Slides
Page 1
A New Approach to Interstitial Lung Disease J.P . Morgan Healthcare Conference Sanjay S. Shukla, M.D., M.S., President and CEO January 16, 2025
Page 2
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 regarding: the potential therapeutic benefits of proteins derived from tRNA synthetase genes and our product candidates and development programs; the ability to successfully advance our product candidates and undertake certain development activities (such as the initiation of clinical trials, clinical trial enrollment, the conduct of clinical trials and announcement of clinical results) and accomplish certain development goals, and the timing of such events; the potential market opportunity for our product candidates; our ability to receive regulatory approvals for, and commercialize, our product candidates; our ability to identify and discover additional product candidates; potential activities and payments under collaboration agreements; 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 Annual Report on Form 10-K, our subsequently filed Quarterly Reports on Form 10-Q, 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. 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. This presentation discusses product candidates that are under clinical study and which have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of these product candidates for the uses for which they are being studied. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involved a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. 2
Page 3
Corporate Highlights 3 BLA = Biologics License Application Strong cash position with runway through key upcoming readouts and subsequent BLA submission for efzofitimod in pulmonary sarcoidosis Major Phase 3 catalyst for multi-billion dollar indication in Q325 Pipeline targeting inflammation and fibrosis built on novel tRNA synthetase biology platform
Page 4
A New Approach to Interstitial Lung Disease (ILD) • ILD are a group of severe inflammatory and fibrotic lung diseases • Persistent inflammation leads to worsening lung function, fibrosis and poor quality of life (QoL) • Progressive fibrosis can result in a survival rate that is worse than many common cancers • Current therapeutic options are toxic and not disease modifying 4 *Schimmel et al. The Endless Frontier of tRNA Synthetases. The Enzymes. 2020 End stage fibrotic lung* Efzofitimod is a first-in-class biologic immunomodulator with a novel mechanism of action in Phase 3 development to address the significant unmet medical need in ILD
Page 5
200K 60K 120K 65K 155K 135K 735K Sarcoidosis SSc-ILD Other CTD- ILD cHP Other ILDs IPF Total aTyr is Advancing Efzofitimod as the Standard-of-Care for ILD 5 Number of U.S. ILD Patients by Type • ILD is an umbrella term for >200 types of rare lung diseases that span a spectrum of inflammation and fibrosis • Patients have poor quality of life with high morbidity and mortality • No disease-modifying therapies available; current options have significant toxicities • aTyr’s current focus estimated at $2-5b global market opportunity (1) • Upside potential in other ILD and related autoimmune diseases (e.g., SSc, lupus, RA) Inflammation Fibrosis Current Focus Upside (1) Based on aTyr internal estimates, Back Bay Life Science Advisors market research and 2024 third party claims data analysis
Page 6
Efzofitimod: First-in-Class Biologic Immunomodulator for ILD 6 OCS = oral corticosteroids No known significant safety issues Targets innate immunity at site of inflammation • downregulates pro-inflammatory and pro-fibrotic pathways via macrophages • addresses complex immune pathology • restores immune balance without evidence of suppression Promising clinical proof-of-concept • Reduced OCS • Improved lung function • Resolved symptoms
Page 7
Pulmonary Sarcoidosis A Major Form of Interstitial Lung Disease with High Unmet Medical Need
Page 8
Sarcoidosis is an Orphan Lung Disease with High Unmet Medical Need Epidemiology 1) Compatible clinical presentation 2) Non-necrotizing granulomatous inflammation 3) Exclusion of alternative causes 8 200,000 pts 150,000 pts 20,000 pts • 1/12 patients hospitalized for their disease annually • Mortality rising: 1/5 Medicare patients die every 3 years – 60% higher risk than general population • Fibrosis and concomitant pulmonary hypertension biggest drivers of mortality >1 million pts worldwide Diagnosis Prognosis U.S. epidemiology and prognosis confirmed by 2024 third party claims data analysis Disease Pathology • Inflammatory disease of unknown cause • Characterized by granulomas, or clumps of immune cells • Can affect almost any organ; 90% of cases affect the lungs
Page 9
Sarcoidosis Patients Suffer from Both High Disease & Treatment Burden 9 Corticosteroids remain first line SoC Short term benefit, but continued use results in debilitating side effects; getting patients off OCS becomes primary goal 1/5 patients will progress to fibrosis Higher risks of pulmonary hypertension, organ failure & death Major socioeconomic impact Loss of ability to work, potentially disabling Sarcoidosis robs patients of their QoL Nonlinear journey to diagnosis; patients plagued by shortness of breath, persistent dry cough and severe fatigue Limited alternatives available Off-label rheumatology drugs are physicians’ only options, with limited evidence in sarcoidosis
Page 10
Efzofitimod Target Population for Sarcoidosis Efzofitimod Positioning • Front line as a steroid-sparing agent in moderate-to-severe patients • Reduce / eliminate steroids and avoid use of cytotoxic immunosuppressants and anti-TNFs • Addressable population: 50-75% of all sarcoidosis patients(1) (1) Based on 2024 third party claims data analysis OCS = oral corticosteroids; *minimal antifibrotic use10 30% 40% 20% Disease Severity Fibrotic Asymptomatic / Mild Moderate-to- Progressive 25% 75% Current Treatment Steroids OCS with or without other immunomodulators* No treatment / observation
Page 11
Multiple Benchmarks Support Premium Pricing for New Rare Disease Treatments *Estimated annual cost of comparative products based on list price and labeled dosing in the U.S. Efzofitimod is positioned to be the first approved product for sarcoidosis in >60 years with limited competition $200K* Rare disease drug launches in recent years (Tavneos, Livdelzi, Filspari) ILD treatments that slow lung function decline (Ofev, Actemra) Steroid-sparing agents for inflammatory disorders (Tavneos, Nucala, Filspari) 11
Page 12
Efzofitimod First-in-Class Biologic Immunomodulator for Interstitial Lung Disease
Page 13
Efzofitimod: First-in-Class Biologic Immunomodulator for ILD 13 Predicted U.S. commercial exclusivity into 2039 based on composition of matter patents, with expected patent term extension and regulatory exclusivity programs Novel HARS Domain Human IgG1 Fc Anti-inflammatory and anti-fibrotic effects demonstrated in multiple ILD models support clinical development in ILD Innovative engineering for lung enriched HARS creates novel Fc fusion protein with enhanced PK activity Selective binding to NRP2 on macrophages is upstream of other targets in ILD NRP2 expression in sarcoid granulomas and systemic sclerosis skin macrophages provide strong scientific rationale for initial ILD indications Desirable safety profile demonstrated to date Clinical proof-of-concept demonstrated in pulmonary sarcoidosis HARS = histidyl-tRNA synthetase; NRP2 = neuropilin-2
Page 14
