ACADIA Pharmaceuticals (ACAD) investor relations material

Program overview and development strategy

• Remlifanserin, a next-generation 5-HT2A inverse agonist, is being developed for Alzheimer's disease psychosis and Lewy body dementia psychosis, aiming to improve on pimavanserin by reducing QT prolongation and enabling greater dose flexibility.

• The Alzheimer's program is designed with a more robust, adequately powered trial, focusing on higher exposure levels and improved study design compared to previous efforts.

• The trial uses community-based recruitment, biomarker confirmation of Alzheimer's, and the SAPS-H+D endpoint for greater sensitivity to change.

• The master protocol includes a phase II and two phase III parallel group studies, with open-label extension for longer-term safety insights.

• Regulatory strategy is aligned with evolving FDA guidance, aiming for rigorous data collection to support potential registration and black box risk assessment.

Clinical trial design and endpoints

• The phase II trial is powered for a moderate effect size (0.4) with 80% power, using SAPS-H+D and NPI-C as primary and secondary endpoints.

• Raters are highly trained and experienced to distinguish delusions from cognitive symptoms in Alzheimer's patients.

• The study duration is six weeks, with open-label extension to monitor longer-term cognitive and motor effects.

• The trial aims to demonstrate efficacy, safety, and ease of use, with a focus on compliance and minimal drug-drug interactions.

• Data readout is expected between August and October.

Pipeline and future directions

• ACP-211, a selectively deuterated R-ketamine, is in development for major depressive disorder, aiming for ketamine-like efficacy with reduced sedation and dissociation.

• The phase II study for ACP-211 will assess both efficacy and tolerability, with data expected mid-next year.

• Lewy body dementia program includes biomarker subgroups, though biomarker science is less advanced than in Alzheimer's.

• Both Alzheimer's and Lewy body programs are considered complementary, with enthusiasm for both indications.

• The phase II studies are viewed as learning opportunities to inform future phase III designs.