First Patient Dosed With PGN-EDODM1 in Phase 1 FREEDOM-DM1 Trial for Myotonic Dystrophy Type 1


Assessments on PGN-EDODM1's safety, transcript splicing correction, and clinical outcome measures data at the 5 mg/kg dose level from trial is expected this year.

James McArthur, PhD, president and chief executive officer at PepGen

James McArthur, PhD

PepGen recently announced that the first patient has been dosed in its randomized, placebo-controlled, single ascending dose phase 1 FREEDOM-DM1 trial evaluating PGN-EDODM1, an investigational antisense oligonucleotide (ASO), for the treatment of patients with myotonic dystrophy type 1 (DM1).1 The company expects to obtain proof-of-concept data, including transcript splicing and clinical outcome measures, as well as safety data, later this year.

Originally initiated in Canada, FREEDOM-DM1 intended to enroll approximately 24 adult patients with DM1 to assess safety and tolerability of PGN-EDODM1, as well as oligonucleotide muscle concentrations and correction of mis-splicing of transcripts. Clinical outcomes impacted in DM1 will be assessed at 28 days and at later time point following a single dose of the therapy. Patients will have their dose escalated from 5 mg/kg to 10 mg/kg and then 20 mg/kg, with each dose escalation determined based upon evaluation of safety data from the prior dose cohorts.

Top Clinical Takeaways

  • The dosing of the first patient in the FREEDOM-DM1 trial signifies a crucial step forward in PepGen's commitment to developing transformative therapies for patients with DM1.
  • PGN-EDODM1, an antisense oligonucleotide therapy, holds promise in correcting defects in RNA processing and restoring the production of the DMPK gene responsible for DM1.
  • Regulatory clearances from multiple authorities indicate global recognition of PGN-EDODM1's potential, with proof-of-concept data expected in 2024, marking a potentially significant year for the advancement of DM1 treatment.

“We are pleased to announce we have dosed the first patient in our FREEDOM-DM1 clinical trial, which marks a significant milestone in our commitment to developing transformative therapies with potentially meaningful clinical outcomes for patients living with DM1. We anticipate proof-of-concept data in patients in 2024, including safety, transcript splicing and clinical outcome measures, at the 5 mg/kg PGN-EDODM1 dose level,” James McArthur, PhD, president and chief executive officer at PepGen, said in a statement.1

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An ASO therapy, PGN-EDODM1 is designed to deliver a small molecule that binds to CUG repeats and corrects defects in RNA processing. In turn, this restores the production of DMPK, the gene responsible for DM1, and allows the muscles to function properly again. DM1, also known as Steinert’s disease, affects an estimated 40,000 patients in the US and 70,000 patients in the EU.

“We are also excited to announce the receipt of regulatory clearance to evaluate PGN-EDODM1 from the UK MHRA, marking the third obtained following clearances from the FDA and Health Canada,” McArthur said in a statement.1 “We look forward to continuing our progress and remain steadfast in our dedication to the development of PGN-EDODM1 for individuals around the globe who are living with DM1.”

In a previous announcement, PepGen noted it also anticipates proof-of-concept data, as well as safety data for PGN-EDO51, the company’s lead candidate for the treatment of Duchenne muscular dystrophy (DMD), in mid-2024.2 Designed to deliver a peptide-conjugated ASO to restore cellular function, the agent is currently being assessed in the phase 2 CONNECT1-EDO51 clinical trial of patients with DMD amenable to exon 51 skipping. In 2023, PepGen received a No Objection Letter from Health Canada to initiate the study.

Designed as a multiple-ascending dose trial, CONNECT1-EDO51 will evaluate 3 cohorts of ambulatory and non-ambulatory boys and young men with DMD, with doses starting at 5 mg/kg and plans to escalate to 10 mg/kg and potentially other doses following Drug Safety Monitoring Board review.3 The anticipated data release from that study is expected to be for the 5 mg/kg dose level, and will include outcomes of exon skipping and dystrophin data.

Presented at the 2023 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, March 19-22, in Dallas, Texas, preclinical data from in vitro and in vivo studies of DM1 showed that treatment with PGN-EDODM reduced pathogenic nuclear foci by 54% per nuclei and liberated muscleblind like spicing regulator 1. Ultimately, this resulted in a greater than 68% correction of downstream transcript missplicing events in in vitro DM1 patient cells with 2600 CTG repeats.4

1. PepGen Announces First Patient Dosed in Phase 1 FREEDOM-DM1 Clinical Trial of PGN-EDODM1 for Myotonic Dystrophy Type 1 (DM1). News Release. Published December 18, 2023. Accessed January 3, 2024.
2. PepGen announces FDA has lifted the clinical hold on its investigational new drug application for FREEDOM-DM1 phase 1 study of PGN-EDODM1 for myotonic dystrophy type 1 (DM1). News release. PepGen. October 12, 2023. Accessed January 3, 2024.
3. PepGen announces clearance by Health Canada for PGN-EDO51 to begin the phase 2 clinical trial, CONNECT1-EDO51, for the treatment of Duchenne muscular dystrophy. May 18, 2023. Accessed January 3, 2024.
4. PepGen presents clinical and nonclinical data at the 2023 Annual Muscular Dystrophy Association Clinical and Scientific Conference. News release. March 22, 2023. Accessed January 3, 2024.
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