https://youtu.be/oW2CeH-MLfo

2020’s last Startup Ting was with Curocell, a company developing innovative anti-cancer immune cell therapy, CAR-T. Curocell is a company co-established by Professor Chanhyuk Kim of the Department of Chemical & Biomolecular Engineering at KAIST. The Startup Ting was originally planned as a company visit, but due to COVID-19, it was held online to introduce the company and its technologies, and demonstrate online lab tours.

CEO Gunsoo Kim explained about the history of anti-cancer drugs, and the anti-cancer immune cell therapy under research at Curocell.

Until 2011 there were only anti-cancer drugs, but anti-cancer immune antibodies appeared and the methods of chemotherapy have changed. Previous anticancer drugs worked on a mechanism that directly targets cancer cells, but anticancer immune cells strengthen the immune cells in the body and remove cancer cells through immunity. Anticancer immunotherapy can overcome the limitations of traditional anticancer drugs, and is a very important treatment that will become the lead in the anticancer drug market,

In August 2017, Curocell received the first approval of the FDA for CAR-T anticancer immune cell therapy. The CAR-T therapy separates the immune cells of the patient, manipulates genes, and goes through mass cultivation, and is injected back to the patient. It is the most innovative anticancer drug developed so fat, and is expected to cure terminal patients with one dose. However, the anticancer drug market is at the initial stage, with only two products approved as recent anticancer drugs worldwide. Curocell’s technology will be able to treat terminal patients, and can be checked whether cancer treatment has effectively worked within 30 to 60 days with a single dose. The CAR-T treatment clinical trials are actively being carried out mainly in the U.S. and China, but not in Korea due to the lack of technology and experience. Curocell is preparing to receive a license for clinical tests next year.

CAR-T cell therapy is a new paradigm of chemotherapy, which genetically manipulates a patient’s T cells separated from the cancer cells and inserted back to the body. Curocell manufactures T cells separated from cancer patients by recognizing cancer and self-activating CAR genes. The CAR-T cell therapy is a competitive field amongst global pharmaceutical companies.

Curocell is the corporation developing CAR-T cell therapy which is world-widely taking center stage and has received a cumulative investment of 61.5 billion won as of 2020 since its establishment in 2017. Curocell was founded by collaboration with CEO Gunsoo Kim who has long experience of pharmaceutical company, Prof. Chanhyuk Kim of KAIST and Prof. Hyunbo Sim of Ehwa Womans University.

[About Curocell’s OVIS™ CAR-T technology]

Curocell is developing a new OVIS™ CAR-T technology that combines CAR-T technology and immune suppression technology.

OVercome Immune Suppression

The next generation CD19 CAR-T, which is featured with the 2^nd generation OVIS™ technology, is expected to treat patients more effectively. The company consists of 40 product development-oriented employees who have extensive experience in various fields, such as R&D, GMP production, and clinical development.

The most important thing is to cooperate with hospitals, and Curocell has a strategic partnership with Samsung Medical Center. Establishing a GMP facility in the hospital, Curocell is the world’s first to do a clinical launch of the next generation CAR-T technology that can treat blood cancer as well as solid cancer.

->Here is the competitive advantage that Curocell has:

• Immune suppression CAR-T technology & more: globally leading the OVIS™ CAR-T technology
• Korea’s first clinical launch of the next generation CD19 CAR-T: Next generation CAR-T R&D, GMP production, etc.
• CD22, BCMA, EGFRvlll, CAR-T & more: capabilities to secure pipelines through the company’s technology and open innovation
• Cooperation with Samsung Medical Center and GMP facility for CAR-T: Establishing a close partnership with Korea’s top hospitals.

CEO Kim additionally explained how R&D is done in a pharmaceutical company and about its research institute. There are three main ideas to consider when developing a drug.

• Quality by design (QbD, design-based quality enhancement)
• QTTP (Quality Target Product Profile): how to administer the drug
• CQA (Critical Quality Attribute): drugs must be specific and consider safety and effectiveness based on previously known facts
• CMA (Critical Material Attribute)/ CPP(Critical Process Parameter): must consider the properties of drugs, what materials to use, and how to manage the drugs.

E.g.) Breeding cows

• What kind of cows should we breed? -> QTTP
• What characteristics of the cow is related to good taste and rich amount of meat? -> CQA: usually based on shipment and delivery standards
• How should we breed the cows so that they are healthy and have a good balance between weight and fat ->CPP: usually measured in numbers, modified during processing & CMA: difficult to change the material, type during processing

[QbD for CAR-T Development]

• QTTP: safety, reliability
• CQA: presence of microbial contamination, Non-T cell content, residual content, amount of CAR-T cells, cell survival rate, cytokine secretion, etc.
• CMA/CPP: T-cell separation methods, number of cell cleanings, amount of virus used, types of cell culture mediums, duration of cell culture, final amount of cells, freezing conditions (cell concentration, composition, methods), etc.

Curocell’s R&D center mainly consists of 3 teams – discovery team, process development team, and an analysis method development team. The discovery team works with the research team to design CAR cells for new targets, improve OVIS™ technology and perform adaptive evaluation, and perform effectiveness evaluation using an In-vitro/In-vivo model. The process development team establishes CMA/CPP (experiment planning) on new products, sets a control strategy, and improves the production of CAR-T. The analysis and development team develops analysis and validation methods, analyzes samples for CMA/CPP selection, and sets standards and testing methods. These 3 teams lead to QA (Quality Assurance), Production, and QC (Quality Controls) at the GMP facility. Curocell’s R&D center has the following plans:

• New Blood Cancer OVIS™ CAR-T
• OVIS™ Platform Improvement
• Solid Tumor CAR-T
• Allogeneic CAT-T

There were many questions about solid tumor and CAR-T, so CEO Kim answered questions in relation to CD-19.

[CD-19 negative relapse]

• Re-occurrence rate of 20~30?ter CD19 CAR-T treatment
• 50% of the recurrent patients are CD19 negative leukemia

In solid cancer, one of the causes of failure for CAR-T treatments are immune checkpoint receptors. Curocell is trying various technologies based on PD-1 to improve the immune checkpoint receptors and T-cell-CAR-T treatment.

[Questions about startups]

The founders of Curocell did not invest their own money, but came so far by receiving series A, B, C by appealing the experience and capabilities of the founders and preparing clinical tests. To the question “How should we prepare our career to develop drugs?”, CEO Kim answered that at Curocell there are no graduates from colleges of pharmacy and there are a lot of cases where employees learn while working at the company. Curocell’s Q&A session has a lot of information related to developing new drugs, so please refer to the Youtube video for more details.

Lastly, Curocell showed a video tour of the R&D center. Although the tour was online, it was a time to check out Curocell’s research center and see how the OVIS™ CAR-T was being developed.

During Curocell’s Startup Ting, we realized that it is not long before we conquer cancer! We hope the CAR-T treatment is actively researched and developed to create a new drug for cancer patients. Although there are difficulties of the drug regarding solid cancer, a new drug will be developed by cooperating with hospitals. We hope Curocell receives clinical approval in 2021 for the CAR-T treatment, and shine in the global market!

During Curocell’s Startup Ting, we realized that it is not long before we conquer cancer! We hope the CAR-T treatment is actively researched and developed to create a new drug for cancer patients. Although there are difficulties of the drug regarding solid cancer, a new drug will be developed by cooperating with hospitals. We hope Curocell receives clinical approval in 2021 for the CAR-T treatment, and shine in the global market!