aTYR PHARMA INC (ATYR)·Q4 2024 Earnings Summary

Executive Summary

• Q4 2024 delivered a smaller net loss per share of $(0.18) versus $(0.23)–$(0.23) in Q2/Q3, with no revenue; OpEx declined sequentially as trial costs moderated ahead of EFZO-FIT topline in Q3 2025 .
• EPS beat consensus by $0.046 (actual $(0.18) vs. $(0.226)); revenue was in line at $0.0, reflecting a pre-commercial profile; 10 estimates covered both metrics* .
• Guidance was extended: management now expects cash runway to fund operations for one year post EFZO-FIT readout, including a potential BLA, supported by $75.1M cash at 12/31 and ~$18.8M gross ATM proceeds subsequent to quarter-end .
• FDA Type C meeting simplified the primary endpoint to absolute change in steroid dose from baseline to week 48, which management believes could better capture treatment effect; the study remains >90% powered to show steroid reduction at 3–5 mg/kg doses .
• Near-term stock drivers: ATS baseline patient data (May), SSc-ILD skin interim data (Q2), and EFZO-FIT topline in Q3 2025; four clean DSMB reviews reinforce safety and de-risk the program .

What Went Well and What Went Wrong

What Went Well

• Completed EFZO-FIT enrollment (268 patients across 85 centers/9 countries) and received the fourth positive DSMB review; topline remains on track for Q3 2025 .
• FDA alignment on SAP: “Based on FDA feedback, we will now measure steroid reduction as the absolute change from baseline at week 48,” simplifying analysis while maintaining >90% powering .
• Cash runway extended to fund operations for one year post-readout, aided by $75.1M year-end cash and ~$18.8M ATM proceeds, which also support commercial readiness planning .

What Went Wrong

• Continued zero quarterly revenue; loss from operations persists reflecting ongoing R&D and G&A spend tied to Phase 3 and Phase 2 programs .
• Sequential R&D still elevated versus Q2 (though down in Q4), underscoring sustained trial expenses as EFZO-FIT and EFZO-CONNECT progress .
• Execution risks remain: enrollment variability for EAP by region, and regulatory/biostatistical nuances could affect endpoint interpretation; management remains conservative and blinded regarding EAP uptake .

Financial Results

Quarterly P&L and EPS

Balance Sheet Highlights

Estimates vs Actuals (Q4 2024)

Values with asterisk (*) retrieved from S&P Global.

Program KPIs

Guidance Changes

Earnings Call Themes & Trends

Management Commentary

• “Based on FDA feedback, we will now measure steroid reduction as the absolute change from baseline at week 48. We feel this change creates a more simplified assessment... The statistical powering for the study remains intact.” — Sanjay Shukla, CEO .
• “We ended 2024 with $75,100,000... Subsequent to the end of the fourth quarter, we raised approximately $18,800,000... we believe our cash runway is expected to be sufficient to fund the company’s operations through one year following the Phase III EFZO-FIT readout.” — Jill Broadfoot, CFO .
• “We view efzofitimod as a potential frontline steroid reducing agent in patients with moderate to severe disease, which could address 50% to 75% of all sarcoidosis patients... we estimate a total global market opportunity for efzofitimod in ILD at $2,000,000,000 to $5,000,000,000.” — Sanjay Shukla, CEO .
• “A third party claims analysis... shows that the number of patients diagnosed with lung involvement... is 30% higher than previously estimated… nearly 75% of diagnosed patients are prescribed steroids…” — Sanjay Shukla, CEO .

Q&A Highlights

• Endpoint change and powering: Measuring absolute change baseline→week 48 simplifies analysis and may maximize signal; study remains >90% powered to detect steroid reduction at 3–5 mg/kg vs placebo .
• EAP interest and constraints: Robust investigator/patient interest; site/country regulatory variability limits participation; company remains blinded; EAP viewed as a positive signal but not quantified .
• Baseline demographics at ATS: Investors should watch average prednisone dose (expected slightly below prior Phase 2’s ~11–13 mg baseline due to 7.5 mg enrollment criteria), background immunomodulator use, disease duration .
• Placebo taper and durability: Primary analysis uses a trailing 28-day average at week 48; durability will also be explored via time-to-relapse as a tertiary analysis .
• Limited PFT focus from FDA: Discussions centered on steroid reduction; FEV1 remains tertiary; management reiterated powering and potential to detect ~3 mg absolute steroid delta .
• Commercial readiness: Manufacturing and supply chain transitioned to commercial-grade partner; preparatory investments in launch readiness underway .
• BLA timing & EAP data: BLA timeline will not be slowed to incorporate EAP; potential for parallel investigator-initiated analyses to support durability and safety .

Estimates Context

• EPS beat: Q4 EPS of $(0.18) vs consensus $(0.226), reflecting lower OpEx and higher other income; revenue matched consensus at $0.0, consistent with pre-commercial stage .
• Coverage: 10 estimates for EPS and revenue*; following Q3–Q4 liquidity updates and SAP clarity, estimates may need to reflect extended runway and endpoint measurement that could impact perceived probability of success at topline*.

Values with asterisk (*) retrieved from S&P Global.

Key Takeaways for Investors

• EFZO-FIT is de-risked on safety with four positive DSMB reviews; FDA-aligned primary endpoint could better capture treatment effect and supports confidence into Q3 2025 topline .
• Cash runway now extends one year beyond topline, reducing near-term financing overhang and enabling pre-commercial investments; recent ATM proceeds bolster liquidity .
• TAM may be larger than historically cited: claims analysis suggests 30% higher lung-involvement and ~75% steroid use; payer feedback supportive for on-label biologic with steroid reduction endpoint .
• Watch near-term catalysts: ATS baseline data (May), SSc-ILD skin interim (Q2), and EFZO-FIT topline (Q3); each can shift sentiment ahead of BLA planning .
• Trading lens: EPS beats are less material for a pre-revenue biotech; stock is more likely to react to clinical validation milestones, FDA interactions, and durability signals from EAP .
• Medium-term: If EFZO-FIT hits the steroid reduction primary and supportive symptom/lung function secondary endpoints, a potential BLA filing and commercial readiness could unlock value; manufacturing readiness mitigates CMC risk .
• Partnership optionality: Kyorin collaboration (>$20M received to date; up to $155M milestones) and rising strategic interest may provide non-dilutive capital or commercialization leverage .