MaaT Pharma Reports Preliminary Phase 2a PICASSO Trial Findings Evaluating MaaT013 in Combination With Immunotherapy for Advanced Melanoma
MaaT Pharma, a late-stage clinical biotechnology company and a leader in the development of Microbiome Ecosystem Therapies™ (MET), has announced an update on preliminary findings from its Phase 2a PICASSO clinical trial. The investigator-sponsored study evaluated MaaT013 (Xervyteg®) in combination with immune checkpoint inhibitors ipilimumab and nivolumab in patients with advanced, unresectable or metastatic melanoma who had not previously received anti-CTLA-4, anti-PD-1 or anti-PD-L1 therapies.
The preliminary findings indicate that the study achieved its primary objective of assessing the safety and feasibility of combining MaaT013 with the established immunotherapy combination. The results also provide additional information about the relationship between gut microbiome composition, microbiome diversity and clinical responses to immune checkpoint inhibitor treatment.
The PICASSO study was conducted by Assistance Publique–Hôpitaux de Paris (AP-HP), in collaboration with the French National Research Institute for Agriculture, Food and Environment (INRAE) and Gustave Roussy, a leading cancer research and treatment institution. The trial investigated whether adding MaaT013 to ipilimumab and nivolumab could be safely implemented in patients with advanced melanoma.
According to the preliminary information currently available, no statistically significant difference was observed between the MaaT013 and placebo treatment groups in the incidence of Grade 3 or higher adverse events. The safety profile associated with MaaT013 in combination with ipilimumab and nivolumab was generally consistent with the expected safety profile of the immunotherapy combination.
Response rates, which represented an important secondary endpoint, were comparable between the two treatment arms and consistent with previously reported response rates for ipilimumab and nivolumab combination therapy.
In addition to the safety and response findings, exploratory analyses indicated that baseline gut microbiome composition may influence clinical responses to MaaT013. The treatment was also associated with significant increases in microbiome richness and diversity compared with placebo, supporting its biological activity and confirming its effect on the gut microbiome.
MaaT Pharma stated that the preliminary information was derived exclusively from the study data disclosed in the European Union Clinical Trials Information System (CTIS), following submission by the PICASSO investigators. The company emphasized that these findings should not be interpreted as a final scientific publication. Complete results and detailed analyses are expected to be presented by the investigators at a future scientific congress.
Phase 2a PICASSO Study Meets Primary Safety and Feasibility Objective
The primary objective of the Phase 2a PICASSO trial was to evaluate the safety and feasibility of administering MaaT013 (Xervyteg®) alongside ipilimumab and nivolumab in patients with previously untreated advanced melanoma.
The study specifically enrolled patients with advanced, unresectable or metastatic melanoma who had not previously received immune checkpoint inhibitors targeting CTLA-4, PD-1 or PD-L1.
Immune checkpoint inhibitors have become an important component of modern cancer treatment. These therapies work by targeting regulatory pathways that cancer cells can exploit to avoid detection and destruction by the immune system. By blocking these pathways, checkpoint inhibitors can help restore or enhance immune system activity against tumors.
Ipilimumab is an anti-CTLA-4 immune checkpoint inhibitor, while nivolumab targets PD-1. Their combination is used in the treatment of certain advanced cancers, including melanoma, and is designed to activate complementary immune responses against cancer cells.
However, immune checkpoint inhibitor treatment can also be associated with significant immune-related adverse events. Consequently, evaluating the safety of combining additional therapeutic approaches with established immunotherapy regimens is an important part of clinical development.
The PICASSO investigators assessed whether MaaT013 could be incorporated into this treatment approach without introducing a significant additional safety burden.
The preliminary findings showed that the study met its primary safety and feasibility objective. Specifically, no statistically significant difference was observed in the incidence of Grade 3 or higher adverse events between patients receiving MaaT013 in combination with ipilimumab and nivolumab and those receiving placebo alongside the same immunotherapy combination.
The available data also indicated that the safety profile observed in the MaaT013 treatment group was generally consistent with the expected safety characteristics of ipilimumab and nivolumab.
