Q4 2022 Altimmune Inc Earnings Call
Speaker 2: The conference will begin shortly. To raise and lower your hand during Q&A you can dial star 1-1.
Speaker 3: Good day, ladies and gentlemen, and welcome to the Altamune, Inc. full year and fourth quarter 2022 Financial Results 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. To ask a question during the session, you will need to press star 1-1 on your telephone. There will be two participants who have turned off the volume. Falukul, pellets, will guest Please say your name and add your name to the chat for the given location.
Speaker 4: As a reminder, this call is being recorded. I would now like to introduce your host for today's conference call, Rich Eisenstadt, Chief Financial Officer of Altamune. Rich, you may begin. Thank you, Gigi, and good morning, everyone. Thank you for participating in Altamune's full year and fourth quarter 2022 Financial Results and Business Update Conference Call. Members of the Altamune team joining me on the call today are Vipin Garg, our Chief Executive Officer, Scott 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 full year and fourth quarter 2022 Financial Results was issued this morning.
Speaker 4: 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 coming in caution is that these forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those indicated. For discussion of some of the risks and factors that could affect the company's future results and operations.
Speaker 4: 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 press release issued this morning, and now available on our website. Any statements made on this conference call speak only as of today's date, Tuesday, February 28, 2023, 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.
Speaker 4: As a reminder, this conference call is being recorded and will be available for audio replay on Altamune's website. With that, I will now turn the call over to Dr. Ripengar, Chief Executive Officer of Altamune. Thank you, Rich, and good morning, everyone. We appreciate you joining us today for a discussion of our year end and full squad at 2022 financial results and business update.
Speaker 5: We are excited about the 2022 achievements with PEMV-DU-TIDE, our GLP-1 Glucogon dual receptor agonist. PEMV-DU-TIDE is in development for the treatment of obesity and Nash, two important clinical indications. Altimune achieved key milestones in the development of PEMV-DU-TIDE last year, including completion of our 24-week Phase 1B Nafel-D-Trial with compelling positive data and the initiation of our 48-week Phase 2 Momentum obesity trial. The 24-week data from the Nafel-D-Trial produced a greater than 75% relative liver fat reduction at 24 weeks.
Speaker 5: with over 50% of subjects achieving normalization of liver fat and significant reductions in serum ALT levels and correlated T1 relaxation times in the 1.8 milligram dose group. Serum ALT levels and CT1 imaging are both established markers of liver inflammation. Subjects receiving family due tide also had a mean weight loss of 7.2% if placebo adjusted weight loss of 6% in subjects without diabetes at distors. This is important because access body weight is believed to be a major driver of Nash and its comorbidities and weight loss represents an important therapeutic goal in the treatment of these patients. We believe the robust reduction in liver fat content.
Speaker 5: and markers of liver inflammation together with meaningful weight loss will be important determinants of success in Nash. And because the great majority of people with Nash also have overweight or obesity, we believe Pembedue Tide is uniquely positioned to address these populations effectively. Given these results, we plan to continue development of Pembedue Tide for Nash and expect to initiate a Phase II B Nash trial in mid-2023. Scott Harris will provide more details on this trial shortly. Turning to our Phase II momentum obesity trial, we are looking forward to announcing the top line 24 B-Centrum results of approximately 160 subjects in the second half of March. We believe that a level of weight loss consistent with the class leading obesity drugs may be achieved at the end of 48 weeks of treatment. And that potential will be reflected in the interim data readout.
Speaker 5: We also believe that tolerability profile of MbDU type, together with the absence of dose-titeration, could translate into improved adherence to therapy and ease of administration. And that a reduction in serum and hepatic lipids and blood pressure may afford benefits to patients at risk of cardiovascular events. In contrast to several other agents in development, reductions in blood pressure are being achieved with MbDU type, with minimal increase in heart rate. We believe these attributes could differentiate MbDU type from other drugs in the obesity space and make an important contribution in the treatment of obesity. Finally, enrollment in the Phase II clinical trial of Heptis cell in chronic hepatitis B is over 90% complete. And we expect to have a data read out in the first half of 2024. Recall that this trial is designed to show evidence of antiviral effects against hepatitis B virus, and establish its potential role in combination therapy for the treatment of this important disease. We're excited about the progress of MbDU type and Heptis cell.
Speaker 4: or on liver biopsies. Now to 100% of subjects assessed by CT1 experienced in 80 millisecond or greater change in CT1. We believe these findings could be predictive of success on biopsy endpoints when late stage trials are completed, as well as the likelihood of reduced hepatic and cardiovascular events when outcomes trials are conducted.
Speaker 4: Next, let me tell you about the initiation of a Phase II B NAST trial later this year. This Phase II B vibes you driven NAST trial, we'd be conducted at approximately 60 sites in the US with Dr. Steven Harrison, Medical Director, Pinnacle Reager, Research, and Adject Professor of Medicine, Oxford University, who let her 12-week Nafold D-Trial and 12-week Extension trial, serving as the principal investigator.
Speaker 4: The key end points of this trial will be Nash Resolution and Fibrosis Improvement after 24 weeks of treatment. We also plan to perform correlations with non-invasive tests of Nash Resolution and Fibrosis Improvement and to have discussions with FDA about the use of these biomarkers as primary end points in phase 3. We expect the study to commence mid-2023 and produce top-line results in the first half of 2025. Now let me talk about the phase 2 beam of menoprol of Pemvedutai in obesity. Trial was designed to enroll approximately 320 subjects without diabetes but with obesity or overweight with at least one chromorvidity. Subjects are randomized one to one to one to one to 1 to 1 to 1.2 milligram, 1.8 milligrams, 2.4 milligrams of Pemvedutai or placebo administered weekly for 48 weeks in conjunction with diet and exercise.
Speaker 4: and median liver fat content of approximately 5% as measured in approximately 100 subjects participating in a body composition substudy. The study population is approximately 75% female and approximately 20% of the subjects are of Hispanic ethnicity. As we pointed out previously, the demographics of the subjects in the interim analysis may differ from those in the fully enrolled study population. In addition, unlike the Phase 1B NAPL D trial, the Phase 2B Mementum trial employs endpoints and lifestyle modifications that are standard for multi-center OB-City trials. The primary endpoint of the Mementum trial is the relative percent change in body weight at 48 weeks compared to baseline. With additional readouts including serum lipoprofiles, cardiovascular measures, and glucose homeostasis. Dr. Luaroni from Wild Cornell Medical School, a leading authority in an OB-City clinical trials is serving as the principal investigator.
Speaker 4: We expect to have the results of an interim analysis of the momentum trial in the second half of March. That analysis will be comprised of approximately 160 subjects that received 24 weeks of therapy. The read-out parameters are expected to include weight loss, serum lipids, adverse events, vital signs, glucose control, and study discontinuations. We have also completed an enrollment in our Phase 1 multi-center safety trial, evaluating glucose control, and subjects with type 2 diabetes over 12 weeks of treatment.
