Breaking the Skin Barrier: Dong-A ST's Topical Psoriasis Innovation

SEOUL, South Korea – October 26, 2026 — For decades, the holy grail of dermatological pharmacology has been the ability to deliver large, highly specific therapeutic molecules directly through the skin. The stratum corneum, the skin's outermost layer, is an evolutionary marvel designed to keep foreign substances out, making it notoriously difficult for anything larger than a small molecule to penetrate. This biological fortress has historically forced drug developers to rely on systemic delivery methods—like oral pills or subcutaneous injections—for advanced biologics and peptides, often bringing a host of unwanted systemic side effects.

However, the landscape of dermatological treatment may be on the verge of a significant shift. At the American Association of Pharmaceutical Scientists (AAPS) PharmSci 360 2026 conference in New Orleans this week, South Korean pharmaceutical company Dong-A ST presented compelling preclinical data demonstrating that they have successfully engineered a topical formulation of icotrokinra.

Icotrokinra, recently approved by the U.S. Food and Drug Administration (FDA) in March 2026 as an oral therapy under the brand name Icotyde, is a first-in-class macrocyclic peptide that selectively antagonizes the interleukin-23 (IL-23) receptor. By translating this complex molecule into a localized cream or ointment, Dong-A ST is not just reformulating a drug; they are attempting to solve one of the most persistent biophysical challenges in drug delivery, potentially opening up a massive new frontier in the multi-billion-dollar psoriasis market.

Engineering the Impossible: Delivering Macrocyclic Peptides

To understand the magnitude of Dong-A ST's preclinical findings, one must appreciate the sheer size and complexity of macrocyclic peptides. These molecules bridge the gap between traditional small molecule drugs and massive biologics. While they offer the high target specificity of antibodies, their size, hydrophilicity, and susceptibility to enzymatic degradation typically render them entirely unsuitable for transdermal delivery.

During the AAPS conference, Hae-sun Kim, Principal Scientist on Dong-A ST’s Drug Delivery System (DDS) team, unveiled a scientific poster detailing the company's breakthrough. Titled “Development of a Topical Icotrokinra Formulation for the Treatment of Psoriasis,” the presentation highlighted how the firm leveraged its proprietary DDS platform to overcome these inherent molecular limitations.

The preclinical ex vivo evaluations presented by Kim demonstrated that the optimized formulation successfully penetrated the skin barrier and, crucially, retained the active icotrokinra within the targeted dermal layers. This retention is vital; a successful topical therapeutic must not only breach the surface but also linger in the epidermal and dermal tissues long enough to exert its pharmacological effect without simply washing into the systemic bloodstream.

"Achieving localized delivery of a macrocyclic peptide without compromising its structural integrity is a monumental formulation achievement," noted an independent formulation scientist reviewing the data. "If these ex vivo retention profiles translate into human clinical trials, it represents a paradigm shift in how we view the druggable space for topical dermatology."

Localized Precision: Targeting the IL-23 Pathway

The clinical implications of a topical IL-23 receptor antagonist are profound. The IL-23 signaling pathway is a well-established master regulator in the pathogenesis of psoriasis, responsible for driving the downstream production of pro-inflammatory cytokines that cause the characteristic red, scaly plaques of the disease.

Currently, the most effective IL-23 inhibitors are injectable biologics. While highly efficacious, they suppress the immune system systemically, leaving patients vulnerable to infections and requiring regular clinical monitoring. The recent FDA approval of oral icotrokinra provided a more convenient systemic option, but the fundamental issue of whole-body exposure remains.

Dong-A ST's animal model data addresses this directly. In induced skin inflammation models, the topical formulation significantly attenuated inflammatory responses. More specifically, it drastically reduced the gene expression of interleukin-17A (IL-17A), interleukin-17F (IL-17F), and interleukin-22 (IL-22). These are the key downstream culprits in the psoriatic inflammatory cascade.

By shutting down the IL-23 receptor right at the site of the plaque, a topical formulation offers the tantalizing prospect of biologic-like efficacy with the safety profile of a localized cream. For patients dealing with mild-to-moderate psoriasis, or those hesitant to initiate systemic immunosuppressive therapy, a targeted peptide could offer a life-altering alternative to traditional corticosteroids, which carry risks of skin thinning and rebound flares with long-term use.

The Next Non-Steroidal Blockbuster?

From a market perspective, Dong-A ST is aiming at a rapidly expanding and highly lucrative target. The commercial appetite for non-steroidal topical treatments for inflammatory skin diseases has exploded in recent years, driven by patient and prescriber fatigue over the limitations of topical steroids.

The current market leaders illustrate the sheer velocity of this segment. Incyte’s Opzelura, a topical JAK inhibitor, generated an impressive $678 million in net product revenue in 2025, with projections estimating it will cross the $1 billion blockbuster threshold by the end of 2026. Similarly, Arcutis Biotherapeutics’ Zoryve, a topical PDE4 inhibitor, saw its sales surge by 123% in 2025 to reach $372.1 million. Even Organon’s Vtama, an aryl hydrocarbon receptor agonist, has carved out a solid niche, commanding over $1,500 per tube without insurance.

However, none of these existing non-steroidal topicals target the IL-23 pathway, which is widely considered the most direct and effective intervention point for plaque psoriasis. Bank of America has already projected that the oral formulation of icotrokinra could achieve peak annual sales of $4.5 billion. If Dong-A ST can successfully bring a topical version to market, it could easily disrupt the current hierarchy dominated by JAK and PDE4 inhibitors, capturing a significant share of the multi-billion-dollar dermatological space.

Navigating the Intellectual Property and Regulatory Path

Despite the immense promise of the preclinical data, the road from AAPS poster to pharmacy shelves is fraught with regulatory and legal complexities. The most immediate hurdle for Dong-A ST is the intellectual property landscape surrounding icotrokinra.

The molecule was jointly discovered by Protagonist Therapeutics and Johnson & Johnson (J&J), with J&J retaining exclusive worldwide rights to develop and commercialize the drug across all indications. While Dong-A ST has demonstrated the technical feasibility of formulating the peptide for topical use utilizing its proprietary DDS platform, commercializing this innovation will almost certainly require a complex licensing agreement or strategic partnership with J&J.

Industry insiders suggest that J&J, which is heavily invested in maximizing the lifecycle and franchise value of icotrokinra, would be highly motivated to explore a topical application. A partnership would allow J&J to dominate both the systemic and localized psoriasis markets simultaneously, leveraging Dong-A ST's formulation expertise.

Beyond the boardroom, rigorous clinical validation awaits. The preclinical success in ex vivo human skin and animal models must now be replicated in human subjects. Dong-A ST has acknowledged that further studies are required to establish clinical safety and efficacy, indicating that an Investigational New Drug (IND) application has not yet been filed. Future Phase 1 and Phase 2 trials will need to meticulously track not just skin clearance metrics—such as PASI score reductions and Investigator's Global Assessment (IGA) improvements—but also rigorously monitor for any unintended systemic absorption of the peptide.

The translation of a macrocyclic peptide from a systemic therapy into a localized topical treatment is no small feat. It requires a convergence of advanced formulation science, strategic corporate maneuvering, and flawless clinical execution. Yet, the data presented in New Orleans this week provides a compelling glimpse into the future of dermatology. By pushing the boundaries of what is biophysically possible in drug delivery, developers are moving closer to a reality where the most powerful targeted therapies can be applied exactly where they are needed, and nowhere else.