F2G and Shionogi Present Full Data Set from Pivotal Phase 2b Study at Trends in Medical Mycology (TIMM) 2023 Demonstrating Positive Therapeutic Responses in Patients with Invasive Fungal Infections Treated with Oral Olorofim

• An overall success rate of 28.7% was seen at day 42, the primary endpoint, and 27.2% at day 84, as determined by a data review committee (DRC) using the EORTC-MSG criteria
• The success rate rose to 75.2% at day 42 and 63.4% at day 84 when stable disease was counted as success
• All-cause mortality (ACM) at day 42 and day 84 was 11.4% and 15.8%, respectively

MANCHESTER, United Kingdom and OSAKA, Japan, Oct. 21, 2023 (GLOBE NEWSWIRE) -- F2G Ltd. and Shionogi & Co., Ltd., today announced full results from the pivotal Phase 2b open-label study (Study 32, NCT03583164) of olorofim in patients with proven invasive fungal infections (IFI) or probable pulmonary invasive aspergillosis and limited or no treatment options. These findings were submitted as a late breaking abstract and exceptionally accepted for an oral presentation during the 11^th Congress on Trends in Medical Mycology (TIMM) 2023 held in Athens, Greece, from 20-23 October 2023. Altogether, ten olorofim-related abstracts from F2G and independent experts were accepted for presentation at TIMM, one of the largest global meetings in which scientists and clinicians from all over the world present their latest advances and research findings in medical mycology.

“We are excited about this data as it builds on the previous findings we announced at IDWeek 2022 demonstrating that olorofim has the potential to address a high unmet need in treating infections due to moulds including species considered resistant to all approved antifungals,” said John H. Rex, MD, Chief Medical Officer of F2G.

Juan Carlos Gomez, Chief Medical Officer of Shionogi & Co., Ltd. added, “In 2022, the World Health Organization published the fungal priority pathogens list, recognizing the burden of invasive fungal infections and highlighting the need for more antifungal agents to overcome increasing antifungal resistance and rare fungal pathogens. We are encouraged by these data because they demonstrate olorofim was generally well tolerated and has the potential to treat patients with life-threatening fungal infections.”

Johan Maertens, MD, PhD, Professor of Hematology at University Hospitals Leuven (Belgium) who presented the data for Study 32, added, “There is a critical need for novel antifungal therapies because lifesaving medical interventions such as organ transplants and cancer therapies, along with an ageing population, have created an increase in immunocompromised people who are at risk of invasive fungal infections from pathogens, and many of these are becoming harder to treat. I am optimistic about olorofim’s potential to address this need.”

Key findings:

• Data came from a Phase 2b open-label study of oral olorofim in 203 patients with limited treatment options for proven IFI or probable pulmonary invasive aspergillosis (IA).
  • 202 patients had IFI meeting the modified ITT (mITT) criteria for analysis
  • Causative organisms included Aspergillus species (101, including 22 cases with azole-resistant strains), Lomentospora prolificans (26), Scedosporium spp. (22), Coccidioides spp. (41), Scopulariopsis spp (6) and other fungi (8).
  • All patients had limited alternative treatment options including 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.
  • Treatment was for up to 84 days +/- 7 days with extended therapy permitted when clinically indicated.
• The median dosing duration in the main phase of the study was 84 days. When including extended therapy, the median treatment duration was 308 days.
• Olorofim demonstrated an acceptable benefit-risk profile in a well-defined population of patients with limited or no treatment options for infections due to moulds including species considered resistant to all approved antifungals.
  • The overall success rate at day 42 (primary endpoint), as determined by an independent DRC applying the EORTC-MSG criteria¹, was 28.7% at day 42 and 27.2% at day 84.
  • The overall success in patients with an IFI other than coccidioidomycosis (n = 161), was 36.0% at day 42 and 34.2% at day 84.
  • For patients with coccidioidomycosis (n = 41, none of whom achieved overall success due to inability to prove fungal eradication in the 84-day study period), benefit (symptoms/signs) was obtained in 31 patients (75.6%, CI 59.7,87.6) achieving complete or partial clinical response at day 42, and 30 patients (73.2%, CI 57.1, 85.8) at day 84.
  • When considering stable disease as a successful clinical response, the rates of successful outcome for the whole population at day 42 and day 84 rose to 75.2% and 63.4%, respectively.
• ACM at day 42 and day 84 was 11.4% and 15.8%, respectively (IA: 17.8% and 25.7%; non-IA infections 5.0% and 5.9%, 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) and were managed by dose reduction/pause.
  • Changes in the liver biochemistry led to permanent discontinuation in 2.5%.
  • 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. F2G has commercial responsibility for olorofim in North America, and Shionogi has commercial responsibility for olorofim in Europe and Asia Pacific. 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).

About Olorofim

Olorofim (formerly, F901318) is F2G’s leading candidate from the orotomide class. A Phase 2b single-arm open-label study in patients who have limited treatment options for difficult-to-treat invasive fungal infections due to mould such as azole-resistant aspergillosis, scedosporiosis, lomentosporiosis, and other rare mould infections has completed enrollment. To expand on the studied patient population, 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 proven or probable invasive fungal infection due to Aspergillus species (NCT05101187). Olorofim has received orphan drug designation from the FDA for the treatment of coccidioidomycosis, scedosporiosis (including lomentosporiosis), invasive Scopulariopsis, and invasive aspergillosis. Olorofim has also received orphan drug designation from the European Medicines Agency (EMA) for the treatment of invasive aspergillosis, invasive scedosporiosis (including lomentosporiosis), and invasive Scopulariopsis. 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 FDA Breakthrough Therapy Designation for both “treatment of invasive fungal 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.” Olorofim is not approved by the FDA or any other regulatory agency.

Invasive fungal infections cause substantial morbidity and mortality, particularly among immunosuppressed patients, and can cause significant morbidity in otherwise healthy individuals when they get into soft tissues, bones and joints, requiring both antifungal therapy and major surgical interventions. Effective antifungal therapies do not currently exist for some of these fungi. Even when therapies exist, some patients with invasive infections may be refractory or unable to tolerate existing antifungal treatments, thus underscoring the need for new and effective treatments.

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

About Shionogi

Shionogi & Co., Ltd. is a 145-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 and CNS disorders.
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 http://www.shionogi.co.jp/en/.
Shionogi B.V. is the European headquarters of Shionogi & Co., Ltd. For more information on Shionogi B.V., please visit www.shionogi.eu.

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:
Gloria Gasaatura
LifeSci Communications
+1 646 970 4688
ggasaatura@lifescicomms.com

SHIONOGI Website Inquiry Form https://www.shionogi.com/global/en/contact.html.
EU Media: pressoffice:shionogi.eu

^{_____________________________________
1} 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. Clin Infect Dis. 2008 Sep 1;47(5):674-83. doi: 10.1086/590566. PMID: 18637757; PMCID: PMC2671230.