Lyra Therapeutics, Inc. (LYRA)·Q4 2024 Earnings Summary

Executive Summary

• Q4 2024 reflected continued operating discipline and preparation for the ENLIGHTEN 2 Phase 3 readout in Q2 2025; cash and equivalents were $40.6M at year-end and management reiterated runway into Q1 2026 .
• Quarterly OpEx trended lower post-restructuring: R&D was $6.4M and G&A $3.6M in Q4 (vs. Q3 R&D $5.9M and G&A $3.9M), with net loss of $11.0M (vs. $11.9M in Q3 and $15.7M in Q3’23) .
• Strategic/regulatory: FDA Type C written feedback established alignment on key elements for a potential Phase 3 study in CRSwNP; management highlighted encouraging post‑hoc signals in the nasal polyp cohort and expects ~65 total polyp patients across ENLIGHTEN 1/2 .
• Capital markets update: the company plans to seek shareholder approval for a reverse stock split to meet Nasdaq’s $1.00 bid requirement, adding a near‑term corporate action catalyst ahead of the Q2 2025 clinical readout .
• Street estimates comparison was not available via S&P Global for Q4 2024 due to data access limits; we therefore cannot assess beats/misses versus consensus for revenue/EPS this quarter.

What Went Well and What Went Wrong

What Went Well

• Regulatory visibility improved: FDA Type C responses provided alignment on co‑primary endpoints, sample size, inclusion criteria, and in‑study assessments for a potential CRSwNP Phase 3, reducing development uncertainty for that subgroup .
• Strength in nasal polyp subgroup: post‑hoc and 52‑week extension analyses showed symptom and polyp-size improvements in polyp patients, consistent with earlier ENLIGHTEN 1 findings; management emphasized building evidence for therapeutic potential in CRSwNP .
• Operating discipline and runway: year‑end cash and equivalents of $40.6M with runway into Q1 2026; Q4 OpEx remained controlled post-restructuring (Q4 R&D $6.4M; G&A $3.6M) .

Selected management quote: “We eagerly await the upcoming readout from the ENLIGHTEN 2 Phase 3 study in Q2 2025… [to] gain further insight about the potential efficacy of LYR‑210 across a broad CRS population, including both patients with and without nasal polyps.”

What Went Wrong

• Lack of a quarterly revenue/EPS catalyst and limited disclosures: no specific Q4 revenue or EPS per share provided; headline remains clinical timing and cash versus P&L growth .
• FY 2024 loss widened on non‑recurring items: full‑year net loss rose to $93.4M, driven by impairments of right‑of‑use assets ($22.8M) and restructuring charges ($10.9M), overshadowing OpEx reductions later in the year .
• Listing pressure: management plans a reverse split to maintain Nasdaq listing compliance, which can be a negative signal for some investors despite its technical nature .

Financial Results

Notes:

• LYRA is a clinical-stage company with immaterial collaboration revenue; margin metrics are not meaningful this quarter.
• Periods are presented oldest → newest: Q2 2024, Q3 2024, Q4 2024.

Revenue and EPS

• Q4 collaboration revenue and EPS per share were not provided in the Q4 press release/8‑K; full‑year 2024 collaboration revenue totaled $1.534M .

Operating Expenses, Net Loss, and Cash

Additional context:

• Cash, cash equivalents, and short-term investments were $51.6M at 9/30/24 and management reiterated runway into Q1 2026 at both Q3 and Q4 checkpoints .

Segments and KPIs

• No reportable segments; key KPIs for this stage are clinical progress and cash runway. Q4 highlights: FDA Type C alignment for CRSwNP Phase 3 and expectation of ~65 total polyp patients across ENLIGHTEN 1/2 .

Guidance Changes

Earnings Call Themes & Trends

Note: No Q4 2024 earnings call transcript was available in the document set; themes below reflect company press releases/8‑Ks across quarters.

Management Commentary

• Strategic focus: “We eagerly await the upcoming readout from the ENLIGHTEN 2 Phase 3 study in Q2 2025… [to] gain further insight about the potential efficacy of LYR‑210 across a broad CRS population, including both patients with and without nasal polyps.” – Maria Palasis, Ph.D., President & CEO .
• Polyp subgroup: “We continue to be encouraged about the positive post‑hoc data analyses in the CRS patient cohort with nasal polyps… consistent with the previously-reported positive results from the polyp cohort of the ENLIGHTEN 1 main study stage.” .
• Regulatory pathway: Based on FDA Type C exchange, “there is alignment on various elements of a potential Phase 3 pivotal study [in CRSwNP]” including co‑primary endpoints and sample size .
• Financial posture: “Cash and cash equivalents as of December 31, 2024 were $40.6 million… sufficient to fund… into the first quarter of 2026.” .

Q&A Highlights

• No Q4 2024 earnings call transcript was located in the document set, and we did not find an “earnings-call-transcript” for the period via our document search; as a result, there are no Q&A highlights to report for Q4.

Estimates Context

• Consensus estimates (S&P Global) for Q4 2024 revenue and EPS were unavailable due to data access limits at the time of this analysis; we cannot assess beats/misses versus Street for the quarter.
• Given the clinical-stage profile and immaterial revenue, we would expect investor focus to remain on cash runway and clinical milestones rather than quarterly P&L variability .

Key Takeaways for Investors

• Near-term stock driver is binary: ENLIGHTEN 2 Phase 3 topline in Q2 2025 remains the primary catalyst; management’s narrative is shifting toward the nasal polyp subgroup where signals are stronger .
• Regulatory de-risking in CRSwNP: FDA Type C alignment on key Phase 3 design elements is a positive datapoint for a potential registration path in this subgroup .
• Leaner operating model established: Post-restructuring OpEx has normalized; Q4 net loss ($11.0M) was in line with Q3 and significantly below the Q2 level impacted by non-recurring charges .
• Cash runway through Q1 2026 provides time to reach the ENLIGHTEN 2 readout, but a favorable outcome would likely be required to avoid future financing risk .
• Reverse split approval process in Q2 2025 is a technical overhang to monitor ahead of the clinical catalyst .
• Polyp‑focused upside scenario: If ENLIGHTEN 2 corroborates polyp cohort benefits and safety holds, the CRSwNP path could become the lead value driver; otherwise, strategic alternatives remain a consideration given prior ENLIGHTEN 1 miss in the non‑polyp primary endpoint .

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Appendix: Documents Read

• Q4 2024 press release and attached financials (March 13, 2025): Fourth Quarter and Full Year 2024 Financial Results .
• Form 8‑K (Item 2.02) for Q4 2024 (March 13, 2025) including Exhibit 99.1 .
• Q3 2024 press release and 8‑K (Nov 12, 2024) .
• Q2 2024 press release and 8‑K (Aug 14, 2024) .
• Relevant Q4 2024 press release: ENLIGHTEN 2 fully enrolled (Oct 15, 2024) .