Atyr Pharma, Inc. · NASDAQ:ATYR
Atyr Pharma — Investor Presentation (January 2016)
35 slides from Atyr Pharma's investor presentation, Jan 11, 2016
Slide 1: New Promise for Rare Disease Patients with Immune & Fibrotic Pathologies
New Promise for Rare Disease Patients with Immune & Fibrotic Pathologies January 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
Tissue Restoration in Rare Diseases of Muscle & Lung Strong Team, Results Driven Physiocrine* Disruptive Opportunity Resolaris: One Protein Many Rare Diseases Autonomous Pipeline New biology, new therapeutic intervention points Natural modulators of immune & fibrotic pathways Immune/fibrotic nexus i
Slide 4: Resolaris Improves Muscle & Lung Immune/Fibrotic Components
Two weeks of treatment in Statin myopathy & Bleomycin IPF* models Resolaris Improves Muscle & Lung Immune/Fibrotic Components First Program Resolaris *Idiopathic Pulmonary Fibrosis (“IPF”), a subset of Interstitial Lung Disease (“ILD”)
Slide 5: Immuno/Fibrosis Modulation Pipeline
1st in class candidates for rare diseases with an immune or fibrotic component Immuno/Fibrosis Modulation Pipeline 1 Facioscapulohumeral Muscular Dystrophy 2 Limb-girdle Muscular Dystrophy 3 Interstitial Lung Disease Therapeutic Focus Preclinical Rights Phase 1 Phase 1b/2 Discovery Paradigm shift In
Slide 6: Leadership Team
Leadership Team Experienced Industry Veterans Melissa Ashlock, M.D. SVP, Translational Medicine & Therapeutics John McKew, Ph.D. VP, Research Kelly Blackburn VP, Clinical Operations Andrew Cubitt, Ph.D. VP, Product Protection Sanuj Ravindran, M.D. Chief Business Officer John Blake, CPA VP, Finance J
Slide 7: Discovery of Physiocrine Proteins: Alternative Splicing of Ancient Genes Leads to New Biology
Discovery of Physiocrine Proteins: Alternative Splicing of Ancient Genes Leads to New Biology
Slide 8: Dual Roles of tRNA Synthetases
Dual Roles of tRNA Synthetases: Protein Synthesis & Potential for Physiological Regulation Intracellular Function: 23 genes in humans Protein synthesis tRNA Synthetases: In all cellular life forms 4 billion years old Extracellular Function: ~300 Physiocrines Splice variants offer new biology Genetic
Slide 9: Primer on Physiocrines
Primer on Physiocrines Potential for novel physiological modulation in disease Extracellular functions of intracellular tRNA synthetases New class of modulators of tissue homeostasis Conserved, genetic gain of function over time ~300 proteins varying in size (40-500AA) Work via GPCRs, TLRs, cytokine
Slide 10: Physiocrine Mutations in Disease
Physiocrine Mutations in Disease Organ Phenotypes Genetic Evidence of the Importance Of Physiocrines No mutations reported to date (6) CNS Muscle Heart Eye/Ear Liver Lung Domain location of mutation: Physiocrine Catalytic (may overlap with Physiocrine domain) tRNA synthetases targeted by autoantibod
Slide 11: Leading Journal Publications: Science & Nature
Leading Journal Publications: Science & Nature Published in Lo et al., Science, 2014; Weiwei, He, et al., Nature 2015. Graphics are visual representations for illustrative purposes.
