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Focusing Biocytogen
Biocytogen is an international biotech company that drives the research and development of new drugs with innovative technologies. With the mission of focusing on technological innovation, sustaining new drug production and protecting human health, it is committed to becoming the birthplace of new drugs in the world.With the implementation of “RenMice HiTS Platform” for the large-scale antibody drug development, the company will focus more on new drug development.
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Relying on the new drug R & D system covering the whole process of drug R & D, we focus on the field of immunotherapy and build many R & D pipelines for the fields of cancer, autoimmunity, metabolism and anti-infection. Dedicated to provide patients with efficient and safe antibody drugs and face global health problems together.
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Based on the unique RenMice platform, we have established a full platform system for antibody drug discovery technology including GPCR technology platform, TCR mimic antibody, and bispecific antibody platform to effectively accelerate the development process of large-scale innovative antibody drugs.
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BEIJING and BOSTON, June 1, 2021 /PRNewswire/ -- Eucure Biopharma will present findings from two Phase I clinical trials at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, held from June 4th to 8th. The first trial (poster #2580; NCT04481009) is designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor efficacy of YH003 (an anti-CD40 monoclonal antibody (mAb)) combined with Toripalimab (Tuoyi®; an anti-PD-1 mAb) in subjects with advanced solid tumors. As of December 31, 2020, there were no dose-limiting toxicity (DLT) events or severe adverse events (AE) observed in 9 subjects/3 dose levels (ranging from 0.03 to 0.3 mg/kg). Of the 5 subjects that completed at least one tumor assessment, one subject with ocular melanoma who failed prior Opdivo and Opdivo/Yervoy combination therapy achieved partial remission (PR), and two patients maintained stable disease (SD). The second trial (poster #2577; NCT04357756) is a Phase I clinical study to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor efficacy of an anti-CTLA-4 antibody, YH001, combined with Toripalimab in subjects with advanced solid tumors. As of December 31, 2020, no DLT or severe AE were observed at 4 dose levels (ranging from 0.05 to 1 mg/kg). Seven of 10 subjects completed at least one tumor assessment, of which 4 subjects maintained SD. As of March 1, 2021, one subject with GEJ cancer that maintained SD in the first tumor assessment achieved PR in the second assessment, with a 60.9% reduction in the target lesion compared to baseline. About YH003 YH003 is a humanized IgG2 agonistic monoclonal antibody that targets CD40 signaling. Preclinical studies demonstrated that YH003 promotes antigen-presenting cell activation and infiltration of effector T cells into tumors. YH003 demonstrated potent anti-tumor effects in Biocytogen's humanized CD40 mice, both alone and in combination with anti-PD-1 monoclonal antibodies. YH003 has been approved to enter Phase II trials in Australia for pancreatic cancer and PD1-resistant melanoma. About YH001 YH001 is a humanized IgG1 monoclonal antibody that blocks the association of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) with CD80/CD86. YH001 can trigger antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) to remove CTLA-4 expressing cells, especially regulatory T cells, to enhance T-cell-mediated antitumor immune responses. Preclinical data indicates that YH001 outperforms Ipilimumab (a currently approved CTLA-4 drug) in CTLA-4 binding affinity and inducing ADCC activity. About Eucure Biopharma Eucure Biopharma is a biopharmaceutical company focused on the development of innovative immunotherapies to meet clinical needs of patients around the world. Relying on a strong clinical development team with extensive experience, the company has established a product pipeline for more than 10 targets. Eucure Biopharma is a wholly owned subsidiary of Biocytogen. For more information, please visit www.eucure.com.
