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spk02: Good day, ladies and gentlemen, and welcome to the Altamune, Inc. full year and fourth quarter 2023 financial results conference call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. To ask a question during the session, you will need to press star 1-1 on your telephone. As a reminder, this call is being recorded. I would now like to introduce your host for today's conference call, Rich Eisenstadt, Chief Financial Officer of Altamune. Rich, you may begin.
spk10: Thank you, Michelle, and good morning, everyone. Thank you for participating in Altamune's full year and fourth quarter 2023 Financial Results and Business Update conference call. Members of the Altamune team joining me on the call today are Vipin Garg, our Chief Executive Officer, Scott Roberts, our Chief Scientific Officer, and Scott Harris, our Chief Medical Officer. Following the prepared remarks, we will hold a question and answer session. The press release with our lean mass preservation data and our full year and fourth quarter 2023 financial results was issued this morning and could be found on the investor relations section of the company's website. Before we begin, I'd like to remind everyone that remarks about future expectations, plans, and prospects constitute forward-looking statements for purposes of safe harbor provisions under the Private Securities Litigation Reform Act of 1995. ought to mean cautions that these forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those indicated. For discussion of some of the risks and factors that could affect the company's future results and operations, please see the risk factors and other cautionary statements contained in the company's filings with the SEC. I'd also direct you to read the forward-looking statement disclaimer in our press release issued this morning and now available on our website. Any statements made on this conference call speak only as of today's date, Wednesday, March 27, 2024, and the company does not undertake any obligation to update any of these forward-looking statements to reflect events or circumstances that occur on or after today's date. As a reminder, this conference call is being recorded and will be available for audio replay on Altamune's website. With that, I will now turn the call over to Dr. Vipengard, Chief Executive Officer of Altamune.
spk03: Thank you, Rich, and good morning, everyone. We appreciate you joining us today for a discussion of our year-end and fourth quarter 2023 financial results and business update. We are excited about the 2023 achievements with pembidutide, our GLP-1 glucagon dual receptor agonist, which is in development for the treatment of obesity and MASH, two important clinical indications. Altimmune achieved key milestones in the development of pembidutide last year, including compelling positive data from our 48-week Momentum Phase II obesity trial and initiation of the IMPACT biopsy-driven Phase IIb trial in MASH. We are also extremely pleased with the results of our body composition analysis from the Momentum Phase II obesity trial of pembidutide. showing that 74.5% of weight loss came from fat and only 25.5% from lean mass. Our chief medical officer, Scott Harris, will review these results in greater detail shortly. The MOMENTUM trial showed that subjects receiving pembidutide had a mean weight loss of 15.6% and over 30% of subjects achieved 20% or more weight loss on 2.4 milligrams of pambidutide at week 48, along with robust reductions in BMI and serum lipids, as well as improvements in blood pressure without imbalances in cardiac events, arrhythmias, or clinically meaningful increases in heart rate. In addition to the impressive body composition data, further distinguishes pambidutide from other compounds, in development for the treatment of obesity. Turning to our impact biopsy-driven Phase IIb MASH trial, we are looking forward to announcing the top-line 24-week results anticipated in the first quarter of 2025. We are confident this trial will be successful considering the positive results from our 24-week Phase Ib trial of pembidutide in subjects with MASH-LD where a greater than 75% relative reduction in liver fat content was achieved at the 1.8 milligram and 2.4 milligram doses as 24 weeks, along with robust reductions in ALT and CT1, both myomarkers of liver inflammation. A recently completed preclinical study demonstrating a direct antifibrotic activity of amigutite provides evidence of a potential second mechanism for reducing fibrosis in MASH patients. With that, I will now turn the call over to our Chief Medical Officer, Dr. Scott Harris, to discuss our data and clinical plans. Scott?
