Atyr Pharma, Inc. · NASDAQ:ATYR
Atyr Pharma — American Academy of Neurology 2017
32 slides from Atyr Pharma's conference presentation, Apr 24, 2017
Slide 1: Advancing New Therapeutic Horizons For Patients With Rare Muscular Dystrophies
NASDAQ: LIFE Advancing New Therapeutic Horizons For Patients With Rare Muscular Dystrophies Harnessing Novel Pathways in Immunology to Promote Homeostasis in Muscle aTyr Pharma, Inc. Resolaris™ Update American Academy of Neurology April 2017 Exhibit 99.2
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: LIFE Value Proposition and Opportunities
>175 issued/allowed patents Strong Leadership Team associated with 18 approved drugs $76M cash 2016 EOY Pursuing partnership(s) for one or more of the above programs to accelerate clinical and preclinical pipeline Pioneers of new therapeutic intervention points in immunology Promoting Homeostasis LI
Slide 4: The Power of Physiocrines
The Power of Physiocrines Orchestrating Homeostasis New Class of Proteins from Alternative Splicing of Ancient Genes
Slide 5: What are Physiocrines?
Nature 2015 Science 2014 Nature 2013 Nature 2010 Science 1999 What are Physiocrines? Extracellular Signaling Regions Physiocrine Biology Protein synthesis Original Primordial Function Intracellular 23 genes in humans Physiocrine regions of tRNA synthetases in a gene Extracellular signaling 4 billion
Slide 6: LIFE's Therapeutic Paradigm: Promote Homeostasis
Promote Homeostasis LIFE’s Therapeutic Paradigm Homeostasis Disease Healthier Patients Physiocrine insufficiency Physiocrine agonists
Slide 7: Evidence for Homeostatic Role of Resokine in Humans
Evidence for Homeostatic Role of Resokine in Humans Disrupting the Resokine Pathway Promotes Muscle and Lung Disease Disease-antibodies Homeostasis Imbalance ↑ Immune cell invasion/activity Resokine Pathway Diseased Muscle Diseased Lung Healthy muscle Healthy lung 100% (18 of 18) anti-synthetase syn
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Free Resokine Pathway in Anti-Synthetase Patients Diminished Unpublished data from aTyr and collaborator Statistics: Mann-Whitney test Resokine Pathway in Humans 69% at or below limit of detection 51/52 diagnosed with myositis
Slide 9: Agonists of the Resokine Pathway in Immune Driven Models
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 be limited to these cells. Resokine Pathway Im
Slide 10: Resolaris
Resolaris Harnessing the Resokine Pathway to Treat Multiple Rare Muscle Diseases
Slide 11: First Physiocrine For Patients: Resolaris
First Physiocrine For Patients: Resolaris Skeletal muscle secretes Resokine Resokine, an agonist, plays a role in homeostasis & T cell responses in muscle Recombinant version of Resokine Demonstrated favorable safety profile and potential clinical activity in two rare muscular dystrophy indications
Slide 12: Resolaris Tempers Activated T cells
Resolaris Tempers Activated T cells Demonstrated effect as an immuno-modulator In Vitro T Cell Modulation Resolaris with Activated T-cells Promotes a More Resting T-cell Phenotype On the Left: Gated on CD4+ T cells. Resolaris at 100 pM. 24 hours stimulation with anti-CD3/CD28 Abs. On the Right: T ce
Slide 13: Rare Myopathies with an Immune Component
Rare Myopathies with an Immune Component Chronic damage, homeostasis disrupted Genetic Mutation Multiple proteins Dysferlin proteins Dystrophin proteins FSHD LGMD2B DMD Aberrant Protein Expression Localized T Cell Invasion/Proliferation Potential to link genotype to specific T cell phenotype FSHD LG
Slide 14: T Cells Central to Pathophysiology of RMICs
T Cells Central to Pathophysiology of RMICs Frisullo et al. J Clin Immunol 2011 Gallardo et al. Neurol. 2001 Yin et al.Int J Clin Exp Pathol 2015 Endomysial infiltrates, in which CD8+ cells predominated (Fig. 2b–d), and perivascular infiltrates, mainly constituted by CD4+ cells (Fig. 2f) in all samp
Slide 15: Resolaris: One Product, Multiple RMICs
Resolaris: One Product, Multiple RMICs Promise for severely afflicted myopathy patients 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 estimated in US population. 1
Slide 16: Resolaris Phase 1b/2 Clinical Trials
Resolaris Phase 1b/2 Clinical Trials Trial Indication(s) Patients Highest Dose Design 002 Adult FSHD 3 dose cohorts (n=20 Total) 3.0 mg/kg Weekly (12 weeks) Placebo controlled, Double blinded; Interpatient Dose Escalation up to 12 weeks 003 Early onset FSHD (n=8) 3.0 mg/kg Weekly (6 weeks) Open-labe
