Eucure Biopharma, a wholly owned subsidiary of Biocytogen Group and a biopharmaceutical company focused on developing proprietary antibodies, announced today that its anti-CD40 monoclonal antibody YH003 has received regulatory approval to enter Phase II clinical trials in Australia. This clinical study was designed to evaluate the efficacy and safety of anti-CD40 monoclonal antibody in combination with an anti-PD-1 monoclonal antibody (toripalimab) in patients with pancreatic cancer and PD1-resistant melanoma.
As a humanized agonistic antibody targeting CD40, YH003 promotes the activation of antigen-presenting cells and positively regulates the effector activity of anti-tumor T cells by binding specifically to CD40 receptors. To date, studies have shown that CD40 activation is a key regulatory point for tumor immunotherapy, effectively transforming "cold tumors" with poor immune cell infiltration into "hot tumors" that respond well to tumor immunotherapy. During the preclinical antibody screening stage, Eucure Biopharma used the humanized CD40 mouse model developed by Biocytogen to rapidly screen for monoclonal antibodies that completely inhibit tumor growth in mice. YH003 demonstrated potent anti-tumor effects in mice against a variety of tumor models, whether alone or in combination with anti-PD-1 monoclonal antibodies. Pharmacodynamic studies in mice showed that YH003 significantly increased the proportion of anti-tumor T cells among tumor-infiltrating cells. Significantly, YH003 demonstrated an excellent safety profile both in mice and monkeys, even at very high doses.
In May 2020, Eucure Biopharma has initiated a Phase I dose-escalation study of YH003 (the world’s first human clinical study) in Australia to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor efficacy of YH003 in combination with toripalimab in patients with advanced solid tumors. The trial consisted of an introductory phase of YH003 monotherapy for one cycle to explore the safety and tolerability of YH003 monotherapy, followed by the combination therapy phase starting from the second cycle to further explore the safety and tolerability of YH003 in combination with toripalimab at various dose levels over a dose-escalation process. As of April 26, 2021, 16 subjects with advanced solid tumors have been enrolled. All subjects have received at least one dose of the study drug, and four subjects had received at least five cycles of treatment. Whether alone or in combination with toripalimab, YH003 has demonstrated good tolerability, with most adverse events below Grade 3. There was one Grade 3 drug-related adverse event, one adverse event leading to discontinuation, and no deaths due to AE. Efficacy data showed that, out of a total of nine subjects evaluable on imaging, one subject with ocular melanoma in the 0.1 mg/kg dose group who had failed prior anti-PD-1/CTLA-4 therapy achieved partial remission (PR). One subject in each of the 0.03, 0.1, and 0.3 mg/kg dose groups achieved stable disease (SD), two of whom were subjects who had failed previous immunotherapy. The results of this study showed that YH003 had good safety and tolerability, whether as monotherapy or in combination with toripalimab. In addition, YH003 produced preliminary anti-tumor activity in patients with advanced solid tumors when administered in combination with toripalimab, with particular clinical benefits for subjects who had failed previous immunotherapy.
Based on a comprehensive assessment of Phase I clinical data, the Australian regulatory authority has approved the Phase II clinical trial of YH003 in combination with toripalimab. As a key component of the clinical development plan, the Phase II clinical trial of YH003 in Australia will first evaluate the potential of YH003 as a new treatment option for pancreatic cancer and PD1-resistant melanoma, thus providing patients with additional treatment options.
“As an innovative biotechnology company rooted in China with a global perspective, Eucure Biopharma builds on its solid foundation in scientific innovation and puts patient welfare first. Our mission is to bring the latest therapeutic ideas and new drugs to patients in China and around the world. We are excited to launch the first Phase II clinical trial in Australia, which is a significant milestone for Eucure Biopharma,” remarked Dr. Yuelei Shen, CEO of Eucure Biopharma. "This marks the official kick-off of Eucure Biopharma’s global Phase II clinical trial and its rise as a fast-growing innovative drug company.”
About Phase II Clinical Trial of YH003 in Australia
This study is a trial evaluating the initial anti-tumor efficacy and safety of YH003 in combination with toripalimab for the treatment of advanced unresectable/metastatic melanoma and pancreatic ductal adenocarcinoma. The protocol design will include three parallel cohorts: Patients with unresectable/metastatic melanoma who have failed PD-1/L1 +/- CTLA-4 therapy, those with locally advanced unresectable or metastatic pancreatic cancer who showed disease progression after first-line chemotherapy, and those with locally advanced unresectable or metastatic pancreatic cancer who are systemic therapy-naïve and will be treated in combination with chemotherapy. Twenty subjects will be enrolled in each cohort, and the subjects will receive the recommended Phase II dose of YH003 in combination with toripalimab +/- chemotherapy to assess the efficacy and safety/tolerability of YH003 combination therapy.