spk11: Thank you, Vipin, and good morning, everyone. First, let me tell you about the compelling body composition analysis from the Momentum trial. which showed that 74% of weight loss came from adipose tissue and only 25.5% due to lean mass, comparable to the effects historically associated with diet and exercise programs. These data are among the best results achieved with incretin-based obesity drugs. With an increasing number of anti-obesity candidates in development, there is growing evidence, emphasis on the type and quality of weight loss where the ability to preserve lean body mass has been viewed as an important differentiator in the treatment of patients with obesity. Excessive lean mass loss has been associated with negative outcomes, such as sarcopenia and bone fractures, especially in women and the elderly. Additionally, we saw the participants' momentum preferentially lost visceral fat over subcutaneous fat, an important result. as visceral fat, like hepatic fat content, increases metabolic dysfunction and is highly associated with increased cardiovascular risk. We expect to present a complete analysis of these body composition data at an upcoming scientific meeting. Keep in mind that these favorable body composition data only add to the improvements we observed in serum lipid profile, where up to a 20% reduction in total cholesterol, 21% reduction in LDL cholesterol, and nearly 56% reduction in triglycerides were observed in Momentum participants with elevated baseline serum lipids. This strengthens our view that Pembedugia has the ability to treat not only obesity, but its key morbidities like cardiovascular disease and MASH. Recalled in our Momentum Phase II obesity trial, Subjects receiving 2.4 milligrams pembazutide had a mean weight loss of 15.6%, and over 30% of these subjects achieved 20% or more weight loss at week 48. What was equally exciting is that the 2.4 milligram weight loss curve remained linear, with no indication of plateauing at week 48. Along with the previously mentioned effects on serum lipids, Pempdutide also demonstrated improvements in blood pressure without imbalances in cardiac events, arrhythmias, or clinically meaningful increases in heart rate. Glucose homeostasis was maintained with no significant changes in fasting glucose or hemoglobin A1C. Dr. Luoroni, lead investigator for the MOMENTUM trial, will present the results of this trial at an upcoming scientific conference. Now let me talk about the IMPACT biopsy-driven Phase 2b trial. Approximately 190 subjects with or without diabetes are being randomized 1 to 2 to 2 to 1.2 milligrams, 1.8 milligrams, or 1.8 milligrams pembidutide or placebo administered weekly for 24 weeks. The key endpoints will be mass resolution or fibrosis improvement after 24 weeks of treatment with subjects followed for an additional 24 weeks for assessment of safety and additional biomarker responses. Enrollment is going well, and we expect to have top-line results of the IMPACT trial in the first quarter of 2025. We believe that the rapid rate of enrollment reflects the eagerness of MASH patients to achieve significant weight loss in addition to treatment of their liver disease. This past fall, We also reported that FDA granted fast track designation to pembidutide for the treatment of MASH based on the robust and rapid reduction in liver fat content and biomarkers of fiber inflammation observed in our phase 1B mass LD trial. We look forward to working closely with the agency in the development of pembidutide for this important indication. Finally, turning to our phase 2 clinical trial of hep T cell and chronic hepatitis B, The overall response in the recently completed trial was insufficient for further development, so we are stopping all further development. With that, I will now turn the call over to Dr. Scott Roberts, our Chief Scientific Officer, to discuss some recent preclinical findings. Scott?
spk06: Thanks, Scott. Good morning, everyone. I'd like to tell you about two studies that we've recently completed. The first represents an important development related to the therapeutic mechanism of pembidutide for NASH. We now have evidence for a direct anti-fibrotic effect of pembidutide in reducing liver fibrosis. The preclinical model used a chemical treatment to induce fibrosis as opposed to more typical NASH models based on obesity and high liver fat content. The chemical model allows for the separation of direct anti-fibrotic effects from the activity following potent defatting of the liver by pembidutide. The data showed a significant 33% reduction in the amount of fibrosis after only two weeks of pembidutide treatment in the presence of continued chemical exposure. These data bolster our optimism about obtaining a successful 24-week readout in the IMPACT trial in the first quarter of 2025. In a separate unrelated study, we demonstrated that pembidutite treatment increased the efficiency of an important process called reverse cholesterol transport, or RCT. RCT is the process by which excess cholesterol is removed from tissues and eliminated from the body. It is widely understood that LDL can cause the accumulation of cholesterol in the arteries, leading to atherosclerosis and increased risk for cardiovascular events. In the study, we demonstrated that Pembidutide treatment was able to increase the amount of cholesterol eliminated by the liver by 300% while lowering serum cholesterol levels. Clinically, we have shown that Pembidutide not only lowers serum LDL cholesterol by up to 21%, but also shifts the size of LDL particles towards larger particle sizes that cannot enter the vasculature as easily. The demonstration of increased RCT activity together with the established reductions in serum lipids and liver fat support a potentially broad role for pembidutide in improving cardiovascular risk in addition to its robust weight loss effects. I will now hand the call over to Rich Eisenstadt to give an update on our third quarter financial results. Rich?
spk10: Thank you, Scott, and good morning, everyone. It's actually our fourth quarter financial results. For today's call, I will be providing a brief update on Altamunion's full year and fourth quarter 2023 financial and operating results. More comprehensive information will be available in our Form 10-K to be filed with the SEC later today. Altamunion ended the fourth quarter of 2023 with approximately $198 million of cash, cash equivalents and short-term investments, compared to $184.9 million at the end of 2022. We project that our existing cash funds us into the first half of 2026, which fully funds our impact trial and match, including the anticipated Q1 2025 readout of top line 24-week biopsy data. Turning to the income statement, revenue was negligible in the fourth quarter and full years 2023 and 2022. Any revenue reported during such periods was for indirect rate adjustments on a government contract that we are closing out. Research and development expenses were $16.9 million in the fourth quarter of 2023, compared to $19.2 million in the same period of 2022. Approximately $11.4 million of this total for the fourth quarter of 2023 were direct expenses for the conduct of our clinical programs, including $10.3 million in direct costs related to development activities for Pembedutide, and $1.1 million in direct costs related to development activities for hep T cell. R&D expense in the fourth quarter of 2022 included $13.4 million in direct expenses associated with the development of Pembedutide and $1.9 million in direct expenses related to hep T cell development activities. Research and development expenses were $65.8 million in full year 2023 compared to $70.5 million in the prior year. In full year 2023, we incurred $35.8 million in direct costs associated with the impact and momentum trials for PENVADU diet, and $6.6 million in direct costs associated with the hefty cell campaign. General and administrative expenses were $4.3 million and $3.8 million in each of the fourth quarters of 2023 and 2022. For the full year 2023, general administrative expenses were $18.1 million versus $17.1 million for the full year 2022. The $1 million increase was primarily due to increased stock compensation expense as well as additional labor-related costs in 2023. An impairment loss on intangible asset of $12.4 million was recognized during the fourth quarter of 2023, related to the acquired in-process research and development, or IPR&D, asset associated with hep D cell. As previously discussed, the overall response in the Phase II trial is deemed to be insufficient to warrant further advancement in clinical trials, and as a result, we have stopped any further development related to hep D cell. Our quarterly non-cash operating expenses for the fourth quarter of 2023 was $15.1 million, including the IP R&D write-off, or $2.6 million for just the recurring expenses. For the full year, total non-cash operating expenses was $23.8 million, or $11.3 million for just the non-recurring items. Or, I'm sorry, for the recurring items. I apologize. Net loss for the three months ended December 31st, 2023 was $31.6 million, or 54 cents net loss per share, compared to net loss of $21.7 million, or 43 cents net loss per share, for the fourth quarter of 2022. The increase in net loss in the quarter was primarily attributable to the $12.4 million non-cash impairment charge, partially offset by $2.3 million lower research and development expenses. Net loss for the year ended December 31, 2023, was $88.4 million, or $1.66 net loss per share, compared to $84.7 million or $1.81 net loss per share for the year ended December 31st, 2022. The increase in net loss for the year is primarily attributed to the non-cash impairment charge, partially offset by lower research and development expenses in 2023 and a $4.5 million increase in interest income earned on our cash equivalents and short-term investments. I will now turn the call back over to Vipin for his closing remarks. Vipin?
spk03: Thank you, Rich. Operator, that concludes our formal remarks. We would like to open the line to take questions. Could you please instruct the audience on Q&A procedure?
spk02: Thank you. As a reminder, if you'd like to ask a question, please press star 1-1. If your question hasn't answered and you'd like to remove yourself from the queue, please press star 1-1 again. Our first question comes from Yasmeen Rahimi with Piper Sandler. Your line is open.
spk12: Good morning, team, and thank you for all the updates. I think the first question that we have been getting is, given the continued desirable product profile of Fibumatide, a lot of investors would like to get a little bit more update on where you are with partnership discussions currently. That's question number one. Question number two is, have you had the opportunity to engage with the agency in regards to the phase three design for obesity and what those would look like? And then the third one, how could we think you showed really compelling lean mass preservation results at week 48? How could we think about this magnitude to be further improved over time in patients? And thank you for allowing me to ask these questions.
spk03: Scott, you want to take the questions first, and I will come back to the partnering question.
spk11: Okay, Yasmin. So I'll take your second and third questions, and then Vipin will answer the partnering discussions. So our plan is to have a meeting with the agency in the second half of this year to discuss our Phase III program in obesity. And at that time, we'll have final conclusions about the design of the program and the trials. But, you know, the template for this has been established. with other programs, and we think that we would have a similar development program in phase three. Regarding the body composition data and the results that we saw at week 48, yes, the results are compelling and among the best in class for incretin agents, and very similar to the percentage of lean mass seen with healthy weight loss with diet and exercise, And this is what obesity experts are emphasizing, is to get the lean loss down to avoid the comorbidities of losing lean mass. As you may be aware from the bariatric and weight loss literature, the percentage of weight loss that is lean mass decreases over the course of time. So whereas we were 25.5% in week 48, there's potential to go to even lower numbers if the subjects were followed out to week 68 or 72. Dipen?
