Hackman Pharmaceuticals at BofA Conference: Alzheimer’s Drug Progress

On Wednesday, 14 May 2025, Hackman Pharmaceuticals (NASDAQ:ABOS) presented at the BofA Securities 2025 Healthcare Conference, providing a strategic overview of its Alzheimer’s drug, sabrutinib. The presentation highlighted both promising results from early trials and the challenges of a competitive landscape. While the company expressed optimism about sabrutinib’s potential, it remains cautious about interim data analysis to maintain study integrity.

Key Takeaways

• Hackman Pharmaceuticals discussed sabrutinib, a monoclonal antibody targeting amyloid beta oligomers.
• Phase I INTERCEPT AD study showed a favorable safety profile and promising biomarker effects.
• ALPITUDE AD Phase II study has completed enrollment with no interim data analysis planned.
• The company is exploring combination therapies and enhanced drug delivery methods.

Introduction and Background

• Hackman Pharmaceuticals’ main program, sabrutinib, targets soluble aggregates of amyloid, believed to be a primary cause of Alzheimer’s.
• The drug aims to neutralize the toxic effects of amyloid beta oligomers through a selective approach.

INTERCEPT AD Phase I Study Results

• Conducted with early Alzheimer’s patients to assess safety, pharmacokinetics, target engagement, and tolerability.
• Demonstrated a lower incidence of ARIA compared to plaque-directed antibodies.
• Showed robust target engagement with a reduction in amyloid PET signal by 20-25% at high doses.
• Biomarker improvements observed in plasma and CSF, including A beta 40/42 ratio and phosphorylated tau.

ALPITUDE AD Phase II Study

• Enrollment of 542 patients completed in 10 months across 80 sites in 5 countries.
• Study design includes two active dose cohorts versus placebo, focusing on the iADRS endpoint.
• No interim data analysis will be conducted to preserve study integrity for potential regulatory submission.

Competitive Landscape and Future Modalities

• Acknowledgement of limitations in current Alzheimer’s treatments, with room for improvement.
• Exploration of enhanced brain delivery methods and combination strategies with ERTau or anti-inflammatory mechanisms.
• Development of a subcutaneous formulation of sabrutinib alongside the IV version.

In conclusion, Hackman Pharmaceuticals’ presentation at the BofA Securities 2025 Healthcare Conference offered insights into the progress of sabrutinib. Readers are encouraged to refer to the full transcript for a detailed account.

Full transcript - BofA Securities 2025 Healthcare Conference:

Jason Zemanski, Big Cap Analyst, Bank: My name is Jason Zemanski. I’m one of the big cap analysts here at the bank. And this morning, I’m very pleased to have joined me Dan O’Call from Hackman Pharmaceuticals. Dan, thank

Dan O’Call, Executive, Hackman Pharmaceuticals: you so much for coming. Jason, thanks for having us.

Jason Zemanski, Big Cap Analyst, Bank: Well, excellent. Maybe just to start broadly, especially for those newer to the story, can you briefly describe spironoltog and why preferentially targeting amyloid beta oligomers might be a more effective approach than focusing on other species like monomers and soluble forms?

Dan O’Call, Executive, Hackman Pharmaceuticals: Sure. So Acumen is a company dedicated to advancing new treatment options for people living with Alzheimer’s disease. Our main program, sabrutinib is a monoclonal antibody that is highly selective for what we do as the most toxic species of amyloid, principally beta oligomers or amyloid beta oligomers. There’s a host of data to inform and support the notion that soluble aggregates, these are the principal pathogens in Alzheimer’s pathology that propensity to bind to non Alzheimer’s pathology that they have a propensity to bind to neurons and lead to deleterious effects such as circuit disruption, neuronal dysfunction, tau hyperphosphorylation, calcium influx. So sabiratide was really directed to neutralize the consequences of oligomer toxicity.

We think it’s principally different than broadly amyloid lowering, just a lot more directed approaches, which are other routes that people have pursued for improving patient lives.

Jason Zemanski, Big Cap Analyst, Bank: Maybe just on the data. You recently completed Phase I INTERCEPT AD. What do you think are the key takeaways at this point given the study outputs?

Dan O’Call, Executive, Hackman Pharmaceuticals: So INTERCEPT AD was a first in human study that was conducted exclusively in early Alzheimer’s patients. It was designed really to give us really important information about the safety profile of pharmacokinetics, target engagement and general tolerability of sabernatide. It was a single ascending dose and then multiple ascending dose study conducted here in The U. S. And the results were uniformly successful.

I mean we have established the safety profile consistent with the mechanism of targeting E beta lures, which holds that there should be a lower rate of ARIA or low rate of ARIA relative to plaque directed antibodies. We had robust target engagement. We employed a novel assay to quantify the complex of sibertin bound to oligomers in the cerebrospinal fluid patients. And we saw sort of a dose response in terms of the target engagement concentration of the signal relative to the exposure of drug in those patients. Really important finding of first time native oligomer engagement had been demonstrated in a Phase I study.

