管理層發言
Good day, and thank you for standing by. Welcome to the Acumen Pharma First Quarter 2026 Conference Call and Webcast. The operator will provide instructions for the question-and-answer session. 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 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 is bringing us closer to a potentially differentiated treatment option with people living with Alzheimer's. We expect our topline results for ALTITUDE-AD in late 2026. 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 transporter-targeting blood-brain barrier 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 disease, 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 '26. 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?
分析師問答
Please proceed with the question-and-answer session. 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 preclinical Alzheimer's?
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 and mechanism—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 seen to date. What are the key properties and preclinical data that will drive your decision on candidate selection? And with an IND targeted, I believe, mid-2027, could you 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, 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 (multiple ascending dose) phase, we're able to collect data on PET imaging for Aβ, 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.
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 on sabirnetug, especially given the unmet need in early Alzheimer's and the mechanism of the treatment? And then as a follow-up, could you 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, have been deeply involved in gathering feedback. We've done a lot of work at meetings and visited with a number of KOLs and other clinicians who 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. 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 up—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 other question?
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 program. 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.
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? Do you see 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% or more slowing, which is sort of the upper range observed for the current approved agents. So we are hopeful and anticipating that by targeting toxic species in a selective fashion it will unlock greater efficacy. I think the safety profile is also important; there is real-world evidence to suggest overall rates of ARIA and those rates differ by genotype. Those are some of the other elements we'll be looking to establish in terms of ARIA. So it will be the totality of the ALTITUDE data—the risk-benefit profile of sabirnetug with the combination of efficacy and safety—that is the primary means of differentiation relative to the current approved agents. And in terms of subcutaneous dosing, I think we've previously guided that we will be looking at the Phase II data, particularly with respect to the two active doses being investigated in ALTITUDE, to inform precisely where and how we would advance the ongoing work in subcutaneous as part of a Phase III program.
And I might add, Emily, you asked an interesting question around doses. As you know, there are two different doses included in the ALTITUDE study. Those doses were chosen to 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 fascinating to see how that impacts the results from both efficacy and safety perspectives. So that's an interesting feature of the ALTITUDE study—that we've got both of those doses to investigate.
Yes. And just one other point about ARIA: 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. Even if asymptomatic ARIA occurs, symptomatic ARIA and serious adverse events are what you really worry about. Those are less common but have a bigger impact. So those are things we'll be benchmarking carefully when we 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 an article suggesting that use of the currently available anti-amyloid antibodies has been slower than expected. 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 differentiation and overall efficacy to the point that it turns back some of the skepticism?
Jason, in terms of the Cochrane report, I think there's been a good bit of follow-up in terms of the methodology. I think your question 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 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 matters. Acumen and sabirnetug are in an attractive position from a timing perspective to reenergize the space and position next-generation treatment options. The field has progressed over a number of years to develop better insights into clinical trial design, which patients to treat and underlying aspects of pathophysiology. We view sabirnetug as the next position advancing the field forward on the basis of positive data.
I might just add, I was recently at the American Academy of Neurology meeting in Chicago. These are practicing neurologists for the most part, and 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 analyses that raised questions—and again, as Dan mentioned, some of those reports have methodological issues—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.
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? Are things like protocol deviation rate, site-level dropout patterns or any shifts in enrolled patient population profile tracking relative to your original assumptions? More broadly, what distinguishes the quality of this dataset relative to prior anti-amyloid trials?
Thanks, Jim. Jim, do you want to lead out on that and Eric provide some color?
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, at this point, we have been very pleased with the progress of the ALTITUDE study. Any of these studies—it's a 542-subject study—there's a lot of data and a lot of information flowing in. 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. 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.
So thanks for the question. The study is progressing quite well. As you know, we completed enrollment in a very short period of time—10 months. One of the things that we did in our study, which others have also begun to do, and I think is quite innovative, was to use the plasma p-tau217 test as part of the screening procedure. 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 as a screening step before 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 like that approach. I think that's something that could be used in clinical practice. 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. The doses were chosen with the idea in mind that that is the key part of the dynamic range for exposure of soluble oligomers, which is our primary target. There is 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 dose-related differences in efficacy. Although part of what we're testing 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. 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. One might also expect differences in tolerability, consistent with the Phase I data. So we're very excited to see the study results and we'll be looking at all of these things for differential effects at multiple doses. Regarding the EBD programs: 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. We've investigated multiple candidates and been able to vary both sides of that equation—changes to carrier choices from JCR as well as modifications on the cargo side. The quick summary is you're seeing a range of substantial improvements in brain exposure in both rodent studies using humanized transferrin receptor models and in primate studies. We're looking at multiple brain regions in the primate study and seeing substantial improvements; you quoted the range between roughly 15-fold and 40-fold improvements in exposure. We're seeing both improved brain penetration as well as distribution, and we really think it's both properties that make this technology exciting for the treatment of Alzheimer's, specifically for our 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.