Slide 12: The First Physiocrine, the Resokine Pathway
The First Physiocrine, the Resokine Pathway: Potential New Therapies in Rare Muscle & Lung Diseases
Slide 13: Molecules of the Resokine Pathway
Naturally occurring Physiocrines Resolaris™ iMod (slightly truncated from wildtype) (splice variant) ** Molecules of the Resokine Pathway New hope for rare muscle & lung disease patients Engineered Physiocrine iMod.Fc Resokine Franchise Resokine* Pathway Discovery: Immuno-modulatory & fibro-modulato
Slide 14: Ability to Treat Immune Cell Invasion in Muscle
aTyr unpublished data Ability to Treat Immune Cell Invasion in Muscle Control Statin days 1-14 (toxic dose) 0.3 mg/kg Resolaris days 7-14 Statin days 1-14 1.0 mg/kg Resolaris days 7-14 Statin days 1-14 3.0 mg/kg Resolaris days 7-14 Statin days 1-14 Resolaris Preclinical ê Cytokines, ê T-cells and ê
Slide 15: Resolaris: Active In Lung Inflammation & Fibrosis Model
Three week rodent model, two weeks of therapeutic treatment Resolaris: Active In Lung Inflammation & Fibrosis Model Experimental data provided by Stelic CRO CT scans taken at day 14, lung histology taken at day 21 * Activity of mouse Resolaris (3mg/kg) vs vehicle control Pulmonary Inflammation and F
Slide 16: Clinical Development of Resolaris
Clinical Development of Resolaris: Harnessing a Natural Pathway to Treat Multiple Muscle & Lung Diseases
Slide 17: Staging Rare Muscle & Lung Disease Indications
Multiple opportunities for clinical advancement Staging Rare Muscle & Lung Disease Indications Clinical Path for Resolaris™ & iMod.Fc Early Onset FSHD Limb Girdle Muscular Dystrophy Interstitial Lung Disease Resolaris Clinical FSHD Resolaris or iMod.Fc To establish safety and tolerability in patient
Slide 18: Resolaris for Multiple Muscle Indications
Rare myopathies with an immune component (RPIC) Resolaris Clinical Resolaris for Multiple Muscle Indications Facioscapulohumeral Muscular Dystrophy (FSHD) Limb-girdle Muscular Dystrophy 2B (LGMD2B) Pathology Immune component (e.g. T-cells) Toxic loss of function mutation (dysferlin) Muscle group pro
Slide 19: LGMD2B Disease Progression Case History
LGMD2B Disease Progression Case History Difficulty rising from a chair, raising hands above head Uses a cane and leg braces Walks normally, active childhood LGMD2B Diagnosis Abnormal gait Knees locked Difficulty climbing stairs Misdiagnosed w/ polymyositis Part time wheelchair-bound Age Full depende
Slide 20: Early Onset FSHD Case History
Early Onset FSHD Case History Weakness in the lower back/curvature of the spine Leg muscle weakness/walking with a limp Normal early childhood Requires full-time use of wheelchair and assisted living Diagnosed with scoliosis Muscle weakness and early speech impediment Difficulty forming facial expre
Slide 21: Monitoring Muscle-by-Muscle Disease Phenotype
Quadriceps Immunologically driven disease progression assessed by MRI Monitoring Muscle-by-Muscle Disease Phenotype Frisullo et al., J Clin. Immunol., 2011; Also based on unpublished work and communications with investigators and KOLs Conversion to Fat/atrophy T1 for Fat/atrophy MRI Endpoints: T2 fo
Slide 22: Exploratory Study of Resolaris in Adult FSHD
Phase 1b/2 randomized, double-blind, placebo controlled, multiple ascending dose Exploratory Study of Resolaris in Adult FSHD 3 mg/kg Weekly IV 0.3 mg/kg Weekly IV 1 mg/kg Weekly IV Cohort 1 n = 4 Cohort 2 n = 8 Cohort 3 n = 8 Cohort 4 n = 12 Cohort 5 n = 12 Resolaris Clinical COMPLETED COMPLETED Lo
Slide 23: LGMD2B/FSHD: Exploratory Study of Resolaris
