Q1 2025 Altimmune Inc Earnings Call
Ontario Literature Festival.
Thank you. Thank you. Thank you.
Speaker Change: Good morning, ladies and gentlemen, and welcome to the Altimmune First Quarter 2025 Financial Results Conference call.
To withdraw your question, please press star 11 again.
Speaker Change: As a reminder, this call is being recorded. I'll now introduce your host for today's conference call, Lee Roth, president of Burns McClellan, investor relations advisor to Altimmune. Lee, you may begin.
Lee Roth: Thanks GG and good morning everyone. Once again, thank you all for joining us for Altimmune's first quarter, 2025 Financial Results and Business Update Conference call.
Speaker Change: On today's call, you'll hear from Dr. Vipin Garg, our Chief Executive Officer, Dr. Scott Harris, our Chief Medical Officer, and Greg Weaver, our Chief Financial Officer. Dr. Scott Roberts, our Chief Scientific Officer, and Ray Jordan, our Chief Business Officer, are with us for the Q&A session.
Speaker Change: Our first quarter, 2025 results, and corporate update press release was issued earlier this morning, and can be found on the investor relations section of the Altimmune website.
Speaker Change: Before we begin, I'd like to remind everyone that remarks made about future expectations, plans and prospects constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Security's litigation reform act of 1995.
Speaker Change: Altimmune caution for these forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those indicated.
Speaker Change: For a full review of the risk factors that could affect the company's future results and operations, we refer you to the company's filings with the Securities and Exchange Commission.
Speaker Change: I'd also direct you to read the forward-looking statement disclaimer in our press release issued this morning, which is now available on the website.
Speaker Change: Any statements made on this conference call speak only as of today's date, May 13, 2025, and the company does not undertake any obligation to update any of these forward-looking statements to reflect the events or circumstances that may occur on or after today.
Speaker Change: As a reminder, this call is being recorded and will be available for audio replay on the Altimmune
Speaker Change: With that said, it's now my pleasure to turn the call over to Dr. Vipin Garg, President and Chief Executive Officer of Alt
Vipin Garg: Thank you Lee. Good morning everyone and thank you for joining us today for our first quarter financial results and corporate update.
Thank you very much. Good-bye. Thank you.
Vipin Garg: As you can imagine, we are very excited about the upcoming readout of our impact phase 2b-mass trial, which we expect to announce this quarter.
Vipin Garg: based on the class leading liver fat reduction of pemberdutide and the use of biopsy re-reads to minimize placebo response, we are confident of achieving the trial's key efficacy and safety objectives.
Vipin Garg: If successful,? the due tide would become the only input in to achieve statistical significance on match and points at only 24 weeks of treatment.
Vipin Garg: Furthermore, it will be the first therapy of any kind to combine these effects with clinically
Vipin Garg: If approved, we believe that Pendidue Tide could provide a complete solution for the treatment of mash.
Vipin Garg: We announce today that we have entered into a credit facility with Hercules Capital for up to $100 million.
This is strategically important. Thank you.
Vipin Garg: As we build upon our balance sheet strength and provide flexibility to support our continued development of Pemberview Tide.
Vipin Garg: Greg will speak further on our financing later on the call.
Vipin Garg: Our recent R&D Day event marked an important milestone in pursuing our vision of family due tide, becoming the treatment of choice in liver and cardio-marabolic diseases.
Vipin Garg: We unveiled our plans for phase two trials in alcohol use disorder or AUD and alcohol liver disease or ALD.
Vipin Garg: Both AUD and ALDR areas of significant unmathematical need with limited treatment options.
Vipin Garg: Fenvy Dutai had the potential to disrupt the treatment paradigm in both these conditions. If we are able to demonstrate a reduction in alcohol consumption in combination with an amelioration of fat-reduced, induced liver inflammation and fibrosis.
Vipin Garg: This profile of clinical benefits was enthusiastically received by various physician groups and patients which adds to our conviction for developing family due tied in these indications.
Vipin Garg: The expansion into these indications demonstrates our commitment to establish Pambidutai as a potential foundational treatment across multiple phybrotic liver diseases and their primary causes.
Vipin Garg: With that, I'll now turn the call over to Dr. Scott Harris, our chief medical officer, to provide a clinical development update. Scott, thank you, Vipin.
Scott Harris: We were approaching an important milestone in our mash program, the top line data from the impact phase to be trial which are expected in the second quarter.
Scott Harris: We were pleased to report that the trial enrolled a total of two hundred and twelve participants with BFC confirmed F2, F3 Mash, which increased the study power over the original target.
Scott Harris: As a reminder, the dual primary endpoints of our match resolution or fibrosis improvement at 24 weeks.
Scott Harris: We also plan to provide data on key secondary endpoints including weight loss
Scott Harris: Non-intest, Vase of Test of Fibrosis, such as Fibroscan and Elf, liver fat reduction, and serum lipids.
Scott Harris: We also look forward to reporting an adverse event profile that confirms the safety, intolerability, appendodotide.
As Vipin mentioned, it's successful.
Scott Harris: Pemphidutide would be calm, the only anchor to achieve statistical significance on match end points at only 24 weeks of treatment.
Scott Harris: Further, you will be the first therapy of any kind to combine these effects with clinically meaningful weight loss at this early time point.
