8-K: PepGen Pauses Phase 2 DMD Study to Focus on Ongoing Trial and Await Key Data

PepGen Inc. announced a temporary pause of its Phase 2 CONNECT2-EDO51 study for Duchenne muscular dystrophy (DMD) to focus on the ongoing CONNECT1-EDO51 study and review upcoming data.

Summary

• PepGen has decided to temporarily halt the Phase 2 CONNECT2-EDO51 study of PGN-EDO51 in DMD patients.
• This pause will allow the company to focus on the ongoing Phase 2 CONNECT1-EDO51 study and review results from the 10 mg/kg cohort, expected in Q3 2025.
• No new safety issues have been observed in the PGN-EDO51 program since the last update on January 23, 2025.
• The company aims to gather additional safety data and assess the impact of the 10 mg/kg dose on dystrophin levels.
• PepGen is also advancing its FREEDOM studies in myotonic dystrophy type 1 with PGN-EDODM1, following encouraging initial clinical data.
• The FDA has granted PGN-EDO51 Orphan Drug and Rare Pediatric Disease Designations.
• The CONNECT1-EDO51 trial is an open-label, multiple ascending dose Phase 2 trial in Canada.
• The 10 mg/kg cohort in CONNECT1 is fully enrolled (n=4), and participants in the 5 mg/kg cohort (n=3) are continuing to dose.
• PepGen is addressing Health Canada's safety concerns regarding dosing in the CONNECT1 study.
• The CONNECT2-EDO51 trial is a double-blind, placebo-controlled Phase 2 trial designed to evaluate PGN-EDO51 over 24 weeks.
• In December, the FDA issued a clinical hold notice on the IND application for CONNECT2 in the U.S., and PepGen is working to address the FDA's questions.

Sentiment

Score: 5

Explanation: The news is mixed. The pause of the CONNECT2 study is a setback, but the focus on CONNECT1 and the lack of new safety issues are positive. The clinical hold from the FDA adds uncertainty.

Positives

• No new safety issues have been observed in the PGN-EDO51 program.
• The 10 mg/kg cohort in the CONNECT1 study is fully enrolled.
• PepGen is advancing its FREEDOM studies in myotonic dystrophy type 1.
• The FDA has granted PGN-EDO51 Orphan Drug and Rare Pediatric Disease Designations.

Negatives

• PepGen is temporarily pausing the Phase 2 CONNECT2-EDO51 study for DMD.
• The FDA issued a clinical hold notice on the IND application for CONNECT2 in the U.S.
• Health Canada has raised safety concerns regarding dosing in the CONNECT1 study.

Risks

• Delays or failure to successfully complete ongoing and planned development activities.
• Inability to enroll patients in clinical trials.
• Incorrect interpretation of clinical and preclinical study results.
• Product candidates may not be safe and effective.
• Adverse outcomes from regulatory interactions.
• Unexpected increases in expenses.
• Dependence on third parties for manufacturing, research, and testing.

Future Outlook

PepGen expects to review results from the 10 mg/kg cohort of the CONNECT1-EDO51 study in Q3 2025 and continue advancing its FREEDOM studies in myotonic dystrophy type 1.

Management Comments

• 'This will allow us to gather additional safety data, assess the impact of this dose of PGN-EDO51 on dystrophin levels, and potentially improve the design of CONNECT2,' said James McArthur, PhD, President and CEO of PepGen.
• 'This decision enables us to focus resources on completing CONNECT1, as well as rapidly advancing our FREEDOM studies in myotonic dystrophy type 1 with PGN-EDODM1, in which we recently reported encouraging initial clinical data from the Phase 1 FREEDOM-DM1 study.'

Industry Context

The development of oligonucleotide therapies for neuromuscular diseases like DMD is a competitive field, with companies like Sarepta Therapeutics and BioMarin already having approved therapies. PepGen's approach focuses on enhanced delivery of oligonucleotides, which could potentially offer improved efficacy and safety profiles compared to existing treatments.

Comparison to Industry Standards

• Sarepta Therapeutics' Exondys 51 is an approved exon-skipping drug for DMD, targeting the same exon as PGN-EDO51.
• BioMarin's Viltolarsen is another approved exon-skipping drug for DMD.
• PepGen's CONNECT1 and CONNECT2 trials are designed to evaluate the safety and efficacy of PGN-EDO51, with endpoints including dystrophin production and functional outcome measures, similar to other DMD clinical trials.
• The clinical hold on CONNECT2 is not uncommon in drug development and highlights the importance of addressing regulatory concerns regarding dosing and safety data.

Stakeholder Impact

• Patients with DMD may experience delays in accessing potential treatment through the CONNECT2 trial.
• Shareholders may react negatively to the pause of the CONNECT2 study.
• Employees may experience a shift in focus towards the CONNECT1 and FREEDOM studies.

Next Steps

• PepGen will review results from the 10 mg/kg cohort of the CONNECT1-EDO51 study in Q3 2025.
• The company will continue working with the FDA to address questions regarding the CONNECT2 clinical trial.
• PepGen will continue advancing its FREEDOM studies in myotonic dystrophy type 1.
• PepGen is working with Health Canada to address its questions regarding dosing in the CONNECT1 study.

Key Dates