European Patent Office Grants ONK Therapeutics’ Foundational Patent for CISH Knockout in NK Cells for Use in Cancer Therapies

  • The European Patent Office (EPO) has granted WEHI a patent for CISH knockout (KO) in Natural Killer (NK) cells which is exclusively licensed to ONK Therapeutics for cell immunotherapy purposes, giving ONK key IP for CISH KO in human NK cells for use in cancer therapies, irrespective of cell origin
  • The CISH IP forms part of ONK’s broad and growing IP estate covering the optimization of persistence, metabolic profile and cytotoxic potential of its NK cell therapy platform

Galway, Ireland and San Diego, USA, 27 June 2023 – ONK Therapeutics Ltd, an innovative NK cell therapy company, today announced that the European Patent Office (EPO) has granted its licensed patent covering CISH knockout (KO) in NK cells, irrespective of the source of the NK cells, including human cord blood-derived, peripheral blood-derived, and NK cells derived from induced pluripotent stem cells (iPSCs).

The patent granted to ONK’s licensor, WEHI (Walter and Eliza Hall Institute of Medical Research), by the EPO is part of a portfolio which includes granted US, Australian, New Zealand and Japanese patents as well as pending applications in several other countries.

ONK licensed the patent family relating to the KO of CISH in NK cells in an exclusive global patent license agreement from WEHI in 2021. CISH KO has been shown to improve the persistence, metabolic profile, and cytotoxicity of NK cells. The patent granted by EPO specifically covers CISH KO NK cells per se, and cancer therapies that utilize NK cells with CISH KO as well as NK cells engineered with the foundational CISH KO in combination with IL-15 (soluble or engineered), TGFβR2 KO, or TGFβR2 KO and IL-15 (soluble or engineered).

ONK and WEHI continue to prosecute the CISH patent portfolio in a way to maximize its depth and breadth of scope. It forms part of ONK’s broad and growing IP estate covering the optimization of persistence, metabolic profile and cytotoxic potential of its NK cell therapy platform.

ONK Therapeutics’ CEO Chris Nowers said, “Editing of NK cells to knockout CISH has the potential to improve the potency and persistence of NK cell-based therapies and provide greater benefit to patients. We are actively exploring the merits of CISH KO alone or in combination with other gene edits such as TGFβR2 KO and IL-15 knock-in. We believe this is the foundational CISH KO patent, based on the earliest scientific discoveries and covers CISH KO NK cells from any source. We are excited to have this broad and evolving patent estate which underpins our scientific efforts in the field.”

WEHI’s Head of Biotechnology and Commercialisation Dr Anne-Laure Puaux said, “Cell-based therapies have demonstrated their enormous potential as disease-modifying therapies in oncology.  Partnerships and collaborations are key to advancing WEHI’s drug discovery and development programs, to help us take our research from the lab to the clinic. Through this license agreement with ONK Therapeutics, we are excited to support the opportunity to develop more potent cell-based therapies for the future benefit of cancer patients.”

-Ends-

About CISH and the WEHI patent

CIS (encoded by the gene CISH) is a member of the suppressor of cytokine signaling (SOCS) family of proteins. When NK cells are stimulated with growth factors, such as interleukin 15 (IL-15), which encourage their growth, survival, and killing capability, there is an increase in the activity of CIS protein, which acts as a brake or checkpoint, on further NK cell growth and function.

The WEHI team found that when CIS was removed from NK cells by deleting the CISH gene, the NK cells were more responsive to growth factors and had improved survival and killing capacity(1). Later studies found that removing CIS improved the metabolic fitness of NK cells, optimizing their ability to kill tumor cells(2-3).

1. Delconte, R., Kolesnik, T., Dagley, L. et al. CIS is a potent checkpoint in NK cell-mediated tumor immunity. Nat Immunol 17, 816–824, 2016

2. Daher et al., Targeting a cytokine checkpoint enhances the fitness of armored cord blood CAR-NK cells, Blood 137(5), 624-636, 2021

3. Zhu et al., Metabolic Reprograming via Deletion of CISH in Human iPSC-Derived NK Cells Promotes In Vivo Persistence and Enhances Anti-tumor Activity, Cell Stem Cell 27(2), 224-237.e6, 2020

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 NK cell metabolic health, persistence and anti-tumor effect 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.

Follow us on Twitter and LinkedIn.

International

Sue Charles, Charles Consultants – +44 7968 726585 sue@charles-consultants.com

Ireland

Ray Gordon, Gordon MRM – +353 87 2417373 ray@gordonmrm.ie

ONK Therapeutics Named Most Promising Company in BioSpace’s NextGen 2023 List

Galway, Ireland and San Diego, USA, 4 January 2023 – ONK Therapeutics, an innovative company dedicated to developing optimally engineered natural killer (NK) cell therapies to cure patients with cancer, is pleased to announced that it has been included in BioSpace’s NextGen “Class of 2023” list featuring the most promising new life sciences companies of 2023.

