PepGen’s phase 2 myotonic dystrophy type 1 (DM1) data have met analysts’ best-case scenario, causing the biotech’s share price to more than double.
The company generated the data in the 10 mg/kg multiple-ascending-dose cohort of the ongoing phase 2 Freedom2-DM1 trial. The study is testing PGN-EDODM1, which delivers an oligonucleotide to treat the underlying molecular mechanism of the rare muscle disease DM1. Using its delivery technology, PepGen aims to enhance uptake of the oligonucleotide by cells and restore correct splicing.
At Week 13, PepGen reported a mean splicing correction of 46.5% in the six participants who received the drug candidate intravenously every four weeks. Splicing correction exceeded 20% in five patients and topped 50% in four people. Pooling results from two cohorts, PepGen reported a mean splicing correction of 6.8% in four placebo patients.
The data are “potentially the new benchmark for splicing,” Guggenheim Securities analysts said in a note to investors on Tuesday. The analysts compared PepGen’s result to the 25% mean splicing correction that Dyne Therapeutics reported in a phase 1/2 trial of its DM1 candidate, DYNE-101.
Dyne’s stock opened slightly down on Tuesday morning, while PepGen’s share price jumped 163% to $6.28 in early trading from a Monday closing price of $2.39.
PepGen reported a splicing dose response, with the 10 mg/kg dose achieving deeper, more consistent correction results than 5 mg/kg. The biotech has fully enrolled a 12.5 mg/kg cohort and plans to report the first clinical results in the first half of next year.
The company may see “some meaningful increase in terms of the impact on splicing and functional outcomes” at the 12.5 mg/kg dose, PepGen CEO James McArthur, Ph.D., said on a conference call with analysts. PepGen has “the luxury” of exploring the 12.5 mg/kg dose before choosing a registration dose, the analysts said.
Other strengths of PepGen’s readout include the absence of evidence of cumulative renal toxicity and favorable trends across several functional endpoints, the analysts said. Video hand opening time, an objective measure of a muscle symptom, improved by 4.3 seconds at Week 13 and 3.9 seconds at Week 16. PepGen would regard a two- to four-second improvement as a win, the analysts said last month.
The biotech reported improvements in handgrip strength and in assessments of balance, ambulation and mobility. As PGN-EDODM1 restores splicing and protein expression, McArthur said he expects to see the “development of new muscle and new functionality in people living with this disease.” That development informs the CEO’s expectation that many functional outcome measures will improve over time.