IRVINE, Calif., Sept. 11, 2023 /PRNewswire/ — PeproMene Bio, Inc., a clinical-stage biotech company developing novel therapies to treat cancers and immune disorders, today announced that the first dose cohort of its phase 1 relapsed or refractory B-cell Non-Hodgkin Lymphoma (r/r B-NHL) clinical trial of PMB-CT01 (BAFFR-CAR T Cells) has been completed. No Dose Limiting Toxicity (DLT) was observed, and the study has been cleared to proceed with the next cohort.
The PMB-102 trial is taking place at City of Hope, one of the largest cancer research and treatment organizations in the nation. PeproMene licensed intellectual property relating to PMB-CT01 from City of Hope, which developed the therapy.
In the first cohort, administration of 50×106 PMB-CT01 has been extremely well tolerated. Among three treated patients, all three experienced only grade 1 cytokine release syndrome (“CRS”) and two had grade 1 immune effector cell-associated neurotoxicity syndrome (“ICANS”) with full recovery. The Overall Response Rate is 100% (two Complete Response and one Partial Response) at one-month post treatment. Two patients with mantle cell lymphoma had progressed after conventional CD19 CAR T-cell treatment prior to enrollment on PMB-CT01.
“We are pleasantly surprised and thrilled to see such minimal toxicity associated with such a high response rate in heavily pretreated patients who have failed 3-10 prior lines of therapy, including FDA-approved CD19 CAR T-cells”, said Elizabeth Budde, M.D., Ph.D., the principal investigator of this single-center, dose escalation trial (NCT05370430) and associate professor at City of Hope, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation.
“Despite high initial efficacy of CD19-CAR T cell therapy for B-cell lymphoma and leukemia, a significant number of patients still relapse after CD19-CAR T treatment, highlighting the urgent unmet medical need,” said Larry W. Kwak, M.D., Ph.D., vice president and deputy director of City of Hope’s Comprehensive Cancer Center and PeproMene’s scientific founder and compensated chair of its Scientific Advisory Board. Kwak has an equity interest in PeproMene. “Unlike CD19, BAFF-R signaling is required for B cell growth and survival, so it may limit the capacity of B cell tumors to evade therapy by loss of BAFF-R expression. I hope BAFFR-CAR T therapy will offer a clinically meaningful, new option for patients.”
“Although still in early stage, we are encouraged by the initial observation of acceptable safety and preliminary efficacy in the first dose cohort of PMB-CT01 treated B-NHL patients. All 3 treated patients (2 progressed after CD19 CAR T therapy and 1 with CD19/CD20 negative lymphoma) responded to PMB-CT01 treatment,” said Hazel Cheng, Ph.D., COO of PeproMene. “These clinical outcomes are consistent with City of Hope preclinical research data published in Science Translational Medicine in 2019, which showed that PMB-CT01 (BAFFR-CAR T Cells) could overcome CD19 antigen loss in B-cell malignancies.”
PMB-CT01 is a first-in-class BAFFR-targeted, autologous CAR T cell therapy. BAFF-R (B Cell Activating Factor Receptor), a tumor necrosis factor (TNF) receptor superfamily member, is the main receptor for BAFF expressing almost exclusively on B cells. Since BAFF-R signaling promotes normal B-cell proliferation and appears to be required for B-cell survival, it is unlikely tumor cells could escape immune responses via loss of BAFF-R antigen. This unique characteristic makes BAFF-R CAR T therapy a great potential treatment of B cell malignancies. BAFF-R CAR-T was constructed using the anti-BAFF-R scFv (single-chain fragment variable) antibodies with the 2nd generation signaling domains containing CD3ζ and 4-1BB. Our research has found that BAFFR-CAR T cells kill human lymphomas and leukemias in vitro as well as in animal models. PeproMene has licensed intellectual property relating to PMB-CT01, from City of Hope.
PeproMene is a clinical-stage biotech company in Irvine, California developing novel therapies to treat cancers and immune disorders. PeproMene’s lead candidate, PMB-CT01 (BAFFR-CAR T Cells) is currently being investigated in phase 1 clinical trials to treat relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL; NCT04690595) and B-cell non-Hodgkin’s lymphoma (B-NHL; NCT05370430). PeproMene is also developing BAFFR Bispecific T Cell Engager and BAFFR-CAR NK cells.