CCL13

Analysis conducted among 3,743 patients with history of heart failure with mildly reduced ejection fraction or heart failure with preserved ejection fraction (HFpEF) from four clinical trials1 Obesity considered key driver in the development of HFpEF,2 with approximately 80% of people with HFpEF living with overweight or obesity3 Semaglutide is not approved in the US to reduce heart failure outcomes PLAINSBORO, N.J., Aug. 30, 2024 /PRNewswire/ -- Today, The Lancet published a new pooled, participant-level analysis of patients with heart failure with mildly reduced ejection fraction or heart failure with preserved ejection fraction (HFpEF) from the SELECT, FLOW, STEP-HFpEF and STEP-HFpEF DM randomized, placebo-controlled trials.1 According to the analysis, semaglutide led to a 31% reduced risk of combined cardiovascular (CV) death or worsening heart failure (HF) events, based on an incidence of 5.4% in patients assigned to semaglutide versus 7.5% in those assigned to placebo (HR 0.69; 95% CI 0.53-0.89; P=0.0045).1 Semaglutide also led to a 41% lower risk of worsening HF (2.8% versus 4.7% with placebo; HR 0.59 (95% CI 0.41-0.82), P=0.0019).1 There was no significant effect on the incidence of CV death (3.1% with semaglutide versus 3.7% with placebo); HR 0.82 (95% CI 0.57-1.16), P=0.25).1 Statistical analyses were not adjusted for multiplicity and hazard ratios should not be used to infer definitive treatment effects.1 Semaglutide is not approved in the US to reduce heart failure outcomes. The study was a pooled, post hoc participant-level analysis of 3,743 patients with a history of HFpEF from four randomized trials to examine the effects of once-weekly semaglutide (2.4 mg in SELECT, STEP-HFpEF, STEP-HFpEF DM; 1.0 mg in FLOW) on HF events.1 The STEP-HFpEF Program enrolled participants with obesity-related HFpEF; in SELECT (participants with atherosclerotic cardiovascular (CV) disease and overweight/obesity) and FLOW (participants with type 2 diabetes and chronic kidney disease), HFpEF classification was investigator-reported.1 The main endpoint for this pooled analysis was a composite of time to first CV death or worsening HF event (hospitalizations or urgent visits due to HF). Additional endpoints included components of the composite: time to first HF event and time to CV death.1 Obesity is considered a key driver in the development of HFpEF,2 with approximately 80% of people with HFpEF living with overweight or obesity.3 In addition, type 2 diabetes is also highly prevalent in people with HFpEF and is associated with greater symptom burden, worse functional capacity, and more severely impaired quality of life.2,4 "Due in part to the obesity epidemic, HFpEF has emerged as the most common type of heart failure. Patients with obesity-related HFpEF are at high risk for serious complications including hospitalizations and death, and have limited treatment options," said Dr. Mikhail Kosiborod, lead study author and cardiologist at Saint Luke's Mid America Heart Institute. "Collectively, this new analysis is the most comprehensive evaluation of semaglutide to date that assesses clinically relevant HF events, such as CV death and hospitalization." Adverse events leading to treatment discontinuation occurred in 21% of patients in the semaglutide group and 13.9% of patients in the placebo group.1 Gastrointestinal disorders leading to treatment discontinuation occurred in 11.1% of patients in the semaglutide group and 2.7% of patients in the placebo group.1 Fewer semaglutide versus placebo-treated patients experienced serious adverse events across the four trial populations.1 "Combining the HFpEF participant populations across the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM trials allowed us to take a closer look at how semaglutide impacted patients living with this debilitating and often progressive condition," said Michelle Skinner, PharmD, Vice President Medical Affairs, Novo Nordisk. "It is encouraging to have this additional analysis that examines the effect of semaglutide in this vulnerable patient population." About obesity, HFpEF, and type 2 diabetes When the heart is too stiff to fill properly but is capable of pumping out a normal percentage of blood, the condition is called HFpEF.5 This is the most common type of heart failure, comprising approximately 50% of all heart failure cases.6 Despite therapeutic advances in HFpEF, significant unmet needs persist.6,7 The prevalence of obesity is rapidly increasing.8,9 Obesity affects about 4 in 10 US adults and is considered a key driver of HFpEF.2,10 Approximately 80% of people with HFpEF live with overweight or obesity and 40-50% of people with HFpEF have diabetes.2,3 About the SELECT trial (semaglutide 2.4 mg) SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) was a multicenter, randomized, double-blind, placebo-controlled, event-driven superiority trial designed to evaluate the efficacy of semaglutide 2.4 mg versus placebo as an