Earnings call transcript: Acumen Pharmaceuticals Q2 2025 sees EPS miss and stock dip

Acumen Pharmaceuticals reported its second-quarter 2025 earnings with an actual EPS of -$0.68, missing the forecasted EPS of -$0.51. This miss represents a 33.33% negative surprise. Following the earnings release, Acumen’s stock showed a premarket decline of 1.41%, trading at $1.40. The company’s ongoing investments in research and development have significantly impacted its financial results, with a notable increase in R&D expenses.

Key Takeaways

• EPS of -$0.68 missed the forecast of -$0.51 by 33.33%.
• Stock declined by 1.41% in premarket trading.
• R&D expenses rose, impacting overall financial performance.
• Strategic collaboration with JCR Pharmaceuticals continues to be a focal point.

Company Performance

Acumen Pharmaceuticals is focusing on its innovative treatment for Alzheimer’s disease, particularly through the development of Sivernotug, a monoclonal antibody. Despite the financial shortfall this quarter, the company remains committed to its strategic collaborations and ongoing studies, which could position it well in the competitive landscape of Alzheimer’s treatments.

Financial Highlights

• Cash and marketable securities: $166.2 million as of June 30, 2025.
• R&D expenses: $37.1 million, an increase from the previous year.
• General and administrative expenses: $4.6 million, flat year-over-year.
• Net loss: $41 million for the quarter.

Earnings vs. Forecast

Acumen Pharmaceuticals’ EPS of -$0.68 was below the forecast of -$0.51, resulting in a 33.33% negative surprise. This miss is significant compared to previous quarters, highlighting challenges in managing expenses amid ongoing R&D investments.

Market Reaction

Following the earnings announcement, Acumen’s stock fell by 1.41% in premarket trading, reaching $1.40. This movement reflects investor concerns over the company’s financial performance and its ability to manage costs effectively. The stock remains within its 52-week range, with a low of $0.855 and a high of $3.36. InvestingPro analysis indicates the stock is currently undervalued based on its Fair Value model, while analyst consensus remains strongly bullish with price targets ranging from $4 to $11.

Outlook & Guidance

Acumen Pharmaceuticals anticipates its cash reserves will support operations into early 2027. The company is expecting top-line results from its ALPITUDE AD phase two study in late 2026, which could significantly impact its future performance. The collaboration with JCR Pharmaceuticals offers potential milestone payments up to $555 million, providing a positive outlook for further developments.

Executive Commentary

CEO Dan O’Connell emphasized the potential of blood-based biomarkers in transforming Alzheimer’s diagnosis, stating, "We believe blood-based biomarkers will revolutionize the field by making an accurate and potentially earlier diagnosis much more efficient." Chief Development Officer Jim Dougherty highlighted the company’s innovative approach, saying, "We see the opportunity to really lower the delivered dose because you’re going to get a higher fraction of the circulating dose into the brain if the technology works as it’s intended."

Risks and Challenges

• The financial strain from increased R&D expenses could impact future profitability.
• Market competition in Alzheimer’s treatments remains intense.
• Regulatory hurdles for new treatments could delay product launches.
• Dependence on strategic partnerships for technological advancements.
• Volatility in stock performance may affect investor confidence.

Q&A

During the earnings call, analysts inquired about the potential of Acumen’s blood-brain barrier technology and its implications for preclinical Alzheimer’s studies. The company also addressed questions regarding its biomarker strategies and the low ARIA rates observed in current studies, providing insights into its competitive positioning in the market.

Full transcript - Acumen Pharmaceuticals Inc (ABOS) Q2 2025:

Michelle, Conference Call Operator: Good day, and welcome to the Acumen Pharmaceuticals Second Quarter twenty twenty five 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. As a reminder, this call may be recorded. I would now like to turn the call over to Alex Braun, Head of Investor Relations.

Please go ahead.

Alex Braun, Head of Investor Relations, Acumen Pharmaceuticals: Thanks, Michelle. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended 06/30/2025. With me today are Dan O’Connell, our Chief Executive Officer Doctor. Jim Dougherty, our Chief Development Officer and Matt Buga, our CFO and Chief Business Officer. Dan and Matt have some prepared remarks, and then we’ll open the call for questions.

