Calcimedica, Inc. · NASDAQ:CALC
Calcimedica — Investor Presentation (June 2026)
29 slides from Calcimedica's investor presentation, Jun 24, 2026
Slide 1: Investor Update June 2026
Investor Update June 2026 Exhibit 99.3
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements which include, but are not limited to, statements regarding CalciMedica’s business strategy and clinical development plans; the design and potential benefits of CalciMedica’s product candidates; CalciMedica’s ongoing an
Slide 3: Pioneering CRAC channel inhibition in Pulmonary Hypertension
Pioneering CRAC channel inhibition in Pulmonary Hypertension PLATFORM Leader in CRAC channel inhibition Proven Orai1 / CRAC inhibitor clinical experience Proprietary chemistry and internal pipeline Two current drug candidates: CM5480 (oral) and Auxora (IV) IP out to 2041+ (Auxora) and 2046+ (CM5480)
Slide 4: Two well-characterized drug candidates, built on deep CRAC channel expertise
Two well-characterized drug candidates, built on deep CRAC channel expertise CLINICAL · IV Auxora Zegocractin · 4-hour infusion, 3–5 days CLINICAL EVIDENCE Multiple Phase 2 trials: acute pancreatitis, COVID-19 pneumonia, and acute kidney injury Statistically significant reduction in severe respirato
Slide 5: PH-focused pipeline designed to generate human POC data by mid-2027
PH-focused pipeline designed to generate human POC data by mid-2027 with next-gen compound to follow Program Preclinical Phase 1 Phase 2 Phase 3 Anticipated Milestones Auxora – IV1 Pulmonary Arterial Hypertension IND clearance – 2H 2026 Ph1b POC data – mid 2027 CM5480 – Oral Pulmonary Arterial Hyper
Slide 6: CRAC channels: A store-operated calcium signaling system
CRAC channels: A store-operated calcium signaling system STIM1 (ER Ca²⁺ sensor) Endoplasmic reticulum Plasma membrane Ca2+ release channels Orai1 (Ca2+ channel) Ca2+ CRAC channels are “store-operated”: their activity is controlled by the level of Ca²⁺ in the endoplasmic reticulum (ER), the cell’s in
Slide 7: Disease can overdrive CRAC channel signaling, creating a persistent, pathologic calcium signal
Disease can overdrive CRAC channel signaling, creating a persistent, pathologic calcium signal Persistent receptor signaling in inflammatory settings Cell stress Phenotypic change Persistent Orai1-mediated Ca²⁺ influx generates a disease-driving calcium signal1 Inflammatory activation Direct tissue
Slide 8: Pulmonary Hypertension spans diverse etiologies, but RV failure drives prognosis across groups
Pulmonary Hypertension spans diverse etiologies, but RV failure drives prognosis across groups Group 1 Pulmonary Arterial Hypertension (PAH) Idiopathic • Heritable • CTD-associated • Drug-induced Group 2 PH due to Left Heart Disease HFpEF, including CpcPH-HFpEF • HFrEF • Valvular disease Group 3 PH
Slide 9: CRAC channel inhibition as a potential therapy for PAH
CRAC channel inhibition as a potential therapy for PAH "These preclinical results show that targeting Orai1 delivered several key benefits: it improved pulmonary vascular remodeling by reducing pulmonary arterial smooth muscle cell and pulmonary endothelial cell dysfunctions; it improved RVD; and co
Slide 10: CRAC channel inhibition shows activity across pulmonary vasculature, RV, and LV in preclinical PH models
CRAC channel inhibition shows activity across pulmonary vasculature, RV, and LV in preclinical PH models 1. Saint-Martin Willer et al., JCI Insight 2025 2. Masson et al., Circ Res 2022 3. Research results from INSERM lab conducted by Antigny and Sabourin; shared with permission. Unpublished data 4.
