Altimmune, Inc. (ALT) on Q2 2022 Results - Earnings Call Transcript
Operator: Good day, ladies and gentlemen, and welcome to the Altimmune, Inc. Q2 Financial Results Conference all. 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. As a reminder, this call is being recorded. I would now like to introduce your host for todayâs conference call. Rich Eisenstadt, Chief Financial Officer of Altimmune. Richard you may begin.
Richard Eisenstadt: Thank you, Carlo and good morning, everyone. Thank you for participating in Altimmuneâs second quarter 2022 financial results conference call. Members of the Altimmune team joining me on the call today are Vipin Garg, our Chief Executive Officer, 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 2022 financial results was issued this morning and can be found on the Investor Relations section of the Companyâs 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. 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 the ongoing conflict in Ukraine, COVID-19, and the 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 Companyâs future results, please see the risk factors and other cautionary statements contained in the Companyâs filings with the SEC. I would also direct you to read the Forward-Looking Statement disclaimer in our earnings press release issued this morning and now available on our website. Any statements made on this conference call speak only as of todayâs date, Thursday, August 11, 2022. 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 todayâs date. As a reminder, this conference call is being recorded and will be available for audio replay on Altimmuneâs website. With that, I will now turn the call over to Dr. Vipin Garg, Chief Executive Officer of Altimmune.
Vipin Garg: Thank you Rich and good morning everyone. We appreciate you joining us today for a discussion of our second quarter 2022 financial results and business update. We continue to advance multiple clinical trials for our lead obesity product candidate Pemvidutide, a GLP-1 glucagon dual receptor agonists and are excited about reporting important data from these trials in the coming months. One thing that has become abundantly clear over the last 12-months is that we now have two truly effective drugs to combat the obesity epidemic and with promising additional drugs on the horizon. Given the increasingly competitive obesity space, it is important to highlight the potential differentiating features of Pemvidutide. First, we believe that we have the potential to achieve weight loss equal to or exceeding 20% after only 48-weeks of treatment, confirming the benefit of adding glucagon agonism to GLP-1 monotherapy. We also believe the robust reduction of serum lipids observed in our Phase 1 trial could translate into important cardiovascular benefits with long-term use, further increasing the value proposition of our drug candidate. Finally, we believe that the absence of dose titration will be viewed as a major advantage in the minds of prescribers and patients, simplifying management by avoiding the cumbersome use of dose titration over the first four-months to five-months of therapy. We are planning to announce the top line data readout on our Phase 1b multicenter trial in subjects with obesity or overweight and non-alcoholic fatty liver disease, or NAFLD in mid September. The key readouts will include assessment of liver fat, weight loss, serum lipids, and safety at 12-weeks of treatment. Scott Harris will join us shortly to discuss our expectations for that readout. In addition, we are currently executing a 12-week double blind, placebo controlled extension to this trial, and expect data readout after 24-weeks of treatment in Q4 2022. We believe that the 24-week readout will provide valuable information about the weight loss that could be achieved with Pemvidutide at one year of treatment. Our 48-week, Phase 2 momentum trial of Pemvidutide in subject with obesity and overweight is enrolling rapidly. Approximately 25 obesity study centers are now enrolling in the trial across the United States. As of yesterday, August 10th, we had randomized 167 subjects, and we expect to fully enroll the 320 subject trial population by the end of this third quarter. The 24-week interim analysis, which was initially planned at year-end 2022 is now planned for Q1 2023 when we expect that approximately 50% of the subjects have been treated for 24-weeks. We believe the interim readout on 50% of the subjects in our trial would provide a more meaningful and robust data set in our evaluation of Pemvidutide. Scott Harris will talk more about the MOMENTUM trials shortly. A 12-week Phase 1b Multicenter trial in Type 2 diabetics is also ongoing. And we expect this drug to provide important information on parameters of glucose control, such as hemoglobin A1c in subjects with obesity and overweight who have Type 2 diabetes. Finally, we are continuing to enroll in our Phase 2 Multicenter trial of HepTcell in subjects with inactive Chronic Hepatitis B and expect to have a data readout in the second half of 2023. We are excited about the progress of Pemvidutide and HepTcell and the upcoming results of these ongoing trials. With that I would now turn the call over to our Chief Medical Officers, Dr. Scott Harris to discuss our data and clinical plans. Scott.
