Acumen Pharmaceuticals, Inc. Q4 FY2023 Earnings Call

Ladies and gentlemen. Thank you for standing by. Welcome to Acumen Pharmaceuticals Full Year 2023 Conference Call and Webcast. At this time, all participants are in a listen-only mode. After the speakers’ presentation, there will be a question-and-answer session. Please be advised that today’s conference is being recorded. I would like now to turn the conference 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 year ended December 31, 2023. With me today are Dan O'Connell, our Chief Executive Officer; Dr. Jim Doherty, our President and Chief Development Officer; Dr. Eric Siemers, our Chief Medical Officer; and Matt Zuga, our Chief Financial Officer and Chief Business 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 and the related slide presentation 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 2 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. After our prepared remarks, we'll open the call for Q&A. Now I'll turn the call over to Dan.

Thanks, Alex. Good morning, and thanks to everyone who is joining us today. 2023 was a landmark year for Acumen. Our monoclonal antibody for the treatment of early Alzheimer’s disease, ACU193, which recently received its non-proprietary name Sabirnetug, delivered positive and exciting Phase 1 results first presented at AIC last July. You will hear more about these results and how they serve as the cornerstone for establishing Sabirnetug’s differentiated therapeutic profile later on this call. More recently, we welcomed Dr. Jim Doherty to Acumen as President and Chief Development Officer. Jim brings many years of experience in CNS drug development, and we are delighted to have him join our leadership team. We believe Acumen entered 2024 from a position of strength. We remain highly focused on the execution of key program and strategic initiatives to further establish the therapeutic potential of Sabirnetug as a best-in-class treatment option for the substantial early Alzheimer’s patient population. This month we presented additional CSF biomarker data and details about our A-beta oligomer target engagement assay from our Phase 1 INTERCEPT-AD study at the international conference on Alzheimer’s and Parkinson’s disease or ADPD. We will also present analysis at the American Academy of Neurology Meeting in Denver this April, which will introduce the development plan for Sabirnetug and the results from INTERCEPT-AD to this broad group of practicing and academic neurologists. If you haven't already taken a look at our Phase 1 results in their entirety, I encourage you to visit our website, where you can find archived presentations, webcasts, and releases detailing the Sabirnetug data. For us, it's difficult to overstate the significance of these results and how they position Sabirnetug in the broader anti-A-beta field. We knew going into our Phase 1 study that Sabirnetug possessed high selectivity for A-beta oligomers. Why does this matter? Unlike A-beta monomers and insoluble amyloid plaques, A-beta oligomers are toxic and distinct in important ways, particularly to neurons and synapses. Our approach with Sabirnetug is to selectively target toxic A-beta oligomers and, as a consequence, protect synapses in a way that may provide additional therapeutic benefit to patients, especially from an efficacy perspective. The INTERCEPT-AD results exceeded our expectations and provided a substantial amount of data indicating Sabirnetug’s drug effect. Overall, we see multiple paths towards Sabirnetug’s next generation differentiation on efficacy, safety, or both, any of which would be beneficial to patients as compared to existing options. I'm pleased to note that we're making great progress with the launch of our Phase 2 study ALTITUDE-AD, which remains on track to initiate in the first half of this year. Simultaneously, we are also on track to initiate our subcutaneous Phase 1 study expected for mid-2024. With that, I'd like to hand the call over to Eric.

