Q4 2024 Acumen Pharmaceuticals Inc Earnings Call
Okay.
Unknown Executive: Good day and welcome to the Acumen Pharma Fiscal Year 2024 conference call and webcast. At this time, all participants are in a listen-only mode. After this brief presentation, there will be a question and answer session.
Good day and welcome to the acumen farm by fiscal year 2024 conference call and webcast. At this time all participants are in a listen only mode.
After the presentation there'll be a question and answer session and instructions will be given at that time.
Unknown Executive: Instructions will be given at that time. As a reminder, this call may be recorded.
Alex Braun: I would like to turn the call over to Alex Braun, Head of Investor Relations. Please go ahead. Thanks, Michelle.
As a reminder, this call maybe recorded.
Speaker Change: Like to turn the call over to Alex Brown head of Investor Relations. Please go ahead.
Alex Braun: Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the year ended December 31, 2024.
Alex Brown: Thanks Michelle.
Speaker Change: Morning, and welcome to the Acumen conference call to discuss our business update and financial results for the year ended December 31st 2024.
Alex Braun: With me today are Dan O'Connell, our CEO and Matt Zuga, our CFO and Chief Business Matt and Dan have some prepared remarks, and then we'll open the call for questions.
Speaker Change: With me today are Dan O'connell, our CEO and Matt will go I see a filing chief business officer.
Speaker Change: And Dan has some prepared remarks, and then we'll open the call for questions.
Alex Braun: Joining for the Q&A session, we also have Dr. Jim Doherty, our President and Chief Development Officer, and Dr. Eric Siemers, our Chief Medical Officer.
Speaker Change: Joining for the Q&A session. We also have Dr. Jim Doherty, our president and Chief Development Officer, and Dr. Eric Siemers Chief Medical Officer.
Alex Braun: Before we begin, we encourage listeners to go to the investors section of the Acumen website to find our press release issued this morning that we'll discuss today. Please note that during today's conference call, we may make forward-looking statements within the meaning of the federal securities laws, including statements concerning our financial outlook and expected business. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statement. Please see slide two of our corporate presentation, our press release issued this morning, and our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to differ materially from those expressed or implied in the forward-looking statement.
Speaker Change: Before we begin encourage listeners to go to the investors section of the Atlanta website to find our press release issued this morning that we'll discuss today.
Speaker Change: Please note that during today's conference call. We may make forward looking statements within the meaning of the federal securities laws, including statements concerning our financial outlook and expected business plans.
Speaker Change: Statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward looking statements.
Speaker Change: Please see slide two of our corporate presentation. Our press release issued this morning, and our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to differ materially from those.
Speaker Change: That's the or implied in the forward looking statements.
Alex Braun: We undertake no obligation to update or revise the information provided on this call or in the accompanying presentation as a result of new information or future results for development.
Speaker Change: We undertake no obligation to update or revise the information provided on this call or in the accompanying presentation as a result of new information or future results.
Dan O'Connell: So with that, I'll turn the call over to Dan. Thanks, Alex. Good morning, everyone. And thanks for joining us today.
Speaker Change: Uh huh.
Dan O'Connell: So with that I'll turn the call over to Dan.
Speaker Change: Yeah.
Dan O'Connell: Thanks, Alex Good morning, everyone and thanks for joining us today.
Dan O'Connell: Acumen entered 2024 from a position of strength, stemming from our positive results for Sobrena Tug in our Intercept AD Phase 1 study in early Alzheimer's. In Intercept A-D, Sobernatum was well-tolerated, demonstrated novel target engagement of A-beta oligomers, and produced consistent effects on imaging and fluid biomarkers in a dose-dependent manner. I'm proud, though not surprised, that our talented team leaned into this momentum and executed on our enrollment plans for Altitude AD our Phase II study designed to evaluate the clinical efficacy and safety of subornitogin in patients with MCI or mild dementia due to Alzheimer's, also known as early AD.
Speaker Change: Accumulated 2024 from a position of strength stemming from a positive results for some prototypes in our intercept <unk> phase one study in early Alzheimer's patients.
Speaker Change: In intercept <unk> was well tolerated demonstrated novel target engagement of a beta oligomers and produce consistent effects on imaging and fluid biomarkers in a dose dependent manner.
Speaker Change: I'm proud, but not surprised that our talented team leaned into this method and executed on our enrollment plans for altitude.
Speaker Change: Our phase II study designed to evaluate the clinical efficacy and safety of children and patients.
Speaker Change: <unk> with Mci or mild dementia due to all summers also known as early a D.
Dan O'Connell: Last year, our team worked effectively to advance the Sobernatung story, and we believe this underpinned the swift pace of enrollment seen in the Alta We engaged with the research community who recognized and embraced the novelty of Cibernetug's mechanism of action targeting toxic abated oligomers. We also engaged with experienced clinical investigators and trial sites who appreciate the consistency of the phase one results with this mechanism and who also recognize SobornaTUG's potential as a next generation treatment for early AD based on an improved benefit to risk profile. We dosed the first patient in Altitude in May of 2024 and just yesterday announced the completion of enrollment of 542 participants in the study.
Speaker Change: Last year, our team worked effectively to advance for subordinate type story.
Speaker Change: This underpins a swift pace of enrollment change in altitude.
Speaker Change: We engaged with the research community recognize and embrace the novelty of <unk> mechanism of action targeting toxic a beta oligomers.
Speaker Change: We also engaged with experienced clinical investigators and trial sites, who appreciate the consistency of the phase one results with this mechanism and who also recognized <unk> potential as a next generation treatment for early.
Speaker Change: Based on an improved benefit to risk profile.
Speaker Change: We dosed the first patient in altitude and May of 2024.
Speaker Change: Just yesterday announced the completion of enrollment of 542 participants in the study.