adjunct to cardiovascular standard of care for reducing the risk of major adverse cardiovascular events in people with established CVD and overweight or obesity with no prior history of diabetes.11 The trial, initiated in 2018, enrolled 17,604 adults and was conducted in 41 countries at more than 800 investigator sites.11 About the STEP-HFpEF trial (semaglutide 2.4 mg) STEP-HFpEF was a 52-week, double-blind, randomized, placebo-controlled trial designed to investigate the effects of semaglutide 2.4 mg subcutaneous once-weekly on symptoms, physical function, and body weight compared with placebo, both added to standard of care, in patients with HFpEF and obesity. STEP-HFpEF included 529 adults with symptomatic HFpEF (ejection fraction ≥45%) and obesity (BMI ≥30 kg/m2). Dual primary endpoints were change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and percentage change in body weight; with key secondary endpoints of change in 6-minute-walk distance (6MWD), a hierarchical composite endpoint (all-cause death, heart failure events, difference in KCCQ-CSS change and difference of at least 30 meters in 6MWD change) and change in C-reactive protein.12 About the STEP-HFpEF DM trial (semaglutide 2.4 mg) STEP-HFpEF DM was a 52-week, double-blind, randomized, placebo-controlled trial designed to investigate the efficacy of semaglutide 2.4 mg subcutaneous once-weekly on symptoms, physical function, and body weight compared with placebo, both added to standard of care, in patients with HFpEF, obesity, and type 2 diabetes. STEP-HFpEF DM included 616 adults with symptomatic HFpEF (ejection fraction ≥45%), obesity (BMI ≥30 kg/m2) and type 2 diabetes. Dual primary endpoints were change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and percentage change in body weight; with key secondary endpoints of change in 6-minute-walk distance (6MWD), a hierarchical composite endpoint (all-cause death, heart failure events, difference in KCCQ-CSS change and difference of at least 30 meters in 6MWD change) and change in C-reactive protein.13 About the FLOW trial (semaglutide 1 mg) FLOW was a randomized, double-blind, parallel-group, placebo-controlled, event-driven superiority trial comparing injectable once-weekly semaglutide 1.0 mg with placebo as an adjunct to standard of care on kidney outcomes for delaying the progression of renal impairment and lowering the risk of renal and cardiovascular mortality in people with type 2 diabetes and CKD. 3,533 adults were enrolled in the trial which was conducted in 28 countries at around 400 investigator sites. The FLOW trial was initiated in June 2019.14 The primary objective of the FLOW trial was to demonstrate a delay in the progression of CKD and to lower the risk of onset of kidney failure (initiation of long-term dialysis, kidney transplantation, or a reduction in the eGFR to <15 ml per minute per 1.73 m2 sustained for ≥28 days), a sustained (for ≥28 days) 50% or greater reduction in eGFR from baseline, or death from kidney-related or cardiovascular causes. Key secondary endpoints, assessed in a hierarchical order, included annual rate of change in eGFR (total eGFR slope), time to first occurrence of a composite MACE endpoint (non-fatal myocardial infarction, non-fatal stroke, cardiovascular death) and time to occurrence of an all-cause death.14 About Novo Nordisk Novo Nordisk is a leading global healthcare company that's been making innovative medicines to help people with diabetes lead longer, healthier lives for more than 100 years. This heritage has given us experience and capabilities that also enable us to drive change to help people defeat other serious chronic diseases such as obesity, rare blood, and endocrine disorders. We remain steadfast in our conviction that the formula for lasting success is to stay focused, think long-term, and do business in a financially, socially, and environmentally responsible way. With U.S. headquarters in New Jersey and commercial, production and research facilities in seven states plus Washington DC, Novo Nordisk employs approximately 8,000 people throughout the country. For more information, visit novonordisk-us.com, Facebook, Instagram, X, LinkedIn, and YouTube. References Kosiborod, MN, Deanfield J, Pratley R, et al. Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. The Lancet. Published online: August 30, 2024. Borlaug BA, Jensen MD, Kitzman DW, et al. Obesity and heart failure with preserved ejection fraction: new insights and pathophysiological targets. Cardiovasc Res. 2022; 118:3434-3450. Gevaert AB, Kataria R, Zannad F, et al. Heart failure with preserved ejection fraction: recent concepts in diagnosis, mechanisms and management. Heart. 2022; 108:1342-1350. Yap J, Tay WT, Teng TK, et al. Association of diabetes mellitus on cardiac remodelling, quality of life, and clinical outcomes in heart failure with reduced and preserved ejection fraction. J Am Heart Assoc. 