spk03: Yeah, yes. In terms of partnering discussions, the status of partnering discussions, we are having robust discussions with companies that are both scientific and technical in nature, as well as business-related discussions. As you can imagine, each company has their own particular focus, but they're all appropriate. They all appreciate PEMV due to its comprehensive and differentiated profile. So overall, we are pleased with the scientific and business discussions to date, and we will update as things develop in the future.
spk12: Thank you so much, Tim. I'll jump back into the queue.
spk02: Thank you. Our next question comes from Seamus Fernandez with Guggenheim. Your line is open.
spk08: Thanks. So I appreciate the opportunity to ask questions here. The partnering discussions... Vipin, you mentioned scientific and technical discussions, but also business discussions. It seems to me this is predominantly a business discussion at this point. So I'm just trying to better understand the commentary of differentiating those two. If there are scientific and technical discussions, what are the scientific and technical debates that remain relevant? for Pembidutide in the context of a obesity program. And in the past on partnering, you've commented that perhaps there will be separation of the opportunity for obesity being with a partner, but perhaps having NASH or MASH move forward exclusively with Altimmune. Do you still believe that that is a realistic partnering discussion, given the fact that we've now seen hints that Terzepatide has an opportunity potentially to impact fibrosis, and we have another competitor molecule in Cervidutide that's likely to present data in the near term with regard to their own potential fibrosis benefits? And both programs have a very robust obesity program, either planned or well underway.
spk03: Yeah, thank you for that question, Seamus. There's a lot to unpack there, so let me take one at a time, and if I have not completely addressed your question, please come back and repeat the remaining part. But look, in terms of discussions with partners, As you can imagine, different companies have different focus, but everybody's appreciating the cardiovascular benefit of Pembidutide. And that's what is driving these discussions. It's obesity with cardiovascular benefit, all of the things we've been talking about in terms of the lipid profile, the serum lipids, the liver fat content, and blood pressure. So all of these things combined, we believe, would have significant impact, not just people losing weight, but ultimately the cardiovascular outcomes in these. So a lot of the discussions are driven by that. We're very encouraged because that's the value proposition that we think we bring to the table. And people are getting it. People are appreciating it. And the question is, is this an obesity partnership, cardiovascular partnership, or MASH partnership, or all of those combined together? So in terms of MASH, as you know, we're moving forward with the program. We'll have our Phase IIb data. in the first quarter of 2025, and that will drive that program further. Clearly, in MASH, we are highly differentiated. Both in obesity and MASH, we are highly differentiated, but in terms of other glucagon program being there, we are differentiated from that also. Maybe, Scott, you can comment on that.
spk11: Yeah, Seamus, you know, we're encouraged by the results with the other compounds. In MASH, you mentioned terzepatide and also servodutide. We believe that the effects seen with Cervidutide are due to the glucagon component, and we'd remind you that molecule is heavily biased to GLP-1 away from glucagon, and there's not as much glucagon in the molecules in our molecule where we have one-to-one. We feel so confident about the potency of our molecule that we're actually willing to break from the pack and read out the endpoint at 24 weeks. The other compounds are reading at considerably longer periods of time. Also, with regards to servodutide, remind you that the adverse event dropout rate in that trial was very, very high, despite the fact they titrated for 20 weeks. So we don't think the tolerability profile with our compound is comparable. But we think that based on all of our biomarkers, all of the data that we've generated up to date, we're going to have a very, very potent readout. And the confidence that we could actually read that out at 24 weeks rather than 48 weeks represents our confidence in the molecule.
spk08: Great. And maybe just to follow up on the MASH program, can you just remind me, the doses, my recollection was that the plan was to explore only up to the 1.8 milligram dose, but where we saw more meaningful weight loss in the obesity program was at the 2.4 milligram dose. Just wanted to see where the sort of dose range is going. And then, you know, you mentioned weight loss in MASH patients, but my recollection is that there was very limited weight loss in the MASH sort of phase 1B2 program that you ran previously out to 12 weeks. Just trying to get a better understanding because I'm My recollection is you explored the 1.8 milligram dose there, but we didn't see much weight loss. And that, I guess, was partially attributed to the patient population recruited. But just trying to get a better understanding of how this phase two will differ from your initial phase 1D2 program. Thanks.
spk11: Right, Seamus. So we're seeing a different dose response curve for liver fat than we are for weight loss. With weight loss, we're seeing increasing weight loss with increasing doses of drugs. And in fact, we believe that if we were to go to even higher doses of pembidutide in the future, even greater weight loss would be achieved. Very happy with the weight loss that we've achieved in the obesity program. We think it's very compelling along with the other effects that Vipin described, but we have the opportunity to go higher because the dose response curve in obesity continues as you go up. When you get 75 plus percent liver fat reduction at a 1.8 milligram dose, there's really very little place to go further with the 2.4 milligram dose and the dose response. So that's the way the trial was designed, looking at the 1.2 and 1.8 milligram doses. We always have the opportunity to add that on in phase three. That's always that possibility that exists for us. But right now in the phase two design, we're going to be looking only at the 1.2 and 1.8 milligram doses.