Dan O'Connell: Clinical Enrollment Milestone is a key catalyst for our Sobernatyte program. This accomplishment also provides convincing evidence of our team's ability to operationalize and exceed enrollment goals for this sizable multinational phase two trial. The study's primary endpoint is a change from baseline to 18 months on the Integrated Alzheimer's Disease Rating Scale, or IDRIS, which measures cognition and activities of daily living, such as performing common household tasks, engaging in hobbies, and conversing about current events. We've also incorporated the CDR-7 boxes and other typically used secondary measures, including imaging and fluid biomarkers.
Clinical enrollment milestone is a key catalyst for our support of type program.
Speaker Change: Accomplishment also provides convincing evidence of our team's ability to operationalize it exceed enrollment goals for this sizable multinational phase III trial.
Speaker Change: The study's primary endpoint is a change from baseline to 18 months on the integrated all summers disease rating scale, or I guess, which measures cognition and activities of daily living such as performing common household tasks engaging and hobbies and conversing about current events. We've also incorporated the CVR sum of boxes and other.
Speaker Change: Typically used secondary measures, including imaging and fluid biomarkers.
Dan O'Connell: With enrollment now complete, we expect to top-line results in late 2026, inclusive of the key efficacy and safety measures.
Speaker Change: With enrollment now complete we expect top line results in late 2026 inclusive of the key efficacy and safety measures.
Dan O'Connell: We also recently completed our phase one study investigating a subcutaneous administration of Sobernata.
Speaker Change: We also recently completed our phase one study investigating a subcutaneous administration of Savannah type.
Dan O'Connell: This was a pharmacokinetic comparison study comparing subcutaneous and intravenous administrations of Cibernetug in healthy volunteers. We believe a potential subcutaneous formulation of Subernata alongside the IV formulation will create important optionality for patients and providers. For instance, in some cases, greater convenience via subcutaneous administration may be more important and advantageous, whereas more touch points provided by IV infusions may be more appropriate or preferred in other situations. Providing Sobernitug in both formats may also facilitate greater optionality around treatment and induction, excuse me, treatment induction and maintenance phase. Importantly, results from the study showed that subcutaneous subornitine was well-tolerated, with systemic exposure supporting the continued development of this format.
Speaker Change: This was a pharmacokinetic comparison study comparing subcutaneous and intravenous administrations of <unk> in healthy volunteers.
Speaker Change: We believe a potential subcutaneous formulation of <unk> alongside the IV formulation will create important optionality for patients and providers.
Speaker Change: For instance, in some cases greater convenience via subcutaneous administration may be more important and advantageous, whereas more touch points provided by IV infusions may be more appropriate or preferred in other situations.
Speaker Change: Regarding suburban a tug in both formats may also facilitate greater optionality around treatment and induction excuse me treatment induction and maintenance phases.
Speaker Change: Importantly results from this study showed that subcutaneous <unk> was well tolerated with systemic exposure supporting the continued development of this format.
Dan O'Connell: Our next steps for the development of subcutaneous formulation of Ciberna Tug will include ongoing formulation work and other data inputs.
Speaker Change: Our next steps for the development of a subcutaneous formulation of <unk> will include ongoing formulation work and other data inputs inputs.
Dan O'Connell: We remain committed to communicating the development of Sabonotype through presentations at medical conferences and peer-reviewed publications. We've maintained a significant presence at all the major Alzheimer's conferences, ADPD, AAN, AAIC, and CTAD.
Speaker Change: We remain committed to communicating the developments and prototype through presentations at medical conferences and peer reviewed publications, we maintain a significant presence in all the major <unk> conferences ADP D <unk>.
Dan O'Connell: We will present our phase one results at several upcoming medical meetings. These presentations will focus on the importance of our fluid biomarker data that showed consistent trends towards normalization after only three doses in the study.
Speaker Change: <unk> and <unk> we.
Speaker Change: We will present, our phase one results at several upcoming medical meetings.
Speaker Change: These presentations will focus on the importance of our sugar biomarker data that showed consistent trends towards normalization. After only three doses in the study.
Dan O'Connell: I'm very pleased to note as well that our Intercept AD Phase 1 manuscript was published in the Journal of the Prevention of Alzheimer's Disease, or J-PAD, in January 2025. In addition, a related publication detailing the fluid biomarker changes in that study was also published online in J-PAD just last month. You can find both publications online at the journal and linked on our website.
Speaker Change: I am very pleased to note as well that our intercept these days while manuscript was published in the journal of the prevention of all servers disease, where J pad in January 2025.
Speaker Change: In addition, our related publication detailing the fluid biomarker changes in that study was also published online and <unk> just last month.
Speaker Change: You can find both publications online at the journal and linked on our website.
Dan O'Connell: Next week at ADPD, we will also present the use of a plasma P-Tau 217 assay as a screening procedure in Altitude AD, our ongoing Phase II study. The use of this screening assay considerably improved enrollment efficiency and decreased patient burden and cost in the screening process. Feedback on the use of this PTAU 217 assay has been very positive, as evidenced by the rapid pace of our Phase 2 enrollment.
Speaker Change: Next week at ADP D. We will also present the use of plasma <unk> 17 assay as a screening procedure in altitude, our ongoing phase II study.
Speaker Change: The use of this screening assay considerably improved enrollment efficiency and decreased patient burden and cost in the screening process feedback on the use of this <unk> 2017 assay has been very positive as evidenced by the rapid pace of our phase two enrollment.
Dan O'Connell: Utilization of fluid biomarkers in this way is a prime example of innovation in the Alzheimer's space and a clear indication of how fluid biomarkers will continue to advance the field from diagnostic, treatment, and development perspectives.
Speaker Change: Utilization of fluid Biomarkers in this way is a prime example of innovation in the Alzheimers space and a clear indication of how fluid Biomarkers will continue to advance the field.
Speaker Change: <unk> treatment and development perspective.
