Eagle Pharmaceuticals, Inc. · OTC:EGRX
Eagle Pharmaceuticals — Investor Day (December 2022)
144 slides from Eagle Pharmaceuticals's investor day presentation, Dec 6, 2022
Slide 1: Investor Day, December 6, 2022
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 1 2022 Eagle Pharmaceuticals, Inc. All rights reserved. December 6, 2022Investor Day
Slide 2: Forward-Looking Statements
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 2 Forward-Looking StatementsThis presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, and other securities law. Forward-looking statements are statements that are
Slide 3: Eagle Investor Day Agenda
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 33 7:30 AMRegistration and Breakfast 8:00 AMOverview of the Day 8:10AMIntroduction of the SpeakersHerm CukierDr. Joe Pergolizzi & Dr. TJ Gan −Postoperative Respiratory DepressionDr. Eugene Vortsman −Community OverdoseDr. Prem Fort −Apnea of Prema
Slide 4: Eagle Hospital Business Overview
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 4 Eagle Hospital Business Overview RYANODEX Vasopressin Barhemsys Byfavo Landiolol1 CAL022Acute Care Hospital Commercially Available Pipeline & Potential Pipeline ENA-0013 Hospital business currently being commercialized by 50 field resources For
Slide 5: The Evolution of Eagle Pharmaceuticals
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 5 Seek additional strategic transactions Build pipelineinternally Leverage Acaciainfrastructure Move from 505(b)2To longer life NCEs Reinvest cash flow The Evolution of Eagle PharmaceuticalsLegacyBusinessAcaciaPharmaExpandingPipeline RYANODEX Vas
Slide 6: Introduction of the Speakers
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 6 6 Introduction of the Speakers
Slide 7: Patients Served by Acute Care/Hospital Portfolio
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 7 Patients Served by Acute Care/Hospital Portfolio ByfavoRyanodexLandiololENA-001CAL02ByfavoVasopressinLandiololENA-001CAL02BarhemsysByfavoRyanodexVasopressinLandiololENA-001ByfavoVasopressinENA-001BarhemsysRyanodexVasopressinLandiololENA-001Emer
Slide 8: Eagle Speakers
8 8 Eagle SpeakersValentin Curt, MDInterim Chief Medical Officer, SVP Clinical Drug Development, at Eagle Pharmaceuticals, Inc.25+ years of experience in clinical drug development and managing global clinical development plansPrior executive positions held at Imbrium Therapeutics, Purdue Pharma, Dai
Slide 9: KOL Biographies
9 9 KOL BiographiesHerm CukierExecutive Chairman, President, and CEO of Enalare TherapeuticsSuccessful executive with commercial and operational expertise across several global, blockbuster products30+ years industry experience in senior leadership roles with preeminent organizations, including Baye
Slide 10: KOL Biographies
10 10 KOL BiographiesDr. Joseph PergolizziChief Research and Development Officer, Board Member and Co-founder of Enalare Therapeutics Internationally recognized thought leader in areas of perioperative and pain medicines, drug development, and regulatory affairsHighly published in top-tier journals
Slide 11: ENA-001
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 11 11 ENA-001
Slide 12: ENA-001 - Potential to Improve Clinical Outcomes
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 12 ENA-001 -Potential to Improve Clinical Outcomes for Patients Post-operativeCommunity Drug OverdoseApnea of Prematurity Agnostic Respiratory StimulantRapid ActingMultiple FormulationsNovel MoleculeSignificant Medical NeedRespiratory Depression
Slide 13: Respiratory Depression: A Global Health Emergency
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 13 Respiratory Depression: A Global Health Emergency Normal Respiration12-20 breaths/minMinute ventilation of 5 to 8 liter/min (resting)Harmonized balance of O2and CO2 levels in the blood Respiratory Depression<10 breaths/minInadequate minute ven
Slide 14: Partnership with BARDA on Development of ENA-001
CONFIDENTIAL AND INTERNAL 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 14 Partnership with BARDA on Development of ENA-001 as a Rescue Medicine for Drug-induced Respiratory DepressionEnalare/BARDA ENA-001 PartnershipSupports development of an intramuscular (IM) formulation of ENA-001 for us
Slide 15: ENA-001 - Multiple Product Candidates Under Development
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 15 ENA-001 -Multiple Product Candidates Under Development with Potential to Benefit Patients Across the Hospital and Community Settings Setting of UseHospital & Ambulatory (outpatient) clinicsCommunity, First Responders, ERHospital Neonatal Inten
Slide 16: ENA-001: Novel Mechanism of Action
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 16 ENA-001 = A One-of-a-Kind Molecule with a Novel Mechanism of Action TASK 1 TASK 3 BKCa↓O2, ↓pH↑ENA-001 Depolarization of carotid body glomus cells drives breathingChannel agonists decrease potassium conductanceLow oxygen, pH (and doxapram) act
