Scedosporiosis

Infections caused by Aspergillus species of mold are transmitted through inhalation and can lead to symptoms including hypersensitivity reactions and tissue damage. Invasive aspergillosis (IA) is a particularly life-threatening infection that happens in high-risk immunosuppressed people. While these infections can be controlled with antifungals, increasing numbers of cases are becoming resistant to these drugs. At the same time, there is a “paucity of innovation” in the antifungal pipeline, with clinicians relying on just a handful of antifungal classes, said Henry Skinner, CEO of the funding round co-leader AMR Action Fund, in a public statement ​. However, it is challenging to develop new drugs as fungi can become cross-resistant to multiple drugs with similar mechanisms of action, and it is tough to develop drugs that specifically target fungi without harming patients. To tackle this challenge, the first-in-class small molecule drug olorofim blocks a key enzyme in the pyrimidine synthesis pathway called fungal dihydroorotate dehydrogenase, killing fungal cells. The compound, which circumvents the resistance of fungal infections to existing drugs, would likely be used in niche cases of serious invasive, rare fungal disease that cannot be helped by existing treatments, F2G CEO Francesco Lavino told BioPharma Reporter. Olorofim is currently in a phase 2b open-label trial for the treatment of rare fungal mold infections such as azole-resistant aspergillosis, scedosporiosis and lomentosporiosis. The company used data from the first 100 patients in the trial to apply for market approval from the US FDA, but the application was shot down ​ last year due to a lack of data. F2G is now preparing a resubmission of the application with updated data from more than 200 patients and updated historical controls, Lavino said. googletag.cmd.push(function () { googletag.display('text-ad1'); }); F2G is also working with the Japanese company Shionogi to test olorofim in a phase 3 trial comparing it to a drug called liposomal amphotericin B followed by standard of care in patients with invasive fungal disease that cannot take an azole antifungal. The trial is expected to wrap up in late 2025 with market approval aimed for a year after that, said the CEO. Founded in 1998, F2G raised $60.8 million in 2020 ​ and $70 million in 2022 ​ to finance its pipeline development. The company is also running programs for indications including coccidioidomycosis and pediatric fungal infections. Over the coming decade, Lavino sees a growing awareness of the critical threat of fungal infections, which can “spread across ecosystems, making collaborative global efforts essential to controlling them.” This growing awareness is also leading to increasing financial backing for antifungal development, with the AMR Action Fund being a key example. Growing resistance to antimicrobial drugs is one of the top global public health and development threats, causing an estimated 1.27 million deaths globally in 2019, according to the World Health Organization ​. One of the main drivers of the crisis is the misuse of antimicrobials in humans, animals and plants.

Financing is being led by new investor AMR Action Fund with strong participation from new investor ICG Life Sciences and existing investors MANCHESTER, United Kingdom, Sept. 12, 2024 (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 a $100 million financing round. The financing is being led by new investor AMR Action Fund and co-led by ICG, with strong participation from existing investors Novo Holdings, Advent Life Sciences, Sofinnova Partners, Forbion, Blue Owl Healthcare Opportunities, Morningside Ventures, Brace Pharmaceuticals, and Merifin Capital. The proceeds from the financing will enable F2G to complete late-stage development, seek regulatory approval, and prepare for commercialization in the US of olorofim, a novel oral antifungal therapy to treat invasive aspergillosis (IA) and other invasive fungal infections. Henry Skinner, Ph.D., Chief Executive Officer of AMR Action Fund and Toby Sykes Ph.D., Managing Director of ICG Life Sciences, will join the F2G Board of Directors. The financing is subject to customary Foreign Direct Investment (FDI) clearance by local authorities in Austria, where F2G has a 100%-owned subsidiary, and expected to close in the fourth quarter of 2024. Olorofim is the first orotomide antifungal, an entirely novel class of antifungal agents and is the only antifungal medication to be awarded a Breakthrough Therapy Designation for multiple indications by the US 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 pyrimidine synthesis pathway. It is anticipated to be used to treat patients with a serious invasive, rare fungal disease where existing treatments are inappropriate or no longer effective. Francesco Maria Lavino, Chief Executive Officer of F2G, said: “We are delighted to attract this additional capital investment into F2G, and we are thrilled to be working with the AMR Action Fund, an important player in the antimicrobial space, and ICG, a leading alternative asset manager. The addition of Dr. Skinner and Dr. Sykes to our Board will be invaluable as we move to our next stage of growth. This is a pivotal period for the Company as we conclude the final stages of development and preparation for commercialization of olorofim in the US and elsewhere. If approved, olorofim is expected to be the first of a new class of antifungal agents with a novel, differentiated mechanism of action and will address genuine unmet needs in conditions with high morbidity and mortality.” Dr. Skinner commented: “Fungal infections are a growing threat to patients around the world and have a disproportionate impact on vulnerable populations, yet there has been a paucity of innovation in the field of antifungals. For decades, clinicians have relied on a handful of antifungal classes, with few mechanisms of action and significant limitations due to spectrum of activity, drug toxicities, or drug-drug interactions. These therapies are increasingly failing in patients. We are thrilled to support F2G’s team as they develop this urgently needed therapy and seek regulatory approval.” Dr. Sykes commented: “Fungal pathogens continue to emerge and spread. This evolving threat underscores an urgent unmet medical need for advanced antifungal treatments. By investing in the development of novel antifungal drug candidates like olorofim, we hope to address this critical gap, ultimately making a meaningful and sustainable social impact on patients, their caregivers, and healthcare systems.” 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 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 olorofim Olorofim (formerly, F901318) is F2G's leading candidate from the orotomide class and is currently in a Phase 2b open-label study (ClinicalTrials.gov Identifier: NCT03583164) 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 liposomal amphotericin B followed by standard of care (SOC) in patients with invasive fungal disease caused by proven Invasive Aspergillus or probable lower respiratory tract disease by Aspergillus species. 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. About invasive aspergillosis Aspergillosis is a fungal infection caused by Aspergillus species of mold which are commonly found all over the world. Most of these molds, in most people, do not cause disease. However, Aspergillus is transmitted to humans through inhalation and may cause a broad spectrum of disease ranging from hypersensitivity reactions to direct invasion and destruction of tissue, especially in immunocompromised hosts. Invasive aspergillosis is a rare disease that can occur in over 10% of some high-risk immunosuppressed populations with mortality exceeding 80%. Media ContactKristin Politi, Ph.D.LifeSci Communicationskpoliti@lifescicomms.com 646-876-4783

