Lyra Therapeutics (LYRA) Study Result summary

Study background and design

• ENLIGHTEN II (ENLIGHTEN 2) was a Phase III, randomized, blinded, controlled trial evaluating LYR-210, a bioabsorbable nasal implant delivering 7,500 mcg of mometasone furoate over 24 weeks, for chronic rhinosinusitis (CRS) in adults who failed medical management and had no prior ethmoid sinus surgery.

• The trial enrolled 172–180 patients, randomized 2:1 to LYR-210 or sham, with a diverse population from North America and Europe.

• The primary endpoint was change from baseline in the Three Cardinal Symptom (3CS) score at 24 weeks in non-polyp patients; key secondary endpoints included 3CS and SNOT-22 in all patients, CT-based ethmoid opacification, and rescue treatment use.

• CRS affects about 8 million patients annually in the U.S., with 50% failing current therapies, representing a $60 billion market.

• The ENLIGHTEN program includes two Phase III trials (ENLIGHTEN 1 and 2) to assess efficacy and safety in CRS patients with and without nasal polyps.

Efficacy results

• LYR-210 met its primary endpoint, showing statistically significant improvement in 3CS at 24 weeks in non-polyp patients (LS mean difference -1.13, p=0.0078), with effects seen as early as week 8.

• Statistically significant improvement in 3CS for all patients at 24 weeks (LS mean difference -0.9, p=0.0209), with robust effects from week 12.

• SNOT-22 score improved by 8.7 points over sham at 24 weeks (p=0.0101), with a 22-point improvement over baseline, more than double the clinically meaningful threshold.

• Symptom improvement was observed as early as week 4 and sustained through week 24.

• Numerical, but not statistically significant, improvement in CT-based ethmoid opacification at week 20 (LS mean difference -2.15, p=0.1809).

Safety and tolerability

• LYR-210 demonstrated a favorable safety profile with no product or procedure-related serious adverse events reported.

• Most common adverse events included mild epistaxis, upper respiratory tract infection, sinusitis, nasopharyngitis, COVID-19, and headache, with similar rates between LYR-210 and sham groups.