TransThera Sciences (Nanjing), Inc. ("TransThera") announced that the U.S. Food and Drug Administration ("FDA") approved the Investigational New Drug ("IND") application of TT-01488, a non-covalent reversible Bruton's Tyrosine Kinase ("BTK") inhibitor, for the treatment of B-cell lymphomas on January 24, 2022, and TransThera will initiate the Phase I clinical trials in the U.S. soon. TransThera also announced that China National Medical Products Administration ("NMPA") officially accepted the IND application of TT-01488 for the treatment of B-cell lymphomas on February 14, 2022.

According to Frost & Sullivan, the global and China BTK inhibitor market reached USD7.2 billion and RMB1.3 billion in 2020 respectively. The market is expected to continue to expand in the next 5 years, with the CAGR of 22.7% globally and 58.6% in China from 2020 to 2025. As of 2021, there were 5 BTK inhibitors approved in different markets, all being covalent irreversible BTK inhibitors. The mechanism of action for covalent irreversible BTK inhibitors is to form covalent bond with the C481 site of BTK. However, when C481S mutation occurs, they will not be able to maintain the covalent bond, which eventually leads to drug resistance. Long-term follow-up results for the use of irreversible BTK inhibitors, according to Frost & Sullivan, demonstrate cumulative discontinuation rates as high as 40%, which show the large unmet medical needs.

"Non-covalent BTK inhibitors are not affected by the C481S mutation and are expected to overcome acquired resistance developed from marketed covalent BTK inhibitors. In a head-to-head kinase panel screening, TT-01488 demonstrated higher potency and better kinase selectivity on EGFR and TEC than peer non-covalent reversible BTK inhibitor under clinical investigation, indicating a potentially better safety profile. Moreover, in the DLBCL CDX model, TT-01488 showed a superior antitumor effect compared to peer non-covalent reversible BTK inhibitor." Said Dr. Peng Peng, vice president of project management and head of oncology portfolio at TransThera, "The approval by FDA and the acceptance from NMPA for its IND applications are two important milestones in the development of TT-01488. We will actively cooperate with the regulatory authorities to initiate the clinical trials of TT-01488 globally as soon as possible. "

About TT-01488：

TT-01488 is a non-covalent, reversible BTK inhibitor for overcoming acquired resistance mutation developed from marketed covalent BTK inhibitors in various types of B-Cell lymphomas. In preclinical trials, TT-01488 showed potential advantages such as overcoming drug resistance, improved target selectivity, antitumor efficacy and favorable safety.

About TransThera:

TransThera Sciences (Nanjing), Inc. is an R&D-driven, clinical-stage biopharmaceutical company dedicated to developing innovative therapeutics to target diseases with major unmet medical needs via the internal research platform and open innovation. TransThera's current portfolio covers therapeutic areas such as oncology, cardiovascular, and inflammatory diseases.