The plight of antibiotics developers has been well documented: chronically underfunded research, daunting scientific challenges, and little commercial upside even for the ones that make it to the market. But in an adjacent corner of the antimicrobial space, an antifungal player is out to paint a very different picture.
F2G, a UK-Austria hybrid, has raised $60.8 million for its final push toward the clinic. Clearing the test could pave the way for its drug to be the first new antifungal agent in 20 years.
Thats how sparse the landscape has been, CEO Ian Nicholson told Endpoints News.
Its not for the lack of need, Nicholson noted. Much like in the antibacterial space, antifungal resistance is common occurring in 30% of patients taking the mainstay triazoles. Left untreated, the mortality rates for some of these rare mold infections targeted by F2G can be between 90% and 100%. Because fungi are eukaryotes just like humans, it has been difficult to discover new targets and corresponding new chemical entities.
The biotech began as a spinout of the University of Manchester, tapping into technologies that enabled them to manipulate and analyze fungal genes. F2G scientists eventually zeroed in on DHODH or dihydroorotate dehydrogenase, a key enzyme that helps fungi create the building blocks it needs to grow.
As it turned out, this blockade also kills the fungus. Out of this new class of antifungals dubbed orotomides, the lead candidate olorofim has been designated a breakthrough therapy (a first for antifungals, according to Nicholson), an orphan drug as well as a qualified infectious disease product. The ongoing open label Phase IIb study is testing it in a variety of rare mold infections, including invasive aspergillosis, scedosporiosis, lomentosporiosis, fusariosis, scopulariopsosis and coccidioidomycosis (valley fever).
For the upcoming Phase III, though, F2G plans to focus solely on invasive aspergillosis where a single study involving a couple hundred patients is expected to cement approval.
Valley fever is also a top priority in the US, where CMO John Rex, the former head of infection at AstraZeneca, leading a clinical team.
Compared to bacterial infections, fungal infections typically need to be treated for much longer, a matter of months rather than days. Theres no abundance of cheaply priced generics, and payers that F2G has talked to agreed that any new entrants should be priced relatively high.
Its a similar therapeutic area, but in many respects commercially it is much more like a rare disease drug than conventional anti-infective drug, CFO Ralf Schmid said.
Citing Gileads AmBisome as an example and an entrenched rival, Schmid pointed out the drug can cost $1,400 per day despite the availability of generics.
Just to set the context, added Naveed Siddiqi, a partner at Novo Ventures, the big drugs in the states are voriconazole and propiconazole, and they both at peak sold somewhere between $700 million and over $800 million.
Novo came on board for the first $60 million round back in 2016. Morningside Ventures, another existing investor, stepped up for the new funding alongside Brace Pharma Capital, Advent Life Sciences and new backer Cowen.
In addition to funding the clinical trial, the financing is also expected to scale up the current 20-person team in preparation for launch. Nicholson said the growth will be substantial but dont expect it to match the pharma rivals.
Because these infections occur in the context of transplants or cancer, when theyre immunosuppressed, a small company with a relatively limited salesforce and commercial organization can actually address this, Siddiqi said.