UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
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| Item 7.01. | Regulation FD Disclosure. |
On June 14, 2023, CalciMedica, Inc. (the “Company”) posted an updated corporate presentation under the “Investors and Media” section of the Company’s website. The Company may use the corporate presentation from time to time in conversations with analysts, investors and others. A copy of the corporate presentation is included as Exhibit 99.1 to this report and is incorporated herein by reference.
The information in this Item 7.01, including the attached Exhibit 99.1, is being furnished and shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference into any filing made by the Company under the Securities Act of 1933, as amended, or the Exchange Act.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
| Exhibit Number |
Description | |
| 99.1 | Corporate Presentation of the Company, dated June 2023. | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Date: June 15, 2023 | CalciMedica, Inc. | |||||
| By: | /s/ A. Rachel Leheny, Ph.D. | |||||
| Name: | A. Rachel Leheny, Ph.D. | |||||
| Title: | Chief Executive Officer | |||||
Exhibit 99.1 CalciMedica Developing First-in-Class Therapies for Acute Inflammatory Diseases with High Unmet Need June 2023
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 and planned clinical trials; and the timing for CalciMedica’s receipt and announcement of data from its 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 CalciMedica’s product candidates; results from clinical trials may not be indicative of results that may be observed in the future; potential safety and other complications from CalciMedica’s product candidates; 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 most recently filed periodic report, and subsequent periodic reports filed by CalciMedica, under the Securities Exchange Act of 1934, as amended, from time to time and available at www.sec.gov. These documents can be accessed on CalciMedica’s web page at calcimedica.com. These forward-looking statements are based on information available to, and expectations of, CalciMedica of the date of this presentation. CalciMedica disclaims any obligation to update these forward-looking statements, except as may be required by law. 2 Confidential
CalciMedica is Building a Leading Company Dedicated to Treating Life- threatening Proprietary technology targeting CRAC channel inhibition to develop Differentiated first-in-class therapies for life-threatening inflammatory diseases with high Technology unmet need Compelling Auxora has been studied in four completed efficacy trials, demonstrating Proof-of-Concept positive and consistent clinical results and favorable safety profile Data Attractive Lead ~100K target patient population in acute pancreatitis represents a potential Indication $1B+ U.S. market opportunity, with no approved therapies Asparaginase-Induced Acute Kidney Injury (AKI) Acute Pancreatitis (AP) Next Clinical Pancreatic Toxicity IND/Phase 2 (AIPT) Milestones Phase 2b Data (Trial pending additional funding) Phase 1/2 Data Composition of matter (2036), formulation (2038), and methods of use Strong IP (2036-2041+) worldwide patent protection 3 Confidential CRAC: Calcium release-activated calcium
Differentiated Pipeline Addressing Significant Unmet Patient Needs 4 Confidential
Market Opportunity for Auxora Across Acute Inflammatory Diseases AP with SIRS AIPT AKI Stages 2 & 3 1.1M 100K 300 Patients Patients Patients • No approved therapies • No approved therapies • No approved therapies • SOC primarily supportive care • Ultra-orphan pediatric indication • SOC primarily supportive care • Disease progression: • Potentially PRV eligible • Disease progression: o Severe AP • Accelerated approval opportunity o Chronic kidney disease o Pancreatic necrosis • Disease progression: o End stage renal disease o Mortality o Pancreatic necrosis in 50% o Mortality Patient figures represent estimated numbers of annual U.S. cases AP with SIRS: Acute Pancreatitis with systemic inflammatory response syndrome; AIPT: Asparaginase-Induced Pancreatic Toxicity; PRV: Priority 5 Confidential Review Voucher; AKI: Acute Kidney Injury; SOC: Standard of Care Sources: Primary Market Research, KOLs, Healthcare Cost and Utilization Project, Pancreatitis Foundation
