Strictly speaking, the last time Rongchang Biosciences stole the spotlight dates back to 2021.

Back then, business development (BD) globalization had not yet gained the momentum it has today. This Yantai-based biotech company struck a licensing agreement worth up to $2.6 billion with ADC giant Seagen, pushing the record for overseas licensing deals of China’s innovative drugs to a new high.

Since then, however, Rongchang Biosciences has gradually slipped into a downward cycle. The core conflict stemmed from the imbalance between "capital-burning R&D" and "insufficient cash flow generation": from 2021 to 2023, its R&D expenses reached RMB 710 million, RMB 980 million and RMB 1.31 billion respectively. A cash crunch loomed, forcing the company to streamline its pipeline, lay off staff and cut costs. Market confidence teetered on the brink of collapse.

Partly due to dimmed expectations about its fundamentals, when Rongchang Biosciences sealed a licensing deal worth over $4 billion with Vor Bio in June 2025, its stock price defied the positive news and declined instead.

The industry’s doubts were well-founded: just a month earlier, Vor Bio announced the suspension of all clinical trials, bringing its operations to a virtual standstill. It had also laid off 95% of its workforce, retaining only about 8 employees to wrap up operations and terminate trials. Despite Rongchang Biosciences’ optimism about the subsequent cooperation, more compelling evidence was needed to convince investors.

Fortunately, half a year later in January, pharmaceutical giant AbbVie stepped in.

Under the agreement, AbbVie will obtain the exclusive rights to develop, manufacture and commercialize RC148 outside Greater China. Upon regulatory approval for the agreement to take effect, Rongchang Biosciences will receive an upfront payment of $650 million, plus potential milestone payments of up to $4.95 billion, as well as double-digit tiered royalties based on net sales.

Fang Jianmin, CEO of Rongchang Biosciences, stated that RC148 is a globally competitive PD-1/VEGF bispecific antibody in the company’s product pipeline. As a key direction for next-generation tumor immunotherapy, PD-1/VEGF bispecific antibodies are expected to become cornerstone drugs for cancer treatment.

RC148’s clinical progress has also been a major draw. In December 2025, at the ESMO-IO Congress, Rongchang Biosciences officially released phase I/II clinical data of RC148 as monotherapy and in combination therapies for first-line or second-line treatment of non-small cell lung cancer (NSCLC) via poster presentation, with preliminary results demonstrating promising efficacy.

Domestically, as of June 30, 2025, patient enrollment is underway for a multicenter phase I/II clinical study evaluating the efficacy and safety of RC148 as monotherapy and combination therapy in patients with locally advanced unresectable or metastatic malignant solid tumors. Overseas, RC148 obtained FDA clearance for Investigational New Drug (IND) application in August 2025, and phase II clinical trials for multiple advanced malignant solid tumors are being conducted in the United States.

The involvement of the multinational pharmaceutical company will undoubtedly help accelerate the global development and commercialization of RC148, and further endorse the innovation level of the drug to some extent.

Unlike oncology-focused giants such as Roche and Merck & Co., AbbVie’s traditional strength lies in immunology. Nevertheless, its oncology division, as the second-largest business segment, has been expanding continuously.

In recent years, AbbVie has been advancing a diversified pipeline of investigational therapies for various cancer types, including hematologic malignancies and solid tumors, covering multiple targeted treatment modalities such as small molecule therapies, ADCs, immuno-oncology therapies, multispecific antibodies and novel CAR-T platforms.

Interestingly, on January 7, it was reported that AbbVie was in advanced negotiations to acquire Revolution Medicines, an oncology drug developer with no marketed products, in a deal potentially valued at over $20 billion. AbbVie later moved quickly to distance itself from the news, stating that it was not in any discussions with Revolution Medicines.

All things considered, AbbVie has clearly set its sights and chosen to place a big bet on Rongchang Biosciences.

The licensing collaboration between AbbVie and Rongchang Biosciences marks the arrival of a new player in the PD-(L)1/VEGF bispecific antibody arena. Frankly speaking, however, no discussion about this upsurge can bypass another innovative Chinese biopharmaceutical company—Akeso, Inc.

In 2022, Akeso partnered with Summit Therapeutics of the United States, licensing the overseas rights to Ivonescimab to the latter with an upfront payment of $500 million and a total transaction value of up to $5 billion, once again setting a new record for the overseas licensing of China’s innovative drugs at that time. Three years on, Ivonescimab has officially embarked on its FDA approval journey.

On January 12, Summit, Akeso’s collaboration partner, announced that it had submitted a New Drug Application (NDA) to the FDA for Ivonescimab in the fourth quarter of 2025. The indication is for use in combination with chemotherapy for the treatment of patients with EGFR-mutated non-small cell lung cancer (NSCLC) whose disease has progressed after treatment with EGFR tyrosine kinase inhibitors (TKIs).

