ACADIA Pharmaceuticals (ACAD) Stifel 2026 Virtual CNS Forum summary

Program overview and rationale

• Remlifanserin (formerly ACP-204) is a next-generation 5-HT2A inverse agonist developed to improve upon pimavanserin, aiming for reduced QT prolongation risk, faster steady state, and broader dose range.

• Remlifanserin is being studied in both Alzheimer's disease psychosis (ADP) and Lewy body dementia psychosis, with the ADP program currently in phase II/III.

• The molecule is designed to allow higher exposures, potentially increasing efficacy compared to pimavanserin, which showed an exposure-response relationship in prior studies.

• The current trial is more robustly powered and includes biomarker confirmation of Alzheimer's diagnosis, addressing limitations of previous studies.

• The study uses the SAPS-H+D endpoint, considered more sensitive to change than previous scales, and includes additional endpoints like NPI-C.

Clinical trial design and regulatory considerations

• The phase II/III program uses a master protocol with three parallel group studies, aiming for rigorous data suitable for regulatory submission.

• The phase II portion is powered for a moderate effect size (0.4) with 80% power, and includes both efficacy and safety endpoints.

• Raters are highly trained and experienced to distinguish delusions from cognitive symptoms in ADP.

• The trial includes open-label extension to gather longer-term safety and cognitive impact data, though definitive answers will require more time.

• Regulatory strategy is flexible, monitoring FDA's evolving stance on single-study approvals, but planning for a full ICH safety database.

Key expectations and future directions

• Success will be measured by efficacy in ADP, a favorable safety profile (especially regarding QT prolongation), and ease of use for patients.

• The Lewy body dementia program is considered a strong complement, with ongoing efforts to refine patient selection using emerging biomarkers.

• The phase II study is viewed as a learning study to inform phase III design and future development in both ADP and Lewy body dementia.

• Data readout for the ADP program is expected between August and October.

• Another pipeline asset, ACP-211 (selectively deuterated R-ketamine), is in development for MDD, aiming for ketamine-like efficacy with reduced sedation and dissociation.