Q2 2025 Acumen Pharmaceuticals Inc Earnings Call

Michelle: Good day and welcome to the Acumen Pharmaceuticals Inc. second quarter 2025 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 at that time, please press star one one. 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.

Speaker #2: Good day, and welcome to Acumen Pharmaceuticals' second quarter 2025 conference call and webcast. At this time, all participants are in listen-only mode. After the speakers' presentation, there will be a question-and-answer session.

Speaker #2: To ask a question at that time, please press *11. As a reminder, this call may be recorded. I would now like to turn the call over to Alex Braun, Head of Investor Relations.

Speaker #2: Please go ahead.

Alex Braun: Thanks, Michelle. Good morning and welcome to the Acumen Pharmaceuticals Inc. conference call to discuss our business update and financial results for the quarter ended June 30th, 2025. With me today are Dan O'Connell, our Chief Executive Officer; Dr. Jim Doherty, our Chief Development Officer; and Matt Zuga, 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&A session, we also have Dr. Eric Siemers, our Chief Medical Officer. Before we begin, we encourage listeners to go to the Investors section of the Acumen Pharmaceuticals Inc. 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 plan.

Speaker #3: 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, 2025.

Speaker #3: With me today are Daniel O'Connell, our Chief Executive Officer, Dr. Jim Doherty, our Chief Development Officer, and Matt Zuga, our CFO and Chief Business Officer.

Speaker #3: Dan and Matt have some prepared remarks, and then we'll open the call for questions. Joining for the Q&A session, we also have Dr. Eric Seamers, our Chief Medical Officer.

Speaker #3: 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.

Speaker #3: 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.

Alex Braun: 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. With that, I'll turn the call over to Dan.

Speaker #3: 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.

Speaker #3: 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, future results, or developments.

Speaker #3: And with that, I'll turn the call over to Dan.

Dan O'Connell: 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 Dougherty to provide some details about our recently announced Enhanced Brand Delivery, or EBD, program. Then Matt Zuga will detail our quarterly financial results before we open the call for questions. The second quarter was a productive one for Acumen Pharmaceuticals Inc., marked by steady operational progress and an important strategic partnership to expand our portfolio. Following the rapid completion of enrollment in our Phase 2 ALTITUDE-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.

Speaker #4: 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 brand delivery, or EBD, program.

Speaker #4: 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.

Speaker #4: Following the rapid completion of enrollment in our phase two altitude AD study in the first quarter, we continue to make great progress with the study.

Speaker #4: 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 2026, inclusive of the key efficacy and safety measures.

Dan O'Connell: Based on this strong execution, we continue to expect top-line results in late 2026, inclusive of the key efficacy and safety measures. ALTITUDE-AD is investigating sabirnetug, our monoclonal antibody with high selectivity for toxic Aβ oligomers. This selectivity is key to why we believe sabirnetug could unlock potentially greater clinical efficacy and improved safety relative to antibodies targeting amyloid plaques. At AAIC, we also presented data showing sabirnetug achieved the highest selectivity for Aβ oligomers over monomeric Aβ when compared to recombinant lecanemab and aducanumab. The reason why this is important is that Aβ monomer levels are approximately 7,000-fold higher than the low abundance toxic oligomer levels found in the diseased Alzheimer's brain.

Speaker #4: Altitude is investigating suburnata, our monoclonal antibody with high selectivity for toxic A-beta oligomers. This selectivity is key to why we believe suburnata could unlock potentially greater clinical efficacy and improved safety relative to antibodies targeting amyloid plaques.

Speaker #4: At AAIC, we also presented data showing Suburnata achieved the highest selectivity for A-beta oligomers over monomeric A-beta when compared to recombinant Lecanemab and Aducanemab.

Speaker #4: 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.

Dan O'Connell: So, lower affinity for monomeric Aβ, what sabirnetug demonstrates, is going to increase functional selectivity because less of the antibody will be binding to monomer. I would 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 has 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.

Speaker #4: So, a lower affinity for monomeric A-beta that suburnata demonstrates is going to increase functional selectivity because less of the antibody will be binding to the monomer.

Speaker #4: 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.

Speaker #4: 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.

Speaker #4: 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.

Dan O'Connell: We also believe they will help expand the demand for anti-amyloid treatments. It is 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 sabirnetug and potential next-generation CNS delivery products in the future, as there remains a very significant untreated patient population interested in receiving anti-amyloid therapy. We are excited about the potential of sabirnetug to provide a differentiated benefit-to-risk treatment option for patients and the future possibility of building on that with a CNS delivery product or products. Moving to CNS delivery, in July, we announced a strategic collaboration option and license agreement with JCR Pharmaceuticals based in Japan.

