Uncovering a drug’s mode of action with Genevia Technologies

MiNa Therapeutics (MiNaTX) is a London-based biotechnology company that develops therapies based on small activating RNAs (saRNAs). Genevia Technologies helped make sense of the large amount of RNA-sequencing and mass spectrometry data to understand the mechanism of action of their drug.

MiNaTX’s platform exploits the cells’ natural ability to reactivate genes that are suppressed in pathological conditions by using double-stranded saRNAs. C/EBP-α, a transcription factor involved in liver development and cellular differentiation — especially in the white blood cells — became their lead candidate for upregulation with saRNAs in advanced stages of liver cancer. In the clinical trial, where the patients showed a full response to the treatment, the biological mechanism of how this happened was made clear with the help of Genevia picking through the large mass of high-throughput data MINA had accumulated from the trial.

Principal Scientist Vikash Reebye (Vik) from MiNaTX describes the project:

- Our target group was patients with advanced-stage liver cancer who had failed both chemotherapy and surgery. We focused on capturing blood to see if our drug increased the target gene’s mRNA concentration in the white blood cells. Our data confirmed that, and as the trial progressed, we discovered that our drug was priming the patients to respond more efficiently to standard of care drugs for liver cancer such as Sorafenib.

- With the large amount of mRNA data and protein expression data we had accumulated over the course of the trial, we needed help in understanding if the data we had could unravel why our drug was improving clinical response in these patients.

- We were sitting on tons of sequencing and mass-spectroscopy data, not knowing in which direction we should start the analysis; so we contacted Genevia to help us out.

Educational collaboration with a personal touch

Vik appreciates the perseverance and patience of the Genevia team in searching for commonalities and patterns amongst the data. Genevia’s fresh eyes were able to focus on the analysis processes and extrapolate potentially important signaling mechanisms. The bioinformatics project was a significant learning experience for both sides:

- The Genevia team was learning about how they could harness their expertise to help us, and soon they taught us a lot about how to identify patterns in the data that could potentially define key biological pathways.

- It was an enjoyable and educational journey with Genevia; their analyses confirmed our hypotheses and enabled us to recognize which biomarkers to look out for in order to home in on understanding how our drug worked, praises Vik.

Even though the teams were thousands of kilometers apart, the personal touch was successfully delivered via video calls and frequent communication.

- You can always get nicely formatted heat maps and pathway schematics from CROs and be impressed by the graphics; however these often hide key details or complicated algorithms which are difficult to explain to an audience. Genevia’s face-to-face contact and guidance at every step of data analysis meant we were able to share this with full transparency and confidence for our drug discovery programme.

- Perhaps other companies could have also provided the required analyses, but the combination of transparent communication, brainstorming, and troubleshooting made Genevia the perfect bioinformatics partner for us. There were no corporate elements; this was pure collaboration.

From wading across a deep sea of data to uncovering its secrets

Extremely satisfied with the customer experience, Vik intends to return to Genevia with more high-throughput data.

- In the beginning, the amount of data frustrated us. Now, looking back at all the reports from Genevia, we really admire and appreciate their work.

- As a non-specialist in bioinformatics approaching a specialist bioinformatics organization, Genevia was able to teach me a tremendous amount of new things. They reacted to our requests quickly, and their timekeeping was just phenomenal.

- Owing to the personal experience, assurance, and professionalism provided by the Genevia team, I have recommended Genevia to other research fellows. We will absolutely pursue our collaboration with Genevia in the future!