Scott Harris: Thank you Vipin and good morning everyone. First, let me talk about our upcoming readout in our 12-week Phase 1b Multicenter trial of subjects with obesity or overweight and NAFLD in mid September. NAFLD in this trial was defined as a 10% or greater liver fat content as measured by MRI-PDFF. At the conclusion of enrollment, the trial randomized and dose 94 subjects who are randomized one-to-one to one-to-one to 1.2 milligrams, 1.8 milligrams, 2.4 milligrams Pemvidutide or placebo over 12-weeks of treatment. Approximately 29% of the subjects participating in the trial have preexisting Type 2 diabetes. The primary endpoint of this trial is a reduction in liver fat by MRI-PDFF and a key secondary endpoint is weight loss at the end of 12-weeks of treatment. We will report consolidated and stratified data in these and other parameters for subjects with and without diabetes. The readout in September will also include the effects of Pemvidutide on serum lipids, laboratory parameters, including liver function tests and fasting glucose adverse events including adverse events leading to treatment discontinuation, hemoglobin A1c, heart rate and blood pressure. Based on an analysis of the pooled unblinded data, the average BMI of participants is approximately 36, with median weight approximately 101 kilograms, and the median age is approximately 49 years with approximately 50% of subjects - 53% of subjects being female. As you are aware, we are conducting a 12-week EXTENSION trial for participants who complete the initial 12-weeks of treatment, resulting in a total of 24-weeks of treatment. The EXTENSION trial is now fully enrolled, and we expect to read out on these results in Q4 2022. The principal readouts will be weight loss and the continued safety of Pemvidutide administration. The 24-week data may allow us to project the amount of weight loss that could be achieved by Pemvidutide at one year of treatment. Now, let me talk about the Phase 2 momentum trial of Pemvidutide in obesity. The trial is enrolling approximately 320 non-diabetic subjects with either obesity or overweight with at least one obesity related complication across approximately 25 obesity study centers in the United States. Subjects are being randomized one to one to one to one to receive either 1.2 milligrams, 1.8 milligrams, 2.4 milligrams Pemvidutide or placebo administered weekly for 48-weeks as an adjunct to diet and exercise. The primary endpoint of the momentum trial is the relative percent change in body weight in 48-weeks compared to baseline with additional readouts including metabolic and lipid profiles, cardiovascular measures and glucose homeostasis. Dr. Lou Aronne from Weill Cornell Medical College, a leading authority in obesity and clinical trials is serving as the principal investigator. As Vipin mentioned, enrollment in randomization are progressing rapidly. We now plan to perform an inner analysis to assess changes in body weight after 24-weeks of treatment on approximately 50% of expected study participants in Q1 of 2023. We are currently randomizing 25 subjects per week and expect to complete randomization of the full 320 study participants next month. We are also completing enrollment in our 12-week Phase 1 Multicenter trial, evaluating the effects of Pemvidutide on glucose and self control in subjects with Type 2 diabetes. Approximately 48 subjects are planned with readout expected in Q1 2023. Across the trials that I have described, we are rapidly building the safety profile of Pemvidutide with unblinded safety data accrued in over 200 subjects receiving one or more doses of Pemvidutide in clinical trials expected by year end 2022 and approximately 500 subjects by year end 2023. We are all aware of the recent interim readout on the (Ph) select cardiovascular outcomes trial. And like most of us who are following this study, we believe that a positive effect in cardiovascular outcomes will be demonstrated at the final readout. Following on this thought however, I would like to highlight the robust reductions in serum lipids demonstrated in our first-in-human clinical trial of Pemvidutide, where we achieve 20% to 30% reductions in total and LDL cholesterol within 12-weeks of Pemvidutide treatment. These lipid effects are expected to have important implications for cardiovascular disease, such as myocardial infarction, stroke and heart failure. And they compare quite favorably to the limited 3% reduction in total and LDL cholesterol. Total cholesterol and LDL levels observed in a in the Wi goV STEP 1 trial at 68-weeks. We believe the market effects on lipids that we demonstrated in our first-in-human trial speak directly to the superior effects of glucagon on hepatic concern lipids and support our belief that we will achieve more rapid and pronounced outcomes when cardiovascular outcomes trials would Pemvidutide are conducted. We are also making continued progress in the enrollment or our Phase 2 Multicenter clinical trial of HepTcell in subjects with inactive Chronic Hepatitis B and expect the results of this trial in the second half of 2023. Recall that the neurologic effects of HepTcell are being evaluated in chronically infected patients to enable the combination of HepTcell with novel direct acting antivirals as part of combination therapy for Chronic Hepatitis B. I will now hand the call over to Rich Eisenstadt to give an update on our first quarter financial results. Rich.
