IL-23 Peptides Open a New Question for Topical Delivery

A target with more than one delivery question

A $1.275 billion agreement has drawn attention to an oral peptide targeting the interleukin-23 receptor (IL-23R). Gilead agreed to acquire PepStar’s investigational oral program, including HCXT-2001, with the payment due at closing. The company is exploring its potential in inflammatory bowel disease; the agreement remains subject to closing conditions. ^[1]

Meanwhile, Dong-A ST has explored a topical formulation of a different IL-23R peptide, icotrokinra. Together, the two programs illustrate how the value of a target can extend across delivery forms, each with its own development work. ^{[1, 2]}

From an oral medicine to a topical formulation

Icotrokinra already has an approved oral use. In March 2026, the US Food and Drug Administration approved the tablet ICOTYDE for eligible adults and adolescents aged 12 or older, weighing at least 40 kg, with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. ^[3]

The peptide contains 13 amino acids and has a molecular weight of approximately 1,900 daltons. A topical formulation must address a different set of questions: whether enough intact drug can enter the skin, where it remains, and whether local exposure can support a useful effect. ^{[2, 4]}

Dong-A ST compared three formulation platforms after screening solubilizers. In a 72-hour experiment using excised human skin, the team measured permeation and drug retained in the tissue. A lead formulation then advanced to an IL-23-induced rat ear inflammation model. ^[2]

In that model, the increase in ear thickness from day 0 to day 4 was 0.047 mm with the selected formulation versus 0.195 mm in the IL-23 control. The conference abstract also reported lower expression of IL-17A, IL-17F and IL-22. This preclinical work connects formulation screening with a biological readout and provides a basis for further exploration of topical peptides. ^[2]

Turning a molecule into a treatment option

The opportunity for topical development lies in the relationship between the molecule and its intended site of action. Skin penetration alone is only one part of that relationship. Developers also need to understand drug retention in relevant tissue, the duration and variability of exposure, formulation stability, tolerability and systemic exposure.

For teams developing peptides, a topical formulation may open different use settings, including localized lesions. For delivery partners, molecule selection, distribution within skin and dosage form shape the next experiment. As more targeted peptides enter development, combinations of molecular and delivery capabilities may also create new opportunities for research collaboration.

Explore N1 Life’s delivery programs.

Sources

1. Gilead. Agreement to acquire the investigational oral IL-23R inhibitor program HCXT-2001. 2026.
2. Kim HS, et al. Development of a Topical Icotrokinra Formulation for the Treatment of Psoriasis. AAPS PharmSci 360, abstract M1230-03-15, 2026.
3. US Food and Drug Administration. Drug Trials Snapshots: ICOTYDE.
4. DailyMed. ICOTYDE prescribing information.
5. N1 Life. 13亿美元押注的IL‑23环肽，外用递送即将打开更大增长空间. WeChat, 2026-10-28.