Day, and welcome to the Acumen Pharmaceuticals third quarter 2026 conference call and webcast. At this time, all participants are in listen only mode. After the speaker's presentation, there will be a question -and -answer session. To ask a question, you will need to press star one one on your touchtone telephone. Please note this call may be recorded. I would 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, 2026. With me today are Dan O'Connell, our Chief Executive Officer, and Matt Zuga, our CFO and Chief Business Officer. They all have brief prepared remarks, and then we will open the call for questions. Before we begin, we encourage listeners to go to the investor section of the Acumen website to find our press release issued this morning that we will 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 two 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 any accompanying presentation as a result of new information or future results or developments. With that, I will turn the call over to Dan.
Great. Thanks, Alex. Good morning, everyone, and thanks for joining us today. In the third quarter, our team has been very busy readying for the top-line readout from our phase II ALTITUDE-AD trial investigating our lead product candidate, sabirnetug. If you have been following our company for some time, you are likely well aware that these results are highly anticipated. We are testing our central scientific thesis that arresting the harm done by synaptotoxic amyloid beta oligomers in the brain may offer a differentiated approach to treating Alzheimer's disease. Today, I am pleased to confirm that we expect to announce these phase II results this November. We are confident that we are fully evaluating the A-beta oligomer hypothesis with this study. ALTITUDE-AD is a large, well-powered phase II trial with clinically meaningful endpoints.
We are testing two doses of sabirnetug against placebo, carefully considered based on our phase I study in Alzheimer's patients, such that either dose may prove efficacious in the phase II. We have executed the study to a very high operational standard with rapid enrollment, close engagement with study sites and investigators, and high rollover into the open label extension of the study. As previously mentioned, we envision this study as part of a potential registration package and have conducted the study as such with a single confirmatory phase III anticipated following positive phase II results. As previously outlined, ALTITUDE-AD was designed to detect a statistically significant difference between sabirnetug and placebo on the primary efficacy endpoint, iADRS, following 18 months of treatment.
We expect the top-line data set to encompass primary endpoint results, key secondary outcomes, including the CDR-SB, safety evaluations covering adverse events and ARIA rates at a range of informative fluid and imaging biomarkers. We believe that sabirnetug has the potential to demonstrate a differentiated benefit to risk profile given its unique product attributes as a selective anti-A-beta oligomer IgG2 monoclonal. We look forward to sharing the data in November. We also continue to advance our enhanced brain delivery program, or EBD, for the treatment of Alzheimer's disease, representing the only program combining a validated blood-brain barrier penetrating technology with an A-beta oligomer selective therapeutic antibody. As a reminder, we are working on two candidates in the lead-up to an IND filing expected in mid-2027. One candidate, ACU301, is based on a bispecific antibody incorporating sabirnetug.
ACU401 incorporates a novel A-beta selective antibody with differentiated properties known as ACU234. We presented encouraging data at the AAIC meeting in July showing that after intravenous dosing, all tested EBD bispecific antibodies achieved multifold greater brain exposure than unmodified ACU234 alone. ACU401, in particular, achieved up to a 40-fold greater frontal cortex exposure in non-human primates and significant increase in exposures in deep brain regions. The degree of brain penetration we observed in the cynomolgus monkeys, combined with the preserved soluble A-beta oligomer selectivity and a clean hematological profile, exceeded our expectations and give us confidence in the differentiated potential of our EBD program.
The imminent data readout for sabirnetug and the development of our next generation EBD candidates demonstrate both the robustness of our pipeline and our ability to deliver on key priorities, positioning us for an important period of value-creating milestones ahead, both near and longer term. Again, we look forward to updating you in November. With that, I'll turn the call over to Matt.
Thanks, Dan. As a reminder, our third 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 the third quarter with approximately $79 million in cash and marketable securities on our balance sheet, which is expected to support our current clinical and operational activities into early 2027. R&D expenses were $21.1 million in the third quarter. The decrease over the prior year was primarily due to reductions in manufacturing and materials costs, as well as CRO costs, which are both associated with our ALTITUDE-AD clinical trial. G&A expenses were $4.7 million in the third quarter, roughly flat to the same period in the prior year. This led to a loss from operations of $25.8 million and a net loss of $25.4 million in the third quarter.
We look forward to reporting on our phase II ALTITUDE-AD study next month and remain committed to maximizing the potential of our portfolio of A-beta oligomer-targeted antibodies to generate value for patients living with Alzheimer's disease, their caregivers, and our stakeholders. With that, we can open the call for Q&A. Operator?
Thank you. As a reminder, to ask a question, please press star one one. If your question has been answered and you would like to remove yourself from the queue, press star one one again. Our first question comes from Jason Zemansky with Bank of America. Your line is open.
