New Frontier of Bispecific Antibody BD in China After PD-(L)1/VEGF

China’s biopharma industry is cementing its position as a global leader in bispecific antibodies (BsAbs), with license-out deals totaling $9.257 billion in the first half of 2025, surpassing 2024’s full-year figure of $9.154 billion. Upfront payments reached $1.345 billion, nearly matching 2024’s $1.429 billion. A landmark $6.05 billion deal (with $1.25 billion upfront) between 3SBio Inc. and Pfizer Inc. for a PD-1/VEGF BsAb underscores the sector’s momentum. As the PD-(L)1/VEGF track matures, Chinese companies are pivoting to novel target combinations in ophthalmology, hematologic malignancies, autoimmune diseases, and solid tumors. This report explores these emerging opportunities, highlights key players like Jiangsu Hengrui Medicine, Innovent Biologics, and SystImmune, and assesses their competitive edge against global giants like Roche, Amgen, Gilead, Boehringer Ingelheim, and Novartis. With innovative mechanisms and robust clinical data, Chinese BsAbs are poised to drive over $12 billion in deals in 2025, reshaping the global biopharma landscape.

1. Ophthalmology: Ang2/VEGF BsAbs as a Strategic Growth Area

The ophthalmology market offers a high-potential niche for BsAbs, driven by unmet needs in diabetic macular edema (DME) and age-related macular degeneration (AMD). Roche’s faricimab, the only approved Ang2/VEGF-A BsAb, generated $4.4 billion in 2024 by inhibiting dual angiogenesis pathways, reducing retinal exudation, stabilizing vasculature, and extending dosing to every four months. Roche’s next-generation zifibancimig, targeting six-month dosing, is in development, highlighting the demand for longer-acting therapies.

Chinese Pipeline

• Y400 (Youzhiyou/Kangzhe): Phase I/II trials for DME and AMD show early efficacy in vision improvement.
• ASKG712 (Osaikang/Aimu Medical): Phase I DME data reported an 8.7–10.7 letter improvement in best-corrected visual acuity (BCVA) at day 84, with sustained reductions in central subfield thickness (CST) to day 168.
• IBI-324 (Innovent Biologics): Preclinical data showed 4–5x higher VEGF binding affinity and 100x higher Ang-2 activity than faricimab. Phase I DME trials demonstrated improved vision and retinal anatomy.

Global Competitors and Competitive Landscape

• Boehringer Ingelheim’s BI 836880 (Ang2/VEGF) is in Phase II for wet AMD, with interim data expected in Q4 2025. Novartis, with their Brolucizumab, and Regeneron’s Eylea are leading the VEGF space, but Chinese BsAbs are positioning themselves as contenders with potential for longer dosing intervals and favorable safety profiles.

BD Outlook

The Ang2/VEGF track’s high market potential and limited competition make it a prime candidate for license-out deals. Chinese firms delivering Phase II data confirming efficacy and dosing advantages could secure lucrative partnerships.

2. Hematologic Malignancies and Autoimmune Diseases: T-Cell Engagers (TCEs) Expand Horizons

TCE BsAbs, which redirect T cells to target cancer or pathogenic cells, dominate hematologic malignancies, with 9 of 11 globally approved TCEs targeting blood cancers. The core targets—CD3/BCMA, CD3/CD20, and CD3/CD19—account for eight approvals. Amgen’s Blincyto (CD3/CD19) achieved $1.216 billion in 2024 sales, validating the commercial potential.

Chinese TCE Pipeline

• CD3/BCMA: Leading the BD charge, with SystImmune, Keymed Biosciences, UCT Biotech, and Harbour BioMed securing deals worth over $2.6 billion for multiple myeloma therapies.
• CD3/CD20: Data from Chia Tai Tianqing shows 25% ORR in lupus nephritis (Phase I), while Tongrun Bio’s Phase I candidate targeting ITP shows a 20% response rate.

Global Landscape

• Gilead’s Kite Pharma and Amgen lead with CAR-T technologies like Kymriah and Blincyto, which have revolutionized the hematological cancer space. However, Chinese TCEs offer dual oncology-autoimmune applications, providing a competitive edge, particularly in underserved autoimmune markets.

BD Outlook

The CD3/BCMA track is well-positioned for continued deal momentum, while CD3/CD20 and CD3/CD19’s expansion into autoimmune diseases could drive new partnerships as Phase II data emerges.

3. Solid Tumors: TCEs and Dual Pathway Blockade Gain Traction

BsAbs for solid tumors are advancing through TCEs and dual pathway blockade, addressing resistance and the complex tumor microenvironment. Key TCEs in solid tumors, like CD3/DLL3 for SCLC and CD3/CLDN18.2 for gastric cancer, are showing promising early data.

Solid Tumor TCEs in Development

• CD3/DLL3: Amgen’s tarlatamab, approved for SCLC, generated $115 million in H1 2025. Chinese leaders Hengrui and Innovent are advancing their own CD3/DLL3 BsAbs, with Phase I data showing an ~30% ORR.
• CD3/CLDN18.2: Targeting gastric and pancreatic cancers, Qilu Pharmaceutical’s Phase III trial for pancreatic cancer reported a 45% ORR in interim data. Innovent, Lunan Pharma, and Junshi Biosciences are advancing candidates.

Dual Pathway Blockade

• EGFR/c-Met: Johnson & Johnson’s amivantamab has shown significant PFS in NSCLC, with Biotheus/Hansoh (Phase II/III) and Betta Pharmaceuticals (MCLA-129, Phase II) leading Chinese efforts.
• PD-1/LAG3 and PD-1/CTLA-4 Combinations: These are showing promising results, with companies like Akeso (AK104) seeing a 40% ORR in gastric cancer in Phase II trials. This combination is gaining traction and is a likely candidate for BD deals in 2025.

Global Competitors

Global giants like J&J and Bristol Myers Squibb dominate EGFR/c-Met combinations, but Chinese firms are innovating in novel TCEs and PD-(L)1 combinations, offering differentiation in complex solid tumors.

BD Outlook

CD3/CLDN18.2 and PD-(L)1 combinations are high-potential tracks for 2025 deals, driven by strong early data and unmet needs in gastric and pancreatic cancers.

4. Key Players and Emerging Trends

Leading Companies

• Innovent Biologics: IBI-324 (Ang2/VEGF) leads in ophthalmology, with Phase II DME data expected in Q1 2026.
• SystImmune: SMET-12 (CD3/EGFR) and CMDE005 are frontrunners for NSCLC, with BD talks underway.
• Jiangsu Hengrui Medicine: Advancing CD3/DLL3 and CD3/EGFR BsAbs, with Phase II SCLC data due in 2026.
• 3SBio Inc.: The Pfizer deal sets a precedent for high-value partnerships.

Emerging Trends

• Clinical Data as a Driver: Phase II/III data from ASKG712, IBI-324, and SMET-12 will unlock major BD deals.
• Innovative Mechanisms: Masking peptides (e.g., CMDE005) and novel combinations (e.g., PD-(L)1/TIGIT) enhance safety and efficacy.
• Autoimmune Expansion: CD3/CD20 and CD3/CD19 TCEs are gaining traction in SLE and ITP, with early data supporting BD potential.
• Global Leadership: Chinese firms are shifting from followers to leaders, competing with Roche and Amgen in ophthalmology and solid tumors.

5. Conclusion

China’s BsAb sector is entering a transformative phase, with Ang2/VEGF in ophthalmology, CD3/BCMA, CD3/CD20, and CD3/CD19 in hematologic and autoimmune diseases, and CD3/DLL3, CD3/CLDN18.2, CD3/EGFR, and EGFR/c-Met in solid tumors driving the next wave of BD deals. Strong clinical data, innovative mechanisms like masking peptides, and dual oncology-autoimmune applications position Chinese companies as global leaders. With over $12 billion in projected deals for 2025, firms like Innovent, SystImmune, and Hengrui are set to redefine the BsAb landscape.

Sources:

Wang Y. et al., JCO 43, 2527, 2025; BioNTech PR, Feb 3 2025; Akeso pipeline, Jul 2025; Boehringer Ingelheim CTDB NCT03861234, Jul 2025; Amgen 2024 Annual Report; BeiGene Q2 2025; Qilu Pharma pipeline, Jul 2025; SystImmune pipeline, Aug 2025; Innovent pipeline, Aug 2025; Harbour BioMed pipeline, Aug 2025; Regeneron Eylea overview; Pfizer & 3SBio PR, Jul 2025; Yaozhi BsAb tracker, Jul 2025; Synapse by PatSnap asset data (IBI-324, ASKG712, 3SB-210); BioBAY investor decks (Innovent, SystImmune, KeyMed, Akeso), Q2 2025; YZY Biopharma PR, Jun 2025; Ophthalmology Times, Apr 2025; PharmCube NextPharma DB, Aug 2025; ARVO 2025 Abstract;