Opal / Cullinan Therap - LARVOL DELTA

Opal is a conditional 4-1BB agonistic fusion protein comprising trimerized 4-1BB ligand and a high affinity variant of the extracellular domain of PD-1 (AACR 2022) - "4-1BB agonizing monoclonal antibodies have thus far failed to progress beyond early clinical development, either due to hepatic toxicities caused by FcγR-crosslinking (urelumab) or due to low clinical activity (utomilumab). When tumor-bearing mice were treated IP with Opal at 1 mg/kg, 7/10 mice exhibited durable cures without significant body weight loss. Taken together, the preclinical data suggests that Opal may exhibit single-agent activity in solid tumors by conditionally activating effector cells in the tumor microenvironment via 4-1BB agonism while concurrently blocking the PD1/PDL1/PDL2 axis."

IO biomarker • Oncology • Solid Tumor • IFNG • PD-1 • PD-L2

Cullinan Oncology to Present Data Demonstrating Breadth and Progress of Its Immuno-Oncology Portfolio at AACR 2022 (GlobeNewswire) - "Data for the following programs will be presented: (i) Preclinical characterization of CLN-049 and demonstration of its antitumor activity in AML models; (ii) Preclinical data evaluating the ability of CLN-619 to functionally restore the MICA/MICB-NKG2D axis...; (iii) Preclinical data demonstrating robust anti-tumor activity of CLN-617, locally in injected tumors and systemically in uninjected tumors; (iv) Preclinical characterization of CLN-978, a novel CD19/CD3-bispecific construct with extended serum half-life and high potency against target cells expressing very low levels of CD19; (v) Preclinical data assessing Opal, an earlier stage immuno-oncology program designed to simultaneously block the PD-1/PD-L1/2 axis and conditionally activate the 4-1BB/CD137 pathway on T cells."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology