Study Update

Jun 16, 2021

Press Release

Greetings. Welcome to Altimmune, Inc. ALT-eight zero one Interim Data Call. At this time, all participants are in a listen only mode. A brief question and answer session will follow the formal presentation. Please note this conference is being recorded. At this time, I'll now hand the call over to Stacy Jerkerson. Please go ahead, Thank you, Rob, and good morning, everyone. Thank you for joining us. Members of the Altimmune team participating on the call today are Vipin Garg, chief executive officer Scott Harris, chief medical officer Scott Roberts, chief scientific officer and Will Brown, chief financial Officer. Please note that we issued a press release this morning, which is the subject of our discussion today. You may find a copy of this press release on the IR section of our website. Before we begin, I'd like to remind everyone that remarks about future expectations, plans and prospects constitute forward looking statements for purposes of safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Altimmune cautions that these forward looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those indicated, including those related to COVID-nineteen and its impact on our business operations, clinical trials and results of operations. For a discussion of some of the risks and factors that could affect the company's future results, please see the risk factors and other cautionary statements contained in the company's filings with the SEC. Any statements made on this conference call speak only as of today's date, Wednesday, 06/16/2021, and the company does not undertake any obligation to update any of these forward looking statements to reflect events or circumstances that occur on or after today's date. As a reminder, this conference call is being recorded and will be available for audio replay on Altimmune's website. With that, I will now turn the call over to Doctor. Zippengarg to begin today's call. Thank you, Stacy, and good morning, everyone. We're very excited that you could join us today to review the positive interim Phase I clinical data for ALT-eight zero one, our GLP-oneglucagon dual receptor agonist under development for NASH. These study results were announced in a press release this morning. We are very encouraged by these data, which suggests that ALT-eight zero one could be a compelling treatment option in the multibillion dollar GLP-one therapeutic class should future clinical data continue to reflect the trends observed in the initial stage of our first in human clinical trial. The global market opportunity for the GLP-one receptor class of drugs is very large and continues to grow. Most experts believe that this growth will continue for the foreseeable future as trends in obesity and lifestyle factors fuel the rising incidence of metabolic diseases. It is well known that the obesity epidemic, principally evident in developed nations, has contributed to the development of rheumatic diseases, many of which, like NAFLD and NASH, have no approved therapies available. The development of new therapies holds tremendous promise for these patients. If ultimately approved and successfully commercialized, we believe that ALT-eight zero one could experience enormous success. First, we believe ALT-eight zero one holds the promise of a potent therapeutic via its dual mechanism of action. It is designed to combine the activity of GLP-one to reduce appetite and insulin resistance with the activity of glucagon to increase energy expenditure. This may mimic the synergistic effect of diet and exercise that so many of us use to control our weight. Second, the prior preclinical data and the emerging clinical data suggest ALT-eight zero one could have a PK profile that results in improved GI tolerability. This could be a significant attribute as GI intolerability is a major patient compliance issue within this class of drugs, and the single greatest reason behind treatment discontinuation among patients. For these reasons, we are very encouraged both about the profile of ALT-eight zero one and the latest clinical data, which are beginning to provide insights into the potential benefit of ALT-eight zero one's dual agonist approach. I will now turn the call over to Doctor. Scott Harris, our Chief Medical Officer, who will review the interim Phase I clinical data. Scott? Thank you, Vipin, and good morning, everyone. For our call today, I will begin with a review of the data we reported this morning. Following that, I will talk about our clinical development plans for ALT-eight zero one, including proposed NAFLD and obesity studies. The results we shared this morning are from a six week interim analysis of our ongoing twelve week phase one placebo controlled single and multiple ascending dose study of ALT-eight zero one. This study is currently being conducted in Australia under a clinical trial application and is enrolling overweight and obese volunteers. We have completed the single ascending dose phase of the study in the first two cohorts of the multiple ascending dose phase of the trial. The results we have observed so far have been impressive and have exceeded our pre established treatment target of two percent absolute weight loss. Employing a one point eight milligram subcutaneous dose once weekly administered without the use of dose titration, which is the common practice with GLP-one based