MaaT Pharma (EURONEXT: MAAT – the “Company”), a late-stage clinical-stage biotechnology company leading the development of Microbiome Ecosystem Therapies TM (MET) to improve survival in cancer patients through modulation of the immune system, today announced topline results from ARES, a pivotal European Phase 3, multicenter, open-label, single-arm study evaluating the efficacy and safety of MaaT013 in patients with third-line acute graft-versus-host disease with gastrointestinal involvement (GI-aGvHD), i.e., steroid-refractory and refractory or intolerant to ruxolitinib.
The study notably met its primary endpoint, with a significant gastrointestinal overall response rate (GI-ORR) at 28 days of 62%, higher than the expected response rate of 38%. The responses assessed by an Independent Review Committee (IRC) exceed the significance threshold predefined in the protocol and confirm the unprecedented clinical efficacy of MaaT013 in the treatment of GI-aGvHD in third-line settings.
“GI-aGvHD is a devastating disease, particularly for patients who fail to respond to ruxolitinib. These patients face an urgent unmet medical need, with extremely low survival rates and a critical lack of effective treatment options,”
said Professor Mohamad Mohty, Professor of Hematology and Head of the Department of Hematology and Cellular Therapy at Saint-Antoine Hospital and Sorbonne University, Paris France.
“The results of MaaT013 in this Phase 3 trial mark a breakthrough in the third-line treatment of GI-aGvHD. By directly targeting the gut-immune interface, this innovative therapy has the potential to redefine the management of this disease, bringing new hope to patients and clinicians.”
“We would like to thank all patients who participated in this pioneering study. These positive topline results position MaaT013 as a first-in-class treatment for GI-aGvHD, offering a potential new option for patients in need of effective treatments when steroids and ruxolitinib have failed. ARES represents the first-ever positive pivotal clinical study with a microbiota-centric approach, limiting the prolonged use of immunosuppressants, and confirms MaaT Pharma’s leadership in this field. These results also validate the Company’s therapeutic platform, supporting its programs and paving the way for new potential applications in oncology, inflammatory diseases and other therapeutic areas , ”
added Gianfranco Pittari, PhD, MD, Chief Medical Officer, MaaT Pharma.
Treatment options for patients with steroid-refractory and ruxolitinib-refractory or intolerant GI-aGvHD remain very limited given the poor prognosis of this disease, with a one-year survival rate of only 15% (Abedin et al., 2021). MaaT013 has the potential to become the first approved third-line treatment option, significantly improving survival and redefining the long-term outlook for the approximately 3,000 third-line GI-aGvHD patients diagnosed each year in the United States, Canada, and Europe.
Main results:
In the single-arm ARES study, 66 adult patients with steroid-refractory GI-aGvHD who were refractory or intolerant to ruxolitinib were treated with MaaT013 in the third-line setting at 50 European sites (Austria, Belgium, France, Germany, Italy, and Spain).
Patient characteristics:
- Gender: 47% female, 53% male
- Median age: 55.5 years (24-76)
- At inclusion, the classification of aGvHD (according to IRC and investigator assessments):
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- Grade II: 9.1%
- Grade III: 57.6%
- Grade IV: 33.3%
- Steroid refractory: 86.4%
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- Steroid addict: 13.6%
- Refractory to ruxolitinib: 100%
- Intolerant to ruxolitinib: 0%
The study met its primary endpoint (p < 0.0001), namely the GI-ORR response rate at day 28 of treatment with MaaT013, as assessed by the Independent Review Committee (IRC).
Clear, strong and durable response rates, resulting in prolonged survival:
- GI-ORR at day 28 was observed in 41/66 patients (62%) with mainly a complete response (CR) for 25/66 patients, or 38% and a very good partial response (VGPR) for 13/66 patients, or 20%.
- ORR in all evaluable organs was observed in 42/66 patients (64%) and was also associated with high CR (in 24/66 patients, or 36%) and VGPR (in 12/66 patients, or 18%).
- The 12-month overall survival probability was 54% (median survival not reached). The 12-month overall survival probability of responders at day 28 was significantly higher than that of non-responders (67% vs. 28%, respectively, p <0.0001), highlighting the significant clinical benefit of MaaT013 in terms of survival in refractory GI-aGvH.
Recruited patients will continue to be followed for assessment of secondary and exploratory endpoints throughout the duration of the study. Results are expected to be presented at future scientific conferences.
The safety of MaaT013 was already confirmed in October 2023 by the independent Data Safety Monitoring Board (DSMB) in the ARES study, after evaluation of the first 30 patients included. The results showed that the treatment was well tolerated, with no increased risk of infection or serious adverse events related to treatment ( Details here ). Pharmacovigilance and monitoring by the DSMB are ongoing.
With these robust efficacy and safety data, MaaT Pharma is continuing its regulatory dossier review for MaaT013 in Europe, in the third-line treatment of GI-aGvH, with the aim of submitting a centralised marketing authorisation (MA) application to the European Medicines Agency (EMA) in mid-2025, ahead of the initially announced deadlines. The centralised procedure allows for a single authorisation across the entire European Union (27 members), thus facilitating patient access and marketing.
In line with its mission to provide new therapeutic options to address unmet medical needs, MaaT Pharma will continue to ensure access to MaaT013 in Europe for patients with aGvHD (and other indications) through its Compassionate Access Program (EAP), which exceeded 100 applications in 2024. The EAP program will continue throughout the regulatory assessment phase and up to commercialization, expected in late 2026. In addition, the Compassionate Access Program, which was extended to the United States in December 2024 , will continue in parallel, while the Company progresses its preparations for the Phase 3 clinical trial in the United States, which is expected to initiate in 2025, subject to securing the necessary funding.
MaaT Pharma is a late-stage clinical-stage biotechnology company, a leader in the development of gut microbiota-derived drugs dedicated to modulating the immune system of cancer patients and improving their survival. Backed by an expert team committed to making a difference for patients worldwide, the Company was founded in 2014 and is headquartered in Lyon, France.
A pioneer in its field, MaaT Pharma is developing the first immunomodulatory drug candidate based on the intestinal microbiota in oncology, currently in phase 3 of clinical evaluation. Thanks to its proprietary “pooling” technologies (combination of healthy microbiota donations) and microbial co-culture, MaaT Pharma is developing standardized drugs with high bacterial diversity, aimed at improving the survival of cancer patients. MaaT Pharma has been listed on Euronext Paris (MAAT) since 2021.