Experts: Julia Biwer (Abbmira Therapeutics), Marc Creus (Abbmira Therapeutics)
Cancer remains one of medicine’s greatest challenges for healthcare professionals and patients alike. Using in-silico screening and artificial intelligence, Abbmira Therapeutics has identified a component of bacterial cell walls that is capable of reprogramming the environment of different types of tumours. The resulting inflammation flags the tumour for recognition by the immune system and could significantly improve patients’ prognoses.
Picture: National Cancer Institute (Unsplash)
The statistics paint an alarming picture. In Switzerland, 46,500 new cases of cancer are recorded every year, making it the second leading cause of death, accounting for 25 per cent of all fatalities. Despite all the remarkable advances made in terms of drugs and treatments, cancer cells always seem to be one step ahead of medical professionals. This is also the case with PD1 inhibitors, a class of cancer drugs designed to help the immune system detect and fight cancer cells. Though they entered the field as a promising new treatment, up to 70 per cent of patients either develop resistance to the inhibitors within a short period of time or fail to respond to the treatment entirely.
Macrophages are part of our immune system. They respond rapidly to foreign bodies and therefore also play an important role in the body’s fight against cancer cells.
Tumour-associated macrophages – a specialised subtype of macrophages found in the immediate vicinity of tumours – exist in two variants: the pro-inflammatory, immunologically active and tumour-suppressing M1 variant, and the anti-inflammatory, immunologically suppressive and tumour-promoting M2 variant. So, when it comes to cancer, there are good guys and bad guys. The balance between these two forms significantly determines a tumour’s immediate environment and thus also treatment outcomes. Tumours with a large number of the M2 macrophages spell a significantly worse prognosis for patients than tumours where the M1 form dominates.
This insight is exactly what drives the approach developed by Abbmira Therapeutics. As co-founder and COO Julia Biwer explained: ‘We need to reprogram the tumour environment to alert the body that something is wrong. Our approach is breaking new ground.’ If the ratio of specialised macrophages shifts in favour of the M1 form, the body launches an inflammatory response to the cancer, activating the immune system.
Certain strains of bacteria that enter the tumour’s environment either by chance or by design can positively alter the M1 to M2 ratio within the tumour microenvironment, triggering local inflammation and thus effectively flagging the tumour for the immune system. But which component of these bacteria is responsible for the observed effect? Marc Creus, co-founder and CEO of Abbmira Therapeutics, knew where to look: ‘The scientific literature holds the answer.’
Abbmira Therapeutics started data mining – and was suberbly successful too. Thanks to extensive literature studies and the use of artificial intelligence, the team identified a molecule in the bacterial cell wall that triggers inflammatory responses in the immediate vicinity of tumours, thus contributing to positive patient treatment outcomes. The bacterial compound activates receptors in tumour-associated macrophages, promoting M1 formation. As Marc Creus succinctly summed up the situation: ‘The good guys take control.’
Since it does not have its own laboratories, Abbmira Therapeutics outsourced synthesis of its bacterial molecule – codenamed C42 – along with all the biological testing. C42’s efficacy was tested in mouse models for skin cancer, both in combination with a PD1 inhibitor and compared to the PD1 inhibitor as a monotherapy. ‘The data we obtained was the starting signal for both founding the company and conducting further research,’ Julia Biwer noted enthusiastically. Why? Because the combination therapy significantly outperformed monotherapy in reducing tumour growth.
Traditional pharmaceutical research involves screening vast collections of potential active substances with different structures (known as libraries) to examine their efficacy in biological experiments, and then isolating promising candidates. At Abbmira Therapeutics, this screening took place both on the computer and in the mind of Marc Creus, and a single molecule formed the foundation for the development of a future drug. True to the motto: one candidate – one hit. Besides the cost savings, this approach meant that the team already had an in-depth understanding of the molecule and its properties and characteristics, which sped up further development.
Despite C42’s success in the mouse model, it still has a long way to go before clinical trials and potential approval. It must be optimised for pharmaceutical use in terms of structure, drug form and administration form. It will then be necessary to provide evidence of pharmacology and toxicology in animals, manufacturing quality, purity and stability to obtain authorisation to conduct the first phase of a clinical trial. Defining the initial therapeutic application is a key aspect. There are several tumour types with high M2 content where treatment with C42 might be beneficial: colon, ovarian and lung cancers, not to mention glioblastoma (a type of malignant brain tumour).
The young company, founded in September 2024, will benefit from the opportunities offered by the Life Sciences Cluster Basel in the further development of C42. Not only does this give the company access to physical premises; it also links it up with former specialists from the large-scale pharmaceutical industry who now provide their invaluable expertise to support and advise the company.
Echoing the African proverb ‘It takes an entire village to raise a child’, pharmaceutical lead molecules can be described as requiring an entire ecosystem for successful development into a drug. It is only thanks to the innovative environment in Basel that the ‘baby’ C42 can grow up and become a potential game changer in cancer treatment.
