Good day, and welcome to the Acumen Pharmaceuticals second quarter 2026 conference call and webcast. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question, you will need to press star one one on your touch-tone telephone. Please note this call is being recorded. I would now like to turn the call over to Alex Braun, Head of Investor Relations. Please go ahead. Thanks, Michelle. Good morning and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended June 30th, 2026. With me today are Dan O'Connell, our Chief Executive Officer, and Matt Zuga, our CFO and Chief Business Officer. They will have brief prepared remarks and then we will open the call for questions. Joining for the Q&A session, we also have Dr. Jim Doherty, our President and Chief Development Officer, and Dr. Eric Siemers, our Chief Medical Officer. Before we begin, we encourage listeners to go to the investors section of the Acumen website to find our press release issued this morning that we will discuss today. Please note that during today's conference call, we may make forward-looking statements within the meaning of the federal securities laws, including statements concerning our financial outlook and expected business plans. Please see slide two of our corporate presentation, our press release issued this morning, and our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to differ materially from those expressed or implied in the forward-looking statements. We undertake no obligation to update or revise the information provided on this call or any accompanying presentation as a result of new information or future results or developments. With that, I will turn the call over to Dan. Great. Thanks, Alex. Good morning, everyone, and thanks for joining us today. During the second quarter, our focus remained on disciplined execution as we advanced sabirnetug towards the highly anticipated top-line readout from our phase II ALTITUDE-AD trial, which we continue to expect late this year. We believe this will be an important efficacy readout in the Alzheimer's field. ALTITUDE-AD remains a critical test of our central scientific thesis that selectively targeting synaptotoxic amyloid beta oligomers may offer a differentiated approach to treating Alzheimer's disease. A substantial body of evidence support this hypothesis, and we are excited by the opportunity to evaluate that thesis in a well-powered randomized phase II study with clinically meaningful endpoints. Our phase II results have the potential to substantially expand on our phase I results, which include a demonstration of A-beta oligomer target engagement and biomarker changes that we are seeing as early as three months of treatment, as we previously reported. We continue to be encouraged with the engagement of patients, caregivers, investigators, and study sites participating in ALTITUDE-AD, as well as in its 12-month open-label extension study. Their commitment has been instrumental in bringing us to this important inflection point. I believe the strong relationships the Acumen team holds with study sites and investigators is particularly supported by Acumen's patient-centric approach. At AAIC last month in London, we presented patient experience data collected from participants and study partners prior to treatment in ALTITUDE-AD. Results illustrate the diverse ways individuals with early Alzheimer's disease experience, respond to, and cope with cognitive and functional changes, underscoring the importance of capturing patient experience directly to better understand the meaningful benefit at this stage of disease. As we have previously described, ALTITUDE-AD was designed to detect a statistically significant difference on its primary clinical efficacy endpoint, the ADAS-Cog, after 18 months of treatment with sabirnetug compared with placebo. We expect the top-line data set to include results from the primary endpoint, key secondary measures such as the CDR-SB, safety assessments including adverse events and ARIA rates, as well as important fluid and imaging biomarkers. The study is evaluating two dose levels, 35 mg/ kg and 50 mg/kg, compared with placebo. Both these dose levels are within the exposure range previously shown to achieve pharmacodynamic target engagement. While we remain focused on execution and preparation for the readout, enthusiasm across the organization continues to build as we approach this landmark catalyst. We believe that sabirnetug has the potential to demonstrate a differentiated benefit to risk profile given its unique product attributes as an anti-A beta oligomer IgG2 monoclonal. We look forward to sharing the results later this year. In the second quarter, we announced the nomination of two enhanced brain delivery candidates for the treatment of Alzheimer's disease, representing the only program combining a validated blood-brain barrier-penetrating technology with an anti-A beta oligomer selective therapeutic antibody. Building on robust preclinical data from both in vitro and in vivo studies, we exercised our option with JCR Pharmaceuticals and will advance two candidates, ACU301 and ACU401. ACU301 is a bispecific antibody incorporating sabirnetug, and ACU401 incorporates a novel next-generation A beta oligomer selective antibody with differentiated properties. This is known as ACU234. We view our EBD program as expanding the optionality