UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
 
FORM 8-K

CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
May 23, 2017
Date of Report (Date of earliest event reported)
 
ATYR PHARMA, INC.
(Exact name of registrant as specified in its charter)

 	 	 	 	 	
Delaware	 	001-37378	 	20-3435077	
(State or other jurisdiction
of incorporation)	 	(Commission
File Number)	 	(IRS Employer
Identification No.)
 	
3545 John Hopkins Court, Suite #250
San Diego, California 92121
 	
(Address of principal executive offices, including zip code)
 	
(858) 731-8389
 (Registrant’s telephone number, including area code)
 
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligations of the registrant under any of the following provisions:
 
☐	Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)	
 
☐	Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)	
 
☐	Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))	
 
☐	Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))	
 
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 or Rule 12b-2 of the Securities Exchange Act of 1934.
Emerging growth company     ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.     ☒

 
Item 7.01	Regulation FD Disclosure.	
aTyr Pharma, Inc. (the “Company”) is participating at the American Thoracic Society’s (ATS) 113th International Conference to be held May 19 – 24, 2017 in Washington D.C. and will be presenting two poster presentations at such conference.  The posters are titled “Resokine Modulates Immune Cell Infiltration into the Lung and Provides Therapeutic Activity in a Bleomycin-Induced Lung Fibrosis Model,” to be presented on May 23, 2017, and “The Resokine Pathway is Implicated in the Pathology of Interstitial Lung Disease,” to be presented on May 24, 2017. These posters are attached hereto as Exhibit 99.1 and Exhibit 99.2, respectively.
In conjunction with the ATS poster presentations, the Company will host an educational webinar on Tuesday, May 23, 2017 at 8:30 a.m. ET featuring Steven D. Nathan, M.D., FCCP, Director of the Advanced Lung Disease Program and Medical Director of the Lung Transplant Program at Inova Fairfax Hospital, to provide disease education on interstitial lung diseases that are characterized by an immune or fibrotic component. The Company will also provide an overview of the iMod.Fc program (Stalaris) in development for the potential treatment of patients with severe, rare pulmonary diseases characterized by an immune or fibrotic component for whom there are limited treatment options. A copy of the presentation materials for such educational webinar is attached hereto as Exhibit 99.3.  The Company does not undertake to update the presentation materials.  
The information under this Item 7.01, including Exhibits 99.1, 99.2 and 99.3 hereto, is being furnished and shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall such information be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.

 
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Item 9.01                                           Exhibits.
 
(d) Exhibits.

99.1	 	Poster presentation titled “Resokine Modulates Immune Cell Infiltration into the Lung and Provides Therapeutic Activity in a Bleomycin-Induced Lung Fibrosis Model.”	
99.2	 	Poster presentation titled “The Resokine Pathway is Implicated in the Pathology of Interstitial Lung Disease.”	
99.3	 	Educational Webinar Materials of aTyr Pharma, Inc. dated May 23, 2017.	

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SIGNATURE
 
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
 
 	ATYR PHARMA, INC.	

 	By:	/s/ John T. Blake	
 	 	John T. Blake	
 	 	Senior Vice President, Finance	
 	 	 	
Date: May 23, 2017	 	 	

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INDEX TO EXHIBITS

99.1	 	Poster presentation titled “Resokine Modulates Immune Cell Infiltration into the Lung and Provides Therapeutic Activity in a Bleomycin-Induced Lung Fibrosis Model.”	
99.2	 	Poster presentation titled “The Resokine Pathway is Implicated in the Pathology of Interstitial Lung Disease.”	
99.3	 	Educational Webinar Materials of aTyr Pharma, Inc. dated May 23, 2017.	

