Zelluna has announced the submission of its Clinical Trial Application (CTA) to the UK Medicines and Healthcare products Regulatory Agency (MHRA) for ZI-MA4-1, its lead candidate and the world’s first MAGE-A4-targeting TCR-NK cell therapy for solid tumours.
The announcement follows the publication of compelling preclinical data for ZI-MA4-1 in the peer-reviewed journal Immunotherapy Advances, supporting the initiation of first-in-human clinical trials in 2026.
The CTA submission marks Zelluna’s transition from preclinical to clinical development and represents the successful delivery of all key milestones communicated for 2025, including completion of the preclinical data package, locking of the manufacturing process, production and quality testing of GMP clinical material and submission to the UK MHRA.
ZI-MA4-1 is a novel cell therapy that combines two powerful cancer-fighting mechanisms: the precise solid tumour targeting of T cell receptors (TCRs) with the potent and broad cancer-killing ability of Natural Killer (NK) cells.
The therapy targets MAGE-A4, a protein expressed across multiple solid tumours, including lung, ovarian, head and neck cancers and sarcomas.
Preclinical results published in Immunotherapy Advances demonstrated that ZI-MA4-1 effectively killed cancer cells across multiple tumour types, remained active despite common tumour escape mechanisms, triggered multiple anti-cancer immune responses and showed a favourable safety profile.
Manufactured in advance and stored frozen, ZI-MA4-1 is an off-the-shelf therapy that can be administered on demand, enabling repeat dosing and broad patient access.
"Submitting our first CTA is a transformational moment for Zelluna," said Namir Hassan, CEO of Zelluna.
"ZI-MA4-1 will be the first MAGE-A4-targeting TCR-NK cell therapy to enter clinical testing globally and represents the culmination of rigorous scientific, CMC and regulatory work."
"We now enter the most important phase of our journey – demonstrating the potential of TCR-NK therapies for patients with solid tumours."
"This publication validates our approach," added Luise Weigand, Chief Scientific Officer of Zelluna.
"With our preclinical data completed, manufacturing process locked and clinical material ready, we are well-positioned to begin clinical trials in 2026.”
The UK MHRA was selected for its strong track record in advanced therapy approvals and its collaborative early-phase regulatory pathways, providing an efficient and supportive environment for pioneering modalities such as TCR-NK therapies.
About the ZIMA-101 trial
The Phase I ZIMA-101 trial will evaluate ZI-MA4-1 in patients with advanced solid tumours, including ovarian cancer, head-and-neck cancer, squamous non-small-cell lung cancer and synovial sarcoma.
The study will assess safety, tolerability and early signs of efficacy, with initial clinical data expected in mid-2026, subject to regulatory approval.
The trial will be led by Professor Fiona Thistlethwaite at The Christie NHS Foundation Trust (Manchester, UK), with participation from Dr Andrew Furness at The Royal Marsden (London, UK).
"This is a huge step towards bringing the ZIMA-101 study into the clinic," said Professor Thistlethwaite, Chief Investigator for the trial.
"Combining the innate killing activity of NK cells with tumour-antigen-directed TCRs has the potential to deliver the level of potency needed in solid tumours while avoiding tumour escape.”
ZI-MA4-1 is supported by broad intellectual property coverage, including a landmark granted patent providing dominant protection across the TCR-NK field.