Acumen Pharmaceuticals, Inc. Q3 FY2024 Earnings Call

Hello, and welcome to Acumen Pharmaceuticals Q3 2024 Conference Call and Webcast. 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 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 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 sabirnetug, our next-generation A beta oligomer-targeted antibody for the treatment of early Alzheimer’s disease. ALTITUDE-AD, our Phase II study designed to evaluate the clinical efficacy and safety of sabirnetug 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 U.K., and the EU. Enrollment in ALTITUDE has progressed faster than we expected, and we now anticipate the completion of enrollment in the first half of 2025. We believe the ALTITUDE-AD enrollment is due to characteristics stemming from sabirnetug’s mechanism of action, along with enthusiasm from site investigators bolstered by our robust Phase I 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 reinforce the interest in innovative treatment options and the therapeutic potential of sabirnetug. We have also continued to progress our Phase I study of subcutaneous sabirnetug, and we anticipate that 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 the next steps for developing subcutaneous sabirnetug. 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 Alzheimer’s disease. We see Acumen in a strong position to capitalize on this momentum. 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 fundamentally going to 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 pTau 217 enrichment screening approach results in a higher proportion of patients who meet the amyloid PET or CSF-based inclusion criteria 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% compared to our Phase I study and contributed to the rapid enrollment. Second, the first reports of real-world use of Leqembi 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 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 Alzheimer’s 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 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 sabirnetug’s mechanism of action targeting toxic A-beta oligomers, our positive Phase I clinical results, and the Phase II clinical plans for sabirnetug. Additionally, shifting to the organization. Just last week, we announced the appointment of Dr. Amy Schacterle 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 onboard as we further refine our product development strategy ahead of key clinical data for sabirnetug. I’d also like to thank Dr. Janice Hitchcock, who led our regulatory affairs efforts as she retires at the end of the year. Janice has been instrumental in building our regulatory infrastructure, overseeing our regulatory strategy, and in driving sabirnetug 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 sabirnetug 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 II data and as we work to confirm sabirnetug’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 10-Q, which we will file later today. As of September 30, 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 noncash 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 II study and advance a subcutaneous formulation of sabirnetug. 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.

Our question comes from Paul Matteis with Stifel.

It’s Mark on for Paul. Just had one on the subcutaneous study. So what kind of data can we expect there? Any more color? And then for next steps, how do you plan to potentially incorporate that into future studies?

Yes. Thanks, Mark. So the Phase I study is in healthy volunteers, and we’re evaluating the pharmacokinetics and bioavailability of subcutaneously administered sabirnetug compared to 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 subcutaneous format. I think it’s a little bit early for us to prespecify what those next steps will be until we see the data.

Our next question comes from Tom Shrader with BTIG.

For ALTITUDE-AD, can you remind us your thoughts on taking an interim look at 6 months? If it’s better than Lecanemab, 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. Yes. Let me clarify. I think we have no anticipation of looking at interim results in the course of the study. We’re reporting out on the blinded ARIA data. I think that as we perhaps guided previously, the interaction we have with regulatory bodies has led us to run the Phase II as essentially a pivotal study, and we’ve 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.

Yes. Dan, this is Jim. As you say, I think what’s important to us is preserving the statistical power and integrity in the study. 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 studying the completion and read out the data at the end.

Yes. And just maybe one other quick thing just to emphasize the comment Dan made about ARIA reporting. Obviously, this is an important finding for sabirnetug, 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. That’s our plan as far as ARIA goes.

I think a question pretty related to the last one. Are you confident that if subcutaneous becomes a necessity that you will have enough data based on your Phase II and your Phase I for subcutaneous to do a pivotal study? Or do you think it’s very likely you need a Phase 2 with subcutaneous? And again, I appreciate it’s forward-looking.

Sure, Tom. I think we really want to see the Phase I data before we predict what the next step will be for subcutaneous. We anticipate that both IV and subcutaneous formats for this class will be available well into the future. We’re committed to exploring the subcutaneous version of sabirnetug for the purpose of providing a potentially more convenient format. But I think it’s premature to predict exactly how we will proceed.

Our next question comes from the line of Jason Zemansky with Bank of America.

This is Cameron Bozdog on for Jason. So as the Phase II 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? Is it something else? I guess we’re just looking for some potential leading indicators we could focus on to suggest everything remains on track here.

Yes, 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 II in upwards of 540 patients has progressed far more rapidly than we had anticipated. We now expect to complete enrollment in the first half of next year 2025. To set the time frame, we announced the first patient enrolled in this study in the second quarter of this year. From our own planning and expectations, the enrollment has gone exceedingly well. We attribute that to the profile of sabirnetug, the Phase I results that 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 sabirnetug as a next-gen treatment option for patients.

Our next question comes from Pete Stavropoulos with Cantor Fitzgerald.

This is Samantha online for Pete. So my first question is regarding enrolling early Alzheimer’s 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 Centiloid 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. 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.

Yes. Thanks, Dan. No, it’s a great question, and obviously 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 are 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 III studies. One of the things that we looked at in our Phase I study 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. What that does is it pushes your average amyloid load, your SUVR lower because I think the human eye is just 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 I 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 standard in the field now as 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. We’ll get the data at the end of the study, but we think we’ve dialed in the inclusion and exclusion criteria 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 lower so far with sabirnetug? How has the ARIA burden 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 for drugs with a lower risk of ARIA?

Well, yes, another really good question. So our premise all along has been because sabirnetug was developed to be more specific for oligomers and less binding the plaque, we anticipated lower ARIA rates even before we conducted our Phase I study. The fact that our Phase I study showed relatively low rates of ARIA was not a surprise to us. Now, obviously, the Phase I study is pretty small, and we need to replicate that in our Phase II study while looking at that really carefully. In terms of how clinicians are approaching the use of the approved disease-modifying monoclonal antibodies, it’s really controversial. Even at this recent CTAD meeting, there was a debate about the fatalities associated with these drugs. How carefully should we think about even starting them at all? You’ll get different answers from different clinicians, but it's a rapidly developing area. We think that because sabirnetug should have a lower rate of ARIA, that by itself is a good thing. How people manage it when it does happen is something that is rapidly evolving over time.

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. 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.