The purpose of this pilot study is to assess the safety and tolerability of multiple doses of MaaT033 in ALS patients and to analyze the gut microbiota composition and evolution before considering a larger randomized controlled efficacy study.

Start Date08 Jun 2023

Sponsor / Collaborator

Maat Pharma SA

NCT04150393 / CompletedPhase 1

Safety Phase I Evaluation of MaaT033, a Lyophilized Full-ecosystem Gut Microbiota Delayed-release Capsule, In HeMatOlogy Malignant Patients Under iNtensive Chemotherapy (CIMON)

Richness and diversity of gut microbiota are increasingly found to be associated with cancer outcomes. Moreover, an adequately responsive immune system seems to rely on the existence of a functioning gut ecosystem that includes the microbiota and its natural environment.
Cancer by itself, but also cancer treatments - in particular chemotherapy - induce gut dysbiosis, impair the constant reparation mechanisms of the gut epithelium, disrupt immune homeostasis, and stunt immune responsiveness.
The objective of MaaT033 is to (1) prevent the decay of the gut ecosystem (dysbiosis) to preserve immune homeostasis, (2) restore and optimize the gut ecosystem to full functionality including its role in repairing the gut epithelium and healthy gut barrier, and (3) maintain a restored gut ecosystem and fully functional immune homeostasis.
Restoring the full gut ecosystem and its associated microbiota could become an important therapeutic option to improve clinical outcomes and control adverse events of conventional approaches, including immunotherapy in cancer patients.
As a first step, MaaT033 capsules containing lyophilized, pooled, full-ecosystem microbiota in its natural environment are to be tested for their safety and tolerability in hematological malignant patients, who are exposed to intensive rounds of chemotherapy and antibiotics.

Start Date20 Oct 2020

Sponsor / Collaborator

Maat Pharma SA

100 Clinical Results associated with MaaT-033

100 Translational Medicine associated with MaaT-033

100 Patents (Medical) associated with MaaT-033

News (Medical) associated with MaaT-033

07 May 2024

·www.biospace.com

MaaT Pharma Provides a Business Update and Highlights Key Milestones Expected in 2024

