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62.7% relative reduction in mortality at day 30, which persisted through day 60, for patients treated with Auxora versus placebo in subset of patients in CARDEA with AKI LA JOLLA, Calif., March 4, 2025 /PRNewswire/ -- CalciMedica Inc. ("CalciMedica" or the "Company") (Nasdaq: CALC), a clinical-stage biopharmaceutical company focused on developing novel calcium release-activated calcium (CRAC) channel inhibition therapies for acute and chronic inflammatory and immunologic illnesses, today announced that Sudarshan Hebbar, M.D., Chief Medical Officer of CalciMedica, delivered a plenary presentation at the 30th International Acute Kidney Injury and Continuous Renal Replacement Therapy Conference (AKI & CRRT) on March 3, 2025 in San Diego, CA. The presentation outlined the role of CRAC channels in acute kidney injury (AKI) pathophysiology and included new data highlighting the potential of CalciMedica's lead product candidate, Auxora™, in AKI. CalciMedica is currently conducting a Phase 2 trial of Auxora in patients with Stage 2 or Stage 3 AKI and acute hypoxemic respiratory failure, which is expected to read out in 2025. The new data presented were based on a post-hoc analysis from the previously completed Phase 2 CARDEA trial of Auxora in severe COVID-19 pneumonia. The study included 38 patients who enrolled with AKI, defined as an estimated glomerular filtration rate (eGFR) ≤ 60 ml/min/1.73 m², in addition to moderate or severe respiratory failure, which was an inclusion criterion. Within this subset: Patients treated with Auxora showed a 62.7% relative reduction versus placebo in mortality at day 30 which persisted through day 60. 7 out of 15 (46.7%) patients on placebo died by day 30 and day 60 as compared to 4 out of 23 (17.4%) patients on Auxora. Auxora exhibited an absolute reduction in mortality of 29.3%. This reduction in mortality in the patient subset with AKI exceeded that of the entire study population. In the entire population (n = 261), a 56.3% (p = 0.017) relative reduction versus placebo in mortality at day 30 was observed, with an absolute reduction of 9.9% versus placebo. In his presentation, Dr. Hebbar also summarized previously disclosed data supporting the role of CRAC channel inhibition as a potential therapeutic mechanism in AKI. Key data include: In preclinical biomarker studies, rats with AKI following ischemic reperfusion injury had decreased Th17 cells in their kidneys when receiving a CRAC inhibitor versus control, highlighting immunomodulatory effects. In in-vitro experiments, CRAC channel inhibition ameliorated injury to podocyte cells (kidney cells involved in filtration) caused by high glucose or angiotensin II, highlighting tissue-protective effects. In preclinical outcome studies, GFRs recovered more quickly and mortality was reduced in rats with severe or moderately severe AKI that received Auxora versus placebo. In clinical trial biomarker studies, CARDEA patients who received Auxora versus placebo had changes in cardiorenal biomarkers—increases in angiopoietin-1 and decreases in angiopoietin-2 and D-dimers—which have been linked to the prevention of endothelial damage in prior studies and were correlated with improved outcomes in CARDEA. At doses used experimentally and clinically, Auxora potentially provides a therapeutic window to treat acute critical illnesses without increasing risk of infection. "As illustrated by these data, the biological rationale for CRAC channel inhibition as a potential therapeutic mechanism for AKI is compelling," said Sudarshan Hebbar, M.D., Chief Medical Officer of CalciMedica. "The post-hoc analysis from CARDEA is especially relevant given that the 62.7% relative reduction in mortality was observed in patients with both kidney failure and respiratory failure, which mirrors the intended patient population for our ongoing Phase 2 KOURAGE study." The presentation is now available on the Medical Events & Presentations section of CalciMedica's IR website at . About CalciMedica CalciMedica is a clinical-stage biopharmaceutical company focused on developing novel CRAC channel inhibition therapies for inflammatory and immunologic diseases. CalciMedica's proprietary technology targets the inhibition of CRAC channels to modulate the immune response and protect against tissue cell injury, with the potential to provide therapeutic benefits in life-threatening inflammatory and immunologic diseases for which there are currently no approved therapies. CalciMedica's lead product candidate Auxora™ has demonstrated positive and consistent clinical results in multiple completed efficacy clinical trials. CalciMedica has announced data for a Phase 2b trial (called