Auxora’s MOA Addresses Multiple Acute Inflammatory Diseases
Overactivation of CRAC Channels: Immune System Activation and Tissue Cell Injury 7 Confidential
Final Concontration of Zegocractin in Blood Assay (nM) Proprietary IV Formulation Provides Rapid Onset of Action Without Long- Term Risk of Immune-Suppression Auxora IV Formulation: Ideal Characteristics for Acute Care Setting Relationship of Pharmacodynamic Readout with Assay Concentration of Zegocractin in Human (Mean ± SEM, n = 4 AP patients) 50 600 500 40 400 30 300 20 200 10 -57% 100 0 0 Pre-dose 0.5 hr post Day 2 Discharge Rapid onset of immunomodulatory action reaches peak by the end of 4-hour infusion Recovery within 24-48 hours of dosing may limit the potential for immunosuppression 8 Confidential Zegogractin is the active pharmaceutical ingredient in Auxora Fold Over Baseline IL-2 in the Ex Vivo Whole Blood Assay
Auxora Has Demonstrated Biological Activity and Favorable Safety Profile in Two Ongoing and Four Completed Phase 2 Trials Population Trial Size Results Pancreas Asparaginase-Associated N=9 • Trial ongoing, preliminary results show rapid resolution of pain and food tolerance Pancreatitis N=216 • Trial ongoing Acute Pancreatitis Planned N=7 • Target engagement of CRAC channels in peripheral lymphocytes Acute Pancreatitis* • Rapid increase in patients tolerating solid diet (potential trial pivotal endpoint) Acute Pancreatitis* N=21 Accompanied by SIRS and Hypoxemia • >2 day reduction in hospital stay and 50% reduction SIRS Lung • 56% statistically significant decrease in mortality at Day 30 COVID-19 with Respiratory • 33% reduction in ventilation N=314 • >2-day shorter hospital stay Failure on LFO and HFNC 2 • 40% reduction in reported acute kidney injury COVID-19 with Respiratory N=9 • Open-label trial with varying doses showing pharmacodynamic response Failure on IMV 9 Confidential * Completed Phase 1 trials in healthy volunteers showed no evidence of dose-dependent safety or tolerability findings through 365 days
Auxora for Acute Pancreatitis
Significant Unmet Need in Treatment of Acute Pancreatitis U.S. Hospitalizations per Year From Acute Pancreatitis: ~275,000 ~40% of patients have SIRS at presentation High risk for moderate to severe disease Patients with SIRS+: ~110,000 Small percentage of patients missed Misdiagnosis, timing constraint, or other Target Patients: ~100,000 Target population is in-hospital patients with SIRS; currently no approved therapy SIRS: Systemic inflammatory response syndrome 11 Confidential Fletcher Spaght Market Research Report (2016) 11
Potential to Offer Significant Clinical Benefits to Patients with Predicted Severe AP 1. Fluid resuscitation Current standard of care is 2. Enteral nutrition for food tolerance 3. Antibiotics for infection limited to supportive therapy 4. Minimally invasive therapy for local complications Patient Journey: 48-72 hours 2 Weeks 4 Weeks 6 Weeks 40% Transient organ failure and moderately severe AP Mortality <5% Predicted Severe 70% Sterile necrosis; Mortality 10% Walled-off Pancreatitis Persistent organ failure and severe AP pancreatic Mortality 15-20% 30% Infected necrosis; Mortality 30% necrosis Adoption of Auxora potentially driven by 1. Reduction in organ failure 2. Reduction in pancreatic necrosis Three Auxora infusions in the first 72 hours 3. Earlier food tolerance 4. Fewer days in hospital or ICU 12 Confidential Adapted from N Engl J Med 2016;375:1972-81. DOI: 10.1056/NEJMra1505202 12 PROGRESSION AUXORA