ONK is a successful and innovative biotech company developing a leading global position in the fast-growing NK cell therapy space, committed to growing its transatlantic team in Ireland and the USA. It has used its $21.5 million series A financing to make substantial progress in delivering against its ambition to establish a global leadership position within the off-the-shelf NK cell therapy area.

ONK’s optimally engineered NK cell therapy platform designed to improve the metabolic health, persistence and anti-tumor effect has been strengthened through a number of licensing agreements. These include world leading CRISPR/Cas9 gene editing and LNP delivery technologies from Intellia Therapeutics that will enable the company to take full advantage of its suite of proprietary edits, including the CISH knockout technology licensed globally from WEHI (Walter and Eliza Hall Institute of Medical Research), Melbourne, Australia. The company has also continued to progress its manufacturing plan as it drives towards GMP manufacturing and clinical trial supply. Concurrently ONK is strategically building out its corporate structure and diligently expanding its transatlantic team.

BioSpace, the leading source for life sciences news and careers, has been recognizing the most exciting startups in biotech and pharma for the past nine years in its NextGen list. 25 companies were selected this year. Organizations across all therapeutic areas are considered.

BioSpace’s editorial team analyzed multiple components as determining factors: finance, collaborations, pipeline, growth potential and innovation. Points are awarded for each criteria and companies ranked accordingly. This year’s list includes top-scoring organizations that launched between September 2021 and September 2022 with a Series A funding.

The accolade of being one of just 25 companies in BioSpace’s NextGen “Class of 2023” list recognizes ONK Therapeutics series A financing and its growth and achievements during 2022, following its international expansion with the opening of its US subsidiary, ONK Therapeutics, Inc, in 2020. In the US, ONK is based at Johnson & Johnson Innovation – JLABS @ San Diego, in the heart of the San Diego biotech cluster that is home to genomics, precision medicine, cell therapy and microbiome companies. In December 2022 ONK announced the appointment of Bruce McCreedy Ph.D. as Chief Scientific Officer (CSO), a member of the company’s Executive Leadership Team, based in the USA. It also expanded its European operations during the year with the opening of bespoke corporate offices in Galway, Ireland near its research labs.

CEO of ONK Therapeutics, Chris Nowers said, “We are delighted that our progress and innovative approach has been recognized by BioSpace and are thrilled to be included in the 2023 NextGen list. We have grown our experienced team by over 50% over the last year and have made key hires on the research, manufacturing, and corporate fronts. We feel having a transatlantic axis is very productive and we will continue to grow the company in both the USA and Ireland as we progress along our exciting journey to the clinic.”

The complete NextGen “Class of 2023” list can be viewed on BioSpace.

-ENDS-

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 NK cell metabolic health, persistence and anti-tumor effect 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 USA subsidiary, ONK Therapeutics, Inc. based at JLabs @ San Diego. Shareholders include Acorn Bioventures, Cormorant Asset Management, ALSHC (principally Seamus Mulligan), and Enterprise Ireland.

Follow us on Twitter @ONKTherapeutics and LinkedIn.

About BioSpace – www.biospace.com

BioSpace is the digital hub for life science news and jobs. We provide essential insights, opportunities and tools to connect innovative organizations and talented professionals who advance health and quality of life across the globe.

Contacts

For ONK Therapeutics

International
Sue Charles
Charles Consultants
+44 7968 726585
sue@charles-consultants.com

Ireland
Ray Gordon
Gordon MRM
+353 87 2417373
ray@gordonmrm.ie

For BioSpace
Chantal Dresner
Marketing Director, BioSpace
chantal.dresner@biospace.com

ONK Therapeutics Boosts Drug Development Experience and Expands US Presence with the Appointment of Bruce McCreedy Ph.D. as Chief Scientific Officer

  • Bruce McCreedy Ph.D. joins the Executive Leadership Team as Chief Scientific Officer, as the company continues to grow its US-based operations
  • Brings three decades of experience in drug development, including gene-edited cell therapy products
  • Responsible for steering ONK’s pre-clinical, optimally engineered NK cell therapy candidates through final IND-enabling studies and into the clinic
  • Scientific founder and former CSO Professor Michael O’Dwyer remains as an advisor to the company and board director

Galway, Ireland and San Diego, USA,  6 December 2022 – ONK Therapeutics, an innovative company dedicated to developing optimally engineered natural killer (NK) cell therapies to cure patients with cancer, today announced the appointment of Bruce McCreedy Ph.D. as Chief Scientific Officer (CSO). A member of the company’s Executive Leadership Team, he will be based in the USA.

Dr. McCreedy is a renowned immunologist and cell and gene therapy expert, who brings over three decades of experience in drug development, including differentiated gene-edited, cell therapy products. He has been responsible for leading research organizations through the design and execution of highly successful drug development programs including currently marketed products.

He joins ONK Therapeutics from Myeloid Therapeutics, Inc., where as CSO his responsibilities included all IND-enabling pre-clinical studies. Prior to this he served as SVP Cell Therapy and Immuno-Oncology Research at Nasdaq-listed Precision Biosciences, Inc., where he directed all R&D activities to create multiple, novel off-the-shelf allogeneic cell therapies for the treatment of cancer, and advanced three products into Phase I/II clinical studies in only five years. Previous industry positions held by Dr. McCreedy include Executive Vice President and Chief Development Officer for Neximmune, Inc., President and CEO of Fulcrum Pharma Developments, Inc. and Vice President of Clinical Virology and Diagnostics for Triangle Pharmaceuticals, Inc. (now Gilead Sciences). His earlier career involved roles at divisions of Roche and Organon. He received his Ph.D. in microbiology and immunology from the School of Medicine of Wake Forest University, North Carolina.

Dr. McCreedy succeeds ONK’s former CSO and scientific founder Professor Michael O’Dwyer, who is making a planned return to the role of full-time Professor of Hematology, responsible for clinical and translational research in blood cancers at the University of Galway, Ireland, where he has maintained a part-time role whilst CSO at ONK Therapeutics. Professor O’Dwyer remains as a board director of the company and as a scientific advisor providing ongoing expert counsel as ONK continues to grow and progress.

Welcoming Dr. McCreedy to the team, CEO of ONK Therapeutics, Chris Nowers said, “Bruce’s deep R&D leadership experience will be invaluable as ONK executes on its growth ambitions, advancing its portfolio of optimized NK cell therapies through IND and into human clinical trials. I look forward to working with Bruce as he further builds the momentum and expansion of our R&D teams in the USA and Ireland.“

He continued, “As a founder of the company we would like to thank Michael for the very significant input that he has made as we have built the company. His central contribution to our optimally engineered NK cell therapy platform has been invaluable, and we are pleased that the company will have the opportunity to draw on Michael’s extensive experience, as he returns to his full-time academic research role.”

ONK Therapeutics has used its $21.5 million series A financing, raised in December 2021, to make substantial progress in delivering against its ambition to establish a global leadership position within the off-the-shelf NK cell therapy area. ONK’s optimally engineered NK cell therapy platform designed to improve the metabolic health, persistence and anti-tumor effect has been strengthened through a number of licensing agreements. These include world-leading CRISPR/Cas9 gene editing and LNP delivery technologies from Intellia Therapeutics that will enable the company to take full advantage of its suite of proprietary edits, including the CISH knockout technology licensed globally from WEHI (Walter and Eliza Hall Institute of Medical Research), Melbourne, Australia. The company has also continued to progress its manufacturing plan as it drives towards GMP manufacturing and clinical trial supply. Concurrently ONK is strategically building out its corporate structure and diligently expanding its transatlantic team.

Bruce McCreedy Ph.D., CSO of ONK Therapeutics said, “I am excited to be joining ONK Therapeutics at a pivotal time in its development as it navigates its path towards clinical trials. I have been impressed by ONK’s innovative approach to developing optimally engineered NK cell therapies which I believe have the potential to make a significant contribution to the growing arsenal of cell-based therapies to treat and even to cure cancer, offering new hope for patients.”

-ENDS-

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 NK cell metabolic health, persistence and anti-tumor effect 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 USA subsidiary, ONK Therapeutics, Inc. based at JLabs @ San Diego. Shareholders include Acorn Bioventures, Cormorant Asset Management, ALSHC (principally Seamus Mulligan), and Enterprise Ireland.

Follow us on Twitter @ONKTherapeutics and LinkedIn.

International

Sue Charles, Charles Consultants – +44 7968 726585 sue@charles-consultants.com

Ireland

Ray Gordon, Gordon MRM – +353 87 2417373 ray@gordonmrm.ie

ONK Therapeutics Presents Promising In-Vivo Data of its Optimized Affinity CD38 CAR-NK Candidate, Being Developed for the Treatment of Multiple Myeloma

ONK Therapeutics Presents Promising In-Vivo Data of its Optimized Affinity CD38 CAR-NK Candidate, Being Developed for the Treatment of Multiple Myeloma

  • First in-vivo data for ONKT102, a fully human, optimized affinity CD38 CAR-NK cell therapy
  • Data showed potent anti-tumor activity in-vitro and in-vivo of cord-derived ONKT102 in a CD38 positive tumor model of multiple myeloma
  • Poster presented at the International Myeloma Society 2022, 25-27 August 2022, Los Angeles, USA by CSO Prof. Michael O’Dwyer

Galway, Ireland and San Diego, USA,  29 August 2022 – 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.

-ENDS-

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.

Follow us on Twitter @ONKTherapeutics and LinkedIn.

International

Sue Charles, Charles Consultants – +44 7968 726585 sue@charles-consultants.com

Ireland

Ray Gordon, Gordon MRM – +353 87 2417373 ray@gordonmrm.ie

ONK Therapeutics Brings in US Financial Experience with the Appointment of Dr. Allan Reine as Independent Non-Executive Director

  • Allan Reine joins the Board as independent Non-Executive Director
  • Brings significant experience as CFO of NASDAQ-listed biotechs, where he helped raise over $700 million
  • Over 20 years in the biotechnology industry with relevant experiences as a biotech CFO, portfolio management, sell-side analyst and investment banking

Galway, Ireland and San Diego, USA, 23 March 2022 – ONK Therapeutics, an innovative company dedicated to developing optimally engineered natural killer (NK) cell therapies to cure patients with cancer, today announced that it has appointed Allan Reine as independent Non-Executive Director to its Board.

