MaaT Pharma is focused on developing microbiome-related therapies and its lead candidate is MaaT013, a treatment for acute graft-versus-host disease (aGvHD) with gastrointestinal involvement.
GvHD occurs when patients who receive allogeneic hematopoietic stem cell transplantation or a bone marrow transplant have a severe immune reaction. The transplanted cells attack the host cells and cause inflammation of the skin, liver and/or gastrointestinal tract.
MaaT013 is designed to treat aGvHD involving the gut and comprises a pooled donor microbiome that has a high diversity of healthy microbes including a group of bacterial species that produce anti-inflammatory short-chain-fatty acids.
The phase 3 ARES study took place across sites in Austria, Belgium, France, Germany, Italy and Spain. It included 66 patients aged 24 to 76 years who experienced aGvHD with gastrointestinal involvement and were resistant to other treatments. The patients were given an enema treatment of MaaT013 and were followed up after 28 days.
The primary endpoint was a significant gastrointestinal overall response rate at 28 days. The estimated response was 38% but this was exceeded and 62% of patients responded. Overall, 38% had a complete gastrointestinal response to treatment and 20% had a very good partial response.
Including all organs impacted by the aGvHD, 36% had a complete response and 18% had a very good partial response.
Notably, 12-month survival was 67% in patients who responded to the treatment at day 28 versus 28% in those who did not.
“Gastrointestinal involvement in aGvHD is a devastating condition, particularly for patients who do not respond to ruxolitinib. These individuals face an urgent unmet medical need, with alarmingly low survival rates and a critical lack of effective treatment options,” commented Mohamad Mohty, Professor of Hematology and Head of the Hematology and Cellular Therapy Department at Saint-Antoine Hospital and Sorbonne University, in a press statement.
“The results for MaaT013 in this phase 3 trial represent a groundbreaking advancement in third-line treatment for gastrointestinal-aGvHD. By directly targeting the gut-immune interface, this innovative therapy has the potential to redefine disease management, bringing new hope to patients and clinicians, alike.”
Advancing microbiome therapeutics to fulfill an unmet need
Microbiome therapeutics are still at a fairly early stage, with only two approvals by the U.S. FDA to date. These are both fecal transplant-based treatments to treat recurrent Clostridioides difficile infection, Seres Therapeutics and Nestlé’s Vowst and Ferring/Rebiotix’s Rebyota.
MaaT is one of the pioneers in this field and is aiming for approval in a different indication but using a similar treatment. There are few treatment options for aGvHD, which affects up to 50% of patients undergoing an allogeneic hematopoietic stem cell transplantation.
Steroids are the first treatment option, but if people are resistant to steroid treatment, then mortality can be up to 80%. The Janus kinase inhibitor ruxolitinib is another treatment option for aGvHD patients resistant to steroids, but again not all patients respond to this treatment and side effects can be problematic.
Now that MaaT013 has succeeded at phase 3 the company plans to file for approval in the EU later this year for treatment of patients resistant to both steroids and ruxolitinib. There is an Early Access Program for U.S. patients, but the company needs to compete a U.S. phase 3 trial before filing with the FDA.
The company also has a late-stage therapy, MaaT033, in development to help cancer patients needing an allogeneic hematopoietic stem cell transplantation. This therapy is currently at phase 2.