Slide 11: CRAC channels (Orai1/STIM1) are upregulated in lung vasculature in patients with PAH & PVOD
CRAC channels (Orai1/STIM1) are upregulated in lung vasculature in patients with PAH & PVOD PVOD = Pulmonary Veno-Occlusive Disease; Masson et al., Circulation Research 2022 and Saint-Martin Willer et al., JCI Insight 2025 Lung Tissues from PAH Patients Lung Tissues from PVOD Patients Control PVOD
Slide 12: CRAC channels are upregulated in both sides of the heart under pressure overload
Additionally, CRAC channels (Orai1/STIM1) are upregulated in both sides of the heart when under pressure overload Note: Glycosylated form of Orai1 refers to functional (membrane-localized) Orai1; STIM1L is a long splice isoform of STIM1 that enables faster, repetitive SOCE activation. Sources: Barto
Slide 13: Prior studies linked Orai1 to remodeling/hypertrophy in pulmonary arteries and the heart
Prior studies linked Orai1 to remodeling/hypertrophy in both the pulmonary arteries and the heart Masson et al., Circ Res 2022;131:e102–e119; Voelkers et al., J Mol Cell Cardiol 2010;48:1329–1334 PASMC = Pulmonary Artery Smooth Muscle Cell PASMCs: Orai1 inhibition reverses proliferative, migratory,
Slide 14: CM5480 demonstrated anti-remodeling activity in the lung and reduced pulmonary vascular resistance
CM5480 demonstrated anti-remodeling activity in the lung and showed reduction in pulmonary vascular resistance (PVR) in MCT PAH model Note: PVR (Pulmonary Vascular Resistance) = RVSP / CO CM5480 as Monotherapy Reduced PVR CM5480 in Combination with SOC Reduced Pulmonary Vascular Remodeling PVR Reduc
Slide 15: CM5480 improved cardiac output and RV remodeling in MCT PAH model
CM5480 has been shown to improve cardiac output and RV remodeling in MCT PAH model 1. Fulton index and RV/tibia length measure RV hypertrophy; Fulton index = weight ratio of RV to the sum of the LV + septum Publication: Saint-Martin Willer et al., JCI (Journal of Clinical Investigation) Insight 2025
Slide 16: CM5480 demonstrated direct RV-protective activity in the PAB model
CM5480 demonstrated direct RV-protective activity in the PAB model 1. From CalciMedica discussions with INSERM team; MOA = Mechanism of Action Source: F. Antigny and J. Sabourin (INSERM), personal communication; shared with permission. Unpublished data. Purpose of Model Endpoints Assessed CM5480 Dem
Slide 17: Left ventricular function rescue under pressure overload: Rationale in Group II PH
Left ventricular function rescue under pressure overload: Rationale for CRAC channel inhibition in Group II PH TAC mouse model surgically induced LV pressure overload and systolic dysfunction mimicking LV pathology in Group II PH Orai1 inhibition preserved LV systolic function and improved left vent
Slide 18: CM5480 reversed PAH-mediated genetic changes in lung and right ventricle
CM5480 reversed PAH-mediated genetic changes in both the lung and right ventricle of the heart Publication: Saint-Martin Willer et al., JCI (Journal of Clinical Investigation) Insight 2025 CM5480 is potentially disease-modifying and potentially restores RV function in PAH Transcriptomic profiling of
Slide 19: Efficient path to potentially validate CRAC channel inhibition in PH and expand across indications
Efficient path to potentially validate CRAC channel inhibition in PH and expand across multiple indications Note: Lighter shading indicates activities not reflected in the current cash runway. 2025 2H Preclinical & IND-enabling CMC, tox, translational models Ph1/1b Healthy volunteers + patient cohor
Slide 20: Auxora Ph1b: PAH data with CRAC channel inhibitor anticipated by mid-2027
Auxora Ph1b: PAH data with CRAC channel inhibitor anticipated by mid-2027 1. Measurement frequency dependent on endpoint RHC = Right Heart Catheterization; CMR = Cardiac Magnetic Resonance; TAPSE = Tricuspid Annular Plane Systolic Excursion; mPAP = mean Pulmonary Artery Pressure; PCWP = Pulmonary Ca
Slide 21: Anticipated milestones
Anticipated milestones Auxora in PAH Ph1b proof-of-concept data extpected mid-2027 CM5480 in PH Additional preclinical data in PH models expected 2H 2026 IND submission expected mid-2027 Cash Runway Cash expected to fund current operations into 2H 2027 Auxora in AP FDA feedback on pivotal program de
Slide 22: Appendix: Auxora for Acute Pancreatitis (AP)
Appendix: Auxora for Acute Pancreatitis (AP)
Slide 23: AP: common, costly, and without approved treatments
AP: common, costly, and without approved treatments 1, Peery AF et al. Gastroenterology. 2022;162(2):621–44; 2. Machicado JD et al. United European Gastroenterol J. 2021;9(2):139–49.; 3. Singh VK et al. Clin Gastroenterol Hepatol. 2009;7(11):1247–51.; 4. Boxhoorn L et al. Lancet. 2020;396(10252):726
Slide 24: CARPO Phase 2b clinical trial in AP with SIRS
CARPO Phase 2b clinical trial in AP with SIRS Endpoints Time to solid food tolerance (primary endpoint) Severe organ failure Respiratory failure Length of hospital stay Time to medically indicated discharge Necrosis Primary Objective: Dose Response on Primary and Secondary Endpoints Daily in-patient
Slide 25: Auxora prevented new severe respiratory failure
Auxora prevented new severe respiratory failure Observed 100% reduction in new severe respiratory failure1 Observed 60% reduction in severe organ failure2 1. mITT excluding baseline respiratory failure (n=197) 2. mITT (N=214); severe organ failure includes severe respiratory failure, severe renal fa
Slide 26: Win-ratio analysis favors Auxora across key clinical outcomes
Win-ratio analysis favors Auxora across key clinical outcomes Win-ratio (Finkelstein-Schoenfeld): Patient pairs compared hierarchically across endpoints. Percentages represent proportion of comparisons won. Totals <100% because 10.3% of comparisons were ties. CI = confidence interval Endpoint Placeb
Slide 27: Advancing towards a potential pivotal program in AP
Advancing towards a potential pivotal program in AP Ongoing constructive discussions with the FDA regarding the design of a pivotal program in AP Leveraging AI-enabled analyses with Telperian to refine patient selection and endpoint strategy, with the goal of an enriched, efficient study design FDA
Slide 28: Appendix: Additional Slides
Appendix: Additional Slides
Slide 29: CRAC channel pathway does not interfere with pathways targeted by existing PAH therapies
To-date, CRAC channel pathway demonstrated that it does not interfere with and is not modulated by pathways targeted by existing PAH therapies PASMC = pulmonary artery smooth muscle cell Publication: Saint-Martin Willer et al., JCI (Journal of Clinical Investigation) Insight 2025 Drug Class Drug Ora