GREM1

Current osteoarthritis treatment manages symptoms rather than addressing the underlying disease, but a new study has shown the condition may be treatable and reversible. Current osteoarthritis treatment manages symptoms rather than addressing the underlying disease, but a new University of Adelaide study has shown the condition may be treatable and reversible. Osteoarthritis is the degeneration of cartilage and other tissues in joints and is the most common form of arthritis in Australia, with one in five people over the age of 45 having the condition. It is a long-term and progressive condition which affects people's mobility and has historically had no cure. Its treatment cost the Australian health system an estimated $3.9 billion in 2019-20. Often described as a 'wear and tear' condition, factors such as ageing, obesity, injury and family history contribute to the progression of osteoarthritis. University of Adelaide researchers discovered a novel population of stem cells -- marked by the Gremlin 1 gene -- responsible for the progression of osteoarthritis. Treatment with fibroblast growth factor 18 (FGF18) stimulated the proliferation of Gremlin 1 cells in joint cartilage in mice, leading to significant recovery of cartilage thickness and reduced osteoarthritis. Gremlin 1 cells present opportunities for cartilage regeneration and their discovery will have relevance to other forms of cartilage injury and disease, which are notoriously challenging to repair and treat. It challenges the categorisation of osteoarthritis as wear and tear. "The findings of our study reimagine osteoarthritis not as a 'wear and tear' condition but as an active, and pharmaceutically reversible loss of critical articular cartilage stem cells," said the University of Adelaide's Dr Jia Ng from the Adelaide Medical School, who co-led the study. "With this new information, we are now able to explore pharmaceutical options to directly target the stem cell population that is responsible for the development of articular cartilage and progression of osteoarthritis." While Dr Ng describes current treatments for osteoarthritis as a "Band-Aid approach," this new understanding could lead to a pharmaceutical treatment that reverses osteoarthritis and helps to address health outcomes associated with the disease. "Known comorbidities of osteoarthritis include heart, pulmonary, and kidney disease, mental and behavioural conditions, diabetes, and cancer," said Dr Ng. "Our study suggests that there may be new ways to treat the disease rather than just the symptoms, leading to better health outcomes and quality of life for people who suffer from osteoarthritis." Though this discovery is limited to animal models, Dr Ng said there are genetic similarities to human samples, and human trials are ongoing. "We look forward to the outcome of these trials and to contribute to the better understanding of a pharmaceutical mechanism to treat osteoarthritis," she said. Results of a five-year clinical trial study using FGF18, known clinically as Sprifermin, were published in 2021 with potential long-term clinical benefit and no safety concerns. Phase 3 of the Sprifermin trial is ongoing, and researchers envision public access to this treatment soon.

SUZHOU, China, March 22, 2023 /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 the successful dosing of first patient in the U.S. Phase I Study of TST003 (NCT05731271), its first-in-class, high affinity humanized monoclonal antibody targeting Gremlin1, for the treatment of solid tumors. NCT05731271 is an open-label, dose escalation, FIH study designed to evaluate the safety, tolerability, and pharmacokinetics profile of TST003 as a treatment in patients with solid tumors. TST003 is a high affinity monoclonal antibody targeting Gremlin1, a member of the TGF-β superfamily. Gremlin1 protein is a highly conserved secreted protein and has shown to play important roles during embryonic development and promote epithelial mesenchymal transition. Gremlin1 is upregulated in multiple solid tumors. TST003 has demonstrated promising single agent and combination activities in patient-derived xenograft tumor models from the difficult-to-treat solid tumors resistant to checkpoint inhibitors including castration resistant prostate cancer and microsatellite stable colorectal cancer. " The enrollment and dosing of the first patient in the US marks a very significant milestone for TST003: our carefully designed phase 1 will provide the necessary clinical and translational data to achieve the full potential of targeting Gremlin-1 as a single agent or in combinations with standard of care, in particular in indications with high unmet need like MSS CRC or CRPC." said Dr. Caroline Germa, Transcenta's Executive Vice President, Global Medicine Development and Chief Medical Officer. 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 Princeton, US and in Beijing, Shanghai and Guangzhou of China, 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 and . SOURCE Transcenta Holding Limited

SUZHOU, China, March 22, 2023 /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, today announces that two preclinical studies in relation to TST003, a First-in-Class mAb Targeting GREMLIN-1, and TST010, an ADCC enhanced anti-CD25 mAb will be presented as posters at the American Association for Cancer Research (AACR) Annual Meeting 2023. This year's meeting will be held from April 14-19, 2023, in Orlando, Florida, USA. The AACR Annual Meeting is the focal point of the cancer research community, where scientists, clinicians, other health care professionals, survivors, patients, and advocates gather to share the latest advances in cancer science and medicine from institutions all over the world. A brief summary of the presentations is as follows: Title: The Preclinical Characterization of TST003, a First-in-Class mAb Targeting GREMLIN-1 Overexpressed by Cancer-Associated Fibroblasts and Tumor Cells Abstract#: 465 Session Category: Experimental and Molecular Therapeutics Session Title: New Drug Targets Session Date and Time: Sunday Apr 16, 2023 1:30 PM - 5:00 PM (EDT) Title: ADCC enhanced anti-CD25 mAb (TST010) exhibited potent anti-tumor activity by depleting Treg cells and increasing CD8+T/Treg ratio in preclinical tumor models Abstract#: 1546 Session Category: Experimental and Molecular Therapeutics Session Title: Antibody Drug Conjugates Session Time: Monday Apr 17, 2023 9:00 AM - 12:30 PM (EDT) About TST003 TST003 is a high affinity monoclonal antibody targeting Gremlin1, a member of the TGF-β superfamily. Gremlin1 protein is a highly conserved secreted protein and has shown to play important roles during embryonic development and promote epithelial mesenchymal transition. Gremlin1 is upregulated in multiple solid tumors. TST003 has demonstrated promising single agent and combination activities in patient-derived xenograft tumor models from the difficult-to-treat solid tumors resistant to checkpoint inhibitors including castration resistant prostate cancer and microsatellite stable colorectal cancer. About TST010 Using immune tolerance breaking antibody platform, Transcenta generated a humanized IgG1 subtype anti-CD25 monoclonal antibody with reduced fucose (TST010). TST010 binds to human CD25 with high affinity and selectivity, but does not block IL-2 binding to CD25. Non-blocking activity to IL-2 signaling on human PBMC has been further confirmed by the phosphorylation of STAT5. By reducing fucosylation during cell culture process, TST010 mAb gains the enhanced ADCC activity in vitro and anti-tumor activity by depleting Treg cells and increasing CD8+T/Treg ratio in preclinical tumor models. 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 Princeton, US and in Beijing, Shanghai and Guangzhou of China, 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 and . SOURCE Transcenta Holding Limited