Inflammasome Therapeutics, a private, clinical-stage biotech company developing novel, first-in-class, dual inflammasome inhibitors for prevalent ophthalmic and neurodegenerative diseases, announced completion of enrollment of a multicenter Phase II dose-ranging trial (NCT06164587) for its dual inflammasome inhibitor, K8, for geographic atrophy (GA).

Thirty patients with bilateral GA were recruited at nine centers throughout the U.S. In this 6- month trial, patients received 3-month biodegradable, intraocular implants containing 0.3, 0.7 or 1.05 mg K8 in one eye, with the contralateral untreated eyes serving as controls. After 3 months, patients receive a second injection and are followed for another 3 months.

The primary endpoints of the trial are safety and efficacy assessed by changes in GA lesion size growth, which is graded by an independent, masked reading center.

In September of this year, the company reported that in the first cohort (0.3 mg K8), the 10 treated eyes showed a greater than 50% reduction in lesion growth compared to the 10 untreated control eyes) after 3 months.

“GA is the most serious form of dry macular degeneration, affecting over one million people in the U.S. It is a multifactorial disease, and K8 targets multiple GA disease pathways via a novel mechanism of action,” said Paul Ashton, Ph.D., co-founder and Chairman/CEO of Inflammasome Therapeutics. "We are delighted that this trial has completed enrollment and are optimistic that the 6 month data will continue to show a strong reduction in lesion growth with few side effects,” he continued.

Jayakrishna Ambati, M.D., co-founder of Inflammasome Therapeutics, explained that in GA multiple toxic substances, including various forms of complement, amyloid beta, retrotransposons, oxidative stressors, trigger inflammasome activation that causes cells in the macula to slowly die (atrophy). Over time, the area of atrophy grows in size and can lead to vision loss. The two FDA-approved drugs for GA, SYFOVRE® and IZERVAY™, each target a different form of complement and can reduce lesion growth by approximately 20% with monthly intraocular injections, but did not reduce vision loss over 12 months in their Phase III clinical trials. The K8 implant is designed to block multiple disease pathways with intraocular injections every 3 months. “Based on the preliminary data from this trial, we are very encouraged by the magnitude of the effects seen so far with the K8 implant,” Dr. Ambati said.

K8 is a member of a new class of inflammasome-inhibiting drugs, called Kamuvudines, that were discovered by Dr. Ambati. They are derivatives of a class of anti-HIV drugs, NRTIs. NRTIs themselves have potential for repurposing as treatments for these diseases but unfortunately have significant systemic toxicity that may hinder their use. Kamuvudines retain the anti-inflammasome activity of NRTIs but are designed to be safer. Earlier pre-clinical work on Kamuvudines has been described in:

https://www.science.org/doi/10.1126/science.1261754

https://www.science.org/doi/10.1126/sciadv.abj3658

https://www.nature.com/articles/s41392-021-00537-z

Inflammasome Therapeutics (https://www.inflam.com) is a private, clinical-stage biotech company developing novel, first-in-class treatments for ophthalmic and neurodegenerative diseases (a sustained release biodegradable K8 implant for eye diseases and K9, an oral treatment for eye and systemic diseases). Phase I/II trials for these drugs are focused on Geographic Atrophy (NCT06164587), Diabetic Macular Edema (NCT06781255) and Thyroid Eye Disease (NCT06467435). Inflammasome Therapeutics recently announced it would be collaborating with The Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital to design a new Healey ALS MyMatch trial evaluating oral K9 in individuals with ALS.

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