Acumen Pharmaceuticals (NASDAQ:ABOS) Q2 2026 Earnings Call

0:00 Good day and welcome to the Acumen Pharmaceuticals Second Quarter twenty twenty six Conference Call and Webcast. At this time, all participants are in a listen only mode. After the speakers' presentation, there will be a question and answer session. Please note this call is being 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 06/30/2026. 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.

0:47 Joining for the Q and A session, we also have Doctor. Jim Dougherty, our President and Chief Development Officer, and Doctor. 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 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.

1:33 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 sabranatog towards the highly anticipated top line readout from our Phase II ALPITUDE 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.

2:24 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 Available target engagement and biomarker changes that were seen as early as three months of treatment as we previously reported. We continue to be encouraged with the engagement of patients, caregivers, investigators and study sites participating in ELTIPDE AD, as well as in its twelve 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.

3:18 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've previously described, ALTITUDE AD was designed to detect a statistically significant difference on its primary clinical efficacy endpoint, the IDRIS, after eighteen months of treatment with subveratone compared with placebo. We expect the top line data set 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.

4:16 The study is evaluating two dose levels, thirty five milligrams per kilogram and fifty milligrams per kilogram, 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 ciforadenant has the potential to demonstrate a differentiated benefit to risk profile given its unique product attributes as an anti ABeta ligamer 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 abeta ligamer selective therapeutic antibody.

5:11 Building on robust preclinical data from both in vitro and in vivo studies, we exercised our option with JCR Pharmaceuticals, and we'll advance two candidates, ACU-three zero one and ACU-four zero one. ACU-three zero one is a bispecific antibody incorporating sibernathog, and ACU-four zero one incorporates novel next generation abetoligomer selective antibody with differentiated properties. This is known as ACU-two 34. We view our EBD program as expanding the optionality in our pipeline, and we'll continue to evaluate both candidates in the lead up to support a filing with IND. Confirming our mouse data in nonhuman primates is a pivotal step in this work. And at last month's AAIC conference we presented data showing that after intravenous dosing, all three EVD bispecific antibodies achieved greater brain exposure than unmodified ACU-two thirty four alone.

6:06 ACU-four zero one in particular achieved up to a 40 fold greater frontal cortex exposure in nonhuman primates and significant increase in exposures in deep brain regions. The degree of brain penetration reserved in monkeys combined with preserved soluble selectivity in a clean hematological profile exceeded our expectations and gives us confidence in the differentiated potential of our EVD program's approach. We continue to anticipate an IND filing for our lead EVD candidate in mid-twenty twenty seven. 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 helpful review for the Acumen investment thesis prior to ALPITUDE Phase II data readout.

6:59 The events of the Suburbanipug in 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 EVD program and on our Phase II results for Cimbernitug late this year. And with that, I'll turn the call over to Matt. Thank you, Dan. As a reminder, our second quarter twenty twenty six 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 $110,200,000 in cash and marketable securities on our balance sheet, which is expected to support our current clinical and operational activities into early twenty twenty seven.

7:51 R and D expenses were $27,800,000 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 and A expenses were $4,700,000 in the second quarter, roughly flat to the same period in the prior year. This led to a loss from operations of $32,600,000 and a net loss of $32,700,000 in the second quarter. We are confident in our scientific innovation and strong track record of execution as we work toward our phase two ALPITUDE AV readout later this year and advance our EVD program.

8:39 We remain dedicated to building value with our portfolio of abeta oligomer targeted antibodies for Alzheimer's patients, caregivers, and stakeholders. And with that, we can open the call for Q and A. Operator? Thank you. As a reminder, if you'd like to ask a question, please press 11. Our first question comes from Paul Matteis with Stifel. Your line is open. Hi there. Good morning. This is Matthew on for Paul. Thank you so much for taking our question. I guess another company doing an oligomer specific approach read out some blinded data recently.

