TYK2 Selectivity And Allosteric Binding Set Zasocitinib Apart

“We are very lucky to be in dermatology treating psoriasis in this day and age. We have more than 13 biologics to treat. We have some oral treatments coming into the pipeline,” said Leon Kircik, MD, in a recent interview.

Kircik, a dermatologist, clinical professor of dermatology at the Icahn School of Medicine at Mount Sinai, medical director of Derm Research, PLLC and Physicians Skin Care, PLLC, and principal investigator for the LATITUDE PsO studies, recently discussed palmoplantar psoriasis data with zasocitinib (Takeda) presented at the 2026 American Academy of Dermatology (AAD) Innovation Academy.¹

Kircik reviewed sub-analysis data from the LATITUDE PsO 3001 (NCT06671483) and 3002 (NCT06671496) phase 3 trials in patients with moderate palmoplantar psoriasis. He addressed the allosteric binding mechanism of zasocitinib and safety findings from its phase 3 studies..^1,2

In a previous interview, Kircik discussed zasocitinib scalp psoriasis clearance rates.

Allosteric Binding Distinguishes Zasocitinib From Other JAK Inhibitors

Kircik explained TYK2 selectivity carries importance not only in hard-to-treat areas but across psoriasis treatment overall. Most JAK inhibitors rely on orthosteric inhibition at the ATP binding site, known as the JAK1 site, according to Kircik. Zasocitinib instead binds the pseudo domain, an allosteric regulatory site not competing directly with ATP binding, changing the domain's morphology.

"The allosteric binding makes this very unique for TYK2 versus zasocitinib, and clinically it reflects on the adverse event profile in a positive manner," Kircik said.

Kircik noted zasocitinib shows more than 1 million-fold greater binding selectivity for TYK2 compared with JAK1, JAK2 and JAK3. He described this selectivity, combined with allosteric rather than orthosteric binding, as central to the drug's distinct profile.

Safety Data Show No New Signals Through Week 24

Kircik pointed to safety findings comparing the placebo-controlled period at week 16 with data through week 24. No new safety signals emerged between the two timepoints, he said. Acne was the most common adverse event, consistent with expectations for TYK2 inhibitors.

"In dermatology, we know how to deal with acne. We know how to treat acne. We are not dealing with cancers, leukemias, lymphomas, or any other things out of our realm," Kircik said.

Kircik also cited nasopharyngitis, diarrhea, headaches, and nausea among adverse events commonly reported across studies. One death occurred in the zasocitinib arm, happening the day after baseline.

"This patient, unfortunately, the death happened the day after the baseline after taking the medicine, and it was not considered related to the study drug," Kircik said.

Zasocitinib Adds To A Growing Psoriasis Treatment Armamentarium

Kircik placed the phase 3 findings within a broader shift in psoriasis care. Dermatologists now have more than 13 biologics available, with additional oral treatments advancing through development. He contrasted current options with scalp psoriasis treatments used decades ago, including mixed tar, salicylic acid and topical steroids, calling such approaches malpractice by today's standards.

"We are very lucky to be in dermatology treating psoriasis at this day and age," Kircik concluded.

Zasocitinib's phase 3 efficacy and safety data mark a welcome addition to the treatment armamentarium, according to Kircik.

References

1. Takeda's zasocitinib demonstrates consistent, high rates of skin clearance across the body, including hard-to-treat and high-impact sites, in phase 3 psoriasis studies. News release. Takeda. July 16, 2026. Accessed August 10, 2026. https://www.takeda.com/newsroom/newsreleases/2026/zasocitinib-phase-3-psoriasis-skin-clearance/
2. Armstrong AW, et al. Zasocitinib, a once-daily oral TYK2 inhibitor, demonstrates efficacy at high impact sites in adults with moderate-to-severe plaque psoriasis: results from two randomized phase 3 trials (LATITUDE-PsO-3001 and 3002). Presented at: 2026 American Academy of Dermatology Innovation Academy; July 16, 2026; New York, NY.