This NDA is based on the overall results of the global Phase III clinical trial HARMONi. Summit expects the FDA to make a decision in the fourth quarter of 2026. This means that China’s first independently developed PD-1/VEGF bispecific antibody is just one step away from entering the world’s largest pharmaceutical market.

Ivonescimab once took the industry by storm with the results of the HARMONi-2 study—to a certain extent, it single-handedly ignited the current upsurge in the development and transaction of PD-(L)1/VEGF bispecific antibodies.

In the first-line treatment of patients with PD-L1-positive NSCLC, compared with Keytruda, Ivonescimab prolonged the median progression-free survival (PFS) from 5.82 months to 11.14 months, reducing the risk of disease progression or death by 49%. Since these data were released in 2024, Akeso’s stock price has risen by over 180%.

Nevertheless, scientific doubts have not dissipated—the real challenge lies in the overall survival (OS) data.

In 2025, Summit updated the global Phase III clinical data of HARMONi, showing that despite the significant PFS advantage, the OS data have not yet fully met the preset statistical threshold. This result has attracted widespread attention and discussion in the market.

The FDA’s approval standards are becoming increasingly stringent. Also in 2025, the FDA issued the Draft New Guidance for Overall Survival Assessment in Cancer Clinical Trials, explicitly setting requirements for overall survival in a systematic framework for the first time.

According to this document, which had been in the making for more than two years, overall survival should serve as the primary endpoint of clinical trials when feasible. Even if overall survival is not designated as the primary endpoint, pharmaceutical companies must collect and submit survival data to support the final evaluation of a drug’s safety and efficacy. In other words, the main theme of oncology drug development from now on will be “overall survival reigns supreme”.

However, in the view of some clinical experts, “statistical significance of overall survival is not as important as improvement in clinical value”, and Ivonescimab has already met the threshold of a promising drug.

From the perspective of comprehensive data, the value positioning of Ivonescimab should be guided by an overall perspective. In this context, some industry insiders point out that since Ivonescimab has achieved the clinical endpoint for progression-free survival with sustained improvement in overall survival, it still stands a good chance of entering the U.S. market.

In November 2025, Summit and Akeso announced that Ivonescimab had demonstrated a statistically significant overall survival benefit for the first time in trials involving Chinese patients. The study compared Ivonescimab combined with chemotherapy versus chemotherapy alone, targeting a subtype of lung cancer not typically covered by Keytruda. Summit’s management is fully confident that Ivonescimab will ultimately prove its ability to prolong survival globally.

Now, with the official submission of the NDA, Ivonescimab has become the first domestic PD-(L)1/VEGF bispecific antibody to make a push for FDA approval. The final outcome will further shape the evolution of the entire niche market.

The bustling PD-(L)1/VEGF bispecific antibody track has not only seen partnerships formed, but also collaborations dissolved.

Just days before Rongchang Biosciences and Akeso, Inc. announced the latest progress of their novel drugs, another piece of news sent ripples across the industry. On January 6, Immunotech Biopharma declared the termination of its partnership with Instil Bio, regaining the global rights to its PD-L1/VEGF bispecific antibody IMM2510 and CTLA-4 antibody IMM27M.

Back in 2024, when Immunotech Biopharma entered into the collaboration with Instil Bio, the PD-(L)1/VEGF bispecific antibody sector had already started to heat up.

Instil Bio promised an upfront payment of $50 million, plus near-term milestone payments, subsequent milestone payments totaling over $2 billion, as well as sales royalties for the products.

While the total amount seemed substantial, over a year later, the market landscape had transformed entirely. Multinational pharmaceutical corporations (MNCs) such as Pfizer, Merck & Co., and BMS have swarmed into this space, engaging in cut-throat competition that has only intensified over time.

Yet Instil Bio, as the collaboration partner, has appeared sluggish in advancing development progress.

Immunotech Biopharma stated that Instil Bio’s pace of conducting clinical trials in the United States was relatively slow. Continuing to push forward with the trials would mean requiring greater budgetary input, as well as fulfilling milestone payment commitments to Instil Bio, leading to mounting challenges ahead.

Since the partnership was inked, Instil Bio has only enrolled 3 patients in its overseas clinical trials, a situation underpinned by its strained cash flow. As of the end of Q3 2025, Instil Bio’s cash and cash equivalents stood at a mere $5.8 million, insufficient to fund the overseas clinical development of the two novel drugs.

During the media briefing, Tian Wenzhi, CEO of Immunotech Biopharma, admitted that the company and Instil Bio had sought to pursue a secondary BD transaction, and had also engaged in active discussions with multiple MNCs, some of which expressed interest in the assets. However, Summit’s disclosure of underwhelming overall survival (OS) data triggered a wait-and-see sentiment in the market, which delayed their timeline for the secondary BD deal.