Slide 17: 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 Abnormal gait Knees locked Difficulty climbing stairs and running Age <15 16 – 18 19 – 27 28 - 34 https://www.youtube.com/watch?v=JLqHis1yPUI h
Slide 18: LGMD2B Patients Manual Muscle Strength Progressively Declines
LGMD2B Patients Manual Muscle Strength Progressively Declines Treatment with Deflazacort was for 6 months in each arm. Single site, placebo controlled, cross over design (n=25) Manual muscle strength assessed bilaterally by the modified Medical Research Council Scales (MRC) CIDD (Clinical Investigat
Slide 19: Manual Muscle Test Scores LGMD2B Patients
Manual Muscle Test (MMT) Scores LGMD2B Patients 004 Study: Individual Patient Changes from Baseline (%) *1-week follow-up is earlier than week 14 for 2 early discontinuations; Manual Muscle Testing (MMT) a validated assessment of muscle function/strength in 14 muscle groups † One patient in 004 Tria
Slide 20: Compiled Data from Three Phase 1b/2 Clinical Trials
Compiled Data from Three Phase 1b/2 Clinical Trials Relatively Stable or Improved Muscle Function Observed n = 4 n = 2 n = 4 n = 8 n = 9 Overall Mean MMT* Change Week 14 by Dose Group FSHD & LGMD2B Patients From 002, 003, 004 Trials Mean Change from baseline (%) Decrease Muscle Function Increase Mus
Slide 21: Robust Safety & Tolerability Dossier
Low-level anti-drug antibody assay signals did not result in clinical symptoms Protocol discontinuations primarily driven by transient infusion related reactions Robust Safety & Tolerability Dossier 44 patients have received Resolaris for a total drug exposure of 149 patient months No observed signs
Slide 22: Study Early Onset FSHD
Study 003 Early Onset FSHD
Slide 23: Early Onset FSHD Case History
Early Onset FSHD Case History Early progression, devastating disease impact 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 imp
Slide 24: Study 003 Design: Early Onset FSHD
Purpose: to evaluate the safety/tolerability of Resolaris in adolescents and young adults with early onset FSHD Design: multicenter, open label, intra-patient dose escalation Sites: 5 sites in the US, France, and Italy Population: genetically confirmed FSHD and signs/symptoms of FSHD by age 10 years
Slide 25: MMT Scores Early Onset FSHD Patients
MMT Scores Early Onset FSHD Patients Individual Patient Changes from Baseline (%) Study 003 * Manual Muscle Testing (MMT) a validated assessment of muscle function/strength in 14 muscle groups
Slide 26: INQoL Scores Early Onset FSHD Patients
* Individualized Neuromuscular Quality of Life (INQoL) score is a validated patient reported outcome measuring a patient’s level of disease burden ** Excludes two patients due to (1) no baseline and (2) discontinuation before week 14 INQoL Scores Early Onset FSHD Patients Individual Patient Changes
Slide 27: Study Safety and Other Assessments
003 Study Safety and Other Assessments Safety Resolaris was generally well tolerated in patients ages 16 to 20 years in the study Adverse Events (AEs) were mild to moderate in severity and consistent with overall Resolaris safety profile No Serious Adverse Events No observed signs of general immunos
Slide 28: Resolaris Status and 2017 Development Goals
Second Half First Half Resolaris Status and 2017 Development Goals Clinical Results: Early Onset FSHD Patient Trial (003) Clinical Trial: Kick off next trial post partnership* Biomarker/MOA: Introduce Mechanistic/PD Assay Established a favorable safety profile and identified an active dose Muscle Fu
Slide 29: Building a New Class of Therapeutics For Patients
Building a New Class of Therapeutics For Patients Foundation for the Future
Slide 30: LIFE Leaders
LIFE Leaders Foundation for the Future Andrea Cubitt, Ph.D. VP, Product Protection John Blake, CPA SVP, Finance Sanjay Shukla, M.D. Chief Medical Officer Holly D. Chrzanowski VP, Enterprise Talent and Organization Ashraf Amanullah, Ph.D. VP, Manufacturing John Mendlein, Ph.D. Chief Executive Officer
Slide 31: LIFE 2017 Goals and Financial Guidance
LIFE 2017 Goals and Financial Guidance *Operational cash burn only, excludes cash from financings 2017 Goals Partner One or More Programs Advance Pipeline with Two Molecules in the Clinic Declare 3rd IND Candidate from Physiocrine Discovery Engine Financial Guidance $76M cash 2016 EOY Operations fun
Slide 32: Thank you!
Thank you! Gracias Merci ありがとう Danke Khop Khun Mak Kha Obrigado Takk 감사합니다 Dziekuje Spasiba Grazie Mahalo Efharisto Sukria Nandri Cпасибо .תודה 谢谢 Shukran Terima kasih 多謝 متشکرم