Transcenta Announces Global Pivotal Trial of Claudin18.2 Monoclonal Antibody TST001, the Second Most Advanced Globally with Broad Market Potential

On March 22, Transcenta Holding announced that it had entered into a global clinical research collaboration agreement with Bristol Myers Squibb to conduct a global clinical trial evaluating the combination of Transcenta’s investigational humanized monoclonal antibody against Claudin18.2, TST001, and Bristol Myers Squibb’s PD-1 inhibitor Opdivo® (nivolumab) for the treatment of patients with unresectable locally advanced or metastatic gastric cancer and gastroesophageal junction cancer.

This collaboration encompasses two open-label, multicenter, global Phase I/II clinical trials to be conducted in China and the United States. The studies aim to evaluate the safety, tolerability, and antitumor efficacy of TST001 in combination with Opdivo® in patients with unresectable locally advanced or metastatic gastric cancer and gastroesophageal junction adenocarcinoma expressing Claudin 18.2, regardless of prior treatment history.

TST001 is a high-affinity humanized antibody independently developed by Transcenta Holding, which specifically targets tumor cells expressing Claudin 18.2 and can induce potent NK cell-mediated tumor-killing activity. Combination therapy of TST001 with checkpoint inhibitors such as Opdivo® may provide greater clinical benefits for patients with locally advanced or metastatic gastric cancer/gastroesophageal junction cancer.

Dr. Qian Xueming, CEO of Transcenta Holding

Dr. Qian Xueming, CEO of Transcenta HoldingTranscenta Holding stated: “Over the past year, Transcenta has made significant progress in advancing its pipeline. First, our core product, the Claudin18.2 monoclonal antibody TST001, has achieved major clinical milestones and is scheduled to initiate global registrational trials in the second half of this year. Second, we have established and advanced a diverse, complementary, and synergistic portfolio of other oncology candidates; these drugs can be used not only as monotherapies but also in combination with TST001. Third, our highly differentiated orthopedic products and global first-in-class assets have begun entering clinical development. Fourth, we have made substantial strides in commercial manufacturing: our continuous manufacturing technology platform has been continuously upgraded, achieving more than a tenfold increase in production efficiency compared to conventional fed-batch processes. Our Hangzhou facility has completed upgrades to support regulatory filings for commercial launch and meet production demands. Currently, our flagship product, the Claudin18.2 monoclonal antibody TST001, has been manufactured at commercial scale using the continuous manufacturing platform, and all drug supplies for registrational clinical trials have been fulfilled. The recent global clinical research collaboration agreement with Bristol-Myers Squibb further underscores the advantages and appeal of TST001.”

Transcenta Group is a clinical-stage biopharmaceutical company with comprehensive, integrated capabilities in biologics discovery, research and development, process development, and manufacturing. It was listed on the Main Board of The Stock Exchange of Hong Kong Limited on September 29 last year, with stock code: 06628.

Transcenta Holding places great emphasis on new drug R&D. In its first annual performance report released half a year after its listing, the company disclosed that its R&D expenditures increased from RMB 200 million in the previous year to RMB 344 million in 2021, to drive progress in its pipeline. Moreover, Transcenta Holding’s R&D expenditures for the 2019 and 2020 fiscal years were RMB 215 million and RMB 200 million, respectively. This demonstrates a continuous increase in R&D spending, aimed at accelerating the advancement and expansion of its pipeline.

As of now, Transcenta Holding’s development pipeline hasTen Novel Therapeutic Antibody Molecules Covering Oncology, Orthopedics, and NephrologyAmong them, the core product TST001, a humanized monoclonal antibody targeting Claudin18.2, is being developed simultaneously in China and the United States. It is currently in Phase II clinical trials and is expected to enter international Phase III clinical trials in the second half of 2022.Clinical development ranks second globally and first in China.

Dr. Shi Ming, Executive Vice President of Global R&D and Chief Medical Officer at Transcenta HoldingIt was stated that TST001 is a high-affinity humanized monoclonal antibody targeting Claudin 18.2. In ongoing clinical trials, TST001 has demonstrated a favorable safety profile, both as monotherapy and in combination with chemotherapy, and has shown encouraging signals of anti-tumor activity in patients with gastric cancer and other solid tumors expressing Claudin 18.2.

Claudin 18.2 is a pan-cancer target that is highly expressed exclusively by gastric epithelial cells in normal tissues, but is also highly expressed in gastric cancer, pancreatic cancer, gallbladder and biliary tract cancers, esophageal cancer, and lung cancer. Due to its highly selective and stable expression in specific tumor tissues and its involvement in the proliferation, differentiation, and migration of tumor cells, Claudin 18.2 represents a promising molecular target for anti-tumor therapeutics.

According to Dr. Shi Ming, TST001 is a highly differentiated product.First, Claudin18.2 is a clinically validated target.TST001 is the second Claudin 18.2-targeted antibody therapeutic candidate developed globally, following Astellas Pharma’s Claudin 18.2-targeted antibody product, Zolbetuximab (IMAB362). Earlier, the Phase II FAST clinical trial data for IMAB362 validated Claudin 18.2 as a novel target with high potential for antitumor efficacy.

Secondly, IMAB362 targets a relatively small population with high expression in gastric cancer. It is currently in Phase III clinical trials globally and has demonstrated good efficacy; however, its therapeutic effect is not significant in patients with low Claudin 18.2 expression. The criteria set for TST001 are even higher than those for IMAB362,TST001 not only efficiently kills gastric cancer cells with high Claudin18.2 expression but is also effective against those with moderate-to-high expression, making it a first-in-class therapy for patients with low-to-moderate expression levels.。

Finally,TST001 exhibits stronger antitumor activity than IMAB362.Over the past year, Transcenta Holding has been making every effort to rapidly advance the clinical development of TST001 and has achieved significant progress, including:

• In China, the monotherapy dose-escalation trial of TST001 in solid tumors has been completed, and a confirmed partial response was achieved at a dose of 6 mg/kg Q3W in a patient with Claudin 18.2-positive disease who had received multiple prior lines of therapy, including chemotherapy, PD-1 inhibitors, and VEGF inhibitors.

• Initiated a Phase IIa study of monotherapy for advanced gastric cancer and pancreatic cancer.

• Initiated a Phase IIa cohort expansion study of combination chemotherapy as first-line treatment for gastric cancer.

• Granted Orphan Drug Designation by the U.S. FDA for the treatment of gastric cancer and gastroesophageal junction cancer.

• The company developed an immunohistochemistry detection antibody that specifically binds to Claudin18.2, which was validated by a central laboratory for patient screening and enrollment.

• Completed process optimization and lock-in for registration clinical trials and commercial production, and completed the manufacturing of drug products for registration clinical trials.

• Supported an investigator-initiated Phase IIa clinical study of TST001 for the treatment of advanced biliary tract cancer with Claudin18.2 overexpression.

• Conducted multiple translational research projects in collaboration with Peking University Cancer Hospital, the Dana-Farber Cancer Institute of Harvard Medical School, and Shanghai Zhongshan Hospital.

In addition to TST001, Transcenta Holding has established and advanced a diverse, complementary, and synergistic portfolio of other oncology product candidates spanning multiple therapeutic areas, including oncology, orthopedics, and nephrology. These clinical-stage candidates have achieved varying degrees of progress and can be used not only as monotherapies but also in combination with TST001.

For instance, TST005, a PD-L1/TGF-β dual-function antibody candidate for solid tumors such as lung cancer, entered clinical development in 2021. TST002, a humanized anti-sclerostin monoclonal antibody candidate for osteoporosis developed in collaboration with Eli Lilly and Company, has received clinical trial approval from the China National Medical Products Administration (NMPA), enabling the direct initiation of Phase I clinical trials in patients with low bone mineral density. TST004, a humanized anti-MASP-2 monoclonal antibody candidate for IgA nephropathy, developed in partnership with Libang Pharmaceutical, has completed process development and GMP-compliant material production, and has initiated GLP-compliant toxicity studies. TST003, targeting an original novel target, has demonstrated monotherapy efficacy in PD-L1-negative tumors in preclinical models, with an Investigational New Drug (IND) application planned for submission this year.

According toMs. Xia Qin, Vice President of Business Planning and Business Development at Transcenta HoldingIntroduction: Due to the clinical development strategy and differentiated characteristics of TST001, it has a broader beneficiary population than Astellas’ products, laying the foundation for future commercial success.

China is a country with a high incidence of gastric cancer, which ranks as the second most common malignant tumor. According to data from the World Health Organization, there were 1.8 million new cases of gastric cancer globally in 2020, including 688,600 new cases in China, indicating a significant clinical demand for gastric cancer medications.

Ms. Xia Qin stated, “TST001 is primarily being developed for the indication of gastric cancer., as TST001 also demonstrates strong efficacy in gastric cancer patients with low-to-moderate Claudin 18.2 expression, the proportion of the patient population covered by this therapy is twice that of IMAB362.”

