MCM998 / Novartis - LARVOL DELTA

Identification and Development of PHE885: A Novel and Highly Potent Fully Human Anti-BCMA CAR-T Manufactured with a Novel T-ChargeTM Platform for the Treatment of Multiple Myeloma (ASH 2021) - P1 | "In addition to its unique phenotype, PHE885 secretes up to 25 fold more target specific IL-2 and ~7 fold more IFN gamma in vitro , when comparing to the TM products either using the same lentiviral vector (TM_PHE885) or a clinically validated anti-BCMA vector (MCM998) . Based on these results, a Phase 1, open-label trial assessing PHE885 in patients with r/r MM (NCT04318327) was initiated. Initial data from the dose escalation portion of the Phase 1 study will be presented separately."

IO biomarker • Graft versus Host Disease • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Multiple Myeloma • Oncology • CCR7 • IFNG • IL2RA • TNFRSF9

Novel Benchmark Scaling Method for First-in-Human Dose of CAR-T Therapies (ASGCT 2022) - P1 | "Result The development of a CD19-targeted CAR-T (YTB323) and a BCMA-targeted CAR-T (PHE885) with a new optimized manufacturing method (T-ChargeTM) are used as examples...Assuming a comparable safety profile based on the same mechanism of action as CTL019, an YTB323 dose up to 2.8×107 cells (highest CTL019 dose with manageable AEs from another study UPCC03712 of 1.1×109 cells divided by 40) should be tolerable...In a second example, the target starting dose for PHE885 was derived based on preclinical comparison and clinical data generated with MCM998, another BCMA-targeted CAR-T previously tested in r/r multiple myeloma patients (NCT02546167)...Conclusion The proposed method to calculate FIH starting dose mitigates the current limitation in preclinical-to-clinical translation in CAR-T therapy. Examples of two CAR-Ts with different targets and indications demonstrated the general utility of the approach."

P1 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • CD19 • IFNG