Acumen Pharmaceuticals Q1 2023 Earnings Call Transcript

Quartr
Provided by Quartr
May 9, 2023

Key Takeaways

  • Acumen Pharma completed enrollment in its Phase 1 INTERCEPT AD trial of ACU-193, with topline safety, CSF PK, and target engagement results expected in Q3 2023.
  • ACU-193 is a monoclonal antibody with high selectivity for amyloid-β oligomers—the most neurotoxic species—and may offer a more favorable safety profile (lower ARIA-E) than plaque-targeting antibodies.
  • Preliminary CSF pharmacokinetic data from the 25 mg/kg cohort showed antibody concentrations substantially above reported oligomer levels, supporting every-4-week dosing in the next study.
  • Momentum in Alzheimer’s therapeutics from lecanemab and donanemab validates the amyloid hypothesis, and Acumen plans a Phase 2/3 design with an interim analysis to potentially expand directly to a registrational trial.
  • Acumen ended Q1 with approximately $184 million in cash and marketable securities, expecting runway through 2025 while advancing ACU-193 development.
AI Generated. May Contain Errors.
Earnings Conference Call
Acumen Pharmaceuticals Q1 2023
00:00 / 00:00

There are 10 speakers on the call.

Operator

Good day and thank you for standing by. Welcome to the Acumen Pharma Q1 2023 Conference Call and Webcast. At this time, all participants are in a listen only mode. After the speakers' presentation, there will be a question and answer Please be advised that today's conference is being recorded. I would now like to hand the conference over to Alex Braun, Head of Investor Relations.

Speaker 1

Thanks, Jill. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended March 31, 2023. With me today are Dan O'Connell, our Chief Executive Officer Doctor. Eric Stiemers, our Chief Medical Officer and Matt Zuga, our Chief Financial Officer and Chief Business Officer. Before we begin, may 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.

Speaker 1

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 the accompanying 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 any accompanying presentation as a result of new information or future results or developments. After our prepared remarks, we'll open the call for Q and A.

Speaker 1

I'll turn the call over to Dan.

Speaker 2

Thanks, Alex. Good morning and thank you everyone for joining us today. The Q1 of 2023 marked the completion of enrollment in our Phase 1 INTERCEPT AD trial evaluating AC193 in early Alzheimer's patients. The study is near completion with top line results expected in the Q3. For those of you who may be new to Acumen, our product candidate AC193 is differentiated from other monoclonal antibodies studied in Alzheimer's disease based on its high selectivity for abeta oligomers.

Speaker 2

Scientific consensus asserts that oligomers are the most toxic form of abeta And once they bind to neurons, they inhibit synaptic function and induce neurodegeneration. We are pleased that our top line results are positioned to provide important Clinical proof of mechanism data for a monoclonal antibody developed to selectively target toxic abeta lignors in the effort to develop the next generation therapeutic for Alzheimer's INTERCEPT AD will provide valuable information required to finalize the design of our next phase for the program, including dose selection. At present, we have growing confidence that every 4 week dosing is a viable scenario for AC-one hundred and ninety three. In addition, as previously disclosed, Preliminary CSF PK data from Cohort 3, our 25 milligram per kilogram single ascending dose cohort, showed ACU-one hundred and ninety three concentrations substantially above reported levels of abeta oligomers, indicating this may be a dosing option to include in our next study. We continue to prepare for Phase twothree activities in anticipation of successful results from our Phase 1 study and end of Phase 2 meeting with the FDA to discuss the design of the next trial is anticipated to be held in the Q4.

Speaker 2

As previously disclosed, the study design incorporates an interim decision to expand the size of the study from a Phase 2 to a Phase 3 study, which is the most expeditious route to a BLA registration. We along with the rest of the field are encouraged by the positive momentum in the evolving Alzheimer's landscape, we are keen to see upcoming outcomes for the LakenaMAb's advisory committee meeting, PDUFA date And any shift in CMS coverage decision, which would increase access and uptake for this therapeutic option for patients. We are also highly interested in digesting the full dataset from denanumab's TRAILBLAZER II Phase 3 study announced last week. We recognize that robust plaque clearance has shown clinical benefit, albeit modest and with safety caveats. We believe there is Potential better option for patients that involve selective targeting of toxic species more closely related to disease pathology and that AC193 embodies that product profile.

