The Phase 2 Orbit study reported a 67% reduction in the annualized fracture rate with setrusumab. Can you elaborate on the clinical significance of this finding for patients with osteogenesis imperfecta?

How do the sustained reductions in fracture rates observed at 14 months compare with other available treatments for OI, and what implications does this have for long-term patient management?

Setrusumab treatment resulted in a median annualized fracture rate of 0.00. How does this outcome impact the overall prognosis and quality of life for patients with OI?

The study showed a mean increase in lumbar spine bone mineral density (BMD) of 22% after 12 months. Can you discuss the importance of this improvement and how it correlates with fracture risk reduction?

The mean improvement in BMD Z-score was +1.25 at 12 months. What does this substantial normalization in Z-score indicate about the efficacy of setrusumab in bone health restoration?

Considering the absence of treatment-related serious adverse events, how does the safety profile of setrusumab compare to other treatments currently available for OI?

The Phase 2 portion of the Orbit study included patients aged 5 to 25 years across various OI sub-types. How do the consistent improvements in BMD and fracture rates across these sub-groups influence the broader applicability of setrusumab?

With the Phase 3 Orbit and Cosmic studies fully enrolled, what are the next steps in the development and potential approval process for setrusumab, and how might these studies impact the treatment landscape for OI?