Bristol-Myers Squibb (BMS) has signed a whopping $3.6 billion deal to pair its Opdivo and Yervoy with Nektar’s NKTR-214 in a range of tumor types. The two companies have agreed to co-develop NKTR-214 in combination with PD-1 antagonist Opdivo (nivolumab) and CTLA4 inhibitor Yervoy (ipilimumab) in more than 20 indications across nine cancers, including melanoma, renal cell carcinoma, non-small-cell lung cancer, bladder cancer and triple-negative breast cancer. Pivotal trials in RCC and melanoma are due to start before the end of the year.

BMS is paying $1.85 billion upfront, with another $1.43 billion in the offing if the alliance passes development and regulatory milestones and another $250 million if it meets sales targets. The companies will share global profits on NKTR-214, with Nektar receiving 65% and BMS 35%.

“We are excited to bring our leading capabilities and expertise in developing cancer therapies together with Nektar’s innovative science to jointly develop and commercialize NKTR-214 in combination with Opdivo and Opdivo plus Yervoy,” said Giovanni Caforio, chairman and chief executive officer, BMS. “Bristol-Myers Squibb has established Opdivo plus Yervoy as the only approved immunotherapy combination for cancer patients and built a robust oncology pipeline. With this commitment to the development of NKTR-214, an investigational therapy designed with a unique approach to harnessing the full potential of the interleukin-2 pathway, we now have a third validated I-O mechanism that has demonstrated a clinical benefit in patients, and holds significant potential to expand the benefits that these immuno-oncology agents can bring to patients with cancer.”

The two companies have been working together on NKTR-214 since 2016, when they signed an agreement to test Opdivo and NKTR-214 in a phase I/II trial in bladder, RCC and NSCLC. NKTR-214 is a CD122-biased agonist designed to stimulate the patient’s own immune system to fight cancer, working to expand T cell and natural killer (NK) cell populations that attack tumors as well as increasing PD-1 expression on cancer cells.

“Bristol-Myers Squibb, the global leader in immuno-oncology, is the ideal collaborator to enable us to establish NKTR-214 as a backbone immunotherapy in the treatment of cancer,” said Howard Robin, president and chief executive officer, Nektar. “NKTR-214’s ability to grow tumor infiltrating lymphocytes (TILs) in vivo and replenish the immune system is critically important as many patients battling cancer lack sufficient TIL populations to benefit from approved checkpoint inhibitor therapies. This strategic collaboration allows us to very quickly develop NKTR-214 with the leading approved PD-1 immune checkpoint inhibitor in numerous registrational trials. We look forward to our continued relationship with Bristol-Myers Squibb as we work together to advance cancer treatment for patients around the world.”

Under the terms of the deal, BMS will fund upwards of two thirds of the clinical programs, on a scale depending on whether it is testing one or both of its drugs, and it will lead the global commercialization of regimens that include NKTR-214, with Nektar retaining co-marketing rights in the U.S., major EU markets and Japan.