Slide 17: ENA-001 Unique Product Profile
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 17 ENA-001 = A Unique Product Profile with Potentially Broad Applications to Stimulate Breathing ENA-001hydrogensulphatesalt2-N,O-dimethylhydroxylamino-4,6-bispropylamino-s-triazineAgnostic:Potential to stimulate breathing irrespective of the cau
Slide 18: ENA-001 Well Tolerated Across Five Clinical Studies
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 18 ENA-001 = Well Tolerated Across Five Clinical Studies Totaling >110 Subjects StudyDescription# of SubjectsGAL-021-101Single, ascending dose study in healthy subjects.30GAL-021-102Extended the dose range -established the maximum respiratory sti
Slide 19: Clinical Study 104
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 19 Clinical Study 104: Respiratory Stimulatory Effects in Subjects with Impaired Respiratory Drive due to an Opioid Study Design:Healthy volunteersAdministered low and high levels of alfentanil, a potent opioid, to induce moderate to severe respi
Slide 20: Clinical Study 106
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 20 Clinical Study 106: Rising Multiple Dose 5-day Study of ENA-001Objectives: Safety, Tolerability, Pharmacokinetics (PK) Standard Double Blinded, Placebo Controlled Study Infusions: 12 hours x 5 daysThree Dose Levels (0.125, 0.25, 0.5 mg/kg/h) S
Slide 21: Clinical Study 108
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 21 Clinical Study 108: Respiratory Stimulatory Effects in Subjects with Impaired Respiratory Drive due to an Anesthetic To determine the safety, tolerability, and ventilatory response of low and high doses of ENA-001 under both hypoxic and hyperc
Slide 22: ENA-001 Timeline
CONFIDENTIAL AND INTERNAL 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 22 Post-op (Fast-track)Start fentanyl tox study ~ in early 2023Expect to start Phase 2 enrollment ~ as early as 3Q23Potential for Phase 2 topline data ~ in 2Q24Community Drug Overdose (BARDA and NIH funding)Currently exe
Slide 23: Real World Experience Respiratory Depression
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 23 Real World Experience Respiratory DepressionDr. TJ GanDivision Head of Anesthesiology, Critical Care and Pain Medicine MD AndersonEmergency Medicine PhysicianClinical Director of Addiction Medicine and Disease Management Northwell HealthNeonat
Slide 24: The Burden of Respiratory Depression
24 The Burden of Respiratory Depression T. J. Gan, M.D., M.B.A., F.R.C.A., M.H.S. Professor and Division Head Anesthesiology, Critical Cre and Pain Medicine UT Texas MD Anderson Cancer Center Founding President, American Society for Enhanced Recovery (ASER) aserhq.org | enhancedrecovery.org Presiden
Slide 25: Postoperative Pulmonary Complications
25 Postoperative Pulmonary Complications (PPC) PPC is any event that occurs in the postoperative period that produces physiologic dysfunction or clinical diseaseIncidence 2 -40%2.73.4% of patients undergoing non-cardiac surgery (NSQIP database)9.6% in elective abdominalsurgeries in VApatientsLawrenc
Slide 26: Prediction and Monitoring for PORD are Poor
26 Prediction and Monitoring for PORD are Poor Unable to accurately predict which patient will have an episode of PORD PACU Staff routinely miss low oxygen, <90% of episodes1Incidence of post-operative hypoxemia underestimated1Up to 62% transferred from floor to ICU had serious abnormalities 8-48 ho
Slide 27: Manifestations of PPC
27 Manifestations of PPC Respiratory failurePneumoniaAtelectasisDyspneaProlonged mechanical ventilationUnexpected reintubationHypoxemia (blood gas or SpO2)Administration of naloxoneBranson Rd et al. Respir Care 2013;58(11):1974 1984
Slide 28: PPC Risk Factors
28 Postoperative Pulmonary Complications (PPC) Risk Factors Miskovic A and Lumb AB. British Journal of Anaesthesia, 118 (3): 31734 (2017)
Slide 29: Unanticipated Early Postoperative Intubation
29 NSQIP database >220,000 patientsIncidence of unanticipated early postoperative intubation (UEPI) 0.9%Ramachandran SK et al. Anesthesiology 2011; 115:4453
Slide 30: Claims Due to Respiratory Depression
30 Out of 9,799 claims, 92 were due to RD88% occurred within 24 h of surgery97% were judged as preventable with better monitoring and responseMedian payment -$216,750 Lee L et al. Anesthesiology 2015; 122:659-65
Slide 31: Average Cost of a Complication
Average cost of a complication > $10,000J AmColl Surg2004;199:531537 31
Slide 32: Postoperative Opioid-induced Respiratory Depression
32 Postoperative Opioid - induced Respiratory Depression Patients with ≥1 respiratory depression episode had a longer length of stay (6.4 vs 5.0 days) and higher hospital cost ($21,892 vs $18,206) Respiratory depression episodes includeRespiratory rate ≤ 5 bpm,Oxygen saturation ≤ 85%,End-tidal carbo
