In Orlando this week, in one of the American Society of Hematology’s packed session rooms, a French microbiome company did something that not long ago would have sounded optimistic at best, wishful at worst: it showed pivotal Phase 3 data suggesting that reforming the gut microbiome can help pull some of the sickest transplant patients back from the brink.

MaaT Pharma, based in Lyon and listed on Euronext Paris, unveiled the final results of its ARES Phase 3 trial of Xervyteg® (MaaT013), a pooled-donor microbiome ecosystem therapy delivered by enema. The drug was tested as a third-line treatment in adult patients with severe, gastrointestinal acute graft-versus-host disease (GI-aGvHD) who had already failed both systemic corticosteroids and ruxolitinib. This is the part of the treatment pathway where options run out and survival curves typically fall off a cliff.

In ARES, 1-year overall survival reached 54%, and median overall survival was not reached at the time of analysis, meaning more than half of the patients were still alive at 12 months. For this population, that is a striking number rather than just another incremental gain. 

Why these patients are so hard to treat

Acute graft-versus-host disease is a well-known and feared complication of allogeneic stem cell or bone marrow transplantation. Within about 100 days of the transplant, the donor immune cells can begin to attack the recipient’s tissues, inflaming skin, liver, and—most devastatingly—the gastrointestinal tract. When the gut is involved, patients can experience massive diarrhea, abdominal pain, bleeding, infections, malnutrition, and organ failure. Mortality climbs fast, especially in those with severe GI disease. 

Standard first-line therapy is systemic steroids. Patients who don’t respond are considered steroid-refractory and move to second-line agents. Over the past few years, ruxolitinib, a JAK1/2 inhibitor, has become the reference second-line therapy for steroid-refractory aGvHD based on the REACH studies and regulatory approvals in both the US and Europe. 

Even so, survival remains disappointing for patients who fail both steroids and ruxolitinib. In pediatrics, a mesenchymal stromal cell product, remestemcel-L, was approved in the US in 2024 as a second-line option, but there is still no well-established third-line standard, and for adults, choices are a patchwork of off-label immunosuppressants, clinical trials, or best supportive care. In that context, the ARES data are not just another dataset; they test whether reshaping the gut ecosystem can meaningfully shift outcomes in a setting where traditional immunosuppression has already come up short.

Inside the ARES trial

ARES was a single-arm, open-label Phase 3 study that enrolled 66 adults with severe GI-aGvHD across 50 centers in six European countries. These were heavily pre-treated patients: all had failed ruxolitinib after being either steroid-resistant (the vast majority) or steroid-dependent, and 91% had Grade III–IV acute GvHD with gastrointestinal involvement—the sickest end of the spectrum. 

Xervyteg was given as a third-line intervention. The primary endpoint was gastrointestinal overall response rate (GI-ORR) at Day 28, capturing complete responses and very good partial responses. Secondary endpoints included all-organ response rates at different time points and overall survival.

By Day 28, GI-ORR was 62%, with 38% of patients achieving a complete response and another 20% reaching a very good partial response. All-organ response at the same time point was similarly high at 64%, again driven mainly by complete and very good partial responses. Those numbers would be encouraging in any late-line context; in ruxolitinib-refractory GI-aGvHD, they are notable.

What mattered just as much to clinicians in the room was durability. At Day 56, GI-ORR remained 47% and all-organ ORR 45%, with most responses still complete. At three months, both GI-ORR and all-organ ORR were 44%, again with a predominance of complete responses. In other words, this was not just a transient blip in symptoms; a substantial share of patients maintained meaningful disease control over time on the back of a short course of microbiome therapy. 

Survival: separating responders from non-responders

Response is encouraging, but survival is what ultimately counts. In ARES, the 12-month overall survival rate for the entire cohort was 54%, with median overall survival not reached at the time of analysis. That already compares favorably with historical expectations for this high-risk population, though of course cross-trial comparisons must always be handled with caution. 

The survival split between responders and non-responders is where the signal becomes particularly striking. Patients who achieved a GI response at Day 28 had a 12-month overall survival of 68%, while non-responders had a survival rate of just 28%. Median overall survival for non-responders was a mere 54 days. Statistically, the difference was highly significant (p<0.0001), but even without the p-value, the clinical message is clear: if Xervyteg induces an early gut response, those patients are far more likely to still be alive a year later.

From a mechanistic standpoint, this makes intuitive sense. Severe GI-aGvHD is driven by a vicious cycle of mucosal damage, dysbiosis, inflammation, and barrier breakdown. If you can interrupt that loop early—restore barrier function, dampen inflammation, and rebuild a more tolerant immune-microbiome relationship—you don’t just relieve diarrhea. You remove a major engine of systemic complications.

Safety in ARES was described as acceptable for such a fragile population, with continuous oversight from an independent Data and Safety Monitoring Board. There was no new safety signal linked to the use of a pooled-donor microbiome product in this context, which will be reassuring to regulators and clinicians accustomed to worrying about infectious risks with any fecal-derived therapy.

What exactly is Xervyteg?

Xervyteg (MaaT013) is not a single-strain probiotic capsule. It is a so-called Microbiome Ecosystem Therapy™: a standardized, off-the-shelf preparation derived from pooled stool from carefully selected healthy donors, co-cultivated and manufactured under cGMP conditions, and delivered as an enema in the hospital setting. 

