Participants

Alex Braun; Head of Investor Relations; Acumen Pharmaceuticals Inc

Daniel O'Connell; Chief Executive Officer, Director; Acumen Pharmaceuticals Inc

W. Matthew Zuga; Chief Financial Officer, Chief Business Officer; Acumen Pharmaceuticals Inc

James Doherty; President, Chief Development Officer; Acumen Pharmaceuticals Inc

Eric Siemers; Chief Medical Officer; Acumen Pharmaceuticals Inc

Jason Zemansky; Analyst; Bank of America

Pete Stavropoulos; Analyst; Cantor Fitzgerald

Ting Liu; Analyst; UBS

Thomas Shrader; Analyst; BTIG

Julian Pino; Analyst; Stifel

Ananda Ghosh; Analyst; H.C. Wainwright & Company

Presentation

Operator

Good day, and welcome to the Acumen Pharma fiscal year 2024 conference call and webcast. (Operator Instructions) As a reminder, this call may be recorded. I would now like to turn the call over to Alex Braun, Head of Investor Relations. Please go ahead.

Alex Braun

Thanks, Michelle. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the year ended December 31, 2024. With me today are Dan O'Connell, our CEO; and Matt Zuga, our CFO and Chief Business Officer. Matt and Dan have some prepared remarks, and then we'll open the call for questions. 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.
Before we begin, we encourage you 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 plans. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements.
Please see slide 2 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 statements. 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 or developments.
So with that, I'll turn the call over to Dan.

Daniel O'Connell

Thanks, Alex. Good morning, everyone, and thanks for joining us today. Acumen entered 2024 from a position of strength, stemming from our positive results for sabirnetug in our INTERCEPT-AD Phase I study in early Alzheimer's patients. In INTERCEPT AD, sabirnetug 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.
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 sabirnetug in patients with MCI, or mild dementia due to Alzheimer's, also known as early AD.
Last year, our team worked effectively to advance the sabirnetug story, and we believe this underpins the swift pace of enrollment seen in ALTITUDE. We engaged with the research community who recognize and embrace the novelty of sabirnetug's mechanism of action, targeting toxic A-beta oligomers.
We've also engaged with experienced clinical investigators and trial sites, who appreciate the consistency of the Phase I results with this mechanism and who also recognized sabirnetug'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. This clinical enrollment milestone is a key catalyst for our sabirnetug program. This accomplishment also provides convincing evidence of our team's ability to operationalize and exceed enrollment goals for this sizable multinational Phase II trial.
The study's primary endpoint is a change from baseline to 18 months on the Integrated Alzheimer's Disease Rating Scale, or IADRS, 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 sum of boxes and other typically used secondary measures, including imaging and fluid biomarkers.
With enrollment now complete, we expect the top line results in late 2026 inclusive of the key efficacy and safety measures. We also recently completed our Phase I study investigating a subcutaneous administration of sabirnetug. This was a pharmacokinetic comparison study comparing subcutaneous and intravenous administrations of sabirnetug in healthy volunteers.
We believe a potential subcutaneous formulation of sabirnetug 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 sabirnetug in both formats may also facilitate greater optionality around treatment and induction -- excuse me, treatment induction and maintenance phases. Importantly, results from the study showed that subcutaneous sabirnetug was well tolerated, with systemic exposure supporting the continued development of this format. Our next steps for the development of subcutaneous formulation of sabirnetug will include ongoing formulation work and other data inputs.
We remain committed to communicating the developments of sabirnetug through presentations at medical conferences and peer review publications. We've maintained a significant presence at all the major Alzheimer's conferences, AD/PD, AAN, AAIC and CTAD.
We will present our Phase I 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 3 doses in the study. I'm very pleased to note as well that our INTERCEPT AD Phase I manuscript was published in the Journal of the Prevention of Alzheimer's disease, or JPAD, in January 2025. In addition, our related publication detailing the fluid biomarker changes in that study was also published online in JPAD just last month. You can find both publications online at the Journal and linked on our website.
Next week at AD/PD, we will also present the use of a plasma, p-tau217, 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 burdening cost in the screening process. Feedback on the use of this p-tau217 assay has been very positive, as evidenced by the rapid pace of our Phase II enrollment.
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. At Acumen, we are staunchly committed to our strategic goal of advancing the clinical development of sabirnetug 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.
The 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 bodies.
We believe the adoption of anti-A-beta treatments will continue to grow and ultimately 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-amyloid therapies and in the future combination approaches.
We believe in the promise of sabirnetug as a next-generation treatment option for Alzheimer's patients based on an improved benefit to 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 II data readout next year.
And with that, I'll turn the call over to Matt for the financials.

W. Matthew Zuga

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 10-K 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 ALTITUDE-AD trial, which 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 and the net loss of $102.3 million during the year after accounting for interest income.
I'm pleased with Acumen's execution on every level as we continue to work to interrogate the promise of sabirnetug for the treatment of early AD. With enrollment now complete in our ALTITUDE-AD Phase II 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.
And with that, we can open the call for Q&A. Operator?

Question and Answer Session

Operator

(Operator Instructions) Jason Zemansky, Bank of America.

Jason Zemansky

Congrats on the progress. 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, 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?

Daniel O'Connell

Thanks, Jason. So right now, we are extremely focused on the execution in ALTITUDE-AD in this early AD population. 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.
And I think we can also envision where the mechanism of sabirnetug 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 PCs, such as sabirnetug could be highly useful or valuable for that population. But at present, we really are focused on conduct and execution in ALTITUDE-AD.

Jason Zemansky

Got it. And then maybe just a quick follow-up. In terms of layering in the subcu formulation in ALTITUDE-AD, what are the possibilities here?

Daniel O'Connell

Jim, do you want to jump on that one?

James Doherty

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. And now that we have our Phase I data in 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 include further work in the sabirnetug program. So right now, we are still working on which of those options is going to be most efficient pathway forward. But 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 sabirnetug program.

Operator

Pete Stavropoulos, Cantor.

Pete Stavropoulos

And team, congrats on getting the ALTITUDE study fully enrolled and the subcu data. First questions are, there's been a number of recent disclosures over the past year in the Alzheimer's space, many of which suggest that the changes in certain biomarkers start to appear far in advance of symptoms as well as the underlying pathology.
And I'm sure we will get more at upcoming conferences. Just how do these updates inform your approach and assumptions about the disease and the clinical studies? And what are the key biomarkers that you think you may emphasize upon the data readout? And understanding that the data is going to be in late 26, what do you expect to show at the top line?

Daniel O'Connell

Thanks, Pete. Jim, do you want to take a first pass at that? So you're a little vague on which of these disclosures or biomarkers.

Pete Stavropoulos

In our biomakers, any of the key biomarkers that are appearing up at the medical conferences.

James Doherty

Yes. Happy to take that question, Pete. Obviously, the -- 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, that -- 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 AD/PD 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 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 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 sabirnetug goes, we are investing quite a bit in including biochemical biomarkers in our study, as you know. Certainly, we believe that the phospho-tau217, p-tau217, is a really important marker. Eric will be presenting next week on our use of p-tau217 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. 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.

Eric Siemers

Yes. And maybe if I could just briefly add something to that, Pete. I think you had sort of 2 questions embedded in there. One, as far as ALTITUDE, just to remind you that the primary outcome measure is the IADRS. So it's a clinical cognitive and functional measure.
So based on the strength of our Phase I data, ATTITUDE, you can really think of as -- it's a Phase IIb registration quality study. So we -- the primary outcome is the IADRS. Now as you've heard, we're spending a lot of time moving at biomarkers, and 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, that's a topic of conversation for the field. Right now, we're just focused primarily on an altitude and sabirnetug along with the subcutaneous formulation.

Alex Braun

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.

Daniel O'Connell

Yes. So to be, certainly, as Eric was just saying, the primary analysis, the primary endpoint for the study is IADRS. 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. 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.

Operator

Ting Liu, UBS.

Ting Liu

This is Ting from Trung's team. Congrats on the recent progress. Could you elaborate a bit more on the use of p-tau217 fluid biomarker during patient screening for the Phase II? If all patients have positive p-tau217, how will that translate to tau pathology to detect by tau path? And should we consider patients enrolled to ATTITUDE-AD a baseline kind of resemble to donanemab Phase III trial?

Daniel O'Connell

Thanks, Ting. Eric, why don't you -- you plan to cover that one.

Eric Siemers

Yes. So thanks for the question. It really is an active area of research right now. So the -- part of your question was how p-tau217 will relate to tau path, which is a very good question. But because of the characteristics of p-tau217 and the screening process, we actually use that as a way of screening for being amyloid positive, and that being amyloid positive could be based on either path or spinal fluid.
So what we found, and we'll present this again at AD/PD next week, is that as a screening tool, plasma p-tau217 works very, very well. 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 plasma p-tau217 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.

Operator

Tom Shrader, BTIG.

Thomas Shrader

Really, a couple of thought questions. Most of the work on subcu antibodies has been after plaque removal when 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 subcu formulation?
And then probably an Eric question. IADRS address versus CDR sum of boxes, what's the difference in your mind is I think every antibody that's worked and is measured both has hit for both Why one over the other? Is there any real advantage to IADRS you can have us think about?

Eric Siemers

Yes. I can grab the IADRS first and then we'll go back. So yes, you're right. In the Phase III studies, if you hit on the CDR sum of boxes, you also hit on the IADRs. In our view, there's less subjectivity and less variability with the IADRS compared to the CDR summer boxes, but there are some similarities.
But I might just point out that in the Phase II study of donanemab that Lilly did, they did reach statistical significance on IADRS, but they actually missed statistical significance on the CDR sum of boxes. So I think that's a good example of IADRS actually is a less variable, less objective scale.

James Doherty

Yes. Tom, and when it comes to the MOA for sabirnetug and the focus on soluble oligomers rather than plaque, 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 sabirnetug on plaques. And not surprising because, of course, the plaques are a complex dynamic environment. There's soluble oligomer decorating around plaques. And so I think that piece of the story is yet to be completely told, and that's part of what we're going to get out of ALTITUDE-AD. But I think being able to sequester those soluble oligomers, we feel, and of course, this is the hypothesis we're testing that, that combination of effects is going to have a meaningful effect on cognitive performance and perhaps even the -- 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.

Operator

Paul Matteis, Stifel.

Julian Pino

This is Julian on for Paul. Congrats on the progress. I guess, just really quickly, anything else you can say about enrollment? Obviously, it's ahead of schedule, but 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 subcu. Did the results come in line with your expectations? Or was anything unusual? Would be grateful to hear.

James Doherty

Yes, Julien, 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 -- 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 its own.
And really, I think we've got the appropriate entry criteria to select the right patients for the study in this early AD space. So we're very happy. We're certainly very happy to be enrolled. 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 ALTITUDE. 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. What -- and the major conclusion is we're not seeing any new safety signals.
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 OMX.
And then on the PK side, 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. We do -- 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. 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.

Eric Siemers

Yes. And maybe if I could just add one quick thing about the patient population because it's been like on a previous question. If you compare the donanemab studies with the lecanemab 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 lecanemab studies.
Our population, certainly for INTERCEPT, the Phase I study, look really very similar to the lecanemab population because we did not have a tau requirement. So it looked similar to lecanemab. 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 donanemab studies are a little bit of an outlier because they have a tau requirement.

Operator

Ananda Ghosh, H.C. Wainwright & Company.

Ananda Ghosh

One of -- might be a macro question. By the time the ALTITUDE-AD completes, there will be plasma biomarkers, which will be approved by FDA probably sometime this year. There will be new data coming from the Brainshuttle-based antibodies. And we'll probably know more about A-beta immunotherapy adoption scenario across US and other ex US countries.
So with those in the background, how are you thinking about positioning sabirnetug as the ALTITUDE-AD approaches to completion?

Eric Siemers

Sure. So Ananda, thanks for the question. I think at a very high level, we envisioned sabirnetug 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 the continued adoption of anti-A-beta treatments that where there is recognizable room for improvement in terms of a risk benefit profile and where other blood-based biomarkers will continue to enable the appropriate diagnosis and presumably adoption of further products for this underserved population.
So we're excited to have, as Jim mentioned,, 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 a great setup.

Operator

I'm showing no further questions at this time. I'd like to turn the call back over to Alex Braun for closing remarks.

Alex Braun

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.

Operator

Thank you for your participation. You may now disconnect. Everyone, have a great day.