This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk19: Thank you for standing by, and welcome to the Acumen Pharmaceuticals second quarter 2023 update call. At this time, all participants are in a listening mode. There will be a brief overview followed by a question and answer session. If you would like to ask a question, please press star 11 on your telephone, and you will hear an automated message advising your hand has been raised. If you would like to take yourself out of the queue, please press star 11 again. Today's call is being recorded, and I would now like to turn the call over to Alex Brunn, Head of Investor Relations. Please go ahead.
spk16: Thank you, Lisa. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended June 30th, 2023. With me today are Dan O'Connell, our Chief Executive 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 investor section of the Acumen website to find our press release issued this morning and related slide presentation 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 two 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 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.
spk07: Thanks, Alex. Good morning, and thanks to everyone who has joined us today. A few weeks ago, Acumen presented compelling clinical data in support of ACU193, our asset for the treatment of early Alzheimer's disease. Our positive phase one top-line results solidify ACU193's potential as a future option in the Alzheimer's treatment paradigm. The success of our novel target engagement assay, robust study design, and committed execution enabled us to demonstrate convincing proof of mechanism inclusive of significant amyloid plaque reduction. ACU193 was shown to be safe with a broad therapeutic index and with attractive dosing options for our next phase of development. We believe these results substantially de-risk our asset beyond our expectations at this stage in its clinical development. I'm extremely proud of our team's achievement and would like to thank our employees, site investigators and staff, and patients and caregivers for their dedication to advance AC-193 as a potential best-in-class treatment in this important field. If you have not already done so, I encourage you to go to the investor section of our website and view the webcast from July 17th with our full presentation of the Intercept-AD phase one top line results. Moving forward, we are firmly committed to harnessing the optionality provided by the phase one data set. We have a knowledgeable and adept clinical regulatory and CMC team at Acumen with significant large pharma experience in Alzheimer's drug development. Given the positive intercept AD trial data, including the observed rapid plaque reduction by AC193, our team is working urgently to integrate the findings into both our future clinical plans and our broader strategic priorities. We continue to analyze the data from this study and expect further biomarker data to be available in the fourth quarter. We are also finalizing our doses for our next clinical trial, which Eric will discuss. We have made modest changes to our planned Phase 2-3 design, given AC193's ability to rapidly reduce plaque, such as incorporating amyloid PET into interim analyses. As previously disclosed, our Phase 2-3 design incorporates interim analyses to inform the potential of expanding the size of the study from a Phase 2 to a Phase 3 study, which we believe is the most expeditious route to a BLA filing and potential approval. We continue to anticipate an end of Phase 2 meeting with the FDA to discuss this Phase 2-3 design in the fourth quarter. As mentioned on our July 17th call, we are investigating the viability of subcutaneous dosing of ACU193 as we recognize the potential attractiveness of this mode of administration to expand patient dosing options. We have made meaningful progress on this front and aim to have more details to share later this year. I should also comment that we are continuously evaluating strategic partnerships and are committed to exploring value enhancing opportunities that advance AC193's development and align with Acumen shareholders' interests. Before I turn the call over to Eric, I would like to emphasize the degree to which our phase one results have elevated AC193's profile in the field. We believe AC193's high selectivity to bind to toxic soluble A-beta oligomers in the brain, confirmed by our CSF target engagement assay, affords it the potential to differentiate in terms of clinical efficacy. AC193's ability to significantly reduce plaque in only three months, in line with currently approved and under review anti-A-beta antibodies, we believe further de-risks the asset's potential to deliver efficacy. Monthly dosing provides another important point of differentiation. We intend to drive significant momentum from these timely results and look forward to sharing our progress with you as we execute against our operational and strategic priorities in the weeks and months ahead. With that, I'll hand the call over to Dr. Siemers. Eric?
spk02: Thanks, Dan, and good morning, everyone. As I'm sure you can tell, we are very pleased that our Intercept-AD top-line results for ACU193 provided important clinical proof of mechanism data for a monoclonal antibody developed to selectively target toxic A-beta oligomers. We believe these results support our efforts to develop a best-in-class therapeutic for Alzheimer's disease. In addition to the demonstration of ACU193 bound to oligomers in CSF, our measure of target engagement, we were also very encouraged by the rapid dose-related amyloid plaque reduction at our higher doses, 60 milligrams per kilogram every four weeks and 25 milligrams per kilogram every two weeks. Plaque appeared to be reduced at a rate comparable to approved or soon to be approved monoclonal antibodies at a similar time point after starting treatment, in this case around three months. The finding of plaque reduction further demonstrates the evidence of 193's activity in the brain and is a positive development given the established relationship between robust plaque reduction and slowing of cognitive declines. You will see in the data we presented that 193 also demonstrated robust dose-related target engagement, 193 bound to oligomers, as measured by a novel assay developed by Acumen that exceeded expectations. In fact, we observed that our higher doses approached maximal target engagement. This is a finding that we are particularly excited about given that this is the first time in oligomer-targeted antibody has demonstrated target engagement. Taken together, the decrease in plaque load seen at higher doses and clear demonstration of target engagement with oligomers provide substantial evidence of the intended central pharmacology of ACU193 and proof of mechanism. With regard to safety, 193 was well-tolerated with no drug-related SAEs and overall low rates of ARIA-E. Interestingly, we did not observe ARIA-E in six study participants who were dosed with 193 and who were ApoE4 homozygous, and we will continue to monitor this finding in our next study as a potential point of differentiation compared to other monoclonal antibodies for AD. And based on the pharmacokinetic profile observed, monthly dosing is supported. Importantly, Intercept-AD provided valuable information required to design the next phase of the program, including dose selection decisions. We are currently in the process of modeling doses for our phase two study arms. We have provisionally identified a high dose of approximately 50 to 60 milligrams per kilogram and are considering a mid-dose in the range of 25 to 35 milligrams per kilogram. These would be every four week doses. We are confident in our modeling algorithm and are targeting a mid dose that lies in our target engagement Emax curve in an area where substantial target engagement occurs. This is because at that location, we can potentially observe robust target engagement with regard to oligomers. Based on our phase one plaque reduction data, We believe it is likely that the higher dose in our Phase 2-3 study will result in plaque reduction, and at the lower dose, plaque reduction could be demonstrated in a longer-term study. Finally, as far as broader sediment in the Alzheimer's space, we attended the Alzheimer's Association International Conference in Amsterdam this July, and the general tone of the meeting was very positive. With one monoclonal antibody now having traditional FDA approval and a second antibody likely to achieve traditional approval, after decades of attempting to develop disease-modifying therapies for Alzheimer's disease, the field is now seeing early successes. While these new treatments are not a cure for Alzheimer's disease, they represent a substantial step forward for patients and families. We at Acumen hope to further advance disease-modifying treatments for Alzheimer's disease by developing ACU193 as a best-in-class treatment option. And with that, I'll turn the call over to Matt.
