Acumen Pharmaceuticals, Inc. Q1 FY2026 Earnings Call

Good day, and thank you for standing by. Welcome to the Acumen Pharma First Quarter 2026 Conference Call and Webcast. Operator instructions were provided. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Alex Braun, Head of Investor Relations. Please go ahead.

Thanks, Didi. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended March 31, 2026. With me today are Dan O'Connell, our Chief Executive Officer; and Matt Zuga, our CFO and Chief Business Officer. They will have 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 President and 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. 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. With that, I'll turn the call over to Dan.

Great. Thanks, Alex. Good morning, everyone, and thanks for joining us today. I ended last quarter's call by emphasizing the progress we've achieved with sabirnetug and our next-generation blood-brain barrier enhanced brain delivery (EBD) candidates and highlighted the important work and upcoming milestones that lay ahead. That message has not changed. In the first quarter, we continued to advance sabirnetug through our Phase II ALTITUDE-AD trial, building on the clinical momentum established over the past year. The study remains a critical proving ground for our central scientific thesis that selectively targeting synaptotoxic Aβ oligomers rather than amyloid plaques may constitute a more effective and/or safer path forward in Alzheimer's. Execution has stayed on track; participants have been transitioning smoothly into the 12-month open-label extension study and the conversion rate remains high. We see this disciplined progress as bringing us closer to a potentially differentiated treatment option for people living with Alzheimer's. We expect our topline results for ALTITUDE-AD late this year. As we've described, ALTITUDE is designed as a well-powered study to detect a statistically significant difference after 18 months on our primary clinical efficacy endpoint, the amount of slowing as measured by the iADRS. We expect to also report on key secondary endpoints in the topline results, such as the Clinical Dementia Rating - Sum of Boxes, certain safety measures such as adverse event rates, including ARIA rates, and key fluid and imaging biomarkers. The study is designed to evaluate safety and efficacy of two dose levels, 35 and 50 milligrams per kilogram, compared to placebo. Both of the active doses are within the range of exposures shown to have exhibited pharmacodynamic target engagement in our INTERCEPT-AD Phase I trial. Our enhanced brain delivery (EBD) program is also advancing nicely. We are conducting additional preclinical work to fully establish candidate profiles and are very pleased with the output. We intend to submit a notice to exercise our option to license two compounds developed as part of our collaboration with JCR Pharma in the second quarter of 2026. So this development is imminent. We expect to discuss those candidate profiles in greater detail at a future medical meeting and continue to anticipate an IND filing in mid-2027. We view EBD as a way to enhance our antibodies, enabling the potential to develop treatments with increased penetration and distribution in the brain while maintaining a favorable safety profile and allowing for patient-friendly subcutaneous dosing. We recognize there is competition in this space; however, none with an Aβ oligomer-targeted therapeutic cargo. This is where we see the potential to push the therapeutic index even further, attaining efficacy by engaging the soluble toxic species of Aβ throughout the brain. Also, JCR, our collaborator on our EBD program, has clinically validated transferrin receptor-mediated transcytosis technology. JCR has an approved therapy in Japan, which incorporates their technology and has exhibited little to no anemia. This anemia safety profile offers us further potential for differentiation with our carrier-plus-cargo EBD product strategy. Taken all together, our EBD program adds optionality to our pipeline as an additional oligomer-targeted therapeutic strategy. While not currently contemplated in our immediate clinical development plans, an anti-Aβ oligomer EBD therapeutic could also potentially be studied in preclinical Alzheimer's, a population earlier in the disease course that could benefit greatly from a next-generation oligomer-directed approach. The progress we've made with sabirnetug and our next-generation EBD candidates reflect the strength of our science and ability to execute and sets a solid foundation for an exciting remainder of the year. I look forward to updating you on the imminent candidate selections in our EBD program and on our ALTITUDE-AD Phase II results in late 2026. And with that, I'll turn the call over to Matt.

Thank you, Dan. As a reminder, our first quarter 2026 financial results are available in the press release we issued this morning and in our 10-Q we will file later today. We ended March 31 with $128.4 million in cash and marketable securities on the balance sheet, which is expected to support our current clinical and operational activities into early 2027. This increase over the prior quarter is due to the private placement we completed in support of our EBD program that grossed $35.75 million, which we announced in March of this year. R&D expenses were $16.5 million in the first quarter. The decrease over the prior year was primarily due to a reduction in manufacturing and material costs as well as a reduction in CRO costs associated with our ALTITUDE-AD clinical trial, which completed enrollment in March 2025. G&A expenses were $4.7 million in the first quarter; the decrease was primarily due to reductions in legal fees as well as reductions in accounting, consulting and insurance expenses. This led to a loss from operations of $21.1 million and a net loss of $20.7 million in the first quarter. We are confident in our scientific innovation and strong track record of execution as we work toward our Phase II ALTITUDE-AD readout later this year and advance our EBD program. We remain dedicated to building value with our portfolio of Aβ oligomer-targeted antibodies for Alzheimer's patients, caregivers and stakeholders. And with that, we can open the call for Q&A. Operator?