Positive efficacy and safety data of MaaT013 in aGvHD in the Early Access Program presented at the EBMT 2024 annual meeting with 63% GI-ORR at D28, a 49% one year and 42% 18 months Overall Survival (OS) in patients similar to those included in the ARES Phase 3 clinical trial. Primary endpoint readout, GI-ORR at D28, of the ARES Phase 3 clinical trial in aGvHD expected for mid Q4-2024. Production of batches of MaaT013 destined for clinical supply in the US. Participation in a randomized multicenter investigator-sponsored Phase 2 trial evaluating MaaT033 concomitant to anti-PD1 treatment in advanced lung cancer patients. This trial is sponsored by Institut Gustave Roussy, steering cutting-edge research in the microbiome field, as part of the IMMUNOLIFE program, a consortium including researchers and biotech companies. Completion of patient recruitment for the Phase 1 clinical trial IASO, evaluating MaaT033 for patients with Amyotrophic Lateral Sclerosis. LYON, France--(BUSINESS WIRE)-- Regulatory News: MaaT Pharma (EURONEXT: MAAT – the “Company”), a clinical-stage biotechnology company and a leader in the development of Microbiome Ecosystem TherapiesTM (MET) dedicated to enhancing survival for patients with cancer, today provided a business update and highlights its key milestones for 2024. Hervé Affagard, CEO and co-founder of MaaT Pharma said: “We're confidently advancing towards Phase 3 results for MaaT013, meeting milestones and delivering value for shareholders. Recent data at the EBMT annual congress underscores MaaT013's potential in aGvHD where therapeutic options are insufficient. We are also thrilled to partner with Institut Gustave Roussy (IGR), a world-renowned center in cancer treatment to explore MaaT033's impact on immune checkpoint inhibitors’ response in non-small cell lung cancer patients, and therefore deepening our development in immuno-oncology. This collaboration further strengthens MaaT Pharma’s leading position in oncology and the medical community’s interest in microbiome drug candidates.” Pipeline highlights MET-N MaaT013 In hemato-oncology: In March 2024, the Company announced the launch of a retrospective multicenter trial called CHRONOS in Europe. Its objective is to provide the Company efficacy data for 3rd-line therapies for patients not receiving MaaT013 or any microbiome intervention. This study was not requested by regulatory authorities and does not impact cash projections as funding has already been secured. In April 2024, at the 50th annual meeting of the European Society for Blood and Marrow Transplantation (EBMT), the Company presented positive efficacy and safety results in 140 patients treated with MaaT013 in acute graft-versus-host disease (aGvHD) as part of the Early Access Program (EAP). The data presented demonstrates a clear reduction in disease burden and an improved Overall Survival (OS), and highlighted MaaT013's good safety profile. The results in the 49-patient “ARES-like” subgroup, with the same characteristics as those of the Phase 3 ARES trial (NCT04769895) demonstrated 63% GI-ORR at D28 and Overall Survival (OS) of 49% at one year and 42% at 18 months. This represents a significant increase when compared with the historical data published by Abedin et al. (used by the medical community as the most recent reference) which showed a limited 15% OS at one year in a similar population. Primary endpoint readout, GI-ORR at D28, of the ARES Phase 3 clinical trial in aGvHD is expected for mid Q4-2024. In immuno-oncology: In March 2024, the Company informed on the completion of patient recruitment for the Phase 2a clinical trial PICASSO (NCT04988841) sponsored by AP-HP and in collaboration with INRAE and Institut Gustave Roussy, evaluating MaaT013 in combination with Immune Checkpoint Inhibitors (ICI). Topline results expected in Q4 2024/Q1 2025. MaaT033 In immuno-oncology: MaaT Pharma announces its participation in the IMMUNOLIFE RHU1 program, a consortium including academic partners, such as Institut Gustave Roussy (IGR), a world-renowned center in the field of cancer treatment, and biotech companies. IMMUNOLIFE aims to solve the significant problem of primary resistance to immune checkpoint inhibitors (ICI) observed in advanced non-small cell lung cancer (NSCLC) patients following antibiotic uptake. MaaT033, an oral, pooled fecal microbiotherapy, developed by MaaT Pharma will be tested as a concomitant treatment to anti-PD1 therapy to increase the ICI response rate in this Phase 2 randomized multicenter clinical trial including advanced NSCLC patients. Participation in this program will also grant access to clinical and metagenomic data from a large cohort of cancer patients (bladder, lung and renal) which will be used to improve MaaT Pharma’s artificial intelligence (AI) gutPrint® platform. The related costs for MaaT Pharma are limited to clinical product supply in line with previous cash projections. In neurodegenerative diseases: In February 2024, the Company announced that the Data Safety and Monitoring Board (DSMB) reviewed safety data in the first 8 patients with Amyotrophic Lateral Sclerosis (ALS) treated with MaaT033 in the Phase 1 clinical trial IASO (NCT05889572). The DSMB, composed of 4 independent experts, including an ALS patient association representative, concluded that safety was good and recommended that the trial continue without modifications. MaaT Pharma announces the completion of patient recruitment for IASO. MET-C MaaT034 In immuno-oncology: In April 2024, at the American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego, California, the Company presented new in vitro data characterizing the metabolites produced by MaaT034 and their impact on immune modulation. MaaT034 may be the first full-co-cultivated ecosystem therapy for immuno-oncology, combining a diverse array of supportive species with functional networks of interest to improve the response to immune checkpoint inhibitors. The results demonstrate that MaaT034 produced key metabolites, recognized as promoting gut barrier restoration and modulating immune responses. This represents a significant advancement in understanding the mechanism of action (MoA) of co-cultured microbiome therapies developed by MaaT Pharma marking a major step towards clinical evaluation. Corporate update In March 2024, the Company announced the appointment of Jonathan Chriqui, PharmD, as Chief Business Officer and member of the executive management team. Jonathan will be responsible for MaaT Pharma’s business development and partnering strategies, increasing the Company’s ability to secure partnership deals, in line with its strategic objectives. MaaT Pharma has engaged in active discussions with prominent US clinicians in the field of stem cell transplantation to explore the most efficient path forward to introduce MaaT013 to patients in the United States. The Company is pleased to announce the production of batches of MaaT013 destined for clinical supply in the US as the Company pursues the readiness phase in advance of clinical study initiation. The Company believes it has sufficient cash to finance operations to the end of Q3 2024. While the Company does not have sufficient cash to finance its operations for the next twelve months, it has active ongoing discussions to finance operations beyond the end of Q3 2024 and remains confident in extending its cash runway. Key value creation milestones in 2024 MaaT013 Mid-Q4: Primary endpoint readout (GI-ORR at D28) from the ARES Phase 3 clinical trial in aGvHD Q4 2024/Q1 2025: Topline results of the PICASSO Phase 2a clinical trial in metastatic melanoma MaaT033 H2 2024: First DSMB2 of the PHOEBUS Phase 2b clinical trial in allo-HSCT H2 2024: Results of the IASO Phase 1 clinical trial in ALS MaaT034 H1 2024: Candidate selection H2 2024: Start of the production of the first cGMP batch Upcoming investor and business conferences participation June 3-6, 2024 – BIO 2024 June 11-12, 2024 – Portzamparc Mid & Small Caps 2024 Conference June 25-27, 2024 – Stifel European Healthcare Summit Lyon July 10-12, 2024 – Microbiome Movement Drug Development Summit --- About MaaT Pharma MaaT Pharma, a leading clinical-stage biotechnology company, has established a complete approach to restoring patient-microbiome symbiosis in oncology. Committed to treating cancer and graft-versus-host disease (GvHD), a serious complication of allogeneic stem cell transplantation, MaaT Pharma initiated an open-label, single-arm Phase 3 clinical trial in patients with acute GvHD, building on the positive results of its Phase 2 proof-of-concept study. Its powerful discovery and analysis platform, gutPrint®, enables the identification of novel disease targets, evaluation of drug candidates, and identification of biomarkers for microbiome-related conditions. The company’s Microbiome Ecosystem Therapies are produced through a standardized cGMP manufacturing and quality control process to safely deliver the full diversity of the microbiome in liquid and oral formulations. MaaT Pharma benefits from the commitment of world-leading scientists and established relationships with regulators to support the integration of the use of microbiome therapies in clinical practice. MaaT Pharma is listed on Euronext Paris (ticker: MAAT). Forward-looking Statements All statements other than statements of historical fact included in this press release about future events are subject to (i) change without notice and (ii) factors beyond the Company’s control. These statements may include, without limitation, any statements preceded by, followed by or including words such as “target,” “believe,” “expect,” “aim,” “intend,” “may,” “anticipate,” “estimate,” “plan,” “project,” “will,” “can have,” “likely,” “should,” “would,” “could” and other words and terms of similar meaning or the negative thereof. Forward-looking statements are subject to inherent risks and uncertainties beyond the Company’s control that could cause the Company’s actual results or performance to be materially different from the expected results or performance expressed or implied by such forward-looking statements. 1 Contract N° ANR-21-RHUS-0017 – RHU stands for Recherche Hospitalo-Universitaire - University Hospital Research 2 at the recruitment of 60 patients

