PeproMene showcases breakthrough BAFF-R CAR-T results in CD19-escape B-cell malignancies at ASH 2025

US-based cell therapy developer PeproMene Bio announced that its BAFF‑R‑targeted autologous CAR T candidate, PMB‑CT01, has been selected for two oral presentations at the 67th American Society of Hematology (ASH) Annual Meeting, taking place December 7-10, 2025, in Orlando, Florida.

First-in-class target addressing CD19-negative disease

PMB‑CT01 is an autologous CAR T therapy directed at BAFF‑R (B-cell activating factor receptor), a novel antigen highly expressed on B-cell malignancies but minimally on healthy tissue. The therapy is designed to address key resistance mechanisms seen with CD19-targeted CAR T cells, including antigen escape.

The presentations will provide early data from two ongoing Phase 1 trials in B-cell non-Hodgkin lymphoma (B-NHL) and B-cell acute lymphoblastic leukemia (B-ALL).

B-NHL study: Seven patients with heavily pretreated relapsed/refractory disease, including those previously treated with CD19-directed CAR T cells or with CD19-negative tumors, were treated with PMB‑CT01, achieving a 100% complete response rate at 1-3 months post-infusion. Responses have remained ongoing in all patients, with a median follow-up of 17 months (range: 6-32+ months). Reported toxicities were low grade, with no cases of grade >1 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS).

B-ALL study: In a separate trial, six patients with relapsed/refractory B-ALL received PMB‑CT01, with four achieving minimal residual disease (MRD)-negative complete remission, including three patients with CD19-negative disease. All three CD19-negative responders proceeded to allogeneic hematopoietic cell transplant. Safety was again favorable, with no dose-limiting toxicities, one case of grade 2 CRS, and no grade 3 or higher CRS.

The two oral presentations at ASH 2025 are scheduled for December 7 and December 9, covering the B-NHL and B-ALL trials, respectively. Abstracts were released online via the ASH 2025 abstract portal.

PeproMene previously secured USD 11 million of investment from the Institute for Follicular Lymphoma Innovation to support PMB‑CT01’s expansion into additional indications including follicular lymphoma.

The rationale behind BAFF-R targeting

Recent literature highlights growing interest in BAFF-R (B-cell activating factor receptor) as a therapeutic target, particularly in immune-mediated diseases and B-cell malignancies. BAFF-R is crucial for B-cell survival and maturation, making it an attractive target for modulating B-cell function in both autoimmune conditions and cancers.

BAFF-R-targeted drug development efforts include monoclonal antibodies, small molecules, and CAR T-cell therapies for both select B-cell disorders and refractory cancers.

A key challenge in B-cell malignancy treatment, especially with CD19-directed therapies (e.g., CAR T-cells), is antigen loss or exhaustion, leading to relapse. Recent studies demonstrate that BAFF-R is frequently retained on malignant B cells even after CD19 loss, providing a rationale for targeting BAFF-R as an alternative or complementary strategy.

Meanwhile, for auto-immune diseases, BAFF-R’s role in B-cell survival means that its signaling is implicated in the pathogenesis of a range of diseases including autoimmune hepatitis, systemic lupus erythematosus (SLE), and Sjögren’s syndrome. Examples include a BAFF-R-targeted CAR-T under development in China for refractory neuroimmune diseases, and Novartis’s BAFF-R-targeted antibody Ianalumab (VAY736), under study for autoimmune hepatitis and Sjögren’s syndrome, with endpoints focused on disease activity and B-cell depletion.