Atyr Pharma, Inc. · NASDAQ:ATYR
Atyr Pharma — Investor Presentation (November 2016)
39 slides from Atyr Pharma's investor presentation, Nov 7, 2016
Slide 1: New Hope For Severe Rare Muscle & Lung Disease Patients
New Hope For Severe Rare Muscle & Lung Disease Patients Building a New Class of Medicines Physiocrine Based Therapeutics To Promote Tissue Homeostasis Corporate Presentation November 2016
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: aTyr Highlights
1st Resokine pathway agonist muscular dystrophy trial completed Potential activity signals in FSHD 3 ongoing trials readout expected in December 2016 2nd Resokine agonist (iMod.Fc) for lung disease clinical trials in 2017 Building franchises in rare diseases influenced by an immune component Treatin
Slide 4: aTyr Pipeline
Resolaris (ATYR1940) Adult FSHD* Early Onset FSHD Adult LGMD2B* iMod.Fc (ATYR1923) Rare Lung Diseases Physiocrine Research Harnessing the Power of Physiocrines for Patients 1st in class candidates for rare diseases with an immune or fibrotic component Programs aTyr Pipeline Phase 1 Phase 2/3 Phase 1
Slide 5: Potential of Physiocrine Proteins
Potential of Physiocrine Proteins Discovery of a New Class of Proteins from Alternative Splicing of Ancient Genes New classes of biology have led to meaningful medicines TNF Inhibitors (Humira® WW sales over $14B in 2015) Complement inhibitors (Soliris® net product sales over $2.6B in 2015) Insulins
Slide 6: Pioneering New Biology for Meaningful Medicines
Nature 2015 Science 2014 Nature 2013 Nature 2010 Science 1999 Pioneering New Biology for Meaningful Medicines Immune Mediated Disease Strategy Over 300 proteins involved in physiological pathways Potential therapeutics for tissue-by-tissue homeostasis Over 80 issued or allowed patents Focused on hom
Slide 7: Evolution of Homeostasis & Physiocrines
Closed Tissue Homeostasis Complex Tissue Homeostasis Open Tissue Homeostasis Evolution of Homeostasis & Physiocrines Physiocrine hypothesis: physiological modulation from primordial tissue homeostasis Conserved Physiocrine domain structures Cellular Homeostasis Fungi Nematodes Arthropods Vertebrates
Slide 8: Physiocrine Modulation of Specific Systems
Physiocrine Modulation of Specific Systems Physiocrine Orchestration of Homeostasis Vascular Regeneration (stem cells) Immune Remodeling/Fibrosis Physiocrine Proteins Lung Muscle
Slide 9: Harnessing the Resokine Pathway to Treat Multiple Rare Muscle Diseases
Harnessing the Resokine* Pathway Natural Pathway From Skeletal Muscle to Treat Multiple Rare Muscle Diseases *Resokine: for resolution of immune activity
Slide 10: Resokine Pathway Paradigm
Resokine Pathway Paradigm 1st Physiocrine Pathway Modulated in the Clinic Resokine Pathway An extracellular homeostatic pathway that sets T cell responses Arising from histidine aminoacyl tRNA synthetase (HARS) gene Resokine pathway disruption or insufficiency leads to inappropriate immune responses
Slide 11: Model of Resokine Pathway in skeletal muscle
Our Hypothesis - Potential of Resolaris: Model of Resokine Pathway In skeletal muscle health and disease Normal damage (i.e. exercise) Immune cells to treat damaged muscle Acute immune cell invasion/residence Chronic damage (myopathies) Need to increase circulating free Resokine Therapeutic Resolari
Slide 12: Resokine Release From Differentiating Myoblasts
Resokine Release From Differentiating Myoblasts Linking the Resokine pathway to muscle biology Resokine (Western Blot) (~100pM Resokine) Antibodies sufficient to block 100pM Resokine block >50% of differentiation (slower) Pre-Clinical Human myoblasts were isolated from a healthy volunteer properly c
Slide 13: IFN-g Reduces Resokine Release & Myotube Differentiation
IFN-g Reduces Resokine Release & Myotube Differentiation *p<0.05, **p<0.01, ***p<0.001, n=6 (ELISA) or 30 (10 images/well´3 wells) Human myoblasts were isolated from a healthy volunteer properly consented and not in a clinical trial Myotube differentiation Resokine Released from Myotubes Cell viabil
Slide 14: Steroid Treatment Decreases Muscle Growth & Resokine Release
Steroid Treatment Decreases Muscle Growth & Resokine Release Control 5 50 100 10 Myotube (myosin)/Nuclei (Hoechst), Images at 10× magnification; Differentiation Day 0-6 500 Prednisolone (ng/mL) Pre-Clinical Human myoblasts were isolated from a healthy volunteer properly consented and not in a clinic
Slide 15: T Cell Release of Granzyme B Can Cause Muscle Damage
T Cell Release of Granzyme B Can Cause Muscle Damage Excessive immune cell invasion contributes to a disease immune phenotype Diseased Muscle Cell Death Granzyme B expressing cells cause muscle cell damage Immune cell infiltration Boivin et al., Lab Invest., 2009
Slide 16: Treating Immune Cell Invasion in Skeletal Muscle
ê Cytokines, ê T-cells and ê Monocytes with Resolaris administration aTyr unpublished data Treating Immune Cell Invasion in Skeletal Muscle One week of therapeutic treatment in two week Statin myopathy model Control Statin days 1-14 (toxic dose) 0.3 mg/kg Resolaris days 7-14 Statin days 1-14 1.0 mg/
Slide 17: Resokine Pathway Linked to Rare Genetic Muscle Diseases
Resokine Pathway Linked to Rare Genetic Muscle Diseases Aberrant proteins, immune invasion & deteriorated muscles Genetic mutation Frisullo et al., J. Clin. Immunol., 2011 Gallardo et al. Neurology, 2001 Flanigan et al. Human Gene Therapy, 2013 Immune cell infiltration Facioscapulohumeral Muscular D
Slide 18: Resolaris: One Product, Multiple Rare Diseases
Resolaris: One Product, Multiple Rare Diseases Promise for severely afflicted myopathy patients Market Opportunity FSHD: Average prevalence rates of FSHD are approximately 1/17,000. Applying this rate to the US population based on recent census data equals approximately 19,000. LGMD: 16,000 cases es
Slide 19: Resolaris Clinical Development
Resolaris Clinical Development Potential New Therapy for Patients with Rare Muscle Diseases
Slide 20: Clinical Strategy for Resolaris in Skeletal Muscle
1st Physiocrine based therapeutic in clinic To promote muscle homeostasis Focus on Rare Myopathies with an Immune Component (RMIC) 003, 004 & 005 data readouts expected in December 2016 Clinical Strategy for Resolaris in Skeletal Muscle Staging rare muscle disease indications Resolaris Phase 1b/2 Tr
Slide 21: Facioscapulohumeral Muscular Dystrophy (FSHD)
Facioscapulohumeral Muscular Dystrophy (FSHD) A progressive, debilitating muscular disease Pathology Dominant/spontaneous toxic gain of function (↑ Dux4) Immune infiltration by activated T cells 1, primarily CD8+ Defects in biochemical/physical/structural muscle components leading to tissue death St
Slide 22: Limb-Girdle Muscular Dystrophy 2B (LGMD2B)
Clinical Development Limb-Girdle Muscular Dystrophy 2B (LGMD2B) A severe muscle disease with a genetic loss of function Pathology Toxic loss of function mutation (dysferlin) Immune infiltrates consisting of CD4+, CD8+ and macrophages1 Muscle group progression Standard of care No therapeutic treatmen
Slide 23: Adult FSHD (002) Trial
Adult FSHD (002) Trial Clinical Development Evaluate Safety and Tolerability: Build safety dossier for Resolaris Generally well-tolerated at doses tested* Evaluate Potential Activity Assessments: Manual Muscle Test (MMT): Validated endpoint for functional strength Individualized Neuromuscular Qualit
Slide 24: Adult FSHD (002) INQoL Results
% Responder Analysis: Absolute Disease Progression by Patient: INQoL: Validated Patient Reported Outcome Global systematic assessment used in clinical studies and trials (to test for increased disease burden) Encouraging Activity Signals: 5 of 6 patients in cohort 3 (3 mg/kg of Resolaris over 3 mont
Slide 25: Manual Muscle Testing: Validated Endpoint for Functional Strength
Manual Muscle Testing (MMT): Validated Endpoint for Functional Strength Encouraging Activity Signals: A trend for improvement was observed compared to placebo, especially in upper limbs 100% patients with an improved MMT score had an improved INQoL score Resolaris 3 Month Adult FSHD (002) MMT Result
Slide 26: Adult FSHD (002) MMT Results Placebo
Placebo 3 Month Adult FSHD (002) MMT Results Placebo Patient’s MMT results Clinical Development Non-impaired tested muscle Impaired muscles Improvement relative to baseline Worsening relative to baseline Manual Muscle Testing (MMT): All patients on placebo, at 3 months, did not show trends for impro
Slide 27: Modeling Progression of Loss of Muscle Function
Modeling Progression of Loss of Muscle Function Observing Improvement vs. Slowing Progression Time Muscle Function (Δ baseline) 0 Untreated Treated reduction in loss of function A Improvement to slower progression Δ small Δ medium Δ large Δ large Treated Early improvement B Improvement to plateau No
Slide 28: Resolaris Clinical Trial Summary
Resolaris Clinical Trial Summary 2016 Completion of Exploratory Trials Clinical Development Trial Indication(s) Patients Highest Dose Design Data Timing 002 Adult FSHD 3 dose cohorts (n=20 Total) 3mg/kg weekly Placebo controlled, Double blinded; Interpatient Dose Escalation Announced 1Q 2016 003 Ear
Slide 29: iMod.Fc the First Engineered Physiocrine Agonist
iMod.Fc the First Engineered Physiocrine Agonist of the Resokine Pathway to Treat Multiple Lung Diseases
Slide 30: Discovery of the Resokine iMod Domain
Discovery of the Resokine iMod Domain iMod.Fc Program Rodent model of severe immune cell activity induced by administration of trinitrobenzene sulfonic acid (TNBS) Animals administered the iMod domain survived longer than those given either the vehicle control phosphate buffer solution (PBS) or Bude
Slide 31: Blockade of Pathway in Muscle & Lung Disease
Blockade of Pathway in Muscle & Lung Disease Anti-Synthetase syndrome provides evidence in humans of Resokine pathway Immune cell balance Normal Immune cell invasion Jo-1 Patients 85% of Jo-1 patients have ILD* Patients start normal 18 of 18 Jo-1 patients tested positive for Antibodies to iMod Domai
Slide 32: Interstitial Lung Disease Overview
Interstitial Lung Disease Overview iMod.Fc Program Source: Applied Chest Imaging Laboratory – Harvard University Share similar clinical, radiographic, physiologic and pathologic manifestations Well over 100 different forms of ILD have been described, most of which involve an immune and/or fibrotic c
Slide 33: iMod.Fc Leverages Knowledge of Splice Variant Biology
iMod (100% identical to human wildtype) iMod.Fc Leverages Knowledge of Splice Variant Biology Harnessing the iMod. Domain Resokine Parent Protein Physiocrine Region Immuno-modulatory (iMod domain) Splice Variant of parent gene iMod.Fc Program Fc (human antibody) Increase exposure Engineered Physiocr
Slide 34: iMod.Fc an Engineered Physiocrine for Lung Disease
iMod.Fc an Engineered Physiocrine for Lung Disease New Target Product Profile (TPP) and new molecule to open up lung indications Preclinical Status and Goals Activity in industry proven model of IPF (approved drugs: Pirfenidone & Nintedanib) Immuno- & fibro- modulatory activity Successful E. coli pr
Slide 35: Two iMod.Fc Doses Outperform Pirfenidone Doses
iMod.Fc Program Two iMod.Fc Doses Outperform 28 Pirfenidone Doses IPF Model Activity *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 (%)* Vehicle TGF β Ab 3mg/kg IP QOD D0-D 2
Slide 36: Building a New Class of Therapeutics
Building a New Class of Therapeutics Foundation for the Future
Slide 37: Leadership Team
Leadership Team Experienced Industry Veterans John Mendlein, Ph.D. Chief Executive Officer John Blake, CPA VP, Finance Holly D. Chrzanowski VP, Enterprise Talent and Organization Sanuj Ravindran, M.D. Chief Business Officer Ashraf Amanullah, Ph.D. VP, Manufacturing Andrew Cubitt, Ph.D. VP, Product P
Slide 38: aTyr Milestones: Upcoming Catalysts and Financial Guidance
Early Onset FSHD (003) Trial – Data from first 4 patients in Stage 1 LGMD2B/FSHD (004) Trial – Top-line results from 10 LGMD2B, 8 FSHD patients First Extension (005) Trial – Update from these patients December 2016* data readout to select best advancement path for Resolaris iMod.Fc program on track
Slide 39: Revolutionary Drugs Leveraging New Biology
Revolutionary Drugs Leveraging New Biology Opportunity to own a new class of meaningful medicines Pioneer New biology Insulin First product 1923 1968 1989 Coagulation factors Erythropoietin Enzyme replacement therapy TNF pathway VEGF pathway Complement pathway Physiocrine pathways 1990 1998 2004 200