The new research, funded by the U.K based charitable foundation Wellcome, has identified a link between climate change and increasing fungal infections, noting that molds like Aspergillus, prevalent in soil, decaying vegetation, and indoor environments, are becoming more common. These molds’ spores cause infections when inhaled, particularly in immunocompromised individuals. Some fungi are adapting to higher temperatures, increasing their ability to survive in the human body.
A 2024 Chinese study, identifying a new human fungal pathogen resistant to common antifungals, with resistance worsening at higher temperatures, confirms the new findings. The recent research data suggest that Aspergillus could expand to northern Europe, Asia, and North America, covering 77 percent more territory by 2100. Considering that over 90 percent of an estimated 2.5 million fungal species are still unknown, the need for new antifungals is urgent.
Antimicrobial and multidrug resistance
Invasive aspergillosis carries a mortality rate of up to 88 percent in high-risk groups like cancer patients or organ transplant recipients, with some studies reporting up to 100 percent mortality. It is estimated that more than 3 million people worldwide develop chronic pulmonary aspergillosis every year and that roughly one fifth of all sales of antifungal drugs are directed against the Aspergillus pathogen.
Currently, only four classes of systemic antifungal medicines are used in clinical practice, with Azoles discovered in the 1960:s, dominating the antifungal drug market. However, the widespread use of azole fungicides in agriculture, livestock, and industrial applications, like coatings and timber preservation, contributes to resistant aspergillosis in humans.
Drivers of fungal spread and health implications
Warmer temperatures and elevated CO₂ levels enhance Aspergillus flavus growth and toxin production. At 37°C, high CO₂ levels, and 0.95 water activity – a measure of moisture availability crucial for fungal growth – toxin production can increase by nearly 80 times, enhancing fungal virulence and mycotoxin contamination.
With an estimated 6.5 million invasive fungal infections occur annually, it is no surprise that the WHO designates Aspergillus fumigatus as a critical priority pathogen, emphasizing the “growing concern for global public health”.
Biosergen’s response
Biosergen is tackling this crisis with BSG005, a polyene macrolide molecule related to the oldest antifungal drugs we have. Like amphotericin B (often nicknamed “ampho-terrible” for its toxicity), BSG005 works by binding to the fungal cell membrane and forming pores, causing the fungal cell to leak essential ions and die.
In vitro testing of BSG005 against over 200 fungal strains has shown a fungicidal effect against most, including those resistant to azoles and echinocandins, including including Aspergillus, Candida auris, and Mucormycosis.
Unlike fungistatic treatments, BSG005’s fungicidal action reduces resistance risks, and compared to Amphotericin B, it shows a better safety profile in preclinical and phase I trials, with no severe adverse effects.
In 2024, Biosergen launched a clinical trial in India for patients with untreatable fungal infections. The first cohort consisted of five patients: two completely recovered, two saw significant improvements, and one very sick patient passed away because of unrelated causes to BSG005. The first cohort was completed in October. Biosergen’s CEO Tine Olesen commented on the outcome:
– To see improvements in multiple patients resistant to other treatments at relatively low doses of BSG005 is a notable success. However, seeing two patients who had suffered from some of the most severe fungal infections existing in the world today fully recover is truly remarkable.
In February 2025, the second cohort saw 8 of 10 patients complete treatment, all eight showing clinical improvement, with several fully recovering. BSG005’s strong tolerability prompted investigators to request and receive approval for dose escalation, reflecting confidence in its safety, as CEO Tine Olesen noted:
– Such an investigator-request is uncommon and underscores the strong safety profile BSG005 has demonstrated thus far. The investigators’ desire to treat patients longer and at higher doses speaks to their confidence in BSG005’s tolerability and potential.
However, this also resulted in higher-than-planned usage of BSG005 in the second cohort, meaning they now need to replenish the drug supply before the third cohort can be initiated in this Q4 year.
BSG005’s path to global markets
Biosergen advances BSG005 through a partnership with Alkem Laboratories, which funds and manages trials in India, eyeing global expansion. The company has ongoing regulatory interactions in India to determine the optimal pathway for a phase II trial, and in the US, aimed at securing a Pre-IND meeting and submitting an Investigational New Drug (IND) application, allowing Biosergen to initiate a clinical trial. The company is also exploring a potential EU phase II trial.
In parallel, the company is also developing nano-formulations to enhance lung delivery and enable oral administration. To support these efforts, the company is pursuing additional fundraising activities and non-dilutive opportunities such as grants, alongside strengthening its partnering strategy.
The WHO calls for innovation
As the risk of contracting fatal fungal infections increases, the WHO warns of a “profound crisis” in the antifungal pipeline, stating: “Similar to antibacterials, the antifungal pipeline is in a profound crisis. Globally coordinated collaboration, innovation and sustained investment are essential to address the pipeline crisis effectively”.
The bottom line is that current antifungal drugs are struggling to keep up. The mainstays of therapy are decades old, and fungi are evolving defenses against them. This is why the medical community and WHO are clamoring for new antifungals with novel mechanisms of action, to overcome resistant strains and fill gaps in our armamentarium. With BSG005, Biosergen aligns with this call for innovation.