Acute Pancreatitis Phase 2a Clinical Trial Safety, tolerability, and efficacy trial for various doses of Auxora compared to standard of care 13 Confidential
Positive Phase 2a Results on Potential Pivotal Trial Primary Endpoints Rapid Increase in Patients Tolerating Solid Diet >2 Fewer Days Spent in Hospital Potential Pivotal Trial Primary Endpoint Median Hospital Stay 100 SOC patients (n=7) 6.0 days 93% 90 Auxora-treated patients (n=14) 3.7 days 80 70 Only Auxora Patients Improved on CTSI Scores 60 Moderate to Severe CTSI Scores 50% 50 43% SOC patients (n=4) 0/4 40 Auxora-treated patients (n=8) 3/8 30 20 50% Reduction in Persistent SIRS 14% 14% 7% 10 Patients with Persistent SIRS 0 SOC patients (n=7) 5/7 Auxora Standard of Care (n = 14) (n = 7) Auxora-treated patients (n=14) 5/14 24 hours 72 hours Discharge SIRS: systemic inflammatory response syndrome 14 Confidential CTSI: CT Severity Index 14 % of Patients Tolerating Solid Diet
CARPO Phase 2b Clinical Trial in Acute Pancreatitis Ongoing with Data Expected 1H 2024 15 Confidential
Potential to Offer Significant Clinical Benefits to Children with Asparaginase- Induced Pancreatic Toxicity 3,000+ 7-10% 50%+ children with acute of ALL patients develop of patients with AIPT lymphoblastic leukemia asparaginase-induced develop pseudocyst or (ALL) treated with pancreatic toxicity (AIPT) pancreatic necrosis, chemotherapeutic as a result of which can be a life- asparaginase in U.S. asparaginase treatment threatening conditions annually Auxora has potential to rapidly resolve AIPT with improvement in food tolerance and pain while preventing development of further complications such as pancreatic necrosis Sources: Liu C, Yang W, Devidas M, et al. Clinical and Genetic Risk Factors for Acute Pancreatitis in Patients With Acute Lymphoblastic Leukemia. J Clin Oncol. 2016. Abaji R, Gagne V, Xu CJ, et al. Whole-exome 16 Confidential sequencing identified genetic risk factors for asparaginase-related complications in childhood ALL patients. Oncotarget. 2017;8: 43752- 43767. Rank C, Wolthers B, Grell K, et al. Asparaginase-associated pancreatitis in acute lymphoblastic leukemia: results from the NOPHO ALL2008 treatment of patients 1-45 years of age. J Clin Oncol. 2019 38:145-154.
Proof-of-Concept Ongoing in AIPT Pediatric Patients Receiving Auxora Had Rapid Resolution of Pain and Food Tolerance • CRSPA Phase 1/2 Trial in Pediatric Asparaginase-Induced Pancreatic Toxicity (AIPT) – Investigator-initiated, open-label trial being conducted at St. Jude Children’s Research Hospital • Trial Status – Assess the safety in pediatric patients with acute lymphoblastic leukemia (ALL) who have developed AIPT – Estimate the efficacy of Auxora to prevent pseudocyst or necrotizing pancreatitis in pediatric patients with AIPT – Cohort 1 complete; trial being expanded to additional sites and additional patients being enrolled • Preliminary Results – 8 patients received four daily infusions of Auxora and had rapid resolution of pain and food tolerance – 1 patient received less than a single infusion of Auxora and developed pancreatic necrosis Data release planned for 4Q23 17 Confidential 1 St. Jude historical database??
Auxora for Acute Kidney Injury
Early Treatment with Auxora Could Offer Significant Benefits to AKI Patients and Prevent Disease Progression 1. Fluid Resuscitation / Diuretics Current standard of care is 2. Nutrition limited to supportive therapy 3. Correction of underlying cause Disease Progression without Early Intervention Post Injury 7 Days 90 Days Acute End-stage Chronic Acute Kidney Injury Kidney Disease Kidney Disease Renal Disease ~3.7MM AKI hospitalizations annually (U.S.) Adoption of Auxora to potentially be driven by: 71% 17% 12% 1. Reduced need for dialysis Stage 1 Stage 2 Stage 3 2. Reduced risk of mortality ↑ sCr 1.5x ↑ sCr 2x ↑ sCr 3x 3. Greater recovery of renal function Auxora Target Market 1 1.1MM Patients 1) Source: https://www.hcup-us.ahrq.gov/reports/statbriefs/sb231-Acute-Renal-Failure-Hospitalizations.pdf Criteria: Based on RIFLE staging criteria for AKI classification; Serum creatinine increase over baseline 19 Confidential sCr: Serum Creatinine