spk08: Great. Thanks. I'll drop back in the queue.
spk02: Thank you. Our next question comes from Roger Song with Jefferies. Your line is open.
spk05: Great. Thanks for sharing the new data and the update and take our questions. So another question related to the partnership, maybe a little bit more specific. Can you let us know how much discussion is contingent upon this more detailed phase two obesity momentum data as well as your Phase II MASH data, kind of upcoming. And, you know, just remind us if the discussion is combination of both program moving forward or you will, you know, different partner have a different interest in certain program. Thank you.
spk03: Yeah, thanks, Roger. I would say the good news is that most of our partnership discussions are actually focused on both obesity and NASH programs. Most of the players that are looking at pembidutide are interested in both because they're very related indications that you can imagine. So it's going to be hard to separate them anyway, but in terms of developing and commercializing a product, it's a very similar pathway. So the good news is that most of our partnership discussions are focused on both of those programs. So we think ultimately our ideal partner would be a multinational player that has the ability to develop both obesity and MASH and commercialize in both of these and really take these programs forward in parallel. So we're in good shape from that perspective. The partners are clearly getting the message in terms of the value proposition, the differentiation that Benvidutide brings. And therefore, we're very excited about those discussions.
spk05: Got it. Thank you. And another magnetic question. So it seems very compelling, this muscle preservation, which is very interesting. So how do you think about, and vegeta can be differentiated in the maintenance or the weight rebound kind of mechanism, given you are more liver lipid or your additional liver lipid targeting versus the GLP-1 mostly is the hypochloric mechanism.
spk03: Thank you. Yeah, that's a great question, Roger. Scott, do you want to take that?
spk11: Yeah, Roger. We feel that every time we generate data, we're showing the really incredible differentiating effects of glucagon compared to other mechanisms. So we're very familiar with GLP-1 and GIP, and those drugs have very nice effects on weight loss, and they also have other benefits that have been seen in clinical trials that are ongoing or soon to be completed. Glucagon brings a whole different dimension here. that's extremely valuable for not only achieving weight loss, but maintaining weight loss, healthy weight loss, and having long-term effects in cardiovascular outcomes. So we really think in that sense, glucagon is a game changer. We've seen, as you've mentioned, the effects on serum lipids and liver fat. And now on top of that, we're seeing a very potent effect on preserving lean body mass as people lose weight. This has been a very... important point of differentiation and discussion in the obesity circle for the last two years because now people are turning away from the absolute amount of weight loss to the quality of the weight loss. And that's important, especially for long-term maintenance. So the ability to hit a certain number acutely doesn't really matter if someone stops the drug and regains the weight or regains the weight that's mainly fat or not lean. So we think this could be an incredibly important mechanism for maintenance. As you know, there was a suggestion in the obesity data at the 2.4 milligram dose that the weight loss was continuing in an aggressive manner at 48 weeks. We think this could also represent a fundamental effect of Gukigan on intermediate metabolism and energy expenditure that could continue in the future basically changing the metabolic balance and having in that score a real differentiation from the GLP-1s and the GRPs. We don't have that data at this point. It certainly would be of great interest to study this going forward, and it's something that we're strongly considering in our Phase III program.
spk06: You know, the other thing I'd add is this preservation of lean mass has important implications for continued weight loss and for maintaining the weight loss because I think everybody appreciates that because of the sheer amount of muscle that people have, it represents the lion's share of where calories are spent. So by maintaining more lean mass, more muscle, we maintain more of an engine to burn those calories and to reduce weight.
spk05: Excellent. Thank you.
spk02: Thank you. Our next question comes from Lisa Baco with Evercore. Your line is open.
spk13: Hi. I think most of my questions have been answered, but maybe if you could give us a little more, I guess, color on some of the kind of feedback you're getting from potential partners as it relates to dose and phase three strategy. and just wanted to confirm that your plan is to wait for a partner before proceeding into phase three for obesity. Thanks.