in our pipeline and will continue to evaluate both candidates in the lead-up to support a filing of an IND. Confirming our mouse data in non-human primates is a pivotal step in this work. At last month's AAIC conference, we presented data showing that after intravenous dosing, all three EBD bispecific antibodies achieved greater brain exposure than unmodified ACU234 alone. ACU401 in particular, achieved up to a 40-fold greater frontal cortex exposure in non-human primates, and significant increase in exposures in deep brain regions. The degree of brain penetration observed in cynomolgus monkeys, combined with preserved soluble A-beta oligomer selectivity and a clean hematological profile, exceeded our expectations and gives us confidence in the differentiated potential of our EBD program's approach. We continue to anticipate an IND filing for our lead EBD candidate in mid-2027. Coming up, I'd like to flag for investors an anticipated virtual investor relations day to be held on September 16th. Please mark your calendars to view live or as a recording, as we hope this will be helpful review for the Acumen investment thesis prior to ALTITUDE-AD's phase II data readout. The advancement of sabirnetug in our next-generation blood-brain barrier EBD candidates underscores the strength of both our scientific platform and our ability to execute, positioning us well for a significant eventful remainder of 2026. I look forward to updating you on our EBD program and on our phase II results for sabirnetug late this year. With that, I'll turn the call over to Matt. Thank you, Dan. As a reminder, our second quarter 2026 financial results are available in the press release we issued this morning and in our 10-Q we will file later today. We ended the second quarter with $110.2 million in cash and marketable securities on our balance sheet, which is expected to support our current clinical and operational activities into early 2027. R&D expenses were $27.8 million in the second quarter. The decrease over the prior year was primarily due to reductions in manufacturing and materials costs as well as CRO costs as we get into the final leg of our clinical trial. G&A expenses were $4.7 million in the second quarter, roughly flat for the same period in the prior year. This led to a loss from operations of $32.6 million and a net loss of $32.7 million in the second quarter. We are confident in our scientific innovation and strong track record of execution as we work toward our phase II ALTITUDE-AD readout later this year and advance our EBD program. We remain dedicated to building value with our portfolio of A-beta oligomer targeted antibodies for Alzheimer's patients, caregivers, and stakeholders. With that, you can open the call for Q&A. Operator? 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. Our first question comes from Paul Matteis with Stifel. Your line is open. Hi there. Good morning. This is Matthew on for Paul. Thank you so much for taking our question. I guess, another company doing an oligomer-specific approach read out some blinded data recently. Maybe can you talk about what are the differences between their approach versus yours in trial design, and how much can we read through on their clean safety to your upcoming data? Thank you so much. Hey, Matthew. Thanks for the question. We saw the announcement of the blinded interim assessment. This is really early-stage data, so there is not too much we can conclude from that reporting or that announcement. We will be interested to see how that study reads out sometime early next year. We reported phase I results in 2023, which, to our view, established a really robust clinical target engagement of A-beta oligomers. With just three doses in that phase I study, we are seeing effects on both fluid and imaging biomarkers that sort of exceeded our expectations and underpin our confidence in why in a large study, in an efficacy-based study such as ALTITUDE-AD, sabirnetug is positioned for success. Okay. Thank you so much. Maybe a quick follow-up. In the selection of your EBD candidates, what were the parameters that you sought to optimize, and where do you think the second molecule might be better than the bispecific sabirnetug? Thank you so much. Yeah. Thanks. I can quickly comment. I mean, I think for our EBD program, we envision from a product profile standpoint, subcutaneous administration as a convenient form for delivery, as well as preserving the oligomer selectivity, potentially enhancing that selectivity and an efficient transport across the blood-brain barrier using the transfer carrier technology as partnered with JCR. So I think we are looking at safety, efficacy, and broader exposure in a format that would lend itself to convenient subcutaneous dosing. Both of the candidates have, at least so far, demonstrated all of those attributes, and some of that data has been presented at meetings, and we will continue to report on findings in that program as we march towards an IND filing on a lead sometime in mid 2027. Matthew, this is Jim. Maybe I can add a little bit to what Dan has been saying. Of course, when you see the candidates that we announced, those represent the culmination of a process. We had a really robust collaboration with JCR. What it allowed us to do is really look at a bunch of different parameters for optimizing for the