Acumen Pharmaceuticals, Inc.

Thank you for standing by. Welcome to Acumen Pharmaceuticals' full-year 2022 conference call and webcast. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Alex Braun, Head of Investor Relations. Please go ahead.

Thank you, Michelle. Good morning, and welcome to the Acumen Conference Call to discuss our business update and financial results for the year ended December 31st 2022. 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 Investors section of the Acumen website to find our press release issue this morning and related slide presentation that we'll discuss today. Please note that during today's conference call, we may make forward-looking statements within the meaning of the federal securities laws including statements concerning our financial outlook and expected business plans. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Please see slide 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 will open the call for Q&A. Now, I'll turn the call over to Dan.

Thank you, Alex. Good morning, and thank you, everyone, for joining us today. 2022 was a pivotal year for Acumen, marked by significant progress advancing the critical development of ACU193, the first monoclonal antibody tested in Alzheimer's patients that was discovered and developed to selectively target soluble amyloid beta oligomers. Over the course of the year, we received fast-track designation from the FDA, added experienced and talented members to our team to guide our development plan, and completed important CMC work to scale production in anticipation of upcoming Phase II study. In February of this year, we announced the completion of enrollment in our Phase I Intercept AD trial, which sets us up to report top-line results in the third quarter. The Intercept AD results are anticipated to provide important proof-of-mechanism information for AC193, including safety, pharmacokinetic, and target engagement data that Eric will speak to in greater detail shortly. Thus far, we are encouraged by preliminary PK and blinded safety data observed to date. which supports our thesis that at appropriate dose levels, an antibody selected for A-beta oligomers, such as AC193, may provide a differentiated product profile in the fight against Alzheimer's disease. I want to briefly comment on the protocol that we disclosed in early February, just prior to completion of enrollment. Based on the preliminary CSF PK data observed that indicated that AC193 antibody concentrations were in excess of reported A-beta oligomer concentrations, And considering the blinded case of RAE observed in the cohort four at the time, we opted to amend the trial's protocol to reduce the dose level in cohort seven, our last cohort, to 25 mg milligrams per kilogram every two weeks. We believe the 25 mg per kilogram dose every two weeks in cohort seven will provide us with more meaningful dose ranging, safety, and target engagement information in support of establishing clinical proof of mechanism for ACU193 in this study. Looking ahead, we're actively preparing for Phase 2-3 activities in anticipation of successful results from our Phase 1 study in the third quarter. We will request an end of Phase 2 meeting with the FDA to be held in the fourth quarter to discuss the design of our Phase 2-3 study, a design that incorporates an interim decision to expand the study from a Phase 2 size to a Phase 3 study. On the CMC front, we remain well positioned to scale manufacturing to have sufficient drug supply to meet requirements of our current development plan. In addition, we have made meaningful progress in assessing various options for potential development of a subcutaneous formulation as part of our AC193 product development plans. We intend to continue to explore such options based on data generated in our phase one study. On a final note, I would like to acknowledge the significant change in the overall treatment landscape for Alzheimer's disease over the past year. The positive clarity AD results for licanumab in the fall of 2022 meaningfully advanced the field. Because it is a proto-fibril targeting antibody, licanumab has driven renewed interest in the role that soluble aggregated A-beta species, such as A-beta oligomers and A-beta proto-fibrils, may play in the pathology of Alzheimer's. and how targeting these species can contribute to safe and beneficial treatment options for patients. Furthermore, the negative graduate study results for gantanarumab, a plaque-targeting antibody, support the hypothesis that for plaque-targeting antibodies, clinical efficacy can only be achieved with a near-complete removal of amyloid plaque. Most recently, the negative A4 results for selenazumab and A-beta monomer-targeting antibody reinforce the evidence that targeting monomers may not be a viable means to produce clinical benefit, even when intervening at the earliest stages of disease. Aside from these clinical data sets, the field is also seeing advancement with both fluid and imaging biomarkers, which continue to develop rapidly and could offer a diverse set of future alternatives that are predictive of effects in AD beyond amyloid PET imaging. Given the size of the disease burden, we are encouraged by the additional clarity of these data have provided to the field, and look forward to additional upcoming data from many companies with differing approaches. At Acumen, we recognize the importance of these advances and strive to use the learnings to inform our approach to developing AC-193 as a potential disease-modifying therapy in early Alzheimer's patient population. To this end, we look forward to sharing our Intercept-AD top-line data with you in the third quarter, a data set we believe will be informative from a safety target engagement and dose-ranging perspective. With that, I'll hand the call over to Dr. Siemers. Eric?