ONK Therapeutics and Trinity College Dublin Collaborate in an Enterprise Ireland Funded Project to Optimize Metabolism of NK Cells for Improved Cancer Therapies

• Collaboration between ONK Therapeutics and Dr. David Finlay’s group at Trinity College Dublin, Ireland
• Two-year Enterprise Ireland Innovation Partnership Programme (IPP) project grant of €373,295
• Research to explore metabolic reprogramming and engineering of natural killer (NK) cells for improved cancer therapy

GALWAY, Ireland & SAN DIEGO, Calif.--(BUSINESS WIRE)--ONK Therapeutics Ltd, an innovative natural killer (NK) cell therapy company, today announced that it has been awarded an Innovation Partnership Programme (IPP) grant by Enterprise Ireland (EI) to fund collaborative research at Trinity College Dublin, Ireland, led by Dr. David Finlay to optimize the metabolism and engineering of NK cells for improved cancer therapies.

Dr. Finlay, Associate Prof. in Immunometabolism in the Schools of Biochemistry and Immunology, and Pharmacy and Pharmaceutical Sciences, at Trinity College Dublin is a world-leading expert in NK cell metabolism. His group was the first to characterize cellular metabolic pathways in NK cells (reviewed in ⁽¹⁾) and to demonstrate the importance of NK cellular metabolism for the cytotoxic anti-tumor functions of these cells ⁽²⁾.

Active research is ongoing to optimize the efficacy of NK cell therapies against solid tumors by addressing the immunosuppressive tumor microenvironment (TME), where NK cell metabolism is impaired due to low glucose levels, oxygen deprivation (hypoxia), presence of inhibitory cytokines, and the higher concentration of tumor-derived metabolic end products, such as lactate.

To date, such improvement strategies to boost the efficacy of NK cells in the tumor microenvironment of solid cancers have centred on adding cytokines and other factors.

“We are taking a completely novel approach by addressing NK cell metabolism from the inside out, fundamentally engineering NK cells to better treat cancer by increasing their resistance to the adverse metabolic conditions generated by tumors,” said Prof. Michael O’Dwyer, founder and CSO at ONK Therapeutics. “In working with Dr. Finlay, we are collaborating with the pioneering expert in the field of NK immunometabolism.”

Under the terms of the collaboration, Trinity College Dublin retains any intellectual property (IP) arising out of the research collaboration, with ONK Therapeutics having an exclusive option to license the IP.

“In order to understand why cellular cancer immunotherapies are not effective in all cancer patients, scientists are actively trying to identify why certain patients respond and some do not and why some types of cancer can be successfully treated while others cannot. One emerging reason is that tumors can create metabolically unfavorable environments that might impact the effectiveness of immune cell therapies. My laboratory has the foremost expertise in NK cell metabolism placing us in a very strong position to address this challenge,” said Dr. Finlay.

“Manipulating NK cell metabolism to enhance anti-cancer function is completely novel and is only possible based on our discoveries over the past five years,” he said. “Our goal is to discover new targets within NK cells to be edited through CRISPR deletion or overexpression strategies. Detailed evaluation of the resistance of these cells to the adverse environments generated by tumors should support the development of enhanced NK cell therapies. It is an innovative approach to developing improved cellular therapies to treat cancer, in particular solid tumors.”

Lawrence Lee, Manager, Innovation Partnership Programme Enterprise Ireland, said, “We are delighted to support this innovative research that has the potential to generate real and tangible benefits for cancer patients in Ireland and across the globe. The project is aligned with Enterprise Ireland’s strategic goal of supporting world-leading research in Ireland and fostering relationships between industry and academic partners. Research initiatives such as this have the capacity to further advance Ireland’s international research reputation and lay the foundations for the jobs of the future.

The Enterprise Ireland funding⁽³⁾ covers 80% of the €373,295 project costs, with the industry partner, ONK Therapeutics providing €75,000 (20%) of the project costs. Trinity College Dublin will be recruiting two additional post-doctoral scientists into Dr. Finlay’s group over the two years of the project.

Chris Nowers, CEO of ONK Therapeutics, said, “We are highly ambitious in our goal to become a world-leading engineered NK cell therapy company that not only treats, but ultimately cures cancer. Our academic partnerships will deliver rich research insights and reinforce our own expertise as we aim to deliver new therapeutic options for patients in need.”

