Inflammasome inhibitor found to reduce GA lesion area growth in clinical study

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Inflammasome Therapeutics’ first inflammasome inhibitor, Kamuvudine, K8, was recently found to have reduced geographic atrophy (GA) lesion area growth by more than 50% in its first human clinical trial of the drug.¹ K8 is one of many Kamuvudines that the company is developing for ophthalmic and neurological conditions, according to a news release.

The multicenter, 30-patient, 6-month safety and dose-escalation trial was split into 3 cohorts, with patients with bilateral GA receiving low, medium, or high dose implants at baseline and 3 months in 1 eye, with untreated eyes serving as controls.¹

The reduced GA lesion area growth findings were taken from the initial cohort of patients, which was a single-center, open-label, 26-week study that worked to evaluate the safety and treatment efficacy of K8 in patients with GA due to age-related macular degeneration (AMD).

Up to 5 subjects were slated to receive study medication via intravitreal injections, with 7 scheduled visits. Those visits occurred at screening with baseline (injection), safety visit 2 days after injection, week 4, week 13 (injection), safety visit 2 days after injection, week 17, and week 26.²

Examinations in the study look for continuous changes in visual acuity, change in area of GA lesion in diagnostic imaging, response measured by multifocal electroretinogram, change in reading speed, and change in microperimetry response.²

“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 cofounder of Inflammasome Therapeutics. In the release. “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. Vision trends were also positive: eyes receiving the K8 implant had essentially stable vision.”

Ashton also stated in the release that best corrected visual acuity increased an average of 1.4 ETDRS letters in K8-treated eyes, while untreated eyes continued to deteriorate. Specifically, untreated eyes lost an average of 1.9 ETDRS letters.¹ “GA is a slowly progressive disease and over time we would expect vision in untreated eyes to continue to deteriorate,” Ashton said in the release.

“GA affects approximately one million people in the U.S. and more than eight million worldwide,” said Jayakrishna Ambati, MD, cofounder of Inflammasome Therapeutics, in the release. “We are encouraged by both the increased magnitude and duration of the effect seen so far with the K8 implant.”

Now the mid-dose cohort has completed enrollment in the study.¹ “That group will be followed by a high dose cohort, which is currently enrolling,” Ashton said in the release.

Inflammasome activation may also be a key element in other neuroinflammatory and ocular diseases, including Alzheimer disease, ALS, Parkinson disease, multiple sclerosis, and diabetic macular edema, according to the news release. Inflammasome Therapeutics’ Kamuvudines are derivatives of a class of anti-HIV drugs, NRTIs, but are designed to be safer for treatment, the company stated.¹

“GA is a multifactorial disease in which many inflammatory toxic factors such as various forms of complement, amyloid beta, retrotransposons, oxidative stress are upregulated in the diseased eye, which causes upregulation of the inflammasome pathway and atrophy of cells in the macula. Over time, the area of atrophy grows and can lead to vision loss,” said Ambati in the release.

“We believe the impressive result seen in this clinical trial and in numerous preclinical studies are due to the unique mechanism of K8, which inhibits activation of multiple inflammasomes and thereby blocks the effects of numerous inflammatory toxins, including complement.”

References:

1. Inflammasome Therapeutics’ K8 implant cuts lesion growth by more than 50% in geographic atrophy after 3 months. News release. Businesswire. September 11, 2025. Accessed September 12, 2025. https://www.businesswire.com/news/home/20250911932452/en/Inflammasome-Therapeutics-K8-Implant-Cuts-Lesion-Growth-by-more-than-50-in-Geographic-Atrophy-after-Three-Months-in-Multi-Center-Trial

2. University of Kentucky. Evaluation of Kamuvudine-8 in subjects with geographic atrophy (K8 for GA). NCT06164587. Last updated August 7, 2025. https://clinicaltrials.gov/study/NCT06164587?locStr=United%20States&country=United%20States