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Abstracts include a presidential plenary-selected Phase 2 study evaluating the combination of obeticholic acid and bezafibrate in PBC, along with 10 other abstractsMORRISTOWN, N.J., April 30, 2025 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Intercept), part of the Alfasigma Group, today announced 11 submitted abstracts have been accepted for presentation at Digestive Disease Week 2025, including oral presentations of data from a Phase 2 study evaluating the combination of obeticholic acid and bezafibrate in PBC, and investigational data for INT-787, a next-generation FXR agonist. The conference will be held from May 3-6 in San Diego. The abstracts showcase the Company’s breadth of research in the gastrointestinal (GI) and hepatology therapeutic areas. The data encompass multiple areas of high unmet need, including primary biliary cholangitis (PBC); primary sclerosing cholangitis (PSC); severe alcohol-associated hepatitis (sAH), a liver disease increasing in prevalence, especially among women; and chronic intestinal pseudo-obstruction (CIPO), a rare condition characterized by severe impairment of intestinal activity. “We look forward to sharing details of our clinical-development program progress with the scientific community, including our ongoing Phase 2 study of a potential first-in-class treatment for severe alcohol-associated hepatitis,” said Sangeeta Sawhney, M.D., Senior Vice President, Global Head, GI Therapeutic Area, Alfasigma. “We're also going to share the first six-year data for a second-line therapy for PBC, which gives insights into long-term safety and effectiveness." Presentations by Intercept and Alfasigma at DDW 2025: Oral Presentations “COMBINED EFFECT OF OBETICHOLIC ACID AND BEZAFIBRATE IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS AND INADEQUATE RESPONSE OR INTOLERANCE TO URSODEOXYCHOLIC ACID: 6-MONTH RESULTS FROM A PHASE 2 TRIAL” (Presentation #4)Session: AASLD Presidential PlenarySaturday, May 3, 9:15 AM ETChristophe Corpechot, Vaclav Hejda, Heng Zou, Antonio Civitarese, Alejandra Villamil, Frederik Nevens “FXR AGONIST INT-787 INHIBITS INFLAMMATION, FIBROSIS, SENESCENCE, AND APOPTOSIS ARREST IN HUMAN CHOLANGIOCYTES MODELING PSC” (Presentation #879)Session: Cutting-Edge Insights into PSC: From Mechanisms to TherapiesMonday, May 5, 4:45 PM ETFrancesca De Franco, Daniela Passeri, Sanjay Kansra, Luciano Adorini, Mary Erickson, Roberto Pellicciari Poster Presentations “OBETICHOLIC ACID NORMALIZES INFLAMMATORY BIOMARKERS IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS” (Poster #Sa1500)Session: Liver Inflammation and ImmunobiologySaturday, May 3, 12:30 PM ETDavid E. Jones, Christopher L. Bowlus, Arash Thranian, Mary Erickson, Jing Li, Christopher Gasink, Robert G. Gish “US POPULATION–BASED EPIDEMIOLOGY OF PRIMARY BILIARY CHOLANGITIS: EXAMINATION OF PATIENT CHARACTERISTICS AND INCIDENCE OF HEPATIC OUTCOMES IN A US HEALTHCARE CLAIMS DATABASE” (Poster #Su1675)Session: Health Disparities in Patients with Liver DiseaseSunday, May 4, 12:30 PM ETAparna Goel, Bridget L. Balkaran, Chris White, Radhika Nair, Anne Chiplin, Jing Li, Jayashri Desai, Joanna P. MacEwan “REAL-WORLD ADHERENCE TO OBETICHOLIC ACID THERAPY FOR PRIMARY BILIARY CHOLANGITIS” (Poster #Mo1626)Session: Human and Experimental Cholestatic and Autoimmune Liver DiseasesMonday, May 5, 12:30 PM ETRobert G. Gish, Joanna P. MacEwan, Jennifer Hernandez, Radhika Nair, Jing Li, Darren Wheeler, Anh Singhania, Leona Bessonova “PATIENTS WITHOUT BASELINE PRURITUS WHO INITIATE TREATMENT WITH OCA HAVE SIMILAR RISK OF DEVELOPING TREATMENT-EMERGENT PRURITUS AS THOSE WHO ARE NOT ON TREATMENT WITH OCA” (Poster #Mo1618)Session: Human and Experimental Cholestatic and Autoimmune Liver DiseasesMonday, May 5, 12:30 PM ETDavid Jones, Aparna Goel, Ann Moore, Jing Li, Darren Wheeler, Christopher White, and David W. Victor III “STABILIZATION OF ENHANCED LIVER FIBROSIS AND LIVER STIFFNESS MEASURES IN THE OPEN-LABEL EXTENSION OF THE PHASE 3 POISE TRIAL OF OBETICHOLIC ACID FOR THE TREATMENT OF PRIMARY BILIARY CHOLANGITIS” (Poster #Mo1667)Session: Non-Invasive Assessment of Liver DiseaseMonday, May 5, 12:30 PM ET Robert G. Gish, Darren Wheeler, Jing Li, Christopher Gasink, Alan Bonder “FARNESOID X RECEPTOR AGONIST INT-787 PROTECTS HUMAN LIVER ORGANOIDS FROM ALCOHOL-INDUCED INJURY” (Poster #Su1618)Session: Alcoholic-associated Liver Disease Including Alcohol-associated HepatitisSunday, May 4, 12:30 PM ETFrancesca De Franco, Daniela Passeri, Sanjay Kansra, Luciano Adorini, Mary Erickson, Roberto Pellicciari “FARNESOID X RECEPTOR AGONIST INT-787 EXHIBITS HIGH INTESTINAL LOCALIZATION” (Poster #Su1635)Session: Alcoholic-associated Liver Disease Including Alcohol-associated HepatitisSunday, May 4, 12:30 PM ETJennifer Burkey, Sanjay