Inflammasome Therapeutics has received FDA approval to launch a phase 1/2 first-in-class clinical trial that will evaluate its investigational drug candidate for the treatment of geographic atrophy (GA).
Company refresh, please.
Founded in 2016 and based in Newton, Massachusetts, Inflammasome Therapeutics is a science based company focused on developing novel delivery technologies for the release of therapies to potentially treat prevalent degenerative and central nervous system (CNS) diseases:
- Alzheimer’s disease (AD)
- Multiple sclerosis (MS)
- Age-related macular degeneration (AMD)
- Parkinson’s disease (PD)
Why these diseases?
Each of these diseases share a similar pattern where there can be an upregulation of the inflammatory process brought on by the activation of inflammasomes—intracellular multiprotein complexes that help trigger and maintain the inflammatory response as part of the immune system, according to Inflammasome Therapeutics.
However, as part of the diseases, inflammasomes are chronically activated to cause the continual release of inflammatory elements that, as a result, can lead to progressive tissue damage and disease progression.
So what’s the goal?
The company is working to prevent this inflammasome activation by reducing the inflammatory process’s dysregulation.
Which is where Kamuvudines come into play.
I’m listening …
Kamuvudines have been proven to inhibit inflammasome activation in cell culture and animal models.
Further, according to a 2014 study conducted by the University of Kentucky Research Foundation (UKRF) clinical lab of the company’s Co-Founder Jayakrishna Ambati, MD—and published in Science—a number of existing FDA-approved drugs are actually inhibitors of inflammasome activation called nucleoside reverse transcriptase inhibitors (NRTIs).
To note, Kamuvudines are chemical derivatives of NRTIs with the same anti-inflammasome activity as the parent molecule without their side effect profile— specifically mitochondrial toxicity.
And in relation to GA?
The company reported that these Kamuvudines and their precursors have been found to be “highly effective in multiple pre-clinical models of the mediated diseases macular degeneration and type 2 diabetes.”
In fact, Inflammasome Therapeutics also noted that patients taking NRTIs for human immunodeficiency virus (HIV) or hepatitis B have a significantly reduced risk for developing diseases such as AD, GA, MS, and type 2 diabetes.
What might their efficacy be for AMD?
Multiple pre-clinical tests conducted by Dr. Ambati’s lab have reportedly demonstrated Kamuvudines to be “over 1,000 times less toxic than their parent molecules” as well as highly effective against AMD and type 2 diabetes.
According to CEO Paul Ashton, PhD, the development of Kamuvudines for such CNS and degenerative disorders are intended to “target multiple toxic pathways—complement, amyloid beta, iron overload, retrotransposons, etc.—via their common pathway to toxicity, inflammasome activation.”He added: “We believe this approach will have a more profound effect” as opposed to targeting a single aspect of the disease.
Talk about this upcoming trial.
Per the company, participants will receive a tiny sustained release implant of the drug (Kamuvudine) directly into the retinal space for an initial period of 3 months post-injection.
Important note: this drug was designed specifically for retinal delivery, while the implants and injector system are intended specifically for the Kamuvudine.
The resulting effect: Per the company, “for high, therapeutic doses to be maintained in the eye while the drug is undetectable in the systemic circulation.”
What else to know?
The company owns an exclusive global license to all patents from this pre-clinical research. In the U.S. and other countries, 13 patents have been issued thus far.
When can we expect data?
No specific timeline has been set yet.
And the significance?
Per Dr. Ashton, this form of treatment, if replicated in human disease, might prevent the process that causes GA while most of the retina is still healthy.
“It would be as close to a functional cure for GA as one could hope for in a condition where the only approved therapeutic treatments simply slow progression of the disease,” stated Dr. Ambati.