aTyr Pharma (ATYR) Stifel 2024 Healthcare Conference summary

Disease landscape and unmet need

• Interstitial lung diseases (ILDs) are chronic, progressive, and highly morbid, with poor survival rates and limited treatment options, especially for sarcoidosis and scleroderma-related ILD.

• Current therapies, mainly steroids and immunosuppressants, are toxic and not disease-modifying, leading to significant comorbidities and poor quality of life.

• Sarcoidosis affects about 200,000 patients in the U.S., with higher morbidity in Black women and a significant risk of fibrosis and organ failure.

• Steroid use is widespread but comes with severe side effects, creating a high treatment burden alongside the disease burden.

• There is a large, underserved market for safer, more effective therapies, estimated at $2–$5 billion.

Efzofitimod mechanism and development

• Efzofitimod is a first-in-class biologic immunomodulator targeting myeloid cells, specifically macrophages, via the neuropilin-2 receptor.

• The drug is based on a novel HARS domain fragment, restoring immune balance without broad immunosuppression.

• Preclinical and early clinical data show consistent anti-inflammatory and anti-fibrotic effects across multiple animal models and human studies.

• Safety profile is favorable, with no significant immunosuppression or infusion-related issues observed to date.

• Intellectual property protection extends to 2039, supporting long-term commercial potential.

Clinical trial progress and results

• Phase II data demonstrated steroid reduction, improved lung function, and symptom relief, with dose-dependent responses across endpoints.

• Post hoc analysis showed a significant reduction in relapse rates at higher doses (7% vs. 55% for placebo/subtherapeutic).

• Phase III trial (EFZO-FIT) is fully enrolled (268 patients), powered at 92%, and focuses on steroid reduction as the primary endpoint, with global regulatory alignment.

• The trial design includes a real-world steroid tapering protocol, aiming for zero steroid use in the treatment arm.

• Compassionate use program initiated due to patient demand for continued access after trial completion.