When Chinese PD-(L)1/VEGF bispecific antibodies (BsAbs) recently disrupted the global innovative drug R&D market with a total of USD 30.5 billion in business development (BD) deals, a new revolution in the field of immuno-oncology had already begun and continues to unfold.

Looking back to 2014, cancer immunotherapy entered a new era with the emergence of PD-1 inhibitors, marking humanity's grasp of a new powerful weapon against cancer. Over the past decade, PD-(L)1 monoclonal antibodies (mAbs) have also triggered profound transformations in clinical treatments for various cancers.

Yet as PD-(L)1 monotherapy or combination chemotherapy regimens for major cancer types have been exhaustively explored, the efficacy ceiling in response rates has become evident, competition has intensified, and the shadow of patent cliffs looms quietly. The entire industry is thus urgently searching for the next key development to lead the transformation of cancer treatment.

The Setbacks in Pursuing the "Next PD-1" and the New Battleground of BsAbs

The quest for the "next PD-1" was once full of promise. Shortly after the advent of PD-1 drugs, researchers found their monotherapy response rate in cancer patients to be only around 20%. For a time, immune checkpoint inhibitors that could synergise with PD-1 mechanistically became R&D hotspots, including CTLA4, TIM-3, LAG3 and TIGIT.

However, Novartis' TIM-3 frontrunner sabatolimab (MBG453) failed in Phase III trials, Bristol Myers Squibb and MSD's LAG3 mAbs saw Phase III studies terminated, while Roche, MSD and BeiGene's TIGIT mAbs faced repeated setbacks. A decade of exploration and effort seemed to reveal a harsh reality: no single target could replicate the outcomes of anti-PD-1 strategies.

Just as target innovation reached a standpoint, iterative advances in BsAb technology brought a new turning point.

China-based Akeso's PD-1/VEGF BsAb ivonescimab (AK112) demonstrated significant progression-free survival (PFS) benefits in the HARMONi-2 head-to-head study, outperforming global top-seller Keytruda (pembrolizumab). The validation of AK112's clinical value not only highlighted the potential of BsAb technology but also pointed to a new direction for the evolution of cancer immunotherapy.

Major players have already entered the fray, making strategic moves through high-value deals — MSD, Pfizer and Bristol Myers Squibb/BioNTech SE have all invested heavily in licensing China's PD-(L)1/VEGF BsAb programs. This sends a clear signal: the focus of next-generation cancer immunotherapy development has fully shifted to the era of BsAbs. BsAbs are now taking up the torch of innovation, leading the future of cancer immunotherapy.

Immuno-Oncology BsAbs: A New Era in Cancer Therapy

In the race for next-generation cancer immunotherapies, China's innovation muscle cannot be ignored. After achieving global leadership in the PD-(L)1/VEGF BsAb field, the next wave of domestic immuno-oncology BsAbs is accelerating. Among them, Leads Biolabs' PD-L1/4-1BB BsAb LBL-024 has garnered widespread attention at the 2025 American Society of Clinical Oncology (ASCO) conference for its outstanding efficacy, rapidly emerging as a standout in next-generation BsAbs.

LBL-024's ability to secure two oral presentations at ASCO stems from its breakthrough efficacy data in extrapulmonary neuroendocrine carcinoma (EP-NEC), a field long plagued by treatment challenges. Its first-line combination chemotherapy data boasted overall response rate (ORR) of 83.3% and disease control rate (DCR) of 100%, marking a milestone in EP-NEC treatment. Its later-line monotherapy data also impressed with ORR 37.5% and DCR 50.0% in second-line treatment, offering tangible hope to address unmet needs in this area.

Moreover, LBL-024 has taken the global lead in development progress, poised to overcome the druggability challenges of the 4-1BB target. Previously, safety concerns were the key obstacle for 4-1BB-targeting drugs. LBL-024 conditionally activates the 4-1BB co-stimulatory pathway in the tumour microenvironment, minimising hepatotoxicity and widening the therapeutic window. Additionally, its high-affinity PD-L1 binding enables dual mechanisms for potent immune activation, boasting broader-spectrum cancer treatment potential than PD-(L)1 monotherapies. With these innovations, LBL-024 has become the world's first 4-1BB-targeting BsAb to enter pivotal trials.

LBL-024's clinical value extends far beyond EP-NEC. Promising efficacy signals have been observed in small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), biliary tract cancer and other malignancies, highlighting its potential as a next-generation broad-spectrum immuno-oncology BsAb.

This reflects Leads Biolabs' clear and forward-looking BsAb strategy: focusing on next-generation immuno-oncology bispecifics to address patients who are unresponsive to or relapse after traditional PD-(L)1 therapies. With LBL-024 as the vanguard, Leads Biolabs aims to tackle cancer immunotherapy's toughest challenges: drug resistance and unmet clinical needs.

In addition to this, Leads Biolabs has built the LeadsBody™ platform for T-cell engagers (TCEs), synergising with immuno-oncology bispecifics to target cold tumours (those resistant to conventional immunotherapies). Mechanistically, TCEs guide T-cells to cancer cells by binding both tumour surface antigens and T-cell CD3 receptors, offering a potential solution for these malignancies.

Unlike traditional TCEs focused on haematologic cancers, Leads Biolabs has strategically anchored itself in the broader solid tumour space. Another candidate, LBL-033, exemplifies this as world's second MUC16/CD3 BsAb to enter clinical trials, targeting MUC16-high solid tumours like ovarian, cervical and endometrial cancers. Preliminary efficacy signals and favourable tolerability have been observed in Phase I/II trials.

In haematologic malignancies, where TCEs are more established, Leads Biolabs has also built a competitive pipeline. LBL-034 leads globally as the second GPRC5D/CD3 BsAb to enter clinical development, with best-in-class potential. In relapsed/refractory multiple myeloma (r/r MM), it demonstrated strong antitumour activity and safety, achieving ORRs of 88.9% and 100% at 400 μg/kg and 800 μg/kg doses respectively.

Beyond LBL-034, Leads Biolabs is developing LBL-043, a potential first-in-class drug targeting LILRB4, which is highly expressed on acute myeloid leukemia (AML) cells, and CD3 to redirect T-cells against AML and r/r MM cells. This approach delivers potent antitumour activity while significantly reducing off-target toxicity.

TCEs are driving innovation not only in oncology but also in autoimmune diseases. Leads Biolabs' pioneering CD19/BCMA/CD3 trispecific TCE, LBL-051, exemplifies this. In November 2024, Leads Biolabs entered a USD 614 million strategic collaboration with US venture capital firm Aditum Bio via a new joint venture (NewCo) structure. Mechanistically, LBL-051 effectively blocks autoantibody production by B-cells and plasma cells while potentially suppressing B-cell hyperactivation, differentiation and plasma cell conversion, enabling superior therapeutic effects through multi-layered B-cell modulation.

Overall, Leads Biolabs has established a multidimensional TCE portfolio spanning solid tumours, haematologic malignancies and autoimmune diseases, securing its leadership in China's TCE therapy field. Backed by the LeadsBody™ platform, the company maintains sustainable R&D momentum to continuously deliver innovative programs.

Conclusion

The journey of cancer immunotherapy, beginning with PD-1, has spanned over a decade and now passes the torch to the era of immuno-oncology BsAbs. As the wave of innovation surges forward, true winners do not chase trends but forge foundational capabilities that endure through cycles.

The rise of Leads Biolabs in this new era of cancer immunotherapy vividly mirrors the evolution of China's innovative drug development: from being mired in an ocean of PD-1 mAb "fast-follow" strategies to achieving systematic innovation through proprietary technology platforms, ultimately cultivating globally competitive pioneering capabilities. This leap embodies the profound aspirations of the entire industry for China's innovative drug development over the past decade.