Calcimedica, Inc. · NASDAQ:CALC
Calcimedica — Investor Presentation (October 2024)
38 slides from Calcimedica's investor presentation, Oct 30, 2024
Slide 1: Developing Novel Therapies for Acute Inflammatory and Immunologic Diseases
Exhibit 99.2 Developing Novel Therapies for Acute Inflammatory and Immunologic Diseases October 2024 1
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: Investment Highlights
Investment Highlights Proprietary CRAC channel inhibitors for life-threatening inflammatory diseases Technology with high unmet need Compelling Clinical Consistent positive clinical activity and good tolerability in Data six Phase 2 clinical trials in acute critical illnesses Substantial Market ~1 m
Slide 4: Differentiated Pipeline in Acute and Chronic Inflammatory and Immunologic Diseases
Differentiated Pipeline in Acute and Chronic Inflammatory and Immunologic Diseases Phase of Development 1 Indication Anticipated Milestones Program Preclinical Phase 1 Phase 2 Phase 3 Acute Disease (IV) CARPO Phase 2b trial completed and positive data announced; Auxora Acute Pancreatitis Next step:
Slide 5: Overactivation of CRAC Channels: Immune System Activation and Tissue Cell Injury
Overactivation of Calcium Release-Activated Calcium (CRAC) Channels: Immune System Activation and Tissue Cell Injury 5
Slide 6: Acute Inflammation: Underlying Cause Across Many Diseases
Acute Inflammation: Underlying Cause Across Many Diseases Acute Pancreatitis ARDS Acute Kidney Injury Old Paradigm Future Paradigm Treatable Trait A Treatable Trait B Auxora has demonstrated positive clinical results in all 3 of these large, underserved patient populations 6 1) Sources: Reddy, Kiran
Slide 7: Auxora Has Shown Consistent Reduction and Prevention of Acute Respiratory Failure and Mortality
Auxora Has Shown Consistent Reduction and Prevention of Acute Respiratory Failure and Mortality COVID-19 CARDEA: COVID- CARPO: Acute KOURAGE: Acute Acute Pancreatitis Trial Pneumonia 19 Pneumonia Pancreatitis Kidney Injury Phase 2a Phase 2a Phase 2 Phase 2b Phase 2 Year 2019 2020 2021 2024 Expected
Slide 8: IV Formulation Has the Potential to Provide Ideal Benefits for Acute Inflammation
Final Concentration of Zegocractin in Blood Assay (nM) IV Formulation Has the Potential to Provide Ideal Benefits for Acute Inflammation Rapid onset of immunomodulatory action reaches peak by the end of 4-hour infusion Relationship of Pharmacodynamic Readout with 1 Assay Concentration of Zegocractin
Slide 9: Large U.S. Market Opportunity in Acute Inflammatory Diseases
Large U.S. Market Opportunity in Acute Inflammatory Diseases 1 AP with SIRS AKI Stages 2 & 3 AIPT 100K 1.1M 300 Patients Patients Patients • No approved therapies• No approved therapies• No approved therapies 2 • SOC primarily supportive care• SOC primarily supportive care• Ultra-orphan pediatric in
Slide 10: Auxora for Acute Pancreatitis (AP)
Auxora for Acute Pancreatitis (AP) 10
Slide 11: AP Carries a Significant Disease Burden
AP Carries a Significant Disease Burden Disease Progression in Acute Pancreatitis Predicted Severe Hospitalization Organ Failure Mortality Pancreatitis 1 2 2 1,3 300K 100K 20-60K 3-6K US Patients/yr Notes• Standard of care for • Characterized by • Most often • Even without AP limited to support deve
Slide 12: Overactive CRAC Channels Contribute to AP; Auxora Targets Multiple Pathways
Overactive Calcium Release-Activated Calcium (CRAC) Channels Contribute to AP; Auxora, a CRAC Channel Inhibitor, Targets Multiple Pathways Gallstones and excessive alcohol use are the most common causes of AP Acute lung injury and multiple organ failure Bile and fatty acid esters cause 2+ excessive
Slide 13: Initial Signs of Efficacy in Phase 2a Prompted Further Development in Phase 2b
Initial Signs of Efficacy in a Phase 2a Prompted Further Development in a Phase 2b 1 Phase 2a Outcomes Goals for Phase 2b CARPO Trial in AP Patients with SIRS An open-label trial in patients with AP plus Demonstrate dose response and biological activity across multiple SIRs and hypoxemia demonstrate
Slide 14: CARPO Phase 2b Clinical Trial in AP
CARPO Phase 2b Clinical Trial in AP Primary Endpoint Secondary Endpoints • Length of hospital stay • Time to solid food tolerance • Time to medically indicated discharge • Severe organ failure • Respiratory failure • Necrosis as determined by CT MEDIUM DOSE (n=54) Primary Objective: Dose Response on
Slide 15: Baseline Characteristics were Generally Aligned Across Groups
Baseline Characteristics were Generally Aligned Across Groups Baseline Demographics Placebo 0.5 mg/kg 1.0 mg/kg 2.0 mg/kg mITT Population N=53 N=52 N=56 N=53 Median Age 42 (20, 78) 48.5 (23, 85) 43.5 (22, 84) 42 (19, 91) (Minimum, Maximum) Male (%) 33 (62.3) 32 (61.5) 33 (58.9) 33 (62.3) Female (%)
Slide 16: Dose Response Observed on the Primary Endpoint (Time to Solid Food Tolerance)
Dose Response Observed on the Primary Endpoint (Time to Solid Food Tolerance) Time to Solid Food Tolerance gMCP-Mod Analysis mITT Population and Pre-Defined High Time to Solid Food Tolerance Hematocrit (HCT) Sub-Group in the High Hematocrit Group Placebo 200 4 (mITT / High HCT) Auxora 150 (mITT / Hi
Slide 17: Auxora High and Medium Doses Reduced All Types of Severe Organ Failure
Auxora High and Medium Doses Reduced All Types of Severe Organ Failure Severe Organ Failure Placebo 0.5 mg/kg 1.0 mg/kg 2.0 mg/kg N=53 N=52 N=56 N=53 Respiratory 4/53 (7.5%) 5/52 (9.6%) 2/56 (3.6%) 2/53 (3.8%) Renal 1/53 (1.9%) 2/52 (3.8%) 1/56 (1.8%) 0/53 (0.0%) Cardiovascular 1/53 (1.9%) 3/52 (5.8
Slide 18: Dose Response Observed for New Onset Persistent & Severe Respiratory Failure
Dose Response was Observed for both New Onset Persistent & Severe Respiratory Failure Reduced New Onset Persistent Respiratory Failure Prevented New Onset Severe Respiratory Failure Placebo 0.5 mg/kg 1.0 mg/kg 2.0 mg/kg Placebo 0.5 mg/kg 1.0 mg/kg 2.0 mg/kg New Onset Persistent 8/47 5/48 1/52 4/50 N
Slide 19: Auxora High-Dose Demonstrated Improvements in Additional Key Secondary Endpoints
Auxora High-Dose Demonstrated Improvements in Additional Key Secondary Endpoints New Onset Necrotizing Time to Medically Proportion of Patients Pancreatitis (NP) Indicated Discharge (TMID) Remaining in the Hospital NP At Day 30* (%) Diff^(%) TMID Median Hours 31% NP At Day 30* (%) Diff^(%) TMID Medi
Slide 20: Integration of Key Endpoints into Win Ratio Demonstrates Potential Benefits of Auxora
Integration of Key Endpoints into Win Ratio Demonstrates Potential Benefits of Auxora High-Dose Compared to Placebo New Onset Time to All-cause Severe Necrotizing Medically Win Ratio Total Wins Mortality Respiratory Pancreatitis Indicated Failure Discharge Placebo wins 0 0 374 546 920 Auxora 2.0 mg/
Slide 21: Auxora Was Well Tolerated with Few Discontinuations Across all Doses
Overall, Auxora Was Well Tolerated with Few Discontinuations Across all Doses and No Related TESAEs or Deaths for the High Dose Group Safety Summary: Placebo 0.5 mg/kg 1.0 mg/kg 2.0 mg/kg Number of Patients N=53 N=52 N=56 N=53 At least one TEAE leading to 3 (5.7) 2 (3.8) 2 (3.6) 2 (3.8) discontinuat
Slide 22: Primary Objective of Dose Response Achieved with Clinically Meaningful Improvements
The Primary Objective of Dose Response was Achieved While Providing Clinically Meaningful Improvements in Key Outcome Measures The Phase 2b trial results demonstrate Auxora’s potential to reduce mortality and morbidity in AP with SIRs and provide savings to the healthcare system ✓ Dose response obse
Slide 23: Auxora for Asparaginase-Induced Pancreatic Toxicity (AIPT) in Pediatric Patients
Auxora for Asparaginase-Induced Pancreatic Toxicity (AIPT) in Pediatric Patients 23
Slide 24: Potential Clinical Benefits to Children with AIPT
Potential Clinical Benefits to Children with AIPT 7-10% 50%+ 3,000+ 1 of ALL patients of patients with AIPT children with ALL treated with develop AIPT as a develop pseudocyst result of or pancreatic chemotherapeutic asparaginase necrosis, which can asparaginase in U.S. treatment be life-threatening
Slide 25: Proof-of-Concept Ongoing in AIPT: Rapid Resolution of Pain and Food Intolerance
Proof-of-Concept Ongoing in AIPT Pediatric Patients Had Rapid Resolution of Pain and Food Intolerance CRSPA Phase 1/2 Trial in Pediatric AIPT • Investigator-initiated open-label trial being conducted at St. Jude Children’s Research Hospital • Assess the safety in pediatric patients with ALL who have
Slide 26: CRSPA First Cohort Data: Presented at ASH 2023
CRSPA First Cohort Data: Presented at ASH 2023 Total 16 (T16): All AIPT Matched T16 AIPT cohort CRSPA evaluable for efficacy Patients with AIPT 51 16 8 Age: mean (range) 10.3 (2.2-19.4) 9 (2.2-18.4) 8.2 (3.1-17.6) Female (%) 17 (33.3%) 5 (31.3%) 3 (37.5%) Low-risk therapy (%) 9 (17.6%) 1 (6.3%) 2 (2
Slide 27: Auxora for Acute Kidney Injury (AKI)
Auxora for Acute Kidney Injury (AKI) 27
Slide 28: Patient Journey in AKI
Patient Journey in AKI Disease Progression without Early Intervention Post Injury 7 Days 90 Days Acute Chronic End-stage AKI Kidney Disease Kidney Disease Renal Disease ~3.7M AKI hospitalizations annually (U.S.) 71% 17% 12% Stage 2 Stage 1 Stage 3 2 ↑ sCr 2x ↑ sCr 1.5x↑ sCr 3x 1 Auxora Target Market
Slide 29: Potential Clinical Benefits to Patients with AKI
Potential Clinical Benefits to Patients with AKI Current standard of care is • Fluid resuscitation / Diuretics • Nutrition limited to supportive • Correction of underlying cause therapy • Reduced need for dialysis Potential Benefits of • Reduced risk of respiratory failure Auxora • Reduced risk of m
Slide 30: Auxora Improved Kidney Recovery and Survival in Severe AKI Models
Auxora Improved Kidney Recovery and Survival in Severe AKI models Three doses of Auxora or placebo were administered daily starting 6 hours after ischemia/reperfusion injury 30 Note: GFR is Glomerular filtration rate and data is courtesy of David Basile, PhD, Indiana University
Slide 31: Evidence of Renal Protection: Phase 2 CARDEA Trial
Evidence of Renal Protection: Phase 2 CARDEA Trial Ang-2/Tie2 results in endothelial inflammation with Ang-1/Tie2 signaling maintains vascular integrity increased endothelial permeability Angiopoietin-2 Levels Angiopoietin-1 Levels Decrease Significantly with Auxora Increase Significantly with Auxor
Slide 32: KOURAGE: Acute Kidney Injury with Associated AHRF Phase 2 Trial Design
KOURAGE: Acute Kidney Injury with Associated AHRF Phase 2 Trial Design 2.0mg/kg/4 hours at 0 hours and Primary Endpoint 1.6mg/kg at 24, 48, 72, 96 hours 32
Slide 33: Auxora for Acute Respiratory Distress Syndrome (ARDS)
Auxora for Acute Respiratory Distress Syndrome (ARDS) 33
Slide 34: Promising Phase 2 Data from Trials in COVID-19 Pneumonia and Ventilated Patients
Promising Phase 2 Data from Trials in COVID-19 Pneumonia and in Ventilated Patients with Respiratory Failure CARDEA Phase 2 Trial Complete • 56% reduction in mortality at Day 30 (p=0.0165) Severe and Critical COVID-19 • 33% reduction ventilation (p=0.18) Pneumonia Patients • Three-day shorter hospit
Slide 35: Platform Application for CRAC Channel Inhibition
Platform Application for CRAC Channel Inhibition 35
Slide 36: Preclinical Results Supporting Other I&I Indications
Preclinical Results Supporting Other I&I Indications Intended Indication Preclinical Observations Next Steps Formulation In vivo efficacy in a mouse model of CP Chronic Oral using CM5480 Confirm with lead oral candidate Pancreatitis (CP) (Szabo et al, 2023) In vivo efficacy of zegocractin in a Acute
Slide 37: Platform Application for CRAC Channel Inhibition
Platform Application for CRAC Channel Inhibition 37
Slide 38: Anticipated Milestones
Anticipated Milestones CARPO Phase 2b Trial Completed and Positive Data Announced AP Next Step: End-of-Phase 2 Meeting with FDA KOURAGE Trial Underway AKI Data Expected in 2025 CRSPA Initial First Cohort Data Released at ASH 2023 AIPT Trial Expansion Underway; Data Expected in 2025 Current Cash Runw