Sanofi has licensed natural killer (NK) cells from Kiadis Pharma to use in combination with its multiple myeloma drug Sarclisa. The backloaded, €875 million ($986 million) deal gives Sanofi global rights to therapies that could mitigate an efficacy-limiting shortcoming of anti-CD38 antibodies.
Sarclisa and Johnson & Johnson’s rival antibody Darzalex targets CD38, a glycoprotein found at high levels on multiple myeloma cells and at relatively low levels on healthy lymphoid and myeloid cells. The difference in expression levels is large enough for the anti-CD38 antibodies to improve outcomes in multiple myeloma patients without causing intolerable damage to healthy cells.
However, the presence of CD38 on healthy cells is a potential problem. Researchers have linked J&J’s Darzalex to reductions in NK cells, which express higher levels of CD38 than other lymphocytes. As NK cells contribute to the antitumor immune response, their depletion could limit efficacy.
Sanofi has identified NK cells in development at Kiadis as a potential solution to the depletion issue. Kiadis has modified NK cells to prevent expression of CD38, rendering them resistant to Sarclisa. By administering the preclinical prospect, K-NK004, alongside Sarclisa, Sanofi may be able to maintain NK cells at a higher level, thereby boosting the tumor-killing power of its anti-CD38 antibody.
John Reed, global head of R&D at Sanofi, and his colleagues found that prospect interesting enough to pay €17.5 million for the worldwide rights to K-NK004 and two other preclinical assets. Sanofi is also on the hook for up to €857.5 million in milestones and double-digit royalties.
The deal provides an early indication that Kiadis’ pivot to NK cells may pay off. Until late last year, Kiadis was focused on winning conditional approval in Europe for T-cell immunotherapy ATIR101 in patients undergoing transplantation with genetically half-matched hematopoietic stem cells. Kiadis switched gears in November, halting a phase 3 trial of ATIR101 and switching its attention to NK cells.
Kiadis’ overnight transition from a late-phase to early-stage biotech sank its valuation. The Sanofi deal and the external validation it provides have gone a small way toward reversing the decline, driving Kiadis’ share price up 57% as analysts welcomed the agreement.
“We view €875m total deal terms to be impressive given the early stage, with the €17.5m upfront alone representing c.30% of the current market cap for a previously undisclosed asset to which we assigned no value,” analysts at Jefferies wrote in a note to investors. The analysts expect K-NK004 to enter the clinic in 2022 at the earliest.
Sanofi will be responsible for taking K-NK004 to that point and beyond, leaving Kiadis free to work on its internal candidates. Kiadis recently secured clearance to start a phase 1/2 trial of K-NK002 in half-matched haploidentical haematopoietic stem cell transplants. Another prospect, K-NK003, is being evaluated in an early-phase acute myeloid leukemia trial.