TransThera Reports Phase I Results for TT-01488 in B-cell Malignancies

TransThera Sciences (Nanjing), Inc., a prominent biopharmaceutical company, unveiled its latest findings at the 2024 American Society of Hematology (ASH) Annual Meeting. The company presented encouraging results from a Phase I study of TT-01488, a groundbreaking reversible BTK inhibitor, designed for patients suffering from relapsed or refractory B-cell malignancies.

Bruton's tyrosine kinase (BTK) is integral in the B-cell receptor signaling pathway, playing a crucial role in cell proliferation and survival among various B-cell malignancies. Currently, five irreversible BTK inhibitors are approved globally, but they face challenges due to resistance caused by mutations at the covalent binding site (C481S). This has underscored the necessity for developing next-generation BTK inhibitors that can overcome this resistance.

TT-01488, developed by TransThera, is a non-covalent, reversible BTK inhibitor. It has shown remarkable effectiveness in preclinical trials by targeting both wildtype and C481S-mutant BTK. This novel inhibitor aims to address the shortcomings of existing irreversible BTK inhibitors and provide a viable treatment option for patients who have developed resistance.

The Phase I study presented at the ASH Annual Meeting was a comprehensive, open-label, multi-center, dose escalation study. By the data cut-off date on October 2, 2024, the study had enrolled 18 patients, each with previously treated B-cell malignancies and a median of three prior therapy lines. TT-01488 was well-received, with no instances of dose-limiting toxicity, or reports of bleeding, atrial flutter, or atrial fibrillation. The pharmacokinetics and pharmacodynamics assessments showed sustained inhibition of the C481S-mutant pBTK, covering IC­90 at steady state with multiple doses of 150 mg (QD) and 100 mg (BID).

Efficacy evaluations were conducted on 14 patients, revealing a promising objective response rate (ORR) of 57%. Among these, three patients achieved complete remission, while five experienced partial remission. Notably, a 100% ORR was observed in patients with mantle cell lymphoma (MCL), Waldenström macroglobulinemia (WM), and marginal zone lymphoma (MZL). These findings suggest that TT-01488 holds significant potential in treating B-cell non-Hodgkin lymphoma (B-NHL) patients, irrespective of their C481S mutation status or prior exposure to BTK inhibitors.

TT-01488 stands out as an internally developed, highly selective BTK inhibitor that demonstrates significant potency against both wildtype and mutant BTK, with minimal impact on EGFR and Tec. These attributes indicate its potential for effective and safe use in tackling relapsed or refractory hematological malignancies.

TransThera Sciences is dedicated to addressing urgent clinical demands through innovative drug development. Specializing in oncology, inflammatory, and cardiometabolic diseases, the company leverages deep translational medicine studies and advanced drug design to create first-in-class or best-in-class therapies. TransThera is strategically positioned to meet global healthcare needs by focusing on innovative small molecule therapies that address significant clinical challenges.

In summary, the promising results from the Phase I study of TT-01488 highlight its potential as a next-generation treatment for B-cell malignancies. With further development, it could significantly impact the field of hematologic oncology, offering new hope to patients facing resistance to existing therapies.