CARPO – NCT04681066) in patients with acute pancreatitis (AP) and accompanying systemic inflammatory response syndrome (SIRS). The Company has also completed a Phase 2 trial (called CARDEA – NCT04345614) in patients with COVID pneumonia. The Company is currently conducting a Phase 2 trial (called KOURAGE – NCT06374797) in patients with acute kidney injury (AKI) with associated acute hypoxemic respiratory failure (AHRF) with data expected in 2025 and continuing to support the ongoing Phase 1/2 trial (called CRSPA – NCT04195347) in pediatric patients with asparaginase-induced pancreatic toxicity (AIPT) with data expected in 2025. CalciMedica was founded by scientists from Torrey Pines Therapeutics and the Harvard CBR Institute for Biomedical Research, and is headquartered in La Jolla, CA. For more information, please visit . Forward-Looking Statements This communication contains forward-looking statements which include, but are not limited to, results of post-hoc analyses from the previously completed Phase 2 CARDEA trial of Auxora and CalciMedica's ongoing and planned clinical trials and the timing and design thereof, and the expected timing for the release of data from those trials, including its ongoing Phase 1/2 CRSPA trial of Auxora in pediatric patients with AIPT and its ongoing Phase 2 KOURAGE trial of Auxora in AKI with associated AHRF; the potential benefits of Auxora for the treatment of AP, AKI and AIPT; and the potential of CalciMedica's proprietary technology to provide therapeutic benefits in life-threatening inflammatory and immunologic diseases. These forward-looking statements are subject to the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. CalciMedica's expectations and beliefs regarding these matters may not materialize. Actual outcomes and results may differ materially from those contemplated by these forward-looking statements as a result of uncertainties, risks, and changes in circumstances. Risks and uncertainties that could cause actual outcomes and results to differ materially from those contemplated by the forward-looking statements are included under the caption "Risk Factors" in CalciMedica's Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, filed with the U.S. Securities and Exchange Commission (SEC) on November 13, 2024, and elsewhere in CalciMedica's subsequent reports on Form 10-K, Form 10-Q or Form 8-K filed with the SEC from time to time and available at . These documents can be accessed on CalciMedica's web page at ir.calcimedica.com/financials-filings/sec-filings. The forward-looking statements contained herein are made as of the date hereof, and CalciMedica undertakes no obligation to update them after this date, except as required by law. Contact Information Argot Partners Sarah Sutton/Kevin Murphy [email protected] (212) 600-1902 SOURCE CalciMedica, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2 trial, expected to begin in 1H 2024, aims to address the unmet medical need of patients suffering from stage 2 or 3 acute kidney injury with associated acute hypoxemic respiratory failure, a condition associated with a high mortality rate Development of Auxora in AKI is supported by both clinical and pre-clinical evidence, including results from recently completed studies in a rat model of AKI to be presented at the 29th International Acute Kidney Injury and Continuous Renal Replacement Therapy Conference in March LA JOLLA, Calif., Feb. 13, 2024 /PRNewswire/ -- CalciMedica, Inc. (CalciMedica or the Company) (Nasdaq: CALC), a clinical-stage biopharmaceutical company focused on developing novel calcium release-activated calcium (CRAC) channel inhibition therapies for acute and chronic inflammatory and immunologic diseases, today announced the clearance of its Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA) for the Company's lead product candidate, Auxora™, a potent and selective small molecule inhibitor of Orai1-containing CRAC channels, to be evaluated in a Phase 2 trial in acute kidney injury (AKI) with associated acute hypoxemic respiratory failure (AHRF). CalciMedica expects to initiate the trial, named KOURAGE, in the first half of 2024 and data expected in 2025. "The IND clearance for the Phase 2 trial of Auxora in severe AKI is a significant milestone for CalciMedica as we work towards addressing the serious unmet medical need faced by patients suffering from this condition," said Rachel Leheny, Ph.D., Chief Executive Officer of CalciMedica. "Through KOURAGE, we aim to determine how Auxora can benefit patients with severe AKI and potentially reduce the high mortality rate associated with this disease." AKI is classified as stages 1, 2 and 3 depending on the degree of kidney injury. In the presence