Kansra, Antonio Macchiarulo, Kenneth Brouwer, Luciano Adorini, Mary Erickson, Roberto Pellicciari “PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION OF OBETICHOLIC ACID AND BEZAFIBRATE IN HEALTHY VOLUNTEERS” (Poster #Mo1628)Session: Human and Experimental Cholestatic and Autoimmune Liver DiseasesMonday, May 5, 12:30 PM ETJennifer Burkey, Karen Brown, Heng Zou, Jennifer Boston, Mary Erickson “DEVELOPMENT OF A DE NOVO CLINICAL OUTCOME ASSESSMENT FOR CHRONIC INTESTINAL PSEUDO-OBSTRUCTION" (Poster #Mo1258)Session: Patient Report and Clinical Outcomes: IBD, GERC, Functional Disorders, Other Monday, May 5, 12:30 PM ETMadhusudan Grover, Jan Tack, Sara Manzoni, Elena Pasquali, Valeria Scuderi, Vincenzo Stanghellini More information about these presentations will be made available after the respective embargoes, as set by the DDW organizers, are lifted for each presentation. A full list of sessions at DDW 2025 is available at www.ddw.org. Attendees of DDW can visit Intercept at booths #2011 and #2411 throughout the meeting. About Digestive Disease WeekDigestive Disease Week (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW is an in-person and online meeting from May 3-6, 2025. The meeting showcases more than 5,600 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at www.ddw.org. About Primary Biliary CholangitisPrimary biliary cholangitis (PBC) is a rare, progressive and chronic autoimmune disease that affects the bile ducts in the liver and is most prevalent (approximately 1 in 10,000) in women over the age of 40. PBC causes bile acid to build up in the liver, resulting in inflammation and scarring (fibrosis), which, if left untreated, can lead to cirrhosis, a liver transplant or death. About Severe Alcohol-Associated Hepatitis (sAH)Alcohol-related liver disease (ALD) as a cause of chronic liver disease is on the rise in the U.S. and is currently the leading indication for liver transplant listing overall in the U.S. Patients with severe alcohol-associated hepatitis (sAH) are now younger, with an increased representation of females compared to past decades, reflecting changing patterns of alcohol consumption in the U.S. Currently, there are no medicines with an approved indication to treat patients with sAH. About Primary Sclerosing CholangitisPrimary sclerosing cholangitis (PSC) is a rare, life-threatening, chronic cholestatic liver disease characterized by progressive destruction of bile ducts that leads to the development of cirrhosis and end-stage liver disease or cancer in a majority of patients. About the Investigational Obeticholic Acid-Bezafibrate CombinationIntercept has two ongoing Phase 2 studies (747-213 / NCT04594694, 747-214 / NCT05239468) that are exploring a range of therapeutic doses for the combination of obeticholic acid (OCA) and bezafibrate for the potential treatment of individuals with PBC. Obeticholic acid, a farnesoid X receptor (FXR) agonist, is marketed by Intercept as OCALIVA in the United States for the treatment of PBC (see below for full indication and Important Safety Information). Bezafibrate, a pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, is not approved in the United States for any indication. FXR and PPAR are distinct pathways that each play a role in PBC. Simultaneously targeting both pathways may offer the greatest potential to impact bile acid synthesis, metabolism, and clearance that underly cholestatic liver diseases. Published studies establish a clinical proof-of-concept which suggests that the combination of obeticholic acid and bezafibrate may provide additive clinical efficacy and tolerability benefits in the treatment of PBC. Obeticholic acid-bezafibrate combination therapy is investigational; safety and efficacy have not been established. About OCALIVA (obeticholic acid)OCALIVA, a farnesoid X receptor (FXR) agonist, is indicated for the treatment of adult patients with primary biliary cholangitis (PBC) without cirrhosis orwith compensated cirrhosis who do not have evidence of portal hypertension, either in combination with ursodeoxycholic acid (UDCA) with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA. This indication is approved under accelerated approval based on a reduction in alkaline phosphatase (ALP). An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. IMPORTANT SAFETY INFORMATION WARNING: HEPATIC DECOMPENSATION AND FAILURE IN PRIMARY BILIARY CHOLANGITIS PATIENTS WITH CIRRHOSIS Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in primary biliary cholangitis (PBC) patients with either compensated or decompensated cirrhosis. OCALIVA is contraindicated in PBC patients with decompensated cirrhosis, a prior decompensation event, or with compensated cirrhosis who have evidence of portal hypertension. Permanently discontinue OCALIVA in patients who develop