Phase 3 OASIS Top-Line Results

F2G and Shionogi (4507.T) announced the top-line data from the global Phase 3 OASIS (Olorofim Aspergillus Infection Study, NCT05101187) trial on June 18, 2026. The study randomized 225 adult patients with invasive aspergillosis who were refractory to or unsuitable for azole therapy, in a 2:1 ratio, to receive oral olorofim versus intravenous AmBisome (liposomal amphotericin B) plus standard of care. The primary endpoint, all-cause mortality at day 42, was 23.8% for olorofim versus 24.3% for AmBisome plus SoC, meeting the primary objective with a non-inferiority margin of 20% as pre-specified.

Safety – A Significant Advantage of Oral Administration

The incidence of drug-related treatment-emergent adverse events (TEAEs) was significantly lower for olorofim (35.8%) compared to AmBisome (63.9%). The higher incidence of adverse events in the AmBisome group was primarily due to renal toxicity. No new safety concerns were observed with olorofim. The ability to administer oral olorofim as a single agent in the setting of long-term hospitalization in immunocompromised patients represents a significant differentiation in terms of treatment adherence and healthcare costs.

A Fourth Mechanism of Action for Antifungals – DHODH Inhibition

Olorofim is the first drug in the orotomide class, selectively inhibiting fungal dihydroorotate dehydrogenase (DHODH) and blocking the pyrimidine biosynthesis pathway. Its mechanism of action is distinct from existing azoles (ergosterol synthesis inhibitors), echinocandins (glucan synthesis inhibitors), and polyenes (cell membrane binding), resulting in no cross-resistance. The FDA has granted olorofim orphan drug designation, qualified infectious disease product (QIDP) designation, and two breakthrough therapy designations (BTD).

Regulatory Strategy – Accelerated Resubmission Following CRL

F2G previously submitted an NDA through the limited population accelerated approval (LPAD) pathway but received a complete response letter (CRL) from the FDA requesting additional data. The OASIS Phase 3 data will serve as the key evidence for the U.S. resubmission. F2G will be responsible for the North American regulatory submission, while Shionogi will handle the European and Asian submissions. John Keller, Ph.D., Senior Vice President of R&D at Shionogi, stated that this is a promising new development in the field of antifungals, where treatment options have been limited for patients for over 20 years.

Partnership Structure and Market Opportunity

F2G (unlisted, with headquarters in the UK, U.S., and Austria, CEO Francesco Maria Lavino) and Shionogi entered into a strategic alliance in May 2022, under which Shionogi will pay a $100 million upfront payment plus up to $380 million in milestone payments and a double-digit royalty, and the Phase 3 costs will be shared 50:50. The market for invasive aspergillosis treatments is estimated at $1.19 billion in 2026 and is projected to grow to $1.42 billion in 2030 (CAGR of 4.5%). The dual differentiation of oral administration and a novel mechanism of action compared to existing standard treatments such as voriconazole (Pfizer), isavuconazole/Cresemba (Astellas/Basilea), and amphotericin B (AmBisome, Gilead) will be key to market penetration.