Q4 2023 Acumen Pharmaceuticals Inc Earnings Call

Participants

Alex Braun; Head, IR; Acumen Pharmaceuticals, Inc.

Dan O'Connell; CEO; Acumen Pharmaceuticals, Inc.

Eric Siemers; Chief Medical Officer; Acumen Pharmaceuticals Inc

Jim Doherty; President & Chief Development Officer; Acumen Pharmaceuticals, Inc.

Matt Zuga; CFO & Chief Business Officer; Acumen Pharmaceuticals, Inc.

Andrew Fein; Analyst; H.C. Wainwright

Presentation

Operator

Ladies and gentlemen, thank you for standing by. Welcome to Acumen Pharmaceuticals full-year 2023 Earnings Conference Call and webcast. (Operator Instructions)
Please be advised that today's conference is being recorded. I would like now to turn the conference over to Alex Grand, Head of Investor Relations. Please go ahead.

Alex Braun

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 that our Chief Financial Officer and Chief Business Officer.
Following Dan, we encourage listeners to go to the Investors section of the Acumen website to find our press release issued this morning and related slide presentation that we'll discuss today. Please note that during today's conference call, we will 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 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 and the accompanying presentation as a result of new information or future results or developments. After our prepared remarks, we'll turn we'll open the call for Q&A.
Now I'll turn the call over to Dan.

Dan O'Connell

Thanks, Alex, and good morning, and thanks to everyone who's joining us today. 2023 was a landmark year for acumen. Our monoclonal antibody for the treatment of early Alzheimer's disease ACY. 93, which recently received its nonproprietary name. So Bernafon delivered positive and exciting Phase one results. First presented at AIC. last July. You'll hear more about these results and how they serve as the cornerstone for establishing suburban tugs, 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're 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 suburban tech 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 ligand target engagement assay from our Phase one intercept AD study at the International Conference on Alzheimer's and Parkinson's disease or AD/PD in Lisbon, Portugal. We will also present analyses at the American Academy of Neurology meeting in Denver. This April, which will introduce the development plan for Sabrina tug 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 one results in their entirety, I encourage you to go to our website where you can find archived presentations, webcasts and releases detailing the Sabrina type data for us. It's difficult to overstate the significance of these results and how they position so versatile in the broader anti A-beta field, we knew going into our Phase one study that some prototype possess high selectivity for a beta ligand. Why does this matter? Unlike a beta monomers and insoluble amyloid plaque, a beta ligand, ours are toxic and distinct and important ways in particular to neurons and synapses our approach with Suburbia targets to selectively target toxic A-beta oligomers and as a consequence to protect synapses in a way that may provide additional therapeutic benefit to patients, especially from an efficacy perspective, the intercept 80 results exceeded our expectations and provide a substantial amount of data indicating some Brintellix drug effect. Overall, we see multiple paths towards to prototype 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 two study altitude D, which remains on track to initiate in the first half of this year. Simultaneously, we are also on track to initiate our subcutaneous Phase one study expected for mid 2024.
And with that, I'd like to hand the call over to Eric.

Eric Siemers

Thanks, Dan, and thanks to those listening into the call today. I'm very pleased with the progress with the clinical development of the burner time 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 have received from the scientific community, our Phase one intercept AD. results and then review our study design for our next trial, ALPHA two DD. recall recall that our Phase one 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 one 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 suburban tug to its downstream pharmacologic activity as first reported in July, a dose dependent increase in target engagement approaching and Y Max was found in CSF and a reduction in plaque measured by amyloid PET was seen at the highest doses of suburban tug in the multiple ascending dose cohorts.
Importantly, after just three administrations of subordinate TUG 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 to burn attempts, target engagement of neurotoxic oligomers may protect synapses after only three administrations of drug.
As Dan mentioned, our team recently returned from ADPD. in Lisbon. The feedback to our data package at medical conferences has been very positive. The excitement around our Intercept AD. results cause us to be even more enthusiastic about beginning our next study, altitude 80 out of two 80 is planned as a randomized, double-blind, placebo-controlled three arm study designed to evaluate the clinical efficacy, safety and tolerability of suburban type 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 that either.
Is it 18 months as the primary outcome measure studies plan to include a one year open-label extension based on the results from intercept 80 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 one 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 suburban TUG, and we look forward to providing further updates as the study initiates and progresses. In short, our Phase one 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.
Thank you, Eric, and good morning, everyone.

