Full steam ahead at F2G

With a big partner in place and healthy bank balance secured, F2G must now produce the final piece of the puzzle – data. The company is due to present phase 2b results at a medical conference in a couple of weeks' time on its novel antifungal, olorofim, and this will form the basis of a US submission later this year.

The private UK group has not toplined the results, but a positive readout is suggested by last month’s $70m financing and the bullish timelines laid out by its chief executive, Francesco Maria Lavino. If all goes to plan, a US launch could happen by mid-2023, he says in an interview with Evaluate Vantage.

“Olorofim is an anti-infective by mechanism of action but it’s a rare disease drug by value proposition,” Mr Lavino says. “We are very clear on the patients we are going to treat, and the infections we are going to treat. And these are patients with very limited options.”

These characteristics helped F2G access financing, as did a deal with Shionogi that Mr Lavino describes as “very rich”. In May the Japanese developer bought Europe and Asia rights to olorofim in invasive aspergillosis for $100m up front; it also agreed to pay half of all future global development costs, potential milestones of $380m and double-digit royalties.

That deal was followed in August by a $70m series B, co-led by new investors Forbion and Sofinnova, big names in the European venture world. The company now has enough cash to get to break even, Mr Lavino says, though an IPO is still on the cards. F2G needs to pick the right moment to go public, he adds, maybe after a few quarters of sales.

“Recent anti-infective launches, particularly antibiotic launches, have been disappointing. We need to show a different sales trajectory to what investors have seen before,” he says.   

The offering

Olorofim is the most advanced project in a new class of antifungals being developed by F2G, called the orotomides. These work differently from the three major classes currently available – triazoles, polyenes and echinocandins – and could help address some big problems in the antifungal space, F2G believes.

One of these problems is resistance, as seen with antibiotics. But Mr Lavino says drug-drug interactions and breakthrough infections are becoming almost as problematic as resistance for the antifungal field.

Aspergillosis is the biggest culprit when it comes to invasive fungal infections, and the azoles are typically the first-line treatment. Around half of people respond well, but for those who do not there is only one further option – amphotericin B, which has been around since the 1960s. This drug is highly toxic and can cause irreversible kidney damage.

Olorofim, on the other hand, is “very well tolerated and very potent”, Mr Lavino says. “What we are saying is: for aspergillosis, if you can use an azole, please do. But if you can’t, we are a much better option than amphotericin B.”

On top of non-responders, around 10-15% of people cannot tolerate azoles in the first place. And adverse drug interactions prevent their use in patients on some widely used leukaemia treatments, including Imbruvica and Venclexta. These patients are immunosuppressed and prone to infections.

F2G contends that olorofim is also active against rarer moulds, where nothing works well and where olorofim's first-line use is possible.

Wider appeal

This all needs to be proved, of course, hence the importance of imminent results from a phase 2b trial. This allowed invasive infections caused by any resistant fungus, as long as patients lacked other treatment options. The results have been accepted for presentation at Infectious Disease Week later this month.

The company plans to use the FDA’s LPAD pathway to get olorofim swiftly to the market; the project won breakthrough therapy designation in 2019 based on preliminary data from the phase 2b study, which is single-arm and open-label. 

A more rigorous phase 3 trial started earlier this year, pitting olorofim against amphotericin B in invasive aspergillosis in patients resistant or refractory to azoles. All-cause mortality is the primary endpoint.

The end of the line feels close for F2G and olorofim, but this has been a long time coming. Back in 2016, under the company’s previous chief executive, the plan was to have pivotal data in house by 2019. Development instead was refocused on pinning down an appropriate dose for oral administration, F2G says, and investors will have to hope the wait was worth it.

The need for new antifungals has not gone away in the meantime. Demand is growing as the immunocompromised population expands in the west as a result of new anticancer treatments and other potent drugs, as well as a rise in organ transplants.

“The immunosuppressed population is small, but one in which the healthcare system has already invested a lot. They don’t want to lose a patient because of a stupid fungal infection,” Mr Lavino says.

Launch preparations are already under way. “The key word today is access. And you need to prepare for that access. What you get in the first six months post launch is the result of what you have done in the 12 months before the launch,” he says.

It seems to be full steam ahead for F2G. Next stop, the data.