CalciMedica Announces Publication of Peer-Reviewed Article in The Journal of Physiology; Study supports development of CRAC channel inhibitors for acute pancreatitis
LA JOLLA, Calif., March 10, 2022 /PRNewswire/ — CalciMedica Inc. (CalciMedica or the Company), the Calcium Release Activated Calcium (CRAC) channel company, today announced the publication of a research paper describing how the activation of Orai1-mediated bile acids and ethanol damage pancreatic duct cells in AP. The research paper, titled “Bile acids and ethanol-mediated Orai1 activation damages pancreatic duct secretion in acute pancreatitis,” appears in the peer-reviewed publication The Journal of Physiology, and is written by a group led by Joszef MalethMD, Ph.D., Senior Researcher, University of Szeged, Hungary. The results provide a description of the underlying biological mechanisms that may explain the rapid solid food tolerance observed in CalciMedica’s Phase 2a trial of Auxora, its lead product, in AP patients with systemic inflammatory response syndrome ( SIRS) and hypoxemia.
“The relationship between Orai1 inhibition and bile acid and alcohol-induced damage to pancreatic ductal cell secretion has long been worth investigating,” said Dr. Maleth. “Our study demonstrates that inhibiting Orai1 can improve outcomes for patients with acute pancreatitis by restoring this ductal cell function. We are delighted to have such a respected journal as The Journal of Physiology recognize the importance of our findings and are pleased that our work is available to both the public and the scientific community.”
Although intracellular Ca supported2+ overload via overactivation of CRAC and Orai1 channels in pancreatic acinar cells is a known feature of experimental PA, the expression and function of Orai1 in pancreatic duct cells is not well appreciated and warrants further research . The results of this study indicate that inhibition of Orai1 prevents impairment of ductal cell function, as well as acinar cell function in PA caused by both bile acid/gallstones and alcohol. , the main causes of clinical PA, which has implications for improving disease outcomes in PA patients.
“The study led by Dr. Maleth uses our proprietary compound CM5480, one of our CRAC channel blockers, a research tool, which has been used in other proof-of-concept studies,” said Kenneth Stauderman, Ph.D., co-founder and scientific director of CalciMedica. “Protection of pancreatic duct cells by a CRAC channel inhibitor, as demonstrated in Dr. Maleth’s study, allows these cells to perform their normal function of transporting digestive enzymes produced in the pancreas to the intestine, with the bicarbonate, and we believe they help explain why, in our Phase 2a AP trial, patients were able to tolerate solid foods faster after treatment with Auxora compared to placebo Together, these results go a long way to advancing our understanding of the role of CRAC channels in PA and making a difference in the quality of life of these patients.”
Auxora is CalciMedica’s lead candidate and is currently being evaluated in a phase 2b trial for acute pancreatitis accompanied by SIRS. The previous phase 2a trial randomized 21 patients with acute pancreatitis and SIRS accompanied by hypoxemia to receive high or low dose Auxora plus standard therapy or standard therapy alone. From screening to day 5 or discharge, among patients receiving Auxora, fewer experienced persistent SIRS and more experienced rapid restoration of bowel function with improved solid food tolerability within 72 hours of treatment. This allowed for earlier discharge from hospital, leading to a reduction in median hospital stay in the Auxora treatment groups compared to patients receiving only standard care, particularly in patients with acute pancreatitis moderate or severe. Improvements in BP severity were seen in three of eight Auxora-treated patients with moderate to severe BP as evidenced by contrast-enhanced computed tomography (CECT) scans, compared to none of the four patients in the standard treatment group . Efficacy signals were observed in the high-dose and low-dose cohorts.
To view the publication online, click here.
CalciMedica’s lead product candidate is Auxora, a potent and selective small molecule intravenously (IV) formulated CRAC channel inhibitor which, in animal models and in clinical trials, has prevented acute injury to epithelial cells and/or endothelial cells and inflammation in organs, such as the pancreas, lungs and kidneys. Auxora is currently being evaluated in several ongoing clinical trials: a blinded placebo-controlled phase 2b in patients with acute pancreatitis accompanied by systemic inflammatory response syndrome (SIRS), a phase 2 dose-escalation trial in patients with COVID-19 pneumonia and acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation, and an investigator-initiated Phase 1/2 trial in pediatric patients with acute lymphocytic leukemia (ALL) who develop acute pancreatitis following specific chemotherapy. Auxora was evaluated in CARDEA, a randomized, placebo-controlled trial of 284 patients in hospitalized patients with COVID-19 pneumonia that was the second part of a phase 2 trial. The results of the first part of the trial of phase 2, a randomized open-label trial in 30 patients with critical and severe COVID-19 pneumonia, have been published in the peer-reviewed journal, critical carein August 2020. The results of a phase 2a randomized open-label trial in 21 patients with acute pancreatitis with SIRS have been published in the peer-reviewed journal, Pancreasin June 2021.
About CalciMedica, Inc.
CalciMedica is a clinical-stage biopharmaceutical company that offers a new class of drugs designed to act on calcium release-activated calcium channels (CRACs), a group of ion channel targets that are not addressed by any approved drug. CalciMedica is developing CRAC channel inhibitors for unmet needs in severe acute diseases and seeks to expand the potential uses of CRAC channel inhibitors to certain chronic diseases that have inflammation as a common thread in their pathogenesis. The Company has a portfolio of potent and selective small molecule CRAC channel inhibitors, including Auxora, its lead product candidate, which is formulated as a proprietary IV nanoemulsion specifically designed for acute severe disease.
CalciMedica is headquartered in La Jolla, California. For more information, please visit the company’s website at www.calcimedica.com.