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

In a recent review on emerging therapies for atopic dermatitis, 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.1

In his previous HCPLive interview segment, 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.2 In response, Bunick and colleagues outlined a rapidly expanding pipeline of bispecific and trispecific antibodies designed to simultaneously target multiple inflammatory and neuroimmune pathways.1

In this new Q&A segment of his interview with HCPLive, 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:

HCPLive: 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?

Bunick: 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 th two 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.

HCPLive: 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?

Bunick: 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.

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

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. doi: 10.3389/fddsv.2026.1766021.

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.