One the key chronokine targets identified using Alkahest’s platform is eotaxin. Eotaxin is an immunomodulatory chemokine that is increased in normal aging as well as multiple diseases of aging. It has been implicated in Alzheimer’s disease, Parkinson’s disease, retinal diseases and other aging-related diseases that involve systemic inflammation, demonstrating effects both in the CNS and in the periphery. Targeting this chronokine may cause improvements via two mechanisms—a broad anti-inflammatory mechanism and an immune modulatory mechanism through the body’s innate immune cells.
Alkahest is developing AKST4290, an inhibitor against CCR3, the natural receptor for eotaxin. AKST4290 is an orally effective drug designed to block eotaxin from binding to its G-protein coupled receptor (GPCR) CCR3. CCR3 plays an important modulatory role in inflammation, immune cell recruitment, and neovascularization; processes important for the pathogenesis of wet age-related macular degeneration (wet AMD) and other neurological and immunological diseases.
Importantly, AKST4290 is a small molecule that is easy to administer orally as a pill twice a day. This represents a significant convenience benefit for patients in the diseases studied.
AKST4290 is being studied as a treatment for wet AMD, the leading cause of blindness in people over 60 in developed countries. Alkahest has also initiated a Phase 2 trial supported in part by the Michael J. Fox Foundation studying the effects of AKST4290 in patients with Parkinson’s disease, a devastating neuromuscular disorder affecting more than seven million people worldwide.
Two Phase 2a clinical trials for AKST4290 in neovascular AMD were completed in 2018: one in naïve patients and one in refractory wet AMD patients. Data from these trials were presented at Retina World Congress 2019, ASRS 2019, AAO 2019, and Angiogenesis & Exudation 2020.