Eagle Pharmaceuticals, Inc. · OTC:EGRX
Eagle Pharmaceuticals — Technical Presentation (September 2021)
43 slides from Eagle Pharmaceuticals's technical presentation, Sep 9, 2021
Slide 1: CAL02 Investor Update
1 1 CAL02 Investor Update September 9, 2021
Slide 2: Forward-Looking Statements
2 Forward-Looking Statements This presentation contains forward-looking information within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, and other securities laws. Forward-looking statements are statements that are not historical facts. Words and phrases such as “a
Slide 3: Agenda: CAL02 Investor Update
3 Agenda: CAL02 Investor Update Strategic Update Disease State Overview Unmet Need CAL02 Overview, Clinical Data & Development Plan 1 2 3 4 Scott Tarriff Judith Ng-Cashin, MD Andre Kalil, MD Judith Ng-Cashin, MD Samareh Azeredo da Silveira Lajaunias, PhD SPEAKER TOPIC Question & Answer 5 All 8:30 –
Slide 4: Eagle Strategic Update
4 4 Eagle Strategic Update Scott Tarriff
Slide 5: Disease State Overview
5 5 Disease State Overview Judith Ng-Cashin, MD
Slide 6: CAL02 Overview
6 CAL02 Overview ▪ Patented composition ofmatter ▪ Sterile liquid solution ready forinjection ▪ Stable for 36 months when refrigerated (6 months when stored at room temperature) ▪ Route of administration: IV Infusion 2 doses separated 24 hours apart CAL02 (drug product) Specific mixture of re-engine
Slide 7: CAL02 – Novel, First-in-Class Antitoxin Agent Mechanism of Action
7 CAL02 – Novel, First-in-Class Antitoxin Agent Mechanism of Action Address the downstream effects of bacterial Virulence Effectors/ Pore Forming Toxins through competitive inhibition ➢ Binds to virulence effector molecules secreted by infecting bacteria, prohibiting host tissue cell binding ➢ Acts
Slide 8: Pneumonia Overview
8 Pneumonia Overview Pneumonia is defined as "new lung infiltrates plus clinical evidence that the infiltrate is of an infectious origin, which include the new onset of fever, purulent sputum, leukocytosis, and decline in oxygenation”. –The Infectious Disease Society & American Thoracic Society Pneu
Slide 9: Severe Pneumonia - Key Targets
9 Severe Pneumonia - Key Targets TRIGGER MEDIATORS IMPACT OUTCOME PERIPHERAL VASCULATURE MYOCARDIUM CYTOKINES /CHEMOKINES SEPSIS SEPTICSHOCK DEATH SENSORS PLASMA PROTEIN SYSTEMS BLOOD AND LYMPHATIC CELLS VASCULAR AND TISSUECELLS ENDOTHELIAL STRESS RESPONSE CELLDYSFUNCTION INSULTBACTERIA VIRULENCE EF
Slide 10: Complications Associated with Pneumonia: A Significant Unmet Medical Need
10 Complications Associated with Pneumonia A Significant Unmet Medical Need Pneumonia is the most common infection requiring hospitalization and admission to ICU* 3rd most common cause of death globally (2.5million deaths/year)** Admission to ICU and length of hospitalization tightly linked to devel
Slide 11: Bacterial Virulence Effectors (VEs)
11 Bacterial Virulence Effectors (VEs) VEs play a decisive role in the development of long-term, severe, and fatal pneumonia complications – Currently not targeted by established antibiotics VEs are a part of the pathogen’s armory that triggers multiple pathogenic processes: – Promote bacterial colo
Slide 12: Bacterial Virulence Effectors (VEs) Classification
12 Bacterial Virulence Effectors (VEs) Classification – Single largest category (25-30% of cytotoxic bacterial proteins) – Function to perforate membranes of host cells – Classified as α-PFTs and β-PFTs based on the pore-forming mechanism – β-PFTs and most α-PFTs preferentially target cholesterol an
Slide 13: Bacterial Causes of Pneumonia
13 Bacterial Causes of Pneumonia HAP • H. influenzae- early onset HAP • P. aeruginosa • S. aureus (including MSSA and MRSA) • GNEB (K. pneumoniae, E. coli) • Acinetobacter* species- ICU patients • S. pneumoniae- early onset HAP VAP • P. aeruginosa • S. aureus (including MSSA and MRSA) • S. maltophil
Slide 14: Pneumonia Management
14 Pneumonia Management HAP, VAP, CAP suspected Obtain lower respiratory tract sample (and blood if VAP) for culture and microscopy if patient is clinically stable. Begin empiric antimicrobial therapy using local antibiogram unless there is low clinical suspicion for pneumonia and a negative lower r
Slide 15: Pneumonia Treatment
15 Pneumonia Treatment CAP In-Patient Therapy Medical Ward No Recent Antibiotics Recent Antibiotics Clarithromycin Azithromycin PLUS Cefotaxime, Cetriaxone, Ampicillin-sulbactam, or Ertapenem OR Moxifloxacin, Levofloxacin, Gemifloxacin*, Or Gatifloxacin (regimen selected will depend on nature of rec
