Acumen (ABOS) Q2 FY26 earnings call: guidance and Q&A

How does Acumen's oligomer-specific approach differ from competitors like Kisunla and Leqembi, and what are the safety expectations given their real-world experience?

Acumen's approach targets A-beta oligomers, which is differentiated from plaque-targeting antibodies. Sabirnetug is an IgG2 antibody, which has less effector function compared to IgG1 antibodies (like competitors), potentially leading to a better safety profile, especially regarding ARIA rates. Phase I data showed robust target engagement.

“So there's two reasons to think that our safety and tolerability could be quite good. One is that we have this differentiated target, oligomers, and the second is that we have an IgG2 antibody with less effector function and less immune system activation.”

asked by Matthew Ryan Tan · answered by Eric Siemers

What parameters were optimized in selecting the EBD candidates, and how does ACU401 differentiate from ACU301?

Optimization focused on subcutaneous administration, preserved/enhanced oligomer selectivity, and efficient blood-brain barrier transport using transferrin carrier technology. Parameters included affinity for TfR, valency, and potential anemia risk. The goal is to select one lead candidate with the best overall profile.

“We looked at affinity for TfR. We looked at valency, monovalent versus divalent. We looked at a bunch of parameters around the potential risk for anemia and things like that. And so it really represents the culmination of a whole campaign to optimize for what we think is the best fit to deliver these oligomer-targeting antibodies into the CNS.”

asked by Matthew Ryan Tan · answered by James Doherty

With two active doses in ALTITUDE-AD, is each dose independently powered against placebo, and what constitutes a statistically robust positive study if only one succeeds?

Management has not specifically provided details on the powering and analysis. They expect both doses, which have demonstrated target engagement, could emerge as efficacious, and more information will be provided closer to the data readout.

“As we have not specifically provided details on the powering and the analysis. I think, I don't know that we can go into greater detail on that this morning.”

asked by Jason Zemansky · answered by Daniel O'Connell

What work is being done to minimize the interval between Phase II results and Phase III initiation, including regulatory, CMC, partner discussions, and site planning?

Elements of CMC, partner discussions, and site planning are ongoing. Regulatory interactions for Phase III design are not yet underway. The company is actively working to minimize 'white space' and hopes a successful Phase II readout will accelerate moving sabirnetug into a single pivotal Phase III.

“Well, you can imagine there are elements of everything that you mentioned that are ongoing now, with the exception perhaps of regulatory interactions in terms of establishing the Phase III design and so forth.”

asked by Jason Zemansky · answered by Daniel O'Connell

Will MTBR-tau243 be looked at in ALTITUDE-AD, and how could it be leveraged for patient selection in Phase III?

MTBR is a newer biomarker and was not part of the initial ALTITUDE-AD design, but the company has stored plasma samples, allowing for future exploratory analysis of MTBR and other new blood-based biomarkers. These fluid biomarkers are seen as providing valuable information for understanding disease progression and potentially identifying better patient candidates.

“But one of the things that we have talked about is that, we have, a large number of patients and a lot of actually plasma samples that will be stored. And so we have the opportunity to look at things like MTBR, new biomarkers that, especially the blood-based biomarkers, that become interesting after we actually complete the study.”

asked by Samantha Schaeffer · answered by Eric Siemers

Can you explain the Unlearn digital twins tool and its incorporation into Phase II, and how it might be leveraged for Phase III?

Digital twins are individualized digital models based on extensive patient data to predict disease progression. Acumen is using this as an exploratory endpoint in Phase II to evaluate its utility. Potential applications include refining patient selection and serving as a prognostic covariate in analyses, with the goal of understanding the best ways to apply this technology.

“Essentially, these are almost individualized digital models relying on the data from thousands and thousands of patients who have been studied for the progression of their disease in clinical trials and in other formats.”

asked by Samantha Schaeffer · answered by James Doherty

Do you anticipate taking both EBD candidates into humans, starting with healthy volunteers, and what are the patient numbers needed to assess anemia?

The company intends to move one lead EBD molecule into clinical development after identifying the best overall profile. They are actively working on CMC and tox for the mid-2027 IND filing and are still discussing study design, including whether to start in healthy volunteers, aiming for the most efficient path to patients.

“So what we would intend to do is move into clinical development with one molecule, and that'll be the one that we think offers the best of possible profiles.”

asked by Thomas Shrader · answered by James Doherty

Do you expect to go radio silent at some point, and can you provide any guidance on when?

The company expects topline results for ALTITUDE-AD late in 2026. An Investor Relations Day is scheduled for September 16, and they will participate in early fall activities. Public-facing engagement will likely shut down in Q4 closer to the results, but specific dates are not yet set.

“In the fourth quarter, I think we will probably have to shut down some of our public-facing engagement in anticipation of results. But the timing and specific dates for that, can't comment on.”

asked by Thomas Shrader · answered by Daniel O'Connell

What is your view on recent competitor tau data, and is there a way to fast-track a combo proof of concept post-ALTITUDE-AD data?

The recent Biogen BIIB080 tau data is interesting and potentially the first clinical validation of a tau-directed approach. Acumen believes Alzheimer's will ultimately require combination strategies and will evaluate ways to leverage its A-beta oligomer-directed portfolio with other synergistic approaches, including tau or anti-inflammatory treatments.

“Ultimately, I think we take the view that Alzheimer's is a disease that will be more adequately addressed with combination strategies.”

asked by Geoffrey Meacham · answered by Daniel O'Connell

Will biomarker data be included in the topline release, and what should be expected from the September 16 IR Day?

Both imaging and fluid biomarkers will be included in the topline results for ALTITUDE-AD late this year. The September 16 IR Day will be a review of Acumen's investment thesis, covering sabirnetug and the EBD program, intended for those seeking an update before the Phase II data readout.

“So for your first question, the topline results, as I mentioned in the prepared remarks, will include the primary outcome, the iADRS... We intentionally will include both fluid and imaging biomarkers as part of those topline results.”

asked by Dev Prasad · answered by Daniel O'Connell