mucositis, debilitating diarrhea, extreme fatigue, neuropathy, chronic pain, I mean, the list goes on and on and on, should ever, ever be viewed as acceptable or tolerable.

Speaker Change: should ever, ever be viewed as acceptable or tolerable.

Lisa Conte: This belief is a core message of our ongoing Make Cancer Less Shitty campaign, which seeks to broadly acknowledge the rigors of both short-term and perpetual cancer treatments for metastatic patients, which are remarkable, allowing patients to live 5, 10, 15, 20 years with cancer as a chronically managed state, and with the Make Cancer Less Shitty Campaign, which allows patients to share the voices and the stories with a live lived experience. We launched the Make Cancer Less Shitty campaign with three remarkable patient ambassadors, and you can find their stories and our commitment on the campaign website, which is www.

Speaker Change: This belief is a core message of our ongoing

Speaker Change: make cancer, let's

Speaker Change: Transcription by Transcription Outsourcing, LLC.

Speaker Change: Allowing patients to live 5, 10, 15, 20 years with cancer as a chronically managed state. And with the Make Cancer Less Shitty campaign, allowing patients to share the voices and the stories.

Lisa Conte: MakeCancerLessShitty.com. Shitty is S-H-I-T-T-Y. The primary social media channel for the Make Cancer Less Shitty campaign is Twitter, under the handle CancerSuckLess. You will now hear from our CFO, Carol Lizak, regarding the financial highlights from the second quarter of 2024.

Speaker Change: with a live, lived experience.

Speaker Change: We launched the Make Cancerless Shitty campaign with three remarkable patient ambassadors, and you can find their stories and our commitment on the campaign website, which is www.makecancerlessshitty.com. Shitty is S-H-I-T-T-Y.

Speaker Change: The primary social media channel for the Make Cancerless Shitty Campaign is Twitter under the handle CancerSuckLess.

Carol Lizak: Well, now here from our CFO, Carol Lizak, regarding the financial highlights from the second quarter of 2024. And then I will be back. Good morning, Carol.

Carol Lizak: And then I will be back. Good morning, Carol. Good morning.

Carol Lizak: Good morning, Lisa, and thank you to all of you who have joined our webcast. I'll begin my review of our financials for the second quarter of 2024. The combined net second quarter 2024 revenue of approximately $2.72 million for prescription and non-prescription products increased approximately 16% versus net first quarter 2024 revenue of $2.35 million, and 2% versus net second quarter 2023 revenue of $2.67 million. My tested prescription volume increased in the second quarter of 2024 compared to the first quarter of 2024 by 5.2%.

Carol Lizak: Good morning, Lisa, and thank you to all of you who have joined our webcast today.

Carol Lizak: Prescriptions decreased slightly by 0.4% in the second quarter of 2024 compared to the same period in 2023. Prescription volume differs from invoice sales volume, which reflects, among other factors, varying buying patterns among specialty pharmacies in the closed network as they manage their inventory levels. Loss from our operations decreased by $0.9 million from $8.1 million in the quarter ended June 30, 2023 to $7.2 million during the same period in 2024. Non-Gup

Carol Lizak: I'll begin my review of our financials for the second quarter of twenty twenty four.

Speaker Change: The combined net second quarter 2024 revenue of approximately 2.72 million dollars.

Speaker Change: For prescription and non prescription products increased approximately sixteen percent versus net first quarter twenty twenty four revenue of two point thirty five million dollars.

Speaker Change: And 2% versus net second quarter 2023 revenue of $2.67 million.

Speaker Change: My tested prescription volume increased in the second quarter of twenty twenty four compared to the first quarter of twenty twenty four by five point two percent.

Speaker Change: Prescriptions decreased slightly by 0.4% in the second quarter of 2024 compared to the same period in 2023.

Speaker Change: Prescription volume differs from invoice sales volume, which reflects, among other factors, varying buying patterns among specialty pharmacies in the closed network as they manage their inventory levels.

Speaker Change: Loss from our operations decreased by .9 million dollars from 8.1 million in the quarter ended June 30, 2023 to 7.2 million during the same period in 2024.

Carol Lizak: Recurring EBITDA for the second quarter of 2024 and the second quarter of 2023 were a net loss of $8.8 million and $7.7 million, respectively. Net loss attributable to common shareholders decreased by approximately $2.6 million from $12.1 million. The quarter ended June 30, 2023, and nine and a half million dollars in the same period in 2024. Well, that concludes my recap of high-level financials for the second quarter of 2024. And I will now hand the discussion back to Lisa Conte.

