Acumen Pharmaceuticals, Inc. Q3 FY2025 Earnings Call

Good day, and welcome to the Acumen Pharma Third Quarter 2025 Conference Call and Webcast. 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.

Thanks, Michelle. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended September 30, 2025. With me today are Dan O'Connell, our Chief Executive Officer; and Matt Zuga, our CFO and Chief Business Officer. Matt and Dan have some brief prepared remarks, and then we'll open the call for questions. Joining for the Q&A session, we also have Dr. Jim Doherty, our Chief Development Officer; and Dr. Eric Siemers, our Chief Medical Officer. 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 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.

Great. Thanks, Alex. Good morning, everyone, and thank you for joining us today. In the third quarter, we continued our track record of operational execution on two fronts: the steady progression of our Phase II ALTITUDE-AD trial and the generation of additional nonclinical data supporting our Enhanced Brain Delivery or EBD program. Our core hypothesis remains that synaptotoxic A-beta oligomers play a pivotal role in the development of Alzheimer's disease, and as such, stand as a highly attractive therapeutic target for safe and efficacious treatment of AD. ALTITUDE is investigating sabirnetug, our humanized monoclonal antibody with high selectivity for A-beta oligomers. Sabirnetug's selectivity for toxic oligomers is central to why we believe it could unlock potentially greater clinical efficacy and improved safety relative to antibodies targeting amyloid plaque. We've made rapid progress in the substantial 18-month study. Some of the 542 participants enrolled in the trial are already beginning to complete the placebo-controlled phase with the first participants scheduled to be dosed in the open-label extension as soon as today. In the open-label extension, all participants have the opportunity to receive sabirnetug at 35 milligrams per kilogram every four weeks for up to 52 weeks. The OLE represents not only our commitment to the participants involved in ALTITUDE, but will also provide us with valuable long-term safety and additional efficacy data to supplement the broader data package supporting sabirnetug. Based on our strong execution, we continue to expect top line results for ALTITUDE-AD in late 2026, inclusive of the key efficacy and safety measures. For our EBD program, we recognized for some time that pairing a differentiated A-beta oligomer-directed cargo with a validated blood-brain barrier carrier technology could offer an attractive next-generation product opportunity in Alzheimer's. As you heard on our Q2 call in August, we announced a strategic collaboration, option, and license agreement with JCR Pharmaceuticals to develop an Alzheimer's disease product combining our A-beta oligomer selective antibody expertise with JCR's transferrin receptor targeting blood-brain barrier technology. As part of this effort on the cargo or effector side of the construct, we are evaluating sabirnetug and other oligomer selective antibodies from our library, including an antibody we're calling ACU234 that may have even greater selectivity for oligomers over monomers as compared with sabirnetug. For the carrier portion, we're exploring both single-chain and variable heavy domain antibody constructs from JCR's extensive TfR targeting libraries, which we consider cutting-edge approaches in the BBB space. The program is progressing nicely, and we expect to present mirroring data using some of our constructs at upcoming medical conferences. We continue to anticipate a nonclinical data package, inclusive of a nonhuman primate study in early 2026, which will inform our decision to advance up to two development candidates under our exclusive option agreement with JCR. Finally, I would like to highlight the addition of Dr. George Golumbeski to our Board as Chairman. With his addition, the Board has increased to eight, and George brings more than 30 years of experience in the biotechnology industry and is a highly recognized and experienced biopharma leader with a strong track record in business development, licensing, and strategic initiatives. His deep expertise aligns well with our current goals as we continue to advance our ongoing Phase II trial and EBD program to drive value for shareholders and Alzheimer's patients alike. And with that, I'll turn the call over to Matt for the financials.

Matt, I think you might be on mute.