Pooling donors and using MaaT’s proprietary co-cultivation platform is intended to ensure high microbial diversity and batch-to-batch consistency, two features that traditional one-donor fecal microbiota transplantation can struggle with. The product is enriched for what the company calls its “Butycore™” community—bacterial species known to produce butyrate and other short-chain fatty acids with anti-inflammatory properties. The therapeutic idea is to re-establish a symbiotic gut ecosystem that can help recalibrate immune responses, restoring tolerance without broadly suppressing immunity.

For MaaT, Xervyteg is the lead candidate in a broader platform that aims to position microbiome-driven immunomodulation as a new “pillar” in oncology alongside chemotherapy, targeted therapies, and checkpoint inhibitors. Beyond GvHD, the company is also exploring microbiome therapies as adjuncts to immunotherapy in solid tumors and other settings where the gut ecosystem appears to influence response to treatment. 

Regulatory countdown in Europe

The ARES dataset is not just an academic exercise. MaaT has already submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) for Xervyteg in ruxolitinib-refractory GI-aGvHD, with a decision expected around mid-2026. The product enjoys Orphan Drug Designation on both sides of the Atlantic, reflecting the high unmet need in this narrow but very severe indication. 

If the EMA gives a green light, Xervyteg would become the first microbiome-based therapy approved in oncology anywhere in the world and the first authorized third-line treatment for aGvHD in Europe. That would be a symbolic milestone for the microbiome field, which has seen years of hype, a few disappointments, and only a handful of regulatory successes so far, mainly in the prevention of recurrent C. difficile infection.

For transplant centers, an approval would almost immediately force conversations about where Xervyteg should sit in treatment algorithms, how to identify ideal candidates, and how to integrate a microbiome enema into already complex inpatient pathways. For payers, the question will be how to value a therapy that is neither a classic biologic nor a small molecule, but a living ecosystem that potentially prevents ICU stays, invasive infections, and expensive salvage therapies.

Business implications: from platform story to product story

On the business side, MaaT is at an inflection point. For several years, the company has positioned itself as a platform play—leveraging its Microbiome Ecosystem Therapies, bioinformatics tools such as gutPrint®, and a vertically integrated manufacturing footprint. With ARES, Xervyteg becomes a tangible product with a clear clinical value proposition and a defined initial market: adult patients with severe, ruxolitinib-refractory GI-aGvHD across Europe and potentially the UK. 

The company has already moved to prepare for commercialization. In mid-2025, MaaT signed an exclusive licensing, distribution, and commercial supply agreement with Clinigen for Xervyteg in the European Economic Area and the UK. Clinigen will handle distribution and market access in these regions, while MaaT focuses on manufacturing and further R&D, a division of labor that should help a relatively small biotech avoid the costs and delays of building a pan-European commercial infrastructure from scratch. 

Financially, MaaT has supplemented equity capital with non-dilutive funding, including a €37.5 million loan from the European Investment Bank announced in 2025, earmarked to support scale-up of its microbiome manufacturing and expand the oncology pipeline. 

All of this points to a clear strategic arc: secure EMA approval and first commercial revenues in GvHD, demonstrate real-world impact and safety at scale, and then leverage the same technology and know-how into additional oncology indications where the microbiome’s role is increasingly evident.

A new pillar or a niche solution?

From a wider industry perspective, ARES will be watched for at least three reasons.

First, it tests a genuinely new therapeutic modality in a setting where conventional immunosuppression has already failed. If Xervyteg’s benefits are borne out in real-world experience, it will strengthen the case for microbiome ecosystem therapies as more than “supportive care” and push regulators and guideline committees to define their place in serious disease management.

Second, ARES is a pivotal trial in a narrow but clinically important space. That makes Xervyteg unlikely to become a mass-market blockbuster in its initial indication, but it could become a highly valued, high-price, hospital-only product that consolidates MaaT’s reputation and supports further pipeline risk-taking—similar to how some rare disease drugs have underpinned biotech growth stories.

Third, the study will reopen debates about trial design in microbiome therapeutics. ARES is single-arm, without a randomized comparator, which means that comparisons to historical controls are unavoidable but imperfect. Regulators will have to weigh the severity of the condition, the ethical and logistical challenges of randomizing patients who have exhausted approved therapies, and the strength of the survival and response signals. If EMA is satisfied, it could set a precedent for future microbiome products in ultra-high-need indications.

What comes next

For now, MaaT is preparing a full publication of the ARES data in a peer-reviewed journal and working its way through the EMA review process. Clinicians will want to see detailed safety breakdowns, subgroup analyses, and microbiome-response correlations. Health economists and payers will run models on potential cost offsets. Investors will watch for regulatory interactions and any hints on pricing strategy.

But the broader narrative is already emerging. In a disease that strikes the most fragile cancer patients at one of the most precarious moments in their care, a therapy built from restored microbial diversity has delivered durable responses and a survival signal that is hard to ignore. Whether Xervyteg ultimately becomes a new standard third-line option or remains a specialized tool in expert centers, ARES has pushed the microbiome field another step away from theory and closer to routine clinical practice.