Fungemia

Allschwil, Switzerland, September 24, 2024 Basilea Pharmaceutica Ltd, Allschwil (SIX: BSLN), a commercial-stage biopharmaceutical company committed to meeting the needs of patients with severe bacterial and fungal infections, announced today that it has initiated the Fosmanogepix Against Standard-of-care Treatment in Invasive Candidiasis (FAST-IC) phase 3 study. This registrational study evaluates the efficacy and safety of Basilea’s broad-spectrum antifungal fosmanogepix in the treatment of adult patients with candidemia and/or invasive candidiasis, that is Candida yeast bloodstream or deep-seated tissue infections.1 Fosmanogepix is a first-in-class antifungal treatment candidate with a novel mechanism of action. It is available in intravenous and oral formulations and has been evaluated for efficacy and safety in a phase 1 / phase 2 program, including three open-label phase 2 studies for the treatment of Candidemia, including Candida auris, and invasive mold infections.2, 3, 4, 5 Dr. Marc Engelhardt, Chief Medical Officer of Basilea, said: “We are very pleased to have activated the first study center in the phase 3 program for fosmanogepix and look forward to enrolling patients into FAST-IC. Invasive Candida infections are life-threatening complications for many hospitalized patients and associated with high mortality, and fosmanogepix offers a potential new treatment option in this high medical need area. In addition, we are working towards starting the second phase 3 study investigating fosmanogepix in the treatment of adult patients with invasive mold infections around year-end.” FAST-IC is a global, multi-center, randomized, active-controlled, double-blind phase 3 study and investigates intravenous (i.v.) fosmanogepix versus a standard-of-care regimen of i.v. caspofungin in adult patients with candidemia and/or invasive candidiasis. The study is expected to enroll approximately 450 patients, who will be randomized in a 2:1 ratio to either fosmanogepix or caspofungin. There is an optional oral switch to fosmanogepix in the fosmanogepix group and to fluconazole in the caspofungin group. The Swiss-based global company PSI CRO AG will manage the phase 3 program. Basilea acquired fosmanogepix from Amplyx Pharmaceuticals, Inc., an affiliate of Pfizer Inc., in November 2023. Under the terms of the asset purchase agreement, Basilea assumed all rights and obligations from previous agreements, and will make a USD 6.0 million milestone payment under these obligations, upon the enrolment of the first patient, which is fully reflected in Basilea’s most recent financial guidance for the full year 2024. This project has been funded in part with federal funds from the U.S. Department of Health and Human Services (HHS); Administration of Strategic Preparedness and Response (ASPR); Biomedical Advanced Research and Development Authority (BARDA), under OT number: 75A50124C00033. The contract and federal funding are not an endorsement of the study results, product, or company. About fosmanogepix Fosmanogepix is a clinical-stage broad-spectrum antifungal. It has a novel mechanism of action and its active moiety has shown activity against common species of Candida and Aspergillus, including multi-drug-resistant strains, such as Candida auris and Candida glabrata, as well as rare difficult-to-treat molds including Fusarium spp., Scedosporium spp., and some fungi from the Mucorales order.2 Fosmanogepix intravenous and oral formulations have been evaluated in clinical phase 2 studies for the treatment of patients with Candidemia, including Candida auris, and invasive mold infections.2 Fosmanogepix has received Fast Track and Orphan Drug designations from the US Food and Drug Administration for seven separate indications, and is designated as a Qualified Infectious Disease Product (QIDP). About invasive mold infections Invasive aspergillosis and invasive infections with rare molds (e.g., Fusarium spp., Scedosporium spp., and Mucorales fungi) are life-threatening infections that predominantly affect immunocompromised patients, including patients with hematologic malignancies (blood cancer), transplant patients, or patients with other immunodeficiency disorders. These infections are associated with high morbidity and mortality.6, 7 About invasive candidiasis Invasive candidiasis, including deep-seated tissue candidiasis and candidemia, is an increasingly important nosocomial infection, especially in patients hospitalized in intensive care units. Candida