Richard Eisenstadt: Thank you, Scott and good morning again, everybody. For todayâs call, I will be providing a brief update on Altimmune second quarter 2022 financial results more comprehensive information will be available in our Form 10-Q to be filed with the SEC later today. Altimmune ended the second quarter of 2022 us approximately $184.8 million of cash, cash equivalents and short-term investments, compared to $190.3 million at the end of 2021. We drew down approximately $21.3 million in net proceeds off of our ATM during the three-months ended June 30, 2022 and had approximately $32.9 million in availability remaining under the ATM at June 30th. Turning to the income statement, revenue was minimal in the second quarter of 2022 compared to $100,000 in the same period in 2021. Our change in revenue for the quarter was primarily due to the discontinuation of development activities for our T-COVID and NasoShield programs. Research and development expenses were $16 million in the second quarter of 2022 compared to $13.3 million in the same period in 2021. Approximately $10.1 million of this total for the second quarter of 2022 was direct expenses for the conduct of our clinical programs, including $8.7 million in direct costs related to development activities for Pemvidutide and $1.4 million in direct costs related to development activities for HepTcell. Approximately $1.9 million of expense in the second quarter of 2022 was a non-cash expense associated with the achievement of the Phase 2 development milestone for Pemvidutide. General and administrative expenses were $4.4 million in the second quarter of 2022 as compared to $3.7 million in the same period in 2021. The increase year-over-year was primarily attributable to increased labor and labor related expenses, including stock compensation expense. Net loss for the three-months ended June 30, 2022, was $20.1 million or $0.42 net loss per share, compared to $24.8 million or $0.60 net loss per share for the second quarter of 2021. Our existing cash not only fully funds us through all of our ongoing clinical trials where we recurrently estimate that our cash is sufficient to allow us to operate into the second half of 2024. I will now turn back over to Vipin for his closing remarks. Vipin.
Vipin Garg: Thank you, Rich. 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?
Operator: Thank you. Our first question is from the line of Seamus Fernandez of Guggenheim. Your question please.
Seamus Fernandez: So just a couple of things on timelines and expectations, heading into the event. Obviously, you guys are making some very strong statements around what you believe Pemvidutide has the capability to do and incorporating that 20% target into the press release, Iâm sure has people paying attention. I wanted to just get a little bit of incremental color on your conviction around that 20% threshold. It would strike us that even if you were to achieve a high-teens number at 48-weeks that would still be approaching, if not still a best-in-class result relative to the current two assets. So, just wanted to get a better sense of what you guys - what raised your conviction to kind of put that - and really make such a strong statement. And again we can certainly see that, but I have to imagine that perhaps you are seeing something in the Phase 1 data to imply that things are going quite well. Separately, as we just kind of look at the updates on the timing dynamics. Where we saw some push out, I guess, can you talk to us and help us understand what the workup of the patients actually is. We actually think it is good that there is a healthy pace, but perhaps not too fast to the pace of patient enrollment. And while folks may be a little bit disappointed by the timing of the 24-week results. I was just hoping you could give us an update on the participation rate from patients going from the 12-week into the 24-week EXTENSION in the NAFLD study? And then just the last question the diabetes study. Can you just remind us what you are hoping to understand in the Phase 1 basically safety portion study in the diabetic patient population, is that purely drug, drug interaction work or is it possible that we could see treatment related effects in that patient population, just to kind of replicate the 29% of patients that are in NAFLD. I apologize for the series of questions, but just wanted to get those three things out there. Thanks.
Vipin Garg: Yes, absolutely. Good morning, Seamus. All great questions, there is a lot to unpack there. So let me just start with in terms of the magnitude of weight loss. As we have said all along, and we agree with you that it is not about just achieving a number, it is really looking at the entire package that you are bringing to the table. And we have been emphasizing that it is not just the weight loss, it is lack of dose titration, it is our serum lipid profile that we are seeing. So all of that will go into finally distinguishing or differentiating, Pemvidutide from the rest of the field. Based on what we have seen from our Phase 1 study in Australia, as you know, we were able to achieve approaching 8% to 10% weight loss in about 12-weeks. And when you compare that to other agents, it makes sense that we should be able to reach a number approaching 20% in 48-weeks, because we got all of this runway left for the for the drug to work. So that is really where that conviction is coming from. We are totally unblinded to the NAFLD Phase 1 study, so none of this is coming from that. But we continue to believe that Pemvidutide has the potential to be a highly differentiated product in this space. Your second question relates to - Scott, you want to take that?
Scot Roberts: Yes. Hey, Seamus good morning. So you had several parts of your question. And let me make sure I touch on all of them. And please interrupt me if I havenât. We are very confident about the rate of enrollment, we have a really great clinical operations group. We also have even more important than that some very, very experienced obesity study centers, they have conducted many trials through the years. More recently, some of them participated in this STEP or the SURMOUNT or the SURPASS trials. We have a lot of confidence in them. And based on that we are really confident about the quality of the data that we are generating that trial at a very nice rate. We havenât commented yet on the rollovers from the NAFLD 12-week study. To the 12-week EXTENSION, we will make that announcement in the fourth quarter. But we are very happy at this point at the rate of rollover. And finally, regarding your question of the diabetes study, recognize that there are only a limited number of subjects who are diabetic, who are participating in the 12-week NAFLD study, doing a committed diabetes studies allows us to increase those numbers, get more robust readouts, and also put some measures into that study that are considered to be more of an industry standard in assessing diabetic patients such as continuous glucose monitoring, that would be too difficult to incorporate into a NAFLD trial. I wanted to also just clarify on the statement that Vipin made that Vipin may have used the word that were unblinded, I want to make it clear that we are still blinded to the 12-week NAFLD data. So let me just make sure that clarification is heard. Thanks.
