Altimmune, Inc. (ALT) Earnings Call Transcript & Summary

Hi, everyone, and thank you for joining us today at the fireside chat for Altimmune. I'm very pleased to welcome the President and CEO of Altimmune, Vipin Garg, along with the Chief Medical Officer of the company, Scott Harris. And before we get into questions, I'm just going to read a quick research disclosure. So for important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. And if you have any questions, please reach out to your Morgan Stanley sales representative. So just for those in the audience, maybe not as familiar with the Altimmune story, maybe Vipin, you can start.

Just give a brief introduction of yourselves and what you're focused on in the near term.

Absolutely. Well, thank you for having us, Kelly, looking forward to the discussion this afternoon. So Altimmune -- at Altimmune, we are focused on peptide-based therapeutics for liver diseases. Our most advanced drug is called pemvidutide. It's a GLP-1/glucagon dual receptor agonist. As you probably know, GLP-1s have really revolutionized the field of obesity treatment. And what we are doing, we are combining GLP-1 with another mechanism by adding glucagon on top of GLP-1 functionality. The benefit of that, that we see is even a more powerful drug for obesity and liver diseases by combining the 2 functions, GLP-1 for appetite suppression and glucagon for energy expenditure and actually having a direct effect on serum lipids as well as hepatic lipids, liver fat having a direct effect on improvement in liver fat and serum lipids. So we think by combining these 2, we can have a drug that's not only going to have weight loss benefit as an obesity drug but also will have direct impact on cardiovascular health of these subjects. We'll obviously talk more about that. We also have a second program called HepTcell. That's also peptide-based therapeutics for hepatitis B and that's in Phase II development as well. Pemvidutide is in Phase II development as well for both obesity as well as for NASH. And HepTcell is in Phase II trials for hepatitis B, and we expect to have data from that in the first quarter of next year. For pemvidutide we are finishing up. We actually just finished dosing in an obesity -- 48-week obesity study, and we are expecting top line data in the fourth quarter of this year, so -- in a few months here. And then the NASH trial, the Phase II NASH trial that's currently ongoing, we expect to read out on that in the first quarter of 2025.

Terrific. So let's start with the obesity program, given it's very top of mind for everyone. There's been an enormous amount of focus in the GLP-1 class of drugs, and it seems to be evolving week-to-week with new data sets and new drugs in the pipeline. What can pemvi offer that may differentiate it from other GLP-1 drugs in development?

Well, let me get started, and then Scott can provide more details. So as you mentioned, there's been a lot of interest in GLP-1. Now people are looking at what next, what is the next generation of drug that we need for obesity. And clearly, there's no question that we are going to need multiple mechanisms. We need multiple mechanisms of actions to really address a very large obesity population. The market will segment depending upon the patient phenotype. Patients with diabetes might require one type of treatment, patients with dyslipidemia might require a totally different type of treatment. So that's where glucagon comes in. Many of the players who started out with GLP-1s are now adding glucagon to GLP-1. So it's already being validated by multiple parties that adding glucagon to GLP-1 is a good thing in terms of treating obesity as well as NASH. So it really opens the door for both of these indications to have an optimal drug for treating both obesity and NASH. Scott?

The history of the marketplace has been predominantly diabetes focused. These were drugs, obviously, that were initially developed for the treatment of diabetes and at lower doses. And then the discovery was made that they had weight loss properties that were even greater if you went to higher doses. The focus of these drugs is squarely in diabetes, even though glucose control is really only the primary objective in 20% of the obesity marketplace. 70% of that population has dyslipidemia, either high serum lipids or high liver fat, both of which are risk factors for cardiovascular disease. We saw the recent readout on the SELECT trial, which revealed about a 20% decrease in cardiovascular morbidity and mortality within the time frame of dosing but that was accomplished only by weight loss, because GLP-1 therapy really has very little effect on either serum lipids or liver fat. We expect to get at least that level of weight loss in our 48-week readout. But in addition, because of the effects on LDL cholesterol, which is a much stronger surrogate of cardiovascular disease as well as hepatic fat, we are confident that when that trial is done, that we'll have even better effects.