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** Immune System Complex tissue homeostasis human Vascular Systems Closed tissue homeostasis Resokine Modulates Immune Cell Infiltration Into the Lung and Provides Therapeutic Activity in a Bleomycin-induced Lung Fibrosis Model K.M. Ogilvie, M.T. Do, K.P. Chiang, R.A. Adams, S.P. Crampton, L.A. Nangle, A.B. Cubitt, J.C. McKew, M.A. Ashlock, J.D. Mendlein aTyr Pharma, San Diego, CA, USA Introduction and Rationale Protein synthesis Original primordial function Intracellular 23 genes in humans Physiocrine regions of tRNA synthetases in a gene Genetic Evolution 4 billion years of learning bacteria fish worm human Regenerative Systems Open tissue homeostasis Bacteria Protein synthesis Complex systems evolved Extracellular Function ~300 Physiocrines Tissue homeostasis Potential new functions Physiocrines: Novel, Primal Extracellular Signaling Regions During the evolution of complex organisms, aminoacyl-tRNA synthetases (AARS) acquired new domains without an intracellular enzymatic role. A number of these domains, as well as AARS proteins, possess extracellular activities and play important roles in homeostasis1. Histidyl-tRNA synthetase (HARS) and its splice variants exhibit extracellular activities, which are referred to as the Resokine pathway. 1Lo et al. Human tRNA Synthetase Catalytic Nulls with Diverse Functions. Science, 2014. Homeostasis Homeostasis disrupted od Domain iM Antisynthetase syndrome manifests in lung as PM/DM-ILD Functional Knockout of Resokine Associated With Myositis and Interstitial Lung Disease Patients with auto-antibodies specific for Resokine (Jo-1) have notable T-cell infiltration particularly into muscle and lung tissues, which may manifest as susceptibility to myositis and interstitial lung disease (ILD). Therefore, blocking of potential immunomodulatory functions of Resokine may be particularly important in these diseases. DM, dermatomyositis; PM, polymyositis. Control Statin days 1–14 Animals With Elevated Troponin-I CD8a MCP1 IL6 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 Myopathy was induced in female Sprague Dawley rats with 1 mg/kg cerivastatin administered daily for 7 days and then every other day until termination (Day 15). Resolaris was administered daily from days 7–14. Terminal histology (hemotoxylin and eosin), serum troponin I, and muscle mRNA expression data are shown. Resolaris Administration Ameliorates Statin-induced Myopathy Hypothesis: Administration of Resokine proteins may ameliorate lung disease Day 14 Day 21 -600 -500 -400 -300 -200 -100 0 Hounsfield unit (HU) * Vehicle-IV Days 8-21 mResolaris Days 8-21 Normal Lung No BLM Dex-PO Days 0–21 Vehicle-IV Days 8–21 mResolaris Days 8–21 0 1 2 3 4 5 6 Ashcroft Score *** *** * iMod Days 8–21 No BLM Vehicle, IV mResolaris iMod Vehicle mResolaris Resokine Proteins Improve Lung CT Scan and Ameliorate Lung Fibrosis The first 5 animals from groups treated with Vehicle IV or mResolaris (3 mg/kg) were subject to computed tomography (CT) scan on Day 14 (i.e., after 1 week of protein treatment). Hounsfield units were measured from 8 regions of interest (ROI) selected at 2 anatomical planes from the series of ~100 images per animal. The 8 ROIs were averaged for each animal and are represented on the graph. Note that BLM causes an increase in Hounsfield units and mResolaris treatment reduces it toward normal (*p < 0.05, Student’s t test). Lung tissues collected on Day 21 (i.e., after 2 weeks of protein treatment) were stained with Masson’s Trichrome stain. Ashcroft scores were assigned to 20 fields per animal and averaged. BLM induced an increase in fibrosis. mResolaris (3 mg/kg IV) and dexamethasone (0.25 mg/kg PO) significantly ameliorated fibrosis as measured by histological Ashcroft scoring (*p < 0.05; ***p < 0.001 vs. Vehicle IV. One-way ANOVA followed by Dunnett’s post hoc test). iMod (2.5 mg/kg IV) treated samples did not reach statistical significance. BLM, bleomycin; PO, per os, oral dosing. Ashcroft Index Score per Field (0-8) 0 1 2 3 4 5 *** *** *** No BLM BLM Veh PO BID D8–D21 BLM Pirf 0.25 mg/kg 200 mg/kg PO QDPO BID D0–D21 D8–D21 BLM Veh IV QD D8–D21 BLM Resolaris 3 mg/kg IV QD D8–D21 BLM iMod.Fc 0.4 mg/kg IV QW D8, D15 BLM Dex *** *** *** Experiment 1Experiment 2 iMod.Fc administered therapeutically at 0.4 mg/kg QW drives efficacy comparable to or greater than pirfenidone, anti-TGFb antibodies, and dexamethasone Experiment 1: Lung tissues collected on Day 21 (i.e., after 2 weeks of protein treatment) were stained with Masson’s Trichrome stain. Ashcroft scores were assigned to 8-10 fields per animal; all analyzed fields are represented. BLM induced an increase in histological fibrosis. mResolaris (3 mg/kg daily) and iMod.Fc (0.4 mg/kg once weekly) significantly ameliorated fibrosis as measured by histological Ashcroft scoring. iMod, TGFb blockade and pirfenidone did not have significant effects on fibrosis (*p < 0.05; ***p < 0.001 vs. Vehicle IV, Kruskal-Wallis ANOVA followed by Tukey’s post hoc test). Experiment 2: Lung tissues collected on Day 21 (i.e., after 2 weeks of protein treatment) were stained with Masson’s Trichrome stain. Ashcroft scores were assigned to 20 fields per animal; all analyzed fields are represented. BLM induced an increase in histological fibrosis. Resolaris (3 mg/kg daily) and iMod.Fc (0.4 mg/kg once weekly) significantly ameliorated fibrosis as measured by histological Ashcroft scoring (***p < 0.001 vs. Respective Vehicle, Kruskal-Wallis ANOVA followed by Tukey’s post hoc test). PO, per os, oral dosing. 