Acumen Pharmaceuticals, Inc. (ABOS) Earnings Call Transcript & Summary

Good day, and welcome to the Acumen Pharmaceuticals Second Quarter 2026 Conference Call and Webcast. [Operator Instructions] Please note this call is being 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 June 30, 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. You will 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 thanks for joining us today. During the second quarter, our focus remained on disciplined execution as we advanced sabirnetug towards the highly anticipated topline readout from our Phase II ALTITUDE-AD trial, which we continue to expect late this year. We believe this will be an important efficacy readout in the Alzheimer's field. ALTITUDE-AD remains a critical test of our central scientific thesis that selectively targeting synaptotoxic amyloid-beta oligomers may offer a differentiated approach to treating Alzheimer's disease. A substantial body of evidence supports this hypothesis, and we are excited by the opportunity to evaluate that thesis in a well-powered, randomized Phase II study with clinically meaningful endpoints. Our Phase II results have the potential to substantially expand on our Phase I results, which included demonstration of A-beta oligomer t arget engagement and biomarker changes that we're seeing as early as 3 months of treatment, as we previously reported. We continue to be encouraged with the engagement of patients, caregivers, investigators, and study sites participating in ALTITUDE-AD, as well as in its 12-month open-label extension study. Their commitment has been instrumental in bringing us to this important inflection point. I believe the strong relationships the Acumen team holds with study sites and investigators is particularly supported by Acumen's patient-centric approach. At AAIC last month in London, we presented patient experience data collected from participants and study partners prior to treatment in ALTITUDE-AD. Results illustrate the diverse ways individuals with early Alzheimer's disease experience, respond to, and cope with cognitive and functional changes, underscoring the importance of capturing patient experience directly to better understand the meaningful benefit at this stage of disease. As we previously described, ALTITUDE-AD was designed to detect a statistically significant difference on its primary clinical efficacy endpoint, iADRS, after 18 months of treatment with sabirnetug compared with placebo. We expect the topline dataset to include results from the primary endpoint, key secondary measures such as the CDR-SB, safety assessments including adverse events and ARIA rates, as well as important fluid and imaging biomarkers. The study is evaluating two dose levels, 35 mg/kg and 50 mg/kg, compared with placebo. Both these dose levels are within the exposure range previously shown to achieve pharmacodynamic target engagement. While we remain focused on execution and preparation for the readout, enthusiasm across the organization continues to build as we approach this landmark catalyst. We believe that sabirnetug has the potential to demonstrate a differentiated benefit-to-risk profile given its unique product attributes as an anti-A-beta oligomer IgG2 monoclonal. We look forward to sharing the results later this year. In the second quarter, we announced the nomination of two enhanced brain delivery candidates for the treatment of Alzheimer's disease, representing the only program combining a validated blood-brain barrier penetrating technology with an anti-A-beta oligomer-selective therapeutic antibody. Building on robust preclinical data from both in vitro and in vivo studies, we exercised our options with JCR Pharmaceuticals and will advance two candidates, ACU301 and ACU401. ACU301 is a bispecific antibody incorporating sabirnetug, and ACU401 incorporates a novel next-generation A-beta oligomer-selective antibody with differentiated properties. This is known as ACU234. We view our EBD program as expanding the optionality in our pipeline and will continue to evaluate both candidates in the lead-up to support a filing of an IND. Confirming our mouse data in non-human primates is a pivotal step in this work. At last month's AAIC conference, we presented data showing that after intravenous dosing, all three EBD bispecific antibodies achieve 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 observed in cynomolgus monkeys, combined with preserved soluble A-beta oligomer selectivity and a clean hematological profile, exceeded our expectations and gives us confidence in the differentiated potential of our EBD program's approach. We continue to anticipate an IND filing for our lead EBD candidate in mid-2027. Coming up, I'd like to flag for investors an anticipated virtual Investor Relations Day to be held on September 16. Please mark your calendars to view live or as a recording, as we hope this will be a helpful review for the Acumen investment thesis prior to ALTITUDE-ADPhase II data readout. The advance of sabirnetug and our next-generation blood-brain barrier EBD candidates underscores the strength of both our scientific platform and our ability to execute, positioning us well for a significant, eventful remainder of 2026. I look forward to updating you on our program and on our Phase II results for sabirnetug late this year. And with that, I'll turn the call over to Matt.

Thank you, Dan. As a reminder, our second quarter of 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 second quarter with $110.2 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 $27.8 million in the second quarter. The decrease over the prior year was primarily due to reductions in manufacturing and materials costs as well as CRO costs as we get into the final leg of our clinical trial. G&A expenses were $4.7 million in the second quarter, roughly flat for the same period in the prior year. This led to a loss from operations of $32.6 million and a net loss of $32.7 million in the second 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 A-beta oligomer-targeted antibodies for Alzheimer's patients, caregivers, and stakeholders. And with that, you can open the call for Q&A. Operator?

[Operator Instructions] Our first question comes from Paul Matteis with Stifel.

This is Matthew on for Paul. I guess another company doing an oligomer-specific approach read out some blinded data recently. Maybe can you talk about like what are the differences between their approach versus yours and trial design, and how much can we, you know, kind of read through on their clean safety to your upcoming data?