agents. We achieved an absolute mean weight loss of 5.4% in just six weeks of treatment with zero one compared to a weight gain of 0.9% in the placebo group corresponding to a net change in weight between ALT-eight zero one and the placebo groups of 6.3%, which was highly statistically significant. At a lower weekly subcutaneous dose of one point two milligrams, subjects receiving ALT-eight zero one achieved an absolute mean weight loss of 1.8% at week six, which was also statistically significant. Importantly, ALT-one was well tolerated even in the absence of dose titration. With nausea experienced by only fourteen percent and twenty two percent of subjects at the one point two and one point eight milligram doses respectively. With all cases of nausea at the one point eight milligram dose being mild. And no reports of vomiting, diarrhea, or constipation. Notably, gastrointestinal events have required other GLP-one base candidates to dose titrate over sixteen to twenty weeks to maintain adequate tolerability. Based on the relationship between weight loss and liver fat reduction observed in other GLP-one based studies and the additive effects of glucagon on liver fat metabolism, we are optimistic that ALTA-eight zero one could be an effective therapeutic agent for NASH and that the reduction in liver fat in the planned twelve week NAFLD study can parallel the impressive weight loss results reported today. Although we believe that the one point eight milligram dose could show an attractive combination of efficacy, safety, and tolerability, we do plan to explore higher dose cohorts in the ongoing trial and anticipate announcing the twelve week dosing results in the third quarter of twenty twenty one. Because this was a young undiabetic population with a mean age of only 29.8 years, the proportion of recruited subjects with MRI PDFF greater than ten percent was insufficient to perform an analysis of liver fat reduction. Consequently, we plan to conduct a twelve week Phase 1b study of subjects with NAFLD in The United States. This study will expand the enrollment criteria used in the first in human study that's currently ongoing in Australia to include diabetic and older subjects and commence in the third quarter of twenty twenty one. In addition, we expect to initiate a fifty two week biopsy driven NASH trial early next year. Based on the highly encouraging weight loss results from this interim data, we plan to file a second IND in obesity in the 2021 to supplement our ongoing NASH program. The filing of the previously announced IND in NASH is also planned in the third quarter of twenty twenty one. Recall that the preclinical data for ALT-eight zero one demonstrated superiority to semaglutide in overall weight loss, reduction in liver fat, NAS improvement and effects in liver fibrosis. If these results can be substantiated in the clinic and we are now on the path to evaluating this and if ALT-eight zero one were to receive FDA approval, we believe that ALT-eight zero one could become a compelling treatment option in a multibillion dollar metabolic disease space. Turning briefly to AdCOVID, we continue to expect top line data readouts from our Phase one study in June. This will include IgA, IgG and neutralizing antibody data at all dose levels. Based on our current sample processing time estimates, we expect the data will be available around the end of the month. So I'll now turn the call back over to Vipin for his closing remarks. Vipin? Vipin, you're on mute if you're speaking. Thank you for that overview, Scott. We have a significant opportunity before us, and we have ambitious plans to continue clinical development to further expound upon and explore these initial observations. The metabolic space represents a substantial opportunity, and we believe that the unique attributes of ALT-eight zero one could position it as a highly differentiated therapeutic agent in this category. We are especially pleased to have the opportunity to share this data with you, and we look forward to additional data readouts and to advancing ALT-eight zero one in a comprehensive clinical development program in NASH and obesity. Operator, that concludes my formal remarks this morning. Could you please instruct the audience on the Q and A procedure? Yes, thank you. We will now be conducting a question and answer session. To ask a question today please press star one on your telephone and a confirmation tone will indicate your line is in the question queue. You may press 2 if you would like to remove your question from the queue. For participants that are using speaker equipment it may be necessary to pick up your handset before pressing the star keys. Thank you. Our first question comes from the line of Yasmeen Rahimi with Piper Sandler. Please proceed with your question. Hi team. Congratulations on the fantastic data. Have a number of questions for you this morning. Maybe the first question would be can you provide a little bit color on what was the baseline BMI in these patients' weight? And then second question is can you comment on why we didn't see maybe no nausea, no vomiting even at six weeks? So historically should we have picked up GI tolerability at six weeks? And then I have one more follow-up. Hi, Yasmeen. Happy to answer your questions. The average BMI in this study was in the low 30s. You know, we'll have all of that data presented when the