Ivonescimab's Regulatory Momentum and Clinical Differentiation in Lung Cancer: A Strategic Evaluation of Akeso's Position in Next-Gen Immunotherapy

In the rapidly evolving landscape of oncology, next-generation immunotherapies are redefining treatment paradigms, and Akeso Inc. (9926.HK) stands at the forefront with its PD-1/VEGF bispecific antibody, Ivonescimab. This molecule, developed as a dual-action therapy combining immune checkpoint inhibition with anti-angiogenic properties, has demonstrated compelling clinical differentiation in lung cancer trials, positioning Akeso as a key player in the global biopharma race.

Clinical Differentiation: A New Benchmark in Lung Cancer

Ivonescimab's recent Phase III HARMONi trial results underscore its potential to disrupt standard care. In patients with EGFR-mutated, platinum-resistant non-squamous NSCLC, the drug combination reduced progression-free survival (PFS) risk by 48% compared to chemotherapy alone (HR: 0.52; p<0.00001). This marked a statistically significant improvement over existing therapies and was consistent across both Asian and ex-Asia populations. More notably, in a head-to-head comparison against pembrolizumab in PD-L1-positive NSCLC (HARMONi-2), Ivonescimab achieved a median PFS of 11.14 months versus 5.82 months, with a hazard ratio of 0.51—a 49% reduction in progression risk. These results not only highlight Ivonescimab's superior efficacy but also its ability to outperform established PD-1 inhibitors in critical lung cancer indications.

The drug's mechanism—simultaneously blocking PD-1 and VEGF pathways—offers a unique advantage over monotherapies or combination regimens that require separate agents. This dual inhibition addresses both immune evasion and tumor vascularization, two key drivers of resistance in advanced cancers. Furthermore, the safety profile remains favorable, with no new safety signals reported in Phase III trials, despite the addition of chemotherapy.

Regulatory Momentum: Navigating the Path to Approval

While the U.S. Food and Drug Administration (FDA) has emphasized the need for a statistically significant overall survival (OS) benefit for marketing authorization, Ivonescimab's OS trend in the HARMONi trial (HR: 0.79) is clinically meaningful, particularly in a setting where no approved regimens have demonstrated OS improvements. Summit Therapeutics, Akeso's U.S. partner, is actively evaluating the timing of its Biologics License Application (BLA) filing, with data expected to be presented at a major medical conference.

In China, Ivonescimab has already secured two NMPA approvals in 2025: one for first-line PD-L1-positive NSCLC and another for EGFR-TKI-resistant non-squamous NSCLC. These approvals, based on robust Phase III data, have been bolstered by inclusion in the National Reimbursement Drug List (NRDL), ensuring broad patient access. Akeso's ability to navigate regulatory pathways in diverse markets—China, U.S., and beyond—demonstrates its operational agility and deep understanding of global oncology needs.

Strategic Partnerships and Global Expansion

Akeso's partnerships are central to its growth strategy. The collaboration with Summit Therapeutics has enabled global Phase III trials across multiple lung cancer subtypes, including HARMONi-3 (squamous and non-squamous NSCLC) and HARMONi-7 (PD-L1-high NSCLC). Meanwhile, the Pfizer partnership to combine Ivonescimab with antibody-drug conjugates (ADCs) in solid tumors opens new therapeutic avenues. These alliances not only de-risk clinical development but also amplify Akeso's commercial footprint.

The company is also expanding Ivonescimab's indications into pancreatic and triple-negative breast cancers, where its dual mechanism may overcome immunosuppressive tumor microenvironments. With over 12 Phase III trials ongoing, Akeso is building a robust pipeline that positions Ivonescimab as a cornerstone of next-gen immunotherapy.

Market Potential and Shareholder Value

The projected $500 million market size for Ivonescimab in 2025 reflects its growing adoption in China and the Asia-Pacific region, where rising cancer incidence and healthcare investments are driving demand. Akeso's revenue from Ivonescimab and its other blockbuster, cadonilimab, grew 25% year-on-year in 2024 to RMB 2 billion, underscoring its commercial strength. The hospital-administered 100 mg formulation dominates the market, aligning with Akeso's focus on specialized delivery channels.

With a 15% CAGR projected through 2033, Akeso's market share in next-gen immunotherapy is poised to expand further. The company's integrated R&D platforms, including the ACE and Tetrabody technologies, provide a competitive edge in developing first-in-class therapies. Additionally, its first ADC candidate, AK138D1, entering Phase I trials, diversifies its pipeline and enhances long-term value.

Investment Implications

For long-term investors, Akeso's strategic focus on Ivonescimab and its broader pipeline represents a compelling opportunity. The drug's clinical differentiation, regulatory momentum, and global expansion potential align with the growing demand for innovative cancer treatments. While the FDA's OS requirement may delay U.S. approval, the interim OS trend and positive PFS results justify a cautious bullish outlook.

Akeso's ability to balance clinical innovation with commercial execution—evidenced by its NRDL inclusion and revenue growth—positions it to capture significant market share. Investors should monitor the BLA filing timeline and the outcomes of ongoing trials, particularly HARMONi-3 and HARMONi-7, which could unlock new indications and geographies.

In conclusion, Ivonescimab's regulatory and clinical momentum, coupled with Akeso's strategic partnerships and market insights, make it a standout in the next-gen immunotherapy space. For those seeking exposure to a company redefining cancer care, Akeso offers a compelling case for long-term value creation.