Joining for the Q and A session, we also have 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. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward looking statements.

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 in the accompanying presentation as a result of new information or future results or developments. And with that, I’ll turn the call over to Dan.

Dan O’Connell, Chief Executive Officer, Acumen Pharmaceuticals: Great. Thanks, Alex. Good morning, everyone, and thanks for joining us today. I have a few remarks to make before handing the call over to Jim to provide some details about our recently announced Enhanced Brain Delivery, or EBD, program. Then Matt will detail our quarterly financial results before we open the call for questions.

Second quarter was a productive one for Acumen marked by steady operational progress and an important strategic partnership to expand our portfolio. Following the rapid completion of enrollment in our phase two ALPITUDE AD study in the first quarter, we continue to make great progress with the study. At the recent AAIC conference in Toronto, we received positive feedback from site investigators about the study design, patient retention, and our team’s engagement. Based on this strong execution, we continue to expect top line results in late twenty twenty six, inclusive of the key efficacy and safety measures. Altitude is investigating sivernotug, our monoclonal antibody with high selectivity for toxic A beta oligomers.

This selectivity is key to why we believe sivernotug could unlock potentially greater clinical efficacy and improved safety relative to antibodies targeting amyloid plaques. At AIC, we also presented data showing Subirna Tug achieved the highest selectivity for abeta oligomers over monomeric abeta when compared to recombinant lecanumab and aducanumab. The reason why this is important is that A beta monomer levels are approximately 7,000 fold higher than the low abundance toxic oligomer levels found in the diseased Alzheimer’s brain. So lower affinity for monomeric A beta, what Subveratog demonstrates, is going to increase functional selectivity because less of the antibody will be binding to monomer. I’d also like to mention that we are encouraged by the recent comments from commercial players in the space, highlighting the growth of the clinical infrastructure for diagnosing and treating people with Alzheimer’s disease.

Feedback from KOLs and others in the field also have noted greater easing of clinical bottlenecks. Real world long term data from the currently marketed products reported at AAIC demonstrate the clinical benefit of these products growing over time, further supporting their adoption. In addition, the first blood based biomarker has been approved by the FDA and others are being developed. We believe blood based biomarkers will revolutionize the field by making an accurate and potentially earlier diagnosis much more efficient. We also believe they will help expand the demand for anti amyloid treatments.

It’s terrific to see the field moving forward and the clinical infrastructure coming online as well as the increased blood based diagnostic options for the benefit of patients and their families. This momentum, we believe, sets the stage for Suvernatug and potential next generation EBD products in the future as there remains a very significant untreated patient population interested in receiving anti amyloid therapy. We’re excited about the potential of Silvernotug to provide a differentiated benefit to risk treatment option for patients and the future possibility of building on that with an EBD product or products. Moving to EBD, in July, we announced a strategic collaboration option and license agreement with JCR Pharmaceuticals based in Japan. This collaboration is to develop an Alzheimer’s disease product combining our abeta oligomer selective antibody expertise with JCR’s transferrin receptor targeting blood brain barrier penetrating technology.

We chose to partner with JCR as their established leader in the BBB space. Importantly, the partnership extends our portfolio and builds on our confidence in the potential treatment benefit of targeting toxic A beta ligands. We’ve been working closely with JCR for more than a year, and I’m very excited at the potential to develop a differentiated next generation treatment option for patients and shareholders alike. We expect to make a development decision for up to two product candidates in early twenty twenty six based on nonclinical data. I’ll now turn the call over to Jim to expand on our progress and our EBD strategy.

Jim Dougherty, Chief Development Officer, Acumen Pharmaceuticals: Thanks, Dan, and good morning, everyone. Thanks for joining us today. I’d first like to build on Dan’s comments about AIC and the positive sentiment surrounding current Alzheimer’s disease therapies and the potential for next generation treatments. A number of KOLs have recently commented to us that if a patient’s appropriate for one of the available monoclonal antibodies and makes the decision to begin treatment, compliance with the IV infusions and MR monitoring is very high. When used in clinical practice, the safety profile of amyloid targeting antibodies appears similar to what’s been reported from placebo controlled clinical trials.