Speaker 4: Approximately 48 subjects were planned with a readout expected in March 2023. The purpose of this trial is to establish the safety of PEMFEDUTIG in preparation for end-of-phase-to-meeting with the FDA, which is expected early next year. Across the trials I have described, we are rapidly building the safety profile of PEMFEDUTIG with unblinded safety data accrued and over 200 sites. Approximately 200 subjects were received in PEMFEDUTIG and clinical trials at year end 2022 and approximately 500 subjects by year end 2023. We are also making excellent progress in our enrollment of our phase 2 multi-center clinical trial of HEPTSO. The trial was designed to enroll approximately 80 subjects with over 90% now enrolled.
Speaker 4: We expect to read out the results of this trial in the first half of 2024, once all subjects complete the six-month treatment period. Recall that Hepatitis B virus and that the virulotic effects of Hepatitis B are being evaluated in chronically infected patients with partial control over infection to enable the combination of Hepatiso with novel, direct acting, intavirals as part of chronic therapy for chronic hepatitis B. It is believed that effective treatment of chronic hepatitis B will include combination therapy of a direct acting antiviral and an immunotherapeutic agent. I will now hand the call over to Rich Odson set to give an update on our third quarter financial results. Rich, thank you Scott for good morning again. For today's call I will be providing a brief update on Alton Means full year and fourth quarter 2022 financial and operating results. Core comprehensive information will be available in our form 10K to be filed with the SEC later today. Alton Means ended the fourth quarter of 2022 with approximately $184.9 million of cash, cash equivalence, and short-term investments compared to $190.3 million at the end of 2021.
Speaker 4: Turning to the income statement, revenue was negligible in the fourth quarter of 2022 compared to $3.3 million in the same period in 2021. The negligible negative revenue reported in 2022 was due to adjustments to cost reimbursement under the now completed barbed contract. Fourth quarter of 2021 revenue was primarily prior period rate adjustments received in that quarter for earlier government funded research projects. Revenue for the full year 2022 was negligible compared to $4.4 million in 2021. The revenue in 2021 was attributable to the barbed contract and TCOVID programs which were concluded in 2021. Direct expenses for the conduct of our clinical programs including $13.4 million in direct cost related to development activities for PEMVADUTIED and $1.9 million in direct cost related to development activities for HAPD cell. R&D expense in the fourth quarter of 2021 included $12.4 million in direct expenses associated with the development of PEMVADUTIED.
Speaker 4: and 2.4 million dollars in direct expenses related to hefty self development activities, as well as approximately 2.6 million dollars in expense to close out the ad COVID campaign. Research and development expenses were 70.5 million dollars in full year 2022 compared to 74.5 million dollars in prior year. The decrease in R&D expenses primarily the result of a 35.1 million dollar decrease in ad COVID and TCOVID related development costs, which programs were discontinued in 2021. This included the expense of payments made the lawns for the construction of a manufacturing suite. In full year 2022 we incurred $46.8 million in direct costs associated with the NAFL or MMM trials for PEMVATU TIDE and $7.5 million in direct costs associated with the hefty self campaign. General administrative expense were consistent period over period at $3.8 million in each of the fourth quarters of 2022 and 2021.
Speaker 4: For the full year 2022, General Administrative Expense for $17.1 million versus $15.4 million for full year 2021. The $1.7 million increase was primarily due to increased stock compensation expense as well as additional labor-related costs in 2022. Net loss for the three months ended December 31, 2022 was $21.7 million or 43% net loss per share compared to net loss of $23.9 million or 57 cents net loss per share for the fourth quarter of 2021.
Speaker 4: The reduction in net loss is primarily attributable to the $1 million lower research and development expenses $3.3 million in non-recurring expense in 2021 for the recognition of the lawns impairment loss and the $1.3 million increase in interest income Offset by the reduction in contract revenue Net loss for the year ended December 31, 2022 was $84.7 million or $1.81 net loss per share compared to $97.1 million or $2.35 net loss per share for the year ended December 31, 2021. The decrease in net loss is primarily attributable to the lower research and development expenses in 2022.
Speaker 4: $11.4 million in non-recurring expense in 2021 for the recognition of the launch impairment loss and the $2.7 million increase in interest income offset by the reduction in contract revenue. We currently estimate that our research and development expenses for full year 2020-23 will be approximately $90 million. The GNA expenses for the full year 2023 are anticipated to be approximately $18 million. Approximately $10.1 million of these operating costs are for non-cash expenses including stock compensation and depreciation and amortization. We estimate that our existing cash funds are sent to the second half of 2024, which includes completion of the 48-week momentum trial and completion of enrollment of the Phase-2B biopsy NAS trial. Our current cash projection also anticipates investment in 2023 and Phase-3 obesity clinical drug supply as well as funding in 2024 for the initiation of Phase-3 obesity campaign. I will now turn the call back over to Vipin for his closing remarks. Vipin. 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?
Speaker 4: Can you just help us better understand how the recruitment in biopsy driven studies at least has been progressing or perhaps just a general sense of when your 24-week data could potentially be available? I know it's a little bit of a...
Speaker 5: Crystal Ball looking into the future in that regard, but I'm just interested to better understand that thanks. Thanks for the question, Shamus. Good morning. Well, let me take the first question and maybe Scott Harris can take the second one and anybody else can chime in as well. So as far as the what we are looking to are expecting to see at the 24 week in from readout as we have always said.
Speaker 5: that this is not about just one thing, not just about just one number, it's not just the weight loss number. You have to look at the overall target product profile to figure out where does your product will fit in the long run in the obesity land space. Landscapes. So if you think about it at 48 weeks or at the end of treatment approximately a year, what we are looking to achieve is about 15 to 20 percent weight loss. We think that's where one needs to be in order to be competitive from a weight loss perspective. But you also need to bring a number of other attributes which we think our product has. So I think it's really a combination of all those things, lack of toes, titration, better tall ability, serum lipid reduction and serum lipids and so on. So all of that has to be sort of factored into determining the overall competitive profile of the product. So if you back off of that and look at at 24 weeks, we would expect to be on weight to achieving that 15 to 20 percent weight loss. So 24 weeks, you know halfway there, you know 8 to 10 percent is what we've been talking about. We would think we'll have a competitive profile if we're having that kind of weight loss with all of these other attributes together with that weight loss. Got. Hi, good morning, shameless regarding your second question. We think that we're putting together a very strong plan for recruitment. We think that we're going to be able to do that. We've identified a number of very good sites. As you know, Steve and Harrison is serving as the principal investigator of the trial once again. He's a great organizer and there's a very established network under his direction. So we feel very good about the recruitment plan and doing it in the United States. Regarding that, we think that we could have a readout on that 24 weekend point in the first half of 2025.
Speaker 4: Great, thanks very helpful. And then just as a final follow up question, and I'll jump back into Q, as we think about the prospects for 8% to 10% weight loss, I assume just to clarify, is that placebo-subtracted weight loss that you're hoping to see? And maybe just as a little bit of incremental context, can you remind us at 24 weeks what we go via and through Zepatite achieved? Thanks. Hey, Shemus. Yes, as we've said before, that 8 to 10% is placebo-adjusted. You know, as Vipin mentioned, at the end of the year, we'd like to be in that 15 to 20% range.