1. O’Brien KL., Finlay, DK. (2019) Immunometabolism and Natural Killer cell responses. Nature Reviews Immunology, May;19(5):282-290. doi: 10.1038/s41577-019-0139-2
2. Assmann N, O'Brien KL, Donnelly RP, Dyck L, Zaiatz-Bittencourt V, Loftus RM, Heinrich P, Oefner PJ, Lynch L, Gardiner CM, Dettmer K, Finlay DK. (2017) Srebp-controlled glucose metabolism is essential for NK cell functional responses. Nature Immunology. Sep 18. doi: 10.1038/ni.3838
3. IP 2021 0976 – ‘Metabolic reprogramming and engineering of NK cells for improved cancer therapy’

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For full release with image of Dr. Finlay and logos for Ireland’s ESIF, ERDF and Enterprise Ireland is available HERE.

ONK Therapeutics – www.onktherapeutics.com
ONK Therapeutics Ltd is an innovative cell therapy company dedicated to developing the next generation of ‘off-the-shelf’, dual-targeted NK cell therapies targeting solid and hematological cancers.

The company was founded in 2015, by Prof. O’Dwyer MD, of NUI Galway, an expert in translational multiple myeloma research, the tumor microenvironment, and exploitation of NK cells as cellular immunotherapy. Its core proprietary off-the-shelf cell therapy platform is based on a dual-targeted NK cell expressing both a chimeric antigen receptor (CAR) targeting a known tumor antigen and a TNF-related apoptosis-inducing ligand variant (TRAILv) targeting the death receptor pathway (i.e. DR4 or DR5). This unique approach has the potential to enhance efficacy by addressing both intrinsic (e.g. CAR engagement of a tumor-specific antigen) and extrinsic (e.g. signaling through the death receptor pathway) apoptotic pathways and to reduce the susceptibility to possible target antigen escape through the engagement of tumor antigen-independent TRAILv.

Its pre-clinical pipeline comprises four programs:

• The lead program, ONKT101, is a dual-targeted NK cell therapy incorporating a CD19 CAR and TRAILv targeting DR5, intended for the treatment of relapsed/refractory B cell malignancies. This program is partnered with Avectas, with the company having responsibility for development to Phase 1
• ONKT102 combines an optimized affinity CD38 CAR and a TRAILv targeting DR5, intended for the treatment of patients with relapsed/refractory multiple myeloma
• ONKT103 combines a TA-MUC1 CAR with a TRAILv targeting DR5, for the treatment of solid tumors
• ONKT104 combines a CLL-1 CAR with a TRAILv targeting DR4, for the treatment of AML

In addition to the unique off-the-shelf, dual-targeted NK cell therapy platform, the company has a strong focus on engineering strategies to enhance tumor homing and persistence in-vivo, and overcome exhaustion in the tumor microenvironment, including the exploration of proprietary gene edits, such as the deletion of checkpoint inhibitory receptors in NK cells.

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, ALSHC (principally Seamus Mulligan), and Enterprise Ireland.

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Enterprise Ireland – www.enterprise-ireland.com

Enterprise Ireland is the government organisation responsible for the development and growth of Irish enterprises in world markets. We work in partnership with Irish enterprises to help them start, grow, innovate and win export sales in global markets. In this way, we support sustainable economic growth, regional development and secure employment.

Innovation Partnership Programme (IPP0 grants are co-funded by the European Regional Development Fund (ERDF) under Ireland’s European Structural and Investment Funds (ESIF) Programmes 2014-2020.

Trinity College Dublin – www.tcd.ie
Trinity College Dublin, founded in 1592, is Ireland’s oldest university. Today it has a vibrant community of 19,000 students and is recognised internationally as Ireland’s premier university. Cutting-edge research, technology and innovation places the university at the forefront of higher education in Ireland and globally. It encompasses all major academic disciplines, and is committed to world-class teaching and research across a range of disciplines in the arts, humanities, engineering, science, social and health sciences. Trinity College Dublin is Ireland’s leading university and is currently 101st in the QS World University Rankings.

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