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˗ REZLIDHIA induced durable remissions in adult patients with mIDH1 R/R AML SOUTH SAN FRANCISCO, Calif., Feb. 2, 2023 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced a peer-reviewed publication of data in Blood Advances, which summarizes clinical results from the Phase 2 registrational study of REZLIDHIA™ (olutasidenib), a potent, selective, oral, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1)1, in patients with mIDH1 relapsed or refractory acute myeloid leukemia (R/R AML). The published data demonstrate that REZLIDHIA induced durable remissions and transfusion independence with a well-characterized safety profile. The observed efficacy is clinically meaningful and represents a therapeutic advance in this poor prognosis patient population with limited treatment options. The pivotal cohort of the Phase 2 registrational study enrolled 153 adult patients with mIDH1 R/R AML who received REZLIDHIA monotherapy 150 mg twice daily orally. The efficacy evaluable population included 147 patients with centrally confirmed mIDH1. The primary endpoint was a composite of complete remission (CR) plus complete remission with partial hematologic recovery (CRh). CRh is defined as less than 5% blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/microliter and absolute neutrophil count >500/microliter). Key findings from the trial are summarized below: REZLIDHIA demonstrated a 35% (51/147) CR+CRh rate in mIDH1 R/R AML patients. Of the patients who achieved the primary endpoint of CR+CRh, 92% (47/51) were CR. Most patients who achieved CR or CRh responded early, with a median time to response of 1.9 months. The overall response rate was 48% (71/147). Response rates were similar in patients who had and who had not received prior venetoclax. In patients treated with REZLIDHIA, the median duration of CR+CRh was 25.9 months and the median duration of CR was 28.1 months. The median duration of overall response was 11.7 months. Median overall survival (OS) was 11.6 months in the overall population of 153 patients. In patients who achieved CR+CRh, median OS was not reached and the estimated 18-month survival was 78%. Conversion to transfusion independence (TI), another recognized indicator of clinical benefit, was achieved in 34% of patients receiving REZLIDHIA that had been classified as dependent on RBC and/or platelet transfusions at baseline. TI was observed in patients in all response groups. REZLIDHIA was well characterized with an adverse event profile largely representative of symptoms or conditions experienced by patients with AML undergoing treatment. Investigators observed differentiation syndrome in 14% of patients that was manageable in most cases with dose interruption and corticosteroids. The most common adverse events were gastrointestinal and hematologic in nature, and most cases were manageable with dose interruptions or modifications. The paper, titled "Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML," was published online in Blood Advances on February 1, 2023. A link to the publication can be found here. "REZLIDHIA demonstrated both a high rate of response and an extended median duration of complete response of 28.1 months, which is more than a year longer than what is reported with the standard of care," said Jorge E. Cortes, M.D., Director, Georgia Cancer Center, Cecil F. Whitaker Jr., GRA Eminent Scholar Chair in Cancer, and Phase 2 trial investigator. "In addition to these impressive efficacy results that could differentiate REZLIDHIA from other available therapies, I am encouraged by the safety profile. These collective data support REZLIDHIA as a therapeutic advance in this poor prognosis patient population." "The published data adds to our robust body of evidence reinforcing REZLIDHIA as a differentiated and potentially market-leading therapy for mIDH1 R/R AML patients," said Raul Rodriguez, Rigel's president and CEO. "With the recent approval of REZLIDHIA in the U.S., we believe our therapy will be an important new treatment option for this underserved patient population with a high unmet medical need. We are encouraged by this compelling data, particularly the durability of response, and look forward to providing REZLIDHIA to mIDH1 R/R AML patients" On December 1, 2022, the U.S. Food and Drug Administration (FDA) approved REZLIDHIA (olutasidenib) capsules for the treatment of adult patients with R/R AML with a susceptible IDH1 mutation as detected by an FDA-approved test. REZLIDHIA became commercially available in the U.S. on December 22, 2022. REZLIDHIA was added to the latest NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for acute myeloid leukemia (AML) on January 13, 2023, and is now a recommended targeted therapy for adult patients with R/R AML with isocitrate dehydrogenase-1 (IDH1) mutation. On November 10, 2022, Rigel announced the publication of data in The Lancet Haematology summarizing the Phase 1 results of the Phase 1/2 study of olutasidenib. The press release regarding this publication can be found here. About AML Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that in the United States alone, there will be about 20,050 new cases, most in adults, in 2022.2 Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.3 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.4 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need. About REZLIDHIA™ INDICATION REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Differentiation Syndrome REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis. If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence. Hepatotoxicity REZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity. One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months). The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin. Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity. ADVERSE REACTIONS The most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis. DRUG INTERACTIONS Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers. Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs. LACTATION Advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose. GERIATRIC USE No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age. HEPATIC IMPAIRMENT In patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome. Click here for Full Prescribing Information, including Boxed WARNING. To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088). REZLIDHIA is a trademark of Rigel Pharmaceuticals, Inc. About Rigel Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel small molecule drugs that significantly improve the lives of patients with hematologic disorders, cancer, and rare immune diseases. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit www.rigel.com. de Botton S, et al. Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML. Blood Advances. February 1, 2023. doi: https://doi.org/10.1182/bloodadvances.2022009411 The American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML). Revised January 12, 2022. Accessed Aug. 1, 2022 at https://www.cancer.org/cancer/acute-myeloid-leukemia/about/key-statistics.html Leukaemia Care. (2019). Relapse in Acute Myeloid Leukaemia (AML). Version 3. Reviewed October 2021. Accessed Dec 2, 2021 at https://media.leukaemiacare.org.uk/wp-content/uploads/Relapse-in-Acute-Myeloid-Leukaemia-AML-Web-Version.pdf Thol F, Schlenk RF, Heuser M, Ganser A. How I treat refractory and early relapsed acute myeloid leukemia. Blood (2015) 126 (3): 319-27. doi: https://doi.org/10.1182/blood-2014-10-551911

OCA 25 mg demonstrated double the response rate of placebo in reduction of liver fibrosis without worsening of NASH; consistent antifibrotic effect shown across multiple analyses OCA 25 mg showed increased antifibrotic efficacy in patients with advanced fibrosis without cirrhosis Robust safety assessment of 2,477 patients, including 1,000 on study drug for four years, supports chronic administration of OCA REGENERATE data to be presented in late-breaking oral session on Monday, November 7 Company remains on track to resubmit new drug application for OCA in liver fibrosis due to NASH by end of 2022 MORRISTOWN, N.J., Nov. 07, 2022 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT), a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, today announced additional supportive data from its pivotal Phase 3 REGENERATE study of obeticholic acid (OCA) in patients with liver fibrosis due to nonalcoholic steatohepatitis (NASH). These analyses further demonstrate OCA’s consistent and well-defined antifibrotic effect as well as its monitorable and manageable safety and tolerability profile in patients with liver fibrosis due to NASH. These data will be presented on Monday, November 7, 2022, at The Liver Meeting®, the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, D.C. “The antifibrotic effect of OCA has been demonstrated in multiple analyses of REGENERATE. This efficacy, together with extended exposure in the largest safety database in NASH, supports a positive benefit:risk for OCA in patients with fibrosis due to NASH,” said Dr. Arun Sanyal, Chair, Division of Gastroenterology/Hepatology/Nutrition & Director, Stravitz-Sanyal Liver Institute, VCU Health, Department