These findings provide preliminary evidence supporting the feasibility of administering a microbiome-based therapeutic alongside immune checkpoint inhibitors in the studied patient population.
Nevertheless, the absence of a statistically significant difference in severe adverse events should not be interpreted as proof that the two treatment approaches have identical safety profiles. Further evaluation and complete analysis of the clinical data will be important to establish the overall safety characteristics of the combination.
Comparable Response Rates Observed Between Treatment Groups
Response rates were among the key secondary endpoints evaluated in the PICASSO study.
The preliminary findings indicated that response rates were comparable between the MaaT013 and placebo treatment groups. They were also consistent with previously reported response rates associated with ipilimumab and nivolumab combination therapy.
These findings provide additional information about the potential impact of adding MaaT013 to established immune checkpoint inhibitor treatment.
Although the study investigated whether microbiome modulation could influence the clinical activity of immunotherapy, the preliminary response data did not demonstrate an apparent improvement in response rates for the MaaT013 treatment group compared with placebo.
This distinction is important when interpreting the results. While the study provided encouraging information regarding the safety and biological effects of MaaT013, the comparable response rates do not establish an additional clinical efficacy benefit from adding the microbiome therapy in this particular treatment setting.
The company and investigators also evaluated additional secondary endpoints, including longitudinal microbiome assessments and biomarker analyses. These investigations are intended to provide a more detailed understanding of how microbiome characteristics may interact with immune responses during cancer treatment.
Such analyses could help researchers identify patient populations that may be more likely to benefit from microbiome-based therapeutic approaches and support the development of more targeted treatment strategies.
Exploratory Findings Highlight Potential Role of Baseline Microbiome Composition
One of the notable observations from the preliminary PICASSO findings involved the potential relationship between patients’ baseline gut microbiome composition and their clinical response to MaaT013.
Exploratory analyses suggested that the composition of the gut microbiome before treatment may influence clinical responses to the investigational therapy.
The baseline microbiome refers to the collection of microorganisms present in the gastrointestinal tract before a patient begins treatment. Differences in the composition, abundance and diversity of these microorganisms may influence several biological processes, including immune system regulation and inflammatory responses.
The gut microbiome has increasingly attracted attention in oncology research because of its potential role in influencing the effectiveness of cancer immunotherapies.
Researchers are investigating how specific microbial communities may interact with immune cells, influence immune signaling pathways and contribute to the body’s response to treatment.
Variations in microbiome composition could potentially help explain why some patients respond favorably to immune checkpoint inhibitors while others experience limited therapeutic benefit.
The PICASSO findings provide additional exploratory evidence supporting the importance of investigating these relationships in patients receiving microbiome-based therapies.
However, the company emphasized that these observations require further investigation. Additional analyses will be necessary to determine whether baseline microbiome characteristics can reliably predict treatment response and whether they could eventually help guide patient selection.
The identification of potential microbiome-related biomarkers could become an important part of future development strategies for MaaT Pharma.
MaaT013 Demonstrates Increases in Gut Microbiome Richness and Diversity
Another important finding from the PICASSO study was the observed increase in gut microbiome richness and diversity among patients treated with MaaT013 compared with those receiving placebo.
Microbiome richness refers to the number of different microbial species or organisms present within a particular microbial community. Diversity considers both the number of different microorganisms and how evenly they are represented within that community.
These characteristics are commonly evaluated in microbiome research because they provide information about the composition and structure of microbial ecosystems.
The gut microbiome consists of a complex community of microorganisms that interact with the human body and contribute to several biological functions. Changes in microbial composition and diversity may influence gastrointestinal health, metabolic processes, inflammatory pathways and immune system activity.
MaaT Pharma’s Microbiome Ecosystem Therapies are designed to leverage the potential therapeutic properties of complex microbial communities.
The significant increases in microbiome richness and diversity observed following MaaT013 treatment, compared with placebo, provide evidence that the investigational therapy affected the gut microbiome in the studied population.
This finding is particularly relevant to the company’s broader research strategy, which focuses on developing microbiome-based approaches to modulate immune responses and potentially improve outcomes for patients with cancer.
