Slide 1: ENLIGHTEN 2 Study Results
ENLIGHTEN 2 Study Results ENLIGHTEN 2: A Phase III, Randomized, Blinded, Controlled, Parallel-Group Trial to Evaluate the Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis (CRS) in Adults https://clinicaltrials.gov/study/NCT05295459 June 2, 2025
Slide 2: FLS Disclaimer
FLS Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The words “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” and similar expressions are intended to identify forward-look
Slide 3: Chronic Rhinosinusitis (CRS): An "Unrecognized Epidemic"
Chronic Rhinosinusitis (CRS): An “Unrecognized Epidemic”(1) Significant market opportunity in both polyp and non-polyp CRS populations CRS in the United States Annually ~8M ~4M ~$60B CRS patients Annual CRS patients failing medical healthcare treated(2) management(3) expenditure(4) CRS Cardinal Symp
Slide 4: Lyra's Proprietary Drug-Eluting Implant
Lyra’s Proprietary Drug-Eluting Implant Polymer-Drug Complex Designed to deliver 6 months of continuous, local drug therapy with a single placement Engineered Elastomeric Matrix Shape memory intended to keep implant in place Bioabsorbable Mesh Scaffold Designed to maximize surface area for drug rele
Slide 5: Program Design – LYR-210 Phase 3 Program
ENLIGHTEN Program Design – LYR-210 Phase 3 Program Two replicate trials in support of an NDA for the primary indication of CRS without nasal polyps(1) ENLIGHTEN Program Design ENLIGHTEN 1(5) Criteria Daily Saline Irrigation • Two Phase 3 studies of ~180 subjects each, including a combined 64 polyp E
Slide 6: ENLIGHTEN 2: Patient Demographics & Baseline Characteristics
ENLIGHTEN 2: Patient Demographics & Baseline Characteristics ITT Analysis Set LYR-210 Sham (n=111) (n=61) Age in years (mean, SD) 50 (15.5) 49 (12.99) Sex (n, %) Male 65 ( 58.6) 31 ( 50.8) Female 46 ( 41.4) 30 ( 49.2) Race (n, %) White 94 ( 84.7) 51 ( 83.6) Black or African American 9 ( 8.1) 5 ( 8.2
Slide 7: ENLIGHTEN 2: Most Frequent Adverse Events (≥5% of patients)
ENLIGHTEN 2: Most Frequent Adverse Events (≥5% of patients) Favorable safety profile with no product-related serious adverse events LYR-210 (n=111) Sham (n=61) Safety Analysis Set (Preferred Term) n (%) n (%) Any treatment-emergent adverse events (TEAEs) 67 (60.4%) 27 (44.3%) Epistaxis 18 (16.2%) 1
Slide 8: Change from Baseline in 3CS (Primary Endpoint)
ENLIGHTEN 2: Change from Baseline in 3CS at Week 24 (Primary Endpoint)(1) Statistically significant improvement in 3CS at 24 weeks, with consistent improvement over sham control starting as early as Week 8 3CS – Non-Polyp Patients * Statistically significant * Represents p-value < 0.05. (1) Primary
Slide 9: Change from Baseline in 3CS for Full Population
ENLIGHTEN 2: Change from Baseline in 3CS at Week 24 for Full Population (1st Key Secondary Endpoint)(1) Statistically significant improvement in 3CS at 24 weeks, with robust improvement over sham control starting at Week 12 3CS – All Patients * Statistically significant * Represents p-value < 0.05.
Slide 10: Change from Baseline in SNOT-22 (2nd Key Secondary Endpoint)
ENLIGHTEN 2: Change from Baseline in SNOT-22 at Week 24 (2nd Key Secondary Endpoint)(1) Statistically significant improvement in clinically-validated SNOT-22 score at 24 weeks, with robust improvement over sham control starting at Week 4 SNOT-22 – All Patients * Statistically significant * Represent
Slide 11: Change in % Ethmoid Opacification by CT
ENLIGHTEN 2: Change in % Ethmoid Opacification at Week 20 (3rd Key Secondary Endpoint)(1) Numerical improvement in % ethmoid opacification by CT % Ethmoid Opacification – All Patients 0 LS Mean (±SE) CFBL in % Ethmoid -0.55 -1 Opacification by CT -2.15 p=0.1809 -2 -2.70 -3 -4 LYR-210 SHAM N=172 (1)
Slide 12: ENLIGHTEN 1 and 2 Pooled CRS with Nasal Polyps: 3CS Score
ENLIGHTEN 1 and 2 Pooled CRS with Nasal Polyps: Change from Baseline in 3CS Score at Week 24 Consistent, positive trend starting in Week 4 and further improvement at Weeks 20 and 24 with small sample size (n=64) 3CS - All Nasal Polyp Patients Analysis population is the pooled intent-to-treat (ITT) a
Slide 13: ENLIGHTEN 1 and 2 Pooled CRS with Nasal Polyps: SNOT-22 Score
ENLIGHTEN 1 and 2 Pooled CRS with Nasal Polyps: Change from Baseline in SNOT-22 Score at Week 24 Consistent, positive trend in SNOT-22 score starting in Week 4 and throughout Week 24 SNOT-22 - All Nasal Polyp Patients * * Represents p-value < 0.05. Analysis population is the pooled intent-to-treat (
Slide 14: Pooled CRS with Nasal Polyps: Nasal Congestion Score
ENLIGHTEN 1 and 2 Pooled CRS with Nasal Polyps: CFBL in Nasal Congestion Score (NCS) at Week 24 (for Subjects with Baseline NCS ≥2) Consistent, positive trend of improvement in nasal congestion score starting in Week 4 and throughout Week 24 NCS - Moderate to Severe NCS at Baseline * * Represents *
Slide 15: Summary of ENLIGHTEN 2 Results
Summary of ENLIGHTEN 2 Results • ENLIGHTEN 2 study met its primary endpoint ‒ Statistically significant improvement over sham in 3CS at Week 24 in the primary population of CRS patients without nasal polyps, with improvement observed as early as Week 8 • Key secondary endpoints of change in 3CS and
Slide 16: Key Milestones
Key Milestones May 2024: Data readout from ENLIGHTEN 1 Q4 2024: Extension study data from ENLIGHTEN 1 2H 2024: Complete enrollment in ENLIGHTEN 2 2Q 2025: Data readout from ENLIGHTEN 2 Est. 2H 2025: FDA meeting to align on strategy for CRS without Nasal Polyps Est. 1H 2026: Initiate Phase 3 Trial in
Slide 17: Lyra Therapeutics
LI“YRA THERAPEUTICS