Dr. Reine brings significant experience to ONK Therapeutics’ Board from both the life sciences industry and in financial services. His experience as Chief Financial Officer (CFO) at NASDAQ-listed biotech companies and as a life science investor will be invaluable to ONK as it executes on its growth ambitions, progressing its portfolio of NK cell therapies towards human clinical trials.

In addition, as part of his role on the Board of ONK Therapeutics, Dr. Reine will serve as Chair of the Audit Committee.

Dr. Reine currently serves as CFO at Foghorn Therapeutics, Inc. (NASDAQ: FHTX) where he helped lead the company’s initial public offering (IPO). Prior to this, Dr. Reine was CFO of Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS). In these positions, Dr. Reine has been involved in over $700 million of equity and collaboration financing. Prior to his CFO roles, he gained over a decade of experience at New York based financial institutions, managing various healthcare portfolios focused on biotechnology and pharmaceutical companies, most recently at Lombard Odier Asset Management. He started his career at CIBC World Markets where he worked in both biotechnology investment banking and biotechnology equity research.

Dr. Reine received his M.D. from the University of Toronto and a Bachelor of Science in statistical sciences from the University of Western Ontario.

Welcoming Dr. Reine to the Board, Chairman of ONK Therapeutics, Hugh O’Dowd said, “ONK Therapeutics has made very significant progress in delivering against its ambition to establish a global leadership position within the off-the-shelf, NK cell therapy area. Following its recent $21.5 million series A funding and its CRISPR/Cas9 licensing agreement with Intellia Therapeutics, the company is both well financed and well equipped to expand its R&D and manufacturing, as it advances its exciting portfolio of pre-clinical assets through IND enabling studies.”

Dr. Allan Reine, Non-Executive Director of ONK Therapeutics said, “I very much look forward to working with the Board and the Executive Team to support the company, and help steer it through its next stages of growth. I have been impressed by ONK’s innovative approach to developing optimally engineered NK cell therapies which I believe have the potential to make a significant contribution to the growing arsenal of cell-based therapies to treat and even to cure cancer, offering new hope for patients.”

-ENDS-

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.

Follow us on Twitter @ONKTherapeutics and LinkedIn.

International

Sue Charles, Charles Consultants – +44 7968 726585 sue@charles-consultants.com

Ireland

Ray Gordon, Gordon MRM – +353 87 2417373 ray@gordonmrm.ie

Intellia and ONK Therapeutics Announce Collaboration to Advance Allogeneic CRISPR-Edited NK Cell Therapies for the Treatment of Patients with Cancer

  • Collaboration combines Intellia’s genome editing platform with ONK’s optimized natural killer (NK) cell therapy platform
  • Intellia grants ONK non-exclusive rights to its ex vivo genome editing and LNP delivery technologies and exclusive rights to certain guide RNAs for up to five allogeneic CRISPR-edited NK cell therapies
  • ONK is responsible for the research, clinical development and commercialization of engineered NK cell therapies derived from collaboration
  • Intellia to receive global co-development and co-commercialization options for up to two CRISPR-edited NK cell therapies with lead commercialization rights in the U.S.

CAMBRIDGE, Mass., and GALWAY, Ireland and SAN DIEGO, Calif., Feb. 15, 2022 – Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapies leveraging CRISPR-based technologies, and ONK Therapeutics Ltd., an innovative company dedicated to developing optimally engineered natural killer (NK) cell therapies to cure patients with cancer, today announced a licensing and collaboration agreement. NK cells are specialized, naturally occurring immune cells that play a critical role in immune activation against abnormal cells, including cancer cells. NK cells have gained significant attention in the field of cancer immunotherapy and various approaches are being explored to effectively develop and engineer NK cell-based cancer immunotherapy.

The agreement grants ONK a non-exclusive license to Intellia’s proprietary ex vivo CRISPR/Cas9-based genome editing platform and its lipid nanoparticle (LNP)-based delivery technologies to develop up to five allogeneic NK cell therapies. ONK will receive exclusive rights to certain Intellia guide RNAs (gRNAs) resulting from the collaboration for use in engineering those NK cell products. ONK will be responsible for preclinical and clinical development for the engineered NK cell therapies covered under the agreement. Intellia will be eligible to receive up to $184 million per product in development and commercial milestone payments, as well as up to mid-single digit royalties on potential future sales. In addition, the agreement grants Intellia options to co-develop and co-commercialize up to two products worldwide with rights to lead commercialization in the U.S. ONK retains lead commercialization rights ex-U.S. This co-development and co-commercialization option excludes ONK’s lead product ONKT-102, which is being developed for the treatment of patients with relapsed / refractory multiple myeloma, for which ONK retains sole rights. If Intellia chooses to exercise the co-development and co-commercialization option on an investigational product, in lieu of the potential royalties and milestones, Intellia will share 50 percent of any future profit and loss generated by the product.

