Acumen Pharmaceuticals, Inc. (ABOS) Earnings Call Transcript & Summary

All right. Good morning. Welcome to the last day of the BofA Healthcare Conference. My name is Geoff Meacham. I'm the senior biopharma analyst here, and Charlie from my team is on stage with me. So we're thrilled today to do a quick fireside with Acumen Pharma. And speaking on behalf of Acumen, we have CEO, Dan O'Connell. Good to see you.

Thanks, Geoff. Good to see you. Thanks for having us.

Yes, of course.

Good morning, Charlie.

Good morning.

Yes. So Dan, let's just kick it off with kind of the news of the past few weeks, right, about validation of amyloid beta and how you guys put that in context of Acumen's approach with respect to oligomers.

Sure. Thanks, Geoff. So yes, it's a really exciting time in the Alzheimer's space. I think everyone has been anxious to see more progress made against this disease, and we now have several monoclonal antibodies that have been targeting various species of a beta that have demonstrated clinical benefit. And so I think we're at a stage where the field and people are generally recognizing that amyloid removal or targeting is a viable means of producing patient benefit. For Acumen, we've been focusing on soluble A-beta oligomers. So these are soluble aggregates of the A-beta peptide that, over the years, have been demonstrated to be primary neurotoxins. So the thesis for Acumen and our monoclonal ACU193, which is highly selective for these A-beta oligomers, is that by neutralizing that toxicity there is the possibility of increased safety and even better clinical efficacy over time.

So let's talk a little bit about the reimbursement profile and maybe what that could do for you guys. So if you look at access and pricing reimbursement, also, in particular, the diagnostic piece of it, right, so how does all that inform how you could do -- obviously, you're in Phase I now, but Phase II and down the road Phase III to optimize your effect size?

Sure. So as you mentioned, Geoff, we are in Phase I, and we are excited to be reporting our top line results in the third quarter. So we think this study, what we refer to as INTERCEPT-AD, will yield really important information for us for the next stage of development. So that will be principally the safety profile, so inclusive of the ARIA rates in patients; the pharmacokinetics, including sort of insights into the dose strategy for the Phase II/III; and then target engagement. And that's -- an important facet of our program is given that we're targeting oligomers, which is distinct from amyloid plaques, we were going to use a CSF, or cerebrospinal fluid assay to measure the complex of ACU193 bound to oligomers from patient CSF. And we think that's going to be a really important element in the dataset from INTERCEPT-AD that really informs the next stage of development. In terms of diagnostics and reimbursement, we're in an interesting position to observe what happens and how things shake out, right? I think that it's likely we've got some seminal developments that are going to occur. I think, over the course of the second half of this year, we've got a PDUFA date for lecanemab. It looks like there is an evolving mindset at CMS with regard to potentially coverage for a broader set of full approved products. So those are all positive things that we think will help support the field generally. Probably, the infrastructure build-out for these types of products. And 193 moving forward into II/III has -- if we can demonstrate the competitive safety profile and potentially even better efficacy, that would be an easy next-generation product to roll into that infrastructure, right?

So you mentioned about kind of like the diagnostics and the assay. So maybe tell us a little more about the target engagement. What kind of expectation you're looking to see in Phase I from that perspective? And maybe more importantly, from the -- you have the computerized test to test some of the combination function. And what's your expectation over there? What do you expect to see? And then what would be the dataset that you think will be meaningful enough to convince you about the next stage of the development?

Sure. So great question, Charlie. So we're really principally looking for safety profile, differentiation on ARIA rates and a wide dosing window for ACU193, the PK and then target engagement. And in terms of target engagement, I think first level of success is just establishing the concentrations of complex from patient CSF. We mentioned, I think, on our earnings update earlier this week that we have sort of some proof of principal data in the assay development that's ongoing that looks really promising. So there is the possibility that we would establish sort of a dosing stratification on the target engagement assay, which would be really interesting. And then as you know, we have incorporated in this study some other exploratory outcome measures, including a computer battery that will make sort of acute and frequent assessments of cognitive abilities. And so if we were to see something -- signal on any of the -- either the computer battery or the MRI, blood measurements, that would be a provocative result. I think that would really be very supportive of the program. Again, we're not expecting to see something like that, but it's in there, in case there's an observation that would help inform the next step for 193.

So let's say, I guess, hypothetically, you see a great target engagement, good safety profile and -- but let's say, the computerized test just somewhat -- there's no -- I guess, I was -- just given the -- how the small sample size, and you're not really seeing much of a trend there, would that still be enough for you to kind of move into the next stage? Or I guess, like, what kind of signal are you expecting here that you think will be going to be, I guess, good enough?

Yes. So I think the state of play right -- so we are not expecting and demanding of a computer or cognitive signal in the study, right? Like that's not really what the study was intended to do. But what I think we do need to show is, as I mentioned, that safety element is critical because we're -- right now, if you look at the products that are out there, the plaque targeting antibodies, the direct -- plaque directed antibodies, such as donanemab, have about almost 30% rate of ARIA-E. And I think that's going to be a challenging feature to manage in clinical medicine. So I think the first entry point is that safety and good product -- drug product characteristics coming out of the Phase I. This is a Phase I in patients, so we think that is an important aspect of really knowing what -- how the drug performs in patients. And then pushing it into a Phase II/III, I think that's -- the study that is intended to follow INTERCEPT-AD sort of starts as a Phase II, but then has the possibility to expand due to an interim to a full registration study.

Then I guess is there -- so given the lower ARIA rate, like, compared to all the other A-Beta drugs, like how you think about it in terms of the ARIA rate versus kind of efficacy from that perspective? And will you be able to kind of stratify that in your study?

