Atyr Pharma, Inc. · NASDAQ:ATYR
Atyr Pharma — Corporate Update (May 2016)
42 slides from Atyr Pharma's corporate update, May 11, 2016
Slide 1: Building a New Class of Medicines: Physiocrine Based Therapeutics
Building a New Class of Medicines Physiocrine Based Therapeutics 1st Rare Disease Trial Completed New Hope For Muscular Dystrophy Patients May 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: Augmenting Natural Homeostatic Pathways
Augmenting Natural Homeostatic Pathways In patients with rare diseases of muscle & lung Autonomous Pipeline & Unique Business Model Physiocrine* Disruptive Opportunity Resokine: One Pathway Many Rare Diseases Resolaris: Clinical Development Program Pioneering new biology, yielding new therapeutic in
Slide 4: Harnessing the Power of Physiocrines for Patients
Harnessing the Power of Physiocrines for Patients 1 Facioscapulohumeral Muscular Dystrophy 2Limb-girdle Muscular Dystrophy 2B 3RPIC: Rare pulmonopathies with an immune component, including Interstitial Lung Disease (“ILD”) Therapeutic Focus Preclinical Phase 1 Phase 1b/2 Discovery aTyr Pipeline Live
Slide 5: Potential of Physiocrine Proteins
Potential of Physiocrine Proteins Discovery of a New Class of Proteins from Alternative Splicing of Ancient Genes Humira® WW sales over $14B in 2015 (TNF inhibitor) Insulins used by over 3 million Americans to treat diabetes in 2012 Complement inhibitors being studied in a dozen ongoing clinical tri
Slide 6: aTyr Pioneering the New Biology of Physiocrines
Nature 2015 aTyr Pioneering the New Biology of Physiocrines Physiocrine Proteins Science 2014 Nature 2013 Nature 2010 Science 1999 ~300 proteins involved in physiological pathways, >70 issued or allowed patents Focus on natural modulators of immune & fibrotic pathways in vivo Indication selection: p
Slide 7: Potential for Novel Physiological Modulation in Disease
At least 14/23 tRNA Synthetases in family w/ known disease connections Clinical phenotypes present tissue-by-tissue homeostasis Genetic disease paradigm: Genetic aberration à protein absence or abnormality à abnormal function/structure à immune system engagement Soliris® ($2.6B in 2015): example of
Slide 8: Harnessing the Resokine Pathway
Harnessing the Resokine* Pathway Natural Pathway From Skeletal Muscle to Treat Multiple Rare Muscle Diseases *Resokine: for resolution of activated immune & fibrotic pathways
Slide 9: Model of Resokine Pathway in skeletal muscle health and disease
Genetic mutation Structural protein Transcription factors Mitochondrial proteins Auto-Immune Immune system dysregulation Agent Induced Statins Model of Resokine Pathway In skeletal muscle health and disease Resokine Pathway + = IGF induced growth Muscle progenitor cell ResokineA release Resokine rel
Slide 10: 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 Two weeks of therapeutic treatment in 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/kg Resol
Slide 11: Clinical Path for Resolaris in Skeletal Muscle
1st Physiocrine based therapeutics to promote homeostasis Establish & explore: Safety, tolerability Activity/end-point potential Focus on Rare Myopathies with an Immune Component (RMIC) Multiple opportunities for advancement for patients with few or no treatment options Staging rare muscle disease i
Slide 12: Clinical Development of Resolaris
Clinical Development of Resolaris Potential New Therapies for Patients with Rare Muscle Diseases
Slide 13: FSHD: A Severe Skeletal Muscle Disease
Muscle-by-muscle disease progression FSHD: A Severe Skeletal Muscle Disease Pathology Dominant/spontaneous toxic gain of function (↑Dux4) Immune component (e.g. ↑ T cells) Asymmetric muscle loss, fat infiltration Standard of care No therapeutic treatments Only supportive care provided Clinical Debil
Slide 14: Adult FSHD 002 Design & Trial Objectives