of AHRF, stage 2 and stage 3 AKI, both classified as severe, put patients at a 50% or greater risk for death while hospitalized and in the 90 days after discharge.1 Survivors of severe AKI may develop or progress to chronic kidney disease, leading to an eventual need for dialysis. There are approximately 1.1 million patients in the United States suffering from stage 2 and 3 AKI over half of whom have associated AHRF. There are currently no approved therapies for AKI. KOURAGE is a randomized, double-blind, placebo-controlled study that will evaluate 150 patients with stage 2 and 3 AKI who have AHRF and are receiving oxygen by non-invasive mechanical ventilation, high flow nasal cannula or intermittent mandatory ventilation (IMV). Patients will be stratified by classification of stage of AKI as well as the use of IMV. Patients will receive either a four-hour infusion of Auxora or placebo at 1.25 mL/kg as a first dose, after which they will receive Auxora or placebo at 1.0 mL/kg at hours 24, 48, 72 and 96. The primary endpoint of the trial will be evaluation of patients through day 30 to determine days alive, ventilator-free and dialysis-free. Secondary endpoints will include a composite of all-cause mortality, decrease in estimated glomerular filtration rate (eGFR), and the incidence of dialysis over a period of 90 days, also known as MAKE-90 (Major Adverse Kidney Events at 90 days). "The rationale for and design of our Phase 2 KOURAGE study is supported by our prior clinical trials and pre-clinical studies that have indicated the potential benefits of Auxora for the treatment of AKI," said Sudarshan Hebbar, M.D., Chief Medical Officer of CalciMedica. "After the learnings from our CARDEA trial revealed that treatment of severe and critical COVID-19 pneumonia patients with Auxora reduced the reported incidence of AKI and improved the survival of patients with kidney disease, we confirmed this potential benefit of Auxora in specific animal models of AKI. Currently, there are no drugs that treat AKI, and through KOURAGE, we hope to demonstrate that treatment with Auxora translates into a treatment option for this critical acute disease." AKI is a common consequence of severe COVID-19 pneumonia and in CalciMedica's CARDEA trial, which studied Auxora in patients with severe and critical COVID-19 pneumonia, results showed a nearly 40% reduction in reported AKI in Auxora-treated patients as compared to placebo-treated patients. In a post-hoc analysis of CARDEA patients with compromised kidney function (eGFR< 60 mL/min/1.73 m2) at enrollment, the drug was well tolerated and there was a survival benefit for patients treated with Auxora compared to those on placebo. Biomarker analysis from blood samples taken from over 190 CARDEA patients showed that Auxora increased Angiopoietin-1 while decreasing Angiopoietin-2, suggesting stabilization of the endothelium and the potential to treat AKI. Finally, published work from others showed that elevated serum IL–17 levels, a CRAC channel-mediated cytokine, were differentially elevated in critically ill patients with stage 2 and 3 AKI when compared to those without AKI, and the elevation was independently associated with both hospital mortality and long-term adverse outcomes.2 CalciMedica's initial pre-clinical studies in an ischemia/reperfusion injury (IRI) model of AKI were encouraging. A single dose of Auxora after IRI increased GFR by 61% and decreased mononuclear (inflammatory) cell infiltration by 30%. Further details from this study and results from CalciMedica's more recent pre-clinical study of multiple doses of Auxora given over several days and initiated after a greater time interval following IRI were also strong and will be presented at the 29th International AKI & Continuous Renal Replacement Therapy Conference taking place March 12-15, 2024 in San Diego, CA. About AKI Acute kidney injury (AKI) denotes a sudden reduction in kidney function, or the organ's ability to clean and filter the blood, as measured by increased serum creatinine (a cellular waste product) or decreased urine volume. AKI can result as a complication of other serious illnesses such as sepsis, respiratory infections and failure, acute pancreatitis, trauma, surgery and burns. There are approximately 3.7 million hospitalized with AKI in the United States each year. The majority have Stage 1 AKI and recover with supportive care alone. However, approximately 1.1 million of these patients advance to stage 2 and stage 3 AKI, over half of whom have associated AHRF. The risk of serious morbidities and mortality is significant for advanced stage 2 and stage 3 AKI patients. There are currently no approved therapies for AKI. About Auxora™ CalciMedica's