“We look forward to working with ONK in the development of allogeneic NK cell therapies for patients with cancer. This collaboration, which combines Intellia’s industry-leading CRISPR technology platform and ONK’s expertise in NK cell technology, offers yet another powerful example of how we’re leveraging our strategic collaborations to address life-threatening diseases for patients in need,” said Intellia President and Chief Executive Officer John Leonard, M.D.

“We believe combining Intellia’s ex vivo genome editing and LNP delivery platforms with our suite of proprietary NK cell gene edits has the potential to create optimally engineered NK cells with enhanced cytotoxicity, persistence and an improved metabolic profile that hold tremendous promise to advance the treatment of both hematologic malignancies and solid tumors. We are excited to partner with Intellia and are looking forward to a collaboration that allows us to continue to deliver against our strategy, as we evolve into a clinical-stage company,” said ONK Therapeutics Chief Executive Officer Chris Nowers.

About Intellia Therapeutics

Intellia Therapeutics, a leading clinical-stage genome editing company, is developing novel, potentially curative therapeutics leveraging CRISPR-based technologies. To fully realize the transformative potential of CRISPR-based technologies, Intellia is pursuing two primary approaches. The company’s in vivo programs use intravenously administered CRISPR as the therapy, in which proprietary delivery technology enables highly precise editing of disease-causing genes directly within specific target tissues. Intellia’s ex vivo programs use CRISPR to create the therapy by using engineered human cells to treat cancer and autoimmune diseases. Intellia’s deep scientific, technical and clinical development experience, along with its robust intellectual property portfolio, have enabled the company to take a leadership role in harnessing the full potential of genome editing to create new classes of genetic medicine. Learn more at intelliatx.com. Follow us on Twitter @intelliatx.

About ONK Therapeutics

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.

Learn more at www.onktherapeutics.com. Follow us on Twitter @ONKTherapeutics and LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, express or implied statements regarding Intellia’s beliefs and expectations regarding: its strategy, business plans and focus; its ability to quickly and efficiently realize the scope and potential of its genome editing technology; its ability to maintain, expand and maximize its intellectual property portfolio and pipeline as well as accelerate clinical validation for its platform, including through its collaboration with ONK Therapeutics; the therapeutic value and development potential of CRISPR/Cas9 genome editing technologies and therapies; its ability to combine its CRISPR genome editing platform with ONK Therapeutics’ natural killer (NK) cell therapy platform to create successful therapeutic products; and the expected strategic benefits of any current or future collaborations, including the potential to generate revenue from such collaborations and related products, including products developed in collaboration with ONK Therapeutics.

Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events, and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks related to Intellia’s ability to protect and maintain its intellectual property portfolio; risks related to Intellia’s relationship with third parties, including its licensors and licensees; risks related to the ability of Intellia’s licensors to protect and maintain their intellectual property position; uncertainties related to the authorization, initiation and conduct of studies and other development requirements for the new company’s product candidates; the risk that any one or more of the collaboration product candidates will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies; and the risk that Intellia’s collaboration with ONK Therapeutics or its other collaborations will not continue or will not be successful. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Intellia’s most recent annual report on Form 10-K and quarterly report on Form 10-Q filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in Intellia’s other filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release represent Intellia’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Intellia explicitly disclaims any obligation to update any forward-looking statements, except as required by law.

Contacts:

For Intellia:

Investors:
Ian Karp
Senior Vice President, Investor Relations and Corporate Communications
+1-857-449-4175
ian.karp@intelliatx.com

Lina Li
Director, Investor Relations
+1-857-706-1612
lina.li@intelliatx.com

Media:
Matt Crenson
Ten Bridge Communications
+1-917-640-7930
media@intelliatx.com
mcrenson@tenbridgecommunications.com

For ONK:

International:
Sue Charles
Charles Consultants
+44 7968 726585
sue@charles-consultants.com

Ireland:
Ray Gordon
Gordon MRM
+353 87 2417373
ray@gordonmrm.ie

ONK Therapeutics Announces $21.5M Series A Financing to Advance Pipeline of Next-Generation Optimally Engineered Off-the-Shelf NK Cell Therapies

  • $21.5 million Series A round led by current investors Acorn Bioventures and ALSHC, joined by new investor Cormorant Asset Management
  • Financing will drive multiple pre-clinical programs through IND-enabling studies and the continued progression of a GMP manufacturing capability

Galway, Ireland and San Diego, USA, 06 January 2022 – ONK Therapeutics, an innovative NK cell therapy platform company, today announced the closing of its $21.5 million Series A financing, led by current investors Acorn Bioventures and ALSHC, who were joined by Cormorant Asset Management.

The financing will enable ONK to maintain its strong momentum as it advances pre-clinical programs through comprehensive IND-enabling studies, including in-vivo proof-of-concept models across multiple programs. ONK will also continue progress towards a GMP manufacturing capability, as it optimizes both its proprietary cell engineering platform and process development.