*One reversible Infusion Related Reaction (IRR) patient in 002 & two reversible IRR patients in 005 trial Adult FSHD 002 Design & Trial Objectives Objectives Build dossier for Resolaris & new class Safety Tolerability Immunogenicity PK Explore FSHD pertinent readouts Circulating markers of disease T
Slide 15: Establishing the Safety Profile: 1st FSHD Trial
Clinical Development Generally safe and well-tolerated over the dose range/duration studied No SAEs reported by study investigators - One generalized infusion related reaction (IRR) reclassified by aTyr to serious adverse event ADA*’s were of low titer and no demonstrated effect on pharmacokinetics
Slide 16: Global Patient Reported Outcomes: INQoL
Clinical Development Validated neuromuscular assessment tool* Global systemic assessment used in clinical studies and trials Not frequently used in clinical practice Self-administered questionnaire consisting of 45 queries/4 dimensions Life Domains I) Activities II) Independence III) Social Relation
Slide 17: Proportion of Patients with Improved INQoL Overall Scores
Potential dose response and duration response 17 Proportion of Patients with Improved INQoL Overall Scores Clinical Development 1 Month % Response 2/5 1/3 2/4 4/6 5/6 Dose: Placebo Placebo 0/2 3 Months Placebo Resolaris
Slide 18: Multiple Dimensions Improve on INQoL
Multiple Dimensions Improve on INQoL 18 (n=6) (n=5) (n=3) (n=6) (n=4) (n=2) 1 Month 3 Months* Clinical Development INQoL Overall Scores Change from Baseline (%); ITT Population (n=20) Trial not powered to show statistical significance. Data suggest potential improvement in this relatively small clin
Slide 19: Overall INQoL Score Placebo v. 3.0 mg/kg Patients
Overall INQoL Score Placebo v. 3.0 mg/kg Patients Suggestive of patient improvement in 3 months Clinical Development 19
Slide 20: Global Manual Muscle Testing
Testing muscle function/strength 15 muscles evaluated at 4 time points in study Muscles scored individually Composite score calculated Common endpoints for particular muscles Global Manual Muscle Testing Clinical Development Data suggest small trends of slower progression or potential improvement
Slide 21: Limb-Girdle Muscular Dystrophy 2B (LGMD2B)
A severe muscle disease with a genetic loss of function Clinical Development Limb-Girdle Muscular Dystrophy 2B (LGMD2B) Pathology Immune component (e.g.↑ T-cells) Toxic loss of function mutation (dysferlin) Muscle group progression Standard of care No therapeutic treatments Only supportive care prov
Slide 22: Adult LGMD2B and FSHD (Trial-004)
Adult LGMD2B and FSHD (Trial-004) Purpose Evaluate the safety/tolerability of total weekly exposure of 6.0mg/kg in LGMD2B and FSHD Assess drug activity more proximal to dosing Rationale To test whether a total weekly exposure of 6.0mg/kg demonstrates different outcomes than a total weekly exposure o
Slide 23: Early Onset FSHD Case History
Early Onset FSHD Case History Weakness in 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 Early speech impediment Difficulty forming facial expressions
Slide 24: Early Onset FSHD (Trial-003)
Early Onset FSHD (Trial-003) Clinical Development Weeks Total weekly dosage (mg/kg) Purpose Evaluate the safety/tolerability in a potentially different indication Early Onset FSHD Assess drug activity in new patient population and with additional endpoints Rationale Investigate often more severe for
Slide 25: Resolaris: One Product, Multiple Rare Diseases
Promise for severely afflicted myopathy patients Resolaris: One Product, Multiple Rare Diseases Clinical Development 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 ba
Slide 26: Readouts in More Resolaris Trials in 2016
Readouts in 3 More Resolaris Trials in 2016 Next trial(s) based on results of 002, 003, 004 & 005 trials Establishing data dossier on safety Exploring activity assessments & optimal dose Directionality on endpoints for approval Clinical Development Adult FSHD (002) N = 20 Early Onset FSHD (003) N =
