Altimmune, Inc. Q2 FY2021 Earnings Call

Good day, ladies and gentlemen. And welcome to the Altimmune Incorporated Q2 Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time. If anyone should require operator assistance, please press *, then 0 key on your touchtone telephone. As a reminder, this call may be recorded. I would now like to introduce your host for today's conference, Will Brown, Chief Financial Officer of Altimmune. Will, you may begin.

Thank you, Operator. And good morning, everyone. Thank you for participating in Altimmune's Second Quarter 2021 Earnings Conference Call. Leading the call today will be Vipin Garg, our Chief Executive Officer. I will also be presenting during the call, as well as Scot Roberts, our Chief Scientific Officer, and Scott Harris, our Chief Medical Officer. Following the prepared remarks, we will hold a question-and-answer session. A press release with our Second Quarter 2021 financial results was issued last night and can be found on the Investor Relations section of the Company's website. Before we begin, I would 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. All caution 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-19 and its impact on our business operations, clinical trials and results of operations. For a discussion of some of these 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. I would also direct you to read the forward-looking statement disclaimer in our earnings press release issued yesterday and now available on our website. Any statements made on this conference call speak only as of today's date, Wednesday, August 11, 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 Dr. Vipin Garg, Chief Executive Officer of Altimmune.

Thank you, Will. And good morning, everyone. We appreciate you joining us today for a discussion of our Second Quarter 2021 financial results and business update. I want to begin today's call by thanking our employees, our collaborators, and our investors for the tremendous dedication and support they have shown to Altimmune over the last 18 months. In January 2020, upon studying the emerging reports of the devastating COVID-19 virus, our R&D team sprang into action in our labs and began creating a COVID-19 vaccine based on our intranasal platform technology. Our encouraging data from our Phase 2 clinical trials with NasoVAX gave us confidence that an intranasal vaccine could be effective in protecting individuals against this new respiratory virus. Through the most uncertain days of the pandemic and quarantine, our employees and collaborators answered the call to this global crisis with extreme dedication to the task at hand, which came with tremendous personal sacrifice of time with family and loved ones. I was proud and inspired by their resilience and results. Through this work, our confidence was bolstered that AdCOVID could have great potential as a new mucosal vaccine. As we gathered positive animal data, including a potent induction of local mucosal and systemic immune responses, we demonstrated efficacy against the SARS-CoV-2 virus. However, far too many times in our business, we see product candidates that work extremely well in animals, but do not translate to humans. Unfortunately, that was our experience. We were extremely disappointed by the Phase 1 AdCOVID data, and we had to take an honest look at the viability of continuing experiments and clinical tests at a time when the mRNA and other vaccine approaches were working so well. The efficient vaccine rollout and uptake by the general public is a remarkable achievement in the history of vaccine development. We applaud the efforts of the global pharmaceutical community in swiftly developing these new vaccines. With this backdrop of success and always seeking to be good stewards of the resources entrusted to us, we made the swift decision to terminate the AdCOVID program. As you have heard us say many times, one of the central tenets of our philosophy is to maintain and develop a diversified portfolio of assets to ensure that we are positioned for success, no matter what transpires with any one of our product candidates. That philosophy has served us well in 2021 with the clinical development of ALT-801, our GLP-1 glucagon dual-agonist for the treatment of obesity and NASH. As Scott Harris will more fully describe, we observed significant weight loss in just six weeks in our Phase 1 study with no serious gastrointestinal side effects. This fuels our enthusiasm and excitement for ALT-801, especially in light of the recent successful commercial launch of semaglutide for the treatment of obesity. It's further encouraging to compare our six-week interim results against other Phase 1 clinical trials with similar agents, noting that we are at the top of the class in terms of weight loss and tolerability at six weeks, and without the need for dose titration. With this data, we gain the confidence to launch an additional program with ALT-801 in obesity. We expect to file an IND in the Fourth Quarter to enable a Phase 2 trial in obesity, which will follow our previously announced IND for NASH in the Third Quarter. For the remainder of 2021, we look ahead to our Phase 1 ALT-801 twelve-week data from Australia, which we anticipate reporting in September. Following this trial, there are several studies to further explore the effects of our drug in nonalcoholic fatty liver disease (NAFLD) and diabetic subjects, along with a study to test the interaction of ALT-801 with drugs commonly administered to obese and diabetic subjects. These studies will enable meaningful Phase 2 trials in both NASH and obesity, with large studies planned to begin in early 2022. Our other assets within the delivered spaces, HepTcell, an immunotherapeutic for chronic hepatitis B, that is in Phase 2 development. We have HepTcell, one of the most clinically advanced immunotherapy candidates, and we are in the midst of executing on this international trial. Currently, we have sites in Canada, the U.S., Germany, and Spain to follow patients in a six-month dosing regimen. Considering the time to enroll HBV patients in this COVID environment and the duration of dosing, we expect to have data in the second half of next year. So, in Q3 2021, we'll now turn the page to the next chapter of Altimmune. With our focus formerly on obesity, NASH, and chronic hepatitis B, we have exciting drug candidates and an enviable cash position with which we can quickly advance through several near-term data catalysts. With that, I'll now turn the call over to Scott Harris to discuss our six-week data, the upcoming twelve-week data readout, and subsequent advanced trials.

