2.2. Phase II Clinical TrialsWhile no AON candidates other than the aforementioned PMOs with conditional FDA approval have entered Phase III trials, six different candidates are in varying stages of Phase II trials: ATL1102 (Antisense Therapeutics), SCAAV9.U7.ACCA (Astellas Pharma), SRP-5051 (Sarepta), NS-089/NCNP-02 (NS Pharma), WVE-N531 (Wave Life Sciences), and DS-5141B (Daiichi Sankyo).2.2.1. ATL1102 ATL1102 is the most advanced of these candidates, having successfully completed Phase IIa trials in Australia [47]. Unlike other AONs for DMD which aim to restore dystrophin production, ATL1102 is instead focused on treating the inflammation associated with DMD. ATL1102 was designed as a gapmer with a central ribonuclease-inducing DNA core and flanking 2′-O-(2-methoxyethyl) oligos targeted to CD49d mRNA, which encodes for a key subunit of the human very-late antigen (VLA4) associated with inflammation [48]. By recruiting ribonucleases to degrade CD49d transcripts, ATL1102 thus aims to reduce inflammation and inflammation-mediated tissue damage in DMD [49].Results from the completed Phase II trials found that a weekly injection of ATL1102 was generally safe in patients, with no serious treatment-related adverse effects after 24 weeks of treatment [50]. No significant changes were found in blood lymphocyte count, a marker of inflammation, throughout the study, although the authors did note a significant increase in CD3 + CD49d + T lymphocytes 4 weeks after stopping the treatment. Further, no changes in grip strength or pinch strength were noted throughout the study [50]. Based on the favorable safety data and apparent stabilizing effect of ATL1102, the authors expressed optimism in the continued development of this drug. However, no details regarding further trials are yet available.
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