Jim Doherty

At Applied. First to thank Dan and the entire team at acumen for their warm welcome. I've been on board for nearly two months now and in that time have grown even more excited about the potential for a beta ligand, more selectivity to offer a next-generation Alzheimer's treatment at its heart. I see this the burner tip program is testing a very clear hypothesis. A-beta oligomers are neurotoxic amyloid species in the brain.
By targeting these oligomers, Sabrina tub may offer a differentiated profile compared to other AD therapies, including the potential for greater efficacy or reduced side effects like ARIA Phase one, Intercept, a D results show that suburban type can indeed bind to its intended target and improved 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 the Barnett's hubs 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 ag that should provide advantageous for trial recruitment and site readiness.
As Dan mentioned earlier, we are also planning to initiate a Phase one bioavailability study in healthy volunteers for a subcutaneous formulation of Savanna TUG in mid 2024. We believe a competitive product profile for the Barnett hub 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 treatment.
Having just recently joined acumen, I can clearly sense that the team's pride in how the intercept a D 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 drug underscore the potential of Karnataka in targeting a beta oligomers for the treatment of early AD. We believe suburban tugs clinical development will continue to move the field forward from our perspective.
And now I'll hand the call over to Matt to discuss the financials.

Matt Zuga

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 that 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 financial resources to deliver against our strategic objectives. The increase from the prior years due to the net proceeds from our public offering last July of approximately $122 million, as well as approximately $30 million from K. two Health Ventures 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 one 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 two 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 the burn TUG for the benefit of patients caregivers and shareholders. And with that, we can open the call for Q&A.

Question and Answer Session

Operator

(Operator Instructions)
First question comes from Nina, but Trico Garg with DB., your line is open again, thanks for taking my question.

And I was just wondering about I know you mentioned recently that you may consider doing an interim analysis in the altitude AD study. In order to determine whether or not you should start a Phase three study. Can you just walk us through, I guess, the rationale for doing that interim analysis, some of that protocol adjustments that you're expected to make in altitude AV based off of recent regulatory feedback? And then anything you can share in terms of how you're thinking about the criteria for that interim analysis would be great. Thank you.

Dan O'Connell

And actually that this is Dan. Maybe I'll take that quickly. I think that So a great question. In terms of the interim analyses these will these will not be analyses that change in any way, the altitude 80 protocol. They're really intended to provide some visibility on data to allow us to make a decision as to whether to progress towards a Phase three study.
So these are not they're not futility analyses, they're not they're no longer expansion analyses, but they will be employed just for the purposes of getting some early visibility to in an effort potentially minimize the whitespace between the Phase two and the Phase three.

Okay. Got it. That's super helpful. And then I guess, any changes that you may consider making to the altitude AB. design based off of feedback from the plant and AnaMantle AdCom?

Dan O'Connell

It's technical. So I don't think we have any a priori expectations to make changes based on the outcome. The outcome of interesting development for the field certainly should serve as a good venue for exploring some of the considerations associated with the TRAILBLAZER two design and the overall, but the minimum dataset we do as perhaps you're referencing, we anticipate using the address at 18 months as our primary outcome measure in altitude, they die. And barring some unforeseen change in development with the AdCom will continue to use the AutoSeis, our primary.

Awesome. Thank you.

Operator

Thomas Shrader, BTIG.

This is Tom on for Tom. Thanks for taking my questions. Both for subcu maintenance therapy and immediate application for subcu dosing? And what are your thoughts on integrating a subcu dose option in the open-label extension part of the up to 80 study?

