Restore in hemato-oncology:
MaaT Pharma’s therapies for the treatment of acute Graft-vs-host-Disease and the prevention of side-effects of HSCT (hematopoietic stem cell transplantation) aim to restore healthy microbiome functions to correct the impact of stressors such as antibiotics, chemotherapies.
Pioneering a full-ecosystem approach
We are developing a novel class of microbiome therapies
to address severe medical need in oncology.
MaaT Pharma’s pipeline leverages two approaches:
Restore & modulate in immuno-oncology:
MaaT Pharma’s therapies for the treatment of solid tumors aim to restore and modulate the microbiome to improve patient’s response to immune checkpoint inhibitors.
MaaT013: Treating acute Graft-vs-host-Disease
50%
of patient undergoing an allo-HCT develop aGvHD
70-80%
mortality rate in steroid-resistant aGvHD patients
10,000
cases in 2018 in the US, UK, France, Germany, Italy and Japan alone
MaaT013 status
MaaT013 is currently being investigated in a pivotal Phase 3 trial (ARES) in patients with acute Graft-versus-Host-Disease with gastrointestinal involvement (GI-aGvHD) who are refractory to both steroids, the standard of care first-line treatment, and to ruxolitinib used as a second-line treatment.
ARES is the first Phase 3 trial globally for a microbiome-based therapy in hemato-oncology.
Additional information:
– Clinical Trial. gov : NCT04769895
– Press release announcing the first patient dosed in Phase 3 clinical trial ARES
Positive topline data from the Phase 2 HERACLES trial in 24 Grade 3-4, steroid-refractory, gastrointestinal predominant aGvHD patients were made public in March 2021.
Additional promising data from Phase 2 Heracles clinical trial in 24 GI-predominant aGvHD patients having failed a median of 3 lines of treatment and from an ongoing early access program in France (n= 52) was shared at the 2021 ASH Conference.
MaaT033: Improving of HSCT outcomes for leukemia patients
The unmet need
Allogeneic Hematopoietic Stem Cell Transplantation (allo-HCT) is a potentially life-saving procedure for people suffering from blood cancers such as acute myeloid leukemia.
Although potentially life-saving, allo-HCT can be associated with severe complications, such as severe infections, graft-vs-host-disease, neutropenia, contributing to a mortality rate of 34% after 1 year6 in patients over 50 years of age receiving allo-HCT.
20,000
receive first allo-HCT each year in the US, UK, France, Germany, Italy, Spain and Japan.
MaaT033 for improving outcomes in people receiving allo-HCT
Antibiotic and chemotherapy-derived loss of gut diversity is predictive of mortality in allo-HCT patients, as well as graft-vs-host-disease occurrence and infection.2 3 4 7
MaaT033 is a an oral, donor-derived, standardized, high-richness, high-diversity microbiome ecosystem therapies, for ambulatory use, containing ButycoreTM , a group of bacterial species known to produce anti-inflammatory short-chain-fatty acid.
MaaT033 status
MaaT033 is currently undergoing a dose-finding Phase 1 clinical trial (CIMON) in patients with acute myeloid leukemia and positive interim engraftment and safety data have been announced on January 2022.
Based on the data gathered in 21 patients (4 cohorts) at different doses, MaaT Pharma reported a good microbiome engraftment and engraftment persistence, together with a satisfactory safety profile for its second drug-candidate. Complete results for the trial are expected in the first half of 2022 and could support the initiation of a Phase 2/3 trial planned in the second half of 2022.
MaaT033’s proposed mode-of-action is immuno-modulatory:
- Restoration of the full richness and diversity of a healthy microbiome and production of immune-regulating short-chain-fatty-acids known to upregulate Treg cells activity, in order to restore immune homeostasis,
- Restoration of the gut barrier, to prevent infections, especially those related to multi-drug-resistant bacteria (MDRB)
Sources
1 Castilla-Llorente. C, et al. Prognostic factors and outcomes of severe gastrointestinal GVHD after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2014 49(7):966-71. doi:10.1038/bmt.2014.69
2 Peled JU, et al. Role of the intestinal mucosa in acute gastrointestinal GVHD. Blood. 2016 128(20):2395-2402. doi: 10.1182/blood-2016-06-716738.
Staffas A, et al. The intestinal microbiota in allogeneic hematopoietic cell transplant and graft-versus-host disease. Blood. 2017 129(8):927-933. doi: 10.1182/blood-2016-09-691394. Erratum in: Blood. 2017 Apr 13;129(15):2204
Mathewson ND, et al. Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease. Nat Immunol. 2016 505-513. doi: 10.1038/ni.3400. Epub 2016 Mar 21. Erratum in: Nat Immunol. 2016 Sep 20;17 (10 ):1235.
