F2G Receives Second US FDA Breakthrough Therapy Designation for Olorofim

- In Phase 2b development for the treatment of life-threatening fungal infections

- First antifungal agent to receive Breakthrough Therapy Designation

- New second Breakthrough Therapy Designation for CNS Valley Fever (coccidioidomycosis)

MANCHESTER, England and VIENNA, Oct. 22, 2020 /PRNewswire/ --  F2G Ltd, a UK- and Austria-based biotech company developing novel therapies for life-threatening systemic fungal infections, announced today that the US Food and Drug Administration (FDA) has granted an additional Breakthrough Therapy Designation to its lead first-in-class candidate, olorofim, for the indication of 'Treatment of Central Nervous System (CNS) coccidioidomycosis refractory or otherwise unable to be treated with standard of care therapy'. This is the second Breakthrough Therapy Designation for olorofim; a designation was granted previously on 11 November 2019 for 'Treatment of invasive mold infections in patients with limited or no treatment options, including aspergillosis refractory orintolerant tocurrently available therapy, and infections due to Lomentospora prolificans, Scedosporium, and Scopulariopsis species'. Olorofim (formerly F901318) is the first antifungal agent to be granted Breakthrough Therapy Designation.

Olorofim has orphan drug designation in the United States for coccidioidomycosis, an endemic fungal infection with a geographic distribution focused mainly in the desert Southwest of the United States but also including Mexico, Central America, and South America. Infection begins by inhalation and can spread to any part of the body, even in otherwise healthy individuals. Spread to the brain is particularly feared as it produces a devastating illness that cannot always be controlled with any currently available agent.

Patients with coccidioidomycosis are being studied in an ongoing open-label single-arm Phase 2b study (ClinicalTrials.gov Identifier: NCT03583164) in patients with proven invasive fungal disease (IFD) or probable invasive aspergillosis (IA) and either refractory disease, resistance, or intolerance to available agents. Olorofim has been well tolerated across more than 30 years of cumulative patient dosing days with a median therapy duration of 12 weeks. Preliminary data from this study were provided to the FDA as part of the Breakthrough Therapy Designation submission.

Breakthrough Therapy Designation is an FDA process designed to expedite the development and review of drugs that are intended to treat a serious or life-threatening condition and is granted based on preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

Breakthrough Therapy Designation conveys all the features of fast track designation, more intensive FDA guidance on an efficient drug development program, an organisational commitment by FDA to involve senior managers, and eligibility for rolling review and priority review.

Commenting on the news, Ian Nicholson, CEO of F2G Ltd, said:

"The granting of a second FDA Breakthrough Therapy Designation will further support our goal of rapidly developing this novel treatment for patients suffering from serious and life-threatening fungal infections. Olorofim acts via a novel and differentiated mechanism to traditional antifungals, and preliminary data have indicated that it is efficacious in tackling life-threatening invasive fungal infections that cannot be managed with currently approved agents.

"Our Phase 2b programme is on track with over 85 patients recruited in Europe, Asia, and the US. We look forward to working closely with the US FDA to accelerate development of this therapy for patients having limited or no approved treatment options for an invasive mold infection."

Professor George Thompson, UC Davis and Investigator for the Phase 2b study said:

"This news is very exciting for clinicians caring for patients with Valley Fever (coccidioidomycosis) as spread to the brain is the most-feared complication of infection with this fungus. Unfortunately, available drugs are not curative, must be administered as life-long therapy, and are associated with substantial toxicity. The news that olorofim has encouraging preliminary clinical data that support Breakthrough Therapy Designation brings realistic hope that we can change the paradigm for managing this devastating infection."

About Olorofim / Clinical trial

The Phase 2b study for olorofim (ClinicalTrials.gov Identifier: NCT03583164) is a global open-label study in patients who have limited treatment options for difficult-to-treat invasive fungal mold infections such as azole-resistant aspergillosis, scedosporiosis, lomentosporiosis, and other rare mold infections. More than 40 centres are currently open in nine countries (AU, BE, DE, ES, IS, NL, TH, UK, USA) and a further 10 will open in 2020/2021. Olorofim is being developed both as IV and oral formulations.

About F2G

F2G is a world-leading UK- and Austria-based biotech company (F2G Ltd and F2G Biotech GmbH) focused on the discovery and development of novel therapies to treat life-threatening invasive fungal infections. F2G has discovered and developed a completely new class of antifungal agents called the orotomides. The orotomides selectively target fungal dihydroorotate dehydrogenase (DHODH), a key enzyme in the de novo pyrimidine biosynthesis pathway. This is a completely different mechanism from that of the currently marketed antifungal agents and gives the orotomides fungicidal activity against a broad range of rare and resistant fungal mold infections. Olorofim (formerly, F901318) is F2G's leading candidate from this class and is in a Phase 2b open-label study focussing on rare and resistant invasive fungal infections such as aspergillosis (including azole-resistant strains), scedosporiosis (including lomentosporiosis). Olorofim has received orphan drug status from the European Medicines Agency for the treatment of invasive aspergillosis and invasive scedosporiosis. Olorofim has received orphan drug status from the US FDA for the treatment of coccidioidomycosis, lomentosporiosis/scedosporiosis, and invasive aspergillosis. Olorofim has been granted Qualified Infectious Disease Product (QIDP) designation Invasive for aspergillosis, invasive scedosporiosis, invasive lomentosporiosis, coccidioidomycosis, invasive disease due to Scopulariopsis species, and invasive fusariosis. Olorofim is being developed both as IV and oral formulations. www.f2g.com