Christopher G. Bunick, MD, PhD, is an associate professor of dermatology at Yale University School of Medicine.

Christopher G. Bunick, MD, PhD

What Is Next for OX40 Ligand Inhibition in Atopic Dermatitis?

 explored the future potential of amlitelimab in atopic dermatitis, with hosts Christopher Bunick, MD, PhD, and Lindsay Ackerman, MD, emphasizing the importance of maintaining scientific curiosity and clinical perspective as more data emerge regarding OX40 ligand-targeted therapy.

The discussion centered on balancing enthusiasm for a novel therapeutic mechanism with the need for continued investigation into safety signals and patient selection. Bunick argued the field should remain optimistic about amlitelimab’s future, noting that a better understanding of patient-specific risk factors could ultimately help clinicians identify individuals most appropriate for treatment. He compared this approach to the risk stratification strategies dermatologists have already adopted for JAK inhibitors, where clinicians routinely evaluate patients for factors that may increase the likelihood of adverse events before initiating therapy.

Rather than viewing emerging questions about the therapy as a reason to abandon the pathway, Bunick suggested that dermatology should focus on generating more data and demanding greater scientific transparency. In his view, understanding the underlying biology behind observed safety findings will allow clinicians to make more informed, patient-centered decisions while preserving access to potentially valuable treatment options.

Ackerman agreed, describing the OX40-OX40 ligand pathway as an example of why dermatology remains one of the most rapidly evolving areas of medicine. She highlighted the complexity of inflammatory disease biology and suggested that upstream immune modulation may ultimately have implications extending beyond atopic dermatitis. According to Ackerman, the pathway’s broad immunologic relevance could make it important not only for eczema but also for other chronic inflammatory disorders that continue to present therapeutic challenges.

The hosts also discussed the ongoing unmet need in atopic dermatitis despite an expanding therapeutic landscape. Ackerman noted that the disease remains highly heterogeneous, with significant variability in clinical presentation and treatment response. As a result, she argued that continued investment in new mechanisms of action remains essential, even as effective therapies already exist. She pointed to the continued development of amlitelimab as evidence of an ongoing commitment to addressing gaps in care for patients whose disease remains difficult to control.

The conversation then shifted to Ackerman’s firsthand experience as a clinical trial investigator. Drawing on her participation in amlitelimab studies, Ackerman described seeing several patients achieve substantial improvements despite having previously failed multiple therapies. Although she acknowledged that these observations represent only a small number of patients, she noted that some individuals continued to do well even after completing the interventional portion of the study. Ackerman said she had anticipated needing to rapidly transition certain participants to additional treatments after trial completion because of the severity and recalcitrance of their disease, but some had yet to experience significant flares.

Bunick cautioned against drawing broad conclusions from individual cases but viewed those experiences as further reason to remain open-minded. Both hosts ultimately stressed that advancing patient care requires careful scientific investigation, patience, and a willingness to evaluate new therapeutic pathways on the basis of evolving evidence. They concluded that maintaining a patient-centered approach while pursuing deeper mechanistic understanding will be critical as the role of OX40 ligand inhibition continues to develop within atopic dermatitis and potentially other inflammatory diseases.

Editor’s note: This segment was summarized with the help of AI tools.

Relevant disclosures for Bunick include AbbVie, South Beach Symposium, Almirall, Apogee Therapeutics, Arcutis Biotherapeutics, Daiichi Sankyo, Eli Lilly, LEO Pharma, US, Novan, Novartis, Ortho Dermatologics, Palvella Therapeutics, Pfizer Inc., Sanofi, Sun Pharmaceutical Industries Ltd., Timber Pharmaceuticals, and UCB. Relevant disclosures for Ackerman include AbbVie, Alumis, Amgen, Arcutis, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Galderma, L'Oréal, Novartis, Sun Pharmaceutical, and UCB.

Sanofi. Press Release: AAD: new results from Sanofi’s amlitelimab phase 3 studies in atopic dermatitis presented in late-breaking research session. Sanofi.com. Published March 28, 2026. Accessed June 1, 2026. 

https://www.sanofi.com/en/media-room/press-releases/2026/2026-03-28-15-00-00-3264184

Kyowa Kirin. Kyowa Kirin Announces Discontinuation of Rocatinlimab Clinical Trials - Kyowa Kirin. Kyowakirin.com. Published March 3, 2026. Accessed June 1, 2026. 

https://www.kyowakirin.com/media_center/news_releases/2026/e20260303_01.html

Videos

The latest ABCs of Dermatology explored the future potential of amlitelimab in atopic dermatitis and the potential of OX40 ligand-targeted therapy.

What Does New Phase 3 Amlitelimab Data Suggest for Atopic Dermatitis?

, hosts Christopher Bunick, MD, PhD, and Lindsay Ackerman, MD, discussed why the phase 3 amlitelimab data in atopic dermatitis may be more clinically meaningful than headline efficacy numbers alone initially suggest.

Bunick emphasized that understanding the study population is critical when interpreting the results from the COAST 1, COAST 2, and SHORE trials. Across the studies, each enrolled roughly 600 patients with moderate-to-severe atopic dermatitis, representing a sizable late-stage clinical program. He highlighted the diversity of the enrolled population, noting relatively strong representation of Black patients compared with many dermatology trials, alongside a notably large proportion of Asian participants, reflecting a broader global patient population.

The hosts also underscored the substantial disease burden among trial participants. According to Bunick, patients had lived with atopic dermatitis for nearly two decades on average, and many entered the studies with extensive body surface area involvement and high baseline disease severity. A large percentage had also previously received systemic therapies, including biologics, JAK inhibitors, and traditional immunosuppressive agents, suggesting investigators were studying a particularly treatment-resistant population rather than patients with milder disease.

Another point Bunick stressed was the rigor of the statistical analysis. The trials used nonresponder imputation methodology, meaning any participant who discontinued treatment, deviated from protocol, or required rescue therapy was automatically counted as a treatment failure. He argued that this conservative approach makes the efficacy findings more impressive when viewed in context.

Ackerman expanded on the significance of the long-term response patterns seen with amlitelimab, particularly the durability of efficacy through 52 weeks and the similarity between dosing every 4 weeks and every 12 weeks. She contrasted this upstream immune modulation strategy with more downstream approaches such as cytokine blockade or JAK inhibition, suggesting that targeting the OX40 ligand pathway may allow for broader recalibration of immune activity rather than suppression of isolated inflammatory signals.

She also noted that responses appeared to deepen over time, with later efficacy outcomes surpassing those seen at earlier time points despite the increasingly stringent nature of long-term analyses. Ackerman suggested this pattern could reflect gradual restoration of immune balance through preservation of regulatory T-cell function and normalization of aberrant T-cell memory responses, raising the possibility that upstream pathway modulation may eventually reshape how chronic inflammatory diseases such as atopic dermatitis are treated.

Sanofi. Press Release: AAD: new results from Sanofi’s amlitelimab phase 3 studies in atopic dermatitis presented in late-breaking research session. Sanofi.com. Published March 28, 2026. Accessed May 28, 2026. 

Kyowa Kirin. Kyowa Kirin Announces Discontinuation of Rocatinlimab Clinical Trials - Kyowa Kirin. Kyowakirin.com. Published March 3, 2026. Accessed May 28, 2026. 

Amlitelimab was discussed in the ABCs in Dermatology podcast, with the hosts highlighting atopic dermatitis patient demographics and high disease burden.

Hosts breakdown news and updates related to the atopic dermatitis pipeline, specifically examining news surrounding a pair of agents targeting OX40 and OX40 ligand as therapeutic pathways.

ABCs in Dermatology: Understanding OX40L in Atopic Dermatitis

000:00 - Introduction: Why OX40/OX40L Matters in Atopic Dermatitis and Chronic Inflammation

08:37 - Ligand vs Receptor Targeting: Mechanistic Differences and the Role 

26:39 - Phase 2/3 Data for Amlitelimab: Efficacy, Dosing Frequency, and Disease Modification Signals

41:58 - Safety Profile, Patient Selection, and Future Directions for OX40L Inhibition

 is emerging as a central focus of therapeutic development, with OX40–OX40 ligand signaling offering a potential pathway for more durable disease control beyond downstream cytokine blockade. 

, co-hosts Christopher Bunick, MD, PhD, and Lindsay Ackerman, MD, examine the evolving science behind OX40 and OX40 ligand inhibition, with particular focus on how this pathway may alter T-cell activation, memory T-cell formation, and immune homeostasis in chronic inflammatory skin disease. 

The episode, which is supported by Sanofi with independently developed content, frames the pathway as one of the most closely watched areas in atopic dermatitis drug development, particularly as phase 3 data begin to clarify both the promise and remaining questions around upstream immune modulation. Bunick explains that OX40 ligand, expressed on antigen-presenting cells and other cell types such as dermal fibroblasts, interacts with OX40 on activated T cells as a costimulatory signal. 

By targeting this upstream interaction, investigational agents may reduce multiple downstream inflammatory pathways, including TH1, TH2, TH17, and TH22 signaling, while preserving or restoring regulatory T-cell activity. Ackerman emphasizes that this mechanism raises the possibility of disease modification, though both hosts note that the field still needs clearer definitions around what that term means clinically, whether durable remission, reduced treatment frequency, or true off-drug control.

A major portion of the discussion centers on distinguishing OX40 ligand blockade from OX40 receptor inhibition, particularly the implications of T-cell–depleting versus nondepleting antibody designs. That distinction has become increasingly relevant following Kyowa Kirin’s March 3, 2026, announcement that all ongoing rocatinlimab trials would be discontinued after a planned safety update identified emerging malignancy concerns with possible viral or immune-related links, including 1 new confirmed case and 1 suspected case of Kaposi sarcoma in addition to a previously confirmed case. 

Kyowa Kirin noted the overall malignancy rate remained below expected background rates but said the characteristics of the cases raised a plausible biological concern that could not be excluded. Against that backdrop, the hosts review safety considerations in the OX40 pathway more broadly, including pyrexia, chills, headache, and malignancy surveillance. In Sanofi’s phase 3 amlitelimab program, the company reported no Kaposi sarcoma events across COAST 1, COAST 2, or SHORE, with malignancy rates low, below 1%, and generally similar between amlitelimab and placebo groups. 

Sanofi also reported 2 cumulative Kaposi sarcoma cases among 3778 patients exposed to amlitelimab across all indications, both in patients with known risk factors, and no additional cases across an estimated 4630 patients in the full development program, including blinded studies. 

The episode also reviews phase 3 data for amlitelimab, a fully human, non–T-cell-depleting monoclonal antibody targeting OX40 ligand, across COAST 1, COAST 2, and SHORE. The studies enrolled patients aged 12 years and older with moderate-to-severe atopic dermatitis and evaluated amlitelimab given every 4 weeks or every 12 weeks, with both regimens following a loading dose. COAST 1 and COAST 2 evaluated amlitelimab as monotherapy in 601 and 589 participants, respectively, while SHORE evaluated amlitelimab with topical corticosteroids, with or without topical calcineurin inhibitors, in 643 participants. 

Bunick and Ackerman highlight that the amlitelimab data showed progressively increasing efficacy through Week 24, with Sanofi reporting no evidence of plateau across endpoints. In COAST 1, vIGA-AD 0/1 responses were 21.1% with every-4-week dosing and 22.5% with every-12-week dosing, compared with 9.2% for placebo; EASI-75 responses were 35.9% and 39.1%, respectively, compared with 19.1% for placebo. 

In SHORE, where amlitelimab was studied with topical therapy, vIGA-AD 0/1 responses reached 28.7% and 32.3% with every-4-week and every-12-week dosing, compared with 16.8% for placebo, while EASI-75 responses were 48.1% and 46.8%, compared with 32.3%. 

The hosts note that these later-improving response curves are particularly relevant when considering the potential for extended dosing intervals and long-term immune recalibration. They also emphasize the clinical importance of less frequent dosing, given Sanofi’s statement that the data reinforce the potential for every-12-week dosing from the start, while underscoring that amlitelimab remains investigational and has not been evaluated by any regulatory authority.

Sanofi. Press Release: AAD: new results from Sanofi’s amlitelimab phase 3 studies in atopic dermatitis presented in late-breaking research session. Sanofi.com. Published March 28, 2026. Accessed May 27, 2026. 

Kyowa Kirin. Kyowa Kirin Announces Discontinuation of Rocatinlimab Clinical Trials - Kyowa Kirin. Kyowakirin.com. Published March 3, 2026. Accessed May 27, 2026. 

Podcasts

Explore OX40/OX40L inhibition in atopic dermatitis: phase 3 amlitelimab efficacy, safety signals, and what upstream immune control could mean.

In a recent review on emerging therapies for 

, Christopher G. Bunick, MD, PhD, and colleagues highlighted a notable limitation in the treatment landscape: many of those treated with existing monospecific biologics do not achieve optimal or sustained disease control.

, Bunick emphasized that although currently available medications targeting individual pathways have led to improved outcomes, they often fail to fully impact the breadth of inflammation and symptom burden.

 In response, Bunick and colleagues outlined a rapidly expanding pipeline of bispecific and trispecific antibodies designed to simultaneously target multiple inflammatory and neuroimmune pathways.

In this new Q&A segment of his interview with 

, he touched on these emerging therapies being developed to address both immune-driven inflammation and itch signaling concurrently, noting several key points about his team’s findings and their significance:

Based on the early clinical data your team reviewed, what signals would you say are most encouraging in terms of efficacy, itch control, and durability of response?

For me, last year at EADV, we saw our first glimpse of what the multi-targeted biologics could achieve. What I refer to there is an early phase 1 study from galvokimig. Now this is a molecule that's targeting IL-13 with a tralokinumab-like epitope, but also has the ability to target like by bimekizumab, IL-17 A and F. And what this answered for us was a couple of things. Number one, it asked the question, ‘Can tackling some of the cytokines historically associated with psoriasis improve atopic dermatitis?’

We know from a number of molecular studies that there is overlap between psoriasis and atopic dermatitis in terms of some of the molecular drivers; some of the transcriptomic analyses show the overlap between these diseases. Therefore, it actually makes a lot of sense that inhibiting some of the cytokines that go both ways and that can be involved in psoriasis and can be involved in atopic dermatitis, hitting the breadth of those cytokines, it sort of makes sense.

We really didn't have that masterful proof, in my opinion, until we saw galvokimig, the ability of a biologic to achieve that. We saw in this phase 1 study…this was IV galvokimig, not the final product that's ultimately going to end up in atopic dermatitis patients, but this phase 1 study was IV galvokimig. What it did show was that at Week 12, about 47% of patients achieved EASI 90, which is an incredibly high and fast response for that level of response. That really signaled to me that there's now a connection between the underlying scientific data saying that the atopic dermatitis and psoriasis patients can overlap in some of their molecular drivers.

We know this also from the fact that there are a number of atopic dermatitis patients who kind of have this immune phenotype, switching between atopic dermatitis and psoriasis. We know this happens, and certainly, there are also other examples, such as the flare of the head and neck atopic dermatitis, which may be largely IL-22 driven. We see these things in the clinic every day: the psoriasiform type shift in our atopic dermatitis patients, the head and neck atopic dermatitis. The reality is that galvokimig showed that this can, in fact, really push the levels of what a biologic can achieve.

In addition to galvokimig, we also have tilrekimig. This is a tri-specific antibody that targets the cytokines IL-4, IL-13, and TSLP. Some data was just released around the AAD 2026, which showed that this drug, in its phase 2 studies, actually met its endpoint in achieving EASI 75 response. It is now moving onto phase 3. One of the drugs where we saw an effect that we didn't want to see was one of the tri-specifics being developed by Johnson & Johnson, which showed that it didn't hit the efficacy bar that they were looking for in order to advance the program. One of the tri-specific agents in development has already been discontinued. This was targeting IL-4 receptor alpha and IL-31.

While we've had a couple of very positive responses from galvokimig and tilrekimig in some of the early phase 1 and phase 2 data, galvokimig and tilrekimig represent two really good phase 1 and phase 2 responses that give us clues that this multi-target approach is going to work from a biologic perspective and for atopic dermatitis. We also have another bi-specific antibody developed by J&J targeting the IL-4 receptor alpha and IL-31 cytokines that did not hit the efficacy bar that the company was looking for, and they have discontinued further development of that program.

This goes to show that in developing the bi- and tri-specific antibodies for atopic dermatitis, it is not as simple as just mixing and matching. There's a lot of science that goes into trying to develop a bi- or tri-specific that is much more complicated than developing a mono-targeted biologic. Then again, how you target these agents, the sizes of the molecules, the tissue penetration of these molecules, all matter, and they can all differ. I do think that these complexities in both pharmacodynamics and pharmacokinetics of these drugs are very important to pay attention to, and it's not a given just because we see a good itch response from nemolizumab versus dupilumab or any of the other biologics. The reality is, just mixing and matching isn't necessarily guaranteed to work.

We've seen some successes. We've already seen a failure, and it's going to be really interesting to see over the coming months to years, how this entire landscape plays out. I do believe very strongly, regardless of whether a drug succeeds to the very end and gets clinical approval, or whether that drug ultimately doesn't meet that new efficacy threshold and doesn't make it into FDA approval and into the patients and into the clinics. The reality is that we are going to learn a lot about the disease itself. We're going to learn so much about the pathophysiology of atopic dermatitis, how to manipulate different cytokine and receptor pathways underlying atopic dermatitis, as well as other Th2 driven diseases. I think that that is also one of the major benefits of the program that we're seeing in the multi-targeted biologics, [which is] how we're going to learn about other diseases. This is because the reality is, these multi-targeted biologics aren't going to stay combined to atopic dermatitis. They're going to be expanded into other diseases, particularly they're already being explored in hidradenitis suppurativa.

Looking ahead, how do you envision these multi-specific biologics fitting into the current treatment landscape, especially compared with Janus-kinase (JAK) inhibitors and existing biologic options?

Well, right now, when we think about the drugs for atopic dermatitis that have the best chance of hitting an optimal target or a minimal disease activity state for our patients, the reality is the JAK inhibitors, upadacitinib and abrocitinib, and all the network meta-analyses and head-to-head clinical trials that have occurred, that the JAK inhibitors have set the response bar in terms of EASI 90 and EASI 100 in terms of composite EASI 90, and Itch 01. In reality, the JAK inhibitors have raised that ceiling because of their ability to target multiple cytokines driving the atopic dermatitis. That is what they do. They can hit IL-4, IL-13, and IL-31. They can also hit IL-22, TSLP, and interferon gamma. All of that is what underlies the success that we've seen with JAK inhibitors in not only raising how well they treat the skin disease of atopic dermatitis, but how they reduce very quickly the itch burden that our patients feel. That is really what the multi-targeted biologics are trying to accomplish.

They're trying to match or exceed what the JAK inhibitors have been able to do, and that is having greater skin control, greater itch relief, and all the patient-reported outcomes. Can we ultimately improve these patients to the point where the quality of life, from a biologic standpoint, really continues to improve and grow? That is why half-life extension is so important. Because part of that narrative in terms of patient convenience and patient comfort, comes from the fact that if you're going to have to take an injection, it is difficult]. A lot of patients, when they have to take an injection, the injection fatigue can be real. The reality is, if you're taking it every 3 months or every 6 months, it's a lot different than needing to take an injection every 2 weeks.

The quotes used in this summary were edited for clarity.

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

Amid-Toby G, Alani O, Bunick CG. Bispecific and trispecific antibodies in atopic dermatitis: a review of the emerging clinical pipeline. Front. Drug Discov. 6:1766021. 

Bunick C. Bispecific and Trispecific Antibodies in Atopic Dermatitis, With Christopher Bunick, MD, PhD. HCPLive. April 24, 2026. Accessed April 28, 2026. 

https://www.hcplive.com/view/bispecific-trispecific-antibodies-atopic-dermatitis-christopher-bunick-md-phd

Articles

Multi-specific antibodies are being advanced to overcome suboptimal depth and durability seen with many monospecific biologics in atopic dermatitis, aiming to co-modulate inflammatory and pruritic circuitry. Early clinical signals suggest that broadened cytokine coverage can drive rapid, high-level responses, while setbacks underscore that target pairing and molecular engineering are nontrivial. JAK inhibitors currently define the efficacy ceiling through pleiotropic pathway inhibition and rapid itch reduction, setting a benchmark these biologics must meet or exceed. Longer half-lives and less frequent dosing may improve adherence and patient experience.

This Q&A interview highlights emerging therapies for atopic dermatitis, featuring Christopher G. Bunick, MD, PhD of Yale Medicine.