Atyr Pharma, Inc. · NASDAQ:ATYR
Atyr Pharma — American Thoracic Society International Conference 2017
55 slides from Atyr Pharma's conference presentation, May 23, 2017
Slide 1: Interstitial Lung Disease and the Immune System: Introduction to the iMod.Fc Program
Interstitial Lung Disease and the Immune System Introduction to the iMod.Fc Program aTyr Pharma Investor and Analyst ILD and iMod.Fc Educational Webinar American Thoracic Society International Conference May 23, 2017 Exhibit 99.3
Slide 2: Forward-Looking Statements
Forward-Looking Statements The following slides and any accompanying oral presentation contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as “may,” “might,” “will,” “should,” “expect,”
Slide 3: Agenda
Agenda Introduction Mark Johnson, Senior Director Investor Relations, aTyr Pharma Resokine Pathway Sanuj Ravindran, MD, Chief Business Officer, aTyr Pharma ILD Overview Steven Nathan, MD, Director of the Advanced Lung Disease Program and Medical Director of the Lung Transplant Program at Inova Fairf
Slide 4: New Immunological Pathway: Resokine
Evolved from Cellular Homeostasis Genes over 400 Million Years New Immunological Pathway: Resokine
Slide 5: Resokine: Potential Key Regulator of Homeostasis
Resokine: Potential Key Regulator of Homeostasis Evolved with System Complexity Nature 2015 Science 2014 Nature 2013 Nature 2010 Science 1999 Closed Tissue Homeostasis Complex Tissue Homeostasis Open Tissue Homeostasis Conserved Physiocrine domain structures Cellular Homeostasis Protein Synthesis Fu
Slide 6: LIFE's Therapeutic Paradigm
LIFE’s Therapeutic Paradigm Homeostasis Disease Healthier Patients Resokine insufficiency Resokine agonists
Slide 7: Disrupting the Resokine Pathway Promotes ILD
Disease antibodies Homeostasis Imbalance 100% (18 of 18) anti-synthetase syndrome patients tested positive for antibodies for Resokine proteins Diseased Lung Healthy lung ↑ Immune cell Invasion / activity Lung Characteristics Increased T cells in BALF Decreased CD4/CD8 ratio Histology ranges from NS
Slide 8: Free Resokine Pathway in Anti-Synthetase Patients Diminished
Free Resokine Pathway in Anti-Synthetase Patients Diminished Unpublished data from aTyr and collaborator Statistics: Mann-Whitney test 69% at or below limit of detection >85% of patients develop Interstitial Lung Disease (ILD)
Slide 9: Agonists of the Resokine Pathway in Immune Driven Models
Lung Bleomycin Induced Lung Fibrosis Th17/CD4 Agonists of the Resokine Pathway in Immune Driven Models Balancing the immune response to tissue insults In vivo administration of Resokine proteins to animal models of T cell driven disease states. Cell type indicates type of cells involved but may not
Slide 10: Three Distinct Therapeutic Modalities
Three Distinct Therapeutic Modalities Harnessing Knowledge of New Immunological Pathways TPP = Target Product Profile ILD = Interstitial Lung Disease; IPF = Idiopathic Pulmonary Fibrosis iMod domain Human Fc domain of an antibody Resolaris Recombinant version of naturally occurring Resokine iMod.Fc
Slide 11: Overview of Interstitial Lung Disease
Overview of Interstitial Lung Disease Steven Nathan, MD Medical Director, Advanced Lung Disease & Transplant Program Inova Fairfax Hospital Falls Church, Virginia USA Inova Advanced Lung Disease & Transplant Program
Slide 12: Disclosures: Steven Nathan, MD
Disclosures: Steven Nathan, MD Personal financial relationships with commercial interests relevant to this presentation during the past 12 months: Consultant: aTyr Pharma, Bayer Pharmaceuticals, Boerhinger-Ingelheim, Genentech-Roche, Gilead, Third Pole, United Therapeutics. Speaker’s Bureau: Bayer,
Slide 13: Association between Interstitial Lung Abnormalities and All-cause Mortality
Association between Interstitial Lung Abnormalities and All-cause Mortality JAMA 2016;315:672-681 Blue segments of y-axes indicate mortality range from 0% to 20%. P values included in each panel are associated with hazard ratios (HRs [95% CIs]) from the adjusted Cox proportional hazards model includ
Slide 14: Association between Interstitial Lung Abnormalities and All-cause Mortality
JAMA 2016;315:672-681 Blue segments of y-axes indicate mortality range from 0% to 20%. P values included in each panel are associated with hazard ratios (HRs [95% CIs]) from the adjusted Cox proportional hazards model including adjustments for age, sex, race, body mass index, pack-years of smoking,
Slide 15: Categories of Interstitial Lung Disease
Category Diseases Sub-categories/examples Idiopathic Idiopathic Interstitial Pneumonias (IIPs) IPF NSIP Unclassifiable COP RB-ILD DIP AIP LIP PPFE Sarcoidosis Amyloidosis Lymphangiolyomyomatosis PLCH, Eosinophilic pneumonia. Neurofibromatosis, DAH Immunologic Connective Tissue Disorders Inhalational
Slide 16: Spectrum of ILD followed by Inova ALD Program
Spectrum of ILD followed by Inova ALD Program (N=657) 11.6% 8.6% 13.3% 13.3%
Slide 17: SLE MCTD SCL
SLE MCTD SCL SCL
Slide 18: Prevalence of ILD in CTD
Prevalence of ILD in CTD 1,600 deaths in USA annually 25% of all ILD deaths 2% of respiratory deaths RA: 15-20% PM/DM: 5-20% SLE: 5-18% Scleroderma: 50-70% Sjogrens:5-40%
Slide 19: Approach to the Treatment of CTD-ILD
Adapted from Chartrand, Fischer. Sarc Vasc;2015:32:2-21 APPROACH TO THE TREATMENT OF CTD-ILD Disease impairment Subjective: Objective: -functional capacity - 6MWT -dypsnea - HRCT/PFT Mild and non-progressive Clinically non-significant ILD Moderate-severe and/or progressive Clinically significant ILD
Slide 20: Chronic Hypersensitivity Pneumonitis
Chronic Hypersensitivity Pneumonitis Birds, hot tubs, mold, “idiopathic” Insidious in onset May mimic UIP Utility of HP panel uncertain Inspiratory and expiratory CT - air-trapping or “mosaism”
Slide 21: Slide 21
Slide 22: Chronic HP: Pathology
Chronic HP: Pathology
Slide 23: Sarcoidosis: Systemic Disease
Sarcoidosis: Systemic Disease A multisystem disease Unknown etiology Granulomatous disorder Affects individuals world wide Most often affects young adults Prevalence of 10-20 per 100,000 population Incidence is unknown Varies among geographical groups Lifetime incidence in blacks is 2.4%, in whites
Slide 24: Non-Caseating Granulomas
Non-Caseating Granulomas
Slide 25: Slide 25
Slide 26: Treatment of Sarcoidosis
Treatment of Sarcoidosis Not all patients require therapy for sarcoidosis About half never get treated Pulmonary, ocular, neuro, cardiac, hypercalcemia Treatment strategies are different based on phase of disease Acute Chronic Refractory Steroids, methotrexate, azathioprine, mycophenolate, leflunomi
Slide 27: Revised ATS/ERS Idiopathic Interstitial Pneumonia Classification
Revised ATS/ERS Idiopathic Interstitial Pneumonia Classification Major Idiopathic Interstitial Pneumonias Idiopathic Pulmonary Fibrosis Idiopathic nonspecific interstitial pneumonia Respiratory bronchiolitis interstitial lung disease Desquamative interstitial pneumonia Cryptogenic organizing pneumon
Slide 28: NSIP
NSIP
Slide 29: RML – adjacent mild cellular IP
RML – adjacent mild cellular IP
Slide 30: RLL — venulitis
RLL — venulitis y, Woh ae e ra es ) ef ae Ear te Pix — hn: . Fhe Shien Ss 6 se TE CAS BRS seine VEN Siege S sage &, a! So 4, oe hNaee Ue ’ Pot ey a , foe! - ise 077 o= E53 @
Slide 31: Current Definition of IPF
Current Definition of IPF Specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause Occurring primarily in older adults Limited to the lungs ATS/ERS/JRS/ALAT consensus statement Am J Respir Crit Care Med. 2011;183:788-824
Slide 32: Increasing Prevalence of IPF
1. Raghu G et al. Lancet Respir Med. 2014;2:566-572 Medicare Beneficiaries Age ≥65 y Median survival = 3.8 y Factors associated with lower survival Age, index year, male gender Increasing Prevalence of IPF
Slide 33: IPF: Survival at the Turn of the Century
IPF: Survival at the Turn of the Century 2000-2009 (N=521) Median survival: 36 & 42 months Chest 2011;140:221-229
Slide 34: Mortality Rate High in IPF
Mortality Rate High in IPF a + 5 year survival rate (USA) is only 20-40%" + Worse survival rates than many common cancers 20 1 8-year survival (%) 40 60 | 1 Reprinted with permission from Vancheri et al., Eur Respir J 2010" in Eur Respir , omissions or inaccuracies, or for any consequences /09031936
Slide 35: Pathology: UIP Pattern
Pathology: UIP Pattern
Slide 36: T-cells in IPF Lungs
T-cells in IPF Lungs. Immunohistochemical staining shows that abnormal CD3+ T-cell infiltrates (black cells near arrow) in lungs of IPF patients with usual interstitial pneumonia are distributed heterogeneously, and are often especially prominent in proximity to fibroproliferative foci (star). These
Slide 37: P=0.001 Collaborators. N Engl J Med. 2012;366:1968-1977. N Engl J Med 2012;366:1968-77
P=0.001 Collaborators. N Engl J Med. 2012;366:1968-1977. N Engl J Med 2012;366:1968-77
Slide 38: Seismic Treatment Paradigm Shift
IPF…Rx with immunosuppressive therapies Other ILD…Rx with immunosuppressive therapies IPF, IIPs and CTD-ILD= historic parallel treatment paths IPF: say “goodbye” to AZA + Pred IPF: say “hello” to the antifibrotics TREATMENT PARADIGM SHIFT SEISMIC
Slide 39: King TE Jr., et al. N Engl J Med. 2014;370:2083-2092. Richeldi L, et al.
