Key keywords: EMA CHMP, MaaT Pharma, MaaT013, negative marketing authorization opinion, acute graft-versus-host disease (aGVHD), microbiome therapy, steroid-refractory aGVHD, hematopoietic stem cell transplant complications The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has officially issued a negative opinion recommending against the marketing authorization of MaaT Pharma’s lead investigational microbiome therapy MaaT013, marking a major regulatory setback for the French biotech firm and the broader microbiome therapeutic space. MaaT013 is an allogeneic, high-diversity microbiome therapy designed to restore disrupted gut microbiota in patients receiving allogeneic hematopoietic stem cell transplants (allo-HSCT). It was being evaluated for the treatment of grade 3 to 4 steroid-refractory acute graft-versus-host disease (SR-aGVHD), a life-threatening complication of allo-HSCT that occurs when donor immune cells attack the recipient’s healthy tissues, with current standard-of-care options delivering limited efficacy and 1-year mortality rates exceeding 70% for high-risk patients. The CHMP’s negative ruling was based on a full review of data from the pivotal Phase 3 HERACLES trial, which assessed MaaT013 in over 300 patients with SR-aGVHD across multiple global sites. Regulators concluded that the submitted data failed to establish a sufficiently positive benefit-risk profile for the therapy, citing inconsistencies in secondary endpoint outcomes and questions over the generalizability of trial results to the broader European patient population. Prior to the CHMP announcement, MaaT013 was widely viewed as one of the most advanced late-stage microbiome therapies in clinical development, with promising early-phase data leading to high investor and clinical community expectations for the asset. Following the release of the negative opinion, MaaT Pharma’s publicly traded shares dropped by more than 47% in intraday trading on Euronext Paris, erasing nearly €120 million in market capitalization in a single session. MaaT Pharma’s leadership has released a public statement acknowledging the CHMP opinion, noting that the company is conducting a full review of the regulator’s feedback to determine next steps, which may include requesting a re-examination of the opinion, adjusting the clinical development plan for MaaT013, or shifting focus to other global markets including the United States, where the company is currently in discussions with the FDA over potential regulatory pathways for the therapy. Industry analysts note that the ruling highlights the ongoing challenges facing novel microbiome therapies as they move through late-stage regulatory review, with regulators increasingly demanding clear, reproducible clinical benefit data alongside robust validation of mechanism of action for first-in-class assets in this emerging therapeutic category. For patients living with high-risk SR-aGVHD, the ruling means extended wait times for access to new treatment options, as existing standard therapies fail to deliver meaningful survival benefits for a majority of affected populations.