Dyne Therapeutics’ new data on its experimental Duchenne muscular dystrophy drug is being overshadowed by the departure of several top executives.
The biotech announced Tuesday that its chief operating officer, chief business officer and chief medical officer are all leaving, nearly six months after new CEO John Cox stepped into the role. Dyne’s shares $DYN fell 30% Tuesday morning, just weeks after reaching an all-time high.
John CoxIn an interview with Endpoints News, CEO John Cox described the executive changes as “a natural transition as we move Dyne into the next phase of its growth.” Cox joined Dyne in March, replacing Joshua Brumm, who had been CEO since 2019.
The muscle disease company had been riding high on compelling clinical results from its experimental therapies for myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy. Tuesday’s update on its Duchenne treatment, known as DYNE-251, built on previous results reported in May from the Phase 1/2 study. The treatment is an “exon skipping” drug developed for Duchenne muscular dystrophy patients with certain mutations amenable to exon 51 skipping.
In eight male patients who received 20 mg/kg once a month, Dyne said mean absolute dystrophin expression was 3.71% of normal, which it added was “more than 10-fold higher than the 0.3% reported in a clinical trial of the weekly standard of care, eteplirsen,” Sarepta’s approved exon 51-skipping drug that’s marketed as Exondys 51 in the US.
Dyne also said there were “meaningful improvements in multiple functional endpoints,” including on a common measure used for DMD called the North Star Ambulatory Assessment, in both the 10 mg/kg and 20 mg/kg groups.
Dyne “could have two superior assets for DM1 and DMD Exon 51” programs, Jefferies analyst Andrew Tsai wrote in a note, adding that Dyne could have a $2 billion to $3 billion opportunity with the two drugs.
Two patients who received a higher dose of 40 mg/kg experienced serious adverse events potentially related to Dyne’s treatment. One patient experienced acute kidney injury and thrombocytopenia, or low platelet counts, while the other experienced pancytopenia, or low counts of both red and white blood cells.
Dyne said in the footnotes of its presentation Tuesday that 14 patients who started the study at the 40 mg/kg dose are now being dosed at 20 mg/kg “following evaluation of the safety profile at 40 mg/kg.”
“You can anticipate that we would move rapidly with the 20 mg [dose]. I think that’s a reasonable expectation,” Cox said.
Tsai wrote that with the 20 mg/kg dose compared to lower doses, the results “are not necessarily translating to a clean dose-response on dystrophin and functional benefits,” which suggests that the drug’s effect is plateauing, but he noted that “the efficacy data at 10-20 mg/kg thus far (including dystrophin production) still seems stronger than eteplirsen.”
But the surprise management overhaul appears to have startled investors.
CMO Wildon Farwell will be replaced by Doug Kerr, a venture partner at Atlas Venture and formerly a key leader at Biogen behind Spinraza, the first treatment approved for spinal muscular atrophy. Farwell will stay through the end of the year.
COO Susanna High and CBO Jonathan McNeill “have decided to step down from their roles to pursue other opportunities,” according to the press release. Cox affirmed all three had made the choice to leave, and said they had “accomplished what they have wanted to accomplish.”
Dyne is bringing in Johanna Friedl-Naderer as chief commercial officer and Lucia Celona as chief human resources officer.
Dyne is expected to provide an update on its regulatory plans for both this program and its DM1 program by the end of the year. It’s also planning to share additional clinical data on its DM1 program by the end of the year.