of Internal Medicine. “The results of these new analyses – and specifically the consistent response rate for OCA 25 mg on multiple fibrosis endpoints vs. placebo – together with a detailed safety analysis, reaffirm our belief that OCA can be an important treatment for people living with fibrosis due to NASH,” said M. Michelle Berrey, M.D., M.P.H., President of Research & Development and Chief Medical Officer of Intercept. “Importantly, in these new analyses, we found that this antifibrotic effect is even more pronounced in patients with advanced fibrosis without cirrhosis at baseline, which underscores the urgency in treating patients before they progress to liver cirrhosis. We look forward to resubmitting our new drug application for OCA in fibrosis due to NASH by the end of this year based on these positive data.” Interim Efficacy Analysis As previously reported in July 2022, in a second interim analysis of the ITT population from REGENERATE (n=931), 22.4% of subjects randomized to once-daily oral OCA 25 mg met the primary endpoint of achieving at least one stage of fibrosis improvement with no worsening of NASH at Month 18 on liver biopsy compared with 9.6% of subjects on placebo (p<0.0001). There was not a statistically significant difference between OCA 10 mg and placebo; however, there was a clear dose-response across all arms. These results, which used a consensus panel approach to reading biopsies, were consistent with those from the original interim analysis in 2019, which used a single reader approach. Additional Supportive Efficacy Analyses Additional efficacy analyses conducted in the ITT population reinforced consistent antifibrotic effect, showing: Antifibrotic effect was more pronounced in individuals with advanced fibrosis without cirrhosis (F3) at baseline (n=520), with 25.4% of patients in the OCA 25 mg group demonstrating an improvement in fibrosis by at least 1 stage without worsening of NASH as compared to 9.5% in placebo (p=0.0001).In individuals with F2 fibrosis at baseline (n=411), 18.7% of patients in the OCA 25 mg group demonstrated an improvement in fibrosis by at least 1 stage without worsening of NASH as compared to 9.9% in placebo (p<0.04). An additional analysis of the subset of patients in the ITT population who had evaluable biopsies at baseline and Month 18 (n=747) was conducted within each treatment arm to show improvement, worsening or no change in fibrosis stage. Within the OCA 25 mg group, there was a more than two-fold change in improvement relative to worsening, whereas more patients worsened than improved in the placebo arm. Following the original analysis of the ITT population in 2019, an additional 676 patients became eligible for Month 18 biopsies prior to a protocol change in REGENERATE that eliminated this biopsy requirement. An analysis of the 676 patients combined with the ITT population (n=1,607) showed that 21.0% of patients in the OCA 25 mg group demonstrated an improvement in fibrosis by at least 1 stage without worsening of NASH compared to 12.3% in placebo. Safety and Tolerability Safety was evaluated in 2,477 subjects who took at least one dose of study drug (placebo, OCA 10 mg, or OCA 25 mg). As previously reported, patients in this second interim analysis of REGENERATE had significantly longer exposure to study drug compared to the original analysis in 2019 (median 42 months vs. 15 months), yielding more than 8,000 total patient-years and 3.4 times more exposure. Nearly 1,000 subjects had been on study drug for four years. Treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and deaths were generally balanced across the OCA and placebo treatment groups. The most common TEAE was pruritus (24% in placebo, 33% in OCA 10 mg, 55% in OCA 25 mg) and pruritus was the most common cause for treatment discontinuation. Independent groups of experts reviewed certain categories of safety events to provide a blinded adjudication as specifically requested by FDA. These included events pertaining to hepatic safety (excluding clinical outcomes), cardiovascular and renal. Analysis through four years of treatment showed: Most adjudicated hepatic safety events reflected biochemical changes common in patients with advanced fibrosis due to NASH and, for the OCA-treated arms, the effects of FXR agonism. There were a numerically higher number of adjudicated hepatic safety events in the OCA 25 mg arm (111 in placebo, 112 in OCA 10 mg, 140 in OCA 25 mg), the vast majority of which were mild. Across all treatment arms, the number of adjudicated hepatic safety events considered to be highly likely or probably related to IP were low (1 in placebo, 1 in OCA 10 mg, 7 in OCA 25 mg).The number of cases that met biochemical Hy’s Law criteria were low and balanced across treatment arms (7 in placebo, 6 in OCA 10 mg, 6 in OCA 25 mg).The frequency of core major adverse cardiovascular events (MACE), 4-point MACE (defined as core MACE + unstable angina) and 5-point MACE (defined as core MACE + unstable angina and hospitalization for heart failure) was low and balanced among treatment groups. Core MACE: 1.2% in placebo, 0.5% in OCA 10 mg, 1.3% in OCA 25 mg4-point MACE: 1.5% in placebo, 1.0% in OCA 10 mg, 1.6% in OCA 25 mg5-point MACE: 1.8% in placebo, 1.0% in OCA 10 mg, 1.6% in OCA 25 mg There was one adjudicated cardiovascular death in each of the three treatment arms.The number of renal events submitted for adjudication were balanced across treatment arms (33 in placebo, 34 in OCA 10 mg, 33 in OCA 25 mg). Additionally, the number of events adjudicated as acute kidney injury were low and balanced across treatments arms (3 in placebo, 0 in OCA 10 mg, 3 in OCA 25 mg). Additional adverse events of special interest (AESIs) were also captured and monitored: Consistent with its known mechanism of action, higher rates of gallbladder-related adverse events, including gallstones, were seen in the OCA arms (4.0% in placebo, 5.2% in OCA 10 mg, 7.6% in OCA 25 mg). Serious gallbladder-related events, most commonly cholecystitis, were low in all treatment groups (0.7% in placebo, 1.0% in OCA 10 mg, 2.5% in OCA 25 mg).Rates of hyperglycemia or worsening diabetes were balanced across treatment arms (23.0% in placebo, 27.0% in OCA 10 mg, 24.3% in OCA 25 mg). A total of 5 cases of diabetic ketoacidosis (DKA) were reported across all arms (1 in placebo, 2 in OCA 10 mg, 2 in OCA 25 mg).The incidence of pancreatitis TEAEs was low and balanced across study arms (0.8% in placebo, 0.6% in OCA 10 mg, 1.0% in OCA 25 mg). In the placebo arm, there was one fatal case of pancreatitis.Rates of urinary tract stones were similar across all arms (3.9% in placebo, 3.8% in OCA 10 mg, 3.4% in OCA 25 mg). Consistent with its mechanism of action as an FXR agonist, OCA treatment was associated with an increase in LDL at Month 1 which returned to near baseline values by Month 12. Patients who initiated a statin saw a more rapid reduction to near baseline values. Changes in other blood chemistries including, GGT (gamma-glutamyl transferase), AST (aspartate aminotransferase), and ALT (alanine aminotransferase) also showed improvements, supporting the dose-response of OCA. OCA has not been approved for the treatment of NASH by any regulatory authority in any geography and is considered an investigational treatment for this indication. About the REGENERATE Study REGENERATE (Randomized Global Phase 3 Study to Evaluate the Impact on NASH with Fibrosis of Obeticholic Acid Treatment) is an ongoing Phase 3, randomized, double-blind, placebo-controlled, multicenter, international study assessing the safety and efficacy of obeticholic acid (OCA) on clinical outcomes in patients with liver fibrosis due to NASH. A pre-specified interim analysis was conducted in 931 subjects who had a liver biopsy at Month 18 to assess the effect of OCA on liver histology as compared to baseline biopsies. REGENERATE is fully enrolled with 2,480 randomized participants and is expected to continue while collecting data on the incidence of clinical outcomes for verification and description of clinical benefit. The end-of-study primary endpoint will compare the impact of treatment group (placebo, OCA 10 mg or OCA 25 mg daily) on all-cause mortality and liver-related clinical outcomes, as well as on long-term safety. About Intercept Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, including primary biliary cholangitis (PBC) and nonalcoholic steatohepatitis (NASH). For more information, please visit www.interceptpharma.com or connect with the company on Twitter and LinkedIn. About Liver Fibrosis due to NASH Nonalcoholic steatohepatitis (NASH) is a serious progressive liver disease caused by excessive fat accumulation in the liver that induces chronic inflammation, resulting in progressive fibrosis (scarring) that can lead to cirrhosis, eventual liver failure, cancer and death. Advanced fibrosis is associated with a substantially higher risk of liver-related morbidity and mortality in patients with NASH. There are currently no medications approved for the treatment of NASH. Forward-Looking Statements This press release contains forward-looking statements (FLS), including regarding resubmission and timing of Intercept’s new drug application for OCA for treatment of