Thank you, Vipin. And good morning, everyone. During June, we shared results from our six-week interim analysis of two cohorts from the ongoing twelve-week Phase 1 placebo-controlled single and multiple ascending dose study of ALT-801. The study is being conducted in Australia and is enrolling overweight and obese volunteers. We reported two dose levels, 1.2 and 1.8 milligrams, that were administered subcutaneously once a week for six weeks. The six-week data reported weight loss and adverse events. The results we observed were very encouraging and exceeded our pre-established treatment target of 2% absolute weight loss at six weeks. Employing a 1.8 milligram subcutaneous, once weekly dose, we achieved a placebo-adjusted mean weight loss of 6.3% in just six weeks of treatment with ALT-801. During the six weeks, ALT-801 was well tolerated with low rates of nausea and other gastrointestinal side effects. Importantly, there were no patient dropouts at the 1.8 milligram dose level, and the one patient at the 1.2 milligram dose that dropped out did so for reasons unrelated to the drug. This is particularly remarkable, given the fact that we administered ALT-801 without the use of dose titration, which is the practice with virtually all other agents in the class, including the recently launched Wegovy. Gastrointestinal adverse events have required these other GLP-1 based candidates to dose titrate to achieve the therapeutic dose only after slowly increasing the doses over 16 to 20 weeks to maintain adequate tolerability. While the six-week data focused on weight loss and adverse events, we will certainly report these measures with the twelve-week data, and we plan to also report data on a number of other measures, namely pharmacokinetics, lean body mass, caloric intake, resting energy expenditure, glucose homeostasis, insulin resistance, lipids, and inflammatory markers. We believe that the 1.8 milligram dose is likely the level at which we show the most attractive combination of efficacy, safety, and tolerability. However, we are testing higher dose cohorts in the ongoing trial and, today, we announced that we will be reporting twelve-week dosing results for the 1.2 milligram, 1.8 milligram, and 2.4 milligram dose levels. We recently completed dosing in these groups and will take approximately four weeks to analyze and report the data. Accordingly, we expect to report the twelve-week data on these cohorts in September, and we look forward to sharing this data with you. Looking ahead to further development, we are planning three additional trials to initiate this year. These trials are designed to address key questions regarding the activity of ALT-801 early in its development. First, we're in the process of filing the ALT-801 IND for NASH to conduct a twelve-week Phase 1b study of subjects with non-alcoholic fatty liver disease or NAFLD in the United States. This study will expand the enrollment criteria used in the aforementioned first-in-human study in Australia to include diabetic and older subjects, and will commence around the end of September. Based on the relationship between weight loss and liver fat reduction observed in other GLP-1 based studies and the additive effects of glucagon on liver fat metabolism, we are optimistic that ALT-801 will be an effective therapeutic agent for NASH and that the reduction in liver fat in the planned twelve-week NAFLD study will parallel the impressive weight loss that we have observed. Second, we are planning to initiate a dedicated type-2 diabetes trial to study glucose homeostasis in diabetics in Q4 2021. The study will be twelve weeks in duration and will study endpoints that will include continuous glucose monitoring, hemoglobin A1C, and measures of insulin resistance. We expect the observations of glucose control in our current Australian twelve-week study to hold true for the type-2 diabetes population as overweight and obese subjects like the patients currently enrolled typically exhibit insulin resistance or pre-diabetes. Since later-stage NASH and obesity trials will likely include type-2 diabetics, we want to establish this inclusivity. Finally, we're planning to initiate a drug-drug interaction trial. The FDA expects sponsors of GLP-1 based compounds to conduct studies evaluating the impact of alterations of gastric emptying on the kinetics of drug absorption. GLP-1 based compounds with extended half-lives like ALT-801 have not been associated with these changes. As previously announced, we plan to file our second IND for ALT-801 in obesity during the Fourth Quarter to create a parallel development plan to our ongoing NASH development. This IND, and the aforementioned trials, will enable significant Phase 2 clinical development during 2022. At this time, we're planning a Phase 2 obesity study along with a Phase 2, 52-week biopsy-driven NASH study, which could start in the First Quarter of 2022. We look forward to updating you on our Phase 2 plans later this year. ALT-801 is currently administered as a subcutaneous injection. Our development planning includes the use of an auto-injector that can be self-administered by patients, and work is progressing on that front. Equally important, we have initiated development of an oral formulation for ALT-801. I'll turn it over to Scot Roberts, our Chief Scientific Officer, for that discussion.