That said, additional improvements in the modest efficacy and reduced need for safety monitoring with the current drugs would be welcomed. One of the major challenges for treating neurological disorders like Alzheimer’s disease is the restriction of many therapeutic agents from entering the brain in high enough concentrations to provide therapeutic efficacy. The blood brain barrier, or BBB, is a system of epithelial cells that line the blood vessels in the brain that very effectively limit entry into the brain for many therapeutic agents. Selectively leveraging a process called receptor mediated transcytosis has become an exciting technology to improve delivery of therapeutic macromolecules from the bloodstream into the brain. Receptor mediated transcytosis takes advantage of natural systems that selectively transports specific proteins into the brain, thereby delivering substantially higher amounts of enzymes or antibodies to where they need to be.

We have recognized for some time that this approach could benefit our program at Acumen by delivering oligomer targeted therapeutics to the brain in a safe and effective manner. Although a number of receptors have been identified that can serve as access points for RMT technology, we have chosen the transferrin receptor as the appropriate carrier for our program based on clinical experience and the potential to mitigate the risk of ARIA associated with amyloid targeting therapeutic approaches. We conducted an extensive search and evaluation process to assess many technologies, and we’re drawn to JCR because they are an established leader in the blood brain barrier space with an approved therapy in Japan using their technology that is associated with low rates of anemia. J Brain Cargo technology is a proprietary JCR drug delivery system that efficiently delivers drug to target tissues, including central nervous system through receptor mediated transcytosis. It’s applicable to various modalities, including antibodies, enzymes, oligonucleotides, lipid nanoparticles, gene and cell therapy, peptide and decoy receptors.

The first drug developed based on this technology is approved in Japan for the treatment of lysosomal storage disorder exhibits an established safety profile. We have worked with JCR for more than a year on feasibility studies, and in July, we announced a collaboration license and option agreement to investigate the combination of our oligomer targeted antibodies with their transferrin targeted blood brain barrier technology. As you heard Dan discuss, we believe selectivity for synaptotoxic A beta oligomers is a key opportunity for both safe and effective next generation disease modifying antibody therapy. Pairing this differentiated cargo with JCR’s validated carrier technology may offer an attractive next generation product candidate for Alzheimer’s patients. We’re investigating both Suburbanitug and other oligomer selective antibodies from our library, and exploring both single chain and variable heavy domain antibody constructs with JCR, which we consider cutting edge approaches in the blood brain barrier space.

A nonclinical candidate data package inclusive of a nonhuman primate study is expected in early twenty twenty six, at which point Acumen has an exclusive right to exercise our option to deliver up to two development candidates. And now I’ll hand the call over to Matt.

Matt Buga, CFO and Chief Business Officer, Acumen Pharmaceuticals: Thank you, Jim. As a reminder, our second quarter twenty twenty five financial results are available in the press release we issued this morning and in our 10 Q we will file later today. As of June 30, had $166,200,000 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. R and D expenses were $37,100,000 in the first quarter apologies, in the second quarter. The increase over the prior year was primarily due to an increase for manufacturing materials for the ALPITUDE AD clinical trial, as well as an increase in clinical expenses now that we are fully enrolled.

G and A expenses were $4,600,000 in the quarter, roughly flat to the same period in the prior year. This led to a loss from operations of $41,700,000 and a net loss of $41,000,000 in the quarter. Finally, I would like to note that our collaboration with JCR Pharmaceuticals is a highly capital efficient way to expand our portfolio of oligomer targeted candidates. Under the terms of the agreement we announced in July, in addition to an upfront payment that JCR received, if Acumen exercises our exclusive option to develop up to two development candidates, JCR will receive an additional option payment of $9,250,000 JCR will also be eligible to receive future milestone payments of up to $40,000,000 related to development and up to $515,000,000 related to sales for a total of up to $555,000,000 as well as single digit percentage royalties on sales of any products that emerge from the collaboration. We are excited for the optionality and potential value this deal provides and await preclinical candidate data in early twenty twenty six.

We are also confident in our strong execution of Optitude AD and look forward to sharing top line results, which are expected in late twenty twenty six. We remain dedicated to delivering potential next generation treatment options for the benefit of patients, caregivers, and shareholders. And with that, we can open the call for Q and A. Operator?