9:25 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? Thank you so much. Matthew, thanks for the question. Yeah, we saw the announcement of the blinded interim assessment. You know, this is really early stage data, so there's not too much we can conclude from that reporting or that announcement. We'll be interested to see how that study reads out sometime early next year. We reported Phase I results in 2023, which, you know, to our view, established a really robust clinical target engagement of A beta ligamers, and with just three doses in that phase one study, we're seeing both 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, sabrutinib is positioned for success.

10:26 Okay. Thank you so much. And maybe a quick follow-up. In the selection of your EBD candidates, what were the parameters that you thought to optimize? Where do you think your the second molecule might be better than the bispecific submerged drug? Thank you so much. Thanks. I can quickly comment. Mean, I think for our EV 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 inefficient transport across the blood brain barrier using the transferrin carrier technology as partnered with JCR.

11:14 So I think we're looking at safety, efficacy, and broader exposure in a format that would lend itself to convenient subcu 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-twenty seven. And Matthew, this is Jim. Maybe I can add a little bit to what Dan has been saying. You know, of course, when you see the candidates that we announced, those represent the sort of culmination of process. And we had a really robust collaboration with 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.

12:15 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. That's super helpful. Thank you so much. Thank you. Our next question comes from Jason Zamansky with Bank of America. Your line is open. Perfect. Good morning. Thank you so much for taking our question and congrats on the great progress. You described ALTITUDE, I guess, is designed to detect a stat sig difference in IDRIS, but with two active doses, can you clarify the framework and whether each dose is independently powered against placebo?

13:03 If only one succeeds, under what circumstances would constitute a statistically robust positive study? And then a quick follow-up, please. Thanks. Thanks, Jason. Good question. As you know, we have not specifically provided details on the powering and the analysis. So I think, you know, 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 late 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?

13:55 Any regulatory engagement, CMC, partner discussions, site planning? Which activities are sort of gated until the data? Thanks. 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 in anticipation to minimizing the white space, and we're hopeful for a successful readout in altitude that really will help facilitate and accelerate our ability to move sabrinetug into a single pivotal Phase III. Great. Thanks for the color. Thank you. Our next question comes from Pete Stavropoulos with Cantor. Your line is open.

14:47 Hi, this is Samantha on the line for Pete. Thanks for taking our question, and congrats on the quarter. My first question is, there are biomarker data that suggests certain tau fragments like pTau217 can be used as a marker for amyloid pathology, while markers like MTBR tau two forty three identifies tau tangled pathology in Alzheimer's disease. I know that you've incorporated and will look at Ptau217 in the ALPITUDE study, but can you talk about tau two forty three? Do you plan to look at it in ALPITUDE? And how could you incorporate it into a Phase III? Can it be leveraged to help or expedite patient selection? Yeah, so Oh, go ahead, Well, yeah, so this is Eric Siemers. Maybe I can take that one. So yeah, the biomarker world in Alzheimer's is moving really quickly, especially with regard to blood race biomarkers.

15:44 So as I think you probably know, we use pTal217 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 ALPITUDE. 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, you know, new biomarkers that especially the blood based biomarkers that become interesting after we actually complete the study. So yeah, MTBR is one of the things we talk about, but I think it's not just that. It's, you know, any other new blood based biomarker that may look interesting we'll have the opportunity to look at.

16:57 And Samantha, 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.

17:45 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. Thank you so much. 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? Thank you. Yeah, absolutely. This is Jim again. I'm happy to take that one. As you say, we have partnered with a company called Unlearn AI to use these digital twins. And we see it again as another tool, emerging tool that potentially provides some value.

18:33 These are almost individualized digital models, relying on the data from thousands and thousands of patients who have been studied in for the progression of their disease and clinical trials and in other out of the formats. So at this point, there's a tremendous amount of data about how disease progresses over time. And of course, it's incredibly complex and differentiated patient to patient. But what these tools do is allow for using baseline data to predict how their individual course of disease will progress over time. It's a model and I think there have to be lots of questions about how robust the models are, what you can say about them, what you can't say about them. But potentially you have the opportunity to do things like allow you to refine your patient selection.