laboratory or clinical evidence of hepatic decompensation; have compensated cirrhosis and develop evidence of portal hypertension, or experience clinically significant hepatic adverse reactions while on treatment. Contraindications OCALIVA is contraindicated in patients with: decompensated cirrhosis (e.g., Child-Pugh Class B or C) or a prior decompensation eventcompensated cirrhosis who have evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia)complete biliary obstruction Warnings and Precautions Hepatic Decompensation and Failure in PBC Patients with Cirrhosis Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in PBC patients with cirrhosis, either compensated or decompensated. Among post-marketing cases reporting it, median time to hepatic decompensation (e.g., new onset ascites) was four months for patients with compensated cirrhosis; median time to a new decompensation event (e.g., hepatic encephalopathy) was 2.5 months for patients with decompensated cirrhosis. Some of these cases occurred in patients with decompensated cirrhosis when they were treated with higher than the recommended dosage for that patient population; however, cases of hepatic decompensation and failure have continued to be reported in patients with decompensated cirrhosis even when they received the recommended dosage. Hepatotoxicity was observed in the OCALIVA clinical trials. A dose-response relationship was observed for the occurrence of hepatic adverse reactions including jaundice, worsening ascites, and primary biliary cholangitis flare with dosages of OCALIVA of 10 mg once daily to 50 mg once daily (up to 5-times the highest recommended dosage), as early as one month after starting treatment with OCALIVA in two 3-month, placebo-controlled clinical trials in patients with primarily early stage PBC. Routinely monitor patients for progression of PBC, including hepatic adverse reactions, with laboratory and clinical assessments to determine whether drug discontinuation is needed. Closely monitor patients with compensated cirrhosis, concomitant hepatic disease (e.g., autoimmune hepatitis, alcoholic liver disease), and/or with severe intercurrent illness for new evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia), or increases above the upper limit of normal in total bilirubin, direct bilirubin, or prothrombin time to determine whether drug discontinuation is needed. Permanently discontinue OCALIVA in patients who develop laboratory or clinical evidence of hepatic decompensation (e.g., ascites, jaundice, variceal bleeding, hepatic encephalopathy), have compensated cirrhosis and develop evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia), experience clinically significant hepatic adverse reactions, or develop complete biliary obstruction. If severe intercurrent illness occurs, interrupt treatment with OCALIVA and monitor the patient’s liver function. After resolution of the intercurrent illness, consider the potential risks and benefits of restarting OCALIVA treatment. Severe Pruritus Severe pruritus was reported in 23% of patients in the OCALIVA 10 mg arm, 19% of patients in the OCALIVA titration arm, and 7% of patients in the placebo arm in a 12-month double-blind randomized controlled clinical trial of 216 patients. Severe pruritus was defined as intense or widespread itching, interfering with activities of daily living, or causing severe sleep disturbance, or intolerable discomfort, and typically requiring medical interventions. Consider clinical evaluation of patients with new onset or worsening severe pruritus. Management strategies include the addition of bile acid binding resins or antihistamines, OCALIVA dosage reduction, and/or temporary interruption of OCALIVA dosing. Reduction in HDL-C Patients with PBC generally exhibit hyperlipidemia characterized by a significant elevation in total cholesterol primarily due to increased levels of high-density lipoprotein-cholesterol (HDL-C). Dose-dependent reductions from baseline in mean HDL-C levels were observed at 2 weeks in OCALIVA-treated patients, 20% and 9% in the 10 mg and titration arms, respectively, compared to 2% in the placebo arm. Monitor patients for changes in serum lipid levels during treatment. For patients who do not respond to OCALIVA after one year at the highest recommended dosage that can be tolerated (maximum of 10 mg once daily), and who experience a reduction in HDL-C, weigh the potential risks against the benefits of continuing treatment. Adverse Reactions The most common adverse reactions (≥5%) are pruritus, fatigue, abdominal pain and discomfort, rash, oropharyngeal pain, dizziness, constipation, arthralgia, thyroid function abnormality, and eczema. Drug Interactions Bile Acid Binding Resins Bile acid binding resins such as cholestyramine, colestipol, or colesevelam