Since August 2017, the FDA has approved a total of four therapeutic drugs that are different from traditional small molecule drugs and macromolecular drugs. They are Novartis CAR-T drugs Kymriah (tisagenlecleucel-T) and Gilead (Kite). CAR-T drug Yescarta (axicabtagene ciloleucel), Spark gene therapy drug Luxturna (voretigene neparvovec-rzyl) and small interfering RNA (siRNA) drug Onpattro (patisiran).
The clinical advantages of these new “morphological” drugs are obvious, but they are usually expensive, and hundreds of thousands or even millions of dollars in treatment costs are not affordable to most patients. Even if the market prospects of such new therapies are still unclear, there are still many biopharmaceutical companies and investment institutions that believe in their industrial value and do not hesitate to invest heavily.
For example, Kymriah and Yescarta’s sales of $28 million and $106 million in the first half of this year did not match their dazzling aura, but almost all of the top 10 pharmaceutical companies in the world have already been deployed in the field of cell therapy.
In April 2018, Pfizer announced an alliance with Allogene Therapeutics to further develop allogeneic CAR-T therapy (general CAR-T), while Pfizer will acquire a 25% stake in Allogene. It is worth mentioning that Allogene was founded by former Kite CEO and another partner, dedicated to the treatment of solid tumors and blood cancer using generic CAR-T therapy, and $300 million in cash financing in Series A financing. .
The agreement states that Allogene will receive Pfizer’s 16 preclinical CAR-T assets from Cellectis and Servier; and a clinical asset UCART19, licensed from Servier, CD19 is currently developing the same species Allogeneic CAR-T therapy for the treatment of CD19-expressing hematological malignancies.
Pfizer initially partnered with Servier to develop UCART19 for the treatment of acute lymphoblastic leukemia (ALL) and is currently in Phase I development. Allogene and Servier hope to start Phase II research in 2019. Allogene has exclusive development and distribution rights for UCART19 in the United States, and Servier will have exclusive rights to the therapy in other countries.
The TALEN® gene editing technology used by UCART19 was pioneered and held by Cellectis. Pfizer will continue to hold an 8% stake in Cellectis through an equity acquisition agreement reached in 2014.
In August 2017, Kymriah (Tisagenlecleucel) developed by Novartis became the world’s first marketed CAR-T cell therapy product. On August 28, 2018, Kymriah received EU (EC) approval. On September 5th, the National Institute of Health and Clinical Excellence (NICE) agreed to recommend Kymriah for £28,200 (approximately $373,000).
On September 25 of the same year, Novartis announced that it plans to cut about 2,200 jobs in its headquarters in the next four years, mainly involving pharmaceutical production and marketing departments, to boost profitability, and to cooperate with the preparation of cell and gene therapy production base projects.
On September 27th, Novartis and Sibman Bio (CBMG) announced a strategic licensing and cooperation agreement to manufacture and manufacture CAR-T cell therapeutic drugs for Chinese patients in China. Sibman will be responsible for the production and supply of Kymriah, a CAR-T cell therapy drug in China. Novartis has exclusive rights to Kymriah marketing licenses and will be primarily responsible for distribution, product registration and commercialization in China.
In September 2018, Roche announced the acquisition of British biotechnology company Tusk Therapeutics for $758 million (81 million advance payments + 677 million milestone payments). The latter is a privately held immuno-oncology company founded in 2014 by the major shareholder Droia Oncology Ventures, focusing on the discovery and development of therapeutic antibodies that harness the power of the immune system to alter cancer treatment. The company has two targeted antibody therapies targeting CD25 and CD38, respectively.
Tusk pipeline assets
Roche will be responsible for launching this CD25-targeted antibody for human clinical trials in cancer patients by the end of 2019, which is the second attempt by Roche to develop CD25 targeted therapy. Previously, Roche introduced a PA25-targeted antibody drug, Zenapax (daclizumab, daclizumab), for organ transplantation (mainly kidney transplantation) in 1997. However, due to poor sales, the product was in 2009. Officially delisted.
Merck does not have a CAR-T cell layout, but the company recently deployed another cell therapy, NK Cell Therapy.
In October 2018, Merck (MSD) reached a $695 million cooperation agreement with Dragonfly Therapeutics, based in Cambridge, Massachusetts.
Founded in 2015, Dragonfly has a unique technology platform, TriNKET (Tri-specific NK cell Engagement Therapies), which enhances the range and efficacy of immunotherapy through natural killer (NK) cells. The agreement states that Merck will develop and market solid tumor cancer immunotherapy based on the platform.
Sanofi acquired Genzyme in 2011 to acquire cell therapy and regenerative medicine (CTRM). However, in 2014, Sanofi sold the business to Aastrom Biosciences for $6.5 million (including $4 million in cash payments and $2.5 million in notes). At the same time, Aastrom also acquired Sanofi’s global manufacturing and production centers in the US and Denmark.
However, in the past two years, Sanofi has increased its investment in blood diseases and immunotherapy. For example, at the beginning of this year, Sanofi acquired the hemophilia company Bioverativ and Nanoantibody R&D for US$11.6 billion and EUR3.9 billion. Ablynx.
Sanofi’s key partner, Regeneron (co-developing drugs such as Cemitlimab) announced in August this year that it has announced a partnership with another head of CAR-T therapy, bluebird bio, to apply its technology platform to new cancer immune cell therapies. Discovery, development and promotion. Previously, Regeneron has teamed up with Adicet Bio to develop new T cell therapies. So, will Sanofi re-engage with Regeneron on CAR-T?
On August 28, 2017, Gilead acquired Kite Pharmaceuticals for approximately $11.9 billion. On October 18 of the same year, the FDA approved the listing of Kite’s drug Yescarta (axicabtageneciloleucel), which is the second CAR-T therapy currently approved by the FDA.
Kite Pharmaceutical CAR-T Therapy Line
In August of this year, Yescarta received EMA approval for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) treated twice or more.
In January of this year, Gilead also invested in Tmunity Therapeutics with a number of innovative therapies for T cell activation and targeting in vivo.
In December 2017, Johnson & Johnson’s pharmaceutical company, Janssen Biotech, Inc. (“Yangsen”) announced that it has officially signed a global partnership with Legend Biotech USA Inc. and Legend Biotech Ireland Limited (“Legend”), a subsidiary of Kingslife Biotech. The cooperation agreement will pay $350 million to jointly develop, produce and market LCAR-B38M, a chimeric antigen receptor T cell immunotherapy (CAR-T) targeting B cell mature antigen (BCMA).
Nanjing Legend Product Pipeline
The LCAR-B38M is the first CAR-T therapy for CDE acceptance review. Under the agreement, Legend will grant Janssen a worldwide license to develop and commercialize LCAR-B38M for multiple myeloma with its team of experts.
In September 2017, GSK announced a partnership with Adaptimmmune Therapeutics to acquire exclusive rights to develop and market NY-ESO SPEAR T Cell Therapy. The latter’s unique SPEAR (Specific Peptide Enhanced Affinity Receptor) T-cell platform targets and destroys a variety of malignancies, including solid tumors, through the transformation of T cells. Under the agreement, GSK will conduct further development of NY-ESO SPEAR T cell therapy, including indications of synovial sarcoma, non-small cell lung cancer, ovarian cancer, multiple myeloma and many other cancers.
In December 2017, GSK announced that its new CAR-T drug for BCMA targets has entered Phase II of the clinical phase. With a clinical response rate of up to 60% and FDA breakthrough therapy, it is in the BCMA-targeted CAR- The leading position in the field of T immunity.
On June 26, 2018, AbbVie and Calibr announced that they would collaborate on the development of T-cell therapies for tumors such as solid tumors. The latter is a non-profit translation research organization dedicated to the development of next-generation drugs. It has a wide range of research and development products ranging from early discovery to clinical projects. New drug types include small molecules, peptides, biotherapeutics and cell therapy.
Under the agreement, AbbVie will pay Calibr a four-year pre-licensing fee and exclusive access to the Calibr switchable CAR-T platform. The two agencies will work together to develop T cell therapies for solid tumor targets identified by AbbVie.
AbbVie also has the option to develop additional cell therapies for its nominated targets and to obtain permission for the Calibr Cell Therapy Program under development (including Calibr’s primary drug candidate) for blood and solid cancers. Calibr plans to push drug candidates into clinical research in 2019. The two organizations will share the responsibility for preclinical development, AbbVie is responsible for clinical development and promotion, and Calibr is eligible for milestone payments and royalties.
In June 2018, Amgen and the University of Texas MD Anderson Cancer Center announced the signing of two multi-year cooperation agreements to accelerate the development of multiple early oncology therapies for Amgen’s treatment of leukemia , myelodysplastic syndrome, multiple myeloma, small cell lung cancer and other non-lung cancer diseases containing small cell tissue.
Under the agreement, the focus of the cooperation will be placed on Amgen’s BiTE, CAR-T cells and small molecule projects. Amgen is advancing two types of T cell therapy for different targets or, in some cases, for the same target. Prior to this, Amgen also worked with Kate Pharmaceuticals, a subsidiary of Gilead, to develop CAR-T cell therapy.
In addition to the above-mentioned top 10 companies that included PharmExec (American Pharmaceutical Manager Magazine) 2018 global pharmaceutical company’s latest ranking TOP50 list. There are also a number of companies in the field of cell therapy, such as in January this year, the new base announced the acquisition of Juno Therapeutics for about $9 billion. AstraZeneca’s PD-L1 inhibitor Durvalumab is also being combined with Juno’s ongoing research on CAR-T cell product JCAR014 for clinical trials of non-Hodgkin’s lymphoma (NHL). Sangamo announced $84 million in acquisitions of TxCell and next-generation cell therapy technologies.