19:25 They have the opportunity to do things like be used as a prognostic covariance in analyses following trials. I think a number of potential applications, but honestly, the only way to really evaluate how much value these things have is to begin to get in there and work with it yourself. And so that's effectively what we're doing. We're using this at this point as an exploratory endpoint. We're trying to understand how these tools might be useful to us in the future. And I think, as I was saying, there are several potential ways they can be used. So that's what our evaluation will be to understand which ones are the best ways to apply this technology for Acumen. Thanks so much. Thank you. Our next question comes from Tom Schrader with BTIG.

20:13 Your line is open. Good morning. Exciting times. A little background or next steps on the EDD franchise. Do you anticipate you would take both candidates into humans? Do you have to start with healthy volunteers? And any sense of how many patients or people you would need to get a read on anemia? Thanks. Thanks, Jim. Why don't you take that one as well? Yeah, happy to. Some great questions, Tom. These are things that the team is actively working on at this point. So the first question, we have identified and nominated two candidates, ACU-four zero one and ACU-three zero one. You know, we're doing work on both molecules, and it really is intended to identify which one offers what we think is the best overall profile. So, what we would intend to do is move into clinical development with one molecule, and that'll be the one that we think offers the best of possible profiles.

21:14 As far as additional work that we're doing, there's a tremendous amount of work on CMC and talk study preparation in preparation for our plan to file an IND in mid-twenty twenty seven. And, you know, I think we're still working on study design. There's a lot of active discussion around it. We've got a lot of experience from the INTERCEPT study with Suburban Tug that is going to help us identify what's exactly the best trial design to use. I think what I could say at this point is it's really going to come down to what's the most efficient design. We are going to try to get as much information as we can, as we did in the INTERCEPT study, but we also wanted to move this exciting program forward as quickly as we can. So, more details later on what those design choices are going to turn out to be, but I can tell you there's a lot of active discussion right now with the program team trying to land what is going be the most efficient design.

22:14 And are you going to start in healthy volunteers or are you not saying? So, you know, that's one of the things that we're going to see. I think the goal is to transition to patients as quickly as we think is practical because you get a lot of valuable information from patients didn't intercept. But I think exactly when that would be is honestly one of the things that we're still talking about. So, yeah, I just we haven't really made a final decision yet. And one quick one for Dan. Do you expect to go radio silent at some point? Any guidance about when? Tom, we continue to be convinced we'll have the top line results for ALPITUDE AD late twenty six, you know, consistent with our guiding for some time now.

23:04 We have mentioned, as I mentioned on the call, we'll have an Investor Relations Day, September 16, and that'll be a forward looking public facing discussion. We anticipate participating in some of the early fall activities, so we'll visible and accessible at some point, you know, as we get closer to the end of the fourth quarter, think we will probably have to shut down some of our public facing engagement in anticipation of results. But the timing and specific dates for that are I can't comment on. Great. Thank you. Thank you. Our next question comes from Jeff Meacham with Citi. Your line is open. Hey guys, thanks for the question.

23:49 I have two quick ones. The first, I know the focus on oligomers obviously differentiates you from Kisanla and Leukembi. But how would you set expectations on safety and tolerability and the differences there? I guess, as we get more real world experience with these two agents in the commercially. Second question, I want to get your view of the recent competitor tau data when kind of think about the post altitude data, is there a way to fast track perhaps a combo or proof of concept if you think that's a viable strategy? Thank you. Thanks, Jeff. Good questions. I think in terms of safety, tolerability and sabranitug, as we described, you know, ELTITUDE with two active doses is intended to demonstrate a clinical efficacy signal and a risk benefit profile, both inclusive of the clinical efficacy relative to safety that is differentiated from existing treatments. So we're hopeful and enthusiastic about that possibility, really just the magnitude of the study, the duration of exposure, we think it's a well designed study to underpin and validate the oligomer hypothesis as we've positioned it. So that's sort of our expectations for suburbitum and altitude.