Speaker 4: And where we could be at the end of 24 weeks is how you look at the curve. We should point out that at the same time point the 24 weeks, semaglutide, which has been a very successful drug, I think there are over 60,000 scripts written last week alone, was at 8% placebo adjusted weight loss. Terzepatide was at 12%. So the 8% to 10% is certainly within that range. And it's actually in excess of semaglutide. We think that based on our phase one data, we can have very, very good weight loss. But we've constructed our target product profile to include not just a weight loss percentage number, but the full spectrum of what's going to differentiate drugs and get doctors to use them. And the benefits of the drug are going to be well beyond the simple weight loss number. It's going to include all the other attributes that Vipintov. And I would also point out that when we are comparing 15 to 20%, we're looking at 68 to 72 weeks for semaglutide and for Trezepatide versus...
Speaker 6: You know, what we're looking at here is a 48 week study. So there's still a lot of runway left there to achieve additional weight loss beyond 48 weeks. Thank you. Thank you. One moment for our next question. Our next question comes in the line of Yasmeen Rahimi from Piper Sandler. Good morning, Kim. Thank you so much for all the updates and details. Two questions for you. I just wasn't wanting to drill down in the design of the national study. What is the duration of the study? And I just wanted to also clarify, it's the study powered for both end points, national solutions, as well as a one point improvement of fibrosis. And then broadly speaking, what is the size of the study going to be? If you could just drill down there. And then one, sorry, one last question about the diabetes study. A lot of clients are wondering. And given that that study is also reading out at March around the same time as we're expecting in trim momentum.
Speaker 5: How do you plan on sharing that data? And thank you again for taking my long list of questions. Yeah, I mean, let me take the second question, and then Scott, maybe you can take the first one. So as far as the diabetes studies concern, I mean, both the studies are neck and neck. We're prioritizing the momentum study to make sure that that data is out as quickly as possible in the second half of March. But we're also expecting the diabetes data around the same time. It's hard to say exactly what the timing will play out, but I would say it's going to be very close to each other. Yeah, and yeah, thanks for the question about the next study. That study is still in its final stages of design. We're going to share those additional details as soon as we can.
Speaker 4: Well, the primary endpoint of the study will be read out at 24 weeks or six months and we're making a decision about whether to continue to follow a patient for other parameters such as safety or the non-invasive markers for a longer period of time. And that decision is being made right now. But assuming we get the trial commenced mid-digit year this year and then the time period that we anticipate will be necessary to improve.
Speaker 5: the requisite number of patients and then the 24 weeks of treatment follow up. We think that a first half, 2025 data readout is very realistic. Great. Thank you so much and really the best of luck as we're headed in the next few weeks. Thank you again. Thank you. One moment for our next question. Our next question comes in the line of Roger Song from Jeffries. Great. Thank you, Kim, for taking our question. Quick one from us. So one is, you know, given the clear topic effects from the time that the tide. Can you guys just lay out what are the targeted population you want to address, particularly. For them, for the obesity plus minus, not over the national, maybe some other commodity, panverticalize the, you know, better worst position to address. If you can give us some details in terms of the numbers, they'll be very helpful. I'll have a follow up question after that. Thank you. Hey Roger and good morning. So.
Speaker 4: There is a great deal of overlap between the obesity population and the national population. Just made it that 50% of obese patients have naffled in virtually all national patients at least in the United States have obesity. And it's known that they share similar comorbidities. National patients at their terminal stages of liver disease, die of liver disease, but they predominantly die of the cardiovascular complications. And therefore it's important when you treat the national patient to treat not only the process going on in the liver, but also the obesity as well to have a meaningful impact. We also think that doctors when they prescribe to patients will pick drugs for the treatment of national also also offer weight loss, not only because they believe it so, but because patients also want it. And I point out that in the national base, we believe that we're the only drugs that have effective interventions on both national inflammatory and fibiotic activity at the end of the trial, but also weight loss. So when you're looking at the obesity population, clearly right now in its early stages of the marketplace in developed,
Speaker 4: insurance approvals such as reduction in serum lipids, reduction in hepatic fat, meaningful reductions in blood pressure, which we're achieving unlike some other compounds in development with only minimal increases in heart rate. Roger, in that context, it's helpful to also understand that the NIH states that 60 to 70% of obese people are a dysephydemic.
Speaker 5: very quickly on in terms of the Nash. I know it's early stage, you're still finalizing the design, but just in terms of given the the multitude, the effect from Pemberd-Tas, what could be the ideal population you will do like an early stage in terms of the Nash stage.
early stages of Nash, where she needed anti-fibrotic drugs to treat the later stages. That paradigm has been turned on its end because we now have two metabolic active drugs, whereas mid-Arom and the fructose ferment, which have completed phase 3 and phase 2 respectively.
having very meaningful effects when fibrosis. So what that shows is that if you affect the liver and have effective liver fat reduction, you're gonna have effective reduction in inflammatory and fibiotic activity, we're just gonna drive activity not only from fat reduction all the way through fibrosis improvement.
So we actually see the product population for the study being all stages of Nash up until advanced fibrosis. That's been a tough population to treat. And we point out that the greater the reduction in the liver fat, the greater the effects that I just mentioned have been in clinical trials.
very happy about the risk-mitter-owned results, the reduction of liver fat at 24 weeks, plus about 49 to 50%. With a flux of firm and it was about 65 to 70%, we're 70 to 75%. Based on that, we're very, very optimistic about Bob C. results in the future. But with risk-mitter-owned, which we believe will go on to approval, only 25% of people had a response in either a national resolution of fibrosis improvement. We think that's great at least the regulatory precedent.
but we also believe there's a large amount of room for improvement that we think we can fill. Excellent. Thank you. That's a fun one. Thank you. One moment for our next question. Our next question goes on the line of Col Ren Jenkins from Goldman Sachs. Thanks, and good morning. Maybe first for me, just based on what we saw in the Apple study, how do you think the dose titration and the 2.4 mega per kick arm could impact safety compliance, and then maybe don't germinate efficacy in the upcoming momentum rate out? Well, well, thank you for the question, current. So we use we put that short titration in place based on some observation we made in our first in human study with the 2.4 milligram dose. We saw more. We saw the entire ability events and they were curling early on in the first one to 2 weeks. So we thought that before we titration.
would mitigate adverse events and we saw something to that effect in our NAFL D trial. Whether we continue to use that titration going in forward in the future we'll have to see based on the data that we accrue. We think that the end of 24 weeks with a four week titration, it would probably at that point in time have a minimal effect in the overall weight loss and certainly by 48 weeks there be sufficient kind time to minimize the impact of the effect of the titration. We're not committed by the way to using titration going forward. You know we will look at the data we may drop it where we'd point out that we're the only drug development for either obesity or Nash that's in crit and based that can actually dose without dose titration. We have the optionality if we want and this is not something we're doing right now but something that we're quite aware of. If we ever got back research for example market research which we're conducting continuously that patients preferred the tolerability over the titration we could offer a titration as an adjunct either in a late stage trial or as a separate user trial and actually offer that to patients and doctors as a prescribing option.
