Vyne Therapeutics has given up hopes of resuming a plaque psoriasis trial for its BET inhibitor placed on hold by the FDA, but the biotech will persevere with the candidate.
The agency slapped a clinical hold on the phase 1b study of the oral small molecule, called VYN202, in April after testicular toxicity was reported in dogs from a separate, nonclinical test. At the time, the company halted all screening, enrollment and dosing in the trial while it worked with the FDA to resolve the hold.
Since then, the FDA has lifted the hold in relation to female patients receiving 0.25 mg and 0.5 mg doses of VYN202 after concluding that it wouldn't result in adverse effects. However, Vyne did not ask the FDA to sign off on resuming a 1 mg dose “due to its lower toxicological safety margin as compared to the 0.25 mg and 0.5 mg doses,” Vyne explained in a July 2 release.
The FDA said a 12-week toxicology study in dogs would be needed for the agency to consider lifting the hold when it comes to male patients, Vyne said.
Instead, the biotech said it has given up on plans to enroll any further patients in the phase 1b psoriasis study, which will free up the cash to fund the company into the fourth quarter of 2026.
But it’s not the end of the road for VYN202. In the same release, Vyne shared unblinded data from the six patients who received the drug in the study before it was placed on hold.
These data showed that all patients who received VYN202 experienced an improvement in the signs and symptoms of their psoriasis, including a 27% reduction in psoriasis area and severity after one week and a 90% reduction at Week 8. In addition, reductions in serum cytokine levels involved in plaque psoriasis were observed in subjects treated with VYN202 for more than a week, with no similar change seen in the single patient who received a placebo.
After considering this data alongside “promising results from multiple preclinical models,” Vyne said it plans to continue to develop the BET inhibitor as a treatment for patients with serious, immune-mediated diseases with limited treatment options.
Research into the use of BET inhibitors to treat cancer has shown the mechanism can cause hematologic and gastrointestinal adverse effects. Seeking to avoid those outcomes, Vyne designed VYN202 to be selective for the BD2 portion of the protein. The choice reflected evidence that BD2 regulates gene expression of pro-inflammatory mediators, while BD1 modulates cell cycling and homeostatic functions.
The biotech said in this morning’s release that it will begin to lay out a roadmap for VYN202 once it has seen the topline results from an ongoing phase 2 trial of its lead pan-bromodomain BET inhibitor repibresib gel for non-segmental vitiligo. While repibresib also inhibits BD1, the topical gel delivery format sidesteps safety concerns associated with the systemic use of pan-BD BET inhibitors.
Since market open, Vyne's stock has dipped 13%, resting at $1.54 per share at 10:30 a.m. ET.