final readout occurs at the end of twelve weeks. But we allowed subjects in the study between the RAIN a BMI of twenty five to forty. And the second is you are correct. GI tolerability is not always, but almost always seen in the first two weeks of dosing. So while we may still see adverse events in the study, the weight of adverse events should occur early on in the first couple of weeks. Thank you for the color. Did you have any patients discontinue? And what was the size of the study of the interim analysis that you read out? If you could just provide color around the dose, how many patients were per arm in the treatment as well as in the placebo? Right. So we had approximately 10 to 15 per cohort, and the randomization ratio was four to one. And the discontinuations that were that did occur were not directly related to drug as I know it. But, you know, we need to get all of that data in and analyze it. Thank you. And then, were you able to maybe it would be helpful to put a historical rate in context. So typically at six weeks in an overweight patient population that's nondiabetic, what is the rates that we have seen for nausea, vomiting, and diarrhea? Well, there are a wide range of data, Yasmin. It depends on how the study is conducted with titration, without titration, and the dose and the like. The rates have ranged widely between twenty and forty percent or higher, forty five percent even approaching fifty percent. With the predominant or average rates of nausea in the study usually in the 30s and sometimes 40s. But again, it depends on the duration of the study. Thank you Scott. Then one last question. What is the rationale for moving the doses higher? So, you're getting really phenomenal weight loss at, the highest dose. If you could just provide a little bit color of how high of a dosing range you're planning to go in future studies, then that would be helpful. I'll turn Before it back into the we start the study, we did pharmacomimetic modeling in order to estimate our dose range. And quite frankly, we were approximately right on target for that. So we think that the one point eight milligram dose, based not only in the modeling, the actual data, is probably the dose we will have going forward. And that's why we announced, this morning. However, there is an opportunity to explore the characteristics and attributes of the drug in terms of further weight loss levels at which we might have adverse events. We think that going forward in expanding studies to larger numbers of people with greater heterogeneity it would be valuable to have this data. Thank you so much and congrats again. Our next question is coming from the line of Seamus Fernandez with Guggenheim. Please proceed with your questions. Oh, great. Thanks for the questions, and and congrats on the the data, guys. So a a couple of things. First off, you know, just in terms of the the the actual dropout rate in the study, could you just maybe clarify? I mean, I would assume that the dropout rate was quite low, you know, given the small number of patients and the six week duration. But if you could just clarify the number of dropouts. You know, one other question. The analysis, was the analysis on an ITT basis? I assume that it's not on an ITT basis, but I just wanted you know, clarify that. And then, you know, you mentioned the three percent was achieved, I believe, in all but one patient in the press release at the high dose. Just hoping that, you know, in terms of the directionality, so if you look at the weight loss curves at six weeks, you know, what was the frequency of measures? You know, do you just have measures at, you know, every two weeks, or was it every week? And what does the curve look like at six weeks? Are we still seeing I assume we're still seeing evidence of continuing weight loss. If you were to predict, you know, using your PK analysis, what would be the hope for weight loss, you know, at twelve weeks? It looks like we're on a very impressive path here. Right. Well, thanks, Seamus. The dropout data that I presented is all the data that I have right now. Obviously, this was conducted on an ITT basis. If there were dropouts, however, we did not impute data. So if there was if somebody dropped out and I know that one dropout occurred because someone had to go back to work, for example, that we didn't use that weight loss data because it wouldn't make sense to impute missing data in a small study. So while it was intention to treat, the actual weight loss was based on the observed. But I don't think that the dropout data or the dropout rates really affected the messaging that we're giving today. Regarding the weight loss curves, they were continuous. Obviously everyone is interested in knowing how they project, and these curves suggested continued weight loss. What I would emphasize is that the weight loss that is indicated at six weeks should project over the course of treatment, which in the real life world or in clinical trials would be towards fifty two weeks. And we believe that based on the six week data, we'll achieve levels of weight loss comparable, or at least it would if not better than the other drugs. But rather than trying to estimate a point at twelve weeks, I'd rather say that in terms of a more meaningful effect, which is the effect on weight loss with prolonged treatment, we think it's going to be highly impactful. Got it. And just