Evidence for OX40-OX40L Axis Inhibition for Atopic Dermatitis, with Christopher Bunick, MD, PhD

At the 2025 Revolutionizing Atopic Dermatitis (RAD) Conference in Nashville, Tennessee, a range of presentations were given by leaders in the dermatology field on topics related to the treatment of atopic dermatitis.

One such talk, titled ‘Assessing the Evidence for OX40-OX40L Axis Inhibition for the Treatment of Atopic Dermatitis’ was presented by Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale School of Medicine.

OX40 is a protein that is on the surface of activated T cells, playing a part in atopic dermatitis via the promotion of inflammation as well as T cell activation. The approach discussed by Bunick involved the targeting of the OX40 pathway using therapeutics such as rocatinlimab or amlitelimab.

Bunick spoke about some of the most notable takeaways from his presentation in a recent Q&A interview by HCPLive. The contents of his discussion are as follows:

HCPLive: You just gave a presentation about OX40 and OX40-ligand (OX-40L)-targeting biologics, a new class of therapeutics coming into the atopic dermatitis space. What were some of the takeaways?

Bunick: First, I gave a big overview of where these therapeutics stand in the treatment algorithm. For example, current mono-targeted biologics are sort of midstream in the signaling pathway, whereas JAK inhibitors are downstream. OX40 and OX40-ligand targeted biologics are working upstream at either the antigen-presenting cell or at the activated T cell to stop cytokine production. All the different cytokines that are involved in atopic dermatitis, particularly that heterogeneity that we know drives atopic dermatitis.

That being said, stopping cytokines from that interaction between the antigen-presenting cell and the activated T cell isn't all that these targeted biologics of the OX40 and OX40 ligand system can do. They can also increase Treg cells and hopefully decrease memory T cells that may be involved in the persistence in reactivation of atopic dermatitis flares.

HCPLive: What were some of the other highlights of your session on OX40 and OX40L axis inhibition for atopic dermatitis?

Bunick: I then talked about some of the structural biology analysis that my research lab has done, looking at the mechanism of action of OX40 and OX40 ligand targeting biologics, dissecting out how the epitopes for therapies like amlitelimab versus rocatinlimab versus telazorlimab, and how they are molecularly different. Lastly, I walked the audience through the phase 2 and phase 3 data for amlitelimab and rocatinlimab, particularly focusing on the phase 3 data of rocatinlimab and the phase 2b data of amlitelimab.

I talked about the efficacy of these therapies and their ability to achieve reduction in EASI scores from baseline, their ability to achieve IGA 0 or 1, and their ability to achieve EASI-75. I talked about all of these efficacy measures throughout not just 16 or 24 weeks, but out to 52 weeks, as well as looked at the safety data showing that these therapies, based on the clinical trials, appear to be safe options for our atopic dermatitis patients.

HCPLive: What would you say is the biggest takeaway from some of these data that you highlight?

Bunick: With that said, overall, OX40 and OX40-ligand targeting biologics are a new entry into the atopic dermatitis therapeutic landscape. I really had a great time speaking with my friend and colleague, Dr. Johann Gudjonsson, about this topic. And I look forward to seeing more data come out on these therapies in the months ahead.

For any additional information on this topic or related topics in the atopic dermatitis space featured at RAD 2025, view our latest conference coverage.

The quotes used in this summary were edited for the purposes of clarity.