adsorb and reduce bile acid absorption and may reduce the absorption, systemic exposure, and efficacy of OCALIVA. If taking a bile acid binding resin, take OCALIVA at least four hours before or four hours after taking the bile acid binding resin, or at as great an interval as possible.Warfarin The International Normalized Ratio (INR) decreased following coadministration of warfarin and OCALIVA. Monitor INR and adjust the dose of warfarin, as needed, to maintain the target INR range when co-administering OCALIVA and warfarin.CYP1A2 Substrates with Narrow Therapeutic Index Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates. Therapeutic monitoring of CYP1A2 substrates with a narrow therapeutic index (e.g., theophylline and tizanidine) is recommended when co-administered with OCALIVA.Inhibitors of Bile Salt Efflux Pump Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP) such as cyclosporine. Concomitant medications that inhibit canalicular membrane bile acid transporters such as the BSEP may exacerbate accumulation of conjugated bile salts including taurine conjugate of obeticholic acid in the liver and result in clinical symptoms. If concomitant use is deemed necessary, monitor serum transaminases and bilirubin. Please click here for Full Prescribing Information, including boxed WARNING. To report SUSPECTED ADVERSE REACTIONS, contact Intercept Pharmaceuticals, Inc. at 1-844-782-ICPT or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. About InterceptIntercept, part of the Alfasigma Group since 2023, focuses on the development and commercialization of novel therapeutics to treat serious liver and GI diseases, including primary biliary cholangitis (PBC) and severe alcohol-associated hepatitis (sAH). Intercept owns the commercial rights to OCALIVA in the U.S. market. For more information, please visit www.interceptpharma.com or connect with the Company on LinkedIn, and X (formerly Twitter). About Alfasigma Alfasigma is a global pharmaceutical company founded over 75 years ago in Italy, where it is headquartered (in Bologna and Milan). The Group operates in over 100 markets spanning Europe, North and South America, Asia, and Africa. It has offices in many countries, including Italy, the United States (US), Spain, Germany, Mexico, and China; production sites in Italy, Spain, and the US; and R&D labs in Italy (Pomezia and Bergamo). Alfasigma employs approximately 4,000 people dedicated to research, development, production, and distribution of medicinal products contributing to its mission to provide better health and a better quality of life for patients, caregivers, and healthcare providers. It focuses on three main therapeutic areas: Gastroenterology/Hepatology, Vascular, and Rheumatology. Its portfolio spans from primary care to specialty care, rare disease medications, and consumer health products, including medical foods and nutraceuticals. For more information, please visit www.alfasigma.com or connect with the Company on LinkedIn, ContactFor more information about Intercept, please contact: media@interceptpharma.com

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Shorla Oncology (‘Shorla’), a U.S.-Ireland specialty pharmaceutical company, announced today that the U.S. Food and Drug Administration has granted approval for 100 mg/10mL multi-dose vial of TEPYLUTE, a ready-to-dilute formulation of thiotepa to treat breast and ovarian cancer, that eliminates the need for reconstitution and may reduce preparation time and errors offering more scheduling flexibility for their patients. Shorla Oncology Announces FDA Approval of TEPYLUTE® 100mg, First and Only Ready-to-Dilute Multi-Dose Vial of Thiotepa to Treat Breast and Ovarian Cancer and Commercial Launch of TEPYLUTE 15mg and 100mg Vials in the U.S. “We are pleased to offer another viable treatment option for patients with breast and ovarian cancer,” said Sharon Cunningham, Chief Executive Officer and Co-Founder of Shorla Oncology. “Once opened, our 100mg vial of TEPYLUTE is stable for 14 days when properly stored, giving providers the flexibility they need when preparing and administering this very important treatment. TEPYLUTE is a ready to dilute formulation of a well-established, standard of care oncology drug thiotepa that has been manufactured as freeze-dried powder since the 1950s. “This is a huge win for providers because TEPYLUTE avoids the need for complicated and time-consuming reconstitution,” said Orlaith Ryan, Chief Technical Officer and Co-Founder of Shorla Oncology. We are excited to bring TEPYLUTE to the US Market. It provides consistent dosing accuracy and allows for “just in time” preparation, which benefits everyone, especially patients.” said Rayna Herman, Chief Commercial Officer, Shorla Oncology. The American Cancer Society estimates that more than 300,000 