Efzofitimod Modulates Macrophages to Reduce Key Drivers of Inflammation & Fibrosis 14 Immune triggers recruit monocytes, which differentiate to pro-inflammatory macrophages expressing NRP2 If left untreated, persistent macrophage driven inflammation can lead to progressive fibrosis Efzofitimod promotes a less inflammatory macrophage population by downregulating key drivers of inflammation and fibrosis MCP-1 TNFα IL-6 MCP-1 TNFα IL-6 Siefker et al. ATS 2023; Siefker et al. Keystone Symposia: Myeloid Cell Diversity 2024. Efzofitimod acts as an NRP2 agonist
Page 15
Clinical Proof of Concept Demonstrated in Phase 1b/2a Pulmonary Sarcoidosis Trial • Primary objective met: Efzofitimod was safe and well-tolerated (n=37) • Secondary objectives met: Dose-response observed across all three families of pre-specified endpoints compared to placebo • Dose-dependent reduction of inflammatory biomarkers • Improvements in time-to-first steroid relapse and steroid relapse rate for 3.0 and 5.0 mg/kg efzofitimod 15 Reduction in Avg Daily OCS vs Placebo* Lung Function Symptom Improvement vs Placebo OCS = oral corticosteroids *Post-taper
Page 16
Therapeutic Efzofitimod Doses Significantly Improve Multiple Efficacy Measures • Post hoc analysis from Phase 1b/2a study of efzofitimod in pulmonary sarcoidosis • Pooled analysis comparing 3.0 and 5.0 mg/kg efzofitimod (therapeutic group) vs 1.0 mg/kg efzofitimod and placebo (sub-therapeutic group) • Improvements in time-to-first steroid relapse and steroid relapse rate for therapeutic efzofitimod doses Therapeutic Sub-therapeuticSub-therapeutic Therapeutic p = 0.017 p = 0.032 Time to first relapse of steroid taper % Patients with KSQ-Lung >=12 16
Page 17
Phase 3 Trial Design and Endpoints Prioritize Clinically Meaningful Outcomes for Patients 17 First Phase 3 and largest interventional study conducted in sarcoidosis includes primary and secondary endpoints that represent both physiologic and quality of life measures Primary Endpoint — Steroid Reduction Change from baseline in mean daily OCS dose post-taper • Represents a clinically meaningful outcome for patients and providers • Reflective of ERS treatment guidelines that emphasize reducing OCS Secondary Endpoint — FVC • Important measure of lung function in sarcoidosis but limited natural history data Secondary Endpoint — KSQ-Lung • The most relevant patient reported outcome indicative of disease specific pulmonary symptoms End-of-Phase 2 (EOP2) meeting with U.S. FDA conducted in Q122 aligned on prioritization of efficacy parameters FDA = Food and Drug Administration; ERS = European Respiratory Society; OCS = oral corticosteroids; FVC = forced vital capaci ty; KSQ-Lung = Kings Sarcoidosis Questionnaire-Lung
Page 18
Global Phase 3 Trial in Pulmonary Sarcoidosis Ongoing Population: moderate to severe pulmonary sarcoidosis • Diagnosis of pulmonary sarcoidosis for ≥ 6 months • Stable treatment with ≥ 7.5 and ≤ 25 mg/day OCS • Extent of fibrosis < 20% • Symptomatic with KSQ-Lung score ≤ 70 Steroid Taper Protocol Guidelines • Based on Patients Global Assessment (PGA) and Investigator Assessment (IA) conducted every two weeks • If both PGA and IA are stable or improved, patient OCS will need to be tapered; If either PGA or IA has worsened, patient will be rescued with OCS 0 4 8 12 16 20 24 28 Efzofitimod 5 mg/kg (n=88) once monthly IV dosing Efzofitimod 3 mg/kg (n=88) once monthly IV dosing Placebo (n=88) once monthly IV dosing Week Dosing 1:1:1 Randomization Treatment Follow-up Primary objective: Assess the efficacy of efzofitimod in patients with pulmonary sarcoidosis 32 36 40 44 48 52 Begin OCS taper End OCS taper Primary Endpoint Study fully enrolled with 268 patients Topline data expected Q325 18 Individual Patient Expanded Access Program (EAP) is intended to allow access for patients who complete EFZO-FIT and wish to receive treatment with efzofitimod outside of the clinical trial
Page 19
SSc-ILD Indication Expansion Represents Upside Opportunity in Interstitial Lung Disease
Page 20
