Ruxolitinib Phosphate

LYON, France I June 02, 2025 I MaaT Pharma (EURONEXT: MAAT – the “Company”), a clinical-stage biotechnology company and a leader in the development of Microbiome Ecosystem Therapies TM (MET) dedicated to enhancing survival for patients with cancer through immune modulation, today announced the submission of the Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for its lead drug candidate MaaT013, under the registered brand name of Xervyteg ® . If approved, the Marketing Authorization would establish Xervyteg ® as the first microbiota therapeutic approved by the EMA, and the first one globally for a hematology indication. Xervyteg ® would also be the first approved therapy for the treatment of acute Graft-versus-Host Disease including gastro-intestinal involvement (GI-aGvHD) following 2 prior lines of systemic therapy. “Submitting our MAA to the EMA marks a major regulatory milestone for MaaT Pharma and a meaningful advancement for patients with refractory aGvHD—a life-threatening complication of stem cell transplantation with no approved therapies,” said Hervé Affagard, Co-founder and CEO of MaaT Pharma. “We are now closer to providing a much-needed treatment option and remain deeply committed to advancing immunomodulating microbiota technologies in hemato-oncology, where new solutions are urgently needed.” While advancing toward the commercialization of Xervyteg ® (if approved) in Europe, MaaT Pharma is also actively exploring strategic partnerships to ensure broad access in timely fashion. The Company has active discussions with experienced partners who share its mission of delivering meaningful advancements to patients. In parallel to the MAA submission, MaaT Pharma continues to provide access to Xervyteg ® in Europe and the U.S. through its Early Access Program (EAP) 1 for patients with aGvHD and other indications. In 2024, physician demand for Xervyteg ® under the EAP (n=107) increased by 75% compared to 2023, driven by growing adoption across Europe and in the U.S. In France where the EAP first started, MaaT Pharma has captured 25% of the addressable market on a yearly basis in 2024. Overall, this position reflects the increasing recognition of Xervyteg ® as a valuable treatment option for GI-aGvHD patients. aGvHD is the most severe complication of allogeneic stem cell transplantation, a standard-of-care treatment with curative intent offered to patients with blood cancers and some non-malignant hematological conditions. aGvHD refractoriness to current treatments is frequently encountered and severely impacts prognosis. In particular, patients with aGvHD failing both steroid and ruxolitinib typically exhibit a dismal prognosis, with a median survival of 28 days and 85% mortality at one year (Abedin et al 2021). Currently, no therapy is approved for third-line aGvHD, underscoring the urgent need for innovative therapies capable of improving survival and quality of life. The MAA is supported by positive results from the Pivotal ARES study, a single-arm, open-label, multicenter European study evaluating the efficacy and safety of Xervyteg ® in GI-aGvHD as third-line therapy in 66 patients. Notably, the study met its primary endpoint, achieving a gastrointestinal overall response rate (GI-ORR) of 62% at Day 28, significantly exceeding the expected 38% response rate, and an overall response rate across all organs of 64% at Day 28. Among responding patients at Day 28, the majority exhibited full resolution of GvHD clinical manifestations (i.e., complete response), an important finding predictive of durable control of aGvHD clinical manifestations over time. The 12-month probability of survival was 54% (vs 15% Abedin et al, 2021). Importantly, patients who exhibited gastrointestinal response at Day 28 had a significantly better probability of survival than non-responders (67% vs 28% respectively, p <0.0001), indicating that Xervyteg ® -mediated aGvHD control is associated with a remarkable survival benefit. Additional secondary endpoints, including overall survival, will become available in late H2 2025. The Company also integrated supporting safety and efficacy data from 186 aGvHD patients 2 treated under its ongoing EAP, which aligns with the positive topline results of the ARES trial and further supports Xervyteg ® ’s strong efficacy and favorable safety profile in aGvHD. The safety and tolerability of Xervyteg ® has been monitored by an independent Data Safety Monitoring Board (DSMB). In March 2025 , the DSMB reviewed the overall safety of the trial (after all patients completed Day 28 visit or were discontinued earlier) and confirmed that “given the remarkable efficacy results, the study results show an acceptable safety profile and a favourable benefit /risk ratio” . The DSMB members will continue to review safety on an ongoing basis until the 1-year follow-up. The EMA will review the application under the centralized marketing authorization procedure and potentially a marketing authorization could be granted in H2 2026. This centralized procedure means that a single marketing authorization application can be submitted to the EU, and if granted by the European Commission, the authorization is valid in all EU Member States as well as in the European Economic Area (EEA) countries Iceland, Liechtenstein and Norway. About acute Graft-versus-Host Disease Acute Graft-versus-Host Disease occurs in patients within 100 days of undergoing a stem cell or bone marrow transplant, where the transplanted cells initiate an immune response and attack the transplant recipient’s organs, causing inflammation of the skin, liver and/or gastro-intestinal tract and leading to significant morbidity and mortality. GI involvement is associated with severe complications such as profound diarrhea, abdominal pain, intestinal bleeding, and death. These complications are often life-threatening, with increased mortality risk, due to the challenges of managing severe GI inflammation and the associated risks of infection, malnutrition, and organ failure. The standard first line therapy for treating aGvHD is the use of systemic steroids. If patients do not respond to steroids, they are considered Steroid Resistant (SR) and other agents can be administered. Currently the only agent approved for treating SR aGvHD after failure of steroid treatment is ruxolitinib, which is currently approved for this indication in USA and has received approval from the European Medical Agency’s Committee for Human Medicinal Products (CHMP) on March 25, 2022. About Xervyteg ® (MaaT013) 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. Xervyteg ® (MaaT013) is a full-ecosystem, off-the-shelf, standardized, pooled-donors, enema Microbiome Ecosystem Therapy TM for acute, hospital use. It is characterized by a consistently high diversity and richness of microbial species and the presence of Butycore TM (a group of bacterial species known to produce anti-inflammatory metabolites). Xervyteg ® (MaaT013) 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 steroid-resistant, gastrointestinal (GI)-aGvHD. Xervyteg ® (MaaT013) has been granted Orphan Drug Designation by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). 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. SOURCE: MaaT Pharma

iStock, Vanz Studio Leerink Partners previews the drugs likely to be subject to the Inflation Reduction Act’s next price negotiations as the program expands to Medicare Part B and smaller biotechs. Immuno-oncology stalwarts Keytruda and Opdivo are likely to targeted in the Inflation Reduction Act’s next round of price negotiations , as the program expands from focusing solely Medicare Part D to also include Part B drugs, according to a new report from Leerink Partners. This puts therapies that are administered by a healthcare professional during a hospital stay or in an outpatient setting within the purview of the price reduction program for the first time. Leerink’s latest report flags the companies and drugs that are most likely to see their products up for price negotiation as the next round of IRA-prescripted negotiations commences. The targeted medicines will be selected by February of next year with prices to take effect in 2028. In January, the Centers for Medicare & Medicaid Services (CMS) announced the second list of drugs , which included obesity mega-blockbusters, Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound. Those prices will take effect on January 1, 2027. Negotiations for the list ended in August 2024 . Fifteen new drugs will be added in the next negotiations. The drugs with the most Medicare revenue exposure flagged by Leerink are Merck’s Keytruda and Bristol Myers Squibb’s Opdivo, as well as Gilead’s HIV-antiretroviral Biktarvy. For the first two, the companies are gearing up to lose exclusivity in 2028 anyway, whereas Gilead still enjoys patent protection through 2033. The IRA is not the only pricing pressure facing pharma. President Donald Trump has issued a sweeping executive order that attempts to use existing levers of government to force pharma companies to come to the table and set prices in line with other nations where drugs are cheaper. The list of drugs that will be subject has not been issued, but the Department of Health and Human Services recently clarified that it will be targeting branded drugs . GLP-1 weight loss medicines have also been flagged, just as CMS dropped them from coverage . Looking at the IRA’s 2028 list, Leerink notes that smaller companies will bear the brunt after initially being excluded from negotiations. Neurocrine Biosciences’ tardive dyskinesia drug Ingrezza, BeiGene’s lymphoma therapy Brukinsa and Incyte’s polycythemia vera treatment Jakafi are all likely to come up for negotiations. While the first two have exclusivity extending into 2033, Jakafi will lose patent protection in 2028, meaning investors will likely shrug off its inclusion in negotiations, Leerink noted. Leerink expects that CMS will push for steeper reductions than the 22% achieved for 2026 . One stubborn issue that remains a sticking point for pharma is that the so-called “ pill penalty ” remains despite an executive order from President Donald Trump calling for its repeal . This provision of the IRA penalizes small molecule drugs by providing a longer 13-year exclusivity period to biologics, compared to nine years for small molecules. Notably, changes to the pill penalty did not make it into Trump’s sweeping tax reform bill, dubbed the One Big Beautiful Bill Act , which passed through the House of Representatives last week.