Slide 16: Unmet Need
16 16 Unmet Need Andre Kalil, MD
Slide 17: 17 17
17 17
Slide 18: Pneumonia before antibiotics
18 Tilghman Arch Intern Med 1937;59:602–19. Pneumonia before antibiotics
Slide 19: Mortality of hospitalized CAP
19 Mortality of hospitalized CAP German, 2006-2007 N=388,406 hospitalized CAP CRB-65 hospital mortality: 14.1% 1.8% 14.9% Ewig Thorax 2009;64:1062-1069 class 1: 16.55% class 2: 71.55% class 3: 11.91% Mechanical ventilation: 5.1%
Slide 20: Severe CAP
20 Severe CAP P<0.001 Retrospective study of prospective data, N=844 severe bacteremic pneumococcal pneumonia Pitt bacteremic score ≤/>4 Combination 23.4% Monotherapy 55.3% Critically ill pts (30d mortality) Baddour AJRCCM 2004;170:440
Slide 21: Severe CAP
21 Severe CAP (HR, 1.45; 95% CI, 0.96–2.18; p=.07) (HR, 1.69; 95% CI, 1.09–2.60; p=.01) Retrospective study of prospective data, N=529 ICU admitted CAP Shock Y/N β-lactam plus fluoroquinolones (HR, 1.77; 95% CI, 1.01–3.15; p=.05) Monotherapy vs. combination β-lactam plus macrolide (HR, 1.73; 95% CI,
Slide 22: Severe CAP
22 Severe CAP HR 0.48, 95% CI 0.23–0.97, p=.04 Martin-Loeches ICM 2010;36:612 Prospective observational study N=217 SCAP requiring MV Severe sepsis/septic shock 75.5% Therapy according to ATS/IDSA 2007 guidelines, N=100 (45.9%) – Combination with fluoroquinolone (N=46) or macrolide (N=56)
Slide 23: Hospitalized CAP – Treatment failure
23 Hospitalized CAP – Treatment failure 2 open, prospective multicenter studies (moxifloxacin; standard) n = 1236 Treatment failure (15.9%) CURB65≥2 (20.3%, p=.004) LOS (15.4 vs 9.8d, p<.001) Costs (2206 vs 1284€, p<.001) Mortality (17.3 vs 5.2%, p<.001) ✓ 89.1% of group standard received therapy in
Slide 24: Pneumonia and Stroke/AMI
24 Pneumonia and Stroke/AMI 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 0-30 31-90 91-365 Time post discharge (days) OR for new onset IHD or stroke Corales-Medina et al JAMA 2015 CHS (n=5888) ARIC (n=15792)
Slide 25: Pneumonia and New Onset Heart Failure
25 Pneumonia and New Onset Heart Failure 1 3 5 7 9 11 13 31-90 91-180 181-365 1-5 years Time post discharge (days) OR for new onset heart failure Corales-Medina et al Am Heart J 2015
Slide 26: Risks of readmission and death after hospitalization
26 Fig 1 Risks (hazard ratios) of first readmission to hospital and death for one year after hospitalization for heart failure, acute myocardial infarction, or pneumonia. Dharmarajan K et al. BMJ 2015;350:bmj.h411
Slide 27: Mortality Due to CAP
27 Mortality Due to CAP Mortality in the subsequent 2 years Inpatient mortality
Slide 28: Lakbar I et al. Sci Report 2021 Aug 13;11(1):164
28 Lakbar I et al. Sci Report 2021 Aug 13;11(1):164
Slide 29: Suarez-de-laRica et al. Rev Esp Quimiot 2021 Aug;34(4):330-336. doi: 10.37201/req/031.2021
29 Suarez-de-laRica et al. Rev Esp Quimiot 2021 Aug;34(4):330-336. doi: 10.37201/req/031.2021
Slide 30: Acute Pneumonia (Community and Hospital Acquired)
30 Acute Pneumonia (Community and Hospital Acquired) Most common cause of hospitalization Most common cause of Intensive Care Unit admission due to an infection Most common cause of Acute Respiratory Distress Syndrome – ARDS Most common cause of Sepsis Rapidly increasing rate of antibiotic resistanc
Slide 31: CAL02 Overview, Clinical Data & Development Plan
31 31 CAL02 Overview, Clinical Data & Development Plan Samareh Azeredo da Silveira Lajaunias, PhD Judith Ng-Cashin, MD
Slide 32: CAL02 has the potential to be the constant while the care team works through the variables
32 32 CAL02, a novel antitoxin liposomal agent, has the potential to be the constant while the care team works through all the variables The death rate from pneumonia in the U.S. has had little improvement since antibiotics became widespread more than half a century ago. We are not yet winning the b
Slide 33: CAL02 overcomes the limitations faced by drugs targeting virulence so far
33 CAL02 overcomes the limitations faced by drugs targeting virulence so far Pore-Forming Toxins (VE): MoA Inactive soluble PFT Lipid platforms Host cell cytosol Extracellular space Binding to lipid platforms Oligomerization Pore formation Tissue and organ damage Pro-inflammatory response Cell death
Slide 34: CAL02: Activity Against Virulence Effectors
34 CAL02: Activity Against Virulence Effectors CAL02 mimics specific membrane raft-like lipid platforms and acts as a high-affinity trap, winning over cells. We believe “CAL02 overcomes the limitations faced by drugs targeting virulence so far.”