right fit to match the carrier and the cargo to come up with the final product. We looked at a number of things. We looked at affinity for TfR. We looked at valency, monovalent versus divalent. We looked at a bunch of parameters around the potential risk for anemia and things like that. It really represents the culmination of a whole campaign to optimize for what we think is the best fit to deliver these oligomer targeting antibodies into the CNS. That is super helpful. Thank you so much. Thank you. Our next question comes from Jason Zemansky with Bank of America. Your line is open. Perfect. Good morning. Thank you so much for taking our question and congrats on the great progress. You described ALTITUDE-AD, I guess, as designed to detect a stat sig difference in iADRS. With two active doses, can you clarify the framework and whether each dose is independently powered against placebo? If only one succeeds, under what circumstances would constitute a statistically robust positive study? Then a quick follow-up, please. Thanks. Thanks, Jason. Good question. As you know, we have not specifically provided details on the powering and the analysis. I don't know that we can go into great detail on that this morning. Yes, we do have both doses, both of which have demonstrated target engagement. We think both of these doses could emerge as efficacious doses, and we'll be looking forward to providing more information as we get closer to the data readout late this year. Got it. Then maybe without getting too much into the efficacy bar, can you speak to the work you're doing now to minimize the interval between the phase II results and the initiation of a phase III? Any regulatory engagement, CMC, partner discussions, site planning? Which activities are sort of gated until the data? Thanks. Thanks, Jason. Well, you can imagine there are elements of everything that you mentioned that are ongoing now, with the exception perhaps of regulatory interactions in terms of establishing the phase III design and so forth. There's a lot of activity and anticipation to minimizing the white space, and we're hopeful for a successful readout in ALTITUDE-AD that really will help facilitate and accelerate our ability to move sabirnetug into a single pivotal phase III. Great. Thanks for the color. Thank you. Our next question comes from Pete Stavropoulos with Cantor. Your line is open. Hi, this is Samantha on the line for Pete. Thanks for taking our question and congrats on the quarter. My first question is, there are biomarker data that suggests certain tau fragments like pTau217 can be used as a marker for amyloid pathology, while markers like MTBR-tau243 identifies tau tangle pathology in Alzheimer's disease. I know that you've incorporated and will look at pTau217 in the ALTITUDE study, but can you talk about MTBR-tau243? Do you plan to look at it in ALTITUDE, and how could you incorporate it into a phase III? Can it be leveraged to help or expedite patient selection? Thanks, Samantha. Oh, go ahead, Eric. Well, yeah. This is Eric Siemers. Maybe I can take that one. Yeah, the biomarker world in Alzheimer's is moving really quickly, especially with regard to blood-based biomarkers. As I think you probably know, we use pTau217 as part of our screening procedure, actually, for enrolling people into ALTITUDE-AD. But it will also be an outcome measure that we will look at after we are unblinded at the end of the study. MTBR-tau243 is relatively newer, and so it really was not being discussed at the time we designed ALTITUDE-AD. But one of the things that we have talked about is that we have a large number of patients and a lot of actually plasma samples that will be stored. So we have the opportunity to look at things like MTBR-tau243, new biomarkers that, especially the blood-based biomarkers, that become interesting after we actually complete the study. Yeah, MTBR-tau243 is one of the things we talk about, but I think it is not just that. It is any other new blood-based biomarker that may look interesting, we will have the opportunity to look at. Samantha, this is Jim. Maybe just to add a little bit onto what Eric is saying. I think he is totally right. It is really an exciting time in the field for looking at these fluid-based biomarkers. The reason for that is it really provides a lot of information about patients. So I think what we are seeing is people are beginning to measure these multiple markers in a lot of different studies, looking at a lot of different things. It potentially gives you the opportunity to look at where a person is in their progression with disease. It has the ultimate potential, I think, to start identifying patients who might be better candidates than others. I think we are too early days for those kinds of applications, but I do think that is where the field is going. So what we will do, exactly as Eric is saying, is as we go along, we will continue to monitor all this. We will use these tools as we can in our trials, and we have the opportunity to go back and measure some of these things even in a post hoc fashion. So I think this is going to continue to be an important part of our Alzheimer's trials moving forward. Awesome. Thank you so much. Just one quick follow-up. In July, there was an announcement of a collaboration with Unlearn utilizing digital twins. Can you help us understand what this