What is CAR-T therapy? Chimeric antigen receptor T-cell (CAR-T) therapy is a targeted approach to treating cancer that uses a patient’s T cells, which are a type of immune system cell.
Since the first CAR-T therapy approvals in 2017 by the U.S. FDA, CAR-T deal-making has attracted vast sums of money. This article summarizes recent partnerships and deal-making with the CAR-T marketplace.
What is CAR-T Therapy?
CAR-T cells are defined as T-cells (immune cells) that have been modified to match markers present on the outside of cancer cells, allowing them to selectively find and attack them. To create CAR-T cells, physicians extract T-cells from a patient, genetically alter them, expand them in quantity, and re-infuse them to the patient so that the engineered CAR-T cell can selectively attack cancer cells.
CAR-T cell therapy involves the following steps:
- A patients T-cells are collected from their blood
- The T-cells are genetically modified in the lab to include a chimeric antigen receptor (CAR)
- The modified CAR-T cells are infused back into the patient
- The CAR-T cells bind specifically to the cancer cells to destroy them
History of CAR-T Cell Therapy
Until 2017, CAR T-cell therapy had largely been restricted to small clinical trials for patients with blood cancers. However in 2017, two CAR T-cell therapies were approved by the U.S. Food and Drug Administration (FDA):
- Kymriah for the treatment of acute lymphoblastic leukemia (ALL)
- Yescarta for the treatment of advanced lymphoma
Other agencies have since issued approvals for these novel CAR-T cell therapies, creating worldwide interest in this emerging technology.
CAR-T Deal-Making Attracts Vast Sums of Money
Since the first CAR-T cell therapy approvals in 2017, CAR-T deal-making has attracted vast sums of money. Below, we summarize recent partnerships and deal-making across the global CAR-T marketplace.
In one of the earliest deals, bluebird bio elected to enter into a broad strategic collaboration with Celgene Corporation in March 2013 to commercialize CAR T-cell programs.
Pfizer then entered a CAR-T collaboration with Cellectis that was accompanied by $80 million upfront payment and up to $185 million per product with royalties in June 2014.
Next, Bellicum Pharmaceuticals and Agensys, an affiliate of Astellas Pharma, inked a global license agreement in December 2015 that allowed Bellicum to commercialize adoptive cell therapies, including CAR-T cells, for tumors expressing Prostate Stem Cell Antigen (PSCA).
The action gathered substantial momentum when Gilead Sciences acquired Kite Pharma for an astounding $11.9 billion in August 2017.
By December 2017, Johnson & Johnson agreed to pay $350 million to partner with the Chinese CAR-T firm Nanjing Legend Biotech.
Nearly simulaneously, Gilead acquired Cell Design Labs, a biotech company developing novel CAR-T and T cell receptor therapies, in a deal valued at $567 million.
Celgene then grabbed Juno Therapeutics for a shocking $9 billion in January 2018.
In June 2018, AbbVie (NYSE: ABBV) and Calibr, a nonprofit drug discovery division of Scripps Research, announced they are co-developing CAR-T therapies aimed at solid tumors and other cancers. Under the terms of the license agreement, AbbVie is paying Calibr an undisclosed upfront license fee to gain exclusive access to Calibr’s switchable CAR-T platform for up to four years.
In December 2018, Novartis announced it was acquiring the French CDMO, CellforCure, to expand its CAR-T manufacturing network in Europe. Previously, Novartis had hired CellforCure to manufacture Kymriah (tisagenlecleucel) in the E.U. Headquartered in Paris, France, CellforCure has an annual production capability of several thousands of therapeutics batches.
CellforCure also has a partnership with Cellectis to produce its allogeneic CAR-T product, UCART22, which is being explored within U.S. clinical trials for the potential treatment of B-cell acute lymphoblastic leukemia (B-ALL).
By January 2019, Bristol-Myers Squibb Company (NYSE:BMY) announced it was acquiring Celgene Corporation (NASDAQ:CELG) in a cash and stock transaction valued at $74 billion. Of course, Celgene previously bought Juno Therapeutics for $9 billion in January 2018 in a strategic move to acquire the full rights to bluebird bio’s CAR-T program.
By March 2019, MaxCyte (LSE: MXCT, MXCS) announced it had expanded its relationship with Kite, a Gilead Company, by entering into a multi-drug clinical and commercial agreement. Under the terms of the agreement, Kite will use MaxCyte’s Flow Electroporation® Technology to enable non-viral cell engineering for development of multiple CAR-T drug candidates for up to 10 targets.
In November 2019, Allogene Therapeutics (Nasdaq: ALLO), a clinical-stage biotechnology company developing allogeneic CAR T (AlloCAR T™) therapies for cancer, and Notch Therapeutics, an immune cell therapy company creating allogeneic T cell therapies, announced an exclusive worldwide collaboration and license agreement to develop induced pluripotent stem cell (iPSC) AlloCAR™ therapy products.
While Allogene is only paying $10 million upfront to get a 25% stake in Notch, Notch could receive another $7.25 million in research payments and $4 million per target if it meets certain milestones. After that, the amounts skyrocket, with Allogene promising up to $283 million per target and cell type. The partners did not disclose how many targets or cell types this could total.
List of CAR-T Deals
Below is a summary of recent CAR-T deals:
- bluebird bio elected to enter into a broad strategic collaboration with Celgene Corporation in March 2013
- Pfizer entered a collaboration with Cellectis for $80 million upfront and up to $185 million per product in royalties in June 2014
- Bellicum Pharmaceuticals and Agensys entered a license agreement in December 2015
- Gilead Sciences acquired Kite Pharma for $11.9 billion in August 2017
- J&J paid $350 million to partner with Chinese firm Nanjing Legend Biotech in December 2017
- Gilead acquired Cell Design Labs for $567 million in December 2017
- Celgene acquired Juno Therapeutics $9 billion in January 2018 in a strategic move to acquire full rights to the bluebird bio’s CAR-T
- AbbVie entered into a 4 year license agreement with Calibr for an undisclosed sum in June 2018
- Novartis acquired the French CDMO, CellforCure, in January 2019 to expand its CAR-T manufacturing
- Bristol-Myers Squibb Company acquired Celgene Corporation in a cash and stock transaction valued at $74 billion in January 2019. (Celgene previously acquired Juno Therapeutics for $9 billion in January 2018. )
- MaxCyte expanded its relationship with Kite, a Gilead Company, in March 2019, in order to pursue development of multiple CAR-T drug candidates for up to 10
- Allogene partnered with Notch Therapeutics in November 2019, to develop induced pluripotent stem cell (iPSC) AlloCAR™ therapy.
What CAR-T cell therapy companies do you think will partner next? Let us know in the comments below.