Phase 2Phase 1Phase 3Clinical ResultImmunotherapy

15 Apr 2024

·www.fiercebiotech.com

MaaT, eyeing 2026 launch for microbiome therapy, posts 18-month data in aGvHD

MaaT Pharma drilled down into a subset of 49 patients who more closely match those in an ongoing phase 3 trial of MaaT013. A year after a long-running clinical hold was lifted on MaaT Pharma’s pooled fecal therapy, the microbiome biotech has touted 18-month data as proof it’s on track to launch the drug in acute graft-versus-host disease (aGvHD) in two years’ time. The 18-month data are taken from 140 patients with either steroid-refractory or steroid-dependent gastrointestinal aGvHD who received the therapy, dubbed MaaT013, as part of the French biotech’s Pharma Early Access Program. Among these heavily pretreated patients, the data showed a “clear overall survival advantage,” with a 54% rate of overall survival at six months, 47% at 12 months and 42% at 18 months. Overall survival was “significantly higher” in patients who responded to MaaT013 compared to non-responders at 18 months—at 58% versus 24%, respectively—the company noted. The biotech also drilled down into a subset of 49 patients whose disease had proven resistant to treatment by both steroids and Incyte’s Jakafi. Among these patients—who more closely match those in an ongoing phase 3 trial of MaaT013—the gastrointestinal overall response rate was higher, at 63%, than the 52% across the whole group. Overall survival at 18 months remained at 42% among this subset. “The confirmation of an improvement in 18-month survival, compared to the data already presented, by the company, at 12 months, reinforces our confidence in the ongoing development, notably the results of the current phase 3 trial,” MaaT’s CEO Hervé Affagard said in a statement. “Beyond the significant impact for patients, this advancement distinguishes our treatment in a context where current options offer only limited benefits and lead to severe complications,” Affagard added. “Anticipating a positive phase 3 outcome and a potential commercial launch in 2026, we aim to capture a substantial share of the market for third-line patients, thereby marking a turning point in the management of this condition.” MaaT has seen combining stool samples from multiple donors as a way to improve the diversity and standardization of MaaT013. But the practice proved to be a sticking point in the U.S., where the FDA imposed a 20-month hold on moving the drug into a phase 3 for aGvHD that was only lifted in April 2023. As well as the phase 3 study of MaaT013 in aGvHD, the biotech is also testing the therapy for metastatic melanoma in a phase 2 study in combination with immune checkpoint inhibitors. The company’s other clinical-stage asset is MaaT033, another so-called “microbiome ecosystem therapy” that is in a phase 1 trial for amyotrophic lateral sclerosis and a phase 2 study for improving survival among blood cancer patients who have received a bone marrow transplant.

Phase 3Phase 2Microbial therapyClinical Result

15 Apr 2024

·www.biospace.com

MaaT Pharma Presents Positive 18-month Data for MaaT013 Showing a Clear Overall Survival Advantage in aGvHD from the Early Access Program at the 2024 EBMT Event

