-Reinforces PARP7 as a novel therapeutic target and that inhibition of PARP7 induces both antitumor immunity and cancer cell-intrinsic effects–
-Platform identifies several cancer-relevant monoPARPs through multi-omic data mining and drug discovery capabilities for the enzyme family-
CAMBRIDGE, Mass.–(BUSINESS WIRE)–Ribon Therapeutics, a clinical stage oncology company developing first-in-class therapeutics targeting stress response pathways, today announced new data to be presented at the American Association for Cancer Research (AACR) 2020 Virtual Annual Meeting II, taking place from June 22-24, 2020.
“PARP7 is a fundamental regulator of intrinsic stress support pathways and represents a novel cancer cell vulnerability,” said Heike Keilhack, Ph.D., Senior Vice President of Biological Sciences, Ribon Therapeutics. “RBN-2397 is the first potent and selective inhibitor of PARP7 and exhibits potent anti-tumor activity as a monotherapy, as well as in combination with other therapies, including immune checkpoint inhibitors.”
“The posters presented at AACR provide a glimpse into Ribon’s unique ability to interrogate the complex biology of stress support pathways to identify novel therapeutic targets,” said Kevin Kuntz, Ph.D., Senior Vice President of Molecular Discovery, Ribon Therapeutics. “The multi-dimensional, in silico mining tools and bespoke screening assays Ribon has developed were instrumental in the identification of PARP7 and RBN-2397 and are critical components of the platform, which we have assembled to validate new monoPARP and NADase targets and develop novel therapeutics.”
Ribon will present the following from its development program and platform:
Abstract Title: PARP7 negatively regulates the Type I interferon response in cancer cells and its inhibition leads to tumor regression
Abstract ID: 3405
Session Type: Minisymposium (oral presentation)
Session Category: Experimental and Molecular Therapeutics
Session Title: Novel Mechanisms Enabled by Tool Molecules
Date/Time: June 23, 2020, 9:00 – 11:00 a.m. EDT
Presenter: Joseph M. Gozgit, Ph.D.
Summary:
- Data demonstrate that cancer cells use PARP7 to suppress the Type I IFN response to cytosolic nucleic acids. RBN-2397, a first-in-class, potent and selective inhibitor of PARP7 is shown to restore Type I IFN signaling in the tumor and cause complete tumor regressions and adaptive immunity in murine models.
- Targeting cytosolic nucleic acid sensing pathways and the Type I interferon (IFN) response is an emerging therapeutic strategy being explored in oncology. PARP7 expression is increased by cellular stress and aromatic hydrocarbons, and the PARP7 gene is amplified in cancers, especially in those of the upper aerodigestive tract. PARP7 has also been reported to negatively regulate the Type I IFN response by interacting with TBK1 during viral infection. PARP7 is identified as a novel negative regulator of cytosolic nucleic acid sensing in tumor cells.
Title: A bespoke screening platform to study mono(ADP-ribosylation)
Abstract ID: 506 / 2
Session Type: Poster Session
Session Title: Screening, Lead Identification, and Optimization
Date/Time: June 22, 2020, 9:00 a.m. – 6:00 p.m. EDT
Presenter: Tim J. Wigle, Ph.D.
Summary:
- Development of robust, high-throughput biochemical and cellular monoPARP assays that overcome the lack of knowledge around the substrates and construction of a family-wide screening panel. These assays have been used in high-throughput screening campaigns, as well as in the development of potent and selective inhibitors of multiple monoPARP enzymes, including cell active chemical probes for PARP3, PARP7, PARP10, PARP12, PARP14 and PARP16.
Title: A multi-omic characterization of PARP enzymes in cancer to identify novel monoPARP drug targets
Abstract ID: 4381
Session Type: Poster Session
Session Title: Knowledge, Networks, Graphs, and Models for Discovery
Date/Time: June 22, 2020, 9:00 a.m. – 6:00 p.m. EDT
Presenter: Ryan Abo, Ph.D.
Summary:
- The first pan-cancer in silico characterization of the PARP family, revealing a broad molecular and potential mechanistic diversity among the PARPs across cancer. Notwithstanding the lack of traditional oncogenic features, such as mutational hotspots, in the PARPs, analyses highlight several monoPARPs with potential oncogenic roles and further support our focus of targeting these in the clinic.
AACR Virtual Meeting II the second of two virtual meetings being held by AACR; the first, AACR Virtual Meeting I, took place April 27-28, 2020. Presentations from Virtual Meeting I can be accessed at https://ribontx.com/events/.
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 visit www.RibonTx.com
Contacts
Media Contact:
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Scient PR
media@ribontx.com