spk03: Thanks, Lisa. I mean, as you can imagine, partners are looking to differentiate going forward. I mean, if you are a third or fourth or fifth company launching a drug in the obesity space, the idea of having yet another GLP-1 or even a GLP-1 GIP Without differentiation, it's going to be difficult. So therefore, we believe having the mechanism, adding addition of the glucagon mechanism is very attractive, particularly to new players getting into the obesity space because, again, differentiation is going to be the key to commercially to successfully launch a product in obesity space going forward. So we are really very encouraged by the fact that that's what partners are focusing on. Scott talked about the quality of weight loss. That has become a very important component of our conversations because, again, if you're looking longer term, the conversation is now going to shift from just losing weight initially for whatever, 48 to 72 weeks, to how do you maintain that weight loss and what is the maintenance schedule and what's the quality of weight loss at that point. So I think on both of those fronts, we bring a very differentiated approach or a very differentiated product. So we are very encouraged by those discussions, particularly by the fact that the partners are actually getting it and focusing on it.
spk13: And how are they thinking about your titration schedule? I know you're only doing that for the highest dose, for the lower doses you have. Is there any interest in the low dose? What is the thinking on kind of your dosing approach and how much of a differentiating feature is no dose titration or might you actually consider dose titrating to even improve tolerability more?
spk03: Yeah, it's actually a very important feature, particularly the fact that all three doses you're talking about, 1.2, 1.8, and 2.4, they're all active doses. Even at 1.2 milligram, some of our patients are losing 20% or more of their body weight and many patients are losing 10% or more. So 1.2 milligram is a very active dose for many patients out there. The idea is that we can have three doses, we'll take three doses forward in phase three, have approval for all three of them, and for doctors then they have the option, they can start their patient at the lowest dose, at 1.2, and by the way, the tolerability there is just like placebo at 1.2 milligrams, so really no dose titration required. They can start with that dose, see how much weight this patient is losing, And then if they need to lose more weight, they can go to 1.8 and eventually to even 2.4. So that's really, people are really appreciating that differentiation because that simplifies the whole dosing schedule, particularly as this market moves into primary care. Doctors don't want to have to deal with dose titration, but that's, you know, it's a very important differentiating feature of pendidutide. Scott?
spk11: Yeah. Ease of prescription is extremely important. Physicians don't have the time to monitor patients through titration, to give it to physician extenders, or to hire them to spend money on that. And also, with each escalation, many times you have to get approval from insurance companies to escalate. And in all of these titration schemes with other drugs, you're starting on drugs that are not on approved or effective, which are not approved or necessarily effective doses. Patients here would start on the 1.2 milligram dose, Lisa, and that's an active dose. And that will be an approved dose, which has a tolerability similar to placebo. And I think for primary care, to have a mean of 10% weight loss in the 48 weeks and longer with longer therapy with all the benefits is a real win. But we also offer the option of going to higher doses in patients who want to lose more weight.
spk13: Great. Thank you so much.
spk02: Thank you. Our next question comes from Corinne Jenkins with Goldman Sachs. Your line is open.
spk00: Good morning. I guess maybe the partnership's obviously been a huge focus, but as you think about timelines or kind of goals for the management team, I guess is there anything you can share with respect to when you'd hope to have something established and then maybe you could comment too on whether you'd like to have something in place by the time you get to phase three conversations with the FDA later this year? And the other question that we had was just, how many patients were included in this body composition analysis? And is that something you've looked at in prior studies? Just curious how many patients and how robust that data set is.
spk11: Yeah, Corinne, 106 subjects participated in the study. And we have baseline in week 48 data on 70 patients. And we've looked at the data. Its statistical significance is extremely high. So we really feel that this is quality data, and we look forward to presenting it in greater detail at a scientific meeting later this year.
spk00: Helpful. Thanks.
spk03: And, Corinne, in terms of the timelines, as you know, those of us who have done deals, it's very difficult to sort of lay out a timeline, but our focus has been always to have a partner in place before we start Phase 3 in the second half of this year. It would be nice to have a partner alongside with us when we have our end of Phase 2 meeting. It's not critical because it's pretty standard, the end of Phase 2 meeting for obesity programs, so we're very comfortable having that conversation with the FDA, but it would be nice to have a partner alongside with us, and we'll see if that's going to be possible.
spk00: Okay, thank you.
spk02: Thank you. Our next question comes from Mayank Mamthani with B. Reilly. Your line is open.
spk04: Good morning, team. Thanks for taking our questions and appreciate the comprehensive update here. Just a few more precise technical follow-ups here. So regarding the liver fat normalization data up to 79%, which is, you know, a little higher than what you saw in NAFL study, what's the sample size? And I assume it's a pooled analysis from top dose levels? Could you please clarify that?
spk11: Well, the liver fat data, Mayan, comes from the body composition study, right? So patients have MR scans and they got an MRI PDF when the liver was being scanned. So we're seeing a very high rate of liver fat normalization. We think this is very similar to what we saw in patients in the NAFLD study who started with much higher levels of liver fat. The liver fat, mean liver fat in the NAFLD study was about 22% to 23%, and in this study it was about 5%, so the barrier for normalization was less.