Another element that we were looking for in the study were biomarker effects. And so we did both imaging and fluid biomarker assessments. And on the imaging side, at the high dose levels, we actually saw a reduction in the amyloid PET signal pretty much to the rate and magnitude of agents like Leukembi, the AcyBiogen product. So with three administrations of the drug in the high dose cohorts, there was about a twenty percent to twenty five percent reduction in the celluloid value on the PET scans. Almost more intriguing was we looked at both plasma and CSF biomarkers, looking at the standard elements of the A beta 40 to 42 ratio, phosphorylated tau.

And then we also looked at some synaptic markers. So neurogranin and BAT2 being two that are associated with synaptic well-being or health or just normal function. And across all of those biomarkers in CSF and to a lesser degree in plasma, we saw a really robust signal, which gives us confidence that we’ve got a product in ziloretide that sees its target. And as a consequence of engaging with that target, you’re seeing these downstream effects in this patient based trial. So that was really what gave us confidence.

We sort of first read out those results in 2023 and then have moved into a fairly sizable Phase II study where the information coming out of INTERCEPT really helped inform the dosing strategy and set the expectations for what we expect to read out in with the Phase II. Got it. Well, before we move to

Jason Zemanski, Big Cap Analyst, Bank: the Phase II, obviously, INTERCEPT couldn’t focus much on the cognitive impact. But were you able to garner any anecdotal feedback from the trial? And would this be insightful? Yes.

Dan O’Call, Executive, Hackman Pharmaceuticals: So we did look at clinical measures in that study, which is really kind of a safety measure, first and foremost. Mean the study was not powered for clinical effects. And there were no it was really sort of, I would say, call it, noisy to no obvious signal or secondary assumption that we can make about cognitive benefits. Recall, these are the maximum, there are only three doses in the multiple dose cohorts. So it really wasn’t expected to see a clinical effect.

And what I think becomes the basis for the probability of success in the ALPITUDE AD study, the Phase II, is the effects on biomarkers and then a longer duration study where we have a primary outcome at eighteen months. Yes.

Jason Zemanski, Big Cap Analyst, Bank: You kind of touched on this, but let’s return to the subject of ARIA, which has been a big issue for some of your competitors who are currently commercial. But why do you think rates of ARIA in INTERCEPT were much lower? Yes.

Dan O’Call, Executive, Hackman Pharmaceuticals: So in INTERCEPT, the incidence of ARIA was confined to five cases, three at the high dose cohorts and then two at the lower dose cohorts. Interestingly, we had no observations of ARIA in the APOE4 homozygous, which are the population that is at greatest risk for ARIA and the one that really on the current agents, physicians are not treating the homozygous as a consequence of that risk profile. So the principal mechanism to explain the ARIA safety with an agent like sotoratug is that it’s really hitting the soluble aggregates that are diffusible and have a propensity, as I mentioned, to sort of bind to do harmful things to brain cells, whereas plaque directed antibodies are really likely to see vessel bound amyloid plaques and induce essentially an inflammatory response that leads to the RE observations. So we do think it’s our mechanism for sabranitog to have a better safety profile in respect of REE. Got it.

Jason Zemanski, Big Cap Analyst, Bank: Maybe we can delve into the ALPITUDE AD study, which we’re just referring to. I guess, fundamentally, maybe taking a step back, there have been several recent discoveries suggesting that the development of Alzheimer’s is a could be is likely a decade long process. Are we going early enough to have a disease modifying effect? So Jason, yes, I

Dan O’Call, Executive, Hackman Pharmaceuticals: think it is not a controversial concept that Alzheimer’s is occurs over ten to twenty five years. And the good news is we’re getting more reliable tools to help us assess the established pathology, the biological basis of the disease in advance of the symptomology, so the clinical stage of the disease. And I think we think an agent like sivernotub is well positioned in the early AD population, which is a symptomatic population that has both established pathology but also symptomology. But as you think about going earlier, there really is a way to and we probably see this with other chronic diseases like cardiovascular disease and others, where getting intervening early at the first sign of pathology likely affords a better long term outcome. And that’s certainly the future state of the field.

And I think for those that have been paying attention to the Alzheimer’s space generally, I think the field has made tremendous progress over the last two decades in terms of the couple first approved disease modifying drugs, better insights into next generation candidates such as civernotub. And now these fluid based biomarkers are going to streamline and economize our ability to identify patients at the early stages of disease. Got it. Well, on

Jason Zemanski, Big Cap Analyst, Bank: the same lines, as you mentioned earlier, you’re looking at an eighteen month endpoint. That good amount of time to see a change in cognition? And then maybe can you touch upon your selection of the measure there, especially given pivoting away from more conventional tests like CBRS B or the ADAS Cochin study.

