Aclaris' stock sinks further as biotech abandons MK2 inhibitor over latest phase 2 fail

Aclaris Therapeutics has abandoned zunsemetinib after the latest phase 2 fail saw the MK2 inhibitor unable to match placebo on any primary or secondary endpoints in a rheumatoid arthritis (RA) trial.

The Pennsylvania-based biotech found that neither a 20-mg nor a 50-mg dose of the drug along with methotrexate beat placebo in “any measures of efficacy” after 12 weeks, including the primary endpoint of the percentage of patients achieving a 20% or better improvement according to the American College of Rheumatology ACR20 criteria.

The phase 2b trial had enrolled 251 patients with moderate to severe RA whose condition had not adequately responded to methotrexate alone. This morning's readout sent Aclaris’ already battered stock sinking 85% in premarket trading to just 69 cents from a Friday closing price of $4.75.

In the wake of the “deeply disappointing” results, CEO Doug Manion, M.D., said Aclaris would discontinue development of zunsemetinib, including an ongoing phase 2a trial in psoriatic arthritis.

It isn’t the first time that zunsemetinib has disappointed in the clinic. Back in March, the drug failed to improve abscesses in patients with a chronic skin condition called hidradenitis suppurativa. Those phase 2 results halved the company’s stock to less than $6, from which point it has continued to drift down.

“Despite this setback, we continue to look forward to the upcoming results of our phase 2b trial of ATI-1777 in atopic dermatitis and initiating our phase 2 clinical development program for ATI-2138,” Manion added in the Nov. 13 release.

The biotech hopes to publish data from the study of ATI-1777, a topical JAK1/3 inhibitor, at the end of the year. Meanwhile, the phase 2 program for JAK3 inhibitor ATI-2138, which will initially focus on ulcerative colitis, is expected to get off the ground early in 2024, the company said.

“While preliminary data from ATI-1777 … suggest compelling efficacy in AD without the adverse event baggage of the broader class of JAK inhibitors and the positive phase 1 results from ATI-2138 adds an interesting clinical-stage pipeline asset with potential for significant upside, we are cautious given the failure of zunsemetinib in RA and in HS,” William Blair analysts wrote in a note this morning.

Aclaris has another MK2 inhibitor in the works in the form of ATI-2231. While zunsemetinib’s failure has now ended the chances for ATI-2231 to be developed in immuno-inflammatory disease, the drug remains in a phase 1 trial in advanced solid tumors being conducted by Washington University.

The company still has enough financial fuel to drive its pipeline forward into 2025, with $187 million in the bank as of the end of September.