Michelle, Conference Call Operator: Thank you. As a reminder, if you’d like to ask a question, please press 11. Our first question comes from Jason Zamanski with Bank of America. Your line is open.

Jason Zamanski, Analyst, Bank of America: Good morning, thanks so much for taking our question and congrats on the progress. Wanted to talk to you a little bit about AIC, specifically if you look at Roche’s similar sort of brain shuttling technology, the trotanemab initial results there, how to benchmark a potential brain shuttling technology around Subirnatug. And then I guess secondarily, given the overall plaque reduction seen in those patients, you know, what does that mean for your epitope given kind of the focus on the oligomers? Thanks.

Dan O’Connell, Chief Executive Officer, Acumen Pharmaceuticals: Thanks, Jason. Great question. I guess I’d like to direct that to Jim initially, and Eric, you may have some comments as well.

Jim Dougherty, Chief Development Officer, Acumen Pharmaceuticals: Yeah, absolutely. So yeah, thanks, Jason. We’ve obviously been paying close attention to this entire space, including Roche’s program. And I think where I’d start is where we see the opportunity for this technology is significantly enhance the ability to deliver your therapeutic target to the targeted areas in the brain. And you see that certainly with the trintinib, that they see a significant change in the overall profile of the molecule from the days of delivering it directly as cantanerumab to what they’re seeing now when combined with the shuttle to allow them to increase their brain concentrations.

And I think we see the same kind of opportunity with Suburbanitug where of course their difference is in the fundamental targeting of the molecules. So we believe very much that these toxic synaptotoxic oligomers are directly toxic within the brain during the progression of Alzheimer’s disease. And so being able to robustly target that we think is a mechanism that’s going to lead to improvement for patients. Of course, we also see some effect on plaques and there’s a complex biology there. The amyloid biology, although we all refer to amyloid as the target and it certainly is, amyloid biology is pretty complex.

And so there are oligomers associated with plaques and that’s a much longer discussion. But I think where it really lands is that we see the technology as enhancing the ability of Suburban Tug to really effectively access sidewall ligaments and we think that that is going to be a mechanism that will be beneficial to patients. Eric, I

Eric Siemers, Chief Medical Officer, Acumen Pharmaceuticals: don’t know

Jim Dougherty, Chief Development Officer, Acumen Pharmaceuticals: if you can add anything to that.

Eric Siemers, Chief Medical Officer, Acumen Pharmaceuticals: Yeah, the only thing I might add to that is just in terms of where we are in development. Mean Roche has done a great job in terms of their phase one study and they’re obviously starting two phase three studies, which will take a lot of read out. On the other hand, we’re really looking forward to our ALDITUDE AD study with over, well, with five forty two patients that’ll read out the end of next year. So but they’re doing a great job with their development plan, but it’s it’s early. They’re in phase one right now, and we’re looking forward to the results of our phase two ALGATUDE study.

Jason Zamanski, Analyst, Bank of America: Got it. Thanks so much for the color.

Michelle, Conference Call Operator: Thank you. Our next question comes from Jeff Meacham with Citi. Your line

Jeff Meacham, Analyst, Citi: is open.

Ross, Analyst Representative, Citi: Hi, guys. It’s Ross on for Jeff. I guess I just wanted to understand a little bit more kind of what you guys are hearing about the PTL-two seventeen testing using the screening process. Just kind of what you’re hearing or any feedback or color on that from physicians in the practicing end.

Dan O’Connell, Chief Executive Officer, Acumen Pharmaceuticals: Thanks, Raj. Eric, you want to handle that, maybe mention the AIC poster and some of the traction that we were getting from how we used that assay in ALPITUDE?

Eric Siemers, Chief Medical Officer, Acumen Pharmaceuticals: Yeah, sure. Thanks. A great question. Really appreciate that. We, as you probably know, use that as part of the screening process in our phase two altitude study and it worked exceptionally well, think.

We actually, in our phase one study when that wasn’t available, over sixty percent of the PET scans that we obtained as part of the screening process were negative for amyloid, but when we used the screening process and got a p cal two seventeen level first and then allowed people to go on the PET, and seventeen percent of the scans were negative so we didn’t really want to have zero percent negative because then you were too conservative in your set point but in the poster that we had, we actually showed that as part of the screening process that actually reduced the cost by about 40% and I think equally important is it reduces the burden for patients and their families because now you have far fewer patients going on to unnecessary PET scans and lumbar punctures for spinal fluid. So it worked very, very well in our study, we were pleased with those results, but more broadly, I think that’s your question, you know we’re hearing a lot of positive comments from clinicians in terms of the utility of this blood test, and there will be probably other blood tests that will become available, but this is the first one to actually get FDA approval.

So in the future, I think you’ll see a lot of clinicians applying these blood tests as a screening procedure, and that even includes primary care physicians, it’s what we’re starting to see now. So certainly the specialists that we all talk to, the KOLs, they will use this, but I believe the utility of this method will become much more broad, which will get more people into the pipeline to get to these disease modifying therapies. I’ll leave it at that.

Jason Zamanski, Analyst, Bank of America: Thank you.

Michelle, Conference Call Operator: Thank you. Our next question comes from Paul Matisse with Stifel. Your line is open.

Paul Matisse, Analyst, Stifel: Hey, this is Julian on for Paul. Thanks so much for taking our question. Yes, just again, just thinking about comparisons of the TCR technology to, you know, what Roche has shown. Just curious how you think you guys could potentially be differentiated, particularly even on the safety side, if you have any commentary on that? And then just on the same topic, just wondering what you think, we know it’s early, but what the phase two development could potentially look like.

And then sort of separately, just a broader question. There’s been a lot of attention in the investor community on the early Alzheimer’s studies, pre symptomatic studies being conducted by Lilly and Novo. I’m just curious what you guys think of these trials and if you have any commentary there. I’m sorry, Lilly and Eisai is what I meant there. Thanks.

Dan O’Connell, Chief Executive Officer, Acumen Pharmaceuticals: Thanks, Julian. Yeah, so I think I’ll lead out maybe Jim, you want to comment a little bit more on the safety differentiation and then Eric you can comment on what we sort of talked thinking about from a clinical development standpoint. I think, you know, as we envision the JCR collaboration, you know, there are two points of differentiation. It’s principally both on the carrier element and the way the JCR transferrin binding carrier technology may lead to better safety relative to other transferrin mediated delivery modalities that actually induce a level of anemia. So I think that’s one area of interest to us to exploit and potentially validate.

The other is, and Jim mentioned this in his prior comments around the cargo and the preference of oligomer directed antibodies to avert, you know, even further reduce ARIA or other safety, elements. So those are kind of the two primary modes of differentiation we see based on synergistic partnership we’ve established with JCR. Jim, I don’t know if you have more comments to make, and I think we probably should talk a little bit about reference kind of the potential future clinical design for an EBD directed product.

Jim Dougherty, Chief Development Officer, Acumen Pharmaceuticals: Yeah, absolutely happy to. I think, you know, there are a number of elements that could impact a safety profile that we think, and it’s part of the reason we’re excited about this approach. I think at a high level, we see the opportunity to really lower the delivered dose because you’re going to get a higher fraction of the circulating dose into the brain if the technology works as it’s intended, which I think is overall a good thing. I think when you think about safety profiles, can look at it from the perspective of target associated things like ARIA. So that’s obviously something that’s top of mind for anyone developing an amyloid based antibody approach.

We’re overall pleased with the profile we see for Suburbanipug when it comes to ARIA rates, and that comes from our phase one study, which we’ve talked about a number of times. But it is interesting when you look at the work coming from the Roche group that in their case, their antibody, the ARIA rates are much, much lower when you convert gantenerumab to trantenerumab. And there’s a scientific hypothesis around that based on where the transferrin receptors are localized, which can change the entry points for where the antibody is getting across the blood brain barrier. So that’s an interesting hypothesis and offers the opportunity to even further enhance what we think is an already attractive profile for the potential for ARIA risk with cibarnatog. And then as Dan mentioned, there are the transferrin related risks associated with things like anemia, and that’s certainly an element that’s been reported in the Roche program to date.

