Alzamend Neuro is partnering with Massachusetts General Hospital to conduct a Phase 2 clinical trial evaluating AL001, an oral lithium-delivery system, for the treatment of dementia related to Alzheimer's disease. The study will assess AL001's brain levels compared to marketed lithium in both healthy volunteers and individuals with Alzheimer's, with the goal of identifying the lowest effective dose and evaluating its safety.
Trial Objectives and Design
The Phase 2 trial is designed to compare the brain levels of AL001 with those of currently available lithium formulations. The primary objective is to determine the minimum dose of AL001 required to achieve the same therapeutic effectiveness as existing lithium treatments, while also thoroughly evaluating the therapy's safety profile. This approach aligns with the U.S. Food and Drug Administration (FDA) Section 505(b)(2) pathway, which is specifically intended for the review of new formulations or delivery systems of approved therapies.
Rationale Behind AL001
AL001 is an ionic cocrystal of lithium engineered with L-proline and salicylate. This formulation aims to deliver lithium more effectively to the brain, potentially reducing exposure to other organs and minimizing side effects. Alzheimer's disease, the most prevalent form of dementia, is characterized by the accumulation of amyloid plaques and tau tangles, leading to nerve cell death. Evidence suggests that lithium may play a role in preventing or treating Alzheimer's by reducing the accumulation of these proteins and preventing nerve cell death.
Preclinical and Phase 1/2 Data
Preclinical studies have indicated that AL001 prevented cognitive impairment and improved cognitive skills, particularly learning and memory, in a mouse model of Alzheimer's, outperforming other lithium formulations. A completed Phase 1/2 trial (NCT05363293) assessed AL001's safety and pharmacological properties in both Alzheimer's patients and healthy volunteers, suggesting the therapy was generally well-tolerated. The trial also demonstrated that 150 mg of AL001 resulted in similar lithium blood levels as a 300 mg capsule of marketed lithium. Data from the Phase 2 multiple ascending dose portion of the study enabled the company to identify the maximum tolerated dose of AL001, which provided lithium at a lithium carbonate equivalent dose of 240 mg three times daily, potentially eliminating the need for therapeutic drug monitoring (TDM).
Expert Commentary
Stephan Jackman, Alzamend's CEO, stated, "We are elated to partner with Mass General and Dr. [Ovidiu] Andronesi in this pivotal study for our lead therapeutic candidate AL001." He also noted that a next-generation lithium product like AL001, with an improved safety profile and enhanced biodistribution in the brain that would not routinely require TDM, would represent a significant advancement over current lithium-based treatments.