women will be diagnosed with breast cancer in the U.S in 2025.2 About 20,890 women will be diagnosed with ovarian cancer in the U.S. in 2025.3 About Shorla Oncology Shorla Oncology is a privately- held, U.S. and Ireland- based commercial stage specialty pharmaceutical company established by Sharon Cunningham and Orlaith Ryan. The company has an advanced pipeline of innovative oncology drugs for orphan and pediatric cancers. Shorla is focused on indications where existing treatments are limited, in shortage or the drug applications are inadequate for the target population. The company’s growing portfolio brings accessible, affordable and life-saving treatments to patients, delivering a major contribution to patient care. Shorla currently markets three products, Nelarabine for the treatment of T-cell leukemia, JYLAMVO™ for the treatment of acute lymphoblastic leukemia and other indications and IMKELDI for the treatment of Chronic Myeloid Leukemia, Gastrointestinal Stromal Tumors (GISTs) and other indications. For further information, please visit www.shorlaoncology.com. TEPYLUTE® (thiotepa) Injection for Intravenous Use INDICATION TEPYLUTE is an alkylating drug indicated for the treatment of adenocarcinoma of the breast or ovary. IMPORTANT SAFETY INFORMATION WARNING: SEVERE MYELOSUPPRESSION and CARCINOGENICITY • TEPYLUTE may cause severe marrow suppression, and high doses may cause marrow ablation with resulting infection or bleeding. Monitor hematologic laboratory parameters. • TEPYLUTE should be considered potentially carcinogenic in humans. CONTRAINDICATIONS TEPYLUTE is contraindicated in patients with severe hypersensitivity to thiotepa and in concomitant use with live or attenuated vaccines. WARNINGS AND PRECAUTIONS Myelosuppression : For patients receiving TEPYLUTE for treatment of adenocarcinoma of the breast or adenocarcinoma of the ovary, if the bone marrow has been compromised by prior irradiation or chemotherapy, or is recovering from chemotherapy, the risk of severe myelosuppression with TEPYLUTE may be increased. Perform periodic complete blood counts during the course of treatment with TEPYLUTE. Provide supportive care for infections, bleeding, and symptomatic anemia. Inform patients of the possibility of developing low blood cell counts and the need for hematopoietic progenitor cell infusion. Instruct patients to immediately report to their healthcare provider if bleeding or fever occurs. Hypersensitivity: Clinically significant hypersensitivity reactions, including anaphylaxis, have occurred following administration of thiotepa. If anaphylactic or other clinically significant allergic reaction occurs, discontinue treatment with TEPYLUTE, initiate appropriate therapy, and monitor until signs and symptoms resolve. Counsel patients on the signs and symptoms of hypersensitivity and to seek immediate emergency assistance if they develop any of these signs and symptoms. Cutaneous Toxicity: TEPYLUTE and/or its active metabolites may be excreted in part via skin in patients receiving high-dose therapy. Treatment with TEPYLUTE may cause skin discoloration, pruritus, blistering, desquamation, and peeling that may be more severe in the groin, axillae, skin folds, in the neck area, and under dressings. Instruct patients to shower or bathe with water at least twice daily through 48 hours after administration of TEPYLUTE. Change the occlusive dressing and clean the covered skin at least twice daily through 48 hours after administration of TEPYLUTE. Change bed sheets daily during treatment. Skin reactions associated with accidental exposure to TEPYLUTE may occur. Wash the skin thoroughly with soap and water in case the TEPYLUTE solution contacts the skin. Flush mucous membranes in case of TEPYLUTE contact with mucous membranes. Concomitant Use of Live and Attenuated Vaccines: Do not administer live or attenuated viral or bacterial vaccines to a patient treated with TEPYLUTE until the immunosuppressive effects have resolved. Hepatic Veno-Occlusive Disease: Monitor by physical examination, serum transaminases, and bilirubin, and provide supportive care to patients who develop hepatic veno-occlusive disease. Central Nervous System Toxicity: Fatal encephalopathy has occurred in patients treated with high doses of thiotepa. Other central nervous system toxicities, such as headache, apathy, psychomotor retardation, disorientation, confusion, amnesia, hallucinations, drowsiness, somnolence, seizures, coma, inappropriate behavior, and forgetfulness have been reported to occur in a dose-dependent manner during or shortly after administration of high-dose thiotepa. Do not exceed the recommended dose of TEPYLUTE. If severe or life-threatening central nervous system toxicity occurs, discontinue administration of TEPYLUTE and provide supportive