Cinclus Pharma announces positive topline results from the LEED phase II eGERD study

Cinclus Pharma Holding AB (publ) (“Cinclus Pharma”), a pharma company focused on the development of a novel treatment for gastroesophageal reflux disease (“GERD”), today announces positive topline results from the company's phase II study, LEED, on its leading drug candidate linaprazan glurate developed for the treatment of moderate to severe erosive GERD (“eGERD”). The primary endpoint of the study is to support dose selection of linaprazan glurate for phase III studies, through central assessment of four-week endoscopic healing of eGERD, with safety and tolerability as secondary endpoints. The study design included four dose levels of linaprazan glurate and one dose of the active comparator lansoprazole, a proton-pump inhibitor (“PPI”). Two separate cohorts of patients were enrolled, one cohort with patients having moderate to severe eGERD, defined as LA grade [1] C/D, and one with patients having milder eGERD, LA grade A/B, with a history of prior insufficient PPI-treatment.   Results For patients with moderate to severe eGERD, LA grade C/D, the highest four-week healing rate in a linaprazan glurate dosing group was 89%, compared to 38% in the lansoprazole group. While the study was not powered to demonstrate significance towards the comparator lansoprazole, the healing rate of all C/D patients treated with linaprazan glurate was significantly higher than lansoprazole in a post-hoc analysis (Fisher’s exact test, mean harmonic p-value= 0.0404). For all patients treated with linaprazan glurate, the mean healing rate was 80% compared to 69% in the lansoprazole treated group. For patients with milder eGERD, LA grade A/B, the highest four-week healing rate in a linaprazan glurate dosing group was 91%, compared to 81% in the lansoprazole group.  Linaprazan glurate was generally well tolerated and safety data was comparable to that of lansoprazole, with the most reported adverse event being COVID-19, occurring in 4% of the total study population. "Delivering this higher healing rate, 89% versus 38%, combined with a good safety profile, for our primary patient population, moderate to severe eGERD patients, already after four weeks, compared to lansoprazole is a great achievement, especially in a market where most patients are given an eight-week healing course. The results from the LEED study give us confidence in planning the upcoming phase III program and are an important step towards driving a paradigm shift in the treatment of gastric acid related diseases," said Christer Ahlberg, CEO of Cinclus Pharma.   The favorable safety data together with a dose response pattern in the moderate to severe eGERD patient group, will, together with pharmacokinetic and pharmacodynamic data, provide a robust set of data for the selection of the optimal dose in the upcoming pivotal phase III program, expected to be initiated in the fall of 2023.   About the Linaprazan glurate Erosive Esophagitis Dose ranging (LEED) study The LEED trial was conducted in the United States and Europe, including patients with erosive esophagitis (eGERD). Patients were divided into two cohorts, one with patients having moderate to severe eGERD (LA grade C/D) and one with patients having milder eGERD (LA grade A/B) with a history of prior insufficient PPI-treatment.   The primary endpoint of the study was to support dose selection of linaprazan glurate for the phase III program in eGERD, through central assessment of healing of erosive esophagitis after four weeks of treatment. The sample size, i.e. the number of patients needed, for measuring dose related efficacy was based on the patient cohort with moderate to severe eGERD.   After initial endoscopy and other screening procedures, 248 patients were randomized equally into one of five treatment groups, receiving either four weeks treatment with linaprazan glurate in four dose levels, or four weeks lansoprazole in the approved standard eGERD healing dose. Thereafter, an endoscopic evaluation of healing was performed, where healing was defined as no presence of esophageal erosions, i.e., no erosive damage to the esophageal mucosa.   After the endoscopic evaluation, all patient groups received lansoprazole for four weeks in a maintenance phase as requested by competent authorities. As per request from the competent authorities, a retrospective central review of the endoscopy findings was performed, and 162 patients were available for evaluation of the primary endpoint. All enrolled 248 patients were included in the safety analysis. [1] The Los Angeles Classification of GERD. For additional information, please contact: Christer Ahlberg, CEO Phone: +46 70 675 33 30 e-mail: [email protected] Charlotte Stjerngren, IR Phone: +46 70 876 87 87 e-mail: [email protected] About linaprazan glurate Linaprazan glurate is a prodrug of the P-CAB linaprazan, the main and active metabolite, developed originally by AstraZeneca. Linaprazan has been evaluated in 23 phase I studies and two phase II studies exposing a total of approximately 2,600 subjects to linaprazan. Linaprazan glurate is being developed for treatment of moderate to severe erosive gastroesophageal reflux disease (GERD). Linaprazan glurate has the potential to heal esophageal injuries and alleviate GERD symptoms more effectively than current pharmaceutical therapies including PPIs. The beneficial safety, efficacy and pharmacokinetic properties of linaprazan glurate was documented in a phase II study conducted in 2022.   About GERD Gastroesophageal reflux disease (GERD) is a digestive disease that affects the lower esophageal sphincter (LES), the ring of muscle between the esophagus and stomach, causing retrograde flow of gastric content into the esophagus. This leads to erosions, acid regurgitations and heart burn. Approximately 133 million people of the adult population in the United States and the EU-30 suffer from reflux disease. The global acid reflux market is dominated by proton-pump inhibitors (PPIs). More than 20% of all GERD patients take PPIs off-label twice daily to overcome the incomplete symptom relief or supplement their treatment with over the counter-remedies. Despite frequent off-label prescription of high dosage PPIs, many patients still suffer from poor symptom control indicating a clear need for better drugs to treat GERD.   About Cinclus Pharma Cinclus Pharma Holding AB (publ) is a clinical stage pharma company developing a small molecule for the treatment of gastric acid related and upper gastrointestinal diseases. Its leading drug candidate linaprazan glurate represents a new class of drugs, Potassium Competitive Acid Blocker (P-CAB), and provides a fast-acting control of intragastric pH by a different mechanism of action than proton-pump inhibitors (PPIs). For more information, please visit www.cincluspharma.com . Attachments Cinclus Pharma announces positive topline results from the LEED phase II eGERD study

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