PARP7 is a Novel Tumor Dependency, Enabling Cancer Cells to Evade the Immune System
First Ever Clinical Evaluation of a monoPARP Inhibitor
CAMBRIDGE, Mass.–(BUSINESS WIRE)–Ribon Therapeutics, a biotechnology company developing first-in-class therapeutics targeting novel enzyme families activated under cellular stress conditions, today announced the dosing of the first patient in its Phase 1 clinical trial of RBN-2397, the company’s first-in-class PARP7 inhibitor. PARP7 belongs to a family of enzymes activated under cellular stress conditions, known as monoPARPs, which are distinct from polyPARPs such as PARP1/2. Recent science pioneered by Ribon has shown monoPARPs are key regulators of stress responses and are linked to the development of certain diseases, including cancers. The Phase 1 trial of RBN-2397 is the first-ever clinical evaluation of a monoPARP inhibitor.
“With RBN-2397, we are targeting PARP7, which plays a critical role in cancer cell survival. Inhibiting PARP7 has been shown to potently inhibit cancer cell proliferation and also release a ‘brake’ that cancer cells use to evade the immune system,” said Sudha Parasuraman, M.D., Chief Medical Officer, Ribon Therapeutics. “We have seen very strong preclinical evidence supporting the clinical potential of RBN-2397, and we believe it can become a valuable new treatment option for cancer patients.”
“Bringing our lead compound into the clinic is a key milestone for Ribon, demonstrating our ability to advance from program initiation to the clinic in under three years,” said Victoria Richon, Ph.D., President and Chief Executive Officer, Ribon Therapeutics. “This progress validates the utility and efficiency of our platform in rapidly interrogating novel biological pathways and developing clinical drug candidates. The platform has broad potential applications, enabling us to develop first-in-class therapeutics against an expanding set of novel targets in oncology, neurodegeneration and inflammatory disease.”
The Phase 1 clinical trial is a multi-center, open-label, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of RBN-2397, as well as initial signs of anti-tumor activity in patients with advanced-stage solid tumors. The goals of the study are to establish the recommended dose for future clinical investigation and to explore pharmacodynamic readouts and predictive biomarkers. The study is comprised of a dose escalation phase, which will be followed by a number of expansion cohorts evaluating RBN-2397 in patients with various tumor types, including squamous cell carcinoma of the lung, in which PARP7 has been shown to be genetically amplified. Additional information on this clinical trial can be found on www.clinicaltrials.gov.
RBN-2397 – Inhibiting PARP7, a Key monoPARP Cancer Dependency
Ribon’s lead program, RBN-2397, is focused on inhibiting overactive PARP7 in tumors, which has been shown to play a key role in cancer survival. Ribon’s research has discovered that many cancer cells rely on PARP7 for intrinsic cell survival, and that PARP7 allows cancer cells to “hide” from the immune system. Ribon has demonstrated that inhibition of PARP7 with RBN-2397 can potently inhibit the growth of cancer cells and restore interferon signaling, effectively releasing the “brake” cancer uses to hide from the immune system and suppress both innate and adaptive immune mechanisms. In several cancer models, RBN-2397 demonstrated durable tumor growth inhibition, potent antiproliferative activity and restoration of interferon signaling. Ribon plans to initially develop RBN-2397 in squamous cell carcinoma of the lung, where research has shown PARP7 to be genetically amplified. The company also plans to explore RBN-2397 for the treatment of additional cancers, including cancers of the aerodigestive tract, pancreatic cancer and ovarian cancer.
PARP7 is a member of the monoPARP family of proteins, which are key regulators of stress responses that enable cancer cells to survive and also evade immune detection, and emerging science has linked their activity with disease development. MonoPARPs are a family of 12 enzymes that are functionally and structurally distinct from the more well-known polyPARPs, such as PARP1/2. MonoPARPs function across a variety of stress responses relevant to disease development in cancer, inflammatory conditions and neurodegenerative diseases. Ribon has built an integrated technology platform to interrogate monoPARPs to develop first-in-class, small molecule therapeutics.
About Ribon Therapeutics
Ribon Therapeutics is a clinical-stage biotechnology company developing first-in-class therapeutics targeting novel enzyme families activated under cellular stress conditions that contribute to disease. We are exploring novel areas of biology to develop effective treatments for patients with limited therapeutic options. Leveraging a chemical biology approach and our proprietary discovery platform, we are building a pipeline of selective, small molecule inhibitors to numerous NAD+ utilizing enzymes, beginning with monoPARPs, which have applications across multiple therapeutic areas. Our lead program is RBN-2397, a first-in-class PARP7 inhibitor in development for the treatment of cancer. Ribon is located in Cambridge, Massachusetts. For more information, please visit www.ribontx.com.
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Cory Tromblee
Scient PR
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