Good day and thank you for standing by. Welcome to Acumen Pharmaceuticals First Quarter 2024 Conference Call and Webcast. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Alex Braun, Vice President and Head of Investor Relations.

Please go ahead..

Thanks, Norma. Good morning and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended March 31, 2024. With me today are Dan O'Connell, our CEO; and Matt Zuga, our CFO and Chief Business Officer. Dan and Matt has 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 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. And with that, I'll turn the call over to Dan..

Thanks, Alex. Good morning, everyone and thanks for joining us today. As we noted on our year-end call in March, 2024 is a year of execution for Acumen as we work to establish the therapeutic potential of sabirnetug as a best-in-class treatment option for the substantial early Alzheimer's patient population.

I'm pleased to say that we are off to a great start with the first patient dosed in our ALTITUDE-AD Phase II study announced just last week.

ALTITUDE is a randomized placebo-controlled double-blind study with 3 arms designed to evaluate the clinical efficacy and safety of sabirnetug with approximately 180 participants per arm for a total of 540 participants which with MCI or mild dementia due to Alzheimer's disease.

We are highly encouraged by the start of the ALTITUDE study which we attribute to a couple of key factors. First, we received positive feedback from site investigators on our Phase I INTERCEPT results.

The thoroughness of the INTERCEPT data package appears to be resonating, particularly the confluence of biomarker improvements we saw in patients after only 3 doses. Second, the design of the ALTITUDE study has been viewed favorably by many investigators and patients.

Because our Phase I oligomer target engagement data was so informative, we are proceeding in Phase II with 2 dose arms that may prove efficacious. So patients have a greater chance of receiving a therapeutically relevant dose level of sabirnetug.

Additionally, the open-label extension is providing -- proving to be important to patients in the screening process as it provides for 12 months of sabirnetug active treatment following the 18-month placebo-controlled portion of the study.

Overall, I'm extremely pleased with the strong foundation that our team and CRO partner have built with key trial sites, highlighting the benefits of preparation, communication for screening and enrollment efficiency.

In addition, we also recently announced a collaboration agreement with Lonza for manufacturing of sabirnetug for clinical development and commercialization should it be approved. This is important because it allows us to leverage Lonza's regulatory expertise, extensive experience in antibody manufacturing and global manufacturing network.

We are also on track to initiate a Phase I study in healthy subjects 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.

We'll provide more information on the plan for that work stream once we have the PK results in hand. We remain committed to delivering on our strategic priority to efficiently and thoughtfully advance the clinical development of sabirnetug for the benefit of patients, caregivers and shareholders.

I look forward to updating you as we work to achieve ALTITUDE-AD Phase II data that we believe will provide the true value inflection for the sabirnetug program. And with that, I'll turn the call over to Matt for the financials..

Thanks, Dan. As a reminder, our first quarter 2024 financial results are available in the press release we issued this morning and in our 10-Q, we will file later today. As of March 31st, we had approximately $297 million in cash and marketable securities on our balance sheet and continue to expect that cash runway to last into the first half of 2027.

R&D expenses were $12.4 million in the first quarter. The increase over the prior year was primarily due to the increased spending to support the ALTITUDE-AD trial. G&A expenses were $5.3 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 $17.8 million in the quarter. We are off to a strong start with ALTITUDE-AD. We are well capitalized to execute on the study and to develop a subcutaneous formulation of sabirnetug.

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.

Operator?.

[Operator Instructions] And our first question will come from the line of Tom Shrader with BTIG..

I have a couple of quick ones. First for Matt, is R&D about stable now, or are we expecting it to go up significantly? I know you're probably early in enrollment but you probably had some upfront costs.

So where is R&D now compared to what you expect over maybe the next 2 years?.

It's going to trend up for the next couple of quarters and then flatten out and then go down. So it's -- but if you notice, R&D this quarter was more than any quarter that we ever had and it's going to go up and sort of plateau for a couple of quarters and then come down..

Okay. Perfect. And then on the subcu formulation, do you have a sense of what you're looking for? Is the general idea here to do a quick study show you can match AUC and then maybe wait for the field to figure out if AUC is really the deliverable for a subcu antibody.

Is that kind of the plan?.

Thanks, Tom. This is Dan. I'll just quickly comment on that. Maybe Jim or Eric might give. I think -- for us right now, I think the important thing is getting the healthy volunteer study up and evaluating the PK. And I think there is considerable optionality to observe sort of where the field heads, both from a clinical and regulatory perspective.

So I think we're still sort of in the TBD as to the next step for subcu but certainly want to get these Phase I results in hand as quickly as possible..

Yes. And maybe just quickly, yes, for the first study in healthy volunteers, I think the goal was really just a match AUC. The next study which would occur in patients, we haven't develop that, plan that, design that completely by any means.

But since it will be in patients, then we have a lot of other options in terms of biomarkers and target engagement and other things that we did in our INTERCEPT study. But this first study is just based on AUC..

Our next question will come from the line of Paul Matteis with Stifel..