lead clinical compound, Auxora™, is a potent and selective small molecule inhibitor of Orai1-containing CRAC channels that is being developed for use in patients with acute inflammatory and immunologic illnesses. CRAC channels are found on many cell types, including pancreatic acinar cells, lung endothelium cells and immune system cells, where aberrant activation of these channels may play a key role in the pathobiology of acute and chronic inflammatory syndromes. Auxora is currently being evaluated in: (i) a Phase 2b trial for acute pancreatitis (AP) with accompanying systemic inflammatory response syndrome (SIRS), called CARPO, (ii) an investigator-sponsored Phase 1/2 trial called CRSPA being conducted in pediatric patients with asparaginase-induced pancreatic toxicity (AIPT) as a side effect of pediatric acute lymphoblastic leukemia treatment with asparaginase, and (iii) a Phase 2 dose-ranging pharmacodynamic study in critical COVID-19 patients, with a Phase 2 trial in AKI, called KOURAGE expected to initiate in the first half of 2024. There are currently no approved therapies to treat either AP, AIPT or AKI. In previous trials, patients responded well to Auxora regardless of severity or cause of disease. CalciMedica is also exploring the potential of Auxora treatment for other acute indications including acute respiratory distress syndrome . About CalciMedica CalciMedica is a clinical-stage biopharmaceutical company focused on developing novel CRAC channel inhibition therapies for inflammatory and immunologic diseases. CalciMedica's proprietary technology targets the inhibition of CRAC channels to modulate the immune response and protect against tissue cell injury, with the potential to provide therapeutic benefits in life-threatening inflammatory and immunologic diseases for which there are currently no approved therapies. CalciMedica's lead product candidate Auxora™, a proprietary, intravenous-formulated CRAC channel inhibitor, has demonstrated positive and consistent clinical results in multiple completed efficacy clinical trials. CalciMedica is currently conducting a Phase 2b trial for a planned 216 patients (called CARPO – NCT04681066) for AP with SIRS, with topline data expected in the first half of 2024, as well as supporting the ongoing Phase 1/2 CRSPA AIPT study (called CRSPA – NCT04195347), with additional data expected by 2H 2024. CalciMedica plans to initiate a Phase 2 study in AKI in 1H 2024. CalciMedica was founded by scientists from Torrey Pines Therapeutics and the Harvard CBR Institute for Biomedical Research, and is headquartered in La Jolla, CA. For more information, please visit . Sources 1 Faubel, Sarah, and Charles L. Edelstein. "Mechanisms and mediators of lung injury after acute kidney injury." Nature Reviews Nephrology 12.1 (2016): 48-60. 2 Collett, Jason A., et al. "Serum IL-17 levels are higher in critically ill patients with AKI and associated with worse outcomes." Critical Care 26.1 (2022): 107. Forward-Looking Statements This communication contains forward-looking statements which include, but are not limited to, statements regarding CalciMedica's planned and ongoing clinical trials and the timing, design and expected patient enrollment thereof, including its planned Phase 2 clinical trial of Auxora in AKI with associated AHRF, its ongoing Phase 2b trial of Auxora for AP with accompanying SIRS, its ongoing Phase 1/2 trial of Auxora in pediatric patients with AIPT; the potential benefits of Auxora for the treatment of AKI, AP and AIPT; the estimated patient population in the United States for AKI; pre-clinical and clinical studies of Auxora in animal models and critical COVID-19 pneumonia patients, respectively, supporting the rationale for and the design of CalciMedica's planned Phase 2 KOURAGE trial and the potential benefits of Auxora in AKI; plans to present results from CalciMedica's pre-clinical studies in an IRI model of AKI at the 29th International AKI & Continuous Renal Replacement Therapy Conference; CalciMedica's development plans for Auxora; the expected timing for release of data in CalciMedica's ongoing clinical trials. These forward-looking statements are subject to the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. CalciMedica's expectations and beliefs regarding these matters may not materialize. Actual outcomes and results may differ materially from those contemplated by these forward-looking statements as a result of uncertainties, risks, and changes in circumstances, including but not limited to risks and uncertainties related to: the impact of fluctuations in global financial markets on CalciMedica's business and the actions it may take in response thereto; CalciMedica's ability to execute its plans