PD-1/VEGF Bispecific Antibody Landscape 2026: The Hottest Pipeline in Oncology
Ivonescimab just beat Keytruda. $15B+ in licensing deals signed. Here's what every BD executive needs to know about the bispecific revolution.
The Bispecific Inflection Point
In late 2025, Akeso's ivonescimab became the first drug to demonstrate statistically significant superiority over Merck's Keytruda—the world's best-selling drug ($25B+ annual revenue)—in a head-to-head Phase III trial. This single data readout triggered a seismic shift in oncology deal-making and validated PD-1/VEGF bispecific antibodies as the most consequential new modality since checkpoint inhibitors themselves.
Executive Summary
The PD-1/VEGF bispecific antibody class represents the single largest licensing opportunity in oncology for 2026. With ivonescimab's HARMONi-2 data demonstrating superiority over Keytruda in first-line NSCLC, the competitive dynamics of the $50 billion PD-1 market are being fundamentally rewritten.
For business development professionals, the implications are profound. At least nine PD-1/VEGF bispecific candidates are in clinical development globally, the vast majority originating from Chinese biotechs. The Akeso-Summit deal ($5 billion total value) has established the pricing benchmark, but significant white space remains for in-licensing across geographies and indications.
This analysis provides BD teams with a comprehensive landscape assessment: pipeline-by-pipeline clinical positioning, deal structure benchmarks, market sizing, and a strategic framework for evaluating PD-1/VEGF bispecific licensing opportunities.
The Scale of Opportunity
The Science: Why PD-1/VEGF Dual Blockade Matters
For BD professionals evaluating this space, understanding the mechanistic rationale is essential for due diligence. PD-1 and VEGF are two of the most validated targets in oncology, but their co-inhibition in a single molecule creates pharmacological properties that cannot be replicated by simply combining two separate drugs.
PD-1 Blockade: Releasing the Brakes
PD-1 (Programmed Death-1) is an immune checkpoint receptor on T-cells. Tumors exploit PD-1 signaling to evade immune destruction. Blocking PD-1 restores T-cell anti-tumor activity. This mechanism underpins Keytruda ($25B), Opdivo ($9B), and the entire checkpoint inhibitor class.
VEGF Blockade: Starving the Tumor
VEGF (Vascular Endothelial Growth Factor) drives angiogenesis—the formation of new blood vessels that feed tumors. VEGF also creates an immunosuppressive tumor microenvironment. Anti-VEGF agents like bevacizumab (Avastin, $7B peak sales) normalize tumor vasculature and enhance immune cell infiltration.
The Bispecific Advantage: Forced Co-Engagement
A bispecific antibody simultaneously binds PD-1 on T-cells and VEGF in the tumor microenvironment. This creates a physical bridge that concentrates immune activation precisely where the tumor is creating immunosuppressive conditions. This "forced co-engagement" cannot be replicated by co-administering two separate antibodies—and it forms the basis of the bispecific antibody's differentiated IP and clinical profile.
BD Implication: The IP Moat
Pipeline Overview: The Global PD-1/VEGF Bispecific Race
At least nine PD-1/VEGF bispecific antibodies are in clinical development globally. The striking feature of this pipeline is its geographic concentration: the majority originate from Chinese biotechs, reflecting China's emergence as the global epicenter of bispecific antibody innovation.
PD-1/VEGF Bispecific Antibody Pipeline (2026)
| Candidate | Developer | Stage | Origin | Licensing Status |
|---|---|---|---|---|
| Ivonescimab (AK112) | Akeso / Summit | Phase III (Pivotal) | China | Summit (ex-China, $5B) |
| SSGJ-707 | Sunshine Guojian / 3SBio | Phase III | China | Pfizer (ex-China, undisclosed) |
| PM8002 | PharmaBlock / Keymed | Phase II/III | China | Available (select regions) |
| BNT327/PM8002 | BioNTech | Phase III | China/Germany | Licensed from Biotheus |
| HLX301 | Henlius (Shanghai) | Phase II | China | Available |
| IBI363 | Innovent Biologics | Phase II | China | Available (ex-China) |
| JS207 | Jiangsu Junshi | Phase I/II | China | Available |
| ABL202 | ABL Bio (Korea) | Phase I | Korea | Available |
| RC148 | RemeGen | Phase I | China | Available |
The Licensing Window
Clinical Data: The HARMONi-2 Watershed
The HARMONi-2 trial was the defining clinical event of 2025 in oncology—and its implications for the licensing market cannot be overstated.