care. Carcinogenicity: Like many alkylating agents, thiotepa has been reported to be carcinogenic when administered to laboratory animals. Carcinogenicity is shown most clearly in studies using mice, but there is some evidence of carcinogenicity in man. There is an increased risk of secondary malignancy with the use of TEPYLUTE. Inform patients that TEPYLUTE can increase the risk of secondary malignancy. Polyethylene glycol (PEG) 400 toxicity : TEPYLUTE contains a high concentration of PEG 400. Based on findings in animals, administration of high amounts of PEG 400 may cause damage to the kidneys and liver at dosages higher than recommended. When prescribing TEPYLUTE, take into consideration the PEG 400 load from concomitant medications. Embryo-Fetal Toxicity: Based on the mechanism of action and findings in animals, TEPYLUTE can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of TEPYLUTE in pregnant women. Thiotepa given by the intraperitoneal (IP) route was teratogenic in mice at doses ≥1 mg/kg (3.2 mg/m 2 ), approximately 8-fold less than the maximum recommended human therapeutic dose (0.8 mg/kg, 27 mg/m 2 ), based on body-surface area. Thiotepa given by the IP route was teratogenic in rats at doses ≥3 mg/kg (21 mg/m 2 ), approximately equal to the maximum recommended human therapeutic dose, based on body-surface area. Thiotepa was lethal to rabbit fetuses at a dose of 3 mg/kg (41 mg/m 2 ), approximately two times the maximum recommended human therapeutic dose based on body-surface area. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use highly effective contraception during TEPYLUTE treatment and for 6 months after therapy/the last dose. Advise females of reproductive potential to inform their healthcare provider if they are pregnant or become pregnant. Advise males with female partners of reproductive potential to use effective contraception during TEPYLUTE treatment and for 1 year after therapy/the last dose. ADVERSE REACTIONS The most common adverse reactions (incidence greater than 10%) are neutropenia, anemia, thrombocytopenia, elevated alanine aminotransferase, elevated aspartate aminotransferase (AST), elevated bilirubin, mucositis, cytomegalovirus infection, hemorrhage, diarrhea, hematuria, and rash. The clinically significant adverse reactions include myelosuppression, infection, hypersensitivity, cutaneous toxicity, hepatic veno-occlusive disease, central nervous system toxicity, and carcinogenicity. DRUG INTERACTIONS Effect of Cytochrome CYP3A Inhibitors and Inducers: In vitro studies suggest that thiotepa is metabolized by CYP3A4 and CYP2B6 to its active metabolite triethylene phosphoramide (TEPA). Avoid coadministration of strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ritonavir) and strong CYP3A4 inducers (e.g., rifampin, phenytoin) with thiotepa due to the potential effects on efficacy and toxicity. Consider alternative medications with no or minimal potential to inhibit or induce CYP3A4. If concomitant use of strong CYP3A4 modulators cannot be avoided, closely monitor for adverse drug reactions. Effect of TEPYLUTE on Cytochrome CYP2B6 Substrates: In vitro studies suggest that thiotepa inhibits CYP2B6. Thiotepa may increase the exposure of drugs that are substrates of CYP2B6 in patients; however, the clinical relevance of this in vitro interaction is unknown. The administration of thiotepa with cyclophosphamide in patients reduces the conversion of cyclophosphamide to the active metabolite, 4‑hydroxycyclophosphamide; the effect appears sequence-dependent with a greater reduction in the conversion to 4-hydroxycyclophosphamide when thiotepa is administered 1.5 hours before the intravenous administration of cyclophosphamide compared to administration of thiotepa after intravenous cyclophosphamide. The reduction in 4-hydroxycyclophosphamide levels may potentially reduce the efficacy of cyclophosphamide treatment. USE IN SPECIFIC POPULATIONS Pregnancy: TEPYLUTE can cause fetal harm when administered to a pregnant woman based on findings from animals and the drug’s mechanism of action. Limited available data on thiotepa use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, administration of thiotepa to pregnant mice and rats during organogenesis produced teratogenic effects (neural tube defects and malformations of the skeletal system of the fetus) at doses approximately 0.125 and 1 times, respectively, the maximum recommended human daily dose on a mg/m2 basis. Thiotepa was lethal to rabbit fetuses at approximately 2 times the maximum recommended human therapeutic dose based on body-surface area. Consider the benefits and risks of TEPYLUTE for the mother and possible risks to the fetus when prescribing TEPYLUTE to a pregnant woman. Lactation: There is no information regarding the presence of thiotepa