ESK-001: A Conversation with Jörn Drappa, MD, PhD, of Alumis on Breakthrough Data and the Future of Psoriasis Treatment

At the 2025 American Academy of Dermatology Annual Meeting in Orlando, Florida, Alumis Inc. presented promising late-breaker results from the open-label extension (OLE) phase 2 STRIDE clinical trial for ESK-001.¹

The oral therapy showed significant and sustained improvements in clinical outcomes for patients with moderate to severe plaque psoriasis, confirming positive clinical responses and enhanced quality of life for participants after 52 weeks of treatment.²

Jörn Drappa, MD, PhD, chief medical officer at Alumis, shared insights in an interview with Dermatology Times, emphasizing the drug's promising safety and efficacy profile, which sets it apart from current therapies.

Jörn Drappa, MD, PhD

ESK-001's Long-Term Efficacy and Safety in Psoriasis Treatment

ESK-001, an oral tyrosine kinase 2 (TYK2) inhibitor, has demonstrated consistent and increasing efficacy over the course of the trial, which spanned 52 weeks. Patients receiving 40 mg of ESK-001 twice daily showed sustained or increased improvements in clinical outcomes, including a significant percentage achieving a Psoriasis Area and Severity Index (PASI) of 90 (60%) and even PASI 100 (39%) at week 52.

"We have shown that the efficacy over time not only is sustained, but also increases," Drappa said. "The safety remains very benign. We have not seen, really, any safety signals. This gives us great optimism moving forward."

The most frequently-reported adverse events to date have been mild in nature, such as upper respiratory tract infections, nasopharyngitis, and headaches. Importantly, there were no unexpected findings, and the rate of serious adverse events remained low.

Differentiation in the Treatment Landscape

What sets ESK-001 apart from other therapies is its ability to not only improve clinical outcomes but also to significantly enhance patients’ quality of life. In the phase 2 OLE data, over 60% of patients reported no impact from psoriasis on their daily life, as evidenced by a Dermatology Life Quality Index (DLQI) score of 0 or 1.

"What matters to patients is how they feel and function in daily life. That is something we have measured in the long-term extension trial by using instruments such as an itch instrument and the quality of life instrument," Drappa said. "Over 60% of patients at week 52 have reported that there is really no impact anymore of psoriasis on their daily life and their functioning."

He continued, explaining the significance of these findings, "We believe that is highly relevant for patients, and in combination with the high degree of objective improvements in outcome measures, really leads to a very exciting and potentially leading clinical profile."

A Highly Selective TYK2 Inhibitor: A Key to ESK-001's Success

One of the key reasons ESK-001 stands out is its highly selective inhibition of TYK2, a crucial target in treating immune-mediated conditions like psoriasis. This selectivity allows the drug to deliver maximal inhibition while minimizing off-target effects.

"This is an exquisitely specific TYK2 inhibitor that really does not impact any other tyrosine kinases, or, for that matter, any other pathways," Drappa said. "What that allows is [the ability] to dose sufficiently high to completely inhibit TYK2 for the entire day, for the entire dose interval."

The high specificity of ESK-001 also allows for higher dosing without the adverse events seen with other TYK2 inhibitors, which at higher doses have resulted in issues like rashes or cytopenias.

"Among the TYK2 inhibitors to date, we are the only ones that have been able to dose high enough to achieve complete target inhibition without causing side effects," Drappa said.

Additionally, the drug’s pharmacokinetic and pharmacodynamic profiles are highly predictable, making it easier to dose appropriately without concerns about food interactions or drug-drug interactions. Drappa further elaborated on these aspects:

"These are very linear pharmacokinetics; these are very predictable pharmacodynamics. We have no drug-drug interactions. Importantly, there are no food effects, so you can take this with or without food."

Looking Ahead: Phase 3 Trials and Broader Impact

Looking forward to the upcoming phase 3 ONWARD trials, Drappa is optimistic about ESK-001’s potential to revolutionize psoriasis treatment.

"We hope to reproduce the outcomes we have seen in phase 2 in our ongoing phase 3 program," he shared.

The phase 3 studies, which are enrolling patients with moderate to severe psoriasis, are expected to yield results in the first quarter of 2026. If the phase 3 trials replicate the success seen in earlier stages, ESK-001 could provide a valuable alternative for patients with psoriasis who require systemic therapy but are not yet ready for biologics.¹

Drappa discussed how ESK-001 could change the way psoriasis is treated: "Currently, patients step through typically topical treatments for quite a while before they progress to systemic treatments such as biologics. I think we have the potential to be a step that allows early treatment with a safe oral molecule for patients with moderate to severe psoriasis."

Expanding the Potential: Beyond Psoriasis

While ESK-001’s results in psoriasis are promising, the drug’s potential reaches beyond this indication. Drappa pointed out that the same TYK2 inhibition may have benefits in other immune-mediated diseases, including systemic lupus erythematosus and cutaneous lupus.

"ESK-001 has brought applicability beyond psoriasis. We have currently an ongoing large phase 2b trial in lupus that will also read out next year," Drappa explained. "There’s a significant opportunity [in lupus], but also in other type one interferon-mediated diseases."

References

1. Late-breaking ESK-001 phase 2 OLE data presented at 2025 AAD Annual Meeting demonstrate robust clinical responses over 52-weeks in psoriasis. News release. Globe Newswire. March 8, 2025. Accessed March 24, 2025. https://www.globenewswire.com/news-release/2025/03/08/3039351/0/en/Late-Breaking-ESK-001-Phase-2-OLE-Data-Presented-at-2025-AAD-Annual-Meeting-Demonstrate-Robust-Clinical-Responses-Over-52-Weeks-in-Psoriasis.html
2. Late-breaking data at EADV of ESK-001, an oral TYK2 inhibitor for the treatment of psoriasis, demonstrate significant responses with sustained increases over 28 weeks in phase 2 OLE study. News release. Alumis, Inc. September 27, 2024. Accessed March 24, 2025. https://investors.alumis.com/news-releases/news-release-details/late-breaking-data-eadv-esk-001-oral-tyk2-inhibitor-treatment