aTyr Pharma (ATYR) refocuses efzofitimod after EFZO-FIT miss with new Phase 3 sarcoidosis trial
Rhea-AI Filing Summary
aTyr Pharma furnished an investor presentation outlining updated clinical data and plans for its lead biologic immunomodulator efzofitimod in pulmonary sarcoidosis and other interstitial lung diseases. The Phase 3 EFZO-FIT trial, the largest interventional pulmonary sarcoidosis study to date, did not meet its primary endpoint of reducing oral corticosteroid dose versus placebo, but showed higher steroid-free rates and improvements in multiple quality-of-life measures at the 5 mg/kg dose while maintaining lung function and a generally favorable safety profile.
The company describes FDA feedback from a Type C meeting supporting forced vital capacity (FVC) and KSQ-L as clinically meaningful endpoints, with FVC selected as the primary endpoint for a new Phase 3 trial (C-006) in patients with restrictive pulmonary sarcoidosis. Efzofitimod is also being tested in the Phase 2 EFZO-CONNECT study for systemic sclerosis-associated ILD and supported by a broader tRNA synthetase–based pipeline, including preclinical fibrosis candidate ATYR0101 and a proprietary tRNA synthetase library targeting inflammatory and fibrotic diseases.
Positive
- Supportive secondary outcomes and safety for efzofitimod: Despite missing the primary endpoint in EFZO-FIT, efzofitimod 5 mg/kg improved multiple quality-of-life measures, maintained lung function and showed favorable steroid-free rates with a generally well-tolerated safety profile.
- Clear FDA-aligned path for a new Phase 3 trial: A Type C meeting led to regulatory support for FVC and KSQ-L endpoints and informed a new Phase 3 design (C-006) focused on restrictive pulmonary sarcoidosis with Q3W dosing.
- Pipeline and market breadth in ILD and fibrosis: Efzofitimod is being advanced into SSc-ILD via the EFZO-CONNECT Phase 2 study, while preclinical fibrosis candidate ATYR0101 and a broader tRNA synthetase library target an ILD market the company estimates at up to $5B.
Negative
- Phase 3 EFZO-FIT primary endpoint not met: The EFZO-FIT pulmonary sarcoidosis trial did not achieve its primary endpoint of change in oral corticosteroid dose at week 48, delaying efzofitimod’s initial registrational path in this indication.
Insights
Primary endpoint missed, but FDA-aligned path forward and supportive secondary data keep efzofitimod in play.
The EFZO-FIT Phase 3 trial in pulmonary sarcoidosis failed its primary steroid-sparing endpoint, which is a setback for efzofitimod’s initial strategy. However, the dataset still showed higher steroid-free rates, quality-of-life gains, maintained lung function, and a generally balanced safety profile, particularly at 5 mg/kg.
aTyr highlights a subsequent FDA Type C meeting where regulators indicated FVC and KSQ-L are clinically meaningful endpoints. The company now plans a new Phase 3 trial (C-006) focused on patients with restrictive lung physiology, using FVC at week 48 as the primary endpoint and KSQ-L as a key secondary, without mandated steroid taper.
Beyond sarcoidosis, efzofitimod is being evaluated in the EFZO-CONNECT Phase 2 study in systemic sclerosis-associated ILD, and preclinical candidate ATYR0101 targets fibrosis through myofibroblast depletion. The overall impact is mixed: delayed path to approval due to a missed endpoint, but preserved optionality via supportive secondary data, regulatory feedback, and pipeline breadth.
8-K Event Classification
Key Figures
Key Terms
pulmonary sarcoidosis medical
forced vital capacity medical
KSQ-L medical
neuropilin-2 (NRP2) medical
tRNA synthetase technical
systemic sclerosis-associated interstitial lung disease (SSc-ILD) medical
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):
(Exact name of registrant as specified in its charter)
|
|
|||
(State or other jurisdiction of incorporation) |
|
(Commission File Number) |
|
(IRS Employer Identification No.)
|
|
|
|
||
(Address of Principal Executive Offices) |
|
|
|
(Zip Code) |
Registrant’s telephone number, including area code: (
Not Applicable
(Former Name or Former Address, if Changed Since Last Report)
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)) |
Securities registered pursuant to Section 12(b) of the Act:
Title of each class |
Trading Symbol(s) |
Name of each exchange on which registered |
The |
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) intends to use an investor presentation to conduct meetings with investors, stockholders and analysts and at investor conferences, and which the Company intends to place on its website. A copy of the presentation materials is attached hereto as Exhibit 99.1 and is incorporated herein by reference. The Company does not undertake to update the presentation materials.
The information under this Item 7.01, including Exhibit 99.1, is being furnished and shall not be deemed “filed” for the purposes of Section 18 of the Securities and Exchange Act of 1934, as amended (the Exchange Act), or otherwise subject to the liabilities of that section, nor shall they be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Exchange Act, whether made before or after the date hereof, regardless of any general incorporation language in such filing, except as expressly set forth by specific reference in such filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
Exhibit No. |
|
Description |
|
|
|
99.1 |
|
Corporate Presentation Materials of aTyr Pharma, Inc. dated June 2026 |
|
|
|
104 |
|
Cover Page Interactive Data File (embedded within the Inline XBRL document) |
|
|
|
2
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/ Jill M. Broadfoot |
|
|
Jill M. Broadfoot |
|
|
Chief Financial Officer |
|
|
|
Date: June 1, 2026 |
|
|
3
aTyr Pharma Advancing tRNA synthetase biology Efzofitimod in Pulmonary Sarcoidosis and Beyond June 2026 © 2026 aTyr Pharma Exhibit 99.1
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 partnerships and collaborations; 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. | © 2026 aTyr Pharma
aTyr’s Strategic Outlook: Creating First-In-Class Therapies that Modulate New Pathways in Inflammatory and Fibrotic Diseases Efzofitimod is a biologic immunomodulator with a novel complementary mechanism of action: EFZO-FIT: largest interventional pulmonary sarcoidosis trial conducted to date; generated key insights being used to optimize the path forward for efzofitimod Planned Phase 3 study in pulmonary sarcoidosis refines primary endpoint, study design, and dosing EFZO-CONNECT: advancing efzofitimod in Phase 2 SSc-ILD study Efzofitimod for ILD represents up to a $5B market opportunity1 Lead preclinical candidate ATYR0101 in development for fibrosis is currently undergoing IND-enabling studies aTyr retains a robust IP-protected tRNA synthetase library Executive Summary aTyr is advancing a platform based on tRNA synthetase biology to build a pipeline focused on inflammation and fibrosis 1aTyr Pharma, Inc. data on file. Abbreviations: ILD, interstitial lung disease; IP, intellectual property; SSc-ILD, systemic sclerosis-associated interstitial lung disease; tRNA, transfer ribonucleic acid. | © 2026 aTyr Pharma Efzofitimod Active HARS domain Human IgGI Fc
Sarcoidosis is a Serious Orphan Disease in Desperate Need of a Safe and Effective FDA-Approved Treatment 1aTyr Pharma, Inc. data on file. Abbreviations: IST, immunosuppressive therapy; QoL, quality of life; SoC, standard of care, TNF, tumor necrosis factor. Pulmonary Sarcoidosis Disease pathology Inflammatory disease that can affect any organ 90% of cases affect the lungs (pulmonary sarcoidosis) Characterized by noncaseating granulomas resulting from an immunologic cascade driven by proinflammatory macrophages Overexpression of neuropilin-2 (NRP2) in sarcoid granulomas Unmet Need Severely impaired QoL with debilitating symptoms including cough, dyspnea and fatigue Risk of progression and organ failure Increased risk of hospitalization and mortality Limited SoC: steroids, cytotoxic IST and TNF inhibitors have poor clinical evidence and substantial toxicity Commercial Opportunity Large diagnosed rare disease population No FDA-approved therapy in 70+ years Disease and treatment burden cause psychological and socioeconomic impact Underserved market without near-term competition | © 2026 aTyr Pharma Epidemiology Orphan disease with more than 1M patients worldwide; 160k in the US1 More common in women 3X as common in people of African descent >50% of patients experience moderate-severe disease with organ impairment 1 in 5 progress to fibrosis
A New Candidate for Pulmonary Sarcoidosis Efzofitimod A biologic immunomodulator that targets NRP2 on activated macrophage cells to resolve inflammation without immune suppression and may prevent fibrosis progression 1Culver D, et al., CHEST. 2023;163, 881-890. 2Nangle LA, et al. Sci Transl Med. 2025 Mar 12;17(789):eadp4754. Abbreviations: NRP2, neuropilin-2. | © 2026 aTyr Pharma Targets new immune receptor to restore immune balance: Selectively modulates NRP2 Downregulates multiple pro-inflammatory pathways Broad anti-inflammatory effect without immune suppression Preclinical data: Demonstrated anti-inflammatory and anti-fibrotic effects in multiple models of lung inflammation and fibrosis Phase 1b/2a trial in pulmonary sarcoidosis:1 Efzofitimod was safe and well-tolerated Dose-response observed across three families of pre-specified endpoints compared to placebo: lung function; quality of life; steroid reduction Cover photo shows NRP2 expression in sarcoid granuloma2
Follow up EFZO-FIT: Largest Interventional Trial Conducted in Pulmonary Sarcoidosis EFZO-FIT 1268 patients were randomized; 264 patients were randomized and dosed Topline data reported Q3 ‘25. *Time frame BL to W48. Abbreviations: BL, baseline; Dx, diagnosis; KSQ-L, King’s Sarcoidosis Questionnaire-Lung Score; OCS, oral corticosteroids; PE, primary endpoint; Q4W, every four weeks; R, randomized; W, week; WASOG, World Association for Sarcoidosis and Other Granulomatous Disorders. | © 2026 aTyr Pharma Target Population: Moderate to severe pulmonary sarcoidosis Enrollment: N=2681 Dx of pulmonary sarcoidosis for ≥6 mos Stable treatment with ≥7.5 and ≤25 mg/d OCS Extent of fibrosis <20% Symptomatic with KSQ-L score ≤70 Primary Endpoint:* Change from BL in mean daily OCS dose at W48 Protocol-guided steroid taper Global trial conducted at 85 centers in 9 countries: Many trial sites are WASOG centers of excellence Efzofitimod 5 mg/kg (n=88) Efzofitimod 3 mg/kg (n=86) Placebo (n=90) R 1:1:1 2 Begin OCS taper 0 8 12 End OCS taper 16 20 24 28 32 36 40 44 48 PE 52 4 Infusion Q4W for a total of 12 doses Week: EFZO-FIT Study Design
Substantial Steroid Reduction Observed in all EFZO-FIT Groups Provides Important Insights Although the primary endpoint of the study was not met, we learned that patients with chronic, symptomatic pulmonary sarcoidosis can be managed for prolonged periods on lower doses of OCS without worsening of disease Note: The study’s statistical analysis plan was designed on a hierarchical assessment basis. As the primary endpoint did not achieve statistical significance, p-values for other endpoints are reported and should be interpreted as nominal p-values. Abbreviations: BL, baseline; CI, confidence interval; ITT, intention to treat; OCS, oral corticosteroids; W, week. Steroid Free at Week 48 ITT: Mean Change from BL in OCS Dose Over Time (Primary Endpoint) EFZO-FIT | © 2026 aTyr Pharma Weeks Mean Change from BL in OCS Dose (mg/day) Placebo Efzofitimod 3 mg/kg Efzofitimod 5 mg/kg Efzofitimod Placebo N=90 3 mg/kg N=86 5 mg/kg N=88 Steroid free; n (%) 36 (40.2) 45 (51.8) 46 (52.6 Odds ratio (95% CI) — 1.6 (0.9, 3.0) 1.7 (0.9, 3.1) p-value — 0.1172 0.0919
p=0.0479 Weeks Estimates with 95% CIs from MMRM Evidence of Clinical Activity Demonstrated Across Multiple Pre-specified QoL Endpoints EFZO-FIT *Difference in LS Means from Placebo (with 95% CIs) from MMRM. Abbreviations: BL, baseline; CI, confidence interval; KSQ-L, King’s Sarcoidosis Questionnaire-Lung Score; LS, least squares; MMRM, mixed model for repeated measures; QoL, quality of life. | © 2026 aTyr Pharma KSQ-L measures how much pulmonary sarcoidosis affects a patient’s perceived respiratory QoL: By weeks 9-12, KSQ-L was significantly increased in patients on 5.0 mg/kg efzofitimod relative to placebo Increased KSQ-L represents improved QoL Steroid reduction and KSQ-L composite endpoint measures whether patients could both reduce steroids and improve QoL: More patients met the composite of steroid-free with improved KSQ-L on 5.0 mg/kg efzofitimod Efzofitimod 5 mg/kg vs Placebo from Logistic Regression Steroid-free Steroid-free & KSQ-L >-3 (stable) Steroid-free & KSQ-L ≥8 (improvement) Odds Ratio (95% CI) Favors Efzofitimod Differences in KSQ-L Score Change from BL* Efzofitimod 3 mg/kg Efzofitimod 5 mg/kg Placebo p=0.0196
Evidence of Clinical Activity Demonstrated Across Multiple Pre-specified QoL Endpoints EFZO-FIT *Difference in LS Means from Placebo (with 95% CIs) from MMRM. Abbreviations: BL, baseline; CI, confidence interval; FAS, fatigue assessment scale; KSQ-GH, King’s Sarcoidosis Questionnaire-General Health Score; LS, least squares; MMRM, mixed model for repeated measures; QoL, quality of life. | © 2026 aTyr Pharma KSQ-GH measures how much pulmonary sarcoidosis affects a patient’s perceived general health: By weeks 9-12, KSQ-GH was significantly increased in patients on 5.0 mg/kg efzofitimod relative to placebo Increased KSQ-GH represents improved QoL FAS measures how much fatigue affects the patient: By weeks 9-12, FAS was significantly decreased in patients on 5.0 mg/kg efzofitimod relative to placebo Decreased FAS represents improved fatigue Estimates with 95% CIs from MMRM p=0.0197 p=0.0226 Weeks Estimates with 95% CIs from MMRM Differences in KSQ-GH Score Change from BL* Differences in FAS Total Score Change from BL* Efzofitimod 3 mg/kg Efzofitimod 5 mg/kg Placebo Weeks
Forced Vital Capacity Maintained Despite Steroid Taper EFZO-FIT EFZO-FIT enrolled a heterogenous patient population with various pulmonary phenotypes *Difference in LS Means from Placebo (with 95% CIs) from MMRM. Abbreviations: BL, baseline; CI, confidence interval; FVC, forced vital capacity; L, liter; LS, least squares; MMRM, mixed model for repeated measures; W, week. | © 2026 aTyr Pharma Efzofitimod Placebo N=90 3 mg/kg N=86 5 mg/kg N=88 LS means at W48 (mL) 3380.4 3369.7 3395.4 LS means change from BL (mL) -84.5 -95.1 -69.4 Difference in LS mean (mL) (95% CI) — -10.6 (-104.7, 83.5) 15.1 (-77.4, 107.6) p-value — 0.8244 0.7485 FVC at Week 48 (MMRM) Change from BL in FVC (L) Over Time Weeks Average Change in FVC (L) Placebo Efzofitimod 3 mg/kg Efzofitimod 5 mg/kg
Efzofitimod was generally well-tolerated at both the 3.0 mg/kg and 5.0 mg/kg doses, consistent with a previously observed safety profile in all trials conducted to date AEs were mostly mild or moderate in severity and generally assessed as unrelated to the study drug SAEs were limited and balanced between groups Proportion of patients with treatment-related SAEs and events leading to discontinuation was small and balanced between groups Proportion of patients who developed antidrug antibodies was small and balanced between groups Efzofitimod was Generally Well-Tolerated with Consistent Safety Profile EFZO-FIT Abbreviations: AE, adverse event; SAE, serious adverse event. | © 2026 aTyr Pharma
FDA Type C Meeting Informs Future Efzofitimod Development FDA indicated support for FVC and KSQ-L as clinically meaningful endpoints in pulmonary sarcoidosis KSQ-L: FDA recommended the inclusion of wheezing and cough severity as separate measures of patient symptoms, along with new anchors to interpret the clinically meaningful threshold, based on further content validation Our conclusion: FVC is a more appropriate primary endpoint for C-006, considering FDA has not fully endorsed KSQ-L as fit-for-purpose FDA reviewed data presenting the rationale for utilizing FVC as an endpoint in the target population for C-006 based on data from EFZO-FIT FDA acknowledged reasonableness of the proposed Q3W dosing in the proposed patient population in C-006 Aligned with FDA on incorporating additional risk mitigation strategies in the protocol Safety surveillance for the potential for development of anti-synthetase syndrome will be closely and prospectively monitored Data Monitoring Committee will be in place Benefit/risk profile Efzofitimod’s benefit/risk profile supports continued development with Q3W dosing in proposed population Company plans to file IND for C-006 in June 2026 Path Forward Objective: align on the path forward for efzofitimod in pulmonary sarcoidosis Outcome: Company to continue development of efzofitimod in pulmonary sarcoidosis incorporating FDA feedback, including plans to pursue new Phase 3 study (C-006) Abbreviations: FDA, Food and Drug Administration; FVC, forced vital capacity; IND, investigational new drug; KSQ-L, King’s Sarcoidosis Questionnaire-Lung; Q3W, every three weeks. | © 2026 aTyr Pharma
Sarcoidosis has Heterogenous Lung Phenotypes; FVC Relevant Only in Restrictive Phenotype Path Forward FVC has been used as a registrational endpoint in related ILD indications, with approvals being granted for placebo adjusted differences as low as 45 mL *Sharp M, et al. Ann Am Thorac Soc. 2023 Jan;20(1):30-37. †Data on file. Abbreviations: DLCO, diffusing capacity of the lungs for carbon monoxide; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; LLN, lower limit of normal. | © 2026 aTyr Pharma Phenotype Definition* Real-World Data* N=562 (%) EFZO-FIT† N=264 (%) Relevant Endpoint Normal Not having any impairment 246 (43.8) 89 (33.7) — Restrictive FVC < lower limit of normal (LLN) with FEV1/FVC ≥ LLN 149 (26.5) 44 (16.7) FVC Obstructive FEV1/FVC ≤ LLN with FVC ≥ LLN 71 (12.6) 70 (26.5) FEV1 Mixed (combined obstructive/restriction) FVC < LLN and FEV1/FVC < LLN 50 (8.9) 34 (12.9) FVC, FEV1 Isolated diffusion-limited DLCO < LLN with no restrictive or obstructive defect 46 (8.2) 27 (10.2) DLCO
Data from EFZO-FIT Support Our Rationale for FVC as Primary Endpoint in Target Patient Population Baseline characteristics were generally similar to the ITT population with a few notable exceptions Expectedly, the FVCpp in the restrictive subset (~70%) was lower when compared to the ITT population (~88%) AE profile was generally similar to the ITT population with the exception that wheezing was not reported in the restrictive subset Efzofitimod 5 mg/kg showed trends toward greater steroid reduction vs placebo in the restrictive population OCS reduction from baseline observed at W48: 74% vs 58% Steroid free observed at W48: 50% vs 40% Relapse (steroid rescue for >14d) observed at W48: 8% vs 31% Path Forward Clinically meaningful FVC benefit observed at week 48 in patients with restrictive lung disease when treated with efzofitimod W48 window ends on Study Day 351. *Not Restrictive: includes normal, mixed, obstructive, diffusion limited.†Restrictive: BL FVCpp ≤80% & FEV1/FVC Ratio ≥0.7; ‡RCRM delta between 5mg/kg and placebo at W48. Abbreviations: CI, confidence interval; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; FVCpp, forced vital capacity, percent predicted; ITT, intention-to-treat; L, liter; OCS, oral corticosteroids; RCRM, regression coefficient reassessment method; W, week. | © 2026 aTyr Pharma FVC (L) with 95% CIs from RCRM Study Day FVC (L) Over Time By-Phenotype & Treatment (RCRM) Restrictive† Placebo Efzofitimod 5 mg/kg 124 mL‡
Benefit on PROs Observed in EFZO-FIT in ITT Remains Consistent in Restrictive* Population Path Forward *Restrictive by FVCpp: Baseline FVCpp ≤80% & FEV1/FVC ration ≥0.7. †RCRM model est. adj. for Baseline MMLUNGSS. ‡RCRM model est. adj. for Baseline MMGENHSS. §RCRM model est. adj. for Baseline MMFASTOT. Week 48 window ends on Study Day 351. Abbreviations: CI, confidence interval; FAS, Fatigue Assessment Scale; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; FVCpp, forced vital capacity, percent predicted; ITT, intention-to-treat; KSQ-GH, King’s Sarcoidosis Questionnaire-General Health; KSQ-L, King’s Sarcoidosis Questionnaire-Lung; MMLUNGSS, baseline lung symptom score; MMFASTOT, baseline fatigue total score; MMGENHSS, baseline general health score; PRO, patient-reported outcome; RCRM, repeated continuous reassessment method. | © 2026 aTyr Pharma KSQ-Lung with 95% CIs Study Day KSQ-GH with 95% CIs FAS with 95% CIs Placebo Efzofitimod 5 mg/kg KSQ-L Predicted RCRM† KSQ-GH Predicted RCRM‡ FAS Predicted RCRM§
Go-Forward Development Plan Leverages Insights from EFZO-FIT and Engagement with FDA Path Forward Study design to incorporate key changes intended to demonstrate compelling evidence of efficacy and safety on clinically meaningful endpoint Abbreviations: FVC, forced vital capacity; Q3W, every three weeks; Q4W, every four weeks. | © 2026 aTyr Pharma All lung phenotypes Forced steroid taper 5.0 mg/kg Q4W Steroid reduction at week 48 Study design Primary endpoint Dosing Restrictive lung phenotype Stable background treatment FVC at week 48 5.0 mg/kg Q3W EFZO-FIT New Trial
Continue on stable background therapy (OCS 0 to ≤5 mg/d) Continue on stable background IS Screening A Phase 3 Randomized Double-Blind Placebo-Controlled Study to Evaluate Efzofitimod in Patients with Pulmonary Sarcoidosis Target Population: Moderate to severe pulmonary sarcoidosis with restrictive disease Enrollment (N≈372) Primary Endpoint: Change from BL in FVC (mL) at W48 Key Secondary Endpoint: Change from BL in KSQ-L score at W48 No steroid taper protocol: Participants will remain on stable background therapy of OCS and/or IS Path Forward Key endpoints designed to assess how patients function and feel Abbreviations: BL, baseline; D, day; FVC, forced vital capacity; IS, immune suppressant; KSQ-L, King’s Sarcoidosis Questionnaire-Lung Score; OCS, oral corticosteroids; Q3W, every three weeks; R, randomized; W, week. | © 2026 aTyr Pharma Efzofitimod 5 mg/kg (n≈186) Placebo (n≈186) R 1:1 Follow up Infusion Q3W for a total of 17 doses -6W 6 9 12 15 18 21 24 27 30 33 48 Endpoints 54 Safety D1 Week: 3 36 39 42 45 51 C-006 Study Design
Proposed Key Inclusion and Exclusion Criteria Path Forward Study focuses on the right patients for the right endpoints Abbreviations: DLCOpp, diffusing capacity of the lungs for carbon monoxide, percent predicted; FEV1, forced expiratory volume in 1 second; FVCpp, forced vital capacity, percent predicted; HRCT, high-resolution computed tomography; IS, immune suppressant; KSQ-L, King’s Sarcoidosis Questionnaire-Lung Score; MRC, Modified Medical Research Council; OCS, oral corticosteroid. | © 2026 aTyr Pharma Inclusion Criteria Exclusion Criteria Documented history of pulmonary sarcoidosis for at least 6 months Symptomatic pulmonary sarcoidosis: MRC dyspnea scale grade ≥2 KSQ-L score ≤60 Restrictive pulmonary disease: FVC percent predicted (FVCpp) ≥50% to ≤80% Forced expiratory volume in 1 second FEV1/FVC ≥0.7 Stable dose of OCS and/or IS: OCS dose ≤5 mg/day (prednisone equivalent) for at least 4 weeks IS treatment for ≥6 months on stable dose for ≥3 months HRCT fibrosis score >20% DLCOpp <40% Treatment within 4 months with biological immunomodulators, antifibrotics or interleukin inhibitors
*<80% FVCpp; FEV1/FVC ≥0.7. †>20% on HRCT; †Diagnosed pulmonary means ICD10 code D86.0 or D86.2. Sharp M, et al. Ann Am Thorac Soc. 2023 Jan;20(1):30-37; Obi O, et al. Chest. 2024 Apr; 165(4):892-907. Abbreviations: FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; FVCpp, forced vital capacity, percent predicted; HRCT, high-resolution computed tomography; ILD, interstitial lung disease; pp, percent predicted. | © 2026 aTyr Pharma US Pulmonary Sarcoidosis Target Population: ILD Without Advanced Fibrosis Target Population ~160k Diagnosed US pulmonary sarcoidosis patients† ~90k Moderate to severe disease (Symptomatic, functional impairment, with or without fibrosis) Efzofitimod Target Population Patients with restrictive lung disease without advanced fibrosis Upside opportunity in mixed and/or diffusion-limited patients Up to 62k patients in US alone ~18k Obstructive ~24k Mixed/Diffusion-limited ~38k Restrictive* ~10k Advanced fibrosis†
Efzofitimod Targets NRP2 Biology to Reset Pro-Inflammatory Macrophages MOA Nangle LA, et al. Sci Transl Med. 2025 Mar 12;17(789):eadp4754. Abbreviations: CCR2, C-C Chemokine Receptor Type 2; CD14, cluster of differentiation 14; IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; MOA, mechanism of action; NRP2, neuropilin-2; TNF-⍺, tumor necrosis factor-alpha. | © 2026 aTyr Pharma Immune triggers recruit pro-inflammatory macrophages. Persistent inflammation can lead to progressive fibrosis. Pro-inflammatory macrophages express inflammatory factors, as well as NRP2, a regulator of inflammatory state. Efzofitimod binds to NRP2, promoting a less inflammatory macrophage population. Key drivers of inflammation and fibrosis are downregulated. Inflamed lungs Calmed lungs Disease State Efzofitimod MOA Macrophage CD14 CCR2 NRP2 Efzofitimod binds to NRP2 MCP-1 TNF-a IL-6 MCP-1 TNF-a IL-6
ILD is an umbrella term including >200 rare lung disorders characterized by inflammation and scarring of the lung interstitium Many ILDs share common clinical presentations and pathologic features, and are managed similarly to pulmonary sarcoidosis with immunomodulatory therapy Treatment goals are to improve QoL and prevent permanent lung damage caused by fibrosis Current therapies are toxic, slow disease decline at best, and do not improve QoL Most drug development efforts have focused on the fibrotic side of the ILD market (IPF/PPF), leaving the larger inflammatory side of the market untapped and in need of innovation Up to $5B market opportunity1 Interstitial Lung Disease Requires New Treatment Approaches ILD Efzofitimod’s novel and complementary MOA may address the significant unmet medical need in ILD 1aTyr Pharma, Inc. data on file. Abbreviations: ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis; MOA, mechanism of action; PPF, progressive pulmonary fibrosis; QoL, quality of life. | © 2026 aTyr Pharma
SSc-ILD is a Common and Deadly Manifestation of Systemic Sclerosis SSc-ILD Abbreviations: BAL, bronchoalveolar lavage; IL-6, interleukin-6; ILD, interstitial lung disease; MCP-1, monocyte chemoattractant protein-1; SSc, systemic sclerosis; SSc-ILD, systemic sclerosis-associated interstitial lung disease; QoL, quality of life. Disease pathology Chronic, progressive autoimmune disease Characterized by inflammation and fibrosis of the skin and other organs, including the lungs >50% of patients experience ILD Key immune mediators include IL-6, MCP-1 and BAL neutrophil infiltration Epidemiology More than 1.5M patients worldwide with SSc-ILD; ~60k in the US Average age of onset between 45-55 70-90% of ILD develops within first 3 years of SSc diagnosis 30% of patients develop fibrosis Unmet Need Debilitating disease manifestations impacting QoL with high morbidity and mortality 3X greater mortality risk than SSc alone Limited treatment options with only 2 approved therapies Current therapies only slow decline with no QoL benefit | © 2026 aTyr Pharma
