Armata Pharmaceuticals, Inc. · AMEX:ARMP
Armata Pharmaceuticals — Technical Presentation (June 2019)
54 slides from Armata Pharmaceuticals's technical presentation, Jun 26, 2019
Slide 1: Key Opinion Leader Event: Phage-Based Therapeutics for Antimicrobial-Resistant Infections
Key Opinion Leader Event Phage - Based Therapeutics for the Treatment of Antimicrobial - Resistant Infections June 26, 2019 New York, NY
Slide 2: Forward-looking statements
2 I This presentation contains “forward - looking” statements that involve risks, uncertainties and assumptions . If the risks or uncertainties materialize or the assumptions prove incorrect, our results may differ materially from those expressed or implied by such forward - looking statements . All
Slide 3: Introduction
Introduction Todd R. Patrick Chief Executive Officer
Slide 4: Bacteriophages – A Primer
Bacteriophages – A Primer Magda Barbu, Ph.D. Senior Director, Synthetic Biology
Slide 5: Bacteriophages: ubiquitous natural predators of bacteria
5 I The most ubiquitous organisms on Earth Natural predators of bacteria – Bacteria - eater (“ phagein ” – to devour) Highly targeted Prior history as therapeutic agent – Antibiotics displaced phage use, drug - resistant threat revitalized phage use Bacteriophages Phage Micrograph Phage Plaques Sour
Slide 6: Phage Structural and Physiological Characteristics
6 I Phage Structural and Physiological Characteristics Phage Attacking B acteria Myoviridae Siphoviridae Podoviridae Source: Nat Rev Microbiol Vol 16, pp 760 – 773 (2018 ) Source: Dr. Graham Beards
Slide 7: Phage Recognize Specific Bacterial Surface Receptors
7 I Phage Recognize Specific Bacterial Surface Receptors Variety of Receptors Recognized Surface Adsorption T riggers DNA Injection Source: Pearson, UK Source: Nature 483, pp. 182 – 186
Slide 8: Mechanism of Action Distinct From Antibiotics
8 I Mechanism of Action Distinct From Antibiotics Infection Yields Progeny and Results in Bacterial Lysis Source: Prescott Harley Klein’s Microbiology, 7th Ed.
Slide 9: Antibiotics Displaced Phage Use; Drug Resistance Revitalized It
9 I Antibiotics Displaced Phage Use Emergence of Drug - Resistance has Revitalized Phage Use
Slide 10: Deadly Infections Successfully Treated With Phage
10 I Deadly Infections Successfully Treated With Phage
Slide 11: First Phage Therapy Center in US Signals Growing Acceptance
11 I First Phage Therapy Center in US Signals Growing Acceptance
Slide 12: Phage Therapy Now And In the Future
12 I Phage Therapy Now And In the Future Compelling Attributes of Phage • Life - changing outcomes in EIND cases – Sufficient proof to advance to formal clinical trials • Highly specific bactericidal agents – Minimal disruption of microbiome • Mechanism of action distinct from antibiotics • Replicat
Slide 13: Drug Discovery Approach to Engineered Phage Therapeutics
13 I Drug Discovery Approach to Engineered Phage Therapeutics Rapid Design - Build - Test Cycle Adapts Product to Medical Need Engineering Phage Chassis CMC Clinical Efficacy Phage Discovery Clinical Isolate Surveillance Pharmacology Lead Manufacturing Strain Engineering Bacterial Engineering
Slide 14: Improving Natural Phage Through Engineering
14 I Natural Synthetic 0 20 40 60 80 100 E r a d i c a t i o n ( % ) Synthetic Phage Product Candidate Improving Natural Phage Through Engineering Wider Host Range and Improved Growth Wide host range Synthetic Phage 7 68 Phage C Phage A Phage B 4 38 Phage Progenies Natural 70 Synthetic 122 Improved
Slide 15: Synthetic Biology Platform Facilitates Phage Drug Development
15 I Synthetic Biology Platform Facilitates Multiple Facets of Phage Drug Development Screening Test Rapid phage - based Dx Therapeutic Wide host range Improved pharmacology MODULAR & MULTIGENIC DESIGN BYPASSES EVOLVED RESISTANCE ADDRESSES GENETIC DIVERSITY HOST RANGE SYNTHETIC PRODUCTION CMC Engine
Slide 16: Bacteriophage Therapy for Serious Bacterial Infections: Why Now?
