Ribon’s lead program is developing PARP7 inhibitors for the treatment of cancer, beginning with squamous cell carcinoma of the lung. PARP7 is transcriptionally activated by cancer relevant stresses, such as the toxins in cigarette smoke. Overactive PARP7 expression in tumors plays a role in cancer survival via two mechanisms: a direct dependency on PARP7 for intrinsic cancer cell survival, and by enabling cancer cells to “hide” from the immune system by inhibiting Type I interferon production induced by damage associated molecular pattern (DAMP) recognition pathways. Inhibition of PARP7 can inhibit tumor growth by restoring interferon signaling, effectively releasing the “brake” cancer uses to hide from the immune system and suppress both innate and adaptive immune mechanisms. Ribon’s PARP7 inhibitors have exhibited potent anti-proliferative activity, induction of interferon signaling and durable tumor regression in vivo.

Normal airway cell in smokers
Toxins in cigarette smoke induce PARP7 (via AHR activation) which suppresses the innate immune response.

“PARP7 inhibitors represent a novel approach to treating cancer because they act on the tumor in two ways: directly inhibiting tumor proliferation, and shutting down the “don’t kill me” signal the tumor is sending to evade the immune system.”

Heike Keilhack, Ph.D., Vice President of Biological Sciences

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