SOPHIA ANTIPOLIS, France – April 3rd, 2025 │ March 11th, Bristol Myers Squibb (BMS) announced a definitive merger agreement to acquire all of the outstanding shares of 2seventy bio for a total equity value of approximately $286 million. The company 2seventy bio decided to focus exclusively on Abecma which was the first B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) – T cells treatment for relapsed or refractory (R/R) multiple myeloma. Abecma is BMS’ second CAR-T therapy, following in the footsteps of the CD19-targeting Breyanzi, approved in February 2021 for large B-cell lymphoma.
The journey of Abecma: from Bluebird bio and Celgene collaboration to BMS and 2seventy bio partnership
The collaboration for BCMA CAR-T cells therapy began between Bluebird bio and Celgene. In March 2013, Bluebird bio and Celgene entered into a collaboration to develop CAR T cell therapies to target cancer cells. Two years later, the collaboration was amended and restated to focus on developing anti-BCMA CAR T program. At the beginning of 2018, Celgene acquired CAR-T specialist Juno Therapeutics for around $9 billion and in 2019, it is BMS which acquired Celgene. In May 2021, the company 2seventy bio entered the market when it was spun out of Bluebird bio, taking with it the BMS-partnered CAR-T therapy Abecma.
Currently, Abecma is being jointly developed and commercialized in the U.S. as part of a co-development, co-promotion, and profit share agreement between BMS and 2seventy bio. BMS assumes sole responsibility for Abecma drug product manufacturing and commercialization outside of the U.S. The companies’ broad clinical development program for Abecma includes ongoing and planned clinical studies (KarMMa-2, KarMMa-9) for patients with multiple myeloma.
Abecma: personalized CAR T-Cell therapy targeting BCMA in R/R Multiple Myeloma
Idecabtagene vicleucel (brand name Abecma) is a BCMA-directed genetically modified autologous CAR T-cell therapy. Each dose is customized using a patient’s own T-cells, which are collected and genetically modified, and infused back into the patient. BCMA is a protein that is nearly universally expressed on cancer cells in multiple myeloma. The therapy is used for the treatment of adult patients with R/R multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.
FDA approves Abecma: first cell-based gene therapy for multiple myeloma
On March 26, 2021, the FDA approved Abecma for the treatment of adult patients with R/R multiple myeloma after several prior lines of therapy. This is the first FDA-approved cell-based gene therapy for multiple myeloma. Approval was based on KarMMa clinical trial (NCT03361748). Patients received a single infusion of idecabtagene vicleucel, preceded by lymphodepleting chemotherapy with cyclophosphamide and fludarabine. Results of the study are:
- Overall response rate: 72% with stringent complete response (CR) rate of 28%.
- Median duration of response: 11 months in responders (PR or better) and 19 months in patients who achieved stringent CR.
- Serious adverse reactions occurred in 67% of patients evaluated for safety. Grade 3 or higher cytokine release syndrome and neurologic toxicities occurred in 9% and 4%, respectively. Hemophagocytic lymphohistiocytosis/macrophage activation syndrome occurred in 4% with 2 fatalities. Prolonged cytopenia requiring hematopoietic rescue occurred in 2% with 2 fatalities.
The European Commission approves Abecma as first CAR-T therapy for earlier lines of R/R multiple myeloma
In March 2024, the European Commission has granted approval to Abecma for the treatment of adult patients with R/R multiple myeloma who have received at least two prior therapies and have demonstrated disease progression on the last therapy. Abecma is the 1st CAR-T cell immunotherapy approved in the European Union for use in earlier lines of therapy for R/R multiple myeloma. This expanded approval of Abecma covers all EU member states. In the EU, Abecma has maintained its Orphan Designation for the treatment of multiple myeloma.
Identified patent families related to BCMA CAR-T cells
To protect this innovative technology, companies own several patent families covering their developments in BCMA CAR-T cell therapies to fight cancer (see table below). However, there is any patent family co-filled by 2seventy Bio / Bluebird Bio with BMS / Celgene.