Bacteriophage Therapy for Serious Bacterial Infections: Why Now? Robert T. Schooley, MD Professor of Medicine University of California San Diego
Slide 17: Estimates of Burden of Antibacterial Resistance
World Health | Antimicrobial Resistance a Beka; Global Report on Surveillance 2014 Organization Estimates of Burden of Antibacterial Resistance European Union Thailand United States population 500m population 70m ‘Population 300m 25,000 deaths per year >38,000 deaths 23,000 deaths 2.5m extra hospita
Slide 18: 1917 paper at French Academy of Sciences
Paper presented at French Academy of Sciences, Sept. 3, 1917 (translated in Res. Micro. 158 :2007) Courtesy of Ryland Young, Texas A&M University 18
Slide 19: Arrowsmith: Sinclair Lewis
Arrowsmith: Sinclair Lewis 19
Slide 20: Bacteriophage Laboratory advertisement, Paris, 1936
advertisement for the Bacteriophage Laboratory, Paris, 1936 Courtesy of Ryland Young, Texas A&M University 20
Slide 21: The 1930s: A Fork in the Road
The 1930s: A Fork in the Road Western Medicine Russia and Former Soviet Republics 21
Slide 22: 1941: Second AMA report
1941: Second AMA report further discredits the “ d’Herelle ” phage theory 1934 Commissioned JAMA Report Courtesy of Ryland Young, Texas A&M University 22
Slide 23: No Paradigm-Changing Antibiotics Discovered for 20 Years
No Paradigm - Changing Antibiotics Have Been Discovered for 20 Years Antibiotic Resistance Described Antibiotic Deployed 23
Slide 24: A Colleague With Multidrug Resistant A. baumannii
A Colleague With Multidrug Resistant A. baumannii 24
Slide 25: 5000 10000 15000 20000 25000 30000 15-Jan 22-Jan 29-Jan 5-Feb 12-Feb 19-Feb 26-Feb 4-Mar
95 96 97 98 99 100 101 102 103 104 0 5000 10000 15000 20000 25000 30000 15-Jan 22-Jan 29-Jan 5-Feb 12-Feb 19-Feb 26-Feb 4-Mar 11-Mar T max (degrees F) White Blood Cell Count (per mm3) Date WBC Tmax B. thetaiotaomicron / Acinetobacter C. glabrata B. thetaiotaomicron Blood Peritoneal fluid 25
Slide 26: Newly Isolated Lytic Bacteriophages Active against Acinetobacter baumannii
OPEN ACCESS Freely availabe online ‘@PLOS | ove Characterization of Newly Isolated Lytic Bacteriophages Active against Acinetobacter baumannii Maia Merabishvili'***, Dieter Vandenheuvel’, Andrew M. Kropinski®®, Jan Mast’, Daniel De Vos", ert Verbeken', Jean-Paul Noben®, Rob Lavigne*, Mario Vaneechou
Slide 27: The Phage Hunt
The Phage Hunt Texas A&M University Ryland Young, PhD. US Naval Biomedical Defense Command Theron Hamilton, PhD 4 - Phage Cocktail 4 - Phage Cocktail University of California San Diego A. baumannii 27
Slide 28: Intravenous Phage Administration
Intravenous Phage Administration US Navy Cocktail March 17, 2016 11:00 am ~10 9 pfu administered as IV push dose over 2 minutes 28
Slide 29: Thomas Patterson and Theron Hamilton, April 2018
Thomas Patterson and Theron Hamilton, April 2018 29
Slide 30: Save Her Husband From a Deadly Superbug
SAVE HER USBAND FRO ADEAD Y SUPERBUG
Slide 31: Phage Therapeutics at UCSD: Additional Experience
Phage Therapeutics at UCSD: Additional Experience Patient # Age Underlying Condition Organism Outcome 1 67 Disseminated infection A. baumannii Treatment success 2 67 Bilateral Lung Transplant P. aeruginosa Treatment success 3 74 Open Head Trauma A. baumannii Inadequate trial 4 23 CF; Pre Lung Transp
Slide 32: Treatment of an Aortic Graft Prosthesis Infected with P. aeruginosa
Treatment of an Aortic Graft Prosthesis Chronically Infected with P. aeruginosa Chan, et. al. Evol Med Pub Health, 2018 Chan, et, al. Sci Rep 6, 2017 32
Slide 33: Adjunctive bacteriophage therapy for severe Staphylococcal sepsis
, > es Insti The, Las ce NSW@HEALTH uote Adjunctive bacteriophage therapy for severe Staphylococcal sepsis jon.iredell@sydney.edu.au Westmead Hospital Sydney Medical School ID week/ IDSA October 2018 ID Week Abstract 1642
Slide 34: Phage Therapy Day Outcomes
Phage Therapy - 28 Day Outcomes Age Gender WMP0XX Indication(s) Duration of phage therapy Doses IV Clinical outcome at EoT Apache II 28 days mortality 65 M 001 PVE 14 days BID IV 28 success 18 No 47 M 003 PVE 3 days BID IV 6 failure 25 Yes, uncontrolled septic shock 43 F 004 IE (Right) 14 days BID I
Slide 35: Engineered bacteriophages for disseminated drug-resistant M. abscessus
BRIEF COMMUNICATIO mature,, . medicine 437-2 Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus Rebekah M. Dedrick’*, Carlos A. Guerrero-Bustamante"*, Rebecca A. Garlena’, Daniel A. Russell’, Katrina Ford?, Kathryn Harris?, Kimberly C. Gil
Slide 36: Phage Hunt Science Education Alliance
Phage Hunt Science Education Alliance - Phages Hunters Advancing Genomics and Evolutionary Science 36
Slide 37: Bacteriophage Recombineering of Electroporated DNA (BRED)
Bacteriophage Recombineering of Electroporated DNA (BRED) • Co - electroporate phage DNA and DNA targeting sequence into M. Smegmatis expressing the RecE / RecT - like proteins gp60 and gp61 of mycobacteriophage Che9c Marinelli LJ PLoS One . 2008; 3(12): e3957 37
Slide 38: Cutaneous Lesions
Cutaneous Lesions +) o]<|e| Before treatment Post treatment ry
Slide 39: Contemporary Phage Therapy: Lessons Learned from EIND Experiences
Contemporary Phage Therapy: Lessons Learned from EIND Experiences • Safety – With current technologies there are no significant concerns regarding the safety of parenteral administration – Regulatory agencies are quite comfortable with safety profiles including the administration of genetically alte
Slide 40: Where Do We Go From Here?
