Despite izokibep maintaining its newfound winning streak in the clinic, Acelyrin is no longer focusing on its former lead asset as part of a strategic pivot that will see a third of its workforce shown the exit.
On paper, it seems like a bittersweet decision, with Acelyrin revealing in the same earnings release that izokibep has hit the primary endpoint of a phase 3 trial in hidradenitis suppurativa. That news follows hot on the heels of a phase 2b/3 win for the IL-17A inhibitor in psoriatic arthritis in March.
Instead, the California biotech is going all-in on lonigutamab, an anti-IGF-1R monoclonal antibody that Acelryin has been lining up as a potential competitor to Amgen's thyroid eye disease (TED) blockbuster Tepezza.
The strategic shift to lonigutamab means Acelyrin is waving goodbye to about 40 of its 135 employees, equivalent to 33% of its workforce. These changes should stretch out the $635.2 million the company ended June with into mid-2027, the biotech explained in its second-quarter earnings release this afternoon.
“That's a decision that really follows from the program decisions,” Acelyrin CEO Mina Kim told Fierce Biotech in an interview. “We are in a strong financial position. We've got a strong balance sheet with these decisions that we're making, we've got three years of runway, and we feel really good about that.”
The izokibep clinical rollercoaster took off just months after Acelyrin went public in May 2023. The drug failed to beat placebo in a phase 3 trial in moderate to severe hidradenitis suppurativa, causing the biotech’s share price to plummet. Acelyrin later blamed the CRO running the trial, Fortrea, for the failure, saying that a programming error caused some patients to be dosed incorrectly.
But izokibep rebounded in March this year by significantly improving symptoms in patients with psoriatic arthritis. Despite that success, Acelyrin’s founding CEO Shao-Lee Lin, M.D., Ph.D., whose immunology research formed the backbone of the company’s pipeline, left the firm in May 2024. Lin was replaced by current CEO Kim, who previously served as Acelyrin’s chief legal and administrative officer.
In the latest trial results announced today, the drug has been vindicated in hidradenitis suppurativa, with 33% of the patients who received 160 mg of izokibep weekly showing significantly reduced numbers of abscesses and inflammatory nodules compared to 21% in the placebo group.
Acelyrin said it will complete the two ongoing trials in psoriatic arthritis and hidradenitis suppurativa, but won’t put any more money towards those indications. A phase 2b/3 trial of izokibep in uveitis will continue through its primary endpoint, with topline data expected later this year. Once those findings are in, Acelyrin will decide whether or not to keep pursuing izokibep in that indication, Kim told Fierce.
With lonigutamab now in the spotlight, the company is aware that it will have stiff competition from Amgen’s Tepezza. Early data suggested that lonigutamab fared similarly to the Big Pharma's blockbuster treatment, which was approved in 2020 as the first ever for TED and has seen sales fluctuate in the years since.
“Lonigutamab is a potent molecule,” Kim said, pointed out that the drug is designed to be administered subcutaneously as opposed to Tepezza’s intravenous delivery. “We think we've got an opportunity to compete both on efficacy and convenience.”
Acelyrin hypothesizes that because of lonigutamab’s chronic, subcutaneous exposure, with patients having less of the drug in their bodies at any one time, patients will have more durable responses with fewer side effects.
“If you have lower exposure, you might be able to overcome some safety liabilities,” Chief Medical Officer Shephard Mpofu, M.D., said in an interview. “The majority of [TED] patients currently on standard of care do relapse on some of the manifestations over time,” he added. With lonigutamab, Acelyrin hopes to avoid those relapses.
As for the future of izokibep in psoriatic arthritis and hidradenitis suppurativa, Kim said the biotech is open to all options. “Those are large indications and large trials to bring that product to market,” she said.
“It may be better placed with a larger organization that's got an existing footprint in those indications, where they've already got commercial infrastructure,” the CEO added.