Atyr Pharma, Inc. · NASDAQ:ATYR
Atyr Pharma — Investor Presentation (June 2018)
23 slides from Atyr Pharma's investor presentation, Jun 4, 2018
Slide 1: Translating New Immune Pathways into Meaningful Medicines
Translating New Immune Pathways into Meaningful Medicines Corporate Presentation June 2018 Exhibit 99.1
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: Accelerating Value Creation from Novel Immune Pathways
Accelerating Value Creation from Novel Immune Pathways Research: Discover innovative therapeutic candidates based on extracellular functionality of tRNA synthetases Initial focus on Resokine Pathway Lead Product Candidate: ATYR1923 Engineered Resokine protein for the treatment of inflammatory inters
Slide 4: Therapeutic Candidate Pipeline
Therapeutic Candidate Pipeline Resokine Pathway DISCOVERY Preclinical Phase 1 Phase 2 ATYR1923 Interstitial Lung Diseases Resokine antibodies Various Cancers tRNA Synthetase Pipeline DISCOVERY Preclinical Phase 1 Phase 2 Multiple Discovery Programs Internal Programs at aTyr The Scripps Research Inst
Slide 5: Engineered HARS Splice Variant ATYR1923 for the Treatment of Interstitial Lung Diseases
Engineered HARS Splice Variant ATYR1923 for the Treatment of Interstitial Lung Diseases
Slide 6: tRNA Synthetase Genes and Resokine: Extracellular Immunomodulatory Function of HARS
AARS CARS DARS EPRS FARS GARS HARS IARS KARS LARS MARS NARS QARS RARS SARS TARS VARS WARS YARS Extracellular Immunomodulatory Function Intracellular Protein Synthesis Function Secretion (non-canonical) iMod: Extracellular Splice Variant Derived From HARS Gene Histidyl-tRNA Synthetase (HARS) tRNA Syn
Slide 7: Immune Set Point Hypothesis: Resokine Pathway
Immune Set Point Hypothesis: Resokine Pathway Resokine inhibits T cell activation in vitro Inhibits release of inflammatory cytokines (e.g. IL-2, IFN��) and effectors (e.g. granzyme B) Prevents up-regulation of cell-surface activation markers Resokine has activity in a number of animal models of inf
Slide 8: ATYR1923: Program Snapshot
ATYR1923: Program Snapshot ATYR1923: Engineered Fc fusion protein with HARS splice variant Refer to splice variant as the “iMod domain” (iMod for immuno-modulatory function) Mechanism: Regulation of immune system Binds to Neuropilin-2 (NRP-2) Target Population: Primary: Inflammatory interstitial lun
Slide 9: High Unmet Need in Multiple Interstitial Lung Diseases
High Unmet Need in Multiple Interstitial Lung Diseases Represents 1% of U.S. ILD population ~60k patients ~150k patients ~135k patients ~250k patients Sarcoidosis ~150K patients in the U.S. Systemic inflammatory disorder characterized by non-caseating granulomas (CD4+ T cell driven) Advanced pulmona
Slide 10: Interstitial Lung Diseases Share Persistent Immune Engagement
Slide adapted from Dr. Steven Nathan, Medical Director, Advanced Lung Disease and Transplant Program at Inova Fairfax Hospital, Falls Church, VA Interstitial Lung Diseases Share Persistent Immune Engagement Fibrotic Sarcoidosis Systemic Sclerosis – ILD (SSc-ILD) Chronic Hypersensitivity Pneumonitis
Slide 11: ATYR1923 MOA Overlaps with ILD Pathogenesis
ATYR1923 MOA Overlaps with ILD Pathogenesis Bagnoto, Harari, European Respiratory Review, 2015 Cellular players and molecules in ILD Therapeutic intervention with ATYR1923 to downregulate immune insult and consequent fibrosis
Slide 12: Neuropilin-2 (NRP-2) Identified as a Binding Partner for ATYR1923
Neuropilin-2 (NRP-2) Identified as a Binding Partner for ATYR1923 Pleiotropic receptor that can bind to a number of different ligands Well-established role in the development of the neural and lymphatic systems Emerging role in the immune system; present on a number of immune cell types Expressed on
Slide 13: ATYR1923 Inhibits T Cell Activation In Vitro
ATYR1923 Inhibits T Cell Activation In Vitro Effect of 0.3 nM ATYR1923 on T Cell Cytokine Release Effect of ATYR1923 on T Cell Activation Markers *P < 0.05 Note: Presented in a poster at the American Academy of Immunology Annual Meeting in May 2018 aTyr is currently exploring the interaction with AT
Slide 14: Weekly Therapeutic Dosing of ATYR1923 Reduces Fibrosis in Mouse Bleomycin Model
ATYR1923 (0.4 mg/kg) IV QW D8, 15 Vehicle IV Vehicle PO TGFβ Ab (3 mg/kg) IP QOD D0-21 No BLM Pirfenidone (100 mg/kg) PO BID D8-21 Weekly Therapeutic Dosing of ATYR1923 Reduces Fibrosis in Mouse Bleomycin Model Ashcroft Score Study 1 Ashcroft Score Study 2 ATYR1923 administered therapeutically at 0.