Where Do We Go From Here? Execute a series of rigorously designed prospective clinical trials using traditional approaches that would be used to evaluate any new antimicrobial agent 40
Slide 41: Bacteriophage Therapy in 2019: What Has Changed Since 1917?
Bacteriophage Therapy in 2019 What has Changed Since 1917? • Much better understanding of issues related to host range • Major improvements in phage characterization and selection technologies (currently phenotypic - > potentially genotypic later) • Much better technology for expanding and preparing
Slide 42: Moving Beyond Environmental Phages
Moving Beyond Environmental Phages Fully synthetic phages? Rigorous Clinical and Translational Research What are the Shortcomings? Not sufficiently Lytic? enhance lysins Rapid emergence of resistance? Broaden host range Concerns about lysogeny? Delete integrase repressor (or other) genes Genetic eng
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Slide 44: R&D Update
R&D Update Brian Varnum, Ph.D. President and Chief Development Officer
Slide 45: Pipeline: Multiple Opportunities for Value Creation
45 I Pipeline Multiple Opportunities for Value Creation Pathogen Indications Discovery Preclinical Phase 1 Phase 2 Staphylococcus aureus Bacteremia Pseudomonas aeruginosa Respiratory Undisclosed Undisclosed Partnered AP - SA01 Phage libraries to address market expansion and new indications
Slide 46: AP-SA01 Phage Product Candidate Targeting S. aureus
46 I AP - SA01 Phage Product Candidate Targeting S. aureus Drug product 3 phages Covers >95% of S. aureus clinical isolates, including multidrug - resistant isolates Human dosing (US FDA: EIND; Aust TGA: SAS) 15 patients with serious infections not responding to antibiotics • Bacteremia, endocarditi
Slide 47: AP-SA01: Regulatory and Clinical Status
47 I Advanced Through Pre - IND Meeting • Highlighted prior human exposure under expanded access programs in U.S. and Australia • General agreement on proposed trial designs (Phase 1/2) • Nonclinical data not required; in line with FDA’s flexible approach to non - traditional antimicrobials Phase 1/
Slide 48: S. aureus Bacteremia
48 I S. aureus Bacteremia • 1.5 million Americans develop bacteremia each year resulting in ~250,000 deaths 1 • 1 in 3 patients who die in hospital have bacteremia 1 • The most costly condition treated at U.S. hospitals; ~$24 billion annually 2 • S. aureus is the second most common pathogen associat
Slide 49: Pseudomonas Phage Respiratory Development Strategy
49 I Pseudomonas Phage Respiratory Development Strategy Significant Medical Need and Synergy With Existing S. aureus Phage Product Pseudomonas aeruginosa • Covers ~20% of hospitalized pneumonia • Present in ~70% of chronic CF patients over age 25 – Major predictor of morbidity, mortality Staphylococ
Slide 50: Pseudomonas Phage Product Candidate
50 I Pseudomonas Phage Product Candidate Phage discovery effort provide basis for engineering Phage families with attractive attributes identified Cocktails developed for pneumonia and cystic fibrosis Engineer super fit phage Incorporating best attributes from a family Improved bactericidal and biof
Slide 51: Pseudomonas Phage Production and Formulation
51 I • Liquid formulation for first - in - human trial – Suitable for IV and inhalation • Successful manufacturing of first 2 Pseudomonas phage – GMP lots at intended Phase 1 scale Pseudomonas Phage Production and Formulation Utilizing Armata’s Proprietary Phage - Specific GMP Test Specification Pha
Slide 52: Anticipated Milestones 2019/2020
52 I AP - SA01 • Initiate Phase 1/2 clinical study in bacteremia Pseudomonas phage product candidate • Conduct Pre - IND meeting and file IND • Initiate first - in - human clinical study Anticipated Milestones 2019/2020
Slide 53: Investment Highlights
53 I Investment Highlights A World - Leader in Phage Therapeutics Lead candidate, AP - SA01, positioned to enter clinical development Natural phage discovery and synthetic biology yield robust pipeline Merck partnership to develop proprietary synthetic phage to target an undisclosed infectious disea
Slide 54: Thank You!
ARMATA PHARMACEUTICALS Thank You! PURPOSEFUL @ PRECISE ¢ POWERFUL
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