0 1 2 3 4 5 *** Ashcroft Index Score per Field (0-8) * * *** BLM Vehicle IV Weekly Therapeutic Dosing of iMod.Fc Ameliorates Fibrosis in Bleomycin- induced Lung Injury Lung Gene Expression IL23r ** BALF IP-10 Cytokine (pg/mL) Cytokine (pg/mL) BALF Cell Count Cytokine (pg/mL) Collagen (ug/mL) 0 50 100 BALF IL-6 0 20 40 60 80 BALF soluble collagen 0 200 400 600 800 1000 BLM Veh IV QD D8–D21 Bronchiolar-alveolar lavage fluid (BALF) cell counts: At euthanasia, the lungs were flushed twice with phosphate-buffering saline (PBS) and fluid was collected. BALF was centrifuged, the erythrocytes were lysed, and the remaining cells were resuspended in PBS. After staining with trypan blue, cells were counted using a hemocytometer. Resolaris significantly decreased the number of immune cells present in the BALF. The number of cells counted was not significantly changed by dexamethasone or nintedanib in comparison to Vehicle PO (*p < 0.05; **p < 0.01 vs. Vehicle IV. One-way ANOVA followed by Dunnett’s post hoc test). Soluble markers in BALF: BALF supernatants were collected after centrifugation as described above and soluble markers measured using commercially available kits. Resokine proteins significantly decreased IP-10 and TGFb, and a tendency for lowering was observed on several other immune and fibrotic markers, including IL-6 and soluble collagen (*p < 0.05; **p < 0.01 vs. Vehicle IV, Kruskal-Wallis ANOVA followed by Dunn’s post hoc test). Lung gene expression: A small sample of lung was collected, frozen, and subsequently processed to isolate RNA. PCR was conducted using the Fluidigm platform. mResolaris significantly decreased expression of several immune cell genes (*p < 0.05; **p < 0.01 vs. Vehicle IV, Student’s t test). PO, per os, oral dosing. Conclusions The Resokine pathway is functional in the lungs of rodents. Therapy with Resokine proteins was efficacious and ameliorated bleomycin-induced lung fibrosis. Certain Resokine pathway proteins may be worthy of exploration for their therapeutic effects in human lung diseases, such as interstitial lung disease. Acknowledgements Scientists and study directors at Stelic MC, TNO, and Biomodels who conducted the experiments on aTyr Pharma’s behalf. aTyr scientists Kenny d’Arigo and Nicole Schultz who were responsible for PK analysis and PCR conduct, respectively. Graphics support was provided by Oxford PharmaGenesis, Inc. and was funded by aTyr Pharma, Inc. Disclosure This study was funded by aTyr Pharma, Inc. Anticodon-binding Domain iMod Domain Molecule Dose (mg/kg) C0 (ng/mL) Vd (mL/kg) CL (mL*h/kg) T1/2AUCinf (h)(ng*h/mL) iMod 8 145,455 119 574 0.5 13,944 Resolaris 10 97,774 128 75 2.5 13,491 iMod.Fc 10 1,407,553 265 1.8 94 633,937 Proteins used in these experiments are depicted above. The endogenous Physiocrine, Resokine, is synonymous with endogenous extracellular histidyl-tRNA synthetase (HARS). The domain structure is represented top left, whereas the 3-dimensional structure is represented top right. Resolaris is a recombinant version of the natural protein expressed in E. coli (middle domain structure) with a slightly truncated C-terminus. In some experiments, the mouse version of Resolaris (mResolaris) was used. The immunomodulatory domain (iMod) is represented to the right. iMod.Fc is represented in the lower left (primary domain structure) and far right (3-dimensional model). PK parameters obtained in Sprague Dawley rats are shown in the table. AUCinf, area under the curve extrapolated to infinity; C0, initial concentration; CL, clearance; PK, pharmacokinetics; T1/2, half-life; Vd, volume of distribution. 0 8 15 21 Bleomycin Termination Days: A)B) BALF TGF- b1 0 20 10 30 40 50 * Soluble Markers in BALF BALF Cell Count Immune and Fibrotic Markers Attenuated by Resokine Proteins Methods Resokine Proteins Resokine Proteins General Experimental Methods C57Bl/6 mice received a single administration of saline (non-diseased control) or bleomycin (2-3 U/kg) intratracheally. Bleomycin-induced animals received Resokine proteins or Vehicle administered intravenously at dose levels and frequencies shown in the figure legends from Day 8 through termination. Anti-TGFb antibody-, pirfenidone-, nintedanib-, or dexamethasone-treated groups were included for comparison. All animals were weighed and evaluated for respiratory distress daily. CT scans were conducted in one experiment. Mice were euthanized on Day 21 and tissues collected, stained, and evaluated for fibrosis and other histological changes by trained personnel who were blind to treatment conditions. Data are expressed as mean ± SEM. CT, computed tomography; TGF, transforming growth factor. Presented at the American Thoracic Society International Conference; 19–24 May 2017; Washington, DC, USA. Results A) B) C) A6428 0.25 mg/kg PO QD D0–D21 60 mg/kg PO QD D0–D21 BLM iMod 2.5 mg/kg IV QD D8–D21 BLM mResolaris 3 mg/kg IV QD D8–D21 BLM Veh IV QD D8–D21 BLM iMod 2.5 mg/kg IV QD D8–D21 BLM mResolaris 3 mg/kg IV QD D8–D21 150 BLM Veh IV QD D8–D21 BLM iMod 2.5 mg/kg IV QD D8–D21 BLM mResolaris 3 mg/kg IV QD D8–D21 Lung Gene Expression BLM Veh IV QD D8–D21 BLM iMod 2.5 mg/kg IV QD D8–D21 BLM mResolaris 3 mg/kg IV QD D8–D21 No BLM BLM Vehicle PO BLM TGFb Ab 3 mg/kg IP QOD D0–D21 BLM Pirfenidone 100 mg/kg PO BID D8–D21 BLM iMod 2.5 mg/kg IV QD D8–D21 BLM mResolaris 3 mg/kg IV QD D8–D21 BLM iMod.Fc 0.4 mg/kg IV QW D8, D15 Resokine human Resokine fly No BLM BLMBLMBLMBLM VehDex Nintedanib Veh BLMBLMBLM Resolaris Resolaris Resolaris 1 mg/kg 3 mg/kg 10 mg/kg IV QD IV QD IV QD D8–D21 D8–D21 D8–D21 PO BID D0–D21 IV QD D8–D21 -5 0 5 * ** -5 0 5 -5 0 5 -5 0 5 -5 0 5 -5 0 5 * ** * log2 (Fold Change) Foxp3 IL6 IL10 log2 (Fold Change) log2 (Fold Change) log2 (Fold Change) log2 (Fold Change) log2 (Fold Change) No BLM BLM Dex 0.25 mg/kg PO QD D8–D21 BLM Veh IV QD D8–D21 BLM mResolaris 3 mg/kg IV QD D8–D21 No BLM BLM Dex 0.25 mg/kg PO QD D8–D21 BLM Veh IV QD D8–D21 BLM mResolaris 3 mg/kg IV QD D8–D21 IFNg No BLM BLM Dex 0.25 mg/kg PO QD D8–D21 BLM Veh IV QD D8–D21 BLM mResolaris 3 mg/kg IV QD D8–D21 No BLM BLM Dex 0.25 mg/kg PO QD D8–D21 BLM Veh IV QD D8–D21 BLM mResolaris 3 mg/kg IV QD D8–D21 No BLM BLM Dex 0.25 mg/kg PO QD D8–D21 BLM Veh IV QD D8–D21 BLM mResolaris 3 mg/kg IV QD D8–D21 No BLM BLM Dex 0.25 mg/kg PO QD D8–D21 BLM Veh IV QD D8–D21 BLM mResolaris 3 mg/kg IV QD D8–D21 CXCR3 Exhibit 99.1