You talked a little bit about some of these concomitant effects that you've seen for patients with both obesity and NASH. Maybe talk about the subgroup of patients that are going to need treatments really for both of those comorbidities and what is the need that you could potentially fill that's not already being solved for there?

The obesity marketplace is predominantly a dyslipidemic marketplace. And the financial rewards, the insurance reimbursement will be more for that rather than the diabetes. So we think that in order to effectively treat obesity and its comorbidities and give what payers really want drugs have to treat the dyslipidemia. When we first came out as a GLP-1 glucagon dual receptor agonist, we were criticized about putting glucagon in the mix. Could it be safe? Would it be effective? And now there's been a turnaround of the paradigm whereas of the ADA meetings last year, they were talking about the virtues of giving diabetics glucagon because of the effects on the metabolic syndrome and also the additive effects on weight loss. And we saw that recently when [indiscernible] added glucagon to tirzepatide to get their triple agonist, they saw effects in both. So we really think that as the marketplace segregates as Vipin mentioned, it's going to be a need for drugs that specifically target that population. The general acknowledgment in the community now is to get there. You have to have glutathione in the mix, where it would be optimal to add it, and we really think that we have a great drug based on efficacy and safety.

Yes, I would just emphasize that there's no question it's going to be a large market. If there was ever a mega blockbuster class, this is it. So therefore, there's actually going to be room for multiple mechanisms. We're not at the end of it. We're just adding glucagon to GLP-1 at this point. And there will be different patient types. So each one of these drugs will have a very substantial market opportunity by addressing these specific phenotypes of patients that require different mechanisms.

Okay. Terrific. And I guess, just looking into your crystal ball, I know you've talked about how the market is going to segment and there's room for really multiple products to succeed here. How will you think that will shift from current on-market therapies to some of these next-generation mechanisms and combination mechanisms? How is that going to shift over time?

Well, it's been said that obesity is the new hypertension. When I trained, which I like to think wasn't so long ago, didn't have effective antihypertensive medicines. Now there are 120 drugs or combinations approved in the United States and 1 billion people treated worldwide. An average primary care doctor looks at the patient who's hypertensive and looks at the phenotype and knows exactly what to treat. And we think the obesity marketplace will go in the same direction. Importantly, right now, obesity is being treated predominantly by specialists, obesity centers and endocrinologists because a lot of the focus has been diabetes. So diabetologists. But right now, we're treating about, I believe, the last time was about $6 billion in sales. But the projection is that it's going to be up to $100 billion. So who's going to prescribe it. It can't be all prescribed at the obesity centers, it's going to have to shift to primary care. So what the primary care doctors want. Well, what they're mainly concerned about is the overall outcome, which we've talked about before, but they also want to have ease of administration. Dose titration is very difficult for doctors. Each level of semaglutide, for example, and many insurance plans had to be separately reimbursed. And we've heard centers that have actually had multiperson reimbursement departments. The primary care specialists can afford. So the idea of having safe, convenient administration is also going to be important as the marketplace matures.

Okay. So let's talk about your MOMENTUM Phase II trial with results coming up shortly here in Q4. And I know you just announced that you've completed dosing in that trial. So congratulations on getting to that point. What should people think about in terms of the benchmarks for success and what can people expect in Q4?

When we read out on our 24-week data, we pointed out that semaglutide, the placebo-adjusted weight loss of the 24-week mark was approximately 8%, which, by the way, was good enough to see the changes in cardiovascular outcomes in the SELECT trial and tirzepatide was about 12%. When we look at the 48-week data, we see semaglutide at about 12.5%, and we see tirzepatide at about 17.5%. We've been cruising in the middle range, and we think that we're probably going to be there at the 48-week readout, but we're also seeing that with glucagon containing compounds, there continues to be weight loss even beyond the end of the treatment period. So it's going to be important to -- for us to project what we're going to have at 72 weeks. We're familiar with tirzepatide achieving 22%, but that was at -- that was at 72 weeks, for example. So I think investors are going to want to know what we predict the weight loss is going to be also at that 72-week time point. So by and large, we think that we -- if we were in the mid-teens, we'd have a drug that will be very, very meaningful in terms of its prescribing and clearly, anything above 12.5%, placebo adjusted would equal to or better semaglutide and then we have the additional benefits that have been mentioned before that would add to the cardiovascular benefit.

