• First placebo-controlled randomized trial in active psoriatic arthritis (PsA) using a Nanobody^® to report positive topline results in support of potential best-in-class profile
• Primary endpoint ACR50 met with up to 47% (p<0.01 versus placebo) of patients on sonelokimab achieving ACR50 as early as week 12
• All key secondary endpoints met including up to 77% (p<0.001 versus placebo) of patients on sonelokimab achieving PASI90 as early as week 12
• Other secondary endpoints also reached statistical significance at week 12, including endpoints focused on deep tissue inflammation, Minimal Disease Activity (MDA) and patient reported outcomes
• High threshold outcomes, including ACR70 and PASI100, continue to improve beyond week 12, consistent with previous studies of sonelokimab
• Discontinuation rate below 4% and safety results of sonelokimab consistent with previously reported studies with no new safety signals

The ARGO trial (M1095-PSA-201), which enrolled 207 patients, met its primary endpoint with a statistically significant greater proportion of patients treated with either sonelokimab 60mg or 120mg (with induction) achieving an American College of Rheumatology (ACR) 50 response compared to those on placebo at
week 12. Specifically, for the 60mg and 120mg doses with induction, respectively, 46% and 47% of patients treated with sonelokimab achieved ACR50 (p<0.01 versus placebo); 78% and 72% of patients achieved ACR20; and 29% and 26% achieved ACR70. The primary analyses were based on the most stringent type of analysis for such trials, intention-to-treat with non-responder imputation (ITT-NRI). As expected, the 60mg dose without induction did not reach statistical significance, confirming the 60mg and 120mg with induction as the potential dose regimens to carry forward into Phase 3.

All key secondary endpoints were met for the 60mg and 120mg doses with induction. The key secondary endpoint Psoriasis Area and Severity Index (PASI) 90 was met for all doses with induction; 77% of patients responding at week 12 to the 60mg dose (ITT-NRI, p<0.001 versus placebo). For this dose, 58% of patients achieved complete skin clearance (PASI100) at week 12. PASI responses across dose arms were consistent with the previously reported Phase 2b data of sonelokimab in moderate-to-severe plaque-type psoriasis, with the 120mg dose achieving the highest responses for PASI100 (close to 60% of patients at week 12, ITT-NRI) in patients with more severe skin lesions (PASI score ≥ 10 at baseline).

Other clinically relevant secondary endpoints, such as Minimal Disease Activity (MDA), the modified Nail Psoriasis Severity Index (mNAPSI), the Leeds Enthesitis Index (LEI) and the patient self-reported Psoriatic Arthritis Impact of Disease (PsAID-12), each show promising levels of response at week 12.

Jorge Santos da Silva, PhD, Founder and Chief Executive Officer at MoonLake, said: “As part of our efforts to elevate outcomes for patients, we set ambitious goals for our Nanobody^® sonelokimab. ARGO is MoonLake’s third Phase 2 trial and the first trial in psoriatic arthritis using a Nanobody^® to report positive topline results, setting another landmark milestone. Again, we met the objectives we set out for ourselves, in this case for PsA. As with our hidradenitis suppurativa program, the preparation of our Phase 3 program in PsA is rapidly advancing and expected timing of end-of-Phase 2 regulatory meetings will be announced in due course.”

Adalimumab was used as an active reference to validate responses across arms (not powered for statistical comparisons to active treatment). Sonelokimab 60mg and 120mg (with induction) numerically outperformed adalimumab on the primary endpoint and all key secondary endpoints, with the observed deltas further supporting the potential for sonelokimab as a future leading therapy.

The patient discontinuation rate in the ARGO trial was low at week 12 (less than 4%), similar to what was observed in previous trials of sonelokimab in psoriasis and hidradenitis suppurativa. The safety profile of sonelokimab in ARGO was consistent with previously reported studies with no new safety signals. Specifically, oral candidiasis was observed in less than 2% of patients on sonelokimab, with no case leading to discontinuation. No cases of inflammatory bowel disease (IBD), major adverse cardiovascular events (MACE) or suicidal ideation and behavior (SI/B) were observed. Overall, sonelokimab continues to show a favorable safety profile. Across the sonelokimab clinical program to date, the company has not seen any signal of SI/B or liver enzyme elevations related to sonelokimab treatment.

The results suggest that, as early as week 12, the Nanobody^® sonelokimab reaches levels of clinical response at or above those seen with other therapies tested in similarly stringent trials. The high performance of sonelokimab and its favorable safety profile continue to support the potential of using a smaller biologic with albumin-binding capacity to inhibit IL-17A and IL-17F for the treatment of inflammatory diseases.

Kristian Reich, MD, PhD, Founder and Chief Scientific Officer at MoonLake, commented: “The positive topline results from the pivotal-like ARGO trial establish the Nanobody^® sonelokimab as an innovative potential treatment in another chronic inflammatory disease, psoriatic arthritis. Importantly, the results confirm our expectations in terms of dosing, clinical responses and safety findings. We believe that we have elevated the therapeutic bar by reaching important clinical outcomes at week 12. The data also support sonelokimab’s unique molecule characteristics and mode of action to effectively inhibit IL-17F in addition to IL-17A in deep tissue inflammation. The positive outcome of the ARGO trial would not have been possible without the support and participation of the patients and investigators to whom we are grateful.”

Joseph F. Merola, MD, MMSc, Professor of Dermatology, Medicine and Rheumatology, Distinguished Chair of Dermatology at UT Southwestern Medical Center added: “Psoriatic arthritis is a chronic, inflammatory, recurrent, and debilitating multidomain disease that has profound and wide-ranging impacts across many aspects of patients’ lives. As a physician, I see tremendous need for new treatment options for people living with PsA, particularly for therapies that reach high thresholds of response (e.g., ACR70, PASI100) and that simultaneously improve the disease domains that matter most for patients. The positive high clinical responses across joint and skin endpoints and stringent composite measures such as minimal disease activity observed with sonelokimab as early as week 12 in the Phase 2 ARGO trial are encouraging, demonstrating its promise as a potential future treatment option.”