A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of the NOX1/4 Inhibitor Setanaxib in Patients With Alport Syndrome

The purpose of the study is to learn about the safety and tolerability of setanaxib in subjects with Alport syndrome, when added to their standard of care treatment. The study will assess how safe setanaxib is when compared to placebo. Study participants will be asked if they are experiencing any side effects at each study visit. In addition, tests in blood, urine and other examinations will be used to look at the safety of setanaxib. The study will also measure how well setanaxib works in comparison to a placebo, by measuring urine protein and certain markers in the blood and urine. The concentration of setanaxib in the blood will also be measured throughout the course of the study.
Setanaxib is planned for use together with the current standard of care to hopefully provide additional therapeutic benefits by preserving kidney function.
The study will be conducted at multiple research sites in the UK, Spain, and Czech Republic. Eligible participants will be randomly assigned to receive either setanaxib or placebo. Setanaxib dose level will depend on age and all participants will receive their standard of care in addition to setanaxib or placebo. The study consists of a Screening period of up to 4 weeks, a 24-week Treatment period and a 4- week Follow-up period.

Start Date27 Nov 2023

Sponsor / Collaborator

Calliditas Therapeutics AB

NCT05323656

/ Active, not recruitingPhase 2

A Phase 2, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Setanaxib, When Administered With Pembrolizumab, in Patients With Recurrent or Metastatic SCCHN

The primary objective of this study is to compare the change in tumour size per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in recurrent or metastatic SCCHN patients treated with setanaxib and pembrolizumab versus patients treated with placebo and pembrolizumab.

Start Date06 Apr 2022

Sponsor / Collaborator-

NCT05014672

/ CompletedPhase 2

TRANSFORM: A 24-week, Randomized, Placebo-controlled, Double-blind, Phase 2b Trial of Setanaxib in Patients With Primary Biliary Cholangitis (PBC) and Elevated Liver Stiffness

The primary objective of this study is to evaluate the effect of setanaxib on alkaline phosphatase (ALP) at Week 24 in participants with PBC and with elevated liver stiffness and intolerance or inadequate response to ursodeoxycholic acid (UDCA).

Start Date14 Feb 2022

Sponsor / Collaborator-

100 Clinical Results associated with Setanaxib

100 Translational Medicine associated with Setanaxib

100 Patents (Medical) associated with Setanaxib

181

Literatures (Medical) associated with Setanaxib

01 Aug 2025·FREE RADICAL BIOLOGY AND MEDICINE

NOX4-driven mitochondrial oxidative stress in aging promotes myocardial remodeling and increases susceptibility to ventricular tachyarrhythmia

Article

Author: Lozhkin, Andrey ; Vendrov, Aleksandr E ; Runge, Marschall S ; Stevenson, Mark D ; Madamanchi, Nageswara R ; Mondragon, Roberto Ramos ; Wang, Shuyun ; Isom, Lori L

Aging-associated mitochondrial oxidative stress has been implicated in ventricular tachyarrhythmias (VT), but the specific proarrhythmic mechanisms of mitochondrial pro-oxidative systems remain unclear. NADPH oxidase 4 (NOX4) expression in the heart increases with age, leading to mitochondrial oxidative stress, dysfunction, and adverse myocardial remodeling. This study investigated the susceptibility to aging-associated ventricular arrhythmia and the associated triggers and substrates using transgenic mice with mitochondria-targeted Nox4 overexpression (Nox4TG mice). Nox4TG mice showed a significantly higher incidence of pacing-induced VT, associated with shorter action potential duration (APD) due to increased transient outward potassium currents. Fractional sarcoplasmic reticulum (SR) Ca²⁺ release and Ca²⁺ leak remained intact despite these changes. However, the frequency of Ca²⁺ sparks was reduced, and ryanodine receptor 2 (RyR2) oxidation was observed. Compensatory upregulation of SERCA expression in response to RyR2 inhibition accelerated SR Ca²⁺ reuptake and improved cardiomyocyte mechanical relaxation. Nox4TG mice exhibited extensive ventricular fibrosis and marked pro-inflammatory macrophage infiltration, with elevated TNF, TGF-β, and MKI67 expression. Treatment with Setanaxib, a NOX1/NOX4 inhibitor, or co-expression of mitochondrial catalase in Nox4TG (Nox4TG+mCAT) mice, mitigated fibrosis, reduced inflammation, and protected against VT. These findings suggest that mitochondrial NOX4 overexpression promotes VT through electrical remodeling and pro-arrhythmogenic structural changes despite RyR2 oxidation and dysfunction. In conclusion, aging-related NOX4-driven mitochondrial oxidative stress increases the risk of VT by promoting changes in the electrical and structural properties of the myocardium, highlighting potential therapeutic strategies that target NOX4 in cardiac pathologies associated with aging.

