WATERTOWN, Mass. — Treeline Biosciences, Inc. has entered into a clinical trial collaboration and supply agreement with Roche to evaluate its investigational BCL6 degrader TLN-121 in combination with Roche’s CD20xCD3 T-cell-engaging bispecific antibodies in patients with B-cell lymphomas.
The agreement covers separate combination cohorts evaluating TLN-121 with glofitamab-gxbm, marketed as COLUMVI, and mosunetuzumab-axgb, marketed as LUNSUMIO, including in patients with diffuse large B-cell lymphoma.
Treeline will sponsor and conduct the Phase 1 dose-escalation and expansion study, while Roche will supply glofitamab and mosunetuzumab for the designated expansion cohorts.
Treeline said it expects to begin combination dosing in the fourth quarter of 2026.
“CD20xCD3 T-cell-engaging bispecific antibodies such as glofitamab and mosunetuzumab have already transformed the treatment of B-cell lymphomas. We are excited to build on that progress in collaboration with Roche,” said Josh Bilenker, M.D., co-founder and CEO of Treeline.
Bilenker said preclinical studies suggest TLN-121 may enhance the anti-tumor activity of both CD20xCD3 bispecific antibodies and CD19-directed CAR-T cell therapies.
TLN-121 is currently being evaluated as a single agent in an ongoing Phase 1 clinical trial. Treeline said the drug has shown activity, including complete responses, in heavily pretreated patients with diffuse large B-cell lymphoma, follicular lymphoma and T follicular helper peripheral T-cell lymphoma.
BCL6 is a transcriptional repressor involved in B-cell lymphoma biology and can suppress genes that support interactions between T cells and B cells.
In preclinical studies, Treeline said TLN-121 restored expression of T-cell-recruiting cytokines and genes involved in immune synapse formation.
In one mouse model of aggressive diffuse large B-cell lymphoma, the combination of TLN-121 with a CD20xCD3 bispecific antibody produced complete tumor regressions in four of six mice, compared with none of six treated with TLN-121 alone and one of five treated with the antibody alone.
In a separate model, the combination of TLN-121 and CD19 CAR-T cells reduced tumors in four of six mice and produced complete regressions in two of six. Neither treatment alone produced tumor shrinkage or complete regression in that model.