Dan O'Connell: At Acumen, we are staunchly committed to our strategic goal of advancing the clinical development of SobrenaTug in a diligent and efficient manner. We are executing at a very high level as supported by all of the progress reported here today. We remain encouraged by the continued adoption of new Alzheimer's treatments, which we believe illustrates the large underlying demand in this growing and long underserved patient population. Fundamental elements of the Alzheimer's landscape include an aging population, more diagnosed cases driven by the increasing ability to diagnose in earlier stages of disease due to better blood-based biomarkers, and more treated cases due to the availability of options and continued establishment of screening and infusion capabilities for monoclonal antibodies.
And accurate where stocks, we committed to our strategic goal of advancing the clinical development of <unk> and intelligent and efficient manner.
Speaker Change: We are executing at a very high level that is supported by all of the progress reported here today.
Speaker Change: We remain encouraged by the continued adoption of new Alzheimers treatments, which we believe illustrates the large underlying demand in this growing and underserved patient population.
Speaker Change: The following fundamental elements of the Alzheimers landscape include an aging population.
Speaker Change: Diagnosed cases, driven by the increasing ability to diagnose and earlier stages of disease due to better blood based biomarkers and more treated cases due to the availability of options and continued establishment of screening of infusion capabilities for monoclonal antibodies.
Dan O'Connell: We believe the adoption of anti-ABETA treatments will continue to grow and hopefully serve as the cornerstone of AD treatment for the foreseeable future. The dynamics of this patient population also present a great opportunity for improvements with next generation anti-AMYL therapies and in the future combination approach.
Speaker Change: We believe the adoption of anti a beta treatments will continue to grow and ultimately serve as the cornerstone of 80 treatment for the foreseeable future.
Speaker Change: The dynamics of this patient population also presents a great opportunity for improvements with next generation anti amyloid therapies and in the future combination approaches.
Dan O'Connell: We believe in the promises Soberna took as a next generation treatment option for Alzheimer's patients based on an improved benefits risk profile, and are highly motivated to make an outsized impact on this devastating disease, which affects all of us in one way or another. I look forward to providing updates as we progress towards the Altitude AD Phase 2 data readout next year.
Speaker Change: We believe in the promise of <unk> as a next generation treatment option for all <unk> patients based on an improved benefit risk profile and are highly motivated to make an outsized impact on this devastating disease, which affects all of us one way or another.
Speaker Change: I look forward to providing updates as we progress towards the altitude <unk> phase II data readout next year.
Matt Zuga: And with that, I'll turn the call over to Matt for the final. Thank you, Dan. As a reminder, our full year 2024 financial results are available in the press release we issued this morning, and in our 10k we'll file later today. We ended 2024 with $231.5 million in cash and marketable securities on our balance sheet, which is expected to support our current clinical and operational activities into the first half of 2027. R&D expenses were $93.8 million in 2024. The increase over the prior year was primarily due to the increased spending to support the Alpitude AD trial.
Speaker Change: I will turn turn the call over to Matt for the financials.
Matt: Thank you Dan as a reminder, our full year 2020 core financial results are available from our press release, we issued this morning.
Speaker Change: And in our 10-K.
Matt: While labor right.
Matt: We ended 2024 with $231 $5 million in cash and marketable securities on our balance sheet, which is expected to support our current clinical and operational activities into the first half of 2027.
Matt: R&D expenses were $93 $8 million in 2020 for the.
Matt: The increase over the prior year was primarily due to the increased spending to support the alpha trial.
Matt Zuga: began enrollment in May 2024. G&A expenses were $20.2 million in 2024, roughly flat to the same period in the prior year. This led to a loss from operations of $114 million.
Matt: Which began enrollment in may 2024.
Matt: G&A expenses were $22 million in 2020 core roughly flat to the same period in the prior year.
Matt: Led to a loss from operations of $114 million.
Matt Zuga: and the net loss of $102.3 million during the year after accounting for an I'm pleased with Acumen's execution on every level as we continue to work to interrogate the promise of Sobernitug for the treatment of early AIDS. With enrollment now complete in our Altitude AD Phase 2 trial, we look forward to sharing top-line results, which are expected in late 2026. and remain dedicated to delivering a potential next-generation treatment option for the unmet need in this patient population.
Matt: The net loss of $102 $3 million during the year after accounting for interest income.
Matt: I am pleased with documents execution on every level as we continue to work to interrogate the promise of suburban product for the treatment of early.
Matt: With enrollment now complete and our altitude <unk> phase II trial, we look forward to sharing top line results, which are expected in late 2026.
Matt: Remain dedicated to delivering and potential next generation treatment options the unmet need in this patient population.
Unknown Executive: And with that, we can open the call for Q&A. Operator. Thank you.
Matt: With that we can open the call for Q&A operator.
Unknown Executive: If you'd like to ask a question, please press star 1 1. If your question hasn't answered and you'd like to remove yourself from the queue, please press star 1 1 again.
Speaker Change: Thank you if you'd like to ask a question. Please press star one one if your question has been answered and you'd like to remove yourself from the queue. Please press star one again.
Jason Zemansky: Our first question comes from Jason Zemansky with Bank of America. Your line is open. Good morning.
Speaker Change: Our first question comes from Jason's Umansky with Bank of America. Your line is open.
Dan O'Connell: Congrats on the progress and thank you for taking our questions. Maybe a higher level one from us, especially now that you have the good data for the subcutaneous formulation. As the field sort of is continuing to evolve, there seems to be greater interest in looking at the anti-amyloid mechanism earlier in the disease, and certainly a number of your competitors are opening trials where they're looking at preclinical AD. I'm curious, is that on your landscape at all, especially now that the Phase II has completed enrollment? How does that, I guess, rank on your priorities as you move forward?
Jason Umansky: Good morning, Congrats on the progress and thank you for taking our questions maybe a higher level one from us, especially now that you have the good data for the subcutaneous formulation.
Jason Umansky: It feels sort of is continuing to evolve there seems to be greater interest in looking at the anti amyloid mechanism earlier in the disease.
Jason Umansky: Certainly a number of your competitors are opening trials, where you have it.
Jason Umansky: Looking at preclinical.
Jason Umansky: Im curious is that on your landscape at all especially now that the phase two.
Jason Umansky: As has completed enrollment.
How does that I guess rank on your priorities as you move forward.
Dan O'Connell: Thanks, Jason. So right now, we're extremely focused on the execution in altitude AD and this early AD population.
Jason Umansky: Thanks, Jason So so right now we are seeing.
Jason Umansky: Really focused on the execution and altitude and materially AIDS population I think we're obviously cognizant of the possibility of moving into that preclinical population, particularly as I mentioned sort of utility based biomarkers and better profiling of patients.
Dan O'Connell: I think we're obviously cognizant of the possibility of moving into that preclinical population, particularly, as I mentioned, sort of the utility blood-based biomarkers and better profiling of patients. I think we can also envision where the mechanism of subornitone targeting these toxic soluble aggregates. of A-beta are an early and persistent part of the pathophysiology of the disease, and so an agent that's selected for these species, such as Sobernatyte, could be highly useful or valuable for that population. But at present, we really are focused on conduct and execution in Alpitude AV. Got it.
Jason Umansky: We can also envision where the mechanism of Subaru targeting these toxic soluble aggregates.
Jason Umansky: A beta or early persistent part of the pathophysiology of the disease and so an agent that selected for these species such as suburban type could be.
Jason Umansky: Highly useful and valuable for that population, but at present, we really are focused on conduct and execution to date.
Jim Doherty: And then maybe just a quick follow-up. In terms of layering in the sub-Q formulation in Altitude AD, what are the possibilities here?
Speaker Change: Got it and then maybe just a quick follow up in terms of of layering in the sub Q formulation in altitude what are the possibilities here.
Jason Umansky: Yes.
Jim Doherty: Jim, do you want to jump on that one? Yeah, Jason, this is Jim Doherty. Happy to answer that question. Obviously, as we think about the subcutaneous formulation, it really does expand the optionality for patients. And now that we have our phase one data and healthy volunteers, we've got some work to do around further formulation development and planning for dosing. But as we also do those plans, the program team is thinking about what's the best way to to include further work in the Suburban Subprogram. So right now, we are still working on which of those options is going to be most efficient pathway forward.
Jason Umansky: Okay.
Jason Umansky: Jim do you want to jump on that one yes, Jason This is Jim Doherty happy to answer that question, obviously as we think about the subcutaneous formulation. It really does expand the optionality for patients.
Jason Umansky: And now that we have our phase one data in healthy volunteers, we've got some work to do.
Jason Umansky: Around further formulation development and planning for dosing, but as we also do those plans. The program team is thinking about what's the best way to.
Jason Umansky: To include further work in this burns off program. So.
Jason Umansky: Right now we are still working on which of those options is going to be most efficient pathway forward.
Jason Zemansky: But we will, we'll update you on that when we have a bit more information. But certainly, the next steps are going to be designed to fit most efficiently with the ongoing IV studies in the Suburban Subprogram. Got it. Thanks for the updates. Looking forward to Thank you.
Jason Umansky: But we will we will update you on that one we are a bit more information, but certainly.
Jason Umansky: The next steps are going to be designed to fit most efficiently with the ongoing IV studies in the spring it by program.
Jason Umansky: Got it thanks for the updates looking forward to next steps.
Pete Stavropoulos: Our next question comes from Pete Stavropoulos with Cantor. Your line is open. Hi, Dan team.
Speaker Change: Thank you. Our next question comes from Pete Stavropoulos with Cantor Your line is open.
Dan O'Connell: Congrats on getting the Altitude Study fully enrolled and the sub-Q data, and thanks for taking my questions. First questions are, you know, there's been a number of recent disclosures, you know, over the past year in Alzheimer's space, you know, many of which suggest that changes in certain biomarkers start to appear far in advance of symptoms, you know, as well as the underlying pathology. And, you know, I'm sure we will get more at upcoming conferences. Just how do these updates inform your approach and assumptions about the disease and clinical studies? And, you know, what are the key biomarkers that you think, you know, you may emphasize upon the data readout?
Pete Stavropoulos: Hi, Jeff and team congrats on getting the attitude study fully enrolled and the sub Q data and thanks for taking my questions.
Speaker Change: Chris.
Speaker Change: <unk>.
Speaker Change: Theres been a number of recent disclosures over the past year in Alzheimer's space, many of which suggests that the changes in certain biomarkers start to appear far in advance of symptoms as well as the underlying pathology.
Speaker Change: I am sure we will get more in upcoming conferences.
Speaker Change: How do these outpaced inform your approach and assumptions about the disease and clinical studies and what are the key Biomarkers that you think you may emphasize upon the data readout and understanding that the data is in late 2016, what do you expect to show at the topline.
Dan O'Connell: And understanding that the data is in late 26, you know, what do you expect to show at the top?
Dan O'Connell: Thanks, Pete.
Jim Doherty: Jim, do you want to take a first pass at that? And Pete, you're a little vague on which of these disclosures were biomarkers. Yeah, happy to take that question. Obviously, there is an explosion in work going on right now across the Alzheimer's space of trying to better understand the available biochemical biomarkers. And in fact, as the technology improves and the sensitivity improves, there is almost weekly updates in this space, as you're alluding to. We'll be attending the ADPD meeting in Vienna next week, and I'm expecting a whole new raft of information as it comes out.
Jim Doherty: Thanks, Pete Jim do you want to take a first pass at that.
Speaker Change: Peter a little vague on which of these disclosures or biomarkers.
Speaker Change: Our eventual target.
Jim Doherty: Go ahead.
Speaker Change: Key biomarkers that are within our peering up.
Speaker Change: Medical conferences.
Speaker Change: Happy to take that question.
Speaker Change: Obviously, there is an explosion and work going on right now across the Alzheimers space.
Speaker Change: Trying to better understand.
Speaker Change: The available biochemical biochemical biomarkers and in fact that as the technology improves and the sensitivity improves there is.
