Drug Development and Clinical Trials - Efzofitimod is a first-in-class biologic immunomodulator in clinical development for interstitial lung disease (ILD) with orphan drug designations from the FDA for sarcoidosis and systemic sclerosis (SSc) [12] - The EFZO-FIT study, a pivotal Phase 3 trial for efzofitimod in pulmonary sarcoidosis, is currently enrolling up to 264 subjects and aims to complete enrollment by Q2 2024 [14][15] - The Phase 1b/2a clinical trial demonstrated consistent dose response for efzofitimod on key efficacy endpoints, including improvements in lung function and symptom measures compared to placebo [13] - The primary endpoint of the EFZO-FIT study is steroid reduction, with secondary endpoints including forced vital capacity (FVC) and quality of life assessments [14] - The EFZO-CONNECT study for efzofitimod in patients with SSc-ILD was initiated in Q3 2023, with the first patient dosed in October 2023 [17][22] - The ongoing Phase 3 clinical trial, EFZO-FIT, aims to enroll up to 264 patients with symptomatic pulmonary sarcoidosis, evaluating the efficacy and safety of IV efzofitimod at doses of 3.0 mg/kg and 5.0 mg/kg [43] - The Phase 1 clinical trial of efzofitimod in healthy volunteers indicated that the drug was well-tolerated at all dose levels tested, with no significant adverse events [57] - The Phase 1b/2a clinical trial for efzofitimod in pulmonary sarcoidosis demonstrated a 58% overall steroid reduction from baseline and a 22% relative reduction compared to placebo in the 5.0 mg/kg treatment group [51] - The EFZO-CONNECT study, targeting SSc-ILD, is a 28-week trial with a planned enrollment of 25 patients, with the first patient dosed in October 2023 [17] - The Phase 2 clinical trial for efzofitimod in COVID-19 patients showed that a single IV dose was generally safe and well-tolerated, with a signal of activity in the 3.0 mg/kg cohort [56] Financial and Market Considerations - The Kyorin Agreement has generated $20.0 million in upfront and milestone payments, with potential for an additional $155.0 million upon achieving certain milestones [18] - The global market opportunity for pulmonary sarcoidosis and SSc-ILD is estimated to be between $2-3 billion [72] - The company has incurred significant losses since inception and anticipates continued losses for the foreseeable future [10] - The market for ILD treatments remains underserved, presenting a high unmet medical need for effective therapies [12] - The company faces significant uncertainty regarding coverage and reimbursement from third-party payors, which may limit sales of approved products [125][132] - Third-party payors are increasingly scrutinizing pricing and cost-effectiveness, potentially impacting reimbursement rates for approved products [126][129] - The U.S. government and state legislatures are implementing cost containment programs that may reduce the profitability of drug products, including price controls and mandatory discounts [127] Regulatory and Compliance - The FDA requires extensive preclinical and clinical testing before any new biologic can be marketed, which involves significant time and financial resources [96] - A Biologics License Application (BLA) must include all relevant data from preclinical studies and clinical trials, and FDA approval is required before marketing [104] - The FDA may issue a Complete Response Letter (CRL) if the BLA is not ready for approval, outlining deficiencies that need to be addressed [108] - The FDA grants orphan drug designation for drugs treating rare diseases affecting fewer than 200,000 individuals in the U.S., providing financial incentives and exclusivity for seven years if approved first [117][118] - The company is subject to various federal and state healthcare laws, including the Anti-Kickback Statute and the False Claims Act, which could impact operations [136] - The company has implemented safeguards to discourage improper payments under the U.S. Foreign Corrupt Practices Act (FCPA) [135] Research and Development Strategy - The company is focused on advancing efzofitimod toward regulatory approval and exploring its applications in other ILDs [21][22] - The company has advanced two additional tRNA synthetase programs, ATYR0101 and ATYR0750, into preclinical development [23] - The company plans to further elucidate the therapeutic potential of efzofitimod through mechanistic investigations, including in vitro and in vivo preclinical studies [23] - The company plans to invest significant financial and management resources to develop the appropriate commercial infrastructure for its product candidates [75] - The company aims to expand its intellectual property estate by filing patent applications for new methods of treatment and therapeutics [83] Employee and Operational Insights - As of December 31, 2023, the company had 59 employees, with 56 being full-time, including 36 in research and development roles [137] - The company emphasizes the importance of attracting and retaining talented employees to execute its strategy effectively [138] - The company operates in a single accounting segment, indicating a focused business model [141] Drug Mechanism and Efficacy - Efzofitimod targets the NRP2 receptor, which is upregulated during differentiation and activation of myeloid cells, potentially providing a novel therapeutic approach for immune-mediated and fibrotic diseases [32] - Efzofitimod has shown significant reduction in lung inflammation and fibrosis, improving respiratory function parameters in multiple animal models of lung fibrosis [29] - Efzofitimod has been shown to reduce lung and skin fibrosis in an animal model of systemic sclerosis (SSc-ILD), indicating its potential as a therapeutic candidate for this condition [42] - The company has demonstrated that efzofitimod downregulates key inflammatory cytokines such as IL-6, TNF-α, and IFN-γ in both animal models and human clinical trials [29] - Efzofitimod is a novel immunomodulatory Fc fusion protein that selectively modulates NRP2 to downregulate immune responses in inflammatory diseases [24]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2023 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-37378 | --- | --- | --- | |-----------------------------------------------------------------------------------------|------ ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2023 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-37378 Common Stock, par value $0.001 per share LIFE The Nasdaq Capital Market Indicate by check mark whether the registrant (1) ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2023 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-37378 (Exact name of registrant as specified in its charter) Delaware 20-3435077 (State or other jurisdiction of incorporation ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 10-K (Mark One) ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2022 or TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-37378 ATYR PHARMA, INC. (Exact name of registrant as specified in its charter) Delaware 20-3435077 (State or other jurisdiction of incor ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2022 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-37378 ATYR PHARMA, INC. (Exact name of registrant as specified in its charter) (State or other jurisdiction of incorporatio ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2022 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-37378 ATYR PHARMA, INC. (Exact name of registrant as specified in its charter) (State or other jurisdiction of incorporation or ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2022 or (858) 731-8389 (Registrant's telephone number, including area code) Securities registered pursuant to Section 12(b) of the Act: | Title of each class | Trading Symbol(s) | Name of each exchange on which registered | | --- | --- | --- | | Common Stock, par value $0.001 per share | ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2021 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-37378 ATYR PHARMA, INC. WASHINGTON, D.C. 20549 FORM 10-K (Exact name of registrant as specified in its charter) Delaware 20-3435077 (State or other jurisdiction of i ...

For the quarterly period ended September 30, 2021 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE EXCHANGE ACT OF 1934 For the transition period from to UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Commission File Number: 001-37378 ATYR PHARMA, INC. (Exact name of registrant as specified in its charter) Delaware 20-3435077 (State or other jurisdiction of inc ...