Slide 33: The Future of Postoperative Respiratory Care
33 The Future of Postoperative Respiratory Care Cannot prevent all PORDOpioids are not the sole culprit of PORDAnesthetics, paralyzing agents, and sedatives that do not respond to naloxoneProlonged apnea at the end of surgery delays wakeupGoal: Improved respiratory and ventilatory function Proactive
Slide 34: Summary
34 Summary Postoperative respiratory complications are common and preventable1% of postoperative patients require unexpected reintubationPostoperative respiratory complications increase length of stay and substantially increase costApnea and respiratory depression delay wakeup following surgery and
Slide 35: Potential New Tool for Emergency Setting
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 35 Clinical Director of Addiction Medicine and Disease Management: Every day, Emergency Departments around the country struggle managing overdoses with only ONE tool availableleading to dangerous situations for staff and patients.Chair of Pain Ad
Slide 36: Apnea of Prematurity and ENA-001
36 36 Apnea of Prematurity andENA-001 Prem Fort, MDChair-MFNI Research CouncilAssistant Professor of PediatricsJohns Hopkins School of MedicineJohns Hopkins All Childrens Hospital, FLhttps://commons.wikimedia.org/wiki/File:Premature_infant_with_ventilator https://commons.wikimedia.org/wiki/File:Prem
Slide 37: Premature Infants
37 37 Premature Infants 15 MILLION 500,000 US 1 in 10 US <37 weeks
Slide 38: Apnea: Obstructive vs. Central
38 38 Apnea: Obstructive vs. Centralhttps://www.nhlbi.nih.gov/health/sleep-apnea/causesObstructiveCentral https://slidetodoc.com/patterns-of-respiration-by-ahmad-younes-professor-of/
Slide 39: Apnea of Prematurity
39 39 Apnea of prematurity is defined as cessation of breathing for ≥ 20 seconds or < 20 seconds if accompanied by bradycardia (<100 BPM) and/or cyanosis and pallor in infants < 37 weeks gestational age (GA)AAP COFN. Pediatrics 137: 2016Apnea of Prematurity
Slide 40: Apnea of Prematurity
40 40 APNEACessation of Breath 12 million a yearwithAPNEA ofPrematurity https://www.whattoexpect.com/first-year/caring-for-a-premature-baby.aspx
Slide 41: Percentage of Moderate Preterm Infants with Apnea
41 41 Eichenwald et al. Pediatrics 108:928-33, 2001Gestational Age inWeeks30 (n=25)31 (n=40)32 (n=95)33 (n=122)%with apnea92905948Background: Percentage of Moderate Preterm Infants with Apnea
Slide 42: Apnea of Prematurity: How is it treated?
42 42 APNEA OF PREMATURITYHow is it treated?neotechproducts.com respiratory-care-sleep-medicine.advanceweb.com
Slide 43: Apnea of Prematurity: How is it treated?
43 43 APNEA OF PREMATURITYHow is it treated? Apnea/Day 443026221612840PreCaffeineWithCaffeineAranda et al. J Pediatr 90:467, 1977 canva.com
Slide 44: Apnea of Prematurity: Many left untreated
44 44 APNEA OF PREMATURITYMany left untreatedApnea/Day 443026221612840PreCaffeineWithCaffeineAranda et al. J Pediatr 90:467, 1977
Slide 45: Is Caffeine Safe?
45 45 Chavez-Valdez R, Ahlawat R, Wills-Karp M, Gauda EB. Mechanisms of modulation of cytokine release by human cord blood monocytes exposed to high concentrations of caffeine. Pediatric research. 2016;80(1):101-109Elevated Markers of InflammationIs Caffeine Safe?
Slide 46: Caffeine's Limits
46 46 Valdez RC, Ahlawat R, Wills-Karp M, Nathan A, Ezell T, Gauda EB. Correlation between Serum Caffeine Levels and Changes in Cytokine Profile in a Cohort of Preterm Infants. The Journal of pediatrics. 2011;158(1):57-64.e1.The Sweet SpotCaffeine’s Limits
Slide 47: Meta-Analysis and Systematic Review
47 47 Meta-Analysis and Systematic Review
Slide 48: Meta-Analysis and Systematic Review
48 48 Meta-Analysis and Systematic Review
Slide 49: The Effect of Apnea on Hospitalization
49 49 12345 The Effect of Apnea on Hospitalization https://commons.wikimedia.org/wiki/File:Yegorov-Simeon_the_Righteous https://slidetodoc.com/patterns-of-respiration-by-ahmad-younes-professor-of/
Slide 50: Alternate Treatments
50 50 Alternate Treatments Pergolizzi Jr, Joseph V., et al. "The limited management options for apnoea of prematurity."Journal of Clinical Pharmacy and Therapeutics47.3 (2022): 396-401.
Slide 51: References
51 51 AAP. Hospital discharge of the high-risk neonate. Pediatrics 2008;122:1119-26Altman M, Vanpee M, Bendito A, Norman M. Shorter hospital stay for moderately preterm infants. Acta Paediatrica (Oslo, Norway: 1992) 2006;95:1228-33Eichenwald EC, Blackwell M, Lloyd JS, Tran T, Wilker RE, Richardson D
Slide 52: References
52 52 Endesfelder, Stefanie, et al. "Caffeine Protects Against Anticonvulsant-Induced Neurotoxicity in the Developing Rat Brain." Neurotoxicity Research(2017): 1-13Köroğlu, Özge A., et al. "Anti-inflammatory effect of caffeine is associated with improved lung function after lipopolysaccharide-induce