Dan O'Connell

Thank you So it's certainly on. Thanks for your question. And I think the quick answer on that is the next phase of development for subcu beyond the Phase one is yet to be determined and decided. So our immediate focus is on getting this Phase one healthy volunteer bioavailability PK study done as a means to really inform what the next dosing strategy and study might be for Phase two 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 one as the summary gate prior to run describe in greater detail Phase two plans.

Okay.

Operator

Paul Matteis, Stifel.

Hi, this is James on for Paul. Thanks for taking our question. And maybe just a quick one on the Phase two, I guess. Can you talk about how you powered the study and what you're looking to see in terms of, you know, being a clear win there.
And then maybe just quickly on again, following up on this interim at a high level. Curious if you're thinking about biomarkers or clinical scales or just kind of a collection of both of those datasets. Just curious what you can share in terms of what that may actually consist of.
Thanks very much.

Dan O'Connell

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

Eric Siemers

Yes, sure. And I think, Sam, so for our Phase two altitude AD study, as I mentioned, it's 540 participants with 180 per arm that for the IRSI. gives you a pretty typical power for a Phase two study arm. So we feel like that should really answer the question in terms of and how the program develops.
We'll also look at a variety of biomarkers Most of which we looked at in our Phase one study two and so be really interesting to see after 18 months of treatment Paolo's biomarkers response since we actually already saw a response after just three doses in essentially three months. And 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.
And so and again, as Dan mentioned, the utility of that is to reduce the white space between Phase two and a Phase three trial because if the algorithms look positive, one of the things that tells you is that the study design of the Phase two study is good and a lot of times what creates whitespace in drug development programs is redesigning studies. And 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 on top of alcohol.
One moment for them, yes.

Operator

Colin Bristow, UBS.

Hi, this is Kim on for Colin and thank you for taking our questions. And just a quick one following the earlier question on the subcu formulation versus the earlier question was more centered around for maintenance study. So for subcu as the initial therapy like like, if you're asking the upcoming subcu bioavailability study, what dosing trials and dosing schedules are you currently thinking, especially with regard to E. side, recent prospectus for subcu dose as initial therapy, do you think is reasonable to start with some lower doses and test out for the safety first. Thank you.

Dan O'Connell

It's a nice time to do it or you're going to, please. Yes, no, I think those are all great questions and all questions that we really don't have any 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 maybe starting with starting off with IV administration and then switching to subcu as more of a maintenance dose. So that's not just something that we're thinking about it, something that a lot of people are thinking about, but we'll just need to get actual data before we start to narrow things down on those questions.

Okay, thank you. And maybe a quick follow-up question. If we may say how do you view some of the evolving data in the field, including the most recent update from Roche, Argentina care?

Eric Siemers

Sure.I can say that I think we noted the at AD/PD, the Triton I-Mab data, which is early but encouraging. And we take the view that targeting the ligand versus a differentiated mechanism from gantenerumab shuttle, a construct, which is the minimum. And so we're very much committed to exploiting that the ligand targeting mechanism that's tug generating evidence in support of it as a treatment option and feel that the field in general is large enough to accommodate a variety of different product formats and options. So it's so it's interesting and something we're looking at, but staying very focused on execution before Sabrina, one moment for us.

Operator

Geoff Meacham, Bank of America. Your line is open.

Good morning. This is Jason on for Jeff. Thank you so much for taking our questions and congratulations on the progress. Wanted to ask maybe a little bit more broadly, we've seen the publication of a number of recent studies that I've found that a number of the signals are biomarkers for amyloid beta appear on quite some time before the symptoms.

Dan O'Connell

I think was specifically regarding the ratio of A. beta 42 to A-beta 40 pops up 14 years prior to the onset of symptoms. And I'm curious it has that influenced in the design of some of your clinical studies. Do you think you may need to go a little bit earlier, or do you feel that kind of early AD is sufficient enough for for kind of a either a reversal of the symptoms or delaying?