spk23: Thank you, Eric. Good morning, everyone. As a reminder, our second quarter 2023 financial results are available in the press release we issued this morning and in our 10Q that will be filed later today. As of June 30th, we had approximately $172 million in cash and marketable securities on our balance sheet. Following the announcement of our positive phase one results in mid-July, we closed an upsized follow-on offering, which brought in net proceeds of approximately $122.2 million. Our cash on hand is expected to support our current clinical and operational activities into the second half of 2026. Importantly, we believe that we have enough runway to complete a phase two standalone study. As highlighted in our risk factors, this timeline could be affected by clinical trial enrollment rates and other variables, as is typical in the course of clinical development. R&D expenses were approximately $9.1 million in the second quarter of 2023. The increase over the prior year was primarily due to increased costs related to personnel, consulting, and other items related to the Phase I clinical trial, which we completed during the quarter. G&A expenses were $4.3 million in the quarter, 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 $13.5 million in the quarter. We are encouraged by the strong support for the development of ACU193 following our positive phase one results and will remain financially disciplined as we use our capital to advance our clinical program for the asset and deliver value to patients and shareholders. And with that, we can open the call for Q&A. Operator?
spk19: Thank you. If you would like to ask a question, please press star 11 on your telephone. One moment while we compile the Q&A roster. And our first question today will be coming from Colin Bristow of UBS. Your line is open.
spk18: Hey, can you guys hear me okay?
spk20: We can, yep.
spk13: Super. Hey, good morning, guys, and thanks for taking the questions. So I was just wondering, you know, what additional analyses, if any, and sort of referring to CSF and plasma biomarkers, have you done since your top line and anything you could perhaps share with us? And if not, what sort of additional updates and analyses can we expect over the next six to 12 months? And then just maybe, you know, since 193 has a mechanistic profile, which is now sort of closer approximate to the Canamab, Can you maybe just, again, just take us through how you see or what you expect to be the key points of differentiation versus the Canimab? Thank you.
spk02: Well, great. Yeah, so this is Eric. And as far as the biomarker question, it's a really pertinent question. As you well know, CSF and plasma biomarkers is a rapidly developing field. And we've all along said that we are going to follow the field carefully and send off the biomarkers that appear to be the most promising. And so we didn't have all that prearranged at the time we did the study. But what we've now done, and we're in the process of finalizing, is establishing contracts to look at biomarkers to ship the samples to get the results, and those results will come in later in the year. um we'll look at the kinds of things that appear to be promising in the field right now so as you probably know the a beta 42 to 40 ratio especially in csf but also in plasma is receiving a lot of attention p tau especially ptal 217 is receiving a lot of attention we think that gfap because it represents astrocyte function could be very interesting, along with neurogranin because it reflects synaptic function. So we'll be sending the CSF and plasma samples out for those assays. In terms of what results we might anticipate, this was a short study. People got at most three doses of drug. And so it's possible that we would see a drug effect, but not necessarily likely. So the biggest reason for doing these assays in this study is to provide experience for the next study when those biomarkers will actually be very crucial in the development program. So we may see a drug effect in this study, we may not, but the important thing is we'll have then the experience with these assays to apply to our next study. With regard to differentiation, I think I'll just turn that one back to Dan.
spk07: Sure. Thanks, Eric, and thanks, Colin, for the questions. I think in terms of differentiation from licanumab, you know, we're looking at both dimensions of safety and efficacy, you know, with some basis for that supported in the Intercept-AD study, but also, you know, most importantly, the next study being the one to really provide clinical proof of concept and maybe a path towards registration. And those would be the ability to push dose and have better therapeutic coverage over toxic A-beta oligomers is an important aspect of this. And I think the general selectivity for 193, as we've reported it, is 500-fold selected for oligomers over monomer and roughly 90-fold selected for oligomers over fibrils. So we think that the approach that we're taking is to demonstrate comparable or better safety profile, but ultimately we're really looking to drive clinical benefit in terms of efficacy. And that would obviously be a key point of differentiation within the field.
spk13: Great. Thank you very much.
spk19: Thank you. And one moment for our next question. And our next question is coming from Paul Matias. Your line is open.
spk09: Hey there. Thanks for taking my question. I wanted to clarify some of the comments you made around the 25 to 35 mcg per kg once monthly dose that you're planning. What exactly would you expect as it relates to plaque reduction from that dose level? You obviously saw plaque reduction at 25 every other week in this study, and I think in your prior comments, you had talked about CSF exposure data from earlier in this trial supporting that sufficient drug levels were still on board out to, I think, three weeks that you were hopeful in monthly. And so, certainly encouraging that you're pursuing monthly, but I guess, what's the gap there for why you wouldn't expect this dose to match as well on plaque reduction as some of the other A-beta antibodies?