Dan O’Call, Executive, Hackman Pharmaceuticals: So two active dose cohorts versus placebo. So 180 patients per cohort roughly. So five forty patients have been enrolled in the study. We completed enrollment. Didn’t hit on CDR Sum of Boxes.

Subsequently, they hit on both in the Phase III. But I think that for stage and population appropriateness of what we’re doing in ALPHA2AD, IGRAs is the right one. We, of course, will have CDR Sum of Boxes and other secondary measures. And as I mentioned, we’ll be looking at the imaging fluid biomarkers for sure.

Jason Zemanski, Big Cap Analyst, Bank: Yes. Makes sense. You completed enrollment in March, which was fairly rapid. Can you talk a little bit about feedback? I mean what are your takes sort of on the broader state of the market in Alzheimer’s?

Dan O’Call, Executive, Hackman Pharmaceuticals: Yes. Think so ALPITUDE AD enrolled five forty two patients in roughly ten months. And so this is a study being conducted at roughly 80 sites across five countries. We have a small but skillful team. There’s a lot of preparation that went into kind of preceding the launch of that study.

But I think it’s indicative of the awareness that if you have a diagnosis of Alzheimer’s, there are things that you can do. And particularly for ALKSICUTE AD, given the data set and the evidence generated in INTERCEPT, we think there was a lot of momentum to for some of the best sites and the best candidates to rapidly enroll in the study. So pretty encouraged to see how that the pace of adoption and enrollment in the study. And now we’ll be looking at adherence and essentially retention through the course of

Jason Zemanski, Big Cap Analyst, Bank: the study. Got it. I know you’ve downplayed this possibility, but I’m going to press you on it a little bit. Any possibility of having an early look at the data, especially given overall, there seems to be a very open attitude in terms of regulators on having a supporting

Dan O’Call, Executive, Hackman Pharmaceuticals: development here? Yes. So the I think we have consistently said we’re now looking early at data or conducting interim or futility analyses. The goal of ALKS three AD is to actually serve as evidence as part of a submission. So we want to maintain the integrity.

We’re conducting the study in a as if it’s a pivotal study for that particular reason. So I think we are as tempting as it might be, we’re not intending to be looking at interim data.

Jason Zemanski, Big Cap Analyst, Bank: Okay. Well, maybe in the time we have left, can we talk about the competitive landscape? Mean, what’s your assessment there? And any modalities you think might eventually pair well with an anti amyloid beta antibody? Sure.

So it’s

Dan O’Call, Executive, Hackman Pharmaceuticals: a very exciting time in the field. As I mentioned, we’ve got a couple of approved agents that are sort of making their way into the clinic. Those products have acknowledged limitations. And so there’s ample room for improvement. I mean, there’s seven million people in The U.

S. That have dementia associated with Alzheimer’s disease. I think we’re seeing you mentioned modalities. I think we’re seeing ways to improve the delivery of various agents into the brain using brain shuttles or what we refer to as enhanced brain delivery. That’s an area that’s of great interest to us.

And as we think about the profile for sabranatog reading out in ALPHA2 AD, putting a carrier, an ABD type carrier with a sibernatog like asset to even further advance the safety and efficacy of our mechanism, we think, could be a really compelling opportunity for the field.

Jason Zemanski, Big Cap Analyst, Bank: Makes sense. You recently completed a Phase I for subcutaneous formulation of sibernate. How does that read into everything? First, is it possible that you could incorporate that into ALTITEDE? And then I just overall, how valuable is it to have that convenience?

Dan O’Call, Executive, Hackman Pharmaceuticals: Yes. So we are very interested in advancing a subcu formulation of sibertadag, and we’re doing that in parallel with the IV. And I think it’s the two formulations are presumably complementary that having those options as physicians or for patients, I think, important. We’re not yet decided on the precise next step for where subcu goes. We’ve got ongoing formulation and delivery assessments underway.

And there are a couple of obvious options, whether we want to add the subcu to confirmatory Phase III, either in the primary portion of that study or in the OLE is TBD or conduct a standalone subcu Phase II or Phase IIIII type study is still another option that we might consider.

Jason Zemanski, Big Cap Analyst, Bank: Got it. And then kind of dovetailing back into the previous question. In terms of stacking modalities together, any thoughts on a different sort of mechanism of action that might pair well with an antibody, especially if it were in a subcu formation? Yes. So yes, we’re starting

Dan O’Call, Executive, Hackman Pharmaceuticals: to see combination strategies, right? So whether it be IV or subcu, I think it’s the state of play is really like canoparib and amyloid directed approach with ERTau or inflammatory related mechanism or maybe an integrin would be the other modality that might come to play in this space. So all of those possibilities, I think, are worth pursuing. And I’m encouraged to think that we’re making enough progress to keep the momentum in the space going forward.

Jason Zemanski, Big Cap Analyst, Bank: Makes good sense. Dan, thank you so much for joining us.

Dan O’Call, Executive, Hackman Pharmaceuticals: Jason, thank you so much.

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