maybe two last questions. As we think about the opportunity for a partner, Vipin, I think you have talked about this as a clear partnering opportunity with good weight loss data. Just wondering if given the robustness of these data, your bias is to, you know, partner a little bit later rather than sooner, you know, to kind of capture some of that incremental value. But obviously, there's these aren't, you know, particularly cheap programs to execute. So just wondering how you're thinking about the partnering opportunity and some of the timing dynamics. Thanks. Yes. Thanks, Seamus. Well, look, it's hard to speculate on that at this stage of the game. I mean, we continue to generate data. Of course, we will look at any partnership opportunities as they emerge. We know that there's a lot of interest in this class of compounds. Multiple companies have had such programs internally. Many of them still do. And there is, you know, room for multiple products in this category. So this is, to me, this is a mega blockbuster class. And if our data continues to look good as we do the twelve week data, we do the NAFLD study and the biopsy study next year, we think all of that is going to increase the value of this program. So I would say we are very excited about it. And we think potential strategic partners will also be very excited about this data. So we'll keep you posted. As things develop, it's hard to speculate right now. But obviously, we'll look at every opportunity to partner at the appropriate time. Okay. And then maybe just one last question. Would you should we expect to see these data, the six week data at EASD or another obesity medical conference the next few months? Just when might we see the full dataset presented? Think Yeah, I'll let Scott answer that question. I would just say that we would probably want to wait for the entire twelve week data and really present that in a more holistic way as opposed to just six week data. Scott, take it away. Yes, would agree with that answer, Vipin. And obviously, we'll present the data. We haven't chosen this point. Okay, great. Thank you. Our next question comes from the line of Kelsey Seychari with Jefferies. Please proceed with your question. Hello. Thank you for taking my questions, and congratulations on the data here. Just a couple of questions on my end. I guess, first, can you speak to the truth in the nausea rate going from the beginning of the trial to, I guess, at this particular point, six weeks? Did you see an improvement or a reduction in the incidence of nausea? Or any color around that would be great. And my second question is just related to given that this patient population appears to be on the younger side, does that influence the GI tolerability or the nausea rate at all in your view? Thank you. Hi, Fleshy. Thanks for the question. As previously discussed, the effects, the nausea and seen was early on. And we continue to get the impression from our study as with other GLP-one based compound studies that the nausea and vomiting, if they occur, would occur early on. The nausea that we observed was predominantly early nausea, right at the beginning of dosing. In terms of the younger age of the individuals and GI tolerability, that's a really good question. I don't have the specific answer for that. I can speculate as a gastroenterologist that, younger people actually have more intolerability. Just based on my clinical experience, but I think that's highly speculative. I think it's an excellent question. Got it. Got it. Okay. Thank you. Our next question is from the line of Lisa Bayko with Evercore. Please proceed with your question. Hi. Congratulations on the data, and thanks for taking my questions. Just to follow-up on a couple other questions I don't think were really actually answered. Discontinuations, what how many discontinuations were there, and how many of the one point eight mg dose? Lisa, I'm gonna have to get back to you on that data. I don't have it in front of me right now, and I will get that to you. But I don't have that data. I don't have numbers per se right now. But I would emphasize that it was not meaningful Okay. On the overall data. I just don't wanna be harping on exact numbers. But I would tell you overall that any number I provided, and I think it's quite small, it's not gonna impact the messaging from the call today. Okay. And, baseline BMI, I think you asked me and asked about that. Could you tell us about It's in the low thirties. Okay. Thank you. And then was there any exercise or other kind of background things? I know you have placebos that kinda helps you understand the relative, but just curious about sometimes with these single centers we've seen in other NASH studies that, like, you know, investigators are really into, like, diet and exercise. So just wondering what other kind of, you know, kind of treatments were going on in the background. Yeah. That's extremely that's extremely important. So as you know, in the, obesity trials that were done with semaglutide, they were done against a background of either diet and or exercise, diet meaning caloric restriction, restriction, and or exercise, and even behavioral modification. And that these impacted the overall amount of weight loss because it showed up in the placebo groups as much as 2%. We did not implement that in this study. So what you're seeing are raw weight loss weights without diet, that is caloric restriction or exercise or other lifestyle modification. Okay. Good. And you said, the GI talks typically, for GLP ones occurs in the first couple of weeks. Did you see that trend here too that the majority of the events that you saw were early on? Yes. That's the pattern that we observed. Great. Thanks. Our next question is from the line of Mayank Mamtani with B. Riley. Please proceed with your questions. Good morning team. Congrats on the strong early data on the dual agonist and thanks for taking our questions. So in follow-up to the prior discussions, I just wanted to also ask on maybe a few other non invasives that you may have looked at. I think you provided some color on the PDFF, for instance, you just didn't have that to start with in this population. Can you just maybe comment even other biomarkers like ALT or any fibrotic non bases you may have looked at, including on at baseline and as you're continuing to follow this at six weeks and twelve weeks? Any color on that would be helpful. Sure, thanks for the question. So this was aside from being overweight or obese, this was a healthy population. We did allow ALTs, mild elevations up to twofold, lower than you would typically see in a NASH trial. You know, we'll assess that, but we don't have that data, at this point. The important aspects of this study, Kolechi, are looking at things like lipid metabolism over twelve weeks, inflammatory markers. As you know, weight and obese people have elevated levels of inflammatory markers at baseline to see if that would go down. Measures of insulin resistance, glucose metabolism, and also measures such as adiponectin are being assessed in the trial as well as markers of glucagon metabolism. These are all being assessed. We will not have the risk results until we unblind the study at twelve weeks and have a full robust analysis. Got it. And then on the higher dose that that you're looking at, did you sorry if I missed the number. Like, what what what higher doses you are going up to? And and then just to clarify, you would be reporting on all these biomarkers in addition to, obviously, weight loss and GI when you, you know, you come out with a twelve week data in third quarter. Is that is that correct? Right. That is correct. And and specific higher dose, which, how how high are you going with with the Yeah. We haven't announced on that so far, but, you know, that data will be provided, when we unblind the study. Got it. And my final question maybe for Vipin. You clearly have a very well defined NASH next steps, development plan laid out, including the large but expensive fifty two week biopsy study. Do you also have a similar development plan that you're willing to talk about in obesity, just given the regulatory and commercial dynamics, you know, might be very different and maybe more attractive in obesity? Yeah. No. Absolutely right, Mayank. We have been thinking about that for quite some time now as more and more GLP-one mechanism based compounds are showing promise in obesity. And obviously, we know of the recent approval in obesity. So that path is sort of well laid out for us. Obviously, the first step for us is to file an IND, which we are preparing for now, and we'll file that obesity IND. And that would really begin the FDA discussion and sort of the regulatory path that we would have to follow in order to pursue the obesity indication. But we agree with you. There is a very attractive opportunity in obesity, and mechanism of action, you know, has already been demonstrated as validated for obesity indications. So we will share more details as that becomes more clear, the path. But we think that path for obesity could be even more faster than NASH, given the invasive biomarkers that at least one has to focus on endpoints that one has to focus on at the moment that might change in the future. But we're looking at obesity indication as a very attractive opportunity. Excellent. Thanks so much for taking my question and looking forward to the add COVID update at the end of the month. Absolutely. Our next question is from the line of John Wolleman with JMP Securities. Hey, good morning and congrats on the data. I might have missed this earlier, but I'm just wondering if there was any nausea observed in the placebo arm. No. There was no nausea, Jonathan, observed in the placebo arm. And when we're thinking about next steps in subsequent studies, are you comfortable with the rates and the characteristics of the nausea you're seeing at the one point eight mg dose? Or would you want to implement a titration strategy to even knock it down further? Just wondering how you're thinking about that as a differentiator against, the field. Well, the differentiator against the field is clearly the fact that we didn't have to dose titrate to get to those adverse event rates which are impressive. You know, these adverse events, the drug was given without dose titration. And, you know, the importance of dose titration to patients and not having to do it not only in terms of inconvenience but, the, ability to achieve weight loss, even faster which is extremely important for compliance and acceptability. So we really want to highlight the absence of dose titration in this study, the low adverse event rates because of this. And we are considering the possibility of dose titration. Obviously, we considered that before we started the