A recombinant variant of the alpha-2-macroglobulin blood serum protein, targeting proteases responsible for cartilage degradation in osteoarthritis (OA). CYT-108 was engineered for increased protease-inhibition activity against the major classes of proteases that are responsible for the majority of cartilage catabolism in arthritic joints, while maintaining its broad-spectrum anti-protease activity against serine and threonine proteases.
"Our first-in-human clinical trial is the culmination of 6 years of preclinical R&D, during which we overcame many technical challenges in developing our recombinant A2M variant, CYT-108," said Joey Bose, President & CEO of Cytonics.
"The massive size of the engineered protein (720kD) and complex folding structure made GMP production a scientific feat, and the ingenuity and experience of Lewis Hanna, PhD, our Chief Scientific Officer allowed us to surmount this incredible technical challenge.
The preclinical data is compelling, demonstrating signs of CYT-108's protective capabilities not only in the cartilage tissue, but in multiple other joint physiologies that are involved in the pathogenesis of osteoarthritis. Furthermore, we believe that the development of CYT-108 is de-risked by the clinical and commercial success of our first-generation OA therapy, the Autologous Protease Inhibitor Concentrate (APIC) medical device, which has treated over 8,000 patients using autologous A2M selectively concentrated from their own blood."
The Phase 1 study is designed to assess CYT-108's tolerability and efficacy in patients suffering from primary osteoarthritis of the knee. A single dose of the drug will be administered intra-articularly at two timepoints, 90 days apart. Patients will be monitored every few weeks for an additional 90 days to evaluate safety, pharmacokinetics, and efficacy in reducing joint pain, stiffness, and mobility limitations.
About CYT-108:
CYT-108 is a recombinant variant of the endogenous alpha-2-macroglobulin (A2M) blood serum protein. The "bait" region of the protein, which serves as a substrate for proteases, was engineered to increase its affinity for specific proteases that are known to play a significant role in the molecular pathogenesis of osteoarthritis. The combination of both highly specific and broad-spectrum protease inhibition activity of CYT-108 differentiates this novel biologic from other attempts to develop small molecule inhibitors that target single proteases, positioning CYT-108 as an ideal disease-modifying candidate for osteoarthritis. The development of CYT-108 is predicated on the success of Cytonics' first-generation therapy, the Autologous Protease Inhibitor Concentrate (APIC) system, which is a 510(k) medical device that selectively enriches autologous A2M for intra-articular injection into joints containing articular cartilage (knee, shoulder, spine, hip, etc.). The clinical and commercial success of APIC uniquely de-risks the development of CYT-108 because it is already understood that high concentrations of A2M can be introduced into arthritic joints without significant side effects, and the treatment has achieved clinical and commercial success since it was first cleared by the FDA as a 510(k) device and sold in 2015.
About Cytonics Corp:
Cytonics, founded in 2006, is a private research and development company focused on developing molecular diagnostics and therapeutics for chronic musculoskeletal diseases such as osteoarthritis. The company's flagship product was a diagnostic test (the Fibronectin-Aggrecan Complex Test, FACT) which helps identify the source of joint pain and assists physicians in determining the most appropriate course of treatment. Cytonics then developed the Autologous Platelet-Integrated Concentrate (APIC) system which concentrates a therapeutic blood protein, A2M, from patients' own blood and injects the A2M-rich concentrate into damaged joints. APIC has been used to treat over 8,000 patients nationwide, saving thousands of patients from invasive joint replacement surgeries. The company has raised over $25M in private funding and was awarded $1.8M in grants from the NIH to pursue their innovative research. The company is currently pursuing Phase 1 clinical studies for their lead drug candidate, CYT-108, a recombinant variant of the endogenous alpha-2-macroglobulin protease inhibitor. If approved, CYT-108 may be the first and only disease-modifying therapy for osteoarthritis.