And around the 24-week data, there was some discussion around tolerability and discontinuation rates as there is with every GLP-1 trial that we've seen. So how do you plan to mitigate for that over time?

So we did have a higher than we anticipated adverse event dropout rate, which was only at the 2.4 milligram dose, but it was exactly what had been seen in other Phase II trials of tirzepatide and semaglutide where they saw a 25% and 30% dropouts. The bottom line is that Phase II is an opportunity to explore your doses and then you adjust as you go into Phase III. Importantly, we decided not to allow dose reduction. In this trial, we had not seen adverse event dropouts before, unlike other sponsors who allowed it. And in fact, if one looks at the semaglutide or tirzepatide Phase III programs as much as 30% of subjects either didn't get to that top dose or forced to reduce back from it once they got there. We didn't allow either patients had to progress. We did this because as we planned the program, we anticipated based on our pharmacokinetic data and our animal data that we would not have to dose titrate. If we had not done that, we would not have known that pemvidutide is unique and that it does not have to be dose titrated, which is important, as I mentioned, from the primary care center where doctors don't want to dose titrate. So we saw this, but we'll easily, of course, correct this into Phase III by allowing dose reduction. At some point in the future, in fact, we may even look at dose titration as an option for physicians when they may want to add that. So the key thing here is that we have great optionality in order to change those things as we wish. We really don't think there's any place for drugs that have 6, 5 months titration periods to change their regimen. They really have no place to go to extend it? Or is this something that we could always do what we chose. But most immediately will allow dose reduction going forward.

Yes, I would just emphasize a couple of points. First of all, this is not a safety issue. It's a tolerability issue. This is, as you said, has been seen with all GLP-1 program. In fact, the more recent data -- even the recent data coming from the newer programs is showing very similar discontinuation rate. So everybody is going to have to manage that and it's already been shown that it can be easily managed by dose reduction. So this is really not a big deal in terms of drug development. That's -- this is drug development 101.

Sure. Makes sense. And thinking toward that Phase III, you've been pretty open and upfront about your intentions to potentially seek a partner for pemvi as you look to Phase III and obesity. And let us know have any of those plans change and how you're thinking about your business development strategy going forward?

Yes. I mean our strategy has always been that this is going to be a huge market. We need a global player to be a partner in terms of commercializing the drug. And it makes sense, therefore, is to bring on that partner sooner rather than later and really develop the Phase III -- its not a Phase III trial, it's a Phase III program that we'll have to look at multiple indications and multiple comorbidities of obesity. So we want to develop the drug in a holistic way and the best way to do it is to bring onboard a partner. We've been very encouraged on the back of the 24-week data. Those discussions have gone well. We're talking to a number of players. We think that the -- once we have the 48-week MOMENTUM data, that would be the right time to sort of progress these discussions forward. And our goal is to have a partner in place by the middle of next year before we start Phase III. So our plan is to be Phase III ready on the back of the MOMENTUM 48-week data and have a partner in place before we start Phase III.

Makes sense. So maybe just shifting gears to the NASH program. You recently started enrolling the IMPACT Phase IIb trial in NASH. What did you see in your Phase I NAFLD trial that gives you confidence that this is the right move going forward into the NASH phase?

Yes, Kelly. Well, we saw class-leading reductions in liver fat which is the basis of the disease. And there's been a very strong association between the reduction in liver fat and both NASH resolution and fibrosis improvement. So we're extremely encouraged by that fat data, but it's accompanied by data that's showing that the drug within the liver is very anti-inflammatory by 2 strong mechanisms. One is the reduction of an MRR-based scanning technique which is known as corrected T1, which is strongly correlated with NASH resolution and also fibrosis improvement in the past and also the reduction in serum alanine aminotransferase level or ALT. But we also have very strong animal data showing antifibrotic effects that we've spoken to and published on before. So based on all of this, class-leading effects in serum lipids associated with class-leading reductions in liver inflammation and the antifibrotic effects that we see, we think there's a very good possibility of a successful readout when we read out the trial.

