F2G Announces Publication in The Lancet Infectious Diseases of Phase 2b Data Demonstrating Positive Therapeutic Responses in Patients with Serious Invasive Fungal Diseases Treated with Oral Olorofim

Data reinforce olorofim’s potential as a first-in-class treatment for patients with invasive fungal diseases and limited or no antifungal treatment options

/EIN News/ -- MANCHESTER, United Kingdom, June 18, 2025 (GLOBE NEWSWIRE) -- F2G Ltd, a clinical-stage biopharmaceutical company developing olorofim, a novel therapy to treat life-threatening rare fungal infections with high unmet medical need, today announced the publication of the full data set from its Phase 2b open-label study.¹ The study evaluated oral olorofim in patients with invasive fungal diseases (IFDs) who had limited or no treatment options. The results, now published in The Lancet Infectious Diseases (“The Lancet ID”), highlight olorofim’s encouraging therapeutic responses across a broad range of difficult-to-treat fungal pathogens and expands on data presented at the Trends in Medical Mycology (TIMM) meeting in October 2023.

"The publication of our data in The Lancet ID validates our efforts to develop olorofim as a treatment for serious invasive fungal diseases, including those resistant or refractory to all approved antifungals," said John H. Rex, MD, Chief Medical Officer of F2G. "Olorofim, the first in a new class of antifungals, has a novel mechanism of action and shows potential in addressing rare fungal infections in well-defined and high need populations. We are committed to developing olorofim for patients who have exhausted treatment options and are in need of a new effective therapy."

Johan Maertens, MD, PhD, Professor of Hematology at University Hospitals Leuven (Belgium), the study’s Principal Investigator, added, "There is a critical unmet need for novel antifungal therapies as lifesaving interventions. Cancer treatments and organ transplants, combined with an aging population, have led to a rise in individuals at risk of invasive fungal infections—many of which are increasingly difficult to treat. The data published in The Lancet ID show successful global and clinical responses in patients with both brief and lengthy periods from diagnosis to initiation of olorofim treatment, with infections due to highly resistant organisms and those in difficult-to-treat sites such as brain and bone. We were also pleased to see the accompanying editorial by Paccoud and Lanternier² which concludes by noting that ‘these important findings underscore olorofim’s clinical value in addressing unmet needs in the management of difficult-to-treat fungal infections across a diverse patient population.’"

The Phase 2b study (Study 32; NCT03583164) enrolled 202 patients with proven or probable IFDs, including infections caused by Aspergillus spp. (including azole-resistant strains), Lomentospora prolificans, Scedosporium spp., Coccidioides spp., and other rare moulds. Patients were treated with oral olorofim and evaluated for treatment response over 84 days with extended therapy available as needed beyond Day 84.

Patient Demographics and Dosing:

• Phase 2b open-label study of oral olorofim in 203 patients with limited treatment options for IFD.          
  • 202 patients were confirmed by the Data Review Committed to have IFDs defined as proven or probable pulmonary invasive aspergillosis (IA) per EORTC-MSG³ criteria and efficacy analysis was done on those patients that met the modified ITT (mITT) criteria.
  • Causative organisms included Aspergillus species (101, including 22 cases with azole-resistant strains), Lomentospora prolificans (26), Scedosporium spp. (22), Coccidioides spp. (41), and other fungi (12).
• Treatment was given for up to 84 days +/- 6 days with extended therapy permitted when clinically indicated.
  • The mean dosing duration was 73 days in the 203 patients dosed in the main phase of the study and 361 days for 114 subjects who received extended treatment.
  • During the main treatment phase, 61.9% of patients received olorofim entirely as monotherapy and 70.8% received ≤ 7 days of concomitant administration of a potentially effective second antifungal agent.

Efficacy and Safety Results:

• Olorofim demonstrated an acceptable benefit-risk profile. 
  • The rate of successful global response for the entire mITT population at day 42 (primary endpoint), as determined by an independent DRC applying the MSG/EORTC criteria⁴, was 28.7%, and 27.2% at day 84.
  • When considering stable disease as a successful global response, the rates of successful outcome for the entire mITT population at day 42 and day 84 rose to 75.2% and 63.4%, respectively.
  • Successful clinical response was 59.9% and 54.0% at day 42 and day 84, respectively.
  • Clinical response was similar across all levels of immunosuppression
• All-cause mortality at day 42 and day 84 was 11.9% and 16.3%, respectively.
• Olorofim was generally well-tolerated, even with dosing >2 year in extension therapy. 
  • Changes in liver biochemistry that were deemed at least possibly due to olorofim were seen in 9.9% of study subjects overall (main phase + extended therapy). All events were successfully managed by dose modifications (pausing or reducing, including successful restarting).
  • Changes in the liver biochemistry led to permanent discontinuation in 3%.
  • Gastrointestinal intolerance to olorofim, generally self-limiting, was noted in 9.9%.

