Inflammasome Therapeutics Reports Encouraging Early Results for K8 in Geographic Atrophy
Inflammasome Therapeutics, which is developing a new class of inflammasome inhibitors known as Kamuvudines, announced promising early clinical data for its lead ophthalmic candidate K8. Delivered via a sustained-release intraocular implant, K8 reduced geographic atrophy (GA) lesion area growth by more than 50% after 3 months of treatment in the first cohort of patients.
This first-in-human trial (NCT06164587) is a multicenter, 30-patient, 6-month, safety and dose-escalation study with three cohorts. Patients with bilateral GA receive a low, medium, or high dose implant in one eye at baseline and again at 3 months, with the untreated eye serving as the control.
“Patients receiving the 3-month, low-dose implant showed an average 53% reduction in lesion growth compared to untreated eyes at 3 months after a single injection,” said Paul Ashton, PhD, CEO and co-founder of Inflammasome Therapeutics. “The trial is relatively small (10 treated eyes in the first cohort) and was not designed to show statistical significance, so achieving such a large effect with a P value of 0.03 (mixed effect model) is extremely encouraging.”
Visual outcomes also trended positively. Treated eyes maintained essentially stable vision, with best corrected visual acuity (BCVA) increasing an average of 1.4 ETDRS letters, while untreated eyes continued to decline, losing an average of 1.9 ETDRS letters.
The mid-dose cohort has completed enrollment, and the high-dose cohort is currently enrolling.
“GA is a multifactorial disease in which many inflammatory toxic factors—such as various forms of complement, amyloid beta, retrotransposons, and oxidative stress—are upregulated in the diseased eye, which causes activation of the inflammasome pathway and atrophy of macular cells. K8 inhibits multiple inflammasomes, blocking the effects of numerous inflammatory toxins, including complement," said Jayakrishna Ambati, MD, co-founder of Inflammasome Therapeutics.
Kamuvudines: A Novel Class of Inflammasome Inhibitors
K8 is the first clinical candidate from the company’s Kamuvudine platform, derived from nucleoside reverse transcriptase inhibitors (NRTIs) originally developed for HIV. While NRTIs themselves have shown potential to treat neuroinflammatory and ocular diseases, their systemic toxicity limits chronic use. Kamuvudines retain the anti-inflammasome activity of NRTIs but are designed to be safer and more targeted.
Preclinical research supporting the Kamuvudine mechanism has been published in Science, Science Advances, and Signal Transduction and Targeted Therapy (Science 2014, Science Advances 2022, Nature 2021).
Beyond GA, inflammasome activation is implicated in Alzheimer’s disease, ALS, Parkinson’s disease, multiple sclerosis, and diabetic macular edema, offering a broad horizon for Kamuvudine-based therapies, according to Inflammasome.