Speaker Change: Almost weekly updates in this space as Youre alluding to will be attending the <unk> meeting in Vienna next week, and I'm expecting a whole new raft of information as it comes out. So we very much feel that this is something that we need to to stay current on and stay on top of on a pretty much regular basis, because I think as time.
Jim Doherty: So we very much feel that this is something that we need to stay current on and stay on top of on a pretty much regular basis. Because I think as time goes forward, what I'm expecting to see is with more increased precision and an increased number of biomarkers, better and better identification of individual patients, better and better segregation of patients over time. And I think that only benefits treatment. I think as far as Subernata goes, we are investing quite a bit in including biochemical biomarkers in our study, as you know. Certainly, we believe that the Phosphatidyl 217, PTAL 217, is a really important marker.
Speaker Change: Goes forward.
Speaker Change: What I am expecting to see is with more increased precision and an increased number of biomarkers.
Speaker Change: Better and better identification of individual patients better and better segregation of patients over time, and I think that only benefits treatment.
Speaker Change: As far as suburban type goes we are in.
Speaker Change: Investing quite a bit including biochemical biomarkers in our study as you know.
Speaker Change: Certainly we believe that the hospitality <unk> Peter <unk> 17 is a really important marker Eric will be presenting next week on our use of <unk> as a prescreening tool, but we also think that.
Jim Doherty: Eric will be presenting next week on our use of PTAL 217 as a prescreening tool, but we also think that it's going to be helpful for identifying types of patients and their response. And I think it's also very likely to be the case that additional markers that have not yet been as well characterized or maybe even not yet identified will be important in the future.
Speaker Change: It's going to be helpful for identifying types of patients in their response and I think it's also very likely to be the case that additional markers that have not yet been as well characterize or maybe even not yet identified will be important in the future and so another feature of what we're doing with the altitude study is bio banking samples. So we have.
Jim Doherty: And so another feature of what we're doing with the altitude study is biobanking samples. So we have a fairly robust plan for biomarker analysis, but in addition to that, we're also going to be reserving samples with the thought that additional data and additional markers are going to be coming out over time.
Speaker Change: A fairly robust plan for biomarker analysis, but in addition to that we're also going to be reserve examples.
Speaker Change: With the thought that additional data and additional markers are going to be coming out over time.
Dan O'Connell: And maybe if I could just briefly add something to that. Pete, I think you had sort of two questions embedded in there. One, as far as altitude, just to remind you that the primary outcome measure is the ITRIS, so it's a Clinical Cognitive and Functional Measure. So based on the strength of our Phase I data, altitude you can really think of as a Phase IIb registration quality study. So the primary outcome is the ITRIS. Now, as you've heard, we're spending a lot of time looking at biomarkers, and we think those are very important.
Speaker Change: Alright, Thanks, and then maybe if I could just.
Speaker Change: Just briefly add.
Speaker Change: With that Peter I think you had sort of two questions embedded in there.
Speaker Change: One as far as I'll go to.
Speaker Change: Just to remind you that the primary outcome measure is the iris so its a clinical cognitive and functional measure so based on the strength of our phase one data altitude you can really think of as a it's a.
Speaker Change: Phase to be registration quality studies. So we the primary outcome is the hydrus now.
Speaker Change: As you've heard we're spending a lot of time looking at Biomarkers that we think those are very important I think the other part of your question was which biomarkers happened before any clinical symptoms, which gets you into the preclinical space and again thats a topic of conversation for the field right.
Dan O'Connell: I think the other part of your question was which biomarkers happened before any clinical symptoms, which gets you into the preclinical space. And, you know, again, that's a topic of conversation for the field. Right now, we're just focused primarily on altitude and subornitude, along with the subcutaneous formulation.
Speaker Change: Right now we're just.
Speaker Change: Focused primarily on the.
Speaker Change: Altitude.
Speaker Change: <unk>.
With the subcutaneous formulation.
Dan O'Connell: And then Jim and Dan, I don't think you if one of you wants to respond to Pete on his question about what would be involved in the top line. Yeah, so certainly, as Eric was just saying, the primary analysis, the primary endpoint for the study is iDRIS. And so when we talk about top line, although we haven't disclosed the full list of what is going to be available at top line, we're certainly expecting the clinical endpoints to be available at top line. And we're working on our plan for biochemical biomarkers. I wouldn't expect all of that information to necessarily be available when we have the initial top line, the initial clinical readouts.
Speaker Change: Alright, Thank you very much Jim.
Speaker Change: Jim and Dan I don't thank you.
Speaker Change: If one of you want us to respond here Pete on his question about what would be involved in the top line.
Speaker Change: Yes, so to be certainly.
Speaker Change: Because you are saying.
Speaker Change: The primary analysis the primary endpoint for the study as I addressed and so when we talk about top line. Although we haven't disclosed the full list of what is going to be available at top line. We're certainly expecting the clinical endpoints to be available at top line and we're working on our plan for biochemical Biomarkers I wouldn't expect all of that information.
Speaker Change: To necessarily be available when we have the initial top line the initial clinical.
Dan O'Connell: But we will certainly have a plan to get those additional endpoints out as quickly as possible. And you'll hear more from us as time goes forward on the exact timing for various pieces to add to the top line.
Readouts, but we will certainly have a plan to get those additional endpoints.
Speaker Change: Out as quickly as possible.
Speaker Change: And Youll hear more from US as time goes forward on the exact timing for <unk>.
Speaker Change: Various pieces to add to the topline.
Unknown Executive: All right, thank you very much for taking my questions and congrats again on. Thank you. Thanks Steve. Thank you.
Speaker Change: Alright. Thank you very much for taking my questions and congrats again on muscle of enrolment and via subdued data.
Speaker Change: Thank you.
Speaker Change: Great.
Ting Liu: Our next question comes from Ting Liu with UBS. Your line is open.
Speaker Change: Thank you. Our next question comes from Qing Liu with UBS. Your line is open.
Eric Siemers: Good morning and this is Tim from Trung's team, congrats on the recent progress and thanks for taking our questions. Could you elaborate a bit more on the use of P-Tau 217 fluid biomarker during patient screening for the phase 2? If all patients have positive P-Tau 217, how would that translate to tau pathology to detect by tau pad? And should we consider patients enrolled to altitude AD at baseline kind of resemble to the NANIMAPS phase 3 trial? Thank you.
Speaker Change: Hi, Good morning. This is Tim frontrunner team congrats congrats on the recent progress and thanks for taking my question.
Speaker Change: Could you elaborate a bit more on the use of <unk> to 17 biomarker during patient screening for the phase II.
Speaker Change: All patients had positive P. Tau to 17, how would that translate to Tal pathology to detect my top hat and should we consider patients enrolled to altitude.
Speaker Change: And a baseline kind of resemble to the <unk> phase III trial. Thank you.
Eric Siemers: Thanks, Eric, why don't you, you're primed to cover that one. Yeah, so thanks for the question. It really is an active area of research right now. So the part of your question was how PTAL 217 will relate to tau PET, which is a very good question. But because of the characteristics of PTAL 217 and the screening process, we actually use that as a way of screening for being amyloid positive. And being amyloid positive could be based on either PET or spinal fluid. So what we've found, and we'll present this again at ADPD next week, is that as a screening tool, plasma PTAL 217 works very, very well.
Speaker Change: Thanks, Eric.
Speaker Change: Sure.
Speaker Change: Trying to cover that one.
Speaker Change: Yes. So thanks for the question. It really is an active area of research right now.
Speaker Change: So the.
Speaker Change: Part of your question was how <unk> <unk> hundred 17 will relate to tower pad, which is a very good question, but because of the characteristics of <unk> $2 17 in the screening process, we actually use that.
Speaker Change: As a way of screening for being amyloid positive being ammo really positive to be based on either Pat or spinal fluid.
Speaker Change: So what we've found that will present this again at ADP next week.
Speaker Change: Is that as a screening tool plasma pizza out $2 17 works very very well.
Eric Siemers: And we'll present the numbers on that. But it decreases the number of, say, negative PET scans by about half. There's a big, a little bit of a debate in the field right now about could plasma PTAL 217 completely replace PET scans or CSF. My personal opinion is I'm not sure it's quite to that point. But I do think it works very, very well as a screener before you get either PET or CSF. And I think that could be translated actually to clinical practice. So thanks for the question.
Speaker Change: We will present the numbers on that but it decreases the number of say negative pet scans.
Speaker Change: By about half.
Speaker Change: There is a big a little bit of a debate in the field right now about plasma T tell $2 17 completely replace pet scans or CSF.
Speaker Change: My personal opinion is I'm not sure it's quite to that point, but I do think it works very very well.
Speaker Change: Screener before you get either pet, where CSF and I think that could be translated to accelerated clinical practice.
Speaker Change: So thanks for the question.
Speaker Change: Yes.
Speaker Change: Thanks, Gary.
Unknown Executive: Operator Thank you.
Tom Shrader: Our next question comes from Tom Shrader with BTIG. Your line is open. Good morning. Thanks for taking the question. Really, a couple of thought questions.
Speaker Change: Thank you. Our next question comes from Tom Shrader with <unk>. Your line is open.
Speaker Change: Hi, good morning, Thanks for taking the questions are really a couple of thought question.
Eric Siemers: Most of the work on sub-Q antibodies has been after plaque removal, and you have an antibody that may not remove plaque. How are you thinking about that? Do you hope biomarkers will be validated enough to carry the game by the time you're ready? Or do you have some ideas on how you might actually get efficacy data from a sub-Q formulation?
Speaker Change: Most of the work on sub Q antibodies has been aster plaque removal when you have an antibody that may not remove plaque.
Speaker Change: How are you thinking about that you hope biomarkers will be validated enough to carry the game by the time you already or do you have some ideas about how you might actually get efficacy data from a sub Q formulation and then.
Eric Siemers: And then, probably an Eric question, iADDRS versus CDR, some of boxes. What's the difference in your mind? I think every antibody that's worked and has measured both has hit for both. Why one over the other?
Speaker Change: And Eric question, I address versus CVR sum of boxes, what's the difference in your mind is I think every antibody, but its work and is measured modes, both fit for both.
Eric Siemers: Is there any real advantage to iADDRS you can have us think about?
Speaker Change: One over the other or is there any real advantage to address you can.
Eric Siemers: Thank you. Yeah, I can grab the Idris first and then we can go back. So yeah, you're right. In the phase three studies, if you hit on the CDR sum of boxes, you also hit on the Idris. In our view, there's less subjectivity and less variability with the Idris compared to the CDR sum of boxes. But there are some similarities.
Speaker Change: I have a think about thank you.
Jim Doherty: Jim you want to grow.
Speaker Change: Yes, I can grab the <unk> first and then we will go back.
Jim Doherty: So, yes youre right.
Speaker Change: In the phase three studies, if he said on the CVR sum of boxes. You also hit on the Iris in our view there is less subjectivity in less variability with the iris compared to the CVR sum of boxes, but there are some similarities but I might just pointing out that in the phase two study.
Eric Siemers: But I might just point out that in the phase two study of Dinanamab that Lily did. They did reach statistical significance on the IDRS, but they actually missed statistical significance on the CDR sum of boxes. So I think that's a good example of IDRS actually is a less variable, less subjective scale.
Jim Doherty: <unk> of.
Jim Doherty: Dynamic.
He did they did reach statistical significance on the Iris, but they actually missed statistical significance on the CD are somewhat boxes. So I think thats a good example.
Jim Doherty: <unk> actually has a less variable less objective scale.
Dan O'Connell: Yeah, Tom, and when it comes to the MOA for sobranitog and the focus on side boligomers rather than plaques. Now, I think at the end of the day, of course, as Eric was just saying around the clinical endpoints, really the cognitive endpoints, understanding effects on ADLs is really what's going to be most critically important. We, as you know, from the intercept study, we do see some effects of sobranitog on plaques and not surprising because, of course, the plaques are a complex dynamic environment. There's side boligomer decorating around plaques. And so, you know, I think that piece of the story is yet to be completely told.