#611 Presented at the American Thoracic Society International Conference; 19–24 May 2017; Washington, DC, USA. The Resokine Pathway Is Implicated in the Pathology of Interstitial Lung Disease L.A. Nangle1*, Y. Tong2,3, E. Mertsching1, S.P. Crampton1, R.A. Adams1, K.P. Chiang1, K.M. Ogilvie1, P. Schimmel4, J.C. McKew1, D. King1, J.D. Mendlein1 1aTyr Pharma, San Diego, CA, USA; 2Pangu Biopharma, Hong Kong, China; 3IAS HKUST – Scripps R&D Laboratory, Institute for Advanced Study, Hong Kong, China; 4The Scripps Laboratories for tRNA Synthetase Research, The Scripps Research Institute, La Jolla, CA, USA *Corresponding and presenting author: L.A. Nangle, lnangle@atyrpharma.com Rationale The histidyl-tRNA synthetase (HARS) protein has long been identified as the sole target of Jo-1 autoantibodies (Jo-1 Abs), which are, in many cases, accompanied by interstitial lung disease (ILD). Extracellular HARS proteins (Resokine) are found in circulation at physiologically relevant levels in healthy individuals (~200 pM) and are greatly reduced in patients with Jo-1 Abs, leading us to investigate the source of Resokine and explore the possibility that insufficiency plays a role in the pathology of inflammatory myopathies and ILD associated with Jo-1 Abs. Evolution-elaborated Physiological Systems for Homeostasis Closed Tissue Homeostasis Complex Tissue Homeostasis Open Tissue Homeostasis Conserved Physiocrine domain structures Cellular Homeostasis tRNA Synthetase Protein Synthesis Function Resokine fly Resokine human Physiocrine Hypothesis: Physiological Modulation From Primordial Tissue Homeostasis Extraellular, circulating HARS-derived proteins = Resokine Anticodon-binding Domain DomainAminoacylation D Splice Variant (SV9) Newly Evolved Histidyl-tRNA Synthetase iMod Domain and the Resokine Pathway Pathological Remodeling of the Lung in a Model of Resokine Pathway Disruption Naïve Vehicle Mouse HARS Mouse iMod Naïve Vehicle Mouse HARS Mouse iMod 1 10 100 1000100000 Resokine (pM) Naïve Vehicle Mouse HARS Mouse iMod ** * ** ** Naïve Vehicle Mouse HARS Mouse iMod 100 1000 10000 Resokine Titers (EC50) Vaccination of Mice With HARS or iMod Domain Alone (+ Adjuvant) Generates Robust Antibody Response in BALF That Depletes Resokine Resokine BALF LevelsResokine BALF Titers Control Functional Resokine Knockout Weeks: 024 CFA/ antigen IFA/ antigen IFA/ antigen 789 Bleomycin Isoflurane Termination latency Naïve Vehicle-immunized + BLM Mouse HARS-immunized + BLM Mouse iMod-immunized + BLM Lung diffusion capacity Isoflurane latency time * CD44+ CD4+ T-cells * CD44+ CD8+ T-cells * Cells (x 106) Cells (x 106) Latency Time 50 75 100 125 150 Activated T-cells in mediastinal lymph nodes 0 2 4 6 0.0 0.5 1.0 1.5 2.0 Exacerbated Response to Bleomycin-induced Injury in Mice With Resokine-antibody Blockade BALF, bronchoalveolar lavage fluid; BLM, bleomycin; CFA, Complete Freund’s adjuvant; IFA, Incomplete Freund’s adjuvant. Regulation of Resokine Splice Variant in Inflammation Resokine Secretion From Lung Cells Resokine iMod-SV Is Upregulated in Airway Epithelial Cells and Secretion Is Increased in Response to Inflammation IFN-g, interferon gamma; TNF-α, tumor necrosis factor alpha. Regulation of the Resokine Pathway in Lung Inflammation IL-13, TGF-β, TNF-α, IL-1β Fibrocytes EMT Fibroblasts ↑ Resokine agonist therapy Pharmacologic restoration of tissue homeostasis and resolution of immune engagement Natural restoration of tissue homeostasis and resolution of immune engagement Perturbation Injury Infection Genetic Severe tissue remodeling Excess deposition of ECM Pro-inflammation IL-1β, TNF-α, IFN-ɣ Circulation ↑ Natural Resokine levels T cell Macrophage Neutrophil Mast cell Resokine Pathway Promotes Lung Homeostasis Epithelial damage Results We characterized serum from a number of Jo-1–positive patients and found the majority exhibited strong cross-reactivity with the N-terminal portion of Resokine and that a splice variant (SV9), which encodes only the N-terminal domain of the protein, is enriched in human lung tissue. Here, we demonstrate that in the lung-derived adenocarcinoma cell line A549, Resokine is actively secreted following stimulation with the inflammatory cytokines IFN-g and TNF-α, two key players in the initiation of lung inflammation and fibrosis. Secretion is dose dependent and synergistic. SV9, but not the full-length mRNA, is increased following inflammatory cytokine stimulation and its peak expression precedes that of the secreted protein. Repeated vaccination of mice with murine Resokine in the presence of adjuvant can break tolerance and generate auto-antibodies. Resokine was present in bronchoalveolar lavage fluid of controls and undetectable in vaccinated animals. In animals with a high titer to Resokine, infiltration of immune cells (including T-cells) into skeletal muscle and lung was detected. Furthermore, in vaccinated animals receiving bleomycin intratracheally, lung function was more severely impacted and both CD4+ and CD8+ T-cells were increased in the mediastinal nodes. Interestingly, these pathologies were observed only in mice that carry a genetic mutation in dysferlin (and other loci) but not in wild-type mouse strains (e.g., C57bl/6). Conclusion Immune invasion pathologies observed in mice forced to break tolerance to Resokine in the background of another tissue-damaging genetic mutation are similar to activity observed in patients with Jo-1 autoantibodies. This suggests that induction of Resokine insufficiency may disrupt immune homeostasis in a manner that manifests as pathological in lung and muscle. The findings that Resokine circulates at pM levels and the splice variant SV9 is synergistically induced and secreted by lung-derived cells in an inflammatory environment provide evidence for an extracellular niche in which autoantibodies could mediate neutralization of these proteins to induce pathology. References Zhou JJ et al. Secreted histidyl-tRNA synthetose splice variants elaborate major epitopes for autoantibodies in inflammatory myositis. J Biol Chem, 2014. Acknowledgements Alina He (Jo-1 antibody analysis), Kenny D’Arigo/John Bruner (Resokine and Resokine-antibody analysis), Jeanette Ampudia (flow cytometry), Zhiwen Xu, Cario Lo, and Carol Lau (experimental advice, primer design and testing, cell culture). Graphics support was provided by Oxford PharmaGenesis, Inc. and was funded by aTyr Pharma, Inc. Disclosure This study was funded by aTyr Pharma, Inc. Disrupting the Resokine Pathway Promotes Lung Damage Evidence for Homeostatic Role of Resokine in Humans BALF, bronchoalveolar lavage fluid; DAD, diffuse alveolar damage; ILD, interstitial lung disease; NSIP, nonspecific interstitial pneumonia. Reverse primer 1 bp Forward primer 1 *** Normalized mRNA Expression 5 4 3M 2 1 0 Total Leukocytes Bone Marrow Thyroid Lung Heart Pancreas Spleen Liver Kidney Colon Small Intestine Adipose Tissue Skeletal Muscle HARS 1,000 850 650 500 400 300 200 Skeletal muscle M High-titer Patients Jo-1 Autoantibodies Epitope Mapping Percentage of Jo-1 Titer 120 100 80 60 40 20 0 Outside of iMod domain iMod domain iMod domain Depleted Resokine Jo-1 Ab Resokine Splice Variant (SV9) Represents the iMod Domain, the Target of a High Percentage of Disease-linked Jo-1 Antibodies The predominant epitopes are in the N-terminal iMod domain Additional epitopes are present throughout HARS, indicating epitope spreading has occurred Characteristics of Jo-1 Associated ILD Increased T-cells in BALF Decreased CD4/CD8 ratio Histology ranges from NSIP to DAD as severity of disease increases *p < 0.05; **p < 0.01, unpaired t test **p < 0.01 by paired t test ***p < 0.001, one-way Anova **p < 0.01, one-way ANOVA *p < 0.05, one-way ANOVA and Dunnett’s post hoc test *p < 0.05, t test E1 E2 E3 E4 E5 Aminoacylation Domain iMod Domain HomeostasisImbalance Diseased Lung Healthy lung 100% (18 of 18) anti-Jo-1 patients tested positive for antibodies to HARS (known extracellularly as Resokine) with high titers to the iMod domain ∆122 nt HARSiMod HARS Exhibit 99.2