Thank you, Scott. One of the advantages we have with a molecule like ALT-801 is that it is an attractive candidate for oral formulation. Several of the GLP-1 based drugs currently in development are not suitable for oral formulation, owing to their large size. As ALT-801 is structurally similar to semaglutide, which has been successfully formulated for oral administration, we are optimistic about the eventual success of an ALT-801 oral formulation. We view an oral formulation of ALT-801 similarly to our improved tolerability profile and our ability to bypass protracted dose titration. These advantages could increase patient interest and compliance. We look forward to updating you on our progress towards this endeavor in the near future. Finally, I would also like to provide a brief update on our chronic toxicology studies designed to support our longer-term obesity and NASH efficacy studies. The studies are progressing well, with overall observations consistent with the earlier shorter-duration studies. We expect these studies to be completed in the Fourth Quarter to support the Phase 2 obesity and NASH trials planned for 2022. I will now hand the call over to Will Brown to give an update on our Second Quarter financial results.

Thank you, Scott. For today's call, I will be providing a brief update on Altimmune's Second Quarter 2021 financial and operating results. More comprehensive information can be found in our Form 10-Q filed with the SEC last night. Altimmune ended the second quarter with a strong cash position, reporting a balance of approximately $218 million in cash, cash equivalents, and short-term investments compared to $216 million at the end of 2020. The increase in our net cash during the current period is attributable to $52.4 million in net receipts during the year, primarily due to our utilization of the at-the-market offering program, offset by cash used for operating and investing activities. With these resources and the termination of the AdCOVID vaccine program, we have sufficient cash to operate into 2023. Turning to the income statement, revenue in the second quarter was $137,000, compared to $720,000 in the second quarter of 2020. The change in revenue between periods is primarily due to a decrease in BARDA revenue, as we wind up activities under the current NasoShield contract. Revenue attributable to the T-COVID program was completely recognized as of the end of Q1, and we are currently collecting the related accounts receivable as we complete the activities under that contract. Research and development expenses were $13.3 million in the second quarter compared to $16.6 million in the prior period. The change in R&D expense was primarily the result of $13 million in higher non-cash charges in the prior period related to changes in the fair value of continued consideration liability connected with the acquisition and development of ALT-801. This was offset by an increase of $10 million related to development activities for AdCOVID and other programs. General and administrative expenses were $3.7 million in the second quarter of 2021, compared to $2.5 million in the prior period primarily due to increased stock compensation expense and additional labor-related costs. We recognized approximately an $8 million impairment loss on construction during the second quarter, which represents an impairment charge recorded for assets previously capitalized in connection with the manufacturing suite under construction at Lonza. We have not yet terminated that contract, and we are currently evaluating our options with respect to the space. Net loss for the 3 months ended June 30, 2021, was $24.8 million or $0.60 net loss per share compared to $16.8 million or $0.94 net loss per share for the second quarter of 2020. The difference in net loss is primarily attributable to higher R&D impairment and G&A expenses. I will now turn it back over to Vipin for his closing remarks.

