Antisense Therapeutics Limited reported initial positive muscle functional data from a DMD mdx animal study assessing the use of the combination of antisense (ASO) to CD49d with a dystrophin exon skipping restoration drug. The use of the combination improved the specific maximum force of the extensor digitorum longus (EDL) muscle, a lower leg muscle, and the eccentric muscle force remaining following induced damage to the EDL. This functional data supports the potential use of ATL1102 in combination with dystrophin restoration drugs to improve therapeutic outcomes in patients with DMD.

Under the collaborative research agreement with the Murdoch Children's Research Institute's (MCRI), six groups of DMD mdx mice (n=8 per group) were treated for 6 weeks with antisense oligonucleotide to CD49d (mouse equivalent of ATL1102), or control oligonucleotide mismatch or saline treatments, or the morpholino exon skipping dystrophin restoration drug alone and in combination. The muscle physiology of the EDL was assessed for force parameters including specific maximum force and the force drop following 1 to 10 eccentric (lengthening) contraction each involving induced muscle damage by the stretching of the muscle by 10%. The EDL is 1 of 4 muscles in the front of the lower leg whose function is to invert the foot at the ankle.

Another of these muscles is the tibialis anterior (TA) on which the ASO to CD49d has previously reported a benefit in reducing eccentric muscle damage in mdx mice. The ASO to CD49d and morpholino exon skipping combination improved the specific maximum force (the maximum force corrected for size/mass and cross-sectional area of the EDL muscle) and both the eccentric muscle force remaining after a single and 10 repeated lengthening contractions with statistically significant effects compared to saline control. This combination after the 10 repeated lengthening contractions, also showed a significant effect (P<0.001) compared to the exon skipping drug used alone and the exon skipping drug used together with the control oligo.

In addition, the ASO to CD49d showed a significant effect vs the saline and its control oligo. The morpholino exon skipping drug showed a significant effect compared to the saline control. A provisional patent application titled "Combination Compositions and Methods for Treatment of Muscular Dystrophy" is to be filed to cover the use of the ASO to CD49d and the morpholino exon skipping drug combination to seek protection of the combination of ATL1102 with the dystrophin restoration/exon skipping drugs to 2044, well beyond the patent life of the registered dystrophin restoration drugs.

Notably the dystrophin restoration drugs have yet to demonstrate in controlled clinical studies a slowing of the loss of ambulation beyond use of corticosteroids, highlighting the clinical need for a more efficacious therapeutic approach.Further investigations are ongoing in the mdx mouse combination study to determine the possible mechanisms by which the combination approach is providing the observed functional benefits. Muscle RNA and protein samples have been isolated from the mdx mice quadricep muscle for analysis of the dystrophin levels in the muscle to determine if higher levels are seen with the use of the combination than with the dystrophin restoration agent alone. Cellular markers of inflammation and fibrosis including those observed in the ATL1102 DMD Phase II study, will also be assessed to elucidate the potential mechanisms that may be involved.

Results from this analysis are anticipated before the end of the first quarter of current year 2023.