2019; 8:e013114. American Heart Association. Types of heart failure. Available at: . Last accessed: August 2024. Kittleson MM, Panjrath GS, Amancherla K, et al. 2023 ACC expert consensus decision pathway on management of heart failure with preserved ejection fraction: a report of the American College of Cardiology solution set oversight committee. J Am Coll Cardiol. 2023 May 9;81(18):1835-1878. doi: 10.1016/j.jacc.2023.03.393. Borlaug BA. Evaluation and management of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2020 Sep;17(9):559-573. doi: 10.1038/s41569-020-0363-2. World Obesity Federation. World obesity atlas 2024. Available at: . Last accessed: August 2024. World Obesity Federation. Prevalence of obesity. Available at: . Last accessed: August 2024. Centers for Disease Control and Prevention. Adult obesity facts. Available at: . Last accessed: August 2024. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023; 389:2221-2232. Kosiborod MN, Abildstrom SZ, Borlaug BA, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023; 389:1069-1084. Kosiborod MN, Petrie MC, Borlaug BA, et al. Semaglutide in patients with obesity-related heart failure and type 2 diabetes. N Engl J Med. 2024;390:1394-1407. Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391:109-121. © 2024 Novo Nordisk All rights reserved. US24SEMO01152 August 2024 SOURCE NOVO NORDISK INC.

SHANGHAI, Oct. 4, 2023 /PRNewswire/ -- Everest Medicines' (HKEX 1952.HK, "Everest", or the "Company") partner Calliditas Therapeutics AB (Nasdaq: CALT, Nasdaq Stockholm: CALTX) ("Calliditas") presented new biomarker and subgroup analyses from Nefecon®'s Phase 3 NefIgArd study in both posters and oral presentations at the 17th International Symposium on IgA Nephropathy held in Tokyo, Japan. "The positive findings from biomarker and patient subgroup analyses from the Phase 3 NefIgArd study highlights that Nefecon® treatment results in a coordinated immunological response with the potential to modulate the intestinal immune network responsible for IgA production. They also reinforced Nefecon®'s ability to slow kidney function decline by targeting the origin of the disease," said Rogers Yongqing Luo, Chief Executive Officer of Everest Medicines. "Everest participated in the NefIgArd study, and plans to publish the Chinese subpopulation data in a future medical conference. We look forward to bringing this differentiated and disease-modifying treatment to more Asian patients soon." Biomarker Analyses IgA-containing immune complexes (IgA-IC) have previously been shown to accumulate in renal tissue, where they trigger inflammation and scarring of the glomeruli. Investigation of the effect of Nefecon® on circulating levels of IgA-IC in the Part A population of the NefIgArd clinical trial (n=160) revealed that patients treated with Nefecon® 16mg/day exhibited a statistically significant decrease in IgA-IC levels compared to patients who received placebo when evaluated at the 3-, 6- and 9-months post randomization. Suppression by treatment with Nefecon® of both IgA-IC formation and galactose-deficient IgA1 as previously reported offers an unprecedented opportunity to target the fundamental immune abnormalities that drive IgA deposition in the kidney and development of IgAN. An additional analysis of the 160 patients enrolled in Part A of the Phase 3 NefIgArd clinical study was conducted to assess the levels of three soluble factors known for modulating B cell maturation in gut-associated lymphoid tissue (GALT): B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and serum B-cell maturation antigen (sBCMA). Compared to placebo, levels of BAFF were decreased at 3-, 6-, and 9-months after treatment initiation. Levels of APRIL were significantly reduced at the 3- and 6-months timepoints and levels of sBCMA were decreased at the 6-months timepoint. These data further support the potential disease-modifying effect of Nefecon® in IgAN and reinforce the central role of the gut–kidney axis in the pathogenesis of IgAN. To further understand the impact of Nefecon® on chemokine signaling in IgAN patients, the levels of three circulating chemokines known to be present in the intestinal tract at the site of IgA production, CXCL5, CCL13 and CCL11, were assessed in the Part A patient population portion of the NefIGArd trial (n=160). Compared to placebo, the analyses showed that treatment with Nefecon® 16 mg/day resulted in a statistically significant decrease in the levels of CXCL5 and CCL13 and an increase in levels of CCL11 at 3-, 6- and 9-months after treatment initiation. These biomarker data provide additional evidence for a mucosal mechanism of action of Nefecon® in IgAN and support previous observations that disordered lymphocyte trafficking and mucosal dysregulation likely contribute to the pathogenesis of IgAN. Patient Subgroup Analyses The full two-year results of the Phase 3 NefIgArd trial (n=364 patients) were further analyzed to assess potential differences in response to Nefecon® treatment based on self-reported