Ivonescimab: A Game-Changer in Advanced Squamous NSCLC Therapy and a Strong Buy for Akeso, Inc.

The landscape of advanced squamous non–small cell lung cancer (sq-NSCLC) treatment is undergoing a seismic shift with the emergence of ivonescimab, a first-in-class PD-1/VEGF bispecific antibody developed by Akeso, Inc. The HARMONi-6 trial, which evaluated ivonescimab in combination with chemotherapy against tislelizumab plus chemotherapy, has delivered transformative clinical data, positioning the drug as a potential new standard of care. For investors, this represents not just a medical breakthrough but a compelling investment opportunity in Akeso, a company poised to capitalize on its innovative pipeline and regulatory momentum.

Clinical Excellence: PFS, PD-L1 Efficacy, and Quality of Life

The HARMONi-6 trial demonstrated that ivonescimab plus chemotherapy significantly prolonged progression-free survival (PFS) compared to the tislelizumab-based regimen. The median PFS was 11.1 months for ivonescimab versus 6.9 months for tislelizumab, with a hazard ratio (HR) of 0.60 (P < 0.0001) according to the study. This 4.24-month absolute improvement is clinically meaningful in a disease where treatment options remain limited. Notably, the benefit was consistent across all PD-L1 expression subgroups, a critical differentiator in an era where biomarker-driven therapies often exclude subsets of patients.

Beyond survival, ivonescimab also showed a marked improvement in quality of life (QoL). The time to deterioration in global health status was significantly delayed, with an HR of 0.94, suggesting that patients maintained better functional status for longer. This dual benefit-extending life and enhancing its quality-positions ivonescimab as a superior first-line option. Safety data further bolster its case: no new adverse signals were identified, and grade 3 or higher bleeding events were comparable between arms according to ASCO.

Regulatory Momentum and Market Access

Regulatory validation has accelerated ivonescimab's path to market. In July 2025, China's NMPA accepted the supplemental New Drug Application (sNDA) for ivonescimab in combination with chemotherapy for advanced sq-NSCLC. This follows its inclusion in the 2025 National Reimbursement Drug List (NRDL), which has already enhanced patient access and reduced out-of-pocket costs. The NRDL listing is a critical catalyst, as it aligns with China's broader push to improve oncology care and is expected to drive adoption rates.

Globally, Akeso is advancing ivonescimab in the HARMONi-3 trial, comparing it to pembrolizumab plus chemotherapy in both squamous and non-squamous NSCLC according to Akeso's announcement. Success in this trial could unlock broader label expansion and international commercialization, further amplifying revenue potential.

Financial Strength and Strategic Positioning

Akeso's financials underscore its ability to scale and sustain innovation. In the first half of 2025, the company reported commercial sales of RMB1,401.6 million, a 49.2% year-over-year increase, driven largely by ivonescimab's adoption. Despite aggressive R&D spending (RMB731.2 million for H1 2025), Akeso maintains robust cash reserves of RMB7,138.4 million, providing flexibility to fund trials and expand its commercial footprint.

The market potential for ivonescimab is substantial. With a projected CAGR of 18% from $750 million in 2025, the drug is on track to become a blockbuster. This growth is underpinned by its inclusion in the NRDL, its broad PD-L1 efficacy, and Akeso's leadership in global commercialization. Moreover, Akeso's IO2.0 + ADC2.0 strategy, including next-generation ADCs, diversifies its pipeline and strengthens its competitive moat.

Competitive Landscape and Long-Term Outlook

While competitors like Merck's pembrolizumab and Bristol-Myers Squibb's atezolizumab dominate the PD-1 space, ivonescimab's bispecific design offers a unique mechanism combining immune checkpoint inhibition and antiangiogenic activity. This dual action addresses resistance pathways seen in monotherapies, a key advantage in a disease where treatment resistance remains a major hurdle.

Akeso's broader portfolio, including cadonilimab (a PD-1/CTLA-4 bispecific antibody) and multiple ADC programs, further insulates it from single-drug risk. With 13 global registrational trials for ivonescimab and a strong cash position, the company is well-positioned to navigate the high-stakes oncology market.

Conclusion: A Strong Buy for Shareholders

For investors, ivonescimab represents a rare confluence of clinical differentiation, regulatory progress, and financial strength. The HARMONi-6 trial's transformative data, coupled with NRDL inclusion and global trial expansion, creates a clear path to market leadership. Akeso's ability to scale sales, manage R&D costs, and diversify its pipeline further enhances its appeal. As the oncology landscape evolves, ivonescimab is not just a game-changer for sq-NSCLC-it is a catalyst for Akeso's long-term growth and shareholder value.