CalciMedica, Inc. ("CalciMedica" or the "Company") (NASDAQ:CALC), a clinical-stage biopharmaceutical company developing calcium release-activated calcium (CRAC) channel inhibition therapies for serious inflammatory, immunologic, and cardiopulmonary diseases, today announced that, following a Type C Focused Meeting,  the U.S. Food and Drug Administration (FDA) and the Company have aligned on Phase 2b trial endpoints and a patient population enrichment strategy for its planned registration program evaluating Auxora™ in acute pancreatitis (AP).

Auxora is designed to inhibit CRAC channels, which regulate calcium entry into endothelial cells and drive the vascular injury and inflammation seen across acute inflammatory diseases.¹,² In AP, this endothelial injury is believed to contribute to new-onset severe respiratory failure, a major driver of mortality and morbidity in the disease and the endpoint on which FDA and CalciMedica aligned for the Phase 2b trial. In the completed CARPO trial in patients with AP, patients treated with medium and high doses of Auxora experienced a 100% reduction in new-onset severe respiratory failure.3 These findings are consistent with Auxora's observed clinical effects on respiratory compromised patients.

"Acute pancreatitis is a serious disease with no approved therapies, and this alignment with FDA is an important step toward what would be the first U.S. pivotal program evaluating a therapeutic candidate for AP," said Sudarshan Hebbar, M.D., Chief Medical Officer of CalciMedica. "Alignment on a biomarker-based enrichment approach using LDH to potentially identify patients at greater risk of severe disease gives us a clear path to a Phase 2b trial designed to inform a well-powered Phase 3 program."

"There hasn't been a validated and practical way to identify which patients with AP are most likely to progress to severe, life-threatening disease," said Timothy B. Gardner, M.D., Director of Pancreatic Disorders at Dartmouth–Hitchcock Medical Center and senior author of the American College of Gastroenterology's acute pancreatitis clinical guidelines. "Respiratory failure is the primary driver of prolonged hospital stays and mortality in this disease, yet no therapy has been approved for AP, and the field has not established a clinical trial endpoint framework to evaluate treatments. CalciMedica's program will help define that framework directly with FDA, and it reflects how AP actually presents in the clinic."

FDA aligned on new-onset severe respiratory failure as the Phase 2b trial's primary endpoint, with multi-organ failure and time to medically indicated discharge as key secondary endpoints. FDA and CalciMedica also aligned on the Phase 2b trial's role in confirming patient selection criteria and informing the endpoint for the Phase 3 program. The parties agreed to discuss additional Phase 3 program design features at future meetings. Based on its discussions with FDA, the Company believes that new-onset severe respiratory failure could be an important component of the Phase 3 registrational endpoint strategy.

The Phase 2b trial will also prospectively assess whether elevated LDH, a recognized marker of tissue injury and disease severity and a component of the Ranson criteria for AP severity, identifies patients at greater risk of developing severe disease. This approach is supported by an exploratory analysis of the completed CARPO trial, in which elevated LDH was associated with a higher incidence of new-onset severe respiratory failure. The Company believes LDH may offer a rapid and readily available assessment of risk because, in CARPO, higher LDH was associated with higher levels of IL-6, a known correlate of severe outcomes in AP patients. Among the patients with both baseline LDH and IL-6 measurements, those with LDH above 240 U/L (n=30) had a median IL-6 of 134 pg/mL, compared with 49 pg/mL among those with LDH below 240 U/L (n=24) (p=0.004). CalciMedica plans to evaluate the relationship between LDH and events of new-onset severe respiratory failure in the Phase 2b trial to establish that LDH may be used as an enrichment criterion for the Phase 3 program.

CalciMedica continues to advance preparations for the Phase 2b trial, including engaging with a contract research organization and holding discussions with potential clinical sites.