Hey, Matthew, thanks for the question. Yes, we saw the announcement of the blinded interim assessment, but this is really early-stage data. So there's not too much we can conclude from that reporting or that announcement. And we'll be interested to see how that study reads out sometime early next year. We reported Phase I results in 2023, which, to our view, established a really robust clinical target engagement of A-beta oligomers. And with just 3 doses in that Phase I study, we're seeing effects on both fluid and imaging biomarkers that sort of exceeded our expectations and underpin our confidence in why in a large study, in an efficacy-based study such as ALTITUDE-AD, sabirnetug is positioned for success.

Okay. And maybe a quick follow-up. In the selection of your EBD candidates, what were the parameters that you sought to optimize? And where do you think your second molecule might be better than the bispecific sabirnetug?

Thanks. I can quickly comment. I mean, I think for our EBD program, we envision from a product profile standpoint, subcutaneous administration as a convenient form for delivery, as well as preserving the oligomer selectivity, potentially enhancing that selectivity, and an efficient transport across the blood-brain barrier using the transferrin carrier technology as partnered with JCR. So I think we're looking at safety, efficacy, and broader exposure in a format that would lend itself to convenient sub-Q dosing. So both of the candidates have, at least so far, demonstrated all of those attributes, and some of that data has been presented at meetings, and we'll continue to report on findings in that program as we march towards an IND filing on a lead sometime in mid-'27.

Matthew, this is Jim. Maybe I can add a little bit to what Dan has been saying. Of course, when you see the candidates that we announced, those represent the sort of culmination of a process. And we had a really robust collaboration with JCR. And what it allowed us to do is really look at a bunch of different parameters for optimizing for the right fit to match the carrier and the cargo to come up with the final product. And so we looked at a number of things. We looked at affinity for TfR. We looked at valency, monovalent versus divalent. We looked at a bunch of parameters around the potential risk for anemia and things like that. And so it really represents the culmination of a whole campaign to optimize for what we think is the best fit to deliver these oligomer-targeting antibodies into the CNS.

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

You described ALTITUDE, I guess, as designed to detect a stat-sig difference in iADRS, but with two active doses, can you clarify the framework and whether each dose is independently powered against placebo? If only one succeeds, under what circumstances would constitute a statistically robust positive study? And then a quick follow-up, please.

Thanks, Jason. Good question. As we have not specifically provided details on the powering and the analysis. I think, I don't know that we can go into greater detail on that this morning. Yes, we do have both doses, both of which have demonstrated target engagement. We think both of these doses could emerge as efficacious doses, and we'll be looking forward to providing more information as we get closer to the data readout later this year.

Got it. And then maybe without getting too much into the efficacy bar, can you speak to the work you're doing now to minimize the interval between the Phase II results and the initiation of a Phase III? Any regulatory engagements, CMC, partner discussions, site planning? Which activities are sort of gated until the data?

Thanks, Jason. Well, you can imagine there are elements of everything that you mentioned that are ongoing now, with the exception perhaps of regulatory interactions in terms of establishing the Phase III design and so forth. But there's a lot of activity and anticipation to minimizing the white space. And we're hopeful for a successful readout in ALTITUDE-ADthat really will help facilitate and accelerate our ability to move sabirnetug into a single pivotal Phase III.

Our next question comes from Pete Stavropoulos with Cantor.

Hi, this is Samantha on the line for Pete. My first question is there are biomarker data that suggests certain tau fragments like p-tau217 can be used as a marker for amyloid pathology, while markers like MTBR-tau243 identifies tau tangle pathology in Alzheimer's disease. I know that you've incorporated and will look at p-tau217 in the ALTITUDE-ADstudy, but can you talk about tau243? Do you plan to look at it in ALTITUDE, and how could you incorporate it into a Phase III? Can it be leveraged to help or expedite patient selection?

Thanks, Samantha. Go ahead, Eric.

Yes, so this is Eric Siemers. Maybe I can take that one. So, yes, the biomarker world in Alzheimer's is moving really quickly, especially with regard to blood-based biomarkers. As I think you probably know we use p-tau217 as part of our screening procedure actually for enrolling people into ALTITUDE, but it'll also be an outcome measure that we'll look at after we're unblinded at the end of the study. MTBR is relatively newer, and so it really wasn't being discussed at the time we designed ALTITUDE. But one of the things that we have talked about is that, we have, a large number of patients and a lot of actually plasma samples that will be stored. And so we have the opportunity to look at things like MTBR, new biomarkers that, especially the blood-based biomarkers, that become interesting after we actually complete the study. So yes, MTBR is one of the things we talk about, but I think it's not just that. Any other new blood-based biomarker that may look interesting, we'll have the opportunity to look at.

And Samantha, this is Jim. Maybe just to add a little bit onto what Eric is saying. I think he's totally right. It's really an exciting time in the field for looking at these fluid-based biomarkers. And the reason for that is it really provides a lot of information about patients. And so I think what we're seeing is people are beginning to measure these multiple markers in a lot of different studies, looking at a lot of different things. It potentially gives you the opportunity to look at where a person is in their progression with disease. It has the ultimate potential, I think, to start identifying patients who might be better candidates than others. I think we're too early days for those kinds of applications, but I do think that's where the field is going. And so what we'll do exactly as Eric is saying, is as we go along, we'll continue to monitor all this. We'll use these tools as we can in our trials, and we have the opportunity to go back and measure some of these things, even in a post hoc fashion. So I think this is going to continue to be an important part of Alzheimer's trials moving forward.

Awesome. And just one quick follow-up. In July, there was an announcement of a collaboration with Unlearn utilizing digital twins. Can you help us understand what this tool is and how it's incorporated into the Phase II, and how can you possibly leverage it for Phase III?