NOX4

Why some people remain relatively healthy with fatty liver disease and some go onto potentially life-threatening illness has been a mystery. Until now. The global rise in obesity and diabetes is leading to an epidemic in fatty liver disease affecting 20-30 per cent of the world's population. Almost a third of people with fatty liver disease go on to develop an advanced form of the disease, known as non-alcoholic steatohepatitis (NASH) that can progress to cirrhosis and end-stage liver disease, or even liver cancer, and is a major risk factor for cardiovascular disease. Why some people remain relatively healthy with fatty liver disease and some go onto potentially life-threatening illness has been a mystery. Until now. A study published today in The Journal of Clinical Investigation led by Professor Tony Tiganis from Monash University's Biomedicine Discovery Institute, has shown that the levels of the NOX4 protein change as the disease progresses -- rising in the early stages of the disease to protect the liver, but declining as the liver disease gets worse. The researchers found that removing NOX4 in obese mice led to NASH and liver damage. And when NOX4 levels were artificially raised in these mice they were protected from NASH and liver damage. Importantly, the discovery provides evidence for a therapeutic avenue for a disease whose prevalence is predicted to balloon by 63 per cent from 2015 to 2030. According to Professor Tiganis, the precise mechanisms that govern the transition to NASH and liver damage have remained unclear. "It has been perplexing why the majority of patients with fatty liver disease don't progress to more severe disease," he said. The researchers have shown that this is because NOX4 is induced when the liver first starts to accumulate fat and activates a complex adaptive program that protects the liver. It is only when NOX4 levels decline and this adaptive program is abrogated that obese patients with fatty liver progress to NASH and liver damage. Importantly, previous studies by Professor Tiganis and others have shown that the raising of NOX4 levels in skeletal muscle or in the heart after exercise protects against damage and promote muscle and cardiac function and prevent the metabolic decline otherwise associated with ageing. "Compounds that bolster the activity of NOX4, or the adaptive program that NOX4 instigates, may be highly beneficial, countering not only the development of NASH, but also improving skeletal and cardiac function, as well as metabolic health," Professor Tiganis said. Such compounds are found naturally in cruciferous vegetables, such as broccoli or cauliflower.

STOCKHOLM, Jan. 18, 2021 /PRNewswire/ -- Genkyotex SA, a subsidiary of Calliditas Therapeutics AB (publ) ("Calliditas") (Nasdaq OMX - CALTX; NASDAQ - CALT), today announced positive Phase 1 data demonstrating a favorable safety and pharmacokinetic profile of high-dose setanaxib, Genkyotex's lead asset. The Phase 1 study demonstrated that setanaxib is well tolerated at the doses tested, with no safety signal or dose-limiting toxicity being identified. The results provide an opportunity for the company to pursue a pivotal Phase 2/3 clinical trial in patients with primary biliary cholangitis (PBC), based on interactions with the FDA. The study assessed the safety and pharmacokinetics of oral setanaxib at selected doses in 46 healthy adult male and female subjects. The trial consisted of a single ascending dose (SAD) part and a multiple ascending dose (MAD) part with dosing up to 1600mg/day. Previously, doses of up to 800 mg/day were evaluated in a 24-week Phase 2 trial in PBC patients. In that trial, setanaxib dosed at 800 mg/day achieved reductions in markers of cholestasis, including alkaline phosphatase, and in multiple non-invasive markers of liver fibrogenesis, including liver stiffness and PRO-C3 and C3M. Significant improvement in fatigue was also achieved. All doses tested in that trial were well-tolerated, with no safety signal compared to placebo. "This result provides a foundation for a clinical development program using higher doses of setanaxib across a variety of orphan indications. This includes the potential to launch a pivotal phase 2/3 trial with a clearly differentiated drug candidate in PBC but will also allow us to further explore a select number of kidney related orphan diseases in which inflammation and fibrosis play a part.", said CEO Renée Aguiar-Lucander. Calliditas acquired 62.7% of the share capital and voting rights of Genkyotex, in November 2020, before submitting a simplified public mandatory offer to the shareholders of Genkyotex on 26 November 2020. Calliditas controls 86.2% of the share capital and total number of votes of Genkyotex. For further information, please contact: Marie Galay, IR Manager, Calliditas Tel.: +44 79 55 98 12 45, email: marie.galay@calliditas.com The information was sent for publication, through the agency of the contact persons set out above, on January 18, 2021 at 08:00 a.m. CET. About Calliditas Calliditas Therapeutics is a specialty pharmaceutical company based in Stockholm, Sweden focused on identifying, developing and commercializing novel treatments in orphan indications, with an initial focus on renal and hepatic diseases with significant unmet medical needs. Calliditas' lead product candidate, Nefecon, is a proprietary, novel oral formulation of budesonide, an established, highly potent local immunosuppressant, for the treatment of the autoimmune renal disease IgA nephropathy, or IgAN, for which there is a high unmet medical need and there are no approved treatments. Calliditas is running a global Phase 3 study within IgAN and, if approved, aims to commercialize Nefecon in the United States. Calliditas is listed on Nasdaq Stockholm (ticker: CALTX) and the Nasdaq Global Select Market (ticker: CALT). Visit for further information. About Genkyotex Genkyotex (Euronext Paris and Brussels: GKTX) is a leader in NOX therapies. Its unique therapeutic approach is based on a selective inhibition of NOX enzymes, which amplify disease processes such as fibrosis, inflammation, pain processing, cancer development, and neurodegeneration. Genkyotex's discovery platform enables the identification of orally available small-molecules that selectively inhibit specific NOX enzymes. From this, Genkyotex has developed a pipeline of first-in-class product candidates targeting one or multiple NOX enzymes. The lead product candidate setanaxib, a NOX1 and NOX4 inhibitor, demonstrated clinical evidence of anti-fibrotic activity in liver fibrosis and improvement of fatigue in patients in a Phase II trial in primary biliary cholangitis (PBC, a fibrotic orphan disease). Setanaxib is also being evaluated in investigator-initiated Phase II clinical trials in Type 1 Diabetes and in idiopathic pulmonary fibrosis (IPF), a chronic lung disease that results in fibrosis of the lungs. 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 the regulatory pathway for setanaxib, development plans for setanaxib, plans for the conduct of and likelihood of success of planned and ongoing clinical trials of setanaxib, Calliditas' strategy, business plans 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 regulatory filings submissions for setanaxib, the ongoing and planned clinical trials of setanaxib, Calliditas' business, operations, clinical trials, supply chain, strategy, goals and anticipated timelines, competition from other biopharmaceutical companies, and other risks identified in the section entitled "Risk Factors" in Calliditas' reports and other filings 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: View original content: SOURCE Calliditas Therapeutics Company Codes: Stockholm:CALTX, NASDAQ-NMS:CALT, Berlin:LC8, Bloomberg:CALTX@SS, ISIN:SE0010441584, LSE:0A5R, OTC-PINK:CLTEF, RICS:CALTX.ST, Munich:LC8, Stuttgart:LC8