PORTEFEUILLE

Problem: Cancer is one of the leading causes of death worldwide, with estimated 19.3 million new cases and almost 10.0 million deaths in 2020. Besides their limited efficacy, current therapies often have severe side effects, decreasing the quality of life of cancer patients significantly. New developments, such as immunotherapies based on immune checkpoint inhibitors (ICI), are effective in just a fraction of patients while a large proportion of patients do not respond or quickly become resistant. In colorectal cancer (CRC) only 4-5% of all patients respond to ICI therapies. As a result of this limitation of treatment options, about one third of all CRC patients are likely to succumb to the disease and in advanced stages, the 5-year-survival rates are below 15%.
Solution: Based on human microbiome data, we identified specific bacterial species that are less abundant in CRC patients compared to healthy individuals. Oral supplementation of these bacteria causes a very effective anti-tumor activity in multiple cancer models through specific activation of cytotoxic T-cells. Based on this finding, we are developing a life biotherapeutic product (LBP) based on lyophilized bacteria contained in gastric-resistant capsules with colonic release for oral application. We fully characterized the mode of action of our LBP, including the active bacterial metabolite, the target receptor and the activated immune cells that are responsible for the effective anti-tumor immune effect. Characterization of the metabolic pathways of our bacterial strains led us to a specific substrate which, when added to the bacteria, strongly increases the bacterial production of the active anti-cancer metabolite. Through the identification of the mechanism of action of our LBP, we were able to identify and validate a promising new drug target for cancer immunotherapy. Therefore, based on the effect of the bacterial metabolite, we are developing a small molecule compound that targets this immune activating receptor as a second project.
USP: Comparable approaches modulating the microbiota in cancer patients aim to enhance the efficacy of immunotherapies. Our approach is much more effective than current immunotherapy (immune checkpoint inhibitors) in vivo and independent from them. Furthermore, since our products are based on commensal bacteria or small molecules that target the same receptors as beneficial microbiota, we expect higher safety and better tolerability in comparison with the clinical standard-of-care or therapies currently under development. Our Live Biotherapeutic Product (LBP) could even be applied to prevent tumor recurrence or to avoid tumor development in risk patients. In contrast to other approaches that are targeting the microbiota, we have identified and fully characterized the mechanism of action of our LBP. This helps us to optimize the efficacy of our product, define the right dosage and understand possible side effects. Additionally, it enables us to improve patient selection and prediction of treatment response.

Our results show that immune infiltration into the tumor is enhanced when the bacteria are applied. This may circumvent the problem of current immunotherapies, by which tumors with low immune-cell infiltration cannot be effectively treated. As this novel therapeutic approach is purely based on commensal bacteria that are abundantly present in healthy individuals, we expect a high safety and tolerability profile, minimizing the side effects compared to current anti-tumor therapies. Moreover, these characteristics could qualify this therapy to be used to both treat and prevent CRC. This Life Biotherapeutic Product (LBP) is currently being manufactured as a freeze-dried product and being tested for efficacy and safety in vivo.
Bringing a bioinformatics scientist on board thanks to InnoBooster's support was a game-changer. Within a year, we've not only made significant progress in our current project's preclinical phase, but we've also been able to launch entirely new initiatives. A particular focus of ours is the small molecule program. Here, we're capitalizing on the known mechanism of our LBP to identify a small molecule candidate that can activate the immune system against tumors by agonizing the target receptor.