Asian (n=83) or White (n=275) ancestry in patients with IgAN. Treatment with Nefecon® 16 mg/day over a 9-month period resulted in clinically meaningful preservation of kidney function in both subgroups, as evidenced by reduction in proteinuria and stabilization of eGFR in these two subgroups when compared to placebo subgroups. Nefecon® has already been approved and marketed in the United States, the European Union and the UK. The NDA for Nefecon® in mainland China is currently under Priority Review and is expected to be approved in the second half of this year. It was the first non-oncology medicine to receive Breakthrough Therapy Designation in China, reinforcing the urgent need of Nefecon® as a first-in-disease therapeutic option in the nation. Nefecon® has been available for clinical use in Shanghai Ruijin Hospital's Hainan subsidiary through an early-access program since April. About Nefecon® Nefecon® is a patented oral, delayed release formulation of budesonide, a corticosteroid with potent glucocorticoid activity and weak mineralocorticoid activity that undergoes substantial first pass metabolism. The formulation is designed as a delayed release capsule that is enteric coated so that it remains intact until it reaches the Peyer's patch region of the lower small intestine. Each capsule contains coated beads of budesonide that target mucosal B-cells present in the ileum where the disease originates, as per the predominant pathogenesis models. In June 2019, Everest Medicines entered into an exclusive, royalty-bearing license agreement with Calliditas, which gives Everest Medicines exclusive rights to develop and commercialize Nefecon® in Mainland China, Hong Kong, Macau, Taiwan and Singapore. The agreement was extended in March 2022 to include South Korea as part of Everest Medicine's territories. About Everest Medicines Everest Medicines is a biopharmaceutical company focused on developing, manufacturing and commercializing transformative pharmaceutical products and vaccines that address critical unmet medical needs for patients in Asian markets. The management team of Everest Medicines has deep expertise and an extensive track record from both leading global pharmaceutical companies and local Chinese pharmaceutical companies in high-quality discovery, clinical development, regulatory affairs, CMC, business development and operations. Everest Medicines has built a portfolio of potentially global first-in-class or best-in-class molecules, many of which are in late-stage clinical development. The Company's therapeutic areas of interest include renal diseases, infectious diseases and autoimmune disorders. For more information, please visit its website at . Forward-Looking Statements: This news release may make statements that constitute forward-looking statements, including descriptions regarding the intent, belief or current expectations of the Company or its officers with respect to the business operations and financial condition of the Company, which can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates," "confident" and similar statements. Such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, or other factors, some of which are beyond the control of the Company and are unforeseeable. Therefore, the actual results may differ from those in the forward-looking statements as a result of various factors and assumptions, such as future changes and developments in our business, competitive environment, political, economic, legal and social conditions. The Company or any of its affiliates, directors, officers, advisors or representatives has no obligation and does not undertake to revise forward-looking statements to reflect new information, future events or circumstances after the date of this news release, except as required by law. SOURCE Everest Medicines

STOCKHOLM, Sept. 29, 2023 /PRNewswire/ -- Calliditas Therapeutics AB (NASDAQ: CALT) (NASDAQ Stockholm: CALTX) ("Calliditas"), today announced the presentations of new biomarker and subgroup analyses from the Phase 3 NefIgArd study with Nefecon (TARPEYO® (budesonide) delayed release capsules/Kinpeygo®) in adults with Primary IgA nephropathy (IgAN). The data was presented in both posters and oral presentations at the 17th International Symposium on IgA Nephropathy (IIGaNN), held in Tokyo, Japan, on September 25-27, 2023. "We are proud to have showcased new data at this year's International Symposium on IgAN in Tokyo," said Richard Phillipson, Chief Medical Officer at Calliditas. "Taken together, the positive findings from our biomarker and patient subgroup analyses from our Phase 3 NefIgArd study indicate that Nefecon treatment results in a coordinated immunological response with the potential to modulate the intestinal immune network responsible for IgA production. These additional findings further reinforce the potential of TARPEYO in enabling physicians to proactively manage and potentially mitigate the impact of the disease by targeting