Amit: Yes, Amit.
When it comes to the MLA for subordinates hogging, the focus on <unk>, rather than blacks I think at the end of the day of course, as Eric was saying around the clinical endpoints, if they're really the cognitive endpoints understanding effects on Ngls is really what's going to be most critically important.
As you know from the intercept study, we do see some effect of Sabrina talk on plaques and not surprising because of course, the plaques are complex dynamic environment Theyre sidewall oligomer decorating around plaque and so I think that piece of the story is yet to be completely cold and thats part of what.
Dan O'Connell: And that's part of what we're going to get out of altitude D. But I think being able to sequester those side boligomers, we feel, and of course, this is a hypothesis for testing that, you know, that combination of effects is going to have a meaningful effect on cognitive performance and perhaps even on the ADL side. And so that's what we're looking for. We'll tell the story of effects on plaques and how much that's relevant to the overall effect as we get the data in from altitude. And we'll be well positioned to do that between the imaging data, the biochemical data, and perhaps most importantly, the cognitive endpoints.
Amit: We're going to get out of altitude.
Amit: But I think being able to to sequester. The sidewall oligomers, we feel I think versus the hypothesis, we're testing that.
Amit: That combination of effects is going to have a meaningful effect on cognitive performance and perhaps even on the ABL side and so that's what we're looking for well will tell the story of <unk>.
Amit: On <unk> and how much that's relevant to the overall effect as we get the data and from from altitude and we'll be well positioned to do that between the imaging data the biochemical data and perhaps most importantly, the cognitive endpoints.
Unknown Executive: Great.
Unknown Executive: Thank you very much.
Amit: Yes.
Amit: Alright, great. Thank you very much.
Amit: Okay.
Julian: Our next question comes from Paul Matisse with Stiefel. Your line is open. Hey, this is Julian on for Paul. Thanks so much for taking our question and congrats on the progress. I guess just really quickly, anything else you can say about enrollment? Obviously, it's ahead of schedule, but, you know, any color around what gives you confidence you have the right patients for this trial would be helpful. And then just really quickly, if you could share anything else on SubQ, did the results come in line with your expectations? Or was anything unusual? Would be grateful to hear.
Speaker Change: Our next question comes from Paul Matisse with Stifel. Your line is open.
Speaker Change: Hey, this is Julian Entre Paul Thanks, So much for taking my question and congrats on the progress.
Speaker Change: Just really quickly anything else you can say about enrollment obviously, it's ahead of schedule, but any color.
Speaker Change: Around what gives you confidence you have the right patients for this trial would be helpful. And then just really quickly if you could share anything else on sub Q.
Speaker Change: Did the results come in line with your expectations or.
Speaker Change: Was there anything unusual.
Dan O'Connell: Thanks so much. Yeah, Julian, thanks for the questions. So, I think the first question around enrollment, we're very confident that we've got the appropriate patients enrolled in the study between, you know, there are a large number of disease modification studies that have been running over the past years, and our team is certainly very well aware of those studies, and Eric has been involved in quite a number of studies on his own, and really, we've got the appropriate entry criteria to select the right patients for the study. In this early AD space, so we're, we're very happy.
Speaker Change: Would be grateful here. Thanks, so much.
Speaker Change: Yes, Julian thanks for the questions. So I think the first question around enrollment we're very confident.
Speaker Change: That we've got the appropriate patients enrolled in the study between.
Speaker Change: There are a large number of.
Speaker Change: Disease modification studies that have been running over the past years.
Speaker Change: Our team is certainly very well aware of those studies and Eric has been involved in quite a number of studies on its own.
Speaker Change: And really I think.
Speaker Change: Got the appropriate entry criteria to select the right patients for this study and this early ADC space. So we're we're very happy.
Dan O'Connell: Well, we're certainly very happy to be enrolled.
Dan O'Connell: The full study was enrolled in less than a year, in about 10 months time, but even more importantly, at high quality sites, and we think we've got the right patient populations. As time goes forward, we'll be telling you a little bit more about the baseline characteristics of the population that's included in out To your second question around the subcutaneous data, really, at this point, I would say we're very pleased with the study, and I don't think there were that many surprises. You know, what in the major conclusion is we're not seeing any new safety signals.
Speaker Change: We're certainly very happy to be enrolled the full study was enrolled in less and less than a year and about 10 months time, but.
Speaker Change: But even more importantly at high quality sites and we think we've got the right patient populations as time goes forward, we'll be telling you a little bit more about the baseline characteristics of the population that's included in altitude.
Speaker Change: To your second question around the subcutaneous data really at this point I would say, we're very pleased with the study and I don't think there are that many surprises.
Speaker Change: And the major conclusion is we're not seeing any new safety signals.
Dan O'Connell: The major adverse event that we saw was somewhat expected around injection site reactions. We did see a fairly high fraction of injection site reactions at 62.5%, but importantly, they were all mild and sort of consistent with what had been seen previously with this type of co-mix. And then on the PK side, you know, we're seeing exposure levels that are consistent with further development, and that's really, I think, the best way to say it at this point. You know, we have quite a bit more work to do. This is in healthy volunteers. We've got work to do around looking at concentrations and all those sorts of things, and so that's the kind of work that the team will be doing moving forward.
Speaker Change: The major adverse event that we saw was somewhat expected around injection site reactions. We did see a fairly high fraction of insects injection site reactions at 62, 5%, but.
Speaker Change: Importantly, they were all mild and sort of consistent with what had been seen previously with this type of.
Speaker Change: Comex.
Speaker Change: And then on the.
Speaker Change: The PK side, we're seeing exposure levels that are consistent with further development and Thats really I think the best way to say it at this point, we do and we have quite a bit more work to do this is in healthy volunteers, we've got work to do around <unk>.
Looking at concentrations.