Thank you, Will. Operator, that concludes our formal remarks, and we would like to open the lines to take questions. Could you please instruct the audience on the Q&A procedure.

Your first question will come from the line of Seamus Fernandez with Guggenheim.

Great. Thanks so much for the questions. So I appreciate the update as it relates to the plans for the obviously historical program now for vaccine perspective. As you guys pivot to driving the Company towards being a metabolic disease Company, we've obviously seen the robust performance at six weeks. I think it would be helpful to just understand what you're hoping to see specifically in the twelve-week data. And then in terms of the 2.4-milligram dose, I think that's right in line with our expectations for where you would increase the dose to. Again, I think in most cases, the increase in a dose would be 30% to 50%. So right in line with expectations. But how should we think about the relative opportunity for the 2.4-milligram dose? Is this really an exploration of the upper dose range more than anything? Or is it your hope that you could see incremental weight loss above and beyond what we've already seen at the six weeks with the 1.8-milligram dose? Or is your expectation to really see more of a trade-off of tolerability, given the contributions of GLP-1 to the mechanism? And then I have a follow-up question on your oral approach relative to that kind of technology that's necessary to deliver a peptide orally.

Absolutely. Well, thank you, Seamus. Scott Harris, do you want to take that?

Good morning, Seamus. Our expectation for the twelve-week data is that we'll continue to see a strong trend in weight loss. We haven't picked an actual number. I think the most important number is what we achieved, say at 40 to 52 weeks. We did a post on our corporate website the individual responses, which show the trends in the dosing. So we would project that those trends would continue through twelve weeks, which would signify those trends would probably continue to week 52. That would be our expectation. We will also, as you know, have much more data that will be more mechanistic, such as calorie intake, resting energy expenditure, and lean body mass, as well as glucose homeostasis that will not only project the efficacy of the compound but really understand it, and understand what we're achieving with dosing. Regarding the 2.4-milligram dose, as you know, the results that we achieved with 1.8 milligrams, which is less than 2.4, we're already, in our opinion, spectacular. It really didn't leave much to gain by dosing higher in terms of more weight loss. As we announced, the primary reason to dose higher was to establish the dose range within which we could work. As you go to Phase 2, you don't want to have Phase 1 obligations and if for whatever reason, we hadn’t dosed higher and decided to go to that dose later, we'd have to go back to do another Phase 1 study or make a Phase 2 study look like a Phase 1. I think what we're really shooting for is greater tolerability, excuse me, the range of tolerability, and the accepted safety range, rather than achieving higher weight loss. If we achieve higher weight loss, that would be great, but it would be hard to believe that we can achieve much higher weight loss than we got with 1.8 milligrams.

And just, I guess, on the oral, the technology that would need to be employed or can be employed to deliver this peptide technology, just hoping to get a better understanding of that. I think to our understanding, the technology is now 100% owned by Novo Nordisk. And it was only a single amino acid change between liraglutide and semaglutide that actually allowed for that product to be delivered, and bioavailability, I think, is still to some question for those products. Just love to know the technical approach that you're taking and if you've licensed any technology to be able to do that? And if so, if you wouldn't mind disclosing which technology that is? Thank you.

Scot Roberts.