It’s also been seen in other programs targeting the transferrin receptor, something we’ve thought a lot about and obviously went into our evaluation process. And we’ve landed with JCR because we believe that based on their clinical evidence, they’ve seen very low amounts of anemia with their marketed products. And, you know, the reasons for why that might be, I think there are a number of different things we could get into, like affinity ranges for the transferrin receptor. But I think also importantly, a number of different shuttles target the transferrin receptor, but they don’t all necessarily target the same epitope. And so I think we’re learning a lot about how this technology works, but we see opportunity here to really significantly alter and improve the safety profile that we see with Suburban Tug.

And by the way, it’s a profile we’re already pretty proud of. So we think there’s opportunity there. And I think we can talk about phase two study design. It is early days, as you say. The one thing I would point out there is that Eric and the team really did a fantastic job in putting together a progressive study design for SIBERNATUK in phase one.

And I think we can benefit from the approach that we took looking at both fluid and imaging based biomarkers in AD patients with an EBD product. So I think beyond that, we’ll have to see. We’ve got plenty of work to do before we get to that stage. But we’re very proud of the work that the team did in phase one. And we think that that’s there’s some insights that came out of that design that we can apply to the next program in the chain.

And I’ll leave Eric to address your question around what we think about the preclinical studies that are ongoing right now.

Eric Siemers, Chief Medical Officer, Acumen Pharmaceuticals: Yeah, thanks Jim. I think, yeah, definitely for our shuttle technology, the phase one even would be in patients and so we’ll take some learnings from Suburbanipal. But to get to your question about the preclinical studies, that’s something that’s under active discussion. I think based on our phase one data, Subirmatide would be a good candidate for a preclinical trial given its relatively low aurea rates in our phase one study. And so we’re having active discussions about how that might be done.

I think, you know you could take the approach that you could use a blood based biomarker and that’s all you would need to get into a pre clinical study. I’m not sure if that might be just a little bit too aggressive but that’s one of the things we’ve talked about. The other thing is rather than just going straight to a PET scan, you could do essentially what we did in the round of food study where you use the screening test, a blood test first, and then depending on the results of that test, then you go on to either spinal fluid or a PET scan. The other piece to this that is really evolving nicely I think is maybe doing sort of a phase two study for preclinical patients and looking at biomarkers. So you would look at things like PQA217, but also GFAP, a number of other measures, and before you do a very large and very long phase three preclinical study, you get some good evidence that your biomarkers are going the right direction, you’re having the kind of effect you want in a smaller phase two study, and then based on that make a decision to do a much larger Phase three study which would be at that point a registration trial.

So it’s something that’s under active discussion at Acumen right now.

Dan O’Connell, Chief Executive Officer, Acumen Pharmaceuticals: Thanks Eric and I’ll just comment Julie that I think the rationale for an oligomer directed agent in that preclinical population is very strong given the sort of the elevated levels of oligomers that sort of present and persist in that early pre clinical phase of disease progression. So we’re excited about that future opportunity.

Paul Matisse, Analyst, Stifel: Thanks very much for the detailed responses and congrats on the progress guys.

Dan O’Connell, Chief Executive Officer, Acumen Pharmaceuticals: Thank you.

Jeff Meacham, Analyst, Citi: Thank

Michelle, Conference Call Operator: you. Our next question comes from Chung Hung with UBS. Your line is open.

Alex Braun, Head of Investor Relations, Acumen Pharmaceuticals0: Good morning, guys. Thanks for taking the question. Just following up on the asymptomatic question, and you touched upon the blood based markers identifying this population. Just how do you see that being integrated into trying to find patients and then just how do you see it being covered by payers? Is this something that you’ll see covered readily along with PET scans?

Thank you.

Dan O’Connell, Chief Executive Officer, Acumen Pharmaceuticals: Thanks, Trung. Eric, you want to take a first cut at that?

Eric Siemers, Chief Medical Officer, Acumen Pharmaceuticals: Sure, yeah, so there’s a lot actually baked into that question. It’s a good one. When you think about payers, now you’re talking of course about something that’s available commercially and will payers pay for these things. What we’re hearing anecdotally is that payers are reimbursing for this p cal two seventeen blood test that’s the one that’s FDA approved now, And I would expect that that would continue to be the case once you have a drug that you know has a positive clinical effect in this preclinical population. In other words, you want to delay the onset of symptoms, so it is a different study design.

