Akeso's AK130: Pioneering the TIGIT/TGF-β Dual-Pathway Revolution in Pancreatic Cancer

In the high-stakes arena of immuno-oncology, first-mover advantage often defines market leadership. Akeso Inc. (9926.HK) is positioning itself as a trailblazer with AK130, a TIGIT/TGF-β bifunctional antibody fusion protein now in a registrational Phase II trial for advanced pancreatic cancer. This development not only underscores Akeso's strategic agility but also highlights the growing urgency to address one of oncology's most intractable challenges.

AK130: A Dual-Pathway Disruptor

Pancreatic cancer remains a therapeutic black hole, with a five-year survival rate of less than 10% and limited progress in systemic therapies. The tumor microenvironment (TME) is notoriously immunosuppressive, dominated by TGF-β signaling and TIGIT-mediated inhibition of T-cell and NK-cell activity. Akeso's AK130 directly targets these pathways, combining an anti-TIGIT monoclonal antibody with the extracellular domain of the human TGF-β receptor II. This dual blockade aims to reactivate exhausted immune cells while neutralizing the tumor's immunosuppressive defensesAkeso Announces First Patient Dosed in Registrational Phase II Study of TIGIT/TGF-β Bifunctional Antibody Fusion Protein AK130 Combined with Ivonescimab for Advanced Pancreatic Cancer^[1].

The Phase II AK130-202 trial, initiated in September 2025, evaluates AK130 in combination with ivonescimab (a PD-1/VEGF bispecific antibody) for patients with locally advanced or metastatic pancreatic cancer who have failed up to two prior lines of therapyDespite the setbacks, interest in TGF-β remains^[3]. Preclinical data suggest that this combination could synergistically enhance anti-tumor immunity by simultaneously blocking PD-1/PD-L1 and TIGIT/CD155 interactions while inhibiting TGF-β's immunosuppressive effectsAkeso Announces First Patient Dosed in Registrational Phase II Study of TIGIT/TGF-β Bifunctional Antibody Fusion Protein AK130 Combined with Ivonescimab for Advanced Pancreatic Cancer^[1]. This layered approach addresses multiple checkpoints of immune evasion, a critical innovation in a disease where monotherapies have historically failed.

First-Mover Edge in a High-Risk, High-Reward Space

Akeso's lead in TIGIT/TGF-β dual-pathway inhibition is unparalleled. While competitors like Merck KGaA/GSK (bintrafusp alfa) and Novartis (nisevokitug) have faced setbacks in TGF-β-targeted therapies, AK130's unique bifunctional design mitigates some of the risks associated with monospecific agents. According to a report by Oncology Pipeline, Akeso is the only company with a TIGIT/TGF-β bifunctional antibody in registrational trials, a distinction that positions it to capture significant market share if the Phase II results meet expectationsDespite the setbacks, interest in TGF-β remains^[3].

The competitive landscape further amplifies this advantage. Dual anti-PD-(L)1/TGF-β inhibitors like M7824 have shown enhanced antitumor activity compared to monotherapies, validating the potential of combination strategiesDual anti-PD-(L)1/TGF-β inhibitors in cancer immunotherapy – A review^[4]. Akeso's parallel exploration of AK130 with AK112 (an anti-PD-1/CTLA-4 bispecific antibody) in another Phase II trial (NCT07114315) underscores its commitment to optimizing therapeutic synergyA Study of AK130 in Combination With AK112 for the Treatment of Advanced Pancreatic Cancer^[2]. This dual-combination strategy could redefine the standard of care for pancreatic cancer, where current options like chemotherapy and single-agent immunotherapy offer limited durability.

Market Potential: A $5.84 Billion Opportunity by 2030

The pancreatic cancer treatment market is projected to grow at a compound annual growth rate (CAGR) of 12.3%, reaching $5.84 billion by 2030Pancreatic Cancer Treatment Market | Industry Report^[5]. Akeso's focus on TIGIT/TGF-β inhibition aligns with a broader industry shift toward immune checkpoint combinations. The TGF-β superfamily's role in tumor progression and immune evasion makes it a high-priority target, with preclinical evidence suggesting that dual blockade of TIGIT and TGF-β could overcome resistance to PD-1 inhibitorsA Study of AK130 in Combination With AK112 for the Treatment of Advanced Pancreatic Cancer^[2].

Moreover, the global Anti-TIGIT antibody market is forecasted to grow at a CAGR of 18.2%, reaching $2.1 billion by 2033Anti-TIGIT Antibody Market Size, Market Trends & Forecast 2033^[6]. Akeso's early mover status in this segment, coupled with its robust clinical pipeline, positions it to capture a disproportionate share of this growth. The company's bifunctional approach also reduces the complexity and cost of combination therapies, a critical differentiator in a market where multi-drug regimens often face reimbursement hurdles.

Risks and Mitigants

While the potential is vast, Akeso's strategy is not without risks. TGF-β inhibition has historically been associated with off-tumor toxicity, and dual-pathway targeting could exacerbate adverse events. However, Akeso's fusion protein design—which selectively neutralizes TGF-β signaling without systemic suppression—may mitigate these risksAkeso Announces First Patient Dosed in Registrational Phase II Study of TIGIT/TGF-β Bifunctional Antibody Fusion Protein AK130 Combined with Ivonescimab for Advanced Pancreatic Cancer^[1]. Additionally, the company's focus on biomarker-driven patient selection (e.g., TGF-β expression levels, TIGIT ligand density) could enhance therapeutic precision and improve safety profilesDespite the setbacks, interest in TGF-β remains^[3].

Conclusion: A Strategic Bet on Immuno-Oncology's Next Frontier

Akeso's AK130 represents a bold leap into the uncharted territory of dual-pathway immuno-oncology. By combining TIGIT and TGF-β inhibition with complementary bispecific agents, the company is addressing pancreatic cancer's most formidable defenses. With a registrational Phase II trial underway and a growing market hungry for breakthroughs, Akeso's first-mover advantage is not just a strategic asset—it's a potential catalyst for a new era in oncology.