ENMEDIA sat down with Gregory Segala, Ph.D., FluoSphera CEO & Co-Founder, and Clelia Bourgoint, Ph.D., FluoSphera COO & Co-Founder, to discuss their company’s highly innovative drug discovery technology.

Greg, Clelia, thank you for joining us today. You founded FluoSphera around proprietary 3D cell culturing systems for in vitro drug discovery, which enable both systemic and high-throughput evaluations of drug efficacy and toxicity. Unlike some other preclinical approaches we’re aware of, your technology mimics the human body’s complex physiology, biology and disease status, permitting researchers to accurately and precisely model human responses to systemic drug delivery. We’re excited to dive in and better understand your technology.

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1. Greg, how is FluoSphera’s approach differentiated from other in vitro drug discovery companies?

FluoSphera is on a mission to build a fully integrated drug discovery platform that evaluates the effects of new molecules (New Chemical Entities and New Biological Entities) with human systemic relevance. Our platform is the ONLY technology that is both systemic AND high-throughput, providing the flexibility needed to conduct high-throughput phenotype screenings while ensuring the relevance of human biology, including tissue communication. This gives us a unique advantage in the drug discovery process since other approaches – even the most advanced to date – provide either the high-throughput capacity or the systemic relevance, but never both.  

Our platform is the ONLY technology that is both systemic AND high-throughput, providing the flexibility needed to conduct high-throughput phenotype screenings while ensuring the relevance of human biology, including tissue communication.

To determine the effects of molecules on each organoid or spheroid, we leverage the power of fluorescent microscopy. This technique allows us to evaluate up to six different tissue types or donors simultaneously, with multiple readouts. Additional analysis can also be conducted directly on the cell culture. FluoSphera’s multiplexing capacity enhances sensitivity in detecting effects and enables unbiased comparisons, as all exposed tissues are cultured together in the same well with the tested molecules.

2. Clelia, your technology promises to accurately model the human body’s responses to drugs in vitro. How does it re-create the human system in cell culture?

Our technology relies on cell encapsulation using alginate, a natural biopolymer. We can modify the alginate to make it color-coded. This way, cell type recognition is carried out by the capsule rather than through direct cell labeling, which can lead to cellular toxicity. Moreover, alginate is permeable, allowing soluble factors to be released into the co-culture medium where other tissues are located, enabling them to be internalized or sensed by other tissues.

What sets us apart is our inclusion of a hepatic model system within our platform, which metabolizes 60% of molecules (including prodrugs) and modulates the effects of metabolized molecules (metabolites). This systemic relevance ensures that our platform faithfully integrates the human pharmacokinetics and pharmacodynamics profile of a drug, thus delivering reliable insights for drug discovery with unprecedented accuracy and efficiency. We are working to fully validate these findings.

This is how we create an in vitro human system!

3. Greg, tell us how your approach can help mitigate risk and reduce drug discovery costs, which remain significant challenges for companies evaluating pre-clinical drug candidates?

FluoSphera’s technology offers several advantages in mitigating risks and reducing drug discovery costs. Firstly, our platform allows for the accurate and efficient assessment of drug effects across various tissue types, providing comprehensive insights into potential safety risks and/or efficacy of candidate drugs. By leveraging this multi-tissue approach, companies can identify adverse effects earlier in the drug development process, thereby reducing the likelihood of costly late-stage failures.

Additionally, FluoSphera’s high-throughput capabilities enable rapid screening of a large number of drug candidates, accelerating the discovery process and minimizing the time and resources required for preclinical evaluation. This efficiency translates into cost savings for companies by streamlining the drug development pipeline.

Furthermore, our technology facilitates the identification of promising drug candidates with favorable safety, selectivity and with the most potent profiles, helping companies allocate resources more effectively towards compounds with the highest likelihood of success in clinical trials.  

4. Most drug discovery processes use mouse models to evaluate drugs prior to submitting an IND to the FDA. Clelia, will this technology replace mouse models in preclinical research, and if so, how will it be integrated into the pre-IND process?

The FDA Modernization Act 2.0, signed at the end of 2022, allows for the utilization of alternative methods to animal testing, such as cell-based assays and computer models, to assess the safety and efficacy of drugs to file an IND. This renders animal testing for drug testing optional. However, shortly after in 2023, clarifications were made by the FDA to preferably include in vitro animal testing. Overall, this decision marks a significant shift, and therefore the transition will require some time.

We’ve previously discussed how FluoSphera provides human systemic relevance. Another area of focus is addressing the challenge of choosing the appropriate animal species for preclinical studies, including mice, rats, rabbits and monkeys. We’re currently developing methods to encapsulate tissues from the most commonly used animal species in preclinical studies. This will allow us to evaluate efficacy and toxicity in a systemic animal context, aiding in species selection without using animals, and enhancing the translatability of in vitro findings to in vivo settings (clinical studies).

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