SC-2882 as a Potential Therapeutic for DLBCL

Preclinical data was presented at the 65th ASH Annual Meeting & Exposition in San Diego, by Leandro Cerchietti, MD, Richard A. Stratton Associate Professor in Hematology and Oncology at Weill Cornell Medicine in New York City. The data was described today in an oral presentation by Cerchietti during the session entitled "Molecular Pharmacology and Drug Resistance - Lymphoid Neoplasms: Novel Therapeutic Approaches in Lymphoma and Multiple Myeloma".

The new preclinical data covers results for SC-2882, a first-in-class QPCTL inhibitor, as a potential new treatment approach for diffuse large B-cell lymphoma (DLBCL). DLBCL accounts for 25-30 percent 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.

"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," Cerchietti noted.

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