Pucotenlimab

Lepu Biopharma is an innovative biopharmaceutical company focused on the field of oncology treatment, particularly in targeted therapy and immunotherapy. It is dedicated to developing innovative ADCs through an advanced ADC technology development platform, creating optimized and novel medications to better meet the unmet clinical needs of cancer patients. Moreover, the company is developing combination therapies of IO+ADC utilizing its marketed PD-1 monoclonal antibody, Pucotenlimab, taking full advantage of pipeline synergy. Additionally, Lepu Biopharma has expanded and diversified its pipeline by introducing oncolytic virus products through partnerships. At this year's ASCO, Lepu Biopharma presented three studies, with two clinical research findings delivered orally; these included the ADC drugs MRG003, MRG004A, and the PD-1 antibody Pucotenlimab (HX008). 1.MRG003: MRG003 is an ADC composed of an EGFR-targeting monoclonal antibody linked to the potent microtubule inhibitor payload MMAE via a vc linker. It specifically binds to EGFR on the surface of tumor cells with high affinity and, upon internalization into the tumor cell, it releases its potent payload, leading to tumor cell death. Previously, MRG003 was granted Fast Track Designation (FTD) by the U.S. Food and Drug Administration (FDA) for the treatment of advanced nasopharyngeal carcinoma (NPC) and was recognized by the CDE as a breakthrough therapy drug (BTD). Currently, a registrational Phase IIb trial for MRG003 targeting NPC has completed enrollment and is expected to apply for marketing approval in 2024; a Phase III trial for head and neck squamous cell carcinoma (HNSCC) is ongoing; indications for NPC and HNSCC have been granted IND approval in the USA. In a Phase IIa trial targeting NPC, patients who had failed or were intolerant to at least one platinum-based regimen and PD-1/L1 inhibitor treatment received MRG003 at doses of 2.0 mg/kg (n=30) or 2.3 mg/kg (n=31). The primary endpoint was the Overall Response Rate (ORR) assessed by RECIST 1.1 criteria, while secondary endpoints included Disease Control Rate (DCR), Duration of Response (DoR), Progression-Free Survival (PFS), and safety. As of March 15, 2023, the 2.0 mg/kg dose group had 28 assessable patients, showing an ORR of 39.3%, a DCR of 71.4%, a median DoR of 6.8 months, and a median PFS of 7.3 months. In the 2.3 mg/kg dose group, 29 patients were assessable, with an ORR of 55.2%, DCR of 86.2%, median DoR of 6.8 months, and immature median PFS. Regarding safety, the most common treatment-related adverse events (TRAEs) included rash (49.2%), itching (41.0%), anemia (34.4%), and hair loss (31.1%), with most TRAEs being Grade 1 or 2 according to the CTCAE 5.0 standards. The rate of treatment-related severe adverse events (SAE) was 11.5% (7/61). Dose reductions due to TRAEs occurred in 13.1% (8/61) of patients, and treatment was discontinued in 3 patients (4.9%). No treatment-related deaths were observed. 2. MRG004A: MRG004A is an innovative ADC targeting tissue factor (TF) and is obtained by site-specific conjugation. It employs a differentiated design, selecting a humanized anti-TF monoclonal antibody with high TF affinity for rapid internalization, which is observable within one hour and minimizes the impact on coagulation. This drug has been granted Orphan Drug Designation and Fast Track Designation by the FDA. Preclinical studies in multiple TNBC, ovarian cancer, and PDAC CDX and PDX models have demonstrated the in vivo anti-tumor activity of MRG004A. Currently, MRG004A is undergoing Phase I/II clinical trials in the United States and China, and anti-tumor activity signals have been observed in indications such as pancreatic cancer, triple-negative breast cancer, and cervical cancer. How to search for and analyze the development progress of ADC pharmaceuticals?If you want to learn about the latest developments in ADC drugs, you can use the drug search module of the Synapse database. This module supports searching for ADC drugs by classification through Targeting Moiety, Linker, and Payload. On the search results page, you can easily review information related to the ADC's technical category of the drugs. After clicking to enter the drug details page, you can also effortlessly obtain structural information about the ADC drug. Click on the image below to embark on a brand new journey of drug discovery!