01 Nov 2024·LIFE SCIENCES

NADPH oxidase 1/4 dual inhibitor setanaxib suppresses platelet activation and thrombus formation

Article

Author: Yu, Hyunseong ; Oh, Eun Bee ; Park, Ji Won ; Jang, Joara ; Shin, Hye Ji ; Chang, Tong-Shin

AIMS:

The production of reactive oxygen species (ROS) by NADPH oxidase (NOX) is able to induce platelet activation, making NOX a promising target for antiplatelet therapy. In this study, we examined the effects of setanaxib, a dual NOX1/4 inhibitor, on human platelet function and ROS-related signaling pathways.

MATERIALS AND METHODS:

In collagen-stimulated human platelets, aggregometry, assessment of ROS and Ca²⁺, immunoblotting, ELISA, flow cytometry, platelet adhesion assay, and assessment of mouse arterial thrombosis were performed in this study.

KEY FINDINGS:

Setanaxib inhibited both intracellular and extracellular ROS production in collagen-activated platelets. Additionally, setanaxib significantly inhibited collagen-induced platelet aggregation, P-selectin exposure from α-granule release, and ATP release from dense granules. Setanaxib blocked the specific tyrosine phosphorylation-mediated activation of Syk, LAT, Vav1, and Btk within collagen receptor signaling pathways, leading to reduced activation of PLCγ2, PKC, and Ca²⁺ mobilization. Setanaxib also inhibited collagen-induced activation of integrin αIIbβ3, which is linked to increased cGMP levels and VASP phosphorylation. Furthermore, setanaxib suppressed collagen-induced p38 MAPK activation, resulting in decreased phosphorylation of cytosolic PLA₂ and reduced TXA₂ generation. Setanaxib also inhibited ERK5 activation, affecting the exposure of procoagulant phosphatidylserine. Setanaxib reduced thrombus formation under shear conditions by preventing platelet adhesion to collagen. Finally, in vivo administration of setanaxib in animal models led to the inhibition of arterial thrombosis.

SIGNIFICANCE:

This study is the first to show that setanaxib suppresses ROS generation, platelet activation, and collagen-induced thrombus formation, suggesting its potential use in treating thrombotic or cardiovascular diseases.

01 Nov 2024·FREE RADICAL BIOLOGY AND MEDICINE

Nox4 is involved in acute kidney injury associated to intravascular hemolysis

Article

Author: Andrés, Belén de ; Leiva-Cepas, Fernando ; Opazo-Rios, Lucas ; Cortegano, Isabel ; Herencia, Carmen ; Palomino Antolin, Alejandra ; Egido, Jesús ; Vázquez-Carballo, Cristina ; Villalba, José Manuel ; García-Caballero, Cristina ; Decouty-Pérez, Celine ; Guerrero-Hue, Melania ; González-Reyes, José Antonio ; Vallejo-Mudarra, Mercedes ; Egea, Javier ; Moreno, Juan Antonio ; Sánchez-Mendoza, Luz Marina

Massive intravascular hemolysis occurs not unfrequently in many clinical conditions. Breakdown of erythrocytes promotes the accumulation of heme-derivates in the kidney, increasing oxidative stress and cell death, thus promoting acute kidney injury (AKI). NADPH oxidase 4 (Nox4) is a major source of reactive oxygen species (ROS) in the kidney, however it is unknown the role of Nox4 in hemolysis and whether inhibition of this enzyme may protect from heme-mediated injury. To answer these questions, we elicited intravascular hemolysis in wild type and Nox4 knockout mice. We also evaluated whether nephrotoxic effects of heme may be reduced by using Nox4 siRNA and pharmacologic inhibition with GKT137831, a Nox4 inhibitor, both in vivo and in cultured renal cells. Our results showed that induction of massive hemolysis elicited AKI characterized by loss of renal function, morphological alterations of the tubular epithelium and podocytes, oxidative stress, inflammation, mitochondrial dysfunction, blockade of autophagy and cell death. These pathological effects were significantly prevented in Nox4-deficient mice and in animals treated with GKT137831. In vitro studies showed that Nox4 disruption by specific siRNAs or Nox4 inhibitors declined heme-mediated ROS production and cell death. Our data identify Nox4 as a key enzyme involved in intravascular hemolysis-induced AKI. Thus, Nox4 inhibition may be a potential therapeutic approach to prevent renal damage in patients with severe hemolytic crisis.

