Hi, everyone. Thank you for joining us today at the fireside chat for Altimmune. I'm very pleased to welcome the President and CEO, Vipin Garg, along with the Chief Medical Officer, Scott Harris. Before we get into the questions, a reminder of our research disclosure. For important disclosures, please see Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. With that, we begin the Altimmune fireside chat, and we're excited to have you here.
Thank you.
For those who do not know the story of Altimmune, can you give us a brief background of yourselves and a brief background of the company at a higher level and what you're currently focused on?
Absolutely. Thank you for having us. We appreciate it. Vipin Garg, President and CEO of Altimmune, and my colleague, Dr. Scott Harris, our Chief Medical Officer. Happy, excited to tell you about Altimmune. We are developing a GLP-1/glucagon dual receptor agonist for the treatment of serious liver diseases such as NASH. We'll talk more about that. The idea is the drug is called pemvidutide. It's rationally designed to have both direct effects in the liver as well as have metabolic benefits of the drug. Our glucagon works directly in the liver, has direct effects in the liver, whereas GLP-1 provides metabolic components such as weight loss, mainly through weight loss. The best way to treat NASH is really to go to treat the liver, have a direct acting agent in the liver, as well as lose weight at the same time.
About 80% of patients with NASH are either overweight or have obesity. NASH is a disease of obesity. The best way to treat NASH is to not only treat the liver, but also to remove the original insult or the injury that actually caused the disease to begin with. You'll see that everything we're working on relates to serious liver diseases where it would be beneficial to defat the liver. Pemvidutide has very profound reduction in liver fat, liver inflammation, liver fibrosis, and on top of that, has weight loss. Pemvidutide also has a highly differentiated PK profile that improves tolerability, and we'll talk more about that. We are in the middle of our 48-week phase 2b trial for NASH. We recently read out a 24-week endpoint in that. That's really the primary endpoint of the study, and we'll talk more about that.
I'm very excited to now have 48-week data coming out in the fourth quarter of this year. We're also preparing for an end-of-phase 2 FDA meeting in the fourth quarter of this year, and then prepare for our phase 3 trials in NASH in 2026.
Thank you for that. With that, we can expand on the NASH discussion for pemvidutide. You recently reported a 24-week result from the IMPACT phase 2b trial. What are the key learnings, and how did this reinforce your conviction about pemvidutide's potential to disrupt the NASH treatment landscape?
Thank you, Nana, and thank you for having us here. Let me just go over the basic design of the trial. It is a 48-week trial. We had 212 patients enrolled. We had three treatment arms: placebo, 1.2 milligrams of pemvidutide, and 1.8 milligrams of pemvidutide. The treatment is for 48 weeks, and we are following patients up to that time point to monitor their non-invasive tests, which, as you know from recent discussions with the FDA, have really risen to prominence there. We are following non-invasive tests through week 48 and also body weight and weight loss.
The primary endpoint of the study is based on the biopsy, which is done at week 24. We would note also that the 1.2 and the 1.8 milligrams of pemvidutide were administered without any dose titration, which is unique among incretin class agents, and we will talk about the importance of that in a minute. At the biopsy endpoint at week 24, we saw class-leading NASH resolution. The anti-inflammatory aspects of this compound were really robust and were really amazing. That NASH resolution we saw was exceeding NASH resolution seen by other compounds at 48 and 72 weeks. All of the activity is built up front. There were a lot of other readouts of anti-inflammatory activity, such as ALT levels, MRI-PDFF, which is a measure of liver fat content, and also an MRI-based imaging technique called corrected T1 or cT1, which measures liver inflammation.
In all of these non-invasive tests of inflammation and NASH activity, we were class-leading. This NASH resolution drives fibrosis improvement. We also saw great changes in fibrotic activity, whereas we did not meet the endpoint read manually by the pathologists. We did by the computer AI-based algorithms. I think everyone would agree the computer is more accurate than the pathologist reading. Europe has already accepted the standard. There is an application from the company that has produced this technique in front of the FDA. We are hopeful that the FDA is going to act on that in the fourth quarter. If that is the case, we will have met the approvability for fibrosis improvement in the United States as well at week 48. The non-invasive test results that we saw were also class-leading at just 24 weeks. This supported the very robust anti-inflammatory and anti-fibrotic activity of the molecule.
We are going to continue to follow those to week 48. We expect these to grow. There's been a lot of discussion at the FDA recently about the use of non-invasive tests for evaluating patients with NASH. Something very important happened about a week ago where the FDA accepted the application of a company called EchoSense, which produces FibroScan, which is a measure of transient elastography or VCTE. They accepted a letter of intent to use a surrogate endpoint. This has not happened before, and it shows that the FDA is extremely interested in moving ahead with non-invasive tests and that the level of evidence has also risen to that level now. That process could be as long as 6 to 16 months. We really don't know.
