Inflammasome Therapeutics Announces First Patient Dosed in Geographic Atrophy (GA) Clinical Trial

Inflammasome Therapeutics (https://www.inflam.com), a private company developing a new class of inflammasome inhibitor drugs, Kamuvudines, as therapies for prevalent, degenerative diseases, announced the first patient has been dosed in a first-in-class clinical trial for dry AMD. The Phase 1 trial (ClinicalTrials.gov ID NCT06164587) is sponsored by the University of Kentucky and expected to enroll up to five patients with GA due to age-related macular degeneration (AMD).

Trial participants will receive a tiny, sustained release implant (illustration is available) that will provide slow, consistent release of the drug K8 directly into the back of the eye. K8 was specifically designed for retinal delivery and the implants and injector system were crafted to deliver this particular drug. This combined drug and delivery strategy allows high therapeutic doses to be maintained in the eye while the drug is undetectable in systemic circulation.

"This marks the second trial underway with our Kamuvudines in ophthalmology," said Dr. Paul Ashton, President and CEO of Inflammasome Therapeutics, developers of both the compounds and delivery systems for administration.

GA affects approximately one million individuals in the US and more than eight million worldwide. In GA, multiple toxic substances (such as complement, amyloid beta, retrotransposons, iron, and reactive oxygen species) build up in the eye and trigger inflammasome activation that then causes cells in the macula to slowly die (atrophy). This is a very similar process to what goes on in the brain and nervous system in patients with ALS, Alzheimer's disease and multiple sclerosis.

Last year, two drugs (Syfovre and Izervay) were approved for GA that target one of these toxic substances, complement. The drugs do not target other toxic elements and only modestly slow progression of the disease. Unfortunately, they also increase the risk of developing wet AMD. Furthermore, the drugs require an intraocular injection every four to eight weeks.

There is tremendous interest in developing potential GA treatments. There are 38 other interventional clinical trials for GA registered in clinicaltrials.gov., almost all of which target individual toxic substances, but not the underlying cause of the atrophy, inflammasome activation.

"That's where we believe we provide a distinctive and significant difference," said Dr. Ashton. "Our Kamuvudines have been shown in pre-clinical studies to block inflammasome activation caused by multiple toxic pathways ? complement, amyloid beta, iron overload, retrotransposons, etc. If we can block inflammasome activation in the clinic, we believe we can have a profound effect on the disease by blocking multiple pathways."

Dr. Ashton confirmed that the implications for treatments in other neuroinflammatory diseases like Alzheimer's Disease, ALS and Multiple Sclerosis are "extremely interesting. We have Kamuvudines specifically designed for neurological diseases that penetrate into the brain and Central Nervous System from a simple oral tablet. Inflammasome Therapeutics is expected to begin clinical trials in some of these diseases soon as well," he affirmed.

Inflammasome Therapeutics' co-founder, Dr. Jayakrishna Ambati, has spent more than a decade developing Kamuvudines and identifying their role in the inhibition of inflammasome activity that is being found to be the underlying cause of many diseases. In a series of publications in journals such as Science and Nature, he has described the basic research on GA and pre-clinical development of Kamuvudines:

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

https://www.nature.com/articles/nature09830

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

https://www.science.org/doi/10.1126/sciimmunol.abi4493

Dr. Ambati and Dr. Ashton co-founded Inflammasome Therapeutics in 2016 to develop therapies for prevalent, degenerative diseases and to develop novel delivery technologies for the sustained release of therapeutic agents and compounds. The company combines scientific excellence with proven development expertise and works to develop products via a mixture of licensing agreements and internal development, including work with Boehringer Ingelheim and the Gates Foundation.