It's something that the other drugs in development like tears appetite and some acolytides can't do because they're already added forward to five months of titration and the question is how much longer do they need to go? So we think that the titration Based on what we've seen before is helping but is it needed? We don't know We'll let affect the efficacy of 24 weeks. We don't believe it will and certainly not at 48 Healthful and then just a point of clarification from me with the weight loss or sorry with the diabetes that is coming soon will you share weight loss data from that trial or is it going to be primarily focused on the diabetes related endpoint? Right. No, we will share that data will also share the information on the diabetes endpoints. Thanks. Thank you. One moment for our next question. Our next question comes to the line of my aunt Manteunee from Be Rylee.
Good morning team. Thanks for taking our questions and congrats on the progress. So on the face to be nasty, the design, I know you're not commenting on the total number of subjects yet, but this curious, if you're in Terem 24 week readout, you know, will be like the face to be momentum readout where you include sort of a smaller cohort of patients for that 24 week biopsy. How would you have the full population? The strangest of the, you know, how, how, how was excitement that is out there for, you know, enrolling for your national study like we saw in the obesity study. Well, thanks for the question, Mayunk. You know, that readout that would occur in the first step of 2025 would not be an interim analysis. That would be a full readout because it's a readout on the primary endpoint at the established.
time point for reading it out. Now, we may elect to continue following patients, but the efficacy of the study with regards to the primary employment would already be established. So when we read out on the first step of 2025, it will be in the entire study population. And that's in contrast to the readout that we're gonna have in the latter part of March, where we're actually doing a cut of the patients approximately 160 or approximately 150 percent of the patients. It only at about half of therapy. So the readout in the first step of 2025 in that step will be a complete readout.
Thank you for that clarification. And then on momentum seems like the focus here is on, you know, totality of data rather than any specific metrics as a weight loss. Are you able to comment on what your expectation might be on? Maybe the discontinuation rate for Penn V versus the CON. And also, I think a similar comment, if you could have on the hyperglide senior study that you're running in parallel to momentum. I know the follow up there is shorter there to 12 weeks. And I have one final question after that. Yeah, well, we'll have information on the discontinuation rates. I don't anticipate that we'd be talking about other people's data on that readout, but we should have that information for you in both trials. And your expectation for that rate to be in one range. So, you know, historically, you know, B city trials.
you know, in terms of scale that kind of matters, you know, what we've seen with step answer Mount program, you know, which includes an active competitor and our, you know, studying PENB with certain combination regiments. Are you able to share any initial parts on that? Well, we haven't had that discussion with FDA yet.
Obviously, we would have an end-of-phase-to-meeting with FDA to discuss the Phase III program. Everyone is aware of the Phase III programs that were conducted with some of the Blue Tides, and that has been conducted now with Teresepatide and obesity. It's not just been a question of the number of trials, but the number of subjects that you need to have in your safety database in order to file for approval. Typically, companies have fulfilled those requirements for the safety database by doing pivotal trials. In both of this programs have been four pivotal trials.
None of those trials have contute of those pivotals that were followed for approval have included an active comparator. There was a trial that was done in obesity for Teres depti where they compared it to an outdated dose of stomach glutide or a sample for the treatment of obesity. So, you know, I think at this point in time, the questions are there. We have a concept that would look somewhat like the other programs. We need to have that discussion with the agency. Great. Thanks for taking a question. Thank you. One moment for our next question. Our next question comes from the line of John .
for LDL in the range of about 3%, maybe as high as 5%. So these drugs don't really move cholesterol. They do have very potent effects and triglycerides. We've seen with the glucagon mechanism that you can move LDL cholesterol. We saw that in our first trial.
So we would hope to achieve something above that 5% range, hypothetically, maybe in that 10% range would be very nice to see. But again, the number would have to be achieved at 48 weeks in our first inhuman trial.
We were able to see a 20% approximately, 20% reduction in LDL and total cholesterol, and that's directly attributable to the glucagon. And our hope is that we would be, you know, meaningfully above the other drugs when we, look at the trial with 48 weeks. Let's help. And just one on the NAS study, I know you're in the finalization steps with the design, but how are you thinking about dosing the 1.8 milligram dosing to be the most effective, you know, so far is it worth moving forward to 2.4 or is the 1.8, you know, probably the sweet spot? Just wondering how you're thinking about that. Thanks.
Well, that's a question that's on our mind and the decision is going to be done to driven so obviously We'll make decisions about the national based on what we see in momentum Whether we carry the 2.4 milligram does forward. You know, although we haven't seen any convincing data that 2.4 is better than 1.8 We do know at least from the obesity point of view with super obesity which we define is a 110 or 115 kilograms that serum concentrations dropped and with that the risk reduction in the percentage weight loss the patients achieved. Now that wasn't seen with your Zepatide. And then the question is will we as a compound behave more like some agglatide or your Zepatide at this point we've modeled out the data but we're not absolutely certain so we've used the 2.4 milligram dose Essentially is an insurance policy in case we also see that effect. That strategy may be more relevant to obesity than Nash. We are modeling the data there are systems and modeling efforts that you use.
switching here's a little bit to the HEPT cell phase 2. I'm just wondering from the initial readout following the six months on treatment, in terms of both clearance and HEPT-B surface antigen, and zero conversion, how important it is that patients also achieve zero conversion at six months.
I think that, you know, obviously that's a nice to have. I think we're really what we're looking for is the ability to reduce the surface of the Deutschen. And this is still a relatively short trial, even at six months of treatment. And so a short conversion is ...
is certainly being followed, is certainly of interest, but I think that significant reductions in the surface damage and we set the bar at a one-log reduction is really what we're looking for. Again, the purpose of this trial is to establish that Hepticel has as a monotherapy activity against chronic hepatitis B. It's viewed that in the effective treatment of the disease will require combination therapy. And so, you know, we're using this patient population that already is partially controlled, like they might present having received some of the new direct acting antivirals.
And then the immunotherapy, a therapeutic like Hepatisel, being able to drive that clearance of the surface damage in with the presumption of a pseudo-conversion. So that's how we're looking at that trauma.
Thanks so much. Thank you. As a reminder to ask a question, please press star 11 on your telephone and wait for your name to be announced.
At this time, I'm showing no further questions. I would now like to turn the conference back to Vipin Guard for closing remarks. 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. This concludes today's conference call. Thank you for participating. You may now disconnect.
your hand during Q&A. You can dial star 11.
The cup.
I.
Good day, ladies and gentlemen, and welcome to the ultimate ink full year and fourth quarter 2022 financial results conference call. At this time, more participants are in the list in only mode. Later, we will conduct a question and answer session and instructions will follow at that time to ask a question during the session. You will need to press star.