Slide 35: CAL02: Preclinical Data
35 CAL02: Preclinical Data Assays using purified virulence effectors Assays using culture supernatant Assays using direct exposure to bacteria Bacteremia & Pneumonia & Skin Infections Gram+: S. pneumoniae & S. aureus (incl. MRSA USA300) Gram- P. aeruginosa (ongoing) CAL02 monotherapy/CAL02 + antibio
Slide 36: Safety Pharmacology and Toxicology
36 Safety pharmacology studies in rats (respiratory, CNS) and dogs: no safety signals even at the maximum feasible dose, i.e., a maximum tolerated dose (MTD) could not be determined Safety Pharmacology and Toxicology CAL02 is taken up by macrophages and eliminated via the liver, its half-life in hum
Slide 37: CAL02 Clinical Data First-In Human Study Results
37 CAL02 Clinical Data First-In Human Study Results ➢ Randomized, double-blind, placebo-controlled ➢ 3 arms / 19 patients: • CAL02 Low dose (4 mg/kg) + Standard of Care • CAL02 High dose (16 mg/kg) + Standard of Care • Placebo (saline) + Standard of Care ➢ 2 IV administration 24h apart ➢ Severe CAPP
Slide 38: Efficacy Outcomes
38 Efficacy Outcomes Low-dose CAL02(n=3) High-dose CAL02(n=10) Placebo(n=5) Cured at earlytest of cure (day 8) 0 5(56%)* 1(20%) Cured at test of cure (between days 15–22) 2(100%)* 10(100%) 5(100%) Mediantimeto cure (days) 15·0 (14to 16)† 8·0 (6to 16) 10·0 (7to 14) All-causemortality 1(33%) 1(10%) 1(
Slide 39: CAL02: Therapeutic Benefit & Unique Potential
39 CAL02: Therapeutic Benefit & Unique Potential Positive trends over placebo in efficacy parameters*+ ▪ Reduction of mortality risk+ ▪ Potentially faster and complete recovery of organ function + ▪ Shorter duration of mechanical ventilation ▪ Immediate decrease in inflammatory biomarkers (e.g. IL-6
Slide 40: CAL02 Competitive Advantages
40 CAL02 Competitive Advantages Limited use ➢ Restrictions imposed by stewardship measures and purchasers, as antibiotics are inevitably linked to the emergence of new resistances Slow and laborious market penetration ➢ Based on non-inferiority results ➢ Last-resort treatments ➢ Increasingly competi
Slide 41: CAL02 Phase Clinical Development Plan
41 CAL02 Phase 2 Clinical Development Plan Development Costs Through Interim Results $10M Deal Signing Milestone 1 $1M Phase I – Drug-Drug Interaction $21M P2B/3 Multicenter Global Study – Part 1 Through Interim Analysis Results $3M Clinical Trial Materials 1 2 3 4 $35M TOTAL COST ITEM • IND Filing
Slide 42: Therapeutic Benefit & Unique Potential
42 Laterre et al. Lancet Infect Dis 2019 19(6):629-630 Therapeutic Benefit & Unique Potential Positive trends over placebo in efficacyparameters ▪ Reduction of mortality risk* ▪ Faster and complete recovery of organ function * ▪ Shorter duration of mechanicalventilation ▪ Immediate decrease in infla
Slide 43: Question & Answer
Question & Answer PHARMACEUTICALS
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