Acumen Pharmaceuticals - Q2 2024

Transcript

Operator (participant)

Hello, and thank you for standing by. Welcome to Acumen Pharmaceuticals' Q2 2024 conference call and webcast. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. I would now like to turn the call over to Alex Braun, Head of Investor Relations. Please go ahead.

Alex Braun (Head of Investor Relations)

Thank you, operator. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended June 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 our press release issued this morning that we'll discuss today. Please note that during today's conference call, we may make forward-looking statements within the meaning of the federal securities laws, including statements concerning our financial outlook and expected business plans.

These statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Please see slide two of our corporate presentation, our press release issued this morning, and our most recent annual and quarterly reports filed with the SEC for important risk factors that could cause our actual results to differ materially from those expressed or implied in the forward-looking statements. We undertake no obligation to update or revise the information provided on this call or in the accompanying presentation as a result of new information or future results or developments. With that, I'll turn the call over to Dan.

Daniel O'Connell (CEO)

Thanks, Alex. Good morning, everyone, and thanks for joining us today. We've made significant progress in the first half of 2024 as we continue to execute our clinical plans for sabirnetug, our next-generation amyloid 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 sabirnetug in patients with MCI or mild dementia due to AD, is actively enrolling. ALTITUDE-AD is a randomized, double-blind, placebo-controlled, three-arm study with approximately 180 participants per treatment arm for a total of 540 participants. ALTITUDE-AD currently has more than 50 sites active across North America, the U.K., and the E.U., with the first subject dosed in May 2024. At present, enrollment in ALTITUDE-AD is progressing faster than our original projections, which is highly encouraging.

We attribute this to sabirnetug's distinct profile based on its mechanism of action and positive feedback and interest from investigators, supported by our strong Phase one data. Additionally, our team has built highly productive working relationships with quality trial sites in all three regions. These combined factors have translated into an encouraging enrollment rate and underpin the growing interest in novel treatment options for early AD and differentiated treatment potential of sabirnetug. In July, we also announced we had dosed our first subject in a Phase one study of subcutaneous sabirnetug. The study will compare the pharmacokinetics between intravenous and subcutaneous administrations of sabirnetug in healthy volunteers. We view this workstream as an important extension of sabirnetug's product profile, which aims to offer flexibility and convenience in dosing for patients and caregivers.

We anticipate the top-line results from this study will be available in the first quarter of 2025. Once we have the PK bioavailability results in hand, we will be best positioned to discuss next steps in clinical plans for subcutaneous sabirnetug. Turning now to continued learnings from our clinical experience with sabirnetug. The Acumen team recently presented further data analysis from the INTERCEPT-AD trial at the Alzheimer's Association International Conference, or AAIC. Our team presented posters at this major Alzheimer's medical conference detailing patient interviews, biomarker data supportive of sabirnetug's mechanism of action, and Acumen's ultrasensitive method of measuring small amounts of sabirnetug in cerebrospinal fluid. The takeaways from our patient interviews underscore the importance of incorporating the patient voice into trial design and humanizing the unmet need in Alzheimer's disease.

As expected, nearly all patients reported difficulty with memory and cognition, difficulty with getting lost, difficulty with communication, and changes in mood were also commonly reported. Almost 90% of patients would like a treatment to slow the progression or of disease or keep it from getting worse, as well as maintain the ability to recognize loved ones. We also received strong interest in the synaptic biomarker changes observed in our phase one study. Both pre and postsynaptic cerebrospinal fluid proteins, VAMP2 and Neurogranin, showed significant reduction towards normalization, which is consistent with sabirnetug's ability to inhibit amyloid beta oligomer synaptic binding. These posters can be found on the Investor section of our website if you haven't already had a chance to review them. As usual, there was a great deal of interesting information shared at AAIC, including a number of topics relevant to our sabirnetug program....

These topics included the continued development of fluid biomarkers, like p-tau217, as diagnostics for tracking the progression of Alzheimer's, further data on the important role that soluble amyloid beta species play in the pathophysiology of AD, and extended safety and efficacy data on chronic dosing with anti-amyloid monoclonal antibody therapies. We believe the increased acceptance of the toxicity and persistence of soluble amyloid beta species, such as oligomers, will help move the field towards next-generation antibodies, such as sabirnetug. And the confluence of fluid biomarker breakthroughs will support expanded future access to novel treatments in AD. Finally, we are planning to host a virtual R&D day on October second. We intend for this event to provide a deep dive into the scientific rationale supporting sabirnetug's mechanism of action, our phase 1 clinical results, and phase 2 clinical plans for sabirnetug.