Speaker #4: We also believe they will help expand the demand for anti-amyloid treatments. It's terrific to see the field moving forward, the clinical infrastructure coming online, as well as the increased blood-based diagnostic options for the benefit of patients and their families.

Speaker #4: This momentum we believe sets the stage for suburnata 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 suburnata 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.

Speaker #4: 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 A-beta oligomer-selective antibody expertise with JCR's transferrin receptor targeting blood-brain barrier penetrating technology.

Dan O'Connell: This collaboration is to develop an Alzheimer’s disease product combining our Aβ oligomer selective antibody expertise with JCR’s transferrin receptor-targeting blood-brain barrier penetrating technology. We chose to partner with JCR as they are an established leader in the blood-brain barrier space. Importantly, the partnership extends our portfolio and builds on our confidence in the potential treatment benefit of targeting toxic Aβ oligomers. We have been working closely with JCR for more than a year, and I am 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 2026 based on non-clinical data. I will now turn the call over to Jim to expand on our progress and our CNS delivery strategy.

Speaker #4: We chose to partner with JCR as they are an 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 oligomers.

Speaker #4: 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.

Speaker #4: We expect to make a development decision for up to two product candidates in early 2026, based on non-clinical data. I'll now turn the call over to Jim to expand on our progress and our EBD strategy.

Jim Dougherty: Thanks, Dan, and good morning, everyone. Thanks for joining us today. I would first like to build on Dan's comments about AAIC 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 is 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 has 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.

Speaker #5: Thanks, Dan, and good morning, everyone. Thanks for joining us today. I'd first like to build on Dan's comments about AAIC and the positive sentiment surrounding current Alzheimer's disease therapies and the potential for next-generation treatments.

Speaker #5: 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 mRNA monitoring is very high.

Speaker #5: 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.

Jim Dougherty: 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 transport 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.

Speaker #5: 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.

Speaker #5: 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 from many therapeutic agents.

Speaker #5: 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 transport specific proteins into the brain, thereby delivering substantially higher amounts of enzymes or antibodies to where they need to be.

Speaker #5: 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.

Jim Dougherty: 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 were drawn to JCR Pharmaceuticals 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 Pharmaceuticals drug delivery system that efficiently delivers drugs to target tissues, including the central nervous system, through receptor-mediated transcytosis. It is applicable to various modalities, including antibodies, enzymes, oligonucleotides, lipid nanoparticles, gene and cell therapy, peptide, and decoy receptors.

Speaker #5: 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.

Speaker #5: 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.

Speaker #5: J-Brain Cargo Technology is a proprietary JCR drug delivery system that efficiently delivers drugs to target tissues, including the central nervous system, through receptor-mediated transcytosis. It's applicable to various modalities, including antibodies and enzymes, oligonucleotides, lipid nanoparticles, gene and cell therapy, peptides, and decoy receptors.

Jim Dougherty: The first drug developed based on this technology is approved in Japan for the treatment of lysosomal storms disorder, exhibits an established safety profile. We have worked with JCR Pharmaceuticals 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 O’Connell discuss, we believe selectivity for synaptotoxic Aβ oligomers is a key opportunity for a safe and effective next-generation disease-modifying antibody therapy. Pairing this differentiated cargo with JCR Pharmaceuticals’ validated carrier technology may offer an attractive next-generation product candidate for Alzheimer’s patients. We are investigating both sabirnetug and other oligomer-selective antibodies from our library and exploring both single-chain and variable heavy-domain antibody constructs with JCR Pharmaceuticals, which we consider cutting-edge approaches in the blood-brain barrier space.

Speaker #5: 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.

Speaker #5: 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.

Speaker #5: Pairing this differentiated cargo with JCR's validated carrier technology may offer an attractive next-generation product candidate for Alzheimer's patients. We are investigating both suburnata and other oligomer-selective antibodies from our library, and exploring both single-chain and variable heavy-domain antibody constructs with JCR.

Speaker #5: Which we consider cutting-edge approaches in the blood-brain barrier space. A non-clinical candidate data package inclusive of a non-human primate study is expected in early 2026, at which point Acumen has an exclusive right to exercise our option to deliver up to two development candidates.

Jim Dougherty: A non-clinical candidate data package inclusive of a non-human primate study is expected in early 2026, at which point Acumen Pharmaceuticals Inc. has an exclusive right to exercise our option to deliver up to two development candidates. Now I will hand the call over to Matt Zuga.

Speaker #5: And now I'll hand the call over to Matt.

Dan O'Connell: Thank you, Jim. As a reminder, our Q2 2025 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, we had $166.2 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 $37.1 million in the Q1. Apologies, in the Q2. The increase over the prior year was primarily due to an increase for manufacturing and materials for the ALTITUDE-AD clinical trial, as well as an increase in clinical expenses now that we are fully enrolled. G&A expenses were $4.6 million in the quarter, roughly flat to the same period in the prior year. This led to a loss from operations of $41.7 million and a net loss of $41 million in the quarter.