ONK’s pipeline currently has three programs in pre-clinical development across both hematological malignancies and solid tumors. The Company is pioneering optimally engineered natural killer (NK) cell therapies, utilising a suite of engineering strategies to optimize cytotoxic potential, metabolic health and persistence of NK cells, while reducing the potential for their exhaustion in the tumor microenvironment. This is made possible through the Company’s ability to achieve unique proprietary gene edits.

ONK’s comprehensive owned and exclusively licensed patent estate covers CISH knockout (KO) in the field of human NK cells for the treatment of cancer, irrespective of the NK cell source; the expression of high affinity, membrane bound,TNF-related apoptosis-inducing ligand variants (TRAILv); and the deletion of checkpoint receptors in NK cells, including extracellular proteins CD96, TIGIT, Siglec-7 and PD-1.

These different strategies are being employed across the ONK pre-clinical product portfolio, including:

  • ONKT102, the Company’s lead program, an optimized affinity CD38 CAR (chimeric antigen receptor) NK cell therapy being developed for the treatment of patients with relapsed refractory multiple myeloma
  • ONKT104, a CLL-1 CAR-NK program targeting AML stem cells, which is advancing through later stages of its pre-clinical evaluation
  • ONKT103, which is being optimized to treat solid tumors such as Ovarian, Breast and Non-Small Cell Lung Cancer (NSCLC) and is based on tumor associated MUC-1 targeting CAR NK cells

In addition, these programs will explore incorporating further novel gene edits, such as CISH KO and TRAIL variants targeting DR5 or DR4.

ONK has also recently started two programs focused on the potential of highly functional CISH KO NK cells, namely:

  • ONKT105, exploring CISH KO cord blood derived NK cells
  • ONKT106, exploring CISH KO iPSC derived NK cells

The Company also continues to make significant progress on the manufacturing front, optimizing its process development, gene editing capability, efficient expansion techniques and its cryopreservation capability. In combination, these will support manufacturing as part of ONK’s progress towards GMP manufacturing of large numbers of NK cell therapy batches from a single cord.

Chris Nowers, ONK Therapeutics’ CEO said, “We thank our existing investors for their continued support and are pleased to welcome Cormorant Asset Management as a new investor and Andy Phillips to our Board, as we continue against our goal to optimally engineer, off-the-shelf, NK cell therapies to potentially cure patients with cancer. This financing will allow us to continue to deliver against our focused strategy, funding significant program progression, organizational development, and company growth. Within the next 18 months, we have the potential for multiple IND approvals to enable our evolution into a clinical-stage company.”

Commenting on the investment, Isaac Manke, Ph.D., Partner at Acorn Bioventures said, “Over the 12 months of our investment, ONK Therapeutics has made excellent progress in advancing both its innovative next-generation NK cell therapy platform and across its exciting portfolio of pre-clinical assets. We are pleased to continue our support and to have introduced Cormorant Asset Management as a new investor to join with ourselves and founding investor ALSHC.”

Andy Phillips, Ph.D., Managing Director at Cormorant Asset Management said, “We are impressed by the Company’s potential to make a highly innovative contribution to the quickly evolving field of NK cell therapies, which we believe have the opportunity to improve the lives of patients in need of new treatments for their disease. We are pleased to join the current investor groups in financing ONK as it looks forward to important proof of principle in vivo data and additional value catalyzing milestones.”

-ENDS-

About ONK Therapeutics – www.onktherapeutics.com

ONK Therapeutics is an innovative cell therapy company dedicated to developing the next generation of off-the-shelf, optimally engineered natural killer (NK) cell therapies targeting both hematological malignancies and solid tumors.

The Company was founded in 2015, by Prof. Michael 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 optimally engineered NK cells that express not only a specific tumor antigen targeted CAR, but also have undergone different gene edits (e.g. CISH KO and CD38 KO) and additional construct features including a TNF-related apoptosis-inducing ligand variant (TRAILv) targeting the death receptor pathway via DR4 or DR5. This pioneering approach has the clear goal to maximize the cytotoxic potential, metabolic health and persistence of the engineered NK cells.

ONK’s current pre-clinical pipeline comprises three programs:

  • ONKT102 combines an optimized affinity CD38 CAR NK product candidate that incorporates a CD38 KO, intended for the treatment of patients with relapsed/refractory multiple myeloma
  • ONKT103 combines a TA-MUC1 CAR NK product candidate, for the treatment of solid tumors
  • ONKT104 combines a CLL-1 CAR NK product candidate, for the treatment of AML

In addition, these programs will explore incorporating further novel gene edits, such as CISH KO and TRAIL variants targeting DR5 and DR4.

ONK has also initiated two programs focused on the potential of highly functional CISH KO NK cells, namely:

  • ONKT105, exploring CISH KO cord blood derived NK cells
  • ONKT106, exploring CISH KO iPSC derived NK cells

ONK has an exclusive global patent license agreement with Australia’s Walter and Eliza Hall Institute of Medical Research (WEHI) providing the Company with rights to CISH knockout (KO) in the field of human NK cells for the treatment of cancer, irrespective of the NK cell source. CISH KO is a highly researched edit in NK cells for which the first US patent has since been granted to WEHI.

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.

Follow us on Twitter @ONKTherapeutics and LinkedIn.

