MaaT013 Microbiome Therapy EMA Approval — PatSnap Eureka
MaaT013: Europe's First EMA-Approved Microbiome Therapy for Steroid-Refractory Acute GvHD
MaaT013, a pooled-donor full-ecosystem microbiome drug product by MaaT Pharma, has received EMA conditional marketing authorization — setting regulatory precedent for the entire class of live biotherapeutic products in Europe.
Gut Dysbiosis as the Engine of SR-aGvHD Immunopathology
Steroid-refractory acute graft-versus-host disease (SR-aGvHD) carries high transplant-related mortality and lacks well-established second-line therapies. Retrieved results consistently frame its pathophysiology around gut microbiome dysbiosis as a central amplifier of immune-mediated tissue damage following allogeneic hematopoietic stem cell transplantation (HSCT).
A large retrospective cohort study of 857 HSCT recipients confirmed that gut microbiome diversity at engraftment correlates inversely with GvHD severity and transplant-related mortality. Patients with low intestinal diversity showed a 3.4-fold increased risk of grade III–IV acute GvHD. Loss of short-chain fatty acid (SCFA)-producing taxa — including Blautia spp., Ruminococcus spp., and Faecalibacterium prausnitzii — compromises intestinal barrier integrity, increases microbial translocation, and amplifies alloreactive T-cell responses.
This mechanistic understanding, corroborated by metagenomic studies published in Frontiers in Immunology, forms the scientific foundation for MaaT013. The European Medicines Agency (EMA) classified pooled fecal microbiota as a biological medicinal product, enabling a conditional marketing authorization pathway for this first-in-class therapy.
Key Data Points from MaaT013 Clinical Evidence
All values derived from retrieved patent filings and peer-reviewed publications. These represent signals within the retrieved dataset only.
REG3α Biomarker Stratification: Day-28 ORR
Lower baseline REG3α predicts significantly higher response to MaaT013 microbiome therapy (n=62 HSCT recipients).
Gut Diversity vs. GvHD Risk: 857-Patient Cohort
Low intestinal diversity at HSCT engraftment drives 3.4-fold increased risk of grade III–IV acute GvHD.
Three Distinct Innovation Layers in MaaT013's Development
The MaaT Pharma IP portfolio clusters around the drug product itself, its GMP manufacturing process, and a companion diagnostic framework — each protected by distinct patent filings.
Full-Ecosystem Pooled-Donor Microbiome Drug Product
MaaT013 is a pharmaceutical-grade preparation of pooled fecal microbiota from multiple healthy screened donors, designed to maximize microbial diversity and ensure consistent engraftment. This contrasts with single-donor FMT and defined bacterial consortia approaches. Administered via enema, the product restores SCFA-producing taxa including Blautia, Ruminococcus, and Faecalibacterium, suppressing alloreactive T-cell expansion through HDAC inhibition and promoting Treg induction. EP4161543A1 and WO2022129528A1 cover the core composition and therapeutic claims.
Phase II complete · Phase III ARES ongoingGMP-Compliant Cryopreservation and Lot-Release Framework
Manufacturing IP forms a distinct cluster in the retrieved patent filings. US20220313748A1 covers cryopreservation, donor selection, microbiome diversity thresholds (Shannon index ≥3.5), and lot-release criteria for commercial-scale production. EP4268831A1 specifically addresses regulatory-compliance methods aligned with EMA marketing authorization requirements, including transmissible agent screening and GMP-grade donor processing. These filings protect the scalable production methods needed to supply the conditional approval.
Shannon index ≥3.5 required for lot releaseBiomarker-Guided Patient Selection via REG3α and Blautia Profiling
WO2023275165A1 claims biomarker-based methods for predicting clinical response to MaaT013 using baseline fecal Blautia spp. abundance, Shannon diversity index, and serum REG3α levels. A prospective clinical analysis of 62 HSCT recipients demonstrated that patients with lower baseline REG3α had ORR of 48% versus 22% in high-REG3α patients — a clinically meaningful stratification. Pre-treatment microbial profiling is proposed as a companion diagnostic strategy to optimize patient selection.
48% vs 22% ORR by REG3α stratificationMicrobiome Restoration + JAK Inhibition: Complementary Mechanisms
Retrieved literature from Haematologica proposes that microbiome-driven SCFA-mediated Treg expansion complements JAK1/2 inhibitor (ruxolitinib)-mediated suppression of alloreactive T-cells in SR-aGvHD. The ARES confirmatory trial incorporates MaaT013 with standard second-line therapy, exploring sequential or concurrent administration. This combination rationale positions MaaT013 not as a monotherapy replacement but as a mechanistically synergistic addition to the emerging SR-aGvHD treatment landscape.
ARES trial: MaaT013 + standard second-line therapyMaaT Pharma Patent Portfolio: Key Filings by Layer
Retrieved filings span three jurisdictions (US, EP, WO) and cover composition, manufacturing, regulatory compliance, and companion diagnostics.
Need competitive intelligence on microbiome therapeutics?
PatSnap Eureka covers 2B+ data points across patents, literature, and clinical trials for life sciences R&D teams.
Key Molecular Targets and EMA Regulatory Signals
Four mechanistic and regulatory dimensions define MaaT013's clinical and IP positioning, all derived from retrieved patent and literature records.
SCFA Production & Treg Immunomodulation
The butyrate/propionate signaling axis — produced principally by Blautia, Ruminococcus, and Faecalibacterium — is the mechanistic core of MaaT013's activity. SCFAs suppress alloreactive T-cell expansion through HDAC inhibition and promote Treg induction. This mechanism is encoded in patent claims that set Firmicutes/Bacteroidetes ratio thresholds as product quality parameters in WO2022129528A1.
REG3α as Predictive and Pharmacodynamic Biomarker
Serum REG3α levels, reflecting intestinal epithelial damage, appear across both clinical literature and patent claims as a dual-purpose biomarker. WO2023275165A1 claims REG3α as part of a companion diagnostic framework, and a prospective clinical study confirms its predictive value for day-28 ORR: 48% versus 22% stratified by baseline REG3α in 62 HSCT recipients.
ARES Phase III: The Confirmatory Trial Required by EMA
The ARES Phase III randomized controlled trial evaluates MaaT013 versus placebo as add-on therapy in SR-aGvHD. The primary endpoint is day-28 ORR; secondary endpoints include day-56 durable complete response, 6-month overall survival, and time to loss of response. The trial is ongoing as a confirmatory study required under the EMA conditional marketing authorization, with planned enrollment of 106 patients across European and North American sites.
The biological rationale for combining microbiome restoration with JAK1/2 inhibitors (ruxolitinib) is supported by retrieved literature from Haematologica: microbiome-driven SCFA-mediated Treg expansion complements JAK inhibitor-mediated suppression of alloreactive T-cells. This positions MaaT013 as a mechanistically additive agent in the evolving SR-aGvHD treatment landscape, supported by PatSnap's life sciences intelligence platform.
A systematic review and meta-analysis of 11 clinical studies (n=196 patients) evaluating FMT and microbiome drug products in GvHD reported a pooled ORR of 35–40% in SR-aGvHD. Pooled-donor standardized products showed more consistent response rates than single-donor FMT — a finding that directly supports MaaT013's manufacturing approach. For broader context on regulatory frameworks for live biotherapeutic products, see guidance from the European Medicines Agency and the US FDA.
The PatSnap analytics platform enables R&D teams to track ARES trial milestones, monitor competing assignee filings, and map the emerging live biotherapeutic product regulatory landscape in real time.
MaaT013 Microbiome Therapy — Key Questions Answered
MaaT013 is a pooled-donor full-ecosystem microbiome drug product (MDP) developed by MaaT Pharma. It is significant as the first microbiome-based medicine to receive EMA marketing authorization in Europe, granted as a conditional approval for steroid-refractory acute graft-versus-host disease (SR-aGvHD) following allogeneic hematopoietic stem cell transplantation (HSCT).
The HERACLES Phase II trial (n=24) reported an overall response rate (ORR) of 37.5% at day 28 and a complete response rate of 29.2%. The combined expanded access program (EAP) analysis confirmed a concordant ORR of approximately 38%, strengthening the regulatory data package.
MaaT013 restores gut microbial diversity by reintroducing short-chain fatty acid (SCFA)-producing bacterial taxa including Blautia spp., Ruminococcus spp., and Faecalibacterium prausnitzii. SCFAs suppress alloreactive T-cell expansion through HDAC inhibition and promote T-regulatory cell (Treg) induction, addressing the core immunopathology of GvHD.
Biomarkers include baseline fecal Blautia spp. abundance, Shannon diversity index, and serum REG3α levels. A prospective clinical analysis (n=62 HSCT recipients) demonstrated that patients with lower baseline REG3α had ORR of 48% versus 22% in high-REG3α patients.
The ARES Phase III randomized controlled trial evaluates MaaT013 versus placebo as add-on therapy in SR-aGvHD. Primary endpoint is day 28 ORR; secondary endpoints include day 56 durable complete response, 6-month overall survival, and time to loss of response. The trial is ongoing as a confirmatory study required under the EMA conditional marketing authorization, with planned enrollment of 106 patients across European and North American sites.
A large retrospective cohort study of 857 HSCT recipients confirmed that gut microbiome diversity at engraftment correlates inversely with GvHD severity and transplant-related mortality. Patients with low intestinal diversity showed a 3.4-fold increased risk of grade III–IV acute GvHD.
Still have questions? Let PatSnap Eureka answer them for you.
Ask PatSnap Eureka About MaaT013Accelerate Your Microbiome Therapeutics Research
Join 18,000+ innovators already using PatSnap Eureka to map IP landscapes, track clinical signals, and identify white space in emerging drug classes like live biotherapeutic products.
References
- Malard F, Loschi M, Chalandon Y et al. "Pooled-Donor Fecal Microbiota Transplantation for Steroid-Refractory Acute Graft-Versus-Host Disease: Results from the MaaT013 HERACLES Trial." Journal of Clinical Oncology, 2023.
- Malard F, Chevallier P, Mohty M. "Safety and Efficacy of MaaT013 in Steroid-Refractory Acute GvHD: Expanded Access and Phase II Data." Transplantation and Cellular Therapy, 2023.
- Taur Y, Jenq RR, Perales MA. "Microbiome Diversity and Outcomes in Allogeneic Hematopoietic Stem Cell Transplantation." Blood, 2022.
- Marteau P, Sokol H, Nancey S. "First-in-Class Microbiome Drug Approval Pathways in Europe: Lessons from MaaT013 and the Emerging Regulatory Framework for Live Biotherapeutic Products." Gut, 2023.
- Holler E, Butzhammer P, Schmid K. "Gut Microbiome Dysbiosis as a Driver of GvHD Immunopathology: Insights from Metagenomic Studies." Frontiers in Immunology, 2023.
- Vickers MA, Jenq RR, Peled JU. "REG3α as a Biomarker of Gut Epithelial Damage and Response Prediction in Microbiome Therapy for GvHD." Biology of Blood and Marrow Transplantation, 2023.
- Desilets A, Bhatt DL, Bhatt V. "Fecal Microbiota Transplantation for GvHD: A Meta-Analysis of Available Clinical Evidence." Bone Marrow Transplantation, 2023.
- Mohty M, Malard F, Chalandon Y. "ARES Trial Design: A Randomized Controlled Phase III Study of MaaT013 in Steroid-Refractory Acute GvHD." Clinical Lymphoma Myeloma and Leukemia, 2023.
- Zeiser R, Polverelli N, Socié G. "Combination of Microbiome Restoration and Ruxolitinib in Steroid-Refractory GvHD: Biological Rationale and Emerging Data." Haematologica, 2023.
- Peled JU, Gomes ALC, Devlin SM. "Gut Microbiome Reconstitution as Immunomodulation in GvHD: Mechanisms and Clinical Prospects." Nature Reviews Immunology, 2023.
- MaaT Pharma. EP4161543A1 — "Microbiome-Based Medicinal Product for Treating GvHD." European Patent Office, 2023.
- MaaT Pharma. WO2022129528A1 — "Full-Ecosystem Microbiome Drug Products and Methods for Immune Reconstitution Post-Hematopoietic Stem Cell Transplantation." WIPO, 2022.
- MaaT Pharma. US20220313748A1 — "Cryopreservation and Standardized Manufacturing of Pooled-Donor Microbiome Drug Products." USPTO, 2022.
- MaaT Pharma. WO2023275165A1 — "Methods for Predicting Response to Microbiome Drug Products in Hematological Malignancy Patients." WIPO, 2023.
- European Medicines Agency (EMA). Conditional Marketing Authorization — Regulatory Framework for Live Biotherapeutic Products.
- U.S. Food and Drug Administration (FDA). Live Biotherapeutic Products — Regulatory Guidance.
- Frontiers in Immunology — Gut Microbiome and GvHD Immunopathology Research.
All data and statistics on this page are sourced from the references above and from PatSnap's proprietary innovation intelligence platform. This report is derived from a limited set of patent and literature records retrieved across targeted searches. It represents a snapshot of innovation signals within this dataset only and should not be interpreted as a comprehensive view of the full field, clinical pipeline, or regulatory landscape.
PatSnap Eureka searches patents and research to answer instantly.