HARMONi-2 Phase III Key Results (NSCLC 1L, PD-L1 ≥1%)
These results are unprecedented. No drug has ever demonstrated a statistically significant PFS improvement over Keytruda monotherapy in first-line PD-L1-positive NSCLC. The hazard ratio of 0.51 suggests ivonescimab nearly halves the risk of disease progression compared to the current standard of care.
Clinical Context for BD Professionals
From a deal-making perspective, HARMONi-2 established several critical precedents:
- Validated the Bispecific Mechanism: The data confirms that PD-1/VEGF dual blockade in a single molecule provides clinically meaningful benefit beyond what either pathway alone delivers.
- De-Risked Follow-On Candidates: Every PD-1/VEGF bispecific in the pipeline benefits from this mechanistic validation. The probability of technical success for the class has increased substantially.
- Reset Valuation Benchmarks: Pre-HARMONi-2, PD-1/VEGF bispecifics were valued as speculative. Post-HARMONi-2, they are valued as validated potential blockbusters.
- Created Urgency for Big Pharma: Merck, Bristol-Myers Squibb, and Roche—the three largest checkpoint inhibitor franchises—must now develop competitive responses, driving inbound licensing demand.
The Deal Landscape: $15B+ in Bispecific Transactions
The PD-1/VEGF bispecific space has generated some of the largest licensing deals in recent biopharma history. These transactions establish the valuation framework for BD teams evaluating remaining opportunities.
Akeso — Summit Therapeutics: The Benchmark Deal
Akeso Inc. → Summit Therapeutics • PD-1/VEGF Bispecific (Ivonescimab)
Akeso, a Guangdong-based biotech, needed a Western partner to commercialize ivonescimab outside Greater China while retaining full rights in its home market.
Summit Therapeutics acquired exclusive ex-China rights to ivonescimab in a deal valued up to $5 billion, including $500 million upfront and substantial regulatory and commercial milestones.
Summit's market cap surged from ~$200M to over $5B post-deal. The transaction validated the China-to-West licensing model and set the benchmark for PD-1/VEGF bispecific valuations.
Key PD-1/VEGF & Bispecific Licensing Deals (2024-2026)
| Licensor | Licensee | Asset | Total Value | Upfront |
|---|---|---|---|---|
| Akeso | Summit Therapeutics | Ivonescimab (AK112) | $5.0B | $500M |
| 3SBio/Sunshine Guojian | Pfizer | SSGJ-707 | Undisclosed (est. $2B+) | Undisclosed |
| Biotheus | BioNTech | PM8002 (BNT327) | $1.3B+ | $85M |
| Hengrui Medicine | Merck KGaA | SHR-1905 (bispecific) | $1.4B | $160M |
Market Opportunity: The $30B+ Prize
The addressable market for PD-1/VEGF bispecific antibodies is defined by the existing PD-1 inhibitor market—one of the largest therapeutic markets in pharmaceutical history.
PD-1/VEGF Bispecific Market Projection
Indication Expansion Opportunity
PD-1 inhibitors are currently approved across 30+ cancer indications. PD-1/VEGF bispecifics have the potential to improve outcomes in many of these settings, particularly in:
- Non-Small Cell Lung Cancer (NSCLC): The largest indication. HARMONi-2 data positions ivonescimab as a potential first-line standard of care.
- Hepatocellular Carcinoma (HCC): Where the PD-1 + bevacizumab combination (Tecentriq + Avastin) is already standard of care—validating dual blockade.
- Renal Cell Carcinoma (RCC): Another indication where IO + anti-angiogenic combos have succeeded.
- Endometrial, Cervical, and Head & Neck Cancers: Emerging areas where the VEGF microenvironment is highly relevant.
The rNPV Multiplier Effect
Competitive Positioning: Bispecific vs Combination Therapy
The central strategic question for BD teams: does the bispecific format offer durable competitive advantages over combination therapy using two separate approved drugs?