This is James [ph] on for Paul. And maybe just a follow-up on the subcu and just curious how you're kind of thinking has evolved. Do you think you can ultimately get to a plaque busting dose with the subcu, or is the subcu more focused on oligomers? Just kind of curious what your thoughts are there.

And then also maybe just quickly, just curious when you think about, what you're most interested in, in the upcoming donanemab AdComm and what you think some of the implications may be for the broader Abeta space?.

Yes. Well, maybe I'll answer the first one and then pass it over to Dan for the second one, or the others. But anyway, for the subcu, I don't think we look at that as being different than we saw in our INTERCEPT study in terms of plaque reduction versus oligomer target engagement.

I mean it's -- oligomer target engagement is something that's important for this antibody but having some plaque reduction as long as you can do it without a lot of ARIA isn't a bad thing either. So the goal from that standpoint is really no different with the subcu effort versus the IV effort that we had in our Phase I study..

Thanks, Eric. And James, in terms of the AdComm for donanemab, I think the -- that session will principally focus on 2 main concerns that the FDA has raised in terms of the treatment duration and the [indiscernible] stratification. So those will be important discussions to have sort of in a public forum.

And I think they will likely have implications for label and market development.

But ultimately, we do think that donanemab likely will be approved and really will become a commercial marketer of a product in the Alzheimer's space which we take as a positive as this is still sort of the early days of commercial infrastructure build and providing greater access to patients.

So certainly, it was a bit of a curveball for Lilly, presumably but I think the AdComm should go reasonably well and continue to underpin the growth of this treatment modality..

Our next question comes from the line of Pete Stavropoulos with Cantor Fitzgerald..

This is Samantha Schaeffer on the line for Pete. Now that you have presented the P1B data at multiple conferences and have extensively socialize the data, we're curious to hear if you have any updated thoughts on the potential mechanisms behind the lack of ARIA-E and APOE homozygote and observed only in females.

Is this pattern just by chance, or is there a plausible mechanistic reasoning?.

Yes, let me go -- and those are really good questions and we've thought about it a lot, of course. I'm not sure that we have an absolute answer to them. The fact that we didn't have any ARIA in the APOE4 homozygous. First of all, obviously, it's really encouraging for this particular antibody.

But mechanistically, why that would be, just to speculate, we could say not all plaques are exactly the same. Our antibody is targeting oligomers primarily with a little bit of plaque reduction, with some plaque reduction in addition.

So I think as we learn more about sort of plaques in general at a biochemical level, that we're going to start finding more and more that there are differences in plaques and differences in the way antibodies bind to different forms of plaque.

But at this point, it's all speculation, obviously, in our Phase II study, we're going to be looking really carefully for ARIA in APOE4 homozygous. The question you raised about the fact that the ARIA cases were in women is a really good question. And interestingly, nobody has asked it before. But yes, we've thought about that.

And again, it's kind of like the lack of ARIA in the E4 homozygous. It is a small study and that could be by chance the same as with the lack in the E4 homozygous. But it does make you scratch your head a bit.

And I think as we start to understand more about sex differences in whether it's the efficacy of the antibodies or in this case, ARIA rates, there's just a lot that we don't know. And so that's another thing that we'll obviously keep a close eye on in our Phase II study but really good question..

[Operator Instructions] Our next question comes from the line of Jason Zemansky with Bank of America..

Congratulations on the progress. Curious as far as your enrollment expectations for ALTITUDE, especially given the availability of lecanemab and potentially donanemab in the future.

Can you talk a little bit about what you think the implications are and whether or not the availability of either both of those antibodies are going to impact what you see? And then a follow-up, if I may..

Yes, Jason. So thanks for the question. And I think based on the scripted word portion of the call, we were highly encouraged with the early phase of the ALTITUDE study and encouraged that the rate of -- level of interest engagement from sites and how we're doing in the study generally.

So I think for the moment, we feel really good about sort of the Phase I data informing and drawing patients' attention to the study. And I think as we -- we'll see where we get to as donanemab approval and so forth. But right now, we are feeling pretty good about the rate of enrollment in ALTITUDE..

Got it. And then as far as the subcutaneous formulation goes, is there a possibility or at least a protocol where you can use if the healthy volunteer study goes well, use that within ALTITUDE potentially.

Is there some mechanism that would permit bringing that in, or would you have to wait for a separate study?.

So I guess I'd take that one. Yes, in our case, theoretically, of course, it would be possible to try to put it into ALTITUDE. But ALTITUDE is a Phase II study, it's designed -- it's completely designed. So I think that would be a challenge logistically to actually do.

Again, what we will do after our healthy volunteer study for the subcu formulation is moved to patients. And again, we can do a lot of the same things that we're doing in the ALTITUDE study. In fact, we probably will. But I don't think you would try to insert that into the actual Phase II ALTITUDE study..

And this concludes our Q&A portion. I'd like to hand the conference back over to Alex Braun for closing remarks..

Thanks, Norma and thanks for everyone for listening today. If you have any further questions, we're always available at the company; please, reach out. All right. Have a great day..

This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone, have a wonderful day..