With 19 Bispecific Antibodies Swarming the Market, How Did Kelun-Biotech Secure a Spot? Can Bispecifics Replicate the ADC Success Story?

This is not the first time Kelun-Biotech has received an IND approval, but this time carries a different significance. According to incomplete statistics from VCBeat, SKB118 is currently the 19th PD-1 / PD-L1 × VEGF bispecific antibody globally to enter clinical and higher stages, with nearly 79% originating from pharmaceutical companies in China. To date, only Akeso's Ivonescimab has been approved for marketing, but with 18 competing products from companies including Kelun-Biotech closely following, the window of opportunity for later entrants is rapidly narrowing.

Why does Kelun-Biotech choose to enter the market at this very moment? The answer lies in two key terms: tetravalent design and ADC synergy. The differentiation of SKB118 goes far beyond its dual-target profile. Preclinical studies have shown that in the tumor microenvironment with high VEGF expression, SKB118 exhibits significantly enhanced binding efficiency to PD-1. Such self-potentiating capability is a structural advantage brought by its tetravalent design.

More importantly, the true trump card of Kelun-Biotech is not the bispecific antibody itself, but the chemical reaction it has with its own ADC pipeline. What is this company best at? ADC. Now, it is trying to use the key of SKB118 to unlock the synergy door of "bispecific antibody + ADC". But can it continue its previous success in the ADC field?

SKB118 is not an ordinary bispecific antibody. In Kelun-Biotech's announcement, it is explicitly described as a tetravalent bispecific antibody. Compared to the traditional bivalent structure, tetravalent means more binding sites, stronger affinity, and more precise tissue targeting capability.

Its mechanism can be broken down into two layers of logic: The first layer is PD-1 immune checkpoint blockade, a cornerstone pathway in cancer immunotherapy. However, relying solely on PD-1 inhibitors benefits only a portion of patients. The second layer is VEGF angiogenesis inhibition, which not only "starves" the tumor by blocking new blood vessel formation but also enhances the enrichment efficiency of combination therapy drugs in tumor tissues through vascular normalization.

Preclinical studies have revealed an interesting phenomenon: in the presence of VEGF, SKB118 exhibits synergistically enhanced binding capacity and signaling blockade effect against PD-1. In other words, the drug can automatically identify tumor regions with high VEGF expression and concentrate its potency to block immune signaling.

This self-enhancing mechanism is a structural dividend brought by the tetravalent design. However, the market is more focused on another potential of SKB118. The announcement clearly pointed out that the anti-VEGF activity of SKB118 may normalize blood vessels in tumor sites, which is expected to enhance the accumulation and efficacy of combination therapies locally in tumors, such as when used in combination with ADCs.

Dr. Ge Junyou, CEO of Kelun-Biotech, stated after the approval: "The company will continue to explore the combination potential of SKB118 with its own ADC assets based on the ADC+IO strategy, to fully leverage the synergistic value of the product pipeline."

Looking back at the timeline of SKB118, the progress has been unusually rapid. In December 2025, Kelun-Biotech entered into a strategic partnership with Crescent Biopharma, securing exclusive rights for the research, development, manufacturing, and commercialization of SKB118 (also known as CR-001) in Greater China. In January 2026, Crescent announced that the FDA had approved the IND application for SKB118, promptly initiating the global multicenter ASCEND I / II clinical trial (NCT07335497), with plans to enroll 290 patients. From securing the rights in Greater China to obtaining clinical approvals in both China and the U.S., the entire process took less than six months.

This pace is lightning-fast.

Zooming out, the congestion in the PD-1 × VEGF bispecific antibody track may be more exaggerated than most people imagine.

PD-1×VEGF were previously considered to be well-received but not commercially successful. Scientists had long remained interested in them, as the prevailing view at the time was: effective, but with limited results. This changed in September 2024 when Akeso announced data at the World Conference on Lung Cancer (WCLC) showing that AK112 outperformed Keytruda head-to-head, causing a seismic shift in the industry and drawing significant attention.

The industrial consensus on this target rapidly spread, transforming from a few people's attempt into an opportunity for everyone.

To date, a total of 19 bispecific antibodies targeting the same targets have advanced into clinical and later stages worldwide, nearly 80% of which are developed by Chinese pharmaceutical companies. So far, only ivonescimab from Akeso Biopharma has secured marketing approval, while the remaining 18 candidates are all waiting in line in clinical development.

The advantage of being the first mover is continuously amplifying. In 2025, Akeso's new drug sales revenue reached 3.033 billion yuan. Ivonescimab has currently laid out 15 registrational / Phase III studies globally.

Multinational giants such as Merck and AbbVie have also bolstered their presence through massive BD deals. AbbVie introduced RC148 with a $650 million upfront payment and a total deal worth $5.6 billion; LaNova Medicines (later acquired by Sino Biopharm in July 2025) licensed LM-299 to Merck for a $588 million upfront payment, up to $2.7 billion in milestone payments, and a total value of $3.288 billion.

This means that latecomers must provide the best-in-class evidence to possibly carve out a niche in the crowded track.

The structural design differences among various molecules are actually quite significant. Akeso's AK112 adopts a tetravalent IgG1-ScFv structure, with the Fc segment retaining ADCC effector function; LaNova 's LM-299 modifies the Fc end of the anti-VEGF antibody to incorporate two nanobodies targeting PD-1.  Junshi Biosciences' JS207 uses the clinically validated toripalimab as its backbone, with the Fc segment adopting IgG4 to weaken effector functions and optimize the safety window.

SKB118's differentiated narrative currently hinges on two points: the affinity advantage brought by its tetravalent structure, and the potential of anti-VEGF activity to promote vascular normalization and enhance the enrichment of combination therapies. However, for KELUN-BIOTECH, the latter point may hold greater strategic significance. The company’s expertise lies in ADCs, and if the combination of bispecific antibodies + ADC can be realized, it will create a moat that is difficult to replicate.

But the challenges are equally straightforward, with 19 products competing on the same track—patient enrollment, research center resources, and regulatory communication channels — are all being rapidly depleted. The normalization of medical insurance negotiations may leave less pricing room for bispecific antibodies than anticipated. Even if eventually approved, whether they can fetch a good price is another dimension of test.

In the above announcement, Kelun-Biotech's risk warning also specifically pointed out that SKB118 may not be successfully developed and commercialized in the end.

Kelun-Biotech's ADC layout has become quite solid, achieving a revenue of 2.058 billion yuan in 2025, including 543 million yuan from drug sales, marking a significant year-on-year increase of 949.8%. The core TROP2 ADC product SKB264 has been approved for marketing and included in the 2025 National Medical Insurance Catalog, while the HER2 ADC Brodutuzumab was also approved in October 2025.

On this basis, the logic behind Kelun-Biotech’s introduction of SKB118 becomes clear. The efficacy of ADCs highly depends on the drug's enrichment efficiency within tumor tissues. If SKB118’s vascular normalization effect can indeed enhance ADC penetration and accumulation in tumors, then the combination of "bispecific antibody + ADC" is not a simple addition but a synergistic amplification.

The mission of the bispecific antibody is to open pathways, normalize blood vessels to improve the tumor microenvironment, and help ADC drugs penetrate more thoroughly into the tumor. The mission of ADC is precise destruction, releasing toxins to kill tumor cells after entering the tumor. These two mechanisms work together to form a closed-loop of destruction.

This also explains Ge Junyou’s repeated emphasis on the positioning: continuously basing on the ADC+IO strategy, actively exploring the combination potential of SKB118 with its own ADC assets. This might be the real reason why Kelun-Biotech still chose to get an entry ticket during the fiercely competitive bispecific antibody field: not to directly confront Akeso, but to find an enhancer for its vast ADC pipeline.

As described in the announcement: "Anti-VEGF activity promotes vascular normalization and enhances the accumulation of combination therapeutic drugs such as ADCs."

VCBeat has communicated with multiple enterprises engaged in the ADC sector, many of which are also conducting combination development of their own ADCs with other drugs. They clearly recognize that the marketing of ADCs as single-agent therapy is only the first step, while combination therapy represents a strategic battleground all players strive to occupy. Once a combination regimen is approved for first-line or second-line treatment and gains a first-mover advantage, patients will be unlikely to switch to similar ADCs after developing drug resistance, thereby securing a long-term dominant position in clinical practice.

Can the transition from an ADC leader to a player with bispecific antibody layout proceed smoothly? The clinical trial data of SKB118 will provide the answer. Kelun-Biotech’s leap from ADCs to bispecific antibodies represents more than the pipeline evolution of a single company; it reflects a deeper trend among China’s innovative pharmaceutical enterprises: shifting from in-depth cultivation of a single track to the construction of a collaborative ecosystem. When a single molecule can hardly build long-term competitive barriers, a new competitive pattern is taking shape — building a combination therapy moat around proprietary core assets.

The story of the PD-1 × VEGF bispecific antibody track is shifting from who can be the first to make it to who can do it best.

Kelun-Biotech has obtained the entry ticket, but the validity period of this ticket may be shorter than anyone could imagine.

The 290 patients enrolled in the ASCEND trial are acting as the jury in this 19-contender race. Whether SKB118’s tetravalent design represents genuine structural innovation or merely conceptual packaging remains to be seen. Should SKB118 be advanced into combination therapy with the company’s in-house ADC candidates in the future, it will require elaborate clinical trial design to address challenges such as dose escalation and toxicity management. The R&D cycle and costs will be markedly higher than those for single-agent development.

Can Kelun-Biotech's bispecific antibody story continue its success in the ADC track? The answer is not in the announcements, but in the data.