Positive efficacy and safety results in 140 patients treated with MaaT013 in acute graft-versus-host disease (aGvHD) as part of the MaaT Pharma Early Access Program (EAP). Gastrointestinal overall response rate (GI-ORR) of 52% observed at Day (D) 28. Long-term survival data at 18 months with 42% overall survival (OS) in all patients and 58% in responder patients to MaaT013. Used in 3rd line, MaaT013 exhibits a high and durable response rate (with 63% GI-ORR at D28 and 53% at D56), translating to the highest overall survival in this population of patients when compared to reported evidence in the literature (Abedin et al., 2021). A pivotal Phase 3 trial evaluating MaaT013 (ARES trial - NCT04769895; n=75) in patients with corticosteroid and ruxolitinib-refractory GI-aGvHD is currently ongoing with primary endpoint expected in mid Q4-2024. LYON, France--(BUSINESS WIRE)-- Regulatory News: MaaT Pharma (EURONEXT: MAAT – the “Company”), a clinical-stage biotechnology company and a leader in the development of Microbiome Ecosystem Therapies™ (MET) dedicated to enhancing survival for patients with cancer, presents a summary of its oral presentation at the 50th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) currently being hosted in Glasgow, Scotland from 14-17 April 2024. The presentation is scheduled for April 17th by Dr. Malard, Professor of Hematology at Saint-Antoine Hospital and Sorbonne University in Paris and is based on the abstract made available on the website of the event. This presentation will unveil promising extended outcomes from the EAP in Europe, involving 140 patients with steroid-refractory (SR) or steroid-dependent (SD) gastrointestinal acute graft-versus-host disease (GI-aGvHD) treated with MaaT013. Prof. Malard will emphasize a significantly high response rate (Complete Response [CR] and Very Good Partial Response [VGPR]) to MaaT013, demonstrating a clear reduction in disease burden and improved Overall Survival (OS) at 18 months compared to published data. Prof. Malard commented: “MaaT013 shows remarkable efficacy at 18 months, yielding more complete responses in aGvHD patients who have shown resistance to current treatments, as compared to other available therapies. This effect is coupled with reduced toxicity compared to standard immunosuppressive drugs. Notably, these results are achieved with just 3 doses in less than 2 weeks of treatment initiation. This would not only improve patient outcomes, but also significantly enhance their quality of life.” Echoing this feedback, Dr. Jaime Sanz Caballer, Hematologist and coordinator of the Bone Marrow Transplant Unit at the University Hospital La Fe in Valencia, Spain, also commented: “there is a persistent unmet medical need in aGvHD with consistently reported poor survival outcomes. This is particularly noticeable for patients in third-line treatment options where only 15% of patients survive at 12 months1. This underscores the urgent demand for innovative solutions such as MaaT013, presenting a promising immuno-restorative approach." The data presented highlights the strong safety pro MaaT013 (full details here) and translates into increased OS. In this heavily pre-treated population (n=140), the following results were observed: GI-ORR of 52% at D28, with CR observed in 28% of patients; ORR considering all organs was 52% with 24% CR. OS was 54% at 6 months, 47% at 12 months, 42% at 18 months. OS was significantly higher in patients who responded to MaaT013 compared to non-responders (68% versus 24% at 12 months, and 58% versus 24% at 18 months). A subset of the 140 patients (n=49) that is a similar population to that of the ongoing Phase 3 ARES clinical trial (NCT04769895): steroid- and ruxolitinib- refractory corresponding to the third-line treatment demonstrated even better efficacy: GI-ORR of 63% at D28, with almost half of patients demonstrating a CR (49%); global ORR was 61% with 43% with a CR. OS was 52% at 6 months, 49% at 12 months, 42% at 18 months. OS was significantly higher in patients who responded to MaaT013 compared to non-responders (76% versus 6% at 12 months, and 64% versus 6% at 18 months). A pivotal Phase 3 trial (n=75) evaluating MaaT013 (ARES trial - NCT04769895) in patients with corticosteroid and ruxolitinib-refractory GI-aGvHD is currently ongoing to confirm the results from the EAP. The Company previously shared the positive review by the Data Safety Monitoring Board (DSMB) for the Phase 3 ARES trial, including a favorable benefit/risk ratio, with “high efficacy and low toxicity.” “The confirmation of an improvement in 18-month survival, compared to the data already presented, by the company, at 12 months, reinforces our confidence in the ongoing development, notably the results of the current Phase 3 trial,” stated Hervé Affagard, CEO and co-founder of MaaT Pharma. “Beyond the significant impact for patients, this advancement distinguishes our treatment in a context where current options offer only limited benefits and lead to severe complications. Anticipating a positive Phase 3 outcome and a potential commercial launch in 2026, we aim to capture a substantial share of the market for third-line patients, thereby marking a turning point in the management of this condition.” MaaT013, a pooled-donor microbiome ecosystem therapy, has been awarded Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) due to the rarity of the disease, underscoring the need for therapeutic advances. MaaT Pharma also presented its ongoing Phase 2b trial design for MaaT033 developed as an adjunctive therapy to enhance OS in allogeneic hematopoietic stem cell transplantation. This international, multi-center trial (NCT05762211) is the largest randomized controlled study to date of a microbiome-based therapy in oncology, spanning up to 56 sites and aiming to enroll 387 patients. About MaaT Pharma MaaT Pharma, a leading clinical-stage biotechnology company, has established a complete approach to restoring patient-microbiome symbiosis in oncology. Committed to treating cancer and graft-versus-host disease (GvHD), a serious complication of allogeneic stem cell transplantation, MaaT Pharma initiated an open-label, single-arm Phase 3 clinical trial in patients with acute GvHD, building on the positive results of its Phase 2 proof-of-concept study. Its powerful discovery and analysis platform, gutPrint®, enables the identification of novel disease targets, evaluation of drug candidates, and identification of biomarkers for microbiome-related conditions. The company’s Microbiome Ecosystem Therapies are produced through a standardized cGMP manufacturing and quality control process to safely deliver the full diversity of the microbiome in liquid and oral formulations. MaaT Pharma benefits from the commitment of world-leading scientists and established relationships with regulators to support the integration of the use of microbiome therapies in clinical practice. MaaT Pharma is listed on Euronext Paris (ticker: MAAT). Forward-looking Statements All statements other than statements of historical fact included in this press release about future events are subject to (i) change without notice and (ii) factors beyond the Company’s control. These statements may include, without limitation, any statements preceded by, followed by or including words such as “target,” “believe,” “expect,” “aim,” “intend,” “may,” “anticipate,” “estimate,” “plan,” “project,” “will,” “can have,” “likely,” “should,” “would,” “could” and other words and terms of similar meaning or the negative thereof. Forward-looking statements are subject to inherent risks and uncertainties beyond the Company’s control that could cause the Company’s actual results or performance to be materially different from the expected results or performance expressed or implied by such forward-looking statements. 1 Abedin et al, 2021 View source version on businesswire.com: Contacts MaaT Pharma – Investor Relations Guilhaume DEBROAS, Ph.D. Head of Investor Relations +33 6 16 48 92 50 invest@maat-pharma.com MaaT Pharma – Media Relations Pauline RICHAUD Senior PR & Corporate Communications Manager +33 6 14 06 45 92 media@maat-pharma.com Trophic Communications – Corporate Communications Jacob VERGHESE or Priscillia PERRIN +49 151 7441 6179 maat@trophic.eu Source: MaaT Pharma View this news release online at:

Clinical ResultPhase 2Phase 3Orphan DrugMicrobial therapy

100 Deals associated with MaaT-033

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Indication	Highest Phase	Country/Location	Organization	Date
Amyotrophic Lateral Sclerosis	Phase 1	FR	Maat Pharma SA	05 Jun 2023
Hematologic Diseases	Phase 1	FR	Maat Pharma SA	20 Oct 2020
Acute Myeloid Leukemia	Phase 1	-	Maat Pharma SA	-
Hematologic Neoplasms	IND Approval	FR	Maat Pharma SA	27 Mar 2023
Hematologic Neoplasms	IND Approval	DE	Maat Pharma SA	27 Mar 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05889572 (IASO, BusinessWire) Manual	Phase 1	Amyotrophic Lateral Sclerosis	8	MaaT033	lbaprlyimz(cbrfqmbmhl) = MaaT033 has shown a good safety profile and was generally well tolerated in the first 8 patients with ALS treated with MaaT033 used in a chronic setting. ufggynzynv (atihpvegmk )	Positive	29 Feb 2024
NCT04150393 (EBMT2023) Manual	Phase 1	Acute Myeloid Leukemia	20	MaaT033	uaajrszcvs(dtztwfazaa) = 5 serious adverse events (SAEs) were reported in 4 patients: 2 in cohort 2 (hyperkalemia, febrile neutropenia during consolidation), 2 in 1 patient from cohort 3 (colitis & neutropenic colitis during consolidation) and 1 in cohort 4 (enteropathogenic E.coli (EPEC) infectious diarrhea leading to study drug withdrawal) ylxzexqrkh (tleahhfuxi ) View more	Positive	26 Apr 2023
NCT04150393 (CIMON, ASH2022) Manual	Phase 1	Acute Myeloid Leukemia	21	MaaT 033	oeqybnboac(dmbmkdhron) = xhnesvqrqn vszdyohbsr (vslxbilmuk )	Positive	15 Nov 2022
NCT04150393 (CIMON, Biospace) Manual	Phase 1	Hematologic Neoplasms	21	MaaT033	xpngbqgpej(xeeuwkoyib) = an infectious diarrhea event with no detection of the causal pathogen in the administered MaaT033 and patient recovery within four days ltguaxcgyy (hhdglacuur )	Positive	02 Jun 2022

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