PORTEFEUILLE

Problem: Cancer has emerged as a significant global public health concern, imposing a substantial and ever-increasing socioeconomic burden. The gut microbiota has been established as a critical component in regulating host immunomodulation, maintaining cancer immune homeostasis, and modulating the tumor microenvironment.

Solution: Recolony is pioneering a groundbreaking approach to cancer treatment by harnessing the potential of the human microbiota. They have uncovered a specific mechanism, by which the gut microbiota activates the immune system, revealing a novel target for cancer immunotherapy.
Through in-depth analysis of the host-microbiota interactions, they have identified a specific bacterial metabolite that exhibits potent anti-tumor properties. This metabolite has been shown to activate the immune system by binding to a receptor on tumor-residing macrophages, stimulating a pro-inflammatory response that combats cancer. Treatment with the bacterial metabolite showed efficacy in different mouse solid tumor models, validating the target receptor for multiple cancer entities.
Building on this discovery, Recolony is developing a novel small molecule immunotherapy that mimics the natural anti-cancer effects of microbial-derived metabolites, but with enhanced efficacy. Their therapy is designed to optimize treatment outcomes for late-stage cancer patients, offering a promising new hope for those affected by this devastating disease.

USP: Previous attempts to develop microbiome-based cancer treatments have faced challenges due to the complexity of the microbiome and its interaction with the human body. Our approach benefits from a nature-based mechanism of action, while refining the product to solely the active compound. The resulting therapy is targeted to immune cells residing in the tumor, works independently of existing immune checkpoint inhibitors, and demonstrates effectiveness against multiple types of cancer in preclinical studies.
The development of a small molecule derived from a bacterial metabolite opens a new avenue within the immune-oncology space and the chance to clinically validate a potent novel cancer immunotherapy target. Our receptor’s unique mechanism of action can provide a competitive advantage over established therapies and new treatment approaches under development. Current immunotherapies such as immune checkpoint inhibitors often exhibit limited efficacy across different cancers and can cause severe side effects due to a systemic activation of the immune system. The expression of our target receptor is almost exclusively restricted to tumor-associated macrophages, which is why our therapy is activating the immune reaction locally in the tumor, leaving other organs and tissues unaffected. Therefore, we don’t expect significant adverse effects, which increases the therapeutic window and the efficacy of our therapy in comparison to existing immunotherapies.

We have uncovered a specific and potent mechanism, by which the gut microbiota activates the immune system, revealing a novel target for cancer immunotherapy. Our receptor of interest is mainly expressed in macrophages that are residing in the tumor and is virtually absent in immune cells outside of the tumor microenvironment. Therefore, our therapy is targeted to activate immune cells only in the tumor and not systemically. For that reason, we expect a much better safety profile compared to existing immunotherapies, which activate immune cells in an untargeted fashion, often causing autoimmune reactions. We have already produced in vivo proof of concept data with a known agonist for our receptor, which shows a similar anti-tumor efficacy compared to our metabolite (Figure 3). For the development of more potent compounds, several recent publications present detailed structural insights into our target receptor, which facilitates the rational design of novel drugs at Recolony. Understanding the structure and activation mechanisms aids in the development of selective and effective agonists that could be used for cancer therapy.
In order to generate the optimal compound to activate our target receptor, we have developed several approaches for molecule design. In the classical approach, we work with experienced medicinal chemists who design novel compounds based on structural information about the receptor and functional understanding of known agonists and the bacterial metabolite. In a second approach, we have built a CADD platform for the in-silico compound screening of large compound libraries for our target, by which we have screened over 2 million compounds to date. And in a third approach, we developed an AI model for the prediction of new optimized candidate molecules for our target. Through the selected input of training data, the AI model is trained to predict molecules with optimized drug-likeness and high affinity to the target. For all the approaches, we are selecting the best compounds, synthesizing them and testing them in our cell assays, which we have up and running in-house. So far, with only the first sets of compounds synthesized, we have already identified several hits through the classical medicinal chemistry approach and expect to vastly increase number and quality of the hit molecules through the AI technology that we are constantly improving.
As outlined in our compound generation and validation cascade (Figure 4), the best hits from the in vitro assays will be selected for ADME and PK/PD studies and the in vivo cancer models to confirm anti-tumor efficacy.
All the data that we collect from cell assays, ADME and PK/PD studies, and in vivo efficacy studies will be used as training and feedback data for the AI model, which then improves the compound prediction to develop optimized hits. It is important to note that the AI technology we are developing is not specific to our target, but once validated, could be used to develop and optimize molecules for virtually any known drug target. Our own drug development program therefo
Bringing a bioinformatics scientist on board thanks to InnoBooster's support was a game-changer. During the course of this project, 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 bacteria to identify a small molecule candidate that can activate the immune system against tumors by agonizing the target receptor.