These findings were presented during the 2025 ASH Annual Meeting by Florent Malard, MD, PhD, a professor of Hematology at Saint Antoine Hospital and Sorbonne University.
As of the data cutoff on November 11, 2024, the study met its primary end point with a GI overall response rate (GI-ORR) of 62% (95% CI, 49%–74%) among 66 patients treated with MaaT013 on day 28 of treatment, significantly exceeding the historical control of 22% (P <.0001). The all-organ ORR was 64% (95% CI, 51%–75%). Notably, both GI and all-organ responses exhibited a similar average duration of response (DOR) of 6.4 months (95% CI, 4.8–8.0).
Furthermore, data describing key secondary end points revealed that responses were maintained through later time points. At day 56 and month 3, the GI-ORRs were 49% and 44%, respectively; likewise, all-organ ORRs were 48% and 44%. Responses across all time points showed exceptionally high rates of complete response and very good partial response.
Importantly, the deep and durable responses translated into promising survival benefits. A Kaplan-Meier graph displayed a separation of curves between responders and nonresponders beginning shortly after the first administration of MaaT013, widening substantially over the course of 1 year with responders maintaining a clear survival advantage over time. Median overall survival (OS) data were immature at the time of analysis, but the estimated probability of survival at 1 year was 54%, a clinically meaningful improvement for this patient population with historically poor clinical outcomes.
What was the agent's safety profile?
MaaT013’s safety profile was determined to be acceptable. There were 157 serious treatment-emergent adverse events (AEs) reported across 76% of patients, with the most common being escherichia sepsis, general physical health deterioration, and septic shock.
There was a total of 34 treatment-related AEs across 29% of patients, which mainly comprised various bacterial infections and GI disorders. Of these events, 7 were considered serious. There were 26 fatal AEs, with 1 event of septic shock determined to be related to MaaT013 by investigators.
What was the design of the ARES trial?
The phase 3 ARES trial is a single-arm, multicenter, open-label trial in Europe investigating MaaT013, a pooled allogeneic fecal microbiotherapy, as salvage therapy in adult patients with refractory GI-aGVHD.2 The primary end point of the trial is GI-ORR at day 28, assessed by an independent review committee (IRC); secondary end points include GI-ORR at day 56 and month 3, all-organ ORR at day 28, and DOR per IRC and investigator assessment, as well as OS. In the study, MaaT013 was administered as a rectal suspension as a 150-mL enema.
Patients were included if they had undergone allogeneic hematopoietic stem cell transplant, experienced an aGVHD episode with lower GI symptoms per MAGIC guidelines, and were resistant to systemic steroids and either resistant or intolerant to ruxolitinib. Key exclusion criteria included having active cytomegalovirus colitis, lines of aGVHD treatment other than steroids and ruxolitinib, hyperacute GVHD, and active uncontrolled infection.
What next steps are planned for investigating MaaT013 in GI-aGVHD based on results from this study?
Of the 66 total patients, the majority (77%) had aGVHD with involvement limited to the GI tract. Others had GI and skin involvement (17%), GI and liver involvement (3%), and involvement of all 3 organs (3%). Regarding the hypothesized mechanisms of action driving responses in the skin and liver, Malard offered some preliminary insights based on earlier research.
“So far, based on this study, we don’t have the translational data to investigate how this is working, but from the previous [phase 2] HERACLES study [NCT03225937], we already have some data on the fact that we have some systemic immunomodulatory effect of the drug, with some decrease in the proinflammatory cytokine at the systemic level, and also an increase in essential fatty acid… in the serum of the patient,” Malard explained in the question-and-answer session. “We are also going to evaluate in another study all the immune cell subsets, in particular Tregs and so on, to find if this is how it’s working.”
MaaT013 is currently under regulatory review by the EMA following submission of a marketing authorization application in June 2025, with a decision regarding approval anticipated in the second half of 2026.3 If approved, MaaT013 would become the first microbiome-based therapy for the treatment of this high-need disease.
Disclosures: Malard declared receiving honoraria from Priothera, Jazz Pharmaceuticals, Therakos, Sanofi, Novartis, AstraZeneca, and MSD.
References
- Malard, F. MaaT013 for ruxolitinib-refractory acute graft-versus-host disease with gastrointestinal involvement: results from the ARES phase III trial. Presented at: 67th American Society of Hematology Annual Meeting and Exposition; December 6–9, 2025; Orlando, Florida. Abstract 817.
- MaaT013 as salvage therapy in ruxolitinib-refractory GI-aGVHD patients (ARES). ClinicalTrials.gov. Updated October 17, 2024. Accessed December 6, 2025. https://clinicaltrials.gov/study/NCT04769895
- November 3, 2025: Maat Pharma announces positive phase 3 results evaluating Xervyteg® (MaaT013) in acute graft-versus-host disease selected for oral presentation at ASH Congress 2025. News release. MaaT Pharma. November 3, 2025. Accessed December 7, 2025. https://tinyurl.com/su2wha2y