And it wasn't just the magnitude of the effect in terms of liver fat reduction. It was the speed of that reduction that's equally important. I mean, within 12 weeks, we were seeing profound changes in liver fat. That's what you need to really ultimately move the improved liver health so that you can reverse fibrosis.

Okay. Got it. So thinking about the impact trial that you're now -- have started, what can you share with us about the enrollment so far? When is that trial going to read out? And anything you'd highlight about the design of that trial that's important, thinking outpatient -- the criteria for...

So far, enrollment has been brisk. We planned for 60 sites. We have a number of backup sites of necessary. We feel very good about completing enrollment in time for a readout in the first quarter of 2025, if not sooner. The trial is comprised of 190 subjects. The primary comparison is the 1.8 milligram dose versus the placebo. That 1.8 milligram dose, we saw the maximal effects of drug on liver fat. So we didn't think there was a need to go to the 2.4 milligram dose, which by the way, was the dose associated with the higher adverse event dropout rates. We're allowing people in the trial who have F2 and F3 fibrosis because those are the ones that are most likely to have an improvement of liver fibrosis at a biopsy. And the primary readout of the study is at 24 weeks. So we're not going the full year like other GLP-1-based compounds or longer.

Okay. And there's been quite strong data out of the FGF21 drug class. What can we learn from the success of those drugs and maybe compare and contrast our mechanism here?

All the drugs that potently reduce liver fat are drugs, the FGF21s -- let me talk specifically to the FGF21s, because their biopsy data have shown impressive reduction in liver fibrosis. And that appears to be based by the fat mechanism. The magical drug, resmetirom, also had potent reductions in fibrosis based on a lesser amount of liver fat reduction, which is why we think we can do better in the results that they've seen so far. The problem with the FGF21s though is that they do not reduce body weight. So you can imagine a scenario where a patient and a physician are sitting and the physician says, ''I want to prescribe a drug to you," the patient is going to say, ''I want the one that's going to give me the weight loss," because that's what the patient can see. The changes in the liver are silent. So we think that given as good if not better reduction in liver fat, which we think will lead to better improvement of fibrosis, but also the potent weight loss, we think we have the best-in-class drug in NASH.

Yes. The other thing to keep in mind is that there is a school of thought out there that you can actually treat a majority of NASH, particularly F1 -- F2s and F3s using just the weight loss strategy, using GLP-1. So we actually have both. We have the weight loss, the GLP-1 component, but we also have direct effect in the liver. So we are best of both worlds. It's really an ideal drug for NASH as well as for obesity. So it depends if you're trying to treat NASH, you're going to get that weight loss benefit. If you're trying to treat obesity, you're going to get that dyslipidemia and liver fat reduction benefit, which is important for both of these indications.

Got it. Okay. And I know Merck recently had early data for their GLP-1 glucagon mechanism in NAFLD. And so what do we learn from that? And how can that be compared to the program we're running?

We think it's further confirmation of the potent effects of glucagon on the liver. We think that with GLP-1-based therapies alone, you don't have very meaningful effects in the liver because all of the effects of GLP-1 based compounds in the liver are mediated by weight loss and indirect. There are no GLP-1 receptors in the liver. By the way, there are also no GIP receptors in the liver. And if you look at the liver fat reduction from semaglutide and tirzepatide at 24 or 52 weeks, it's not very great, which is why we think they're not at least semaglutide has readout on this, they haven't seen a change in fibrosis. So we think that the readout that you're mentioning, Kelly really typifies what we think we're going to see in the liver when we readout our trial.

Okay. And I know there's more data coming out of the NASH space later this year in the F4 population potentially. What are some of the key questions that remain in this arena in the NASH space?

Yes, it's going to be a question of how much the liver fat reduction can drive the fibrosis improvement and whether it can be seen in the cirrhosis population, which has typically been harder to treat. We saw a negative readout recently from semaglutide, but that's what one would have anticipated because of the absence of the direct liver effects. So now we have the FGF21 stepping to the plate with more of a direct effect, much more patient about double the amount of liver fat reduction, probably associated with better anti-inflammatory activities. Certainly, they have very nice biomarkers of fibrosis response. Perhaps we'll see it in effect. It's possible they won't, but at least we hope that the effect will at least be meaningful and interpreted as a possibility of a better effect when a bigger trial is done.

