ABOS - NASDAQ

Good day and welcome to Acumen Pharma Fiscal Year 2024 Conference Call and Webcast. At this time all participants are in a listen-only mode. After the speakers’ presentation there will be a question-and-answer session and instructions will be given at that time. As a reminder this call may be recorded. I would like to turn the conference over to Alex Braun, Head of Investor Relations. Please go ahead.

Thanks, Michelle. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended December 31, 2024. With me today are Dan O’Connell, our CEO; and Matt

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 am 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 2 trial, we look forward to sharing topline 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?

Thank you. [Operator Instructions] Our first question comes from Jason

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 1 data and healthy volunteers, we've got some work to do around further formulation development and planning for dosing, but as we also do this plant, 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 will 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.

Got it. Thanks for the updates. Looking forward to next steps.

Thank you. Our next question comes from Pete Stavropoulos with Canter. Your line is open.

[Multiple Speakers] any of the key biomarkers that are appearing at the medical conferences.

Yes, happy to take that question, Pete. 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. 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 sabirnetug goes, we are investing quite a bit in including biochemical biomarkers in our study, as you know. Certainly, we believe that the Phospho-Tau-217 -- p-tau217 is a really important marker. Eric will be presenting next week on our use of p-tau217 as a pre-screening tool, but we also think that it's going to be helpful for identifying types of patients in the 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.

Yes. 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 iADRS. So, it's a clinical, cognitive, and functional measure. So, based on the strength of our Phase 1 data, ALTITUDE, you can really think of as a -- it's a Phase 2b registration quality study. So we -- the primary outcome is the iADRS. Now, as you've heard, we're spending a lot of time looking 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 pre-clinical space and you know again that's a topic of conversation for the field. Right now, we're just focused primarily on ALTITUDE and sabirnetug along with the subcutaneous formulation.

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?

Yes, so Pete, 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.

All right. Thank you very much for taking my questions and congrats again on full enrollments in the subcu data.

Thank you. Our next question comes from Ting Liu with UBS. Your line is open.

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-Tau-217 will relate to tau path, which is a very good question. But because of the characteristics of p-Tau-217 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 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 p-Tau-217 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 could plasma p-Tau-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.

Yes. Thanks, Eric.

Thank you. Our next question comes from Tom Shrader with BTIG. Your line is open.

Yes. I can grab the iADRS first and then we can go back. So yes, you’re right. In the Phase 3 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 Sum of Boxes, but there are some similarities. But I might just point out that in the Phase II study of denanimab that Lilly did, they did reach statistical significance on the 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 subjective scale.

Yes, Tom. And when it comes to the MOA for sabirnetug and the focus on soluble ligaments 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 sabirnetug on plaques and not surprising because of course the plaques are a complex dynamic environment, there’s sidewall ligma 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 to D. But I think being able to sequester those soluble lignumors, we feel and of course this is the hypothesis for testing that, 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.

All right, great. Thank you very much.

Our next question comes from Paul Matteis with Stifel. Your line is open.

Hey, this is [Julian] (ph) 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 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. Thanks so much.

Yes. 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, 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, 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 ten 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 -- in 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 co-mix. 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 and 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.

Thank you. And our next question comes from Ananda Ghosh with H. C. Wainwright & Company. Your line is open.

Thanks.

Thank you. I’m showing no further questions at this time. 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.