News (Medical) associated with Setanaxib

02 Oct 2024

·www.prnewswire.com

Ipsen's IQIRVO Approval Has Intensified the Primary Biliary Cholangitis Market Space | DelveInsight

The European Commission has granted conditional approval for Ipsen's IQIRVO (elafibranor) for the treatment of primary biliary cholangitis in adults, marking the first new therapy for this condition to be approved in the EU in almost ten years. With this approval, other companies such as CymaBay Therapeutics, Zydus Therapeutics, GlaxoSmithKline, and others also geared up to bring their candidates into the primary biliary cholangitis market. LAS VEGAS, Oct. 2, 2024 /PRNewswire/ -- Primary biliary cholangitis (PBC), previously referred to as primary biliary cirrhosis, is a long-term liver condition characterized by the gradual destruction of the small bile ducts within the liver, known as intrahepatic bile ducts. Over time, prolonged bile flow obstruction can result in cirrhosis and the development of portal hypertension. As per DelveInsight analysis, in 2023, the total diagnosed prevalent cases of primary biliary cholangitis in the 7MM were approximately 298K. These cases are projected to increase further during the forecast period (2024–2034). In 2023, the United States had the highest proportion of diagnosed prevalent cases of primary biliary cholangitis among the 7MM, comprising approximately 48% of the total cases. DelveInsight's epidemiology model for primary biliary cholangitis estimates a higher prevalence among females across the 7MM. Specifically, in the US in 2023, it suggests approximately 25K cases among males and 117K cases among females, indicating a female predominance. The primary treatment objectives are to reduce the progression rate of the disease and manage symptoms such as itching, osteoporosis, and dry eye/mouth (sicca syndrome). Liver transplantation remains the only life-saving option. Ursodeoxycholic acid (UDCA) is the main medication used to slow disease progression. Patients in the early stages often experience clinical, biochemical, and histological improvements. Studies suggest UDCA postpones the need for liver transplantation and extends survival, though its effectiveness in advanced stages like cirrhosis is uncertain. While initially approved by the US FDA for treating primary biliary cholangitis, UDCA now has generic versions available. The use of corticosteroids in patients without signs of autoimmune hepatitis remains a subject of ongoing research. Studies have shown that combining UDCA with dexamethasone can enhance the activity of the anion exchanger from two alternate promoters in liver cells in vitro. Budesonide is being considered due to its extensive first-pass hepatic metabolism, which may help minimize side effects. Corticosteroids may help relieve symptoms and improve biochemical and histological outcomes, though corticosteroid-induced osteoporosis is a major concern. The criteria for liver transplantation in patients with primary biliary cholangitis are generally the same as those for other chronic liver diseases. However, severe and unmanageable itching is a unique reason for considering a transplant. Fatigue, which may continue after transplantation, is not regarded as an indication for the procedure. Liver transplantation for PBC patients typically offers a better prognosis than for most other chronic liver diseases, with a 5-year survival rate of 84–87% and a 10-year survival rate of 79–84%. In May 2016, the US FDA granted accelerated approval for OCALIVA (obeticholic acid) as a treatment for primary biliary cholangitis. It is approved for use alongside UDCA in adults who do not respond adequately to UDCA, or as a standalone treatment for those who cannot tolerate UDCA. OCALIVA is a semi-synthetic bile acid analog with the chemical structure 6α-ethyl-chenodeoxycholic acid. OCALIVA remains the only approved second-line therapy for this condition. Later, in December 2016, the European Commission gave conditional approval for OCALIVA for the same uses—either in combination with UDCA or as monotherapy for adults unable to tolerate UDCA. Learn more about the FDA-approved primary biliary cholangitis drugs @ Drugs for Primary Biliary Cholangitis Treatment Recently, the European Commission has granted conditional approval for IQIRVO (elafibranor) 80mg tablets for treating primary biliary cholangitis. It can be used alongside ursodeoxycholic acid in adults who have an inadequate response to UDCA or as a standalone therapy for those who cannot tolerate UDCA. This decision follows a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) on July 26, 2024, and the US FDA's Accelerated Approval granted on June 10, 2024. Elafibranor, a pioneering molecule, has been marketed and commercialized in the US by Ipsen under the brand name IQIRVO since June 2024. It was originally developed by GENFIT, from its discovery through the completion of a 52-week Phase III clinical trial. In 2021, Ipsen obtained exclusive global rights to elafibranor, except for China, Hong Kong, Taiwan, and Macau, through a licensing agreement with GENFIT. The EU approval was based on favorable outcomes from the Phase III ELATIVE trial, which demonstrated a 47% clinical benefit of IQIRVO combined with UDCA compared to placebo plus UDCA on the composite primary endpoint. The main objective for cholestasis response was defined as alkaline phosphatase (ALP) being less than 1.67 times the upper limit of normal (ULN), with a ≥15% reduction in ALP and total bilirubin levels within the normal range after one year. Additionally, the treatment showed a reduction in pruritus when compared to placebo. Additionally, in August 2024, Gilead Sciences, Inc. announced that the FDA has granted accelerated approval for LIVDELZI (seladelpar) to treat primary biliary cholangitis. This treatment can be used alongside ursodeoxycholic acid in adults who have not