F2G and Shionogi & Co., Ltd. are collaborating to develop and commercialise olorofim, bringing the novel antifungal therapy to patients with invasive fungal infections. Shionogi has commercial responsibility for olorofim in Europe and Asia Pacific and F2G has commercial responsibility for olorofim in North America, and rest of the world. F2G and Shionogi are currently enrolling patients with invasive aspergillosis in a global Phase 3 study (OASIS) to compare treatment with olorofim versus AmBisome^® followed by standard of care (NCT05101187).

About Study 32 

Study 32 was a 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. It enrolled patients between June 2018 and September 2022.

Enrolled patients received 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 were followed for another four weeks after the end of treatment, while some received extended therapy for as long as thought clinically beneficial. For more information on Study 32, visit ClinicalTrials.gov (NCT03583164). These data enable continued clinical development and support future regulatory and commercial planning.

About Olorofim

Olorofim (formerly, F901318) is F2G's leading candidate from the orotomide class and is currently in a global Phase 3 trial ("OASIS") (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 is an investigational therapy and has not been approved by any regulatory authorities.

About F2G

F2G is a clinical-stage biopharmaceutical 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 pyrimidine biosynthesis pathway, a novel mechanism of action that is distinct from currently marketed antifungal agents. This mechanism provides the orotomides with fungicidal activity against a broad range of rare and resistant fungal mould infections. For more information, please visit: www.f2g.com

About Shionogi & Co. Ltd.

Shionogi & Co., Ltd. is a 147-year-old global, research-driven pharmaceutical company headquartered in Osaka, Japan, that is dedicated to bringing benefits to patients based on its corporate philosophy of “supplying the best possible medicine to protect the health and wellbeing of the patients we serve.” The company currently markets products in several therapeutic areas including anti-infectives, pain, CNS disorders, cardiovascular diseases and gastroenterology. Shionogi’s research and development currently target two therapeutic areas: infectious diseases, and pain/CNS disorders.

For more information on Shionogi & Co., Ltd., please visit https://www.shionogi.com/global/en.

Forward-Looking Statements 

This announcement contains forward-looking statements. These statements are based on expectations in light of the information currently available, assumptions that are subject to risks and uncertainties which could cause actual results to differ materially from these statements. Risks and uncertainties include general domestic and international economic conditions such as general industry and market conditions, and changes of interest rate and currency exchange rate. These risks and uncertainties particularly apply with respect to product-related forward-looking statements. Product risks and uncertainties include, but are not limited to, completion and discontinuation of clinical trials; obtaining regulatory approvals; claims and concerns about product safety and efficacy; technological advances; adverse outcome of important litigation; domestic and foreign healthcare reforms and changes of laws and regulations. Also, for existing products, there are manufacturing and marketing risks, which include, but are not limited to, inability to build production capacity to meet demand, lack of availability of raw materials and entry of competitive products. The company disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information, future events or otherwise.

Media Contact:
Jonathan Pappas
LifeSci Communications
+1 646 970 4688
JPappas@lifescicomms.com

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EU Media: pressoffice:shionogi.eu

¹ Maertens JA, Thompson GR, Spec A, Donovan FM, Hammond SP, Bruns AH, et al. Olorofim for the treatment of invasive fungal diseases in patients lacking suitable therapeutic options. Lancet Infectious Disease. 2025; DOI: 10.1016/S1473-3099(25)00237-3

² Paccoud O, Lanternier F. Olorofim: addressing unmet needs of patients with difficult-to-treat fungal infections. Lancet Infectious Disease. 2025; DOI: 10.1016/S1473-3099(25)00237-3

³ De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clinical Infectious Diseases. 2008;46(12):1813-21.

⁴ Segal BH, Herbrecht R, Stevens DA, Ostrosky-Zeichner L, et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clinical Infectious Diseases. 2008 Sep 1;47(5):674-83. doi: 10.1086/590566. PMID: 18637757; PMCID: PMC2671230.