Scott Harris: While the top-line efficacy data readout will be at 24 weeks of treatment, we are continuing to treat patients for a total of 48 weeks.
Scott Harris: This will allow us to estimate the effective Pembedutide when mass biopsy endpoints using non-invasive tests and determine the additional weight loss achieved by these patients at this time point.
Scott Harris: We are now on the final stages of rereading the biopsies.
The baseline patient demographics and characteristics, including age, sex,
Bodyweight, BMI, diabetes status, ratio of F2 to F3. F3.
Scott Harris: liver-frag content, non-invasive measures of fibrosis and liver function are consistent with expectations and closely approximate other studies in MASH.
Scott Harris: To maximize the integrity and robustness of a hostology readout, both baseline and ended treatment biopsies for all subjects are being re-read in a blinded fashion using independent reads from three pathologists and a modal approach to scoring.
Similar to recent successful studies in this indication.
Scott Harris: President has shown that we be reading both the baseline and end of treatment biopsies, significantly reduces the placebo response rate in mass trials, and implementing this procedure will add to the likelihood of trial success. Thank you for joining us.
Scott Harris: Finally, the most compelling reason we are confident heading into the impact readout is that our phase is one being Matt Mazaldi study demonstrated a dose reduction dependent liver fat reduction of up to 74.76.4%.
Scott Harris: which is greater than that associated with other successful trials and its class leading for
Scott Harris: We call that liver fat reduction has been shown to be the principal driver of mass resolution and fibrosis improvement in mass clinical trials.
Scott Harris: Given our confidence in the upcoming data, we are preparing for the initiation of a Phase 3 trial in MASH and intend to hold the end of Phase 2 meeting with the FDA in the fourth quarter of this year for this indication.
Thank you.
Scott Harris: We are progressing towards phase two trial initiations in these indications in Q2 and Q3 respectively.
Scott Harris: The Phase 2 trial on AUD will evaluate Pemphagyutide versus placebo in approximately 100 patients
Scott Harris: Patients in the Penvadootide Arm will receive the 2.4mg dose, titrated over 8 weeks to maximize tolerability in this patient population.
Scott Harris: The primary efficacy end point is the patient-reported change in heavy drinking days with the timeline follow-back method as established by FDA guidance with key secondary end points of changes in alcohol consumption by path and weight loss.
Scott Harris: Similar to our AUD trial, the Phase II ALD trial will evaluate Pemphiduteide versus placebo in approximately 100 patients, but over a 48 week treatment period.
Scott Harris: We will employ a 2.4mg dose of Pemvedu Tide with the same dose titration method as in AUD.
Scott Harris: The key endpoint changes, change in liver stiffness measurement by fiber scan will be assessed to 24 and 48 weeks, along with key secondary endpoints of change in alcohol consumption and weight loss.
Scott Harris: Both AUD and ALD are large patient populations with treatment options that either have proven ineffective and clinical practice in the case of AUD or don't exist in the case of ALD.
Scott Harris: Marker Research suggests the drug with the target profile of Pemvedu Tide, one that reduces alcohol consumption, liver inflammation and body weight, would be well received by patients and physicians. .
Scott Harris: Furthermore, obesity is recognized to be a key risk factor for poor outcomes in both AUD and ALD and not unexpectedly patients with these conditions have a high incidence of metabolic abnormalities including hypertension and hyperalipidemia.
Scott Harris: If these efficacy trials are successful in AUD and ALD, we believe that Pemberdeutite has the potential to redefine the approach to the treatment of these serious conditions.
Scott Harris: Mazen ALD are the two most frequent conditions leading to liver transplantation in the United States.
Scott Harris: So the long-term potential benefits of Pemphidutide, if positive, are significant. We are excited to initiate the trials and look forward to sharing our progress along the way.
Scott Harris: With that, I'll now turn it over to Greg Weaver or Chief Financial Officer to review our financial results for the first quarter. Greg?
Thank you Scott, and good morning everyone [inaudible]
Thank you.
Speaker Change: Let me begin with adding some color around our cash position, our recent use of the ATM, and today's announcement of the Credit Facility of Attricutley's Capital.
Speaker Change: I'm quite happy with the progress we've made over the recent months in building the cash runway required to support the Pemvedutai Clinical Development Program in Mash, ALD and AUD.
Speaker Change: I'm confident that the cash position we construct will support the needs of the Pimidu-type program over time.
Speaker Change: Briefly about the ATM facility, this is one of several financing tools available to us. We've raised 35 million net off the facility in the first quarter of 2025.
and additional 16 million since April 1st. [inaudible]
Speaker Change: The $100 million credit facility announced this morning is another important piece of the financing strategy, and Hercules is a high quality partner.
Speaker Change: The facility provides tranche funding that is optional, flexible and significantly extends our cash one, cash one way.
Speaker Change: There's a $15 million funding at closing up front and an additional $25 million available in 2025, subject to milestones that align with our business plans.
Speaker Change: The remaining 60 million on the facility is available beginning in 2026 and subject to milestones and conditions.
Thank you. Thank you.
Speaker Change: Terms of the facility include interest only for 24 months, which can be extended up to 42 months.
Speaker Change: The duration of the facility is 48 months, terms are of market rates, and no warrants are included in the facility. We do Hercules as a long-term partner with the ability to grow alongside us as we continue to advance Pemperity Time. [inaudible]
Now to briefly comment on the Q1 financial results.
Speaker Change: We ended the first quarter of 2025 with $150 million in cash, cash equivalents and short term investments as compared to $132 million at year end 2024.
Speaker Change: The increase in our cash balance is related to equity sales off the ATM facility, totaling the 35 million during the first quarter.
Speaker Change: R&D expenses were 15.8 million for the three months ended March 31st, 25 compared to 21.5 million same period of 2024
Speaker Change: R&D expenses in the first quarter included 9.2 million of direct costs related to the development of Pemba Dutai, specifically to upfront CRO costs for the impact trial.
Speaker Change: G&X Benzes were 6 million for the quarter-end of March 31st, 25 compared to 5.3 million in the same period of 24.
Speaker Change: The increase is primarily related to $500,000 increase in noncash.com and other labor-related expense.
Speaker Change: Net loss for the first quarter of 25 was 19.6 million, 26 cents a share compared to in that loss of 24.4 million, or 34 cents a share for the first quarter of the prior year 2024.
Vipin Garg: With that, I'll now turn the call back to Vipin for closing remarks.
open
Vipin Garg: Thank you, Greg. We are entering a truly exciting time for Altimmune, with the upcoming MASH data and the initiation of our AC and ARD Phase 2 trials. We expect 2025 to be a transformative
Vipin Garg: This concludes our formal remarks and we would now like to open the line to take questions, Operator.
Speaker Change: As a reminder to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by when we compile the Q&A roster.
Speaker Change: Our first question comes from the line of Yasmeen Rahimi from Piper Sandler.
Speaker Change: Good morning, team. Thank you so much for all the great updates and very much looking forward to the impact that are you reading out here in 2Q. Do questions. The first one is, Scott, you mentioned that you guys are analyzing the baseline.
Speaker Change: biopsies. Again, is there, have you had a chance to maybe provide some commentary around?
Speaker Change: What the distribution F2 and F3 are in sort of how representative this faith to be population baseline characteristics are. [inaudible]
Vipin Garg: versus maybe some of the other fees to be successful fees to be that we have seen. That's question one. Question two is directed to Vipin. I think speaking with investors, we've always find that they're excited about Povumatide but main need help to think about post impact. [inaudible]
Vipin Garg: What is the ideal population with a mass of bees that would be ideal for pembe? [inaudible]
Vipin Garg: and you could provide color there. That would be really helpful, and then the third one is...
Vipin Garg: Obviously, upon positive data from the impact study, you do have the opportunity to think about partnering this asset. If you could provide also Vipin and team some commentary around how you're thinking about partnership opportunities. So appreciate if you could tackle these three part questions and I'll jump back in the queue.
Scott Harris: Absolutely. Thanks for your questions. Yes. Scott, do you want to take the first question? Yeah. Well, yes, we're
Speaker Change: In the absolute final stages of rereading the biopsies and what we're going to present are the demographics of that qualifying population.
Speaker Change: So, you know, based on that, we can't give you precise numbers. We would say in confidence if you look at the other studies in terms of the age of the patients.
Speaker Change: The average proportion of women, the F2F3 distribution, the distribution of diabetics, the
Speaker Change: The liver fat at baseline, the ALT levels, if you look at what we're seeing in the population that will be evaluated, as that data comes to us, it looks...
Speaker Change: very, very similar to other studies. So I think that investors can look at this and say that this will be very meaningful in terms of its comparability to other studies.
Thank you.
In terms of your question about the patient population, yes.
Speaker Change: What we are doing is we're really leveraging the unique features of Pemby Dutide, which really combines, which combines direct effect in the liver with weight loss.
Speaker Change: So really work the way we look at matches, it's match with obesity.
Speaker Change: As you know, 80% of the patients, 80% to 90% of the patients with the MASH have obesity. So,
Speaker Change: We're treating both the root cause of mass which is obesity as well as the serious condition that results from obesity which is liver fibrosis.
Speaker Change: Features to the table and really we believe that's added value proposition for Mash and even the other indication that we are pursuing. So everything we are doing has a common element here we are looking at obesity as its importance. Let's see.
Speaker Change: Secondary end point. So we think that really gives us an advantage in terms of identify the patient population that would be most benefited from from Pemberdutai.
Speaker Change: With regards to your second question, as far as partnering is concerned, as we have stated, our goal is to move forward into phase three development of Mambi Dutai, as quickly as possible.
Speaker Change: We are putting all of the pieces in place to make that happen along the way we are open to discussions and if a compelling partnership comes together we'll certainly look at it.
Speaker Change: But that's not going to be the gating factor in terms of our ability to move forward with face three in mass as well as in AUD and ALD.
Thank you so much.
Scott Harris: and others. Thanks for joining us. Thanks for having me. I'm Scott Harris. I'll see you next time.
Thank you. One moment for our next question.
Scott Harris: Our next question goes through the line of Lisa Bayko from Evercore.
and more. Thank you. Thank you. Thank you. Thank you.
Lisa Bacow: Hi there, thanks for taking the questions, and congratulations on the progress. Can you talk a little bit about...
Lisa Bacow: You know, what you're seeing in terms of and study in terms of discontinuations, how you're handling the discontinuations in terms of the data. And how should we think about any loss from the rereads and things like that? Curious. Thanks.
