PepGen’s preclinical data of PGN-EDO51, the company’s lead product candidate for the treatment of people living with Duchenne muscular dystrophy whose mutations are amenable to exon 51 skipping, showed in the mdx mouse model that a single, 30 mg/kg dose of PGN-EDO23 (the mouse equivalent of PGN-EDO51) resulted in 52.5% exon 23 skipping and dystrophin production of 22.5% that was sustained for up to four weeks. Exon skipping increased considerably with repeat dosing of 30 mg/kg PGN-EDO23 once every four weeks for a total of four doses achieving 91.5% exon 23 skipping measured by RT-PCT and production of 82.3% normal levels of dystrophin in biceps.
Even more encouraging was the increase in exon 51 skipping as measured by ddPCR in non-human primates (NHPs) dosed with PGN-EDO51 at 20 mg/kg. NHPs receiving a single dose of 20 mg/kg PGN-EDO51 observed 2.5% exon 51 skipping in biceps as measured by ddPCR, the same method employed to measure exon skipping in the EDO51 Phase 1 healthy volunteer (HV) clinical trial. Fourteen-fold higher levels of exon 51 skipping (approximately 35% skipped transcripts) were observed following four doses of PGN-EDO51 every four weeks in NHPs.
The preclinical results, combined with the exon 51 skipping observed in PepGen’s Phase 1 HV study of PGN-EDO51, suggest that repeat-dosing with PGN-EDO51 every four weeks has the potential to result in meaningfully higher levels of exon 51 skipped transcripts and potentially dystrophin levels which we believe could result in meaningful clinical benefit.
“Our preclinical and Phase 1 clinical data that is being presented at MDA highlight the observed ability of PepGen’s EDO technology platform to drive encouraging levels of exon 51 skipped transcripts following a single-dose in NHPs and in humans. Our repeat-dose NHP data we will present here further support the potential stacking of exon 51 skipped transcripts with monthly PGN-EDO51 dosing. We look forward to sharing our PGN-EDO51 clinical development plan in the near future.”Jaya Goyal, PhD, Executive Vice President, Research and Preclinical Development at PepGen
Based on the encouraging nonclinical data, PepGen is planning to initiate two clinical trials to assess the safety and efficacy of repeat doses of PGN-EDO51 in young men living with Duchenne:
- CONNECT1-EDO51 is a Phase 2 open-label multiple ascending dose (MAD) clinical trial to be initiated in Canada in the first half of 2023 that is expected to report dystrophin protein data in 2024.
- CONNECT2-EDO51, a Phase 2, global, randomized placebo-controlled clinical trial, is expected to be initiated in the second half of 2023 to support a potential accelerated approval pathway, subject to alignment with regulators.