18 March 2026, Abbisko Therapeutics Co., Ltd. ("Abbisko Therapeutics" hereafter, HKEX code: 02256) today announced that the first patient has been dosed in an investigator-initiated trial (IIT) in South Korea evaluating its independently developed, highly selective, oral small-molecule FGFR4 inhibitor irpagratinib (ABSK-011).

The study (IAPETUS) is designed to systematically evaluate the safety, tolerability, and efficacy of irpagratinib in combination with atezolizumab and bevacizumab (T+A) as a first-line treatment for patients with FGF19-overexpressing advanced or unresectable hepatocellular carcinoma (HCC). This represents a new exploration of ipagratinib in the first-line treatment of advanced HCC, in addition to the Phase II study evaluating its combination with toripalimab and bevacizumab biosimilar.

Primary liver cancer ranks as the third leading cause of cancer-related mortality worldwide, with HCC accounting for approximately 75%–85% of cases. In recent years, the combination of immunotherapy and anti-angiogenic therapy has become one of the standard first-line treatments for advanced HCC. However, increasing evidence suggests heterogeneous treatment responses across molecular subtypes.

A retrospective study conducted by Tongji Hospital, HUST demonstrated that, compared with patients with low FGF19 expression, those with FGF19 overexpression experienced a significantly shorter median progression-free survival (mPFS) when receiving first-line targeted immunotherapy combinations (6.1 months vs. 11.4 months; p<0.05; HR=0.45, 0.22–0.89) 1. A downward trend in objective response rate (ORR) was also observed (33.3% vs. 45.2%) ¹. The underlying mechanism may be associated with aberrant activation of the FGFR4/FGF19 signaling pathway. Preclinical studies indicate that activation of this pathway can upregulate PD-L1 expression in tumor cells, thereby promoting immune evasion and metastasis, and potentially attenuating the efficacy of immunotherapy-based combinations ^2,3.

Notably, approximately 30% of HCC patients exhibit FGF19 overexpression, representing a population with significant unmet medical needs under the current standard-of-care paradigm. Therefore, integrating FGFR4 inhibitor into existing standard treatment regimens may mechanistically enhance antitumor activity and provide additional clinical benefits for this patient population.

Irpagratinib is a highly selective, orally administered small-molecule FGFR4 inhibitor independently developed by Abbisko Therapeutics. In a previous Phase II study evaluating irpagratinib in combination with atezolizumab for HCC, the combination demonstrated favorable safety and tolerability along with antitumor activity, suggesting potential synergistic effects with immunotherapy. In addition to the IAPETUS study, Abbisko Therapeutics recently completed dosing of the first patient in a Phase II clinical trial evaluating irpagratinib in combination with toripalimab and bevacizumab biosimilar. Looking ahead, as more high-quality clinical studies continue to advance steadily, the evidence supporting irpagratinib as a first-line treatment for advanced HCC is expected to be further strengthened and expanded.

In parallel with combination development, irpagratinib has also achieved significant progress as a monotherapy. In May 2025, the drug was granted Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA), followed by the initiation of a pivotal registrational clinical study across more than 50 research centers nationwide. In February of this year, Abbisko Therapeutics also completed dosing of the first U.S. patient in the expansion phase of the global multicenter Phase I study of irpagratinib, further advancing its global clinical development program.

References

1. Cheng, Q., et al. (2025). 149MO Irpagratinib (ABSK-011) plus atezolizumab in first-line (1L) and immune checkpoint inhibitors (ICIs) treated advanced hepatocellular carcinoma (HCC) with FGF19 overexpression (+): Updated results of the phase II ABSK-011-201 study. Annals of Oncology.

2. Guo C, et al. FGF19/FGFR4 signaling contributes to hepatocellular carcinoma survival and immune escape by regulating IGF2BP1-mediated expression of PD-L1. Biomed Pharmacother. 2024 Jan;170:115955.

3. Xie M, et al. FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2. J Hepatol. 2023 Jul;79(1):109-125.

About Irpagratinib (ABSK-011)

Irpagratinib is a highly-selective FGFR4 small molecule inhibitor designed to target overexpression of the FGF19 signaling pathway. Several epidemiological studies indicate that approximately 30% of HCC patients worldwide exhibit FGF19 overexpression. Development of targeted therapies against FGFR4 represent an innovative and novel approach to the treatment of HCC.

To date, no FGFR4 inhibitor has been granted regulatory approval globally. According to Frost & Sullivan, irpagratinib is expected to become the first breakthrough treatment for the treatment of HCC patients with FGF19 overexpression.

In addition to monotherapy, Abbisko Therapeutics is exploring irpagratinib in combination with atezolizumab, an anti-PD-L1 antibody manufactured by F. Hoffmann-La Roche and Roche (China), in a Phase II study. At the the 2025 ESMO GI Congress, Abbisko presented clinical data showing that the combination of irpagratinib and atezolizumab achieved an objective response rate (ORR) exceeding 50% and a median progression-free survival (mPFS) of more than 7 months in FGF19-overexpressing HCC patients previously treated with immune checkpoint inhibitors.

About Abbisko Therapeutics

Founded in April 2016, Abbisko Therapeutics Co., Ltd. (HKEX: 02256.HK), is an oncology-focused biopharmaceutical company based in Shanghai that is dedicated to the discovery and development of innovative medicines to treat unmet medical needs in China and globally. The Company was established by a group of seasoned drug hunters with rich research & development and managerial expertise from top multinational pharmaceutical companies. Since its founding, Abbisko Therapeutics has built an extensive pipeline of innovative programs focused on precision oncology and immuno-oncology.

Please visit www.abbisko.com for more information.