Background CYNK-001 is a cryopreserved, allogeneic, off-the-shelf natural killer (NK) cell investigational product derived from placental CD34+ cells. CYNK-001 exhibits cytotoxicity against various cancer cell types as well as virally infected cells and secretes immunomodulatory cytokines upon target activation. This is the first study to evaluate the safety and potential efficacy of CYNK-001 to treat patients (pts) with SARS-CoV-2, previously investigated in only solid tumor and hematologic malignancies. Methods Placental CD34+ cells were cultured in the presence of cytokines for 35 days to generate CYNK-001 under the cGMP conditions. Pts with a positive RT-PCR test for SARS-CoV-2 from the nasopharynx and having moderate to severe illness, not requiring intensive care support or mechanical ventilation, were eligible. All enrolled pts received best supportive care. In the Phase 1 trial focused on safety of administration, a total of 14 pts will receive up to 3 CYNK-001 infusions on Days 1 (1.5e8 cells), 4 (6e8 cells), 7 (6e8 cells). Efficacy was measured by SARS-CoV-2 clearance as measured by RT-PCR testing and clinical measures of improvement, including pulmonary status, and inflammatory marker changes. Results Four of 6 pts treated to date were evaluable at the time of submission. All had multiple medical co-morbidities. Peripheral oxygen saturation (Sp02) ranged between 88-92% on up to 8L of supplemental oxygen and all had evidence of multilobar pneumonia on chest radiography. Two pts had received no prior therapy for COVID-19. The other 2 pts received remdesivir and dexamethasone, with the 4th pt also receiving convalescent plasma. In all 4 pts, all infusions were well tolerated. In 3 of 4 pts, oxygenation improved after the first infusion of CYNK-001 and radiographic improvement was noted. The 4th pt developed progressive hypoxemia prior to the administration of the first dose of CYNK-001, requiring more than 30L of supplemental oxygen delivered by facemask to support a Sp02>90%. All 3 doses of CYNK-001 were administered, but oxygen requirements increased. Twelve days after first CYNK-001 dose, the pt declined mechanical ventilation and died of respiratory failure. Attribution to CYNK-001 could not be ruled out. The remaining 3 pts were discharged with an average follow-up of 16 (9-32) days after first infusion. Conclusion In the first study to measure the safety and potential efficacy of CYNK-001 infusions to treat pts with COVID-19 disease, infusions were generally well tolerated with one Grade 5 event of hypoxic respiratory failure. Early efficacy has been seen in 3 of 4 pts with improvement of oxygenation, inflammatory markers, and radiographic findings. Once Phase 1 is completed, the Phase 2 portion of the study will test this approach in a randomized fashion compared to best available therapy to confirm efficacy of this approach.

Citation Format: Corey Casper, Leonid Groysman, Vinay Malhotra, Eric Whitman, Stacy Herb, Erica Rave, Alan Lew, Cristina Goman, Zachary Sagawa, Monica Thakar, Victoria Lacasse, Cherie Daly, Shuyang He, Lin Kang, Sharmila Koppisetti, Tanel Mahlakõiv, Sunday Osokoya, William van der Touw, Junhong Zhu, Greg Berk, Xiaokui Zhang, Andrew Pecora, Robert Hariri. Early report of a phase I/II study of human placental hematopoietic stem cell derived natural killer cells (CYNK-001) for the treatment of adults with COVID-19 (NCT04365101) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT201.