2021.06.01
BOSTON and BEIJING, March 22, 2021 /PRNewswire/ -- Eucure Biopharma, a subsidiary of Biocytogen focused on developing proprietary immuno-oncology antibodies, announced that its anti-CTLA-4 antibody (YH001), in combination with Junshi Biosciences' anti-PD-1 monoclonal antibody, Toripalimab Injection (TUOYI®), has demonstrated encouraging anti-tumor activity in a dose-escalation Phase I clinical trial in Australia. The study was designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of YH001 therapy in combination with Toripalimab in patients with solid tumors. A 64-year-old male with a gastroesophageal junction tumor and liver/lung metastases who failed three prior lines of chemotherapy was enrolled in the 0.3 mg/kg dose cohort on September 17, 2020. The subject received one cycle (21 days) of YH001 monotherapy, followed by combination therapy with 240 mg Toripalimab for 7 cycles (21 weeks). Imaging assessments at 8 weeks post study treatment indicated stable disease with a 12.7% reduction in the summary of diameter of all target lesions relative to baseline. At 15 weeks post study treatment, imaging assessments indicated a partial response, with a 60.9% reduction in the summary of diameter of all target lesions relative to baseline. No dose-limiting toxicity events were observed, and only a Grade 1 adverse event (fatigue) was reported. "We are very pleased to see patients experiencing partial remission of tumor target lesions in this clinical study, which is progressing smoothly in Australia," said Dr. Yuelei Shen, Chairman of Biocytogen and CEO of Eucure Biopharma. Dr. Shen added that a YH001 trial in China will commence "as soon as possible, so as to bring effective and innovative products to Chinese patients." About YH001 YH001 is an anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) humanized monoclonal antibody that blocks the interaction between CTLA4 and CD80/CD86. YH001 can trigger antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) to remove CTLA-4 expressing cells, especially regulatory T cells, to enhance T-cell-mediated antitumor responses. Preclinical data indicates that YH001 outperforms Ipilimumab (a currently approved CTLA-4 drug) in CTLA-4 binding affinity and inducing ADCC activity. About Toripalimab (TUOYI®) Toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing in China. More than thirty company-sponsored clinical studies covering over fifteen indications have been conducted globally, including in China and the US. On December 17, 2018, Toripalimab obtained conditional approval from the National Medical Products Administration (NMPA) for second-line treatment of unresectable or metastatic melanoma. Toripalimab was included in the 2019 and 2020 Guidelines of Chinese Society of Clinical Oncology (CSCO) for the Diagnosis and Treatment of Melanoma. The supplemental NDA of Toripalimab for second-line treatment of metastatic urothelial carcinoma was accepted and received priority review designation from the NMPA in May and July 2020, respectively. In September 2020, Toripalimab was granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) for the treatment of recurrent or metastatic nasopharyngeal carcinoma. In December 2020, Toripalimab was included in the updated National Reimbursement Drug List. In February 2021, the supplemental NDA for Toripalimab in combination with chemotherapy for first-line treatment of patients with advanced, recurrent or metastatic nasopharyngeal carcinoma was accepted by the NMPA. In addition, the NMPA granted toripalimab conditional approval for treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) after failure of at least two lines of prior systemic therapy. Currently, Toripalimab has been granted 1 Breakthrough, 1 Fast Track, and 3 Orphan Drug Designations by the FDA for treatment of mucosal melanoma, nasopharyngeal carcinoma, and soft tissue sarcoma. About Eucure Biopharma Eucure Biopharma is a biotechnology company that focuses on the clinical development of antibody drugs with independent intellectual property rights. Eucure Biopharma has built a strong preclinical and clinical pipeline for over ten targets. Currently, two products have received clinical trial approvals in the US and China. In Australia, three products have entered Phase I clinical development. For more information, please visit http://www.eucure.com/en/. About Junshi Biosciences Founded in December 2012, Junshi Biosciences is a biopharmaceutical company dedicated to the discovery, development and commercialization of innovative therapeutics. The company has established a diversified R & D pipeline comprising 28 innovative drug candidates and 2 biosimilars, with five therapeutic focus areas covering cancer, autoimmune, metabolic, neurological, and infectious diseases. Junshi Biosciences