Microbiome-Targeting Therapy MaaT033 Continues to Show Promise in Final Phase 1 Readout

Gianfranco Pittari, MD, PhD

Final data from a phase 1b pilot study (NCT05889572) showed that investigational MaaT033 (Maat Pharma), an oral microbiome ecosystem therapy, was safe and resulted in slower rate of disease progression in patients with amyotrophic lateral sclerosis (ALS). According to the company, these data will be used to provide insights on the target population for a future phase 2 study.

The exploratory, single-arm phase 1b study, also known as the IASO trial, comprised 15 patients with the disease across 2 centers in France, with data reviewed by an external Scientific Advisory Committee. From symptom onset to baseline, the median ALS Functional Rating Scale (ALSFRS-R) slope was –0.7 points/month (range, –1.2 to –0.3), which slowed to –0.3 points/month (range, –2.4 to +1.0) from baseline to Day 84. At day 84, investigators observed no variation in neurofilament light levels (NfL), a key biomarker of neuroaxonal damage that has been used to support investigational ALS agents.

"These encouraging findings from the IASO Phase 1b trial confirm the favorable safety and tolerability profile of MaaT033 in patients with ALS,” Gianfranco Pittari, MD, PhD, chief medical officer at Maat Pharma, said in a statement.¹ "They also highlight the therapeutic potential of microbiome modulation beyond oncology and open new avenues for development in neurodegenerative diseases, as evidence continues to grow around the gut-brain connection."

A unique agent, MaaT033 is a donor-derived, high-richness, high-diversity oral treatment containing anti-inflammatory Butycore species. The microbiome-targeting medication is developed using “pooling” technology, which allows pooling donations from multiple donors to create a standardized product with high microbial richness and diversity. While the cause of ALS is not fully understood, mounting evidence suggests that the gut-brain axis– the bidirectional communication between the gastrointestinal tract and the central nervous system—plays a role.

READ MORE: Muscle MRI May Serve as Sensitive Biomarker for ALS Disease Progression

In the IASO trial, MaaT033 was considered safe and well-tolerated, with biomarker and microbiome analyses supporting this. In addition, a rapid and sustained engraftment of bacterial species from MaaT033 was observed, mostly occurring within the first month and maintained during the 1-month follow-up period. Overall, these data complimented previously reported data in November 2024 which showed that MaaT033 met its primary end point of safety and tolerability across several dose levels.

MaaT033 is currently being assessed in patients with hematologic malignancies undergoing hematopoietic stem cell transplant (allo-HSCT) through the ongoing phase 2b PHOEBUS trial (NCT05762211). Recently reported data from an unblinded interim safety review of the study showed that MaaT033 had a tolerable and favorable safety profile in these patients, further supporting the study’s continuation. Maat Pharma noted that the next unblinded interim analysis for the study will include mortality monitoring and is scheduled for the third quarter of 2025 once it reaches the 120-patient mark.

Prior to PHOEBUS, the agent was tested in a phase 1 trial dubbed CIMON (NCT04150393), in patients with acute myeloid leukemia or high-risk myelodysplastic syndrome on intensive chemotherapy. Overall, results released in 2022 showed that MaaT033 was safe and resulted in rapid and persistent engraftment with the detection of more than 60% of the MaaT033 microbial communities in the patient’s gut post-exposure at the selected dose. Notably, substantial engraftment was maintained during the treatment period and for at least 3 weeks after the end of treatment.

REFERENCES
1. MaaT Pharma Announces Promising Final Data Readout for Phase 1b Evaluating MaaT033 in Amyotrophic Lateral Sclerosis (ALS). News release. MaaT Pharma. May 12, 2025. Accessed May 12, 2025. https://www.businesswire.com/news/home/20250511855391/en/MaaT-Pharma-Announces-Promising-Final-Data-Readout-for-Phase-1b-Evaluating-MaaT033-in-Amyotrophic-Lateral-Sclerosis-ALS
2. MaaT Pharma announces positive safety interim analysis from DSMB for phase 2b trial evaluating MaaT033 for patients receiving allo-HSCT. News release. MaaT Pharma. April 8, 2025. Accessed May 12, 2025. https://www.maatpharma.com/april-8-2025-maat-pharma-positive-safety-interim-analysis-phase-2b-trial-evaluating-maat033-in-allo-hsct/
3. June 2, 2022: MaaT Pharma Confirms Positive Results from Completed Phase 1b CIMON Study Evaluating MaaT033 in Blood Cancer Patients. News release. Maat Pharma. June 2, 2022. Accessed May 12, 2025. https://www.maatpharma.com/maat-pharma-confirms-positive-results-from-completed-phase-1b-cimon-study-evaluating-maat033-in-blood-cancer-patients/