Celgene, Juno Ink $1 Billion Immunotherapy Deal

Bob Hugin

CEO of Celgene

Celgene has entered into a 10-year collaboration with the cellular immunotherapy company Juno Therapeutics, which includes an initial $1 billion payment, according to a joint statement released by the companies.

The transaction, which has been approved by the boards of directors for both companies, will consist of an upfront cash payment of $150 million and the purchase of more than 9.1 million of Juno’s shares at $93.00 each (total $999,803,496). Over the course of the 10-year collaboration, Celgene will have the right to purchase additional shares of Juno, totaling up to 30% of the company’s common stock. The deal is expected to close in the third quarter of 2015.

"This transaction strengthens Celgene's position in the emerging and transformative area of immuno-oncology," Bob Hugin, chairman and CEO of Celgene, said in a statement. "Juno has assembled world class experts and built impressive capabilities and technologies in the areas of T-cell biology and cellular therapy; we believe this long-term collaboration enhances the potential of both companies to deliver transformational therapies to patients with significant unmet medical needs."

The initial focus of the collaboration will be on the development and commercialization of chimeric antigen receptor (CAR) T-cell therapies and T-cell receptor (TCR) technologies for patients with cancer and autoimmune disease, according to the statement. Celgene will have the option to commercialize these CAR and TCR therapies from Juno, including their lead agent, JCAR015, which is a CD19-targeted CAR-modified T-cell therapy.

JCAR015 was granted an FDA breakthrough therapy designation for patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) in November 2014. In updated findings presented at the 2015 ASCO Annual Meeting,¹ JCAR015 demonstrated a complete remission (CR) rate of 87% in 38 patients with ALL. Of those who achieved a CR, 81% were MRD-negative. The median overall survival (OS) was 8.5 months, with a 6-month OS rate of 59%.

Severe cytokine release syndrome (CRS) has been the primary adverse event (AE) of concern with CAR T-cell therapies. Early in the development of these therapies, this AE caused a number of trials to be halted for safety concerns. The protocols were emended to include early detection of CRS through serum C-reactive protein testing and treatment with corticosteroids or interleukin-6 receptor blockade.

In the updated ASCO findings, severe CRS was seen in 23% of patients. The severity of this adverse event correlated with the overall disease burden and was found to be reversible with intervention. Outside of CRS, 28% of patients treated with JCAR015 experienced grade 3/4 neurotoxicity.

JCAR015 is being investigated in two phase I clinical trials. One trial is examining the agent in precursor B cell ALL, the setting in which the agent gained its orphan drug designation (NCT01840566). In the other trial, patients with relapsed/refractory aggressive B cell non-Hodgkin lymphoma (NHL) are being treated with high dose therapy and autologous stem cell transplantation followed by infusion of JCAR015 (NCT01044069).

In addition to JCAR015, Juno is developing a number of other cellular therapies. At the 2015 AACR Annual Meeting, findings were presented for JCAR017 in pediatric patients with relapsed/refractory ALL.² In this 22-patient trial, the CD19-targeted CAR T-cell therapy JCAR017 demonstrated a 91% CR rate.

Severe neurotoxicity and/or severe CRS were observed in 36% of patients. At the time of the analysis, 4 patients had relapsed—only one of which had CD19-positive disease.

"Celgene is the ideal partner for Juno to help us realize the full potential of our science and clinical research while maintaining the independence we, our employees, partners, and investors believe is so critical for true innovation," Hans Bishop, CEO of Juno, said in a statement. "This unique collaboration is designed to catalyze and create tremendous ongoing scientific and product development synergy by leveraging each company's strengths and assets."

Celgene has a number of already approved therapies for patients with hematologic malignancies and other types of cancer, including pomalidomide, lenalidomide, azacitidine, romidepsin, and nab-paclitaxel. Additionally, the company has a broad research pipeline.

"In addition to its established global presence and commercial reach, Celgene has leading small molecule and protein capabilities that complement Juno's advanced engineered T-cell capabilities," Bishop said. "By doing this together, we believe we can more quickly and effectively develop potentially disruptive therapies in this new field of medicine and make them more readily available to patients worldwide."

A number of companies are currently developing CAR-modified T-cell therapies. The CD19-targeted therapy CTL019 was the first such therapy to receive a breakthrough therapy designation from the FDA for the treatment of adult patients with ALL. CTL019 is manufactured through collaboration between the University of Pennsylvania and Novartis. Additionally, Kite Pharma and Amgen have partnered on the CAR T-cell therapy labeled KTE-C19.

In addition to Juno Therapeutics, Celgene has also formed a relationship with bluebird bio, another player in the CAR T-cell space. In March 2013, Celgene and bluebird entered into a collaboration that included $225 million per product developed.

In early June, the Celgene/bluebird collaboration was narrowed down to one product, bb2121, which targets B-cell maturation antigen (BCMA). This refocused deal included a $25 million payment from Celgene to bluebird. In the Juno deal, BCMA agents were excluded from the collaboration.

References

1. Park JH, Riviere I, Wang X, et al. Efficacy and safety of CD19-targeted 19-28z CAR modified T cells in adult patients with relapsed or refractory B-ALL. J Clin Oncol. 2015;33 (suppl; abstr 7010).
2. Jensen MC. Advancing CAR T cell immunotherapy in Pediatric Oncology. Presented at: 2015 American Association of Cancer Research Annual Meeting.