MaaT Pharma (EURONEXT: MAAT – the “Company”), a clinical-stage biotechnology company and a leader in the development of Microbiome Ecosystem Therapies^TM (MET) dedicated to enhancing survival for patients with cancer through immune modulation, announced that the first patient has been randomized in the IMMUNOLIFE Phase 2 clinical trial, a randomized multicenter study evaluating the potential of an oral pooled fecal microbiotherapy (MaaT033) in combination with Regeneron’s Cemiplimab (CB) in enhancing disease control rate versus best investigator’s choice (BIC) in patients with advanced non-small cell lung cancer (NSCLC) who have developed resistance to PD-1/PD-L1 blockade following antibiotic (ATB) exposure and who present ATB-induced gut dysbiosis.

The IMMUNOLIFE trial is evaluating MaaT033 in combination with CB vs BIC in 162 patients with advanced NSCLC who are refractory to immune checkpoint inhibitors (ICIs) and have received antibiotics. Patients are randomized (1:1) to receive either MaaT033 orally for one week prior to each cycle of CB (administered every 3 weeks for 6 months), followed by CB alone, or BIC. The primary objective is to assess whether the combination is associated with an improved disease control rate at 12 weeks compared to BIC. The study includes 14 centres in France, with patient enrolment of approximately 2 years and total CB treatment duration of 2 years. Primary results after 1-year follow-up post-treatment could be expected in late 2030. An interim futility analysis around H1 2027, after the 81^st randomized patient.

“Gut dysbiosis is increasingly recognized as a risk factor for immunoresistance to immunotherapy. MaaT033 is designed to restore microbiome balance and may help improve patients’ response to treatment,” said Lisa Derosa, MD, PhD at Gustave Roussy and coordinating investigator of the IMMUNOLIFE trial.

“We have built substantial evidence in our hemato-oncology programs that complex donor-derived products restore immune homeostasis in the context of pre-existing dysbiosis. This study represents an opportunity to further explore these findings in immuno-oncology in a well-defined patient population expected to show antibiotic-mediated dysbiosis,” said Hervé Affagard, CEO and co-founder of MaaT Pharma.

This trial, sponsored by Gustave Roussy, is part of MaaT Pharma’s exploratory strategy launched in 2022, which also includes the PICASSO trial, a Phase 2a randomized controlled trial sponsored by AP-HP in Paris evaluating Xervyteg^® (MaaT013) in combination with ICIs, ipilimumab (Yervoy^®) and nivolumab (Opdivo^®) for patients with metastatic melanoma. The Company has been informed by PICASSO's academic sponsor that topline results could not be available in Q4 2025 (as previously announced) and could now be expected in H1 2026. Overall, IMMUNOLIFE and PICASSO studies aim to contribute to the ongoing assessment of the Company’s research strategy, including indication, treatment line, and patient population. This will also inform on the clinical development of MaaT034, a co-cultured microbiome-based therapy and the Company’s next-generation drug candidate, designed to target large indications in solid tumors.

In parallel, data already generated and to be generated during the IMMUNOLIFE consortium will also fuel the Company’s AI platform and support the development of all the Company’s microbiome-based drug candidates.

The IMMUNOLIFE consortium includes leading academic institutions such as Gustave Roussy, INSERM, Paris Saclay University, INRAe, Hospital-University Institute (IHU) Méditerranée Infection and biotech companies. The consortium aims to address the challenge of primary resistance to ICI observed in advanced NSCLC patients following antibiotic exposure. The IMMUNOLIFE consortium receives funding from the French National Research Agency (“ANR-21-5 RHUS-0017 IMMUNOLIFE”).