Operator:.

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'll be a brief overview followed by a question-and-answer session. Today's call is being recorded. And I would now like to turn the call over to John Woolford from Westwicke.

Please go ahead..

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 actual results to differ materially from those described in the forward-looking statements.

Our actual 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 statements.

Daniel O'Connell, President and Chief Executive Officer will begin today's call with a review 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 ACU193.

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?.

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 critical 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 in - 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 with preparing for a future Phase 2/3 trial of ACU193.

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 meetings 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 3 data readouts for bapineuzumabversus gantenerumab and Lilly donanemab 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 ACU193 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?.

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 Aβ oligomers in early Alzheimer's disease, as well as the preclinical evidence to characterize ACU193 selectivity and differentiated profile.

The article is titled, ACU193 and immunotherapeutic poised to 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 AβO 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.

Aβ oligomers had 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 sell that.

ACU193 is unique and differentiated from other monoclonal antibodies studied in Alzheimer's disease, given its high selectivity for Aβ oligomers, relative to other anti-amyloid monoclonal antibodies that are less selective or target different amyloid species, such as Aβ monomers were deposited Aβ 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 slowing.

Given the 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 are, randomized placebo-controlled Phase 1a/B trial as two portions as a 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 two milligrams per kilogram, 10 milligrams per kilogram, 25 milligrams per kilogram 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 16 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 ACU193 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..

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 31, 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. R&D 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 A-1 warrant liability.

The tranche liability and the warrant liability were initially recorded at fair value as a liability on Acumen's balance sheet and are subsequently re-measured 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 at the IPO.

We will continue to work hard over the coming quarters to enroll INTERCEPT-AD 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..

Our first question comes from the line of Paul Matteis from Stifel. You may begin..

Hi, this is James on for Paul, thanks for taking our question.

For the Phase 1 data readout, can you remind us again, we'll it be able to, you know, directly assess percent change in oligomer levels from baseline? And kind of second part there, I guess, what will give you confidence in this readout as you know, we move forward in clinical development, beyond just a dose dependent response on the assay, I guess, how will you know you've reached your kind of target level of pharmaco-dynamic effect, to have confidence moving forward? Thanks..

Yes, 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 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 the 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 antibody 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 dependents would be certainly of interest.

And then finally, the last part of your question, which comes up pretty frequently is you know 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 that sort of thing. But that 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.

But if we get up to 60 mg per kg, 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..

Right, thanks so much..

Our next question will come from the line of Colin Bristow from UBS. Your line is open..

Hi, good afternoon. This is Tin on for Colin, thanks for taking our question and congrats on the quarter. So without first question, our first question, is on your - any thoughts on the same as recent moves for lecanemab and gantenerumab? How do you think things will unfold in the future? And then we've got the second question.

193 particularly, how does a 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..

Hey Tin could you clarify the front part of your question? I heard reference to lecanemab and gantenerumab but I didn't quite follow?.

Oh, yes, sorry it's the same as like, final decision like NCD?.

Oh, sure yes, yes 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 course of supportive Aduhelm 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 ACU193 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 reimbursement perspective. In terms of the plasma half-life for ACU-193 that's we're doing the Phase 1 in patients right now. So we'll have more information that maybe instructive on a comparative basis.

Once we have that data, we don't have that as a as of now, I do think in regards to titration, ACU193 was developed against Aß 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 antibody.

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..

Okay, yes, that's really helpful. Thank you..

Thank you. And I'm not showing any further questions in the queue. I like to talk to Dan O'Connell, President and CEO for concluding oops..

Great, thank you, Victor. Thanks, everyone, for joining us this afternoon. I appreciate your interest in Acumen and ACU193 and we look forward to the next update in the coming in the coming quarter. Thanks..

This concludes today's conference call, thank you for participating. You may now disconnect everyone have a great day..