Aim There is an unmet need for more effective therapies in inflammatory bowel disease (IBD). A single drug that blocks multiple distinct pathogenic pathways may offer therapeutic benefit superior to current monotherapies. PF‐07261271, a bispecific antibody targeting both the p40 subunit of interleukin‐12/23 and tumour necrosis factor‐like cytokine 1A (TL1A), is being investigated as a potential new IBD therapy. This study evaluates the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of PF‐07261271 in healthy participants. Methods This phase 1, randomized, double‐blind, placebo‐controlled study assessed single ascending doses (SAD; intravenous 30–1000 mg) and multiple doses (MD; subcutaneous 300 mg once every 4 weeks) of PF‐07261271 in healthy adults. Safety, PK, immunogenicity and exploratory PD serum biomarkers (total soluble TL1A sTL1A and p40) were evaluated. Results Thirty‐five participants were enrolled (Part A: SAD, N = 27; Part B: MD, N = 8). PF‐07261271 was generally safe and well tolerated; all treatment‐emergent adverse events were mild/moderate. Following peak serum concentration, there was a multi‐phase decline with a trend towards increased terminal half‐life at the higher doses. For the MD cohort, the estimated bioavailability of PF‐07261271 administered subcutaneously was 48%. Dose‐dependent increases from baseline in serum total sTL1A and p40 levels were observed in participants receiving PF‐07261271, demonstrating target engagement. There was no apparent impact of anti‐drug antibodies on safety, PK or PD parameters. Conclusion PF‐07261271 demonstrated p40 and TL1A target engagement and a favourable safety profile. Further studies are warranted to evaluate its safety and efficacy in patients with IBD. ClinicalTrials.gov: NCT05536440.
Neelakantan et al. (Wed,) studied this question.