On December 9, 2023 Scenic Biotech, a pioneer in the discovery of genetic modifiers developing therapeutics to treat severe diseases, reported positive preclinical data for its lead small molecule QPCTL inhibitor, SC-2882 (Press release, Scenic Biotech, DEC 9, 2023, View Source [SID1234638335]). The data was also presented today by Leandro Cerchietti, MD, Richard A. Stratton Associate Professor in Hematology and Oncology at Weill Cornell Medicine, New York, at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in San Diego. The new preclinical data covers results for SC-2882, Scenic’s first-in-class QPCTL inhibitor, as a potential new treatment approach for diffuse large B-cell lymphoma (DLBCL). DLBCL accounts for 25-30% of all non-Hodgkin lymphoma cases, making it the most common cancer of the lymphatic system characterized by rapidly growing tumor mass or enlarging lymph nodes in a nodal or extranodal site.
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"Treatment with SC-2882 in a DLBCL mice model achieved a significant decrease in tumor growth and an increase of CD3+ T cell infiltration within the tumor microenvironment, along with a reduction in immunosuppressive immune cells. This suggests that QPCTL inhibition in DLBCL has anti-lymphoma effects and holds potential as a new therapeutic avenue for this type of cancer," commented Leandro Cerchietti, MD, Associate Professor in Hematology and Oncology at Weill Cornell Medicine, New York, and presenter at the 65th ASH (Free ASH Whitepaper) Annual Meeting & Exposition.
"The positive preclinical data presented today constitute a major step forward in the advance of SC-2882 as a potential treatment for DLBCL, an indication with high unmet medical need especially in post-CART relapsed or refractory DLBCL patients, as well as in earlier lines of treatment with non-chemotherapy or immuno-oncology-based approaches. QPCTL was identified as a new immuno-oncology target through our proprietary Cell-Seq platform, and we view these results as a validation for our approach and our earlier-staged Cell-Seq-generated programs in rare diseases," commented
Jens Würthner, MD, PhD, CMO of Scenic Biotech. "As we finalize IND-enabling studies for SC-2882, we look forward to submitting our initial clinical trial filing to the regulatory authorities in 2024 and moving into clinical evaluation."
QPCTL is an intracellular enzyme that modulates the activity of CD47 and several chemokines in cancer leading to immune escape of cancer cells. SC-2882 targets QPCTL and thereby inhibits the CD47-SIRPα "don’t eat me" checkpoint and lowers immune suppression in the tumor microenvironment. Analysis of DLBCL patient datasets revealed that QPCTL expression negatively correlates with overall and progression-free survival. In a murine model of DLBCL, SC-2882 treatment led to a significant decrease in tumor growth with no evidence of systemic toxicity. Moreover, evaluation of the tumor microenvironment (TME) showed an increased CD3+ T cell infiltration and a reduction in tumor-associated macrophages and regulatory T cells in SC-2882-treated mice, compared to control. These results imply SC-2882 exhibits an anti-tumor effect that involves modulation of immunosuppression in the TME.
The data was described today in an oral presentation by Leandro Cerchietti, MD, Richard A. Stratton Associate Professor in Hematology and Oncology at Weill Cornell Medicine, New York, at 9:30 AM PST/ 18:30 CET during session 605 entitled "Molecular Pharmacology and Drug Resistance – Lymphoid Neoplasms: Novel Therapeutic Approaches in Lymphoma and Multiple Myeloma".