species are ranked as the fourth main cause of bloodstream infections in hospitals in the US.8 The prognosis of invasive candidiasis remains difficult, with a reported mortality rate as high as 40%, even when patients receive antifungal therapy.9 About Basilea Basilea is a commercial-stage biopharmaceutical company founded in 2000 and headquartered in Switzerland. We are committed to discovering, developing and commercializing innovative drugs to meet the needs of patients with severe bacterial and fungal infections. We have successfully launched two hospital brands, Cresemba for the treatment of invasive fungal infections and Zevtera for the treatment of bacterial infections. In addition, we have preclinical and clinical anti-infective assets in our portfolio. Basilea is listed on the SIX Swiss Exchange (SIX: BSLN). Please visit basilea.com. Disclaimer This communication expressly or implicitly contains certain forward-looking statements, such as "believe", "assume", "expect", "forecast", "project", "may", "could", "might", "will" or similar expressions concerning Basilea Pharmaceutica Ltd, Allschwil and its business, including with respect to the progress, timing and completion of research, development and clinical studies for product candidates. Such statements involve certain known and unknown risks, uncertainties and other factors, which could cause the actual results, financial condition, performance or achievements of Basilea Pharmaceutica Ltd, Allschwil to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Basilea Pharmaceutica Ltd, Allschwil is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise. For further information, please contact: Peer Nils Schröder, PhDHead of Corporate Communications & Investor RelationsBasilea Pharmaceutica International Ltd, Allschwil Hegenheimermattweg 167b4123 AllschwilSwitzerland Phone+41 61 606 1102 E-mailmedia_relations@basilea.cominvestor_relations@basilea.com This press release can be downloaded from www.basilea.com. References ClinicalTrials.gov identifier: NCT05421858K. J. Shaw, A. S. Ibrahim. Fosmanogepix:A Review of the First-in-Class Broad Spectrum Agent for the Treatment of Invasive Fungal Infections. Journal of Fungi (Basel) 2020 (6), 239M. R. Hodges, E. Ople, P. Wedel et al. Safety and Pharmacokinetics of Intravenous and Oral Fosmanogepix, a First-in-Class Antifungal Agent, in Healthy Volunteers. Antimicrobial Agents and Chemotherapy 2023 (67), e01623-22J. A. Vazquez, P. G. Pappas, K. Boffard et al. Clinical Efficacy and Safety of a Novel Antifungal, Fosmanogepix, in Patients with Candidemia Caused by Candida auris: Results from a Phase 2 Trial. Antimicrobial Agents and Chemotherapy2023 (67), e01419-22P. G. Pappas, J. A. Vazquez, I. Oren et al. Clinical safety and efficacy of novel antifungal, fosmanogepix, for the treatment of candidaemia: results from a Phase 2 trial. Journal of Antimicrobial Chemotherapy 2023 (78), 2471-2480J. Cadena, G. R. Thompson 3rd, T. F..Patterson. Aspergillosis: Epidemiology, Diagnosis, and Treatment. Infectious Disease Clinics of North America 2021 (35), 415-434M. Slavin, S. van Hal, T. C. Sorrell et al. Invasive infections due to filamentous fungi other than Aspergillus: epidemiology and determinants of mortality. Clinical Microbiology and Infection 2015 (21), 490.e1-490.e10Candidemia (Blood Infection) and Other Candida Infections. 2019 Factsheet by the American Thoracic Society: https://www.thoracic.org/patients/patient-resources/resources/candidemia.pdf (Accessed: September 23, 2024)B. J. Kullberg, M. C. Arendrup. Invasive Candidiasis. The New England Journal of Medicine 2015 (373), 1445-1456 Attachment Press release (PDF).pdf

Initial funding of USD 29 million to support development of Basilea’s clinical stage first-in-class antifungals, fosmanogepix and BAL2062Multi-year Other Transaction Agreement (OTA) allows for potential funding of up to approximately USD 268 million to develop antifungal and antibacterial assets Increasing FY 2024 financial guidance on total revenue, operating result and net profit Ad hoc announcement pursuant to Art. 53 LR Allschwil, Switzerland, September 19, 2024 Basilea Pharmaceutica Ltd, Allschwil (SIX: BSLN), a commercial-stage biopharmaceutical company committed to meeting the needs of patients with severe bacterial and fungal infections, announced today that the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response (ASPR) within the US Department of Health and Human Services, has awarded Basilea an Other Transaction