Manchester, UK-based F2G has patched together another $100 million in funding a little over a year after receiving a CRL for its experimental fungal infection drug known as olorofim, it said Thursday morning. The biotech has met with the FDA multiple times since that June 2023 no-go , and the company plans to ask the US regulator for approval again “toward the end” of 2025, with the goal of securing a green light by mid-2026, CEO Francesco Maria Lavino told Endpoints News . The new financing is tranched, with $62.5 million coming in at first and another $37.5 million that is dependent on milestones, the company told Endpoints. As a Series H, the new financing represents a rare private funding round. Many biotechs will go public or get acquired after netting a handful or less of private rounds from VC firms and other investors. The Series H is also somewhat of an outlier in the current financing environment because it’s an up round, Lavino said, meaning it values the company higher than its last disclosed round of $70 million in August 2022 . It’s been a long time coming for the biotech: F2G was founded in 1998 and was one of the original tenants in the University of Manchester’s incubator facility. But investments for antifungals and anti-infectives have historically paled in comparison to other areas of drug development. Lavino, though, is positioning F2G as a rare disease company. “The way we are developing the drug is more like a rare disease product. We are really focusing on infection that had limited or, in many cases, no option,” Lavino said. “Clearly, that’s a very different value proposition than a more general anti-infective or antibiotic, where you are dealing with a lot of generics.” He said most of the patients are immunocompromised, including those with leukemia. If they don’t get treated, they’ll die, he said. The company also has a compassionate use program that has “daily requests.” After last year’s CRL, F2G met with the FDA last October, March and again in August, thanks in part to the benefit of having breakthrough therapy designation, Lavino said. He described the rejection as “relatively speaking, benign,” and noted the company and regulator have “aligned” on a resubmission plan. “The FDA is still open. We are basically packaging the data in a different way,” Lavino said. F2G will resubmit olorofim for approval based on an open-label Phase 2b and “slightly different historical control data,” Lavino said. F2G will give the FDA data on about 200 patients from the Phase 2b this time around versus the approximately 100 that it delivered the first time, Lavino said. The Phase 2b tested olorofim, formerly F901318, in patients with invasive fungal infections who had limited treatment options. Included were rare mold infections like azole-resistant aspergillosis , scedosporiosis and lomentosporiosis , among others. A Phase 3 study is testing olorofim against liposomal amphotericin B followed by standard of care. Dubbed OASIS, the study is enrolling about 225 patients and is slated to have a primary completion 12 months from now, according to the federal clinical trials database. Shionogi, F2G’s European and Asia licensing partner , will likely wait for that Phase 3 data before submitting for approval in Europe, Lavino said. That could change, though, as more results come in from the Phase 2 study, but “a conditional approval in Europe” is “not part of our baseline,” he added. After securing FDA approval, F2G could consider further dealmaking to expand olorofim’s potential in other regions, including Latin America, Lavino said. For now, it has the money to get on the market in the US thanks to new investors AMR Action Fund and ICG. Existing backers also contributed to the new round, including Novo Holdings, Advent Life Sciences, Sofinnova Partners, Forbion and others.