the source and slowing kidney function decline." Biomarker Analyses IgA-containing immune complexes (IgA-IC) have previously been shown to accumulate in renal tissue, where they trigger inflammation and scarring in the glomeruli. Investigation of the effect of Nefecon on circulating levels of IgA-IC in the Part A population of the NefIgArd clinical trial (n=160) revealed that patients treated with Nefecon 16mg/day exhibited a statistically significant decrease in IgA-IC levels compared to patients who received placebo when evaluated at the 3-, 6- and 9-months post randomization. Suppression by treatment with Nefecon of both IgA-IC formation and galactose-deficient IgA1 as previously reported offers an unprecedented opportunity to target the fundamental immune abnormalities that drive IgA deposition in the kidney and development of IgAN. An additional analysis of the 160 patients enrolled in Part A of the Phase 3 NefIgArd clinical study was conducted to assess the levels of three soluble factors known for modulating B cell maturation in gut-associated lymphoid tissue (GALT) BAFF, APRIL and sBCMA. Levels of BAFF were decreased at the 3-, 6-, and 9-months post treatment mark compared to placebo. Levels of APRIL were significantly reduced at the 3- and 6-months timepoints and levels of sBCMA were decreased at the 6-months timepoint. These data further support the potential disease-modifying effect of Nefecon in IgAN and reinforce the central role of the gut-kidney axis in the pathogenesis of IgAN. To further understand the impact of Nefecon on chemokine signaling in IgAN patients, the levels of three circulating chemokines known to be present in the intestinal tract at the site of IgA production, CXCL5, CCL13 and CCL11, were assessed in the Part A patient population portion of the NefIGArd trial (n=160). Dr. Barratt and colleagues reported that treatment with Nefecon 16 mg/day resulted in a statistically significant decrease in the levels of CXCL5 and CCL13 and an increase in levels of CCL11 at 3-, 6- and 9-months post-treatment when compared to placebo. These biomarker data provide additional evidence for a mucosal mechanism of action of Nefecon in IgAN and support previous observations that disordered lymphocyte trafficking and mucosal dysregulation likely contribute to the pathogenesis of IgAN. Patient Subgroup Analyses The full two-year results of the Phase 3 NefIgArd trial (n=364 patients) were further analyzed to assess potential differences in response to Nefecon treatment based on self-reported Asian (n=83) or White (n=275) ancestry in patients with IgAN. Treatment with Nefecon 16 mg/day over a 9-month period resulted in clinically meaningful preservation of kidney function in both subgroups, as evidenced by ameliorated eGFR and proteinuria in these two subgroups when compared to placebo subgroups. NefIgArd Sub-Analyses Full analysis of the Phase 3 NefIgArd study over the entire 2-year study period of the 364 patients (1:1 patient randomization to Nefecon 16 mg/day or placebo) enrolled in the study revealed clinically meaningful impact on three key markers of IgAN disease progression as evidenced by: A statistically significant benefit of Nefecon over placebo in estimated glomerular filtration rate (eGFR) over the two-year study period, which consisted of nine months of treatment with Nefecon or placebo, followed by a 15-month follow-up period off the study drug. A clinically significant reduction in proteinuria was found to be durable for the entire 15-month follow-up period off the study drug. Relevant decrease in microhematuria was also observed during Part B of the study, with fewer patients in the Nefecon treatment group exhibiting microhematuria at follow up visits compared to the placebo group. Indication TARPEYO® (budesonide) delayed release capsules is a corticosteroid indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g. This indication is approved under accelerated approval based on a reduction in proteinuria. It has not been established whether TARPEYO slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefits in a confirmatory clinical trial. Important Safety Information Contraindications: TARPEYO is contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of TARPEYO. Serious hypersensitivity reactions, including anaphylaxis, have occurred with other budesonide formulations. Warnings and Precautions Hypercorticism and adrenal axis suppression: When corticosteroids are used chronically, systemic effects such as hypercorticism and adrenal suppression may occur. Corticosteroids can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a systemic corticosteroid is recommended. When discontinuing therapy [see Dosing and Administration] or switching between corticosteroids, monitor for signs of adrenal axis suppression. Patients with moderate to severe hepatic impairment (Child-Pugh Class B and C, respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure to oral budesonide. Avoid use in patients with severe hepatic impairment (Child-Pugh Class C). Monitor for increased signs and/or symptoms of hypercorticism in patients with moderate hepatic impairment (Child-Pugh Class B). Risks of immunosuppression: Patients who are on drugs that suppress the immune system are more susceptible to infection than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible patients or patients on immunosuppressive doses of corticosteroids. Avoid corticosteroid therapy in patients with active or quiescent tuberculosis infection; untreated fungal, bacterial, systemic viral, or parasitic infections; or ocular herpes simplex. Avoid exposure to active, easily transmitted infections (eg., chicken pox, measles). Corticosteroid therapy may decrease the immune response to some vaccines. Other corticosteroid effects: TARPEYO is a systemically available corticosteroid and is expected to cause related adverse reactions. Monitor patients with hypertension, prediabetes, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma, cataracts, a family history of diabetes or glaucoma, or with any other condition in which corticosteroids may have unwanted effects. Adverse reactions: In clinical studies, the most common adverse reactions with TARPEYO (occurring in ≥5% of TARPEYO patients and ≥2% higher than placebo) were hypertension (16%), peripheral edema (14%), muscle spasms (13%), acne (11%), dermatitis (7%), weight increase (7%), dyspnea (6%), face edema (6%), dyspepsia (5%), fatigue (5%), and hirsutism (5%). Drug interactions: Budesonide is a substrate for CYP3A4. Avoid use with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, and cyclosporine. Avoid ingestion of grapefruit juice with TARPEYO. Intake of grapefruit juice, which inhibits CYP3A4 activity, can increase the systemic exposure to budesonide. Use in specific populations Pregnancy: The available data from published case series, epidemiological studies, and reviews with oral budesonide use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with IgAN. Infants exposed to in utero corticosteroids, including budesonide, are at risk for hypoadrenalism. Please see Full Prescribing Information. About TARPEYO Calliditas has introduced TARPEYO, the first FDA-approved therapy for the treatment of the autoimmune renal disease primary IgA Nephropathy, or IgAN, to reduce proteinuria in adults with primary IgAN who are at risk of rapid disease progression, generally a UPCR≥1.5g/g. This indication is approved under accelerated approval based on a reduction in proteinuria. It has not been established whether TARPEYO slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial. TARPEYO is an oral, delayed release formulation of budesonide, a corticosteroid with potent glucocorticoid activity and weak mineralocorticoid activity that undergoes substantial first pass metabolism. TARPEYO is as a 4 mg delayed release capsule and is enteric coated and designed to remain intact until it reaches the ileum. Each capsule contains coated beads of budesonide that target mucosal B-cells present in the ileum, including the Peyer's patches, which are responsible for the production of galactose-deficient IgA1 antibodies (Gd-Ag1) causing IgA nephropathy. It is unclear to what extent TARPEYO's efficacy is mediated via local effects in the ileum vs systemic effects. About the NeflgArd Study The global clinical trial NefIgArd is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of TARPEYO 16 mg once daily vs placebo in adult patients with primary IgAN (N=364), as an addition to optimized RAS inhibitor therapy. Part A of the study included a 9-month blinded treatment period and a 3-month follow-up period. The primary endpoint was UPCR, and eGFR was a secondary endpoint. Part B included a 12-month observational period off drug and assessed eGFR over the entire 2-year period for patients who were treated with the TARPEYO or placebo regimen in Part A. The full NefIgArd trial met its primary endpoint. Topline data from the full NefIgArd study were reported on March 12, 20 About Primary Immunoglobulin A Nephropathy Primary immunoglobulin A nephropathy (IgA nephropathy or IgAN or Berger's Disease) is a rare, progressive, chronic autoimmune disease that attacks the kidneys and occurs when galactose-deficient IgA1 is recognized by autoantibodies, creating IgA1 immune complexes that become deposited in the glomerular mesangium of the kidney. This deposition in the kidney can lead to progressive kidney damage and potentially a clinical course resulting in end- stage renal disease. IgAN most often develops between late teens and late 30s. For further information, please contact: Åsa Hillsten, Head of Investor Relations, Calliditas Tel.: +46 76 403 35 43, email: [email protected] The information was sent for publication, through the agency of the contact person set out above, on September 29, 2023, at 14.00 p.m. CET. The following files are available for download: SOURCE Calliditas Therapeutics