SyntheX – Targeting the undruggable
SyntheX is a start up with their sights set on expanding drug design into the ‘undruggable’ space for the treatment of cancer and rare diseases through the usage of an innovative platform in order to accelerate the discovery of drug design. We interviewed SyntheX to find out more about their interesting approach and their advice for others embarking on a biotech/healthcare start up journey.
How is SyntheX unique compared to other therapeutic companies/start ups?
SyntheX is unique in terms of its target selection combined with its drug design approach. We go after Synthetic Lethality – exploiting features unique to tumour cells to obtain selectivity on a molecular basis. There are examples of recent drugs in the market that utilize this concept as their basis (for example PARP inhibitors), but our major advantage is combining these targets with our drug design and discovery platform that enables us to reach previously ‘undruggable’ targets.
How would you describe this untraditional undruggable space and how is SyntheX able to work on this?
Current drug screening approached focus on proteins with a clear biochemical readout such as enzymatic function, but these constitute less than 15% of the proteins within cells. The vast majority of proteins function through interactions with other proteins to direct their localization, stability, and form larger complexes to achieve complex biological functions. The interactions between these proteins are what is considered ‘undruggable’ due to poor assay readouts and the difficulty of achieving disruption with conventional small molecules. By using larger molecules and our novel intracellular live/dead screen readout we can access that ‘undruggable’ space.
What is the innovative platform developed by Synthex and how does it accelerate the discovery and expansion of drug design?
SyntheX is accelerating drug discovery using synthetic biology. We engineered cells to replace medicinal chemists, biochemists, and technicians when it comes to drug discovery. By creating intracellular circuitry that enables us to build and screen drugs within the same cell, we can accomplish a rapid analysis through a huge drug space. We rigged cells to short circuit when two clinically relevant proteins of interest interact, but to thrive when these proteins are specifically disrupted by a compound the cell is making. This allows the cells to select compounds for us. We then identify the compound and use it for subsequent validation screens.
What are your achievements so far?
During our time at IndieBio, we have built our screening platform and validated its efficacy. We also identified compounds that selectively and efficiently block an interaction that is crucial in a DNA repair pathway that is upregulated in a variety of drug resistant cancers. Blocking of that key interaction enables cancer cells to be sensitized to canonical chemotherapy as well as immune-oncology. However, we also discovered that our compound, STX101, is highly potent on its own against currently drug-resistant intrahepatic cholangiocarcinoma cells. Furthermore, this appears to occur via a novel cell death mechanism we are now characterizing. Needless to say, we have been very excited by these findings and are moving the compounds into preclinical development.
Any advice for biotech/healthcare startups? How as your startup journey been as a (co-)founder?
My advice is to go for it. If you have an idea that you believe is valuable and can change the way things are done, it is worth pursuing. Moving from academia to the startup world has been quite the journey. Starting out as a scientist, I had to quickly learn the legal, tax, financial, and corporate landscape. Luckily, being at IndieBio surrounded me with the expertise and advice necessary to guide my decisions making. Building a startup is definitely hard work and a steep learning curve, but it is a privilege. I am thrilled to be building SyntheX, and am very excited to see what the future holds.
SyntheX was founded in January, 2016. Its founders are Maria Soloveychik and Charly Chahwan.
Maria Soloveychik, CEO
Maria completed her HBSc degree in Molecular Genetics and Microbiology at the University of Toronto. During this time, she worked as a staff scientist at a structural genomics and proteomics laboratory and gained extensive experience in biochemistry, structural biology, small molecule screens, and structure based drug design. Her work led to the determination of several structures and identification of many drug leads. Maria received her doctoral training in epigenetics and cancer metabolomics at the University of Toronto, where she studied mechanisms of metabolic regulation of chromatin, gene expression and oncogenesis. She is an entrepreneur with strong experience in project management and team leadership and is keen to apply her skills to directly benefit patients.
Charly Chahwan, Founder and CSO
After completing his HBSc degree in Physiology and Biophysics from the University of Toronto, Charly joined the department of Molecular Biology at the Scripps Research Institute in California. There, he studied molecular mechanisms of DNA repair and cancer for 5 years and published 10 papers in the process. After Scripps, Charly joined the PhD program at the Department of Molecular Genetics at the University of Toronto and continued studying additional mechanisms that control genomic stability. He was awarded multiple governmental grants and set up independent collaborations with scientists all around North America and Europe, resulting in over 20 peer-reviewed publications. Following years of research in molecular biology and genetics, Charly is eager to bring ground-breaking research from the bench to bedside.