CognitionTherapeutics, Inc. has dosed the first patient in a phase 2 trial assessing the efficacy, safety, and tolerability of CT1812, an experimental therapy, for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Give me a rundown on the company first.
Cognition Therapeutics is a clinical-stage biopharmaceutical company focused on developing small-molecule therapeutics for age-related degenerative disorders within the central nervous system (CNS) and retina.
Now CT1812.
CT1812 is an experimental, first-in-class, small molecule currently being investigated for five indications, including dry AMD, and four phase 2 trials for early and mild-to-moderate Alzheimer’s disease and dementia.
The orally-administered drug is designed to penetrate the blood-brain and blood–retina barriers as well as selectively bind to the sigma-2 (σ-2) receptor complex, which is involved in regulating key cellular processes.
Also of note, the FDA cleared CT1812’s investigational new drug (IND) application for GA secondary to dry AMD in March 2023.
How is it administered?
Compared to other dry AMD therapies, which are intravitreally injected, CT1812 is orally-administered.
Gotcha. Any prior clinical data on it?
Yup!
The company previously conducted two Alzheimer’s disease trials that identified GA and macular degeneration as being notably associated with proteomic changes within patient biofluids that were CT1812- compared to placebo-treated.
Other in vitro studies using retinal pigment epithelium (RPE) from induced pluripotent stem cells (iPSC) supported CT1812 administration for allowing the RPE to recycle photoreceptor outer segments—a critical process that could be damaged by stressors.
So talk about this study.
The prospective, multicenter, randomized, double-masked, placebo-controlled phase 2 MAGNIFY study (NCT05893537) has enrolled an estimated 246 patients being assessed over a 104-week treatment period followed by a 28-day post-treatment safety follow-up period.
How about the dosages?
Patients will be randomized into two groups to receive either a single, daily 200 mg dose of CT1812 (n = 123) or a single, daily dose of a placebo (n = 123).
How is patient eligibility determined?
Patients must be ≥50 years old with a best-corrected visual acuity (BCVA) of 24 letters or better—via the Early Treatment Diabetic Retinopathy Study (ETDRS) charts—as well as received a stable pharmacological treatment for any other chronic conditions for at least 30 days before the study’s screening.
They must also not have GA due to causes other than dry AMD or have a history or current evidence of wet AMD.
See here for the full inclusion and exclusion criteria.
What’s being measured?
The primary outcome includes change from baseline in GA lesion area in the study eye over the treatment duration (104 weeks), as measured by fundus autofluorescence (FAF) imaging.
Secondary outcomes included:
- CT1812’s safety and tolerability, as measured by the severity and presence of adverse events (AEs) vs placebo.
- CT1812’s plasma concentration, as measured by a pre-dose plasma concentration.
Significance?
Per Cognition Therapeutics’ President and CEO Lisa Ricciardi:
“Our research suggests that a σ-2 modulator, such as CT1812, has the potential to protect RPE cells from several of these key drivers, which may allow patients to retain their visual acuity for longer.”