Secondly,TST001 Holds Global Rights, in addition to China, the United States, Europe, Japan, Southeast Asia, and other regions are also high-incidence areas for gastric cancer, presenting significant market potential.

“In the United States, gastric cancer is not a high-incidence disease, but there is a high level of unmet need; therefore, we”Adopted Different Business Strategies“Currently, TST001 has been granted Orphan Drug Designation by the U.S. FDA, giving us a significant pricing advantage and thus strong potential in the U.S. gastric cancer drug market,” said Ms. Xia Qin.

Furthermore,In addition to gastric cancer, the product also has a strategic focus on pancreatic cancer and cholangiocarcinoma., given the significant pricing advantages for pancreatic cancer drugs in the United States, this further underscores the market potential of TST001.

“Overall, TST001 has enormous market potential. Based on our market projections, this product is expected to achieve peak sales exceeding USD 2 billion, with a high-end estimate surpassing USD 3 billion, indicating very strong commercial prospects,” added Ms. Xia Qin.

Since its inception, Transcenta Holding has emphasized global expansion, adhering to a dual-filing strategy in China and the United States, with Investigational New Drug (IND) applications generally submitted simultaneously in both countries. It is understood that Transcenta Holding’sThe global clinical development and monitoring teams are located in Beijing, Shanghai, Guangzhou, and Princeton, USA, respectively., and has established international cooperation centers in Boston and Los Angeles, USA, possessing specialized expertise and extensive experience in conducting global clinical trials.

Dr. Shi Ming stated, “Dual filing in China and the United States is one of our major advantages, as demonstrated by TST001. First,”The regulatory approval pathway in the United States is faster, while China boasts a larger patient population and a substantial unmet medical need."Leveraging our advantages in dual filing with China and the United States, we can better strategize for subsequent projects and further optimize our clinical trial designs. Furthermore, as the Center for Drug Evaluation (CDE) increasingly supports international joint development programs, we will maintain close communication with both the CDE and the FDA from the outset of each project to ensure the smooth conduct of clinical trials."

It is understood that while developing TST001, Transcenta Holding alsoConcomitant diagnostics were developed in parallel., can be provided to patients simultaneously upon the drug’s market launch, without the need to wait for or rely on other companies’ products, which has further accelerated the R&D progress of TST001.

“Timing is critical. We launched our global registration-enabling clinical trials in the second half of this year, a full year ahead of schedule, aiming to leverage our advantages in the speed and operational efficiency of international clinical development to secure an early-mover advantage in the market,” added Dr. Qian Xueming.

To provide high-quality and affordable innovative biologics to patients worldwide, Transcenta Holding is actively advancingIntegrated Continuous Biomanufacturing (ICB) PlatformContinuous upgrades leverage technologies such as process intensification, automation, and continuous flow manufacturing to significantly reduce production costs while ensuring drug quality.。

ICB’s continuous manufacturing platform integrates a proprietary, high-productivity continuous upstream perfusion process with an automated continuous downstream production process (co-developed with Merck). Leveraging the power of ultra-high cell density continuous perfusion technology and proprietary cell culture media, the platform has achieved an industry-leading daily volumetric productivity exceeding 6 g/L. It has successfully scaled the perfusion process for TST001 to GMP commercial scale, with yields for multiple cell lines increasing by up to 10- to 20-fold compared to traditional fed-batch processes.

Dr. Qian Xueming stated, “The continuous manufacturing platform can first help accelerate the clinical development of products; second, it ensures product quality and enables rapid capacity expansion to meet demand; and third, it reduces product costs after commercial launch. This truly helps Transcenta Holding fulfill its mission of developing differentiated, affordable products to benefit patients worldwide.”

Looking to the future, Dr. Qian Xueming stated that, in addition to its existing technologies, Transcenta Holding will develop and introduce more advanced technologies, committing to the research and development of more First-in-Class drugs. In the short term, the company will rapidly initiate the first global registration trial for TST001 and actively advance the development of its pipeline products. Furthermore, for its pipeline products in orthopedics and nephrology, the company will fully leverage external resources, strengthen innovative collaborations with domestic and international companies, and drive the commercialization of its products.

In the long term, Transcenta Holding aims to establish a commercialization team, further expand its product pipeline, and truly compete on the international stage by actively advancing the global development and commercialization of its candidate products, thereby benefiting patients worldwide.