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spk01: Thank you for standing by and welcome to the Acumen Pharmaceuticals first quarter 2022 update call. At this time, all participants are in a listen-only mode. There will be a brief overview followed by a question and answer session. To ask a question during a session, you will need to press star 1 on your telephone. Today's call is being recorded and I would now like to turn the call over to John Wolford from Westwick. Please go ahead.
spk03: Thank you, operator. Good afternoon. Thank you for joining us today to review Acumen's first quarter 2022 update on operational progress and financial results. Before we start, we encourage you to read the operational and financial results press release issued this afternoon, which is accessible on our website in the investors section. 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. All these statements are subject to risks and uncertainties that could cause action results to differ materially from those described in the forward-looking statements. Our action results could differ materially due to a number of factors, including the extent and duration of the effects of the COVID-19 pandemic and the timing and extent of recovery from it. Please refer to our recent filings with the SEC for a full review of the risks and uncertainties associated with our business. Forward-looking statements speak only as of the date on which they are made, and Acumen undertakes no obligation to update or revise any forward-looking statement. Dan O'Connell, President and Chief Executive Officer, will begin today's call with a review of select first quarter 2022 business highlights and provide an update on the ongoing Intercept-AD trial. Dr. Eric Siemers, Chief Medical Officer, will then discuss the recent Frontiers in Science article for ACU-193. Next, Matt Zuga, Chief Financial Officer and Chief Business Officer, will provide a brief financial update. We will then open the call for Q&A. I'll now hand the call over to Dan O'Connell, President and Chief Executive Officer. Dan?
spk05: Thank you, John. Good afternoon, and thank you to everyone joining the call today. I'm delighted to be here to review our first quarter and recent progress. We hosted our first public conference call in late March, and during that call we provided a review of our science, the significant differentiation of ACU193 for the potential treatment of Alzheimer's disease, and gave an overview of the ongoing Intercept-AD clinical trial. as well as highlighted our financial resources that are expected to advance ACU193 through multiple clinical milestones and provides a cash runway through 2025. Given that we provided such a detailed update just weeks ago, we're going to keep today's call relatively brief and to the point. To start, we continue to make significant progress with our Intercept-AD clinical trial of ACU193, the first monoclonal antibody developed to selectively target soluble amyloid beta oligomers to enter the clinic. Regarding enrollment, we have experienced continued success in activating new clinical trial sites and enrollment is now ongoing at 11 active sites with four additional sites selected for potential activation. This is up from eight active sites and six additional sites selected when we last spoke at the end of March. Given our progress, we continue to expect to report the top line results from Intercept AD in the first half of 2023. In parallel to conducting the Intercept AD trial, we've also made significant progress in preparing for a future Phase 2-3 trial of AC193. A chronic GLP toxicity study was initiated earlier in the year, and our new drug substance production process and drug product formulation are being finalized. Our team has begun designing the Phase 2-3 study and planning for an end of Phase 2 meeting with the FDA. Our plan is to initiate the next trial, a potential Phase 2-3 trial, rapidly after demonstrating proof of mechanism in the ongoing Intercept-AD trial. As I highlighted during our last call, we've made several senior-level appointments to the company's leadership team across multiple functional areas, and since then we've continued to grow our team, providing additional expertise and experience to support our expected growth over the coming years. In addition to our efforts, we do anticipate growing interest in upcoming clinical and regulatory developments for other novel Alzheimer's disease programs in the coming quarters. including Phase III data readouts for Esai's licanumab, Roche's scantinarumab, and Lilly's dinanumab. While these treatments are targeted primarily at amyloid plaques and protofibrils, not soluble A-beta oligomers, we believe encouraging data from one or more of these programs could lead to additional enthusiasm for ACE193 and its potential in Alzheimer's. I'll now turn the call over to Eric to discuss the recent publication in Frontiers in Neuroscience. Eric? Eric?
