Linerixibat

STOCKHOLM – May 13, 2026. Umecrine Cognition today announced new data from the UK-PBC national cohort, to be presented at the EASL Congress 2026 in Barcelona. The data show that most patients with primary biliary cholangitis (PBC) who experience clinically significant fatigue or cognitive symptoms do not have clinically significant itch, challenging a previously prevailing paradigm. The findings support the need for therapies that specifically address the central nervous system (CNS) symptoms of PBC, alongside recent advances in itch-directed treatment. The analysis, based on PBC-40 symptom assessment tool responses from 1,964 well-characterized patients in the UK-PBC cross-sectional national cohort, found that 57% of patients experienced clinically significant fatigue and 36% reported fatigue with clinically significant cognitive symptoms. Critically, of those with fatigue, 54% did not have significant itch, and of those with cognitive symptoms, 52% did not have itch. The contribution of itch to fatigue appeared to be lowest in the group with “central” fatigue; the form of fatigue with the greatest impact on daily living. While recent advances – including iBAT inhibitors such as linerixibat, as well as fibrates and PPAR agonists – represent important progress for patients with cholestatic pruritus, the new data demonstrate that itch-directed therapy cannot be expected to resolve fatigue or cognitive dysfunction in the majority of affected patients. The findings reinforce the need for dedicated, purpose-built CNS therapies as a complementary pillar in a more individualized symptom franchise for PBC. Umecrine Cognition is developing golexanolone, currently in a Phase 1b/2a study (UCAB-CT-05) in PBC patients with clinically significant fatigue and cognitive symptoms. “These real-world data from nearly 2,000 UK patients make it clear that the quality-of-life burden in PBC cannot be explained by itch alone. Recent progress in cholestatic pruritus is welcome news for patients who suffer from severe itch, but more than half of patients with fatigue and cognitive symptoms will not be reached by those therapies. A dedicated CNS-targeted therapy, such as golexanolone, is needed to complete the PBC symptom franchise and deliver truly personalized care for every patient,” comments Dr. Viktor Drvota, CEO of Umecrine Cognition. The abstract (REG26-2685) “The majority of fatigued primary biliary cholangitis patients do not have clinically significant itch” will be presented by Professor David E. Jones, Newcastle University and Freeman Hospital, Newcastle, UK, at EASL 2026 in Barcelona on May 30 at the session “Immune-mediated and cholestatic disease: Clinical aspects”. For further information, please contact: Viktor Drvota, CEO, Umecrine Cognition AB Phone: +46 73 982 52 02, e-mail: [email protected] About the Phase 1b/2a study UCAB-CT-05 UCAB-CT-05 is a randomized, double-blind, placebo-controlled, two-part Phase 1b/2a study designed to evaluate the safety, pharmacokinetics, and preliminary efficacy of golexanolone in patients with primary biliary cholangitis (PBC) who experience clinically significant fatigue and cognitive symptoms. Part A (5 days, 40 mg twice daily) assessed safety and pharmacokinetics, while Part B (28 days, 40 mg or 80 mg twice daily) is evaluating efficacy using validated patient-reported and clinical measures. Key efficacy assessments include changes from baseline in the PBC-40 domains (cognition, fatigue, itch, social, emotional, and general symptoms), EQ-5D-3L, Epworth Sleepiness Scale, a cognitive test battery (PHES, RAVLT, D-KEFS), and the Clinical Global Impression of Change specific for PBC (CGI-C-PBC). A pre-specified interim analysis supports adaptive sample-size re-estimation based on conditional power. The study, conducted across more than 30 European sites, continues to recruit participants following positive interim data from the first part of the study, presented at The Liver Meeting® 2024 (AASLD). About Umecrine Cognition Umecrine Cognition AB is developing a completely new class of drugs for the treatment of symptoms in the central nervous system related to chronic neuroinflammation – a devastating brain distortion that can lead to severely impaired cognition and fatigue. Chronic neuroinflammation can occur as a result of a number of underlying conditions, including a range of liver diseases as well as neurodegenerative diseases, such as Parkinson’s disease. Results from an internationally acclaimed Phase 2 clinical study indicate that the company's most advanced drug candidate, the GABAA receptor-modulating steroid antagonist golexanolone, normalizes brain signaling and improves cognition and alertness in patients with hepatic encephalopathy. A Phase 2 study is currently ongoing in patients with primary biliary cholangitis. Further, based on intriguing preclinical data, the company is considering pursuing the development of golexanolone in patients with Parkinson’s disease. For more information, visit www.umecrinecognition.com. Attachments Umecrine Cognition will present patient survey data at EASL 2026 suggesting golexanolone addresses critical unmet need in PBC

The Bay Area biotech has a meeting on the books with the FDA in June to discuss a new drug application for volixibat, with submission planned for the second half of the year.\n Mirum Pharmaceuticals is prepping for a new FDA approval application after its small molecule volixibat successfully alleviated itching in patients with a rare liver disease.In 182 patients with primary sclerosing cholangitis (PSC), a chronic disease characterized by inflammation of the bile ducts that causes liver damage and an interminable full-body itch, those given twice-daily volixibat saw their itch severity reduced by 2.72 on an 11-point scale. This significantly topped the 1.08-point improvement in the placebo arm, Mirum announced May 4, hitting the phase 2 trial’s primary endpoint.“We believe this is an outstanding treatment effect,” Mirum’s Chief Medical Officer Joanne Quan, M.D., said in a May 4 call with investors. “The magnitude of improvement is consistent with what we have observed in other cholestatic indications and reflects a meaningful benefit for patients.”The Bay Area biotech has a meeting on the books with the FDA this summer to discuss a new drug application for volixibat, according to the release, with submission planned for the second half of the year.Mirum’s stock jumped about 10% on the news, from $96.53 per share at Friday’s close to $105.20 at 10:00 a.m. ET on Monday.Extreme itchiness, formally known as pruritus, is thought to occur in PSC because of compounds from liver bile that build up throughout the body. The itchiness can be so intense that it leads to suicidal thoughts, and constant scratching can cause sores and open wounds. “Cholestatic pruritus is one of the most common symptoms in PSC, which remains a challenging disease to manage,” Kris Kowdley, M.D., director of Liver Institute Northwest and a professor at Washington State University, who was one of the trial’s investigators, said in the release. “In clinical practice, we have very limited options to effectively address this symptom. Results like these are encouraging, as they suggest the potential for a targeted approach that could represent a meaningful advance for PSC patients.”Discontinuations in the volixibat arm were relatively high, with 9.1% of patients dropping out due to treatment-related adverse events, compared with 2.5% in the placebo arm. One patient in the placebo arm died. Volixibat treatment was associated with elevated levels of liver enzymes and bilirubin, which are biomarkers of damage to the organ.“These patients don\'t have a normal liver,” Quan said during the investor call. Because PSC by itself “can be associated with fluctuations in some of the biochemical abnormalities,” she added, Mirum is now working with an independent team to sort out the full safety profile. Volixibat is an inhibitor of a protein called the ileal bile acid transporter (IBAT), which regulates bile movement in the liver. Mirum already has extensive experience with this class of medicines; the company’s lead product is an IBAT inhibitor called Livmarli, which is approved for pruritus caused by other liver diseases.There are currently no FDA-approved drugs to treat PSC. Mirum is also testing volixibat’s potential in another liver disease, primary biliary cholangitis (PBC), with topline data from a registrational phase 2b trial expected in the first quarter of next year.In PBC, Mirum faces competition from GSK’s recently approved Lynavoy, which the British Big Pharma licensed to Italian outfit Alfasigma just before the FDA nod in a deal worth up to $690 million.