ZI-MA4-1 / Zelluna, UT MD Anderson Cancer Center - LARVOL DELTA

First-in-human Phase I study of ZI-MA4-1, a first-in-class MAGE-A4–targeting TCR-NK cell therapy in advanced solid tumours (ZIMA-101) (ESMO 2026) - No abstract available

First-in-human • Metastases • P1 data • Oncology • Solid Tumor • MAGEA4

Zelluna doses first solid tumour patient with ZI-MA4-1 in the ZIMA-101 Phase 1 trial (GlobeNewswire) - "The first patient was treated at The Christie NHS Foundation Trust in the United Kingdom, the largest single site cancer centre in Europe and the lead clinical site for the study where Professor Fiona Thistlethwaite serves as Chief Investigator for the study. ZIMA-101 is evaluating ZI-MA4-1, the world's first MAGE-A4-targeting TCR-NK cell therapy to enter clinical development, in patients with advanced MAGE-A4-positive solid tumours....Zelluna expects initial clinical data from the ZIMA-101 study to emerge from mid-2026."

P1 data • Trial status • Head and Neck Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Solid Tumor • Synovial Sarcoma

A Study to Test the Safety, Tolerability and Effect of ZI-MA4-1 for Patients With Locally Advanced or Metastatic Solid Malignancies (clinicaltrials.gov) - P1 | N=9 | Recruiting | Sponsor: Zelluna Immunotherapy AS

New P1 trial • Head and Neck Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma • MAGEA4

Preclinical development of ZI-MA4-1, the first optimised “off the shelf” MAGE-A4 targeting TCR-NK cells for advancement into the clinic for the treatment of solid tumors (ASGCT 2026) - "Introduction T cell receptor (TCR)-T cell-based cell therapies have shown clinical efficacy across many cancer types and represent an attractive strategy for targeting solid tumors. Conclusion Combining the innate cytotoxicity of NK cells with an affinity-enhanced MAGE-A4-specific TCR results in a potent and safe cellular product representing a promising and novel therapeutic off-the shelf paradigm for the treatment of multiple solid cancers. The application for the clinical trial, ZIMA-101, assessing ZI-MA4-1 in ovarian cancer, squamous non-small cell lung cancer, synovial sarcoma and head and neck cancer has been submitted and is anticipated to start this year."

Preclinical • Head and Neck Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma • CD8 • MAGEA4

Zelluna ASA: First Quarter 2026 results (The Manila Times) - "Total operating expenses: MNOK 20.4...Total loss: MNOK 20.4...Cash and cash equivalents: MNOK 49.3 as of 31 March 2026...Financial runway: into Q1 2027."

Commercial • Solid Tumor

Zelluna ASA activates first clinical site for ZIMA-101, marking entry into clinical execution (GlobeNewswire) - "This marks the transition of the study from clinical preparation to active trial execution of the ZIMA-101 study. The first activated clinical site is The Christie NHS Foundation Trust in the United Kingdom, where Professor Fiona Thistlethwaite serves as Chief Investigator for the study. ZIMA-101 is a first-in-human Phase 1 trial evaluating ZI-MA4-1, Zelluna’s lead TCR-NK product candidate....Activation of the second clinical site, The Royal Marsden, is expected in the near term....Initial clinical data from the ZIMA-101 study are expected to emerge from mid-2026."

First-in-human • P1 data • Trial status • Solid Tumor

Development of the first optimised "off the shelf" MAGE-A4 targeting TCR-NK cells for advancement into the clinic for the treatment of solid tumors (AACR 2024) - "Interestingly, we observe enhanced proliferation of ZI-MA4-1a cells after activation by MAGE-A4 expressing tumor cells, indicating that TCR-NK cells acquire further proliferative capacity when the TCR is triggered. Finally, we demonstrate higher activity of ZI-MA4-1a compared to KVL-a and benchmark TCR transduced T cells against antigen positive targets, and activity against antigen negative tumor cells escaping TCR-T cell recognition."

IO biomarker • Oncology • Solid Tumor • CD8 • MAGEA4

Zelluna announces collaboration with Etcembly for AI-enabled TCR engineering (The Manila Times) - "AI-enabled collaboration to engineer KKLC1-targeting TCRs for Zelluna's TCR-NK platform; Builds on successful engineering of MAGE-A4 TCR underpinning ZI-MA4-1, approved for clinical testing in February 2026....The engineered receptors will be fully owned by Zelluna and developed for use within Zelluna's proprietary TCR-NK platform. In-vitro data demonstrating safety, specificity and functional activity is now expected in Q4 2026."

Licensing / partnership • Solid Tumor

Zelluna Receives UK MHRA and Ethics Approval to Initiate ZIMA-101 First-in-Human Clinical Trial (The Manila Times) - "Trial to assess safety and preliminary activity in patients with advanced solid cancers; Initial clinical data expected to emerge from mid-2026...ZIMA-101 is designed to assess the safety, tolerability, and preliminary clinical activity of ZI-MA4-1 in patients with advanced solid cancers, including lung cancer, ovarian cancer, head and neck cancer, and sarcomas."