Slide 53: CAL02
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 53 53 CAL02
Slide 54: Disease State Overview
54 54 Disease State OverviewAndre Kalil, MD, MPHProfessor of MedicineUniversity of Nebraska Medical Center
Slide 55: Chest X-ray and CT: Lungs with Pneumonia
55 55 Chest X-ray: Normal LungsChest X-ray: Lungs with pneumoniaComputerized tomography (CT) scan: Lungs with pneumonia
Slide 56: Pneumonia before Antibiotics
56 Tilghman Arch Intern Med 1937;59:602–19. Pneumonia before Antibiotics
Slide 57: Pneumonia Overview
57© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. Pneumonia OverviewPneumonia 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 Infe
Slide 58: CAP Poses a Significant Public Health Burden
58© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. CAP Poses a Significant Public Health Burden In the US, the annual incidence of CAP was 2.4 cases per 1,000 adults with the highest rates among adults ≥651 Globally mortality with CAP is up to 50% in the ICU.2-7 CAP is the second most common
Slide 59: Mortality of Hospitalized CAP
59 Mortality of Hospitalized CAP German, 2006-2007N=388,406 hospitalized CAPCRB-65 hospital mortality: 14.1% 1.8% 14.9% EwigThorax2009;64:1062-1069 class 1: 16.55% class 2: 71.55% class 3: 11.91% Mechanical ventilation: 5.1%
Slide 60: Severe CAP
60 Severe CAP P<0.001 Retrospective study of prospective data, N=844 severe bacteremic pneumococcal pneumoniaPitt bacteremic score ≤/>4 Combination 23.4% Monotherapy 55.3%Critically ill pts (30d mortality) Baddour AJRCCM 2004;170:440
Slide 61: Severe CAP
61 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 CAPShock 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, 1.08
Slide 62: Severe CAP
62 Severe CAP HR 0.48, 95% CI 0.23–0.97, p=.04 Martin-Loeches ICM 2010;36:612 Prospective observational studyN=217 SCAP requiring MVSevere 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 63: Hospitalized CAP Treatment Failure
63 Hospitalized CAP Treatment Failure 2 open, prospective multicenter studies (moxifloxacin; standard)n = 1236Treatment 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 accord
Slide 64: Pneumonia and Stroke/Acute MI
64 Pneumonia and Stroke/Acute MI 11.522.533.544.555.560-3031-9091-365Time post discharge (days)OR for new onset IHD or stroke Corales-Medina et al JAMA 2015 CHS (n=5888) ARIC (n=15792)
Slide 65: Pneumonia and New Onset Heart Failure
65 Pneumonia and New Onset Heart Failure 13579111331-9091-180181-3651-5 yearsTime post discharge (days)OR for new onset heart failure Corales-Medina et al Am Heart J 2015
Slide 66: Risks of Readmission and Death After Hospitalization
66 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 67: Mortality Due to CAP
67 Mortality Due to CAP Mortality in thesubsequent2 yearsInpatient mortality
Slide 68: Mortality and Highly Antimicrobial-Resistant Bacteria
68 Lakbar I et al. Sci Report 2021 Aug 13;11(1):164 Mortality and Highly Antimicrobial-Resistant Bacteria
Slide 69: Secondary Infections in Mechanically Ventilated COVID-19 Patients
69 Suarez-de-laRica et al. Rev Esp Quimiot 2021 Aug;34(4):330-336. doi: 10.37201/req/031.2021Secondary Infections in Mechanically Ventilated Patients with COVID-19
Slide 70: Pneumonia Management
70© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 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 islow cli
Slide 71: Pneumonia Treatment
71© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. Pneumonia Treatment CAP In-Patient Therapy Medical Ward NoRecent Antibiotics RecentAntibiotics ClarithromycinAzithromycinPLUSCefotaxime, Cetriaxone,Ampicillin-sulbactam, orErtapenemORMoxifloxacin,Levofloxacin,Gemifloxacin*,or Gatifloxacin(reg
Slide 72: Complications Associated with Pneumonia: Unmet Medical Need
72© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. Complications Associated with PneumoniaA 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
Slide 73: Unmet Need in Severe CABP
73 Unmet Need in Severe CABP Unknown bacterial speciation upon admission and antibiotic resistance can complicate clinical management Current CABP treatments have limitations and do not address the propagation of the inflammatory response Treatment failure and high mortality rates remain problematic
Slide 74: Unknown Bacterial Speciation and Antibiotic Resistance
74 Unknown Bacterial Speciation Upon Admission and Antibiotic Resistance Can Complicate Clinical Management The microbial etiology of CAP may not be characterized in ~50% of patients.1 Cases of resistant pneumococcal pneumonia in the US result in ~32,000 additional doctor visits and 19,000 additiona
Slide 75: CAL02 Overview & Development Plan
75 75 CAL02 Overview & Development PlanValentin Curt, M.D.
