The new research, funded by the British charitable foundation Wellcome, have identified a link between climate change and increased fungal infections, noting that molds such as Aspergillus, which are commonly found in soil, decaying vegetation, and indoor environments, are becoming more common. These mold spores cause infections when inhaled, especially in people with weakened immune systems. Some fungi are adapting to higher temperatures, which increases their ability to survive in the human body.
Chinese research from 2024, which was able to detect a new fungal pathogen that is resistant to common fungicides and where resistance deteriorates at higher temperatures, strengthens these new findings. The new results indicates that Aspergillus could expand to northern Europe, Asia and North America and cover 77 percent more territory by 2100. Given that over 90 percent With an estimated 2,5 million fungal species still unknown, the need for new fungicides is urgent.
Antimicrobial resistance and multidrug resistance
Invasive aspergillosis has a mortality rate of up to 88 percent in high-risk groups such as cancer patients or patients who are about to receive an organ transplant, while some studies have reported a mortality of up to 100 percent. It is appreciated that more than 3 million people worldwide develop chronic pulmonary aspergillosis each year. At the same time, approximately one fifth of all antifungal drug sales are directed against the Aspergillus pathogen.
Currently, only four classes of systemic antifungal drugs are used in clinical practice, with azoles, discovered in the 1960s, dominating the antifungal drug market. However, the widespread use of azole fungicides in agriculture, livestock, and industrial applications, such as coatings and wood preservatives, contributes to resistant aspergillosis in humans.
Driving forces for fungal spread and health consequences
Warmer temperatures and elevated CO₂ levels reinforces Aspergillus flavus growth and toxin production. At 37°C, high CO₂ levels and 0,95 water activity – a measure of moisture availability that is critical for fungal growth – toxin production can increase by almost 80-fold, increasing fungal virulence and mycotoxin contamination.
Considering that approximately 6,5 one million gets invasive fungal infections annually, it is no surprise that the WHO has designated Aspergillus fumigatus a critical priority pathogen, and emphasizes a “growing concern for global public health”.
Biosergen's response
Biosergen's contribution to solving this problem is BSG005, a polyene macrolide molecule related to the oldest antifungal drugs. Like amphotericin B (often nicknamed “ampho-terrible” due to its toxicity), BSG005 binds to the fungal cell membrane and forms pores, causing the fungal cell to leak essential ions and die.
In vitro testing of BSG005 against over 200 fungal strains has demonstrated antifungal activity against most, including those resistant to azoles and echinocandins, including Aspergillus, Candida auris and Mucormycosis.
Unlike fungistatic treatments, the risk of resistance is reduced by BSG005's antifungal activity, and compared to amphotericin B, the candidate shows a better safety profile in preclinical and phase I studies, with no serious adverse events reported.
In 2024, Biosergen initiated a clinical trial in India for patients with untreatable fungal infections. The first cohort consisted of five patients: two fully recovered, two significantly recovered, while one very ill patient died, although not related to treatment with BSG005. The first cohort was completed in October. Biosergen CEO Tine Olesen commented on the outcome:
“Seeing improvements in multiple patients who are resistant to other treatments at relatively low doses of BSG005 is in itself a remarkable achievement. But to see two patients who have suffered from some of the most serious fungal infections in the world today become completely cured is truly remarkable.”
The second cohort was completed in February this year, with 8 out of 10 patients completing treatment. All eight showed clinical improvement and several made a full recovery. BSG005's strong tolerability prompted the investigator to apply for – and receive approval for – a dose escalation, reflecting confidence in its safety, as CEO Tine Olesen said. noted:
- Such an investigator request is unusual and underscores the strong safety profile that BSG005 has demonstrated to date. The investigators' desire to treat patients for longer and with higher doses speaks to their confidence in BSG005's tolerability and potential.
However, this resulted in a higher than planned use of BSG005 in the second cohort, which means that the drug supply now needs to be replenished before the third cohort can be initiated in Q4 this year.
The path to global markets
Biosergen is developing BSG005 in partnership with Alkem Laboratories, which is funding and managing the clinical studies in India, with a view to global expansion. The Company has ongoing regulatory interactions in India to determine the optimal pathway for a Phase II study, and in the US with the ambition to secure a Pre-IND meeting and submit an Investigational New Drug (IND) application, to enable Biosergen to initiate a clinical study. The Company is also exploring a potential Phase II study in the EU.
In parallel, the company is also developing nanoformulations to improve pulmonary delivery and enable oral administration. To support this work, it is considering various funding options and non-dilutive activities such as grants, while strengthening its partnership strategy.
WHO calls for innovation
While the risk of contracting deadly fungal infections increases, warns WHO for a “profound crisis” for antifungal drugs: “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 cornerstones of today's treatment regimens are decades old, and fungi continue to develop defenses against them. That's why the medical community and WHO are calling for new antifungals with new mechanisms of action to defeat the resistant strains and fill the treatment gaps with new weapons. With BSG005, Biosergen is doing its part, in line with the call for innovation.