Acumen Pharmaceuticals, Inc. Common Stock Investor Day 2026

I'm Alex Braun, Head of Investor Relations, and on behalf of the Acumen team, I'd like to welcome everyone to our virtual Investor Day. Today, we intend to take you on a deeper dive into Acumen's value proposition as we near the phase II readout for our product candidate for the treatment of early Alzheimer's disease, sabirnetug. As a reminder, we will be making forward-looking statements. These statements are subject to risks and uncertainties that may cause actual results to differ materially from those projected. A description of those risks can be found in our most recent 10-Q filing with the SEC. Any forward-looking statements are only as of today's date, and we assume no obligation to update any forward-looking statements made on today's call.

Today's speakers will include Dan O'Connell, our Chief Executive Officer, who will briefly touch on the Alzheimer's landscape and potential of A beta oligomer therapies to treat Alzheimer's disease. Dr. James Doherty, our President and Chief Development Officer, who will explain sabirnetug's mechanism of action and why we believe it could potentially differentiate from other disease-modifying therapies. Dr. Eric Siemers, our Chief Medical Officer, who will review our ongoing phase II study investigating sabirnetug that reads out in late 2026. Dr. Paul Shughrue, VP, Program Lead and Head of Research, who will explain the latest developments in our Enhanced Brain Delivery or EBD program, which we believe to be a promising next generation addition to our pipeline.

Following their presentations, there will be a live Q&A discussion. In addition, there is a question submission box on your screen that will be open throughout the presentations this morning and during the Q&A session to submit written questions. We'll collect those questions throughout the hour and take as many as time allows. With that, I'll hand this over to Dan.

Good morning. I'm Dan O'Connell, CEO of Acumen. Thank you for joining us today. I'm pleased to provide you with an overview of our opportunity and the setup for Acumen and the value proposition and strategy as we seek to bring better treatment options forward for people impacted by Alzheimer's disease. Let's start with the magnitude of the opportunity and unmet need. Today, an estimated 7.2 million Americans are living with early Alzheimer's disease, a stage characterized by symptoms and confirmed amyloid pathology. Absent a cure or effective preventative treatment, that population is expected to nearly double by 2060 to roughly 13.8 million Americans. For the current treatment landscape, two FDA-approved disease-modifying agents are now available and have been shown in clinical studies to slow disease progression. These have ushered in a new era for treatment in Alzheimer's disease.

Global sales of the approved anti-amyloid agents are growing and poised to accelerate. The approved agents, Leqembi and Kisunla, have recently achieved an annual sales run rate exceeding $1 billion. Sales are projected to reach $2 billion in 2028 and reach upwards of $3 billion-$4 billion by 2030. The early market adoption for these amyloid plaque-directed agents has occurred despite systemic infrastructure challenges and debates about the overall efficacy and safety of these agents, including amyloid-related imaging abnormalities, otherwise referred to as ARIAs. Nevertheless, we see this market is poised for continued growth and large enough to support multiple multi-billion dollar products, given the magnitude of the population. One of the primary drivers of market expansion and continued growth and development is the proliferation of blood-based biomarkers. Essentially, a blood test to confirm or inform a diagnosis of Alzheimer's disease.

The use of blood-based biomarkers has already transformed Alzheimer's drug development. As an example, we were early adopters of a phospho-tau blood test, plasma test in our ongoing phase II study. The use of that measure streamlined our screening and enrollment, reduced patient burden and site burden, and reduced the overall cost. It was a real way to innovate within the space and achieve efficiencies in our program. Today, we have four approved blood tests for Alzheimer's disease. These are all being commercially deployed and will continue to, I think, establish and confirm Alzheimer's cases more broadly. Triaging patients in the primary care setting with blood-based biomarkers is expected to allow specialists to really focus their time and attention on treatment options. We see this as really contributing to the growth overall in the space.

As we look at the Alzheimer's market today, we see this as a market that is essentially underdeveloped and poised for continued and significant growth over the next decade. That growth will fundamentally be accelerated through the continued deployment and establishment of the clinical infrastructure to offer treatment options to patients. The adoption of blood-based biomarkers to characterize and potentially confirm more cases in the population. Additionally, other formats of drugs, such as the recently approved subcutaneous version of Leqembi for treatment induction is another way to establish convenience and growth within the marketplace. I think experienced physicians just becoming more familiar with treatment options, risk assessments in terms of ARIA, managing safety considerations for patients will continue to expand the adoption and growth of these agents.

Another concept that will continue to fuel the growth going forward is the combination strategies. Using essentially the anti-Aβ approaches as a cornerstone of treatment are expected to be the future state of care. It is an exciting time in the field and one that is poised for continued growth. In this early phase of AD market development, we see a massive opportunity to improve on the safety and efficacy of current amyloid-targeting approaches. Our goal at Acumen is to develop products with improved benefit to risk profiles, with either increased efficacy or increased safety or potentially both. We see a path to better efficacy and safety and a risk-benefit profile improvement based on our approach, which is to target soluble toxic Aβ oligomers. Oligomers are early instigators and persistent drivers of Alzheimer's pathology.

Jim will talk more about this mechanism in his talk, but we think it is a path towards differentiation distinctly within our pipeline. Suffice to say, there is room for improvement here, and we at Acumen are laser-focused on that opportunity and seeking to have an outsized impact on that disease. 2026 is a pivotal year for our innovative anti-Aβ oligomer pipeline. We have sabirnetug. Our lead program is positioned to read out clinical proof of concept data late this year, really data that we believe will provide the clinical validation of the Aβ hypothesis and usher in a new mechanism within the amyloid space. We also have our EBD program, which is Enhanced Brain Delivery. We have reported positive non-clinical data earlier this year and have two candidates that we are progressing towards an IND in mid-2027.

To summarize our value proposition and strategy, we are still in the early days of effective treatment approaches for what is a very large, growing, and diverse Alzheimer's population in need of better options. Our novel anti-Aβ oligomer approach is differentiated within the clinically validated amyloid space, an exciting possibility to differentiate on a benefit-risk basis. Sabirnetug has already produced compelling phase I results in Alzheimer's patients, increasing the probability of success for it and future anti-Aβ oligomer therapies. Our ALTITUDE-AD phase II trial will read out later this year, which is a hugely exciting milestone for us as a company, and our EBD program gives us future optionality well into the future. Our strategy to expand stakeholder value is based on successful phase II results, expedite the development of sabirnetug with a partner, and seek to advance an EBD candidate through a clinical value inflection point quite rapidly.

With that, I will turn the call over to Jim.

Thanks, Dan. Good morning, everyone, and thank you for joining us today. As we approach the readout of the ALTITUDE-AD trial, I'm pleased to take this opportunity to talk about some of the key reasons why we believe sabirnetug represents a differentiated opportunity for anti-Abeta disease-modifying therapies for the treatment of Alzheimer's disease. I'm going to touch on three related topics today. First, the soluble oligomer hypothesis. Sabirnetug is the first monoclonal antibody targeting Abeta therapy to rigorously test the oligomer hypothesis in a late-phase clinical trial. Critically, as you'll hear later from Eric, the ALTITUDE-AD trial represents a well-powered study focused on the potential benefits of sabirnetug on clinical measures and activities of daily living, as well as safety in a variety of biomarkers. I'll talk about IgG2. Like many other potential therapeutic agents, sabirnetug is a monoclonal antibody of the IgG type.

It's important to consider, though, that subtypes of IgG have different signaling properties in the immune system. Finally, as Dan mentioned in his introductory remarks, there have been a remarkable expansion on the availability and diversity of fluid-based biomarkers that will become increasingly critical in the diagnosis of AD, as well as in clinical practice. Next slide, please. Thinking about sabirnetug, how does sabirnetug differentiate from other approved antibody-based anti-Abeta disease-modifying therapies? Well, like other approved anti-Abeta disease-modifying therapies, sabirnetug is an amyloid protein targeting monoclonal antibody. However, unlike the approved anti-Abeta DMTs, sabirnetug targets soluble Abeta oligomers. Those will have potential effects on efficacy, meaning direct removal of what we believe are the most toxic agents that disrupt cortical function. We'll talk more about that as we go along. And potential effects on the safety profile.