SAN DIEGO--(BUSINESS WIRE)-- Crown Biosciences Inc., a global contract research organization (CRO) and JSR Life Sciences company, has announced that its collaborative work with HanX Biopharmaceuticals, Inc. (“HanX”), employing a unique and broad portfolio of preclinical modeling in support of HanX’s successful FDA Investigational New Drug (IND) application, has been published in Scientific Reports, a journal within the Nature portfolio. The study demonstrated that HX009, an investigational “first-in-class” PD-1 x CD47 bispecific antibody, binds differentially to both PD-1 and CD47 with strong affinity to PD-1 but weakened affinity to CD47. This feature enables better targeting to the tumor microenvironment (TME) and minimizes potential hematological toxicity. In addition, HX009 exhibited enhanced T-cell activating capability over HX008, an approved and marketed anti-PD-1 monoclonal antibody in China. Specifically, this new study showed that HX009 exerted robust anti-lymphoma activity in two cell-derived xenograft (CDX) models (Raji B-lymphoma and Karpas-299 T-lymphoma) with high CD47 expression. Additionally, custom patient-derived xenograft (PDX) models established by Crown Bioscience, further confirmed the efficacy of CD47 targeting by HX009. In addition, an A20-hCD47 mouse B-lymphoma model developed in hSIRPα/hCD47/PD-1/PD-L1 quadruple knock-in genetically engineered mouse models (HuGEMMTM) mice, HX009 exhibited superior anti-lymphoma efficacy compared to CD47 or PD-1 targeting alone. These results imply a synergy between CD47 and PD-1 dual targeting. These Crown Bioscience studies played an important role in supporting the application of HX009 for the treatment of lymphoma in clinical trials. They also played an instrumental role in supporting the clearance of HanX’s FDA Investigational New Drug (IND) application, which has paved the way for a U.S.-based Phase I/II clinical study that will assess HX009 in the treatment of relapsed/refractory lymphoma. This exciting result exemplifies the value that Crown Bioscience brings to its partners as they seek better solutions for advancing their oncology research. Specifically, the collaboration between scientists from both organizations, utilizing an integrated solution approach, leveraged a comprehensive collection of preclinical and translational studies to investigate the anti-lymphoma activity of HX009. While HX009 has been studied in Phase I clinical studies in Australia and China in both solid tumor and lymphoma indications, HanX is now expanding the next phase of clinical development globally in a variety of clinical indications. Henry Li, PhD, Cofounder, Chief Executive Officer and Chief Scientific Officer of HanX, stated: “We are delighted with the exceptional outcomes of our partnership with Crown Bioscience. By leveraging a wide breadth of in vivo solutions such as cell-derived xenograft (CDX), patient-derived xenograft (PDX), and genetically engineered mouse models, together with translational applications, we were able to conduct a comprehensive evaluation of HX009’s anti-lymphoma activity prior to clinical trials.” Ludovic Bourre, PhD, VP, Research and Innovation at Crown Bioscience, added: “Our commitment goes beyond identifying the right candidate drug or drug combination. Crown Bioscience consistently invests in expanding the number and diversity of models for drug development, ensuring that our models accurately represent the relevant clinical disease biology and provide a solid foundation for making informed decisions about novel therapeutics such as HanX's HX009.” This work has laid a robust foundation for the advancement of HX009 as a highly promising therapeutic agent in the treatment of relapsed/refractory lymphoma. To learn more, Crown Bioscience and HanX are hosting an exclusive webinar on Tuesday August 29, 2023, where a team of scientists will discuss the implications of the study. The webinar will provide a unique opportunity to engage with the experts. ### About Crown Bioscience Crown Bioscience, a JSR Life Sciences company, is a global CRO that provides preclinical and translational platforms to help our customers advance their research and development in oncology, immuno-oncology, and immune-mediated inflammatory diseases. We are the exclusive preclinical CRO to offer tumor organoid services with the well-established Hubrecht Organoid Technology. In addition, we have developed the largest commercially available PDX collection in the world. We focus on helping our customers develop novel therapies to maximize the chances that patients receive the right treatment at the right time. Founded in 2006, Crown Bioscience has 14 facilities across the United States, Europe, and Asia. For more information or to get in touch, please visit About HanX HanX is a global biopharmaceutical company that develops innovative immuno-oncology antibody-based drugs, such as novel BsAb antibodies to address significant unmet medical needs. HanX brings together experts from both China and the U.S., to aid in activities ranging from early discovery, process development, business development, and clinical research. The company aims to accomplish its ambitious goals by relying on in-house research and development in combination with external global collaborations.