Benzinga | Dec 13, 2021 07:21AM EST

Biomarker Data From Phase 1b/2 Investigator-sponsored Trial Of Mereo's Alvelestat In Bronchiolitis Obliterans Syndrome At The ASH Annual Meeting

Mereo BioPharma Group plc (NASDAQ:MREO) ("Mereo" or the "Company"), a clinical stage biopharmaceutical company focused on oncology and rare diseases, today announced the presentation of data from the initial seven patients in an investigator-sponsored study of alvelestat in patients with BOS following hematopoietic stem cell transplantation ("HCT"). These data were presented at the 63rd American Society of Hematology (ASH) Annual Meeting in Atlanta, GA by Annie Im, MD, University of Pittsburgh, UPMC Hillman Cancer Center, Pittsburgh, PA.



The Phase 1b/2 study of alvelestat, an oral neutrophil elastase inhibitor (NCT02669251), is being conducted under a Clinical Trial Agreement between Mereo and the National Cancer Institute ("NCI"), part of the National Institutes of Health, led by the Principal Investigator Dr. Steven Pavletic, Immune Deficiency Cellular Therapy Program, Center for Cancer Research, NCI.

Patients received escalating doses of alvelestat over an 8-week period, from 60 mg twice daily to a maximum of 240 mg twice daily, which was tolerated in all patients.

Treatment with alvelestat was associated with improvement in biomarkers of mechanistic efficacy, with ex vivo zymosan stimulated elastase activity showing progressive decrease over the dose escalation period, with some subjects demonstrating 100% suppression. The first evidence of elevated elastase activity in BOS and chronic Graft vs. Host Disease ("GVHD") was demonstrated by the elevation of desmosine/isodesmosine (elastin breakdown fragments) at baseline mean 0.464 (SEM 0.0508) ng/ml, with 6 of 7 subjects above the Upper Limit of Normal (ULN, 0.280 ng/ml). Desmosine/isodesmosine levels progressively declined during the dose escalation period to 0.380 (SEM 0.0419) ng/ml by week 8, representing a mean within subject 16.2% (SEM 6.794) change from baseline. There was also reduction in the collagen synthesis biomarkers PRO-C3 and PRO-C6 following alvelestat treatment which is encouraging for its potential to impact progressive lung fibrosis in BOS. There was consistency of improvement across biomarkers of elastase activity, desmosine/isodesmosine and collagen synthesis in 6 of the 7 treated patients, all of whom had improved or stable lung disease. Six patients had stable disease (2 with an improvement of 9% in FEV1), while 4 had improved symptoms at end of study.

"These data, while early, are highly encouraging as this is the first evidence of elevated elastase activity in patients with BOS and GVHD that can be suppressed by a neutrophil elastase inhibitor," said Dr. Jackie Parkin, Senior Vice President and Therapeutic Head at Mereo. "The potential of alvelestat to impact the progression of lung fibrosis in this patient population is also exciting and warrants further evaluation. We are grateful to Dr. Pavletic and his team at NCI for their work in progressing this study."

BOS is an inflammatory condition that affects the bronchioles, the smallest airways in the lungs. As the disease progresses, the bronchioles may become damaged and inflamed, leading to extensive scarring and blockage of the airways. Allogenic HCT is associated with BOS related morbidity and mortality. BOS following a lung transplant is the leading cause of re-transplantation and mortality.