was the first Chinese pharmaceutical company that obtained marketing approval for anti-PD-1 monoclonal antibody in China. Its first-in-human anti-BTLA antibody for solid tumors was the first in the world to be approved for clinical trials by the FDA and NMPA, and its anti-PCSK9 monoclonal antibody was the first in China to be approved for clinical trials by the NMPA. In early 2020, Junshi Biosciences joined forces with the Institute of Microbiology Chinese Academy of Science and Eli Lilly to co-develop JS016 (etesevimab), China's first neutralizing fully human monoclonal antibody against SARS-CoV-2. JS016 administered with bamlanivimab has received Emergency Use Authorization (EUA) by US FDA in Feb 2021 for the treatment of recently diagnosed, mild to moderate COVID-19 in patients who are at high risk of progressing to severe COVID-19 and/or hospitalization. The JS016 program is a part of our continuous innovation for control and prevention of the global pandemic. Junshi Biosciences has over 2,000 employees in the US (San Francisco and Maryland) and China (Shanghai, Suzhou, Beijing and Guangzhou). For more information, please visit: http://junshipharma.com.   Media Contact: Eucure Biopharma Yuanyuan Li yuanyuan.li@bbctg.com.cn   About Biocytogen Biocytogen is an international biotechnology company committed to becoming the global birthplace of new drugs. Utilizing its innovative gene editing technology, Biocytogen has developed numerous humanized animal models to accelerate drug discovery and development, including its flagship RenMab™ model. For more information, please visit www.biocytogen.com. PRNEWSWIRE ORIGINAL ARTICLE  
2021.03.22
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01
Jun , 2021
Eucure Biopharma to Present Findings From Anti-CD40 and Anti-CTLA-4 mAb Clinical Trials at the 2021 ASCO Meeting
BEIJING and BOSTON, June 1, 2021 /PRNewswire/ -- Eucure Biopharma will present findings from two Phase I clinical trials at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, held from June 4th to 8th. The first trial (poster #2580; NCT04481009) is designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor efficacy of YH003 (an anti-CD40 monoclonal antibody (mAb)) combined with Toripalimab (Tuoyi®; an anti-PD-1 mAb) in subjects with advanced solid tumors. As of December 31, 2020, there were no dose-limiting toxicity (DLT) events or severe adverse events (AE) observed in 9 subjects/3 dose levels (ranging from 0.03 to 0.3 mg/kg). Of the 5 subjects that completed at least one tumor assessment, one subject with ocular melanoma who failed prior Opdivo and Opdivo/Yervoy combination therapy achieved partial remission (PR), and two patients maintained stable disease (SD). The second trial (poster #2577; NCT04357756) is a Phase I clinical study to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor efficacy of an anti-CTLA-4 antibody, YH001, combined with Toripalimab in subjects with advanced solid tumors. As of December 31, 2020, no DLT or severe AE were observed at 4 dose levels (ranging from 0.05 to 1 mg/kg). Seven of 10 subjects completed at least one tumor assessment, of which 4 subjects maintained SD. As of March 1, 2021, one subject with GEJ cancer that maintained SD in the first tumor assessment achieved PR in the second assessment, with a 60.9% reduction in the target lesion compared to baseline. About YH003 YH003 is a humanized IgG2 agonistic monoclonal antibody that targets CD40 signaling. Preclinical studies demonstrated that YH003 promotes antigen-presenting cell activation and infiltration of effector T cells into tumors. YH003 demonstrated potent anti-tumor effects in Biocytogen's humanized CD40 mice, both alone and in combination with anti-PD-1 monoclonal antibodies. YH003 has been approved to enter Phase II trials in Australia for pancreatic cancer and PD1-resistant melanoma. About YH001 YH001 is a humanized IgG1 monoclonal antibody that blocks the association of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) with CD80/CD86. YH001 can trigger antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) to remove CTLA-4 expressing cells, especially regulatory T cells, to enhance T-cell-mediated antitumor immune responses. Preclinical data indicates that YH001 outperforms Ipilimumab (a currently approved CTLA-4 drug) in CTLA-4 binding affinity and inducing ADCC activity. About Eucure Biopharma Eucure Biopharma is a biopharmaceutical company focused on the development of innovative immunotherapies to meet clinical needs of patients around the world. Relying on a strong clinical development team with extensive experience, the company has established a product pipeline for more than 10 targets. Eucure Biopharma is a wholly owned subsidiary of Biocytogen. For more information, please visit www.eucure.com.
