F2G secures $100 million to address antifungal innovation gap

Infections caused by Aspergillus species of mold are transmitted through inhalation, leading to symptoms such as hypersensitivity reactions and tissue damage. Invasive aspergillosis (IA), a severe and potentially fatal condition, primarily affects high-risk immunosuppressed individuals. Although antifungal medications can manage these infections, the rising resistance to these drugs is becoming a significant concern.

Henry Skinner, CEO of the AMR Action Fund, highlighted the scarcity of new developments in antifungal treatments. The antifungal pipeline is limited, with only a few classes of antifungal drugs available. Developing new medications is particularly challenging because fungi can develop cross-resistance to multiple drugs with similar mechanisms of action. Additionally, it is difficult to create drugs that target fungi specifically without harming the host.

To address this issue, a novel small molecule drug named olorofim has been developed. Olorofim targets and inhibits fungal dihydroorotate dehydrogenase, an essential enzyme in the pyrimidine synthesis pathway. This action results in the death of fungal cells and circumvents resistance to existing drugs. F2G’s CEO, Francesco Lavino, mentioned that olorofim might be used for severe, rare fungal diseases that do not respond to current treatments.

Olorofim is undergoing a phase 2b open-label trial for treating rare mold infections like azole-resistant aspergillosis, scedosporiosis, and lomentosporiosis. F2G initially applied for market approval from the US FDA using data from the first 100 patients in the trial. However, the application was rejected last year due to insufficient data. The company is now preparing a resubmission with updated data from over 200 patients and revised historical controls.

F2G is collaborating with the Japanese company Shionogi to test olorofim in a phase 3 trial. This trial compares olorofim to liposomal amphotericin B, followed by standard care in patients with invasive fungal disease who cannot use azole antifungals. The trial is expected to conclude by late 2025, with market approval anticipated the following year.

Founded in 1998, F2G has raised significant funds to support its pipeline development. The company secured $60.8 million in 2020 and $70 million in 2022. F2G is also working on treatments for other fungal infections, including coccidioidomycosis and pediatric fungal diseases.

Lavino believes that awareness of the severe threat posed by fungal infections will grow over the next decade. These infections can spread across ecosystems, emphasizing the need for global collaboration to control them. This increasing awareness is also leading to more financial support for antifungal research and development, with the AMR Action Fund serving as a notable example.

Antimicrobial resistance is one of the most pressing global public health and development issues, contributing to approximately 1.27 million deaths worldwide in 2019. A significant factor driving this crisis is the misuse of antimicrobials in humans, animals, and plants.