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First clinical trial application for gene-edited T-cell drug for solid tumors formally accepted by State Drug Administration (SDA)
2022-10-23
Article Details
According to the open literature, its “PD-1 gene-edited T-cell injection” IIT phase I clinical trial has proved its scientific validity, feasibility and safety, and the relevant results were published in Nature Medicine in April 2020 [1]. Although the first-generation process was used at that time, the results of the phase I clinical study showed that, for 12 patients (lines 4 to 7) who had failed 3 lines of treatment for advanced non-small cell lung cancer, 3 patients achieved an ultra-long-term OS of more than 2 years after the administration of the drug, and the median OS for all patients was 47.1 weeks.
The median PFS was 8.6 weeks and the median OS was 51.6 weeks for patients with a drug exposure time of 2 months or more (two or more courses of treatment), and the median PFS was 17.9 weeks and the median OS was 96.7 weeks for patients with a drug exposure time of 3 months or more (three or more courses of treatment). With the same drug exposure time, the Company's product has a significant advantage over publicly reported K and O drugs in terms of OS, the most important metric for advanced solid tumors (OS 96.7 Weeks for 4th line patients vs. 41.6/42.8 Weeks for 2nd line patients [2-3]).
Dr. Yu Koon, CTO of Chengdu MedGenCell, said, “In the biomedical research industry, ‘those who use their strengths imitate and those who use their minds create’. Although the scientific validity and safety of the gene-edited cell products have been proved in the IIT Phase I clinical trial, we have not been in a hurry to start the IND filing immediately. Instead, we have focused on the iterative optimization of the process and fine-tuned the process to form a more efficient, low-toxicity and stable editing and cell engineering expansion system. The editing efficiency has increased from 20-30% in the first generation of the process to a stable 90%+ at present, and the success rate of edited cell expansion is as high as 90% or more, with a more stable and controllable pharmacological process. Meanwhile, it was observed that the epigenetic panorama of T cells was altered, the diversity of TCR library was significantly increased, and the proportion of stem T cells was up to 30% or more, which would produce more durable and efficient anti-tumor effects after their return to the body [4], significantly improving their drug-ability. The product's long-term iterative process development history fully reflects the company's development philosophy: science for the benefit of mankind, craftsmanship forged the brand.
Blocking PD-1/PD-L1 has become the focus of cancer immunotherapy, and with more widespread patient application, more and more cases of PD-1 and PD-L1 monoclonal antibody resistance have been found. International immunotherapy authority, one of the important contributors to the discovery of PD-1/PD-L1 immunotherapy, Prof. Liping Chen, published an article in Nature Reviews Drug Discovery in June 2022, proposing that one of the future solutions to deal with antibody immunotherapy resistance is PD-1 monoclonal antibody combined with cellular immunotherapy [5]. Chengdu MedGenCell has strategically laid out this therapeutic direction in advance, taking the lead in the industry and achieving initial results, let's look forward to the early launch of this product for the benefit of patients.
-------About Chengdu MedGenCell-------
Chengdu MedGenCell is a high-tech enterprise focusing on research and product development in the fields of cellular medicine, gene editing and epigenetics. The company has developed the world's first clinical GMP-grade gene-edited T-cell drug, and completed the world's first gene-edited cell anti-tumor therapy phase I clinical trial with West China Hospital of Sichuan University, and the relevant results were published in April 2020 in the journal “Nature Medicine”. The company was selected as one of the top innovation and entrepreneurship teams in Sichuan Province and Chengdu City in 2016, and was selected as one of the “Top 50 Most Valuable Enterprises in China” by Zero2IPO Group, Softbank, and other investment organizations, as well as “Top 50 Most Innovative Enterprises in China's Biomedicine”. We have also been selected as one of the “Top 50 Most Innovative Biomedical Companies in China”.
References：
[1] You Lu,Jianxin Xue,Tao Deng,et al. Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer. Nature Medicine 2020 May;26(5):732-740.
[2] Roy S Herbst,Paul Baas,Dong-Wan Kim,et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010) a randomised controlled trial. Lancet(London,England).2016 Apr 9;387(10027):1540-1550.
[3] Scherpereel A, Mazieres J, Greillier L,et al. Nivolumab, anti-programmed death-1 (PD-1) monoclonal antibody immunotherapy:Role in advanced cancers. HUMAN VACCINES &
IMMUNOTHERAPEUTICS 2016, VOL. 12, NO. 9: 2219–2231.
[4] Sri Krishna, Frank J Lowery,et al. Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer. Science 2020 Dec 11;370(6522):1328-1334.
[5] Tae Kon Kim, Esten N Vandsemb,et al. Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities. Nature Review Drug Discovery. 2022 Jul;21(7):529-540
