Pioneering a full-ecosystem approach

We are developing a novel class of microbiome therapies
to address severe medical need in oncology.

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MaaT Pharma’s pipeline leverages two approaches:

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.

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

The unmet need

GvHD is a frequent and severe complication of allogeneic Hematopoietic stem cell transplantation (allo-HCT), in which the grafted cells attack the host.

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

Steroids are the first line of treatment for aGvHD. Antibiotic and chemotherapy-derived loss of gut diversity is predictive of graft-vs-host-disease occurrence, as well as poor outcomes and lower survival in patients receiving allo-HCT. 2,3, 4,

MaaT013 for the treatment of aGvHD 

MaaT013 is a donor-derived, standardized, high-richness, high-diversity microbiome ecosystem therapy, containing ButycoreTM , a group of bacterial species known to produce anti-inflammatory short-chain-fatty acids.

70

patients treated to date

MaaT013 status

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.

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

Posters

Oral communications