Slide 27: iMod.Fc the First Engineered Physiocrine
iMod.Fc the First Engineered Physiocrine Augmenting a Natural Pathway to Treat Multiple Lung Diseases
Slide 28: An Engineered Physiocrine for Lung Disease: iMod.Fc
An Engineered Physiocrine for Lung Disease: iMod.Fc New TPP and new molecule to open up lung indications Rationale for iMod.Fc* Resolaris TPP: Weekly dosing; limits lung applications Develop new molecule with new TPP: potentially once-monthly dosing Product Concept Two iMod domains per Fc of an anti
Slide 29: iMod.Fc Program
iMod.Fc Program 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 is the a
Slide 30: Building a New Class of Therapeutics
Building a New Class of Therapeutics Foundation for the Future
Slide 31: Leadership Team
Leadership Team Experienced Industry Veterans Kelly Blackburn VP, Clinical Operations Andrew Cubitt, Ph.D. VP, Product Protection and Interim Head of Research John Mendlein, Ph.D. Chief Executive Officer John Blake, CPA VP, Finance Sanjay Shukla, M.D. Chief Medical Officer Holly D. Chrzanowski VP, E
Slide 32: Focused Execution with Strong Cash Position
Resolaris for LGMD2B/Adult FSHD Resolaris for Early Onset FSHD Resolaris for Adult FSHD Resolaris for Adult FSHD Focused Execution with Strong Cash Position Balance sheet well-aligned to achieve near-term catalysts Phase 1b/2 Trial (002) Phase 1b/2 Trial (004) Phase 1b/2 Trial (005) Long-term extens
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 pathways 1990 1998 2004 200
Slide 34: Appendix
Appendix
Slide 35: Properties of Physiocrines
Extracellular functions of 4 billion year old gene family, tRNA Synthetases Genes yield ~300 proteins (e.g. alternative splicing, etc.) of new function Potential new class of modulators of tissue homeostasis Properties of Physiocrines Muscle Heart Liver Brain/CNS Lung Physiocrine Proteins Work via G
Slide 36: FSHD Molecular Pathology
FSHD Molecular Pathology Links Loss of Epigenetic Control to Immune Status with Disease Statland, J., C. M. Donlin-Smith, et al. Journal of Neuromuscular Diseases, 2014. Lemmers, E. et al, Gene Reviews 2014 FSHD Muscle Phenotype 4th Chromosome Terminal Repeats DUX 4 Non-Germline Gene Expression Skel
Slide 37: Study Demographics
Study Demographics Resolaris Placebo Patients 15 5 Age (years), Median 46 52 Male/Female (%) 53/47 80/20 Patients with 3 D4Z4 repeats or less 2 0 Completed Study 100%* 100% Elevated cytokines of interest 1/15 1/5 Baseline FSHD Clinical Severity Score, Mean (SD) 3.2 (0.8) 2.7 (0.7) Resolaris Clinical
Slide 38: Targeted MRI & Circulating Markers
MRI used to evaluate immune components in a targeted muscle did not record a difference between placebo and 3.0 mg/kg group - To be followed through extension study No evidence of immune suppression was observed with exploratory circulating cytokines, as well as immune cells Assessment of selected c
Slide 39: Resolaris Phase 1b/2 Program Summary
* Targeted MRI only if qualified with Stir+ muscle at baseline. ** Only for Cohort 3 subjects Resolaris Phase 1b/2 Program Summary Trial Patient Populations N Highest Ending Dose Weekly (mg/kg) MRI (+) Entrance MRI Broad Readout MRI Targeted Readout INQoL MMT Immune Markers Readout Timing 002 Adult
Slide 40: 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 41: Non-Human Primate and Rodent PK and Safety
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 pro-inflammatory cytokine signal No clinical observations No changes in body or tissue weights Attractive PK
Slide 42: iMod.Fc for Multiple Lung Indications
Severe, rare disorders with high unmet medical need iMod.Fc Clinical > 80 RPIC Forms Including Interstitial Lung Diseases 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