Inflammasome Therapeutics is a science-based company founded to develop therapies for prevalent, degenerative diseases such as Alzheimer's disease, multiple sclerosis, macular degeneration, and Parkinson's disease. The precise causes of these diseases are unknown, but they share many of the same risk factors: smoking, obesity, hypertension, and age. They are all multifactorial diseases, with multiple biochemical factors, many shared, contributing to their progression.
It is now recognized that these diseases 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. Inflammasome Therapeutics' focus is on reducing this dysregulation by preventing aberrant inflammasome activation.
This represents a new approach. To date, the main strategy 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 geographic atrophy, including amyloid-beta, complement, Alu RNA, and iron, all cause or are products of inflammasome activation. Inhibition of inflammasome activation effectively treats these diseases in animal models.
Kamuvudines
In 2014, our co-founder's lab first reported in the journal Science that some existing FDA-approved drugs used in the treatment of HIV and hepatitis B are powerful inhibitors of inflammasome activation. These molecules, nucleoside reverse transcriptase inhibitors (NRTIs), have been approved for decades. By analyzing health claims databases covering over 100 million people in the US, we found that patients taking NRTIs for HIV or hepatitis B had a significantly reduced risk of developing Alzheimer's disease, geographic atrophy, type 2 diabetes, and multiple sclerosis compared to well-matched patients who did not take these drugs.
Unfortunately, the side effects of NRTIs, primarily mitochondrial toxicity, preclude their use in conditions that are not life-threatening. Kamuvudines are chemical derivatives of NRTIs that retain the same anti-inflammasome activity as the parent molecules yet cannot undergo the same metabolism and have no detectable mitochondrial toxicity. In multiple preclinical tests they have been found to be over 1,000 times less toxic than their parent molecules.
Patents
We hold an exclusive worldwide license to the patents arising from Dr. Ambati's laboratory at the University of Kentucky, through the University of Kentucky Research Foundation. These patents cover use of 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.
Key Company Highlights [SPECIAL TREATMENT]
- Clinical-stage company with three active IND programs (IND# 162078 and IND# 170554)
- First-in-class dual NLRP3/NLRC4 inflammasome inhibition platform derived from FDA-approved drug class
- K8 (ocular implant): 66% reduction in GA lesion growth vs. untreated eyes (p=0.029) in Phase I/II
- K9 (oral): reduces neurofilament light chain by 98% in neurodegeneration models vs. ~50% for QALSODY
- K9 penetrates both blood-brain and blood-eye barriers from a single oral compound
- Real-world evidence from over 100 million patients supports reduced disease risk in NRTI users
- 13 issued patents; exclusive worldwide license from the University of Kentucky Research Foundation