tool is and how it's incorporated into the phase II, and how can you possibly leverage it for a phase III? Thank you. Yeah, absolutely. This is Jim again. I'm happy to take that one. As you say, we have partnered with a company called Unlearn.AI to use these digital twins. We see it again as another tool, another emerging tool that potentially provides some value. Essentially, these are almost individualized digital models relying on the data from thousands and thousands of patients who have been studied for the progression of their disease in clinical trials and in other formats. At this point, there's a tremendous amount of data about how disease progresses over time. Of course, it's incredibly complex and differentiated patient to patient. But what these tools do is allow for using baseline data to predict how their individual course of disease will progress over time. It's a model, and I think there have to be lots of questions about how robust the models are, what you can say about them, what you can't say about them. But potentially, they have the opportunity to do things like allow you to refine your patient selection. They have the opportunity to do things like be used as a prognostic covariate in analyses following trials. I think there's a number of potential applications. But honestly, the only way to really evaluate how much value these things have is to begin to get in there and work with it yourself. That's effectively what we're doing. We're using this at this point as an exploratory endpoint. We're trying to understand how these tools might be useful to us in the future. I think, as I was saying, there are several potential ways they can be used. That's what our evaluation will be to understand which ones are the best ways to apply this technology for Acumen. Thanks so much. Thank you. Our next question comes from Tom Shrader with BTIG. Your line is open. Good morning. Exciting times. A little background or next steps on the EBD franchise. Do you anticipate you would take both candidates into humans? Do you have to start with healthy volunteers? Any sense of how many patients or people you would need to get a read on anemia? Thanks. Thanks, Tom. Jim, why don't you take that one as well? Yeah, happy to. Some great questions, Tom. These are things that the team is actively working on at this point. To the first question, we have identified and nominated two candidates, ACU401 and ACU301. We're doing work on both molecules, and it really is intended to identify which one offers what we think is the best overall profile. So what we would intend to do is move into clinical development with one molecule, and that'll be the one that we think offers the best of possible profiles. As far as additional work that we're doing, there's a tremendous amount of work on CMC and tox study preparation in preparation for our plan to file an IND in mid 2027. I think we're still working on study design. There's a lot of active discussion around it. We've got a lot of experience from the INTERCEPT-AD study with sabirnetug that is going to help us identify what's exactly the best trial design to use. I think what I could say at this point is it's really going to come down to what's the most efficient design. We are going to try to get as much information as we can, as we did in the INTERCEPT-AD study. We also wanted to move this exciting program forward as quickly as we can. So more details later on what those design choices are going to turn out to be. I can tell you there's a lot of active discussion right now with the program team trying to land what is going to be the most efficient design. Are you going to start in healthy volunteers or are you not saying? That's one of the things that we're going to see. I think the goal is to transition to patients as quickly as we think is practical because you get a lot of valuable information from patients as in INTERCEPT-AD. I think exactly when that would be is honestly one of the things that we're still talking about. So yeah, we haven't really made a final decision yet. And one quick one for Dan. Do you expect to go radio silent at some point? Any guidance about when? Tom, we continue to be convinced we'll have the top line results for ALTITUDE-AD late 2026, consistent with our guiding for some time now. We have mentioned, as I mentioned on the call, we'll have an investor relations day September 16th, and that'll be a forward-looking, public-facing discussion. We anticipate participating in some of the early fall activities. So we'll be visible and accessible. At some point as we get closer to the end of the fourth quarter, I think we will probably have to shut down some of our public-facing engagement in anticipation of results. But the timing and specific dates for that, can't comment on. Great. Thank you. Thank you. Our next question comes from Geoff Meacham with Citi. Your line is open. Hey, guys. Thanks for the question. I had two quick ones. The first, I know the focus on oligomers obviously differentiates you from Kisunla and LEQEMBI. But how would you set expectations on safety and tolerability and the differences there? I guess particularly as we get more real-world experience with these two agents commercially. Second question, I want to get your view of the recent competitor of tau data. Is there a way to fast track perhaps a combo proof