responded adequately to UDCA or as a standalone therapy for those unable to tolerate UDCA. Livdelzi is not advised for patients with or who develop decompensated cirrhosis. Seladelpar (MBX-8025) is a potent and selective PPARδ agonist, administered orally, and is currently being developed for patients with PBC who either do not respond to or cannot tolerate UDCA. In March 2024, Gilead Sciences completed its acquisition of CymaBay and announced the validation of a Marketing Authorization Application (MAA) for Seladelpar by the European Medicines Agency (EMA). Seladelpar has been granted Breakthrough Therapy Designation (BTD) by the US FDA, PRIME status by the EMA, and Orphan Drug Designation (ODD) from both agencies, which may accelerate the approval process. To know more about primary biliary cholangitis treatment options, visit @ New Treatment for Primary Biliary Cholangitis With this approval, several companies have also geared up to bring their lead assets into the market. The expected launch of emerging therapies, such as Saroglitazar Magnesium (Zydus Therapeutics), Linerixibat (GlaxoSmithKline), Setanaxib (Calliditas Therapeutics AB), Bezafibrate + obeticholic acid (Intercept Pharmaceuticals/Alfasigma), Volixibat (Mirum Pharmaceuticals), EP547 (Escient Pharmaceuticals), and others are expected to create a positive impact on the market. Other therapies in the early stages of the trial are also being developed. Discover which therapies are expected to grab major primary biliary cholangitis market share @ Primary Biliary Cholangitis Market Report Saroglitazar (LIPAGLYN) comprises two primary types of PPAR agonists: PPARα (alpha) and PPARγ (gamma). This medication simultaneously reduces lipid and glucose levels, effectively decreasing elevated triglycerides and blood sugar while enhancing insulin sensitivity. The US FDA has awarded Saroglitazar orphan drug designation (ODD) and fast track designation (FTD) for primary biliary cholangitis (PBC). It is presently undergoing Phase II/III trials for this condition. Linerixibat (GSK2330672) is a medication under development for patients with primary biliary cholangitis who suffer from itching. It is a small molecule inhibitor of the ileal bile acid transporter (IBAT) that is minimally absorbed and taken as an oral tablet. By preventing the reabsorption of bile acids in the small intestine, linerixibat lowers the levels of pruritic bile acids in the bloodstream. In 2019, the FDA designated it as an orphan drug (ODD). It is currently being evaluated in a Phase III trial for treating cholestatic pruritus in individuals with PBC. Discover more about drugs for primary biliary cholangitis in development @ Primary Biliary Cholangitis Clinical Trials The anticipated launch of these emerging therapies for primary biliary cholangitis are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the primary biliary cholangitis market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the primary biliary cholangitis market saw a significant emergence of a dominant treatment modality, valued at USD 1.1 billion in the 7MM. This modality likely reflects advancements in therapeutic approaches such as first-line agents like UDCA, second-line treatments like obeticholic acid, and potentially emerging biologics or combination therapies aiming to address the complex pathophysiology of PBC, thus enhancing patient outcomes and market share. DelveInsight's latest published market report titled as Primary Biliary Cholangitis Market Insight, Epidemiology, and Market Forecast – 2034 will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the primary biliary cholangitis country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The primary biliary cholangitis market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Diagnosed Prevalent cases of Primary Biliary Cholangitis Gender-specific Diagnosed Prevalent cases of Primary Biliary Cholangitis Age-specific Diagnosed Prevalent cases of Primary Biliary Cholangitis The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM primary biliary cholangitis market. Highlights include: 11-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis up to 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this primary biliary cholangitis market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the primary biliary cholangitis market. Also, stay abreast of the mitigating factors to improve your market position in the primary biliary cholangitis therapeutic space. Related Reports Primary Biliary Cholangitis Pipeline Primary Biliary Cholangitis Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key PBC companies, including Genfit, Zydus Discovery, Ohara Pharmaceutical, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Novartis, CymaBay Therapeutics, among others. Primary Biliary Cholangitis Epidemiology Forecast Primary Biliary Cholangitis Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and PBC epidemiology trends. Liver Cirrhosis Market Liver Cirrhosis Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key liver cirrhosis companies, including Madrigal Pharmaceuticals, Inc., Galectin Therapeutics Inc., Grifols Therapeutics LLC, CymaBay Therapeutics, Akero Therapeutics, Inc., NGM Biopharmaceuticals, Inc., Gilead Sciences, Novo Nordisk A/S, Cellaion, Promethera Therapeutics, Lipocine Inc., Bristol Myers Squibb, Prism Pharma, Ohara Pharmaceutical, Shionogi, among others. Liver Cirrhosis Pipeline Liver Cirrhosis Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key liver cirrhosis companies, including Versantis AG, Mirum Pharmaceuticals, Sagimet Biosciences, TenNor Therapeutics, Prism Pharma, Vedanta Biosciences, Intercept Pharmaceuticals, Boehringer Ingelheim, Ohara Pharmaceutical, Ocelot Bio, Calliditas Therapeutics, Galecto Biotech, Pharmicell, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 3Drug ApprovalOrphan DrugClinical ResultBreakthrough Therapy