Alton Munes, full year and fourth quarter 2022 financial results and business update conference call. Members of the Alton Munee team joining me on the call today are Fippengaard, our chief executive officer, Scott 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 full year and fourth quarter 2022 financial results was issued this morning 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 Security's litigation reform act of 1995. Optimine costs are set these forward-looking statements are subject to risks and uncertainties that can cause actual results to differ materially from those indicated.
For discussion of some of the risks and factors that could affect the company's future results and operations, please see the risk factors and other cost-inary statements contained in the company's followings with the SEC. I would also direct you to read the four-looking statement disclaimer in our press release issued this morning at now available on our website. Any statements made on this conference call speak only as of today's date, Tuesday, February 28, 2023, and the company does not undertake any obligation to update any of these four-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 Altamune's website. With that, I will now turn the call over to Dr. Vipengar, Chief Executive Officer of Altamune. Thank you, Rich, and good morning, everyone. We appreciate you joining us today for a discussion of our year-end and full squad of 2022 financial results and business updates. We are excited about the 2022 achievements with PEMVDU TIDE, our GLP-1 Blue Cogon Dual Receptor Agonist. PEMVDU TIDE is in development for the treatment of obesity and Nash, two important clinical indications. Altamune achieved key milestones in the development of PEMVDU TIDE last year.
including completion of our 24-week Phase 1B Nafel-D trial with compelling positive data and the initiation of our 48-week Phase 2 Momentum OVC-D trial. The 24-week data from the Nafel-D trial produced a greater than 75% relative liver fat reduction at 24 weeks, with over 50% of subject achieving normalization of liver fat and significant reductions in serum ALT levels and correlated T1 relaxation times in the 1.8 milligram dose group. Serum ALT levels and CT1 imaging are both established.
loss will be important determinants of success in Nash. And because the great majority of people with Nash also have overweight or obesity, we believe Pembedue Tide is uniquely positioned to address these populations effectively. Given these results, we plan to continue development of Pembedue Tide for Nash and expect to initiate a phase to be Nash trial in mid-2023. And we will continue to continue development of Pembedue Tide for Nash.
Scott Harris will provide more details on this trial shortly. Turning to our Phase 2 momentum obesity trial, we are looking forward to announcing the top line 24-week interim results of approximately 160 subjects in the second half of March. We believe that a level of weight loss consistent with the class leading obesity drugs may be achieved at the end of 48 weeks of treatment. And that potential will be reflected in the interim data readout. We also believe that tolerability profile of them we do tied together with the absence of those titration could translate into improved adherence.
to therapy and ease of administration. And that a reduction in serum and hepatic lipids and blood pressure may afford benefits to patients at risk of cardiovascular events. In contrast to several other agents in development, reductions in blood pressure are being achieved with PEMVIDUTIED with minimal increase in heart rate. We believe these attributes could differentiate PEMVIDUTIED from other drugs in the obesity space and make an important contribution in the treatment of obesity. Finally, enrollment in the Phase II clinical trial of HAPTI-SAO in chronic hepatitis B is over 90% complete.
and we expect to have a data readout in the first half of 2024. Recall that this trial is designed to show evidence of antiviral effects against hepatitis B virus and establish its potential role in combination therapy for the treatment of this important disease. We're excited about the progress of Pemby, Dutide and Hepatisal and the upcoming results of these ongoing trials. With that...
I'm now done to call over to our chief medical officer, Dr. Scott Harris, to discuss our data and clinical plans. Scott? Thank you, Vipin. Good morning, everyone. First, let me briefly review the results of our Phase 1B Nafolde Trial. As Vipin noted, a 75% relative liver fat reduction was achieved in the 1.8 milligram dose at 24 weeks of 30 with over 50% of subjects achieving normalization of liver fat.
Deists effects on liver fat content were accompanied by significant reductions in corrected T1 in theorem-aligning immunotransferase, both markers of hepatic inflammation. CT1 is a measure of fibroinflammatory activity in the liver, an elevated CT1 score has been correlated with hepatic and cardiovascular events in clinical trials.
Specifically, an 80 millisecond reduction has been shown to correlate with a two-point improvement in naffledy activity score on liver biopsies. Now, to 100 percent of subjects assessed by CT1 experienced in 80 millisecond or greater change in CT1. We believe these findings could be predictive of success on biopsy endpoints when late-stage trials are completed. As well as the likelihood of reduced hepatic and cardiovascular events when outcomes trials are conducted.
Next, let me tell you about the initiation of a Phase II B NAST trial later this year. This Phase II B Bives You Driven NAST trial, we'd be conducted at approximately 60 sites in the U.S. With Dr. Steven Harrison, Medical Director, Pinnacle Reager, Research, and Adject Professor of Medicine, Oxford University, who let her 12-week Nafold D-Trial and 12-week Extension Trial, serving as the principal investigator. The key points of this trial will be NAST resolution and FI-FIRSUS improvement after 24 weeks of treatment.
We also plan to perform correlations with non-invasive tests of Nash resolution and fibrosis improvement and to have discussions with FDA about the use of these biomarkers as primary endpoints in phase three. We expect the study to commence mid-2023 and produce top-line results in the first half of 2025. Now let me talk about the phase two VMemmento-trol of Pesidutai in obesity.
Trial was designed to enroll approximately 320 subjects without diabetes but with obesity or overweight with at least one chromorbidity. Subjects are randomized one to one to one to one to 1.2 milligrams, 1.8 milligrams, 2.4 milligrams of pentaidutide or placebo administered weekly for 48 weeks in conjunction with diet and exercise. Baseline characteristics of the fully-wrote world study population include median body weight and body mass index of approximately 101 kilograms and 36 kilograms per meter scare squared respectively and median liver fat content of approximately 5%.
as measured in approximately 100 subjects participating in a body composition substudy. The study population is approximately 75% female and approximately 20% of the subjects are of Hispanic ethnicity. As we pointed out previously, the demographics of the subjects in the interminalysis may differ from those in the fully enrolled study population. In addition, unlike the Phase I B NAPL D trial, the Phase II B Mementum trial employs endpoints and lifestyle modifications that are standard for multi-center obesity trials. The primary end point of the Mementum trial is the relative percent range and body weight at 48 weeks compared to baseline.
with additional readouts, including serum lipoprofiles, cardiovascular measures, and glucose homeostasis. Dr. Luaroni from Wild Cornell Medical School, a leading authority in obesity and obesity clinical trials is serving as the principal investigator. We expect to have the results of an interim amount analysis of the momentum trial in the second half of March. That analysis will be comprised of approximately 160 subjects that received 24 weeks of therapy. The readout parameters are expected to include weight loss, serum lipids, adverse events, vital signs, glucose control, and study discontinuations.
We have also completed an enrollment in our Phase 1 Multi-Center Safety Trial, evaluating glucose control in subjects with Type 2 diabetes over 12 weeks of treatment. Approximately 48 subjects were planned with a readout expected in March 2023. The purpose of this trial is to establish the safety of Pemphiduteide in preparation for end-of-phase-to-meaning with the FDA, which is expected early next year. Across the trials I have described, we are rapidly building the safety profile of Pemphiduteide with unblinded safety data accrued and over 200 subjects receiving Pemphiduteide in clinical trials.
at year end 2022 and approximately 500 subjects by year end 2023. We are also making excellent progress in our enrollment of our Phase 2 multi-center clinical trial of HEPTSO. The trial was designed to enroll approximately 80 subjects with over 90 percent now enrolled. We expect to read out the results of this trial in the first half of 2024, once all subjects complete the six-month treatment period. Recall that HEPTSO is an immunotherapeutic against hepatitis B virus.
And that the virulotic effects of heptis cell are being evaluated in chronically infected patients with partial control over infection to enable the combination of heptis cell with novel direct acting antivirals as part of chronic therapy for chronic hepatitis B. It is believed that effective treatment of chronic hepatitis B will include combination therapy of a direct acting antiviral and an immunotherapy of immunotherapy. I will now hand the call over to to reach out to the stats given up date in our third quarter financial results. Rich?
Thank you Scott, good morning again. For today's call I will be providing a brief update on Altamune's full year and fourth quarter 2022 financial and operating results. Core comprehensive information will be available in our form 10K to be filed with the SEC later today. Altamune ended the fourth quarter of 2022 with approximately $184.9 million of cash, cash equivalents and short term investments compared to $190.3 million at the end of 2021. Turning to the income statement.
Revenue was negligible in the fourth quarter of 2022 compared to $3.3 million in the same period in 2021. The negligible negative revenue reported in 2022 was due to adjustments to cost reimbursement under an now completed bar of a contract. Fourth quarter of 2021 revenue was primarily prior period rate adjustments received in that quarter or earlier government funded research projects. Revenue for the full year 2022 was negligible compared to $4.4 million in 2021. The revenue in 2021 was attributable to the bar of a contract and TCOVID programs which were concluded in 2021.
Research and development expenses were $70.5 million in full year 2022 compared to $74.5 million in the prior year. The decrease in R&D expenses primarily the result of a $35.1 million decrease in ad COVID and TCOVID related development costs with programs were discontinued in 2021. This included the expense of payments made the launch of for the construction of a manufacturing suite.
In four year 2022, we incurred $46.8 million in direct costs associated with the NAFEL or my Madam Trials for Pemphiduteide and $7.5 million in direct costs associated with the HAPD cell campaign. General and administrative expense were a consistent period over a period at $3.8 million in each of the fourth quarters of 2020-2021. For the four year 2022, General and administrative expense were $17.1 million versus $15.4 million for full year 2021. The $1.7 million increase was primarily due to increased stock compensation expense, as well as additional labor-related costs in 2022. Net loss for the three months ended December 31st, 2022, was $21.7 million or $43.3 million.
since net loss per share compared to net loss of $23.9 million or $57.0 net loss per share for the fourth quarter of 2021. The reduction in net loss is primarily attributable to the $1 million lower research and development expenses, $3.3 million in non-recurring expense in 2021 for the recognition of the Lonson Permanent Loss and the $1.3 million increase in interest income offset by the reduction in contract revenue. Net loss for the year ended December 31, 2022 was $84.7 million or $1.81 net loss per share.
compared to $97.1 million or $2.35 net loss per share for the year ended December 31, 2021. The decrease in net loss is primarily a trivial to the lower research and development expenses in 2022. $11.4 million in non-recurring expense in 2021 for the recognition of the loss in the impairment loss and the $2.7 million increase in interest income offset by the reduction in contract revenue. We currently estimate that our research and development expenses for full year 2020-23 will be approximately $90 million.
DNA expenses for the full year 2023 are anticipated to be approximately $18 million. Approximately $10.1 million of these operating costs are for non-cash expenses, including stock compensation and depreciation and amortization. We estimate that our existing cash funds are sent to the second half of 2024, which includes completion of the 48-week momentum trial and completion of enrollment of the phase 2B biopsy NAS trial. Our current cash projection also anticipates investment in 2023 and phase 3 obesity clinical drug supply, as well as funding in 2024 for the initiation of phase 3 obesity campaign. I will now turn the call back over to Vipin for his closing remarks. Vipin.
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? As a reminder to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by when we compile the Q&A roster. Of course the discussion will be staffed, there will be questions related to your telephone.
Our first question comes in the line of shame is Fernandez from Guggenheim Securities. Great, thanks so much for the question. So two questions for the team here. First and foremost, if you could lay out what you would hope to see in the momentum study just from a weight loss perspective that would be, you know, from your perspective clinically relevant and likely successful as an obesity agent at 24 weeks.
perhaps even generating strategic interests or potential partnership opportunities. We'd love to just hear how the team is thinking about those levels and thresholds and perhaps, you know, comparable products that, you know, make sense in that regard. And then second, as it relates to the NASH study, can you just help us better understand how the recruitment in biopsy-driven studies at least has been progressing or perhaps just the general sense of when your 24-week data could potentially be available? I know it's a little bit of a...
product profile to figure out where does your products will fit in the long run in the obesity land space. Landscapes. So if you think about it at 48 weeks or at the end of treatment approximately a year, what we are looking to achieve is about 15 to 20% weight loss. We think that's where one needs
serum lipid reduction and serum lipids and so on. So all of that has to be sort of factored into determining the overall competitive profile of the product. So if you back off of that and look at 24 weeks, we would expect to be on weight to achieving that 15 to 20 percent weight loss. So 24 weeks, you know halfway there.
Regarding your second question, we think that we're putting together a very strong plan for recruitment. We think we've identified a number of very good sites. As you know, Steve and Harrison are serving as the principal investigator of the trial once again. He's a great organizer and there's a very established network under his direction. So we feel very good about the recruitment plan and doing it in the United States.
Regarding that, we think that we could have a readout on that 24-week endpoint in the first half of 2025. Great. Thanks, very helpful. And then just as a final follow-up question, and I'll jump back into Q, you know, as we think about the prospect for 8% to 10% weight loss, you know, I assume just to clarify, is that placebo-subtracted weight loss that you're hoping to see?
Maybe just a little bit of incremental context. Can you remind us at 24 weeks what we go with the Anne Terzepiti to achieve? Thanks. Hey, Shamis. Yes, as we've said before, that age of 10% is placebo-adjusted. As Vipin mentioned at the end of the year, we'd like to be in that 15 to 20% range. And where we would be at the end of 24 weeks is how you look at the curve. We should point out that at the same time point, the 24 weeks semaglutide, which has been a very successful drug. I think there are over 60,000 scripts written last week alone was at 8% placebo-adjusted weight loss.
Terzepetide was at 12%. So the 8 to 10% is certainly within that range and it's actually in excess of the hemidlutide. We think that, you know, based on our Phase 1 data, we can have very, very good weight loss. But we've constructed our target product profile to include not just a weight loss percentage number, but the full spectrum of what's going to differentiate drugs and get doctors to use them. And the benefits of the drug are going to be well beyond the simple weight loss number. It's going to include all the other attributes that Vipin talked about. Yeah, and I would also point out that when we are comparing 15 to 20%.