Sure. Hey, Seamus. So one of the things that we saw right off when we were acquiring ALT-801 was its potential suitability for oral formulations. And with the six-week data validating the potency of this for our compound for weight loss and presumably mobilizing fat out delivers, we'll see in the NAFLD study. I think that that only becomes more important and more real for us. So we're very excited about this project. At a general level, the hurdles that have to be surrounded by anybody who is trying to make a peptide orally, is to get it through the stomach first of all and protect it from proteases. Then essentially, you need to create a lipophilic environment for the peptide so that it can then cross the cell membrane in the intestine and enter the bloodstream and do its work there. So there are a number of approaches, obviously, Novo Nordisk has used specific technologies to achieve this. I'm not going to go into a lot of detail about the approaches that we're looking at here; we'll update you in the future. But suffice it to say that the similarity of our molecule to semaglutide, which is a small lipid-filled chain, leads us to believe that we have a high likelihood of success here. So we look forward to updating you on that in the near future.

Great.

And Seamus just adds that yes, indeed, we are looking at a proprietary technology to make this work. But at this point, we'll disclose it at the appropriate time later on.

Okay. Great. I'll jump back in the queue out of respect for the other analysts on the call.

Your next question will come from the line of Yasmeen Rahimi with Piper Sandler.

Hi team, thank you for addressing my questions and for the updates. To start, could you provide some insight into the number of patients per cohort for the data we should expect? I reviewed your corporate deck, which mentions the obesity study involving a hundred patients, showing weight loss among the nine patients in the 1.8 milligram cohort and four in placebo. As we approach September, could you clarify how many patients are in placebo and how many are part of the three-dose cohorts? That information would be very useful. I also have two follow-up questions.

Right. Hey, Yasmeen. Good morning. We are enrolling 10 to 15 per cohort. The randomization ratio between those who receive ALT-801 and those who receive placebo is 4-1. It obviously varies a bit between cohorts, but that will be the general advice that we were given.

Okay, another question for you is around expectations and weight loss going into week 12. When we look at historical data comparing weight loss in an overweight population that is non-diabetic, you see the magnitude to be two-fold. I guess why can we not make the assumption? Maybe correct me if I’m wrong. You are getting 6% at week 6; should you be getting at least over 10% at week 12? And the significance of that, like is there a chance that that might not fall in and that there is not a linear relationship between week 6 and week 12. So if you could just comment on that, that would be helpful.

Right. So, I think the most important thing is that to the eye of the trends are continuing. If we focus on specific numbers, especially with small numbers, we may not really get the right impression. So I think the most important thing is that visually when you look at the data, you’re convinced that it’s linear, that it's continuing. And that we don't actually cite a specific number; and we think that that will be the right approach. I just don't want us to get hung up on a decimal place for success.

Thank you. Can you provide an update on the current discontinuation rates? I recall from your six weeks of data that there was one patient who discontinued. Are you able to share information on the discontinuation rate at this point?

Yes.

Your study?

We haven't been public on that, Yasmeen. We obviously will with the twelve-week data.

I want to understand the reasoning behind your plan to start a 52-week NASH study in the first quarter. Is the 52-week toxicity package complete, and what is its current status? This will help ensure you're ready to begin the 52-week data collection as soon as the IND is approved. I'm a bit unclear about this.

So let's go through the timeline quickly. The IND for NASH will be filed imminently. As Scott mentioned during his presentation, we have completed chronic toxicology up to thirteen weeks that enables our twelve weeks of dosing. We are in the process of completing the chronic rat and cyano toxicology that will enable a long-term NASH studies. So that will be completed later this year, well in advance. That toxicology study will be completed later this year well in advance of either a 52-week NASH trial or a long-term obesity trial. So there is a comfortable timeline there that we feel comfortable about hitting.

Thanks. I will jump into the queue. Thanks.

Your next question will come from the line of Kelechi Chikere with Jefferies.

Good morning, and thank you. Just two questions on my end, I guess, based on the current preclinical and clinical data, is your expectation that you would use the same dose in both NASH and obesity? Just trying to get a sense of that, given that the glucagon component of ALT-801 has beneficial effects on the liver. So, just trying to determine there what the dose could potentially be.