13 Aug 2024

·www.prnewswire.com

Calliditas Interim Report January to June 2024

STOCKHOLM, Aug. 13, 2024 /PRNewswire/ -- Calliditas Therapeutics AB (NASDAQ: CALT) (STO: CALTX) : April to June 2024 (compared to April to June 2023) Net sales amounted to SEK 559.8 million, of which TARPEYO® net sales amounted to SEK 493.4 million, for the three months ended June 30, 2024. For the three months ended June 30, 2023, net sales amounted to SEK 269.4 million, of which TARPEYO net sales amounted to SEK 259.2 million. Operating loss amounted to SEK 31.5 million and SEK 75.2 million for the three months ended June 30, 2024, and 2023, respectively. However, expenses related to the Asahi Kasei offer and expenses related to provisions for social security contribution for incentive programs were included in the second quarter, totaling SEK 101.7 million. Excluding these expenses, the adjusted operating profit1 amounted to SEK 70.2 million for the three months ended June 30, 2024. Loss per share before and after dilution amounted to SEK 0.88 and SEK 1.71 for the three months ended June 30, 2024, and 2023, respectively. Cash amounted to SEK 797.3 million and SEK 866.2 million as of June 30, 2024, and 2023, respectively. January to June 2024 (compared to January to June 2023) Net sales amounted to SEK 855.3 million, of which TARPEYO® net sales amounted to SEK 771.6 million, for the six months ended June 30, 2024. For the six months ended June 30, 2023, net sales amounted to SEK 460.7 million, of which TARPEYO net sales amounted to SEK 444.9 million. Operating loss amounted to SEK 235.3 million and SEK 255.2 million for the six months ended June 30, 2024, and 2023, respectively. However, expenses related to the Asahi Kasei offer and expenses related to provisions for social security contribution for incentive programs were included in the second quarter, totaling SEK 101.7 million. Excluding these expenses the adjusted operating loss1 amounted to SEK 133.6 million for the six months ended June 30, 2024. Loss per share before and after dilution amounted to SEK 5.47 and SEK 5.21 for the six months ended June 30, 2024, and 2023, respectively. Key takeaways from Q2, 2024 In April, Calliditas read out positive data from the Nefecon Open Label Phase 3 Extension trial. In May, Calliditas read out positive topline results from the setanaxib Phase 2 trial in head and neck cancer. In May, Calliditas' partner Everest Medicines announced the commercial launch of Nefecon in China. In May, Calliditas' partner STADA received a positive CHMP opinion recommending full approval for Kinpeygo® in EU for the treatment of IgA nephropathy. In June, Calliditas announced the issuance by the United States Patent and Trademark Office (USPTO) of a new patent for setanaxib for treatment of cancer. The patent will have an expiration date in 2039. Key events after the reporting period In July, Calliditas partner STADA received European Commission decision for full approval of Kinpeygo® for the treatment of IgA Nephropathy. In July, Calliditas announced positive TRANSFORM Phase 2b topline data in primary biliary cholangitis. Asahi Kasei Offer Asahi Kasei Corporation announced on May 28, 2024, a public cash offer to acquire all shares in Calliditas for SEK 208 in cash per share (SEK 416 in cash per ADS). The Offer represents a premium of 83 per cent compared to the closing price of the Shares on Nasdaq Stockholm on May 27, 2024. The acceptance period of the offer commenced on July 18, 2024, and expires on August 30, 2024, subject to any extensions. Outlook 2024: Updated Calliditas expects continued revenue growth: Total net sales from the Nefecon franchise, including milestones, are