Clinical data for HLB’s FGFR2-targeted anti-cancer drug, 'lirafugratinib,' were presented at the ESMO Congress 2025 (European Society for Medical Oncology).

Professor Richard Kim of the Moffitt Cancer Center in the U.S., who participated as a clinician in the study, discussed lirafugratinib’s differentiation, clinical significance, and potential for future approval with DailyPharm at the conference.

Professor Kim explained, "Biliary tract cancer (BTC) remains a rare cancer with limited treatment options. The small patient population and high development difficulty have slowed the introduction of new drugs," and added, "In the U.S., about 12,000-14,000 new cases are diagnosed annually, and FGFR2 fusions are confirmed in 10-15% of these patients."

He further stated, "The first-line standard of care is chemotherapy combined with immunotherapy. For second-line and later lines, FOLFOX is primarily used, but response rates are low. Identifying the FGFR2 mutation is a key step that opens new treatment opportunities."

Selective FGFR2 inhibition…reduces toxicity, overcomes resistance

In the poster presentation at ESMO Congress 2025, Professor Kim shared data on the response rate and tolerability of lirafugratinib in patients with BTC and non-BTC solid tumors harboring FGFR2 alterations.

This presentation expanded on the interim results previously disclosed at ENA 2024 ('ReFocus' study), strengthening the follow-up clinical evidence focused on the FGFR2 mutation.

Professor Kim said, "Existing approved drugs, such as pemigatinib (Pemazyre) and futibatinib (Lytgobi), are Pan-FGFR agents that inhibit FGFR1-4, often leading to FGFR1-related toxicity." He emphasized, "Lirafugratinib significantly enhances safety by selectively inhibiting only FGFR2."

According to HLB, lirafugratinib is designed as an irreversible FGFR2-selective inhibitor. Through a motion-based drug design strategy based on molecular dynamics (MD) simulations, it minimizes binding to FGFR1, 3, and 4, thereby lowering toxicity while enhancing FGFR2 selectivity.

In the clinical trial, treatment-related adverse events (TRAEs) reported were mostly low-grade, reversible, and manageable with dose adjustments, with a treatment discontinuation rate of less than 2%. Off-isoform toxicities, such as hyperphosphatemia and diarrhea, were rarely observed.

Professor Kim assessed that "Lirafugratinib has more potent FGFR2 inhibition compared to existing drugs and showed activity even in areas where existing drugs have shown resistance, such as gatekeeper mutations and kinase domain mutations," and added, "Anti-cancer activity was observed not only in FGFR2 fusions but also in amplification and mutations."

" Response observed in resistant patients…a 2nd-generation inhibitor"

At ESMO Congress 2025, Professor Kim defined lirafugratinib as a 2nd-generation FGFR inhibitor that addresses the limitations of 1st-generation FGFR inhibitors.

He noted, "If pemigatinib and futibatinib are 1st-generation, lirafugratinib is a 2nd-generation FGFR2 inhibitor capable of overcoming resistance and managing multiple mutations." He added, "Anti-cancer response was observed not only in patients without prior FGFR inhibitor experience but also in patients who developed resistance to existing drugs."

According to the ReFocus clinical results presented at the ESMO Congress 2025 and the ENA 2024, the objective response rate (ORR) was 37% in patients with non-CCA (non-biliary tract cancer) solid tumors harboring FGFR2 fusions. The median duration of response (DoR) was 7.3 months, and the 6-month response maintenance rate was 61%.

Notably, response rates of 75% were reported in NSCLC patients, 46% in pancreatic cancer, and 67% in ovarian cancer, showing meaningful therapeutic effects across various solid tumors with FGFR2 alterations.

Expanded uner the tumor-agnostic strategy…"Targeting the FGFR2 mutation"

Another core aspect of lirafugratinib development is its 'tumor-agnostic' strategy.

The FGFR2 mutation is commonly found in over 10 types of solid tumors, including BTC, pancreatic, lung, breast, ovarian, and gastric cancers.

Professor Kim stated, "Lirafugratinib targets the FGFR2 mutation itself, not a specific cancer type." He added, "This approach provides a basis for future expansion into various solid tumors as a combination or monotherapy."

The ReFocus study also showed that the non-BTC patient population accounted for over half of the total patients, and a similar anti-cancer response pattern was observed across various solid tumors with FGFR2 mutations. This strategy differs from existing FGFR inhibitors, which primarily target a single cancer type.

Currently, HLB reportedly plans to submit a New Drug Application (NDA) for lirafugratinib's BTC indication to the U.S. FDA as early as this year, or by early next year.

Professor Richard Kim expressed an optimistic outlook regarding the likelihood of future approval.

Professor Kim emphasized, "Based on the data so far, we believe approval is possible. Once the clinical results are finalized, it will be a sufficiently strong candidate for FDA approval."

He also said, "Lirafugratinib is a well-balanced drug in terms of both efficacy and safety," and added, "As more clinical evidence accumulates, its introduction as a first-line treatment that could potentially replace chemotherapy is considerable."

Meanwhile, HLB and its subsidiary, Elevar Therapeutics, are preparing to present the primary efficacy data for lirafugratinib at ASCO GI 2026.