3 Taur Y, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood. 2014 124(7):1174-82. doi:10.1182/blood-2014-02-554725.
Jenq RR, et al. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J Exp Med. 2012 903-11. doi: 10.1084/jem.20112408.
4 Jenq RR, et al. Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2015 1373-83. doi:10.1016/j.bbmt.2015.04.016.
Peled JU, et al. Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation. J Clin Oncol. 2017 1650-1659. doi:10.1200/JCO.2016.70.3348
5 Global Data GVHD Epidemiology Report, Jan 2020.
6 EBMT data 2021
7 Malard, F., Vekhoff, A., Lapusan, S. et al. Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients. Nat Commun 12, 3084 (2021). https://doi.org/10.1038/s41467-021-23376-6
MaaT03X: Increasing response rate to ICI in solid tumors
The unmet need
Immune checkpoint inhibitors (ICI) have proved a formidable therapeutic option for the treatment of solid tumors. They have notably improved survival in more than 15 oncology indications to date. However, not all patients respond to ICI. In some indications, it has been suggested that the gut microbiome plays a role in the response to ICI.
80%
of patients fail to respond to ICI depending on the indication.
MaaT03X for the treatment of solid tumors
Recent research has suggested that a patient’s gut microbiome diversity and richness, as well as its composition, impacts response rate to ICI and overall survival rate in multiple indications (melanoma, non-small cell lung cancer, renal cell carcinoma…).
The first product candidate of this range, MaaT03X, is designed to improve response rate to ICI in an undisclosed solid tumor indication.
Using our gutPrint platform, we are designing indication-specific product candidates (MET-F) combining high richness and diversity and indication-specific functional bacterial networks aiming to improve response to ICI. Each product is designed based on AI-driven analysis of healthy subjects’ and patients’ data and manufactured using a unique, ground-breaking, patented, ecosystem co-fermentation technology allowing to replicate and leverage, at large industrial scale, the richness and diversity of native-based microbiomes while tuning the resulting product to an indication-specific composition.
MaaT03X Status
The first MaaT03X candidate is currently in preclinical testing.
Scientific publications
Article & review
- Malard F. et al. (2018). High gastrointestinal microbial diversity and clinical outcome in graft-versus-host disease patients. Bone Marrow Transplantation.
- Malard F. et al. (2021). Restoration of gut microbiota diversity with autologous fecal microbiota transfer in acute myeloid leukemia patients. Nature communications.
Posters
- Malard F. et al. (2019). Successful and safe treatment of intestinal Graft-versus-Host Disease (GvHD) with pooled-donor full ecosystem microbiota biotherapeutics. Blood. ASH congress
- Malard F. et al. (2019). Heracles: a phase II single-arm prospective study to assess the efficacy of fecal microbiota transfer (FMT) in the treatment of steroid-refractory gastro-intestinal predominant aGVHD post allo-HSCT. EBMT congress
- Mohty M. et al. (2018). The Odyssee Study: Prevention of Dysbiosis Complications with Autologous Fecal Microbiota Transfer (FMT) in Acute Myeloid Leukemia (AML) Patients Undergoing Intensive Treatment: Results of a Prospective Multicenter Trial. Blood. ASH congress
- Mohty M. et al. (2017). Prevention of dysbiosis complications with autologous fecal microbiota transplantation (auto-FMT) in acute myeloid leukemia (AML) patients undergoing intensive treatment (ODYSSEE study): first results of a prospective multicenter trial. Blood. ASH congress
Oral communications
- Malard F. et al. (2021). 262 Pooled Allogenic Fecal Microbiotherapy MaaT013 for the Treatment of Steroid-Refractory Gastrointestinal Acute Graft-Versus-Host Disease: Results from the Phase IIa Heracles Study and Expanded Access Program. ASH congress
- Malard F. et al. (2021). Successful and Safe Treatment of Intestinal Graft-Versus-Host Disease (GvHD) with Pooled-Donor Full Ecosystem Microbiota Biotherapeutic: Results from a 29 Patient-Cohort of a Compassionate Use/Expanded Access Treatment Program. EBMT congress
- Malard F. et al. (2020). Successful and Safe Treatment of Intestinal Graft-Versus-Host Disease (GvHD) with Pooled-Donor Full Ecosystem Microbiota Biotherapeutic: Results from a 29 Patient-Cohort of a Compassionate Use/Expanded Access Treatment Program. Blood. ASH congress
- Malard F. et al. (2020). Successful and safe treatment of intestinal graft-versus-host disease (GvHD) with pooled-donor full ecosystem microbiota biotherapeutics. EBMT congress
- Malard F. et al. (2019). The odyssee study: prevention of dysbiosis complications with autologous fecal microbiota transfer in acute myeloid leukemia patients undergoing intensive-treatment: results of a prospective multicenter trial. EBMT congress
