The PI of this project, Dr. Alice Yu, has organized a multidisciplinary team including research development group, management group and scientific advisory board to facilitate the development of FnCTP-based immunotherapeutics. The research development group includes Drs. Alice Yu (CGU), John Yu (CGMH), Chia-Cheng Wu (DCB) and Jung-Tung Hung (CGMH) for the preclinical development of FnCTP-BsAb and FnCTP-MNC-Herceptin. Dr. Jui-lian Huang (AP Biosciences) will lead the business development in collaboration with Drs. Alice Yu and John Yu. The scientific advisory board consists of Drs. Hsieng S. Lu (retired from Amgen), Chyong-Huey Lai (CGMH) and Sue-Jane Chen (expert in IP and Tech Transfer).
Research development group:
- Academician Alice Yu (PI): Dr. AL Yu is a world leader in cancer immunotherapy targeting glycolipids and a renowned physician-scientist in translational cancer research. She led the development of a chimeric anti-GD2 Ab dinutuximab from IND to the phase I/II/III. Dinutuximab was approved by FDA and EMU for high-risk neuroblastoma at 2015. She is one of the inventors of CTP platform patent.
- Dr. John Yu (Co-PI): Dr. J Yu is a distinguished stem cell researcher and the Director of ISCTCR, which consists over 60 outstanding researchers with unique expertise. He is leading the development of several mAbs against cancer stem cell antigens, AAV-derived gene therapy and cell therapy. He is also one of the inventors of CTP platform patent.
- Dr. Chia-Cheng Wu: Dr. Wu is the Director of the Institute of Biologics at DCB. He has led the development of several biologics and technology platform.
Advisor for business development
- Dr. Jui-lian Huang: Dr. Huang is the Chairperson of AP Biosciences (Taiwan) now. She was also the CEO of DCB (Taiwan) and VP/COO of Canji Inc. (San Diego).
Advisor for scientific development
- Dr. Hsieng S. Lu: Dr. Lu is the former Director of research at Amgen Inc. for 3 decades and led the development of large molecule drugs and CMC, leading to successful launching of several new biologics onto the market.
- Dr. Chyong-Huey Lai: Dr. Lai is a physician-scientist and now is Deputy Superintendent of Chang Gung Memorial Hospital at Linkou and Director of Clinical Trial Center. She has extensive experience in clinical trials of cancer treatment.
Advisor for intellectual property and technology transfer
- Dr. Shu-Jan Chen: Dr. Chen is an expert in IP and technology transfer and had joined several biotech companies in US. Dr. Chen also assisted several successful technology transfers in Academia Sinica.
Goals and Plan
Advanced ovarian cancer is eligible for the preferential measures of FDA for orphan disease. Thus, after submitting the IND application, we will focus on advanced ovarian cancer as the first indication for clinical development of FnCTP-BsAb and FnCTP-MNC-Herceptin to seek “Fast Track” or “Breakthrough Therapy” designation by FDA. Once one of the prototype products is proven successful, a series of new products will be developed as the expansion of concentric circles by conjugating a variety of anti-cancer agents to the FnCTP platform.
CTPs developed by our team can not only recognize more than 11 types of cancer (> 40 cancer cell lines) but also cancer stem cells, without binding to normal cells. Thus, FnCTP-conjugated drugs can treat a broader-spectrum of cancers with greater safety profile than the usual anti-cancer antibodies, which only target to single cancer-associated antigen. Serving as the “warhead”, the FnCTPs can be conjugated to various “payloads”, including BsAb, anti-cancer small molecules, radio-isotopes, liposomal drugs, antisense oligo/siRNA, and CAR-T, etc., to develop a new generation of “one for all” cancer therapeutics.
The asymmetric bispecific IgG antibody platform developed by DCB can enhance the half-life and the production yields. After conjugation with FnCTPs, the anti-CD3 BsAb only activates T-cells upon targeting to the cancer cells. The MNC loaded with Herceptin has demonstrated a longer blood half-life than Herceptin. Conjugation of MNC-Herceptin with FnCTP will further enhance the intra-tumoral Herceptin concentration, thereby achieving a greater anti-cancer efficacy at reduced Herceptin dosage, with less adverse effects.
The major focus of global biopharmaceutical industries is antibody drug. It is estimated that for 2016, six of the top 10 best sellers of global pharmaceuticals are antibody drugs. However, most antibody drugs can only target a particular cancer-associated antigen, which limits its application in cancer treatment. The FnCTP-BsAb developed by our team is a first in class product that can not only treat a broader-spectrum of cancers, but also eliminate cancer stem cells. Under patent protection, the characteristics of FnCTP-BsAb is superior to the current antibody drugs on the market, and will likely replace the traditional monoclonal antibodies in the markets of ovarian, gastric and lung cancer.
So far, ovarian cancer is not an approved indication for Herceptin. However, CTP-MNC-Herceptin will enhance delivery of Herceptin to tumors leading to greater inhibition of ovarian cancer with less adverse effect, suggesting its potential for market exclusivity. Its indication can be expanded to HER2+ gastric and breast cancer, which may exceed market share of Herceptin.