Good morning. Congratulations on the progress. Looking forward to the results. This may seem like a random question now, but as we think about the evolving treatment paradigm, it looks like Biogen is now positioning LEQEMBI as a follow-on after donanemab clears plaque. The argument is that soluble species sort of keep driving disease after the plaque is gone. So it seems like a natural place for an oligomer selective antibody. How do you think about sabirnetug in addition to sort of a primary role, but as a maintenance after plaque clearance or in combination with a plaque clearer, and could anything in the ALTITUDE-AD data set inform that? Thanks so much.
Thanks, Jason. Great question. We have always been advocates for chronic dosing essentially while patients are stable within an early AD stage of disease, as we believe these soluble aggregates are present and persistent in driving disease pathology. It would be a logical extension to consider sabirnetug or an oligomer-selective antibody as a post-plaque clearance follow-on. In the primary mode, we are focused on the primary outcome for sabirnetug and ALTITUDE-AD with an 18-month primary using the iADRS. I think we will have the first clear evidence is really out of that phase II moving towards phase III, but the therapeutic rationale for sabirnetug as a follow-on would make sense to us as we sit here today.
Great. Thanks so much for the color.
Thank you. Our next question comes from Paul Matteis with Stifel. Your line is open.
Hi, this is Emily on for Paul. We were just wondering if you could talk a little bit about your dose selection and what might you expect to see in this upcoming readout that would look different on efficacy and safety between those two doses. Thank you.
Thanks, Emily. So for the phase II, we chose doses of 35 mg/kg and 50 mg/kg, and this is IV dosing every four weeks. We arrived at those doses as a consequence of the dose exposure and some of the pharmacodynamic effects we observed in the phase I. So a combination of the phase I results with some dose modeling allowed us to select these two doses. And importantly, we think both 35 and 50 each are within the zone that could be efficacious. It may be that the higher dose of 50 mg/kg may have perhaps more observed effects on the amyloid PET signal, but we will see how that reads out in the weeks ahead. We are getting close to that data set, so very excited to see it.
But important to establish that both of these doses, we think, are within that zone of efficacy in conjunction with the safety profile that we think could offer a benefit to risk profile that is attractive to patients.
Thank you. Our next question comes from Pete Stavropoulos with Cantor Fitzgerald. Your line is open.
Good morning, and congrats on the execution. Looking forward to the data next month, and thanks for taking our questions. A couple from me. I am wondering what your current thinking is in terms of the bar, or what is the minimum you would like to sort of see out of ALTITUDE-AD to move forward, especially since this is the first time that the oligomer hypothesis is being tested. So the bar for both clinical scales and biomarker data. And would we expect any OLE data in the readout?
Thanks, Pete. As you may recall, we have been guiding towards a clear clinical success of 30% slowing on the iADRS after 18 months of a placebo control period. We think that is a zone in which that would give us the basis for moving forward. In terms of the safety profile, the overall adverse event profile, inclusive of ARIA rates and infusion site reactions and other elements of the safety profile, is going to be a part of this top-line readout. We would anticipate low double-digit ARIA-E in totality and maybe consistent across the genotypes as part of the support of the oligomer hypothesis and the grounds on which sabirnetug would be moving forward to phase III. That is kind of how we are thinking about that. Your second question, Pete? OLE data.
As you are good to point out, our open label extension is a 12-month open label extension. We have had high rollover, essentially greater than 95% of people eligible to participate in the open label extension have elected and consented to do so. That portion of the study we will be reading out over an extended period of time. We do think that that will
generate evidence into 2027 and likely will not be part of the top-line results. I think important to establish, however, the top-line results, as I just mentioned on the scripted call, will be inclusive of the primary and secondary, both efficacy and safety, and include biomarker effects, both imaging and fluid. We will be looking at the amyloid PET as a conventional imaging measure. We will also be looking at fluid biomarkers, CSF, and plasma. I think we will principally be looking at things such as the p-tau217 as a measure of disease status, potentially progression. I think that is going to be a complete data set to inform stakeholders on the merits of sabirnetug and provide evidence in support of the oligomer hypothesis.
All right. Thank you for that. Just a question on EBD. How are you thinking about the other path forward for ACU301 over ACU401, the MAD/SAD studies? Are you going to go straight into patients or healthy volunteers first? The length of time you would sort of aim to have patients in the MAD study, and what optionality do these candidates offer?
Yeah, thanks, Pete. We think there's a lot of optionality in our EBD program, and I think having both ACU301 and ACU401 in the mix is really helpful because it affords us a bit of diversity in terms of the profiles and ways to move the program forward. I think we've learned so much in the development of sabirnetug, both initially with INTERCEPT-AD, which was our phase I study exclusively in Alzheimer's patients that gave us really a solid phase I proof of mechanism data in support of sabirnetug. That, of course, as I just mentioned, informed dosing strategy and the plan for phase II. I think the team's still working on refining precisely what we want to do with EBD in the early phase and translational studies.
