After escaping a clinical hold several years back, Dyne Therapeutics has revealed new phase 1/2 data for its Duchenne muscular dystrophy (DMD) therapy DYNE-251. The readout notes several serious treatment-emergent adverse events (TEAEs), including acute kidney injury.
At the same time, three executives at the biotech have also resigned, according to a separate company release shared the same day.
Investors seem rattled by Dyne’s double announcement this week, with the company’s stock trading down about 32% as of Tuesday morning.
In the new data drop, Dyne’s candidate in male DMD patients with DMD suited to exon 51 skipping therapy posted functional improvements in ambulatory performance, 10-meter walk/run time and time to rise from floor—but statistical significance wasn’t mentioned.
Dyne’s latest DMD assessment wrapped in 6-month biomarker and functional data from eight male patients who received either 20 mg DYNE 251 or placebo once every four weeks. The assessment also included 12-month functional data from six participants in the 10-mg cohort. The overall study has an estimated enrollment of 88 male patients between the ages of 4 and 16 years.
Meanwhile, Dyne’s chief business officer, Jonathan McNeill, M.D., and the biotech’s chief operating officer, Susanna High, tendered their resignations at the company, according to a recent securities filing. McNeill’s resignation became effective Tuesday while High will remain on board with the company until Oct. 1.
Both executives have entered a consulting agreement with Dyne to provide advisory services to the company through Dec. 31, the Securities and Exchange Commission filing states.
Wildon Farwell, M.D., Dyne’s chief medical officer, is also stepping down, though he’ll remain at the company through the end of 2024 to help steer Dyne’s clinical ambitions in DMD and myotonic dystrophy type 1 (DM1), according to Dyne’s release.
Dyne has tapped Doug Kerr, M.D., Ph.D., a partner at Atlas Venture, to replace Farwell as CMO. The company has also recruited Johanna Friedl-Naderer, a previous Vir Biotechnology executive, as its new chief commercial officer, alongside Lucia Celona, who is taking up the mantle as chief human resources officer.
Digging deeper into the DMD data, Dyne said its drug candidate demonstrated “unprecedented dystrophin expression” and functional improvement across multiple cohorts.
In Dyne’s phase 1/2 DELIVER study, patients who received a 20 mg dose of DYNE-251 experienced a mean absolute dystrophin expression of 3.71% of normal, which was more than 10 times higher than the 0.3% reported in a clinical trial of weekly standard-of-care eteplirsen, Dyne said. However, the DELIVER study was not a head-to-head comparison with eteplirsen.
Dyne’s drug also helped patients chart "meaningful improvements" on multiple metrics of functioning across both 20 mg and 10 mg cohorts, the company said. In particular, DYNE-251 helped patients chalk up wins on the North Star Ambulatory Assessment (NSAA), Stride Velocity 95th Centile, 10-meter walk/run time, and time to rise from the floor.
Based on those results, Dyne said it is initiating registrational cohorts in the DELIVER trial and aims to provide an “update on the path to registration” by year-end.
Still, safety concerns could temper Dyne’s hopes, as revealed in a company presentation from the biotech’s phase 1/2 DELIVER trial.
On a slide covering DYNE-251’s safety profile, the biotech flagged three "serious TEAEs potentially related to study drug in two participants.” Those side effects included one instance of acute kidney injury, one instance of thrombocytopenia and one instance of pancytopenia, where there is a lower-than-normal number of red and white blood cells and platelets in the blood.
Prior to Dyne pushing its DMD prospect into the clinic, the company’s trial application was put on pause by the FDA in January 2022 after the regulator requested more clinical and nonclinical information.
The agency ultimately lifted its hold on the drug in July of that same year.
Dyne’s therapy leverages exon skipping—a form of RNA splicing that allows cells to “skip” over faulty or misaligned sections of the genetic code. In DMD patients, one or more of the 79 exons in the dystrophin gene are deleted, thus interfering with the rest of the gene being pieced together.