estimated to be USD 165-185 million for the year ending December 31, 2024. Investor Presentation Today, 13 August at 2.30 p.m. CET Link to webcast: To participate via conference call register via this link: After registration, you will receive a phone number and a conference ID to log in to the conference call. There will be no Q&A following the presentation. For further information, please contact: Åsa Hillsten, Head of IR & Sustainability, Calliditas Tel.: +46 76 403 35 43, Email: [email protected] The information in the report is information that Calliditas is obliged to make public pursuant to the EU Market Abuse Regulation and the Securities Market Act. The information was sent for publication, through the agency of the contact person set out above, on August 13, 2024, at 7:00 a.m. CET. 1Management uses and presents IFRS results as well as the non-IFRS measure of adjusted operating profit to evaluate and communicate its performance. While non-IFRS measures should not be construed as alternatives to IFRS measures, management believes non-IFRS measures are useful to further understand Calliditas's current performance, performance trends, and financial condition. Adjusted operating profit is defined as IFRS operating profit (loss), less provisions for social security contributions for incentive programs and advisor fees for the Asahi Kasei public offer. A reconciliation of adjusted operating profit to operating profit (loss), which is the most directly comparable IFRS measure, is set forth on page 31 of the attached report. About Calliditas Calliditas Therapeutics is a biopharma company headquartered in Stockholm, Sweden, focused on identifying, developing, and commercializing novel treatments in orphan indications with significant unmet medical needs. Calliditas' common shares are listed on Nasdaq Stockholm (ticker: CALTX) and its American Depositary Shares are listed on the Nasdaq Global Select Market (ticker: CALT). Visit Calliditas.com for further information. Forward Looking Statements This Press Release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding Calliditas' strategy, business plans, revenue and other financial projections, and focus. The words "may," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue," "target" and similar expressions are intended to identify forward-looking statements, although not all forward looking statements contain these identifying words. Any forward-looking statements in this Press Release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this Press Release, including, without limitation, any related to Calliditas' business, operations, commercialization of TARPEYO, Kinpeygo and Nefecon, clinical trials, supply chain, strategy, goals and anticipated timelines for development and potential approvals, competition from other biopharmaceutical companies, revenue and product sales projections or forecasts, including 2024 total net sales guidance and cash runway, all statements regarding the public offer by Asahi Kasei Corporation, profitability and other risks identified in the section entitled "Risk Factors" in Calliditas' reports filed with the Securities and Exchange Commission. Calliditas cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. Calliditas disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this Press Release represent Calliditas' views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. This information was brought to you by Cision The following files are available for download:

Clinical ResultDrug ApprovalPhase 3Financial StatementPhase 2

26 Jul 2024

·www.fiercebiotech.com

Calliditas' liver disease trial hits primary endpoint after sweeping changes to design