Eric Siemers

Yes. So Daniel, let me take that one great question. So yes, that one of the ways that the field has made some real progress in the last 10 years and maybe the last 20 years is the understanding of this fact that as you point out that you develop the plaques are 15 to 20 years before you develop any symptoms.
And there has been a thought in the field that if you were going to target Android or a beta in one way or another that because of that time period, you actually had to do it before people had any symptoms at all. And there are ongoing studies and there have been ongoing there have been studies of what's called preclinical Alzheimer's disease. So in other words, you have the plaques, but you don't have any symptoms yet thus far, none of those studies have been successful. I think there's a lot of reasons for that.
Partly it's the study design is much more complicated. The studies need to be longer. Some technical reasons why that's a challenge. But what's really important, I think is that for drugs like look here at I-Mab and demand, I-Mab and potentially even aducanumab, you're seeing a signal in people who have either MMCI. or mild dementia with Alzheimer's pathology.
And the reason why that's so important is that means you don't have to go all the way back to that preclinical stage where the study designs are much more challenging, did not as well worked out. So we feel really good about the fact that we are in this population of MCI. plus mild dementia, other drugs are starting to see a signal there. And apparently what that means is that's not too late in the process. And that's, I think, a really good insight for the field broadly.

Interesting, thanks for the color. And then maybe a quick follow-up, if I may. The FDA released draft guidance for Alzheimer's earlier this month. I think one of the big takeaways here, is that really codified the driver push to maybe shorten the length of clinical studies on potentially using again kind of biomarkers and other indicators rather than waiting for several years that it might take to detect a meaningful change. Again, kind of curious, has that translated to your discussions with the regulators? And again, are we thinking ahead to maybe a shorter Phase 3 , if need be?

Dan O'Connell

Yes, having read the draft guidance like a lot of times for these draft guidance, it's a little hard to read between lines. And they certainly did have some language in there about shortening and time lines based on using biomarkers, but then they talk about a validated biomarker. But what is validated to really mean. So there's still a number of things that it needs to be worked out. It may be that they were directing some of those comments to just taking an antibody that is IV and then converting it to subcu. I think that's probably the most straightforward case for more of a reliance on the biomarkers.
But at this early stage, we've not really considered using a biomarker alone to get accelerated approval for some burn attack because, of course, the payers, at least to this point haven't really offered to reimburse for accelerated approval so we'll continue to watch that very closely. But at this point, I don't think we have enough information to make any real changes in what we would anticipate would be our Phase three design product.

Thank you again for the color.

Operator

Andrew Fein, H.C. Wainwright.

Andrew Fein

You I think you know, the first question is, David, what are some of the advantages of IDR is over CDRSE. and the rationale behind choosing IVRS or CDRSB. for the altitude study.
And the second thing is, you know, there has been lot of correlations Belle Meade based on how much of block reductions you are seeing and what's the probability of success in terms of some of these anti EBITDA immunotherapy trials or are there other, you know, associations which has been done with other biomarkers such as tau wanting to order two and seven, where you know where we are at least some modeling based studies can tell you to what extent do you might see a change you might need to see a change in these two biomarkers, so as to kind of have an impact in in either CDR-SB or ideas?
Thanks.
But yes, any again, I tried to take that one, too. As far as the uses of hydrous 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. And I've actually presented at the 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 sort of the only scale. But what they did say in this most recent draft guidance is that a scale that's a composite of cognitive measures and functional measures.
They have real utility. And that's what the hydro assets. It's a combination of cognitive measures from need us cognitive and functional measures from a scale called the ADCSADL. So we think that is very positive actually in terms of our use of the iris, I would assume that Lilly sits in the Trailblazer studies. That's their primary.
They were happy to see that. And so yes, I think that's a really good clarification from FDA in terms of that those kind of scales in terms of correlations between plaque reduction and clinical benefit. I think what's really unique from the consensus opinion now is that you actually have to get plaque below a certain threshold and this is something that we had active and I've been saying for a long time is that if you're going to target plaque, you have to basically get rid of it.
And so the our goal seems to be based on existing data that you want to get below 25, say Centroid or most 30. So if you were to if your target is plaque. That's what you need to do. But again, our targets not plaque are targeted as oligomers. So it'll be interesting to see what effects we have on plaque. But with our differentiated mechanism. That's really the construct of our development plan.

Operator

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

Alex Braun

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.

Operator

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