spk02: So, yeah, I guess I can take that. This is Eric. So we've spent a lot of work, obviously, looking at doses for the next study, and we are narrowing down the ranges, as you point out, but we haven't finalized those. So one of the things to be aware of, and this is a little bit of an anecdote, but when we first designed the intercept study, our phase one study, there was a post-dose PET scan in there, and a few people at Acumen said, well, why do you need that? We don't target plaque. And, you know, my reply was, you know, that's the theory. Let's find out what happens. And so when we got the data, you know, we saw we did see this plaque reduction at the higher doses. And I think it's just an important lesson for drug development generally is, you know, don't expect that you know what the results are going to be, but you have to look for those results. And so that's really exactly what we're going to do actually even for both doses in our next study. So I think at the higher dose, based on our intercept data, we have a pretty high likelihood that we'll see plaque reduction at that higher dose. At the lower dose, we really will see what we get. You know, we got some plaque reduction at 25 mg per kg, but every two weeks, so a total of 50 mg per kg every month. But that was only with three administrations of drug. So the next study will be 18 months, so it'll be a longer study, and we'll see what will happen to plaque at that lower dose. Now, again, you know, our target is actually oligomers, our original target. The plaque reduction Um, is not, it's not a bad thing, but it's not necessary for us to have efficacy or at least that's our view. And so I think it's, you know, this is why you do the studies to get the results. And so whether we'll see plaque reduction at the lower dose or not, I think is an open question at this point. Um, but either way, once you get into a phase two, three study, it's all about clinical efficacy. And that's what you really need to be starting to focus on. So it's a great science experiment. We're going to do it. But we're also sort of shifting to where the emphasis is going to be on some of the clinical measures.
spk09: Okay. Thanks, Eric. Appreciate it. And then just one question on the sub-Q. I know it's early, but based on some of your preliminary modeling work, what do you think you might be looking at in terms of you know, the range of different drug volumes you might test and also the frequency of potential injections.
spk07: Yeah, thanks, Paul. I'll hear that. I mean, I think it's a little early for us to comment on those little details. Sorry, there's a little feedback. So, you know, in the fourth quarter, you know, this work is ongoing. We've got some good insights into where we're headed. I do think that the We do not anticipate a high dose of 50 or 60 mgs per kg to be amenable to sub-Q format. I think we could be clear on that. But I do, but we'll have more details, I think, on precisely the plan and how we expect to proceed with the sub-Q in the fourth quarter.
spk08: Okay. All right. Thank you.
spk19: Thank you for your question. One moment for the next question. And our next question will be coming from Tom Schrader of BTIG. Your line is open.
spk05: Good morning. Thanks for taking the call. Given the robustness of your oligomer binding assay, how interested are you in the level of 193 you need to saturate oligomer once plaque is gone? And do you think you'll get those data from the next trial? And then a second inclusion trial is how appealing is to do some screening for tau? I think Lily has shown... or suggested you can really increase the separation between treated and untreated if you screen for tau? Thank you.
spk02: So, yeah, thanks, Tom, for the question. In terms of essentially being in antibody excess versus oligomers, I mean, that's something that we've spent a lot of time thinking about. One sort of detail that I think it addresses the point is that if you take 193, the antibody, and just spike it into spinal fluid from a person with Alzheimer's, you get a little bit of a signal on that target engagement assay, but not very much. But when you give it to people intravenously, and then it obviously goes through brain interstitial space and whatnot, you get a much bigger signal. So it tells us, or at least I would think that that means that it's going through a compartment where the oligomer concentrations are substantially higher than in CSF, which I think intuitively, you know, makes a lot of sense. So in terms of, you know, when are you really in antibody excess? So you're talking about antibody excess in a compartment, bringing in interstitial fluid that you can't directly sample. So it's a tricky thing to figure out. We do know that, and we're constantly doing additional analyses on these data. But if you look at plaque load with regard to target engagement signal, there's no relationship there. There was some thought that maybe the oligomers were sort of attached to the plaques. And the more plaque you had at baseline, the bigger target engagement signal you would get. And there's no real clear evidence that that's the case. So these oligomers are in a compartment. that it appears to be independent, really, of plaque, but it's different than spinal fluid. So the team is working on an assay now to look at free oligomers in spinal fluid, with all the caveats that spinal fluid's not really the compartment where the action is. But the team's working on an assay to do that. It's technically really difficult. Oligomer concentrations in spinal fluid are really low. They're less than 2 picomolar. to start with, and then with the antibody, they'll become even lower. So it's technically a difficult thing to do, but the team is working on that. And then the other thing, just briefly in terms of tau and using that to select patients, that again, which obviously is what Lilly did, it's a really wonderful science experiment. I'm not sure. how that will play out in terms of clinical medicine. Because that means that people have to be amyloid positive based on a PET scan or spinal fluid. And then on top of that, you have to be tau positive, but right in the right range of tau positive. And basically it means that one out of 10 people that you screen for the therapy will be essentially eligible for it. So it's really interesting from a scientific standpoint. I'm just not sure that practically that would be something you could do in the clinic. So we're going to obviously look at tau at baseline and see if that co-varies with efficacy and all that. But we have made the decision not to include tau as an inclusion exclusion criteria. We will, of course, make amyloid positivity an inclusion exclusion criteria, but we're not going to specify a certain level of tau.
spk04: Great. Thanks for the thoughtful answers.
spk19: Thank you. One moment for the next question. And our next question will be coming... One moment, please. Our next question will be coming from Pete Stavropoulos of Cantor Fitzgerald. Your line is open.
spk11: Hi, Dan, Matt, and Eric. Thank you for taking our questions. So, you know, now that you've had several weeks to socialize the data internally and externally, just curious to hear if your thoughts have evolved in terms of possible reasons from a mechanistic standpoint on the lack of ARIA, you know, in APOE homozygotes and observed only in females. You know, is it by chance or is there some plausible mechanistic reasoning? And thank you.