Faced with the emergence of more peer products and the aggressive catch-up of latecomers, even the promising IMM2510 could not afford to be complacent.

In terms of molecular design, IMM2510 boasts certain differentiated competitive advantages. It incorporates a VEGF receptor "trap" structure, enabling it to bind to multiple VEGF receptor ligands beyond VEGF-A, and exhibits antibody-dependent cell-mediated cytotoxicity (ADCC) effects.

Data on IMM2510 presented at the 2025 World Conference on Lung Cancer (WCLC) showed that among 17 evaluable patients with squamous non-small cell lung cancer (squamous NSCLC), the objective response rate (ORR) reached 35.3%, and the disease control rate (DCR) hit 76.5%; the median progression-free survival (mPFS) was 9.4 months, ranking among the top tier of similar PD-(L)1/VEGF products.

Tian Wenzhi described this "breakup" as "well-timed", because the company can now directly engage with potential partners and seize greater initiative.

Moving forward, Immunotech Biopharma still intends to prioritize advancing collaborations with MNCs, and has updated materials for multiple interested MNCs. The collaboration format can be either a full rights transfer or joint development. In addition, Immunotech Biopharma will also consider engaging with mid-sized biotech companies with urgent needs to expand their layout in this field, exploring the possibility of joint development.

More importantly, unlike in 2024, Immunotech Biopharma now holds more robust and solid clinical data in hand, which will serve as a strong bargaining chip in negotiations with potential buyers.

The story of the PD-(L)1/VEGF bispecific antibody track is far more than the ups and downs of just these few companies. It represents a complete cycle, evolving from scientific exploration to a commercial boom, and now into a phase of rational differentiation.

In 2024, the release of the first head-to-head clinical trial data between Yivomolimab and Keytruda quickly ignited market enthusiasm for PD-(L)1/VEGF bispecific antibodies. Multinational corporations (MNCs), plagued by the "patent cliff", flocked to China to "scout for promising drug candidates", with transaction values repeatedly setting new records.

For instance, Pfizer secured the rights to 3SBio's PD-1/VEGF bispecific antibody with a $1.25 billion upfront payment and $4.8 billion in milestone payments; Merck & Co. licensed LYXC's LM-299 with a potential total consideration of up to $3.288 billion; following Promiseland's acquisition by BioNTech, its original PD-L1/VEGF bispecific antibody PM8002 ultimately led to a multi-billion-dollar follow-up collaboration with Bristol Myers Squibb (BMS)...

Chris Boerner, CEO of BMS, stated plainly: "Competition will be extremely fierce. We do not want to be the fourth player, because market share will be captured by the first or second."

Capital's enthusiasm stems from immense market potential. Kaiyuan Securities pointed out that PD-(L)1/VEGF bispecific antibody drugs are expected to gradually replace the PD-(L)1 monoclonal antibody market, with the global market size projected to reach nearly $70 billion by 2028.

According to incomplete statistics, there are 29 PD-(L)1/VEGF bispecific antibodies under research worldwide, 21 of which are developed in China. As competition intensifies, differentiation within this track has already begun.

On one hand, MNC giants, leveraging their substantial financial resources and rich clinical experience, are rapidly advancing large-scale, multi-indication clinical trials. On the other hand, small biotech firms are facing increasingly high R&D barriers and financial pressures; any misstep could leave them struggling to keep pace.

From an industry-wide perspective, the competition in PD-(L)1/VEGF bispecific antibodies is shifting from the early "proof-of-concept" stage to a "proof-of-capability" phase that requires robust large-sample clinical data to validate value. This means that in the future, the players who can leverage efficient execution to be the first to obtain solid clinical data will have a greater chance of success.

Separately, the achievement of technology transfer milestones marks the entry of collaborations into a new phase.

In July 2025, the technology transfer of LM-299—the PD-1/VEGF bispecific antibody co-developed by LYXC and Merck & Co.—was successfully completed, triggering a $300 million milestone payment and representing the first major milestone fulfilled under the agreement. Technology transfer is a critical prerequisite for the global commercialization of drugs; this milestone signifies that Merck & Co. has officially taken over subsequent clinical development and production, paving the way for international multi-center trials.

The groundbreaking head-to-head trial achievement by Akeso is not an isolated case.

In October 2025, Junshi Biosciences announced that its PD-1/VEGF bispecific antibody JS207 had obtained FDA approval to initiate Phase II/III clinical trials. The trial will conduct a head-to-head comparison against BMS's PD-1 inhibitor Opdivo for the neoadjuvant treatment of patients with stage II/III, resectable, driver-gene negative non-small cell lung cancer.

Despite the numerous challenges ahead, this wave of PD-(L)1/VEGF bispecific antibody development, led by Chinese pharmaceutical companies, is reshaping the global landscape of cancer immunotherapy innovation.