MoonLake Immunotherapeutics Reports Positive Sonelokimab Phase 2 Results in Axial Spondyloarthritis

Switzerland-based MoonLake Immunotherapeutics announced positive topline results from the S-OLARIS Phase 2 trial evaluating sonelokimab in axial spondyloarthritis, with 81% of treated patients achieving an ASAS40 response at Week 12. Sonelokimab is a humanized Nanobody® — a small-format biologic derived from camelid heavy-chain antibodies — that inhibits both IL-17A and IL-17F by neutralizing the IL-17A/A, IL-17A/F, and IL-17F/F dimers implicated in inflammatory and osteoproliferative pathways. The data mark the fifth indication in which MoonLake has generated positive clinical results for sonelokimab across Phase 2 and Phase 3 programs, and arrive as the company prepares for a BLA submission in hidradenitis suppurativa later this year.

Trial Specifics: The S-OLARIS Axial Spondyloarthritis Study

The S-OLARIS trial (M1095-axSpA-201) is a Phase 2, single-arm, biomarker-controlled study that enrolled 26 adult patients with active axial spondyloarthritis, including both radiographic (ankylosing spondylitis) and non-radiographic subtypes. Patients received sonelokimab 60 mg administered subcutaneously. Rather than employing a placebo comparator, the trial used an integrated panel of imaging and molecular biomarkers as internal controls for treatment effect — a design MoonLake described as innovative relative to conventional axSpA trial architectures.

The primary endpoint was the change from baseline in 18F-NaF SUVmax signal at Week 12 in the sacroiliac joints and spine, measured by PET. This tracer quantifies osteoblast activity, the cellular process underlying pathologic new bone formation that drives irreversible spinal fusion in axSpA. The trial reported a statistically significant reduction in this PET signal, which the company characterized as evidence of reduced osteoblast activity in affected joints.

Clinical endpoints reinforced the imaging findings. Using modified non-responder imputation, 81% of patients achieved ASAS40 — a composite measure requiring at least 40% improvement across domains of pain, function, inflammation, and patient global assessment, and the primary endpoint used in recent axSpA registration programs. More than 80% of patients also met the threshold for clinically important improvement on the ASDAS-CRP score, and SPARCC MRI scores in the sacroiliac joint confirmed reductions in inflammation and bone injury by Week 12. Peripheral blood and tissue biopsy analyses showed rapid and sustained suppression of immune pathways linked to inflammation and ossification.

The safety profile was consistent with previous sonelokimab trials across indications, and no new signals were detected. Granular adverse event data were not disclosed in the topline announcement.

MoonLake's Chief Scientific Officer, Kristian Reich, stated that the complementary clinical, imaging, and biomarker data "confirm our hypothesis of SLK's ability to access deeper tissue, which is essential to optimally control this chronic rheumatological condition and prevent irreversible mobility restriction." The company held an Investor Day the following day, at which management discussed the axSpA data alongside updates on the HS BLA strategy, interim Phase 3 HS data beyond Week 16, and the MLTX financial results for 2025. MoonLake ended Q4 2025 with USD 394 million in cash, cash equivalents, and short-term marketable debt securities, and reported an amended debt facility with Hercules Capital providing up to USD 400 million in non-dilutive funding. No specific Phase 3 axSpA trial has been announced, though the company listed a planned Phase 3 program in palmoplantar pustulosis and upcoming Phase 3 readouts in psoriatic arthritis among its 2026 catalysts.

Research Context: IL-17 Dual Inhibition and the axSpA Landscape

Sonelokimab is a ~40 kDa trivalent Nanobody® composed of three VHH domains connected by flexible linkers. Two domains bind IL-17A and IL-17F with high affinity, while a third binds human serum albumin, extending the molecule's half-life and — according to MoonLake — facilitating enrichment at sites of inflammatory edema. The small molecular size relative to conventional monoclonal antibodies is proposed to enable deeper tissue penetration, a property the company considers relevant to reaching the entheseal and intra-osseous compartments where axSpA pathology concentrates.

The rationale for targeting both IL-17A and IL-17F in spondyloarthritis rests on evidence that both cytokines contribute to the inflammatory and tissue-remodeling programs that characterize the disease. Elevated IL-17 levels have been documented in the blood and synovial fluid of axSpA patients, and the IL-23/IL-17 axis is considered central to entheseal inflammation and downstream osteoproliferation. While IL-17A-selective antibodies have established efficacy in axSpA, the hypothesis that broader dimer coverage — neutralizing IL-17F/F and IL-17A/F in addition to IL-17A/A — could yield enhanced pathway suppression has driven interest in dual inhibitors.