22
Mar , 2021
Eucure Biopharma Announces Breakthrough Phase I Results for Anti-CTLA-4 Therapy in Combination with Junshi Biosciences' Anti-PD-1
BOSTON and BEIJING, March 22, 2021 /PRNewswire/ -- Eucure Biopharma, a subsidiary of Biocytogen focused on developing proprietary immuno-oncology antibodies, announced that its anti-CTLA-4 antibody (YH001), in combination with Junshi Biosciences' anti-PD-1 monoclonal antibody, Toripalimab Injection (TUOYI®), has demonstrated encouraging anti-tumor activity in a dose-escalation Phase I clinical trial in Australia. The study was designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of YH001 therapy in combination with Toripalimab in patients with solid tumors. A 64-year-old male with a gastroesophageal junction tumor and liver/lung metastases who failed three prior lines of chemotherapy was enrolled in the 0.3 mg/kg dose cohort on September 17, 2020. The subject received one cycle (21 days) of YH001 monotherapy, followed by combination therapy with 240 mg Toripalimab for 7 cycles (21 weeks). Imaging assessments at 8 weeks post study treatment indicated stable disease with a 12.7% reduction in the summary of diameter of all target lesions relative to baseline. At 15 weeks post study treatment, imaging assessments indicated a partial response, with a 60.9% reduction in the summary of diameter of all target lesions relative to baseline. No dose-limiting toxicity events were observed, and only a Grade 1 adverse event (fatigue) was reported. "We are very pleased to see patients experiencing partial remission of tumor target lesions in this clinical study, which is progressing smoothly in Australia," said Dr. Yuelei Shen, Chairman of Biocytogen and CEO of Eucure Biopharma. Dr. Shen added that a YH001 trial in China will commence "as soon as possible, so as to bring effective and innovative products to Chinese patients." About YH001 YH001 is an anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) humanized monoclonal antibody that blocks the interaction between CTLA4 and CD80/CD86. YH001 can trigger antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) to remove CTLA-4 expressing cells, especially regulatory T cells, to enhance T-cell-mediated antitumor responses. Preclinical data indicates that YH001 outperforms Ipilimumab (a currently approved CTLA-4 drug) in CTLA-4 binding affinity and inducing ADCC activity. About Toripalimab (TUOYI®) Toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing in China. More than thirty company-sponsored clinical studies covering over fifteen indications have been conducted globally, including in China and the US. On December 17, 2018, Toripalimab obtained conditional approval from the National Medical Products Administration (NMPA) for second-line treatment of unresectable or metastatic melanoma. Toripalimab was included in the 2019 and 2020 Guidelines of Chinese Society of Clinical Oncology (CSCO) for the Diagnosis and Treatment of Melanoma. The supplemental NDA of Toripalimab for second-line treatment of metastatic urothelial carcinoma was accepted and received priority review designation from the NMPA in May and July 2020, respectively. In September 2020, Toripalimab was granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) for the treatment of recurrent or metastatic nasopharyngeal carcinoma. In December 2020, Toripalimab was included in the updated National Reimbursement Drug List. In February 2021, the supplemental NDA for Toripalimab in combination with chemotherapy for first-line treatment of patients with advanced, recurrent or metastatic nasopharyngeal carcinoma was accepted by the NMPA. In addition, the NMPA granted toripalimab conditional approval for treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) after failure of at least two lines of prior systemic therapy. Currently, Toripalimab has been granted 1 Breakthrough, 1 Fast Track, and 3 Orphan Drug Designations by the FDA for treatment of mucosal melanoma, nasopharyngeal carcinoma, and soft tissue sarcoma. About Eucure Biopharma Eucure Biopharma is a biotechnology company that focuses on the clinical development of antibody drugs with independent intellectual property rights. Eucure Biopharma has built a strong preclinical and clinical pipeline for over ten targets. Currently, two products