Amphotericin B

Fungal infections are becoming deadlier as drug resistance spreads and treatment options stall. Researchers at McMaster University discovered that a molecule called butyrolactol A can dramatically weaken dangerous fungi, allowing existing antifungal drugs to work again. Instead of killing the fungus directly, the molecule sabotages a vital internal system, leaving the pathogen exposed. The breakthrough could help revive an entire class of antifungal medicines once thought obsolete.Fungal infections claim millions of lives every year, yet treatment options have failed to keep pace with the growing danger. Scientists at McMaster University now report a discovery that could shift that balance. They have identified a molecule called butyrolactol A that targets a highly dangerous disease-causing fungus known as Cryptococcus neoformans. Cryptococcus infections can be life-threatening. The fungus often triggers pneumonia-like illness and is especially hazardous for people with weakened immune systems, including cancer patients and individuals living with HIV. It is also known for resisting many available drugs. Other fungal threats show similar behavior, including Candida auris and Aspergillus fumigatus. Like Cryptococcus, both have been designated priority pathogens by the World Health Organization. Despite the severity of these infections, doctors are limited to just three major antifungal treatment options. Limited Treatments and Toxic Side Effects The most effective antifungal drugs belong to a class called amphotericin. However, these drugs are notorious for harming patients as well as pathogens. Gerry Wright, a professor in McMaster's Department of Biochemistry and Biomedical Sciences, jokes that amphotericin is often referred to as "amphoterrible" because of its severe toxic effects on humans. "Fungal cells are a lot like human cells, so the drugs that hurt them tend to hurt us too," he says. "That's why there are so few options available to patients." The remaining two antifungal drug classes, azoles and echinocandins, are far less effective, particularly against Cryptococcus. According to Wright, azoles only slow fungal growth instead of killing the organism. Echinocandins have become useless against Cryptococcus and several other fungi due to widespread resistance. Turning to Helper Molecules for a New Strategy With few approved drugs, little progress in the antifungal pipeline, and rising resistance, researchers are now focusing on a different approach using compounds known as adjuvants. "Adjuvants are helper molecules that don't actually kill pathogens like drugs do, but instead make them extremely susceptible to existing medicine," explains Wright, a member of the Michael G. DeGroote Institute for Infectious Disease Research (IIDR). To find an adjuvant that could make Cryptococcus more vulnerable to treatment, Wright's team screened thousands of compounds from McMaster's extensive chemical library. Rediscovering an Overlooked Molecule The researchers quickly identified a promising candidate. Butyrolactol A is a molecule produced by certain Streptomyces bacteria that had been known for decades but largely ignored. When paired with echinocandin drugs, the compound enabled those drugs to kill fungi they could not eliminate on their own. At first, the team did not understand how the molecule worked and nearly dismissed it. "This molecule was first discovered in the early 1990s, and nobody has ever really looked at it since," Wright says. "So, when it showed up in our screens, my first instinct was to walk away from it. I thought, 'it's a known compound, it kind of looks like amphotericin, it's just another toxic molecule, not worth our time.'" Persistence Pays Off Wright says the project continued thanks to the persistence of postdoctoral fellow Xuefei Chen. "Early on, this molecule's activity appeared to be quite good," says Chen, who works in Wright's lab. "I felt that if there was even a small chance that it could revive an entire class of antifungal medicine, we had to explore it." Years of detailed investigation followed, which Wright describes as "painstaking sleuthing and detective work." That effort ultimately revealed how butyrolactol A functions. How the Molecule Disarms Deadly Fungi Chen discovered that butyrolactol A blocks a protein complex that is essential for Cryptococcus survival. Wright describes the effect vividly. "When it's jammed, all hell breaks loose." Once this critical system is disrupted, the fungus becomes fully exposed to drugs it previously resisted. Further experiments showed the molecule has similar effects on Candida auris. The team worked alongside researchers in the lab of McMaster Professor Brian Coombes, also a member of the IIDR. These results suggest the discovery could have broad clinical potential beyond a single pathogen. More Than a Decade in the Making Wright says the findings, recently published in the journal Cell, represent more than ten years of research. "That first screen that put butyrolactol A on our radar took place in 2014," he notes. "More than eleven years later, thanks almost entirely to Chen, we have identified a legitimate drug candidate and an entirely new target to attack with other new drugs." The breakthrough marks the second antifungal compound and the third new antimicrobial discovered by Wright's lab within the past year.

Ad hoc announcement pursuant to Art. 53 LR Allschwil, Switzerland, November 04, 2025 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 continued strong sales performance of the antifungal Cresemba® (isavuconazole) by its license partner Pfizer Inc. in Europe exceeded the threshold triggering a USD 30 million sales milestone payment. David Veitch, Basilea’s Chief Executive Officer, stated: “This further milestone payment for Europe reflects the significant medical need and strong growth momentum of Cresemba in the region. We are pleased to see that Cresemba continues to address this need in patients suffering from life-threatening invasive mold infections.” Cresemba is approved and marketed in more than 70 countries, including the United States, most EU member states and additional countries inside and outside of Europe. According to the latest available market data, total global in-market sales of Cresemba amounted to USD 652 million in the 12 months between July 2024 and June 2025, a 27 percent growth year-on-year.[1] About Cresemba® (isavuconazole) Cresemba, with the active ingredient isavuconazole, is an intravenous (i.v.) and oral azole antifungal. Basilea has entered into several license and distribution agreements for isavuconazole covering approximately 115 countries. In the European Union, Iceland, Liechtenstein, Norway and the United Kingdom, isavuconazole for intravenous administration is approved for patients from one year of age for the treatment of invasive aspergillosis and for the treatment of mucormycosis in patients for whom amphotericin B is inappropriate. Cresemba capsules for oral administration are approved for adults and for pediatric patients six years of age and older who weigh 16 kg or more.[2] Isavuconazole is also approved in the United States (US), Japan and several additional countries in Europe and beyond, including in the Asia Pacific region.[3] It has orphan drug designation in the US, the European Union, the UK and other countries for its approved indications. 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 or 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.cominvestor_relations@basilea.com This ad hoc announcement can be downloaded from www.basilea.com. References IQVIA Analytics Link, June 2025. In-market sales reported as moving annual total (MAT) in US dollars. European Public Assessment Report (EPAR) Cresemba: https://www.ema.europa.eu/en/medicines/human/EPAR/cresemba [Accessed: November 03, 2025]The registration status and approved indications may vary from country to country. Attachment Press release (PDF)