Alumis' TYK2 Inhibitor Advances in Psoriasis Trial Post Series C

Alumis recently announced positive findings from its Phase II STRIDE study, which indicates that the company's experimental TYK2 inhibitor, ESK-001, is effective in reducing the severity of lesions in individuals suffering from moderate to severe plaque psoriasis. The data was unveiled at a special session during the annual gathering of the American Academy of Dermatology and revealed that all dosages and administration schedules of ESK-001 led to a significant increase in the number of patients who achieved a 75% improvement on the Psoriasis Area and Severity Index (PASI), a standard metric for assessing psoriasis severity.

By the 12th week of the study, 64.1% of participants who received a 40-mg dose twice daily reached the PASI-75 milestone. Additionally, 56.4% of those who took a 20-mg dose twice daily or a 40-mg dose once daily also achieved the same outcome. These results were markedly superior to the placebo group where no one reached the PASI-75 threshold. Even the lowest dosage of 10-mg once daily showed a significantly higher rate of PASI-75 improvement compared to the placebo.

Alumis' Chief Medical Officer, Jörn Drappa, commented that the results are indicative of ESK-001's potential to become a leading treatment for psoriasis, highlighting that patients exhibited substantial clinical improvement by week 12, which continued to progress over time.

The company is now gearing up to move ESK-001 into Phase III trials, aiming to introduce it as an oral medication that offers superior efficacy compared to existing treatments, according to Alumis CEO Martin Babler. The drug candidate is also being considered for other immune-mediated diseases.

ESK-001 is an orally administered, highly selective allosteric inhibitor of the TYK2 protein, which works by reducing the signaling through IL-12, IL-13, and interferon-α receptors, thus moderating the body's immune and inflammatory reactions. In the STRIDE study, this mechanism also enabled ESK-001 to achieve important secondary endpoints. At the highest dosage—40-mg twice daily—38.5% of the participants achieved PASI-90, and 15.4% reached PASI-100, signifying a complete resolution of psoriasis.

In terms of safety, ESK-001 was generally well-tolerated with no serious adverse events related to the treatment. The rate of participants withdrawing from the study due to side effects was minimal, and no toxicities associated with JAK inhibition were observed.

The open-label extension phase of STRIDE, which continued to monitor patients for up to 16 weeks, also demonstrated that the responses to the PASI endpoints increased further and that ESK-001 remained well-tolerated.

This announcement follows Alumis' successful completion of a $259 million Series C funding round, which will support the advancement of ESK-001 into the later stages of development. The drug candidate is set to compete with Bristol Myers Squibb's Sotyktu, a TYK2 inhibitor that received FDA approval in September 2022 for treating moderate-to-severe plaque psoriasis.