Shanghai, China July 14, 2021- 3D Medicines Inc., a China-based late clinical stage biopharmaceutical company, announced that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has approved the Investigational New Drug (IND) application submitted by 3D Medicines to participate in Aravive’s international AVB-500 (3D-229) Phase 3 platinum resistant ovarian cancer (PROC) clinical trial. (ClinicalTrials.gov Identifier: NCT04729608) This is expected to be a registrational Phase III multi-regional clinical trial (MRCT), in China, of AVB-500 (3D-229) IV infusion, a GAS6/AXL inhibitor, in patients with PROC. This is the first international Phase III clinical trial approved for GAS6/AXL inhibitor in China.
3D-229 is one of the flagship products of Xuzhou 3D Medicines Pharmaceutical Co., Ltd. under 3D Medicines Inc. 3D Medicines obtained exclusive authorization from Aravive Inc. to develop and commercialize 3D-229 in the oncology field in the Greater China region. Due to its efficient implementation, it took only 6 months between the transfer of the technical documents to this IND application. The rapid review of international trials by the CDE clearly reflects the importance of innovative clinical trials guided by clinical value and unmet medical needs.
About the Phase 3 PROC Trial
The global, randomized, double-blind, placebo-controlled adaptive trial (GOG-3059/ENGOT OV-66) is designed to evaluate efficacy and safety of AVB-500 at a dose of 15 mg/kg in combination with paclitaxel. The trial is expected to enroll approximately 300-400 patients with high-grade serous ovarian cancer who have received one to four prior lines of therapy at approximately 165 sites in North America, Europe, and Asia. The primary endpoint for the trial is progression-free survival and the secondary endpoint is overall survival. Exploratory endpoints include objective response rate, duration of response, quality of life, clinical benefit rate, pharmacokinetic and pharmacodynamic profile, and sAXL/GAS6 ratio. A prospectively defined interim analysis will determine whether randomization will continue with all patients, regardless of prior bevacizumab treatment, or only with patients medically ineligible to receive bevacizumab or who choose not to receive bevacizumab. This trial is being conducted in partnership with The GOG Foundation, Inc. (GOG-F), through the GOG Partners program in the USA, and in partnership with the European Network for Gynaecological Oncological Trial (ENGOT) groups in Europe. The Phase 3 trial is listed on clinicaltrials.gov NCT04729608.
Dr. Zhaolong Gong, Chairman and CEO of 3D Medicines, pointed out, "We are very pleased to see the IND-approved Phase III clinical trial protocol of 3D-229. 3D Medicines has been committed to providing clinical value as a development-oriented approach for many years, listening to the voice of patients, and developing innovative therapies for difficult-to-treat cancers." There is a broad market strategy for 3D-229 to provide more effective treatment options for a wide range of cancers. We will continue to develop more innovative drugs so that cancer patients in China can receive global first-in-class drugs as soon as possible and at the same time that they are made available in developed countries to obtain the latest treatment options."
Gail McIntyre, Ph.D., DBAT, Chief Executive Officer, said, “We have a strong partnership with 3D Medicines, and we are enthusiastic about the progress they have made with development of AVB-500 (3D-299) in China. Our companies are dedicated and working together to improve patient survival and bring hope to women with advanced ovarian cancer. This IND approval by the CDE in China is the second development milestone achieved by Aravive since we entered into our agreement with 3D Medicines in November 2020.”
About Ovarian Cancer
Ovarian cancer (OC) is one of the most common gynecological malignancies and a gynecological tumor with a high mortality rate. According to Frost & Sullivan report, the incidence of OC in China reached approximately 55,300 in 2020 and is expected to reach approximately 62,700 in 2030. Ovarian cancer has a poor prognosis, 70-80% of patients diagnosed at intermediate and advanced stages, with a 5-year survival rate of only 40% . It is highly susceptible to relapse, and approximately 70-80% of patients who are sensitive to platinum therapy eventually become resistant to platinum-based chemotherapy after multiple relapses . Patients with platinum-resistant recurrent ovarian cancer have a substantial unmet clinical need due to limited available treatment options and poor response. According to Frost & Sullivan's latest statistics, China's OC drug market size reached 142.3 million US dollars in 2020 and is expected to reach $1 billion in 2030. Therefore, PROC therapy has excellent market potential.
AVB-500 is a therapeutic recombinant fusion protein that has been shown to neutralize GAS6 activity by binding to GAS6 with very high affinity in preclinical models. In doing so, AVB-500 selectively inhibits the GAS6-AXL signaling pathway, which is upregulated in multiple cancer types including ovarian cancer. In preclinical studies, GAS6-AXL inhibition has shown anti-tumor activity in combination with a variety of anticancer therapies, including radiation therapy, immuno-oncology agents, and chemotherapeutic drugs that affect DNA replication and repair. Increased expression of AXL and GAS6 in tumors has been correlated with poor prognosis and decreased survival and has been implicated in therapeutic resistance to conventional chemotherapeutics and targeted therapies. AVB-500 is currently being evaluated in clinical trials and has been granted Fast Track Designation by the U.S. Food and Drug Administration in platinum resistant recurrent ovarian cancer. Analysis of all safety data to date showed that AVB-500 has been generally well-tolerated with no dose-limiting toxicities or unexpected safety signals.
About 3D Medicines Inc.
3D Medicines Inc. is a commercialization stage bio-pharmaceutical company, focused on the field of cancer treatment. With a mission to help people with cancer live longer and better, we commit to developing a new generation of therapies for cancer patients around the world, following a future when cancer is managed as a chronic disease. Our differentiated or world-leading portfolio of 12 drug candidates with clinical benefit includes eight in clinical or commercialization stage. Our global first subcutaneously injectable PD-L1 antibody Envafolimab co-developed by partner has submitted BLA in China. The global first-in-class peptide cancer vaccine 3D189 and GAS6 decoy protein 3D229 are in an ongoing global Phase III trial. Our in-house developed multi-target kinase inhibitor 3D011 has also entered clinical development. The other 4 products targeting FGFR123 \ EP4 \ COX2 \ CD47 are also entering the clinical stage at home and abroad. In addition, the world-leading bispecific anti-CD3 x PD-L1 is also in preclinical stage. We currently have a strong international team of more than 200 R&D, manufacture, and commercialization members of new drugs to explore better therapies for cancer patients worldwide.
For more information, please visit: http://www.3d-medicines.com
Aravive, Inc. is a clinical-stage oncology company developing innovative therapeutics to treat life-threatening diseases. Aravive’s lead therapeutic, AVB-500, is a first-in-class ultra-high affinity decoy protein that targets the GAS6-AXL signaling pathway associated with tumor cell growth, tumor metastasis, resistance to treatment and decreased survival. AVB-500 has the potential to be combined with multiple anti-cancer therapies across several tumor types, due to its novel mechanism of action and favorable safety profile. AVB-500 has been granted Fast Track Designation by the U.S. Food and Drug Administration in platinum resistant recurrent ovarian cancer. The Company is currently evaluating AVB-500 in a registrational Phase 3 trial in platinum resistant ovarian cancer and a Phase 1b/2 trial in clear cell renal cell carcinoma. Aravive plans to initiate a Phase 1b/2 trial evaluating AVB-500 in first-line treatment of pancreatic cancer in the second half of 2021. The Company is based in Houston, Texas and received a Product Development Award from the Cancer Prevention & Research Institute of Texas (CPRIT) in 2016. For more information, please visit www.aravive.com.
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