spk06: Thanks, Dan. Good afternoon, everyone. Before I turn the call over to Matt, I wanted to highlight that we announced that Frontiers in Neuroscience published the well-supported rationale for targeting soluble A-beta oligomers in early Alzheimer's disease, as well as the preclinical evidence to characterize ACU193's selectivity and differentiated profile. The article is titled, ACU193, an immunotherapeutic poised test the amyloid beta oligomer hypothesis of Alzheimer's disease. We believe there is an emerging scientific consensus that oligomers are the most toxic form of A-beta and that the development of a product that reduces toxicity of oligomers is one of the most promising approaches for the potential treatment and prevention of the progression of Alzheimer's disease. As detailed in the publication, Studies suggest that oligomer-mediated neuronal toxicity is directly responsible for Alzheimer's-associated memory and cognitive problems. A-beta oligomers have been found to interact within synapses of brain cells called neurons, leading to altered neuronal function, which may initiate and perpetuate the process of neurodegeneration, ultimately leading to cell death. ACU193 is unique and differentiated from other monoclonal antibodies studied in Alzheimer's disease, given its high selectivity for A-beta oligomers relative to other anti-amyloid monoclonal antibodies that are less selective or target different amyloid species, such as A-beta monomers or deposited A-beta amyloid plaques. We believe this may lead to improved clinical efficacy compared to other monoclonal antibodies and importantly, an expected lack of ARIA-related safety concerns, which are seen with some other monoclonal antibodies. We also believe there is some potential for possible cognitive improvement in addition to disease swelling. Given this strong rationale and differentiation, we look forward to reporting top-line data from Intercept AD in the first half of next year. As a reminder, Intercept-AD, our randomized placebo-controlled phase 1A-B trial, has two portions as is standard, including a single ascending dose portion and a multiple ascending dose portion. The single ascending dose portion includes four cohorts with eight patients per cohort at doses of 2 mg per kg, 10 mg per kg, 25 mg per kg, and 60 milligrams per kilogram or placebo. The multiple ascending dose portion includes three cohorts with 10 patients per cohort at doses of 10 milligrams per kilogram and 60 milligrams per kilogram dosed every four weeks and 60 milligrams per kilogram dosed every two weeks or placebo. Included in the trial design is the ability to initiate the first cohort of the multiple ascending dose portion after safety and tolerability is demonstrated in the second cohort of the single ascending dose portion. The trial is being conducted in patients with early Alzheimer's disease, those with mild cognitive impairment and mild dementia. To participate in the trial, the patients must be amyloid positive as determined by PET scans. A key objective of the trial is to demonstrate target engagement and proof of mechanism as determined by demonstrating that ACU193 is bound to oligomers in cerebral spinal fluid. Other important outcomes include the evaluation of safety and tolerability, pharmacokinetics, and measures of cognition. The trial is expected to provide a significant amount of data that will be crucial in the design of the planned Phase 2-3 trial, as well as our regulatory strategy. Assuming Intercept-AD demonstrates acceptable safety and tolerability, shows ACU-193 gets into the central compartment, and confirms target engagement, we plan to advance the program into a Phase 2-3 study. With that, I will turn the call over to Matt Zuga, our Chief Financial Officer and Chief Business Officer.
spk04: Thank you, Eric, and thanks to everyone for joining. To start, I want to emphasize that as a result of planning and executing on our private and public financing strategy in 2020 and 2021, we are well capitalized and have the resources to achieve multiple clinical development milestones. As of March 31st, 2022, we had approximately $217 million in cash and marketable securities. Looking ahead, based on our current operating plan, we expect our cash runway to last through 2025. Our strong balance sheet is the result of the proceeds from Series B and IPO financings completed in 2021. Our complete financial results for the first quarter of 2022 are available in the press release we issued this afternoon and in our 10-Q, which will be filed shortly. I'm not going to review our results in detail, but I do want to highlight a few items. RMD expenses were approximately $6 million in the first quarter. The increase over the prior year period was primarily due to the increased activity in the ongoing Intercept-AD trial compared to Q1 2021. G&A expenses were $3.2 million in the quarter, with the increase over the prior year period primarily the result of increased headcount and the cost of going public and being a public company following the IPO. This led to a loss from operations of $9.2 million in the quarter. Note that our comprehensive loss for the quarter was $9.7 million compared to $27 million in the prior year period. The loss in 2021 was primarily driven by a non-cash expense of $23.2 million that represents the changes in fair value of our Series B tranche liability and our Series A1 warrant liability. The tranche liability and the warrant liability were initially recorded at fair value as a liability on Ackerman's balance sheet and are subsequently remeasured at fair value at the end of each reporting period. Both liabilities were extinguished by the conversion of our preferred shares and warrants to common shares of the IPO. We will continue to work hard over the coming quarters to enroll Intercept ADE and look forward to reporting top-line data in the first half of 2023. Importantly, we will continue to operate Acumen efficiently and cost-effectively to ensure our cash runway is maintained through 2025. We thank our shareholders and partners for their ongoing trust and support, and we'll now open up the floor for questions.