trial. Results that we're reporting out on right now is with straight dosing. Which we believe is the dose that we have. We believe that we've captured a viable dose, which is one point eight milligrams straight to dosing to take forward going into future studies. That's helpful. One last one for me. The release this morning mentioned expanding the enrollment criteria. And I just wanted to be clear. Does that how are you expanding the enrollment criteria? And then does that mean that we will see liver fat data in the update in 3Q? Or will that not be until the next Phase 1b study where you'll be including diabetics as well? There's not enough patients with high enough MRI PDFF to have a meaningful analysis of that data in the current study. So that's why we planned another study. And by including diabetics we'll not only be including that, the diabetics tend to be older. And we think that the availability and the COVID situation, which has improved greatly in The US, will allow us now to get these, older people. So the primary expansion, Jonathan, is age and the allowance of diabetics. And clearly the incidence of fatty liver is much greater in older people and diabetics. And that's why we didn't have enough patients with high enough MRR PDFF to do an analysis in this study. Got it. Perfect. Thanks for taking the questions and congrats again. Thank you. Our next question is from the line of Patrick Trucchio with H. C. Wainwright. Please proceed with your questions. Hi, thanks. Good morning and congrats on the data. I just have a quick follow-up. So ALT-eight zero one appears on track to demonstrate weight loss that's highly competitive with the competing GLP-one agonist. And I'm wondering if it's a function of the bias towards GLP receptor affinity versus glucagon receptor agonism. Are there other aspects of the mechanism that are contributing to the apparent improvement efficacy in combination with this lower burden of GI side effects that were demonstrated after six weeks? Yes, hi Patrick. We will sort that out when we unblind the study. We're obviously looking at calorie counts. And we'll also do some markers of resting energy expenditure to allow us to look at the rate of energy burn. Based on the animal data from the studies that we've discussed previously, about two thirds of the effects in weight loss, and this was a rodent study, were due to the glucagon component. Now if that translates to human, that would mean that most of the weight loss that we're seeing in these patients is due to the vabucagon effect. And that would make sense because of the low incidence of adverse events which track more closely to the GLP-1s. That's why we're able to separate out the weight loss and the adverse events by having more of the glucagon effects. We don't have that data right now. We hope based on the analyses that I've talked about to have that data when the final results are discussed. Yep, that's helpful. And then just in terms of the clinical development path in obesity versus NASH, I'm just wondering if it would be possible for perhaps the obesity program to advance quicker than the NASH program. Just, you know, kind of given the precedent with some of these other GLP-one agonists in obesity and then some of the other programs in NASH. You know, that's a hard one to call. What I would point out is that obesity trials are not driven by biopsies. The inclusion criteria are somewhat more relaxed but also perhaps more cumbersome because of the comorbidities of the population. I think the important point to emphasize is that there's been a shift in the certainty around or the risk around the regulatory pathways in the last couple of years. When we initiated the development of ALT-eight zero one, our impression was that NASH was a more secure regulatory pathway in the obesity space, was stigmatized by older compounds, it's usually in catecholamine mechanisms, with adverse events and very ineffective weight loss. And many dropouts in the field despite approval. In the last year and a half to two years, that VISTA has really changed. We've seen the complete response letter that INTERCEPT got and the need for surrogate endpoints and the like. And in the meantime, we see the compounds in the GLP-one space forging ahead with great weight loss data, which is going to create very interesting conversations with the agency. And you saw just last week semaglutide got approved without a complete response letter. So the regulatory space is really clearly shifting in risk, less risk in the obesity space compared to the NASH space. I don't want to comment on the speed of the trials and the enrollment. But what I would say is that one has to look at obesity now as a very attractive space to be in. Perhaps more attractive than NASH. Our strategy is to co develop with filing INDs in both to provide two shots in goal. And as we've talked about repeatedly, ALT-eight zero one is a platform and a drug. It gives us multiple, multibillion shaw dollar shots on goal. Yep. That's really helpful. Thank you very much. Thank you. At this time, I will turn the floor back to management for further remarks. Well, thank you, everyone, for participating today. Have a nice day. We'll look forward to updating you further on our progress. Thank you. Thank you. This will conclude today's conference. You may disconnect your lines at this time. Thank you for your participation.