We will communicate the registration details and agenda closer to the event. We remain committed to delivering on our strategic priority to efficiently and thoughtfully advance the clinical development of sabirnetug and are encouraged by the direction the Alzheimer's field is headed, with new data and an updated understanding of the disease that is in line with our science. I look forward to updating you as we work towards phase two data that we believe will provide a significant value inflection for the program and demonstrate sabirnetug's true potential as a next gen treatment with a highly compelling benefit to risk profile. And with that, I'll turn the call over to Matt for the financials. Thank you.

Matthew Zuga (CFO and Chief Business Officer)

Thanks, Dan. As a reminder, our second quarter 2024 financial results are available in the press release we issued this morning and in our 10-Q, which we will file later today. As of June 30, we had approximately $281 million in cash and marketable securities on our balance sheet and continue to expect the cash runway to last into the first half of 2027. R&D expenses were $19.5 million in the second quarter. The increase over the prior year was primarily due to the increased spending to support the ALTITUDE-AD trial. G&A expenses were $4.8 million in the quarter, with the increase over the prior year primarily the result of increased headcount. This led to a loss from operations of $24.4 million in the quarter.

I'm very pleased with our clinical execution thus far in 2024. We are well-resourced for our phase two study and to develop a subcutaneous formulation of sabirnetug, and are committed to delivering on the opportunity ahead of us for the benefit of patients, caregivers, and shareholders. With that, we can open the call for Q&A. Operator?

Operator (participant)

Thank you. Ladies and gentlemen, to ask the question, please press star one one on your telephone and then wait to hear your name announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Tom Shrader with BTIG. Your line is open.

Cameron Bozdog (Analyst)

Good morning. Thanks for taking the question and the updates. I have a question on the phase two trial and what patients you're getting. What is enrollment like in the U.S. with two approved products? Is it tricky or are patients highly compelled by the potential for less ARIA? And I would expect enrollment in Europe, people are very enthusiastic, but are you gonna limit, or are you gonna require some number of U.S. patients? Thank you.

Daniel O'Connell (CEO)

Hi, Tom. Yeah, thanks. Great question, and as I mentioned earlier in the prepared remarks, we are encouraged at the enrollment rate, and to date, it has exceeded our expectations from our original forecasts. I think this is a consequence of the unmet need in this population, as well as the phase one data that really underpin the differentiation of sabirnetug. Lastly, the study design itself, the feedback from sites and investigators have been very favorable in that, you know, the study incorporates two active doses plus versus placebo and then an open-label extension. So in terms of choice and participation, we're seeing a lot of demand to participate in the ALTITUDE-AD study. And we do anticipate a split between North America and Europe.

Haven't preset those, those mix, but I think we'll have patients covering each of the territories or regions that I mentioned earlier.

Cameron Bozdog (Analyst)

Okay, great. Thank you.

Matthew Zuga (CFO and Chief Business Officer)

Maybe I just add a little bit to that. Yeah, the rate at which we're seeing patients really exceeds our projections and expectations, which is great. You might, you know, ask yourself why that might be, and as Dan mentioned, it's probably multifactorial, but I think partly it's the strength of our phase one data that was done in patients. We've seen a lot of biomarker changes that are really encouraging for the drug. And secondly, what we've heard from the sites is that they do like the protocol design. It's a phase two study, but really it's like a small phase three study with an open label extension, and the sites like that.

We started the study in the U.S., and that's where currently we have most of our patients, but now we're adding sites. We've already added sites in Canada, the U.K., and then Europe. So we'll be enrolling more patients in those other geographies.

Cameron Bozdog (Analyst)

... Okay, great. Thank you.

Operator (participant)

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

Cameron Bozdog (Analyst)

Hi, good morning. This is Cameron Bozdog, on for Jason. Congrats on the quarter, and, and thanks for taking our question. So in thinking about the anti-A beta commercial landscape, you know, what do you think have been the major challenges or gating factors? Is it educating physicians, you know, engaging with patients, or has it been an issue of infrastructure, payer access, reimbursement? And then appreciating it's early, but do you see opportunities for sabirnetug to potentially differentiate itself, or is it more that, you know, the broader market needs to finish undergoing maturation itself? Thank you.

Daniel O'Connell (CEO)

Thanks, Cameron. I think you've listed out the multifactorial sort of issues that are basically inhibiting or at least metering out the ramp and the growth and expansion of these treatments, these first couple of approved products. We think that it's interesting now with Lilly coming into the marketplace, the infrastructure will continue to be built out, that awareness around the possibility of seeking treatment will continue to draw more awareness and patients into this new treatment paradigm. There are also, I think one of the points we made from the AAIC meeting is that the anticipation of fluid biomarkers, you know, blood-based diagnostics is likely to impact the growth and expansion of this field. So it is multifactorial.

