Bristol-Myers Squibb (BMS) and Nektar Therapeutics have announced a partnership deal worth up to $3.6 billion that will lay out a new path for immuno-oncology (I/O) combination therapies. Under the terms of the deal, BMS will make the payment, including a $1 billion upfront payment, for Nektar’s NKTR-214 early-stage I/O drug, which stimulates the expansion of T cells and natural killer cells within the tumor micro-environment.
BMS will have an exclusive development period to investigate combination treatments of NKTR-214 in 20 indications with its own I/O products Opdivo and Yervoy. The development program will span nine tumor types including non-small cell lung cancer (NSCLC), melanoma, bladder cancer, and breast cancer. Studies in renal cell carcinoma and melanoma are expected to begin in mid-2018. The partnership deal will also have BMS make an equity investment of $850 million in Nektar.
BMS and Nektar entered into a collaboration in 2016 to evaluate the combination of Opdivo and NKTR-214 to treat five tumor types across seven indications. That agreement also gave BMS first right, over the next two years, to negotiate a license for the therapy. Additionally, BMS had the option to match any other company’s offer for the drug until September 2018. The value of NKTR-214 was demonstrated in November 2017 when data from a Phase ½ trial showed it boosted the efficacy of checkpoint inhibitors by expanding T cells and natural killer cells.
Research firm GlobalData notes that many companies are beginning to exhaust the label expansion for monotherapy applications approved for the same indications. As a result, they have increasingly started to look both internally and externally for combination candidates that could boost the clinical efficacy of their drugs, while at the same time increasing the potential for further approvals. Currently there are five programmed cell death protein 1 (PD-1) and programmed death-ligand (PD-L1) drugs approved, with more on the way. This makes for a competitive market for drugs approved for the same indications, and could result in sponsors having multiple development partners via non-exclusive partnerships.
Other partnerships in this area include Incyte partnering with BMS (Opdivo) and Merck (Keytruda) for combination trials in melanoma, NSCLC, and head and neck cancer. Incyte is also partnered with AstraZeneca and Roche for combination therapies in NSCLC. AstraZeneca is also partnered with NewLink Genetics on an IDO inhibitor for pancreatic cancer. Roche has a similar partnership in place with New Link Genetics to develop next-generation IDO pathway inhibitors.
With this latest deal, both BMS and Nektar, for a specified period of time, will not commence development with overlapping mechanisms of action in the same indications as those noted in the clinical development plan.
There is clearly a frantic pace of deal making in the I/O space, as evidenced by the high number of partnerships that are occurring. The approach of engaging in multiple partnerships allows sponsors to hedge their bets while awaiting clinical data. However, with this announcement, BMS is making a huge bet on NKTR-214 as a combination regimen partner. GlobalData notes this move could spur other big players, such as Merck and Roche, to similarly look for their own exclusive deals. If true, this could place companies like Incyte and NewLink Genetics in a position to reap large investments as well.
Terms of the latest agreement has Nektar eligible to receive an additional $1.78 billion in milestone payments. Development and regulatory milestones will comprise $1.43 billion, while the remainder will be linked to sales. If NKTR-214 is approved, 65 percent of worldwide profit will go to Nektar with the remaining 35 percent going to BMS.
“Bristol-Myers Squibb has established Opdivo plus Yervoy as the only approved immunotherapy combination for cancer patients and built a robust oncology pipeline,” notes BMS chairman and CEO in a company press release. “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.”
"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,” added Howard Robin, president and CEO of Nektar. “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."