And detail. Two questions for you. I just wasn't wanting to drill down in the design of the Nash study. What is the duration of the study? And I just wanted to also clarify, is the study powered for both end points, Nash revolution, as well as a one point improvement of fibrosis. And then broadly speaking, what is the size of the study going to be?
taking my long list of questions. Yeah, I mean, let me take the second question, and then Scott, maybe you can take the first one. So as far as the diabetes studies concern, I mean, both the studies are neck and neck. We're prioritizing the momentum study to make sure that data is out as quickly as possible in the second half of March. But we're also expecting the diabetes data around the same times. It's hard to say exactly what the timing will play out, but I would say it's going to be very close to each other.
We'll need to be worked out, but the hope would be that we could power for both. But again, that's going to depend on the sample size, and that hasn't been finalized at this point either. But we do hope to get you those details as soon as possible.
Thank you, Scott. Just a clarification question. Given that, you hope to have the data. I guess in the first half of 2025, can we assume that the study will be a one-year duration or rather than six months or a little premature to make these wrong assumptions when everyone ????????
Well, the primary endpoint of the study will be read out of 24 weeks or six months and we're making a decision about whether to continue to follow a patient for other parameters such as safety or the non-invasive markers for a longer period of time. And that decision is being made right now. But assuming that we get the trial commenced mid-digit year this year.
And then the time period that we anticipate will be necessary to improve the requisite number of patients. And then the 24 weeks of treatment follow up, we think that a first half, 2025 data readout is very realistic. Great. Thank you so much and really the best of luck as we're headed in the next few weeks. Thank you again. Thank you. One moment for our next question. Our next question comes in the line of Roger Song from Jeffries. Great. Thank you Kim for taking our questions.
So one is given the clear topic effects from the penvertitized, can you guys just lay out what are the targeted populations you want to address, particularly for the obesity plus minus math over the Nash, maybe some other pulmability penvertitized with you know, better or worse, the position to address. If you can give us some details in terms of the numbers, they'll be very helpful. I'll have a follow-up question after that. Thank you. Hey Roger and good morning. So there is a great deal of overlap between the obesity population and the Nash population.
Just made it that 50% of obese patients have naffled in virtually all national patients in the United States have obesity. And it's known that they share similar comorbidities. Nash patients at their terminal stages of liver disease die of liver disease but they predominantly die of the cardiovascular complications.
And therefore, it's important when you treat the national patient to treat not only the process going on in the liver, but also the obesity as well to have a meaningful impact. We also think that doctors, when they prescribe to patients, will pick drugs for the treatment of national, also offer weight loss, not only because they believe it so, but because patients also want it. And I point out that in the national base, we believe that we're the only drug that have effective interventions on both national inflammatory and phybrotic activity at the end of the trial, but also weight loss.
So, when you're looking at the obesity population, clearly right now in its early stages of the marketplace and development, people are looking at one thing, they're looking at the percentage weight loss. That would be nice of insurance companies, we're looking at that as well. We know that the primary dose of through Zepatide that's being prescribed right now is not the 15 milligram dose.
But the 5 milligram dose gives you an idea of the kind of weight loss that prescribers and patients might want right now, and despite the fact that your zephytide had a higher percentage weight loss than semiglutide in clinical trials that semiglutide is being prescribed quite nicely. Our projection for the percentage weight loss is actually greater than semiglutide at 24 weeks. But we think in terms of the target product profile, what will it include? It will include meaningful weight loss. Meaning, as Vipin pointed out, in that 15 to 20 percent range, although at the end of 48 weeks.
Although we think that based on our phase one study results, we can achieve more than that. We believe a successful target product profile would include that as a base case. But we think it's important that it also be replete with the treatment of the cum morbidities that are ultimately going to drive prescriptions and insurance approvals such as reduction in serum lipids, reduction in hepatic fat, meaningful reductions in blood pressure, which we're achieving unlike some other compounds in development with only minimal increases in heart rate.
Roger, in that context, it's helpful to also understand that the NIH states that 60-70% of obese people are a dyslipidemic. And the ability of Gukagon to drastically change the metabolism of lipids and lower serum lipids and liver fetus scutches indicated certainly creates a special target population in that respect. Thank you.
Excellent. Thank you. Appreciate other comments, Lerga. Very quick one in terms of the Nash. I know it's early stage, you're still finalizing the design, but just in terms of given the the multitude, the effect from Pemberday Thai, what could be the ideal population you will do like an earlier stage in terms of the Nash stage or some other consideration you will.
have for the patient population. Thank you. Well, thanks for the question, Roger. So it had been said early on in Nash development that metabolic drugs treated the early stages of Nash, whereas you needed anti-fibrotic drugs to treat the later stages. That paradigm has been turned on at 10, because we now have two metabolic active drugs, whereas mid-Arom and Afroxocermin, which have completed phase three and phase two respectively, having very meaningful effects on fibrosis.
So what that shows is that if you affect the liver and have effective liver fat reduction, you're going to have effective reduction in inflammatory and fibiotic activity, which is going to drive activity not only from fat reduction all the way through fibrosis improvement. So we actually see the product population for the study being all stages of Nash up until advance fibrosis. That's been a tough population to treat. And we point out that the greater the reduction in the liver fat, the greater the effects that I just mentioned have been in clinical trials. Very happy about the risk of the risk minimum results, the reduction of liver fat at 24 weeks.
was about 49 to 50 percent. With a flux of firm and it was about 65 to 70 percent, we're 70 to 75 percent. Based on that, we're very, very optimistic about Bob C. results in the future. But with res mid-Arom, which we believe will go on to approval, only 25 percent of people had a response in either a national resolution of fibrosis improvement. We think that's great at least the regulatory precedent, but we also believe there's a large amount of room for improvement that we think we can fill. Excellent. Thank you. Thank you. One moment for our next question.
Our next question goes on the line of Col Ren Jenkins from Goldman Sachs. Thanks and good morning. Maybe first for me just based on what we saw in the Apple study, how do you think the dose titration and the 2.4 meg per kick arm could impact safety compliance and then maybe don't dream about efficacy in the upcoming momentum rate out? Well, thank you for the question, Corinne. So we put that short titration in place based on some observation we made in our first in human study. With the 2.4 milligram dose, we saw more.
GI, Intolerability events, and they were curling early on in the first one to two weeks. So we thought that a four week titration would mitigate adverse events, and we saw something to that effect in our NAFL detrial. Whether we continue to use that titration going in forward in the future, we'll have to see based on the data that we accrue. We think that at the end of 24 weeks with a four week titration, it would probably at that point in time have a minimal effect in the overall weight loss, and certainly by 48 weeks, there'd be sufficient time.
to minimize the impact of the effect of the titration. We're not committed by the way to using titration going forward. You know, we'll look at the data, we may drop it. We'd point out that we're the only drug development for either obesity or Nash that's in-credits and based that can actually dose without dose titration. We have the optionality if we want, and this is not something we're doing right now, but something that we're quite aware of. So if we ever got back research, for example, market research, which we're conducting continuously, that patients preferred the tolerability over the titration. We could offer titration as an adjunct either in a late-stage trial or as a separate user trial.
and actually offer that to patients and doctors as a prescribing option. It's something that the other drugs and development like tears appetite and insumacletized can't do because they're already added four to five months of titration and the question is, how much longer do they need to go? So we think that the titration based on what we've seen before is helping, but is it needed? We don't know. We'll let effect the efficacy of 24 weeks. We don't believe it will and certainly not at 48.