While the observed microbiome changes demonstrate a biological effect, they do not independently establish an improvement in clinical outcomes. Additional research will be needed to understand whether these changes translate into meaningful therapeutic benefits.
The longitudinal microbiome and biomarker analyses being conducted as part of PICASSO may provide further insights into the relationship between microbiome modification and cancer immunotherapy responses.
PICASSO Trial Enrolled 70 Patients Across Five French Centers
The Phase 2a PICASSO clinical trial randomized a total of 70 patients across five clinical centers in France.
The preliminary analysis included 69 patients, divided between the two treatment groups.
Of these participants, 34 patients were assigned to the MaaT013 (Xervyteg®) treatment arm, while 35 patients received placebo.
The study was designed to evaluate MaaT013 in combination with ipilimumab and nivolumab in patients with advanced melanoma who had not previously received the specified immune checkpoint inhibitor therapies.
MaaT Pharma provided both MaaT013 and placebo for the study. The company also generated shotgun metagenomic profiles of patients using its proprietary gutPrint® research engine.
Shotgun metagenomic sequencing is a molecular analysis technique used to examine the genetic material present in a microbial community. Unlike approaches that focus on identifying a limited number of microbial targets, this technology can provide broader information about the microorganisms present in a sample.
The use of gutPrint® enabled the company to generate microbiome profiles to support the investigation of microbial composition and changes during the study.
These analyses are particularly relevant to the exploratory objectives of PICASSO, which included evaluating longitudinal microbiome characteristics and potential biomarkers associated with clinical responses.
By combining clinical observations with microbiome profiling, the investigators aim to better understand how microbial ecosystems may interact with immune checkpoint inhibitor treatment.
The study is registered under ClinicalTrials.gov identifier NCT04988841 and European Union Clinical Trial number 2024-516100-42-00.
Study Conducted Through French Academic and Clinical Research Collaboration
The PICASSO study was conducted through a collaboration involving several French healthcare and research organizations.
The investigator-sponsored trial was led by Assistance Publique–Hôpitaux de Paris (AP-HP), in collaboration with INRAE and Gustave Roussy.
AP-HP is a major public hospital network in France, while INRAE conducts research across agriculture, food and environmental sciences, including areas relevant to microbiome research. Gustave Roussy is a specialized cancer research and treatment institution.
The study was fully funded by the Directorate of Health Care Supply, known as DGOS (Direction Générale de l’Offre de Soins), and operated by the French National Cancer Institute, known as INCa (Institut National du Cancer).
The funding was provided under the French national clinical research project program through project PHRC-K19-183.
This collaborative research structure brought together clinical oncology expertise, microbiome research capabilities and institutional support to investigate the potential role of microbiome-based therapy in cancer treatment.
The participation of multiple research centers also enabled the enrollment of patients across five locations in France, supporting the evaluation of the investigational combination in a multicenter clinical setting.
MaaT Pharma Highlights Importance of Treatment Setting and Patient Selection
Hervé Affagard, Chief Executive Officer and co-founder of MaaT Pharma, highlighted the importance of the preliminary findings and their potential contribution to the company’s broader immuno-oncology development strategy.
Affagard explained that PICASSO provides important controlled safety and feasibility data regarding the administration of a microbiome therapy alongside immune checkpoint inhibitors.
He also emphasized that the findings offer additional insight into the importance of treatment setting and patient selection when evaluating microbiome-based approaches in oncology.
According to Affagard, the findings, together with the planned microbiome analyses, will help inform the company’s immuno-oncology strategy as it continues advancing MaaT034 for patients who are refractory to immune checkpoint inhibitor treatment.
His comments highlight the importance of using clinical and biological findings to guide the development of future microbiome-based cancer therapies.
The observations regarding baseline microbiome composition may be particularly relevant to this strategy, as they could help researchers better understand which patients may be more likely to benefit from microbiome modulation.
The company intends to use the available information to support its ongoing development efforts and refine its approach to investigating microbiome-based treatments in patients with cancer.
Findings to Inform Future MaaT034 Development
The PICASSO findings form part of MaaT Pharma’s broader efforts to develop Microbiome Ecosystem Therapies designed to enhance survival for patients with cancer through immune modulation.