Speaker 2

We look forward to sharing our INTERCEPT AD top line data with you in the Q3 of this year, a dataset that will be informative from a safety, target engagement and dose ranging perspective. With that, I'll hand the call over to Doctor. Siems. Eric?

Speaker 3

Thanks, Dan, and good morning, everyone. We continue to work diligently as we near the finish line of our Phase 1 trial. As Dan highlighted, the totality of the data from INTERCEPT AD will be important for choosing doses for subsequent studies of ACU-one hundred and ninety three. This includes data on safety, CSFPK and CSF target engagement. As I mentioned on our last call at the end of March, The assay for our target engagement is designed to measure the complex of A beta oligomers bound to ACU-one hundred and ninety three in CSF.

Speaker 3

We have since run preliminary assay tests using CSF from patients, which have increased our confidence that the assay is performing as intended. Recall that all of our concentrations in CSF are generally reported to be less than 2 picomoleur, which means that our target engagement assay must be very sensitive. We also anticipate announcing exploratory data with our top line results from our Phase 1 study, including CogState computerized cognitive testing as well as arterial SPIN labeling pulse sequences on MRI, which will determine if cerebral blood flow is increased after treatment with ACU-one hundred and ninety three. While these analyses are exploratory and may not result in a clear signal in the small study with a short duration of treatment, These techniques may be employed in the subsequent larger clinical trial using ACU-one hundred and ninety three. As a reminder, we have included typical clinical measures like the CDR summa boxes and the ADAS COG in our Phase 1 study.

Speaker 3

However, because this is a small short study, it is unlikely that those measures will show a drug effect. During the Q1, our team also presented a poster at ADPD in Sweden that demonstrated the utility of a human in vitro model of induced pluripotentstem cell derived excitatory neurons for a better understanding of which Forms of A beta oligomers contribute to the pathogenesis of AD in the human brain. This study found that Voluble A beta size may influence synaptic binding. Low molecular weight soluble A beta species such as monomers, dimers and trimers demonstrated the lowest levels of detectable synaptic binding compared to those of mid and high molecular weight defined as greater than 150 kilodaltons. We believe that these research efforts can contribute to the development of next Generation therapies with higher selectivity for toxic soluble amyloid species that are the most relevant to Alzheimer's pepatogenesis such as ACU-one hundred and ninety three.

Speaker 3

Finally, the success of denatumab in the trailblazer ALKS 2 study announced last week provides further scientific support for the amyloid beta hypothesis broadly. These results build on the success of leucanumab reported in the Phase 3 CLARITY trial. While broadly speaking, these antibodies are both related to The amyloid hypothesis, there are important differences between them. Denanumab targets deposited amyloid plaques and reduces plaque load substantially with dosing every 4 weeks. Leucanumab targets abetaprotofibrils but also reduces plaque growth with every 2 week dosing.

Speaker 3

The rate of ARIA E with bonanumab in trailblazer ALTZ2 was reported to be 24%, while for lekinumab the rate of RIAE was reported to be 12.6%. For both antibodies, about 20% to 25% of RAE cases were symptomatic. We believe that ACU-one hundred and ninety three Targeting oligomers has the potential to have lower rates of ARIA E with equal or better efficacy compared to denanumab and lekanumab. We applaud the well run study results from Trailblazer ALTS-two in CLARITY that solidify forward momentum in the field. While these treatments are a good first generation start, ACU-one hundred and ninety three may further improve the benefit risk profile of a disease modifying treatment for patients and families navigating Alzheimer's disease.

Speaker 3

And with that, I'll turn the call over to Matt.

Speaker 4

Thank you, Eric. Good morning, everyone. As a reminder, our Q1 2020 Free financial results are available in the press release we issued this morning and in our 10 Q that will be filed later today. As of March 31, we had approximately $184,000,000 in cash and marketable securities on the balance sheet and continue to expect that cash to last through 2025. R and D expenses were approximately $8,700,000 in the Q1.

Speaker 4

The increase over the prior year was primarily due to the increased activity in the ongoing INTERCEPT AD trial. G and A expenses were $4,400,000 in the quarter with the increase over the prior year primarily the result of increased headcount as we built the company to for INTERCEPT AD. This led to a loss from operations of $13,100,000 in the quarter. We are encouraged to report top line data for INTERCEPT AD in the Q3 and will remain financially disciplined as we use our capital to advance our clinical program for ACU-one hundred and ninety three and deliver value to patients and shareholders. And with that, we can open the call for Q and A.

