GALWAY, Ireland & SAN DIEGO–(BUSINESS WIRE)–ONK Therapeutics, an innovative company dedicated to developing optimally engineered natural killer (NK) cell therapies to cure patients with cancer, today announced the first in-vivo data for ONKT102, a fully human, optimized affinity CD38 CAR-NK cell therapy.
The positive data, presented in a poster at the International Myeloma Society late on Friday 26 August by ONK Therapeutics CSO Prof. Michael O’Dwyer showed potent anti-tumor activity for ONKT102 in-vitro and in-vivo in a CD38 positive MM.1S-LUC tumor model of multiple myeloma.
ONK Therapeutics is developing a pipeline of off-the-shelf, optimally engineered natural killer (NK) cell therapies expressing a chimeric antigen receptor (CAR), further modified to enhance tumor homing, persistence and metabolism, and to overcome exhaustion in the tumor microenvironment. Currently it has four programs in pre-clinical development across hematological malignancies and solid tumors. ONKT102 is the company’s most advanced program, and is being advanced towards clinical development as a potential treatment for patients with relapsed or refractory multiple myeloma (MM).
CD38 is an established immunotherapeutic target in MM. In this study, expanded cord blood (CB) derived NK cells first underwent CRISPR gene editing to knock out CD38 to prevent fratricide, following which they were genetically modified to express the optimized affinity CD38 CAR, using Tc Buster, a non-viral transposon approach developed by BioTechne. The anti-tumor efficacy of the optimized CD38 CAR-NK cells was then evaluated in NOD scid gamma (NSG) mice inoculated with MM.1S-LUC cells. Mice underwent weekly bioluminescient imaging to monitor tumor burden. The results showed that CD38 CAR-NK cells significantly reduced tumor burden and improved survival versus control CB NK cells and vehicle control.
Prof. Michael O’Dwyer, founder and CSO at ONK Therapeutics said, “These results suggest that non-virally engineered, optimized affinity CD38 CAR-NK CD38 KO cells have potent anti-tumor activity in-vitro and in-vivo in a CD38 positive tumor model.
“We are encouraged by these data and future work at ONK Therapeutics aims to optimize the dose and schedule, confirm the favorable safety profile and potential beneficial immune modulatory effects of our approach, as well as the added benefit of gene-editing with CRISPR/Cas9 to knock out CISH to enhance persistence.”
DETAILS OF THE POSTER PRESENTATION
Conference: International Myeloma Society 2022, 25-27 August 2022, Los Angeles, USA
Poster: P-018: CB derived, optimized affinity CD38 CAR-NK cells with CD38 KO show promising in-vivo activity in a Multiple Myeloma model
Authors: S. Brophy, ONK Therapeutics et al
Timing: Friday 26 August, 19.30-20.30 (Pacific time)
Location: West Hall A
View the poster HERE.
About ONK Therapeutics – www.onktherapeutics.com
ONK Therapeutics is an innovative cell therapy company dedicated to developing the next generation of optimally engineered, off-the-shelf, natural killer (NK) cell therapies. With a growing pre-clinical pipeline targeting both hematological malignancies and solid tumors, ONK is advancing multiple cell therapy candidates towards the clinic, including its lead program, ONKT102, an optimized affinity CD38 CAR-NK product, intended for the treatment of patients with relapsed/ refractory multiple myeloma. Read about the pipeline here.
The company’s optimally engineered NK cell therapy platform utilizes a suite of proprietary gene edits and cell modification strategies to optimize cytotoxic potential, persistence and the metabolic health of NK cells, while reducing the potential for their exhaustion in the tumor microenvironment. These include CISH knockout (KO); the expression of high affinity, membrane bound, TNF-related apoptosis-inducing ligand variants (TRAILv) targeting DR5 or DR4; and the deletion of inhibitory receptors, including extracellular proteins for example CD96, and Siglec-7. Read about the platform here.
ONK Therapeutics is headquartered in the med-tech hub of Galway, Ireland, with a wholly-owned US subsidiary, ONK Therapeutics, Inc. based at JLabs @ San Diego. Shareholders include Acorn Bioventures, Cormorant Asset Management, ALSHC (principally Seamus Mulligan), and Enterprise Ireland.