It’s not slowing your rate of decline because these people aren’t impaired. It’s delaying them until you start to have cognitive decline. But I think from a payer standpoint, and this will require some discussion, but from a payer standpoint, it’s to their benefit within the Medicare population, let’s say, that it’s to their benefit to delay the onset of cognitive decline because that’s where healthcare costs start going up. So I think there’s a lot of potential for this to play out clinically, But the first step obviously is we’ve got to do the studies to show that this strategy actually works, but I think it’s got a lot of potential.

Alex Braun, Head of Investor Relations, Acumen Pharmaceuticals0: Great, thanks.

Michelle, Conference Call Operator: Thank you. Our next question comes from Pete Stavropoulos with Cantor Fitzgerald. Your line is open.

Alex Braun, Head of Investor Relations, Acumen Pharmaceuticals1: Hi, Dan and team. Congrats on the progress and thank you for taking our question. As you were mentioning before, there was a lot of excitement around biomarkers, some of which show change biomarkers start to appear far in advance of symptoms, as well as some of the underlying pathology like various Tau species. How do these updates, including new biomarker data at AAIC, inform your approach and assumptions about clinical studies? Are there any that stands out to you as ones you may look at with samples at ALPITUDE studies that you haven’t disclosed before or incorporate into a Phase III study?

And also curious to know if you’re seeing ARIA rates from the ALPITUDE study on a blinded basis. And if so you know any commentary around that?

Dan O’Connell, Chief Executive Officer, Acumen Pharmaceuticals: Thanks Pete, lot in that question. I’m going to direct it to Eric for a quick comment on biomarkers at AIC and future development opportunities.

Eric Siemers, Chief Medical Officer, Acumen Pharmaceuticals: Yeah sure, let me just talk about the biomarker question first. I mean as much as we all are impressed by PCAL217, there’s a lot of additional work going on with additional biomarker, PPR is one of the ones that is getting a lot of attention right now. So we continue to just watch that field, you know, very very closely. Again, the results that we’ve had with PTL217 were I think quite good, and we as you know, in our phase one study we also looked at TAL181, we looked at GFAT, we looked at the A beta 42 over 40 ratio, I mean there’s a whole series of these biomarkers that you can look at and one of the strengths of doing that actually is when directionally they’re all going in the direction you want them to move, I think that’s good evidence that you’re having the right on the biology of the disease. So to get to your question about ARIA, I mean we’re obviously in the midst of an ongoing blinded phase two study, but what I can tell you is that we’ve not seen any data that are inconsistent with what we reported for our phase one study, so that’s what I can tell you at this point.

Jim Dougherty, Chief Development Officer, Acumen Pharmaceuticals: Maybe I can layer a little bit on biomarkers. As Eric was saying, I think there are more and more biomarkers that are coming out. And you know, at a fairly high level, what I see is an improving resolution to be able to understand disease progression. We know that Alzheimer’s disease is a progressive disorder. Patients progress over time.

And existing diagnostics can sort of help do that diagnosis, but it’s a relatively low resolution. So as more and more markers are being studied, of course they’re all peaking at different points in the disease course. And over time, multiple groups work is going to pull together, I believe, a much more high resolution ability to understand where a given patient is in their progression of disease. And hopefully that leads to more differentiated treatment. But I think, you know, that’s the long term opportunity that I’m seeing in the blood based biomarkers coming along.

Of course, it goes without saying, you’ve also got the benefits of convenience and cost savings and things that go along with that, but it is that ability to sort of understand disease progression at a much higher resolution that I think ultimately is going to be the biggest impact.

Alex Braun, Head of Investor Relations, Acumen Pharmaceuticals1: All right, thank you for that color. Just one more question, if you don’t mind, on the blood brain barrier technology. Any commentary around optionality in terms of the design to find an optimized candidate? Will you be grafting sibernitub’s FAB fragment onto JCR’s Fc backbone? Or will you graph the transferrin receptor binding domain onto your antibody?