I think there's been good progress made and there will continue to be the infrastructure rolled out. In terms of sabirnetug and its differentiation, we absolutely have high conviction that its mechanism is differentiated and yet, as a consequence of that, has the promise of differentiating either or both on efficacy and safety. And that's really our single focus is to offer early AD patients an improved treatment option in terms of benefit to risk profile. So that's, I think that addresses most of your questions. I don't know, Jim or Eric, if you have any follow-on comments.

Operator (participant)

Thank you.

Daniel O'Connell (CEO)

Thanks.

Operator (participant)

Please stand by for our next question. Our next question comes from the line of Paul Matteis with Stifel. Your line is open.

Cameron Bozdog (Analyst)

Hey, this is Mark, on for Paul. Thanks for taking our question. So, we were curious, what does the path forward look like, for the subQ formulation for sabirnetug? And then, you know, would that be assessed in parallel to the intravenous formulation, if the phase one were successful? And then separately on that, you know, what dose could you pursue, and would that, you know, enable robust plaque target engagement, or would that be more of like an oligomer dose? And then if you could provide any additional details for the ALTITUDE-AD interim analysis, that would be great as well. Thank you.

Daniel O'Connell (CEO)

Sure. I want to direct that one to Jim, as our lead on development efforts.

James Doherty (President and Chief Development Officer)

Sure. Happy to take it, Dan. Mark, the answer to your question, I think is we're... The first step really for the subcutaneous development program is to understand the bioavailability of the subQ version. So that's the goal of the first study here in healthy volunteers, is to really align the PK from the subQ administration with the Halozyme formulation, with what we're learning from the IV studies from INTERCEPT-AD, and ongoing work with ALTITUDE-AD. You know, I think beyond that, we have a number of options on how to proceed. I think from the point of view of dosing, the targeting of the dosing is intended to hit the same range that we're targeting with the IV formulation.

And the purpose of that, of course, is based on our target engagement data from Phase one. We've got high confidence that we are targeting a range that's having an effect dose-dependently on a soluble oligomer in the brain, and also, as we've demonstrated from Intercept, some evidence for plaque reduction as well. And I think, you know, we see these as both effects of sabirnetug. We're focused around the hypothesis that reduction of soluble oligomers is gonna be beneficial to synaptic function and to overall cognitive function in AD. And I think no reason to think that would be different for the subcutaneous formulation. So that's sort of where we stand at this point.

Our efforts are to complete the ongoing phase one subQ study by the end of the year, and then we'll, based on a data-driven analysis, move forward with next steps.

Cameron Bozdog (Analyst)

Thank you.

Operator (participant)

Thank you. Thank you. Please stand by for our next question. Our next question comes from the line of Pete Stavropoulos with Cantor Fitzgerald. Your line is open.

Cameron Bozdog (Analyst)

Hi, this is Samantha on the line for Pete. Thanks for taking our question. The ALTITUDE-AD study is enrolling patients with early AD. Considering the outcomes from other A-beta antibodies in the subpopulations that showed greater clinical benefits, such as those with low tau versus high tau, how are you thinking about the patient population you would like to ideally enroll? Are you looking to have patients with a higher proportion, with specific baseline characteristics like Centiloid levels, plaque, or tau, to perhaps increase the likelihood of seeing efficacy signals? Thanks so much.

Daniel O'Connell (CEO)

Thanks, Samantha. Eric, do you want to take that one?

Matthew Zuga (CFO and Chief Business Officer)

Yeah, sure. So, yeah, great question. We're targeting actually the same patient population that we used for the phase one study, which is patients with MCI and mild dementia, which is frequently being called early symptomatic Alzheimer's disease now. You know, as you point out, people who have less tau based on other antibodies may have a better response. Those results carefully. What we've done in our trial is that people can enter the trial based on either a PET scan, an amyloid PET scan, or CSF. For the PET scans in particular, we're using a visual read, which is what's used in practice right now. But by doing that, you tend to get people with a little bit lower centiloid. It's people who are relatively a little bit earlier in the disease.

And so, we feel pretty confident that we've targeted the right population here. So there are obviously people who have amyloid, and they have Alzheimer's disease, but they're relatively early in the course of it, both based on symptoms and based on PET scans or CSF.

James Doherty (President and Chief Development Officer)

And maybe just to add to that a little bit, Samantha, this is Jim. I, I think part of the reason we're investing so much in both imaging and fluid-based biomarkers in the altitude study is that the space is still evolving and understanding exactly what the diversity is among patient populations. And so I think, as Eric's pointing out, we're very intentionally targeting the early Alzheimer's space. But I think as our understanding as a field grows in this area, Acumen is gonna be very well positioned to understand the importance of individual biomarkers and how that's gonna relate to the emerging understanding around different patient populations. So we think we're in pretty good shape at this point.

Cameron Bozdog (Analyst)

Thanks so much.

Operator (participant)

Thank you. Please stand by for our next question. Our next question comes from the line of Truong with UBS. Your line is open.

Cameron Bozdog (Analyst)

Hi, guys, Truong Nguyen from UBS. Thanks for taking my questions. Just on the subQ administration, I've got a couple on there. So do you have any details on this? Is it an autoinjector? Can it be done at home or in the hospital? And what's the injection volume that you're using? Just trying to get an idea of the convenience for this product. And then, can you just give us any color on what could be presented in 1Q with this data? In particular, could we see any safety data? Thanks very much.

Daniel O'Connell (CEO)

Thanks for the question. I'll just quickly—we will have safety data, and we'll have bioavailability data. At this point, we're not guiding or disclosing sort of volumes and so forth. I do think that we're trying to establish the bioequivalence of subQ versus IV dosing in that therapeutic range that we're using in ALTITUDE-AD. And I think we will have look for a variety of different delivery formats. We have a fairly clear view as to what we wanna deliver on in terms of dosing frequency and volumes, but at this point, I'm not prepared to comment.

We're fortunate to be partnered up with Halozyme on this program, and they've brought to bear a good bit of information and content and been good partners to help us assess how to advance a subcutaneous formulation of sabirnetug.

Matthew Zuga (CFO and Chief Business Officer)

Yeah, and maybe just to expand on that a little bit, just to remind you that this study is in healthy volunteers. It's not in patients. And so ARIA really shouldn't be an issue in terms of safety. So, the safety is more just injection site reactions and that sort of thing, but we anticipate that that should be quite good.

Cameron Bozdog (Analyst)

Just following up, you mentioned a partnership with Halozyme there. Should we expect what the financials there, should we expect to pay our way here? I know it's a bit down the line.

Daniel O'Connell (CEO)

Yeah, so it's, it's down the line. I mean, the terms and are not disclosed publicly. I think it is, it's been a matter of public record, though. It's a non-exclusive arrangement with Halozyme.

Cameron Bozdog (Analyst)

Thanks very much.

Operator (participant)

Thank you. As a reminder, ladies and gentlemen, that's star one one to ask the question. Please stand by for our next question. Our next question comes from the line of Ananda Ghosh with H.C. Wainwright. Your line is open.

Ananda Ghosh (Analyst)

Yeah, hi, congrats on the quarter. I have two questions. The first one is, can p-tau217 predict a low and high tau patient population? Are there data from the prior clinical trials, you know? And the second question is, with the lecanemab data at the AAIC showing a long-term benefit, due to its specificity for neutralizing protofibril, what's the read-through for ACU193?

Daniel O'Connell (CEO)

Thanks, Ananda. Eric, do you wanna address that question?

Matthew Zuga (CFO and Chief Business Officer)

Yeah. So as far as the p-tau217, great question. You know, intuitively, you would sort of think that, well, this is a form of p-tau, so it should correlate with tau PET. As it turns out, it's such a sensitive early marker, it actually tends to correlate with amyloid PET, which-

Mm.

is not as sensitive. So what we've actually done in our trial is to use p-tau 217 as a screening measure for people who go on then to PET or CSF. And what we've found is by doing that, we reduce the number of negative PET scans and negative CSF by about 50%. So it seems to be working quite well as a screening procedure, and we actually think that that's something that could play out in clinical practice, that a physician, but yet a, a, you know, blood p-tau 217, and, you know, a lot of people who otherwise would go on to have a negative PET scan. So I think it's a really good biomarker. And, I'm sorry, I didn't quite catch your second question.

Ananda Ghosh (Analyst)

You know, with the lecanemab, a long-term study, they are showing that, you know, that-

Matthew Zuga (CFO and Chief Business Officer)

No, no

Ananda Ghosh (Analyst)

patients have this continued benefit based on, you know, their ability to target protofibrils. So what's the read-through, you know, with the sabirnetug?

Matthew Zuga (CFO and Chief Business Officer)

Well, yeah. So we've followed that very carefully, and there's really interesting data. And I think what the field is learning, and we're learning along with the field, is that if you just look at amyloid based on PET scans, it's a very slow increase once you've reduced the amyloid that's there. But what you also see is that apparently, PET scans are not that sensitive because some of the other pathology increases in GFAP, increases in various forms of p-tau. Those things come back a lot sooner than your PET scan gets worse.

So in our view, that's a good indication that, partly because, or it may be because, lecanemab targets these protofibrils, that when you stop treatment with it, the pathology comes back relatively quickly, and you don't pick that up just based on an amyloid PET scan. We think that's completely consistent with our hypothesis of targeting these soluble oligomers.

Ananda Ghosh (Analyst)

Hmm. Got it. Thanks, very, very helpful.

Operator (participant)

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

Alex Braun (Head of Investor Relations)

Great. Thanks, everyone, for joining the call today, and for your interest in the company. Please don't hesitate to reach out to us if you have any follow-up questions, and have a great day.

Operator (participant)

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