TransThera Sciences (Nanjing), Inc. (the "TransThera"), a clinical demand-oriented, registrational clinical stage biopharmaceutical company focusing on discovering and developing innovative small molecule therapies for oncology, inflammatory and cardiometabolic diseases, announced the poster presentation at the 2024 American Society of Hematology (ASH) Annual Meeting to discuss the phase I study results of TT-01488, a novel reversible BTK inhibitor for patients with relapsed or refractory B-cell malignancies.

Bruton's tyrosine kinase (BTK) plays a critical role in the B-cell receptor signaling pathway, functioning as an important regulator of cell proliferation and cell survival in various B-cell malignancies. Currently there are 5 approved irreversible BTK inhibitors (BTKis) in the world. Due to the emergence of acquired mutation in the inhibitor's covalent binding site (C481S), there is a high unmet medical need to develop next-generation BTKi to overcome the resistance.

TT-01488 is a next-generation, non-covalent, reversible BTKi which can overcome the acquired resistance to irreversible BTKis. In the preclinical study, TT-01488 potently Inhibits both wildtype and C481S-mutant BTK.

The Phase I study of TT-01488 presented at ASH Annual Meeting was an open, multi-center, dose escalation study. As of the data cut-off date on October 2, 2024, 18 patients with pre-treated B-cell malignancies were enrolled, with the median 3 lines of prior therapies. TT-01488 was well-tolerated in all patients. Neither dose limiting toxicity (DLT) occurred nor any bleeding, atrial flutter or atrial fibrillation was reported. In pharmacokinetics and pharmacodynamics study, sustained pBTK C481S-mutant inhibition covering IC­₉₀ was observed at steady state following multiple dosing at both 150 mg (QD) and 100 mg (BID) dose levels. Among 14 efficacy evaluable patients, objective response rate (ORR) was 57% (8/14)，including 3 complete remission (CR) and 5 partial remission (PR). 100% (7/7) of ORR was achieved in mantle cell lymphoma (MCL), Waldenström macroglobulinemia (WM) and marginal zone lymphoma (MZL). Overall, TT-01488 showed encouraging efficacy in B-cell non-Hodgkin lymphoma (B-NHL) patients, regardless of C481S status and with/without prior cBTKi therapy.