Slide 76: Severe Pneumonia - Key Targets
76© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. Severe Pneumonia -Key Targets TRIGGERMEDIATORSIMPACTOUTCOMEPERIPHERAL VASCULATUREMYOCARDIUMCYTOKINES /CHEMOKINESSEPSISSEPTICSHOCKDEATHSENSORSPLASMAPROTEINSYSTEMSBLOOD ANDLYMPHATICCELLSVASCULAR AND TISSUECELLSENDOTHELIAL STRESSRESPONSECELLDYSF
Slide 77: Bacterial Virulence Factors
77© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. Bacterial Virulence Factors (VFs)VFs play a decisive role in the development of long-term, severe, and fatal pneumonia complicationsCurrently not targeted by established antibioticsVFs are a part of the pathogens armory that triggers multiple
Slide 78: Bacterial Virulence Factors Classification
78© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. Bacterial Virulence Factors (VFs) ClassificationSingle largest category (25-30% of cytotoxic bacterial proteins)Function to perforate membranes of host cellsClassified as α-PFTs and β-PFTs based on the pore-forming mechanismβ-PFTs and most α-
Slide 79: Bacterial Causes of Pneumonia
79© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. Bacterial Causes of Pneumonia HAP H. influenzae-early onset HAPP. aeruginosaS. aureus (including MSSA and MRSA)GNEB(K. pneumoniae, E. coli)Acinetobacter*species-ICU patientsS. pneumoniae-early onset HAP VAP P. aeruginosaS. aureus (including M
Slide 80: CAL02 Targeting Virulence Factors
80© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. We believe CAL02, a novel first-in-class broad-spectrum anti-virulence agent being developed for the treatment of severe community-acquired bacterial pneumonia, could potentially overcome the limitations faced by current approachestargeting v
Slide 81: CAL02 Mechanism of Action
81© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. CAL02 Mechanism of Action Against Virulence Factors CAL02 is a novel first-in-class broad-spectrum anti-virulence agent being developed for the treatment of severe community-acquired bacterial pneumonia. It is being developed to neutralize vi
Slide 82: CAL02 Product Overview
82© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. CAL02Product Overview ▪Patented composition ofmatter▪Sterile liquid solution ready forinjection▪Stable for 36 months when refrigerated (6 months when stored atroom temperature)▪Route of administration: IV Infusion2 doses separated 24 hours ap
Slide 83: CAL02 Novel, First-in-Class Virulence Neutralizer
83© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. CAL02 Novel, First-in-Class Virulence Neutralizer AgentMechanismof ActionAddress the downstream effects of bacterial VFs/PFTs through competitive inhibitionBinds to virulence factor molecules secreted by infecting bacteria, prohibiting host t
Slide 84: CAL02 Non-Clinical Program Proof-of-Concept
84© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. CAL02 Non-Clinical Program Proof-of-Concept2022CombioxinSA.Allrights reserved. Improvedsurvival Decreasedpro-inflammatoryresponses Shielded immunedefense Organprotection(lung,heartinjury,tissuenecrosis)
Slide 85: CAL02 Non-Clinical Safety Pharmacology and Toxicology
85© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 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 determinedCAL02 Non-Clinical Safety Pharmacology and Toxicology CAL02 is ta
Slide 86: CAL02 Clinical Data: Safety Outcomes
86© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. CAL02 Clinical Data in Humans: Safety Outcomes First-In-Human Study ResultsRandomized, double-blind, placebo-controlled3 arms / 19 patients:CAL02 Low dose (4 mg/kg) + Standard of CareCAL02 High dose (16 mg/kg) + Standard of CarePlacebo (salin
Slide 87: CAL02 Clinical Data: Efficacy Outcomes
87© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. CAL02 Clinical Data in Humans: Efficacy Outcomes Low-dose CAL02(n=3)High-dose CAL02(n=10)Placebo(n=5)Curedatearlytestofcure(day8)05(56%)*1(20%)Curedattestofcure(betweendays15–22)2(100%)*10(100%)5(100%)Mediantimetocure(days)15·0(14to16)†8·0(6t
Slide 88: CAL02 Phase 2 Study Design
88© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. CAL02 Phase 2 Study Design DesignAn adaptive, randomized, multicenter, double-blind, placebo-controlled study to assess the efficacy and safety of CAL02 administered intravenously in addition to standard of care in subjects with severe commun
Slide 89: CAL02 Potential Competitive Advantages
89© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. CAL02 Potential CompetitiveAdvantagesLimited useRestrictions imposed by stewardship measures and purchasers, as antibiotics are inevitably linked to the emergence of new resistancesSlow and laborious market penetrationBased on non-inferiority
Slide 90: CAL02: Potential Unique Therapeutic Benefit
90 90 CAL02: Potential Unique Therapeutic BenefitAndre Kalil, MD, MPHProfessor of MedicineUniversity of Nebraska Medical Center
Slide 91: CAL02: Potential Unique Therapeutic Benefit
91© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. CAL02: Potential Unique Therapeutic BenefitPositive trends over placebo in efficacyparameters*+▪Reduction of mortality risk+▪Potentially faster and complete recovery of organ function+▪Shorter duration of mechanicalventilation▪Immediate decre
Slide 92: Barhemsys and Byfavo
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 92 92 Barhemsysand Byfavo
Slide 93: Hospital Environmental Trends Bolster Acute Care Portfolio
