Acumen Pharmaceuticals Inc
NASDAQ:ABOS
Earnings Call Analysis
Q4-2023 Analysis
Acumen Pharmaceuticals Inc
Acumen showcased promising signs of clinical progress during the call. Following a successful Phase I trial, the team is focused on advancing sabirnetug, a novel therapeutic for early Alzheimer's disease (AD). Key to this strategic trajectory is a Phase I study in mid-2024, aimed at developing a subcutaneous formulation for sabirnetug, enhancing the drug's convenience, and potentially its competitive edge.
Financially, Acumen presents a strong position with $306 million in cash and marketable securities at the end of 2023, a notable increase due primarily to a public offering and debt financing. Matt Zuga, the executive spearheading the financials, indicates that this should sustain operational activities into the first half of 2027. However, there's an observable hike in R&D and G&A expenses, which led to an operational loss of $61.1 million; despite this, the company is poised to finance the upcoming Phase II ALTITUDE-AD study and further develop sabirnetug.
The Phase II ALTITUDE-AD study, with 540 participants across three arms, aims to provide sufficient power to determine the drug's efficacy using the iADRS at 18 months as a primary outcome measure. Despite no immediate plans to modify the study based on recent regulatory feedback, such feedback is anticipated and will be explored if relevant to the donanemab Adcomm findings.
While the company's short-term focus remains on the Phase I bioavailability study, there's an open discussion around the possibility of integrating a subcutaneous (subcu) dose option in the later stages of the ALTITUDE-AD study, showcasing Acumen's proactive planning for sabirnetug's administration methods.
Acumen is prepared to adapt based on interim analysis outcomes, which are designed to offer early insights and potentially minimize delays between the completion of Phase II and the initiation of Phase III studies. This adaptability extends to the design of drug development programs, aiming to reduce potential 'white space' by avoiding unnecessary study redesigns. While specifics of the interim analysis algorithm are under wraps, it's clear they place value on a multivariate approach that includes both biomarkers and clinical scales.
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Ladies and gentlemen, thank you for standing by. Welcome to Acumen Pharmaceuticals Full Year 2023 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 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 Daniel 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 related slide presentation 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. 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's 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 nonproprietary name sabirnetug delivered positive and exciting Phase I results first presented at AAIC last July. You'll 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'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 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 abeta oligomer target engagement assay from our Phase I INTERCEPT-AD study at the International Conference on Alzheimer's and Parkinson's disease or ADPD 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 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 I results in their entirety, I encourage you to go to 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-abeta field. We knew going into our Phase I study that sabirnetug possess high selectivity for abeta oligomers. Why does this matter? Unlike abeta monomers and insoluble Amyloid plaques, abeta oligomers are toxic and distinct in important ways, in particular, to neurons and synapses. Our approach with sabirnetug is to selectively target toxic abeta 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 AD results exceeded our expectations and provide 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 are making great progress with the launch of our Phase II 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 I study expected for mid-2024. And with that, I'd like to hand the call over to Eric.
Thanks, Dan, and thanks to those listening into 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 have 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 I 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 I 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 3 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 2 main pathologic hallmarks of Alzheimer's disease. Remarkably, there were additional clear effects on synaptic biomarkers and suggesting sabirnetug's target engagement of neurotoxic oligomers may protect synapsis after only 3 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 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 3-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 1-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 4 weeks. Extensive PK/PD modeling of our Phase I 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 I results have allowed us to move to our next study that will more definitively investigate how uniquely targeting abeta 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 prefer to thank Dan and the entire team at Acumen for their warm welcome. I've been onboard for nearly 2 months now. And in that time, I've grown even more excited about the potential for abeta oligomer selectivity to offer a next-generation Alzheimer’s treatment. At its heart, I see the sabirnetug program as testing a very clear hypothesis. Abeta 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 I 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 advantageous for trial recruitment and site readiness. As Dan mentioned earlier, we are also planning to initiate a Phase I 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 to 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 3 administrations of drug underscore the potential of sabirnetug in targeting abeta oligomers for the treatment of early AD. We believe sabirnetug's clinical development will continue to move the 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 I 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 II 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. Operator?
[Operator Instructions] The first question comes from Neena Bitritto-Garg with DB.
So 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 III study. Can you just walk us through, I guess, the rationale for doing that interim analysis, some of the protocol adjustments that you're expected to make in ALTITUDE-AD 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.
Tate, this is Dan. Maybe I'll quickly take that. So great question. In terms of the interim analysis, these will not be analysis 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 it progress towards a Phase III 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 to potentially minimize the white space between the Phase II and the Phase III.
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 A-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, we 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.
The next question comes from Thomas Shrader with BTIG.