spk04: Got it, Scott. And a related question I have on the body composition data, the methodology used here, you just clarified that MR-based, but, you know, there are additional approaches like DEXA, BOD-POD, you know, that could be helpful to also compare against what we have for SEMA and terzavetide. Are those analyses being conducted and could be presented in the future, or was that not part of the protocol?
spk11: Well, MRI is the preferred technique for body composition. We think that many experts think the DEXA is not a good surrogate for the specificity and sensitivity of MRI. So that's the technique we relied on for this study.
spk04: Okay, understood. And then on the impact mass trial execution, in any color you can provide on pace of enrollment and if you'd expect later in the year doing a placebo-controlled study could be impacted now that an approved MASH therapy is on the market and to the prior commentary you had that some of the approved drugs will start showing more pronounced antifibrotic effects than we've seen before. Anything on the MASH trial execution through the course of the year we should be aware of?
spk11: Yeah, so enrollment in the trial is going quite well, and the feedback we get from investigators and their subjects is that they prefer to come into their trial because patients can lose weight. So faced with the possibility of choosing amongst different trials available to them in community, we're seeing patients come into our trial because this trial offers weight loss and also potent effects. We believe that that reflects the commercial potential of the drug when these drugs are being offered. We're seeing resmideron recently being approved, but there's no weight loss associated with that, and we think head to head we're going to do extremely well in that regard. Regarding the other benefits of the drug, you know, remind you that we're seeing class-leading effects in liver fat reduction and other biomarkers of inflammation, which are going to allow us to actually read out and differentiate from the pack in this area by reading out on fibrosis improvement in 24 weeks. And we think that we can do that. But, you know, repeatedly, the effects of glucagon here are being shown to be very differentiating and very valuable, especially with regards to the quality of the changes that are being seen, especially in the weight loss front. And we look forward to generating more data in the future.
spk03: And, Scott, you may want to talk about the direct anti-fibrotic effect that we are seeing.
spk06: Sure. But actually, before I get there, I just wanted to, you know, reaffirm that, you know, we're in this sweet spot. When it comes to mesh, we're in this sweet spot. You know, Scott just talked about, you know, Res Mineram. And also the FGF21s are doing great jobs on directly acting on the liver, but there's no weight loss associated with those. With drugs like Terzepatide, they're hitting mesh resolution, but the liver defatting of a straight GLP or a GLP-GIP is just not that great. And that's why we believe the fibrosis endpoint wasn't hit. So here we have a direct acting agent that can defat the liver very quickly and control inflammation very quickly, but we also have the weight loss. And you don't find those two qualities in the competitors that are out there. As far as the direct anti-fibrotic effect, we think that the data we talked about here today are exciting and really offer a second mechanism that could certainly push things along for F2, F3, which is our intended population and it is the population in our impact study. but also may have implications for late-stage fibrosis F4, for example. So we're continuing to look at that and try to understand the mechanisms by which this is occurring, but we're excited about the data, and we think that it certainly adds to the value of Empidutide for MASH.
spk04: And just maybe staying with you, Scott, final question on that. Preclinical anti-fibrotic study data, you report, I think, 33% liver fibrosis in less than two weeks. In the same experiment, chemical experiment with incretin and non-incretin drugs, are you able to comment on what we've seen? And then also, lastly, an update on the oral formulation of FEMV, as I believe you were pursuing a couple of technologies there. Is there any early biofuel and data merging that you can talk about of the oral peptide format? And thanks again for taking our question.
spk06: Sure, absolutely. So as far as, you know, a comparison with other there's really not a lot out there for mass drugs that have really looked at this non-steatotic, non-obese model. So it's been difficult to really tease apart, are we defatting the liver and that's why we're getting antifibrotic effects, or is there some direct activity? I will mention that Lanofribinor, for example, has done the same sort of study that we've done, very similar, and we see comparable effects on the amount of fibrosis reductions. And as you know, Lanifibrinor is certainly demonstrating anti-fibrotic effects in the clinic and is currently in phase three testing. So there's not a lot out there, but I think that that's an important touch point there with the Lani data. As far as the oral formulation, we are making good progress there. When we look at the levels of PEMBI that are detected in the in vivo studies, we're seeing a significant fraction of what we achieve clinically, for example, at the 1.8 or 2.4 milligram dose. We know what those levels are. And in these dogs, we're able to achieve a significant fraction of that. And so we feel we're on the right road here. We still have two different approaches that we're evaluating, and both of them look promising. So I think that that effort is looking good, and we hope to report that will putting a, one of those candidates into IND development by the end of the year.
spk04: Thank you.