Calliditas Therapeutics’ press release lacks details of the next steps for setanaxib in primary biliary cholangitis. Calliditas Therapeutics’ slimmed-down, truncated and rethought primary biliary cholangitis (PBC) drug has hit its primary endpoint. But the biotech, which changed the midphase trial to cut costs, only saw a positive trend on liver stiffness and reported a higher rate of treatment-related dropouts on the study drug.The Stockholm-based biotech set out in 2021 to enroll more than 300 patients in a 52-week phase 2b/3 trial. Management rethought the study late last year, dropping the phase 3 part, cutting the enrollment target to 70 and the duration to 24 weeks and switching the primary endpoint to reduction in the liver enzyme ALP. Calliditas made the changes to reduce its R&D costs for the trial for 2024 and 2025.This morning, Calliditas reported that the study met its revised primary endpoint. The trial ultimately compared two doses of setanaxib to placebo in 76 patients with PBC and elevated liver stiffness. More than 40% of participants took ursodeoxycholic acid and either Intercept Pharmaceuticals’ Ocaliva or the PPAR agonist bezafibrate during the study. Thirteen percent of subjects were on all three drugs.From baseline, Calliditas tracked improvements in ALP of 19% on the high dose and 14% on the low dose. The biotech said the changes in ALP, a liver enzyme that is raised in PBC patients, were statistically significant versus placebo at both doses. Calliditas named liver stiffness and fatigue as the two other measures to look out for on an earnings call in May. The biotech reported “positive trends on liver stiffness” in the phase 2 readout. The top-line data release makes no mention of fatigue.Setanaxib was generally well tolerated, according to Calliditas, with similar rates of treatment emergent adverse events (TEAEs) in the placebo and treatment cohorts. The frequency of TEAEs leading to study discontinuation was higher in patients receiving setanaxib compared to placebo.Calliditas’ press release lacks details of the next steps for setanaxib in PBC. The biotech did highlight two upcoming readouts in other indications. A phase 2, investigator-led idiopathic pulmonary fibrosis trial is scheduled to report results around the end of the year. Calliditas’ phase 2 Alport syndrome study is set to deliver data in 2025.The studies form part of a multifront R&D program that has seen setanaxib tested in a range of settings including head and neck cancer. The breadth of the program reflects Calliditas’ belief that the potential anti-fibrotic effects of setanaxib have applications in a range of indications.

Phase 2Clinical ResultPhase 3Clinical Trial Failure

100 Deals associated with Setanaxib

External Link

KEGG	Wiki	ATC	Drug Bank
-	Setanaxib	-	-

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Nephritis, Hereditary	Phase 2	Austria	Calliditas Therapeutics AB	27 Nov 2023
Nephritis, Hereditary	Phase 2	Czechia	Calliditas Therapeutics AB	27 Nov 2023
Nephritis, Hereditary	Phase 2	France	Calliditas Therapeutics AB	27 Nov 2023
Nephritis, Hereditary	Phase 2	Spain	Calliditas Therapeutics AB	27 Nov 2023
Nephritis, Hereditary	Phase 2	United Kingdom	Calliditas Therapeutics AB	27 Nov 2023
Idiopathic Pulmonary Fibrosis	Phase 2	Sweden	Calliditas Therapeutics France SAS	30 Jan 2022
Type 1 diabetes mellitus with established diabetic nephropathy	Phase 2	Australia	Calliditas Therapeutics France SAS	12 Dec 2017
Primary Biliary Cholangitis	Phase 2	United States	Calliditas Therapeutics AB	26 Jun 2017
Primary Biliary Cholangitis	Phase 2	Belgium	Calliditas Therapeutics AB	26 Jun 2017
Primary Biliary Cholangitis	Phase 2	Canada	Calliditas Therapeutics AB	26 Jun 2017