Bispecific Antibody vs Combination Therapy: Strategic Comparison
| Dimension | In-Licensing | Out-Licensing |
|---|---|---|
Mechanism How targets are engaged. | Single molecule, dual target | Two separate molecules co-administered |
Efficacy Potential Theoretical pharmacological advantage. | Forced co-engagement on same cell | Independent target engagement |
Dosing Patient convenience and compliance. | Single infusion | Two separate infusions |
Manufacturing Production scalability. | Complex (single bispecific) | Standard (two known molecules) |
IP Position Patent protection and exclusivity. | Novel composition of matter | Limited (combo of existing drugs) |
Pricing Power Commercial margin potential. | Premium (novel biologic) | Constrained (biosimilar pressure on components) |
The verdict from a BD perspective is clear: bispecifics offer superior IP protection, pricing power, and potentially superior efficacy. The manufacturing complexity is the primary trade-off, but companies like Samsung Biologics and Lonza are rapidly building bispecific-capable manufacturing capacity to address this bottleneck.
The China Innovation Engine
Perhaps the most striking feature of the PD-1/VEGF bispecific landscape is that 7 of 9 clinical-stage candidates originate from Chinese biotechs. This is not coincidental—it reflects China's emergence as the global leader in bispecific antibody innovation, driven by several structural factors:
Massive Oncology Patient Pool
China's 4.8 million new cancer diagnoses annually provide clinical trial enrollment speed that is structurally impossible in the West. Ivonescimab's HARMONi-2 trial enrolled faster than comparable Western trials.
Antibody Engineering Talent
Chinese institutions have invested heavily in protein engineering capabilities. The density of bispecific antibody expertise—particularly in the Guangdong, Shanghai, and Jiangsu biotech clusters—is now world-leading.
Cost-Efficient Discovery
The cost of taking a bispecific antibody from discovery through Phase I in China is approximately 30-40% lower than in the US or EU—creating an innovation arbitrage that sophisticated licensees can capture.
BIOSECURE Act Considerations
BD Strategy: How to Evaluate PD-1/VEGF Bispecific Opportunities
For BD teams actively evaluating PD-1/VEGF bispecific licensing opportunities, we recommend the following diligence framework:
Assess Clinical Differentiation vs Ivonescimab
Ivonescimab is the first-mover. Any follow-on candidate must demonstrate either superior efficacy, a better safety profile, an improved dosing schedule, or clinical data in indications where ivonescimab is not yet being developed. Generic "me-too" bispecifics will struggle to justify premium deal terms.
Evaluate Manufacturing Readiness
Bispecific antibodies are significantly more complex to manufacture than standard monoclonal antibodies. Assess the candidate's CMC package, including expression yield, purification strategy, stability data, and whether a GMP-ready process exists for non-Chinese manufacturing.
Model Multi-Indication rNPV
The value of a PD-1/VEGF bispecific is not in a single indication—it is in the franchise potential across 10+ cancer types. Use the Akeso-Summit deal as a comp and model probability-weighted rNPV across NSCLC, HCC, RCC, endometrial, cervical, and emerging indications.
Negotiate Regional Carve-Outs
Most Chinese biotechs prefer to retain China/Greater China rights. Smart deal structuring can carve out US/EU, Japan, or emerging market territories—enabling smaller licensees to access these assets without competing for global rights against Big Pharma.
Conclusion: The Bispecific Era Has Arrived
The PD-1/VEGF bispecific antibody class is not speculative—it is clinically validated, commercially de-risked, and backed by $15+ billion in licensing transactions. For business development teams, this represents the most significant in-licensing opportunity in oncology since the original checkpoint inhibitor wave.
The window for early-mover advantage is closing. With ivonescimab heading toward FDA filing and several follow-on candidates advancing through Phase II/III, the remaining unlicensed assets will not stay available for long. BD teams that move decisively—armed with rigorous clinical and commercial diligence—will secure access to a multi-decade oncology franchise.
At Vision Lifesciences, our team has deep expertise in cross-border oncology licensing, with direct relationships across China's bispecific antibody ecosystem. We help Western pharma companies identify, diligence, and structure licensing deals for novel oncology assets—from first contact through term sheet to close.