Development of a stress kinase inhibitor therapeutic candidate for Alzheimer's Disease and related dementia

There is an urgent need for disease modifying therapeutic approaches to Alzheimer’s disease, a major health crisis that lacks disease modifying therapies. Neurokine Therapeutics (NKT) has a unique phase 2 ready clinical asset, MW01-18-150SRM (= MW150), that represents a paradigm shift from the field’s dominant focus on amyloid pathway targeted therapeutic candidates. MW150 has a unique portfolio of target recognition and engagement, preclinical and clinical safety, and orally bioavailable drug exposure. The portfolio provides rational explanations for some of the off-target effects, adverse pharmacology, and clinical challenges encountered with prior art in the same therapeutic class, only one of which exhibited brain exposure. Therefore, NKT seeks to rapidly fill a key gap for clinical development and future commercialization through leveraging of the NIA SBIR program. Even with covid-19 pandemic delays, NKT anticipates an exceptional phase 2a ready portfolio before the potential start date of a Fast Track SBIR investment by NIA. MW150 development was based on the perspective that Alzheimer’s and related diseases are disorders of progressive synaptic dysfunction with a common neuroinflammation component. Therefore, our novel approach to disease modifying therapeutic intervention was to target pathophysiology progression pathways, with the neuroinflammation-synaptic dysfunction axis being an underlying element across multiple diseases. The activity of the druggable serine/threonine protein kinase, p38alphaMAPK is increased in both neurons and glia, raising the potential for efficacy through a novel pleiotropic pharmacological mechanism in which a single molecular target drug is modulated in distinct cellular pathophysiology processes. Our specific aims are: Aim 1, Generate, qualify and transfer to the Columbia University (CU) site drug product and placebo capsules. Commercial scale drug substance is on hand, GMP drug product batch processes are established and CU has an experienced and qualified Research Pharmacy; Aim 2A, Prepare, recruit, and conduct a phase 2a clinical study of MW150. We will study 24 Alzheimer’s patients, randomized to once daily administration of test article (MW150: 42 and 84 mg) or placebo (3:1 ratio); Aim 2B. Evaluate safety and pharmacokinetics and monitor response biomarkers. Key milestones for SBIR part I deal with delivery of sufficient validated drug product to the clinical site research pharmacy. Key milestones for part II deal with clinical treatment and evaluations of safety and PK. Outcomes will fill a critical gap in MW150’s commercial and clinical development portfolio as well as provide a firm foundation required for follow-on phase 2b studies in Alzheimer’s Disease. The potential longer-term impact would be filling a void in safe, disease modifying therapeutics for a set of related neurologic disorders.