Acumen Pharmaceuticals, Inc.

Hello, and welcome to Acumen Pharmaceuticals Q3 2024 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 the question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. I would now like to hand the conference over to Alex Braun. You may begin.

Thanks, Tawanda. Good morning, and welcome to the Acumen Conference Call to discuss our business update and financial results for the quarter-ended September 30, 2024. With me today are Dan O'Connell, our CEO, 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. 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 a 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 meeting of the Federal Securities Laws, including statements concerning our financial outlook and expected business plans. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Please see slide two of our corporate presentation, our press release issued this morning, and our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to differ materially from those expressed or implied in the forward-looking statements. We undertake no obligation to update or revise the information provided on this call or in the accompanying presentation as a result of new information or future results or development. So with that, I'll turn the call over to Dan.

Thanks, Alex. Good morning, everyone, and thanks for joining us today. The third quarter was one of focused execution as we continue to progress our clinical efforts for Subirnatug, our next-generation A-beta oligomer-targeted antibody for the treatment of early Alzheimer's disease. Altitude AD, our phase two study designed to evaluate the clinical efficacy and safety of subornatide in roughly 540 patients with mild cognitive impairment or mild dementia due to Alzheimer's, currently has more than 75 sites active and enrolling across North America, the UK, and the EU. Enrollment in Altitude has progressed faster than we expected, and we now anticipate completement of enrollment in the first half of 2025. We believe the altitude AD enrollment is due to characteristics stemming from Sobernatug's mechanism of action, along with enthusiasm from site investigators as bolstered by our robust phase one data. Furthermore, our team has done well to establish effective collaborations with top trial sites across all three regions. These factors have contributed to a promising enrollment rate and reinforced the interest in innovative treatment options and the therapeutic potential of Sobernatug. We have also continued to progress our phase one study of subcutaneous CBRNTUG and anticipate the top line results for this study will be available in the first quarter of 2025. Once we have the PK results in hand, we will be best positioned to formulate next steps for developing subcutaneous CBRNTUG. Moving on to our time at the CTAD meeting in Madrid, it was clear at the meeting that the Alzheimer's field is moving ahead on both the clinical and research fronts, particularly with anti-A-beta disease modifying treatments for AD. We see Acumen in a strong position to capitalize on this momentum. And I want to share a couple of key takeaways that underpin how the field is advancing into a new and exciting era. First, blood-based biomarkers were a frequent topic in multiple presentations during the meeting, including our own. Blood-based biomarkers are going to fundamentally enable new innovations in both clinical research and drug development settings. This impact is happening right now. Our presentation focused on data from our validated research-use plasma phospho-tau-217 assay, which we are using to screen potential participants in the ongoing Phase II altitude AD clinical trial. At CTAD, we reported that this p-tau-217 enrichment screening approach results in a higher proportion of patients who meet the amyloid PET or CSF-based inclusion criteria as compared to our Phase I intercept AD trial, which did not use this approach. Furthermore, the enrichment approach is resulting in a more efficient participant selection process that reduces unnecessary amyloid PET scans or lumbar puncture procedures among people who are not eligible to continue screening. Thus far in the study, it has reduced the screening incidence of negative amyloid PET scans by about 50% as compared to our Phase 1 study and contributed to the rapid enrollment. Second, the first reports of real-world use of Lekembe were presented from researchers from the U.S. and Japan, highlighting adoption protocols and the feasibility of treatment delivery in diverse geographies and populations. Though the currently marketed products have acknowledged limitations and are not for all patients, we support making them available for the right patients and under the management of the right clinical teams. Further, we believe the adoption of anti-A-beta treatments will continue to grow and ultimately serve as the cornerstone of AD treatment for the foreseeable future. In October, we hosted a virtual R&D day with members of the Acumen team and key opinion leaders in the Alzheimer's space. If you haven't had a chance to view the webcast, I encourage you to watch the replay that is available on our website. The event provides a deep dive into the scientific rationale supporting Sobernatug's mechanism of action, targeting toxic abate oligomers, our positive phase one clinical results, and the phase two clinical plans for Sobernatug. Additionally, shifting to the organization, just last week, we announced the appointment of Dr. Amy Shatterly as chief regulatory officer and head of quality. Amy brings to Acumen over 30 years of experience in regulatory affairs, quality assurance, and therapeutic development with a focus on CNS disorders. Given Amy's deep expertise and experience in global product development, we are thrilled to have her on board as we further refine our product development strategy ahead of key clinical data for Smyrna Tech. I'd also like to thank Dr. Janice Hitchcock, who led our regulatory affairs efforts amidst retiring at the end of the year. Janice has been instrumental in building our regulatory infrastructure, overseeing our regulatory strategy, And in driving Sobernatug into the clinic, we wish her the best in her retirement. At Acumen, we are focused on our strategic goal of advancing the clinical development of Sobernatug in a diligent and efficient manner. The recent developments in the Alzheimer's field, along with new data and a refined understanding of the disease, align with our scientific approach and development strategy. I look forward to providing updates as we progress towards phase two data and as we work to confirm Sobernatug's promise as a next generation treatment option with a strong benefit-to-risk profile. And with that, I'll turn the call over to Matt for the financials.

