Trispecific antibodies are emerging as one of the most exciting drug classes in biopharma, building on the clinical success of bispecific antibodies to deliver even greater efficacy and precision. By simultaneously engaging three distinct targets, these new molecules are designed to address some of the key limitations seen with earlier cancer immunotherapies, such as antigen escape, tumor heterogeneity, and suboptimal immune activation. Meanwhile, they could also be extremely promising in autoimmune and inflammatory indications due to their ability to block multiple pathways.
Although still solely in clinical development, with no trispecific antibodies having been approved yet, these therapies are already generating strong interest across the biopharma industry, with early clinical data looking very promising indeed.
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What are trispecific antibodies?
Trispecific antibodies are essentially a new class of engineered drugs designed to bind to three different targets at the same time. This builds on the idea behind monoclonal and bispecific antibodies, but takes it a step further by packing multiple functions into a single molecule.
Many of the trispecific antibodies currently in development are designed to help the immune system better recognize and kill cancer cells. A common approach is to bind to two different markers on a tumor cell, while also attaching to a protein such as CD3 on T cells. This effectively brings immune cells into close contact with cancer cells and activates them at the same time. And, because they target more than one tumor marker, these drugs may also reduce the chances of the cancer evading treatment by simply switching off or losing a single antigen, which is a known limitation of some existing therapies.
But this is a complex drug class, and not all trispecifics are built the same way. Some are designed to combine different immune-modulating effects, such as blocking checkpoint proteins or interfering with growth signals that tumors rely on. Others include features that improve how long the drug stays in the body. The overall goal, though, is ultimately similar to combination therapy – except it is delivered in a single, more controlled format.
While cancer is the main focus for trispecific antibody companies – particularly blood cancers like multiple myeloma and, increasingly, solid tumors – researchers are also exploring applications in other diseases, like autoimmune and inflammatory conditions, where these drugs could be used to dial down harmful immune activity more precisely, potentially avoiding the broad immune suppression seen with some current treatments. There is also some very early interest in infectious diseases, where hitting multiple viral targets at once could make it harder for pathogens to escape.
That said, the added complexity of trispecific antibodies comes with some trade-offs. Designing and manufacturing these molecules is more challenging than for standard antibodies, and ensuring they are both safe and stable remains a key hurdle.
With early clinical results starting to emerge, trispecifics are quickly moving from an experimental concept to a serious area of focus across the biopharma industry, with top pharma taking a huge interest in the field over the past year or so – something that usually signals a particular field could be set to take off, with the first approval potentially just around the corner.
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Trispecific antibodies in clinical trials: What are some of the most promising candidates in the field?
Although no trispecific antibody has yet received regulatory approval, more than 100 candidates are currently in development worldwide. Here, we look at some of the most promising assets in clinical development.
Attracting the attention of big pharma: Johnson & Johnson, AbbVie, Pfizer, and Sanofi all have a hand in promising trispecific candidates
Getting involved in the trispecific antibody field certainly felt like a natural next step for top pharma after its strong interest and success in the bispecifics space.
March 2026 saw Pfizer score a big win for its trispecific antibody candidate tilrekimig in a phase 2 trial. However, the study was not for a cancer indication as one might expect; instead, the drug was tested in patients with moderate to severe atopic dermatitis. The trial met its primary endpoint of demonstrating a statistically significant increase in the percentage of patients who saw the size and severity of their eczema reduce by more than 75% at week 16 across all three of the once-monthly doses of tilrekimig. Based on these results, Pfizer now plans to accelerate its asset into phase 3, with a pivotal study in atopic dermatitis on track to start sometime this year.
Also in March this year, Sanofi agreed to pay $180 million upfront to Kali Therapeutics to license a trispecific T-cell engager that has the potential to treat a broad range of B-cell-mediated autoimmune diseases. The candidate in question is called KT501 and is designed to bind to CD3, CD19, and BCMA, thereby targeting a broad range of B cell populations. It is currently being evaluated in a first-in-human study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics in participants with rheumatoid arthritis. In prior non-human primate studies, the asset has demonstrated potent B cell depletion in peripheral and tissues and significantly reduced cytokine production.
Meanwhile, last year, AbbVie paid Ichnos Glenmark Innovation (IGI) $700 million upfront for rights to a CD38×BCMA×CD3 trispecific antibody named ISB 2001 for oncology and autoimmune diseases. At the time of the deal, the candidate was being investigated in a phase 1 study in patients with relapsed/refractory multiple myeloma. If successful, the drug could well be a rival to Johnson & Johnson (J&J)’s Tecvayli, Pfizer’s Elrexfio, and Regeneron’s Lynozyfic, all of which target BCMA and CD3; adding CD38 as an extra target could boost binding to tumor cells with low expression of BCMA and stop cancers from becoming resistant by downregulating the antigens.
