Bispecific and Trispecific Antibodies in Atopic Dermatitis, With Christopher Bunick, MD, PhD

In a recent review, titled ‘Bispecific and trispecific antibodies in atopic dermatitis: a review of the emerging clinical pipeline,’ Christopher G. Bunick, MD, PhD, and colleagues highlight a growing therapeutic gap in atopic dermatitis, emphasizing that many patients treated with current monospecific biologics fail to achieve optimal disease control.1,2

Bunick, known for his role at the Yale School of Medicine, spoke about his team’s work in an interview with HCPLive, noting atopic dermatitis is not driven by a single cytokine pathway, but rather a complex network, including interleukin (IL)-4, IL-13, IL-31, thymic stromal lymphopoietin (TSLP), interferon gamma, IL-22, and IL-17. This contributes to significant clinical and molecular heterogeneity and this complexity, Bunick et al argue, necessitates a shift toward multi-targeted approaches.

“I felt that this was a much needed topic to cover, because the innovation in atopic dermatitis is exploding,” Bunick expressed. “In particularly there's a lot of innovation around multi targeted agents.”

His team’s review outlines a rapidly expanding pipeline of bispecific and trispecific antibodies designed to simultaneously inhibit multiple inflammatory and neuroimmune pathways. Bunick and coauthors detailed how such next-generation biologics are designed to improve upon current medications by providing patients with more sustained skin clearance, better control of pruritus, and potentially longer dosing intervals.

They also reviewed advances in antibody engineering, including half-life extension technologies potentially enabling dosing intervals as infrequent as every 3 - 6 months, as well as Fc-region modifications to optimize safety and immune effects. Overall, the team positions multi-specific biologics as a promising strategy.

In his interview, Bunick expanded on these data, first acknowledging his co-authors’ contributions and noting that the review was developed in response to a surge of innovation in the atopic dermatitis treatment landscape. He emphasized that the central unmet need remains the inability of many patients to reach minimal disease activity with existing therapies, which typically target a single cytokine or receptor.

Bunick explained that this limitation stems directly from the heterogeneous biology of atopic dermatitis, where multiple cytokines and pathways drive both inflammation and symptom burden. While current agents such as IL-4/IL-13 or IL-31 inhibitors provide benefit, they do not fully address the breadth of disease drivers. As a result, emerging bispecific and trispecific therapies are being designed to simultaneously target two or more pathways to achieve more comprehensive disease control.

Bunick also noted the importance of mechanistic insights connecting immune signaling and neurobiology. Increasing evidence shows that cytokine receptors are expressed not only on keratinocytes and immune cells but also on sensory neurons, directly influencing itch. According to Bunick, effective treatment of atopic dermatitis will require addressing both inflammatory pathways and neuroimmune itch signaling. Such a dual-targeting approach is a key rationale behind many pipeline agents, especially those incorporating IL-31 or TSLP inhibition.

For any additional information, view Bunick’s interview segment posted above.

Bunick has reported receiving consultant fees or serving as an investigator for AbbVie, Incyte, LEO Pharma and Pfizer.

References

1. Amid-Toby G, Alani O and Bunick CG (2026) Bispecific and trispecific antibodies in atopic dermatitis: a review of the emerging clinical pipeline. Front. Drug Discov. 6:1766021. doi: 10.3389/fddsv.2026.1766021.

2. EichenfieldL.GradaA.KnappK.MunozB.CrawfordJ.SilverbergJ. (2024). Persistent inadequate disease control and therapeutic inertia in moderate-to-severe atopic dermatitis: a 12-month longitudinal analysis of real-world outcomes from the TARGET-DERM AD registry. SKIN J. Cutan. Med.8 (6), s462. 10.25251/skin.8.supp.462.