When we look at the prospect of being able to go into phase 3 using non-invasive tests, I think that based on non-invasive tests, we'll probably have the most anti-fibrotic molecule that's out there with a high probability of success. Using these non-invasive tests would allow us to conduct much smaller trials, trials that would execute faster, and also get us to NDA faster, and also cost considerably less. We're really excited about the readout, as Vipin mentioned. We have another readout coming up as a catalyst in the fourth quarter. We're meeting with the FDA in the fourth quarter to discuss their phase 3 program. Part of that will be a discussion about taking our study and designing it in such a way that we can flip it from biopsy-based endpoints to non-invasive test-based endpoints in the trial.
We get agreement from the FDA that we can do that and make that switch over during the course of the trial if FDA approves these NITs.
That's great. Are there any specific areas that you would like to seek alignment on with the FDA during the end-of-phase 2 meeting as it relates to dose regimen and endpoints?
Right. Taking the last one first, as I mentioned before, we want to get agreement with the FDA that we can move, that we can design a trial such that we have all the non-invasive tests that they need and that we can flip that switch in the middle of the trial if that conversion is to take place. Dose-wise, we achieved really remarkable dose with only 1.8 milligrams of pemvidutide, which is not the highest dose we've employed in clinical trials. At the 2.4 milligram dose in a prior trial, the weight loss of 2.4 milligrams is 40% more than 1.8. That means if we had employed the 2.4 milligram dose in our trial, we would have seen weight losses of about 8%. You can hypothesize what that result would be at the end of one year of treatment. Very competitive, as good as other compounds in development.
One thing about pemvidutide is that it combines the direct effects in the liver, which are potent, with very, very good weight loss. The combination is very important for NASH patients because they die of cardiovascular complications. Up until the point they develop cirrhosis, they die of the cardiovascular complications before they die of the NASH complications. The agreement will be to align on the endpoints, to align on the doses. In addition, we want to get alignment on the size of the phase 3 program. Typically, NASH programs have been about 1,800 patients. We recognize that we're coming into this discussion with 600 patients in obesity. We hope to have a discussion with the FDA to reduce the size of the study.
We also have some innovative design features that I can't talk about until the FDA gives us a go-ahead on it, but that would also shrink the time required to conduct the trial.
Sounds good. For the 24-week results that you reported, are there any key learnings that are likely to inform the phase 3 trial design as a whole?
Yeah. One thing I didn't mention was that we had essentially no adverse event discontinuations, which is unique among all drugs for NASH, and also recognize that we accomplish that without dose titration. Hepatologists are now facing the approval of semaglutide. It was approved last week or about two weeks ago, and they're facing the use of this compound or adding it to their clinical practice. They'll tell you when they see patients on semaglutide, they're not seeing them on the 2.4 mg dose. Obesity specialists are used to titrating very slowly over the course of a year, year and a half to get up to that level, and many patients stop before the 2.4 mg dose. Hepatologists are really not interested in titrating.
What you're going to see here is a lot of patients taking semaglutide who, because of titration, are not getting up to that 2.4 mg dose, which is the only dose that we know works in NASH. In contrast, at the 1.2 and 1.8 mg doses we have here, because they're so well tolerated, we can give them the dose needed for the treatment of NASH starting on day one. The tolerability of the compound here, the impressive tolerability, was really a tremendous learning from the study. We learned about the very, very potent anti-inflammatory effects, and the fibrotic effects were very potent as well.
Yeah. You know, looking back at the 24-week readout, there were really four key messages that came out of that. We are clearly showing direct effect on the liver. We're showing significant weight loss, excellent tolerability, actually class-leading tolerability for any NASH treatment out there, and no dose titration. You put that together, that really makes a very compelling story for NASH. It's really a complete solution for the treatment of NASH.
For the ongoing 48-week trial, is there anything we can extrapolate from the 24-week data to the 48?
Absolutely. Scott, do you want to?
Nana will be able to project the non-invasive tests at week 48, and we'll see the growth of that. Remind you that if this is the basis of approval in the future for NASH resolution and fibrosis improvement, we will have some of the most potent NITs that are out there. We'll also be able to see the weight loss at week 48, which will grow over the course of time. Then just the continued tolerability of the compound. The dropout rate in our trial was very low in the first 24 weeks, which is typically where dropouts occur. This is one of the fastest enrolling NASH trials to date. Patients really like this drug. Docs like prescribing it. We had no problems getting people who wanted to come into the study. We think that says a lot about the uptake of the drug once it's on the marketplace.