Finally, J&J’s trispecific antibody JNJ-79635322 (JNJ-5322) produced promising phase 1 results in June last year in patients with relapsed or refractory multiple myeloma. Among the 36 patients who received the recommended phase 2 dose, the overall response rate was 86.1%. Meanwhile, in the 27 patients who were naive to BCMA and GPRC5D-directed therapies, the overall response rate was 100%. Furthermore, the toxicity profile of the drug did not appear to increase grade 3 or higher adverse events, and some of the GPRC5D-related toxicity was improved compared to that of bispecifics.
Innovent Biologics’ IBI3003 receives FDA fast track designation
In January 2026, Innovent Biologics’ trispecific antibody, IBI3003, was granted fast track designation from the U.S. Food and Drug Administration (FDA) for the treatment of relapsed or refractory multiple myeloma in patients who have received four or more lines of previous anti-myeloma therapies.
The candidate is an anti-GPRC5D/BCMA/CD3 trispecific antibody, meaning it works by simultaneously binding to BCMA and GPRC5D, two proteins found on tumor cells, while also attaching to CD3 on T cells. It is currently undergoing a phase 1/2 trial in patients with relapsed or refractory multiple myeloma in China and Australia, with plans to soon initiate a phase 1/2 clinical trial in the U.S. as well.
Clinical data presented by Innovent at the American Society of Hematology (ASH) Annual Meeting in December 2025 demonstrated a tolerable safety profile and promising efficacy signals for IBI3003; among the patients who received the drug at a minimum of 120 μg/kg, the overall response rate was 83.3%, with four patients achieving a stringent complete response, seven having a very good partial response, and nine experiencing a partial response.
Excalipoint Therapeutics launches with $68.7 million seed financing to advance trispecific antibody programs
Chinese biotech Excalipoint Therapeutics launched with $68.7 million in seed financing in March to advance next-generation T cell engager therapies, which are specialized bispecific or trispecific antibodies that have become extremely popular among drug developers and investors in recent years. Although at least a dozen T cell engagers have already received approval from the FDA, these have all been bispecifics, and most have been approved to treat blood cancers.
But Excalipoint is working on bringing trispecific T cell engagers to the clinic; the company believes that creating therapies with three targets instead of two could overcome the key biological barriers that have thus far limited T cell engager therapies, including converting “cold” tumors into “hot” tumors, addressing the tumor microenvironment, and enabling targeting of difficult-to-drug tumor antigens.
The T cell engager company’s lead program, EXP011, targets the cancer protein DLL3 and two T cell targets, CD3 and 4-1BB. It is being developed for small cell lung cancer (SCLC), neuroendocrine tumors, and other DLL3-expressing malignancies. The company recently initiated a phase 1/2 trial, with the first patient dosed in October 2025. Excalipoint’s pipeline also includes a second trispecific antibody, named EXP012, which targets CDH17, CD3, and 4-1BB, and is being developed to treat colorectal, gastric, and pancreatic cancers. Both of these assets were licensed for $10 million upfront from Lepu Biopharma.
Meanwhile, the company also has four other candidates listed in its pipeline.
A field set for take off: The future of trispecific antibodies
Although no trispecific antibodies have yet been approved, and most are still at a relatively early stage of development, there is no denying that momentum across the field is building quickly. In many ways, the sector is following a similar path to bispecific antibodies, which moved from a highly experimental concept to one of the most active areas in biopharma over the past decade. Furthermore, the success of bispecific therapies, particularly in oncology, has helped validate the broader idea that engineered antibodies can be used to precisely direct immune responses and improve on traditional monoclonal antibody approaches.
Trispecific antibodies are now aiming to take that concept a step further; by engaging three targets simultaneously, companies hope to address some of the key challenges that emerged with earlier bispecific therapies, including tumor escape, limited durability, and safety concerns such as cytokine release syndrome. When it comes to cancer, the ability to recognize multiple tumor antigens at once, as trispecifics do, could help tackle tumor heterogeneity and reduce the chances of cancer cells avoiding detection. Ultimately, the goal of these therapies is to maintain efficacy while simultaneously improving tolerability.
The field is also benefiting from advances in antibody engineering and manufacturing technologies that were not available during the early development of bispecifics. Improved protein design, half-life extension strategies, and more sophisticated multispecific formats are helping companies build increasingly stable and manufacturable molecules. At the same time, growing clinical experience with T cell engagers and other immune-based therapies is giving companies a clearer understanding of how to manage toxicity and optimize dosing strategies.
As more candidates enter the clinic and assets like those mentioned in this article continue to generate promising results, first approvals for trispecific antibodies are expected by 2028, according to a report from last year.
If this is correct, then it might not be long before we see top pharma’s bet on the field pay off, as these complex therapies are increasingly viewed as a natural next step in the evolution of multispecific therapeutics.