SSc-ILD is Common and Deadly Manifestation of Systemic Sclerosis Epidemiology 20 >1.5 million patients worldwide Current Treatments • Efzofitimod positioned as 2nd line in patients who progress on or cannot tolerate MMF / CYC • Addressable population in major markets: >50k(1) • Upside potential: improve underlying systemic disease 1) ILD diagnosed secondary to underlying SSc 2) Confirmed with imaging, PFTs and blood work Diagnosis Disease Pathology • Autoimmune disease also known as scleroderma • Characterized by inflammation and scarring, or fibrosis, of skin and other organs, including the lungs (1) Back Bay Life Science Advisors
Page 21
Phase 2 POC Trial Enrolling in SSc-ILD Population: SSc with progressive ILD • Patients with SSc (ACR/EULAR criteria), and ILD (baseline HRCT) • Progressive disease (recent onset, evidence for inflammation, diffuse cutaneous SSc) • On background mycophenolate therapy or equivalent Primary Endpoint • Lung function: forced vital capacity Key Secondary Endpoints • Symptom control: PROs • Skin: histopathology, gene profiling, biomarkers, mRSS 21 -4 0 4 8 12 16 20 24 28 Efzofitimod 450 mg (n=10) once monthly IV dosing Efzofitimod 270 mg (n=10) once monthly IV dosing Placebo (n=5) once monthly IV dosing Interim skin assessments Primary efficacy analysis Safety follow-up Week Dosing Stable background regimen Screening Treatment Follow-up Primary objective: Assess the efficacy of efzofitimod on pulmonary, cutaneous, and systemic manifestations in SSc-ILD POC = Proof of Concept Patients who complete the study are eligible to participate in a 24-week open-label extension. Interim data expected Q225
Page 22
A New Approach to Interstitial Lung Disease
Page 23
Efzofitimod Leads Growing Pipeline of First-in-Class tRNA Synthetase Derived Biologics PROGRAM tRNA SYNTHETASE TARGET/MOA INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Efzofitimod HARS NRP2 modulator Pulmonary Sarcoidosis(1) SSc-ILD Other ILD (CTD-ILD; CHP) ATYR0101 DARS LTBP1 modulator Fibrosis ATYR0750 AARS FGFR4 modulator Liver Disorders tRNA Synthetase Candidates (2) 23 Topline data Q3 2025 Interim data Q2 2025 (1) In partnership with Kyorin Pharmaceutical Co., Ltd. for the development and commercialization of efzofitimod for ILD in Japan (2) Pipeline candidates in development based on additional tRNA synthetases from IP portfolio SSc-ILD = Scleroderma-related ILD; CTD-ILD = Connective Tissue Disease-ILD; CHP = Chronic Hypersensitivity Pneumonitis Japan Partner
Page 24
Corporate Summary 24 Lead candidate efzofitimod for ILD represents $2-5b market opportunity • First-in-class biologic immunomodulator with upstream target for ILD with little competition • Topline data from Phase 3 EFZO-FIT study in pulmonary sarcoidosis expected in Q325 and interim data from Phase 2 EFZO-CONNECT study in SSc-ILD expected in Q225 • U.S. FDA orphan drug designations for sarcoidosis and SSc; Fast Track designations for pulmonary sarcoidosis and SSc-ILD; E.U. orphan drug designations for sarcoidosis and SSc • Commercial exclusivity in the U.S. anticipated into at least 2039 Disruptive tRNA synthetase biology platform • Extracellular tRNA synthetases represent potential new class of medicines • IP directed to more than 200 synthetase fragments represents unique and validated drug discovery method Growing pipeline targeting inflammation and fibrosis • Multiple tRNA synthetase candidates in preclinical development • Candidates bind targets in novel ways with potential implications in high value markets Strong financial fundamentals • ~$68.9m in cash, restricted cash, cash equivalents and investments as of Q324; additional $19.4m in gross proceeds raised from at-the-market (ATM) offering subsequent to Q324 • Cash runway through filing of a Biologics License Agreement (BLA) for efzofitimod in pulmonary sarcoidosis • Partnership with Kyorin Pharmaceutical for efzofitimod for ILD in Japan
Page 25
Thank You