spk02: Yes. Go ahead. That's a great question, too. In terms of it just occurring in females, I honestly don't have a good explanation for that. You know, it could be chance. We'll see. I mean, Alzheimer's disease is a bit more common in females, but still, I don't have an off-the-top answer on that. In terms of the ApoE homozygous, there was a preprint of a paper that just came out this week that actually showed that people who were ApoE4 carriers had a different morphology to their plaque than people who were non-carriers, which would suggest that one possibility is that ACU193 targets an epitope that's maybe a little bit different than the plaque-targeting antibodies that have this relationship between ARIA and ApoE. So the first thing, well, and the other thing, even in terms of the homozygote, I mean, this is small sample size phase one study. We need to see if it replicates. But if it does replicate, I think that is a clear point of differentiation for ACU193, and we'll have to have a lot of further discussions about what the mechanism might be. But it clearly would differentiate ACU193. All right.
spk10: Thank you for taking my questions.
spk19: Thank you. One moment for the next question. And the next question will be coming from Judah, former of Credit Suisse. Your line is open.
spk24: Hey, guys. This is Nick for Judah. Thanks for taking our question. So, with Wakanumab reimbursement and post-infusion monitoring seemingly getting more traction recently, We're just wondering, what's the read-through for 193, if the safety profile that we saw last month holds up? I know we were just talking about differentiation from Lecanumab, but just wanted to confirm, is the ARIA occurrence that we see with Lecanumab, is that the right bar that you'd be looking to be with 193? Thanks.
spk06: Yeah, thanks, Nick.
spk07: I mean, I think clearly we do think that the RA rate for leucanumab is the benchmark for sort of a safety profile in the syndication. And we think 193 can be as good or better on that score. So that is our intent to demonstrate that in a longer duration study.
spk00: Thank you. And our next question.
spk19: Our next question is coming from Charlie Yang of Bank of America. Your line is open.
spk00: Hello.
spk21: Hey, Charlie. Hi. Oh, hey, sorry. I think I missed that earlier. Yes, thanks for taking the question. This is Charlie for Jeff. I have two questions, please. First, can you clarify, you know, regarding the reason for not specifying the tau level? I mean, I understand that it's scientifically interesting, but I think given the consistency in terms of what Lily has shown, you know, with the trial as well as I guess somewhat more of a preliminary or post hoc data with the CanonMAP that also shows some variability in terms of the efficacy in the lower to intermediate tau patients. I'm just wondering, wouldn't it make sense to have that as an inclusion or exclusion criteria to improve the probability of success? That's number one. And number two, can you just discuss... the cash runway that you have, I think just given how long the trial will run for phase two, it seems like by the end of the cash runway, that's around the timing when you'll end up with your cash. So what's the outlook in terms of doing another raise or perhaps having some sort of partnership prior to the actual readout?
spk07: Thanks, Charlie. If you want to hit the first one, I can take the second.
spk02: Yeah, exactly. Again, in terms of using tau as an inclusion-exclusion criteria, which essentially, and we'll see what the label ends up being for the nanomab, but more than likely, you'll have something in the label that will track with that. Again, I think it's a great science experiment. I don't think I think it'll be a real challenge in terms of making that work in the world of clinical medicine. Now, what we are doing in our study, and so our patient population is in early Alzheimer's disease, right? And so these are people with either MCI or mild dementia, but not beyond that. So the lowest mini mental score you can have is 22, for instance. We've also, and this is some ongoing research, analyses that we're doing is in our intercept study, we actually used a hybrid model of looking at amyloid positivity. So it wasn't just based on a PET scan SUVR. It could also be based on a visual read, which may actually be able to allow you to pick up people who are amyloid positive, but not so blatantly that they cross an SUVR threshold. And so that, I think, will help us dial in with this milder population without having to take the extra step of a tau PET scan. Now, looking to the future, and I don't think the field is there just yet, but there may be some time in the future when one of these plasma tau, phospho-tau assays could be useful. You know, we'll obviously continue to track that. But in terms of our next trial, which is a phase two slash three. So if it becomes a phase three trial, that's a registration trial. We have to make that mere clinical practice as it exists more or less today. And so that's that was the overall thought process in terms of the design of the phase two, three trial. So, for the cash question.
spk07: Yeah, thanks. Thanks. Thanks, Eric. So, Charlie, at the current time, we have runway through the interim readouts anticipated for our Phase 2-3 study. Based on our current assessment today, we believe that we have enough runway to finish a Phase 2 standalone study should we not expand it to Phase 3 following a positive interim analysis. Of course, the timeline, you know, this could be affected by the pace of, you know, clinical site initiation, enrollment rates, et cetera. But generally, based on our current planning, we do have cash run way through a standalone phase two study subject to the qualifiers that I mentioned. In terms of partnering, we think the optionality of using a phase two, three design with the potential to expand to phase three, as I mentioned earlier on the call, is the fastest potential path to a BLA filing and potential approval And we would anticipate and continue to have engagement from prospective partners as to potentially working with us, particularly in terms of the phase three portion of the development of AC193. So those things are kind of part of our bread and butter of our strategy and will continue to evolve over the course of the next year itself.
spk21: Great. Thanks so much.
spk19: Thank you. This concludes the Q&A session. I don't see any more questions in queue. And I'd like to turn the call back over to management for closing remarks.
spk16: Great. Thanks, Lisa. Thank you, everyone, today for listening in. We here at the company are always available if you have further questions.
spk19: This concludes today's conference call. Thank you all for joining. You may now disconnect. Everyone, have a great day. Bye. Thank you. Thank you. Thank you. Thank you.
spk01: Bye. you
spk19: Thank you for standing by and welcome to the Acumen Pharmaceuticals second quarter 2023 update call. At this time, all participants are in a listening mode. There will be a brief overview followed by a question and answer session. If you would like to ask a question, please press star 11 on your telephone and you will hear an automated message advising your hand has been raised. If you would like to take yourself out of the queue, please press star 11 again. Today's call is being recorded, and I would now like to turn the call over to Alex Brunn, Head of Investor Relations. Please go ahead.
spk16: Thank you, Lisa. Good morning, and welcome to the Acumen conference call to discuss our business update and financial results for the quarter ended June 30th, 2023. With me today are Dan O'Connell, our Chief Executive Officer, Dr. Eric Siemers, our Chief Medical Officer, and Matt Duga, our Chief Financial Officer and Chief Business Officer. Before we begin, we encourage listeners to go to the investor section of the Acumen website to find our press release issued this morning and related slide presentation 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 two 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 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.
spk07: Thanks, Alex. Good morning, and thanks to everyone who has joined us today. A few weeks ago, Acumen presented compelling clinical data in support of ACU193, our asset for the treatment of early Alzheimer's disease. Our positive phase one top-line results solidify ACU193's potential as a future option in the Alzheimer's treatment paradigm. The success of our novel target engagement assay, robust study design, and committed execution enabled us to demonstrate convincing proof of mechanism inclusive of significant amyloid plaque reduction. ACU193 was shown to be safe with a broad therapeutic index and with attractive dosing options for our next phase of development. We believe these results substantially de-risk our asset beyond our expectations at this stage in its clinical development. I'm extremely proud of our team's achievement and would like to thank our employees, site investigators and staff, and patients and caregivers for their dedication to advance AC-193 as a potential best-in-class treatment in this important field. If you have not already done so, I encourage you to go to the investor section of our website and view the webcast from July 17th with our full presentation of the Intercept AD phase one top line results. Moving forward, we are firmly committed to harnessing the optionality provided by the phase one data set. We have a knowledgeable and adept clinical regulatory and CMC team at Acumen with significant large pharma experience in Alzheimer's drug development. Given the positive intercept AD trial data, including the observed rapid plaque reduction by AC193, our team is working urgently to integrate the findings into both our future clinical plans and our broader strategic priorities. We continue to analyze the data from this study and expect further biomarker data to be available in the fourth quarter. We are also finalizing our doses for our next clinical trial, which Eric will discuss. We have made modest changes to our planned Phase 2-3 design, given AC193's ability to rapidly reduce plaque, such as incorporating amyloid PET into interim analyses. As previously disclosed, our Phase 2-3 design incorporates interim analyses to inform the potential of expanding the size of the study from a Phase 2 to a Phase 3 study, which we believe is the most expeditious route to a BLA filing and potential approval. We continue to anticipate an end of Phase 2 meeting with the FDA to discuss this Phase 2-3 design in the fourth quarter. As mentioned on our July 17th call, we are investigating the viability of subcutaneous dosing of ACU193 as we recognize the potential attractiveness of this mode of administration to expand patient dosing options. We have made meaningful progress on this front and aim to have more details to share later this year. I should also comment that we are continuously evaluating strategic partnerships and are committed to exploring value enhancing opportunities that advance AC193's development and align with Acumen shareholders' interests. Before I turn the call over to Eric, I would like to emphasize the degree to which our phase one results have elevated AC193's profile in the field. We believe AC193's high selectivity to bind to toxic soluble A-beta oligomers in the brain, confirmed by our CSF target engagement assay, affords it the potential to differentiate in terms of clinical efficacy. AC193's ability to significantly reduce plaque in only three months, in line with currently approved and under review anti-A-beta antibodies, we believe further de-risks the asset's potential to deliver efficacy. Monthly dosing provides another important point of differentiation. We intend to drive significant momentum from these timely results and look forward to sharing our progress with you as we execute against our operational and strategic priorities in the weeks and months ahead. With that, I'll hand the call over to Dr. Siemers. Eric?
spk02: Thanks, Dan, and good morning, everyone. As I'm sure you can tell, we are very pleased that our Intercept-AD top-line results for ACU193 provided important clinical proof-of-mechanism data for a monoclonal antibody developed to selectively target toxic A-beta oligomers. We believe these results support our efforts to develop a best-in-class therapeutic for Alzheimer's disease. In addition to the demonstration of ACU193 bound to oligomers in CSF, our measure of target engagement, we were also very encouraged by the rapid dose-related amyloid plaque reduction at our higher doses, 60 milligrams per kilogram every four weeks and 25 milligrams per kilogram every two weeks. Plaque appeared to be reduced at a rate comparable to approved or soon to be approved monoclonal antibodies at a similar time point after starting treatment, in this case around three months. The finding of plaque reduction further demonstrates the evidence of 193's activity in the brain and is a positive development given the established relationship between robust plaque reduction and slowing of cognitive decline. You will see in the data we presented that 193 also demonstrated robust dose-related target engagement, 193 bound to oligomers, as measured by a novel assay developed by Acumen that exceeded expectations. In fact, we observed that our higher doses approached maximal target engagement. This is a finding that we are particularly excited about given that this is the first time oligomer-targeted antibody has demonstrated target engagement. Taken together, the decrease in plaque load seen at higher doses and clear demonstration of target engagement with oligomers provide substantial evidence of the intended central pharmacology of ACU193 and proof of mechanism. With regard to safety, 193 was well-tolerated with no drug-related SAEs and overall low rates of ARIA-E. Interestingly, we did not observe ARIA-E in six study participants who were dosed with 193 and who were ApoE4 homozygous. And we will continue to monitor this finding in our next study as a potential point of differentiation compared to other monoclonal antibodies for AD. And based on the pharmacokinetic profile observed, monthly dosing is supported. Importantly, Intercept-AD provided valuable information required to design the next phase of the program, including dose selection decisions. We are currently in the process of modeling doses for our phase two study arms. We have provisionally identified a high dose of approximately 50 to 60 milligrams per kilogram and are considering a mid-dose in the range of 25 to 35 milligrams per kilogram. These would be every four week doses. We are confident in our modeling algorithm and are targeting a mid dose that lies in our target engagement EMACS curve in an area where substantial target engagement occurs. This is because at that location, we can potentially observe robust target engagement with regard to oligomers. Based on our phase one plaque reduction data, We believe it is likely that the higher dose in our Phase 2-3 study will result in plaque reduction, and at the lower dose, plaque reduction could be demonstrated in a longer-term study. Finally, as far as broader sediment in the Alzheimer's space, we attended the Alzheimer's Association International Conference in Amsterdam this July, and the general tone of the meeting was very positive. With one monoclonal antibody now having traditional FDA approval and a second antibody likely to achieve traditional approval, after decades of attempting to develop disease-modifying therapies for Alzheimer's disease, the field is now seeing early successes. While these new treatments are not a cure for Alzheimer's disease, they represent a substantial step forward for patients and families. We at Acumen hope to further advance disease-modifying treatments for Alzheimer's disease by developing ACU193 as a best-in-class treatment option. And with that, I'll turn the call over to Matt.
spk23: Thank you, Eric. Good morning, everyone. As a reminder, our second quarter 2023 financial results are available in the press release we issued this morning and in our 10Q that will be filed later today. As of June 30th, we had approximately $172 million in cash and marketable securities on our balance sheet. Following the announcement of our positive phase one results in mid-July, we closed an upsized follow-on offering, which brought in net proceeds of approximately $122.2 million. Our cash on hand is expected to support our current clinical and operational activities into the second half of 2026. Importantly, we believe that we have enough runway to complete a phase two standalone study. As highlighted in our risk factors, this timeline could be affected by clinical trial enrollment rates and other variables, as is typical in the course of clinical development. R&D expenses were approximately $9.1 million in the second quarter of 2023. The increase over the prior year was primarily due to increased costs related to personnel, consulting, and other items related to the Phase I clinical trial, which we completed during the quarter. G&A expenses were $4.3 million in the quarter, 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 $13.5 million in the quarter. We are encouraged by the strong support for the development of ACU193 following our positive Phase I results and will remain financially disciplined as we use our capital to advance our clinical program for the asset and deliver value to patients and shareholders. And with that, we can open the call for Q&A. Operator?
spk19: Thank you. If you would like to ask a question, please press star 11 on your telephone. One moment while we compile the Q&A roster. And our first question today will be coming from Colin Bristow of UBS. Your line is open.
spk18: Hey, can you guys hear me okay?
spk20: We can, yep.
spk13: Hey, good morning, guys, and thanks for taking the questions. So I was just wondering, you know, what additional analyses, if any, and sort of referring to CSF and plasma biomarkers, have you done since your top line and anything you can perhaps share with us? And if not, what sort of additional updates and analyses can we expect over the next six to 12 months? And then just maybe, you know, since 193 has a mechanistic profile, which is now sort of closer approximate to the Canamab profile, Can you maybe just, again, just take us through how you see or what you expect to be the key points of differentiation versus licanumab? Thank you.
spk02: Well, great. Yeah, so this is Eric. And as far as the biomarker question, it's a really pertinent question. As you well know, CSF and plasma biomarkers is a rapidly developing field. And we've all along said that we are going to follow the field carefully and send off the biomarkers that appear to be the most promising. And so we didn't have all that prearranged at the time we did the study. But what we've now done, and we're in the process of finalizing, is establishing contracts to look at biomarkers to ship the samples to get the results, and those results will come in later in the year. We'll look at the kinds of things that appear to be promising in the field right now. So, as you probably know, the A beta 42 to 40 ratio, especially in CSF, but also in plasma, is receiving a lot of attention. P tau, especially P tau 217, is receiving a lot of attention. We think that GFAP, because it represents astrocyte function, could be very interesting, along with neurogranin because it reflects synaptic function. So, we'll be sending the CSF and plasma samples out for those assays. In terms of what results we might anticipate, this was a short study. People got at most three doses of drug. And so, it's possible that we would see a drug effect, but not, you know, necessarily likely. So the biggest reason for doing these assays in this study is to provide experience for the next study when those biomarkers will actually be very crucial in the development program. So we may see a drug effect in this study, we may not, but the important thing is we'll have then the experience with these assays to apply to our next study. With regard to differentiation, I think I'll just turn that one back to Dan.
spk07: Sure. Thanks, Eric, and thanks, Colin, for the questions. I think in terms of differentiation from Leucanumab, you know, we're looking at both dimensions of safety and efficacy, you know, with some basis for that supported in the Intercept-AD study, but also, you know, most importantly, the next study being the one to really provide clinical proof of concept and maybe a path towards registration. And those would be the ability to push dose and have better therapeutic coverage over toxic A-beta oligomers is an important aspect of this. And I think the general selectivity for 193, as we've reported it, is 500-fold selected for oligomers over monomer and roughly 90-fold selected for oligomers over fibrils. So we think that the approach that we're taking is to demonstrate comparable or better safety profile, but ultimately we're really looking to drive clinical benefit in terms of efficacy. And that would obviously be a key point of differentiation within the field.
spk13: Great. Thank you very much.
spk19: Thank you. And one moment for our next question. And our next question is coming from Paul Matias. Your line is open.
spk09: Hey there. Thanks for taking my question. I wanted to clarify some of the comments you made around the 25 to 35 mcg per kg once monthly dose that you're planning. What exactly would you expect as it relates to plaque reduction from that dose level? You obviously saw plaque reduction at 25 every other week in this study. And I think in your prior comments, you had talked about CSF exposure data from earlier in this trial. supporting that sufficient drug levels were still on board out to, I think, three weeks that you were hopeful in monthly. And so, certainly encouraging that you're pursuing monthly, but I guess, what's the gap there for why you wouldn't expect this dose to match as well on plaque reduction as some of the other A-beta antibodies?
spk02: So, yeah, I guess I can take that. This is Eric. So we've spent a lot of work, obviously, looking at doses for the next study, and we are narrowing down the ranges, as you point out, but we haven't finalized those. So one of the things to be aware of, and this is a little bit of an anecdote, but when we first designed the intercept study, our phase one study, there was a post-dose PET scan in there, and a few people at Acumen said, well, why do you need that? We don't target plaque. And, you know, my reply was, you know, that's the theory. Let's find out what happens. And so when we got the data, you know, we saw we did see this plaque reduction at the higher doses. And I think it's just an important lesson for drug development generally is, you know, don't expect that you know what the results are going to be, but you have to look for those results. And so that's really exactly what we're going to do actually even for both doses in our next study. So I think at the higher dose, based on our intercept data, we have a pretty high likelihood that we'll see plaque reduction at that higher dose. At the lower dose, we really will see what we get. You know, we got some plaque reduction at 25 mg per kg for every two weeks, so a total of 50 mg per kg every month, but that was only with three administrations of drug. So, the next study will be 18 months, so it'll be a longer study, and we'll see what will happen to plaque at that lower dose. Now, again, you know, our target is actually oligomers, our original target. The plaque reduction Um, is not, it's not a bad thing, but it's not necessary for us to have efficacy or at least that's our view. And so I think it's, you know, this is why I should do the studies to get the results. And so whether we'll see plaque reduction at the lower dose or not, I think is an open question at this point. Um, but either way, once you get into a phase two, three study, it's all about clinical efficacy. And that's what you really need to be starting to focus on. So it's a great science experiment. We're going to do it. But we're also sort of shifting to where the emphasis is going to be on some of the clinical measures.
spk09: Okay. Thanks, Eric. Appreciate it. And then just one question on the sub-Q. I know it's early, but based on some of your preliminary modeling work, what do you think you might be looking at in terms of you know, the range of different drug volumes you might test, and also the frequency of potential injections.
spk07: Yeah, thanks, Paul. I'll hear that. I mean, I think it's a little early for us to comment on those little details.
spk06: Sorry, there's a little feedback.
spk07: So, you know, in the fourth quarter, you know, this work is ongoing. We've got good insights into where we're headed. I do think that the We do not anticipate a high dose of 50 or 60 mgs per kg to be amenable to sub-Q format. I think we could be clear on that. But we'll have more details, I think, on precisely the plan and how we expect to proceed with the sub-Q in the fourth quarter.
spk08: Okay. All right. Thank you.
spk19: Thank you for your question. One moment for the next question. And our next question will be coming from Tom Schrader of BTIG. Your line is open.
spk05: Good morning. Thanks for taking the call. Given the robustness of your oligomer binding assay, how interested are you in the level of 193 you need to saturate oligomer once plaque is gone? And do you think you'll get those data from the next trial? And then a second inclusion trial is how appealing is to do some screening for tau? I think Lily has shown... or suggested you can really increase the separation between treated and untreated if you screen for tau? Thank you.
spk02: So, yeah, thanks, Tom, for the question. In terms of essentially being in antibody excess versus oligomers, I mean, that's something that we've spent a lot of time thinking about. One sort of detail that I think it addresses the point is that if you take 193, the antibody, and just spike it into spinal fluid from a person with Alzheimer's, you get a little bit of a signal on that target engagement assay, but not very much. But when you give it to people intravenously, and then it obviously goes through brain interstitial space and whatnot, you get a much bigger signal. So it tells us, or at least I would think that that means that it's going through a compartment where the oligomer concentrations are substantially higher than in CSF, which I think intuitively, you know, makes a lot of sense. So in terms of, you know, when are you really in antibody excess? So you're talking about antibody excess in a compartment, bringing interstitial fluid that you can't directly sample. So it's a tricky thing to figure out. We do know that, and we're constantly doing additional analyses on these data. But if you look at plaque load with regard to target engagement signal, there's no relationship there. There was some thought that maybe the oligomers were sort of attached to the plaques. And the more plaque you had at baseline, the bigger target engagement signal you would get. And there's no real clear evidence that that's the case. So these oligomers are in a compartment. that it appears to be independent, really, of plaque, but it's different than spinal fluid. So the team is working on an assay now to look at free oligomers in spinal fluid, with all the caveats that spinal fluid's not really the compartment where the action is. But the team's working on an assay to do that. It's technically really difficult. Oligomer concentrations in spinal fluid are really low. They're less than two peak a molar. to start with, and then with the antibody, they'll become even lower. So it's technically a difficult thing to do, but the team is working on that. And then the other thing, just briefly in terms of tau and using that to select patients, that again, which obviously is what Lilly did, it's a really wonderful science experiment. I'm not sure. how that will play out in terms of clinical medicine. Because that means that people have to be amyloid positive based on a PET scan or spinal fluid. And then on top of that, you have to be tau positive, but right in the right range of tau positive. And basically it means that one out of 10 people that you screen for the therapy will be essentially eligible for it. So it's really interesting from a scientific standpoint. I'm just not sure that practically that would be something you could do in the clinic. So we're going to obviously look at tau at baseline and see if that co-varies with efficacy and all that. But we have made the decision not to include tau as an inclusion exclusion criteria. We will, of course, make amyloid positivity an inclusion exclusion criteria, but we're not going to specify a certain level of tau.
spk04: Great. Thanks for the thoughtful answers.
spk19: Thank you. One moment for the next question. And our next question will be coming... One moment, please. Our next question will be coming from Pete Stavropoulos of Cantor Fitzgerald. Your line is open.
spk11: Hi, Dan. Matt Merrick. Thank you for taking our questions. So, you know, now that you've had several weeks to socialize the data internally and externally, just curious to hear if your thoughts have evolved in terms of possible reasons from a mechanistic standpoint on the lack of ARIA, you know, in APOE homozygotes and observed only in females. You know, is it by chance or is there some plausible mechanistic reasoning? And thank you.
spk02: Yes. Go ahead. That's a great question, too. In terms of it just occurring in females, I honestly don't have a good explanation for that. You know, it could be chance. We'll see. I mean, Alzheimer's disease is a bit more common in females, but still, I don't have an off-the-top answer on that. In terms of the APOE homozygous, there was a preprint of a paper that just came out this week that actually showed that people who were ApoE4 carriers had a different morphology to their plaque than people who were non-carriers, which would suggest that one possibility is that ACU193 targets an epitope that's maybe a little bit different than the plaque-targeting antibodies that have this relationship between ARIA and ApoE. So the first thing, well, and the other thing, even in terms of the homozygote, I mean, this is small sample size, phase one study. We need to see if it replicates. But if it does replicate, I think that is a clear point of differentiation for ACU193, and we'll have to have a lot of further discussions about what the mechanism might be. But it clearly would differentiate ACU193. All right.
spk10: Thank you for taking my questions.
spk19: Thank you. One moment for the next question. And the next question will be coming from Judah, former of Credit Suisse. Your line is open.
spk24: Hey, guys. This is Nick for Judah. Thanks for taking our question. So, with Wakanumab reimbursement and post-infusion monitoring seemingly getting more traction recently, We're just wondering, what's the read-through for 193, if the safety profile that we saw last month holds up? I know we were just talking about differentiation from Lecanumab, but just wanted to confirm, is the ARIA occurrence that we see with Lecanumab, is that the right bar that you'd be looking to be with 193? Thanks.
spk06: Yeah, thanks, Nick.
spk07: I mean, I think clearly we do think that the RA rate for leucanumab is the benchmark for sort of a safety profile in the syndication. And we think 193 can be as good or better on that score. So that is our intent to demonstrate that in a longer duration study.
spk00: Thank you. And our next question.
spk19: Our next question is coming from Charlie Yang of Bank of America. Your line is open.
spk00: Hello. Hey, Charlie.
spk21: Hi. Oh, hey, sorry. I think I missed that earlier. Yes, thanks for taking the question. This is Charlie for Jeff. I have two questions, please. First, can you clarify, you know, regarding the reason for not specifying the tau level? I mean, I understand that it's scientifically interesting, but I think given the consistency in terms of what Lily has shown, you know, with the trial as well as I guess somewhat more of a preliminary or post hoc data with the Canada map that also shows some variability in terms of the efficacy in the lower to intermediate tau patients. I'm just wondering, wouldn't it make sense to have that as an inclusion or exclusion criteria to improve the probability of success? That's number one. And number two, can you just discuss the cash runway that you have, I think just given how long the trial will run for phase two, it seems like by the end of the cash runway, that's around the timing when you'll end up with your cash. So what's the outlook in terms of doing another raise or perhaps having some sort of partnership prior to the actual readout?
spk07: Thanks, Charlie. If you want to hit the first one, I can take the second.
spk02: Yeah, exactly. Again, in terms of using tau as an inclusion-exclusion criteria, which essentially, and we'll see what the label ends up being for the nanomab, but more than likely, you'll have something in the label that will track with that. Again, I think it's a great science experiment. I don't think I think it'll be a real challenge in terms of making that work in the world of clinical medicine. Now what we are doing in our study, and so our patient population is in early Alzheimer's disease, right? And so these are people with either MCI or mild dementia, but not beyond that. So the lowest mini mental score you can have is 22, for instance. We've also, and this is some ongoing, analyses that we're doing is in our intercept study, we actually used a hybrid model of looking at amyloid positivity. So it wasn't just based on a PET scan SUVR. It could also be based on a visual read, which may actually be able to allow you to pick up people who are amyloid positive, but not so blatantly that they cross an SUVR threshold. And so that, I think, will help us dial in with this milder population without having to take the extra step of a tau PET scan. Now, looking to the future, and I don't think the field is there just yet, but there may be some time in the future when one of these plasma tau, phospho-tau assays could be useful. you know, we'll obviously continue to track that. But in terms of our next trial, which is a phase two slash three, so if it becomes a phase three trial, that's a registration trial, we have to make that mere clinical practice as it exists more or less today. And so that was the overall thought process in terms of the design of the phase two, three trials. So for the cash question.
spk07: Yeah. Thanks. Thanks. Thanks. So, so Charlie, at the current time, we have runway through the interim readouts anticipated for our phase two, three study, uh, based on our current assessment today, we believe that we have enough runway to finish a phase two standalone study. Should we not expand it to phase three, uh, following up a positive interim analysis, of course, the timeline, you know, this could be affected by the patient, you know, uh, clinical site initiation, enrollment rates, et cetera. But generally, based on our current planning, we do have cash run way through a standalone phase two study subject to the qualifiers that I mentioned. In terms of partnering, we think the optionality of using a phase two, three design with the potential to expand to phase three, as I mentioned earlier on the call, is the fastest potential path to a BLA filing and potential approval And we would anticipate and continue to have engagement from prospective partners as to potentially working with us, particularly in terms of the phase three portion of the development of AC193. So those things are kind of part of our bread and butter of our strategy and will continue to evolve over the course of the next year and so forth.
spk21: Great. Thanks so much.
spk19: Thank you. This concludes the Q&A session. I don't see any more questions in queue. And I'd like to turn the call back over to management for closing remarks.
spk16: Great. Thanks, Lisa. Thank you, everyone, today for listening in. We here at the company are always available if you have further questions.
spk19: This concludes today's conference call. Thank you all for joining. You may now disconnect. Everyone have a great day.
Disclaimer