Cognition Therapeutics Presents Data Supporting a Phase 2 Clinical Trial with CT1812 in Geographic Atrophy Secondary to Dry AMD

Cognition Therapeutics announced that the scientific rationale, supporting proof-of-concept data and design of the planned phase 2 trial of CT1812 in geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD) will be communicated in an oral presentation at the 2022 Dry AMD Therapeutic Development Summit. 

“There are currently no approved drugs for dry AMD, and given the severe consequence of disease and enormous patient population, it’s imperative that we work towards a treatment,” Lisa Ricciardi, president and CEO of Cognition Therapeutics, said in a company news release. “Complement inhibition has shown potential in clinical trials but must be given via intravitreal injection to each affected eye. We believe that a noninvasive oral therapeutic with a novel mechanism of action that can penetrate the blood-retina barrier and treat both eyes simultaneously would be a significant advantage to the millions of people at risk for permanent vision loss.”

CT1812 is an experimental oral sigma-2 (σ-2) receptor modulator currently in phase 2 clinical trials for both Alzheimer's disease and dementia with Lewy bodies (DLB). An unbiased pathway analysis from two Alzheimer's disease clinical trials identified GA and macular degeneration as two diseases most significantly associated with proteomic changes in CT1812- vs placebo-treated patient biofluids. Further analysis of the proteomes identified key proteins and pathways impaired in dry AMD and GA that were significantly impacted by CT1812 treatment, providing evidence that a σ-2 receptor modulator may have therapeutic potential in dry AMD.

Subsequently, in vitro studies were conducted using RPEs derived from induced pluripotent stem cells (iPSC) that were exposed to amyloid beta oligomers and oxidative stress. Results from these studies demonstrated that administration of CT1812 can rescue the ability of RPEs to recycle photoreceptor outer segments (POS), a vital process that is damaged by stressors including oxidative stress and pathogenic proteins.

“The proteomic analyses from our clinical studies in neurodegenerative disease were instrumental in identifying dry AMD as an indication of interest,” said Mary Hamby, PhD, VP of biology at Cognition Therapeutics. “Published genetic and preclinical findings from independent laboratories supported the role of the σ-2 receptor in dry AMD and our data provide evidence that modulation of the σ-2 receptor may protect sensitive RPE cells and rescue functional deficits. Our next step is to test this novel mechanistic approach in the clinic.”

Based on several lines of evidence including these clinical proteomic analyses and preclinical data in RPE cell models, Cognition has entered discussions with the FDA to initiate a phase 2 clinical trial in over 200 people with GA. The full complement of evidence supporting Cognition's advancement of CT1812 into the clinic, along with the design of the proposed phase 2 study, will be presented at the Dry AMD Therapeutic Development Summit.

Presentation details: