Acumen Pharmaceuticals, Inc.

Good day, ladies and gentlemen. Thank you for standing by. Welcome to Acumen Parma third quarter 2023 conference call and webcast. At this time, all participants are on 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 automatic message advising your hand is raised. Please note that today's conference is being recorded. I will now hand the conference over to your speaker host, Alex Ross, Head of Investillations, please go ahead.

Thank you, Livia. Good morning, and welcome to the Acumen Conference Call to discuss our business update and financial results for the quarter ended September 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 presentations 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, a 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. So now I'll turn the call over to Dan.

Thanks, Alex. Good morning, and thanks, everyone, for joining us today. Throughout the third quarter and into November, our team has focused on advancing ACU193, our monoclonal antibody for the treatment of early Alzheimer's disease, to the next phase of clinical development. We recognize the importance of additional treatment options for Alzheimer's patients and caregivers living with this disease. And we believe that ACU193's high selectivity for toxic amyloid beta oligomers may lead to differentiation via increased clinical efficacy and improved safety and convenience as compared to approved and under-reviewed antibodies. We have made significant regulatory, operational, and strategic progress to this end, supported by the deep Alzheimer's development expertise of our team. Today, we have positive updates to share regarding the CSF biomarkers from our phase one study. our recent FDA interaction, and the newly announced development partnership and financing to pursue a subcutaneous form of AC193. Starting with the biomarker data, when we disclosed our Intercept-AD phase one top line results this past July at the Alzheimer's Association International Conference, or AAIC, our team had not yet had an opportunity to analyze the corresponding fluid biomarker data from the trial. CSF biomarker data are now available and plasma biomarker data will be received in the near future. Today, I'm pleased to share positive results for AC193 on CSF biomarkers that further reinforce downstream pharmacology in addition to the previously presented target engagement and amyloid PET data for AC193. Consistent drug effects were observed in the multiple ascending dose cohorts in the Intercept-AD trial for phosphotau181 total tau, neurogranin, and the A-beta 42 to 40 ratio. Statistically significant improvement was seen with reductions of neurogranin at 60 milligrams per kilogram MAD dose level, as well as significant correlation between target engagement and the change in neurogranin concentrations. These effects are particularly notable since with only three administrations of ACU-193 in the multiple semi-dose cohorts, Any movement in CSF biomarker effects was not entirely expected. The fact that we have seen such movement is highly supportive of our antibodies downstream pharmacological effects in the brain and is also tied to A-beta-oligomer target engagement. Eric will walk you through the CSF biomarker data in more detail shortly. This October, we presented a deeper dive into our Phase I results at the Clinical Trials for Alzheimer's Disease Meeting, or CTAD, which was very well received by the medical community. Overall, we continue to be very pleased with the quality of the data generated in our Intercept-AD Phase I trial and the corresponding insights that have helped to guide the design of our Phase II study, such as our compelling target engagement, amyloid plaque reduction, and now CSF biomarker effects. Importantly, as part of our presentation at CTAD, we announced the doses we are taking forward in Phase 2. The two treatment arms versus placebo are 50 milligrams per kilogram and 35 milligrams per kilogram. Both administered IV every four weeks. These doses were selected based on extensive PK-PD modeling of our Phase 1 data that showed direct target engagement of A-beta oligomers at near-maximal effect. In other words, on the basis of the phase one data and subsequent PKPD modeling, we have confidence that at both these doses of AC193 will adequately saturate our intended target, toxic A-beta oligomers in the brain. As we think about the phase two study and the dosing strategy, we anticipate the 50 milligram per kilogram dose level will replicate and presumably extend the plaque reduction observed in phase one. And a 35 milligrams per kilogram dose may achieve sufficient oligomer target engagement but possibly with a lower rate of RAE than the 50 milligram or kilogram dose cohort. To be clear, both of these dose levels may produce clinical efficacy, and we are keen to see whether they will differentiate in terms of therapeutic index or overall benefit-risk ratio. Turning to our regulatory update, recently we met with the FDA in an end-of-Phase II meeting to discuss our next clinical study, ACU193-201, which we are calling Altitude AD, The agency indicated that it is aligned in principle with the study design. We were planning the study as a randomized, double-blind, placebo-controlled, three-arm study designed to evaluate the clinical efficacy, safety, and tolerability of ACU193 with up to 180 participants per arm for a total of 540 participants with mild cognitive impairment or mild dementia due to AD. We will initiate Altitude AD as a standalone Phase II study with an 18-month treatment duration commencing in the first half of 2024. The study plan incorporates an adaptive design with interim analyses to inform the possibility of expanding the size of the study from a Phase II to a Phase III study, which we believe is the most expeditious route to a BLA filing and potential approval. As a reminder, these interims are not futility analyses and in alignment with guidance from the FDA and to avoid bias and to protect the study's integrity as a potential registration study, the timing of and data from interims will not be disclosed publicly. Now, I'd like to provide an update on our efforts to assess the viability of subcutaneous dosing of AC-193. We recognize the attractiveness of this mode of administration to offer additional flexibility and convenience for patients and caregivers. Over the last nine to 12 months, we have evaluated several delivery technologies to support the doses we are exploring in our clinical studies. We are very excited about our recently signed global collaboration and licensing agreement with Halazine. Using Halazine's commercially validated enhanced drug delivery technology, we plan to initiate a phase one study to compare the PK of subcutaneous form of HC193 to the IV form in mid-2024. Based on our dose modeling, we believe there is a potential for competitive commercial product profile of a subcutaneous dosage form of AC193, which may ultimately be commercialized alongside every four-week IV AC193 to potentially broaden treatment options for patients. Today, we also announced that we've secured a credit facility for up to $50 million with K2 Health Ventures, a healthcare-focused specialty finance company. I'll let Matt tell you more on how this funding provides us with additional operational flexibility. Taking a look back at 2023, the year thus far has been a transformational one for Acumen. Our positive phase one top line results enabled us to demonstrate convincing proof of mechanism for AC193 further supported by the CSF biomarker data shared today. We received encouraging feedback from the FDA on the design of our next phase of clinical development, which we are operationalizing as we speak. Our partnership with Halazan for the development of a subcutaneous option of AC193 extends its product profile in pursuit of greater patient choice and convenience. And the additional financing to support subcutaneous development provides the capital to support the focus of our talented team working to solidify AC193's potential as a future differentiated and potential best-in-class option for early Alzheimer's treatment. And with that, I'll turn the call over to Eric.