spk02: Thank you. Our next question comes from Jonathan Wollombin with JMP. Your line is open.
spk07: Hey, good morning and thanks for taking the questions. A couple thoughts on the body composition study. I wonder if you could give some context for how what you're seeing with pembidutide compares to semaglutide and terzepatide, and if you'd expect to see similar changes with other dual and triple agonists that include glucagon, or if this is specific to pembidutide. Thanks.
spk11: Yeah, thanks, Jonathan. So, in the same analysis, remind you that we were at 25.5%, semaglutide is at 40%. So compared to semaglutide, we're clearly preserving more lean mass. Within the semaglutide prescribing information, the higher rate of bone fractures in women and the elderly is highlighted. We believe that that's associated with the lean mass loss. And it emphasizes the importance of preserving lean mass as people lose weight and to get as close to the ratio seen with diet and exercise, which is about 25%, and we've achieved that. The triseptide data has only been presented in abstract form. It's a bit difficult to see the exact number, but we believe it's at about 26%. So clearly, we're in that class of the leading drugs in this space. And Retatrutide reported out a lean ratio, in other words, how much lean was being lost compared to body weight, of about 37 to 38% in a recent trial. Now, we believe that the effects that we're seeing are being driven by glucagon. We would point out that we believe that we have more glucagon in our molecule than Retatrutide, and that's why we're differentiating on the body composition. So we think the more glucagon, the better in a variety of areas, including reduction of lipids, reduction of liver fat, and now better preservation of lean mass.
spk02: Thank you. And our last question comes from Patrick Truccio with HC Wainwright. Your line is open.
spk09: Thanks. Good morning. Just a first clarification on the lean mass data. I'm wondering how the lean mass preservation and body composition compared across dose levels of Pembidutide or if it was consistent across the doses. And then separately, I'm wondering if the updated preclinical or clinical data reported today has impacted the way you're thinking about a potential phase three program and obesity in terms of trial design, such as dosing, titration, or endpoints. And separately, can you tell us how the data reported today would be expected to read through to the impact program?
spk11: Thanks, Patrick. I guess I'll take that. So the lean to total loss ratio that we quoted a 25%, 25.5% was the same in all dose groups. So you achieve that ratio regardless of the dose. So 25%, 25%, 25% at all three doses. The data on body composition clearly has to be thinking, make us think about incorporating this into a phase three design. The largest change that we've made in the program so far has been allowed dose reduction, which we think is going to remarkably improve the tolerability of the compound of the program in phase three. We certainly have the optionality to look at longer titrations. That's not a decision that's been made yet with a partner, but that is something that we could consider if there's felt to be value there. Our current position is that we do not feel that we need to longer dose titrate, we think As Vipin mentioned, especially at the 1.2 milligram dose, it is differentiating for other compounds against other compounds, particularly for primary care. But is the opportunity in a future program to go to higher doses if we chose? All the evidence suggests is we would get higher weight loss, but I want to emphasize that we are very happy with the fixed 15.6% weight loss that we achieved at 48 weeks getting even larger with longer durations of treatment. The endpoints in these studies are pretty much established by the FDA, at least for the non-diabetes and diabetes trial. We'll look to see if we actually do a study that includes body composition. We have other options to look at as well that we can detail in the future. In terms of the MASH program, I think We've always had confidence in our ability to differentiate against the other drugs in MASH. Everyone has mentioned the anti-fibrotic potential of gerazepatide and cervidutide. We think that based on the glucagon content of the molecule, we're going to get even better effects. You'll be able to demonstrate that potency by getting statistical significance at 24 weeks of treatment rather than 48 weeks of treatment. The anti-fibrotic data that Scott described on the call also increases our confidence that we're going to hit the fibrosis endpoint because we're not only moving fibrosis by reducing liver fat, we're having a direct anti-fibrotic effect, which is very important as well.
spk03: Yeah, just only one thing I would add to that, that in terms of looking at the phase three plans, I mean, as you know, for phase three, we're going to need thousands of patients, particularly for a safety database. So that gives us the opportunity to actually have multiple patient populations that we can test, we can study under the Phase III program, particularly given the differentiation of pembidutide. For instance, we might be able to have a subpopulation looking at high serum lipids and show that benefit and try to get that on the label. So those are the kind of discussions and considerations that we are going through in terms of how we design the Phase III program. Great.
spk09: Thanks so much.
spk02: Thank you. This concludes the question and answer session. I'd like to turn the call back over to Vipin Garg for Nicole's remarks.
spk03: Thank you, everyone, for participating today. We appreciate this opportunity to share our results and outlook with you, and thank you for your continued interest. Have a nice day.
spk02: Thank you for your participation. This doesn't include the program. You may now disconnect. Good day.
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