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05323656 (GSN000400, CTgov)	Phase 2	Squamous cell carcinoma of head and neck metastatic	55	Pembrolizumab+Setanaxib (Setanaxib 1600 mg and Pembrolizumab 200 mg)	xuxgmbzczg(hlismlfvov) = fykylzgomg fibhymbpmp (ilhkphpggi, 9.323) View more	-	09 May 2025
				Placebo+Pembrolizumab (Placebo and Pembrolizumab 200 mg)	xuxgmbzczg(hlismlfvov) = cckaqmotzq fibhymbpmp (ilhkphpggi, 8.977) View more
NCT05014672 (TRANSFORM, CTgov)	Phase 2	Primary Biliary Cholangitis \| Stiffness	76	Setanaxib (Setanaxib 1200 mg/Day)	wkobdyjzry(chuuwocymz) = fopwehvqvy pirhonicli (nrcrvviyex, uzqrnghqhp - nbkyhwusdu) View more	-	24 Apr 2025
				Setanaxib (Setanaxib 1600 mg/Day)	wkobdyjzry(chuuwocymz) = wfghvpekzi pirhonicli (nrcrvviyex, kzktrusyhc - haspvdpbll) View more
NCT02010242 (CTgov)	Phase 2	Diabetes Mellitus, Type 2 \| Type 2 diabetes mellitus with established diabetic nephropathy \| Albuminuria	136	GKT137831 (GKT137831)	cpvivkmkjs(dppxweuuhc) = frbeldlxah qhdulalhqp (zmobumunkd, eehuakgppe - rfdrjpaxvt) View more	-	28 Feb 2025
				Placebo (Placebo)	cpvivkmkjs(dppxweuuhc) = zxvzbrmlph qhdulalhqp (zmobumunkd, ywpnrsljht - dzlbxdnaxl) View more
NCT05323656 (GSN000400, ESMO2024) Manual	Phase 2	Squamous Cell Carcinoma of Head and Neck First line	55	Setanaxib 800 mg BID + Pembrolizumab 200 mg IV every 3 weeks	eptmwfmqyo(cmonmqjuct) = cppmjgxjzs lsqhzgyejb (accmoxdsjn, 9.323) View more	Positive	14 Sep 2024
				Placebo + Pembrolizumab 200 mg IV every 3 weeks	eptmwfmqyo(cmonmqjuct) = nakgfvxvsb lsqhzgyejb (accmoxdsjn, 8.997) View more
NCT05014672 (TRANSFORM, PRNewswire) Manual	Phase 2	Primary Biliary Cholangitis	76	setanaxib	wfvcpodunv(qrqizibclu) = Patients treated with setanaxib showed statistically significant improvements in the primary endpoint of ALP of 19% in the 1600mg arm and 14% in the 1200mg arm and showed positive trends on liver stiffness assessed by FibroScan® at 24 weeks. laymzwrbdj (topnvuosep ) Met View more	Positive	26 Jul 2024
				Placebo
NCT05323656 (PRNewswire) Manual	Phase 2	Squamous Cell Carcinoma of Head and Neck	55	Setanaxib+Pembrolizumab	zlpmzzigxj(feblposrrv) = kdzitshslq llkeoqmvyh (crhxrgdxhe ) View more	Positive	06 May 2024
				Pembrolizumab + Placebo	zlpmzzigxj(feblposrrv) = oybpymivuz llkeoqmvyh (crhxrgdxhe ) View more
NCT03226067 (Pubmed)	Phase 2	Primary Biliary Cholangitis Second line	111	Setanaxib 400 mg OD	maukcxsutz(fgqeehmzit) = lmtqdizkff wsioftduxt (xpqzchfyax, 59.6) View more	Positive	15 May 2023
				Setanaxib 400 mg BID	maukcxsutz(fgqeehmzit) = lxwvxgpzmz wsioftduxt (xpqzchfyax, 28.9) View more
NCT03226067 (CTgov)	Phase 2	Primary Biliary Cholangitis	111	Placebo oral capsule+GKT137831 (GKT137831 400mg Once Daily)	suokdsbrso(kiatpgkxjd) = hebwdfpmev wkkybdtqnl (fldxiuhsav, 59.58) View more	-	31 Mar 2022
				GKT137831 (GKT137831 400mg Twice Daily)	suokdsbrso(kiatpgkxjd) = budnlsptkj wkkybdtqnl (fldxiuhsav, 28.89) View more
NCT03226067 (GlobeNewswire) Manual	Phase 2	Primary Biliary Cholangitis	111	Setanaxib	beycefljal(gcwpmeluxu): P-Value = <0.002 View more	Positive	24 Jun 2019
				Placebo
EASL2019	Phase 2	Primary Biliary Cholangitis ALP \| GGT \| liver transaminases ... View more	111	GKT831 400 mg BID	jizmlrbxba(ejvjxhkqjs) = wduqbxhodi inoryjxfxx (yxuvlchimu )	Positive	11 Apr 2019
				Placebo	nbqjyjooer(ovgfshrctx) = emfpdutjeo fykxnkvlig (kfornzcyec ) View more

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis