Acumen Pharmaceuticals, Inc. Common Stock 12th Annual Cantor Fitzgerald Global Healthcare Conference

Thanks, Pete, and thanks to you and your colleagues at Cantor Fitzgerald for inviting us to this year's conference. I'm Dan O'Connell. I'm the CEO of Acumen. I've been in the life sciences space for the majority of my career. I've been focused on working in building small neuroscience-focused companies. Acumen has been a core element of that effort, and excited to share more with you today on the story.

Yep, good to see you, Pete. My name's Jim Doherty. I'm President and Chief Development Officer for Acumen. Neuroscientist by training. I've worked in CNS drug discovery, drug development for quite a long time now, both in large companies and in small companies.

In terms of Acumen's profile and status, we are a publicly traded company working to advance better treatment options for patients impacted by early Alzheimer's disease. Our current pipeline includes sabirnetug, which is a monoclonal antibody that is highly selective for what we view as the most toxic species of Aβ, principally referred to as Aβ oligomers or amyloid beta oligomers, which have been shown over a couple of decades of research to be potent neurotoxins at the synaptic and neuronal level. And we think sabirnetug, based on its selectivity, has the ability to unlock greater efficacy and safety for early Alzheimer's patients. In addition to sabirnetug, which as I mentioned, will read out phase II clinical proof of concepts data late this year. We are advancing a couple of candidates in what we refer to as Enhanced Brain Delivery.

This is using a receptor-mediated transport technology that we've sourced from a partner in Japan called JCR Pharmaceuticals that has a transferrin-directed moiety that allows for the binding of the transferrin receptor and the delivery of large molecules. They have programs in other disease indications, rare and otherwise. We are their only partner in Alzheimer's disease, and we're using the JCR carrier technology to deliver Acumen Aβ oligomer selective payloads, including sabirnetug and a sabirnetug-like molecule. That program is still finalizing the profiles on two candidates with the goal of filing an IND in mid 2027.

Thanks, Pete. Amyloid lowering is now the therapeutic space that broadly characterizes a variety of different species of Aβ in amyloid pathology. We're principally focused on neutralizing these small, soluble toxic aggregates of the Aβ42 peptide that have been shown to bind to neurons at synapses and induce tau hyperphosphorylation, induce calcium influx, and basically be a prime instigator of Alzheimer's pathology and a persistent contributor to ongoing pathology. The current agents, one from Eli Lilly and Company, one from Eisai and Biogen, those are directed at other species, including amyloid plaques, which really represent the end stage of amyloid accumulation over 15 to 25 years. It has been shown clinically, amyloid lowering strategies have been clinically validated. There are two approved agents. There's also now growing commercial traction for those agents.

We're in the era of optimizing within the amyloid space, and we think sabirnetug and oligomer-directed approaches have a unique value proposition to patients and physicians based on that mechanism.

I think there's a possibility. I think that the primary mode of toxicity for these species is disruption of circuit function. Alzheimer's itself is a disease of loss of synapses. We do think that it's hard to predict in a large ongoing phase II study when effectively there will be a separation on clinical measures. But we're hopeful that, not only at 18 months, which is our primary outcome measure, but potentially sooner in the course of treatment, there's an observable effect on clinical measures in addition to biomarker effects. I think that's another point to make is that the field has progressed pretty dramatically over the last 10 years, whereby we have a much greater panoply of tools available to us to help inform development decisions and pharmacodynamic effects.

We think that's going to be an important. It's contributed to the conduct of the phase II study and will help in terms of the translatability of sabirnetug outcomes to inform our strategy for the Enhanced Brain Delivery program.

Yeah. Sorry, go ahead. Thinking about the amyloid hypothesis and the soluble oligomer hypothesis, part of the reason why it's such an exciting time in Alzheimer's disease right now is that we have been able to translate a finding that's been known for a long time, that this amyloid protein is one of the core pathophysiologies in AD.

To now, for the very first time, that we've been able as a field to demonstrate that you can alter clinical course by sequestering that protein. Which is fantastic. But it's also still complex biology. Amyloid encompasses a lot of different types of protein. It's all one protein, but the different forms of the protein are highly relevant. There's actually quite a lot of evidence to support that the small soluble oligomers, as Dan was saying, are acutely neurotoxic and cytotoxic and synaptotoxic.

That is, I think, the core part of the soluble oligomer hypothesis that we're trying to test, is that we'd like to expand the thinking around how amyloid can best be addressed as a treatment for Alzheimer's disease.