of concept if you think that's a viable strategy? Thank you. Thanks, Geoff. Good questions. I think in terms of safety, tolerability, and sabirnetug, as we described ALTITUDE-AD with two active doses is intended to demonstrate a clinical efficacy signal and a risk-benefit profile, both inclusive of the clinical efficacy relative to safety that is differentiated from existing treatments. So we're hopeful and enthusiastic about that possibility. And really just the magnitude of the study, the duration of exposure, we think it's a well-designed study to underpin and validate the oligomer hypothesis as we've positioned it. So that's sort of our expectations for sabirnetug and ALTITUDE-AD. I think you mentioned, I think you're referring to the Biogen BIIB080 program that was reported at AAIC in July. And I think those are interesting data. It looks as though they'll move into a phase III study for that molecule, and I think it serves as depending on how you view it, the first clinical validation of a tau-directed approach. Ultimately, I think we take the view that Alzheimer's is a disease that will be more adequately addressed with combination strategies. So we'll continue to evaluate ways to leverage not only our portfolio of A-beta oligomer-directed approaches or treatments with other potentially synergistic combinations, whether it be tau or anti-inflammatory approaches. But it just sort of underpins the stage we're at in terms of establishing better treatment options for patients. And we think the future is quite bright for safer, more efficacious, and more robust treatment for the early stages of the disease. And, as I'm sure folks on the call are aware, the move into the preclinical population, which would be hopefully a way to avert or otherwise delay the onset of symptoms. So it's a really robust innovation ecosystem right now in the space, and we think that will continue to accelerate, both commercially with products being adopted and grown in the marketplace, and then with further research innovations that will continue to build on better options for patients. Yeah. This is Eric. Maybe if I could just expand on that a little bit. In terms of safety and tolerability, there's two aspects of that that are differentiated with sabirnetug. First of all, it's the target. It's very selective for oligomers rather than plaque, and we think that that has some potential benefits in terms of safety. The other thing that is important to keep in mind, I think, is that this is what's called an IgG2 antibody rather than an IgG1 antibody. Without going into too many details, the IgG, all the other monoclonal antibodies are IgG1s, and they have more what's called effector function. In other words, they call in your immune system to get rid of things that you don't want there. In the case of these monoclonals, it's typically plaque. That can lead to problems like ARIA. But for an IgG2, there's less of this effector function, so it's less effect on calling in immune cells. For our mechanism targeting oligomers, you really don't need that to happen anyway. So there's two reasons to think that our safety and tolerability could be quite good. One is that we have this differentiated target, oligomers. The second is that we have an IgG2 antibody with less effector function and less immune system activation. So we're looking forward to seeing the data from ALTITUDE, obviously. Great. Thanks, guys. Thank you. Our next question comes from Dev Prasad with Lucid Capital Markets. Your line is open. Hi. Thank you for taking our question. Just a couple of follow-up questions. First is to follow up on the biomarker data question. Will that biomarker data be in the top-line release, or will it follow later? The second is what should we expect from September 16 IR day? Will it include new EBD data or preview of ALTITUDE-AD analysis plan or a venue to select EBD lead candidate? Thank you. Thanks, Dev. For your first question, the top-line results, as I mentioned in the prepared remarks, will include the primary outcome, the iADRS, which is a composite including both cognitive and functional measures involving the ADAS-Cog as well as the ADCS activities of daily living. We will also have the CDR Sum of Boxes, again, another cognitive functional endpoint familiar to the agency and others in the field. We intentionally will include both fluid and imaging biomarkers as part of those top-line results. We really want the ALTITUDE-AD readout to be a robust readout that really determines sabirnetug's safety and clinical efficacy as part of the study design. So yes, we do anticipate having both imaging and fluid biomarkers with the top-line results late this year. And then- Sorry. And your- For IR day. I would expect that to be more of a review of the investment thesis of Acumen. So whoever would like to get up to speed on sabirnetug and our EBD program prior to that phase II data, that would be a good event for viewers to tune into. So please keep it on your calendar. Great. Thank you. Thank you. I am showing no further questions at this time. I would like to turn the call back over to Alex Braun for closing remarks. Thanks, Michelle, and thanks to everyone for tuning in today. As always, we are at the company for follow-up questions. I hope everyone has a wonderful day. Thank you for your participation. You may now disconnect.