Hidradenitis suppurativa promise sends Moonlake soaring
Strong mid-stage data seem to show sonelokimab, a Merck KGaA cast-off, beating bigger rivals.
Investors found few holes to pick in Moonlake Therapeutics’ hidradenitis suppurativa data this morning, with ballooning hopes for sonelokimab causing the developer’s valuation to surge 60% in early trade. One big question does remain, however: why did Merck KGaA let the asset go?
The German developer licensed out sonelokimab in 2021, a decision that it could come to rue should the project live up to Moonlake’s bullish projections. True, today’s topline data from the phase 2 Mira trial need proper scrutiny and confirming in further studies, but the project appears to be looking better than some big names in the autoinflammatory world: Abbvie’s Humira, UCB’s Bimzelx and Novartis’s Cosentyx.
Caution is always warranted when comparing across trials, though Moonlake’s claims are strengthened somewhat by the inclusion of a Humira arm in the phase 2 trial presented today, which supported sonelokimab’s superiority. Humira is the only biological agent approved for HS, while Novartis and UCB's drugs are heading to regulators.
HS is an autoinflammatory disease of the hair follicles, causing painful, recurring boils in areas of the body with sweat glands.
Moonlake focused its presentation on placebo-adjusted numbers, but sonelokimab also looks competitive against the absolute response rates reported by its rivals in phase 3. On HiSCR50, Bimzelx produced responses in the 45-59% range, Cosentyx 42-46% and Humira 42-59%, against 66% for 120mg of sonelokimab, Moonlake’s chosen phase 3 dose.
On HiSCR75, which Moonlake used as its primary endpoint and which it claims is a tougher measure, sonelokimab at 120mg produced a 43.3% response rate, for a p value of 0.0002 versus placebo, which also beat these agents on absolute terms.
Mira trial of sonelokimab: cross-trial comparison
It is worth pointing out that a higher 240mg dose of sonelokimab did not perform as well as the lower dose, a signal that would typically raise eyebrows. Moonlake execs brushed this off, saying the trial had proved the optimal dose to be 120mg, which is already being used in an ongoing psoriatic arthritis study.
Sonelokimab is a trispecific nanobody that hits IL-17A and F as well as albumin, a design that allows more effective tissue penetration than other molecules working in similar ways, the company claims.
Impressive results on measures that quantify changes in tunnels, nodules and abscesses show sonelokimab to be a “game changer”, it contended; the data suggest that after as little as 12 weeks' treatment the agent changes the morphology of the drainage tunnels that form in the skin of sufferers.
Mira also produced a statistically significant reduction, versus placebo, in patient reported outcomes including pain.
“This is not an incremental benefit, this is changing the game. We firmly believe we are now at the top of the heap,” Moonlake's chief executive, Jorge Santos da Silva, said on the call.
The Swiss group’s executives contend that Mira’s robust and “pivotal-like” design gives high confidence in the reproducibility of these data; at 234 subjects the trial was large for a phase 2, albeit around half the size of the pivotal trials run by its big pharma rivals.
The group is working on the assumption that two phase 3 studies will still be needed, although this has yet to be discussed with regulators; much of today’s share price rise could be investors betting that only one further trial might be required.
That would clearly be a huge boon for this small company, which today confirmed cash of around $64m, enough to last until the end of 2024. A pivotal programme consisting of two phase 3s would cost $200-250m, Moonlake executives estimate; whatever the regulators decide a fundraising is on the way. With a market cap now north of $2bn further funds should be securable.
Finally, spare a thought for Merck KGaA, which must be wondering whether it made a mistake to let this project go. It originally licensed sonelokimab from Ablynx back in 2008, and took it into the clinic in psoriasis in 2014; under the terms of the deal with Moonlake the German group is owed milestones of around $325m and low-mid-teen royalties. At end of 2022 it owned 25% of Moonlake's Class C ordinary shares, and 6.3% total voting power, according to Moonlake's most recent 10-K.
With Moonlake talking up the opportunities for sonelokimab's mechanism in a broad range of other conditions – data in psoriatic arthritis are due later this year – the prospect of buying it back just got a lot more expensive.