ASTEROID Phase IIb study on track

BPS-804 (setrusumab) is a fully humanised monoclonal antibody targeting sclerostin (SOST); a protein secreted by the osteocyte cell that plays a pivotal role in bone metabolism. It is being developed by Mereo BioPharma for the orphan disease osteogenesis imperfecta (OI), which is better known as brittle bone disease. BPS-804 is one of the two Orphan Drug programmes that Mereo BioPharma intends to commercialise itself; the other being MPH-966 (alvelestat), an oral small molecule in development for α₁-antitrypsin deficiency (AATD).

OI is characterised by different genotypes with varying degrees of skeletal fragility. Most types (usually classified into eight categories) are caused by disruption or mutations of one or both of two genes (COL1A1 or COL1A2) that carry instructions for the production of type 1 collagen. The hallmark of OI is bone fractures that occur with only minimal to moderate trauma. Type I is the least severe form of the disease and is associated with comparatively fewer fractures to other categories of OI, whereas Type II is the most severe and causes babies to be born with multiple fractures and die within a few weeks of birth. Breaks can occur in any bone, but lower limb breakage (often the femur) is the most common. In general, the earlier the fractures occur in life, the more severe the disease is.

ASTEROID is a 112 adult patient, double-blind Phase IIb clinical trial being performed in the US, Europe and Canada. Patients are Type I, III, and IV with the defect in COL1A1/2 gene confirmed by genetic testing; these three types account for c 80% of OI patients. Of the 112 patients enrolled, 69 have Type I OI, 29 have Type IV OI, and 14 have Type III OI. Recruitment, despite complex logistics (eg standardising transport for such delicate patients) to 27 specialist sites, completed on track in October 2018. The study design includes three double-blinded, active arms, evaluating differing intravenous doses (low, mid, and high), and one open-label arm at the top dose. The open-label arm was initially the placebo arm before the study was amended in August 2018 following consultation with regulators, investigators and patient groups.

The primary endpoint, measured at twelve months, is changes in trabecular volumetric bone mineral density (Tr vBMD) of the radius (at the wrist) measured by high resolution peripheral quantitative CT (HRpQCT) and changes in bone strength on finite element analysis (FEA). Secondary endpoints include: Tr vBMD measured by HRpQCT at six months; BMD measured by traditional two-dimensional dual-energy X-ray absorptiometry (DXA); additional measures of bone parameters on HRpQCT; bone turnover markers and quality of life scores.

The open-label arm posted interim 13 and 26-week data showing promising improvements in both primary and secondary endpoints, with patients of all three major phenotypes represented. Twelve patients were measured at three months and 11 at six months, with a mean increase of 1.4% in Tr vBMD at the radius at three months and a 3.2% increase at six months. Six month data for areal BMD at the lumbar spine using DXA measurements were available for twelve patients and these showed a 3.5% increase over baseline. Importantly, BPS-804 had a clean side-effect profile with no cardiovascular safety signals.

The headline results from the blinded dose ranging part of the study and the 12 month data from the open label arm are expected in Q419.

Exhibit 1: Summary of financials

Source: Company, Trinity Delta; Notes: Our estimates exclude the costs associated with the pivotal Phase III paediatric study with BPS-804, because the timing of the trial is yet to be decided. We include in FY20 long-term debt (other financing cash flow) of £25m, which is indicative of our estimate of the company’s capital requirement; this could be achieved through an equity raise, debt of proceeds from partnering non-rare disease assets.