Thank you, Dan. As a reminder, our third quarter 2024 financial results are available in the press release we issued this morning. And in our 10Q, we will file later today. As of September 30th, we had approximately $259 million in cash and marketable securities on the balance sheet. and continue to expect that cash runway to last into the first half of 2027. R&D expenses were $27.2 million in the third quarter. The increase over the prior year was primarily due to the increased spending to support the Altitude AD trial. G&A expenses were $5 million in the quarter, roughly flat to the same period in the prior year. This led to a loss from operations of $32.3 million and a net loss of $29.8 million in the quarter. Our net cash burn in the quarter was approximately $23 million, which includes the impact of $2.5 million in net interest income, $2.4 million in non-cash stock compensation expense, and the impact of expense accruals. I'm very pleased with our ongoing execution in the third quarter. We have the resources necessary to support our phase two study and advance a subcutaneous formulation of Subirnatug. We are dedicated to capitalizing on the opportunities ahead to benefit patients, caregivers, and shareholders alike. And with that, we can open the call for Q&A. Operator?

Thank you. Ladies and gentlemen, as a reminder to ask the question, please press star 11 on your telephone and then wait for your name to be announced. To withdraw your question, please press Start11 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Paul Matias with CIFL. Your line is open.

Hey, it's Mark on for Paul. Thanks for taking our question. Just had one on the subcutaneous study. So what kind of data can we expect there? Any more color? For next steps, how do you plan to potentially incorporate that into future studies? Thank you.

Yeah, thanks, Mark. So the phase one study is in healthy volunteers, and we're evaluating the pharmacokinetics and bioavailability of subcutaneous administered subcutaneous with IV. So principally, it's a PK bioavailability study that will then help inform what precise next steps we want to take with advancing a sub-Q. I think it's a little bit early for us to pre-specify what those next steps will be until we see the data. Thanks. Thank you.

Thank you. Will you stand by for our next question? Our next question comes from the line of Tom Schrader with BTIG. Your line is open.

Good morning. Thank you for taking some questions. For altitude AD, can you remind us your thoughts on taking an interim look at six months? If it's better than Leucanumab, it seems like you should know. And similarly, do you expect to release at least blinded ARIA data as you go, or are we waiting for everything?

Thanks, Tom. Yeah, so let me clarify. I think we have no anticipation of looking at interim results in the course of this study or reporting any unblinded data. ARIA data. I think that as we perhaps guided previously that the interaction that we had with regulatory bodies has led us to run the Phase II as essentially a pivotal study, and we dropped the notion of using interims in the interest of preserving the registration eligibility of the study. I don't know, Jim or Eric, if you care to comment as well.

Yeah, Dan, this is Jim. As you say, I think that What's important to us is preserving the statistical power and integrity in the study. And so, given the pace that we've been able to enroll a study, and because of the regulatory issues that Dan highlighted, we think it's important and most effective to continue to study the completion and read out the data at the end.

Yeah, and just maybe one other quick thing, just to emphasize the comment Dan made about ARIA reporting. Obviously this is an important finding for suburnatug, but this is a blinded ongoing trial and we really won't, we can't disclose any results regarding ARIA until the end of the trial when we're unblinded. So that's our plan as far as ARIA goes.

I think a question pretty related to the last one. Are you confident that if sub-Q becomes a necessity, that you will have enough data based on your phase two and your phase one for sub-Q to do a pivotal with sub-Q, or do you think it's very likely you'd need phase two with sub-Q? And again, I appreciate it's forward-looking.

Sure, Tom. So I think we really want to see the phase one data before we predict what the next step will be for sub-Q. We do anticipate that both IV and sub-Q formats for this class will be available well in the future, and we're committed to explore subcutaneous version of subprototype for the purpose of providing a potentially more convenient format. But I think precisely what the next study is required to advance the program, I think, again, it's kind of premature to predict exactly how we will proceed.

Fair enough. Thanks for taking the time.

Thank you. Please stand by for our next question. Our next question comes from the line of Jason Zemanski with Bank of America. Your line is open.

Hey, this is Cameron for Jason. Congrats and thanks so much for taking our question. So as the phase two altitude gets underway, what sort of things are you looking for that would give you and maybe investors confidence? Is it the pace of enrollment? You know, something else I guess we're just looking for some potential leading indicators we could focus on to suggest everything remains on track here. Thank you so much.

