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ONK Therapeutics Enters into a Research Agreement with University of Galway to Support Optimization of its Dual-Targeted NK Cell Therapy against AML 

• Agreement with University of Galway, supervised by leading expert in the cellular environment in Acute Myeloid Leukaemia (AML), Dr. Eva Szegezdi
• Funded by ONK Therapeutics, the research will support engineering and optimization of its dual-targeted NK cell therapy candidate for AML (ONKT104)
• Aims to explore the potential added benefit of certain gene edits to enhance NK cell cytotoxicity, cytokine production and persistence in the cancer microenvironment in the context of AML

ONK Therapeutics Ltd, an innovative natural killer (NK) cell therapy company, today announced that it has entered into a research collaboration with the National University of Ireland, Galway (University of Galway) which provides access to unique expertise in evaluating the cancer cell microenvironment in Acute Myeloid Leukaemia (AML) and targeting of AML stem cells in models mimicking the bone marrow microenvironment. The research will support the optimization of ONK Therapeutics’ dual-targeted NK cell therapy program, ONKT104, being developed for the treatment of AML.

ONK Therapeutics will fund a year-long research program in the laboratory of Dr. Eva Szegezdi, lecturer in Biochemistry, University of Galway, Head of the Blood Cancer Network Ireland. She has particular expertise in the AML microenvironment as well as cell death pathways, especially those initiated by ‘so-called’ death ligands (e.g. TRAIL) used by effector immune cells. 

AML is the most common form of acute leukemia in adults. It is estimated that some 21,000 patients in the US and 18,000 in Europe are diagnosed with AML each year. It has a high unmet medical need having the lowest survival rate of all types of leukemia.

ONKT104 is a dual-targeted NK cell engineered to express a humanized scFv targeting the leukemic stem cell antigen CLL-1 (also known as CLEC12A) obtained through an option license agreement from Cellerant Therapeutics, together with ONK Therapeutics’ proprietary high-affinity TRAIL variant, targeting death receptor 4 (DR4). CLL-1 is selectively expressed on leukemic stem cells with no expression on normal hematopoietic stem cells, which ensures safer targeting and a lower risk of prolonged toxicity to normal bone marrow cells.  In pre-clinical research studies, a monoclonal antibody therapy targeting CLL-1 has revealed potential efficacy against AML cells and shown to be effective in reducing AML burden in a xenograft model. In addition, a CLL-1 CAR-T cell model has shown promising pre-clinical activity and has recently entered the clinic.

ONK Therapeutics believes its dual-targeted NK cell therapy approach may have several advantages over a CAR-T approach including shorter persistence of NK cells, reducing the risk of sustained neutropenia; proven inherent anti-AML activity of NK cells; the reduced likelihood of toxicity due to cytokine release syndrome or neurotoxicity; and the logistically simpler allogeneic, off-the-shelf nature of NK cells, reducing time to treatment once suitable patients are identified.

AML is a very challenging disease in which to achieve sustained, long term disease control due to the high plasticity and adaptability of AML stem cells, and the tendency for resistant cells to emerge and grow. In addition to targeting CLL-1, this project will evaluate multi-targeted approaches by combined targeting of other leukemia stem cell antigens.

ONK Therapeutics’ founder and CSO Prof Michael O’Dwyer said, “Alongside our in-house research, the project team at University of Galway will explore construct design, as well as the potential added benefit of certain gene edits to enhance NK cell cytotoxicity, cytokine production and persistence in the context of AML strengthening our ONKT104 program. The aim is to select an optimized candidate to take forward into clinical development as a treatment for patients with relapsed/refractory AML.”

Dr. Eva Szegezdi said, “The project will evaluate different constructs that may be able to achieve synergistic killing of cancer cells and reduce the emergence of disease resistance. These include the co-expression of CARs targeting other AML antigens, in addition to CLL-1, such as CD96, TIM3, and CD38 alongside the TRAIL variant.”

ONK Therapeutics was formed based on technology and intellectual property developed at University of Galway by Prof. Michael O’Dwyer, who retains his academic position as Professor of Haematology, Consultant Haematologist and HRB Clinician Scientist, alongside his role at the company. Over the past 12 months, ONK Therapeutics has expanded its team and operations at its headquarters and R&D facility in Ireland’s med-tech hub in Galway, where it now has 16 employees, with an additional 5 employees based in its US subsidiary in San Diego.

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