Speaker 4

Operator?

Operator

Great. Thank you. At this time, we'll conduct a question and answer session. Our first question, I believe this is James on the phone for Stifel.

Speaker 5

Hi, this is James here. Thanks for taking our question on for Paul Matteis. We were just wondering how are you thinking about the different scenarios for what Your Phase 2 could look like and what exactly you'll be able to test. For example, let's say 193 were to have a similar effect Size as the A beta antibodies, would this study be powered for stats on these clinical scales or would you be looking at something else As at the interim and basing your decision to expand the trial, any color there would be great. Thanks so much.

Speaker 2

Thanks, James. I'm going to invite Eric to comment on that question. Good question.

Speaker 3

Yes, sure. So yes, thanks. Great question. So the team has been working hard on finalizing the design of that study. It's not completely finalized yet.

Speaker 3

But To get to the question that you've raised, we'll look at a number of different things in order to make the decision whether to continue the study as a Phase 2 or to increase the size of the study And make it a Phase 3 registration trial. So that interim analysis involves an algorithm that will look at a number of different things. So of course, they'll look at things like the IGRIS, which will be actually our primary outcome, but also the CDR sum of boxes, the ADAS That sort of thing. Obviously, if you would have statistical significance on one of those Clinical measures and an interim analysis, I think that would be a fairly clear signal to scale up to a Phase 3. But we'll look at a variety of other things.

Speaker 3

And those things may include things like the Computerized cognitive testing that we're using in our Phase 1 study, and also a variety of biomarkers. And just to give you one example of that, phosphorylated tau, both in blood and spinal fluid seems to be a Quite good biomarker for effects of drugs on downstream pathology in Alzheimer's disease. So in other words, If your drug affects amyloid plaques or in our case, A beta oligomers, if you see a change in phospho tau, that really gives you a sign that You're having an effect on the underlying disease process. So we have an algorithm put together. We'll look at several different things like that.

Speaker 3

And then that will trigger the decision of do you increase the size of the study to a Phase 3 Or do you just continue it out as a Phase 2 study? So hopefully that addresses to the question that you brought up.

Speaker 5

Yes, very helpful. Thank you.

Operator

Great. I will move the next question into queue. Hold on, please. Okay. Our next question comes from Tom Schroeder with BTIG.

Operator

Go ahead with your question.

Speaker 6

Good morning. Thanks for taking the question. You're doing all this elegant work with, I think, one of the biggest Questions in the field, which is which oligomers really matter. Is it changing your thoughts on target engagement? I assume you'd like to have antibody levels that only hit the relevant particles.

Speaker 6

So is it are you learning That 2 picomoles is an overestimate or do you think you need to get most of the particles in order to be safe or is That's something you need to read out from clinical data. Thanks.

Speaker 3

So maybe I'll take that one too. So again, I always have to So thanks, Calvin, another good question. But I

Speaker 2

always have to preface

Speaker 3

just like I'm a clinical trialist by nature. And so I think the real answers Ultimately have to come from the clinic. But as our poster illustrated at ADPD, There's a lot that we're still learning about what are the most toxic species. We Thus far, it would appear that the species that ACU-one hundred and ninety three targets are the ones that are relatively more toxic. I mean the most toxic that we've been able to find We're going to put it the other way around.

Speaker 3

We don't see any evidence that AC193 binds to species that are not toxic. But again, the proof is always in the clinic. The one other point that's some interest So this is a little bit more hypothetical, but the concentrations of oligomers in spinal fluid as mentioned are very low, less than 2 picomolar. But no one knows really the concentration of oligomers in interstitial space in the brain. So our antibody AC193 Has to exit the arterial system and then enter the interstitial space and there the actual Maybe higher.

Speaker 3

So again, we've had some Positive results regarding our target engagement assay. We think that assay appears to be working well and We're really looking forward to seeing those results along with all the others in INTERCEPT AD. Great. Thank you.

Operator

Okay, great. I'll bring our next call up to the stage. Hold on, please. And now we have Judah Frommer with Credit Suisse. Go ahead with your call.

Speaker 7

Yes. Hi, good morning. Thanks for taking the questions. First, just as we think about potentially having 2aBID antibodies on the market and any evolved thinking Around including a comparator or a combination arm with another ABNA antibody in any subsequent trials, Whether it's for a potential Phase 3 or beyond that and how could that affect 193s Clinical profile and then separately, can you just remind us or give us some direction on cash runway And potential to get you through Phase 2 or how you would deal with moving into the Phase 3 given the cash position? Thank you.