Right. So the initial answer to that question, Kelechi, would be yes. We do expect the doses to be similar, but you brought up a good point that glucagon has independent effects on weight loss. So potentially, the dose in NASH could be lower, but recognize that when you're treating NASH, you're not just treating the liver, you're treating the whole patient. So we would think that we would try to administer doses to NASH patients that would not only achieve optimal fat reduction in the liver but also optimal weight loss because of the non-hepatic comorbidities.

Got it. Thank you. That's very helpful. And I guess my second question, big picture, wanted to get your latest thoughts on the development and potential commercialization of ALT-801 in these two large indications, I guess particularly as it relates to partnering. Is that a possibility? Are you having those discussions right now? And based on those discussions, if you're having them, do you have a sense of the type of data partners are hoping to see?

Hey Kelechi, this is Vipin. Yeah, so, in terms of thinking long-term strategically, as you can see the kind of trials that we're designing, our goal is to answer as many critical questions as possible. The idea really is to build significant value in this asset quickly. At this point, we just have Phase 1 data from six weeks; obviously, twelve-week data is important, but then we've designed a number of studies that will answer some critical questions. One thing we do know is that there is significant interest in assets like this from large players, from strategic partners. I can name a dozen companies that would be interested in this. So at this point, we're keeping all our options open. We are in a good position to execute this plan. We've got a lot of optionality and we will continue to monitor the situation. Our goal is to increase the value of this asset over the next 12 to 18 months, and as more data becomes available, there is no doubt that they would be interested in an asset like this from multiple players.

Got it. That's very helpful. Thank you.

Your next question will come from the line of Mayank with B. Riley Securities.

Thank you. Good morning, team. Thanks for taking our question. I appreciate the resilience and a data-driven approach to advancing your pipeline. Regarding the ALT-801 program, could you comment on whether there was a planned look for the six-week, 2.4 milligram dose level, or are you just proceeding to the twelve-week without any interim analysis?

Right. Mike, there was no interim analysis on the six-week interim and the 2.4 milligram dose.

I understand. Regarding the expectations for the twelve-week NASH study, what can we learn from these twelve-week obese nondiabetic patients based on their baseline liver fat content or liver enzymes? Should we anticipate gaining insights from the refract during this twelve-week readout in September?

I'll start by saying that we believe the results from this study will be applicable to other populations. Based on the patient profiles, including their age and BMI, we know that these factors correlate with positive outcomes in the semaglutide trials over the long term. However, we did not measure liver fat content in this trial, so I can't comment on that aspect. Additionally, since this is not a NASH population, I wouldn't anticipate sufficient baseline ALT elevations to provide any insights that would predict outcomes in NASH. I believe that the weight loss we are observing will be beneficial on its own, independent of any specific analysis of liver fat. Based on existing studies, a weight loss of around 10% could positively impact NASH, and achieving that weight loss could occur faster than initially expected.

Great. And then just on the preclinical toxicology work that is going on, particularly for the INDs, the two more visible INDs and then maybe for the oral GLP-1. Could you just comment on what might be the requirements here that are different for NASH versus obesity?

There are two questions here. First, the toxicology work we are currently conducting will support both the NASH program and the NASH IND, and the NASH IND will actually proceed ahead of the toxicology work based on previous studies. The chronic toxicology study will specifically facilitate the longer-term NASH and obesity trials, but will support both. Regarding the IND for the oral formulation, we have not gone public with that information. We are currently conducting studies to assess it, and once we receive specific guidance on when we can file an IND, we will inform you.

Yes. My apologies. This is too early to project in terms of when we might be going into IND on oral. We hope to update everybody on our progress with the oral ALT-801 by the end of the year, and based on that, we'll figure out what would be the timeline for filing an IND and update folks accordingly.

Great. Do you have any initial thoughts on how you might approach managing the program internally versus outsourcing to an external partner, considering everything you've learned this year? With the different indications and formulations, capital investment will be necessary to achieve the best value. What aspects seem most appealing to you at this stage?

Yeah, that's a good question, Mayank. Obviously, first thing's first: we need to generate all the data that we're talking about. We are well-funded in terms of reaching all these milestones. And that data will really guide us should we proceed with obesity ahead of NASH, for instance. That question we will address right now. We think there is value in both of these indications. That's why we're pursuing them in parallel and generating all that data, which would be important for anybody to be able to value this program and make that determination as to whether we go after both of these indications or just one before the other, and so that's really the focus right now. But over time, as the data becomes available, we will certainly be able to make a call about which indication we pursue ahead of the other.

Great. Thanks for taking my questions.

Your next question comes from the line of Jon Wolleben with JMP Securities.

Good morning, and thanks for taking the questions. Just a couple from me. When we think about the twelve-week readout and the new biomarkers we'll be getting, I was hoping you could provide some color on which will be particularly informative and that could give more differentiation from ALT-801 versus the other GLP-1 candidates that we've seen?

Hey, Jon. This is Scott. Again, thanks for joining the call this morning. I think that all of the readouts will be informative. We recognize they're based on small numbers of subjects. So based on the amount of variability we've seen within each of the measurements, there will be a higher or lower contribution to the overall program. I think the things that we want to understand based on the readouts is glucose homeostasis, which is more for safety than for efficacy, but we want to make sure that we're not being disruptive to glucose metabolism. Obviously, if we see a beneficial effect, it will be very helpful. We've already talked about the fact that the best way to control diabetes over the long term is to lose weight, so we're optimistic that over the course of a year, we're going to have better control of diabetes, regardless of what we see in the beginning. But I would emphasize that we haven't seen any evidence of any loss of glucose control in healthy volunteers we're studying right now. Mechanistically, we'll look at insulin resistance, which will help us understand the changes in glucose homeostasis that we're seeing. We will get some mechanistic information that will help us look at the relative balance of the GLP-1 versus glucagon effects. I think all-in-all, all of them will probably give us a much better feel for the compound. What we're emphasizing here is that the primary readout of importance is going to be weight loss. I think that's what's really driving how we're going to apply the molecule, how we envision the molecule, and how we designed studies in the future.

Got it. And for the diabetic study. I know historically, we see differential weight loss responses in diabetics versus non-diabetics. Do you have any sense on what degree you might see a difference there, that's going to be in line with what we've seen historically? Or there might be some differential response based on ALT-801 activity or relative GLP-1 glucagon specificity?

That's a great question. Historically, if you take all the compounds, I'm talking about through the other GLP-1s, semaglutide and to some extent others, although it's early, you typically see about 60% of the weight loss in diabetics that you would see in non-diabetics. That would apply to those compounds which are predominantly GLP-1 based. Would that translate to the weight loss that we would see in diabetics with our molecule? We don't know. It's a different molecule. It's somewhat unique in that it's not only a GLP-1 glucagon co-agonist, it's a one-to-one. I think that, in terms of general description, yes, based on the literature, you'd expect to see less weight loss in diabetics, but we have a different compound. We're just going to have to see what we see in diabetics, and whether we get better weight loss than the other compounds that had previously been studied in diabetics.

And one more, if I may, just on the timing of data. The twelve-week Phase 1b in NAFLD patients. Do you want to see that data before starting the 52-week biopsy for any kind of information for design or inclusion criteria? Or when is that data going to come relative to the start of the 52-week studies?

We'll have that data before the start of the 52-week study; whether we wait for the full readout at twelve weeks or do an interim analysis to drive the decision-making, we'll have to make that decision. But right now, we could wait for that data, or we could take an interim cut to look at the data.

Got it. Thanks for the color.

At this time, there are no further questions. Do you have any closing remarks?

Yes. Thank you, everyone, for participating today. We appreciate the opportunity to share our results and outlook with you, and thank you for your continued interest. Have a nice day.

Ladies and gentlemen. Thank you for participating. You may now disconnect.