Interstitial Lung Disease and the Immune System Introduction to the iMod.Fc Program aTyr Pharma Investor and Analyst ILD and iMod.Fc Educational Webinar American Thoracic Society International Conference May 23, 2017 Exhibit 99.3

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,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” “opportunity,” or “continue,” and other similar expressions are intended to identify forward-looking statements.  For example, all statements we make regarding the potential therapeutic benefits of Physiocrines and our product candidates, including Resolaris™ and our iMod.Fc program, the ability to successfully advance our pipeline or product candidates, the timing within which we expect to initiate, receive and report data from, and complete our planned clinical trials, and our ability to receive regulatory approvals for, and commercialize, our product candidates, our ability to identify and discover additional product candidates, our projected cash expenditures, and the ability of our intellectual property portfolio to provide protection are forward-looking statements. All forward-looking statements are based on estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that we expected. These risks, uncertainties and other factors are more fully described in our filings with the U.S. Securities and Exchange Commission, including our most recent Quarterly Report on Form 10-Q, our Annual Report on Form 10-K and in our other filings. The forward-looking statements in this presentation speak only as of the date of this presentation and neither we nor any other person assume responsibility for the accuracy and completeness of any forward-looking statement. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. We own various U.S. federal trademark applications and unregistered trademarks, including our company name and Resolaris™. All other trademarks or trade names referred to in this presentation are the property of their respective owners. Solely for convenience, the trademarks and trade names in this presentation are referred to without the symbols ® and ™, but such references should not be construed as any indicator that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto.

