Aclaris slashes staff as it trims its pipeline

Aclaris Therapeutics has said it will cut 46% of its workforce after deciding to discontinue the development of lead drug zunsemetinib (ATI-450) for immuno-inflammatory indications.

The redundancies among Aclaris’ 100-plus workforce will start immediately and should conclude by the middle of 2024, said the Pennsylvania biotech in a statement.

Zunsemetinib failed a phase 2b trial in moderate to severe rheumatoid arthritis last month, and also a phase 2a trial in the skin disorder hidradenitis suppurativa earlier this year. It was also in a phase 2a trial in psoriatic arthritis.

In the latest update, Aclaris’ chief executive Douglas Manion said the failure of the drug for immuno-inflammatory diseases meant the company had to take steps to reduce its spending and streamline the organisation, which it expects "to meaningfully preserve capital.”

It isn’t the end for the drug – the lead candidate in Aclaris’ oral small molecule MK2 inhibitor programme – as it will be developed as a potential treatment for pancreatic cancer and metastatic breast cancer, as well as in preventing bone loss in patients with metastatic breast cancer.

That decision means, however, that another oral MK2 inhibitor codenamed ATI-233, which had been in early-stage clinical testing for cancers, is also being shelved “due to ATI-450’s more advanced clinical development package.”

Aclaris’ share price has been in freefall since the failure of the arthritis study and is currently trading at around $1, having started 2023 at almost $17, with its market cap now around $72 million. It is still reasonably secure financially, ending the third quarter with $187 million in cash and equivalents, and its burn rate should drop with the termination of the zunsemetinib studies.

The biotech is now highlighting the lead drug in its immuno-inflammatory programme, so-called ‘soft’ topical JAK 1/3 inhibitor ATI-1777, which recently showed efficacy in a phase 2a trial in moderate-to-severe atopic dermatitis.

The spray-on drug is designed to minimise systemic exposure to the JAK inhibitor, a class which has been associated with side effects, including serious infections, cancer, and blood clots when administered orally. After exerting its effects in the skin, it is rapidly metabolised and inactivated in the blood.

Aclaris is now holding out for phase 2b results with the drug in January 2024, which if positive will lead it to seek out a commercial partner, said Manion.

In the meantime, the company is also “reassessing the most effective pathway” for ATI-2138, an oral ITK/JAK3 inhibitor ready for mid-stage development for ulcerative colitis, in light of the increasingly competitive environment in the treatment of the inflammatory bowel disease.