Operator instructions were provided. And our first question comes from Pete Stavropoulos of Cantor Fitzgerald.

Congratulations on the continued execution of ALTITUDE. A question sort of about ALTITUDE. ALTITUDE is looking at Alzheimer's disease, similar to the approved amyloid beta antibodies. However, there are ongoing studies for preclinical Alzheimer's with a Phase III readout starting in 2027, assuming that ALTITUDE is positive and you move forward with sabirnetug. Could you just give us your current thoughts on which populations or patient types you would target in Phase III studies, and what would trigger you to expand to the preclinical Alzheimer's population?

Thanks Pete, I can address that real quickly. In terms of our focus, we remain focused on the early AD population such as we've enrolled in ALTITUDE-AD and see that as the path forward for sabirnetug in a future registration study. I think our interest in the preclinical population remains quite high, and as I mentioned, potentially part of the future opportunities ahead principally for an EBD candidate. So that's not an immediate part of our plans, but certainly I think the science—neutralizing toxic oligomers in the early course of the pathogenesis of disease—is something that is promising on the horizon.

And another question, please, on the EBD program. You do have different versions of 193 and 234. They have different PK profiles at least which we've shown to date. What are sort of the key properties and preclinical data that will drive you or drive the decision on candidate selection? And with an IND targeted, I believe, mid-2027, could you just walk us through how you're thinking about development plans and trial designs?

Sure. That's a lot, Pete. So I think, as you know, we've explored a lot of diversity in the EBD program, both from a carrier and cargo perspective, and we like having the ability to evaluate a series of candidates. We are down to the short list, and as I mentioned, we anticipate exercising our option for two candidates in the second quarter and remain confident that we will be filing an IND mid-2027. I don't know that we can go into the details of specific PK properties, but as we have characterized, I mean, the advantages of EBD you really have to do with broad brain distribution, potentially a wider safety margin and the subcutaneous dosing convenience. So those are elements of what we are using as part of the filter for prioritizing candidates in that program. Jim Doherty, who's on the call—I don't know, Jim, if you want to add some additional color to comment on Pete's question.

Yes. No, I think that sounded great, Dan. I guess, Pete, the only other thing I would add— you asked about the clinical program. I mean it's early days, so we're still thinking about what the early phase clinical program is going to look like. But I think we have a huge benefit in having conducted the INTERCEPT study with sabirnetug; it really gave us quite a lot of data, not only the safety and tolerability and PK data you typically get in a Phase I study, but since we were looking at Alzheimer's patients in the MAD phase, we're able to collect data on PET imaging for Aβ, and biochemical biomarkers for a number of different things. And that's really helped us with the sabirnetug program. And so we're actively discussing how to incorporate that kind of thinking into the early clinical studies for the EBD program. So more to come, but we're modeling what we've done on the sabirnetug program as a way to go forward.

And our next question comes from Geoff Meacham of Citi.

This is Mary Kate Davis on for Geoff. Just was wondering, could you please walk us through the early physician interest and feedback of sabirnetug, especially given the unmet need in early Alzheimer's and mechanism of the treatment. And then as a follow-up, could you just walk us through the ongoing regulatory interactions and anticipated discussions for the late-stage development of the program?

Thanks, Mary Kate. Actually, Jim, why don't you take that. Jim and Eric, I think on the feedback we've received, we've done a lot of work at meetings and visited with a number of KOLs and other clinicians that have provided a broad set of feedback on the sabirnetug program in particular.

Yes, happy to do that, Mary Kate. And as Dan says, we've spoken to quite a number of KOLs about the sabirnetug program. And I think there's a lot of interest, obviously. I mean, we're testing a hypothesis that is slightly different than what's been tested so far with the approved therapeutics. And I think we can talk about both what those therapies have been able to do in treating patients and where there's opportunity. And we do think that the sabirnetug approach offers a differentiated opportunity from what's been done to date. And I think that's generally understood by KOLs. So I think everyone is very much looking forward to seeing the data as we release the results for the ALTITUDE trial in late 2026. But I think at this point, there's a level of anticipation to see that potential for a differentiated response.

