Inflammasome Shares Early K8 Data in GA

Inflammasome Therapeutics has announced encouraging early clinical results for its lead ophthalmic candidate, K8, in the treatment of geographic atrophy (GA). Administered via a sustained-release intraocular implant, K8 demonstrated more than a 50% reduction in GA lesion growth over a three-month period in the first patient cohort of a first-in-human trial.

First-in-Human Trial Shows Over 50% Lesion Growth Reduction

The ongoing Phase 1 trial (ClinicalTrials.gov Identifier: NCT06164587) is a multicenter, 6-month, 30-patient, dose-escalation study designed to evaluate the safety and preliminary efficacy of K8. Patients with bilateral geographic atrophy receive an intraocular implant delivering either a low, medium, or high dose in one eye, while the fellow eye remains untreated to serve as a control.

In the low-dose cohort, a single 3-month implant led to an average 53% reduction in GA lesion growth in treated eyes compared to untreated fellow eyes. This result, achieved with a p-value of 0.03 (mixed-effect model), is notable given the small cohort size of 10 treated eyes and the study’s primary focus on safety rather than statistical significance.

Visual Outcomes Show Stability in Treated Eyes

In addition to anatomical improvement, visual acuity outcomes also trended favorably. Treated eyes demonstrated a mean gain of 1.4 ETDRS letters in best corrected visual acuity (BCVA), while untreated eyes lost an average of 1.9 letters over the same period, suggesting potential preservation of vision with K8 therapy.

The mid-dose cohort has completed enrollment, and recruitment for the high-dose cohort is currently underway.

Targeting Inflammation in Geographic Atrophy

Geographic atrophy is a complex, multifactorial disease driven by various inflammatory toxic factors, including complement proteins, amyloid beta, retrotransposons, and oxidative stress. These elements trigger activation of the inflammasome pathway, leading to macular cell degeneration.

According to Jayakrishna Ambati, MD, co-founder of Inflammasome Therapeutics, K8 inhibits multiple inflammasome types, thereby blocking several upstream inflammatory processes simultaneously. This broad mechanism of action positions K8 as a potentially impactful therapy for inflammation-driven retinal degeneration.

Kamuvudines: A Novel Platform for Inflammasome Inhibition

K8 is the first clinical candidate from Inflammasome Therapeutics' Kamuvudine platform, a new class of inflammasome inhibitors derived from nucleoside reverse transcriptase inhibitors (NRTIs), originally developed for HIV treatment. While traditional NRTIs have shown promise in treating neuroinflammatory and ocular diseases, their systemic toxicity limits long-term use.

Kamuvudines are chemically modified NRTIs that retain anti-inflammasome activity but offer improved safety and tissue targeting, making them suitable for chronic indications such as GA.

Supporting preclinical data for this mechanism has been published in Science (2014), Science Advances (2022), Nature (2021), and Signal Transduction and Targeted Therapy, underscoring the scientific foundation behind the Kamuvudine platform.