Speaker #6: Thank you, Jim. As a reminder, our second quarter 2025 financial results are available in the press release we issued this morning, and in our 10Q, we will file later today.

Speaker #6: As of June 30th, we had $166.2 million in cash and marketable securities on our balance sheet, which is expected to support our current clinical and operational activities into early 2027.

Speaker #6: R&D expenses were 37.1 million dollars in the first quarter. Apologies, in the second quarter. The increase over the prior year was primarily due to an increase for manufacturing and materials for the altitude AD clinical trial, as well as an increase in clinical expenses now that we are fully enrolled.

Speaker #6: G&A expenses were 4.6 million dollars in the quarter, roughly flat to the same period in the prior year. This led to a loss from operations of 41.7 million dollars and a net loss of 41.1 million dollars in the quarter.

Dan O'Connell: 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 Pharmaceuticals Inc. exercises our exclusive option to develop up to two development candidates, JCR will receive an additional option payment of $9.25 million. JCR will also be eligible to receive future milestone payments of up to $40 million related to development and up to $515 million related to sales for a total of up to $555 million, 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 2026.

Speaker #6: 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 $9.25 million.

Speaker #6: JCR will also be eligible to receive future milestone payments of up to 40 million dollars related to the two development and up to 515 million dollars related to sales for a total of up to 555 million dollars.

Speaker #6: 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 pre-clinical candidate data in early 2026.

Dan O'Connell: We are also confident in our strong execution of ALTITUDE-AD and look forward to sharing top-line results, which are expected in late 2026. We remain dedicated to delivering potential next-generation treatment options for the benefit of patients, caregivers, and shareholders. With that, we can open the call for Q&A. Operator.

Speaker #6: We are also confident in our strong execution about the two-day D and look forward to sharing top-line results, which are expected in late 2026.

Speaker #6: 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&A.

Speaker #6: Operator?

Michelle: Thank you. As a reminder, if you would like 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, please press star one one again. Our first question comes from Jason Zemansky with Bank of America. Your line is open.

Speaker #2: Thank you. As a reminder, if you'd like to ask a question, please press star one-one. If your question has been answered and you'd like to remove yourself from the queue, please press star one-one again.

Speaker #2: Our first question comes from Jason Zemanski with Bank of America. Your line is open.

Dan O'Connell: Good morning. Thanks so much for taking our question and congrats on the progress. I wanted to talk to you a little bit about AAIC. Specifically, if you look at Roche's similar sort of brain-shuttling technology, the tratinumab initial results there, and how to benchmark a potential brain-shuttling technology around sabirnetug. Then, I guess secondarily, given the overall plaque reduction seen in those patients, what does that mean for your epitope given kind of the focus on the oligomers? Thanks.

Speaker #7: Good morning. Thanks so much for taking our question, and congrats on the progress. I wanted to talk to you a little bit about AAIC, specifically if you look at Roche's similar sort of brain-shuttling technology, the trontinumab, initial results there, and how to benchmark a potential brain-shuttling technology around suburnata. Then I guess secondarily, you know, given the overall plaque reduction seen in those patients, what does that mean for your epitope given kind of the focus on the oligomers?

Speaker #7: Thanks.

Jim Dougherty: Thanks, Jason. Great question. I guess I would like to direct that to Jim initially, and Eric may have some comments as well.

Speaker #4: Thanks, Jason. Great question. I guess I'd like to direct that to Jim initially, and Eric, you may have some comments as well.

Dan O'Connell: Yes, absolutely. So, thanks, Jason. We have obviously been paying close attention to this entire space, including Roche's program. I think where I would start is where we see the opportunity for this technology is to significantly enhance the ability to deliver your therapeutic target to the targeted areas in the brain. You see that certainly with the trantinumab, they see a significant change in the overall profile of the molecule from the days of delivering it directly as cantanurumab to what they are seeing now when combined with the shuttle to allow them to increase their brain concentrations. I think we see the same kind of opportunity with sabirnetug, where, of course, their difference is in the fundamental targeting of the molecules. We believe very much that these toxic synaptotoxic oligomers are directly toxic within the brain during the progression of Alzheimer's disease.

Speaker #5: Yeah, absolutely. So, yeah, thanks, Jason. You know, we've obviously been paying close attention to this entire space, including Roche's program, and I think where I'd start is, you know, 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.

Speaker #5: And you see that certainly with the trontinumab, that they see a significant change in the overall profile of the molecule from the days of delivering it directly as cancer neuromab to what they're seeing now when combined with the shuttle to allow them to increase the brain concentrations.

Speaker #5: And I think we see the same kind of opportunity with Suburnata, where of course they're different in the fundamental targeting of the molecules.