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 93 Hospital Environmental Trends Bolster the Value Proposition of Eagles Acute Care Portfolio Rising costs of supplies, wages, and operationsNegative reimbursement trendsContinued staffing shortages Shifting of surgical and procedural volume to o
Slide 94: Barhemsys: Compelling Clinical and Commercial Proposition
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 94 BarhemsysCompelling Clinical and Commercial Proposition O Post Operative Nausea and Vomiting (PONV) is associated with increased length of Post Anesthesia Care Unit (PACU) stay and greater resource utilization PONV contributes to patient dissa
Slide 95: Byfavo: Compelling Clinical and Commercial Proposition
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 95 ByfavoCompelling Clinical and Commercial Proposition O No new approved drugs in the sedation space for over 20+ yearsCustomers seeking fast and predictable effect with rapid recovery for quick dischargeShort recovery time enabling efficiency a
Slide 96: Barhemsys: Management of Postoperative Nausea and Vomiting
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 96 96 Barhemsys:Management of Postoperative Nausea and Vomiting
Slide 97: Management of PONV: The Role of Amisulpride
97 Management of PostoperativeNausea and Vomiting.The Role of Amisupride.T.J. Gan, M.D., M.B.A., F.R.C.A., M.H.S.Division Head of Anesthesiology, Critical Care and Pain Medicine, The University of Texas MD Anderson Cancer Center Founding President, American Society for Enhanced Recovery (ASER) aserh
Slide 98: PONV Is Common and Complex
98 PONV Is Common and Complex A common complication of surgery and anesthesia Despite prophylaxis, 30% of patients still experience PONV in the PACUUnpleasant and associated with patient discomfort and dissatisfaction with perioperative careA greater concern for patients than avoiding postoperative
Slide 99: Patients Perceive PONV to Be Worse than Pain
99 Patients Perceive PONV to Be Worse than Pain1. Eberhart LH, et al. Anesthesiology. 2002;89(5):760-761. 2. Hill RP, et al. Anesthesiology. 2000;92:958-967. 3. Gan TJ, et al. Br J Anaesth.2004;92(5):681-688. 11%13%27%49%Relative Importance of Patient Postoperative Recovery Concerns (%) (N=220)1PONV
Slide 100: Shifting Towards Patient-Centered Care
100 Shifting Towards Patient-Centered Care1Provider Satisfaction Volume-Based CareValue-Based Care1Triple Aim of CarePatient ExperienceOAS CAHPS2Fourth AimHealthcare EfficiencyHealthcare QualityMIPS Measure 4303Provider SatisfactionQuality of PONV Management Is Measured by National Performance Metri
Slide 101: Number of Publications on PONV
101 Number of Publications on PONV 0200040006000800010000120001st (2003)2nd (2007)3rd (2014)4th (2020)PONV Consensus Guidelines PubMed Search: Postoperative Nausea, Vomiting
Slide 102: PONV Risk Factors - Adults
102 PONV Risk Factors -Adults Risk FactorsPointsFemale Gender1Non-Smoker1History of PONV1Postoperative Opioids1Sum of points1-4 123450%20%40%60%80%100%Number of Risk FactorsGan TJ et al. Anesth Analg 2020;131:41148Apfel C, et al. Acta Anaesthesiol Scand 1998;42:495-501
Slide 103: Etiology and Pathophysiology of Nausea and Vomiting
103 Etiology and Pathophysiology of Nausea and Vomiting Are Complex Peripheral MechanismsCentral Mechanisms Peripheral1 Vomiting center Vomiting reflex In GI tract2: 5-HT3 receptorsMechanoreceptors Chemoreceptors Higher cortical centers1,2 Vestibular system1,2 CTZ1 5-HT3=5-hydroxytrytamine type 3. C
Slide 104: Nausea and Vomiting Mediated by Multiple Neurotransmitters
104 ReceptorAntagonistNeurotransmitterCholinergic muscarinicM3/M5receptorD2/D3receptorH1receptor5-HT3receptorNK-1 receptor AcetylcholineDopamine Histamine Substance P/NK-1 Serotonin CTZNausea and Vomiting Are Mediated by Multiple Neurotransmitters and Their Receptors1-4D=dopamine. H=histamine. M=mus
Slide 105: Main Drug Classes Manage PONV
105 Anticholinergics(transdermal scopolamine) Antihistamines(dimenhydrinate, promethazine) Dopamine antagonists(droperidol, haloperidol) 5-HT3antagonists(ondansetron, granisetron, palonosetron) NK-1 antagonists(aprepitant, rolapitant) Corticosteroids(dexamethasone, methylprednisolone)They are classi
Slide 106: Combination Therapy May Reduce Incidence of PONV
106 Monotherapy Combination therapy with 3 antiemetics PONV Incidence 52 Combination therapy with 2 antiemetics No antiemetic0123Number of AntiemeticsPONV Incidence (%) 372822Combination Therapy in Patients at Moderate or High Risk May Reduce Incidence of PONV Therapy TypeApfel CC. N Engl J Med. 200
Slide 107: Breakthrough PONV Occurs Despite Prophylaxis
107 can experiencePONV despite prophylaxis3,4can experiencePONV1,2 can experiencevomiting4can experiencenausea4,5 In high-risk patients In patients who failed prophylaxis NEARLY80%MORE THAN30%MORE THAN95%MORE THAN20%Breakthrough PONV Occurs Despite Prophylaxis1. Gan TJ, et al. Anesth Analg. 2014;118
Slide 108: Limited Treatment Options for Patients Failing Prophylaxis
108 For patients failing typical pre-or perioperative prophylaxis with 5-HT3 antagonist, rescue treatment choices are limited.1Limited Treatment Options Exist for Patients Failing Prophylaxis Rescue Treatment ChoiceChallenges5-HT3 antagonistsNo benefits if reused within 6 hours2MetoclopramideInadequ
Slide 109: Barhemsys Characteristics
109 Barhemsys CharacteristicsAmisulpride (active ingredient of Barhemsys)1 Substituted benzamide (C17H27N3O4S)1,2Dopamine antagonist with high affinity for D2/D3receptors1,2 ‒Regional preference for D2and D3receptors in limbic, but not striatal structures2-4‒No appreciable affinity for any other rec
