LONDON – Bridgebio Inc. has made a huge turn on the initial $65 million it invested in 2018 to acquire rights to infigratinib from Novartis AG, sealing a $2 billion commercialization deal with Swiss oncology specialist Helsinn Group for the fibroblast growth factor receptor (FGFR) inhibitor just over three years later.

Helsinn will work with Bridgebio affiliate QED Therapeutics Inc. on U.S. co-commercialization of infigratinib in oncology and all other indications apart from skeletal dysplasias, with profits and losses shared on a 50-50 basis.

In addition, Lugano, Switzerland-based Helsinn will have exclusive rights to co-develop, manufacture and commercialize the orally available drug elsewhere in the world, apart from China, where the product was licensed to Lianbio in August 2020, as part of a $531.5 million agreement.

For Helsinn, this is a further step in moves to diversify away from a sole focus on cancer supportive care and into targeted cancer therapies.

The FDA has accepted the new drug application for infigratinib in the treatment of advanced chemotherapy-resistant bile duct cancer (cholangiocarcinoma) with a FGFR2 gene fusion or rearrangement. The application is being reviewed under FDA’s real-time oncology review pilot, and has a PDUFA date in mid-May.

The product also is being reviewed in Australia and Canada under the FDA’s project Orbis, which allows for concurrent submission and review of oncology drugs among regulators that are part of the project.

Riccardo Braglia, CEO of Helsinn Group said some of the $2 billion is to be paid up front, with milestones to come on U.S. approval in bile cancer and further milestones on approvals in future indications.

In addition to extending to first-line treatment in bile cancer, infigratinib is in phase III development for the adjuvant (post-surgery) treatment of invasive urothelial carcinoma, and recently started an investigator-led trial in recurrent high-grade glioma driven by FGFR genetic alterations. The primary objective when the trial started last July was to assess how effectively infigratinib can cross the blood-brain barrier.

“We will continue to develop [infigratinib] in the U.S., but in parallel European development will start. We are interacting with EMA to move to Europe, and also looking at other countries,” Braglia told BioWorld.

Some way down the road that will include moving manufacturing of infigratinib to Helsinn’s manufacturing plant in Dublin, Ireland.

Braglia said Helsinn U.S. already has experience in promoting targeted cancer therapies, built around Valchlor (chlormethine, European brand name Ledaga) a treatment for the rare skin cancer mycosis fungoides‐type cutaneous T‐cell lymphoma, which it acquired from fellow Swiss pharma Actelion Pharmaceuticals three years ago.

The U.S. subsidiary is poised to begin co-promotion of infigratinib as soon as FDA approval comes through, Braglia said. “The sales team is targeting oncologists and specialists in the indication, like they already do with Valchlor,” he said.

Partnering with Helsinn will “significantly strengthen the upcoming launch” and the ongoing research to extend infigratinib into other indications, said Neil Kumar, co-founder and CEO of Bridgebio.

There are around 20,000 cases of cholangiocarcinoma in the U.S. and the EU each year, with FGFR2 genetic aberrations present in approximately 15% to 20% of patients. Treatment options are limited and the current five-year survival rate is 9%.

The most recent data, presented to the American Society of Clinical Oncology in May 2020, involved a retrospective analysis of 37 patients, receiving third- or fourth-line therapy in the phase III study of infigratinib, who were treated on the basis of having an FGFR2 gene fusion. Those patients showed a better tumor response than when they received second-line chemotherapy. The median progression-free survival was 6.8 months for third- or fourth-line infigratinib treatment, compared to 4.6 months for second-line chemotherapy.

While specific terms were not disclosed, Bridgebio put $65 million into QED, inclusive of a “substantial up-front payment” to Novartis when it acquired infigratinib in January 2018. Novartis has an equity stake in QED and is also in line to receive development and sales milestones, plus royalties.

In the deal with Lianbio, Bridgebio received up-front payments of $26.5 million, with up to $505 million to follow in future milestone payments and tiered royalties on sales of both infigratinib and another product, BBP-398, a SHP2 (SH2 domain-containing protein tyrosine phosphatase-2) inhibitor.

Shanghai, China-based Lianbio is taking part in the ongoing phase III study in first-line cholangiocarcinoma in China as part of the global study and has plans for studies in gastric cancer and other FGFR-driven tumors. Braglia said Helsinn will support those efforts.