Agreement (OTA), under OTA number 75A50124C00033. As a result, Basilea increases its financial guidance for the full year 2024. David Veitch, Chief Executive Officer of Basilea, said: “Basilea has been working with BARDA since 2013. In continuing this partnership through an OTA, we will be leveraging our strong portfolio and the capabilities of our organization to develop urgently needed novel antifungals and antibacterials. We believe this long-term partnership will also lead to the successful implementation of our strategy to become a leading anti-infectives company.” Under the terms of the OTA, BARDA will support the development of designated novel, first-in-class antifungals and antibacterials in Basilea’s portfolio with a total potential non-dilutive funding of up to approximately USD 268 million over up to twelve years, if all additional options to extend the contract are exercised by BARDA upon successful completion of pre-defined milestones, including clinical and regulatory activities. With the signing of the OTA, initial BARDA funds of USD 29 million have been committed to support the development of the antifungals fosmanogepix and BAL2062. BARDA’s financial contribution is assumed to be about 60% of the total costs over the term of the OTA. Under the OTA, BARDA and Basilea can jointly decide to move candidates into and out of the portfolio based on product performance, technical risk, and programmatic need. This flexibility results in significant time, effort, and cost savings to both partners. Increasing full-year (FY) 2024 financial guidance Reflecting the near-term impact of the OTA, Basilea updates its financial guidance for the full year 2024. Development costs under the OTA will continue to be reported under research and development expenses. The BARDA reimbursements will be reported under other revenue, resulting in increased total revenue and unchanged operating expenses. Also, additional deferred taxes are recognized due to the expected positive effect of the OTA on the company's medium-term financial outlook. This results in a higher operating result and net profit for FY 2024. (In CHF million) FY 2024e(new) FY 2024e(previous) FY 2023 Cresemba and Zevtera-related revenue ~190 ~190 150.3 of which royalty income ~92 ~92 78.9 Total revenue ~203 ~196 157.6 Cost of products sold ~40 ~40 26.8 Operating expenses ~120 ~120 111.7 Operating result ~43 ~36 19.2 Net profit ~60 ~42 10.5 About fosmanogepix Fosmanogepix is a clinical-stage broad-spectrum antifungal. It has a novel mechanism of action and its active moiety has shown activity against common species of Candida and Aspergillus, including multi-drug-resistant strains, such as Candida auris and Candida glabrata, as well as rare difficult-to-treat molds including Fusarium spp., Scedosporium spp., and some fungi from the Mucorales order.1 Fosmanogepix is available in intravenous and oral formulations and has been evaluated for efficacy and safety in a phase 1 / phase 2 program, including three open-label phase 2 studies for the treatment of Candidemia, including Candida auris, and invasive mold infections.1, 2, 3, 4 Basilea will initiate shortly a double-blind non-inferiority phase 3 study in invasive yeast infections.5 Fosmanogepix has received Fast Track and Orphan Drug designations from the US Food and Drug Administration for seven separate indications, and is designated as a Qualified Infectious Disease Product (QIDP) for the treatment of four indications. About BAL2062 BAL2062 is a first-in-class antifungal, derived from a natural product, and has demonstrated fungicidal activity against clinically important molds such as Aspergillus spp., including azole-resistant strains.6 Safety and tolerability have been demonstrated in a previously completed phase 1 study with single and multiple ascending intravenous (i.v.) doses.7 The drug candidate has Qualified Infectious Disease Product (QIDP), Orphan Drug and Fast Track designation from the US Food & Drug Administration (FDA) for invasive aspergillosis. About invasive mold infections Invasive aspergillosis and invasive infections with rare molds (e.g., Fusarium spp., Scedosporium spp., and Mucorales fungi) are life-threatening infections that predominantly affect immunocompromised patients, including patients with hematologic malignancies (blood cancer), transplant patients, or patients with other immunodeficiency disorders. These infections are associated with high morbidity and mortality.8, 9 About invasive candidiasis Invasive