Seamus Fernandez: Great, thanks. I really appreciate that. And just on the diabetes study, can you guys clarify, did you increase the number of patients that are going to be participating in that diabetes study. And that is the reason that we are going to see those data in the first quarter of next year. And the reason is, is to ensure that you have more robust data or just has enrollments and a little bit more challenging in that study and maybe you could just help us understand why that might be some of that, and then I will drop back into queue.
Vipin Garg: Yes. I donât want to talk about our final enrollments, Seamus let me say, it is a combination of factors, we felt that we were much more comfortable announcing the first quarter, rather than the fourth quarter.
Seamus Fernandez: Okay. Got it.
Operator: Our next question is from the line of Yasmeen Rahimi from Piper Sandler. Go ahead with your question please.
Yasmeen Rahimi: Good morning team and thank you so much for taking my question and thanks for quite additional color presented in the press release and your prepared remarks. Few questions, Iâm going to go one-by-one. The first question I would like to understand. I know in the past, you guys have said that in NAFLD study, the target diabetic population was 50%. And now we are at about 29%. So obviously, with less number of insulin resistant patients in the study, it is going to influence the mean weight loss. So just kind of provide us some commentary on what your expectations are in the diabetic and non-diabetic population in this NAFLD study at a 12-week endpoint. So if you could address that first, and then I have couple little follow-up as well.
Scott Harris: Sure, very happy to address that Yasmeen. If you look at the natural depopulation in general, there are some studies out there that capture this. The rate of diabetics and the NAFLD depopulation is approximately 25%. It gets higher in the actual NASH population, but remember this was NAFLD population with some NASH patients, and not a committed NASH trial. When we saw our initial enrollment, it did look like 50% of subjects who were coming into the trial were diabetics. And that is what we had informed investors about. But actually, we came down to the expected number around 25% and in fact were 29%. So we think that we are right in-line with where we should be. Although the initial estimates were higher, we are where we should have landed. Regarding the mean weight loss, I would direct you to focus on the fact that we are reporting out the weight losses and the diabetics and non-diabetic separately, as well as the consolidated figure, I think that is the best way to understand the data, because they are separate populations. So as I mentioned in my remarks we will report the weight loss and other data in three subsets of patients or sets of patients. The first will be those who donât have diabetes, which would be a standard readout. The second would be those with diabetes and then finally, we will consolidate but we will allow everyone to see exactly what the separate effects are Pemvidutide to non-diabetics and diabetics, despite the ratios.
Yasmeen Rahimi: Thank you Scott. And then just with various analysts are maybe having different views on, what is the expected bar in this upcoming 12-week time point for NAFLD. Can you help us understand what is an acceptable range and weight loss in your view, that you think you hope to achieve, if you could, and Iâm sorry that I keep asking this, but we get this question quite a bit from our investors as we head into middle of September data. So just give us some color on what you are expecting in terms of an acceptable weight loss range?
Scot Roberts: Yes, I think that a nice starting point is to look at the TIRZEPATIDE or the semaglutide data in 12-weeks. Yasmeen. And realize that those were obesity trials conducted over a baseline of diet and exercise intervention. So that automatically gives you about 2% to work with even without drug effects. So when you look at the placebo adjusted semaglutide rate, it is 4% if you look at the TIRZEPATIDE rate, the placebo adjusted a 6%. Clearly to be interesting, I think we should be in that range. Although we think that we have properties with an emphasize with glucagon that even if we are kind of somewhere in that range and not exceeding it, I guess that is not our expectation. But, even if we are just in that ballpark given the other superior properties of Pemvidutide, the amazing lipid effects that we are seeing and also the absence of dose titration, we think that we are extremely competitive. We really are looking towards the safety of the compound in this readout, we think that that is as important as anything else to move forward. And then as you know, investors are looking at 12%, because they are interested in what is going to happen at 48-weeks. And I think that that is really what - we are trying to really understand what is going to happen at that point, certainly the 24-week data that we are going to generate in the fourth quarter with the extension of this trial is going to be extremely informative and certainly as interesting, if not more interesting than the 12-week readout.
Yasmeen Rahimi: Thank you, Scott. And then last question, can you really help us understand what type of safety data at your previous two - on blinded basis, as you know the safety data set is going to be critically important as we head into the September readout. Just the broad strokes, what are the type of things that you see on a blinded basis and if you could provide some commentary how satisfied you are with those with the things you are seeing would be great. And thank you and I will jump back into the queue?
Scot Roberts: Yes, thanks, Yasmeen. Well, it is well known that as a sponsor, being responsible for the safety study subjects were always alerted to panic values. That would be ALT elevations, glucose elevations, safety, severe adverse events, serious adverse events and the like. We donât see the aggregate data by treatment group, at least until the end of the study the same time you do. But you know, based on what we are getting the information that we are getting in the trial on those metrics which has been very, very happy so far. So I would say that based on that blinded understanding of the data, we are just extremely encouraged.
Yasmeen Rahimi: Excellent. Thank you.
Operator: Thank you. Our next question is from the line of Roger Song of Jefferies. Go ahead please.
Roger Song: Great. Thank you for taking the question. A couple of questions on this. So the first one maybe just be a little bit more specific, given you will have your Phase 2 obesity study readout after the Phase 1 NAFLD even the 24-week data so maybe just you can just contextualize this for us and investors how shall we make read throw from one to the other from NAFLD study to obesity given its slightly different population baseline characteristics, et cetera? Thank you.
Vipin Garg: Yes. So clearly, so you get to 24-weeks with NAFLD, you get an obesity readout. We are going to have to look at that population at 12-weeks and 24-weeks to see if there is any impact on preexisting liver fat on the weight loss. It is not something that has been well characterized in the literature, our initial impression is that there shouldnât be an effect. But we are just going to have to look at the data.
Scott Harris: And there are differences in trial design, obviously, you have already emphasized that point. But I want to reemphasize that the lack of diet and exercise from one study to the other that also has to be taken into account. But we will be able to sort through all of that once we have the data. I mean, there is no question that there would be some read through from one study to the other because these are these patients are also obese patients. So we are expecting to see significant weight loss in them both at 12-weeks and 24-weeks.
Roger Song: Okay, great. And again so for NAFLD understanding the primary endpoint, efficacy endpoint is the diversity reduction. Can you just provide some color around the expectation for the liver fat reduction given your Phase 2 when they have like a 90% plus liver fat reduction even at 60-weeks time point? Thank you.
Vipin Garg: So we are really impressed even though the numbers were small Roger, in that Phase 1 first-in-human trial. The effects are so consistent, it gave us a great deal of confidence in the readout. I think once again, the more liver fat reduction that you get, the greater the effects that you were going to see on NASH resolution and fibrosis improvement. Especially the speed with which we are seeing it, because as you recall, with a semaglutide trial, which did not have a significant effect on fibrosis improvement in their 72-week trial. The amount of liver fat they moved was very small, only about 34% at 24-weeks. And although they had 50%, at the end of the year, the speed was not enough to see within that same time period of one year moving and fibrosis. We are seeing very robust effects and only six-weeks. If you place it against other drugs in the class, we saw the FXRS coming in and that 40% range. We saw magical the Resmetirom thyroid agonist coming in at about 50%. We are seeing the FGF21 coming in about 60% to 70%. We like to believe that we are going to be as good if not better than those drugs.
Roger Song: Excellent. Thanks you. Yes that is it for me. Thank you.
Operator: Our next question is from the line of Mayank Mamtani of B. Riley. Go ahead please.
Mayank Mamtani: Good morning team. Thanks for taking my question. So first, just a quick follow-up on the NAFLD study. The total enrollment looks higher than, I think what you had originally planned. Can you just maybe comment why is that and then the baseline - I think you have commented on BMI age proportion of female, male, but if you are able to give any color on baseline liver enzymes levels like should we see these NAFLD studies? We have seen anything ranging from introduced to mid 60s to mid 70s or you believe there. So anything you could comment on that would be great. And then I have a follow-up?
Vipin Garg: Yes. So Mayank, we obviously see the 94 subjects as being a real plus. The patient who go into the 12-week trial, are the same patients who go into the 24-week trial, in other words, who go into the EXTENSION. And you have to understand that when patients came into that first 12-week trial, they came with the understanding that they were going to come in for 12-weeks, they are offered another 24-weeks, but a lot of people didnât have the time, or set aside the commitment to go into for a full 24-weeks. So that has to be understood. Nonetheless, we are happy with the rollover rate, but that 94 patients really allowed us to move a robust number of patients from the 12-week study to 24-weeks. So we see that as being a real positive on the readout that we are going to have 24-weeks in the EXTENSION trial. So with regards to the liver enzymes, we will have that data. This is not a NASH trial. So the level of liver enzyme elevations are not going to be great. But we are allowing for some liver function elevations at baseline. And we should be able to see a meaningful change in ALT, for example, over the course of treatment of 12-weeks.
Mayank Mamtani: Thank you. And then having that less proportion of diabetics in the NAFLD study, just curious, what does that mean to the weight loss contribution, I think it would be helpful to put in context what weight loss, we saw in the semi - TIRZEPATIDE studies, diabetes versus non-diabetes patients and maybe from your earlier Phase 1 studies you had any diabetes versus non-diabetes patients?
Vipin Garg: Yes, so I will take the second part of the question, first. Our first study was conducted entirely with non-diabetics. So we canât really use any information from that study to predict what we would see in type two diabetics in the upcoming trial readout. I would emphasize, however that 40% of the subjects who participated in the Phase 1 study, were pre-diabetics, and we saw a reduction in insulin resistance in our population, we saw the majority of those patients who were pre-diabetics becoming non-pre diabetic. Regarding the lower percentage of patients who have Type 2 diabetes in this trial, I would emphasize again, the fact that we are going to read out separately in the three populations. The first being the non-diabetics, so that will compare directly to step one, which is the semaglutide first pivotal. The second would be in diabetics, I would compare to step two, and then a combination. Although I donât think that the combination is meaningful, and that is why the change in the percentage of diabetics is really not meaningful as well, because what we are interested in is the separate effects of non-diabetics and diabetics. With your correct understanding that typically in clinical trials diabetics lose less weight than non-diabetics.
Mayank Mamtani: Got it. And my final question on the 48-week, full readout timeline, just trying to understand that gap between when you have the 24-week interim analysis in first quarter, and that 48-weeks full analysis, which Iâm assuming is going to be at the total sample size of 320 subjects. Could you just provide what that gap could look like in terms of timelines and just maybe some color on what is the screen failure rate. I think it gave a screening number of per week of about 25 subjects. Just curious if you could comment on how that rate is increasing month-over-month and what is the failure rate look like?
Vipin Garg: Yes. So to be clear, Mayank that 25 subjects per week is not a screening rate. That is an actual randomization and dosing rate. This subjects are actually being dosed and put into the final data set. So based on that, we will have dosed our final patient by the end of September. The screening rate is obviously higher than that. We havenât gone public and what the screen failure rate is, but we are very, very happy with that, but it is obviously a lot higher or somewhat higher than that 25 subjects, because of the screen failures. We are confident obviously about the readout of 24-weeks in the first quarter. And with the completion of the first patients receiving their first dose by the end of September, you can estimate where the 48 readout would approximately occur in 2023.
Mayank Mamtani: Got it. I will hop back in the queue. Thanks for taking our questions.
Operator: Thank you. Next question is from the line of Jon Welandon of JMP Securities. Go ahead please.
Jon Welandon: Hey good morning and thanks for taking the questions. A couple on the NAFLD study. I was hoping you could clarify I might have missed this if diet and exercise instruction is part of this Phase 1 study that wasnât part of your prior Phase 1. And then you mentioned the average baseline weight is about 101 kilograms, which is substantially higher than you saw in Phase 1 wondering how you are thinking about, how that might affect the weight loss you see here versus the prior study. And Scott do you said this study was fully enrolled, but just looking for clarity on what percentage of patients rolled over into the 12-week EXTENSION? Thanks.
Vipin Garg: Thanks Jonathan So you are absolutely correct. We did not use diet and exercise in our initial first-in-human study. And we are not using diet and exercise in the current 12-week NAFLD study. So consequently, when we look at this, we are not going to see the 2% benefit of placebo, because remember that the STEP and SURMOUNT and even the SURPASS trials were conducted over a baseline of diet and exercise. And the reason is because when a drug is approved for the treatment of obesity in the U.S., it is approved as an adjunct to diet and exercise. So it actually has to be in the study. The NAFLD study was designed without diet and exercise, the same as the initial Phase 1 study. However, the momentum Phase 2 trial, which is committed obesity study follows FDA guidances. This is designed exactly like STEP 1 and SURMOUNT1 and with that we do have an intensive diet and exercise program. With regards to the higher weight, the mean weights or median weights, I should say that we saw on the Phase 1 study, were approximately 90 to 95 kilograms depending on the cohort. So this is somewhat higher, but it is not a lot higher. Our initial evaluations from our Phase 1 study suggested that we did not see an effect of body weight on either our serum concentrations or the amount of weight that people lost. But I would also caution that that was a small number of subjects. And we will have to see if that holds true as we go into this readout with a larger number of subjects. The EXTENSION study is fully enrolled, we are happy with the rollover rate, we are happy with the additional patients have gone into the study, following the increase of the size of the BASE study to 94. We havenât gone public on the percentage of rollover, we will obviously have that data when we announce it 24-weeks, but it will be a very nice dataset.
Jon Welandon: Got it. Thanks again for taking the questions.
Vipin Garg: once of this read out with a larger number of subjects. The EXTENSION study is fully enrolled, we are happy with the rollover rate, we are happy with the additional patients who have gone into the study, following the increase of the size of the base study to 94. We havenât gone public on the percentage of rollover, obviously .
