CalciMedica Presents AKI Data from a Post-Hoc Analysis of the Phase 2 CARDEA trial of Auxora™ in Severe COVID-19 Pneumonia at the 30th International AKI & CRRT Conference

Rhea-AI Summary

CalciMedica (CALC) presented new data from a post-hoc analysis of their Phase 2 CARDEA trial studying Auxora™ in severe COVID-19 pneumonia patients with Acute Kidney Injury (AKI). The analysis revealed:

- A 62.7% relative reduction in mortality at day 30 (sustained through day 60) in AKI patients treated with Auxora versus placebo
- Only 17.4% (4/23) Auxora-treated patients died compared to 46.7% (7/15) on placebo
- An absolute mortality reduction of 29.3% in the AKI subset

The study included 38 patients with AKI (defined as eGFR ≤ 60 ml/min/1.73 m²) and moderate/severe respiratory failure. Preclinical studies showed CRAC channel inhibition reduced Th17 cells in rat kidneys, protected podocyte cells, and improved GFR recovery. The company is currently conducting a Phase 2 trial of Auxora in Stage 2/3 AKI patients with acute hypoxemic respiratory failure, with results expected in 2025.

Positive

• 62.7% relative reduction in mortality at day 30 and 60 in AKI patients
• 29.3% absolute reduction in mortality in AKI subset
• Positive preclinical data showing improved GFR recovery
• Ongoing Phase 2 trial with results expected in 2025

Negative

• Small AKI patient subset (only 38 patients)
• Results based on post-hoc analysis rather than primary endpoint

Insights

Biotech Analyst

CalciMedica's post-hoc analysis from their Phase 2 CARDEA trial reveals striking efficacy in a critical patient subset. The 62.7% relative reduction in mortality for AKI patients treated with Auxora represents a significant clinical benefit that persisted through day 60. With an absolute mortality reduction of 29.3%, these results exceed the already impressive mortality benefits seen in the overall trial population.

This data strengthens the scientific rationale for Auxora's mechanism of action in AKI through CRAC channel inhibition. The supporting preclinical and biomarker evidence demonstrates both immunomodulatory and tissue-protective effects, potentially addressing multiple pathways in kidney injury.

What's particularly valuable about this analysis is how it aligns with CalciMedica's ongoing Phase 2 KOURAGE study, which targets a similar patient population with kidney and respiratory failure. The substantial mortality benefit observed provides encouraging validation for their clinical development strategy.

While post-hoc analyses have inherent limitations, the magnitude of effect seen here warrants attention. The sample size is modest (38 patients), but the consistent mortality benefit, coupled with mechanistic rationale from multiple complementary studies, suggests Auxora may represent a meaningful advancement for a condition with few treatment options.

Clinical Research Physician

From a clinical perspective, this post-hoc analysis reveals intriguing therapeutic potential for Auxora. The 62.7% relative mortality reduction in the AKI subset is substantial, particularly given the complex pathophysiology of kidney injury in critically ill patients.

What strengthens this finding is the comprehensive mechanistic evidence supporting CRAC channel inhibition in AKI. The preclinical data showing decreased Th17 cells in injured kidneys highlights important immunomodulatory effects, while the protection of podocytes demonstrates direct cellular benefits. These dual mechanisms suggest Auxora could address both inflammatory and direct tissue injury pathways in AKI.

The biomarker data showing favorable changes in angiopoietin-1/2 and D-dimers provides valuable translational evidence connecting the preclinical observations to clinical outcomes. These biomarkers strongly correlate with endothelial protection, a critical factor in preserving kidney function during systemic illness.

Though this analysis comes from COVID-19 patients, the pathophysiological mechanisms of AKI extend beyond specific triggering conditions. The consistent benefit seen across preclinical models and this clinical subset analysis suggests potential applicability to broader AKI populations. The upcoming KOURAGE trial results will be important for confirming these promising signals in the specific population CalciMedica is targeting.

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 30^th 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 https://ir.calcimedica.com/news-events/medical-events-publications.

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 www.calcimedica.com.

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 www.sec.gov. 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
calcimedica@argotpartners.com
(212) 600-1902

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SOURCE CalciMedica, Inc.

FAQ

What were the mortality reduction rates for CALC's Auxora in AKI patients during the CARDEA trial?

Auxora showed a 62.7% relative mortality reduction vs placebo at day 30 (sustained through day 60), with 17.4% mortality in Auxora group vs 46.7% in placebo group.

How many patients with AKI were included in CalciMedica's CARDEA trial analysis?

The post-hoc analysis included 38 patients who had AKI (eGFR ≤ 60 ml/min/1.73 m²) and moderate or severe respiratory failure.

What are the key preclinical results for CALC's Auxora in treating Acute Kidney Injury?

Preclinical studies showed reduced Th17 cells in rat kidneys, protected podocyte cells, improved GFR recovery, and decreased mortality in rats with severe/moderate AKI.

When will CalciMedica's Phase 2 KOURAGE trial results for Auxora in AKI patients be available?

Results from the Phase 2 trial studying Auxora in Stage 2/3 AKI patients with acute hypoxemic respiratory failure are expected in 2025.