Target Population: SSc with progressive ILD Enrollment: N=25 Patients with SSc (ACR/EULAR criteria), and ILD (BL HRCT) Progressive disease (recent onset, evidence for inflammation, diffuse cutaneous SSc) On background mycophenolate therapy or equivalent Primary Objective: Assess the efficacy of efzofitimod on pulmonary, cutaneous, and systemic manifestations in SSc-ILD Primary Endpoint: Lung function: FVC Secondary Endpoints: Symptom control: PROs Skin: histopathology, gene profiling, biomarkers, mRSS Stable background regimen Follow-up Screening Phase 2 Study to Evaluate the Efficacy, Safety, and Tolerability of Efzofitimod in Patients with SSc-ILD EFZO-CONNECT Interim analysis report in Q2 2025; enrollment completion expected in 1H 2026 Abbreviations: ACR, American College of Rheumatology; BL, baseline; EULAR, European League Against Rheumatism; FVC, forced vital capacity; HRCT, high-resolution computed tomography; ILD, interstitial lung disease; PE, primary endpoint; PRO, patient reported outcome; mRSS, modified Rodnan Skin Score; Q4W, every 4 weeks; SSc, systemic sclerosis; SSc-ILD, systemic sclerosis-associated interstitial lung disease; W, week. | © 2026 aTyr Pharma Efzofitimod 450 mg (n=10) Efzofitimod 270 mg (n=10) Placebo (n=5) Infusion Q4W for a total of 6 doses -4W 8 12 Interim skin assessments 16 20 24 PE 28 Safety 0 Week: 4 EFZO-CONNECT Study Design
Our tRNA Synthetase Library: Potential Candidates in a New Class of Medicine Full-length tRNA synthetases Natural fragments and variants Novel extracellular functions gained through evolutionary intelligence Pipeline products Pipeline | © 2026 aTyr Pharma WHEP WHEP Fc Fc Efzofitimod D-N1 D-N1 Fc Fc ATYR0101 C-Ala C-Ala Fc Fc ATYR0750 HARS WHEP Catalytic Anti-codon binding Domains: Abbreviations: C-Ala, C-terminal alanine-binding domain; D-N1, N-terminal domain 1; Fc, fragment crystallizable region (of an antibody); HARS, histidyl-tRNA synthetase; tRNA, transfer ribonucleic acid; WHEP, domain named after the proteins in which it was first identified: tryptophanyl-tRNA synthetase (W), histidyl-tRNA synthetase (H), and glutamyl-prolyl-tRNA synthetase (EP). WHEP Catalytic Anti-codon binding
PROGRAM tRNA SYNTHETASE MOA INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Efzofitimod HARS NRP2 modulator Pulmonary Sarcoidosis SSc-ILD Other ILD ATYR0101 DARS Myofibroblast depleter Fibrosis ATYR0750 AARS FGFR4 modulator Fibrosis tRNA Synthetase Candidates1 Multiple Multiple Multiple Efzofitimod Leads a Growing Pipeline of tRNA Synthetase-Derived Biologics 1Pipeline candidates in development based on additional tRNA synthetases from IP portfolio. Abbreviations: AARS, alanyl-tRNA synthetase; DARS, aspartyl-tRNA synthetase; FGFR4, fibroblast growth factor receptor 4; HARS, histidyl-tRNA synthetase; ILD, interstitial lung disease; IP, intellectual property; MOA, mechanism of action; NRP2, neuropilin-2; SSc-ILD, systemic sclerosis-associated interstitial lung disease; tRNA, transfer ribonucleic acid. Pipeline | © 2026 aTyr Pharma
Pulmonary sarcoidosis Efzofitimod opportunity Pipeline, IP and cash Efzofitimod is a biologic immunomodulator with a novel and complementary mechanism of action Efzofitimod in position to be first to market in pulmonary sarcoidosis without near term competition aTyr retains a robust IP-protected tRNA synthetase library EFZO-FIT: largest interventional pulmonary sarcoidosis trial conducted to date generated key insights being used to optimize the path forward for efzofitimod Therapeutic potential beyond sarcoidosis - advancing efzofitimod in SSc-ILD Advancing additional pre-clinical candidates for fibrosis Planned Phase 3 study in pulmonary sarcoidosis refines primary endpoint, study design, and dosing Efzofitimod for ILD represents up to a $5B market opportunity1 ~$68.3M in cash, restricted cash, cash equivalents and available-for-sale investments as of March 31, 2026 aTyr’s Strategic Outlook Advancing a platform based on tRNA synthetase biology to build a pipeline focused on inflammation and fibrosis 1aTyr Pharma, Inc. data on file. Abbreviations: ILD, interstitial lung disease; IP, intellectual property; SSc-ILD, systemic sclerosis-associated interstitial lung disease; tRNA, transfer ribonucleic acid. | © 2026 aTyr Pharma
Thank You © 2026 aTyr Pharma = Branded 2D science visualization