Speaker #5: 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.

Dan O'Connell: Being able to robustly target that, we think is a mechanism that is going to lead to improvement for patients. Of course, we also see some effect on plaques, and there is 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. There are oligomers associated with plaques, and that is a much longer discussion. I think where it really lands is that we see the technology as enhancing the ability of sabirnetug to really effectively access soluble oligomers, and we think that that is going to be a mechanism that will be beneficial to patients. Eric, I do not know if you want to add anything to that.

Speaker #5: 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.

Speaker #5: 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 Suburnata to really effectively access soluble oligomers. We think that that is going to be a mechanism that will be beneficial to patients.

Speaker #5: Eric, I don't know if you want to add anything to that.

Eric Siemers: The only thing I might add to that is just in terms of where we are in development. Roche has done a great job in terms of their Phase 1 study, and they are obviously starting two Phase 3 studies, which will take a lot of read out. On the other hand, we are really looking forward to our ALTITUDE-AD study with over, well, with 542 patients that will read out the end of next year. They are doing a great job with their development plan, but it is early. They are in Phase 1 right now, and we are looking forward to the results of our Phase 2 ALTITUDE-AD study.

Speaker #7: Yeah, the only thing I might add to that is just in terms of where we are in development. I mean, Roche has done a great job in terms of their Phase 1 study, and they're obviously starting two Phase 3 studies.

Speaker #7: Which will take a while to read out. On the other hand, we're really looking forward to our ALTITUDE AD study with over 542 patients that'll read out at the end of next year.

Speaker #7: And so what they're doing a great job with their development plan, but it's early, they're in phase one right now. And we're looking forward to the results of our phase two altitude study.

Dan O'Connell: Got it. Thanks so much for the color.

Speaker #5: Got it. Thanks so much for the color.

Michelle: Thank you. Our next question comes from Jeff Meacham with Citi. Your line is open.

Speaker #2: Thank you. Our next question comes from Jeff Meacham with CITI. Your line is open.

Matt Zuga: Hi, guys. It is Russell for Jeff. I guess I just wanted to understand a little bit more what you guys are hearing about the p-tau217 assay testing used in the screening process, just what you are hearing or any feedback or color on that from physicians in the practicing end.

Speaker #8: Hi, guys. It's Russell for Jeff. I guess I just wanted to understand a little bit more about what you guys are hearing regarding the pTau217 test being used in the screening process—just kind of what you're hearing or any feedback or color on that from physicians on the practicing end.

Dan O'Connell: Thanks, Russ. Eric, if you want to handle that, maybe mention the AAIC poster and some of the traction that we were getting from how we used that assay in ALTITUDE-AD.

Speaker #4: Thanks, Russ. Eric, do you want to handle that? Maybe mention that AAIC poster and some of the traction that we were getting from how we used that assay in altitude?

Eric Siemers: 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 2 ALTITUDE-AD study, and it worked exceptionally well, I think. We actually, in our Phase 1 study, when that wasn't available, over 60% 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-tau217 assay level first and then allowed people to go on the PET, only 17% of the scans were negative. We didn't really want to have 0% negative because then you were too conservative in the step 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%.

Speaker #6: Yeah, sure. Thanks. That's a great question, really appreciate that. We as you probably know, used that as part of a screening process in our phase two altitude study.

Speaker #6: And it worked really well, I think. In our Phase 1 study, when that wasn't available, over 60% of the PET scans that we obtained as part of a screening process were negative for amyloid.

Speaker #6: But when we used the screening process and got a pTau217 level first, and then allowed people to go on the PET, only 17% of the scans were negative.

Speaker #6: So we didn't really want to have 0% 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%.

Eric Siemers: I think equally important, 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're pleased with those results. But more broadly, to kind of get to your question, we're hearing a lot of positive comments from clinicians in terms of the utility of this blood test. 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. That even includes primary care physicians. We're starting to see now. Certainly, the specialists that we'll talk to, KOLs, they will use this.

Speaker #6: And I think equally important 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.

Speaker #6: So it worked very, very well in our study, and we were pleased with those results. But more broadly, to kind of get to your question, you know, we're hearing a lot of positive comments from clinicians in terms of the utility of this blood test.

Speaker #6: 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.

Speaker #6: And that even includes primary care physicians, as we're starting to see now. So certainly, the specialists that we'll talk to, the KOLs, they will use this.

Eric Siemers: 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.

Speaker #6: 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.

Speaker #6: I'll leave it at that.

Dan O'Connell: Thank you.

Speaker #5: Thank you.

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

Speaker #2: Thank you. Our next question comes from Paul Matisse with STIFAL. Your line is open.