Agenda Introduction Mark Johnson, Senior Director Investor Relations, aTyr Pharma Resokine Pathway Sanuj Ravindran, MD, Chief Business Officer, aTyr Pharma ILD Overview Steven Nathan, MD, Director of the Advanced Lung Disease Program and Medical Director of the Lung Transplant Program at Inova Fairfax Hospital, Falls Church, Virginia iMod.Fc Program Sanjay Shukla, MD, MS, Chief Medical Officer, aTyr Pharma Question & Answer Session

Evolved from Cellular Homeostasis Genes over 400 Million Years New Immunological Pathway: Resokine

Resokine: Potential Key Regulator of Homeostasis Evolved with System Complexity Nature 2015 Science 2014 Nature 2013 Nature 2010 Science 1999 Closed Tissue Homeostasis Complex Tissue Homeostasis Open Tissue Homeostasis Conserved Physiocrine domain structures Cellular Homeostasis Protein Synthesis Function tRNA Synthetase Fungi Nematodes Arthropods Vertebrates Mammals Prokaryotes Physiocrines DNA insertions Guo et al. Nature 2010 Resokine fly Resokine human

LIFE’s Therapeutic Paradigm Homeostasis Disease Healthier Patients Resokine insufficiency Resokine agonists

Disease antibodies Homeostasis Imbalance 100% (18 of 18) anti-synthetase syndrome patients tested positive for antibodies for Resokine proteins Diseased Lung Healthy lung ↑ Immune cell Invasion / activity Lung Characteristics Increased T cells in BALF Decreased CD4/CD8 ratio Histology ranges from NSIP to DAD as severity of disease increases BALF = bronchoalveolar lavage fluid; NSIP = non specific interstitial pneumonia; DAD = diffuse alveolar damage Disrupting the Resokine Pathway Promotes ILD Evidence for Homeostatic Role of Resokine in Humans

Free Resokine Pathway in Anti-Synthetase Patients Diminished Unpublished data from aTyr and collaborator Statistics: Mann-Whitney test 69% at or below limit of detection >85% of patients develop Interstitial Lung Disease (ILD)

Lung Bleomycin Induced Lung Fibrosis Th17/CD4 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. Immune Targets Disease Model Resokine Homeostatic Effect Skeletal Muscle Statin Induced Myopathy CD4/CD8 & macrophages Colon TNBS Induced Colitis Th17/CD4 Skin IL23 Induced Psoriasis Th17/CD4

Three Distinct Therapeutic Modalities Harnessing Knowledge of New Immunological Pathways TPP = Target Product Profile ILD = Interstitial Lung Disease; IPF = Idiopathic Pulmonary Fibrosis iMod domain Human Fc domain of an antibody Resolaris Recombinant version of naturally occurring Resokine iMod.Fc ORCA Preclinical activity to id entify IND candidate in 2017 Clinical data in multiple rare muscular dystrophies Generally favorable safety profile in 44 patients dosed to date Human Fc domain: increased exposure to potentially enable TPP = once monthly dosing Indications: Rare ILDs characterized by immune cell infiltration Indications: Rare muscular dystrophies characterized by immune cell infiltration Preclinical activity in industry proven model of IPF (approved drugs Pirfenidone & Nintedanib) Biologics program based on aTyr's knowledge of new pathways in immunology Engineered fusion protein with Resokine splice variant ( iMod ) 3 rd therapeutic modality

Overview of Interstitial Lung Disease Steven Nathan, MD Medical Director, Advanced Lung Disease & Transplant Program Inova Fairfax Hospital Falls Church, Virginia USA Inova Advanced Lung Disease & Transplant Program

Disclosures: Steven Nathan, MD Personal financial relationships with commercial interests relevant to this presentation during the past 12 months: Consultant: aTyr Pharma, Bayer Pharmaceuticals, Boerhinger-Ingelheim, Genentech-Roche, Gilead, Third Pole, United Therapeutics. Speaker’s Bureau: Bayer, Boerhinger-Ingelheim, Genentech, Gilead, Grifols, United Therapeutics. Research Funding: Actelion, Bayer, Boerhinger-Ingelheim, Gilead, Genentech-Roche, United Therapeutics, Veracyte.

Association between Interstitial Lung Abnormalities and All-cause Mortality JAMA 2016;315:672-681 Blue segments of y-axes indicate mortality range from 0% to 20%. P values included in each panel are associated with hazard ratios (HRs [95% CIs]) from the adjusted Cox proportional hazards model including adjustments for age, sex, race, body mass index, pack-years of smoking, current or former smoking status, and GOLD stage of COPD (except in AGES-Reykjavik where GOLD stage was not available). AGES indicates the Age Gene/Environment Susceptibility.