First-in-human • New P1 trial • P1 data • Head and Neck Cancer • Lung Cancer • Ovarian Cancer • Sarcoma

Preclinical assessment of MAGE-A4-specific TCR-NK cells against solid tumors. (PubMed, Immunother Adv) - "Lastly, TCR-NKs are not activated when co-cultured with normal cells, displaying a safe profile. Combining the innate cytotoxicity of NKs with MAGE-A4-specific targeting of an affinity-enhanced TCR, results in a potent and safe cellular product representing a promising and novel therapeutic off-the-shelf paradigm for the treatment of many solid cancers."

Journal • Preclinical • Hematological Disorders • Oncology • Solid Tumor • MAGEA4

Zelluna Reaches Major Milestone and Submits Clinical Trial Application in the UK for First-in-Human Study of ZI-MA4-1 (ZIMA-101), the World’s First MAGE-A4-Targeting TCR-NK Cell Therapy for Solid Tumours (GlobeNewswire) - "The Phase I clinical 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 data expected mid-2026 (subject to regulatory approval)."

New P1 trial • P1 data • Head and Neck Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Synovial Sarcoma

Zelluna Publishes Compelling Preclinical Data for ZI-MA4-1, the World's First MAGE-A4-Targeting TCR-NK Therapy for Solid Tumours (GlobeNewswire) - "Key results: Kills cancer cells effectively across multiple tumour types; Works even when tumours try to hide – remains active despite common escape mechanisms; Enhanced immune response – triggers multiple anti-cancer mechanisms; Good safety profile in preclinical studies....Strong preclinical data support planned clinical trial initiation in 2026....Zelluna plans to submit its Clinical Trial Application (CTA) in late 2025, with first patient data expected mid-2026."

New trial • Preclinical • Solid Tumor

Zelluna Receives Positive MHRA Feedback and Strengthens UK Clinical Strategy for ZI-MA4-1 Paving the Way for First-in-Human Trials in the UK (The Manila Times) - "This feedback provides alignment on the preclinical, manufacturing, clinical and regulatory pathway for ZI-MA4-1 and supports Zelluna’s planned Clinical Trial Application (CTA) submission later this year...'we are building strong momentum towards initiating a UK-based trial that could generate the first safety and efficacy data in 2026.'..Subject to CTA approval, the proposed Phase I trial will be an open-label, dose-escalation basket study evaluating the safety, tolerability and preliminary efficacy of ZI-MA4-1 across multiple solid tumours."

New P1 trial • Solid Tumor

Zelluna Q1 2025 slides highlight TCR-NK manufacturing breakthrough post-merger (Investing.com) - "The first quarter of 2025 was transformative for Zelluna, marked by the completion of its business combination with Ultimovacs ASA on March 3, 2025, accompanied by a private placement of MNOK 51.7...Zelluna’s pipeline consists of three main programs: ZI-MA4-1 targeting MAGE-A4, ZI-KL1-1 targeting KK-LC-1, and ZI-PR-1 targeting PRAME...Zelluna provided an update on the MultiClick Technology and UV1 Program inherited from Ultimovacs....two remaining trials, LUNGVAC and DOVACC, have completed enrollment with topline results expected during 2025....Zelluna outlined several key upcoming milestones that could serve as value inflection points. In the second half of 2025, the company expects to complete preclinical work, begin GMP manufacturing, and submit IND/CTA applications. Initial clinical readouts are anticipated in the first half of 2026."

Clinical data • M&A • Cervical Cancer • Gastric Cancer • Head and Neck Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Cancer • Sarcoma • Synovial Sarcoma

Development of the first optimised 'off the shelf' MAGE-A4 targeting TCR-NK cells for advancement into the clinic for the treatment of solid tumors (SITC 2024) - "Ethics Approval All ethical approval was obtained for this work. Use of human material was provided by the Regionale Komiteer for Medisinsk og helsefaglig forskningsetikk – REK:231235."

IO biomarker • Oncology • Solid Tumor • CD8 • MAGEA4 • TGFB1

A novel ‘off the shelf’ TCR-NK cell therapy platform for the treatment of solid tumours: development of optimised MAGE-A4 targeting TCR-NK cells for advancement into the clinic (SITC 2023) - "Conclusions Taken together, these data demonstrate the feasibility and potential of generating optimised TCR-NK cells from PB-NK resulting in a highly potent cell product combining TCR-mediated and innate NK killing functions. Based on the potency and safety profile, ZI-MA4–1 has advanced into manufacturing with a preclinical package underway to enable a clinical trial for treatment of patients with advanced solid tumours."

IO biomarker • Oncology • Solid Tumor • CD8 • MAGEA4