CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Ribon Therapeutics, a clinical stage oncology company developing therapeutics targeting stress support pathways, today announced that it will present one oral and four poster presentations at the American Association for Cancer Research (AACR) 2021 Virtual Annual Meeting (Week 1), taking place from April 10 to 15, 2021. Abstracts are available at: www.aacr.org.

“The breadth of new pre-clinical data that we are presenting this year at AACR further validates our BEACON⁺ platform targeting novel cellular stress pathways,” said Heike Keilhack, Ph.D., Senior Vice President of Biological Sciences, Ribon Therapeutics. “We are particularly encouraged by our research further elucidating the mechanism of action of our PARP7 inhibitor and lead asset, RBN-2397, and its potential for efficacy in numerous types of cancer.”

Ribon Therapeutics will present the following from its development program and platform:

Abstract Title: RBN-2397: A potent and selective small molecule inhibitor of PARP7 that induces tumor-derived antitumor immunity dependent on CD8 T cells
Presenter: Joseph M. Gozgit, Ph.D., Director, Biological Sciences, Ribon Therapeutics
Date & Time: Sunday, April 11, 2021 at 2:00 PM ET
Session Type: Minisymposium
Session Title: New Therapeutics Targeting Molecular Drivers in Cancer
Abstract ID: 48
Summary:

• RBN-2397 restores Type I interferon (IFN) signaling in cancer cells and researchers demonstrate that this is an on-target effect of inhibiting the catalytic activity of PARP7 and not PARP1. Researchers further show that the adaptive immune response was required for the antitumor effects of RBN-2397.

Abstract Title: Elevated PARP7 expression in select cancers identifies a target population for RBN-2397 therapy
Presenter: Jodie Wong, Research Associate, Ribon Therapeutics
Date & Time: Available for online viewing starting at 8:30 AM on Saturday, April 10
Session Type: E-Poster Session
Session Title: Biomarkers Predictive of Therapeutic Benefit
Abstract ID: 381
Summary:

• RBN-2397 is a PARP7 inhibitor that induces cancer cell autonomous and immune stimulatory effects in preclinical models through enhanced Type I IFN signaling in cancer cells. Elevated PARP7 expression or amplification may identify cancer patients who could derive benefit from treatment with RBN-2397. Researchers showed the presence of PARP7 amplifications as well as high expression levels in several tumor types including non-small cell lung carcinoma, breast, and pancreatic ductal adenocarcinoma, providing evidence for the therapeutic relevance of PARP7 inhibition and highlighting potential patient selection strategies to identify those patients more likely to benefit from RBN-2397 treatment.

Abstract Title: Investigating the mechanism of PARP7 inhibition in Type I interferon signaling by arrayed CRISPR screening
Presenter: Bin Gui, Ph.D., Senior Scientist, Ribon Therapeutics
Date & Time: Available for online viewing starting at 8:30 AM on Saturday, April 10
Session Type: E-Poster Session
Session Title: Cellular Responses to Anticancer Drugs
Abstract ID: 1021
Summary:

• To investigate the underlying mechanism of PARP7 inhibition and to determine the drivers of the differential sensitivity across cell lines, researchers performed arrayed CRISPR knockout screens, targeting approximately 240 genes in the nucleic acid sensing and IFN signaling pathways, in the presence and absence of PARP7 inhibition. The arrayed screens confirmed multiple hits from a previous genome-wide pooled synthetic/lethal CRISPR dropout screen, shedding light on the mechanism by which PARP7 acts as a critical suppressor of the innate immune response in tumor cells and demonstrating both redundancy and crosstalk between different nucleic acid-sensing pathways.

Abstract Title: Targeted Degradation of PARP14 Using a Heterobifunctional Small Molecule
Presenter: Tim J. Wigle, Ph.D., Senior Director, Biochemical & Cellular Pharmacology, Ribon Therapeutics
Date & Time: Available for online viewing starting at 8:30 AM on Saturday, April 10
Session Type: E-Poster Session
Session Title: Novel Targets and Pathways
Abstract ID: 1348
Summary:

• RBN012811 is a heterobifunctional small molecule based on a catalytic inhibitor of PARP14 that binds in the enzyme’s NAD⁺-binding site and recruits the E3 ligase cereblon to ubiquitinate PARP14 and selectively target it for degradation. Researchers found that in PARP14 expressing cells, RBN012811 has a half-maximal degradation concentration (DC₅₀) of 0.005 μM and it does not cause degradation of other PARP enzymes. In human primary macrophages, PARP14 degradation by RBN012811 led to a dose-dependent decrease of IL-10 release induced by IL-4 stimulation.

Abstract Title: Small molecule inhibitor of CD38 modulates its intra- and extracellular functions leading to antitumor activity
Presenter: Prashant B. Shambharkar, Ph.D., Senior Scientist, Ribon Therapeutics
Date & Time: Available for online viewing starting at 8:30 AM on Saturday, April 10
Session Type: E-Poster Session
Session Title: Novel Targets and Pathways
Abstract ID: 1344
Summary:

• Inhibition of CD38 with a small molecule affects both intra- and extra-cellular CD38 activity and modulates key metabolites playing an important role in immunomodulation. Further, data indicate that CD38 is expressed at baseline in cancer and further increased by immune checkpoint inhibitor treatment. Finally, catalytic inhibition of CD38 can lead to antitumor activity in mouse cancer models.

Following its AACR presentations, Ribon Therapeutics expects to make the poster presentations available on its corporate website via the following link: https://ribontx.com/publications/.

About RBN-2397

RBN-2397, is an orally available small molecule inhibitor of PARP7 that we are 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. 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 Therapeutics is a clinical stage biotechnology company developing 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 our proprietary BEACON⁺ (Blocking the Enzyme Activity Component of NAD⁺) 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 PARP7 inhibitor in clinical development for the treatment of cancer. Ribon is located in Cambridge, Massachusetts. For more information visit www.RibonTx.com.

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