liver fibrosis due to NASH. Important factors could cause actual results to differ materially from the FLS. For example, our resubmission could be delayed or be unsuccessful because of efficacy, safety, or tolerability concerns, problems with our clinical studies and their data or methods, or our inability to address to the satisfaction of the FDA the issues raised in their complete response letter of June 2020 responding to our earlier submission. CONTACT For more information about Intercept, please contact: For investors:Nareg Sagherian, Executive Director, Global Investor Relationsinvestors@interceptpharma.com For media:Karen Preble, Executive Director, Global Corporate Communicationsmedia@interceptpharma.com

OCA 25 mg met the agreed primary endpoint of improvement in liver fibrosis without worsening of NASH at 18 months (p<0.0001), consistent with the original REGENERATE analysis OCA 25 mg demonstrated double the response rate in reduction of liver fibrosis without worsening of NASH vs. placebo Includes larger and more robust safety database of 2,477 patients with nearly 1,000 on study drug for 4 years Intercept to resubmit new drug application (NDA) in liver fibrosis due to NASH; pre-submission meeting with FDA scheduled later this month Company to host conference call at 8:30 a.m. ET today MORRISTOWN, N.J., July 07, 2022 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT), a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, today announced positive topline results from a new interim analysis of its ongoing pivotal Phase 3 REGENERATE trial of OCA in patients with liver fibrosis due to nonalcoholic steatohepatitis (NASH). This is the second analysis in which OCA has met the primary endpoint for the intent-to-treat (ITT) population in REGENERATE and based on these results, Intercept will be re-submitting its NDA for OCA in liver fibrosis due to NASH. In this new interim analysis of the ITT population from REGENERATE (n=931), 22.4% of subjects randomized to once-daily oral OCA 25 mg met the primary endpoint of achieving at least one stage of fibrosis improvement with no worsening of NASH at month 18 on liver biopsy compared with 9.6% of subjects on placebo (p<0.0001). These results are consistent with the original positive analysis announced in February 2019, which also showed that OCA 25 mg had a statistically significant effect on fibrosis improvement (p=0.0002). The population in this new interim analysis mirrored the original analysis population from 2019 but used a consensus panel approach to histology reads, in line with recent U.S. Food and Drug Administration (FDA) guidance, while the original analysis relied on results from individual central readers. A numerically greater proportion of individuals in the OCA 25 mg treatment group compared to placebo achieved the endpoint of resolution of NASH with no worsening of liver fibrosis but, consistent with the original analysis, this did not reach statistical significance. For the primary objective to be met, the study was required to achieve only one of the two primary endpoints. Safety was evaluated in 2,477 subjects who took at least one dose of study drug (placebo, OCA 10 mg, or OCA 25 mg). Compared to the original analysis, the safety population in this new interim analysis had significantly longer exposure to study drug (median 42 months vs. 15 months), yielding more than 8,000 total patient-years and 3.4 times more exposure. Nearly 1,000 subjects had been on study drug for four years. Treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and deaths were generally balanced across the OCA and placebo treatment groups. The most common TEAE was pruritus (24% in placebo, 33% in OCA 10 mg and 55% in OCA 25 mg) and pruritus was the most common cause for treatment discontinuation. Serious gallbladder-related events occurred in <3% of subjects in any treatment group and, consistent with its known mechanism of action, OCA 25 mg had higher rates of biliary events including gallstones. Independent groups of experts reviewed certain categories of safety events to provide a blinded adjudication as specifically requested by FDA. These included events pertaining to hepatic safety (excluding clinical outcomes), cardiovascular and renal. Topline analysis through four years of treatment showed a numerically higher number of adjudicated hepatic safety events for OCA 25 mg, the vast majority of which were mild in severity. For adjudicated core major adverse cardiovascular events and adjudicated acute kidney injury events, frequency of events was low and balanced across treatment groups. Consistent with its