Core Insights - PepGen Inc. has received a U.S. patent for its proprietary PGN-EDODM1 molecule, which is a significant addition to its patent portfolio and is expected to provide exclusivity until the second half of 2042 [1][2]. Group 1: Patent and Exclusivity - The newly issued composition of matter patent covers PGN-EDODM1, which utilizes PepGen's Enhanced Delivery Oligonucleotide (EDO) platform [1][2]. - The patent is expected to offer exclusivity in the U.S. until the second half of 2042, with potential for extension following FDA approval [1][2]. Group 2: Product Development - PGN-EDODM1 is designed to treat myotonic dystrophy type 1 (DM1), a severe neuromuscular disease with no approved therapies targeting its underlying cause [2][3]. - The investigational therapy aims to restore normal splicing function of MBNL1, addressing the negative effects of CUG repeat expansion in DMPK transcripts [3]. Group 3: Company Overview - PepGen Inc. is a clinical-stage biotechnology company focused on developing next-generation oligonucleotide therapies for severe neuromuscular and neurological diseases [4]. - The EDO platform is based on over a decade of research, utilizing cell-penetrating peptides to enhance the uptake and efficacy of oligonucleotide therapeutics [4].

PGN-EDODM1 for DM1 - PGN-EDODM1 targets the pathogenic CUGexp repeats in DM1, aiming to restore correct splicing by liberating MBNL1[29, 30, 31, 32, 33] - In DM1 patient cells, PGN-EDODM1 treatment resulted in a 54% reduction in toxic foci and a 69% correction of mis-splicing[36] - Preclinical studies showed that multiple doses of PGN-EDODM1 led to a 99% correction of myotonia, compared to a single dose[41] - In the FREEDOM Phase 1 trial, a single 10 mg/kg dose of PGN-EDODM1 produced a mean 29% splicing correction[57] PGN-EDO51 for DMD - In a healthy volunteer study, PGN-EDO51 demonstrated exon skipping, with levels reaching 1.4% at Day 10 and 2% at Day 28 in the 15 mg/kg cohort[76] - CONNECT1 study showed that PGN-EDO51 generated encouraging levels of muscle adjusted dystrophin production of 0.70% and total dystrophin production of 0.26% after just 3 months and 4 doses at 5 mg/kg[95] - CONNECT1 study also showed high levels of mean exon 51 skipping of 2.15% after just 3 months and 4 doses at 5 mg/kg[95] EDO Platform - PepGen's EDO platform is designed for nuclear delivery of oligonucleotide therapeutics, showing up to 25X higher nuclear uptake[7, 17, 19] - EDO technology has been shown to increase cellular uptake and endosomal escape up to 24-fold[21]

PGN-EDODM1 for DM1 - PepGen's EDO platform aims to deliver higher levels of oligonucleotide to the nuclei, potentially improving the lives of people with severe neuromuscular and neurological diseases[3] - The FREEDOM-DM1 (Phase 1) trial observed a favorable emerging safety profile and a mean splicing correction of 29% after a single dose of 10 mg/kg at 28 days post-dosing[22] - Preclinical studies showed that multiple doses of PGN-EDODM1 led to greater improvement in splicing correction and myotonia compared to a single dose[35] - In DM1 patient cells, PGN-EDODM1 treatment resulted in a 54% reduction in toxic foci and a 69% correction of mis-splicing[33] - The FREEDOM trial showed a dose-dependent increase in drug tissue concentration, with approximately 12% splicing correction at 5 mg/kg and approximately 29% splicing correction at 10 mg/kg[56] PGN-EDO51 for DMD - The company is voluntarily discontinuing development of PGN-EDO51 for DMD due to the CONNECT1-EDO51 Phase 2 study results not achieving target dystrophin levels[63] - In the CONNECT1-EDO51 trial, a mean maximal exon skipping of 426% (mean increase of 35%) and a mean maximal dystrophin of 059% (mean increase of 036%) were observed after four doses of 10 mg/kg[63] EDO Platform Technology - PepGen's EDO platform is designed to solve the problem of inefficient penetration of muscle cells and the nucleus by naked oligonucleotides[13] - PepGen's EDO platform can result in up to 25X higher nuclear uptake of oligonucleotide[16] - EDO technology has been shown to increase cellular uptake and endosomal escape up to 24-fold[18]