Improved GFR* and Decreased Inflammatory Cell Infiltrates Within 24 Hours in AKI Model A single dose of Auxora or placebo was administered 30 min after bilateral kidney ischemia/reperfusion Mononuclear Cells in Kidney of GFR in Rats After Rats after Ischemia/Reperfusion Kidney Ischemia/Reperfusion 7 1.5×10 0.6 *p < 0.042 by t test *p = 0.0053 by t test 7 1×10 0.4 6 5×10 0.2 0.0 0 Placebo Auxora Placebo Auxora Data courtesy of David Basile, PhD, Indiana University 20 Confidential *GFR: Glomerular filtration rate GFR (ml/min/100g BW) Mononuclear Cells/Gm Kidney
Phase 2 CARDEA Trial Showed 40% Reduction in Reported Acute Kidney Injury in COVID Pneumonia Patients Ang-2/Tie2 results in endothelial inflammation Ang-1/Tie2 signaling maintains vascular integrity with resulting endothelial cell activation and increased endothelial permeability Angiopoietin-1 Levels Angiopoietin-2 Levels Increase Significantly with Auxora Decrease Significantly with Auxora (Means ± SEM) (Means ± SEM) 8000 250 p = 0.0107* ns* p = 0.0107* 6000 0 4000 -250 ns* 2000 -500 0 -750 * ANCOVA model * ANCOVA model -2000 -1000 Placebo Auxora Placebo Auxora 21 Confidential Change in Angiopoietin-1 from Screening to 96 hours (pg/mL) Change in Angiopoietin-2 from Screening to 96 hours (pg/mL)
Auxora for Acute Respiratory Distress Syndrome
Clinical Evidence in Phase 2 COVID-19 Pneumonia and Ventilated Patients Demonstrate Promising Data in Respiratory Failure CARDEA Phase 2 Trial Complete • 56% reduction in mortality at Day 30 (p=0.023) Severe and Critical COVID-19 • 33% reduction ventilation (p=0.18) Pneumonia Patients • Three-day shorter hospital stay (p=0.09) N=284 Trial Ongoing; Data Analysis Underway Phase 2 • Reduction in inflammatory cell-type gene expression by COVID-19 Ventilated Patients macrophages in lungs N=9 • No reduction in mitochondrial and ribosomal gene expression Data Analysis of Biomarker and Mechanism-of-Action in Ventilated Patients to Inform Development Plan for ARDS 23 Confidential
CARDEA Phase 2 Trial Auxora in Severe COVID-19 Pneumonia 24 Confidential
CARDEA Phase 2 Positive Results on Key Endpoints Reduction in Mortality and Ventilator Use in COVID-19 Pneumonia Patients 25 Confidential
Platform Applications for CRAC Channel Inhibition
Preclinical Results Supporting Other 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) (Submitted for publication) In vivo efficacy of zegocractin in a mouse Acute Ulcerative Ongoing discussions investigators about IV model of inflammatory bowel disease potential clinical trials Colitis (AUC) (Letizia et al., 2022) In vivo efficacy of zegocractin in a mouse IV or Inhaled Allergic Asthma model of allergic asthma Pursue strategic partnership (Kahlfuss et al., 2022) In vivo efficacy of CM5480 in a mouse Traumatic Brain Confirm results with lead oral compound or IV or Oral model of TBI Auxora Injury (TBI) (Mizuma et al., 2018) 27 Confidential *CM5480 is a CalciMedica portfolio compound
Anticipated Milestones
Existing Cash Provides Runway through 2H24 With Key Clinical Readouts by 1H24 Acute P Phas hase e 2b D 2b Dat ata E a Ex xpec pectted ed iin 2H n 1H23 24 Acute Pancreatitis Pancreatitis P Phas hase 3 e 2/3 I Initni iat tiat ion E ion x in X pecX ted i XXn 2024 Asparaginase- Initial First Cohort Data Release Expected in 4Q23 Induced Pancreatic Trial Expansion Underway Toxicity A Acu cut te K e Kiidney dney IND filing Expected in 2H23 Injur Injury y Phase 2 Clinical Trial Initiation 1H24 (pending funding) Phase 2 Data in Ventilated COVID Patients Publication Expected in 2H23 ARDS Will inform the development plan for ARDS AIPT: Asparaginase-Induced Pancreatic Toxicity 29 Confidential ARDS: Acute respiratory distress syndrome 29