Phase 1b/2 open-label, intra-patient dose escalation study LGMD2B/FSHD: Exploratory Study of Resolaris Immunology Assessments Muscle & Patient Assessments Three Month Dosing Resolaris Clinical ON-GOING Placebo FSHD n = up to 4 LGMD & FSHD n = up to 4 n = up to 4 Week 10-13 3 mg/kg Twice weekly IV We
Slide 24: Early Onset FSHD: Exploratory Study of Resolaris
Phase 1b/2 open-label, intra-patient dose escalation study Early Onset FSHD: Exploratory Study of Resolaris Week 1 Placebo Week 2-13 Intra-patient dose escalation 0.3 – 3.0 mg/kg Weekly IV Resolaris Clinical ON-GOING Early Onset FSHD n = up to 16 Stage 1 Ages 16-25 n = up to 8 Immunology Assessments
Slide 25: Resolaris: One Product, Multiple Rare Diseases
Promise for grave, recalcitrant myopathy patients Resolaris: One Product, Multiple Rare Diseases Commercial 19,000 US FSHD 16,000 US LGMD 16,000 US DMD 51 45 53 44 52 50 Other exons FSHD: Average prevalence rates of FSHD are approximately 1/17,000. Applying this rate to the US population based on re
Slide 26: Interstitial Lung Disease: Severe, rare disorders with high unmet need
Severe, rare disorders with high unmet medical need Resolaris Clinical Interstitial Lung Disease > 80 RPIC Forms Pathogenesis Lung damage leading to alveolar inflammation or fibrosis Worst prognosis: lower DLCO and rapid decline of DLCO over three years Clinical manifestations Shortness of breath an
Slide 27: An Engineered Physiocrine for Lung Disease: iMod.Fc
An Engineered Physiocrine for Lung Disease: iMod.Fc New TPP to open more lung indications Rationale for iMod.Fc*: Resolaris TPP: Weekly dosing; limits lung applications Develop molecule for new TPP: potentially once-monthly dosing Product Concept: Two iMod domains per Fc of an antibody Extend exposu
Slide 28: iMod.Fc
iMod.Fc Fc (human antibody) iMod (100% identical to human wildtype)
Slide 29: Second IND Candidate iMod.Fc
Second Ind Candidate iMod.Fc 1/250th of Pirfenidone dose Better than 10 TGFβ Ab doses Established IPF rodent model Improves inflammation & fibrosis Differentiated mechanism Two iMod.Fc Doses Outperform 28 Pirfenidone Doses * *The Ashcroft scale for the evaluation of bleomycin-induced lung fibrosis i
Slide 30: iMod.Fc: Non-Human Primate and Rodent PK and Safety
Non-GLP double-dose study No clinical observations No pro-inflammatory cytokine signal Attractive PK iMod.Fc: Non-Human Primate and Rodent PK and Safety Supports potential for monthly dosing in patients Non-Human Primates Rodents Non-GLP toxicology 1-month study at dose level 25x efficacious dose No
Slide 31: Building a New Class of Therapeutics: Foundation for the Future
Building a New Class of Therapeutics: Foundation for the Future
Slide 32: Broad IP Protection for Physiocrine Composition of Matter
Broad IP Protection for Physiocrine Composition of Matter Resolaris Program Strategic Assets for Programs and Class Global Patent Estate ~300 Physiocrines discovered Over 200 Physiocrines interrogated via protein expression and functional assays >200 pending applications worldwide 70 issued or allow
Slide 33: Revolutionary Drugs Leveraging New Biology
Opportunity to own a new class of meaningful medicines Revolutionary Drugs Leveraging New Biology Pioneer New biology Insulin First product 1923 1968 1989 Coagulation factors Erythropoietin Enzyme replacement therapy TNF pathway VEGF pathway Complement pathway Physiocrine pathway 1990 1998 2004 2007
Slide 34: Immuno/Fibrosis Modulation Pipeline
Immuno/Fibrosis Modulation Pipeline 1 The expected timing of the anticipated next milestones for our clinical programs for Resolaris in FSHD, LGMD and RPIC is based on our current estimates and is subject to change based upon a variety of risk factors. Therapeutic Focus Preclinical Phase 1 Phase 1b/
Slide 35: MAINTAIN HOMEOSTASIS
MAINTAIN HOMEOSTASIS