and strategies; the ability to obtain and maintain regulatory approval for Auxora; results from clinical trials or preclinical studies may not be indicative of results that may be observed in the future; potential safety and other complications from Auxora; the scope progress and expansion of developing and commercializing Auxora; the size and growth of the market therefor and the rate and degree of market acceptance thereof; economic, business, competitive, and/or regulatory factors affecting the business of CalciMedica generally; CalciMedica's ability to protect its intellectual property position; and the impact of government laws and regulations. Additional risks and uncertainties that could cause actual outcomes and results to differ materially from those contemplated by the forward-looking statements are included under the caption "Risk Factors" in CalciMedica's Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 and elsewhere in CalciMedica's subsequent reports on Form 10-K, Form 10-Q or Form 8-K filed with the SEC from time to time and available at . These documents can be accessed on CalciMedica's web page at ir.calcimedica.com/financials-filings/sec-filings. CalciMedica Contact: Investors and Media Argot Partners Sarah Sutton/Kevin Murphy [email protected] (212) 600-1902 SOURCE CalciMedica, Inc.

A new study found individuals with spherical hearts were 31% more likely to develop atrial fibrillation and 24% more likely to develop cardiomyopathy, a type of heart muscle disease. Curious to know if you're at risk for two common heart conditions? Your doctor may want to check the shape of your heart. Investigators from the Smidt Heart Institute at Cedars-Sinai have discovered that patients who have round hearts shaped like baseballs are more likely to develop future heart failure and atrial fibrillation than patients who have longer hearts shaped like the traditional Valentine heart. Their findings, published in Med -- Cell Press' new peer-reviewed medical journal -- used deep learning and advanced imaging analysis to study the genetics of heart structure. Their results were telling. "We found that individuals with spherical hearts were 31% more likely to develop atrial fibrillation and 24% more likely to develop cardiomyopathy, a type of heart muscle disease," said David Ouyang, MD, a cardiologist in the Smidt Heart Institute and a researcher in the Division of Artificial Intelligence in Medicine. The risk was identified after investigators analyzed cardiac MRI images from 38,897 healthy individuals from the UK Biobank. Using this same database, researchers then used computational models to identify genetic markers of the heart that are associated with these cardiac conditions. "By looking at the genetics of sphericity, we found four genes associated with cardiomyopathy: PLN, ANGPT1, PDZRN3, and HLA DR/DQ," said Ouyang. "The first three of these genes were also associated with a greater risk of developing atrial fibrillation." Atrial fibrillation, the most common type of abnormal heart rhythm disorder, greatly increases a person's risk of having a stroke. The condition is rising in prevalence and projected to affect 12.1 million people in the U.S. by 2030. Cardiomyopathy is a type of heart muscle disease that makes it harder for the heart to pump blood to the rest of the body and can eventually lead to heart failure. The main types of cardiomyopathies -- dilated, hypertrophic, arrhythmogenic and restrictive -- affect as many as 1 of every 500 adults. Cedars-Sinai cardiologists say the shape of one's heart changes over years, typically becoming rounder over time and especially after a major cardiac event like a heart attack. "A change in the heart's shape may be a first sign of disease," said Christine M. Albert, MD, MPH, chair of the Department of Cardiology in the Smidt Heart Institute and a study author. "Understanding how a heart changes when faced with illness -- coupled with now having more reliable and intuitive imaging to support this knowledge -- is a critical step in prevention for two life-altering diseases." Ouyang says the findings provide more clarity on the potential use of cardiac imaging to diagnose more effectively -- and prevent -- many conditions. He also emphasized the need for additional studies. "Large biobanks with cardiac imaging data now offer an opportunity to analyze and define variation in cardiac structure and function that was not possible using traditional approaches," said Ouyang. "Deep learning and computer vision also allow for faster as well as more comprehensive cardiac measures that may help to identify genetic variations affecting a heart -- up to years or even decades before any obvious heart disease develops."