Mereo BioPharma Group plc (NASDAQ: MREO) has provided an update on its pipeline programs, highlighting advancements in the development of setrusumab for Osteogenesis Imperfecta (OI) and alvelestat for Alpha-1 Antitrypsin Deficiency-associated Lung Disease (AATD-LD). The company also announced a global licensing agreement for leflutrozole and reiterated its cash runway guidance, expecting current funds to support operations into 2026.
Setrusumab for Osteogenesis Imperfecta
Setrusumab (UX143), being developed in partnership with Ultragenyx Pharmaceutical Inc., is currently undergoing Phase 3 clinical trials. The global Phase 2/3 Orbit study, initiated in mid-2023, is expected to complete enrollment around the end of the first quarter of 2024. This pivotal study includes up to 195 patients aged 5 to <26 years, randomized 2:1 to receive setrusumab or placebo. The primary efficacy endpoint is the annualized clinical fracture rate, excluding fractures of the fingers, toes, skull, and face.
In parallel, the Cosmic study, a global Phase 3 open-label, randomized, active-controlled trial, is evaluating setrusumab against intravenous bisphosphonates in approximately 65 patients aged 2 to <7 years. This study, initiated in the second half of 2023, is anticipated to be fully enrolled in the first half of 2024. The primary endpoint is the reduction in total fracture rate, including morphometric vertebral fractures.
Data from the Phase 2 portion of the Orbit study, reported in October 2023, demonstrated a 67% reduction in the annualized fracture rate in 24 patients treated with setrusumab for at least 6 months. This reduction was associated with significant improvements in bone mineral density (BMD). The drug was well-tolerated, with no drug-related serious adverse events (SAEs) reported.
If approved by the FDA and EMA, setrusumab would be the first approved treatment for Osteogenesis Imperfecta (OI).
Alvelestat for Alpha-1 Antitrypsin Deficiency-associated Lung Disease
Mereo BioPharma has been in continued discussions with the FDA regarding the Phase 3 study design of alvelestat (MPH-966) for the treatment of Alpha-1 Antitrypsin Deficiency-associated Lung Disease (AATD-LD). Following interactions with the Division of Pulmonology, Allergy and Critical Care (DPACC) and the Division of Clinical Outcome Assessment (DCOA), the company has aligned on a Phase 3 study design using the St George’s Respiratory Questionnaire (SGRQ) Total Score as the primary endpoint, with a functional assessment as a key secondary endpoint.
Data from the ATALANTa and ASTRAEUS studies support the use of the SGRQ Total Score as the primary endpoint, based on benefits observed in patients with the severe Pi*ZZ phenotype, including those in the early stages of lung disease. The EMA has indicated that lung density by computed tomography (CT) scan with a relaxed p value (p<0.1) may be sufficient for full regulatory approval if the study is successful.
The company remains engaged with potential partners for the development and commercialization of alvelestat.
Licensing Agreement for Leflutrozole
Mereo BioPharma has entered into an exclusive global license agreement with ReproNovo SA for the development and commercialization of leflutrozole, a non-steroidal aromatase inhibitor. ReproNovo will be responsible for all future development and commercialization efforts. Mereo received an upfront payment and is eligible to receive up to $64.25 million in future milestones, as well as tiered mid-single-digit royalties on global annual net sales.
Financial Update
Mereo BioPharma anticipates its existing cash and short-term deposits will fund its committed clinical trials, operating expenses, and capital expenditure requirements into 2026.
