SYDNEY: Antisense Therapeutics Limited (ASX: ANP) announced that new plasma protein data from the Phase II trial of ATL1102 in Duchenne Muscular Dystrophy (DMD) was presented at the Muscular Dystrophy Association (MDA) Clinical & Scientific Conference in the poster presentation titled “ATL1102 treatment in non-ambulant boys with DMD modulates plasma proteins with roles in TGF-beta mediated fibrosis, and cartilage and bone physiology”.
As previously reported ATL1102 was assessed in an open label Phase II study in adolescent non-ambulant patients with DMD. As part of the Phase II study, a large-scale protein analysis (known as a proteomics analysis) of retained blood plasma samples was undertaken to identify proteins affected to provide further insight into the mode of action and biological activity of ATL1102.
Following on from the previously reported positive data from this proteomics analysis (refer ASX announcement 24 September 2021) the further ongoing analysis of the 7,000 plasma proteins assessed in the assay has led to the new plasma protein data reported herein.
Statistically significant mean increases in BMP-5 (46.2%) and BMP-6 (34.4%) were observed at 24 weeks compared to baseline levels (FDR p-value <0.0005). When compared to an external healthy adult proteomics dataset used as a control, the baseline BMP-5 and BMP-6 levels of patients in the Phase II study were below average with the levels of each protein increasing to near the external healthy adult control mean by the end of the 24 week ATL1102 dosing period.
BMP-5 and BMP-6, are both members of the TGF-beta superfamily of proteins and both play a role in cartilage and bone formation. ATL1102’s effect in increasing blood levels of BMP-5 and BMP-6 to healthy controls suggests the potential for ATL1102 to improve bone density in DMD.
Notably it has been reported that higher serum BMP-6 levels are associated with improved elbow flexion in patients with DMD, which appears to correlate with the positive effects seen on elbow function as assessed in the ATL1102 Phase II trial.
BMP-5 and BMP-6 levels are reduced with use of corticosteroid (CS), and the prior administration of CS appears to have reduced baseline levels to below normal in the non-ambulant DMD boys in the Phase II trial. Patients with DMD have an increased risk of bone fractures due to bone fragility through progressive muscle weakness affecting bone strength.
Prolonged corticosteroid use also reduces bone density and significantly increases risk of bone fractures (Ward et al 2018).
In addition to previously reported reduction of Thrombospondin-1 (TSP-1) and increases in Latent TGF-beta-binding protein 4 (LTBP4) levels, two proteins that modify the rate of loss of ambulation in DMD related to blocking TGF-beta mediated fibrosis, and increase CXCL16 which can promote muscle regeneration, this new plasma BMP-5 and BMP-6 data reported today adds further compelling evidence of ATL1102’s unique and highly relevant mechanism of action in its application as a potential DMD treatment.