spk01: As a reminder, to ask a question, you need to press star 1 on your telephone, and to withdraw your question, just press the panel key. Please stand by while we compile the Q&A roster. Our first question will come from Paul Matias from Stiefel. You may begin.
spk02: Hi, this is James on for Paul. Thanks for taking our question. For the phase one data readout, can you remind us again, will we be able to, you know, directly assess percent change in oligomer levels from baseline? And kind of second part there, I guess, you know, what will give you confidence in this readout as, you know, we move forward in clinical development, you know, beyond just a dose-dependent response. On the assay, I guess, you know, how will you know you've reached your kind of target level of pharmacodynamic effect, you know, to have confidence moving forward? Thanks.
spk06: Yeah. Hi. So, this is Eric. Great question. In terms of looking at something like a percent change in oligomers, just to remind you, what we're really going to be measuring is the concentration of antibody acu193 bound to oligomers so obviously before you've been dosed the the concentration of that is zero you don't have any antibody there so what we'll really be looking for is the presence of acu193 bound to oligomers after dosing those are actually fairly challenging assays to develop, but we've got a really good crew that are actively developing them. I think as a minimum, we would want to demonstrate that we did have antibody and spinal fluid binding to oligomers. We showed this in brains of transgenic mice, so in a sense, this is just confirming it, but still it's something that we definitely need to do. So I think at a minimum we want to say there's antibodies that got in and it binds to oligomers. Depending on the assay sensitivity and just what the data shows, if we can show a dose dependence for that, that would be even better. I don't know that that's a necessary requirement, but dose dependence would be certainly of interest. And then finally, the last part of your question, which comes up pretty frequently, is how much is enough? When you're dealing, I think, especially with these monoclonal antibodies, I think the answer is typically you give as much as you can as long as it's safe. And now at some point you get into some commercial difficulties with just cost of goods and that sort of thing. But up to that limit, if you're safe, the more the better, basically. And so that's one of the reasons why safety is such an important part of this study is But if we get up to 60 mgs per keg and we can do it safely, then I think that would be at least one of the doses to take forward into the next Phase 2-3 study.
spk02: Great. Thanks so much.
spk01: Our next question will come from Colin Bristow from UBS. Your line is open.
spk07: Oh, hi, good afternoon. This is Ting for Colin. Thanks for taking our question and congrats on the quarter. So we go first question. Our first question is on your any thoughts on the same as recent moves for education map and getting your map. How do you think things will unfold in the future? And then we got the second question on 193 particularly. How does the plasma half-life of 193 look like compared to other anti-amyloid antibodies? And do you envision any titration will be needed for 193 when at a higher dose level? Thank you.
spk05: Ting, could you clarify the front part of your question? I heard reference to aducanumab and gantanarumab, but I didn't quite follow.
spk07: Oh, yeah, sorry. It's the CMS, like, final decision, like, NCD.
spk05: Oh, sure. Yeah, right. So I think generally I think there's been a good bit of consternation and frustration within the Alzheimer's space about the CMS decision and certainly Biogen's decision to pull back from the commercial support of at a helm is a bit of a setback, certainly for the company, but we are optimistic that the field has more to offer patients going forward, and that's why we're diligently and strongly committed to developing AC-193 for patients. I think we'll see what the other readouts for some of these later stage products deliver in terms of risk benefit safety profile. And that should be more information for us to learn from both a regulatory and a reimbursement perspective. In terms of the plasma half-life for AC193, we're doing the phase one in patients right now, so we'll have more information that may be instructive on a comparative basis once we have that data. We don't have that as of now. I do think in regards to titration, you know, AC-193 was developed against deviate oligomers, and on the basis of the selectivity for oligomers, we don't think it will have the rates of ARIA that are observed with plaque-targeting antibodies. So we don't anticipate a safety titration, if you will, like some of the other plaque-targeting antibodies have had to undergo. But again, we've got to generate data in the clinic to support some of the underpinnings of that part of the profile.
spk07: Okay, yeah, that's really helpful. Thank you.
spk01: Thank you. And I'm not showing any further questions in the queue. I just want to call back to Dan O'Connell, President and CEO, for concluding remarks. Great.
spk05: Thank you, Victor. Thanks, everyone, for joining us this afternoon. We appreciate your interest in Acumen and AC193, and we look forward to the next update in the coming quarter. Thanks.
spk01: This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.
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