International

Sue Charles, Charles Consultants – +44 7968 726585 sue@charles-consultants.com

Ireland

Ray Gordon, Gordon MRM – +353 87 2417373 ray@gordonmrm.ie

USPTO Grants ONK Therapeutics’ Foundational Patent for CISH Knockout in NK Cells for Use in Cancer Therapies

  • The US Patent and Trademark Office (USPTO) has granted ONK Therapeutics’ patent for CISH knockout (KO) in Natural Killer (NK) cells based on the earliest scientific discoveries
  • The patent, under exclusive global license from WEHI, gives ONK key IP for CISH KO in human NK cells for their use in cancer therapies, irrespective of cell origin
  • The CISH IP adds to ONK’s broad and growing IP estate covering the optimization of persistence, metabolic profile and cytotoxic potential of its NK cell therapy platform

Galway, Ireland and San Diego, USA, 9 September 2021 – ONK Therapeutics Ltd, an innovative NK cell therapy company, today announced that the US Patent and Trademark Office (USPTO) has granted its licensed patent that covers CISH knockout (KO) in NK cells, irrespective of the source of the NK cells, including, for example, human cord blood-derived and human induced pluripotent stem cell (iPSC)-derived cells (Patent No. 11104735).

Earlier this year ONK entered into an exclusive global patent license agreement with Australia’s Walter and Eliza Hall Institute of Medical Research (WEHI) providing it rights to CISH KO in the field of human NK cells for the treatment of cancer, with the right to sublicence.

“We are excited to have this unparalleled opportunity to explore the potential of CISH KO in human NK cells. We believe this is the foundational patent, based on the earliest scientific discoveries which cover CISH KO NK cells from any source, and we intend to evaluate this edit in both umbilical cord blood and iPSC-derived NK cells,” said ONK Therapeutics’ CEO Chris Nowers.

CISH KO has been shown to improve the persistence, metabolic profile, and cytotoxic potential of NK cells. While several other companies and academic centers are exploring the potential of a CISH KO on NK cells, the research team at WEHI, in 2015, was the first to show the critical role CIS, the protein encoded by CISH, plays in negatively regulating the function of NK cells.

Prof. Michael O’Dwyer, founder and CSO of ONK Therapeutics said, “Editing of NK cells to knock out CISH has the potential to improve the potency of the NK cell-based therapies and provide greater benefit to patients.”

We are building an unrivaled and broad IP estate against multiple NK cell checkpoint receptors, including extracellular proteins CD96, TIGIT, Siglec-7 and PD-1 as part of our innovative strategy to engineer a highly differentiated NK cell therapy platform that has broad potential across both hematological malignancies and solid tumors.”

WEHI’s Head of Biotechnology and Commercialisation Dr Anne-Laure Puaux said, “Cell-based therapies have demonstrated their enormous potential as disease-modifying therapies in oncology.  By licensing our intellectual property to ONK Therapeutics we are supporting the opportunity to develop more potent cell-based therapies for the future benefit of cancer patients.”

In addition to this granted CISH KO US patent, ONK Therapeutics has filed a US continuation patent application. Parallel filings are also under review in the EU by the European Patent Office (EPO) as well as in China, Japan, Australia and New Zealand, thus providing excellent coverage for the company’s commercial interests.

-Ends-

About CISH and the WEHI patent

CIS (encoded by the gene CISH) is a member of the suppressor of cytokine signaling (SOCS) family of proteins. When NK cells are stimulated with growth factors, such as interleukin 15 (IL-15), which encourage their growth, survival, and killing capability, there is an increase in the activity of CIS protein, which acts as a brake or checkpoint, on further NK cell growth and function.

The WEHI team found that when CIS was removed from NK cells by deleting the CISH gene, the NK cells were more responsive to growth factors and had improved survival and killing capacity(1). Improving the metabolic fitness of NK cells to enhance glycolysis and oxidative phosphorylation is important for optimizing the anti-tumor activity of NK cells, especially against solid tumors(2-3).

1. Delconte, R., Kolesnik, T., Dagley, L. et al. CIS is a potent checkpoint in NK cell–mediated tumor immunity. Nat Immunol 17, 816–824 (2016) https://www.nature.com/articles/ni.3470?proof=t

2. Daher et al., Targeting a cytokine checkpoint enhances the fitness of armored cord blood CAR-NK cells Blood Sept 9, 2020

3. Zhu et al., Metabolic Reprograming via Deletion of CISH in Human iPSC-Derived NK Cells Promotes In Vivo Persistence and Enhances Anti-tumor Activity Cell Stem Cell Sept 3, 2020

Caption: CISH gene knockout confers enhanced metabolic profile on NK cells, created with BioRender.com

Copyright: ONK Therapeutics Ltd

About 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:

  • 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 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.

Follow us on Twitter and LinkedIn.