have received clinical trial approvals in the US and China. In Australia, three products have entered Phase I clinical development. For more information, please visit http://www.eucure.com/en/. About Junshi Biosciences Founded in December 2012, Junshi Biosciences is a biopharmaceutical company dedicated to the discovery, development and commercialization of innovative therapeutics. The company has established a diversified R & D pipeline comprising 28 innovative drug candidates and 2 biosimilars, with five therapeutic focus areas covering cancer, autoimmune, metabolic, neurological, and infectious diseases. Junshi Biosciences was the first Chinese pharmaceutical company that obtained marketing approval for anti-PD-1 monoclonal antibody in China. Its first-in-human anti-BTLA antibody for solid tumors was the first in the world to be approved for clinical trials by the FDA and NMPA, and its anti-PCSK9 monoclonal antibody was the first in China to be approved for clinical trials by the NMPA. In early 2020, Junshi Biosciences joined forces with the Institute of Microbiology Chinese Academy of Science and Eli Lilly to co-develop JS016 (etesevimab), China's first neutralizing fully human monoclonal antibody against SARS-CoV-2. JS016 administered with bamlanivimab has received Emergency Use Authorization (EUA) by US FDA in Feb 2021 for the treatment of recently diagnosed, mild to moderate COVID-19 in patients who are at high risk of progressing to severe COVID-19 and/or hospitalization. The JS016 program is a part of our continuous innovation for control and prevention of the global pandemic. Junshi Biosciences has over 2,000 employees in the US (San Francisco and Maryland) and China (Shanghai, Suzhou, Beijing and Guangzhou). For more information, please visit: http://junshipharma.com.   Media Contact: Eucure Biopharma Yuanyuan Li yuanyuan.li@bbctg.com.cn   About Biocytogen Biocytogen is an international biotechnology company committed to becoming the global birthplace of new drugs. Utilizing its innovative gene editing technology, Biocytogen has developed numerous humanized animal models to accelerate drug discovery and development, including its flagship RenMab™ model. For more information, please visit www.biocytogen.com. PRNEWSWIRE ORIGINAL ARTICLE  
03
Feb , 2021
Eucure Biopharma Announces Encouraging Antitumor Activity of Its anti-CD40 Antibody in PD-1 Refractory Ocular Melanoma when Combined with Junshi Biosciences' Toripalimab
BOSTON and BEIJING, Feb. 3, 2021 /PRNewswire/ -- Eucure Biopharma, a biopharmaceutical company dedicated to developing immuno-oncology antibody drugs, announced that its investigational anti-CD40 antibody drug (YH003), when combined with Junshi Biosciences' anti-PD-1 antibody Toripalimab (TUOYI®), demonstrated encouraging anti-tumor activity in an ongoing Phase I/II clinical trial in Australia. The trial is a multicenter, open label study, with an initial multiple-dose-escalation phase designed to assess the safety, tolerability, pharmacokinetics and preliminary efficacy of YH003 in combination with Toripalimab in subjects with advanced solid tumors. The second phase is a cohort extension phase to assess the safety and preliminary efficacy of YH003/Toripalimab with or without chemotherapy in PD-1 refractory, advanced unresectable/metastatic melanoma and pancreatic ductal adenocarcinoma. A 68-year-old female subject with ocular melanoma and liver metastases who failed prior immunotherapy, including first-line Nivolumab (an anti-PD-1 antibody) and second-line Nivolumab/Ipilimumab (an anti-CTLA-4 antibody) combination therapy, was enrolled in the 0.1 mg/kg cohort. The subject received a single three-week cycle of YH003 monotherapy, followed by three cycles of YH003/Toripalimab combination therapy over a total of 12 weeks. Imaging assessments indicated a partial response at week 10 post-treatment, with a 38.5% reduction in the total diameter of all target lesions. No dose-limiting toxicity (DLT) was observed in the study, and the drug was well tolerated in the first two cohorts and in the ongoing third cohort. In response, Dr. Yuelei Shen, Chairman of Biocytogen and CEO of Eucure Biopharma, commented, "We are pleased to see a patient experiencing partial remission in this first YH003 trial, which is going fast and smoothly