Neither study achieved its primary endpoint of reduction in annualized clinical fracture rate compared to placebo (ORBIT) or bisphosphonates (COSMIC)

Both studies achieved secondary endpoint of improvements in bone mineral density with strong statistical significance

Mereo BioPharma Group plc  a clinical stage biopharmaceutical company focused on rare diseases, announced results from the Phase 3 ORBIT and COSMIC studies for setrusumab (UX143) in Osteogenesis Imperfecta (OI). Neither study achieved statistical significance against the primary endpoints of reduction in annualized clinical fracture rate compared to placebo or bisphosphonates, respectively. Both studies achieved their secondary endpoints of improvements in bone mineral density (BMD) against comparators (placebo and bisphosphonates) with strong statistical significance. There was no change in the safety profile observed.

“Whilst we are disappointed by these results, we will be conducting additional analyses on the data, to assess next steps and the best path forward for the program, especially in pediatrics given the totality of the data and lack of other treatment options for individuals with OI. In the meantime, we are carefully managing our cash resources with immediate reductions in our pre-commercial and manufacturing activities, and we are continuing to advance partnering discussions for alvelestat,” said Dr. Denise Scots-Knight, Chief Executive Officer of Mereo.

ORBIT and COSMIC bone mineral density (BMD) improvements

In the ORBIT study, participants experienced statistically significant and substantial improvements in BMD compared to placebo, at levels consistent with the treatment effect observed in Phase 2 studies. These BMD changes were not accompanied by a corresponding reduction in annualized fracture rates and there was a low fracture rate in the placebo group.

In the pediatric COSMIC study, patients had a substantially higher baseline fracture rate compared to the patients enrolled in ORBIT. In this younger patient population, meaningful improvements in BMD were associated with a reduction in annualized fracture rate for setrusumab treated patients over bisphosphonate treated patients, though the reduction did not meet statistical significance.

Additional analyses on the data across both studies are being conducted, including in other bone health and clinical endpoints beyond fractures.

Mereo’s cash balance was $48.7 million at the end of the third quarter of 2025. The Company will tightly control costs in parallel with conducting further analysis of the setrusumab data to determine the best path forward. Meanwhile the Company will continue to seek to maximize value in its owned and partnered programs, including:

• Alvelestat for AATD-lung disease – in partnering discussions 
• Vantictumab for osteopetrosis – partnered with āshibio
• Leflutrozole for male infertility – partnered with ReproNovo.