Jim Dougherty: Hey, this is Julian on for Paul. Thanks so much for taking our question. Just again, just thinking about comparisons of the JCR Pharmaceuticals technology to 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. Then just on the same topic, just wondering what you think, you know it's early, but what the Phase 2 development could potentially look like. 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, preclinical Alzheimer’s populations 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. Sorry, Lilly and APPCI is what I meant there. Thanks.

Speaker #7: Hey, this is Julian on for Paul. Thanks so much for taking our question. Yeah, just again, thinking about comparisons of JCR technology to what Roche has shown.

Speaker #7: 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, you know it's early, but you know what the phase 2 development could potentially look like?

Speaker #7: 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. You know, pre-symptomatic studies being conducted by Lilly and Novo.

Speaker #7: I'm just curious, you know, what you guys think of these trials, and if you have any commentary there. And sorry, Lilly and ASI is what I meant there.

Speaker #7: Thanks.

Matt Zuga: Thanks, Julian. I think I will 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 are talking about from a clinical development standpoint. I think, as we envision the JCR Pharmaceuticals collaboration, there are two points of differentiation. It is principally both on the carrier element and the way the JCR Pharmaceuticals 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 is 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 even further reduced ARIA or other safety elements.

Speaker #4: 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've sort of talked thinking about from a clinical development standpoint.

Speaker #4: I think, you know, as we envision the JCR collaboration, 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.

Speaker #4: 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 even further reduced ARIA or other safety elements.

Matt Zuga: So, those are kind of the two primary modes of differentiation we see based on the synergistic partnership we have established with JCR Pharmaceuticals. Jim, I do not 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.

Speaker #4: So those are kind of the two primary modes of differentiation we see based on the 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.

Dan O'Connell: Yeah, absolutely. Happy to. I think there are a number of elements that could impact a safety profile that we think, and it is part of the reason we are excited about this approach. At a high level, we see the opportunity to really lower the delivered dose because you are going to get a higher fraction of the circulating dose into the brain if the technology works as it is intended, which I think is overall a good thing. I think when you think about safety profiles, you can look at it from the perspective of target-associated things like ARIA.

Speaker #5: Yeah, absolutely. Happy to. And 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.

Speaker #5: 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. I think this is overall a good thing.

Speaker #5: I think when you think about safety profiles, you 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.

Dan O'Connell: That is obviously something that is top of mind for anyone developing an amyloid-based antibody approach. We are overall pleased with the profile we see for sabirnetug when it comes to ARIA rates, and that comes from our Phase 1 study, which we have talked about a number of times. 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 trontinemab. There is 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. That is an interesting hypothesis and offers the opportunity to even further enhance, we think, is an already attractive profile for the potential for ARIA risk with sabirnetug.

Speaker #5: We're overall pleased with the profile we see for suburnata when it comes to ARIA rates, and that comes from our Phase 1 study, which we've talked about a number of times.

Speaker #5: But it is interesting when you look at the work coming from the Roche group that, in their case, their antibody-related ARIA rates are much, much lower when you convert cancer neuromab to trontinumab.

Speaker #5: 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.

Speaker #5: 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 suburnata.

Dan O'Connell: As Dan O’Connell mentioned, there are the transferrin-related risks associated with things like anemia, and that is certainly an element that has been reported in the Roche program to date. It has also been seen in other programs targeting the transferrin receptor, something we have thought a lot about and obviously went into our evaluation process. We have landed with JCR Pharmaceuticals because we believe that based on their clinical evidence, they have seen very low amounts of anemia with their marketed products. 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. I think also importantly, a number of different shuttles target the transferrin receptor, but they do not all necessarily target the same epitope.

Speaker #5: 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.

Speaker #5: 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.

Speaker #5: 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.

Dan O'Connell: I think we are 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 sabirnetug. By the way, it is a profile we are already pretty proud of. So, we think there's opportunity there. I think we can talk about Phase 2 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 sabirnetug in Phase 1. 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. I think beyond that, we'll have to see.

Speaker #5: 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 suburnata.

Speaker #5: 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.

Speaker #5: 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 Suburnata in Phase One.

Speaker #5: 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.

Speaker #5: 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 there are some insights that came out of that design that we can apply to the next program in the chain.

Dan O'Connell: 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 1, and we think that there's some insights that came out of that design that we can apply to the next program in the chain. I'll leave Eric to address your question around what we think about the preclinical studies that are ongoing right now.

Speaker #5: And I will leave Eric to address your question around what we think about the preclinical studies that are ongoing right now.

Eric Siemers: Yeah, thanks, Jim. I think, yeah, definitely for shuttle technology, that Phase 1 even would be in patients, so it takes some learnings from sabirnetug. But to get to your question about the preclinical studies, that is something that is under active discussion. I think based on our Phase 1 data, sabirnetug would be a good candidate for a preclinical trial given its relatively low ARIA rates in our Phase 1 study. So, we are 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 is all you would need to get into a preclinical study. I am not sure if that might be just a little bit too aggressive, but it is one of the things we have talked about.

Speaker #6: Yeah, thanks, Jim. I think, yeah, definitely for shuttle technology, the phase one even would be in patients and so it takes some learnings from suburnata.

Speaker #6: 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, suburnata would be a good candidate for a preclinical trial given its relatively low ARIA rates in our phase one study.

Speaker #6: 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 preclinical study.

Speaker #6: I'm not sure that that might be just a little bit too aggressive, but with some 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 our altitude study where you use the screening test, a blood test first, and then depending on the available back test, then you go on to either spinal fluid or a PET scan.

Eric Siemers: The other thing is, rather than just going straight to a PET scan, you could do essentially what we did in our ALTITUDE-AD study, where you use a screening test, a blood test first, and then depending on the oil product 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 using maybe doing sort of a Phase 2 study for preclinical patients and looking at biomarkers. So, you would look at things like p-tau217 assay, but also GFAP, a number of other measures. And before you do the very large and very long Phase 3 preclinical study, you get some good evidence that your biomarkers are going in the right direction. You are having the kind of effect you want in a smaller Phase 2 study.

Speaker #6: The other piece to this that is really evolving nicely, I think, is using maybe doing sort of a phase two study for preclinical patients and looking at biomarkers.

Speaker #6: So you would look at things like pTau217, but also GFAP, a number of other measures, and before you do the 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.

Eric Siemers: And then, based on that, make a decision to do a much larger Phase 3 study, which would be at that point a registration trial. So, it is something that is under active discussion at Acumen Pharmaceuticals Inc. right now.

Speaker #6: So it's something that's under active discussion at Acumen right now.

Matt Zuga: Thanks, Eric. I will just comment, Julian, that I think the rationale for an oligomer-directed agent in that preclinical population is very strong, given the elevated levels of oligomers that present and persist in that early preclinical phase of disease progression. So, we are excited about that future opportunity.

Speaker #4: Thanks, Eric. And I'll just comment, Julian, that I think the rationale for an oligomer-directed agent in that preclinical population is very strong, given the sort of elevated levels of oligomers that sort of present and persist in that early preclinical phase of disease progression.

Speaker #5: So we're excited about that. Future opportunity.

Dan O'Connell: Thanks very much for the detailed responses, and congratulations on the progress, guys.

Speaker #6: Thanks very much for the detailed responses and congrats on the progress, guys.

Matt Zuga: Thank you.

Speaker #4: Thank you.

Michelle: Thank you. Our next question comes from Chuang Han with UBS. Your line is open.

Speaker #2: Thank you. Our next question comes from Chonghun with UBS. Your line is open.

Matt Zuga: 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? Then just how do you see it being covered by payers? Is this something that you will see covered readily along with PET scans? Thank you. Thanks, Chuang. Eric, do you want to take a first cut at that?

Speaker #7: 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?

Speaker #7: Is this something that you'll see covered readily along with PET scans? Thank you.

Speaker #4: Thanks, Chong. Eric, do you want to take a first cut at that?

Eric Siemers: Sure, yeah. There is a lot actually baked into that question. It is a good one. When you think about payers, now you are talking, of course, about something that is available commercially, and will payers pay for these things? What we are hearing anecdotally is that payers are reimbursing for this p-tau217 assay, the one that is FDA approved now. 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 Alzheimer’s populations. In other words, you want to delay the onset of symptoms. It is a different study design. It is not slowing the rate of decline because these people are impaired. It is delaying until you start to have cognitive decline.

Speaker #7: Sure. Yeah, so there's a lot actually baked into that question, but the 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.

Speaker #7: What we're hearing anecdotally is that payers are reimbursing for this pTau217 blood test that one that the 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.

Speaker #7: In other words, you want to delay the onset of symptoms. So it is a different study design. It's not slowing the rate of decline, because these people aren't impaired.

Speaker #7: It's delaying 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.

Eric Siemers: I think from a payer's standpoint, and this will require some discussion, but from a payer's standpoint, it is to their benefit within the Medicare population, let us say, that it is to their benefit to delay the onset of cognitive decline because that is where healthcare costs start going up. I think there is a lot of potential for this to play out clinically. The first step, obviously, is we have got to do the study to show that this strategy actually works. But I think it has got a lot of potential.

Speaker #7: 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.

Speaker #7: But I think it's got a lot of potential.

Dan O'Connell: Great, thanks.

Speaker #6: Great, thanks.

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

Speaker #2: Thank you. Our next question comes from Pete Stavropolos with Cantor Fitzgerald. Your line is open.

Matt Zuga: 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 in 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 stand out to you as ones you may look at with samples at ALTITUDE-AD studies that you haven't disclosed before or incorporate into a Phase 3 study? Also curious to know if you're seeing ARIA rates from the ALTITUDE-AD study on a blinded basis. If so, any commentary around that? Thanks, Pete.

Speaker #8: Hi, Dan and team. Congrats on the progress, and thank you for taking our question. You know, as you were mentioning before, there's a lot of excitement around biomarkers.

Speaker #8: You know, some of which show change in biomarker start to appear far in advance of symptoms, as well as, you know, some of the underlying pathology like various tau species.

Speaker #8: You know, out of these assays, you know, including new biomarker data at AAIC, you know, inform your approach and assumptions about clinical studies. You know, are there any that stand out to you?

Speaker #8: As ones you may look at, with samples at altitude studies that you know you haven't disclosed before or incorporate into a phase three study?

Speaker #8: And also curious to know if you're seeing ARIA rates from the altitude study on a blinded basis. And if so, you know, any commentary around that?

Speaker #4: Thanks, Pete. A lot in that question. I'm going to direct it to Eric for a quick comment. On biomarkers at AAIC and future development opportunities.

Matt Zuga: A lot in that question. I am going to direct it to Eric for a quick comment on biomarkers at AAIC and future development opportunities.

Eric Siemers: Yeah, sure. Let me just talk about the biomarker question first. As much as we all are impressed by p-tau217 assay, there is a lot of additional work going on with additional biomarkers. TCBR is one of the ones that is getting a lot of attention right now. So, we continue to just watch that field very, very closely. Again, the results that we have had with p-tau217 assay were, I think, quite good. And we, as you know, in our Phase 1 study, we also looked at P-CHAL191. We looked at GFAT. We looked at the Aβ 42 over 40 ratio. There is a whole series of these biomarkers that you can look at.

Speaker #7: Yeah, sure. So let me just talk about the biomarker question first. I mean, as much as we all are impressed by pTau217, there's a lot of additional work going on with additional biomarkers that need to be is one of the ones that is getting a lot of attention right now.

Speaker #7: So we continue to just watch that field, you know, very, very closely. Again, the results that we've had with pTau217 were I think quite good.

Speaker #7: And we, as you know, in our phase one study, we also looked at pTau181. We looked at GFAP. We looked at the A-beta 42 over 40 ratio.

Speaker #7: 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 effect on the biology of the disease.

Eric Siemers: And one of the strengths of doing that, actually, is when directionally they are all going in the direction you want them to move, I think that is good evidence that you are having the right effect on the biology of the disease. So, to get to your question about ARIA, we are obviously in the midst of an ongoing blinded Phase 2 study. But what I can tell you is that we have not seen any data that are inconsistent with what we reported for our Phase 1 study. So, that is what I can tell you at this point.

Speaker #7: So, to get to your question about ARIA, I mean, we're obviously in the midst of an ongoing blinded Phase 2 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 1 study.

Speaker #7: So that's what I can tell you at this point.

Dan O'Connell: Yeah, and Pete, maybe I can layer a little bit on the biomarkers. As Eric was saying, I think there are more and more biomarkers that are coming out. At a fairly high level, what I see is an improving resolution to be able to understand disease progression. Know that Alzheimer's disease is a progressive disorder. Patients progress over time. Existing diagnostics can sort of help do that diagnosis, but it's a relatively low resolution. As more and more markers are being studied, of course, they're all peaking at different points in the disease course. 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. Hopefully, that leads to more differentiated treatment. I think that's the long-term opportunity that I'm seeing in the blood-based biomarkers coming along.

Speaker #4: And maybe I can layer a little bit on the biomarkers. As Eric was saying, I think, you know, there are more and more biomarkers that are coming out.

Speaker #4: 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.

Speaker #4: 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.

Speaker #4: And over time, multiple groups' work is going to pull together, I believe, you know, a much more high resolution ability to understand where a given patient is in their progression of disease.

Speaker #4: 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.

Dan O'Connell: 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.

Speaker #4: 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 than I think ultimately is going to be the biggest impact.

Matt Zuga: All right, thank you for that color. Just one more question, if you do not 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 sabirnetug's FAB fragment onto JCR's FC backbone, or will you graft the transferrin receptor binding domain onto your antibody? Any details would be helpful. What were some of the non-clinical or data from the feasibility studies that you found encouraging and influenced the decision to enter the agreement?

Speaker #5: I think thank you for that color. Just one more question, if you don't mind. On the blood-brain barrier technology, do you have any commentary around optionality in terms of the design to find an optimized candidate?

Speaker #5: Will you be grafting, you know, suburnata, you know, FAB fragment onto JCR's FC backbone, or will the graft will you graft the transferrin receptor binding domain onto your antibody?

Speaker #5: Any details would be helpful. And what were some of the non-clinical or data from or data from the feasibility studies that, you know, you sort of found encouraging and influenced the decision to enter the agreement?

Dan O'Connell: Thanks, Jim. Go ahead. I think that is for you, Jim. 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 Pharmaceuticals side of things. JCR Pharmaceuticals' technology is somewhat flexible. So, it allows us to investigate coupling different carrier molecules that are going to have different properties. So, we are looking at things like the overall PK profile that is generated, the rates at which the drug enters into the brain, things like that. I think, obviously, you are always interested in understanding safety profile.

Speaker #4: Thank you. Go ahead. I think that's for you, Jim.

Speaker #7: Yeah, thanks, Dan. Absolutely.

Speaker #5: Yeah, Pete, so I think the opportunity here that we see, and it's 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.

Speaker #5: And JCR's technology is somewhat flexible, so it allows us to investigate coupling different carrier molecules that are going to have different properties. We're looking at things like the overall pharmacokinetic (PK) profile that is generated, the rates at which the drug enters into the brain, things like that.

Speaker #5: And I think obviously you're always interested in understanding safety profile. And then on the cargo side of things, suburnata is of course our flagship antibody, but we do also have other antibodies in the library that suburnata came from that all have their own properties that we've characterized over time.

Dan O'Connell: On the cargo side of things, sabirnetug is, of course, our flagship antibody, but we do also have other antibodies in the library that sabirnetug came from that all have their own properties that we have characterized over time. So, you can imagine at this stage in the collaboration, we are looking at what are the best components to put together. We have talked about looking at single-chain variable fragments. We have talked about looking at VHHs. I think, combining numerous different flavors of carriers with a couple of different possible cargos is the exercise that we are going through. It is 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.

Speaker #5: 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.

Speaker #5: We've talked about looking at VHHs. And I think, you know, combining numerous different flavors of carriers with a couple of different possible cargoes is the exercise that we're going through.

Speaker #5: And 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.

Dan O'Connell: From a little bit of color around the types of studies, we are obviously interested in ensuring that we have not 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. So, 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.

Speaker #5: 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.

Speaker #5: 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.

Speaker #5: So 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.

Matt Zuga: All right, thank you very much for taking our questions, and congrats once again.

Speaker #5: All right, thank you very much for taking our questions and congrats once again.

Michelle: Thank you. Again, to ask a question, please press star one one. Our next question comes from Tom Schrader with BTIG. Your line is open.

Speaker #2: Thank you. Again, to ask a question, please press star one-one. Our next question comes from Tom Schrader with BTIG. Your line is open.

Matt Zuga: 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 MMSEs in your trial, and how often are cognition tests given? Is it every six months, or is it more often than that? Thank you.

Speaker #9: Good morning. This is Jenny on for Tom, and I want to ask a couple of questions about your trial. Will there be any data on the range of MMSCs in your trial, and how often are cognition tests given?

Speaker #9: Is it every six months or is it more often than that? Thank you.

Eric Siemers: Yeah, I think, I deserve to let me go ahead and take that.

Speaker #7: Yeah, as Eric, you want me to go ahead and take that?

Matt Zuga: Please share.

Speaker #4: Please, yeah.

Eric Siemers: Yeah, so, we will have MMSE as the 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 will also be looking at the CDR summer boxes, since that is frequently used in trials. We have a number of other secondary outcomes that affect things like quality of life and that sort of thing. Most of the main cognitive assessments are done every three months in the study. Then, of course, we will also have a lot of biomarker data just to put that out to you. We are 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 do not become available at exactly the same time, especially some of the biomarker data.

Speaker #7: Yes, we will have MMSC as a secondary outcome. As many know, our primary outcome is a scale called the IGRIS, which combines a cognitive measure and a functional measure.

Speaker #7: We'll also be looking at the CDR sum of boxes. That's frequently used in trials. We have a number of other secondary outcomes that assess things like quality of life and that sort of thing.

Speaker #7: 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 put that out too.

Speaker #7: And so we're looking forward to really looking at a package of data though. 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.

Speaker #7: Especially some of the biomarker data; it takes a while to run those assays. Our top-line results will include top-line efficacy and safety.

Eric Siemers: It takes a while to run those assays. Our top-line result 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. When we do have our top-line results, again, we will have top-line efficacy and safety, but we will also have some additional strictly biomarker results that we will be rolling out in the subsequent weeks. I hope that answers your question.

Speaker #7: 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.

Speaker #7: But we'll also have some additional especially biomarker results that will be rolling out in the subsequent week. So I hope that answers your question.

Matt Zuga: That does. Thank you very much.

Speaker #9: That does. Thank you very much.

Michelle: Thank you. I am sure no further questions at this time. I would like to turn the call back over to Alex Braun for closing remarks.

Speaker #2: 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: Thanks, Michelle. 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.

Speaker #3: 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.

Speaker #3: So please contact us. Have a great day.

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