Ribon Therapeutics, a clinical stage biotechnology company developing therapeutics targeting stress support pathways, today announced the first publication in the peer-reviewed journal, Cancer Cell, of preclinical data from its lead asset, RBN-2397, a small molecule inhibitor of PARP7. The published data demonstrate that inhibition of PARP7 can activate antitumor immune responses in cancer cells through restoration of Type I interferon (IFN) signaling and cause complete regressions in preclinical models. These preclinical findings support Ribon’s development program for RBN-2397 and validate targeting of PARP7, a key vulnerability in cancer stress support pathways, as a therapeutic strategy.
PARP7 is overexpressed in a number of tumors, including squamous cell carcinoma of the lung (SCCL), which represents approximately 30% of all non-small cell lung cancers. PARP7 is the first monoPARP to be targeted therapeutically and RBN-2397 is the first potent and selective PARP7 inhibitor to enter clinical development.
“This publication in Cancer Cell demonstrates RBN-2397’s mechanism of action of inhibiting a key stress response pathway in cancer cells, illustrating how inhibition of PARP7 can elicit complete tumor regression in preclinical models, as well as tumor-specific adaptive immune response, through restoration of Type I IFN signaling in tumor cells,” said Heike Keilhack, Ph.D., Senior Vice President of Biological Sciences, Ribon Therapeutics. “We are pleased that these data provide further evidence of the critical role PARP7 plays in cancer and antitumor immunity, independent of other PARPs, as well as a strong rationale for clinical development of RBN-2397.”
Key findings of the publication are summarized below:
PARP7 is a monoPARP that acts as a brake in cytosolic nucleic acid sensing in a TBK1-dependent manner blocking Type I IFN signaling and antitumor immunity
RBN-2397 is a potent and selective inhibitor of PARP7, and drug effects in tumor models are dependent on PARP7, but not PARP1
Inhibition of PARP7 by RBN-2397 induces complete tumor regression in a lung cancer xenograft and tumor-specific adaptive immune memory in an immunocompetent mouse cancer model by restoration of Type I IFN signaling
“These findings illustrate the foundational science behind RBN-2397 and our preclinical programs, which we have identified by combining our deep understanding of the critical roles of NAD+-utilizing enzymes in cancer and inflammatory diseases, with our team’s drug development expertise, to bring novel treatments to patients with limited options,” said Victoria Richon, Ph.D., President and Chief Executive Officer, Ribon Therapeutics. “We look forward to providing updates on our clinical studies with RBN-2397 and the rest of our pipeline leveraging our BEACON+ platform.”
Ribon recently completed the dose-escalation portion of its Phase 1 trial evaluating RBN-2397 as a monotherapy in patients with advanced solid tumors. In June 2021, data from this portion of the study, presented at the 2021 American Society of Clinical Oncology Annual Meeting, showed RBN-2397 was well tolerated with evidence of PARP7 inhibition and preliminary signs of antitumor activity.
The expansion portion of the Phase 1 trial is currently enrolling patients in a number of defined cohorts, including SCCL. Ribon plans to initiate a Phase 1b/2 study with checkpoint inhibitors in SCCL in the second half of 2021.
About RBN-2397
RBN-2397 is an orally available small molecule inhibitor of PARP7 that Ribon Therapeutics is developing for the treatment of solid tumors. PARP7 is upregulated in response to cellular stress, including genomic instability in cancers, and acts as a brake on the cellular stress response by negatively regulating the Type I interferon response. By inhibiting PARP7 in tumor cells, RBN-2397 has been shown to directly inhibit cellular proliferation and restore interferon signaling to stimulate an innate and adaptive antitumor immune response. RBN-2397 is currently in a Phase 1 clinical trial as a monotherapy in patients with advanced solid tumors (NCT04053673). PARP7 is overexpressed in a number of tumors, including squamous cell carcinoma of the lung, or SCCL, which represents approximately 30% of all non-small cell lung cancers.
About Ribon Therapeutics
Ribon The...
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