PepGen reports 46.5% splicing correction in six treated patients
Eight participants completed the placebo-controlled cohort; extension data are expected in January 2027 while a partial FDA hold remains.
Adrian Kessler
Splicing correction averaged 46.5 per cent in six treated patients as PepGen Inc. NASDAQPEPG reported Phase 2 myotonic dystrophy results on Tuesday. Hand opening improved by 3.9 seconds at Week 16, compared with 0.2 seconds on placebo.
The randomized, double-blind FREEDOM2-DM1 cohort assigned six participants to drug and two to placebo. All completed the assessment after four intravenous doses administered every four weeks.
PepGen is a small Boston-based clinical biotechnology company developing oligonucleotide medicines for rare genetic diseases.
PepGen shares NASDAQPEPG closed at US$2.39 on Nasdaq at 4:00 p.m. EST on Nov. 9, before the announcement. In its Nov. 10 financial update, the company reported US$104.8 million in cash, cash equivalents and marketable securities at Sept. 30. Management projects funding into 2028 and expects extension data in January 2027, while a partial FDA clinical hold remains a regulatory hurdle.
Functional Gains Accompany Splicing Correction
The trial, registered as NCT06667453, tests PGN-EDODM1 in myotonic dystrophy type 1, or DM1. The drug is designed to free a protein trapped by abnormal RNA, restoring its role in RNA splicing.
The 46.5 per cent splicing result was measured at Week 13 using a 22-gene panel. The comparison was 6.8 per cent in four pooled placebo participants across the first two cohorts.
Grip strength increased by 6.3 points in maximum predicted percent normal at Week 16, versus 0.9 points with placebo. Timed Up and Go improved by 0.6 seconds while placebo worsened by 0.5 seconds. Walk/run time over 10 metres improved by 0.4 seconds, versus 0.2 seconds with placebo.
These are small-cohort comparisons: PepGen supplied no p values or confidence intervals for them in its topline results. Patient-reported outcomes were inconclusive, with mixed health-index scores as all groups improved and baseline measurements differed.
Read more: Satellos changes BASECAMP trial endpoint after FDA feedback
All treatment-emergent adverse events were mild or moderate, with no serious events, dose-limiting toxicities or discontinuations in this cohort. Four renal adverse events were reported, all mild; transient urine-protein increases declined with later doses.
"The relationship between splicing correction and improvements in myotonia is particularly interesting, and longer-term follow-up will be important to better understand the durability and clinical relevance of these findings," FREEDOM2 investigator Hanns Lochmüller said in the release.
Regulatory Meeting Depends On Hold Removal
PepGen said the FDA's partial hold, announced in March, concerns nonclinical findings in mice. The company is conducting mouse studies and discussing additional work with the agency; its planned end-of-Phase 2 meeting in the second half of 2027 depends on removal of the hold.
The separate open-label extension now includes 19 participants, according to Tuesday's update. That study has had one discontinuation for a hypersensitivity reaction, distinct from the absence of discontinuations in the newly reported randomized cohort.
Read more: Cabaletta Bio reports year-long rese-cel responses in six myositis patients
The listed DM1 peer group includes Dyne Therapeutics, Inc. NASDAQDYN. Its Sept. 29 announcement reported additional one-year results from the Phase 1/2 ACHIEVE study of z-basivarsen.
The iShares Biotechnology ETF NASDAQIBB closed at US$219.57 on Nasdaq at 4:00 p.m. EST on Nov. 9. Both that benchmark and PepGen's quoted close precede Tuesday's clinical disclosure.
PepGen's quarterly loss widened to US$19.4 million for the period ended Sept. 30, from US$18.0 million a year earlier. Its runway estimate applies to currently planned operations. The company also plans an expansion cohort to collect longer-term data alongside the fully enrolled higher-dose cohort.
January 2027 is the next scheduled clinical update, covering extension-study safety at 10 mg/kg and clinical results at 5 mg/kg. Results from the 12.5 mg/kg randomized cohort are expected in the first half of 2027, adding evidence for the proposed regulatory discussion.