Operator: Thank you. Next question is from the line of Patrick Trucchio of H.C. Wainwright. Go ahead please.
Patrick Trucchio: Good morning. Iâm wondering, you know, in discussing the potential points of differentiation of Pemvidutide, if you can talk about the expected advantages, specifically in Type 2 diabetic patients, particularly in areas of glucose control and lipid counts relative to other mechanisms in the field. And if you could also remind us the proportion of patients with obesity that would also be expected to present with Type 2 in the real world setting?
Vipin Garg: Thanks, Patrick. So regarding your first question, in Type 2 diabetes, the immediate and I want to stress the word immediate target product profile for Pemvidutide is not to have at least like a GLP-1 monotherapy, acute glucose lowering effects. We have balance in the compound between GLP-1 and glucagon and we believe that that at the base case is going to be maintaining glucose. And we saw that in our Phase 1 study where glucose and hemoglobin A1c were maintained. So but over the course of time recognize these patients lose weight. And it was stressed at the recent ADA meeting, that the focus in the treatment of patients with Type 2 diabetes should focus not so much of the focus should change from the treatment or the control of blood sugar to the loss of body weight because the loss of body weight has a much more meaningful effect on their hemoglobin A1c over the course of time than the anti-diabetic effect. So consequently, we are very confident given the amount of weight loss that we are seeing that we are going to achieve drops in hemoglobin A1c over the course of more extended treatment. We are fairly confident we will see that at 48-weeks. We are hoping we are going to see it at 24-weeks, but it is a shorter period of time with less weight loss. We may see it at 12-weeks, that would certainly be only a plus that we saw a drop. But at the same time our base case is that we wonât necessarily see a drop. Now recognize that one of the principal factors in blood sugar elevations and Type 2 diabetics is insulin resistance. And the great portion of that comes from the liver and it is related directly to liver fat. And when you see liver fat being decreased as dramatically as we are with Pemvidutide and that is been looking on effects, we think we are going to see a drop in insulin resistance, that is also going to contribute to the blood sugar decreases over time. So just to reiterate, we do feel confident that this is an anti diabetic drug over say 48-weeks perhaps 24-weeks. Our base case that 12-week is that we wonât see it. But because the hemoglobin A1c averages out the blood sugar for 12-weeks even when you donât initially have weight loss. But an upside would be that we saw a drop in hemoglobin A1c or fasting blood sugar in the diabetic population. Regarding the lipids and diabetics, it should be clear that diabetics do suffer from the effects of blood sugar. And those elevations result in microangiopathy, such as diabetic eye disease, diabetic kidney disease. But the predominant reason for death in Type 2 diabetics is serum lipids. And consequently, drugs that more effectively move serum lipids are going to have better cardiovascular outcomes that those that donât and I want to again contrast the reductions in serum lipids that we saw, particularly total LDL cholesterol in our Phase 1 study at 20%, 30%. And contrast that to the only 3% reductions in total and LDL cholesterol in the STEP1 clinical trial. And we think that ultimately that is going to have major benefits on cardiovascular outcomes when we conduct those clinical trials. Regarding your question, Patrick about the percentage of obese patients who have Type 2 diabetes, it is about 20%.
Patrick Trucchio: Got it. That is really helpful and then just another follow-up question. We look to the first quarter of next year, you are going to have the interim data for MOMENTUM, you will also have the Phase 1b NAFLD study 12-week and 24-week data and as well, but Phase 1 study data in diabetic subjects, so additional Phase 3 data. Iâm just wondering, do you think at that point, you would have sufficient data to have a meeting with the FDA, depending on the outcome of all of these studies to move directly into a Phase 3 program and obesity or do you anticipate needing the full data set from momentum before you can move ahead to Phase 3?
Vipin Garg: Yes. Great question Patirck. The initial advice that we got from FDA and I want to stress initial was that they would like to see the full 48-week data before moving ahead to Phase 3, but we could certainly look at what we have in the first quarter and see if that discussion should be held again. Again, when we approach them, which was the filing of the IND for obesity and that was - we filed that at the end of 2021. We only had Phase 1 data and unlimited subset of patients and data prevails at those meetings. So when you propose meetings, they want to have as much possible. So their initial impression and I not surprised is letâs see 48-week data, but it is possible with the abundance of data that we are going to be generating in the first quarter that we could have that discussion earlier.
Patrick Trucchio: Great. Thank you very much.
Operator: Thank you. And we have a follow-up question from the line of Seamus Fernandez. Go ahead please.