Slide 110: Barhemsys: Evaluated in ~2000 Patients
110 Barhemsys: Evaluated in ~2000 Patients Over 4 Pivotal Clinical Trials11. Barhemsys [Prescribing Information], Indianapolis, IN. Acacia Pharma; 2021.2. Candiotti KA, et al. AnesthAnalg. 2018. 3. Habib AS, et al. Anesthesiology. 2019;130(2):203-212. 4. Gan TJ, et al. Anesthesiology. 2017;126(2):26
Slide 111: Barhemsys for Rescue Treatment
111 Barhemsys for Rescue TreatmentThe First and Only Antiemetic Indicatedto Treat PONV After FailedProphylaxis
Slide 112: Rescue Treatment Clinical Trial Design
112 PONV prophylaxis (N=2285)* SurgeryElective ambulatory or in-patient surgery under general anesthesia PONV in 0-24 hours? Qualifying Event Nausea ~98% Emesis ~20%YesNo Barhemsys 5 mg(n=237) Placebo(n=235) Barhemsys 10 mg(n=230)RANDOMIZED (N=702) Exit trial Assessment period for 24 hours postdosin
Slide 113: Patient Baseline Characteristics
113 Barhemsys 10 mg (n=230)Placebo (n=235)Age, median (range)47 (18-85)45 (18-81)Sex, female90.4%90.2%5-HT3antagonist76.5%77.4%Dexamethasone67.8%61.7%Other12.2%8.9%1 antiemetic52.6%51.1%≥2 antiemetics47.4%46.0%Patients with emesis17.4%24.3%Patients with nausea99.1%97.0%PONV in PACU 73.5%73.2%PONV 0-
Slide 114: Patients with Complete Response at 24 Hours
114 Patients with Complete Response at 24 Hours*Defined as: No Emesis or Use of Rescue Medication 42% of patients who received Barhemsys 10 mg after failing prophylaxis had complete response at 24 hours 13%(5%, 22%)Difference (95% CI) Barhemsys 10 mg(n=230)42%P=0.003Placebo(n=235)29% Barhemsys Was M
Slide 115: Kaplan-Meier Curves of Complete Response Over Time
115 The secondary endpoints listed were prespecified. These endpoints were not adequately powered, nor error controlled, and observed treatment differences cannot be regarded as statistically significant.Kaplan-Meier Curves of Complete Response Over Time* 01.0 0.8 0.6 0.4 0.2 0 24 14 15 16 17 18 19
Slide 116: Secondary Endpoints: PACU and Hospital Length of Stay
116 050100150200250PACU length of stay, minutes 176(218) 141(174) Barhemsys 10 mg-treated patients had35 minutes shorter mean PACU length of stay than placebo-treated patientsMinutes (SD) 404550556065Hospital length of stay, hours 56(73) 50(80) Hours (SD)Barhemsys 10mg (n=230) Placebo(n=235) Seconda
Slide 117: Patient Characteristics: Treatment Success vs Failure
117© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. Patients characteristicsTreatment Success (N=82)Treatment Failure(N=30)p-valueAge years, mean (SD)A48.7 (18.0)47.4 (16.2)0.73BMI-Kg/m2, median (IQR)B28.6(24.4,35.5)34.1(29.9,41.00.003RaceCCaucasianBlackAsianOther/Not Reported62(75.6%)5(6.1%)
Slide 118: Patient Characteristics: Treatment Success vs Failure
118© 2022 Eagle Pharmaceuticals, Inc. All rights reserved. Patients characteristicsTreatment Success (N=82)Treatment Failure(N=30)p-valueAge years, mean (SD)A48.7 (18.0)47.4 (16.2)0.73BMI-Kg/m2, median (IQR)B28.6(24.4,35.5)34.1(29.9,41.00.003RaceCCaucasianBlackAsianOther/Not Reported62(75.6%)5(6.1%)
Slide 119: Summary
119 Summary*PONV is common and causes patient distress and significant patient dissatisfactionPONV is multifactorial and mediated by multiple receptor systemsThe risks of PONV are predictableMultimodal prevention strategy is considered the standard of careAmisulpride is a new dopamine antagonistAlmi
Slide 120: Byfavo: Clinical Perspective
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 120 120 Byfavo: Clinical PerspectiveRichard P. Dutton, MD MBA
Slide 121: My Credentials
CONFIDENTIAL AND INTERNAL 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 121 My Credentials Adjunct Professor, Texas A&MAnesthesiologist, Baylor University Medical CenterChief Quality Officer, US Anesthesia Partners2009-2015: Executive Director, ASA Anesthesia Quality Institute 1994-2011: Pro
Slide 122: USAP in 2022
CONFIDENTIAL AND INTERNAL 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 122 USAP in 2022 13 states, 16 platforms (cities), 60+ practices5,000 clinicians:–1,600 physician partners majority owners of the practice–800 employed physicians–2,600 CRNAs and AAs700 facilities served:–200 hospitals–2
Slide 123: Major Issues Confronting Anesthesiology Workforce
CONFIDENTIAL AND INTERNAL 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 123 Major Issues Confronting Anesthesiology Workforce: Too much demand, not enough supplyDriven by Non-Operating Room Anesthesia casesExacerbated by fragmentation, retirement, burnoutHospitals generally want more anesthe
Slide 124: Value Proposition: Hospitals
CONFIDENTIAL AND INTERNAL 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 124 Value Proposition: Hospitals Increased access OR timeCoverage for NORAIncreased efficiencyDecreased cancellationsReduced adverse eventsReduced transfusionsIncreased patient satisfactionReduced use of expensive medsDe
Slide 125: Value Proposition: Payers
CONFIDENTIAL AND INTERNAL 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 125 Value Proposition: Payers Increased outpatient surgeryDecreased:margin:10pt 0pt 10pt 0ptLength of staymargin:10pt 0pt 10pt 0ptCost of post-acute caremargin:10pt 0pt 10pt 0ptPreoperative testingmargin:10pt 0pt 10pt 0p
Slide 126: Workforce Solutions: New Models of Care
CONFIDENTIAL AND INTERNAL 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 126 Workforce Solutions: New Models of Care Extended care team coverage ratiosAutonomous CRNA practiceNon-anesthesia physician coverageFire and forget regional anesthesia blocksExpansion of non-anesthesia nursing sedatio