We'll be looking at the ALTITUDE results, in particular, to assess dosing strategy as well as biomarker strategy for the EBD program. We think one of the advantages we at Acumen have is all of the experience we've undertaken with sabirnetug, not only through phase I but through a robust phase II, that really serves as a foundation for our strategy for developing the EBD candidates.
All right. Thank you very much, and congrats on the progress once again.
Thanks, Pete.
Thank you. Our next question comes from Tom Shrader with BTIG. Your line is open.
Good morning. I guess we'll all hold our breath for 30 days, but I think one of the interesting things about sabirnetug is that it might act faster given the monomer binding, things like that. The question is, how set up are you to capture that? When are you looking at patients? When are you scanning? When are you taking soluble biomarkers? I think a fantastic readout from this might be that your next phase III could be shorter because the drug works faster. The question is, how set up are you to catch some sort of readout like that? Thank you.
Yeah. Thanks, Tom. Good morning. With sabirnetug's high selectivity for toxic A-beta oligomers, the thesis holds that neutralizing those toxic species early in the early course—
Yes
—of disease could have not only a slowing of disease, but some other potentially sort of symptomatic benefit. I think that's an interesting possibility. I do know that our plans have incorporated elements of observing or essentially capturing that possibility. I think we will know a lot in the coming weeks as the ALTITUDE-AD reads out as to whether, given the mechanism, there is a potential to look at earlier time points for establishing a drug effect going forward. As you mentioned, we think ALTITUDE-AD is a robust test of this central scientific hypothesis and are eagerly awaiting the unblinding and interpretation of those results.
Okay. Fantastic. Good luck again.
Thanks, Tom.
Thank you. Our next question comes from Geoff Meacham with Citi. Your line is open.
Good morning. This is [inaudible] for Geoff. Thanks for taking our question. Could you speak to some of the KOL feedback you are receiving on sabirnetug and the ALTITUDE-AD program? Maybe what are physicians looking for in a treatment, and how could sabirnetug address these needs? Then just as another one, maybe what feedback do they have on the mechanism here as well? Thank you.
Great. So, in our travels and interactions with KOLs, they are mostly principally focused on better treatment options for patients. And I think as such, sabirnetug with a different mechanism, not a plaque-busting agent, but rather something that targets these soluble toxic species is something of high interest and given that potential. So they are keenly, as is everybody in the field, I think, kind of looking at ALTITUDE-AD as a differentiated study where sabirnetug could shift some people's thinking on what the primary mode of treatment should be, whether it be oligomers versus plaque and so forth.
We think there is a lot of anticipation going into next month's readout, and we do think that the study has a mix of data outcomes and readouts that will be very informative as to the merits of sabirnetug and underpin the attractiveness of targeting toxic oligomers in a primary, selective, and direct fashion.
Great. Thank you.
Thank you. Our next question comes from Dev Prasad with Lucid Capital Markets. Your line is open.
Hi. Congrats on the progress and thank you for taking our question. A couple of questions. One is, as we approach the readout, can you comment on patient retention and maybe how should we think about the impact of missing data or discontinuation on primary efficacy analysis? Another one is on subcutaneous. I believe the SubQ work was on hold until the dosage chosen. Wondering, do you plan to initiate that work after the phase II trial? Thank you.
Thanks, Dev. In terms of retention in the primary ALTITUDE-AD study, as we mentioned, we've conducted the study to a very high standard. Our retention within the primary portion of the study has exceeded our expectations, which is great, and we've had high rollover into the open label extension. Objectively, we think people that are participating in the study like the study and have been inclined to stay in and/or extend their involvement in the study. That's encouraging and yet it's obviously still blinded data. In respect to your question on missing data, I think we will be addressing those issues in a conventional and per-protocol basis. I don't know that there's more specifics I can offer on that question.
Thirdly, in terms of the SubQ, yes, we completed a healthy volunteer, essentially a bioavailability study that read out in early 2025. We think we have what we need in terms of the contrast between IV dosing and subcutaneous dosing of the sabirnetug formulation. We anticipate using the phase III in one direction or another to incorporate a subcutaneous advancement. I think we can look at some predicates out there. If you look at what Eisai and Biogen did with LEQEMBI, excuse me, incorporating the SubQ as part of the open label extension in phase III. That could be analogous to how we would be moving forward in the future with a subcutaneous option.
Great. Thank you.
Thank you. This concludes the question -and -answer session. Thank you for your participation. You may now disconnect. Good day.