- Casitas B-lineage lymphoma b (Cbl/b) is an E3 ubiquitin ligase that has been shown to be a key regulator of the activation of T and natural killer (NK) cells in the absence of CD28 costimulation
- GRC 65327 has been identified by IGI as a novel, nanomolar potent, selective, and orally bioavailable Cbl/b inhibitor
Under the CRADA, IGI and NCI will collaborate on evaluating IGI's proprietary Cbl/b small molecule, GRC 65327. "GRC 65327 is a best-in-class, novel, selective, orally active, Cbl-b inhibitor that demonstrates good in vitro potency, in vivo efficacy and an acceptable non-clinical toxicity profile,” said Nagaraj Gowda, PhD, Vice-President, Head of Small Molecule Research at IGI.
In the research covered by the CRADA, NCI will first characterize and then test GRC 65327 in immune-competent models of triple-negative breast cancer (TNBC) with the intent of generating preclinical data to support a clinical trial in late-stage TNBC at NCI. Stan Lipkowitz, M.D., Ph.D., Chief of Women's Malignancies Branch, Deputy Director of the Center for Cancer Research at the NCI, and his team will build on their substantial achievements in early Cbl/b research that include initially cloning the gene and having identified Cbl/b's role as a negative regulator of the adaptive immune system.
"Small molecule inhibitors of Cbl/b may enhance adaptive anti-tumor activity by increased signaling through the costimulatory pathway in T cells and innate immunity via enhanced NK cell activity,” said Dr. Lipkowitz. "My group will test the novel Cbl/b inhibitor developed by IGI in in vitro, cell-based, and in vivo mammary cancer models to evaluate its activity as Cbl/b inhibitors and modulators of adaptive and innate immune response to breast cancers.”
"We believe in the power of collaboration to drive innovation. Partnering with Dr. Lipkowitz and the NCI to advance our scientific understanding of GRC 65327 is expected to speed its potential development in TNBC, a cancer with few effective treatment options for patients,” said Cyril Konto, M.D., President, Executive Director and CEO of IGI. "In addition, the work of Dr. Lipkowitz's laboratory in late-stage TNBC complements the program IGI has developed to advance GRC 65327 in other solid tumors.”
About IGI's GRC 65327-Casitas B-Lineage Lymphoma b (Cbl/b) Program: Casitas B-lineage lymphoma b (Cbl/b) is an E3 ubiquitin ligase that has been identified as a key inhibitor of T and NK cells activation in the absence of CD28 costimulation, regulate immune cells activity in PD-1, CTLA4 and TIGIT positive cells. As an intracellular master regulator, Cbl/b inhibition may lead to robust immune cell activation in immune-suppressed tumor microenvironment and induce strong single-agent activity. A first-in-human clinical trial in patients with relapsed/refractory solid tumor indications is expected to start in early 2025. IGI plans to present the preclinical data package for GRC 65327 at an upcoming scientific conference.
About Ichnos Glenmark Innovation: Ichnos Glenmark Innovation (IGI) is an alliance between Ichnos Sciences Inc., a global fully-integrated clinical-stage biotech company developing multispecifics™ in oncology, and Glenmark Pharmaceuticals Ltd. (Glenmark), with the aim to accelerate new drug discovery in cancer treatment. IGI combines Ichnos' research and development proficiencies in novel biologics with those of Glenmark's in new small molecules to continue developing cutting-edge therapy solutions that treat hematological malignancies and solid tumors. Harnessing the combined proficiency of over 150 scientists and a robust pipeline of novel molecules, this collaboration will leverage the capabilities of its three global centers of innovation spread across the USA, Switzerland and India to propel Innovation. For more information, visit www.iginnovate.com.
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