IL-17A Inhibitor (C4XD)

Despite a positive phase 3 trial for its lead candidate, izokibep, California biotech Acelyrin revealed plans to cease investments in the IL-17A inhibitor, instead focusing on its thyroid eye disease (TED) candidate. The "refocused pipeline strategy" will use the company's existing cash resources to prioritize lonigutamab, a mid-stage subcutaneous anti-IGF-1R treatment. Acelyrin is currently testing different doses and dose regimens with a goal of establishing a minimum effective dose and selecting the dose regimen for the phase 3 program, which the biotech anticipates starting in the first quarter of 2025. The strategic shift will also come with a 33% workforce reduction, which the company anticipates will extend its cash runway to mid-2027 and fully fund both phase 3 trials for lonigutamab. In the same press release, Acelyrin revealed that its phase 3 trial of izokibep in chronic skin disease, hidradenitis suppurativa (HS), had achieved its primary endpoint of HiSCR75 (75% reduction in total abscess and inflammatory nodules) at 12 weeks. While the company plans to complete the drug's ongoing trials in HS and active psoriatic arthritis, going forward, it will suspend new investment in the indications. “While today’s positive HS data and previously announced psoriatic arthritis (PsA) data support a path to approval for izokibep, we have determined that a program of this breadth and size is best brought to market by a larger organization with the resources and existing footprint in these indications,” said Mina Kim, Acelyrin CEO. Acelyrin was one of the biggest biotech IPOs of 2023, raising $540 million in May 2023.

Acelyrin said Tuesday it will be cutting approximately 33% of its staff as it redirects its efforts towards the development of lonigutamab for thyroid eye disease (TED). The move comes despite positive Phase III data for the company's former lead asset izokibep, an IL-17A inhibitor, in hidradenitis suppurativa (HS).The trial succeeded on multiple efficacy endpoints, including 33% of patients receiving izokibep 160 mg weekly achieving HiSCR75 at 12 weeks, compared to 21% for placebo. Acelyrin has also been dosing patients in a placebo-controlled manner through week 16 and has data from two-thirds of patients showing "continued deepening of HiSCR responses over time."It hasn't been smooth sailing for the HS programme, however. A few months after pulling in $540 million in an upsized IPO last year, Acelyrin reported that izokibep had failed a Phase IIb/III trial for the treatment of moderate-to-severe HS.Despite the turnaround reported Tuesday, the company has decided to suspend new investments in izokibep for both HS and psoriatic arthritis, another indication the compound is being tested in, although it will complete ongoing trials for both. Meanwhile, an ongoing Phase IIb/III trial of izokibep in uveitis will continue through its primary endpoint, with top-line data expected in the fourth quarter.Explaining the rationale behind the move, CEO Mina Kim said that "while today's positive HS data and previously announced psoriatic arthritis data support a path to approval for izokibep, we have determined that a programme of this breadth and size is best brought to market by a larger organisation with the resources and existing footprint in these indications."The focus has clearly shifted to lonigutamab, an anti-IGF-1R monoclonal antibody under development for TED, a disease targeted by Amgen's Tepezza (teprotumumab-trbw).Acelyrin is sidestepping its original plan for a Phase IIb/III study of lonigutamab and advancing the drug right into Phase III in the first quarter of 2025, potentially with concurrent trials. At the moment, the company is testing different doses and regimens to establish an optimal dosing strategy for the late-stage programme."We have decided to focus our efforts toward rapidly advancing lonigutamab through late-stage development with our existing cash resources," Kim said. Combined with the reduction in force, she said the shift will allow Acelyrin to extend its runway to mid-2027 and fully fund both Phase III trials for lonigutamab.The company had $635.2 million in cash, cash equivalents, and short-term marketable securities as of the end of June.