Yes. And I might just add, we have spent a lot of time thinking about the differentiation of sabirnetug. And I think to sum it—well, obviously, we don't have the data right now; we're in a blinded trial—but when we get the data one of the things that we'll look at, number one, would be efficacy because, again, we target oligomers which is different than the two approved drugs. And then the second thing is we'll look to see if we can differentiate on safety because our antibody is an IgG2; the two approved antibodies are IgG1s. IgG1s have more effector function and the potential for more ARIA. And so we're going to look at the safety data very carefully when those become available.

Yes.

And to your question around regulatory interactions, the ALTITUDE study, of course, is running in multiple countries across multiple jurisdictions. So we're obviously speaking to regulatory agencies in the U.S. and Canada and in Europe as part of all that. And then thinking strategically about the program, we're, of course, engaging with regulators about the overall progress of both of our programs, both the sabirnetug program as well as our EBD programs. And so that's something we'll continue to do. Obviously, it's quite important to stay in contact and to keep them apprised of progress. And so that's just the fundamental thing that we're always doing.

And our next question comes from Paul Matteis of Stifel.

This is Emily on for Paul. I wanted to say congrats on the quarter and just two quick questions from us. As it relates to the upcoming Phase II readout, what do you think would be a clear win that would prove sabirnetug to be a unique alternative to donanemab and lecanemab? And do you see kind of different scenarios at the different doses? And then as a follow-up to that, assuming success in Phase II, would you be able to incorporate a subcutaneous arm in a Phase III program? And maybe any color on the subcutaneous timelines would be helpful, too.

Thanks, Emily. So I think in terms of a clear win in ALTITUDE-AD would be an efficacy signal—at least a 30% slowdown, which is sort of the upper end of the boundary for the current approved agents. So we are hopeful and anticipating that by targeting toxic species in a selective fashion that it will unlock greater efficacy. I think the safety profile is also important; there is now real-world evidence to suggest what the overall rates of ARIA are, and of course those rates of ARIA differ by genotype. And so those are some of the other elements of what we'll be looking to establish. So it will be the totality of the ALTITUDE data and really the risk-benefit profile of sabirnetug—the combination of efficacy and safety—is positioned as the primary means of differentiation relative to the current approved agents. And in terms of subcutaneous, I think we've previously guided that we will be looking at the Phase II data, particularly in respect of the two active doses that are being investigated in ALTITUDE, to inform precisely where and how we would advance the ongoing work in subcutaneous as part of the Phase III program.

And I might add, Emily, I think you asked an interesting question as well around doses. As you know, there are two different doses included in the ALTITUDE study, and those doses were chosen to sort of bracket the range of oligomer clearance as measured by our target engagement assay in Phase I. So we think we've got an interesting range of doses chosen, and it will be—I'll be very curious to see how that impacts the results both from a point of view of efficacy and safety, as Dan said. And so that's an interesting feature of the ALTITUDE study: we have both of those doses to investigate.

Yes. And just one other point about the ARIA. I think one of the concepts across the field now that's being better appreciated is that it's really symptomatic ARIA that you're most concerned about. And even if ARIA is symptomatic and it's a serious adverse event, that's what you really worry about. Those are not as common, but obviously they have a bigger impact. And so that's one of the things that we'll be benchmarking pretty carefully when we do get our data.

Our next question comes from Jason Zemansky of Bank of America.

Congrats on the great progress. I wanted to ask a question maybe from a different perspective here. Over the last several weeks, we've seen both the Cochrane report questioning the value of the anti-amyloid class. And a few days ago, there was an article that detailed that use of the current commercially available anti-amyloid antibodies has been slower than expected. So as we take a step back and think about both the overall unmet need and the overall view of the class, what do you think is necessary from ALTITUDE and any Phase III you do to really demonstrate that there's a level of differentiation here as well as overall efficacy to the point that it turns back some of the skepticism?

Jason—I think in terms of the Cochrane report, there has been a good bit of follow-up in terms of the methodology there. I do think there's a broader question about the merits of the approach from a methodology standpoint. I'm familiar with the STAT article as well. I think it speaks to two things: the unmet need and the demand for better options, and the fact that the clinical infrastructure is now established and continues to adopt and make available these first couple of agents and build out essentially the marketplace. I think what the market is looking for is a clearer value proposition in terms of the risk-benefit profile. That's really where reading out ALTITUDE and validating the oligomer hypothesis is important. I think Acumen and sabirnetug stand in an attractive position from a timing perspective to reenergize the space and position next-generation treatment options. The field has progressed over years to develop better insights into clinical trial design, which patients to treat, and underlying aspects of the pathophysiology of the disease. We view sabirnetug as a next step advancing the field forward on the basis of positive data.