in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions, including the potential for tumorigenicity shown for thiotepa in animal studies, advise patients not to breastfeed during TEPYLUTE treatment and for 1 week after therapy/the last dose. Females and Males of Reproductive Potential: TEPYLUTE can cause fetal harm when administered to a pregnant woman. Pregnancy Testing - Verify the pregnancy status of females of reproductive potential before initiating TEPYLUTE therapy. Contraception for Females - Advise females of reproductive potential to avoid pregnancy during TEPYLUTE treatment and for 6 months after therapy/the last dose. Advise females to immediately report pregnancy. Contraception for Males - TEPYLUTE may damage spermatozoa and testicular tissue, resulting in possible genetic abnormalities. Males with female sexual partners of reproductive potential should use effective contraception during TEPYLUTE treatment and for 1 year after therapy/the last dose. Infertility - Based on nonclinical findings, male and female fertility may be compromised by treatment with TEPYLUTE. Advise patients that TEPYLUTE can produce infertility. Inform male patients about the possibility of sperm conservation before the start of therapy. Pediatric Use: Safety and effectiveness of TEPYLUTE in neonates have not been established. Safety and effectiveness of TEPYLUTE for the treatment of adenocarcinoma of the breast and adenocarcinoma of the ovary in pediatric patients have not been established. Geriatric Use: Clinical studies of thiotepa for treatment of adenocarcinoma of the breast and adenocarcinoma of the ovary did not include sufficient numbers of subjects aged 65 years and over to determine whether elderly subjects respond differently from younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreasing hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Renal Impairment: In patients with moderate (creatinine clearance [CLcr] of 30 mL/min to 59 mL/min) renal impairment, decreased renal excretion may result in increased plasma levels of thiotepa and TEPA. This may result in increased toxicity. Monitor patients with moderate to severe (CLcr <30 mL/min) renal impairment for signs and symptoms of toxicity following treatment with TEPYLUTE for an extended period of time. Hepatic Impairment: Thiotepa is extensively metabolized in the liver. Patients with moderate (bilirubin levels greater than 1.5 times to 3 times the upper limit of normal and any AST) hepatic impairment may have increased plasma levels of thiotepa. This may result in toxicity. Monitor patients with moderate to severe (bilirubin levels greater than 3 times the upper limit of normal and any AST) hepatic impairment for signs and symptoms of toxicity following treatment with TEPYLUTE for an extended period of time. To report suspected adverse reactions, contact Shorla Oncology at 1-844-668-3940 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. For Print: Please see the accompanying full Prescribing Information, including Boxed Warning. For Digital: Please click here for full Prescribing Information, including Boxed Warning. All trademarks are the property of Shorla Oncology. ©SHORLA ONCOLOGY® 2025. PRO-TEP-1377-v1 04/2025

- Label includes full spectrum of PKU patients - - European launch preparations underway - WARREN, N.J., April 25, 2025 /PRNewswire/ -- PTC Therapeutics, Inc. (NASDAQ: PTCT) announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion on the marketing authorization application for Sephience™ (sepiapterin) for the treatment of children and adults living with phenylketonuria (PKU). The opinion includes a broad label inclusive of all ages and disease severities. "This positive opinion is great news for the PKU patient community in Europe for whom there remains a significant unmet medical need," said Matthew B. Klein, M.D., Chief Executive Officer of PTC Therapeutics. "We look forward to initiating the European launch immediately following the adoption of this positive opinion by the European Commission. The data collected to date continue to support the potential for Sephience to provide a safe and effective treatment that not only lowers phenylalanine levels but also enables diet liberalization even for those with the most severe disease subtypes." Launch planning in Europe is well underway with priorities in Germany and other key European markets where named patient access will be immediately available. PTC expects the European Commission to ratify the marketing authorization for Sephience in approximately two months. The decision will be applicable to all 27 European Union member states, as well as Iceland, Norway and Liechtenstein. The New Drug Application (NDA) for sepiapterin is under review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of July 29, 2025. Review