Nature Cancer publishes the results of a collaborative study conducted by scientists from Transcenta and Shanghai Jiao Tong University

Preclinical Studies on the Potential Application of Transcenta’s Gremlin1 First-In-Class Targeting Antibody in the Treatment of Androgen Receptor Negative/Low Androgen Receptor Prostate Cancer

SUZHOU, China, May 30, 2022 /PRNewswire/ — Transcenta Holding Limited (“Transcenta”) (HKEX:06628), a clinical-stage biopharmaceutical company with fully integrated capabilities in the discovery, research, development and manufacturing of antibody therapies, announces that Nature Cancer, an international authoritative journal society in the field of oncology, publishes the results of preclinical studies of by Transcenta first antibody targeting Gremlin1 (TST003) in the treatment of castration-resistant prostate cancer. This research was carried out in collaboration between Transcenta and the team of professors Helen He Zhu and Wei-Qiang Gao at Renji Hospital, Shanghai JiaoTong University School of Medicine. Teacher John T. Isaacsan internationally renowned expert in prostate cancer research, wrote an editorial and commented that neutralizing antibodies against Gremlin1 could be a potential treatment for androgen receptor negative/weak prostate cancer.

In this study, researchers from Transcenta and Shanghai Jiao Tong University investigated the therapeutic potential of anti-Gremlin1 for prostate cancer in an aggressive mouse model of CRPC (Pbsn-Cre4; Ptenfl/fl; Trp53fl/fl GEMM) and patient-derived xenograft (PDX), using TST003, a humanized antibody targeting Gremlin1 and a surrogate antibody generated by Transcenta. The study found that the expression of Gremlin1 increases with the progression of prostate cancer from a localized state to a metastatic state, as well as from a castration sensitive state to a castration resistant state. Additionally, elevated Gremlin1 expression in prostate cancer tumors is associated with shorter progression-free and overall survival. Study results revealed that the Gremlin1 protein can promote lineage plasticity and promote castration resistance in prostate cancer. Gremlin1-specific antibodies can effectively control tumor growth in androgen receptor negative/weak prostate cancer. The study also demonstrated synergistic activity between the anti-Gremlin1 antibody and enzalutamide against patient-derived castration-resistant prostate cancer models in vitro and in vivo. While previous studies indicate that Gremlin1 inhibits the BMP signaling pathway, the present work shows that Gremlin1 can activate FGFR1, which phosphorylates the ERK/MEK signal transduction pathway. Anti-Gremlin1 antibody can block Gremlin1 functions and inhibit activation of FGFR1 and ERK/MEK signaling.

Professor Wei-Qiang Gao, an internationally renowned expert in the field of prostate cancer, director of the Med-X Research Institute of Shanghai Jiao Tong University and the Stem Cell Clinical Research Center of Shanghai Renji Hospital, said, “Research results indicate that Gremlin1 plays a crucial role in prostate cancer tumor cell plasticity and castration resistance formation, and for the first time, the receptor to androgens (AR) has been shown to downregulate the transcriptional expression of Gremlin 1. With the widespread use of AR inhibitors, an increasing number of patients with prostate cancer The novelty of the present work is that , while previous studies indicate that Gremlin1 inhibits the classical BMP signaling pathway, Gremlin1 can bind to FGFR1 and activate the FGFR1/MAPK signaling pathway as a novel ligand for FGFR1. antibody monotherapy alone can potently inhibit the growth of castration resistant androgen receptor negative prostate cancer (CRPC) and a combination of Gremlin1 antibodies with AR inhibitors can better control the growth of CRPC with low activity AR. We believe that the results of this study provide a promising therapeutic target for androgen receptor negative/weak CRPC and have important clinical translational significance. »

“Transcenta is focused on developing highly innovative treatments,” said Dr. Xueming QianCEO of Transcenta, “TST003, an antibody targeting Gremlin1, is being developed by Transcenta. Preclinical study shows that Gremlin1 plays an important role in the growth of multiple solid tumors, especially in solid tumors unresponsive to immune checkpoint inhibitors. We are fortunate to have the opportunity to collaborate with Professors Zhu and Gao from Jiao Tong University on the potential use of the Gremlin1 targeting antibody for the treatment of castration-resistant prostate cancer. publication of the study results in Nature Cancer speaks to its novelty and clinical translational value.Also an attempt to develop first-class therapies through collaborative efforts between industry and academia in China. This year, Transcenta will submit an IND application for this world-leading antibody and advance it to clinical trials, hoping to develop a potential new treatment option for patients with prostate cancer with AR activity. negative / low in the world, a population without effective treatment and therefore very high unmet medical needs. »

About TST003

TST003 is a first-in-class, high-affinity humanized monoclonal antibody targeting Gremlin-1, a regulatory protein highly expressed by stromal cells in various human carcinomas, particularly in esophageal cancer, pancreatic cancer, stomach cancer, colon cancer and lung cancer. , breast cancer and prostate cancer, among others. TST003 has shown significant anti-tumor activities both in vitro and in vivo in preclinical studies. TST003 has the potential to become a novel cancer treatment, either as a monotherapy or in combination with an immune checkpoint inhibitor and/or other anti-tumor agents.

About Transcenta Holding Limited

Transcenta (HKEX: 06628) is a clinical-stage biopharmaceutical company with fully integrated capabilities in the discovery, research, development and manufacturing of antibody-based biotherapeutics.

Transcenta has established a global footprint, with headquarters and a clinical and translational research center in Suzhou, a process and product development center and a manufacturing facility in Hangzhouand clinical development centers in beijing, Shanghai and Canton in China and in Princetonin the United States and at the external partnership center of Boston and Los Angeles, WE. Transcenta also launched the construction of the group headquarters and the second high-end biopharmaceutical facility with ICB as the core technology in Suzhou Industrial Park. Transcenta is developing ten therapeutic antibody molecules for oncology and certain non-oncology indications, including bone and kidney disorders.

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