Excellent. On the study, the participant that enrolled for the phase 2b had were in biopsy stage F2 and F3.
Exactly.
What are the plans to include the F4 stage participant in future studies?
We will have that discussion with the FDA. That is a program that we are very interested in, and we think that we would have a very high probability of success in F4 based on all of the data that we've seen so far.
Got it. Are there any key questions that still need to play out in the NASH arena?
It's just the beginning of drug approvals in the NASH space. We just have a second. We now have two drugs. We have Resdiffa, which is a direct acting agent in the liver. We've got semaglutide recently approved, which is more working through the metabolic component through weight loss. I think the key question is that if you combine these two effects, both effect in the liver and the metabolic components, what is the benefit of that? That's really what we need to, what we would like to emphasize, that really the ideal treatment is a combination of these two approaches. That's what needs to be played out. Our discussions with KOLs and prescribers clearly show that doctors want their patients to lose weight in addition to improving their liver health. They really are interested in that.
That makes sense because the large proportion of patients with NASH would benefit from losing weight. Really, that's the unique advantage of pemvidutide. It's combining these two mechanisms in a single molecule.
Got it. Still in that space, we've seen strong data from the FGF21 analog class. What can we learn from the success of those drugs, and how can the mechanism of MV be differentiated?
Once again, they're emphasizing the need for direct effect in the liver. FGF21 works very effectively in the liver. That's there, and that's what we are delivering as well through the glucagon component. FGF21s have no weight loss. There's already a lot of discussion about combination therapies, combining FGF21 with GLP-1 so you can have both of these benefits. Why would you want to use two drugs if you can have a single drug do the same thing? It's very complicated to do combination therapy. Two different PK profiles, two different tolerabilities, could be even two different modes of administration. We think it's a much better solution to have a single drug doing both of these, delivering both of these mechanisms.
Got it. With that, we can actually talk about the obesity program. You recently had a successful end-of-phase 2 FDA meeting and agreed on the design of the phase 3 registrational program for pemvidutide. What would you highlight about the phase 3 trial design and the expected benchmark for success?
Okay. Let me quickly review the results of the phase 2 study because they're important. The drug was well tolerated. The weight loss that was achieved at the 2.4 milligram dose at 48 weeks was 15.6%. If you look at the trajectory of the curve, there was a lot more weight loss to be there. If you take it out to the tirzepatide time point at week 68 or the semaglutide time point at week 72, the weight loss would have been extremely competitive. We maintained glycemic control. There were no cardiac adverse events of any note. We certainly didn't see any arrhythmias, which has been a problem with some other programs. The overall increase in heart rate was minimal, no more than was seen with any other GLP-1. We came out of that study with 600 exposures.
We had a meeting with the FDA where they agreed that there were no safety signals in the program. There was no need, for example, for a cardiac outcomes trial, which has been placed on other sponsors in the obesity space as well. A great deliverable from that program, in addition to efficacy with tolerability and safety, which we carry forward now into our NASH program, as well as our program in alcoholic liver disease and AUD. I think we established very clearly in discussion with the FDA in November of last year that pemvidutide was safe, and it would be safe across the indications for which it's being pursued. We had a robust meeting with the agency. We announced four different trials. One of them was in lean mass preservation.
Another important feature of pemvidutide is that when weight loss occurs, the amount of loss that comes from lean mass is lower than other incretins. That's very important because of the high rates of bone fractures and falls in people over the age of 60, particularly postmenopausal women. In fact, in the semaglutide program, they saw a higher rate of bone fractures. Their what we call lean loss ratio, which is the amount of lean mass loss divided by the amount of total weight loss, was about 40%. That's been seen in several of their studies, and it's not really been fully explained, but it's a real concern. They have a warning in their prescribing information about the higher rate of bone fractures in elderly and women. Even retatrutide, which has gotten a lot of attention, was 38%.
When you lose weight naturally, if all of us here went into diet, the amount of lean loss as a ratio of the total weight loss would be about 25%. That gives you perspective. Now, pemvidutide was 21.9%. There's been a lot of attention given to the fact that this compound through glucagon preserves lean mass. That's very important in our NASH program because patients with advanced liver disease have sarcopenia. They have low muscle mass. If you give them a GLP-1 like semaglutide, that could have a very critical effect on their health. We immediately come into a program like F4 with really good safety just based on the compound itself, plus the fact that we don't inflict damage on their metabolic balance, their muscle mass. That's very important as well. We actually created four studies. We call them VELOCITY.
One of them looked at the reduction of LDL cholesterol in people with elevated levels at baseline. FDA was very excited about that because they saw synergy between pemvidutide and statins because we got very good LDL lowering effects, greater than 20% in people with elevated levels. We saw it even in patients taking statin therapy. There's been a real problem with statins and the ability to reach LDL goals with statins and compliance with it. FDA saw the possibility of driving compliance through the desire of people to get weight loss and then taking the two compounds together to get to their goals.
