Summary of Mereo Biopharma Group FY Conference Call Company Overview - **Company**: Mereo Biopharma Group (NasdaqCM:MREO) - **Industry**: Rare disease biopharmaceuticals - **Focus**: Development of therapies for rare diseases, specifically osteogenesis imperfecta (OI), alpha-1 antitrypsin deficiency, and osteoporosis Core Points and Arguments Clinical Programs - Mereo has three clinical programs: - **Setrusumab** for osteogenesis imperfecta (OI) - Phase 3 results reported with partner Ultragenyx - **Alvelestat** for alpha-1 antitrypsin deficiency - Phase 3-ready, endpoints agreed with FDA and EMA - **Vantictumab** for osteoporosis - Phase 2 study planned for the second half of the year [3][5][20] Financial Position - Mereo reported approximately **$41 million** in cash at the end of 2025, providing a runway into mid-2027 [5] Setrusumab Data - Two Phase 3 studies (Orbit and Cosmic) did not meet primary endpoints, but showed: - Robust changes in bone mineral density (BMD) - Statistically significant improvements in pain and daily activities for OI patients [7][19] - In the Cosmic study, a **21% reduction** in annualized fracture rate (AFR) compared to bisphosphonates was observed, although not statistically significant [17] - A **59% reduction** in vertebral fractures was noted in setrusumab-treated patients compared to bisphosphonate-treated patients [17] - The placebo arm showed a **50% reduction** in AFR, complicating the ability to demonstrate a difference [14] Patient Impact - Pain is the primary symptom affecting OI patients, and setrusumab treatment resulted in statistically significant reductions in pain scores [15][32] - Anecdotal evidence suggests improved mobility and quality of life for patients on setrusumab, with reports of children engaging in activities they previously could not [35] Future Plans - Mereo is conducting further data analyses to prepare for potential regulatory discussions regarding setrusumab [19][41] - Plans for additional data presentations later in the year, including analyses correlating AFR and BMD in OI patients [39] Alvelestat and Vantictumab - Alvelestat is focused on severe patients with the PIZZ genotype, with a study design involving **220 patients** over 18 months [20] - Vantictumab is set to enter the clinic in the second half of the year, with previous studies indicating increased osteoclastic activity [22] Important but Overlooked Content - The significance of BMD changes in the context of OI, where patients often start with very low Z-scores, making any improvement clinically meaningful [28] - The potential for a placebo effect in the studies, as many patients reported feeling better, which may have influenced the outcomes [35] - The ongoing collection of data from patients who transitioned from bisphosphonates to setrusumab, which may provide insights into long-term efficacy [40] This summary encapsulates the key points from the Mereo Biopharma Group FY Conference Call, highlighting the company's focus on rare diseases, the status of its clinical programs, financial position, and future plans.

Pipeline Programs - Setrusumab for Osteogenesis Imperfecta (OI) Phase 3 results were reported around the end of 2025, partnered with Ultragenyx, but neither study achieved the primary endpoint of reduction in AFR compared to placebo or bisphosphonates[8, 11] - Alvelestat for Alpha-1 Antitrypsin Deficiency-associated Lung Disease (AATD-LD) activities are ongoing to support the initiation of Phase 3, following an agreement in principle on the primary endpoints[8] - Vantictumab for osteopetrosis is out-licensed to āshibio, with EU rights retained, and an IND is planned for H2 2026[8] Financial Status - The company has approximately $41 million in cash and cash equivalents as of December 31, 2025, providing a cash runway into mid-2027[8] Setrusumab Clinical Trial Results - In the Orbit study (Setrusumab vs placebo), 19.5% of patients met rescue criteria at 12 months, primarily due to fractures, with a larger number of placebo patients exiting the study[14] - In the Cosmic study (Setrusumab vs bisphosphonates), there was a 59% reduction in vertebral fractures on setrusumab (p=0.081), despite more severe type III/IV patients on setrusumab (65% setrusumab vs 54% IV-BP)[31] - Setrusumab patients in the Orbit study showed improvements in disease severity (PGIS) in peds/teens, as well as improvements in pain/comfort and sports/activity[20] Market Opportunities - Osteogenesis Imperfecta affects approximately 60,000 patients across the US & Europe[9] - Severe Alpha-1 Antitrypsin Deficiency affects an estimated 50,000 patients in North America and 60,000 in Europe[9] - Osteopetrosis has an incidence of 1 in 20,000 in North America and Europe, with onset typically in late childhood[9]