Okay. And we have a few minutes left. So I want to make sure we at least get to HepTcell, which is -- maybe what are the next key catalysts for that program? And what will we learn?

Well, we've finished enrollment in that trial. We've announced it. and we'll have a readout on that trial in the first quarter of 2024. This is an immunotherapeutic. The hepatitis or chronic hepatitis B population is even as much if not more in need than the NASH population and the size and the value of the indication is as great as NASH. We have drugs right now that can bring hepatitis B to a standstill, but not actually cure it or eliminate it. So there's a large effort going on now in the pharmaceutical industry in 2 areas: drugs to reduce the hepatitis B surface antigen burden and then drugs that are immunotherapeutics that will wipe out the virus. It appears that for the immunotherapeutics like HepTcell to work, we've got to get the load of hepatitis B surface antigen down in order to make the drug effective because the surface antigen makes the patient immunotolerant, and it doesn't allow the immune system to recognize the virus. There's a masking effect. So we see our drug as being ideal used in combination therapy with some of these newer direct-acting agents like the small inhibitory RNA, the anti-nucleotides and the antibodies. The trial that we're specifically doing right now that we'll announce on in the first quarter is in a population with naturally low hepatitis B surface antigen levels that we think can respond to this immunotherapeutic is monotherapy. It turns out that worldwide for the hepatitis B -- chronic hepatitis B population, it actually comprises about 2/3 of the population. So there's also a separate indication there. So we have optionality when we complete the trial. We can combine it. We do not have a direct acting agent, but we would work with a partner. We've been talking to companies about combining it with their drugs to take patients with active disease, get the antigen down with their direct-acting agent and then combine it with immunotherapeutic to achieve a functional cure or directly treating the patients with chronic low levels of the antigen and effect to curing them as well.

Okay. And as we look to that Q1 2024 data set, are there direct comparators that we're going to be able to draw comparisons to? And how do you just more broadly see this potentially fitting into the treatment paradigm as a combo therapeutic?

There have been some other programs, immunotherapeutics that have had early readouts. What's clear about those readouts as they are combining their drugs with immunostimulants which can actually have safety problems, PD-L1 agents as well, even in low dose with the serendipity of the drug can lead to safety problems, or general immunosuppressions or immunostimulants that can have great side effects. The beauty of hepatitis of hep B cell is that it's very specifically geared towards the hepatitis B proteome without any overlap with the human proteome. And consequently, we're seeing an excellent safety profile of the compound. So we think that it will be something we tolerated by all subjects and be very safe in all populations.

Yes. And there are really very few immunotherapeutics out there that are being developed. I mean, there have been lots of efforts. Unfortunately, it's been very hard not to crack in terms of bringing this antigen -- surface antigen level down and create this environment where you can eliminate the disease. So it is a very significant achievement. If we can get that, that would be very significant in terms of advancing this field of treatment of hepatitis B.

Okay. That's a very, very helpful overview. Maybe I'll just wrap up with Vipin. What are you most excited for as you think about the end of this year and looking into next year? And what are your key strategic priorities here?

So we see pemvidutide as a major opportunity, playing a significant role in a very large market and very differentiated product profile. So ultimately, we don't need any more GLP-1. So we don't need 5 different GLP-1s. We need different mechanisms of action. So that's exactly what we're bringing to the table. We're adding GLP-1 with glucagon. This additional functionality we believe, gives us a unique advantage in terms of going -- treating those subjects that would not be served sufficiently with just a GLP-1-based agent. We think the opportunity is tremendous. We're looking forward to the data in the fourth quarter of this year and then preparing for our Phase III program for obesity. Of course, we'll also look forward to our NASH data in the first quarter of 2025. And having this optionality of really developing the drug for both of these indications gives us a very significant opportunity.

Okay. Well, with that, thank you, Vipin. Thank you, Scott, for joining us at the Morgan Stanley Healthcare Conference, and we're wishing you a lot of good luck in your upcoming data readouts, and we'll be tracking the story.

Thank you.

Thank you.