Speaker Change: Non-Govt. Recurring EBITDA for the second quarter of 2024 and the second quarter of 2023 were a net loss of $8.8 million and $7.7 million, respectively.

Speaker Change: Net loss attributable to common shareholders decreased by approximately $2.6 million from $12.1 million in the quarter ended June 30, 2023 to $9.5 million in the same period in 2024.

Speaker Change: Well, that concludes my recap of high level financials for the second quarter of 2024. And I will now hand the discussion back to Lisa Conte.

Lisa Conte: Thank you, Carol. Thank you, Kathy.

Lisa Conte: Thank you, Carol. Thank you, Kathy. Thank you, Pravin. Thank all of you who joined this webcast and are interested in support Jaguar Health.

Lisa Conte: Thank you, Pravin. Thank all of you who joined this webcast and are interested in supporting Jaguar Health. And I also would like to thank Peter Hodge, who handles our investor relations.

Lisa Conte: Again, our mission at Jaguar and the family of NAPO companies is to change patients' lives, of course, for the better. Our mission is unwavering, and we're inspired by the potential that Grafellner's novel and paradigm-shifting mechanism of action may have to impact outcomes for certain Complex Diseases by providing that supportive care. We're also very excited about our upcoming GelClaire launch in October, just around the corner this year.

Speaker Change: and I also would like to thank Peter Hodge who handles our investor relations.

Speaker Change: Again, our mission at Javvar and the family of NAPO companies is to change patients' lives, of course, for the better.

Speaker Change: Our mission is unwavering, and we're inspired by the potential that Grafelimer's novel and paradigm-shifting mechanism of action may have to impact outcomes.

Lisa Conte: Lisa Conte, MSWordDoc Word.Document.8

Lisa Conte: Patients are and always will remain at the heart of our mission. Through the process of sustainably bringing clofelamur from a tree in the rainforest to an FDA-approved prescription product, and that is, of course, the trade name Mitesi, in pharmacies across the United States for supportive care indication for the indication currently approved as adults living with HIV-AIDS who have non-infectious diarrhea. We have gained a great deal of experience in educating health care professionals, patients, and payers about the Novel Paradigm Shifting Mechanism.

Lisa Conte: through the process of sustainably bringing felmur from a tree in the rainforest

Lisa Conte: to an FDA-approved prescription product, and that is, of course, the trade name Mitesi, in pharmacies across the United States for supportive care indication.

Speaker Change: for and the indication currently approved as adults living with HIV AIDS who have non-infectious diarrhea. We have gained a great deal of experience about educating healthcare professionals and patients and payers.

Lisa Conte: We've learned also from the veterinary and pet parent response to our crophelomer prescription product, Canolevias A1, which is conditionally approved by the FDA, interestingly, for the treatment of chemotherapy-induced diarrhea in dogs. Yes, if you are a dog in the United States with cancer and diarrhea, you can receive a prescription for cropheloma.

Speaker Change: about the Novel Paradigm Shifting Mechanism.

Speaker Change: We've learned also.

Speaker Change: From the Veterinary and Pet Parent Response to our Cropheloma Prescription Product, Canolevias A1.

Speaker Change: which is conditionally approved by the FDA, interestingly, for the treatment of chemotherapy-induced diarrhea in dogs. Yes, you are a dog in the United States.

Speaker Change: With cancer on chemotherapy and diarrhea, you can receive a prescription for crofilamer.

Lisa Conte: We thank you, our shareholders, for your support and your dedication to our mission to bring innovative and novel prescription products to patients in need or around the world, plant-based products from our basic enabling discovery technology. Thank you for your... Unknown Speaker Your persistence and your patience as Drug Development is a long process, and we thank you once again for joining today's webcast. All please be well.

Speaker Change: We thank you, our shareholders, for your support and your dedication.

Speaker Change: to our mission to bring innovative and novel prescription products to patients in need or around the world. Plant-based products from our basic enabling discovery technology. Thank you for your...

Speaker Change: Your persistence and your patience as drug development is a long process, and we thank you once again for joining today's webcast. All please be well.

unknown: This concludes our teleconference today. You may disconnect your lines at this time. Thank you for your participation.

Speaker Change: Thank you. This concludes our today's teleconference. You may disconnect your lines at this time. Thank you for your participation.

unknown: Screenplay, directed by Music, and Editing by Motion [music]

Speaker Change: Hello, I'm Lisa Conte. I'm Lisa Conte. I'm Lisa Conte. I'm Lisa Conte. I'm [inaudible]

unknown: Carol Lizak, Lisa Conte, Pravin Chaturvedi Carol Lizak, Lisa Conte, Pravin Chaturvedi