Speaker 3

Yes. Let me maybe take your first question and then turn it over to Matt for your second question. But in terms of comparators, That question has come up a lot, especially since last week with the dasanumab announcement. I think there's a pretty broad agreement that well, first of all, a head to head trial with drugs like that is very difficult You have to do what's called a non inferiority study, which requires really huge studies. And at least of all the people I've talked to, I don't think anyone really would expect certainly regulatory agencies to require that kind of head to head comparison at this point.

Speaker 3

The other thing that's really of interest is how quickly these things will be taken up In clinical medicine, there was actually a at the American Academy of Neurology meeting a couple of weeks ago, they have what they call fireside chat and Someone who is a, I think a lead investigator in the CLARITY style for lucanumab was talking about all the things that you would have to do to use that in your clinical practice. So these are practicing neurologists. And there was a lot of A bit of angst, I might say, among the clinical neurologists that this is really complicated because the infrastructure for PET scans and MRIs and all that just Isn't there yet. I think denanimab actually will be even more complicated because they have this tau requirement. So now you have to get Maybe an amyloid PET scan and then a tau PET scan.

Speaker 3

So the uptake in the marketplace, I think, is Not going to be overnight. The infrastructure needs to be built that actually to some degree works to our favor because by the time We would launch with AC193 that infrastructure should be much more better developed. So, yes, Stay tuned, but for right now, we do not expect there to be any requirement for a head to head trial. And so Matt, I'll turn it over to you.

Speaker 4

Thanks, Eric. Judah, with regard to the cash, until we Meet with the FDA and know exactly which clinical trial we're going to run next. It's hard for me to tell you exactly when the cash might run out. However, all the forecasting that we've done gives us confidence that our current cash will last to 2025. With that said, As we've disclosed in our filings, any next trial that we do is likely to take us out past 2025.

Speaker 4

And how far out past 2025 we have to go just simply depends on our Interactions with FDA. So, we can get very far down the road, but if we're running a Phase twothree clinical trial, then at At some point, we're going to have to finance. And even if we run a very large Phase 2 clinical trial to be determined, We would have to finance at some point after 2025. I hope that helps.

Speaker 3

Got it. Thank you.

Operator

Okay, great. I'll bring the next question up. Next, we have Collyn Bristow with UBS. Collyn, go ahead with your question.

Speaker 8

Hi, good morning. This is Ping on for Colin. Thanks for taking our question. So at ACPD, Doctor. Selkow from HMS, he presented some interesting findings from his lab That the previously thought that soluble oligomers from the supernatant of the homogenized AD brain, They can actually be repalitated and led to the discovery of new spaces, which they call short cyber wins.

Speaker 8

So that somehow raises the question, if the neurotoxicity and bioactivity previously observed with those soluble brain Drugs are solely attributable to the oleghmos. I think some of the first work were from the same as work from another HMS lab. We've seen that over this finding and we are just wondering like out of curiosity, besides Solubility, how differentiated are this soluble fibrill split from protofibrillase or oligomers, For example. Thank you.

Speaker 3

Yes. So thanks. Doctor. Silko, of course, does some really Cutting edge research and I think your question is a good example of just where the cutting edge is in the field right now. So, one of the things we've talked about before is that AC193 of course targets oligomers.

Speaker 3

Lecanumab was designed to target protofibrils. Now, partly this gets into definitions and Doctor. Selkow in the past and currently We would sort of define anything that's soluble as an oligomer. So protofibril is actually one type of oligomer if you We're going to use that definition, but he recently presented and I think this was part of the ADP presentation that how you define soluble can vary. So in other words, what happens is you centrifuge things and whatever ends up in the pellet is not soluble and whatever ends up And the supernatant is soluble.

Speaker 3

But if you centrifuge it faster and harder, you can change what Is in the pellet and what's in the supernatant. So all of these things are kind of evolving and including Ajay, just to get back to the protofibril differentiation with what ACU-one hundred and ninety three targets, protofibrils are linear structures. The structures that ACU-one hundred and ninety three targets are globular. So the appearance is different On atomic force microscopy. So they're not exactly the same thing.