mechanism of action as an FXR agonist, OCA treatment was associated with an increase in LDL at Month 1 which returned to near baseline values by Month 12. Changes in other blood chemistries including ALP (alkaline phosphatase), GGT (gamma-glutamyl transferase), AST (aspartate aminotransferase), and ALT (alanine aminotransferase) also showed evidence of FXR mediated activity, supporting the dose-response of OCA. “Achieving a statistically significant histology endpoint has proven to be an extremely high bar in clinical trials for NASH. We are thrilled that OCA has demonstrated consistent improvement in fibrosis based on a second methodology and we now have two positive, statistically significant results for this primary endpoint from our pivotal REGENERATE trial. These results demonstrate the antifibrotic effect of OCA and are consistent with our belief that OCA can be an important treatment for people living with fibrosis due to NASH,” said Jerry Durso, President and Chief Executive Officer of Intercept. “The weight of evidence in both safety and efficacy has notably increased and provides a more robust benefit:risk profile of OCA. We look forward to our meeting with FDA later this month to discuss the resubmission of our NDA for OCA in fibrosis due to NASH.” Dr. Arun Sanyal, Chair, Division of Gastroenterology/Hepatology/Nutrition & Director, Stravitz-Sanyal Liver Institute, VCU Health, Department of Internal Medicine, said, “Today marks a significant milestone for patients with fibrosis due to NASH, a disease that currently has no approved therapy. These data demonstrate that once daily oral OCA has the potential to improve fibrosis. Further, the safety and tolerability profile of OCA based on a sizeable dataset should give clinicians confidence that we are a step closer to a treatment option.” Analysis Methodology and Efficacy Results In REGENERATE, patients with biopsy-proven stage 2 or 3 liver fibrosis due to NASH were randomized 1:1:1 to receive placebo (n=311), OCA 10 mg (n=312), or OCA 25 mg (n=308) once daily. A second biopsy was conducted in these 931 subjects at Month 18 for the planned interim analysis. The new interim analysis was based on a reassessment of the baseline and Month 18 liver biopsies using a consensus reading methodology. Consensus panels were comprised of three board-certified pathologists who demonstrated accuracy and reproducibility in their assessments of liver biopsies during proficiency testing. The consensus panels in this new interim analysis reviewed digitized whole slide images of the same glass slides of liver biopsy tissue that were evaluated in the original analysis using individual central readers. The results of the new interim analysis from REGENERATE are shown in the following table: Placebon=311OCA 10 mgn=312OCA 25 mgn=308At least one stage of fibrosis improvement with no worsening of NASH*9.6%14.1%p=NS22.4%p<0.0001 Resolution of NASH‡ with no worsening of liver fibrosis3.5%6.1%p=NS6.5%p=NS *Defined as no worsening of hepatocellular ballooning, no worsening of lobular inflammation and no worsening of steatosis‡Defined as the overall histopathologic interpretation of (i) no fatty liver disease or (ii) fatty liver disease (simple or isolated steatosis) without steatohepatitis AND a nonalcoholic fatty liver disease (NAFLD) activity score of 0 for ballooning and 0-1 for inflammation Intercept plans to share these data in an upcoming scientific forum. OCA has not been approved for the treatment of NASH by any regulatory authority in any geography and is considered an investigational treatment for this indication. About the REGENERATE Study REGENERATE (Randomized Global Phase 3 Study to Evaluate the Impact on NASH with Fibrosis of Obeticholic Acid Treatment) is an ongoing Phase 3, randomized, double-blind, placebo-controlled, multicenter, international study assessing the safety and efficacy of obeticholic acid (OCA) on clinical outcomes in patients with liver fibrosis due to NASH. A pre-specified 18-month interim analysis was conducted on 931 subjects who had scheduled biopsy at Month 18 to assess the effect of OCA on liver histology comparing Month 18 biopsies with baseline biopsies. REGENERATE is fully enrolled with 2,480 randomized participants and is expected to continue through clinical outcomes for verification and description of clinical benefit. The end-of-study analysis will evaluate the effect of OCA on all-cause mortality and liver-related clinical outcomes, as well as long-term safety. About Intercept Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, including primary biliary cholangitis (PBC) and nonalcoholic