Seamus Fernandez: Great, thanks guys. so just two quick follow-up. The first question, there was a publication from Novo Nordisk highlighting a relatively robust study of their own glucagon agonist in combination with I believe their GLP-1 semaglutide. Just wondering if you guys could comment, whether it be on that study, or at least on the safety of Pemvidutide as it relates to heart rate elevations. I think the GGG agonist that Eli Lilly in their early Phase 1 data, saw substantial heart rate elevations that know clearly would require some factors there. But it is also our understanding that that is also tends to be associated with GLP-1. So are you guys seeing anything related to heart rate elevations outside of what we would see normally with the GLP-1 in your datasets at all? Just wanted to start there, just because that has been a critique from Novo Nordisk, but we are not sure if it applies, here or perhaps it is even just purely molecule specific? And then the second question was just, as we think about the possibility of entering larger Phase 3, it would seem to us the size of the overall obesity efforts likely would have you guys with strong interest from potential partner, especially if you can achieve the profile that you are talking about. How are you guys thinking about the timing of when you think it is best to engage with potential partners from a strategic discussion prospective? Thanks.
Scott Harris: Hey, thanks, Seamus. I will answer the first question, and then I will turn to Vipin to answer the second question. So as you know, in that GGG study, the effects on heart rate were striking. Then they announced that with multiple dosing, they saw increases of about 10 pre beats per minute. But actually, in their single ascending dose study earlier than that, they actually got 30 beats per minute. So why is that? Is that because you simply add a glucagon to the molecule? Well, we say a couple of things about that. The first is the amount of glucagon and GGG, as we understand it, and I want to emphasize that is small. That molecule appears to be TIRZEPATIDE, slightly lower ratio of JYP to GLP-1. I think TIRZEPATIDE 15 to one, it looked like based on the data they presented, that is eight to one, but want to emphasize that the ratio of GLP-1 to glucagon that molecule is 10 to one is only one-tenth, the relative amount of activity in that molecule compared to the GLP-1. So if there is any effect of that molecule is the GLP-1, and we have seen those heart rate increases before. How do we explain it and why arenât we seeing it with our compounds? We believe it is probably the pharmacokinetic effects. If you look at the time to maximal concentration, about compound, as we understand it, as presented in graphs at the meeting, it looks like it is very short about 12-hours. And again, I want to say it is about because Iâm estimating it from slides, they present it without actually seeing the raw data. What that means is that when that drug is given, there is a surge of drugs into the bloodstream with higher P concentrations and immediate effect. Contrast that with Pemvidutide where we see a maximal concentration. That is actually several times greater than that not 12-hours but 70-hours with a lower C max. We have estimated that our C max compared to comparative doses of semaglutide is about one-third. So what we have is an onset that is slower and perhaps more gentle, using a non biological term. But we think that that accounts for the lack of heart rate increases. Now, we presented that data at the ADA meeting, that we are not seeing the heart rate increases of semaglutide. It is probable that as we go further in development, because this is a GLP-1 based compound that we will see some increase, that the initial data suggests that it is not going to be significant any more than a GLP-1. But again, I want to emphasize that we have a small number of patients, and we will just observe that as we go. But we think that the heart rate increase that we are seeing with glucagon containing compounds, were not due to glucagon, we think it was nature, the nature of the pharmacokinetics. So for the second question, we will turn that over to Vipin.
Vipin Garg: Yes. Seamus, I mean, we agree with you that this kind of data package that we are putting together, and if we are able to maintain the profile that we have been highlighting that we expect, when we do type to have that we expect to have significant interest in strategic interest in this program. So we will explore that we have right now we are focused on generating this data. We think that is whatâs going to drive the value proposition here.
Seamus Fernandez: Thanks so much guys.
Operator: And we have another follow-up question from Mayank Mamtani. Go ahead please.
Mayank Mamtani: Thanks for taking my follow-up. And maybe just another kind of follow-up - forward-looking kind of question. In terms of doing a CD outcome trial, you expect that to be in parallel to your Phase 3 or more sequentially post Phase 3. And as you know, the reason I asked you this question, is that the recent Novo update with the SELECT study. But also, I mean, you are trying to get to weight loss levels, comparable to TIRZEPATIDE in two thirds of the time. So, Iâm just curious as you look forward, like when doing an outcome study, invalid doing your Phase 3. There is good long-term, these are important to reimbursement and payer dynamics for the market?
Vipin Garg: Yes Mayank it is a great question. I want to emphasize, first that the conduct of a cardiovascular outcome trials will not be gating to approval that we do it in parallel with Phase 3 or afterwards. These drugs are approved without having these trials up front. So we saw that recently with Mounjaro tirzepatide. I think it is intriguing to think that we could do it in parallel. It is not something that we have carefully looked at. We think it is a very nice suggestion, and we will certainly take a better look at it.
Mayank Mamtani: Thank you.
Operator: Thank you and now I would like to turn the conference back to Vipin for closing remarks.
Vipin Garg: Thank you everyone for participating today. We appreciate this opportunity to share our results and outlook with you and thank you for your continued interest. Have a nice day.
Operator: This concludes todayâs conference call. Thank you for participating. You may now disconnect.
