Infections caused by Aspergillus species of mold are transmitted through inhalation and can lead to symptoms including hypersensitivity reactions and tissue damage. Invasive aspergillosis (IA) is a particularly life-threatening infection that happens in high-risk immunosuppressed people. While these infections can be controlled with antifungals, increasing numbers of cases are becoming resistant to these drugs.
At the same time, there is a “paucity of innovation” in the antifungal pipeline, with clinicians relying on just a handful of antifungal classes, said Henry Skinner, CEO of the funding round co-leader AMR Action Fund, in a public statement. However, it is challenging to develop new drugs as fungi can become cross-resistant to multiple drugs with similar mechanisms of action, and it is tough to develop drugs that specifically target fungi without harming patients.
To tackle this challenge, the first-in-class small molecule drug olorofim blocks a key enzyme in the pyrimidine synthesis pathway called fungal dihydroorotate dehydrogenase, killing fungal cells. The compound, which circumvents the resistance of fungal infections to existing drugs, would likely be used in niche cases of serious invasive, rare fungal disease that cannot be helped by existing treatments, F2G CEO Francesco Lavino told BioPharma Reporter.
F2G has completed a phase 2b open-label trial of olorofim for the treatment of rare fungal mold infections such as azole-resistant aspergillosis, scedosporiosis and lomentosporiosis. The company used data from the first 100 patients in the trial to apply for market approval from the US FDA, but the application was shot down last year due to a lack of data. F2G is now preparing a resubmission of the application with updated phase 2b data from more than 200 patients and updated historical controls, Lavino said.
F2G is also working with the Japanese company Shionogi to test olorofim in a phase 3 trial comparing it to a drug called liposomal amphotericin B followed by standard of care in patients with invasive fungal disease that cannot take an azole antifungal. The trial is expected to wrap up in late 2025, and could lead to with market approval in Europe and other regions; US approval is based on the phase 2b study and may occur before the other regions aimed for a year after that, said the CEO.
Founded in 1998, F2G raised $60.8 million in 2020 and $70 million in 2022 to finance its pipeline development. The company is also running programs for indications including coccidioidomycosis and pediatric fungal infections.
Over the coming decade, Lavino sees a growing awareness of the critical threat of fungal infections, which can “spread across ecosystems, making collaborative global efforts essential to controlling them.” This growing awareness is also leading to increasing financial backing for antifungal development, with the AMR Action Fund being a key example.
Growing resistance to antimicrobial drugs is one of the top global public health and development threats, causing an estimated 1.27 million deaths globally in 2019, according to the World Health Organization. One of the main drivers of the crisis is the misuse of antimicrobials in humans, animals and plants.
