HiSQOL Scores, Avidity, and the Case for Dual IL-17 Inhibition in Hidradenitis Suppurativa

At the 2026 American Academy of Dermatology (AAD) Annual Meeting in Denver, Colorado, Kristian Reich, MD, PhD, a dermatologist and the founder and chief scientific officer of MoonLake Immunotherapeutics, spoke with Christopher Bunick, MD, PhD, associate professor of dermatology at Yale School of Medicine and editor in chief of Dermatology Times, to discuss late-breaking phase 3 data for sonelokimab in hidradenitis suppurativa (HS). Their conversation covered patient-reported outcomes, the novel mechanistic profile of the nanobody-based dual inhibitor, and the company's expanding pipeline across Th17-driven inflammatory diseases.^1,2

In the first part of their discussion, Bunick and Reich discussed the Hidradenitis Suppurativa Clinical Response (HiSCR) 75 and HiSCR 100 rates from the phase 3 trial.

HiSQOL Data Signal a Shift From Severity to Near-Remission

A central focus of the late-breaker presentation was the HS Quality of Life score (HiSQOL) data, which Reich described as particularly compelling in the context of quality of life. The HiSQOL instrument used in MoonLake's phase 3 program consists of 17 questions addressing domains that patients themselves identify as most burdensome—including pain, odor, mobility, ability to work, and the frequency of wound dressing changes.

“At baseline, the average HiSQOL indicated very severe disease. In our phase 3 program, at week 40, the average HiSQOL indicated absent or mild disease,” Reich said. “So for the vast majority of patients, the drug not only made the lesions and the pain go away, but it actually dramatically improved their quality of life.”

Reich emphasized that the decision to make the HiSQOL a ranked end point in the phase 3 program represents a methodological novelty that elevates patient-centric measurement alongside traditional clinical assessments. Bunick supported the clinical significance of pairing objective lesion response with validated patient-reported outcomes, noting that the combination will reshape expectations for what constitutes meaningful treatment success in HS.

Dual IL-17A/F Inhibition

The mechanistic conversation turned to what distinguishes sonelokimab from other biologic agents targeting the IL-17 pathway. As a nanobody construct, sonelokimab features 2 variable heavy-chain homodomain (VHH) arms connected by flexible spacers, enabling it to simultaneously bind a heterodimer containing both IL-17A and IL-17F—or 2 IL-17F molecules—within a single interaction.

“Sonelokimab can actually bind one dimer if it contains an A and an F, or 2 F’s at the same time, and this will bring a very much higher avidity when we talk about IL-17F,” Reich explained. “We have high affinity to A, we have an equally high affinity to F, and we have a very strong avidity to F.”

Reich cited emerging evidence suggesting that while IL-17A may drive acute inflammation, IL-17F plays a more prominent role in disease chronicity—a distinction with direct relevance to HS, a condition characterized by persistent, relapsing inflammatory cycles.³ This mechanistic profile may help explain the durability of sonelokimab's long-term efficacy signals.

“A seems to be more the driver of acute inflammation, F is more responsible for the chronicity of skin diseases like HS. That could also explain why our long-term data is so shining, because sonelokimab [is a] particularly strong inhibitor of F,” Reich said.

Pipeline Expansion Reflects the Breadth of Th17-Driven Disease

Looking beyond HS, Reich outlined a pipeline shaped by the company's conviction that IL-17A and F function as independent, co-operative drivers across a broad class of Th17-mediated inflammatory conditions. MoonLake is actively investigating sonelokimab in psoriatic arthritis—with first phase 3 results expected in 2026—as well as in palmoplantar pustulosis, a condition Reich described as severely undertreated with no approved therapies in either the United States or Europe. Axial spondyloarthritis rounds out the rheumatology program.

“We want to make sure that we bring what I currently consider the spearhead of A and F inhibition to as many diseases as possible where we know that A and F are the cornerstone of the pathophysiology,” Reich said.

References

1. MoonLake announces week 40 results from its phase 3 clinical trials of sonelokimab in hidradenitis suppurativa at the 2026 AAD Annual Meeting. News release. MoonLake Immunotherapeutics. March 28, 2026. Accessed April 7, 2026. https://ir.moonlaketx.com/news-releases/news-release-details/moonlake-announces-week-40-results-its-phase-3-clinical-trials
2. Kimball A. Sonelokimab in moderate-to-severe HS: long-term results through week 40 of two phase 3 trials. Presented at: 2026 American Academy of Dermatology Annual Meeting; March 27-31, 2026; Denver, CO.
3. Glatt S, Baeten D, Baker T, et al. Dual IL-17A and IL-17F neutralisation by bimekizumab in psoriatic arthritis: evidence from preclinical experiments and a randomised placebo-controlled clinical trial that IL-17F contributes to human chronic tissue inflammation. Ann Rheum Dis. 2018;77(4):523-532. doi:10.1136/annrheumdis-2017-212127