Benzinga | Jun 2, 2021 08:19AM EDT

Mereo BioPharma Highlights Biomarker Data From Interim Analysis For Bronchiolitis Obliterans Syndrome Study Candidate

Mereo BioPharma Group plc (NASDAQ:MREO) ("Mereo" or the "Company"), a clinical stage biopharmaceutical company focused on oncology and rare diseases, today announced positive data from an interim analysis of an investigator-initiated study of alvelestat in patients with Bronchiolitis Obliterans Syndrome ("BOS") following hematopoietic stem cell transplantation ("HCT").

The Phase 1b/2 study, being conducted under a Clinical Trial Agreement between Mereo and the National Cancer Institute, plans to recruit a total of 30 patients. The primary endpoints of the study are to define the safety and the optimal biological dose, based on neutrophil elastase inhibition measured using biomarkers at 8 weeks (Phase 1b, total of 10 patients) and clinical efficacy at 6 months (Phase 2, an additional 20 patients).

Interim data from the first seven patients in this open-label study were presented at the 2020 American Society of Hematology (ASH) Annual Meeting in December 2020. In this phase 1 study, maximum-tolerated dose (MTD) was not reached and alvelestat was well tolerated. Six patients had stable disease, while one patient had progression in the setting of pneumonia. Notably, two patients had improvement in forced expiratory volume in one second (FEV1) of 9%, and four patients experienced improvement in symptoms.

Subsequent analysis of the elastin breakdown biomarker desmosine, has recently been completed. This demonstrated that all six patients with elevated desmosine levels at baseline (pre- treatment) showed a reduction in desmosine the within subject dose escalation period by week 8. A median reduction of 13.9% from baseline was observed at week 8, with a maximum reduction of 52%, supporting an effect of alvelestat to inhibit elastase in this population.

These changes in plasma desmosine, were supported by additional analysis of peripheral blood neutrophil elastase release in response to zymosan stimulation and taken from patients during the study. These showed suppression of elastase release, with a signal of increasing suppression over the dose escalation period. In some patients, there was complete suppression of elastase production, confirming the effect of alvelestat on the target mechanism of human neutrophil elastase inhibition and consistent with the desmosine changes.

"We have demonstrated that neutrophil elastase inhibition is well tolerated and shows a signal of stabilizing disease in patients with advanced BOS," said Dr. Jackie Parkin, Mereo SVP and Therapeutic Head, "Based on the data from these interim analyses, we believe that further study of the clinical efficacy of alvelestat in BOS after HCT is warranted, especially at an earlier stage of disease and longer duration of drug administration."

Additional biomarker analyses of the first seven patients are being conducted by Dr. Pavletic and his team, supported by Mereo, and are expected to be presented at ASH 2021. These accumulating data in BOS associated with chronic Graft versus Host Disease following allogeneic HCT and the existing scientific data on the role of neutrophil activation and elastase in lung transplant related BOS, are expected to further inform the clinical development plan for alvelestat in BOS indications.

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. Allogeneic HCT is associated with significant morbidity and mortality and BOS following a lung transplant is the leading cause of re-transplantation and mortality.