Thanks, Dan. And thanks to those listening in to the call today. I'm very pleased with the progress with the clinical development of Sabirnetug last year and thus far in 2024. With our achievements last year, we are well positioned to potentially deliver a differentiated treatment to the Alzheimer's community. I'll provide a brief update on feedback we've received from the scientific community on our Phase 1 INTERCEPT-AD results, and then review our study design for our next trial ALTITUDE-AD. Recall that our Phase 1 top line results were announced in July of last year at AIC, and we had subsequent updates throughout the second half of the year on the fluid biomarker results as those were analyzed. The totality of the Phase 1 data has only recently become available and can now be evaluated by the broader external community. We believe the fluid biomarker results have helped to relate the mechanism of Sabirnetug to its downstream pharmacologic activity. As first reported in July, a dose-dependent increase in target engagement approaching an Emax was found in CSF, and a reduction in plaque measured by amyloid PET was seen at the highest doses of Sabirnetug in the multiple-ascending dose cohorts. Importantly, after just three administrations of Sabirnetug in the multiple ascending dose portion of the study, patients demonstrated downstream improvements across TAU and amyloid biomarkers in CSF, which are the two main pathologic hallmarks of Alzheimer's disease. Remarkably, there were additional clear effects on synaptic biomarkers suggesting Sabirnetug's target engagement of neurotoxic oligomers may protect synapses after only three administrations of the drug. As Dan mentioned, our team recently returned from ADPD in Lisbon. The feedback on our data package at medical conferences has been very positive. The excitement around our INTERCEPT-AD results caused us to be even more enthusiastic about beginning our next study, ALTITUDE-AD. ALTITUDE-AD is planned as a randomized, double-blind, placebo-controlled three-arm study designed to evaluate the clinical efficacy, safety, and tolerability of Sabirnetug with approximately 180 participants per arm for a total of 540 participants with MCI or mild dementia due to Alzheimer's disease. We intend to use the iADRS at 18 months as the primary outcome measure. The study is planned to include a one-year open-label extension. Based on the results from INTERCEPT-AD, the doses for ALTITUDE-AD will be 35 milligrams per kilogram and 50 milligrams per kilogram, both dosed every four weeks. Extensive PK/PD modeling of our Phase 1 data, especially with regard to target engagement and consideration of safety data led to the selection of these doses. Both of these dose levels may produce clinical efficacy, and we are keen to see whether they will differentiate in terms of the overall benefit-risk ratio. Importantly, this study is designed as a registration-eligible study for Sabirnetug, and we look forward to providing further updates as the study initiates and progresses. In short, our Phase 1 results have allowed us to move to our next study that will more definitively investigate how uniquely targeting A-beta oligomers may lead to a best-in-class treatment for patients with Alzheimer's disease. And with that, I'll turn the call over to Jim.

Thanks, Eric, and good morning, everyone. I would like to thank Dan and the entire team at Acumen for their warm welcome. I've been onboard for nearly two months now, and in that time, I've grown even more excited about the potential for A-beta oligomer selectivity to offer a next-generation Alzheimer’s treatment. At its heart, I see the Sabirnetug program as testing a very clear hypothesis. A-beta oligomers are neurotoxic amyloid species in the brain. By targeting these oligomers, Sabirnetug may offer a differentiated profile compared to other AD therapies, including the potential for greater efficacy or reduced side effects like ARIA. The Phase 1 INTERCEPT-AD results show that Sabirnetug can indeed bind to its intended target and improve downstream Alzheimer's biomarkers. We believe there is great potential for this approach to be beneficial to patients, and it's incumbent on us to progress our clinical program efficiently and strategically to maximize Sabirnetug's value for patients and shareholders. To support the ALTITUDE-AD trial, we have contracted with a highly experienced CRO with a strong track record in AD that should provide advantages for trial recruitment and site readiness. As Dan mentioned earlier, we are also planning to initiate a Phase 1 bioavailability study in healthy volunteers for a subcutaneous formulation of Sabirnetug in mid-2024. We believe a competitive product profile for Sabirnetug includes a subcutaneous option to offer additional flexibility and convenience for patients and caregivers, and we have a productive collaboration with Halozyme for that work stream. Before I turn the call over to Matt, I'd like to take a moment to highlight the excitement we observed at the 2024 ADPD Conference a few weeks ago. We are clearly entering a new era for the diagnosis and treatment of Alzheimer's disease with novel therapeutics, increasingly more precise biomarkers, and diagnostics that will in turn help the field develop even better treatments. Having just recently joined Acumen, I can clearly sense the team's pride in how the INTERCEPT-AD biomarker data have contributed to the perception that AD is a treatable disease. In particular, the effects observed on downstream fluid biomarkers after only three administrations of the drug underscore the potential of Sabirnetug in targeting A-beta oligomers for the treatment of early AD. We believe Sabirnetug's clinical development will continue to move this field forward from this perspective. And now I'll hand the call over to Matt to discuss the financials.

Thanks, Jim. As a reminder, our full year 2023 financial results are available in the press release we issued this morning and in our 10-K we will file later today. We ended 2023 with approximately $306 million in cash and marketable securities on the balance sheet, which provides us with the financial resources to deliver against our strategic objectives. The increase from the prior year is due to the net proceeds from our public offering last July of approximately $122 million as well as approximately $30 million from K2 HealthVentures as part of the debt financing we announced in November of up to $50 million. Our cash on hand is expected to support our current clinical and operational activities into the first half of 2027. R&D expenses were approximately $42.3 million in 2023. The increase over the prior year was primarily due to increased costs related to materials, drug manufacturing costs, consulting, and personnel. G&A expenses were $18.8 million in 2023, with the increase over the prior year primarily the result of costs related to personnel and consulting. This led to a loss from operations of $61.1 million in 2023. Our positive Phase 1 results in 2023 are a clear reflection of our strong drug development capabilities, which we have further elevated with Jim's experience and insight. We are well capitalized to execute on our upcoming Phase 2 ALTITUDE-AD study and to develop a subcutaneous formulation. We are committed to delivering on the opportunity ahead of us and look forward to providing additional updates this year as we advance Sabirnetug for the benefit of patients, caregivers, and shareholders. And with that, we can open the call for Q&A.

Thank you. The first question comes from Neena Bitritto-Garg with DB. Your line is open.

Hey guys, thanks for taking my question. I was curious about your recent mention of considering an interim analysis in the ALTITUDE-AD study to decide if you should begin a Phase 3 study. Could you explain the reasoning behind conducting that interim analysis, any protocol adjustments you anticipate making in ALTITUDE-AD based on recent regulatory feedback, and any thoughts on the criteria for that interim analysis? Thank you.

Thanks, Neena. This is Dan. Maybe I'll quickly take that. So great question. In terms of the interim analysis, these will not be analyses that change in any way the ALTITUDE-AD protocol. They're really intended to provide some early visibility on data to allow us to make a decision as to whether to progress towards a Phase 3 study. So these are not futility analyses, and they're not expansion analyses, but they will be employed just for the purposes of getting some early visibility in an effort to potentially minimize the white space between the Phase 2 and the Phase 3.

Okay, got it. That's super helpful. And then I guess any changes that you may consider making to the ALTITUDE-AD design based off of feedback from the planned Donanemab AdComm?

Thanks, Neena. So I don't think we have any priority expectations to make changes based on the AdComm. The AdComm is an interesting development for the field, certainly should serve as a good venue for exploring some of the considerations associated with the Trailblazer 2 design and the overall Donanemab data set. We do, as perhaps you’re referencing, anticipate using the iADRS at 18 months as our primary outcome measure in ALTITUDE-AD, and barring some unforeseen change in development with the AdComm, we'll continue to use the iADRS as our primary.

One moment for our next question. The next question comes from Thomas Shrader with BTIG. Your line is open.

Hey, good morning. This is Sam on for Tom. Thanks for taking our questions. So for subcutaneous, is maintenance therapy an immediate application for subcutaneous dosing, and what are your thoughts on integrating any subcutaneous dose option in the open-label extension part of the ALTITUDE-AD study? Thank you.

So Sam, thanks for your question. And I think the quick answer on that is the next phase of development for subcutaneous beyond the Phase 1 is yet to be determined or decided. So our immediate focus is on getting this Phase 1 healthy volunteer bioavailability PK study done as a means to really inform what the next dosing strategy and study might be for a Phase 2 or, as you mentioned, there are a couple of different options that might be available to us in the future. But I think for the near term, we're focused on executing the Phase 1 as the primary gate prior to describing in greater detail the Phase 2 plans.

One moment for the next question. The next question comes from Paul Matteis with Stifel. Your line is open.

Hi, this is James for Paul. Thanks for taking our question. Could you provide some insight on how you powered the Phase 2 study and what your key indicators of success will be? Additionally, relating to the interim data, are you considering biomarkers, clinical scales, or a combination of both? What can you share about the types of data you expect to collect? Thank you.