25:16 I think that, you know, you mentioned the I think that you're referring to Biogen FIB 80 program that was reported at AIC in July, and I think those are interesting data. It looks as though they'll move into a Phase III study for that molecule, and I think it serves as, depending on how you view it, the first clinical validation of a tau directed approach. Ultimately, I think we take the view that Alzheimer's, you know, is a disease that will be more adequately addressed with combination strategies. So we'll continue to evaluate ways to leverage not only our portfolio of abeta ligaments directed approaches or treatments with other potentially synergistic combinations, whether it be tau or anti inflammatory approaches, but it just sort of underpins sort of the stage we're at in terms of establishing better treatment options for patients.

26:13 We think the future is quite bright for safer, more efficacious and more robust treatment for the early stages of the disease. As I'm sure folks on the call are aware, the move into the preclinical population, which would be, you know, a way to avert or otherwise delay the onset of symptoms. So it's a really robust innovation ecosystem right now in the space, and we think that will continue to accelerate both commercially with products being adopted and grown in the marketplace, and then with further research innovations that will continue to build on better options for patients. And this is Eric. Maybe if I could just expand on that a little bit in terms of safety and tolerability. There's sort of two aspects of that that are differentiated with Subrinitug.

27:04 So first of all, it's the target. It's very selective for oligomers rather than plaque and we think that that has some potential benefits in terms of safety. And the other thing that is important to keep in mind I think is that this is what's called an IgG2 antibody rather than an IgG1 antibody. So without going into too many details, the IgG all the other monoclonal antibodies are IgG1s, And they have more what's called effector function. In other words, they call in your immune system to get rid of things that you don't want there. In the case of these monoclonals, it's typically plaque. And that can lead to problems like ARIA.

27:53 But for an IgG2, there's less of this effector function, so it's less effect on calling in immune cells. And for our mechanism targeting oligomers, you really don't need that to happen anyway. So there's two reasons to think that our safety and tolerability could be quite good. One is that we have this differentiated target oligomers, and the second is that we have an IgG2 antibody with less effector function and less immune system activation. So we're looking forward to seeing the data from ALDITUDE, obviously. Great. Thanks, guys. Thank you.

28:40 Our next question comes from Dev Mersad with Lucid Capital Markets. Your line is open. Hi. Thank you for taking our questions. Just a couple of follow-up questions. First is to follow-up on the biomarker data question. Will that biomarkers data will be in the top line release, or it will follow later? And the second is what should we expect from September 16 IR Day? Will it include new EBD data or a preview of altitude analysis plan or a venue to select EBD lead candidate? Thank you. Thanks, Deb. So for your first question, the top line results, as I mentioned in the prepared remarks, will include the primary outcome, the IBRIS, which is a composite including both cognitive and functional measures involving the ADAS Cog as well as the ADCS activities of daily living. We'll also have the CDR Sum of Boxes, again, another cognitive functional endpoint familiar to the agency and others in the field.

29:45 We intentionally will include both fluid and imaging biomarkers as part of those top line results. We really want the ALPITUDE readout to be a robust readout that really determines Suvirnatug's safety and clinical efficacy as part of the study design. So yes, we do anticipate having both imaging and fluid biomarkers with the top line results late this year. Then for IRJ, yeah, I would expect that to be more of a review of the investment thesis of Acumen. So whoever would like to get up to speed on Suburbanipug and our EBD program prior to that phase two data, that would be a good event for viewers to tune into.

30:41 So yeah, please keep it on your calendar. Great, thank you. Thank you. I'm showing no further questions at this time. Like to turn the call back over to Alex Braun for closing remarks. Thanks, Michelle, and thanks to everyone for tuning in today. As always, we are at the company for follow-up questions, and I hope everyone has a wonderful day. Thank you for your participation. You may now disconnect.