Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, announces that FDA has granted it clearance to proceed with TranStar 301 global Phase III pivotal trial of Osemitamab (TST001) in combination with Nivolumab and chemotherapy as first-line treatment in patients with HER2-negative, CLDN18.2 expressing locally advanced or metastatic gastric or gastroesophageal (G/GEJ) adenocarcinoma. This clearance marks a major step forward in the global development of Osemitamab (TST001) and another important milestone following the approvals by the Center for Drug Evaluation (CDE) in China and MFDS in South Korea for the Phase III pivotal trial of Osemitamab (TST001) in July 2023.

This milestone marks a crucial advancement in the progression of Osemitamab (TST001) toward becoming a global therapy that elevates the current standard of care for HER2-negative metastatic gastric or gastroesophageal (G/GEJ) adenocarcinoma. By specifically targeting CLDN18.2 and combining it with Nivolumab and chemotherapy, Osemitamab (TST001) is poised to reshape the treatment paradigm for G/GEJ cancer.

Stomach cancer remains an important cancer worldwide and is responsible for over one million new cases in 2020 and an estimated 769,000 deaths (equating to one in every 13 deaths globally), ranking fifth for incidence and fourth for mortality globally¹. Combinations of platinum and fluoropyrimidine represent the backbone chemotherapy regimen for patients with HER2-negative advanced gastric cancer². Nivolumab was approved in combination with chemotherapy for first-line treatment of patients with advanced or metastatic gastric cancer. Though treatment outcomes have improved, the median overall survival of nivolumab plus chemotherapy is still less than 14 months³.

Osemitamab (TST001) is a second-generation humanized CLDN18.2 targeting antibody with improved CLDN18.2 binding affinity and enhanced antibody-dependent cellular cytotoxicity ("ADCC"). It has shown anti-tumor activities in preclinical tumor models with a broad range of CLDN18.2 expression.

To support the global Phase III trial application and FDA EOP2 meeting, Transcenta has conducted Phase II clinical trials in both the U.S. and China of the combination of Osemitamab (TST001) with chemotherapy or nivolumab and chemotherapy with multiple Osemitamab (TST001) doses cohorts to optimize the dose for the global Phase III trial. Furthermore, Transcenta has developed a CLDN18.2 specific companion diagnostic assay with a credible CDx developer in the U.S.

At the 2023 ASCO annual meeting and 2023 ESMO GI conference, Transcenta presented encouraging efficacy data of Osemitamab (TST001) in combination with CAPOX as the first-line treatment of G/GEJ cancer. A total of 64 patients were enrolled and treated with Osemitamab (TST001) at doses ranging between 1 and 8mg/kg Q3W in a dose escalation and dose expansion cohort. CLDN18.2 positivity (defined as: IHC membrane staining ≥10% tumor cells with ≥1+ intensity per LDT assay, selecting approximately 55% of the screened patients) was required for the efficacy expansion. The data showed that the estimated median progression-free survival (PFS) was 9.5 months for all dose groups, consistent across all CLDN18.2 expression levels, with a median duration of response (DOR) of 9.9 months. PFS and DOR data for the 49 patients treated at the dose of 6mg/kg Q3W in the efficacy expansion will be presented at ESMO 2023. These data also show that the CLDN18.2 positive patients benefiting from the addition of Osemitamab (TST001) to standard of care could represent more than 55% of all G/GEJ adenocarcinomas.

"We are delighted with the positive outcome of the EOP2 meeting," said Dr. Caroline Germa, Transcenta Executive Vice President, Global Medicine Development and Chief Medical Officer. "The interim safety, clinical pharmacology and efficacy data we presented fostered a productive dialogue with the FDA. Securing FDA endorsement on critical program elements represents a pivotal milestone in advancing our Phase III trial in the U.S."