Shares of MoonLake Immunotherapeutics closed the day lower by 90% to $6.25 per share on Monday, September 29th, as it had reported results from two phase 3 studies from its VELA program. Both of these late-stage studies are known as VELA-1 and VELA-2, and both encompass the evaluation of the IL-17 inhibitor sonelokimab for the treatment of patients with hidradenitis suppurativa (HS). Both of these trials were identical and recruited adult patients who had moderate-to-severe disease. The primary endpoint for both was HiSCR75, comparing that of drug versus placebo. This was a high bar that the company had set, and it signifies the percentage of patients who achieve a greater than or equal to 75% reduction in total abscesses and inflammatory nodules from baseline.
The patients in both of these phase 3 VELA studies were treated and assessed based on this primary efficacy endpoint. The VELA-1 phase 3 study easily met this bar, achieving a statistically significant response rate of 34.8% using 120 mg of sonelokimab. The problem stemmed from the other phase 3 VELA-2 study, whereby an HiSCR75 response of 35.9% was obtained. The thing is that VELA-2, as a trial, ran into a problem where the placebo rate was enormously high at 25.6%. With such a higher-than-expected placebo rate in place, this trial failed to achieve statistical significance. This is what caused the stock price to trade significantly lower.
Where MoonLake might have some momentum is in terms of two key items. One item being that the combined pooled data across both late-stage VELA studies showed the drug to achieve statistical significance with all secondary efficacy endpoints. This is good in that it might allow it to possibly use another endpoint for regulatory approval, although something like that has to be discussed with regulators. The second item deals with the pooled analysis data just noted, which is that across both trials all primary and secondary endpoints were achieved, with a statistically significant value with a p-value of p<0.001.
The thing is that the company set a higher bar, and it may or may not have backfired on it. The reason why is because typically, these studies use HiSCR50 as the primary endpoint. The reason why MoonLake chose to go with the higher bar of HiSCR75 is because of the data it obtained in the prior phase 2 MIRA trial (M1095-HS-201). It was noted that in a randomized phase 2 study, HS patients given 120 mg of sonelokimab achieved a 29-point difference over placebo on the HiSCR75 primary endpoint over a 12-week period, with a p-value of p=0.0002. Headlines were made then because it was the first time that a drug was able to achieve this specific primary endpoint measure for these patients.
This primary endpoint was yet again achieved in the phase 3 VELA-1 study, but not the VELA-2 one, and that is where the entire issue lies. Despite the primary endpoint not being met in VELA-2, all is not entirely lost. That’s because the company is setting forth to show regulators this interim data to obtain feedback. This is going to be crucial for it because based on the totality of the data obtained thus far in MIRA and VELA studies, it is possible that the FDA and other regulators might be lenient with allowing a regulatory application to be filed based on this interim data. For now, the company continues on, expecting to release 52-week data from both of the VELA studies of sonolekimab targeting these HS patients in the second quarter of 2026.
Besides the potential to obtain positive feedback for regulators for a BLA or regulatory submission of sonelokimab for the treatment of patients with HS, the company has a host of other indications it is in the process of evaluating the use of this drug for. These other indications are axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Along with another inflammatory disorder known as palmoplantar pustulosis (PPP), being explored in the phase 2 LEDA study. The importance of this is that it may provide the company with another inflection point that may or may not allow for the stock price to recover. It expects to release results from this mid-stage trial treating these patients with this disorder in the fourth quarter of 2025.
PPP is a disorder characterized as a chronic inflammatory skin disorder whereby pustules form on the soles or palms of a patient. These pustules are filled with neutrophils, and it is due to the inflammation caused by this disorder. In essence, the higher the neutrophil levels that someone has, the more indicative of disease presence being noted. It is not fully understood what triggers this disease, but T-cells and cytokines are said to play a role in triggering the immune cascade. What sets apart sonelokimab compared to other IL-17 inhibitor drugs of the same class is that it has three VHH domains, which then allow it to target and bind to two cytokines, IL-17A and IL-17F.
The importance of this is then allowing the inhibition of naturally occurring dimers of IL-17A/A, IL‑17A/F, and IL-17F/F, which play a role in driving inflammation seen in PPP. The development of this nanobody is further being investigated in several other indications. Beyond the scope of the release of data from the phase 2 LEDA study in the fourth quarter of 2025, results from the phase 2 S-OLARIS trial in axSpA and the phase 3 IZAR trials in PsA are expected in the first quarter of 2026 and first half of 2026, respectively.
Another point of possible redemption for the HS treamtent program would be the phase 3 VELA-TEEN study, which is using sonelokimab to treat adolescents with HS. Trial data from this late-stage study program is expected in the first half of 2026. It remains to be seen if MoonLake obtains clearance from the FDA to be able to file a BLA for potential approval of its IL-17 inhibitor for the treatment of adult HS patients, but it definitely has a considerable amount of data in place to state its case.