Kiadis Pharma N.V.’s licensing deal with Sanofi SA for its preclinical K-NK004 programs – kept under wraps until now – brings €17.5 million (US$19.7 million) up front with as much as €857.5 million more if preclinical, clinical, regulatory, and commercial goals are reached, as well as royalties potentially into the double digits.

The deal covers Amsterdam-based Kiadis’ CD38 knockout (CD38KO) K-NK therapeutic for combination with anti-CD38 monoclonal antibodies, including Sanofi’s recently approved Sarclisa (isatuximab-irfc) for patients with multiple myeloma (MM). Sanofi, of Paris, gained the FDA’s go-ahead for Sarclisa in March. Included as well for Sanofi are exclusive rights to use Kiadis’ K-NK platform with two undisclosed preclinical programs.

Treatment of MM with anti-CD38 antibodies such as Sarclisa depletes the patients’ own natural killer (NK) cells, since NK cells also express CD38. Kiadis’ CD38KO K-NK cells have been modified to prevent that, providing an adjunctive infusion that reinvigorates the synergy between NK cells and antibodies to attack tumors.

Under the terms, Sanofi will be responsible for and will bear all costs related to R&D, manufacturing, regulatory and commercial activities related to the licensed K-NK programs. Kiadis will supply PM21 particles and select universal donors for Sanofi, paid for by the latter. In May, Kiadis unveiled new data related to the K-NK platform at the International Society of Cell & Gene Therapy virtual meeting. Findings showed how cytokine pre-activation enhances Kiadis’ PM21-particle-driven NK cell expansion. NK cells from healthy donor-derived peripheral blood mononuclear cell were stimulated overnight with interleukin-12 (IL-12), IL-18 and IL-15 and then expanded with the particles, which yielded a significantly increased further expansion of NK cells than with PM21 by itself. Also, the preactivated NK cells pumped out even larger amounts of interferon gamma and proved very responsive to activation by K562 tumor cells or cytokines, the company noted.

Last year, Kiadis acquired Cytosen Therapeutics Inc., of Dallas, for the firm’s NK platform whereby a proprietary algorithm identifies optimal donors for universal NK cell therapies, based on activating KIR receptors and optimized mismatching of HLA-KIR genes, as well as favorable NKG2A/NKG2C ratios. The expansion process incorporates native membrane particles expressing membrane-bound IL-21 and 41bbL, which does away with the need for feeder cells, Piper Sandler analyst Edward Tenthoff pointed out in a June 25, 2020 report, maintaining a neutral rating on Kiadis. IL-21 specifically elongates telomerase and prevents senescence. The stock-based Cytosen transaction was valued at just €19.4 million (then US$21.9 million) at the start but could be worth up to €77.5 million altogether if six development and regulatory goals are reached, including U.S. approval of a product.

Sanofi’s license does not include rights to K-NK002 and K-NK003 or any other current and future Kiadis programs. In June, Kiadis said the first patient had enrolled in phase I study sponsored by Ohio State University in relapsed/refractory acute myeloid leukemia and myelodysplastic syndromes with off-the-shelf K-NK003. Data from the recent virtual European Hematology Association and American Society of Clinical Oncology meetings bespoke promising proof-of-concept for the FC21 NK cell therapy on which K-NK003 is based. The dose-finding study will evaluate safety and overall response rate, with first data due to roll out next year. Gatekeepers have cleared the IND for Kiadis’ K-NK002 phase I/II NK-Realm study to test the prospect with post-transplantation cyclophosphamide in patients undergoing a haploidentical hematopoietic stem cell transplant. Also likely to provide preliminary data next year, the effort will measure post-transplant relapse.

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