And then just a point of clarification from me with the diabetes coming soon. Will you share weight loss data from that trial or is it going to be primarily focused on the diabetes related endpoints? Right. Now we will share that data. We'll also share the information on the diabetes endpoints. Thanks. Thank you. One moment for our next question. Our next question comes to the line of Mayan Manthani from Be Riley. Good morning team. Thanks for taking our questions and congrats on the progress. So on the face to be nasty, design, I know you're not commenting on the total number of subjects yet, but this curious, if you're in Terem 24 week readout, you know, will be like the face to be momentum readout where you include sort of a smaller cohort of patients for that 24 week biopsy or would you have the full population just trying to see, you know, how.
How is excitement better out there for enrolling for your NAS study like we saw in the obesity study? Thanks for the question, Mayunk. You know, that readout that would occur in the first step of 2025 would not be an inter-minalysis. That would be a full readout because it's a readout on the primary endpoint at the established time point for reading it out. Now, we may elect to continue following patients, but the efficacy of the study with regards to the primary endpoint would already be established. So, when we read out on the first half of 2025, it will be in the entire study population. And that's in contrast to the readout that we're going to have in the latter part of March, where we're actually doing a cut of the patients approximately 160 or approximately 150% of the patients. It only at about half of therapy. So, the readout in the first step of 2025 in that NAS trial will be a complete readout. Thank you for that clarification. And then on momentum, seems like the focus here is on the value of data rather than any.
one specific metric that's a weight loss. Are you able to comment on what your expectation might be on? Maybe the discontinuation rate for Penn V versus Pacific Evo and also I think a similar comment if you could have on the hyperglide senior study that you're running in parallel to momentum. I know the follow up there is shorter there 12 weeks and I have one final question after that. Yeah, well, we'll have information on the discontinuation rates. I don't anticipate that we'd be talking about other people's data on that read out but we should have that information for you in both trials. And your expectation for that rate to be in one range. Yeah.
So, you know, historically, in obesity trials, up until the recent couple of years, the discontinuation rates were quite high. We've seen them come down recently that I 20 to 30 percent range. The other thing to comment on is the fact that discontinuations in any trial like this are not a continuous process, they're probably going to be front and loaded. So that has to be taken into consideration. And when you look at the discontinuations that are reported at the 24 week readout, we'll have that information. We'll share it with you and we're happy with what we're seeing so far. Great. And in the final sort of big picture question, is he prepared for that end of phase two of DM meeting? I know it's a bit early to talk about that, but just curious if, you know, you're thinking of a late stage program, you know, in terms of scale that kind of mirrors, you know, what we've seen with step and surround program, you know, which includes an active competitor and our, you know, studying, studying family with certain combination measurements. Are you able to share?
for Terzephatide where they compared it to an outdated dose of stomach gluteide or a sample for the treatment of obesity. So, you know, I think at this point in time, the questions are there. We have a concept that would look somewhat like.
the other programs will we need to have that discussion with the agency? Great. Thanks for taking that question. Thank you. One moment for our next question. Our next question comes from the line of John Woolivan from JMP Securities. Hey, good morning. Thanks for taking the question. You touched on this a little bit about the serum lipid data that you're going to release as well. I was just wondering if you gave us a little more context on what you consider to be a meaningful reduction when we're looking across the class for both 24 and 48 weeks. And how important do you think that attribute is moving forward for these ultimate utilization? Well, thanks, John . So.
Ultimately, the lipid reduction we want to get is going to be at 48 weeks. It's probably going to be progressive improvement of the course of time. So with the other programs like Turs Epitides, I'm agglatized, the reduction in total LDL cholesterol has been minimal. My recollection is for LDL in the range of about 3%, maybe as high as 5%. So these drugs don't really move cholesterol. They do have very potent effects and triglycerides. We've seen with the glucagon mechanism that you can move LDL cholesterol. We saw that in our first trial. So we would hope to achieve something, you know.
Above that 5% range, hypothetically, maybe in that 10% range would be very nice to see. But again, the number would have to be achieved at 48 weeks in our first inhuman trial. We were able to see a 20% approximately, 20% reduction in LDL and total cholesterol. And that's directly attributable to the glucagon. And our hope is that we would be meaningfully above the other drugs when we look at the trial with 48 weeks. That's helpful.
Is it worth moving forward the 2.4 or is the 1.8 probably the sweet spot? Just wondering how you think about that. Thanks. Well, that's a question that's on our mind. The decision is going to be done to driven. So obviously, we'll make decisions about the natural based on what we see in momentum, whether we carry the 2.4 milligram does forward. You know, although we haven't seen any convincing data that 2.4 is better than 1.8, we'll be doing it.
We do know at least from the obesity point of view with a semi-glutide that when they got to super obesity, which we define as a 110 or 115 kilograms, that serum concentrations dropped. And with that, there was a reduction in the percentage weight loss that patients achieved. Now that wasn't seen with your zephytod. And then the question is, will we as a compound behave more like some agglutide or tersephytod? At this point, we've modeled out the data, but we're not absolutely certain. So we've used the 2.4 milligram dose. Essentially is an insurance policy in case we also see that effect. That strategy may be more relevant to obesity than Nash.
We are modeling the data. There are systems and modeling efforts that you use, among them, things like population PK. So we'll use that information that we're developing in-house in the menum data, make a decision about the cadosis going forward. And that in many ways will drive the sample size, which was one of the earlier questions. If we have multiple arms in the study, including 2.4, that would require more patients to achieve adequate power if we're not going to do 2.4, the study would be smaller and we could get it done more quickly. And that's what's being considered right now, which is why we're not making an announcement about the design or the numbers. We want to see the results of the menum trial, finish our modeling, and then we'll come up with a conclusion. And as soon as we have that, we'll share that conclusion and the design of the trial with the street.
Very helpful color. Thanks, Scott. Thank you. One moment for our next question. Our next question comes in the line of Patrick Tuchio from H.C. Wayne Wright. This is Joe on for Patrick. Thank you for taking the question. Switching gears a little bit to the HEPKey cell phase two. I'm just wondering from the initial readout following the six months on treatment in terms of both clearance and HEPKey surface antigen and zero conversion. How important is it that patients also achieve zero conversion at six months? I think that, you know, obviously that's that that's a nice to have. I think we're really what we're looking for is the ability to reduce the surface antigen and you know, this is still a relatively short term. We've tried to leave an at six months of treatment and so zero conversion is is is you know, certainly being followed is certainly of interest. But I think that significant reductions in the in the surface antigen. We set the bar at one.
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. This concludes today's conference call. Thank you for participating. You may now disconnect.