steatohepatitis (NASH). For more information, please visit www.interceptpharma.com or connect with the company on Twitter and LinkedIn. About Liver Fibrosis due to NASH Nonalcoholic steatohepatitis (NASH) is a serious progressive liver disease caused by excessive fat accumulation in the liver that induces chronic inflammation, resulting in progressive fibrosis (scarring) that can lead to cirrhosis, eventual liver failure, cancer and death. Advanced fibrosis is associated with a substantially higher risk of liver-related morbidity and mortality in patients with NASH. There are currently no medications approved for the treatment of NASH. Conference Call on July 7, 2022 at 8:30 a.m. ET Intercept will hold a conference call to discuss the new data analysis from its Phase 3 REGENERATE study in patients with liver fibrosis due to NASH today at 8:30 a.m. ET. The conference call will be available via a listen-only webcast on the investor page of our website at http://ir.interceptpharma.com. To join the webcast, click here. Participants who wish to ask a question may register here to receive dial-in numbers and a unique PIN to join the call. While not required, it is recommended you join 10 minutes prior to the event start. A replay of the call will be available on our website shortly following the completion of the call and will be available for one year. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to, statements regarding: The progress, timing, and results of our REGENERATE clinical trial, including the safety and efficacy of obeticholic acid (“OCA”) for the treatment of liver fibrosis due to nonalcoholic steatohepatitis (“NASH”), and the use of a consensus panel biopsy-reading methodology.Our planned New Drug Application (“NDA”) pre-submission meeting with the FDA regarding OCA for the treatment of liver fibrosis due to NASH.Our planned resubmission of an NDA to the FDA for OCA for the treatment of liver fibrosis due to NASH, and the potential timing, review, acceptance, and approval of the NDA.The potential commercial success of OCA for NASH, as well as our strategy, future operations, future financial position, future revenue, projected costs, prospects, plans, and objectives. These statements constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “possible,” “continue” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release, and we undertake no obligation to update any forward-looking statement except as required by law. These forward-looking statements are based on estimates and assumptions by our management that, although believed to be reasonable, are inherently uncertain and subject to a number of risks. The following represent some, but not necessarily all, of the factors that could cause actual results to differ materially from historical results or those anticipated or predicted by our forward-looking statements: The success of our existing business and operations, including Ocaliva for PBC.Our ability to successfully commercialize Ocaliva for PBC and, if approved, OCA for NASH.Our ability to maintain our regulatory approval of Ocaliva for PBC.Our ability to timely and cost-effectively file for and obtain regulatory approval of our product candidates on an accelerated basis or at all, including OCA for NASH.Our ability to address the issues raised in the complete response letter (“CRL”) received in June 2020 with respect to OCA for NASH.Any advisory committee recommendation or dispute resolution determination that OCA for NASH should not be approved or approved only under certain conditions.Any future determination that the regulatory applications and subsequent information we submit for our product candidates, including OCA for NASH, do not contain adequate clinical or other data or meet applicable regulatory requirements for approval.Conditions that may be imposed by regulatory authorities on our marketing approvals for our products and product candidates, including OCA for NASH, such as the need for clinical outcomes data (and not just results based on achievement of a surrogate endpoint), any risk mitigation programs such as a REMS, and any related restrictions, limitations and/or warnings contained in the label of any of our products or product candidates.Any potential side effects associated with Ocaliva for PBC, OCA for NASH, or our other product candidates that could delay or prevent approval, require that an approved product be taken off the market, require the inclusion of safety warnings or precautions, or otherwise limit the sale of such product or product candidate, including in connection with our update to Ocaliva prescribing