of approval applications is ongoing in several other countries including Japan and Brazil. About Sephience™ (sepiapterin) Sephience, an oral formulation of synthetic sepiapterin, has a dual mechanism of action to increase activity of the phenylalanine hydroxylase (PAH) enzyme. First, Sephience is a precursor compound that is rapidly absorbed and converted intracellularly to tetrahydrobiopterin (BH4), a critical cofactor of PAH. Sephience also has an independent pharmacological chaperone effect, correcting PAH misfolding to enhance the enzyme function. Through this dual mechanism of action, Sephience effectively reduces blood phenylalanine (Phe) levels and has the potential to treat a broad range of PKU patients. About Phenylketonuria Phenylketonuria (PKU) is a rare, inherited metabolic disease, which affects the brain. It is caused by a defect in the gene that helps create the enzyme needed to break down phenylalanine (Phe). If left untreated or poorly managed, Phe – an essential amino acid found in all proteins and most foods – can build up to harmful levels in the body. This causes severe and irreversible disabilities, such as permanent intellectual disability, seizures, delayed development, memory loss, and behavioral and emotional problems. Newborns with PKU initially don't have any symptoms, but symptoms are usually progressive, and damage caused by toxic levels of Phe in the first few years of life is irreversible. Diagnosis of PKU usually takes place during newborn screening programs. There are an estimated 58,000 people living with PKU globally. About PTC Therapeutics, Inc. PTC is a global biopharmaceutical company that discovers, develops and commercializes clinically differentiated medicines that provide benefits to children and adults living with rare disorders. PTC's ability to innovate new therapies and to globally commercialize products is the foundation that drives investment in a robust and diversified pipeline of transformative medicines. To learn more about PTC, please visit us at and follow us on Facebook, X, and LinkedIn. For More Information: Investors: Ellen Cavaleri +1 (615) 618-6228 [email protected] Media: Jeanine Clemente +1 (908) 912-9406 [email protected] Forward-Looking Statement This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this release, other than statements of historic fact, are forward-looking statements, including statements regarding: the future expectations, plans and prospects for PTC, including with respect to the expected timing of clinical trials and studies, availability of data, regulatory submissions and responses, commercialization and other matters with respect to its products and product candidates; expectations with respect to Sephience, including any regulatory decision made by the European Commission; PTC's strategy, future operations, future financial position, future revenues, projected costs; and the objectives of management. Other forward-looking statements may be identified by the words, "guidance", "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions. PTC's actual results, performance or achievements could differ materially from those expressed or implied by forward-looking statements it makes as a result of a variety of risks and uncertainties, including those related to: the outcome of pricing, coverage and reimbursement negotiations with third party payors for PTC's products or product candidates that PTC commercializes or may commercialize in the future; expectations with respect to Sephience, including any regulatory submissions and potential approvals, commercialization and the potential achievement of regulatory and sales milestones and contingent payments that PTC may be obligated to make; significant business effects, including the effects of industry, market, economic, political or regulatory conditions; changes in tax and other laws, regulations, rates and policies; the eligible patient base and commercial potential of PTC's products and product candidates; PTC's scientific approach and general development progress; and the factors discussed in the "Risk Factors" section of PTC's most recent Annual Report on Form 10-K, as well as any updates to these risk factors filed from time to time in PTC's other filings with the SEC. You are urged to carefully consider all such factors. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially successful, including Sephience. The forward-looking statements contained herein represent PTC's views only as of the date of this press release and PTC does not undertake or plan to update or revise any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or projections, or other circumstances occurring after the date of this press release except as required by law. SOURCE PTC Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED