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

Christopher G. Bunick, MD, PhD

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.

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

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

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 

, emphasizing that many patients treated with current monospecific biologics fail to achieve optimal disease control.

Bunick, known for his role at the Yale School of Medicine, spoke about his team’s work in an interview with 

, 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.

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. 

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. 

Videos

Christopher Bunick, MD, PhD, and colleagues conducted a review bispecific and trispecific antibodies in atopic dermatitis.

ABCs in Dermatology: Late Breaking Data Spotlight at AAD 2026

For dermatologists and the dermatology community, the 

American Academy of Dermatology (AAD) Annual Meeting

 has earned the reputation as a platform the next wave of practice-changing advances in the field. The 2026 AAD annual meeting served as a prime example of why, with more than a dozen phase 2 or phase 3 trials headlining the conference—showcasing new data in psoriasis, atopic dermatitis, and more.

hosts Chris Bunick, MD, PhD, of Yale School of Medicine, and Lindsay Ackerman, MD, of US Dermatology Partners, break down a trio of late-breaking trials from the meeting and share their perspective on additional data of note across multiple disease states.

On March 28, 2026, Eli Lilly announced positive phase 3b results from the TOGETHER-PsA trial evaluating concomitant ixekizumab (Taltz) and tirzepatide (Zepbound) versus ixekizumab alone in adults with active psoriatic arthritis and obesity or overweight.

In the randomized, open-label trial of 271 participants, the combination arm met the primary endpoint, ACR50 response plus ≥10% weight reduction at 36 weeks, in 31.7% of patients versus 0.8% with ixekizumab monotherapy, with improvements in disease activity, fatigue, physical function, and cardiometabolic markers also favoring the combination. Adverse events in the combination arm were generally mild to moderate and consistent with the established profiles of each agent, with nausea, diarrhea, and constipation among the most common.

Eli Lilly indicated detailed findings will be discussed with regulators, though no submission timeline was disclosed.

On March 23, 2026, Apogee Therapeutics announced positive 52-week maintenance data from Part A of the phase 2 APEX trial evaluating zumilokibart, an extended half-life anti-IL-13 monoclonal antibody, in adults with moderate-to-severe atopic dermatitis.

Based on the trial's maintenance phase, EASI-75 response was maintained at week 52 in 75% and 85% of week 16 responders receiving every-3-month and every-6-month dosing, respectively, with deepening of response observed across lesional and itch endpoints in the full treated population through 52 weeks. Zumilokibart's extended half-life design supports dosing as infrequently as twice yearly, compared with up to 26 annual injections for currently available therapies, with a safety profile consistent with other agents in the IL-13 class.

Part B 16-week induction data are expected in the second quarter of 2026, with phase 3 initiation in moderate-to-severe atopic dermatitis planned for the second half of 2026.

On March 28, 2026, Takeda announced positive phase 3 results from the Latitude PsO 3001 and 3002 trials evaluating zasocitinib, a once-daily oral selective TYK2 inhibitor, in adults with moderate-to-severe plaque psoriasis.

In the randomized, double-blind, placebo- and active comparator-controlled trials, 71.4% and 69.2% of zasocitinib-treated patients achieved sPGA 0/1 at week 16 versus 10.7% and 12.6% with placebo and 32.1% and 29.7% with apremilast (

<.001), with PASI 75 responses observed as early as week 4 and more than 90% of week 40 responders maintaining response through week 60. The safety profile was consistent with phase 2b data, with upper respiratory tract infection, nasopharyngitis, and acne among the most common adverse events and no new safety signals were identified.

Takeda plans to submit a New Drug Application to the FDA starting in fiscal year 2026.


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.

Eli Lilly and Company. Phase 3b data presented at AAD Annual Meeting show Lilly’s Taltz (ixekizumab) plus Zepbound (tirzepatide) delivered superior efficacy for adults with psoriatic arthritis and obesity | Eli Lilly and Company. Eli Lilly and Company. Published March 28, 2025. Accessed April 2, 2026. 

https://investor.lilly.com/news-releases/news-release-details/phase-3b-data-presented-aad-annual-meeting-show-lillys-taltz

Apogee Therapeutics. Apogee Therapeutics Announces Positive Phase 2 Part A 52-Week Data of Zumilokibart (APG777), Demonstrating Maintenance and Deepening of Responses with Every 3- and 6-Month Dosing in Moderate-to-Severe Atopic Dermatitis | Apogee Therapeutics, Inc. Apogee Therapeutics, Inc. Published March 23, 2026. Accessed April 2, 2026. 

https://investors.apogeetherapeutics.com/news-releases/news-release-details/apogee-therapeutics-announces-positive-phase-2-part-52-week-datq

Takeda. Takeda’s Zasocitinib Delivered Rapid and Durable Skin Clearance in a Convenient Once-Daily Pill, Affirming Promise to Reshape Psoriasis Care. Takeda.com. Published March 28, 2026. Accessed April 2, 2026. 

https://www.takeda.com/newsroom/newsreleases/2026/zasocitinib-phase3-clinical-trial-results/

Podcasts

Late-breaking AAD 2026 trials spotlight PsA weight-loss combo, twice-yearly IL-13 dosing for atopic dermatitis, and a rapid oral TYK2 pill for psoriasis.

Hosts Drs. Bunick and Ackerman preview the 2026 American Academy of Dermatology Annual Meeting.

ABCs in Dermatology: Previewing the 2026 AAD Annual Meeting

The 2026 American Academy of Dermatology (AAD) Annual Meeting convenes in Denver with a scientific agenda promising to showcase the latest advances and breakthroughs in dermatologic care. 

, hosts Chris Bunick, MD, PhD, of Yale School of Medicine, and Lindsay Ackerman, MD, of US Dermatology Partners, survey the landscape ahead of the meeting and walk through the sessions each will be presenting on-site.

Bunick reframes antibiotics in acne as anti-inflammatory agents rather than antimicrobials—a distinction he argues is clinically meaningful for patient adherence and prescribing confidence. The talk addresses antibiotic stewardship, the role of narrow-spectrum agents such as sarecycline in preserving gut microbiome integrity while retaining full anti-inflammatory efficacy, and the understudied pathophysiologic distinctions between teenage and adult female acne. Sarecycline's inability to cross the blood-brain barrier, minimal vestibular disturbance, and lowest resistance profile among tetracyclines are highlighted as precision-medicine advances entering the acne space.

Mechanism of Action, Safety & Systemic Inflammation in JAK Inhibition


Bunick presents a comprehensive reappraisal of JAK inhibitor safety and systemic inflammation, anchored in what he describes as a widespread misreading of the ORAL Surveillance study. Because the trial used an active comparator only—with no placebo arm—it cannot support conclusions about absolute cardiovascular risk for either tofacitinib or TNF-alpha inhibitors. The session will present transcriptomic evidence linking psoriasis and atopic dermatitis to shared atherosclerotic risk pathways, introduce his "diaper to diaper" hypothesis tracing systemic inflammation from growth stunting in pediatric AD to cardiovascular disease in adults, and close with a five-year comparative analysis of JAK inhibitor and IL-13-targeted safety data.

Maintenance of IHS4 Response to Upadacitinib in Moderate-to-Severe Hidradenitis Suppurativa

Ackerman presents maintenance-of-response data for upadacitinib in moderate-to-severe HS using the IHS4 severity scoring system—extending previously published week-12 results to week 40 across patients achieving IHS4 55, 75, and 90 response thresholds. Durability is framed as the defining clinical imperative in HS: even patients without active lesions carry substantial anticipatory psychological burden between flares. Ackerman positions JAK1 inhibition as mechanistically well-suited to HS given its broad reach across the disease's heterogeneous cytokine architecture, and signals optimism for the emerging oral and adjuvant JAK inhibitor pipeline—including abrocitinib and povorcitinib—as the field moves beyond its current injectable-only approved options.

Chris Bunick, MD, PhD, and Lindsay Ackerman, MD, preview the 2026 American Academy of Dermatology Annual Meeting.