Acumen Pharmaceuticals, Inc. Q3 FY2025 earnings call

• Continued operational execution on two fronts: steady progression of Phase II ALTITUDE-AD trial and generation of additional nonclinical data supporting EBD program. • ALTITUDE-AD trial with 542 participants, some completing placebo-controlled phase, first participants scheduled for open-label extension. Expect top line results for ALTITUDE-AD in late 2026. • EBD program: strategic collaboration with JCR Pharmaceuticals, evaluating sabirnetug and other oligomer selective antibodies, exploring TfR targeting constructs from JCR's libraries, expect nonclinical data package including nonhuman primate study in early 2026. • Addition of Dr. George Golumbeski to Board as Chairman.

No specific product segment financial performance with revenue contribution % provided in the transcript.

• Expect top line results for ALTITUDE-AD in late 2026. • EBD program will have more to share in early 2026.

• Forward-looking statements subject to risks and uncertainties that could cause actual results to differ materially from those described. • Please see Slide 2 of corporate presentation, press release, and recent SEC filings for important risk factors.

Q: Congrats on the progress. Two, if I may, please. Can you disclose what you're looking for in the early transferrin data in terms of a go/no-go decision? I mean, what does it take to feel confident the delivery mechanism is efficient enough? And then maybe secondarily, can you talk a little bit about the evoke trials, the Novo studies of Wegovy in Alzheimer's? And if it's positive, how does that impact the space and your approach?

A: Daniel O'Connell invited Jim Doherty, Chief Development Officer, to comment. Jim Doherty discussed looking at enhancing sabirnetug's profile, not an absolute target number, and watched evoke trials, thinking science is interesting, evolving space, and other complementary mechanisms could be interesting to pair with amyloid approaches like sabirnetug.

Q: You made an interesting comment about possibly replacing sabirnetug with something that's more oligomer focused. Maybe you can outline your thoughts there because what the shuttles allow you to do is remove plaque safely. So the other approach is to use something that's more plaque focused, because if you can do it safely, you might as well. So I'm just curious the thoughts of insiders. And then for early data for the shuttle, is the sense that the -- it's all about anemia. Is the sense that the anemia goes entirely with the shuttle domain so that your anemia should really be based on data from your partner? Or is the anemia potentially also related to the actual payload, your actual antibody?

A: Daniel O'Connell made a quick comment and invited Jim Doherty to add. Jim Doherty said JCR collaboration is to explore diversity of constructs, not seeking to replace sabirnetug but explore possibilities, and anemia-related effects are likely from transferrin-based construct as final product is combination of cargo and carrier, and JCR has track record in clinic to minimize risk.

Q: We had a question on the nonclinical data package. Specifically, we're curious what data we could expect to see and specifically in regards to what biomarkers you would be looking at.

A: Daniel O'Connell invited Jim Doherty to comment. Jim Doherty said data package for candidate selection in early 2026 includes preclinical studies on target profile, PK profile, murine animal models, primate PK study, and biomarkers like A-beta 40, 42 levels, pTau levels, neurogranin, VAMP2.

Q: On the shuttle program, I was wondering will these candidates -- will both candidates be advanced in unison? Or is there a chance of advancing one and then waiting for the ALTITUDE results before advancing the other? And in terms of selecting the other non-sabirnetug candidate, other than specificity, were there other things you considered that might be optimized?

A: Daniel O'Connell said it's too early to say, data dependent in early '26, looking at combination of factors around sabirnetug and other candidates, intrigued by other profiles beyond primary sabirnetug.

Q: I know we're about a year or so away from ALTITUDE data, but I'm wondering what your current thinking is in terms of the bar and what's the minimum you'd like to see out of this study to move forward from both a clinical scale perspective and biomarker data? And then I just have a quick follow-up.

A: Daniel O'Connell invited Jim Doherty and Eric Siemers to respond. Jim Doherty said looking at testing oligomer hypothesis, primary outcome iADRS, considering safety and efficacy together, and Eric Siemers added primary outcome is iADRS, looking at safety and efficacy combination, and biomarkers seen in Phase I study could be potential for differentiation.