LIV-1

PRINCETON, N.J. and SUZHOU, China, Dec. 12, 2024 /PRNewswire/ -- Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a global clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, announced late-breaking presentation of preclinical study results of novel humanized LIV-1 antibody based ADCs at 2024 San Antonio Breast Cancer Symposium (SABCS). The ADCs (ADC-1 and ADC-2) were engineered using Transcenta's proprietary antibody with site-specifical conjugation of Topoisomerase I Inhibitor payloads and these ADCs demonstrated significantly higher tumor regression activities than MMAE based ADCs in triple-negative breast cancer (TNBC) tumor models. Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and has the highest rate of recurrence. The predominant standard of care for advanced TNBC is systemic chemotherapy with or without immunotherapy; however, the responses are typically short lived. Thus, there is an urgent need to develop more effective treatments [1]. LIV-1, a member of the zinc transporter family and an estrogen-regulated gene in metastatic breast cancer, is overexpressed in a high prevalence in breast cancer (93%), including both TNBC and hormone receptor positive breast cancer, as well as in melanoma (82%), prostate (72%), ovarian (48%) and uterine (30%) cancer. This makes LIV-1 an attractive cell surface target for developing ADC therapeutics. To develop next generation LIV-1 targeting ADC, Transcenta generated a proprietary novel humanized anti-LIV-1 mAb, 48D6, which displayed unique epitope form benchmark antibody, high binding affinity, specificity, excellent internalization ability. The conjugation method also eliminated FcR binding which resulted in significantly reduced non-specific FcR mediated binding and clearance, and improved pharmacokinetics profile in mice. In vitro studies indicated that breast tumor cells, such as MDA-MB-468 and MCF-7, are more sensitive to Topo I inhibitor than MMAE. Consequently, Transcenta developed two Topo I inhibitor-based ADCs (ADC-1 and ADC-2) using glycotransferase mediated site-specific conjugation. Both ADC-1 and ADC-2 have a drug-to-antibody ratio (DAR) of 4 but with two different Topo I inhibitor payloads. A MMAE based ADC (ADC-3) with the same site-specific conjugation and DAR4 was also synthesized as the control. Although ADC-1 and ADC-2 displayed similar and specific cytotoxic activities against human LIV-1-expressing tumor cells in vitro, as compared to SGN-LIV1A analog (DAR4) or ADC-3, they exhibited much higher maximal tumor cell killing than SGN-LIV1A analog in vivo. In addition, both ADC-1 and ADC-2 demonstrated a strong bystander effect which is important to overcome tumor heterogeneity. In vivo pharmacology study revealed that ADC-1 or ADC-2 exhibited dose-dependent and more potent anti-tumor activities than the SGN-LIV1A analog or ADC-3 in the human LIV-1 transfected MDA-MB-468, a TNBC tumor model. At 3 mg/kg the tumor growth inhibition (TGI)% were: ADC-1 92.4%, ADC-2 94.7%, ADC-3 68.5% and SGN-LIV1A analog 57.0% on Day 30. However, the overall response rate (ORR, 50% reduction of tumor volume from baseline) at 3mg/kg for SGN-LIV1A analog or ADC-3 was 0%, while ORRs of ADC-1 and ADC-2 were 40% and 70%, respectively. At 6 mg/kg, on Day 42, ORRs of ADC-1 and ADC-2 were 90% and 100%, respectively, and complete response (CR) rates were 90% and 100% respectively. The body weight of mice didn't change significantly at either 3 or 6 mg/kg for ADC-1 or ADC-2. "The significantly enhanced anti-tumor activities of ADC-1 and ADC-2 are likely due to the high affinity binding of 48D6 to LIV-1 and the high cytotoxicity of Topo I inhibitor for breast tumor cells." said Dr. Xueming Qian, Chairman of the Board and CEO at Transcenta, "These data warrant further investigation of the lead LIV-1 targeting ADCs (ADC-1 and ADC-2) as potential next-generation therapeutic agent in LIV-1 positive breast cancer and other solid tumors." The 47th San Antonio Breast Cancer Symposium (SABCS) held from December 10 to 13, 2024, in San Antonio, Texas, USA. This Symposium is designed to provide state-of-the-art information on the experimental biology, etiology, prevention, diagnosis, and therapy of breast cancer and premalignant breast disease to an international audience of academic and private physicians and researchers. About Transcenta 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 is developing 14 therapeutic antibody molecules for oncology and selected non-oncology indications including bone and kidney disorders. Media contact: Bryan Cheng, [email protected] SOURCE Transcenta Holding Limited WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