And I might just add, I was recently at the American Academy of Neurology meeting in Chicago, and these are practicing neurologists for the most part. There was a great deal of interest and enthusiasm for information concerning the two approved drugs, lecanemab and donanemab. So even though there have been some negative analyses, and again as Dan mentioned, the Cochrane report had methodological issues, I think if you actually talk to neurologists, they understand that the infrastructure has been rate-limiting but that infrastructure is going to continue to improve. There is a lot of interest from neurologists at the AAN meeting.

And our next question comes from Tom Shrader of BTIG.

This is Jimmy Kim on for Tom Shrader. As ALTITUDE-AD approaches the late 2026 topline readout, could you give us some additional color on the blinded operational metrics that are tracking—things like protocol deviation rate, site-level dropout patterns, or any shifts in enrolled patient population profile relative to your original assumptions? More broadly, what distinguishes the quality of this data set relative to prior anti-amyloid trials?

Jenny, I'll give you a first pass and then ask Eric to weigh in. I think probably the best thing to say is that we, at this point, have been very pleased with the progress of the ALTITUDE study. Any of these studies—a 542-subject study—there's a lot of data and a lot of information flowing in the study. But we've been relatively pleased with the conduct of the study. It's a great team that is working extremely hard across multiple geographies to deliver the data. And I think to date, we have been tracking to the assumptions that we built into our study design. So we have confidence in our study design as well. I'll turn it over to Eric to give you any specific commentary.

Thanks for the question. The study is progressing quite well. As you know, we completed enrollment in a very short period of time—in 10 months. One of the things that we did in our study, which is being done in other studies and which I think is quite innovative, was to use the plasma p-tau217 test as part of the screening procedure. So in other words, when we did our Phase I study to get into the study, you had to have a positive PET scan and it turned out that about 60% of the time the PET scans were negative. When we added this blood test, a simple blood test as a screening step before you got to PET scans, the rate of negative PET scans dropped from around 60% to under 20%. So it made the screening process much better. We heard feedback from the sites that they really liked that approach. I think that's something that could be used in clinical practice. And actually at the American Academy of Neurology meeting, there was a lot of discussion about how you would use these plasma biomarkers as part of your screening process for patients. So we were really very pleased with how that worked out in our trial, and we're looking forward to seeing that utilized in clinical practice.

Our next question comes from Dev Prasad of Lucid Capital Markets.

Congrats on the progress. Just following up on the previous question regarding Phase II doses: how much separation between 35 mg and 50 mg do you expect? And what would you need to see to select a Phase III dose? Also on the EBD program, can you provide more detail on the 15- to 40-fold higher brain exposure that you observed in primates? What differentiated those exposures—such as dose, route, brain distribution, et cetera?

Thanks, Dev. Jim, I'm going to direct those straight to you.

Yes, Dev, happy to take those questions. So when we think about dosing for the ALTITUDE study first: the doses are 35 mg per kg and 50 mg per kg. As I was mentioning earlier, the doses were chosen with the idea in mind that that is what looks to be a key part of the dynamic range and exposure of soluble oligomers, which, of course, is our key primary target. And I think there's the opportunity to see differential effects of the two doses in a couple of different ways. We'll have to wait and see what the data actually show, but one possibility is differences in efficacy. You might expect to see dose-related differences in efficacy, although I think part of what we're testing there is the role of soluble oligomers and how that's different from what you've seen to date with more plaque-targeting antibodies. So in some ways, the lower dose may give more of an oligomer-specific signal, although we do expect some contribution from other species of Aβ even at that dose. And then certainly, as you go to a higher dose, you would expect some additional effects on larger species as we've seen in the INTERCEPT study in Phase I. And I think also, one might expect there could be some differences in tolerability; that would be consistent with the Phase I data. So very excited to see the study at the end of the year, and we'll be looking at all of these things for differential effects at multiple doses. And then your other question around the EBD programs: of course what we're trying to achieve is both an improvement in brain penetration and the brain distribution of our oligomer-targeting antibodies by coupling with the carrier technology from JCR. What we've done is we've investigated multiple candidates and we've been able to vary both sides of that equation, looking at changes to the carrier choices from JCR as well as modifications on the cargo side. The quick way to summarize it is you're seeing a range of substantial improvements in brain exposure, and that's in both rodent studies using humanized transferrin receptor models and also in primate studies. We're looking at multiple brain regions in the primate study and seeing substantial improvements in exposure. You quoted the range between roughly 15-fold and 40-fold improvements in exposure. We're seeing both improved brain penetration as well as improved distribution. We really think it's both properties that are part of what makes this technology so exciting for the treatment of Alzheimer's and specifically for the soluble oligomer approach. We're keeping a close eye on which are the best candidates to give us the broadest distribution in multiple brain regions.

Thank you, this concludes our question-and-answer session and also today's conference call. Thank you for participating, and you may now disconnect.