International

Sue Charles, Charles Consultants – +44 7968 726585 sue@charles-consultants.com

Ireland

Ray Gordon, Gordon MRM – +353 87 2417373 ray@gordonmrm.ie

ONK Therapeutics’ CSO Prof. M O’Dwyer and his Academic Group Present New Data Showing the Benefit of Knocking Out the Inhibitory Receptor CD96 on Human NK Cells in the Context of Multiple Myeloma at EHA 2021

  • The checkpoint inhibitor CD96 was shown conclusively to be an inhibitory receptor on human NK cells in the presence of multiple myeloma (MM) cells expressing CD155
  • CD96 knock out (KO) using CRISPR/Cas9 gene editing enhanced both NK cell cytotoxicity and cytokine release
  • Efficient engineering of NK cells to genetically eliminate inhibitory receptor expression has the potential to overcome exhaustion and immune evasion in the tumor microenvironment

Galway, Ireland and San Diego, USA, 11 June 2021 – ONK Therapeutics Ltd, an innovative natural killer (NK) cell therapy company, welcomes new data presented by John Daly from the academic lab of CSO, Prof. Michael O’Dwyer at the Annual European Hematology Association 2021 Virtual Congress illustrating the merit of knocking out the checkpoint inhibitory receptor for CD96 on NK cells in the context of MM.

The data is based on research studies carried out at the National University of Ireland, Galway (NUI Galway), College of Medicine, Nursing and Health Sciences, by Prof. O’Dwyer’s academic research group.

Contradictory data had previously shown that CD96 could be both an activating and an inhibitory receptor on human NK cells, depending on the tumor type being examined.  The data presented during the poster presentation demonstrate conclusively that in the case of MM cells expressing CD155, CD96 is a human NK cell inhibitory receptor, regulating both cytotoxicity and cytokine release. Experiments using CRISPR/Cas9-mediated KO of CD96 in primary NK cells resulted in enhanced cytotoxicity and cytokine release compared to controls. Studies carried out in parallel also demonstrated a similar beneficial effect of CRISPR/Cas9-mediated KO of TIGIT in primary NK cells.

Furthermore, NK cells obtained from MM patient bone marrow had particularly high levels of CD96 expression, suggesting NK cells in the bone marrow of MM patients are more likely to be susceptible to CD155 mediated immune-evasion.

These new insights support knocking out inhibitory checkpoint receptors, including CD96 KO and TIGIT KO as a promising approach to improving the functionality of off-the-shelf engineered NK cell therapies for the treatment of cancer.

E-poster presentation title: Knockout of CD96 or TIGIT using CRISPR/Cas9 enhances NK induced
cytotoxicity and cytokine production in the presence of CD155 expressing myeloma cells.

Author(s)/Presenters: John Daly, Mark Gurney, Michael O’Dwyer.

Session title: Myeloma and other monoclonal gammopathies – Biology & Translational Research.

Abstract number: EP941

Date and Time: Available on the virtual platform as an e-poster Friday, June 11 at 9:00 CEST.

Download a copy HERE.

Chris Nowers, ONK Therapeutics’ CEO said, “The studies carried out by Prof. O’Dwyer’s academic research group are expanding our deep understanding of NK cell biology and are helping to confirm certain gene constructs and edits that will enhance NK cell cytotoxicity, cytokine production and persistence in the tumor microenvironment.  Gene edited NK cells lacking CD96 and/or TIGIT could therefore be beneficial for treating CD155 expressing malignancies, such as Multiple Myeloma.”

ONK Therapeutics was formed based on technology and intellectual property developed at NUI Galway by Prof. O’Dwyer. The Company is developing off-the-shelf, optimized NK cell therapies for cancer that utilize dual-targeting of the death receptor pathway in addition to incorporating a CAR, along with further strategies that utilize novel gene editing approaches to enhance persistence, metabolic profile, and cytotoxic potential. ONK has exclusive licenses to a broad intellectual property (IP) against a wide range of NK cell checkpoints, including CD96 and TIGIT.

-Ends-

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

Follow us on Twitter and LinkedIn.

Media enquiries (for ONK Therapeutics)

International

Sue Charles, Charles Consultants – +44 7968 726585 sue.charles59@outlook.com

Ireland

Ray Gordon, Gordon MRM – +353 87 2417373 ray@gordonmrm.ie

 

 

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 and San Diego, USA, 8 June  2021 – 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’

-Ends-

Caption: Dr. David Finlay, Associate Professor, Trinity College Dublin, Ireland
Copyright: Dr. David Finlay
Profile: https://www.tcd.ie/Biochemistry/research/finlay/
Twitter: @DavidFinlayTCD
LinkedIn: www.linkedin.com/in/david-finlay-tcd/

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.

Follow us on Twitter and LinkedIn.

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.

Media enquiries 

For ONK Therapeutics 

International

Sue Charles, Charles Consultants – +44 7968 726585 sue.charles59@outlook.com

Ireland

Ray Gordon, Gordon MRM – +353 87 2417373 ray@gordonmrm.ie

For Enterprise Ireland

Paul Daly, Press Office, Enterprise Ireland +353 87 2235197 paul.daly@enterprise-ireland.com

For Trinity College Dublin

Thomas Deane, Media Relations Officer, Communications – +353 1 896 4685 / 086 787 0748  deaneth@tcd.ie