SHANGHAI, Nov. 7, 2023 /PRNewswire/ -- BioRay Pharmaceutical Co., Ltd. (hereinafter referred to as BioRay) announced that the first patient has been dosed in the Phase I Clinical trial of BRY812, a third-generation antibody-drug conjugate (ADC) targeting LIV-1 for the treatment of advanced malignant tumors. The leading institution of this clinical trial is Sun Yat-sen Memorial Hospital of Sun Yat-sen University, and the principal investigators are academician Song Erwei and Professor Yao Herui. LIV-1, also known as SLC39A6 or ZIP6, is a multipass transmembrane protein belonging to the ZIP superfamily of zinc transporters, possesses zinc transporter and metalloproteinase activities. LIV-1 directly participates in the homeostasis metabolism of intracellular zinc ions, facilitating the transport of zinc ions from the extracellular space or intracellular organelles to the cytoplasm, influencing cell growth. To date, there are no approved drugs worldwide that target LIV-1, making BioRay's BRY812 the first LIV-1 ADC in China and the second to enter clinical trials globally. BRY812 uses the proprietary CysLink™ irreversible chemical conjugation technology platform and highly stable linker to conjugate the antibody with the toxin. BRY812 has shown significant tumor growth inhibition in preclinical studies, and demonstrated excellent anti-tumor activity that is potentially superior to similar drugs. Compared to other drugs of the same class, it exhibits higher circulation stability, effective release of the payload within the tumor while significantly reducing toxin shedding and exchange in serum. This provides BRY812 with a great safety profile and an improved therapeutic window. Furthermore, BRY812 can also induce immunogenic cell death (ICD) and enhance the anti-tumor effects of immunotherapies such as anti-PD-(L)1. Dr. Zhu Wei, CMO of BioRay, stated, " The significant market potential of ADCs requires differentiation in the market competition and expanding coverage to a broader patient population. As the first domestic ADC targeting LIV-1 to enter clinical trials, BRY812 is expected to treat various advanced malignant tumors, meet more clinical medication needs, and provide more treatment options for patients." About BioRay BioRay is a pioneer in China's biopharmaceutical industry focusing on immune-mediated diseases. Its extensive autoimmune and oncology portfolio includes six marketed products and over 10 clinical-stage drug candidates. Operating a fully integrated platform with end-to-end capabilities across drug discovery, clinical development, manufacturing, and commercialization, BioRay has over 1,500 employees globally, with main sites in Taizhou, Hangzhou, Shanghai, and San Diego. SOURCE BioRay Pharmaceutical Co., Ltd

ZUG, Switzerland and BOSTON, Sept. 27, 2023 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, today announced poster presentations of preclinical data at the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting, taking place in San Diego, CA or virtually from November 1 to 5, 2023. Title: Development of CTX112 a next generation allogeneic multiplexed CRISPR-edited CAR T cell therapy with disruptions of the TGFBR2 and Regnase-1 genes for improved manufacturing and potency Abstract Number: 274 Location: Exhibit Halls A and B1 Date and Time: Saturday, November 4, 2023, 9:00 a.m. – 8:30 p.m. Title: Allogeneic CAR T cells targeting Liv-1 for Breast Cancer Abstract Number: 324 Location: Exhibit Halls A and B1 Date and Time: Saturday, November 4, 2023, 9:00 a.m. – 8:30 p.m. Title: Development of allogeneic, potency-edited, anti-GPC3 CAR-T cells for the treatment of hepatocellular carcinoma Abstract Number: 264 Location: Exhibit Halls A and B1 Date and Time: Saturday, November 4, 2023, 9:00 a.m. – 8:30 p.m. About CRISPR Therapeutics CRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic partnerships with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Boston, Massachusetts and San Francisco, California, and business offices in London, United Kingdom. For more information, please visit . CRISPR THERAPEUTICS® word mark and design logo and CTX112™ are trademarks and registered trademarks of CRISPR Therapeutics AG. All other trademarks and registered trademarks are the property of their respective owners. Investor Contact: Susan Kim +1-617-315-4600 susan.kim@crisprtx.com Media Contact: Rachel Eides +1-617-315-4493 rachel.eides@crisprtx.com