Speaker Change: Concentrations and all those sorts of things and so that's the kind of work that the team will be doing moving forward, but we're happy today to be talking about taking next steps with the subcutaneous formulation and having the exposure from that study that we think we need to work with.
Dan O'Connell: But we're happy today to be talking about taking next steps with the subcutaneous formulation and having the exposure from that study that we think we need to work with to move the program forward. Yeah, and maybe if I could just add one quick thing about the patient population, because it came up in a previous question. If you compare the Denanumab studies with the Leucanumab studies, for the Lilly Trailblazer studies, because they had a tau requirement, those people, if you look at baseline characteristics, are always a little bit worse than the people in the Leucanumab study.
Speaker Change: To move the program forward.
Speaker Change: Yeah, and maybe if I could just add one quick thing about the patient population because it came up in a previous question.
Speaker Change: If you compare the.
Speaker Change: Demand <unk> studies with the retailer lab studies.
Speaker Change: For the Lilly Trailblazer studies, because they had a tower requirement those people. If you look at baseline characteristics are always a little bit worse than the people in the <unk> studies.
Dan O'Connell: Our population, certainly for Intercept, the Phase I study, looked really very similar to the Leucanomab population, because we did not have a TAU requirement. So it looked similar to Leucanomab. And again, we just finished enrollment, but looking at the baseline data so far, the patient population for Altitude looks very similar to the patient population for Intercept. But I think the important thing is the Leucanomab studies are a little bit of an outlier, because they have a TAU requirement. Thanks so much for the color.
Speaker Change: Our population certainly for intercept the phase one study look really very similar to the la Cantera population, because we did not have a tower requirement. So it looks similar to <unk> and again, we just finished enrollment but looking at the baseline data so far.
Speaker Change: The patient population for altitude looks very similar to the patient population for <unk>.
Speaker Change: Intercept but I think the important thing is the.
Speaker Change: <unk> studies are a little bit of an outlier because they have a tower requirement.
Speaker Change: Thanks, so much for the color.
Ananda Ghosh: Thank you. And our next question comes from Ananda Ghosh with H.C. Wainwright & Company. Your line is open. Hi, Dan and Tim. Thanks for the question. One of the, you know, might be a macro question. By the time the Altitude Eddy completes, there will be plasma biomarkers, which will be approved by FDA, probably sometime this year. There will be new data coming from the brain shuttle based antibodies, and, you know, we'll probably know more about the A-beta immunotherapy adoption scenario across US and other ex-US countries.
Speaker Change: Thank you and our next question comes from Amanda <unk> with HC Wainwright <unk> Company. Your line is open.
Amanda: Hi, Donald.
Speaker Change: Politically.
Speaker Change: Wonderful.
Speaker Change: Might be a macro question and by the time the antigen daily completes.
Speaker Change: Plasma biomarkers that can be approved by FDA, probably sometime this year they.
Speaker Change: There will be new data coming from the main shuttle based antibody.
Speaker Change: And we'll probably know more about the EBITDA immunotherapy adoption for that.
Speaker Change: Video across U S ex U S countries. So.
Dan O'Connell: So, you know, with those in the background, how are you thinking about positioning subornate egg as the Altitude Eddy approaches to completion? Sure. So, Ananda, thanks for the question. I think at a very high level, you know, we envision Sobernatog reading out late next year as a differentiated, highly differentiated next generation treatment option will be timely for all of those elements that you described, including, you know, the continued adoption of anti-A-beta treatments that where there's, you know, recognizable room for improvement in terms of a risk-benefit profile, and where other, you know, blood-based biomarkers will continue to enable the appropriate diagnosis and presumably adoption of further products for this underserved population.
Speaker Change: We will go and go background, how are you thinking about positioning for lunar Doug.
Speaker Change: <unk> approaches.
Speaker Change: The competition.
Speaker Change: Sure. So thanks for the question I think at a very high level, we envision <unk> reading out late next year as a differentiated highly differentiated next generation treatment option will be timely for all of those elements that you described including.
Speaker Change: The continued adoption of it the a beta treatments that where there's recognizable room for improvement in terms of the risk benefit profile.
Speaker Change: Sure.
Speaker Change: Blood based Biomarkers will continue to enable the.
Speaker Change: Appropriate diagnosis and presumably adoption further products for this this underserved population.
Dan O'Connell: So, we're excited to, as Jim mentioned, I mean, we enrolled Altitude AD in roughly 10 months, pretty sizable 542 patient study, and now to be looking at reading that out next year in an environment where there's more optimism and enthusiasm for addressing this unmet need is really exciting to us. So, it looks like a great setup.
Speaker Change: We're excited to as Jim mentioned, I mean, we enrolled altitude roughly 10 months pretty sizeable 542 patient study and that would be looking at reading that out next year in an environment, where there is more optimism in.
Speaker Change: Duly hasnt poor.
Speaker Change: Addressing the unmet need is really exciting to us so it looks like a.
Speaker Change: Great setup.
Unknown Executive: Thanks.
Speaker Change: Thanks.
Speaker Change: Yes.
Unknown Executive: Thank you.
Unknown Executive: I'm showing no further questions at this time.
Speaker Change: Thank you I'm showing no further questions at this time I'd like to turn the call back over to Alex Brown for closing remarks.
Alex Braun: I'd like to turn the call back over to Alex Braun for closing remarks. Great. Thanks, Michelle. And thank you to everyone for listening today and for your interest in Acumen. If you have any further questions, we're always available at the company. All right. Thanks. Have a great day. Thank you for your participation. You may now disconnect. Everyone, have a great day.
Alex Brown: Thanks, Michelle and thank you everyone for your interest.
Speaker Change: And if you have any further questions. We're always available at the company I.
Harper Gopal: Harper Gopal.
Harper Gopal: Thank you for your participation you may now disconnect everyone have a great day.
Harper Gopal: Okay.
Harper Gopal: Okay.
Harper Gopal: [music].
Harper Gopal: Okay.