information in May 2021 contraindicating Ocaliva for patients with PBC and decompensated cirrhosis, a prior decompensation event, or compensated cirrhosis with evidence of portal hypertension.The initiation, timing, cost, conduct, progress, and results of our research and development activities, preclinical studies and clinical trials, including any issues, delays or failures in identifying patients, enrolling patients, treating patients, retaining patients, meeting specific endpoints, or completing and timely reporting the results of our NASH or PBC clinical trials.The outcomes of interactions with regulators, including the FDA, regarding our clinical trials.Our ability to establish and maintain relationships with, and the performance of, third-party manufacturers, contract research organizations and other vendors upon whom we are substantially dependent for, among other things, the manufacture and supply of our products, including Ocaliva for PBC and, if approved, OCA for NASH, and our clinical trial activities.Our ability to identify, develop, and successfully commercialize our products and product candidates, including our ability to successfully launch OCA for NASH, if approved.Our ability to obtain and maintain intellectual property protection for our products and product candidates, including our ability to cost-effectively file, prosecute, defend, and enforce any patent claims or other intellectual property rights.The size and growth of the markets for our products and product candidates and our ability to serve those markets.The degree of market acceptance of Ocaliva for PBC and, if approved, OCA for NASH or our other product candidates among physicians, patients, and healthcare payors.The availability of adequate coverage and reimbursement from governmental and private healthcare payors for our products, including Ocaliva for PBC and, if approved, OCA for NASH, and our ability to obtain adequate pricing for such products.Our ability to establish and maintain effective sales, marketing, and distribution capabilities, either directly or through collaborations with third parties.Competition from existing drugs or new drugs that become available.Our ability to attract and retain key personnel to manage our business effectively.Our ability to prevent or defend against system failures or security or data breaches due to cyber-attacks, or cyber intrusions, including ransomware, phishing attacks and other malicious intrusions.Our ability to comply with data protection laws; costs and outcomes relating to any disputes, governmental inquiries or investigations, regulatory proceedings, legal proceedings or litigation, including any securities, intellectual property, employment, product liability or other litigation.Our collaborators’ election to pursue research, development and commercialization activities.Our ability to establish and maintain relationships with collaborators with development, regulatory and commercialization expertise.Our need for and ability to generate or obtain additional financing.Our estimates regarding future expenses, revenues and capital requirements and the accuracy thereof.Our use of cash, cash equivalents and short-term investments.Our ability to acquire, license and invest in businesses, technologies, product candidates and products.Our ability to manage the growth of our operations, infrastructure, personnel, systems and controls.Our ability to obtain and maintain adequate insurance coverage.Continuing threats from COVID-19, including additional waves of infections, and their impacts including quarantines and other government actions, delays relating to our regulatory applications, disruptions relating to our ongoing clinical trials or involving our contract research organizations, study sites or other clinical partners, disruptions relating to our supply chain or involving our third-party manufacturers, distributors or other distribution partners, and facility closures or other restrictions, and impact of the foregoing on our results of operations and financial position.The impact of general economic, industry, market, regulatory, or political conditions.The other risks and uncertainties identified in our periodic filings filed with the U.S. Securities and Exchange Commission, including our latest Annual Report on Form 10-K and/or Quarterly Report on Form 10-Q. CONTACT For more information about Intercept, please contact: For investors:Nareg Sagherian, Executive Director, Global Investor Relationsinvestors@interceptpharma.com For media:Karen Preble, Executive Director, Global Corporate Communicationsmedia@interceptpharma.com