2seventy Bio / Bluebird Bio own 8 patent families on BCMA CAR-T cells published between 2015 and 2020. First, the patent portfolio described the CAR construct, a humanized anti-BCMA antibody with a CTLA-4 or PD-1 transmembrane domain that reduces cytokine release syndrome of the CAR. Then, manufacturing methods are detailed to construct the CAR T cells. For example, T cells are activated and stimulated by phosphatidylinositol-3 kinase (PI3K) inhibitor (e.g., ZSTK474), and they are transduced with a viral vector comprising a polynucleotide encoding a CAR. To detect anti-BCMA CAR expression on T cells, an anti-BCMA CAR antibody is produced and described in some patent families. Finally, a composition is realized with immune effectors cells transfected with the CAR construct and a pharmaceutical carrier. In human clinical trials, the therapeutically effective amount of anti- BCMA CAR T cells in patients with R/R multiple myeloma is between 5×107 and 45×107 cells. No dose limiting toxicities, neurotoxicity and Grade 2, 3 or higher cytokine release syndrome have been observed. The composition is formulated for intravenous administration in a single dose.
BMS / Celgene / Juno Therapeutics own 12 patent families on BCMA CAR-T cells published between 2020 and 2024. These patent families mainly describe methods of treatment or methods of predicting treatment response. For example, before administrating immune cells expressing BCMA CAR T cells in subject with multiple myeloma, the level of soluble BCMA is determined. Moreover, previously CAR T treatment, the subject can receive prior cancer therapy such as topoisomerase or proteasome inhibitor therapies. However, the subject was treated with no more than three lines of prior therapy (e.g., dexamethasone, doxorubicin, cisplatin, doxorubicin, etoposide, an anti-CD38 antibody, elotuzumab), and there is evidence of progressive disease within 60 days of the most recent line of prior treatment. The patient can also have an early relapse, an inadequate response, or a suboptimal response to one or more anti-myeloma drugs. For CAR T cells treatment in patients with R/R multiple myeloma, the immune cells can be administered in a dosage between 150 × 106 and 450 × 106 cells. Then, for predicting treatment response, the level of one or more inflammation-related soluble factors in serum is determined. If the level is similar to that in serum from a patient responsive to CAR T cells, a therapeutically effective dose of the CAR T cells is administered. For example, in a study, results identified IgG, sBCMA, and PT-INR test as negative correlates of complete response (CR), and vector copy number in drug product as a positive correlate of CR. As sBCMA is an indicator of tumor burden and can affect therapies targeting BCMA, selecting patients with low tumor burden and controlling tumor burden during manufacturing or bridging therapy may be important in achieving CR.
| Patent assignee (filed by) |
Patent assignee (owned by) |
Patent no | Title | Family legal status | 1st pub date | Object of the invention |
| BLUEBERD BIO | 2SEVENTY BIO | EP3172231 | Bcma chimeric antigen receptors | GRANTED | 2016-01-28 | CAR description |
| BLUEBERD BIO | 2SEVENTY BIO | EP3534968 | Anti-bcma car t cell compositions | GRANTED | 2018-05-11 | A composition |
| BLUEBERD BIO | 2SEVENTY BIO | EP3828265 | Improved t cell compositions | GRANTED | 2015-12-10 | Manufacturing method |
| BLUEBERD BIO | 2SEVENTY BIO | US20190194615 | T cell compositions | GRANTED | 2017-06-15 | Manufacturing method |
| BLUEBERD BIO | 2SEVENTY BIO | EP3640262 | Bcma chimeric antigen receptors for use in the treatment of a hematological malignancy | GRANTED | 2016-06-16 | A composition |
| BLUEBERD BIO | 2SEVENTY BIO | EP3813878 | Anti-bcma car antibodies, conjugates, and methods of use | GRANTED | 2019-12-19 | Antibody description |
| BLUEBERD BIO | 2SEVENTY BIO | EP3946355 | Manufacturing anti-bcma car t cells | GRANTED | 2020-10-08 | Manufacturing method |
| BLUEBERD BIO | 2SEVENTY BIO | EP4076522 | Anti-bcma car antibodies, conjugates, and methods of use | PENDING | 2021-06-24 | Antibody description |
| CELGENE | BMS | EP4103224 | Anti-bcma therapy in autoimmune disorders | PENDING | 2021-08-19 | Method of treatment |
| CELGENE | BMS | EP4142722 | Methods of treating cytokine-related adverse events | PENDING | 2021-11-04 | Method of treatment |
| CELGENE | BMS | EP4272002 | Uses of chimeric antigen receptor (car) t-cell therapies in combination with inhibitors of inflammation-related soluble factors | PENDING | 2022-06-09 | Method of predicting treatment response |
| CELGENE | BMS | EP4426339 | Chimeric antigen receptors specific for b-cell maturation antigen for use in treating myeloma | PENDING | 2023-05-11 | Method of treatment |
| CELGENE | BMS | EP4054622 | Uses of anti-bcma chimeric antigen receptors | GRANTED | 2021-05-06 | Method of treatment |
| CELGENE | CELGENE, Subsidiary of BMS |
EP3820515 | Uses of anti-bcma chimeric antigen receptors | PENDING | 2020-01-16 | Method of treatment |
| CELGENE | CELGENE, Subsidiary of BMS |
WO2023/220641 | Methods and uses related to t cell therapy and production of same | PENDING | 2023-11-16 | Method of treatment |
| CELGENE | CELGENE, Subsidiary of BMS |
WO2024/097905 | Methods of treatment with t cell therapy and immunomodulatory agent maintenance therapy | PENDING | 2024-05-10 | Method of treatment |
| JUNO THERAPEUTICS | CELGENE, Subsidiary of BMS |
EP4241278 | Car t cell therapy in patients who have had prior anti-cancer alkylator therapy | PENDING | 2022-05-12 | Method of treatment |
| JUNO THERAPEUTICS | CELGENE, Subsidiary of BMS |
EP4322991 | T cell therapy in patients who have had prior stem cell transplant | PENDING | 2022-10-20 | Method of treatment |
| JUNO THERAPEUTICS | CELGENE, Subsidiary of BMS |
EP4322959 | Combination therapies with bcma-directed t cell therapy | PENDING | 2022-10-20 | Method of treatment |
| CELGENE | CELGENE, Subsidiary of BMS |
EP4151722 | Improved t cell manufacturing process | GRANTED | 2020-05-22 | Method of treatment |
Table 1: patent families owned by BMS or 2seventy Bio and describing BCMA CAR-T cells.
From autologous to allogeneic CAR-T cells: a necessary evolution?
Autologous CAR-T cells are now an established treatment for patients with R/R B cell lymphomas, B cell acute lymphoblastic leukemia and multiple myeloma. Data on the outcomes of patients shows that remissions induced by anti-BCMA CAR-T cells have generally limited long-term toxicities but are more short-lived.
Moreover, several disadvantages of autologous CAR therapy are widely described, such as an expensive process, manufacturing failure in some patients, and too long manufacturing times. These problems have led some scientists to develop other approaches, such as allogeneic CAR. To produce allogeneic CAR-T cells, a source of third-party healthy T lymphocytes is needed. These T cells are genetically modified to express a CAR. Then, T cells are expanded and selected. Finally, vials are filled with allogeneic CAR T cells, stored, frozen, and shipped to hospitals when needed. These “off-the-shelf” CAR T-cells, from healthy donors, could potentially address major issues of autologous CAR therapy. However, this brings with it new risks such as graft versus host disease (GVHD). To avoid GVHD, many solutions are evaluated by companies and academics in allogeneic CAR area and they are described in our report: Allogeneic CAR – 2023.
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About the author
Fabienne Massa, PhD., works for Knowmade in the field of Biotechnology and Life Sciences. She holds a PhD in Molecular and Cellular Biology from the IPMC (Sophia Antipolis, France). She also holds a Master of Business Management from IAE (Nice, France) and she previously worked in the pharmaceutical industry.
About KnowMade
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