JAMA 2016;315:672-681 Blue segments of y-axes indicate mortality range from 0% to 20%. P values included in each panel are associated with hazard ratios (HRs [95% CIs]) from the adjusted Cox proportional hazards model including adjustments for age, sex, race, body mass index, pack-years of smoking, current or former smoking status, and GOLD stage of COPD . COPD, chronic obstructive pulmonary disease; ECLIPSE, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ILA, interstitial lung abnormalities. Association between Interstitial Lung Abnormalities and All-cause Mortality

Category Diseases Sub-categories/examples Idiopathic Idiopathic Interstitial Pneumonias (IIPs) IPF NSIP Unclassifiable COP RB-ILD DIP AIP LIP PPFE Sarcoidosis Amyloidosis Lymphangiolyomyomatosis PLCH, Eosinophilic pneumonia. Neurofibromatosis, DAH Immunologic Connective Tissue Disorders Inhalational Inorganic Asbestosis, Silicosis Organic: Chronic hypersensitivity pneumonitis Bird fanciers disease, Farmer’s lung Iatrogenic Antiarrhythmics Antimicrobials Chemotherapy agents Biologics Radiation  Infectious Viral CMV, influenza Fungal Pneumocystis carinii Chronic CHF Neoplastic Lymphangitic carcinomatosis Bronchoalveolar carcinoma   Inflammation Fibrosis +/- + +++ ++ ++ ++ +/- +++ - +++ ++ +++ + - + + - +++ ++ ++ - ++ ++ + - + N/A N/A N/A N/A N/A N/A N/A N/A

Spectrum of ILD followed by Inova ALD Program (N=657) 11.6% 8.6% 13.3% 13.3%

SLE MCTD SCL SCL

Prevalence of ILD in CTD 1,600 deaths in USA annually 25% of all ILD deaths 2% of respiratory deaths RA: 15-20% PM/DM: 5-20% SLE: 5-18% Scleroderma: 50-70% Sjogrens:5-40%

Adapted from Chartrand, Fischer. Sarc Vasc;2015:32:2-21 APPROACH TO THE TREATMENT OF CTD-ILD Disease impairment Subjective: Objective: -functional capacity - 6MWT -dypsnea - HRCT/PFT Mild and non-progressive Clinically non-significant ILD Moderate-severe and/or progressive Clinically significant ILD Clinical surveillance q3-6 months Treat Non-pharmacologic Smoking cessation Pulm Rehab Oxygen Immunizations PJP prophylaxis GERD PH CTEPH Pharmacologic Induction High dose oral or pulsed IV steroids Maintenance Steroid-sparing agent: MMF, CSA, AZA, FK506, CSA Cyclophosphamide in severe cases Evaluate treatment response (q3-6 months) Stable or improved -continue Rx -continue clinical surveillance Progressive disease, consider: -maintain/titrate up steroids -Change agents (consider cyclophos) -Severe refractory-consider rituximab - ?lung transplant

Chronic Hypersensitivity Pneumonitis Birds, hot tubs, mold, “idiopathic” Insidious in onset May mimic UIP Utility of HP panel uncertain Inspiratory and expiratory CT - air-trapping or “mosaism”

Chronic HP: Pathology

Sarcoidosis: Systemic Disease A multisystem disease Unknown etiology Granulomatous disorder Affects individuals world wide Most often affects young adults Prevalence of 10-20 per 100,000 population Incidence is unknown Varies among geographical groups Lifetime incidence in blacks is 2.4%, in whites 0.85%

Non-Caseating Granulomas

Treatment of Sarcoidosis Not all patients require therapy for sarcoidosis About half never get treated Pulmonary, ocular, neuro, cardiac, hypercalcemia Treatment strategies are different based on phase of disease Acute Chronic Refractory Steroids, methotrexate, azathioprine, mycophenolate, leflunomide, infliximab, acthar gel

Revised ATS/ERS Idiopathic Interstitial Pneumonia Classification Major Idiopathic Interstitial Pneumonias Idiopathic Pulmonary Fibrosis Idiopathic nonspecific interstitial pneumonia Respiratory bronchiolitis interstitial lung disease Desquamative interstitial pneumonia Cryptogenic organizing pneumonia Acute interstitial pneumonia Rare Idiopathic Interstitial Pneumonias Idiopathic lymphoid interstitial pneumonia Idiopathic pleuroparenchymal fibroelastosis Unclassifiable idiopathic interstitial pneumonias Am J Respir Crit Care Med 2013;188:733-748

NSIP

RML – adjacent mild cellular IP

RLL – venulitis

Current Definition of IPF Specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause Occurring primarily in older adults Limited to the lungs ATS/ERS/JRS/ALAT consensus statement Am J Respir Crit Care Med. 2011;183:788-824

1. Raghu G et al. Lancet Respir Med. 2014;2:566-572 Medicare Beneficiaries Age ≥65 y Median survival = 3.8 y Factors associated with lower survival Age, index year, male gender Increasing Prevalence of IPF

IPF: Survival at the Turn of the Century 2000-2009 (N=521) Median survival: 36 & 42 months Chest 2011;140:221-229

Mortality Rate High in IPF

Pathology: UIP Pattern

T-cells in IPF Lungs. Immunohistochemical staining shows that abnormal CD3+ T-cell infiltrates (black cells near arrow) in lungs of IPF patients with usual interstitial pneumonia are distributed heterogeneously, and are often especially prominent in proximity to fibroproliferative foci (star). These infiltrates include both CD4+ and CD8+ T-cells (not shown). Similar associations between infiltrating T-cells and fibroproliferation are present in other chronic human diseases. Image courtesy of G. Rosen. (10x).

