MoonLake Reports Positive Phase 2 results for Nanobody Rare Skin Condition

Rare Daily Staff

Swiss biotech MoonLake Immunotherapeutics reported positive top-line results from its global phase 2 MIRA trial evaluating the efficacy and safety of the nanobody sonelokimab in patients with rare and chronic skin condition moderate-to-severe hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a severely debilitating condition resulting in irreversible tissue destruction. HS manifests as painful inflammatory skin lesions, typically around the armpits, groin, and buttocks. Over time, uncontrolled and inadequately treated inflammation can result in irreversible tissue destruction and scarring. The disease affects 0.05–4.1 percent of the global population, with three times more females affected than males. Onset typically occurs in early adulthood and HS has a profound negative impact on quality of life, with a higher morbidity than other dermatologic conditions. There is increasing scientific evidence to support IL-17A- and IL-17F-mediated inflammation as a key driver of the pathogenesis of HS, with other identified risk factors including genetics, cigarette smoking, and obesity.

Sonelokimab is an experimental humanized nanobody that selectively binds with high affinity to IL-17A and IL-17F, thereby inhibiting the IL-17A/A, IL-17A/F, and IL-17F/F dimers. A third central domain binds to human albumin, facilitating further enrichment of sonelokimab at sites of inflammatory edema.

Nanobodies represent a new generation of antibody-derived targeted therapies. They consist of one or more domains based on the small antigen-binding variable regions of heavy-chain-only antibodies. Nanobodies have a number of potential advantages over traditional antibodies, including their small size, enhanced tissue penetration, resistance to temperature changes, ease of manufacturing, and their ability to be designed into multivalent therapeutic molecules with bespoke target combinations. The terms nanobody and nanobodies are trademarks of Ablynx, a Sanofi company.

The MIRA trial, which recruited 234 patients, is the first randomized, double-blind, placebo-controlled trial to use Hidradenitis Suppurativa Clinical Response (HiSCR) 75 as its primary endpoint, a higher measure of clinical response versus the HiSCR50 measure used in other clinical trials, therefore representing a landmark milestone in HS clinical development.

The trial met its primary endpoint with a significantly greater proportion of patients treated with both sonelokimab 120 mg and 240 mg achieving HiSCR75 compared to those on placebo at week 12. The results suggest that, as early as week 12, the nanobody sonelokimab, relative to placebo, the company said.

The safety profile of sonelokimab was consistent with previously reported studies with no new safety signals observed. Overall, sonelokimab continues to show a favorable safety profile, in line with the known profile of IL-17 inhibitors.

“As part of our efforts to elevate outcomes for patients, we set an ambitious goal for our Nanobody sonelokimab to ‘meet or beat’ the best results shown in pivotal-like trials of competitors,” said Jorge Santos da Silva, founder and CEO at MoonLake Immunotherapeutics . “We have achieved our ‘beat’ goal with the positive outcome of the phase 2 MIRA trial. In doing so, we have raised the bar for what can be accomplished for HS and these positive topline data provide us with even greater confidence as we look forward to our next steps and our aspiration to become a leader in the inflammation and immunology space.”

Photo: Jorge Santos da Silva, founder and CEO at MoonLake Immunotherapeutics