Slide 127: Unmet Need in Procedural Sedation: An Ideal Sedative
CONFIDENTIAL AND INTERNAL 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 127 Unmet Need in Procedural Sedation: An Ideal Sedative Characteristics1-5Pharmacokinetics1-5Pharmacodynamics1-3,6Short time to onsetLinear kineticsA predictable dose-response relationAbility to titrate to the desired r
Slide 128: Current Select Standards of Care Have Limitations
CONFIDENTIAL AND INTERNAL 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 128 Current Select Standards of Care Have Limitations Rapid onset and offset anesthetic with narrow therapeutic index1Dose-related cardiorespiratory depression, pain at injection site1Non-linear dosing effects due to ind
Slide 129: Soft, Ester-Based Drug Design
CONFIDENTIAL AND INTERNAL 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 129 Soft, Ester-Based Drug Design Due to the addition of a carboxylic ester linkage, Byfavo is rapidly hydrolyzed by tissue esterases to an inactive metabolite, with no meaningful contribution by CYP450 enzymes.3,4 Midaz
Slide 130: Byfavo Rapid Onset/Offset Benzodiazepine
CONFIDENTIAL AND INTERNAL 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 130 ByfavoRapid Onset/Offset Benzodiazepine *A sedative effect was defined as a MOAA/S score of ≤4. At 1 and 1.5 minutes, 40% and 62% of patients had a MOAA/S score of ≤4, respectively.1. Byfavo [package insert]. Indiana
Slide 131: Patients Rapidly Achieved Adequate Sedation with Quick Recovery
CONFIDENTIAL AND INTERNAL 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 131 Patients Rapidly Achieved an Adequate Level of Sedation for Procedure Start with a Quick Recovery Bronchoscopy, ASA I-III543210MOAA/S Score, Mean (95% CI)01020304050607080Minutes After Start of Study Medication (0=Fi
Slide 132: So What? Why Byfavo?
CONFIDENTIAL AND INTERNAL 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 132 So What..Why Byfavo? –Predictable effect reducing hemodynamic compromise–Reliable safetySedation without post-procedure neurologic dysfunction in at-risk patients–Safely administered by non-anesthesia clinicians–Pote
Slide 133: Byfavo Candidate Populations
CONFIDENTIAL AND INTERNAL 2022 Eagle Pharmaceuticals, Inc. All rights reserved. 133 Byfavo Candidate Populations –Short CV procedures: cardioversion, TEE, pacemaker battery change, etc. in fragile patients–GI, Pulmonary, Radiology sedation in at-risk patients (older, frail)–Bedside sedation (ED, PAC
Slide 134: Landiolol
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 134 134 Landiolol
Slide 135: Overview of Landiolol
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 135 135 Overviewof Landiolol: An Ultra-Short-Acting Intravenous β-adrenergic Blocker
Slide 136: Landiolol Overview: NDA Under Review by FDA
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 136 Landiolol Overview: NDA Under Review by FDA Ultra-short acting cardioselective beta1-blockerRapid rate control Supraventricular tachycardiaVentricular rateSimple intravenous dosingMultiple use settingsCritical/Intensive CarePerioperativeEmerg
Slide 137: Proposed Indications of Use
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 137 Proposed Indications of Use*Landiolol is an ultra-short-acting β1-antagonist with limited effect on blood pressure and inotropy1,2Proposed Indication3Short-term reduction of ventricular rate in patients with supraventricular tachycardia, incl
Slide 138: Landiolol Potentially Addresses an Important Unmet Clinical Need
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 138 Landiolol Potentially Addresses an Important Unmet Clinical NeedDesigned for potential use in acute-care patients in whom it is necessary to safely and rapidly reduce heart rate with limited effect in blood pressure and inotropy (e.g. patient
Slide 139: Landiolol Features
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 139 Landiolol Features Minimal negative inotropic action due to limited effect on the refractory period of the action potential in cardiomyocytes2 Limited effect on blood pressure due to pure S-enantiomer molecular structure2,3 Rapid onset of act
Slide 140: Landiolol Features
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 140 Landiolol Features Compatible in patients with respiratory disease (eg, asthma, COPD) due to high cardioselectivity (β1/β2-selectivity = 255:1) among β1 blockers1,4 Low volume of distribution (0.3-0.4 L/kg) leading to less distribution to tis
Slide 141: Comparison of Landiolol and Other Rate/Rhythm Control Agents
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 141 Comparison of Landiolol and Other Rate/Rhythm Control Agents MedicationOnset of ActionElimination Half-LifeDuration of Effectβ1:β2 RatioEffect on HR and BPBeta BlockersLandiolol1-31 min4 min15 min255HR ↓↓ BP →Esmolol1,4,52 min9 min10-20 min33
Slide 142: Landiolol Conclusions
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 142 Landiolol Conclusions Landiolol is intended to be a differentiated, ultra-short acting cardio-selective beta blocker that results in rapid control of ventricular rate Landiolol potentially addresses important unmet clinical needs If approved,
Slide 143: Question & Answer Panel
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 143 143 Question & Answer Panel
Slide 144: Thank You!
2022 Eagle Pharmaceuticals, Inc. All rights reserved. 144 144 144 2022 Eagle Pharmaceuticals, Inc. All rights reserved. Thank You!