Speaker Change: Scott Harris, Scott Harris, Andrew Shutterly, Vipin Garg, Lee Roth, Scott Harris, Andrew
Yeah, Lisa, let me answer that question.
Speaker Change: I can't give you absolute numbers and study discontinuations, but what I can say is looking across the trial.
Speaker Change: to the discontinuations that we're seeing and also those due to adverse events.
Speaker Change: We're very very happy with the data that we're seeing so far. The trial has been going very well especially with regards to discontinuations. Obviously we'll have that data at the time of the readout.
Speaker Change: The discontinuations are handled in different ways, in trials, as you know, some compounds that look to completer analyses.
Speaker Change: Others have done what's called the full intention to treat. We're all discontinuations or treating as non-responders and then there's the Midway, which is an imputation method which has been used in other trials as well.
Speaker Change: Our goal was to have all that information available at the time of the readout.
Speaker Change: I can't give you finite information on the rereads at this point, but it's what we're seeing is in line with what we had projected for patients who qualify.
Okay.
Speaker Change: Okay, great. And then just one more question. I've been getting some questions on the importance of weight loss in this study because it really is obviously a, you know, a mass first study and weight loss is sort of secondary. So I guess, how do you see the importance and how do we think about benchmarking? [inaudible]
Speaker Change: Weight Loss in this study, I know you said to expect something like stomach blue tide, but what does that actually really mean? And I know this study will have, you know, a combination of patients with mesh, diabetic. [inaudible]
Speaker Change: You know, they won't be encouraged necessarily on lifestyle and other factors. So, you know, taking that all together, how should we think about how much weight loss to expect in a study like this. Thank you.
Speaker Change: Yeah, great question, Lisa, Weight Loss is extremely important. You know, if you look at the patient population,
Speaker Change: Up through F3, they'd be predominantly of the comorbidities of obesity and the cardiovascular risk.
Speaker Change: and if you don't achieve meaningful weight loss in the treatment of mass patients, you're really pigeonholing the product into a late F3F4 type population to treat fibrosis.
Speaker Change: and the goal is to be holistic and treat all the patients from the least severe to the most severe and we think we have that in our products. As Vipin mentioned before, his comments and I repeated that.
Speaker Change: First of all, we'll be the only Anchor-10, reading out at 24 weeks.
Speaker Change: and that will differentiate us from the other compound because speed is effectiveness.
Speaker Change: as being your factor. You need to have direct action within the liver and our ability to read out at 24 weeks.
Speaker Change: is really going to differentiate us from the Incrotens because we'll have both the weight loss and the direct acting effects.
Speaker Change: and compared to the other compounds reading out of 24 weeks, particularly the FGF-21s.
We'll have meaningful weight loss.
Speaker Change: So we will be a complete solution for mash. We think that with successful readout both in the mash end points in the weight loss we will be highly differentiated not only against the anchor tins but all compounds.
Speaker Change: Now, regarding your question about the weight loss that we expect, as you know in the semi-glutide trial, they had a weight loss of about 10% at 72 weeks. That has to be scaled back to what you would expect the 24 weeks.
You know, going one third of the amount of time. [inaudible]
Speaker Change: So our position is that any clinically significant, clinically meaningful weight loss that we see will be highly differentiating but I think that we can roughly project .
that would be very similar.
Speaker Change: to Semma Glutette. As you mentioned, left-style interventions like diet and exercise are not used in mass trials, that compares against weight loss trials where it is, so you tend to have lower placebo response rates. [inaudible]
Speaker Change: So all in all, I think that comparing this to the semi-gluetide trial of the 24 weeks [inaudible]
Speaker Change: Something that's meaningful and clinically significant will be very similar to semi-gluetide and its weight loss then clearly differentiate from the FGF-21s by providing significant weight loss which these compounds don't have. Now, one other point is as I mentioned in my comments,
Speaker Change: Although we're reading out now this quarter at 24 weeks, we all also reading out by the end of the year at 48 weeks [inaudible]
Speaker Change: so that we will have a lot of information, another catalyst in the second half of the year.
We're going to have 48-week weight loss.
Speaker Change: We're also going to have noninvasive testing that will allow us to predict what the biopsy results would have been at week 48 had we done a biopsy at that point, as you know, from other studies the biopsy response grows with time. [inaudible]
Speaker Change: So anything we see at 24 weeks will be magnified and even greater in the 48-week read-up [inaudible]
Thank you. Thank you. Thank you.
Speaker Change: Very helpful. Thank you. And then just final question from me. As you think about phase three, and I know you'll be pending all this data, meeting with FDA towards the end of the year, is taking the higher dose into phase three consideration. And also I know you're really focused on kind of like how rapid the responses and how you think about potentially earlier six months end point. Thank you.
Speaker Change: Well, those are great questions, Lisa. So, we're strongly considering taking the 2.4 milligram dose into phase three.
Speaker Change: and it's not because we expect better mass effects, it's that...
We expect to get better weight loss.
Speaker Change: Reminding you that the 1.8mg dose that we have in this trial is not the optimal dose for achieving weight loss pertinent to your prior question, has to be understood and looking at the data that we will get higher weight loss.
Speaker Change: if we employ the 2.4 milligram dose in phase 3 as we intend. Now, let's move on to the next round.
Speaker Change: Now, regarding the more rabid response, the FDA and their guidance does not provide a time course for these trials.
One possibility here, as you mentioned, would be...
Speaker Change: to do readouts at not only the end of a year, 48 or 52 weeks, but also at six months.
That's something we're strongly considering for two reasons. Let's see what happens.
Speaker Change: The first is that it would then also make, put a stake in the ground for earlier, more rapid, more rapid mass effects.
Bits, Second,
Speaker Change: It would also allow us to read out the trial results six months earlier.
Speaker Change: So both of those elements, adding the 2.4mg dose and doing an earlier read or something that's strongly being considered.
Speaker Change: We are writing that program as we speak. We are well ahead of our timeline for having an interface to meeting with the FDA in the fourth quarter. And these two things that we'll discuss with them.
and I think they'll be very open to that discussion. Thank you.
Thank you so much for answering all my questions.
Thank you. Thank you. Thank you.
Thank you. One moment for our next question.
Speaker Change: Our next question comes in the line of Roger Song from Jeffries.
Excellent.
Speaker Change: The Translation to the Mash Baruti, so how you think about that index will all collaborate with the fibrosis improvement? Well, thank you.
Speaker Change: Yeah Roger, well as you mentioned the trial is extremely well-powered and by enrolling additional patients we've even added to the likelihood of trial success.
Roger: Historically, the fibrosis improvement endpoint has been harder to hit than the mass resolution endpoint. I think that's a well-established fact.
Roger: In our trial, we have dual endpoints with Chmeen that we can hit either match resolution or fibrosis improvement to be successful, but that being the case, we believe that we'll be successful in both endpoints based on all the factors that were mentioned. Thank you very much.
Speaker Change: In terms of what was presented at ESOL, that was a new index developed by Rohit Loomba at UCSD.
Roger: who also developed a concept of a 30% decrease in liver fat content was also associated.
with Mass Resolution, and he's continued to evolve this. [inaudible]
Roger: to getting a index that's even more sensitive and specific than that. [inaudible]
and this mass resolution index combines liver fat reduction.
the change in ALT level and baseline AST level.
Roger: and it has an area under the curve in an ROC analysis approaching point nine, which is very, very predictive with high sensitivity and specificity based on that index, applying it to our original data.
Roger: In 1.8 mL of REM dose group or highest dose group over 90% of patients, we're behitting mass resolution. That's extremely important. What it comes down to Roger is basically this.
Roger: River Fat Reduction continues to be the greatest driver of mass resolution of fibrosis improvement shown consistently in all trials in pretty much accepted by experts as being the primary driving force for hitting mass resolution and also fibrosis improvement.
Roger: and we also have the highest liver-fed content, a highest liver-fed content reduction, and if any compound that's right now an act development for MASH, you know, so based on all this factor is the power of the study.
The readouts that we keep having by...
Roger: Applying indices like the Mash Resolution Index, or liver fat reduction, what we know about the science.
Roger: We were very, very confident about the trial's success. I would also add to that as I did before in my comments that controlling the placebo response is key to obtaining statistical significance. Thank you.
Roger: And the best way to do that is to use a method of taking all the biopsies at the end of the trial scrambling them so the pathologist is blind as to when the biopsy actually was done and then rereading them on a blinded basis.
We know that Papsi results.
Roger: Or upgraded in severity early in the trial and downgraded later in the trial for a variety of reasons it's shown consistently based on that a placebo patient who biologically has no change. [inaudible]
that three important factors first.
Roger: Or a magnitude of lower fat reduction. Second, the sample size that we're using going into the readout. And third, the rereading of the biopsies all move us towards trial success.
Action, thank you, thank you Scott.
Thank you. One moment for our next question.
Speaker Change: Our next question comes from the line of Annabel Samimy from Stiefl.
Annabelle Samimi: Hi, thanks for taking my questions. I just wanted to follow on the comments about the phase 3 program. You know, we all know the issue, one of the issues that played mass development is
Annabelle Samimi: The Long Development Pathway, so if you're successful here in achieving the fibrosis response in six months, I realize that you're going to design the Phase 3 program with a six month program. But do you see any avenue to tighten the development timelines or will FGAB still sticking with its typical? [inaudible]
Annabelle Samimi: New Year's Long Pathway, and how do you see this evolving over time?
Annabelle Samimi: especially as we see additional movement on these biomarkers at the recent conferences. Do you see greater acceptance from the FDA from that?
Annabelle Samimi: and I guess I have to ask the follow-up question to that, just generally speaking, how have your interactions with FDA changed with all the movement there, anything to the positive or negative that you're seeing. Thanks.
Speaker Change: Hey, thanks Annabel. Let me handle those questions. We believe we have the opportunity here to shorten that development path.
Speaker Change: For one, we could have a readout at six months. We may combine that by the way, with having two readouts, one at six months and one at twelve months.
Speaker Change: in different patient populations so that patients only have to go through.
Speaker Change: Two biopsies, one at baseline, and one at either six months, or a separate cohort in 12 months again.
Speaker Change: We have not made final decisions about that. I think Lisa and her prior comments was absolutely correct. There's an opportunity that has to be looked at but again we have to look at it with the FDA. So we can't make any firm announcements about that only the fact that we're looking at that.
Speaker Change: We're very encouraged by the enrollment rate that we had in the impact trial. We've been told it's the fastest and rolling trial to date.
Speaker Change: It shows that patients like the drug and then investigators enjoy putting their patients in the trial, and one of the big motivating factors
Speaker Change: was the fact that people could lose weight, but they also like the tolerability of the drug we think that will play out in the final results of the trial, the tolerability and adverse events.
Speaker Change: So we think that combining a faster enrollment ramp, we could also accelerate the timeline. You're absolutely correct that there's a great deal of interest in biomarkers. I think that there's greater and greater acceptance over the course of time.
It has to meet the FDA's legal standards, ultimately FDA. Okay.
Speaker Change: We think that going into our program that we're probably going to need by at the endpoints for efficacy, but those non-invasive tests...
Speaker Change: We could use that to model. The response, we saw that in the recent data with <unk>, where they were able to give a forecast of their response <unk> with their fiber scan results in our open label study at one and two years, we believe that using that biomarker data. We're four weeks creates a very important catalyst for us.
Speaker Change: Also at the end of the year.
Speaker Change: Regarding your last question about FDA interactions, we haven't noticed any difference.
Speaker Change: Not aware that there's been any meaningful changes in any of the FDA divisions, with which we interact with mash that we'd be liver and nutrition, we have not seen any changes we've not had any formal interactions.
Speaker Change: With the agency.
Speaker Change: Since our last meeting with them.
Speaker Change: But.
Speaker Change: We will be meeting with them in the fourth quarter of this year and we don't anticipate there will be any difference from our interactions in the past.
Speaker Change: And I just wanted to add one more point to the the trial size and the efficiency of drought.
Speaker Change: One thing to keep in mind that we have a very large safety database on Prem who died unlike other <unk> programs because of our database and obesity as well as the very successful end of phase II meeting they've already had with the FDA from a safety perspective safety and Tolerability perspective, so that should give us additional reason.
Speaker Change: In terms of designing the trial for phase III for mash with you might be able to get more efficiency in other words, we may not need as many patients.
Speaker Change: Exposed to drug because they already have a sizable safety database.
Speaker Change: Fantastic. Thank you.
Speaker Change: Thank you one moment for our next question.
Operator: Our next question comes from the line of Ellie Merle from UBS.
Speaker Change: Hi, This is jasmine for LTE.
Operator: Thanks for taking my question.
Speaker Change: So with.
Speaker Change: With the FDA for your end of phase two after impact do you expect to discuss.
Speaker Change: Josh for cirrhosis with them at that time and respect can you say about your latest plans and timelines there.
Speaker Change: And then second question can you just confirm for US your cash trading with Hercules facility and are there any specifics you can share on what that runway and clean.
Speaker Change: Thanks.
Speaker Change: Want to take the first question yes.
Speaker Change: Jasmine and I will take the first question then I'll hand, it over to Greg for the second so we are extremely interested in F. Four we believe that we will be successful in a four.
Speaker Change:
Speaker Change: If you look at the population of four that are enrolled in trials to date, it's been an earlier for patients who are considered Charles Abe.
Speaker Change: But by the child's future cloud classification is for people, who have good liver synthetic functions, who haven't developed the complications of cirrhosis.
Speaker Change: And they also have high liver fat.
Speaker Change: So consequently, although they are technically a four there but they are behaving like their F. Three.
Speaker Change: And we think we're going to be extremely successful in that three and I think that forecast, we're going to be extremely successful at a four so yes, we have drawn out and therefore trial now.
Speaker Change: Can't give you details on that until we get confirmation with the agency but.
Speaker Change: To your question.
Speaker Change: We intend to discuss F. Four.
Speaker Change: With the FDA I would imagine that we would have a fibrosis improvement.
Speaker Change: While that we would use for accelerated approval and therefore as well will follow these people to outcome to full approval. So you're absolutely right. We're very interested this is going to be a big part of our meeting and I think we're going to have a high probability of success and therefore I want to also.
Speaker Change: And everyone that.
Speaker Change: Our drug has both metabolic.
Speaker Change: And direct effects on.
Speaker Change: On mash.
Speaker Change: So back to my original point and <unk> point about the importance of weight loss.
Speaker Change: We're clearly be able to treat the metabolic abnormalities of zero F. One up to and even at three we have the direct effects are going to be potent for <unk> four.
Speaker Change: So unlike some other drugs that might be restricted to certain points and match developments ADF J F 'twenty ones to F three or four.
Speaker Change: The other <unk> <unk> F. One and F. Two we have the opportunity to treat all of mash in other words, we can be a complete solution for the disease. Both F zero, while from <unk> for Greg.
Speaker Change: Thanks, Scott and adjustment that good question.
Speaker Change: A lot of color around our Hercules facility that we announced this morning and the effect on the runway positive effect on our runway.
Speaker Change: The facility's broken into four tranches.
Speaker Change: First was.
Speaker Change: We will be funded this week upon closing we disclosed that.
Speaker Change: $15 million.
Speaker Change: The second tranche.
Speaker Change: Available later this year and then the balance across 2026.
Speaker Change: Break down the runway answer in two steps first on today's cash position gives us runway into Q3 of 2026.
Speaker Change: And if you layer on top the optional drawers, if we were to draw all of them. It could extend the runway for as much as another year now.
Speaker Change: That's.
Speaker Change: More details to be disclosed in the 10-Q filed later today.
Speaker Change: Okay Super helpful. Thanks, so much.
Speaker Change: Thank you one moment for our next question.
Speaker Change: Our next question comes from the line of my Yang Maam Tani from B Riley.
Speaker Change: And thanks for taking my question and congrats on the recent progress.
Speaker Change: Slide I don't know if I saw it from yield could you could you comment on the range of placebo responses youre expecting on fibrosis, and Nash resolution endpoint as you mentioned, you've seen a relatively broad range and implies droughts and.
Speaker Change: And if you're able to garment Dod side to push ahead on the CMA demand at ACO and <unk> baseline date is that a <unk> priority.
Speaker Change: They won't be naphtha steady if you could maybe comment on that and then I will follow up.
Speaker Change: Mike I'm, sorry, I didn't hear the second part of the question I heard the first part about the range of placebo response could you repeat the second and then I'll yes.
Speaker Change: Sorry, yes, the female domain ratio and then the baseline weight was added at the prior phase <unk> study to below baseline demographics question.
Speaker Change: Yes.
Speaker Change: The first question of the range of placebo response has been wide in these trials.
Speaker Change: And the <unk> phase II trial, it was 32%.
Speaker Change: And we've seen other readouts and 20%, we've even seen readouts in single digits.
Speaker Change: We think that the unifying.
Speaker Change: Factor here.
Speaker Change: Is how you handle the placebo response in the trials.
Speaker Change: Have re read their biopsies by scrambling them, we're seeing placebo responses for fibrosis improvement between about seven and 13%.
Speaker Change: So we can't.
Speaker Change: To be absolute about what our placebo responses, we think that our trial is very well powered because we have a better treatment effect in a larger sample size than those trials read out successfully but we would hope that we would drive down that placebo response to those ranges.
Speaker Change: Regarding the baseline characteristics as I mentioned before.
Speaker Change: We are in the final stages of rereading the biopsies.
Speaker Change: So the exact numbers are not available to us, but we think we're very close and rather than getting into numbers that we're just going have to re announce which could be confusing to people. We think it's better to say that the range of females to mills things like the baseline weight will be very.
Very similar not only to other trials in this space. If you line them up and we've done that but also is what our targets were so I think youre going to be very happy when you see that but until we have the final numbers were a little reluctant to put them out there because it could create confusion.
Speaker Change: Understood. Thank you and with secondary endpoints you may include as I don't see a top line release next month, and obviously wanted to understand which it should be focused on at this 24 week time.
Speaker Change: Brian versus maybe the slide eight week because.
Speaker Change: The 48 week would be important as you also think about the long term borrowing in the long term outcomes trial silo failure.
Speaker Change: Phase two FDA discussion. So if you could maybe segment that would be helpful.
Speaker Change: Alright, I want to first start by saying that we.
Speaker Change: We don't believe that we need the 48 week data to meet with the FDA. There are sponsors that met with 24 week data. It will be helpful. In the discussions and we can certainly added in but Youre correct. Those noninvasive tests are going to be extremely helpful for us to predict and model.
The changes in the liver biopsy results that would have occurred had we done the biopsy week 48.
Speaker Change: So the primary end.
Speaker Change: Points that will readout will be matched resolution of fibrosis improvement.
Speaker Change: The FDA guideline definitions.
Speaker Change: Key secondary endpoints will be things such as weight loss.
Speaker Change: Ever fat reduction changes in noninvasive tests, such as fiber scan and elf.
Speaker Change: We will also have liver fat reduction by MRI IPD Ff.
Speaker Change: And we will have adverse events discontinuation study demographics I believe that would be a comprehensive view of what we'll have.
Speaker Change: And probably will also have a week 48 as well.
Speaker Change: Understood and lastly could you touch on the impact you believe based on 10. These mechanism would be on bone and muscle health and I'll pass along thanks for taking the questions.
Speaker Change: Well bone health is extremely important.
Speaker Change: Youre seeing.
Speaker Change: Accelerated bone loss of other compounds there was a recent readout.
Speaker Change: <unk> was also published.
Speaker Change: A 5% bone mineral density loss versus placebo in cirrhotic patients you have to also recognize and are cirrhotic population placebos or losing bone density.
Speaker Change: And it could be as much as 5% over the trial duration of 96 weeks based on what we know from other databases, so adding in the natural 5% with the 5% that you'd lose with FGF 20 ones.
Speaker Change: That's significant that's 10%.
Speaker Change: And that has to be looked at very carefully and it's not something that we're seeing with <unk>, we're not seeing it with the <unk> with the <unk> ones.
Speaker Change: As Youre aware lean mass preservation is extremely important in this population we know that in the <unk> data where in two trials. They lost approximately 40% of their body weight as lean mass.
Speaker Change: A 4% to seven fold higher rate of pelvic and hip fractures and this was seen as susceptible populations. That's the key that you see it in the elderly and you see it in post menopausal women, which is not an insignificant number or proportion of the patients that are being treated with these drugs.
Speaker Change: So consequently, these are extremely important features of drugs.
Mayak: As you as you are saying here Mayak, it's important not just to look at the mash effects in the weight loss, but holistically at the whole patient and we believe the fact that we have class leading affectionately mass preservation.
Mayak: We lose only 21, 9%.
Mayak: All of our body weight loss is lean mass over 48 weeks glucagon.
Mayak: Here's to preserve muscle and lean mass and that's going to be extremely important in all populations that are obese and overweight not just in obesity population, but a mashed population with obesity as well.
Speaker Change: Thank you and the quality of their data.
Speaker Change: Thank you one moment for our next question.
Speaker Change: Our next question comes from the line of Jon will have been from citizens.
Katherine: Hi, This is Katherine on for John real.
Speaker Change: A quick question about the speed that you expect.
Speaker Change: Kind of liver fat as well.
Speaker Change: Histologic change with the DLP glucagon agonist, whether you expect any differentiation from some of the others that we've seen I guess, mainly service do tied to any reason to believe that <unk> tied to be faster and also in terms of biomarkers are there any that you expect to change from the 24 week readout to the 48 week.
Speaker Change: <unk> out in particular or is it more of you are expecting to see sustained improvements.
Speaker Change: The later time point thank you.
Speaker Change: Yes, great question, Catherine So speed is important.
Speaker Change: First of all implies efficacy.
Speaker Change: The faster you worked in more efficacious.
Speaker Change: You are and speed is important to patient <unk> III patients compress to cirrhosis and.
Speaker Change: And complications within two years, we know that from the data.
Speaker Change: And.
Speaker Change: Yes.
Speaker Change: Change in liver fat content predicts histological change at 24 weeks.
Speaker Change: No.
Speaker Change: Speed of liver fat content reductions speed of histologic changes now the 76, 4% as at 24 weeks. We also have very similar effects at 12 weeks data has been published and Jay Herpetology and in fact in our own internal data, we're even seeing these effects as early as <unk>.
Speaker Change: Six weeks.
Speaker Change: So we believe that we not only have the most potent drug but also the fast acting drug now.
Speaker Change: Now regarding server do Todd.
Speaker Change: That molecule has.
Speaker Change: A ratio of <unk>, one glucagon of eight to one we are one to one.
Speaker Change: We have a much greater amount of glucagon in a molecule in this the glucagon that's driving the.
Speaker Change: Change in liver fat reduction.
Speaker Change: What it is so we.
Speaker Change: We believe that what we're seeing at 24 weeks would not be achievable by a compound with lower glucagon compound content. We believe that it's contributing some to serve with you Todd but if you look at their liver fat reduction, it's lower it's in the range of 58% to 62%.
Speaker Change: So we believe that we have a molecule with more glucagon more liver fat reduction faster liver fat reduction faster histological change and that we are an agent that can read out of 24 weeks in contrast to <unk>, we don't think that they could do it. So we believe that will be.
Speaker Change: Differentiated against all of the prior anchor tenants that have read out not only to his appetite.
Speaker Change: <unk>.
Speaker Change: <unk>, but also server do Todd as well.
So regarding your second question.
Speaker Change: We believe the biomarker response will grow between 24 and 48 weeks there has been a lot of talk in this.
Speaker Change: And this.
Speaker Change: Conference call.
Speaker Change: Regarding knits and the fact, they are becoming more and more reliable and predictive of what's going on we saw a lot of attention being placed on the change in the fiber scan data in the cirrhotic cohorts and the resume on trials. So biomarkers are getting their there in fact.
Speaker Change: We think that what we see at 24 weeks and we'll report out on that will grow over 48 weeks, we think there'll be all of them. They all move in tandem.
Speaker Change: <unk> and fiber scan are felt to be at this point the best Noninvasive tests and in fact, there is even talk now of combining the two for prognosis a combined score itself in fiber scan. We think we can have meaningful results in both and we think those results at 24 weeks will be even better at 48 weeks and we will.
Speaker Change: Will it be an indicator of how we would have done at 48 weeks with a biopsy at that time point and that will be in the fourth quarter of this year.
Speaker Change: Thank you so much.
Speaker Change: Thank you one moment for our next question.
Speaker Change: Our next question comes from the line of Andy Shay from William Blair.
Speaker Change: Great.
Speaker Change: We're taking our questions one quick one for us.
Speaker Change: We're just wondering about the overlap between clinical sites that you used for obesity and Nash compared to.
Speaker Change: Potential place for <unk>, and <unk> that you'll look to activate in the coming quarters. Thank you.
Speaker Change: Hi, Andy Thanks for the question.
Speaker Change: There is some overlap.
Speaker Change: I don't have the data in front of me right now I can't give you percentages, but you know.
Speaker Change: The underlying unifying feature of all of these patients is obesity.
Speaker Change: Many sites specialized in this area as well as they would obesity and liver disease are matched to this obviously going to be some overlap, but offhand I don't have those numbers in front of me right now.
Speaker Change: Yes.
Speaker Change: So.
Speaker Change: <unk>.
Speaker Change: The the sites.
Speaker Change: That we pick for <unk> LD will also have some overlap with the Nash and obesity populations as well, but again I don't have that number in front of me to provide for you on this call.
Vipin Garg: Thank you at this time I would now like to turn the conference back over to Vipin Garg for closing remarks.
Vipin Garg: Thank you everybody for joining our call today as always we appreciate your continued support and look forward to keeping you updated in the months ahead and have a wonderful rest of your day.
Vipin Garg: This concludes today's conference call. Thank you for participating you may now disconnect.
Vipin Garg: Okay.
Vipin Garg: [music].
Vipin Garg: Okay.
Vipin Garg: [music].