Acumen Pharmaceuticals, Inc. Common Stock Citigroup’s Biopharma Back to School Summit 2026

Sure. Yeah, sure. Thanks, Geoff. Thanks to you and your colleagues for including us in this year's meeting. We're glad to be here. Yeah, it's an exciting time for us in the Alzheimer's space, principally as the market continues to develop and reflect the broad and large unmet need of the growing Alzheimer's population. We at Acumen have a pipeline that includes phase II assets, sabirnetug, that will read out later this year. We'll talk more in detail on that in a minute. As well as a preclinical, nonclinical program working towards an IND in 2027 that involves some transferrin-directed transport to the brain. So very excited about our portfolio and pipeline to position new and better treatment options for people impacted by Alzheimer's disease. I think it is important to recognize we are still in the early innings from a commercial market development standpoint.

We have two approved agents that have been shown in studies to slow the disease, its progression relative to placebo. Those two agents have now achieved annual sales run rates exceeding $1 billion and are expected to be north of $2 billion by 2028 and $3 billion-$4 billion in 2030. So it's a growing market in demand of better treatment options, and that's really where Acumen is positioned. We're now at a point where I think there's clinical commercial regulatory validation of amyloid targeting strategies as a cornerstone to disease modification. We at Acumen have a unique riff or scientific hypothesis associated with a species of amyloid or A-beta that is potently toxic, and one that we think by neutralizing A-beta oligomers we have the ability to potentially unlock greater efficacy and safety for patients in this population.

Of course. Just because I am joined here by my colleague, James Doherty, our Chief Development Officer and President, I invite Jim to comment.

Yes As the neuroscientist in the room and someone that has been tracking this field for a couple of decades.

Yeah, happy to do so, Dan, and good morning, Geoff. Yeah. It is a really good question. As Dan said, A-beta amyloid is now a validated target for the treatment of Alzheimer's disease, and that is a huge step forward in any endeavor to find new therapies. Really, when you look at the biology of amyloid beta, the protein has a normal function, and it normally exists as monomer single units. Something happens, and it is not entirely clear yet what that core thing is, but it leads to misfolding and misaggregation of that protein. So now instead of doing its normal job, it is coming up the works. I say it that way intentionally because there is all the things known about the larger things like amyloid plaques.

Really, the best evidence for true toxicity causing damage to synapses, causing damage to cells, preventing plasticity in the brain, and ultimately progressing, interfering with cognitive function, is really associated with the small soluble oligomers, at least when it comes to the in vitro and preclinical settings. So a lot of evidence that these small aggregates of amyloid protein are actually interfering with key synaptic functions, so messing up signaling. It is an early element in disease. We all know that Alzheimer's is a progressive disorder, and so this dysfunction associated with oligomers occurs early in the course of disease, and it is persistent. So that is a really interesting place to go from a neurobiological point of view. Given that targeting of soluble oligomers with sabirnetug, we are really excited to be testing the oligomer hypothesis really for the first time by getting cognitive data in the ALTITUDE-AD trial.

Yeah. There's really Oh, go ahead.

Okay. Oh, I was just going to say that, yeah, as Jim was suggesting, there's a couple of decades of evidence in support of these A-beta oligomers as being a primary toxin.

Of course, the origins of our lead program, sabirnetug. Sabirnetug was designed to neutralize and selectively target these species. So it has a high selectivity for oligomers versus monomer and versus plaques. Based on that mechanism and based on some successful phase I data, we do think sabirnetug is positioned for success and differentiation through this robust 542-patient phase II study that reads out later this year.

Yes. So ALTITUDE-AD is a double-blind, placebo-controlled study, 18-month double-blind period followed by a 12-month open label extension. There are three arms in the study, two active arms at 35 and 50 milligrams per kilogram IV, once monthly IV administration, relative to a placebo arm. Primary endpoint is the iADRS scale, which is a combined scale of ADAS-Cog, which is a cognitive function scale, as well as another scale for activities of daily living. So it really is that combination of cognitive impairment as well as impact that has on daily living. We have a number of other cognitive scales also in the study, including CDR Sum of Boxes and a variety of others. As I was just saying, we see the critical test for the oligomer hypothesis, and given that, we really want to, as closely as we can, be measuring cognitive performance.

In addition to that, we're also looking at a number of different biomarkers, and I think that's a really interesting area to be talking about these days for Alzheimer's therapies. We are certainly well-represented when it comes to biomarker analysis. That includes imaging biomarkers like PET scans. We'll be doing amyloid PET as well as a small tau PET sub-study. MR imaging from a safety perspective, and a number of biochemical plasma-based biomarkers. That's the overall design, 542 subjects enrolled in the study, about 180 per arm then. We are rapidly approaching the conclusion of the study, so we're very excited.