I would just add that, you know, internally, we are focusing on really treating serious conditions that result from obesity rather than going after pure obesity. As you can see, we have lots of data that pemvidutide produces very significant weight loss, and we have a lot of data on the safety profile of the drug. The question is, how do we take that and how do we create maximum value from that? We think the way to do it is to go after serious liver diseases rather than pure obesity marketplace. That's really what we are doing. We're bringing in the weight loss benefit to liver diseases across, you know, NASH, AUD, ALD. People with overweight and obesity have poor outcomes, but they will all benefit from losing weight. All of these trials, we have a phase 2 trial going on in AUD, one in ALD.
Across all of these trials, we'll be reporting on weight loss as well. For instance, in NASH, even though our main indication or our primary indication would be treatment of NASH, weight loss would be an important secondary endpoint, and we hope to have that on the label.
Yeah, that's very excellent. Thanks for touching on the AUD and ALD programs. We would like to understand how pemvidutide fits in the treatment landscape for those two major disease areas.
Absolutely, Scott. ALD, alcohol use disorder, and ALD, alcoholic liver disease, are both areas of huge unmet need. Alcoholism is at an all-time high in the United States. Alcohol-related comorbidities is actually doubled because obesity worsens the outcome in alcohol use disorder and alcoholic liver disease. With the epidemic of obesity, we're seeing more complications in AUD and ALD. It makes a lot of sense to have a drug that treats both AUD and obesity, ALD and obesity. The literature on GLP-1 effects on alcohol craving intake is well established. We have our own data in animal models showing a very dramatic reduction in the intake of alcohol, free intake of alcohol by animals given pemvidutide. We're now conducting a phase 2 study in alcohol use disorder. The study kicked off in May of this year, and we hope to read out in the second half of 2026.
That IND passed, and we're conducting that study, and we're very happy with the way it's going. That reduction in alcohol intake is probably driven predominantly, at least as far as we know, by GLP-1s. What glucagon gives you is the potential to heal any injury in the liver due to fat because the pathology of alcoholic liver disease is almost identical to that of NASH. It's basically fat-driven inflammation going to fibrosis and cirrhosis. We know the effects of pemvidutide on that sequence: liver fat, liver inflammation, and fibrosis. It's very attractive to think that the GLP-1 in alcoholic liver disease would reduce the craving, whereas the glucagon would heal the liver damage that occurred. That trial was kicked off in July of this year and is also enrolling. We haven't updated the street yet on what we think the completion date of that trial is.
The enrollment is a bit too early to know at this point in time. It's key to note that we've got agreement from the FDA to assess the liver damage in ALD with a NIT. That NIT is VCTE, vibration-controlled transient elastography, or FibroScan, which is the same NIT that was in the headlines a week ago because of the letter of intent in NASH. It means that there's an endpoint here that's being recognized across two indications. There's a lot of data to show that VCTE is the primary assessment for liver damage and fibrosis in alcoholic liver disease. We have agreement to use it as the primary endpoint in the ALD trial and to read out on that. We'll do that after the trial itself is 48 weeks. Like the IMPACT trial, we'll read that out at 24 weeks based on the NIT.
I think based on the NIT results, the VCTE results that we saw in the IMPACT trial, we're very optimistic about a positive readout in ALD as well.
I just wanted to point out we recently got fast track status for AUD as well, just a few weeks ago. We're the only drug in development that has fast track status for AUD.
Thank you. On that note, I wanted, you've been upfront about your intentions to partner pemvidutide ahead of the phase 3 trial for obesity. Can you discuss your business development plan? Has anything changed?
No. I mean, as far as obesity is concerned, as I've mentioned, our focus is not to go primarily after obesity as the main indication. In our partnership discussion, that's clearly an option that our partner can pursue. We think we bring much more value by going after serious liver diseases. Also, there's going to be tremendous pricing pressure on obesity drugs as more and more drugs get approved. Already with just two drugs, we are seeing a significant price war out there. Whereas if you are going after a serious disease that results from obesity, it's a totally different value proposition. We plan to stick with that strategy and really move forward full speed ahead in NASH. We'll look forward to getting the data from AUD and ALD as well.
As Scott lined up earlier with NASH, you know we are expecting the 48-week data, a very important milestone coming up, as well as the end-of-phase 2 meeting with the FDA coming up. Looking forward to then really talking about our phase 3 program next year.
Thanks, Vipin. Thanks, Scott. Thanks for joining us here at Morgan Stanley for the conference.
Thank you very much. Thank you for having us.