P=0.001 Collaborators. N Engl J Med. 2012;366:1968-1977. N Engl J Med 2012;366:1968-77

IPF…Rx with immunosuppressive therapies Other ILD…Rx with immunosuppressive therapies IPF, IIPs and CTD-ILD= historic parallel treatment paths IPF: say “goodbye” to AZA + Pred IPF: say “hello” to the antifibrotics TREATMENT PARADIGM SHIFT SEISMIC

King TE Jr., et al. N Engl J Med. 2014;370:2083-2092. Richeldi L, et al. N Engl J Med. 2014;370:2071-2082.

Fibrosis CTD-ILD occult CTD +serologies IPF Interstitial pneumonia with autoimmune features Systemic sclerosis sine scleroderma Amyopathic ILD Rheumatoid arthritis Systemic sclerosis PM/DM SLE INTERSTITIAL LUNG DISEASE: A SPECTRUM Inflammation

Fibrosis CTD-ILD occult CTD +serologies IPF INTERSTITIAL LUNG DISEASE: A SPECTRUM Inflammation SARCOIDOSIS Non-Specific Interstitial Pneumonia Chronic Hypersensitivity Pneumonia

Same Case with Differing Pathology

Disease Evolution Time Biochemical + pathways + cellular events Pathological alterations Radiographic changes Symptoms Physiologic alterations Clinical Syndrome

Disease Evolution Time Biochemical + pathways + cellular events Pathological alterations Physiologic alterations Symptoms Radiographic signs Clinical Syndrome Fibrosis and honeycombing Fibroblastic foci granulomas Focus of OP Inflammation

Progression of interstitial process Therapy ImmunoRx ?antifibrotic* ?PAH therapy * CTD-ILD: conceptual framework for future therapeutic approach *not recommended, await RCT evidence Acute exacerbation ?role and timing of biologics, IVIG, plasmapheresis*

Adult Lung Transplants Kaplan-Meier Survival by Diagnosis (Transplants: January 1990 – June 2012) 2014 JHLT. 2014 Oct; 33(10): 1009-1024 http://www.ishlt.org/registries/slides.asp?slides=heartLungRegistry Accessed 9/15/2015

Lung Physiocrine Engineered to Treat Multiple Pulmonary Diseases iMod.Fc Program

Resokine Promotes Lung Homeostasis Epithelial damage IL-13, TGFβ, TNF, IL-1β Resokine agonist therapy Pharmacologic restoration of tissue homeostasis and resolution of immune engagement Natural restoration of tissue homeostasis and resolution of immune engagement Perturbation Injury Infection Genetic Fibrocytes EMT Fibroblasts Severe tissue remodeling Circulation Natural Resokine levels Pro-inflammation IL-1β, TNF, IFNɣ T Cell Neutrophil Macrophage Mast Cell

iMod.Fc Overview Opportunity for Lung Patients iMod domain Fc domain of an antibody Engineered Physiocrine iMod.Fc iMod domain: Resokine splice variant relatively more expressed in lung than other tissues Fc domain: increased exposure to potentially enable once-monthly dosing in humans Engineered result: iMod.Fc ~350x increased exposure vs. iMod; while retaining T cell modulation activity 1st molecule from internal Fc platform

iMod Domain in Lung Splice Variant Express Data for iMod in Lung Splice variant for the iMod domain is relatively more expressed in lung than other tissues Zhou et al. The Journal of Biological Chemistry 2014

Functional Knockout of Resokine Pathway Increases T Cell Invasion Post Disease Induction Rodent functional knockout inducing idiopathic pulmonary disease using Bleomycin * p < .05

Functional Knockout of Resokine Pathway Increases T Cell Invasion Post Disease Induction Rodent functional knockout inducing idiopathic pulmonary disease using Bleomycin * p < .05

iMod.Fc (Resokine Pathway) Outperforms Current Treatments Established Rodent Model for Idiopathic Pulmonary Fibrosis (IPF) *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 (%)* (Reduction in Fibrosis) TGF β Ab 3mg/kg IP QOD D0-D 21 Pirfenidone 100 mg/kg PO BID D8-D 21 iMod.Fc 0.4 mg/kg IV mg/kg D8, D15 33 Total drug amt (mg/kg) 2,800 0.8 iMod.Fc outperformed pirfenidone at 1/3500th total dose Two doses of iMod.Fc outperformed 11 TGFβ Ab doses Superior activity in established IPF fibrotic model Vehicle

Biomarker/MOA: Introduce mechanistic/PD assay GMP Manufacturing: Complete initial clinical trial supply IND Enabling: Initiate preclinical safety studies Activity in industry proven model of IPF (approved drugs Pirfenidone & Nintedanib) GMP manufacturing kicked off Rat/non-human primate non-GLP safety & PK data support advancement to IND Milestones: 2017 Development Goals: iMod.Fc: Status and 2017 Development Goals Clinical Trial: Initiate first in human clinical trial

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