Any details would be helpful. And what were some of the nonclinical or data from the feasibility studies that you sort of found encouraging and influencing the decision to enter the agreement?

Dan O’Connell, Chief Executive Officer, Acumen Pharmaceuticals: You. Go ahead. I think that’s for you, Jim.

Jim Dougherty, Chief Development Officer, Acumen Pharmaceuticals: Yeah, thanks Dan, absolutely. Yeah Pete, so I think the opportunity here that we see and this is why we talk about it in terms of combining the cargo from the Acumen side of things with the carrier from the JCR side of things. And JCR’s technology is somewhat flexible, so it allows us to investigate coupling different carrier molecules that are going to have different properties. And so we’re looking at things like the overall PK profile that is generated, the rates at which the drug enters into the brain, things like that. And I think obviously you’re always interested in understanding safety profile.

And then on the part of side of things, Suburbanipug is of course our flagship antibody, but we do also have other antibodies in the library that Suburbanipus came from that all have their own properties that we’ve characterized over time. And so you can imagine at this stage in the collaboration, we’re looking at what are the best components to put together. And so, you know, that we’ve talked about looking at single chain variable fragments. We’ve talked about looking at VHHs. And I think, you know, numerous different flavors of carriers with a couple of different possible cargoes is the exercise that we’re going through.

It’s a really very interesting exercise because it really offers lots of different optionality. So that will be the process we need to finish up to make some decisions about which, if any, molecules to take forward. And then from a little bit of color around the types of studies, we’re obviously interested in ensuring that we haven’t altered the properties of the cargo by coupling to the carrier. We also want to make sure that the carrier is giving us the right targeting when it comes to PK and to brain penetration. There are a number of studies that are ongoing in preclinical species that will include a primate study to really kind of give us the characterization of the different possible combinations to pick the best ones.

Alex Braun, Head of Investor Relations, Acumen Pharmaceuticals1: All right, thank you very much for taking our questions and congrats once again.

Michelle, Conference Call Operator: Thank you. Our next question comes from Tom Schrader with BTIG. Your line is open.

Jeff Meacham, Analyst, Citi: Good morning. This is Jenny on for Tom, and I want to ask a couple of questions on your trial. Would there be any data on the range of MMSCs in your trial, and how often are cognition tests given? Is it every six months, or is it more often than that? Thank you.

Eric Siemers, Chief Medical Officer, Acumen Pharmaceuticals: Yeah. Hi. This is Eric. Do want me to go ahead and take that?

Jim Dougherty, Chief Development Officer, Acumen Pharmaceuticals: Please. Yeah.

Eric Siemers, Chief Medical Officer, Acumen Pharmaceuticals: Yeah. So, yeah, we will have MMSE as a secondary outcome. As you may know, our primary outcome is a scale called the IGRIS, which combines a cognitive measure and a functional measure. We’ll also be looking at the CER Sum of Oxen, since that’s frequently used in trials, and we have a number of other secondary outcomes that assess things like quality of life and that sort of thing. Most of the main cognitive assessments are done every three months in the study and then of course we’ll also have a lot of biomarker data just to get that out too and so we’re looking forward to really looking at a package of data.

The one thing I might mention in terms of our data readout at the end of next year, all the data don’t become available at exactly the same time, especially some of the biomarker data. It takes a while to run those assays, and so our top line results will include top line efficacy and safety, but some of the other more detailed biomarker results may take a little more time to become available. So when we do have our top line results, again, we’ll have top line efficacy and safety, but we’ll also have some additional specialty biomarker results that we’ll be rolling out in the subsequent week. So I hope that answers your question.

Jeff Meacham, Analyst, Citi: That does. Thank you very much.

Michelle, Conference Call Operator: Thank you. I’m showing no further questions at this time. I’d like to turn the call back over to Alex Braun for closing remarks.

Alex Braun, Head of Investor Relations, Acumen Pharmaceuticals: Thanks, Michelle, and thanks to everyone for joining us today and taking the time to listen in. If you have any further questions, we are always available at the company, so please contact us. Have a great day.

Michelle, Conference Call Operator: Thank you for your participation. This does conclude the program. You may now disconnect.

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