Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, announced new in vivo preclinical data for FT596, its off-the-shelf, multi-antigen targeting natural killer (NK) cell product candidate derived from a clonal master engineered induced pluripotent stem cell (iPSC) line. The data were featured during the 61st American Society of Hematology (ASH) Meeting and Exposition as part of the organization’s CAR-T and Beyond press program, which spotlighted promising next-generation cancer immunotherapies having the potential to overcome the key limitations of patient-specific chimeric antigen receptor (CAR) T-cell therapy.
“Current patient- and donor-specific CAR T-cell immunotherapies recognize only one antigen and fail to address the significant risk of relapse due to antigen escape. FT596 is ground-breaking in that it is designed to be available off-the-shelf for timely patient access and to promote deeper and more durable responses by targeting multiple tumor-associated antigens,” said Bob Valamehr, Ph.D., Chief Development Officer of Fate Therapeutics. “Additionally, since FT596 is manufactured from a renewable master engineered iPSC line, the complexities of patient-by-patient genetic engineering and production are greatly reduced and, for the first time, we are able to mass produce multi-functional cellular immunotherapies in a uniform and cost-effective manner.”
FT596 is the first cellular immunotherapy engineered with three active anti-tumor components to be cleared for clinical investigation by the FDA. In addition to a proprietary CAR targeting CD19, FT596 expresses a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor that has been modified to augment antibody-dependent cellular cytotoxicity, enabling coincident targeting of CD19 and additional tumor-associated antigens such as CD20. FT596 also expresses an interleukin-15 receptor fusion (IL-15RF), a potent cytokine complex that promotes survival, proliferation and trans-activation of NK cells and CD8 T cells without the need for systemic cytokine support. Together, these features of FT596 are intended to maximize potency and minimize toxicity in treated patients. The Company plans to initiate enrollment of a first-in-human clinical trial of FT596 in early 2020.
New preclinical data presented at ASH showed that FT596 administered as a monotherapy exhibited durable tumor clearance and extended survival in vivo similar to primary CAR T cells in a humanized mouse model of CD19+ lymphoma. Additionally, when combined with the anti-CD20 monoclonal antibody rituximab, FT596 showed enhanced killing of CD20+ lymphoma cells in vivo as compared to rituximab alone. These data confirm previously presented in vitro findings that demonstrate the unique multi-antigen targeting functionality of FT596, and the product candidate’s potential to effectively overcome CD19 antigen escape.
The Company also announced that, in preparation for Phase 1 initiation, it had recently completed GMP production of FT596. In a single small-scale manufacturing campaign, the Company produced over 300 cryopreserved, infusion-ready doses of FT596 at a cost of approximately $2,500 per dose. The Company’s iPSC product platform unites stem cell biology and precision genetic engineering to create renewable master engineered iPSC lines that can be repeatedly used to mass produce cancer-fighting immune cells, replacing the high production costs, weeks of manufacturing time, and complex manufacturing processes required for current-generation CAR T-cell immunotherapies with a lower-cost, easier-to-manufacture, well-characterized, off-the-shelf product that has the potential to reach many more patients.
FT596 is the third off-the-shelf, iPSC-derived NK cell product candidate from the Company’s proprietary iPSC product platform cleared for clinical investigation by the FDA in the past twelve months. On Saturday, the Company announced that the first patient treated for acute myeloid leukemia in its Phase 1 clinical trial of FT516, an off-the-shelf, iPSC-derived NK cell cancer immunotherapy engineered to express hnCD16, showed no morphologic evidence of leukemia, chimerism of FT516 in the bone marrow, and hematopoietic recovery, including complete neutrophil recovery without growth factor support (>1,000 per µL), after receiving three once-weekly doses of FT516 and IL-2 cytokine support.
Piper Jaffray analyst Edward Tenthoff called the NK cell FT500 data reported this weekend at the ASH meeting by Fate Therapeutics “platform validating,” adding that in addition to the efficacy reported to date that the safety remains “exceptionally clean.” The company also reported “surprise early FT516 data,” noted Tenthoff, who pointed out that both iPSC NK cell therapies have exhibited a clean safety profile. He maintains an Overweight rating and $28 price target on Fate shares.
The stock is set to soar when pre-market trading begins on Monday, December 9, 2019. Keep in mind that these clinical stage companies often do secondary offerings whenever their stocks spike.