Counting China's CAR-T R&D companies: Many have investment value

On July 19th, with the growing demand for patients, the regulatory system continued to advance, cooperation at home and abroad became increasingly close, and a large amount of funds were continuously invested in research and development. The domestic CAR-T cell therapy industry has developed rapidly, and there are nearly 100 different scales. The company is investing in the development of CAR-T cell therapy.

Although the development of domestic CAR-T cell therapy continues to heat up, from the perspective of enterprise R&D progress, the number of companies and projects that are really close to the product is still small:

1. Nearly 100 companies invested in the research and development of CAR-T cell therapy, but as of the author's writing date, 23 R&D projects of only 16 companies in China entered the IND stage of CDE;

2, CDE has accepted 23 CAR-T projects of 16 companies of IND. As of the author's writing date, only 2 projects of 2 companies have been approved for IND application.

As a newcomer to current tumor immunotherapy, CAR-T cell therapy is one of the hottest technologies in the field of precise tumor therapy. With the future of immune cell therapy will become the Red Sea market, those in research and development, research targets and indications, CAR-T industry Domestic companies that stand out in terms of degree of differentiation are expected to occupy a favorable market in time.

At present, a number of CAR-T enterprises with their own characteristics and unique investment value have emerged in China. The author has analyzed three enterprises, which are the fastest-growing Nanjing legendary creatures, specializing in Koji biology for solid tumor treatment. Focus on industrialization of Berson Gianke.

Nanjing Legend Biotechnology Co., Ltd. is a wholly-owned subsidiary of Jinruisi Biotechnology Co., Ltd., established in 2014. The company's 'LCAR-B38M CAR-T cell autologous reinfusion preparation (abbreviation: LCAR-B38M cell preparation)' is The first domestically approved CAR-T product accepted by CDE according to the 'New Class 1 for therapeutic biological products', and obtained the priority for evaluation.

On March 12, 2018, the product obtained the clinical trial approval of CDE, becoming the first CAR-T cell therapy approved in the drug application clinical trial in China. The listing of this product also marks that the cell therapy industry in China has already bid farewell to the exploration period. Formally entered an orderly era in accordance with the path of drug listing.

LCAR-B38M cell preparation is a CAR-T cell therapy developed by Nanjing Legend to target B cell mature antigen (BCMA). BCMA is present on the surface of mature B cells and belongs to the TNF receptor family. It is an extremely important B cell. Biomarkers. BCMA RNA is almost always found in multiple myeloma cells, and this protein has also been found on the surface of malignant plasma cells in patients with multiple myeloma, and is therefore an important potential therapeutic target.

Multiple myeloma is a blood tumor with abnormal proliferation of bone marrow plasma cells. More than 124,000 people worldwide are diagnosed with multiple myeloma each year, and 87,000 people die from multiple myeloma. Over the past decade, in myeloma Significant progress has been made in the treatment, but patients who relapse after the first or second treatment and/or who are resistant to treatment have had little success in treatment and there is a huge unmet medical need.

According to the clinical data of LCAR-B38M cell preparation published by Nanjing Legend, 35 patients with relapsed or drug-resistant multiple myeloma have an objective response rate of 100% after receiving treatment.

On December 22, 2017, Johnson & Johnson's pharmaceutical company Janssen Biotech, Inc. announced that it has signed a global cooperation agreement with Nanjing Legend Bio to jointly develop, produce and sell LCAR-B38M cell preparations. Yang Sen will pay Nanjing Legendary Creatures $3.5 billion in advance funding, and will pay for related payments in the later stages of R&D, production, management and sales milestones.

Unlike many CAR-T R&D companies that have developed CD19 targeting, Nanjing Legend has selected CAR-T cell therapy targeting BCMA, which will effectively avoid fierce market competition and help to capture market share in the future.

Koji Bio medicine (Shanghai) Co., Ltd. was established in 2014 to create new tumor-targeting immune cell therapy. Keji Bio is the first clinical trial of solid tumor CAR-T cell therapy in China. enterprise , launched the world's first CAR-T clinical trial for GPC3 target treatment of hepatocellular carcinoma, targeting CAR-T for EGFR/EGFRvIII dual-target therapy for glioblastoma, and treating Claudin 18.2 target for gastric cancer, pancreatic cancer Clinical trial of CAR-T.

In addition, a clinical study of humanized CD19 CAR-T in the treatment of leukemia and lymphoma, and a full-body BMCA CAR-T treatment of multiple myeloma were also conducted.

As of the date of the author's writing, Koji Bio has three products entering the IND acceptance phase of CDE.

Keji Bio was in Renji, affiliated to Shanghai Jiaotong University School of Medicine in 2015. hospital Launched the world's first clinical trial of CAR-T cells for hepatocellular carcinoma, using GPC3 as a target. According to the results of clinical trials published by Koji Biology, the product demonstrated initial efficacy and good safety. In the completed phase I clinical trial, 13 patients with refractory/recurrent hepatocellular carcinoma who were treated were well tolerated, with no dose-limiting toxicity or grade 3 or higher. Adverse reactions Among the global Ib/II clinical trials, among the 5 observers who had received the same treatment, one patient had partial remission, two patients had stable disease, and two patients had disease progression. In addition to the death of patients with disease progression, the remaining 4 patients have survived for more than 14 months, 20 months, 14 months and 10 months respectively.

On December 28, 2017, autologous T cells targeting the phosphatidylinositol-3 polysaccharide antigen receptor-modified antigen obtained the IND of CDE; on January 29, 2018, the product was included in the priority review, including reasons For the use of advanced formulation technology, innovative treatments, with obvious therapeutic advantages drug Registration application ' .

This is the first attempt by Koji Bio to target solid tumors. It also has a good product reserve for other solid tumors such as lung cancer, stomach cancer, and pancreatic cancer.

Based on its own research team and the research team of Shanghai Cancer Research Institute, Keji Bio has high-quality clinical resources such as Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine, and explores new tumor markers, antibody screening and optimization, lentivirus. The carrier production work optimization, cell culture and amplification have strong technical strength, and stand out among many CAR-T R&D competitors.

Boss Gianke Cell Technology Co., Ltd. is a joint venture between Boshengji and Anke Biotech in 2015, focusing on the research and development, industrialization and clinical application of CAR-T cells. Boshengji and Anke Bio hold respectively Boss Gianco has 51% and 49% of the shares. At the same time, Anke Bio holds a 20% stake in Boshengji.

The 'targeting CD19 autochimeric antigen receptor T cell infusion agent' developed by Berson Gianco was accepted by CDD IND on January 8, 2018. Currently, the pharmacy, pharmacology and toxicology, clinical status review of this product Has been completed.

Treatment of adult refractory or relapsed B-cell lymphoma (B-ALL) (19 in group) and non-Hodgkin's lymphoma (NHL) according to CD19-CAR-T published by Berson Gianco (2 in enrollment) Clinical trial data shows that the efficacy and safety of this CAR-T product has been well validated. The evaluated B-ALL patients have an overall effective rate of 100% and a complete response rate of 90%; 2 NHL patients The complete remission rate reached 100%. The main side effects were 2-3 cytokine release syndrome, only 2 cases of neurotoxicity, no case of death.

In addition to excellent clinical data, Berson Gianco has taken CAR-T cell therapy quality assurance system, industrialization and process optimization as one of the key research and development directions. It is reported that the company has established more than 2000 square meters in line with GMP requirements. CAR-T cell production workshop, perfect quality control system and treatment control facilities and equipment to meet the clinical trial requirements of CAR-T cell products.

In addition, in January 2018, Berson Gianco announced the signing of the Memorandum of Cooperation with Germany's Murray Biotech Co., Ltd., in-depth cooperation in the field of CAR-T cell therapy, including: In the construction of Hefei based on CliniMACS Prodigy and MACSQuant The platform's fully automated CAR-T cell preparation plant; 默天旎 provides strong support for B-Gian's CAR-T cell therapy, including stable supply relationships, joint development of customized reagents, and joint development of immunotherapy research and development projects.

The whole process quality control in the preparation of CAR-T cell products is a must. The Prodigy technology platform used by Berson Gianco from the starting sample to the end product of the cell, covering cell washing & gradient centrifugation, MACS cell sorting, Genetic modification, cell culture and other aspects, using automated and closed disposable tubes, make complex cell operations intelligent and quality controllable.

Fully enclosed, automated CAR-T cell preparation is the preferred choice for the wide application and final commercialization of this treatment model. The advantage of Berson Gianco is to go beyond the standardization and intelligentization of complexity, personalization and labor-intensiveness. By optimizing the process and industrialization, we can achieve quality control and reduce costs, so that it will occupy a favorable position in the fierce market competition in the future.