F2G announces data from Phase 2b study at ID Week 2022 showing positive therapeutic response in patients with invasive fungal infections treated with Olorofim

• Data are based on analysis of the first 100 patients from an ongoing Phase 2b study of patients who have limited or no treatment options for invasive fungal infections
• Overall, a 44% response rate, defined as complete or partial response, was seen across fungi at day 42, the primary endpoint
• All-cause mortality (ACM) at day 42 and day 84 were 15% and 20%, respectively

MANCHESTER, United Kingdom, Oct. 21, 2022 (GLOBE NEWSWIRE) -- F2G Ltd, a clinical-stage biopharmaceutical company focused on the discovery and development of novel therapies to treat life-threatening rare fungal infections with a high unmet medical need, today announced at IDWeek 2022 positive data from the first 100 patients who completed study treatment in its ongoing Phase 2b open-label study (Study 32, NCT03583164) of oral olorofim as a treatment for invasive fungal infections.

“Invasive fungal infections are a major problem, particularly among immunosuppressed patients. Patients may be refractory or unable to tolerate existing antifungal treatments and, in some cases, fungi are resistant to available therapies, underscoring the need for new and effective antifungal treatments. Approximately 75% of patients in this analysis had moderate to high levels of immunosuppression, with about half suffering from fungal infections due to Aspergillus. Other causes of infection included filamentous fungi such as Lomentospora prolificans and dimorphic fungi such as Coccidioides species (which causes Valley Fever),” said John H. Rex, MD, chief medical officer of F2G. “We are encouraged by these results because they demonstrate a positive risk-benefit profile for olorofim as an oral therapeutic option for the treatment of serious or life-threatening invasive fungal infections in patients who have limited or no treatment options.”

Key findings:

• Data came from 100 patients with proven invasive fungal infection or probable pulmonary invasive aspergillosis (IA). Causative organisms included Aspergillus spp., Lomentospora prolificans, Scedosporium spp., Scopulariopsis spp., Coccidioides spp., and other olorofim-susceptible fungi. Patients had limited alternative treatment options; reasons for this included failure of available therapy, resistance of infecting isolate to all licensed agents, intolerance to available therapy, inability to manage drug-drug interactions, and/or inability to produce therapeutic drug levels.
• The median dosing duration in the main phase of the study was 84 days; patients (n=42) who entered the extension phase of the study were dosed for a median of 308 days.
• Olorofim demonstrated a positive risk-benefit profile
  • At day 42, 44% of patients had a complete or partial response to treatment
  • With stable response rate included, the overall response rate was 69%
• All-cause mortality (ACM) at day 42 and day 84 were 15% and 20%, respectively.
• Olorofim was generally well tolerated
  • The only significant serious adverse event was drug-induced liver injury (DILI) which was thought to be possibly related to olorofim in 8 (8%) study patients; only 2 (2%) patients required discontinuation of olorofim due to DILI.
  • Other non-serious adverse events observed included diarrhea, nausea, and vomiting.

“Mortality remains unacceptably high in patients with severe and life-threatening fungal infections being treated with currently available therapies. Developing new antifungals, like olorofim, that can meet this clear unmet need is a priority. With its novel mechanism of action, olorofim has shown activity against a wide range of fungi, including some for which there is currently no approved treatment. These data provide evidence that we are on the path to meeting this need in patients currently with limited or no treatment options,” added Johan Maertens, MD, PhD, Professor of Hematology at University Hospitals Leuven (Belgium) and primary author for Study 32.

Olorofim is the only antifungal medication to be awarded Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA). Olorofim works through a novel mechanism of action, different from existing classes of antifungals, exerting fungicidal activity through inhibition of the enzyme dihydroorotate dehydrogenase (DHODH) in the pyrimidine synthesis pathway. It is active in vitro against Aspergillus spp. (including azole-resistant and cryptic species), rare molds (e.g., Lomentospora prolificans, Scopulariopsis), and dimorphic fungi (e.g., Coccidioides spp.)

About Study 32
Study 32 is an ongoing multicenter, open-label, Phase 2b study to evaluate the safety and efficacy of olorofim (formerly F901318) in patients ≥ 18 years of age with probable pulmonary invasive aspergillosis or proven invasive fungal infections due to Lomentospora prolificans, Scedosporium spp., Aspergillus spp., and other resistant fungi with limited or no treatment options.

Enrolled patients receive an initial loading dose of 150 mg BID (twice a day) of oral olorofim on day one, and subsequent oral doses of 90 mg BID for up to 90 days. Patients are followed for another four weeks after end of treatment, while some receive extended therapy for as long as thought useful. For more information on Study 32, visit ClinicalTrials.gov (NCT03583164).

About Olorofim
Olorofim (formerly, F901318) is F2G's leading candidate from the orotomide class and is currently being investigated in a Phase 2b open-label study in patients who have limited treatment options for difficult-to-treat invasive, rare fungal mold infections such as azole-resistant aspergillosis, scedosporiosis, lomentosporiosis, and other rare mold infections. F2G has initiated a global Phase 3 trial ("OASIS") to compare treatment with olorofim versus AmBisome® followed by standard of care (SOC) in patients with lower respiratory tract invasive fungal disease caused by proven or probable infection with Aspergillus species (NCT05101187). Olorofim has received orphan drug status from the European Medicines Agency for the treatment of invasive aspergillosis and invasive scedosporiosis. Olorofim has also received orphan drug status from the FDA for the treatment of coccidioidomycosis, scedosporiosis, and invasive aspergillosis. Olorofim has been granted Qualified Infectious Disease Product (QIDP) designation for invasive aspergillosis, invasive scedosporiosis, invasive lomentosporiosis, coccidioidomycosis, invasive disease due to Scopulariopsis species, and invasive fusariosis. Olorofim has received Breakthrough Therapy Designation for both “treatment of invasive mold infections in patients with limited or no treatment options, including aspergillosis refractory or intolerant to currently available therapy, and infections due to Lomentospora prolificans, Scedosporium, and Scopulariopsis species” and “treatment of Central Nervous System (CNS) coccidioidomycosis refractory or otherwise unable to be treated with standard of care therapy.” The scientific information discussed in this news release related to olorofim is preliminary and investigative. Olorofim is not approved by the U.S. Food and Drug Administration, and no conclusions can or should be drawn regarding its safety or efficacy.

About F2G
F2G is a biotech company with operations in the UK, US, and Austria focused on the discovery and development of novel therapies to treat potentially life-threatening invasive fungal infections. F2G has discovered and developed a completely new class of antifungal agents called the orotomides which selectively target 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. For more information, please visit: www.f2g.com

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