This is Sam on for Tom. So for subcu, is 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 ALTITUDE-AD study?
So Sam, thanks for your question. And I think the quick answer on that is it's the next phase of development for subcu beyond the Phase I is yet to be determined or decided. So our immediate focus is on getting this Phase I healthy volunteer bioavailability PK study done as a means to really inform what the next dosing strategy and study might be for a Phase II 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 I as the primary gate prior to describing in greater detail the Phase II plans.
The next question comes from Paul Matisse with Stifel.
This is James on for Paul. Maybe just a quick one on the Phase II. I guess, can you talk about how you powered the study and what you're looking to see in terms of being a clear win there? And then maybe just quickly on -- again, following up on this interim. Just at a high level, curious if you're thinking about the biomarkers or clinical scales or just kind of a collection of both of those data sets? Just curious what you can share in terms of what that may actually consist of.
Thanks, James. And Eric, do you want to take that one?
Yes, sure. Thanks, Dan. So for our Phase II ALTITUDE-AD study, as I mentioned, it's 540 participants with 180 per arm. That for the iADRS gives you pretty typical power for a Phase II study. So we feel like that should really answer the question in terms of how the program develops. We'll also look at a variety of biomarkers, most of which we looked at in our Phase I study too. And so it will be really interesting to see after 18 months of treatment, [ tau's ] biomarkers response since we actually already saw a response after just 3 doses in essentially 3 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. And so -- and again, as Dan mentioned, the utility of that is to reduce the white space between a Phase II and a Phase III trial because if the algorithms look positive, one of the things that tells you is that the study design of the Phase II study is good. And a lot of times, what creates white space 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.
The next question comes from Colin Bristow with UBS.
This is King on for Colin. Just a quick one following the earlier question on the subcu formula. Since the earlier question was more centered around for maintenance study. So for subcu as initial therapy, like as in the upcoming subcu bioavailable study, what dosing charts and dosing schedules are you currently thinking, especially with regards to Eisai's recent pushbacks for subcu dose as initial therapy, do you think is reasonable to start with some lower doses and test out for the safety first.
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 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's 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. And maybe a quick follow-up question, if we may. So how do you view some of the evolving data in the field include the most recent update from Roche trontinemab.
Sure. I can take that. I think we noted the ADPD the trontinemab data, which is early but encouraging. We took the view that targeting oligomers as a differentiated mechanism from a gantenerumab shuttle construct, which is the trontinemab. And so we're very much committed to exploiting the oligomer targeted mechanism of sabirnetug and 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 interesting and something we're looking at but staying very focused on execution for sabirnetug.
The next question comes from Geoff Meacham with Bank of America.
This is Jason on for Jeff. Congratulations on the progress. I wanted to ask maybe a little bit more broadly. We've seen the publication of a number of recent studies that have found that a number of the signals or biomarkers for amyloid beta appear quite some time before the symptoms, I think 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, has that influenced 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 kind of either a reversal of the symptoms or delaying them?
Yes. So Dan, do you want me to take that one great question. So yes, one of the ways that the field has made some real progress in the last 10 years and maybe even the last 20 years is the understanding of this fact that, as you point out, that you develop the plaques 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 amyloid or abeta 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 they 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 or some technical reasons why that's a challenge. But what's really important, I think, is that for drugs like lecanemab and donanemab and potentially even aducanumab, you're seeing a signal in people who have either MCI 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 and 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. 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 potentially using, again, kind of biomarkers and other indicators rather than waiting for several years that it might take to detect a meaningful change. And I'm again kind of curious, has that translated to your discussions with the regulators? And again, are we thinking ahead to maybe a shorter Phase III if need be?
Yes. Having read the draft guidance like a lot of times for these draft guidance. It's a little hard to read between the lines, and they certainly did have some language in there about shortening timelines 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 need 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 try to get accelerated approval for sabirnetug 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 III design.
The next question comes from Ananda Ghosh with H.C. Wainwright.
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 were seeing? And what's the probability of success in terms of some of these anti-abeta immunotherapy trials. Are there other associations, which has been done 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 2 biomarkers so as to kind of have an impact in either CDR-SB or iADRS.
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. And they've 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 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 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 [indiscernible] the trailblazer studies, that's their primary. They were happy to see that. 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 becoming a consensus opinion now is that you actually have to get plaque below a certain threshold. And this is something that we at Acumen 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 goal seems to be based on existing data that you want to get below 25, say, [indiscernible] or most 30. So if you want to -- if your target is plaque, that's what you need to do. But again, our target is not plaque. Our target is oligomer. 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.
This concludes today's conference call. Thank you for your participation. You may now disconnect.