BEST IN CLASS INNATE IMMUNITY PROGRAM

ENPP1 INHIBITION: UPREGULATES INNATE IMMUNE RESPONSE IN TUMORS

Activating innate immune response may improve immunotherapy responses. Previous intra-tumoral STING agonism (Aduro and Merck Phase 1-2) - Shows Pharmacodynamic (PD) effects in injected tumor (proof of principle) - But failed to produce a robust abscopal (ripple) effect. Direct systemic STING agonism may cause auto-immunity (lupus, Aicardi-Goutières). ENPP1 inhibition is superior to targeting STING directly. ENPP1 is primed by DNA damage and cytoplasmic DNA leaks (safer, specific) •ENPP1 inhibition has a broader immune repertoire: It targets both Innate (STING) and Adaptive (Adenosine) •ENPP1 is a player in DNA damage response and chemo-resistance. SR-8541A is a small molecule with Excellent preclinical efficacy and oral bioavailability, likely safe and tolerable, since both Knockout animals are viable - ENPP1 germline mutations in humans are handled with bisphosphonate supplementation – and preliminary rodent tolerability is safe.

 “PIPELINE IN A TARGET” ENPP1 INHIBITORS may HAVE A LARGE POTENTIAL IN:

Infectious Diseases Mycobacterial diseases: CDNP is a “bacterial ENPP1” that promotes virulence by inhibiting cGAS-STING-IFN signaling pathway. Stingray has compounds that hit CDNP and ENPP1 for mycobacterium avium (MAC) and mycobacterium tuberculosis, Hepatitis B and other DNA viruses. STING Pathway is vital in the host response to clear HBV. Covid-19 dramatically suppresses interferon response. Auto-antibody Diseases Hemophilia, Anti-Factor VIII antibody disease, Lupus Nephritis long lived plasma cells rely on ENPP1.