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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."

Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones. A Drug to Regrow Nerve Cells Damaged in Spinal Cord Injury Investigators at Washington University School of Medicine in St. Louis identified a compound that can help sensory neurons in the central nervous system to heal. Working with mice with injured sensory neurons, the researchers gave the animals a drug called fenofibrate. The drug is approved by the U.S. Food and Drug Administration (FDA) to treat high cholesterol. In their experiments, fenofibrate activated the support cells that surround sensory neurons, helping them regrow about twice as fast as the control group’s sensory neurons. They published their research in eLife. “When people think of spinal cord injury, they tend to think of paralysis, but there are a lot of problems with sensory processing and pain after spinal cord injury as well,” said Valeria Cavalli, senior author and the Robert E. and Louise F. Dunn Professor of Biomedical Research, and a professor of neuroscience. “Addressing those sensory issues could go a long way toward improving quality of life for survivors. Our data indicate that fenofibrate has the potential to activate these support cells and improve recovery, which means we could potentially repurpose this FDA-approved compound to help restore sensory function after nerve injuries.” The research team compared gene expression in five different support cells in the ganglion after injury to the peripheral and central branches of the sensory neuron. In their tests, the gene expression patterns in the support cells were different depending on which piece of the neuron was injured. For example, satellite glial cells increased expression of a group of genes called the PPAR-alpha pathway, which is involved in fat metabolism, only after there was injury to the peripheral axon branch. The pathway never increased activity after injury to the central axonal branches and was actually decreased after spinal cord injury in the CNS. The researchers believe this suggests the PPAR-alpha pathway could promote regeneration. New Mechanism Identified that Regulates Breast Cancer Metastasis Researchers at the University of Turku, Finland, identified a new mechanism that cells utilize to circulate integrins on the cell surface. Aggressive breast cancer cells leverage this to metastasize throughout the body. The researchers found a new mechanism that highly aggressive triple-negative breast cancer cells exploit to circulate integrins and spread to other tissues. These cancer cells use the molecule swiprosin-1 to direct the integrin adhesion receptors onto CG endocytosis mechanism, which is described as being like a conveyor belt that transports nutrients into cells. The cancer cells basically hijack the conveyor belt. They found that high expression of the swiprosoin-1 molecule is associated with more metastases and breast cancer malignancy. Possible New Treatment for Glaucoma Glaucoma is internal pressure in the eye, where fluid doesn’t properly drain. It can apply pressure to the optic nerve and lead to loss of vision. Researchers at Northwestern University, working in mice, identified possible new treatment targets for glaucoma, including a possible preventive for a severe pediatric form of glaucoma. They tested a long-lasting and non-toxic protein (Hepta-ANGPT1) in the mice, which allows them to replace the function of the genes that were missing in one model of glaucoma. The next step, they say, is to develop a delivery system and produce it. Pregnant Women Produce Robust Antibody Responses to COVID-19 Vaccines/Illness Studies out of Massachusetts General and Brigham and Women’s Hospitals into the effects of COVID-19 in pregnant women found that pregnant and lactating women produce robust antibody responses to both COVID-19 infection and vaccination. The twist is associated with why COVID-19 affects male adults, children, and infants harder than females. In one of the new studies, they found that in response to COVID-19 in mothers, male placentas turned on more pro-inflammatory immune activation genes than the placentas in the female fetuses. In general, males are more likely to become severely ill and die from COVID-19 than females. It appears to be associated with a slower response to the virus in males which then create more pro-inflammatory molecules, which leads to the cytokine storms. Nanoparticles that Communicate with Cancer Cells Scientists at the Advanced Science Research Center, Graduate Center, CUNY, designed nanoparticles that can be activated to self-assemble when they run into cancer cells and send messages to instruct the cells to slow their growth. The nanoparticles only communicate with the cancer cells, leaving normal cells alone. The nanoparticles respond to specific factors secreted by cancer cells that help them destroy surrounding tissue, specifically matrix metalloproteinase-9 (MMP-9), an enzyme that degrades collagen. Then the nanoparticles, when triggered by MMP-9, start assembling into large aggregates in the vicinity of the cancer cells. The cancer cells eat the aggregates, and the size of the aggregates causes physical distress to the cancer cells, slowing their ability to grow and live. Junk DNA is Not So Junky, Involved in Mammalian Development For decades there was the idea that 98% of the human genome is made up of junk DNA, which has no particular function. But study after study continues to find parts of this “junk” to have an important function. Scientists at the University of California, Berkeley and Washington University found that one particular bit of junk DNA, the promoter of a virus-based transposon, is important to cell proliferation and the timing of embryo implantation in mice. These promoters link to genes that played a role in the development of other mammals, including humans. Working with mice, they found that by knocking out a specific transposon in mice, half the mouse pups died before birth. They then analyzed the genomes of seven other mammalian species, including humans, and also found virus-derived regulatory elements tied to cell proliferation and embryo implantation timing. It appears to play a crucial role in early embryonic development in all mammals. “The mouse and humans share 99% of their protein coding genes in their genomes — we are very similar to each other,” said Lin He, UC Berkeley professor of molecular and cell biology and senior author of the study. “So, what constitutes the differences between mice and humans? One of the major differences is gene regulation — mice and humans have the same genes, but they can be regulated differently. Transposons have the capacity to generate a lot of gene regulatory diversity and could help us to understand species-specific differences in the world.”