The company is particularly interested in the potential interaction between gut microbiome composition and the immune system, including how microbiome-based treatments may influence responses to cancer immunotherapy.
The preliminary findings from PICASSO provide several areas for further investigation, including the safety and feasibility of combining MaaT013 with checkpoint inhibitors, the biological effects of treatment on microbiome richness and diversity, and the potential influence of baseline microbiome characteristics on clinical response.
MaaT Pharma plans to incorporate insights from these analyses into its immuno-oncology strategy, including the continued development of MaaT034 for patients who do not respond adequately to immune checkpoint inhibitor treatment or whose disease becomes refractory to these therapies.
The company believes that a better understanding of the relationship between microbiome composition and treatment response could help guide future clinical development and patient selection strategies.
However, further clinical evidence will be required to establish the potential therapeutic role of these approaches and determine whether microbiome modulation can improve outcomes in specific cancer populations.
Complete PICASSO Results Expected at Future Scientific Congress
MaaT Pharma clarified that the currently reported findings are based exclusively on information made available through the European Union Clinical Trials Information System following submission by the PICASSO investigators.
The company emphasized that the preliminary data should not be considered a final scientific publication or a comprehensive presentation of the trial results.
The full results, including detailed clinical findings and additional microbiome and biomarker analyses, are expected to be presented by the investigators at a future scientific congress.
The complete scientific presentation is expected to provide a more comprehensive assessment of the study’s findings and help clarify the implications of the observed microbiome changes and clinical outcomes.
For now, the preliminary results establish that the study met its primary safety and feasibility objective, while demonstrating significant changes in gut microbiome richness and diversity following MaaT013 treatment.
The Phase 2a PICASSO findings represent an important source of clinical and biological information for MaaT Pharma as it continues developing microbiome-based therapies in oncology.
Although response rates were comparable between the MaaT013 and placebo groups, the study provided preliminary evidence supporting the feasibility of combining MaaT013 with ipilimumab and nivolumab. The observed increases in microbiome richness and diversity also confirmed the treatment’s effect on the gut microbiome.
Additionally, exploratory findings suggest that patients’ baseline microbiome composition may influence their clinical response, highlighting a potential area for further research and patient selection strategies.
MaaT Pharma plans to use these insights, together with additional microbiome analyses, to inform its immuno-oncology development strategy and support the advancement of MaaT034 in immune checkpoint inhibitor-refractory patients.
With complete PICASSO results expected at a future scientific congress, the company continues to focus on understanding the relationship between microbiome ecosystems and cancer immunotherapy while advancing its broader Microbiome Ecosystem Therapies platform.
About MaaT Pharma
MaaT Pharma is a leading, late-stage clinical company focused on developing innovative gut microbiome-driven therapies to modulate the immune system and enhance cancer patient survival. Supported by a talented team committed to making a difference for patients worldwide, the Company was founded in 2014 and is based in Lyon, France.
As a pioneer, MaaT Pharma is leading the way in bringing the first microbiome-driven immunomodulator in oncology. Using its proprietary pooling and co-cultivation technologies, MaaT Pharma develops high diversity, standardized drug candidates, aiming at extending life of cancer patients. MaaT Pharma has been listed on Euronext Paris (ticker: MAAT) since 2021.
About MaaT013 (Xervyteg®)
MaaT Pharma’s Microbiome Ecosystem Therapies (MET) are designed to leverage a full microbiome ecosystem to restore balance and maximize clinical benefits for patients with severe, treatment-induced dysbiosis in acute diseases. MaaT013 (Xervyteg®) is a full-ecosystem, off-the-shelf, standardized, pooled-donors, enema Microbiome Ecosystem TherapyTM for acute, hospital use.
It is characterized by a consistently high diversity and richness of microbial species and the presence of ButycoreTM (a group of bacterial species known to produce anti-inflammatory metabolites). MaaT013 (Xervyteg®) aims to restore the symbiotic relationship between the patient’s functional gut microbiome and their immune system to correct the responsiveness and tolerance of immune functions and thus reduce the symptoms of steroid-resistant, gastrointestinal (GI)-aGvHD. MaaT013 (Xervyteg®) has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).