Science and Technology
The Role of Inflammasomes in Degenerative Disease
It is now recognized that Alzheimer's disease, multiple sclerosis, macular degeneration, and Parkinson's disease are all characterized by upregulation of the inflammatory process, driven by prolonged activation of inflammasomes. Inflammasomes are intracellular multiprotein complexes that help trigger and maintain the inflammatory response normally, as part of the innate immune system. In these degenerative diseases, however, inflammasomes become chronically activated, causing the continual release of caspase-1, IL-18, and IL-1beta, which in turn cause progressive tissue damage and disease progression.
Why This Approach Is Different
To date, the main strategy in developing therapies for Alzheimer's and geographic atrophy has been to attack a single causal element: amyloid-beta for Alzheimer's, and various forms of complement for geographic atrophy. These attempts have all failed in large-scale clinical trials. We believe that targeting a single factor may not be optimal when multiple factors are present. The multiple elements elevated in tissues of patients with these diseases all cause or are products of inflammasome activation. In preclinical models, administration of these factors initiates inflammasome activation and disease symptoms. Inhibition of inflammasome activation effectively treats these diseases in animal models.
Why This Is Novel: Summary for Due Diligence
- Mechanism: Upstream inhibition of the full inflammatory cascade, not a single downstream target
- Differentiation: Dual NLRP3 and NLRC4 inhibition, broader than single-inflammasome approaches
- Real-world evidence: Analysis of over 100 million patients shows significantly reduced disease risk in NRTI users vs. matched controls
- Competitive white space: No approved small-molecule inflammasome inhibitor exists for any of the company's target diseases
- Safety precedent: Derived from FDA-approved drug class (NRTIs) with decades of documented human safety data
- Barrier penetrance: Both blood-brain and blood-eye barrier crossing, enabling ocular and CNS applications from one platform
The Kamuvudine Platform
In 2014, our co-founder's lab first reported in the journal Science that existing FDA-approved drugs used to treat HIV and hepatitis B are powerful inhibitors of inflammasome activation. These molecules, NRTIs, have been approved for decades. NRTIs were highly effective in multiple preclinical models of macular degeneration and type 2 diabetes, and health claims data from over 100 million people confirmed significantly reduced disease risk in NRTI users. The barrier to clinical use was mitochondrial toxicity, a side effect of the intracellular metabolism of these drugs that is unrelated to their anti-inflammasome activity. Kamuvudines are chemical derivatives engineered to retain the anti-inflammasome mechanism while eliminating that toxicity entirely. In preclinical tests they are over 1,000 times less toxic than their parent molecules.
K8 — Ocular Implant (Kamuvudine-8)
K8 is a powerful inflammasome inhibitor formulated as a tiny, bioerodible, injectable ocular implant. Delivered to the vitreous, the implant provides sustained drug release to the posterior segment of the eye while avoiding systemic exposure. This delivery format was purpose-built for ocular disease settings where consistent local drug levels drive efficacy.
K9 — Oral (Kamuvudine-9)
K9 is a stable, water-soluble drug with good oral bioavailability and a 2-hour half-life in the blood. It readily penetrates both the blood/brain and blood/eye barriers. This dual penetrance is what makes K9 the lead candidate not only for current ocular clinical programs but for the full neurodegenerative pipeline. Preliminary Phase I data show target engagement and significant reductions in inflammatory markers.
Intellectual Property
We hold an exclusive worldwide license to patents from the University of Kentucky Research Foundation covering NRTIs and Kamuvudines for dry AMD, GA, Parkinson's disease, Alzheimer's disease, multiple sclerosis, rheumatoid arthritis, and diabetes. Thirteen patents have been issued in the US and other countries, with additional applications in process.