Sonelokimab originated at Ablynx, the Belgian Nanobody® company that was itself a spinout from the Vrije Universiteit Brussel. Merck KGaA held development rights through a licensing partnership with Ablynx and conducted early clinical work before transferring global rights to MoonLake Immunotherapeutics in 2021, when the company was formed around the asset. Sanofi's 2018 acquisition of Ablynx transferred platform ownership but did not affect the sonelokimab license. MoonLake (Nasdaq: MLTX) now holds full worldwide development and commercialization rights.

Sonelokimab remains unapproved globally. No US FDA designations — including Fast Track, Breakthrough Therapy, or Orphan Drug — have been publicly disclosed for the axSpA indication. The company's most advanced program is in hidradenitis suppurativa, where Phase 3 VELA trial data were reported in September 2025 and a BLA submission is planned for H2 2026.

Axial spondyloarthritis affects an estimated 0.5% to 1.5% of the global population and typically presents in young adults with chronic inflammatory back pain. Progressive disease can lead to pathologic bone formation and joint fusion, causing irreversible restriction of spinal mobility. Current biologic therapies — TNF inhibitors and IL-17A inhibitors — provide symptomatic relief and reduce MRI-detected inflammation, but evidence of disease modification, defined as prevention of structural progression, remains limited and contested. The S-OLARIS PET data suggesting reduced osteoblast activity are therefore of particular mechanistic interest, though the small sample size and absence of a control arm constrain the strength of causal inference.

The axSpA treatment landscape already includes several approved and late-stage IL-17 pathway agents. Key competitors include:

• UCB's bimekizumab (Bimzelx), a dual IL-17A/IL-17F monoclonal antibody that has completed Phase III development in axSpA with 52-week data from the BE MOBILE 1 and BE MOBILE 2 trials demonstrating sustained ASAS40 responses, and which has received regulatory approvals in multiple markets for ankylosing spondylitis and non-radiographic axSpA. Bimekizumab is the most direct mechanistic comparator to sonelokimab, sharing dual IL-17A/F inhibition but using a conventional monoclonal antibody format rather than a Nanobody®.
• Novartis's secukinumab (Cosentyx), an IL-17A-selective monoclonal antibody approved for both radiographic and non-radiographic axSpA, with extensive Phase III and long-term follow-up data across the MEASURE and PREVENT trial programs.
• Eli Lilly's ixekizumab (Taltz), another IL-17A-selective monoclonal antibody approved for axSpA, with Phase III data from the COAST-V and COAST-W programs in both biologic-naïve and TNF-inadequate responder populations.
• AstraZeneca/Viatris's brodalumab (Siliq), targeting the IL-17 receptor A subunit (IL-17RA), which has reported Phase III results in axSpA though its development trajectory in this indication has been less prominent than the IL-17A and IL-17A/F ligand-targeting agents.
• Biocad's netakimab, an IL-17A inhibitor developed primarily for the Russian market, with Phase III ASTERA trial data reported in ankylosing spondylitis.

The differentiation MoonLake claims for sonelokimab relative to these agents centers on the Nanobody® format's smaller size and proposed capacity for deeper tissue penetration — attributes that the S-OLARIS imaging data are intended to support. Whether this translates into clinically meaningful advantages over bimekizumab, which shares the same target profile but uses a full-size antibody, or over the established IL-17A-selective agents, will require larger controlled trials with head-to-head or structural progression endpoints. The 81% ASAS40 rate at Week 12 in a 26-patient open-label study, while numerically high, cannot be directly compared with placebo-controlled Phase III response rates from competing programs without appropriate trial design adjustments.

MoonLake's near-term pipeline catalysts are concentrated in other indications: 52-week HS data, Phase 3 PsA readouts from IZAR-1 and IZAR-2, and the HS BLA submission are all expected through H2 2026. The path from S-OLARIS Phase 2 to a potential axSpA registration program has not been specified, and the company's prioritization of this indication relative to its HS and PsA programs will be a key strategic question as MoonLake manages its cash runway, which it projects will extend into the second half of 2027.

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