FDA approval secured in under 2 years after licensing rights

Direct US sales model cuts out middlemen, boosts margins

Supply launch set for Q4; liver cancer resubmission in the works

HLB's healthcare business division. [Provided by HLB Group]
HLB's healthcare business division. [Provided by HLB Group]

South Korean biotech HLB has unveiled a new global business model — licensing in promising drug candidates from overseas biotechs and seeing them through to FDA approval and commercialization via its US subsidiary.

HLB's US subsidiary Elevar Therapeutics announced Wednesday (local time) that its fibroblast growth factor receptor 2 (FGFR2)-targeted anticancer drug Lyfgenia (lirafugratinib) had received US FDA approval as a second-line treatment for adult patients with locally advanced or metastatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements.

Neither early tech transfer nor 20-year in-house development — a hybrid 'license-in and go the distance' model

The achievement is being recognized as a new alternative that overcomes the limitations of the commercialization paths long followed by South Korea's biotech industry.

Until now, Korean pharmaceutical and biotech companies pursuing global new drugs faced two extreme options: license out early-stage compounds to global big pharma at the preclinical or Phase 1 trial stage in exchange for milestones and royalties, or have the domestic headquarters bear enormous capital and failure risk alone over 10 to 20 years to push through the entire clinical process.

Early licensing reduces risk but limits returns to roughly 10 percent of US sales revenue in royalties — the market where drug prices are highest — while going it alone demands prohibitive time and capital.

HLB exploited the blind spots of both approaches. The company selectively licensed in overseas pipeline candidates whose efficacy had already been validated in Phase 1/2 trials, then entrusted a US-based subsidiary — well-versed in American regulatory requirements and networks — with full responsibility for approval and direct sales. The result is a hybrid model that skips the early-stage gamble without surrendering the commercial upside.

The original developer of Lyfgenia is Relay Therapeutics, a US precision oncology biotech. Relay Therapeutics had discovered and designed the compound using its proprietary protein dynamics platform, advancing it through early clinical trials under the code name RLY-4008, before Elevar secured worldwide exclusive licensing rights in December 2024.

Elevar then systematically reanalyzed the existing global clinical data and independently formulated a regulatory strategy, winning FDA new drug application (NDA) approval in less than two years after acquiring the rights. The company bypassed the decade-plus early-discovery phase and cleared the most critical regulatory hurdle through a localization strategy.

Targeting a rare-cancer niche — high selectivity cuts off-target side effects

Cholangiocarcinoma, the primary target indication for Lyfgenia, is a rare cancer that forms in the bile ducts carrying bile from the liver to the duodenum. It is typically diagnosed late due to a lack of early symptoms, and its high recurrence rate after surgery leaves a significant unmet medical need worldwide. According to the American Cancer Society, about 8,000 new cases are reported in the United States each year.

Lyfgenia is an irreversible, orally administered targeted anticancer drug that precisely blocks FGFR2 mutations. Unlike previously approved pan-FGFR inhibitors — which indiscriminately suppressed other receptors including FGFR1, 3 and 4, causing serious off-target toxicities such as hyperphosphatemia, nail detachment and dry eyes — Lyfgenia was designed to bind selectively and potently to FGFR2 alone.

The global Phase 1/2 ReFocus trial, which formed the basis for approval, confirmed strong therapeutic efficacy. In patients with FGFR2 fusion or rearrangement cholangiocarcinoma who had previously received systemic chemotherapy, the drug achieved an objective response rate of 45.7 percent and a median duration of response of 11.8 months. Median progression-free survival reached 11.3 months (95% CI, 9.2–14.8), and the 12-month progression-free survival rate was 49.2 percent, approaching 50 percent. The safety profile was also demonstrated to be manageable through dose adjustment.

Allison Schram, a medical oncologist at Memorial Sloan Kettering Cancer Center — one of the world's leading cancer institutions and a participant in the clinical research — said Lyfgenia "has demonstrated durable responses and a manageable safety profile, opening a new treatment opportunity for patients with FGFR2 fusion-positive cholangiocarcinoma." She added that early molecular testing from the time of diagnosis is critical for appropriate patient selection.

Direct US sales to launch in Q4; European filing and solid tumor basket trial expansion underway

Elevar plans to launch Lyfgenia directly across the United States in the fourth quarter of this year, using its own established sales network. By bypassing big pharma and having the US subsidiary handle distribution entirely, the direct-sales structure allows both the subsidiary and HLB's Korean headquarters to capture the full margin from high US drug prices — positioning the drug as a key cash cow going forward.

Global expansion is also advancing on multiple fronts. Elevar submitted a marketing authorization application (MAA) for Lyfgenia in cholangiocarcinoma to the European Medicines Agency on Sept. 14, entering formal review. The company also plans to significantly broaden the drug's indications through ReFocus202, a tumor-agnostic basket trial covering various cancer types with FGFR2 mutations, including breast and gastric cancers.

Kim Dong-geon, chief executive of Elevar, said the approval means the company can now offer "a definitive second-line treatment option to cholangiocarcinoma patients and their families who had limited choices," adding that it would "fully activate the commercial supply chain to get the drug to physicians and patients as quickly as possible."

Can HLB clear three CRLs for liver cancer? Resubmission in preparation

The FDA approval of Lyfgenia carries significant symbolic weight for HLB, marking the first regulatory clearance in the company's roughly 20-year pursuit of new anticancer drugs.

HLB's flagship pipeline and blockbuster-targeting liver cancer first-line combination therapy — rivoceranib plus camrelizumab — has stalled at the threshold after receiving three complete response letters (CRLs) from the FDA over chemistry, manufacturing and controls (CMC) issues and production facility inspection findings.

HLB said key obstacles have recently been resolved — including manufacturing facility deficiencies being downgraded to a voluntary action indicated (VAI) classification — and the company plans to soon file a resubmission of the new drug application together with Hengrui Pharmaceuticals after compiling the final supplementary documentation.


silverpaper@heraldcorp.com