Yes. Apologies. Thank you, Dan. As a reminder, our third quarter 2025 financial results are available in the press release we issued this morning and in our 10-Q we will file later today. As of September 30, we had $136.1 million in cash and marketable securities on the balance sheet, which is expected to support our current clinical and operational activities into early 2027. R&D expenses were $22 million in the third quarter. The decrease over the prior year was primarily due to a reduction of CRO costs associated with the ALTITUDE-AD clinical trial, for which we completed enrollment in March 2025 following dosing of the first patient in May 2024. G&A expenses were $4.5 million in the third quarter. The decrease was primarily due to reductions in legal fees, audit and other accounting services expenses, and recruiting expenses. This led to a loss from operations and a net loss of $26.5 million in the quarter. 2026 will be a very exciting year for Acumen. We are confident in our strong execution of ALTITUDE-AD, and we look forward to sharing top line results in late 2026. Our EBD program also offers optionality and further unlocking the potential of targeting synaptotoxic A-beta oligomers for improved outcomes in treating Alzheimer's disease, and we will have more to share on that in early 2026. Through this two-pronged approach, we remain dedicated to delivering potential next-generation treatment options for the benefit of patients, caregivers, and shareholders. And with that, we can open the call for Q&A.

Our first question comes from Jason Zemansky with Bank of America.

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?

I'm actually going to invite Jim Doherty, our Chief Development Officer, to comment on both of those questions. I think Jim is a good source of response.

Yes, I'm happy to, Dan. When we consider the EBD program, we see significant opportunities and potential by enhancing the penetration of sabirnetug or similar antibodies in the brain. While we don't have a specific target for the fold increase we're aiming for, we remain very confident in sabirnetug's overall profile and are excited about our progress in Phase II. In terms of a next-generation approach, we're focused on improving the overall profile of sabirnetug. Given that monoclonal antibodies generally have low penetration into the CNS, even a moderate increase in exposure could yield positive effects in various areas. We see opportunities regarding efficacy and potentially safety, particularly based on findings involving monoclonal antibodies used with EBD in treating Alzheimer's disease, as well as improvements in drug delivery. We're aiming for a meaningful increase in overall exposure, and we believe that can be achieved at relatively low levels due to the strong effects of sabirnetug. On the Evoke front, we are closely monitoring the GLP-1 studies from Novo, which we find quite interesting. It’s clear that improving metabolic profiles is affecting numerous patient groups, and there’s compelling science suggesting that a better metabolic profile could significantly benefit Alzheimer's patients. We're eager to see the trial results. The crucial aspect will always be how effectively these agents are delivered into the CNS, which is an important consideration for both Evoke and Evoke+. We're glad to see progress in other complementary mechanisms for treating Alzheimer's. Many patients need assistance, and these alternative approaches could be valuable alongside amyloid treatments like sabirnetug.

Our next question comes from Tom Shrader with BTIG.

You mentioned the possibility of replacing sabirnetug with something that focuses more on oligomers. Could you share your thoughts on that? The shuttles enable safe plaque removal, so using a more plaque-focused approach could be beneficial if safety is maintained. I'm interested in hearing the views of insiders. Regarding early data for the shuttle, is the consensus that it's primarily about anemia? Should the anemia data come solely from your partner, or could it also be linked to the actual payload, your specific antibody?

I'll make a quick comment and then Jimmy might want to add to it. One of the important aspects of the JCR collaboration was for us to explore a variety of constructs. We're not aiming to replace sabirnetug, but rather to investigate what other possibilities might be available as we navigate this discovery phase. This principle is key when considering options beyond sabirnetug. We see this as an opportunity to introduce some redundancy and diversity in our early-stage program. So far, we've observed some intriguing results and are looking forward to completing the data package by early next year. Jim, do you want to address Tom's question on anemia and our thoughts on epitopes and selectivity?

Yes, I'm happy to, Dan. Tom, we and others are really excited about the technology, and there is a lot of opportunity. It fundamentally comes down to the combination of cargo and carrier, as Dan mentioned earlier in the call. The final product will include aspects of both, meaning that the overall profile will be influenced by the components. When considering risk factors, the risk associated with transferrin-based approaches has been linked to the technology. However, we have no reason to believe that the profile of sabirnetug shows any signs of those issues, although they are present with the technology. Currently, we are focused on understanding the combination of a monoclonal A-beta for soluble oligomers with transferrin. As we conduct tests on individual constructs, we are examining the risks or potential for anemia-related effects. We believe that if we observe such effects, they will likely stem from the transferrin-based construct. Ultimately, this is why we conduct testing and select a specific candidate molecule to optimize benefits and minimize risks. From a foundational perspective, we expect that any risks would originate from the transferrin technology. Additionally, one of the reasons we chose JCR as a partner is because of their proven ability in the clinic to reduce that risk with their constructs.

Our next question comes from Geoff Meacham with Citi.

It's Ross on for Jeff. 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.

