The timing of the partial hold is “odd,” according to analysts at Stifel, who noted that the preclinical data the FDA took issue with were filed in mid-2024.
The FDA has slapped a partial clinical hold on PepGen’s Phase 2 FREEDOM2 study in myotonic dystrophy type 1 after finding issues with preclinical data—a delay analysts at Stifel dubbed “an oddity.”
Writing to investors on Wednesday, Stifel called the study pause a “surprise” given that FREEDOM2 continues to progress and even escalate dosing in sites abroad. “The timing here is confusing,” the analysts said, “and clouds things a bit” for PepGen.
In FREEDOM2, PepGen is studying its therapeutic oligonucleotide PGN-EDODM1, which works by restoring the function of a key RNA splicing protein that in myotonic dystrophy type 1 (DM1) is otherwise disrupted. The FDA had previously granted the asset its orphan drug and fast track designations for this indication.
Multiple-ascending dose data for the trial nevertheless “remains on-track for a March readout” the firm added.
PepGen shares dipped more than 17% to $5.55 apiece in pre-market trading Thursday. The biotech was trading at $6.76 per share at market close on Wednesday.
Details were scarce in PepGen’s news release on Wednesday, which revealed only that the partial hold was linked to questions about “previously submitted preclinical pharmacology and toxicology studies.” In imposing the freeze, the FDA did not raise issues with Phase 1 clinical data submitted by PepGen before initiating FREEDOM2.
Stifel, however, was able to obtain more information from the biotech, and said in its note that the FDA had questions “regarding a subchronic mouse study,” outcomes of which PepGen had filed in mid-2024. These mice apparently experienced a reduction in blood pressure linked to the investigational drug.
PepGen also filed mouse data showing that slower infusion of the drug did not lead to such a change in blood pressure, according to Stifel. Findings from non-human primates and a Phase 1 single-ascending dose study likewise did not find safety signals related to hypotension.
“The timing of this partial hold is odd,” Stifel wrote. PepGen has filed additional analyses with the FDA, including recently unblinded Phase 1 data, according to its press release.
Despite the pause on FREEDOM2 in the U.S., the study continues dosing in the U.K. and Canada and clearance has recently been granted to start administering treatment in South Korea, Australia and New Zealand, the biotech added. With these international sites moving forward, Stifel believes that PepGen remains on-track to deliver initial multiple-ascending dose data this month.
“Any FDA setback, even one that seems surmountable, does increase the risk for any stock,” Stifel wrote. Still, the firm remains optimistic about PepGen’s program, given that the biotech “can make the case that this was a mouse-specific finding, and they can share actual clinical data with FDA.”