candidiasis, including deep-seated tissue candidiasis and candidemia, is an increasingly important nosocomial infection, especially in patients hospitalized in intensive care units. Candida species are ranked as the fourth main cause of bloodstream infections in hospitals in the US.10 The prognosis of invasive candidiasis remains difficult, with a reported mortality rate for invasive candidiasis as high as 40%, even when patients receive antifungal therapy.11 About Basilea Basilea is a commercial-stage biopharmaceutical company founded in 2000 and headquartered in Switzerland. We are committed to discovering, developing and commercializing innovative drugs to meet the needs of patients with severe bacterial and fungal infections. We have successfully launched two hospital brands, Cresemba for the treatment of invasive fungal infections and Zevtera for the treatment of bacterial infections. In addition, we have preclinical and clinical anti-infective assets in our portfolio. Basilea is listed on the SIX Swiss Exchange (SIX: BSLN). Please visit basilea.com. Disclaimer This communication expressly or implicitly contains certain forward-looking statements, such as "believe", "assume", "expect", "forecast", "project", "may", "could", "might", "will" or similar expressions concerning Basilea Pharmaceutica Ltd, Allschwil and its business, including with respect to the progress, timing and completion of research, development and clinical studies for product candidates. Such statements involve certain known and unknown risks, uncertainties and other factors, which could cause the actual results, financial condition, performance or achievements of Basilea Pharmaceutica Ltd, Allschwil to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Basilea Pharmaceutica Ltd, Allschwil is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise. For further information, please contact: Peer Nils Schröder, PhD Head of Corporate Communications & Investor RelationsBasilea Pharmaceutica International Ltd, Allschwil Hegenheimermattweg 167b4123 AllschwilSwitzerland Phone +41 61 606 1102 E-mail media_relations@basilea.com investor_relations@basilea.com This ad hoc announcement can be downloaded from www.basilea.com. References K. J. Shaw, A. S. Ibrahim. Fosmanogepix:A Review of the First-in-Class Broad Spectrum Agent for the Treatment of Invasive Fungal Infections. Journal of Fungi (Basel) 2020 (6), 239M. R. Hodges, E. Ople, P. Wedel et al. Safety and Pharmacokinetics of Intravenous and Oral Fosmanogepix, a First-in-Class Antifungal Agent, in Healthy Volunteers. Antimicrobial Agents and Chemotherapy 2023 (67), e01623-22J. A. Vazquez, P. G. Pappas, K. Boffard et al. Clinical Efficacy and Safety of a Novel Antifungal, Fosmanogepix, in Patients with Candidemia Caused by Candida auris: Results from a Phase 2 Trial. Antimicrobial Agents and Chemotherapy2023 (67), e01419-22P. G. Pappas, J. A. Vazquez, I. Oren et al. Clinical safety and efficacy of novel antifungal, fosmanogepix, for the treatment of candidaemia: results from a Phase 2 trial. Journal of Antimicrobial Chemotherapy 2023 (78), 2471-2480ClinicalTrials.gov identifier NCT05421858K. J. Shaw. GR-2397: Review of the Novel Siderophore-like Antifungal Agent for the Treatment of Invasive Aspergillosis. Journal of Fungi (Basel) 2022 (8), 909ClinicalTrials.gov identifier NCT02956499: M. P. Mammen, D. Armas, F. H. Hughes et al. First-in-Human Phase 1 Study To Assess Safety, Tolerability, and Pharmacokinetics of a Novel Antifungal Drug, VL-2397, in Healthy Adults. Antimicrobial Agents and Chemotherapy 2019 (63), e00969-19J. Cadena, G. R. Thompson 3rd, T. F..Patterson. Aspergillosis: Epidemiology, Diagnosis, and Treatment. Infectious Disease Clinics of North America 2021 (35), 415-434M. Slavin, S. van Hal, T. C. Sorrell et al. Invasive infections due to filamentous fungi other than Aspergillus: epidemiology and determinants of mortality. Clinical Microbiology and Infection 2015 (21), 490.e1-490.e10Candidemia (Blood Infection) and Other Candida Infections. 2019 Factsheet by the American Thoracic Society: https://www.thoracic.org/patients/patient-resources/resources/candidemia.pdf (Accessed: September 18, 2024)B. J. Kullberg, M. C. Arendrup. Invasive Candidiasis. The New England Journal of Medicine 2015 (373), 1445-1456 Attachment Press release (PDF)

Study finds that mesalamine, a common anti-inflammatory drug, can fight the fungus Candida albicans in the gut, potentially preventing the risk of invasive candidiasis in patients with blood cancers. A team of UC Davis Health researchers discovered that a common anti-inflammatory drug, mesalamine, can replace the work of good bacteria in fighting the nasty fungus Candida albicans in the gut. C. albicans, or candida, is known to cause yeast infections. In some cases, it develops into invasive candidiasis, a potentially fatal infection occurring mostly in patients with compromised immunity. The researchers found that this fungus can't grow without an oxygen supply. Their study in mice showed that the drug can maintain a low oxygen (hypoxia) environment that prevents fungal bloom in the gut. Their study appears today in Cell Host & Microbe. Antibiotic use may lead to fungal bloom in the gut The team studied how C. albicans colonizes the gut. The fungus, best known for causing vaginal yeast infections, is usually treated with a topical or oral antifungal without serious side effects. It also harmlessly lives in the gut of around 60% of people. Yet, when the body's immunity goes down due to cancer or chemotherapy, the fungus may grow beyond the colon and spread throughout the body. In such cases, the patient develops invasive candidiasis. "Invasive candidiasis is a potentially deadly infection with a mortality rate of around 50%. That's even with the best available treatment," explained the study's lead author Andreas Bäumler. Bäumler is a distinguished professor in the Department of Medical Microbiology and Immunology. Patients with leukemia and other blood cancers may need to take antibiotics. This use may cause an imbalance in the gut's microbial community. It reduces Clostridia, a group of bacteria that promotes resistance to fungi colonization in the gut. With less Clostridia, C. albicans grows and colonizes in the tract. "A bloom of C. albicansin the gut during antibiotic therapy is the most common cause of candidemia in people treated for blood cancers," Bäumler explained. Candidemia is the presence of fungi or yeast in the blood. Bäumler and his team wanted to understand the factors involved in antibiotic-induced colonization of C. albicans in the gut. Candida loves simple sugars and oxygen They first colonized germ-free mice with Candida to see what the fungus consumed to bloom. They realized that Candida really liked simple sugars, similar to those found in high-sugar diets. Then, they tested its growth in a petri dish. They placed Candida with simple sugars in an aerobic (with oxygen) setting, and the fungi bloomed. "A healthy gut has low oxygen. So, we repeated the test in a hypoxia setting," Bäumler said. The fungi didn't grow despite the presence of sugars. This meant oxygen is a necessary condition for Candida growth. The role of probiotics in preventing fungal growth The team did a series of experiments that showed antibiotic use reduced Clostridiain the gut. Giving mice probiotics, such as Clostridia, prevented C. albicans from growing in the gut. Yet, probiotics can be killed by antibiotics and cancer therapy. For this reason, probiotics would not help patients with leukemia or other blood cancers. "Probiotics are often not safe in patients at the highest risk for invasive candidiasis," Bäumler said. "Finding a therapy that can function like probiotics but can endure the impact of cancer treatment and antibiotics was important." Anti-inflammatory drugs as faux-biotics The team explored 5-aminosalicylic acid (5-ASA) as a safer way to control C. albicansin the gut. 5-ASA, also known as mesalamine, is an anti-inflammatory drug. It is used to treat inflammatory bowel diseases (IBD) like Crohn's disease and ulcerative colitis. The team tested 5-ASA in mice treated with antibiotics. They found that the drug could replace the work of probiotics by preventing oxygen in the colon and C. albicans from expanding in the gut. "Limiting oxygen in the gut by replacing the function of good bacteria could be a strategy for reducing invasive candidiasis," Bäumler said. "Our study opens a totally new treatment option for fatal fungal infections, especially for patients with cancer. After all, fungi cannot become resistant against hypoxia." The team proposed the term "faux-biotics" to refer to products, such as 5-ASA, that mimic the function of probiotics like Clostridia. The first coauthors of the study are Hannah Savage, Derek Bays and Connor Tiffany. The other co-authors are Mariela Gonzalez, Eli Bejarano, Thaynara Carvalho, Zheng Luo, Hugo Masson, Henry Nguyen, Renato Santos, Krystle Reagan and George Thompson of UC Davis.