in Australia. This result further assured us that our anti-CD40 compound YH003 has great potential to be developed into an oncology therapy in this post PD-1 era. We will take advantage of expedited regulatory programs to hopefully put this product on the market as soon as possible. Then, we will explore the full potential of this compound in a broad spectrum of indications." About YH003 YH003 is a humanized agonistic antibody that promotes CD40 activation on antigen-presenting cells, and thus stimulates the effector activity of anti-tumor T cells. Whether used alone or in combination with anti-PD-1 antibodies, YH003 demonstrated potent anti-tumor effects in Biocytogen's CD40 humanized mice, and significantly increased the proportion of anti-tumor T cells. YH003 demonstrated an excellent safety profile at very high doses, both in mice and primates. About Toripalimab (TUOYI®) Toripalimab is the first anti-PD-1 monoclonal antibody to obtain a marketing approval in China. So far, more than thirty company-sponsored clinical studies covering more than fifteen indications have been conducted globally, including in China and the United States. On December 17, 2018, Toripalimab obtained a conditional approval from the NMPA for the second-line treatment of patients with unresectable or metastatic melanoma. Supplemental NDAs of Toripalimab for the third-line treatment of recurrent/metastatic nasopharyngeal carcinoma and second-line treatment of metastatic urothelial carcinoma were accepted by the NMPA in April and May 2020, respectively. Both supplemental NDAs received priority review designations from the NMPA in July 2020. In December 2020, Toripalimab was included in the National Reimbursement Drug List (NRDL) for the treatment of melanoma by the China National Healthcare Security Administration (NHSA). In the United States, the FDA has granted Toripalimab breakthrough therapy designation for the treatment of recurrent/metastatic nasopharyngeal carcinoma, Fast Track designation for mucosal melanoma, and orphan drug designation for the treatment of nasopharyngeal carcinoma, mucosal melanoma and soft tissue sarcoma. About Eucure Biopharma Eucure Biopharma is a wholly owned subsidiary of Biocytogen focused on clinical development. Eucure Biopharma has built up a strong pipeline with over ten targets at different preclinical and clinical stages, among which three are in Phase I clinical development. For more information, please visit http://www.eucure.com/en/. About Junshi Biosciences Founded in December 2012, Junshi Biosciences (HK: 1877; SH: 688180) is an innovation-driven biopharmaceutical company dedicated to the discovery, development and commercialization of innovative therapeutics. The company has established a diversified R & D pipeline comprising 27 innovative drug candidates and 2 biosimilars, with five therapeutic focus areas covering cancer, autoimmune, metabolic, neurological, and infectious diseases. Junshi Biosciences was the first Chinese pharmaceutical company that obtained marketing approval for anti-PD-1 monoclonal antibody in China. Its first-in-human anti-BTLA antibody for solid tumors was the first in the world to be approved for clinical trials by the FDA and NMPA, and its anti-PCSK9 monoclonal antibody was the first in China to be approved for clinical trials by the NMPA. In early 2020, Junshi Biosciences joined forces with the Institute of Microbiology Chinese Academy of Science and Eli Lilly to co-develop JS016, China's first neutralizing fully human monoclonal antibody against SARS-CoV-2, which has entered clinical trials and is now a part of our continuous innovation for disease control and prevention of the global pandemic. Junshi Biosciences has over 2,000 employees in the United States (San Francisco and Maryland) and China (Shanghai, Suzhou, Beijing and Guangzhou). For more information, please visit: http://junshipharma.com. About Biocytogen Biocytogen is an international biotechnology company committed to becoming the global birthplace of new drugs. Utilizing its innovative gene editing technology, Biocytogen has developed numerous humanized animal models to accelerate drug discovery and development, including its flagship RenMab™ model. For more information, please visit www.biocytogen.com. PRNewswire Original Article