In this study, again, we're not looking for efficacy. I think in subsequent studies, it will be important to show the risk-benefit, basically demonstrate a lower rate of ARIA and a competitive and potentially superior efficacy signal.

And just on that background, when you look at kind of symptomatic versus asymptomatic ARIA in donanemab versus lecanemab, how do you guys think about potential differentiation there? And just again -- and trying to maximize the effect size and later trials for you guys?

Yes. I mean, I think if we look at both lecanemab and donanemab, to our eye, lecanemab clearly has a better safety profile. I mean, that's demonstrable. I think the efficacy looks equivocal in the comparable population. So it's going to be interesting to see how those products kind of find their way into the marketplace and how payers and prescribers address those products. Lecanemab, I think, is probably the benchmark for us in ACU193. I mean, it has about a 12% rate of ARIA, and about 25% of those are symptomatic. I think if you look -- and our Chief Medical Officer, Eric Siemers, has been looking closely at all of these developments. I think we now have enough information on these A-beta antibodies that the ARIA rates are basically 75% asymptomatic, 25% symptomatic, whether that's at the aggregate level, depending on whether you're 30% ARIA or 10% ARIA.

Right. And we talked in the beginning about biomarker. So what would you say the TRAILBLAZER ALS2 data do to your enthusiasm for using tau stratification? Do you think that now going forward is going to be kind of a standard in larger-scale efficacy studies?

Geoff, I don't think that's going to be a standard going forward. I think Lilly did a remarkable job of translating their Phase II results into Phase III, and that tau stratification was a really useful way to control the experiment in Phase II and replicated in Phase III. I don't know that that's a practical element for large-scale studies and just the clinical practice of medicine. I think Lilly has the advantage of having A-beta and tau tracers. And so it was sort of pulling something off the shelf and employing it in a useful drug development way, but I don't think that's something that we'll adopt. I think we will look at some of the plasma and potentially blood tau biomarkers as a means of enriching the population or basically making sure that it is a controlled population that's enrolled in subsequent studies.

Right. And then as a follow-up to that, when you look at the -- from the ALS2 study, the 6 months or less really, the clear plaque, what is your view updated or not on speed of plaque clearance? Is it worth it to have 193 on board when there's no plaque?

I mean -- scientifically, I mean, particularly with donanemab where they're stopping dosing once plaque is removed, those patients are still progressing. And I think there's other evidence to suggest that, even with plaque clearance, there are other species present that are contributing to pathology. So it is conceptually a pass that 193 would be an add-on or follow-on to a post-induction treatment with donanemab or a plaque-clearing agent of some other nature.

So induction, then perhaps maintenance approach, right? Yes.

And that's really where I think for 193 really demonstrating the safety early is sort of a basis for assessing that sort of versatility of 193 as either a monotherapy or add-on therapy, what have you.

And I guess, we'll see data at AIC, the full details. From what we know of, lecanemab today, are there any other biomarkers or any other strategies that you could employ in future studies for you guys?

Well, I do think all of the fluid biomarkers are really advancing pretty rapidly, and there's a whole bunch of different species within the tau realm that I think are going to be instructive as to how we manage and conduct studies, whether that's for patient enrollment and screening, whether it's for interim assessment on drug effects. These are all tools that I think we'll have available to us in the next phase of development.

Yes. Perfect. And from a capital perspective, so help us with kind of what partnering versus not partnering, sources of non-dilutive capital and investments outside of 193 that you guys are making.

Sure. So in terms of capital, we're in a fairly healthy position in that we report having $183 million in cash at the end of the first quarter. We've guided that we'll have $155 million roughly in the third quarter when we report results. That cash will run us through 2025. I do -- with the next study, it's likely to take the form and size based on the results from the Phase I. So I think we're not yet ready to pencil in precisely the size and duration of the next study. It's likely that, that study will have a readout or at least some interim assessment in 2026, and that will require additional capital. In terms of partnering, I mean, this is an exciting time in the field, right? We've got fingers crossed, and I think the expectations are realistic that lecanemab will gain full approval, that likely donanemab at some point shortly thereafter, they've built their file, and that likely gets approved as well. And so I think in the neuro space, generally in Alzheimer's in particular, the major players are going to be paying more attention to innovative opportunities to advance assets against this huge unmet need. So I think we don't have -- I think we're fairly agnostic in terms of sources of capital. I think that the partnering environment seems to be improving from where it was 2, 3, 4 years ago. And I think whether it's capital markets or partnering, we'll have to weigh those options based on the dataset.

Right. And then in terms of earlier sort of discovery stuff, can you just give us some highlights there?

Yes. So in terms of pipeline expansion, I mean, we still maintain a strong interest in growing the pipeline and expanding sort of the value potential of the enterprise. I think we are not going to do discovery research as an organization. I think we will seek to in-license complementary assets that are either within the -- certainly in the neuro space, potentially could be synergistic or complementary to what we're doing with ACU193.

Got you. And then final question. You just mentioned the interim analysis. What other strategies could you guys deploy to kind of speed up the ultimate filing time?

So I think we've maintained that a full approval on a Phase III study is the most viable path to reimbursement and commercial success. So you basically need a dataset that patients and physicians are convinced of the risk-benefit of a particular product. So I do think that we are unlikely to move plaque in the way that some of the plaque targeting directed antibodies have done, and that accelerated approval is something we'll have to weigh and evaluate at some point in the future. But it is not -- our plan is certainly to move quickly into a Phase II study that has that potential to be a Phase III as the fastest path to a BLA.

Great. Okay. Thank you, Dan.

Yes. Thanks, Geoff. Great seeing you.