Preclinical Studies on the Potential Application of Transcenta's First-In-Class Gremlin1 Targeting Antibody in the Treatment of Androgen Receptor-Negative/Low Prostate Cancer
SUZHOU, China, May 31, 2022 /PRNewswire/ -- 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 Nature Cancer, an international authoritative journal in oncology field, publishes the results of preclinical studies of Transcenta's first-in-class Gremlin1 targeting antibody (TST003) in the treatment of castration resistant prostate cancer. This research was conducted 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. Professor John T. Isaacs, an 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/low 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 Gremlin1-targeting antibody, and a surrogate antibody generated by Transcenta. The study found that Gremlin1 expression becomes increased with prostate cancer progression from a localized to a metastatic state, as well as from a castration-sensitive to a castration-resistant state. Furthermore, high Gremlin1 expression in prostate cancer tumors is associated with shorter progression-free and overall survival. The study results revealed that Gremlin1 protein can promote lineage plasticity and drive castration resistance in prostate cancer. Gremlin1-specific antibodies can effectively control tumor growth in androgen receptor-negative/low prostate cancer. The study also demonstrated a 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 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's functions and inhibit the activation of FGFR1 and ERK/MEK signaling.
Professor Wei-Qiang Gao, an internationally renowned expert in the field of prostate cancer, Director of Shanghai Jiao Tong University's Med-X Research Institute and Clinical Stem Cell Research Center of Renji Hospital, said: "The research results indicated that Gremlin1 plays a crucial role in prostate cancer tumor cell plasticity and castration-resistance formation, and for the first time, the androgen receptor (AR) was found to negatively regulate Gremlin1 transcriptional expression. With the widespread use of AR inhibitors, an increasing number of patients with prostate cancer are becoming resistant to them. 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. Anti-Gremlin1 antibody monotherapy alone can potently inhibit the growth of androgen receptor negative castration resistant prostate cancer (CRPC) and a combination of Gremlin1 antibody with AR inhibitors can better control the growth of CRPC with low AR activity. We believe that the results of this study provide a promising therapeutic target for androgen receptor-negative/low CRPC and have important clinical translational significance."
"Transcenta is focused on developing highly innovative therapeutics," said Dr. Xueming Qian, CEO of Transcenta, "TST003, a Gremlin1 targeting antibody, is developed by Transcenta. Preclinical study shows that Gremlin1 plays an important role in the growth of multiple solid tumors, especially in solid tumors insensitive 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 Gremlin1 targeting antibody for the treatment of castration resistant prostate cancer. The publication of the study results in Nature Cancer speaks for its novelty and clinical translational value. This is also an attempt for developing first-in-class therapeutics through collaborative efforts between industry and university in China. This year, Transcenta will submit IND application of this global first-in-class antibody, and advance it into clinical testing, with the hope to develop a potential novel treatment option to prostate cancer patients with negative/low AR activity worldwide, a population without effective treatment and thus very high unmet medical needs."
About TST003
TST003 is a first-in-class, high affinity humanized monoclonal antibody targeting Gremlin-1, a regulatory protein that is highly expressed by stromal cells in diverse human carcinomas, especially in esophageal cancer, pancreatic cancer, gastric cancer, colon cancer, lung cancer, breast cancer and prostate cancer, among others. TST003 has displayed 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 monotherapy or in combination with 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 antibody-based biotherapeutics discovery, research, development and manufacturing.
Transcenta has established global footprint, with Headquarters and Discovery, Clinical and Translational Research Center in Suzhou, Process and Product Development Center and Manufacturing Facility in Hangzhou, and Clinical Development Centers in Beijing, Shanghai and Guangzhou in China and in Princeton, US, and External Partnering Center in Boston and Los Angeles, US. Transcenta has also initiated the construction of the Group Headquarters and the second high-end biopharmaceutical facility with ICB as its core technology in Suzhou Industrial Park. Transcenta is developing ten therapeutic antibody molecules for oncology and selected non-oncology indications including bone and kidney disorders.
For more information, please visit www.transcenta.com and https://www.linkedin.com/company/transcenta.
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