Jim, you want to take that?

Yes, as we consider the data package, there are a couple of aspects to focus on. One relates to the data package for candidate selection, which we aim to finalize by early 2026. Here, we will conduct several preclinical studies to assess the target profile of the new construct. It is essential for us to ensure that the properties similar to those of sabirnetug remain unaffected by the addition of the cargo and carrier construct. We are also keen to examine how the carrier construct influences the pharmacokinetics, particularly regarding increased brain penetration. This analysis will vary among candidates, so we will evaluate the pharmacokinetic profiles, the binding to oligomer and other A-beta targets, and explore various murine models to confirm profiles consistent with our previous sabirnetug findings. Importantly, we will also include a primate pharmacokinetic study, as it is paramount to observe the effects in a primate brain, especially with transferrin receptor constructs, which differ slightly from the murine version. This is our approach for selecting a candidate for advancement. After that, we will leverage our existing knowledge gained from sabirnetug, which is in mid-stage clinical trials. We have dedicated significant effort to understanding the biomarker profiles relevant to the original sabirnetug. This provides a valuable opportunity as we enter early-phase clinical development, where we will utilize many of the same biomarkers we examined in the sabirnetug program. This includes monitoring plasma-based biomarkers for A-beta 40 and 42 levels, pTau levels, including pTau217, and downstream synaptic markers like neurogranin and VAMP2. This foundation allows us to comprehensively gauge the progress of the carrier-enhanced sabirnetug program.

Our next question comes from Paul Matteis with Stifel.

This is Matthew standing in for Paul. Congratulations on the progress. Regarding the shuttle program, will both candidates be advanced simultaneously, or is there a possibility of advancing one and then waiting for the ALTITUDE results before proceeding with the other? Additionally, when selecting the other non-sabirnetug candidate, aside from specificity, were there other factors considered that might be optimized?

I think it's too early for us to say whether we'll be advancing one or two and which of the two might move forward. So I think this is going to be data dependent in early '26. I do think we're looking at a combination of factors around the sabirnetug, the two, three, four. I mean, we're still generating more data around selectivity and other properties, but are intrigued to think that there's other profiles even still beyond primary sabirnetug that could be candidates for further development.

Our next question comes from Pete Stavropoulos with Cantor.

This is Samantha on the line for Pete. Congrats on the progress. So my first question, 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.

Jim or Eric, do you guys want to provide a primary response on that?

Yes, let me start, and I’ll invite Eric to join in. It’s great to hear from you, Samantha. The answer to your question is that we discuss testing the oligomer hypothesis a lot, and we believe there is significant evidence suggesting that oligomers play a crucial role in the pathophysiology of Alzheimer's disease. Our Phase I data thus far supports this. The key value in the ALTITUDE study lies in its being the first true demonstration evaluated using clinical scales. Therefore, the main impact of the study is to understand the effects on those clinical scales. We are, of course, aiming for a clear and demonstrable effect regarding the change in progression rate. Additionally, we will assess the overall impact and the effects of sabirnetug across multiple scales. While iADRS is our primary scale, various other scales will also be considered. Beyond seeking a clear signal, we will focus on the nature of the responses in those different scales. We are also very enthusiastic about the biomarker signals we are observing after three months of dosing from the INTERCEPT study. This offers us much more data over an extended period with an 18-month primary endpoint. That’s how we are approaching the readout itself. Now, let me turn it over to Eric to see if he has anything else to add.

It's a great question. At the conclusion of a significant Phase II study like ALTITUDE, the focus is on safety and efficacy. Our primary outcome measure is the iADRS scale, which assesses both cognition and function. This will serve as our main efficacy indicator, although we have several secondary measures as well. Safety must also be considered, and it is the combination of safety and efficacy that establishes the therapeutic index. With a large study like ALTITUDE involving 542 participants, we can gain a clear understanding of that therapeutic index. In our Phase I study, we observed notable biomarker responses, indicating not only target engagement with oligomers but also effects on the underlying pathology of Alzheimer's disease. We will continue to seek such biomarkers in ALTITUDE, and the promising results from our small Phase I study suggest we may have a unique treatment option compared to others.

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

Thanks, Michelle, and thanks to everyone who tuned in today to listen to our Q3 update. We are always available at the company for any further questions. So please don't hesitate to get in touch. With that, have a great day.

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