Entrada Therapeutics saw a 2.36% dystrophin increase in patients treated with its oligonucleotide asset—a number that fell short of the company’s prior guidance of a double-digit improvement.
Entrada Therapeutics’ investigational oligonucleotide increased dystrophin concentrations in a Phase 1/2 Duchenne muscular dystrophy but not to the degree that analysts or the company had been expecting.
In the first dosing cohort of the Phase 1/2 ELEVATE-44-201 trial, ENTR-601-44 elicited a 2.36% increase in normalized dystrophin levels in muscle tissue six weeks after the last dose, according to a Thursday release—well short short of Entrada’s prior guidance of a double-digit jump.
Shares of the Boston-based biotech plummeted 50% before the opening bell on Thursday, hitting $8.01 apiece.
Oppenheimer analysts called ENTR-601-44’s performance “disappointing,” noting that the result puts Entrada’s dystrophin benefit lower than that of competitor Avidity Biosciences. In a Thursday morning investor note, the firm pointed to a September 2025 readout in which Avidity reported an approximately 25% increase in the protein for its own oligonucleotide therapy del-zota after one year of treatment. Importantly, no trials directly comparing the two have been conducted.
William Blair had a similar assessment of Entrada’s readout. “Measurements of dystrophin protein expression after ENTR-601-44 treatment, the main efficacy-based endpoint of focus for investors, showed a 2.36% increase from baseline, which missed our base case of 10% and also management’s expectations,” the analysts wrote in a Thursday note.
On a more positive note, Oppenheimer homed in on ENTR-601-44’s effects on time-to-rise (TTR) velocity, a robust measure of functional performance that, according to Entrada, is “used as an early prognostic factor for disease progression and loss of ambulation.”
Thursday’s readout demonstrated an average TTR improvement of 0.08 in patients treated with Entrada’s molecule. Oppenheimer called this magnitude of effect “clinically significant” and noted it is “larger than competitors, suggesting a potential clinical benefit.”
As for safety, Entrada touted a favorable overall profile for a 6-mg/kg dose of ENTR-601-44, with no serious side effects or adverse events triggering discontinuation. Oppenheimer found the “clean” safety profile encouraging, explaining that it “allows for dose escalation to 12-18mg/kg that can ultimately deliver a competitive profile.”
With Thursday’s data, ELEVATE-44-201 will continue on to its second patient cohort, which will receive a 12-mg/kg dose of the drug. Dosing for this leg of the study has started, with data expected by year-end.
ENTR-601-44 is an oligonucleotide therapy that binds to exon 44 in the dystrophin pre-mRNA, allowing the cell’s splicing machinery to skip over the faulty exon, according to Entrada’s website. This ultimately results in a shorter but functional dystrophin protein, helping maintain the function and integrity of muscle cells, which in patients with Duchenne muscular dystrophy (DMD) otherwise undergo progressive degeneration. Common complications of the disease include heart and lung problems, often leading to death.
Sarepta Therapeutics’ Amondys 45 and Vyondys 53 work similarly to ENTR-601-44, removing faulty exons from the final mRNA transcript and facilitating the expression of truncated but functional dystrophin. In November last year, the drugs failed their confirmatory Phase 3 study, unable to elicit significant motor improvements in patients over placebo. Sarepta has nevertheless submitted supplemental applications to the FDA for both drugs.
Vyondys 53 was first approved in 2019 and Amondys 45 in 2021, both under the agency’s accelerated pathway.