Yeah, sure. So, great question. So, real quickly, I mean, we have, as we mentioned earlier on the call, the enrollment rate for Altitude AD, the Phase 2, in upwards of 540 patients, has progressed far more rapidly than we had anticipated, and we now are expecting to complete enrollment in the first half of next year, 2025. And just to sort of set the timeframe, we announced the first patient enrolled in this study in the second quarter of this year. So from our own planning and expectations, the enrollment has gone exceedingly well. And I think we attribute that to kind of the profiles of Bernatug, the phase one results that sort of established this proof of mechanism around target engagement of oligomers. and a safety profile that we find participants and investigators find exciting and potentially informing Subirnatug as a next-gen treatment option for patients.

Thank you. As I remind you, ladies and gentlemen, that's star 11 to ask the question. Please stand by for our next question. Our next question comes from the line of Pete Stavropoulos with Canterford's Jail. Your line is open.

Hi, this is Samantha on the line for Pete. Thanks for taking our questions. So my first question is regarding enrolling early AD patients into altitude AD, considering findings from other anti-amyloid betas that show greater clinical benefit in specific subpopulations like those with high tau or low tau, how are you thinking about the patient population you would ideally enroll into altitude? Are you looking to have a higher proportion of certain baseline characteristics, such as sensory plaque levels or tau levels, to potentially increase the likelihood of seeing efficacy signals? If you could provide some color on that, that would be fantastic.

Thanks, Sam. And I'm going to direct that question over to Eric. He's best equipped to address the population that we're enrolling in altitude AD.

Yeah, thanks, Dan. And no, it's a great question. And obviously, I guess one that we've spent a lot of time thinking about and talking about. So we've targeted this patient population for people who have mild cognitive impairment, MCI, or mild dementia, when you cross that line to dementia, with demonstrated Alzheimer's pathology. In the case of our study, that is based on amyloid PET or CSF. We did not have any specific requirement for tau pathology, although, as you know, the field is watching that carefully. One of the major things that we talked about was that the data, and some of this data is actually very recent, would suggest that it's patients who were earlier in the disease course and at an earlier stage based on biomarkers and their pathology that have a better response to the drugs that have read out in these larger phase three studies. One of the things that we looked at in our phase one study actually is that our amyloid PET readings were sort of a hybrid between a visual read and just based on an SUVR measure. But the visual reads were important, and we did have quite a few of those. And what that does is it pushes your average amyloid load, your SUVR, lower because I think the human eye is just, you know, more sensitive and you can pick up people who are positive, but it wouldn't come across with an SUVR. So as these data have emerged and we realized based on our phase one data that using a visual read tends to give you less, at least amyloid pathology, we think that's a good thing. So we really feel like From a clinical standpoint, we're doing what is kind of standard in the field now, is we identify people with MCI or mild dementia. But from a biomarker standpoint, we would anticipate seeing people with relatively low amyloid plaque loads based on their SUVR. So obviously, we'll get the data at the end of the study, but we think we've dialed in the inclusion-exclusion criteria is about as well as you can based on the current state of knowledge.

That's great. And one more follow-up question on ARIA, if you don't mind. We've actually asked this in the past, but curious to hear your thoughts again on why ARIA burden has been less so far with Subirnatug and how the ARIA burden has impacted clinical study enrollment When speaking to physicians, how do they view ARIA? Are they getting more comfortable with administering anti-amyloid antibodies? Or do you think some are still waiting on the sidelines, waiting for drugs with lower risk of ARIA?

Well, yeah, another really good question. So our premise all along has been because Subiratog was developed to be more specific for oligomers and less binding to plaque, we really anticipated lower ARIA rates before we even did our Phase I study. And so, the fact that our Phase I study showed relatively low rates of ARIA was not a surprise to us. Now, obviously, Phase I study is pretty small. We need to replicate that in our Phase II study, and of course, you know, we're looking at that really carefully. In terms of how clinicians are approaching using the approved disease-modifying monoclonal antibodies, it's really controversial. And even at this recent CTAT meeting, there was a bit of a debate about, you know, if you've had people who've actually had fatalities using these drugs, how carefully should you think about even starting them at all? And I think you'll get different answers to that question from different clinicians, but it's a rapidly developing area. We think because Suburta Tug should have a lower rate of ARGA, that by itself is obviously a good thing, but how people manage it when it does happen is something that is rapidly evolving over time.

Really appreciate it. Thanks.

Thank you. Ladies and gentlemen, I'm showing no further questions in the queue. I would now like to turn the call back over to Alex for closing remarks.

Great. Thanks, Tawanda. And thanks to everyone who listened in today. If there are any remaining questions, always please feel free to reach out to us at the company and have a wonderful day.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.