King TE Jr., et al. N Engl J Med. 2014;370:2083-2092. Richeldi L, et al. N Engl J Med. 2014;370:2071-2082.
Slide 40: Interstitial Lung Disease: A Spectrum
Fibrosis CTD-ILD occult CTD +serologies IPF Interstitial pneumonia with autoimmune features Systemic sclerosis sine scleroderma Amyopathic ILD Rheumatoid arthritis Systemic sclerosis PM/DM SLE INTERSTITIAL LUNG DISEASE: A SPECTRUM Inflammation
Slide 41: Interstitial Lung Disease: A Spectrum
Fibrosis CTD-ILD occult CTD +serologies IPF INTERSTITIAL LUNG DISEASE: A SPECTRUM Inflammation SARCOIDOSIS Non-Specific Interstitial Pneumonia Chronic Hypersensitivity Pneumonia
Slide 42: Same Case with Differing Pathology
Same Case with Differing Pathology
Slide 43: Disease Evolution
Disease Evolution Time Biochemical + pathways + cellular events Pathological alterations Radiographic changes Symptoms Physiologic alterations Clinical Syndrome
Slide 44: Disease Evolution
Disease Evolution Time Biochemical + pathways + cellular events Pathological alterations Physiologic alterations Symptoms Radiographic signs Clinical Syndrome Fibrosis and honeycombing Fibroblastic foci granulomas Focus of OP Inflammation
Slide 45: CTD-ILD: Conceptual Framework for Future Therapeutic Approach
Progression of interstitial process Therapy ImmunoRx ?antifibrotic* ?PAH therapy * CTD-ILD: conceptual framework for future therapeutic approach *not recommended, await RCT evidence Acute exacerbation ?role and timing of biologics, IVIG, plasmapheresis*
Slide 46: Adult Lung Transplants Kaplan-Meier Survival by Diagnosis
Adult Lung Transplants Kaplan-Meier Survival by Diagnosis (Transplants: January 1990 – June 2012) 2014 JHLT. 2014 Oct; 33(10): 1009-1024 http://www.ishlt.org/registries/slides.asp?slides=heartLungRegistry Accessed 9/15/2015
Slide 47: Lung Physiocrine Engineered to Treat Multiple Pulmonary Diseases
Lung Physiocrine Engineered to Treat Multiple Pulmonary Diseases iMod.Fc Program
Slide 48: Resokine Promotes Lung Homeostasis
Resokine Promotes Lung Homeostasis Epithelial damage IL-13, TGFβ, TNF, IL-1β Resokine agonist therapy Pharmacologic restoration of tissue homeostasis and resolution of immune engagement Natural restoration of tissue homeostasis and resolution of immune engagement Perturbation Injury Infection Geneti
Slide 49: iMod.Fc Overview
iMod.Fc Overview Opportunity for Lung Patients iMod domain Fc domain of an antibody Engineered Physiocrine iMod.Fc iMod domain: Resokine splice variant relatively more expressed in lung than other tissues Fc domain: increased exposure to potentially enable once-monthly dosing in humans Engineered re
Slide 50: iMod Domain in Lung
iMod Domain in Lung Splice Variant Express Data for iMod in Lung Splice variant for the iMod domain is relatively more expressed in lung than other tissues Zhou et al. The Journal of Biological Chemistry 2014
Slide 51: Functional Knockout of Resokine Pathway Increases T Cell Invasion
Functional Knockout of Resokine Pathway Increases T Cell Invasion Post Disease Induction Rodent functional knockout inducing idiopathic pulmonary disease using Bleomycin * p < .05
Slide 52: Functional Knockout of Resokine Pathway Increases T Cell Invasion
Functional Knockout of Resokine Pathway Increases T Cell Invasion Post Disease Induction Rodent functional knockout inducing idiopathic pulmonary disease using Bleomycin * p < .05
Slide 53: iMod.Fc Outperforms Current Treatments
iMod.Fc (Resokine Pathway) Outperforms Current Treatments Established Rodent Model for Idiopathic Pulmonary Fibrosis (IPF) *The Ashcroft scale for the evaluation of bleomycin-induced lung fibrosis is the analysis of stained histological samples by visual assessment Improvement in Ashcroft Score (%)*
Slide 54: iMod.Fc: Status and 2017 Development Goals
Biomarker/MOA: Introduce mechanistic/PD assay GMP Manufacturing: Complete initial clinical trial supply IND Enabling: Initiate preclinical safety studies Activity in industry proven model of IPF (approved drugs Pirfenidone & Nintedanib) GMP manufacturing kicked off Rat/non-human primate non-GLP safe
Slide 55: Questions?
Questions?
aTyr Pharma — American Thoracic Society International Conference 2017 on 6ix