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

Yes, sure. Thanks, Dan. So for our Phase 2 ALTITUDE-AD study, as I mentioned, it's 540 participants with 180 per arm. That provides pretty typical power for a Phase 2 study. So we feel like that should answer the question in terms of how the program develops. We'll also look at a variety of biomarkers, most of which we examined in our Phase 1 study too. And so it will be really interesting to see after 18 months of treatment, TAU's biomarkers response since we already saw a response after just three doses in essentially three months. So we're looking forward to that. In terms of what goes into the interim analyses, we're not going to get into details about that. I guess I can say that it's an algorithm that doesn't include just one thing. Again, as Dan mentioned, the utility of that is to reduce the white space between a Phase 2 and a Phase 3 trial because if the algorithms look positive, one of the things that it tells you is that the study design of the Phase 2 study is good. And a lot of times, what creates white space in drug development programs is redesigning studies. If we don't have to do that, that will cut down on our white space. So that's how we plan to use those algorithms.

One moment for the next question. The next question comes from Colin Bristow with UBS. Your line is open.

Oh, hi, this is Kim on for Colin. And thank you for taking our questions. Just a quick one following the earlier question on the subcutaneous formula. Since the earlier question was more centered around maintenance study. So for subcutaneous as initial therapy, like in the upcoming subcutaneous bioavailability study, what dosing charts and dosing schedules are you currently thinking, especially with regards to Eisai's recent pushbacks for subcutaneous dose as initial therapy? Do you think it is reasonable to start with some lower doses and test out for safety first? Thank you.

Go ahead, please.

Yes. No, I think those are all great questions and all questions that we really don't have an answer to at this early point. I mean we don't have even our healthy volunteer data yet. So those are all things to be considered. I think it's interesting that broadly in the field, people are talking about starting off with IV administration and then switching to subcutaneous as more of a maintenance dose. So that's not just something that we're thinking about. It's something that a lot of people are considering. But we'll just need to get actual data before we start to narrow things down on those questions.

One moment for the next question. The next question comes from Ananda Ghosh with H.C. Wainwright. Your line is open.

Hey, hi, thank you. The first question is probably what are some of the advantages of iADRS over CDR-SB and the rationale behind choosing iADRS over CDR-SB for the ALTITUDE study? And the second thing is there has been a lot of correlations made based on how much of plaque reductions you're seeing and what's the probability of success in terms of some of these anti-A-beta immunotherapy trials. Are there other associations, which have been made with other biomarkers such as TAU 181 or 217, where at least some modeling-based studies can tell you to what extent you might need to see a change in these two biomarkers so as to kind of have an impact in either CDR-SB or iADRS? Thanks.

Yes, I can try to take that one, too. As far as the use of the iADRS versus the CDR Sum of Boxes, one of the things that was interesting in the recent draft guidance was that they no longer called out the CDR Sum of Boxes. They actually presented it at public meetings, the idea that in the previous draft guidance where they did mention the CDR Sum of Boxes, they didn't mean to endorse that as the only scale. But what they stated in this most recent draft guidance is that a scale that's a composite of cognitive measures and functional measures may have real utility. And that's what the iADRS is. It's a combination of cognitive measures from ADAS-Cog and then functional measures from a scale called ADCS-ADL. So we think that it's very positive, actually, in terms of our use of the iADRS. I would assume that the Trailblazer studies, that's their primary. They were happy to see that. So yes, I think that's a really good clarification from the FDA in terms of those kinds of scales. In terms of correlations between plaque reduction and clinical benefit, I think what's really becoming a consensus opinion now is that you have to get plaque below a certain threshold. This is something that we at Acumen have been saying for a long time: if you're going to target plaque, you have to basically get rid of it. The goal seems to be based on existing data that you want to get below 25, say—or at most 30. If you want to—for your target is plaque, that's what you need to do. But again, our target is not plaque. Our target is oligomers. So it will be interesting to see what effects we have on plaque, but with our differentiated mechanism, that's really not the construct of our development plan.

I show no further questions at this time. I would now like to turn the call back over to Alex Braun for closing remarks.

Thanks, Michelle, and thanks for everyone for taking the time to tune in today. We are always available at the company for any follow-up questions, please be in touch and have a great day. Thanks.

This concludes today's conference call. Thank you for your participation. You may now disconnect.