Eli Lilly has dropped (PDF) the lead candidate from its $2.4 billion takeover of Dice Therapeutics, shifting the focus of its oral IL-17 psoriasis program to a follow-up molecule. Lilly kicked DC-806 to the curb as part of a third-quarter cull that also affected the PD-1 autoimmune prospect peresolimab.
Dice designated DC-806 as the lead candidate in its oral IL-17 program. As part of Lilly, Dice kicked off a series of phase 1 and 2 trials of the molecule, including a mid-stage study that compared the molecule to placebo in 229 people with moderate-to-severe plaque psoriasis. The placebo-controlled study wrapped up earlier this year.
Wednesday, Lilly removed the DC-806 psoriasis program from its phase 2 pipeline. The decision increases the focus on DC-853, another oral IL-17 candidate that Dice designated as a fast follower of its lead asset. Lilly has thrown its weight behind DC-853, which Dice designed to have improved potency and metabolic stability. A Lilly spokesperson said DC-853 is “a more potent molecule” in an emailed statement.
Having started two phase 1 trials of DC-853 in March and April, Lilly has begun a further three studies of the asset in recent months. The series of study starts culminated with the recent initiation of a phase 2 trial that will randomize 220 adults with moderate-to-severe plaque psoriasis to take DC-853 or placebo.
Peresolimab, the other phase 2 asset affected by the third-quarter update, is an antibody that agonizes the PD-1 inhibitory receptor to suppress T-cell activation. A Lilly spokesperson explained the removal of a phase 2 trial of peresolimab from the pipeline.
“Lilly decided to terminate its phase 2b study (KDAF) of peresolimab in rheumatoid arthritis following Lilly’s analysis of the overall benefit/risk profile of peresolimab. This decision by Lilly was made specific to the phase 2b KDAF study of peresolimab for rheumatoid arthritis,” the spokesperson said. “Lilly will consider future development of peresolimab, but have not made any final decisions at this time.”
The company has voiced excitement about the asset in the past. Lilly published phase 2a data on the candidate, which is also known as LY3462817, in rheumatoid arthritis last year. By then, the company had started the phase 2b trial in rheumatoid arthritis and was evaluating other autoimmune diseases.
Speaking at a Morgan Stanley event in September 2023, Daniel Skovronsky, chief scientific officer at Lilly, called the phase 2a rheumatoid arthritis data “incredible” and talked up the “whole new way of treating immune diseases that we're uncovering at Lilly.”
Multiple other companies are working to uncover that way of treating disease. AnaptysBio is running phase 2b trials of its PD-1 agonist rosnilimab in rheumatoid arthritis and ulcerative colitis. Rheumatoid arthritis results are due in the first quarter of 2025, with the ulcerative colitis data scheduled to drop around one year later. AnaptysBio stock opened down 18% at $25.21 on Wednesday.
Johnson & Johnson lists its PD-1 drug candidate, JNJ-4703, in phase 2 in atopic dermatitis and phase 1 in rheumatoid arthritis. Boehringer Ingelheim and Gilead also have programs in phase 1. Gilead bought its way into the space through the $405 million acquisition of MiroBio in 2022.
Lilly also removed an APOC3 small interfering RNA candidate from its phase 1 pipeline. The company identified APOC3, which is involved in the regulation of triglyceride transport, as a drug target that could improve the treatment of cardiovascular disease. Other companies have reached similar conclusions.
Ionis’ olezarsen is an investigational antisense oligonucleotide that blocks the production of APOC3 and is undergoing FDA review. Arrowhead Pharmaceuticals’ plozasiran is a phase 3 RNAi therapeutic that is designed to cut production of APOC3.