Slide 15: ATYR1923 Returns Breathing to Normal in Rat Bleomycin Model
ATYR1923 Returns Breathing to Normal in Rat Bleomycin Model Late and early intervention commenced on Days 9 and 2, respectively Respiratory Volume = amount of air inhaled/exhaled/min; Nintedanib dosed daily (Days 9-21) Note: Presented in a poster at the American Thoracic Society International Confer
Slide 16: Favorable Safety Profile Observed in 1- and 3-Month GLP Toxicology Studies
Favorable Safety Profile Observed in 1- and 3- Month GLP Toxicology Studies Nonhuman Primates 2 weekly IV doses of 3 mg/kg No increase in ~30 serum immune markers 1- and 3-month weekly IV dose at 0, 10, 30, and 60 mg/kg No adverse test article–related findings Systemic exposure increased with increa
Slide 17: ATYR1923 Phase I Healthy Volunteer Study
ATYR1923 Phase I Healthy Volunteer Study 5 mg/kg 3 mg/kg 1 mg/kg 0.3 mg/kg 0.1 mg/kg 0.03 mg/kg Randomized, double-blind, placebo-controlled, single-ascending-dose 6 Cohorts; 6 healthy volunteers/cohort; 2:1 randomization (N=36 HVs total) 30-day assessment-follow-up period Safety & Tolerability Phar
Slide 18: Strategic Focus to Create Long-Term Shareholder Value
Strategic Focus to Create Long-Term Shareholder Value Phase 2 Trial – Interstitial Lung Disease Several translational animal studies ongoing to better inform clinical direction Understanding the interaction of Neuropilin-2 as a binding receptor for ATYR1923 Collaborating with industry leading pulmon
Slide 19: Appendix: Neuropilin-2 (NRP-2) Overview
Appendix: Neuropilin-2 (NRP-2) Overview
Slide 20: Neuropilin-2 Structure and Function
CUB: Complement C1r/s, UEGF, BMP-1 homology domain. FV/FIII: Factor V/VIII homology domain. MAM: Meprin, A5, mu phosphatase homology domain Neuropilin-2 Originally identified based on its role in axon guidance during neuronal development Subsequently shown to be a pleiotropic receptor that can regul
Slide 21: NRP-2 Utilizes Common Mechanisms to Regulate Diverse Pathways
Adapted from Parker et al., (2012) Biochemistry 51, 9437-9446 NRP-2 Utilizes Common Mechanisms to Regulate Diverse Pathways Semaphorin 3F VEGF-C NRP-2 NRP-2 VEGF-R3 Plexin A3 Plexin driven signaling VEGFR driven signaling CONFIDENTIAL
Slide 22: NRP-2 is Highly Expressed in Alveolar Macrophages
NRP-2 is Highly Expressed in Alveolar Macrophages Ye Aung et al., (2016) PLOS One DOI:10.1371/journal.pone.0147358 Fig 2. NRPs expression in tissue-specific macrophages compared to immunostaining with a cocktail of anti-CD68 and anti-CD163 antibodies. Expression was detected in alveolar macrophages
Slide 23: Recent Publications
Recent Publications Schellenberg et al. Role of Neuropilin-2 in the Immune System. Mol. Immunology. 2017 Roy at al. Multifaceted Role of Neuropilins in the Immune System: Potential Targets for Immunotherapy. Frontiers in Immunology. 2017 Immormino et al. Neuropilin-2 Regulates Airway Inflammatory Re