Speaker 3

We think of those as cousins. So they're both Soluble by usual definitions, they're both toxic, but they don't have exactly the same structure. And so one of the things that's really unique then about AC193 Is that we're targeting a type of oligomer that's unique. I mean, there's no other antibody that targets what we target that's currently in the clinic. So I hope that helps, but it's a complicated question.

Speaker 8

Yes. That's really helpful. Thank you much, Eric. We have a follow-up question. So you mentioned we'll use IGRAs for the FID II as a primary endpoint.

Speaker 8

In Dmab's TBOS to top line, there seems to be some disconnection on Idris benefit for the Hytau Group versus CDR SB, we see CDR SB benefit was more consistent across the tau subgroups. So what's your thoughts on the dMAb data and as well as what were some of your primary reasons to use Idris instead of CDR SB for the FIFTS primary endpoint? Thank you much.

Speaker 3

Yes, right. So, one of the things Just to remind everybody is that we only have a press release from Lilly on the denanimab data. So there's they included quite a bit in their press release, which was great, but they didn't include Everything. So questions like that, how did the ICREIS perform compared to whatever else, the CDR sum of boxes in the high tau group versus the Intermediatao Group, those are things I think we just have to wait for the presentation at AIC to really better evaluate. But our decision and again, things can change depending on new data, But our decision to use the Idris is really based on everything up until this point in time.

Speaker 3

It actually appears to be a very good Scale and as you know, that's what Lilly has used as their primary outcome. So we will be looking forward to Seeing more of those data from Trailblazer ALTS too and we will always Further refine our choices depending on new data.

Speaker 8

Okay. Thank you, Eric. If we may, maybe one last like sub cap question from our side. Will there be additional PKPD or safety updates ahead of the 3Q update? Thank you.

Speaker 3

Yes. We don't anticipate any new disclosures prior to our top line results in the 3rd quarter. And the study was going well. I mean, if there were some new safety information or something, Obviously, we'd have to say something about that. But at this point in any study, even though we're all blinded, We're feeling pretty comfortable about the safety profile.

Speaker 3

And so I wouldn't anticipate any new disclosures before our top line results.

Speaker 8

Thank you so much, everyone.

Operator

Okay, great. And now looks to be our last question. And this is from Charlie Yang with BofA. Go ahead with your question.

Speaker 9

Hi, thanks for taking the question. This is Charlie Yang for Jeff Meacham. Can you talk about just given like the dynamics data potentially to kind of include What was the A beta drugs in your Phase II, Phase III trial?

Speaker 3

I'm sorry, I'm not sure I quite understood the question. Would we include other abeta drugs in our Phase twothree?

Speaker 9

Right. Okay. As a potential combination therapy given the recent.

Speaker 3

Right, got you. Now well, so combination therapy is an important topic and it's something that we at Acumen have certainly had some discussions about. Now Our approach to that would probably be the combination would be a drug that different complementary mechanism, Rather than another one that's related to AAV8 or amyloid in one way or another. In terms of our Phase twothree study, we don't have any Safety data from animal studies based on combinations, say, of leucanumab or tinanumab with ACU-one hundred and ninety three. And so I don't think it would make a lot of sense for our Phase twothree study to allow that kind of combination.

Speaker 3

Obviously, that would make it a lot more Complicated study too. But as we've thought through this, as I mentioned previously, I think that sort of clinical uptake It's going to be pretty slow actually for both lecanumab and denanumab. And so I think for us to run a placebo controlled trial for our Phase twothree is certainly going to be feasible. But looking down the road in terms of combination therapies, which is The future, I think we all agree for Alzheimer's disease. I think it would make more sense to use some complementary mechanism.

Speaker 3

So you would use something that's related to tau, something It was related to inflammation, something like that to combine with ACU-one hundred and ninety three to see whether you get additive or even synergistic effects.

Speaker 5

Thank you.

Operator

Great. I'd now like to turn the call back over to Dan O'Connell.

Speaker 2

Thanks, Jill, and thank you everyone for joining this morning's call. We are very much looking forward Just sharing the INTERCEPT AD top line data in the 3rd quarter, data that will be informative on ACU-one hundred and ninety three as a Selective agent neutralizing Proxic A beta oligomers. So thanks again for joining. We look forward to speaking with you again soon.

Operator

Thank you all for your participation in today's call. This does conclude the program and you may now disconnect.

Powered by Quartr