Profile: Mark Smythe
While some scientists are driven by innate curiosity and a pursuit of knowledge for its own sake, Mark Smythe is cut from a different cloth.
His career has been driven by the singular desire to create products that make a tangible difference to people’s lives.
This passion has led him to a successful career in biotech, founding start-ups that tackle pain, cardiovascular and inflammatory diseases.
A desire to create impact
“I don’t want to do science for the sake of science. I want to create something,” Smythe says.
This philosophy has allowed Smythe to stay focused on his goal, even declining opportunities that didn’t align with his vision.
Smythe started his career as an environmental chemist in the mines. When offered a PhD scholarship, he turned it down because the projects didn’t match his vision.
A scholarship that suited Smythe better was then advertised; an industrial PhD at Melbourne University working with drug discovery company Biota.
“This PhD ticked my boxes of enhancing my scientific skills, but with a product-goal in mind,” Smythe said. “That’s what interested me, and what set me off down the path as a medicinal chemist.”
During his doctoral studies, Smythe worked on macrocyclic peptides as influenza inhibitors and supported carbohydrate-based discovery.
His involvement in the discovery of Relenza, the world’s first anti-flu drug, ignited a passion for drug development that would shape his future career.
Founding a billion-dollar company
After completing his PhD, Smythe honed his skills during a postdoctoral position in the United States. There, he learnt programming to leverage the emerging technique of molecular modelling: designing drugs via 3D structures on computers.
After three years, Smythe was looking to return to Australia, and accepted a job at The University of Queensland. It was here that the genesis of his first company would occur.
Smythe joined the Centre for Drug Design and Development, which later merged with the Centre for Molecular and Cellular Biology to become the Institute for Molecular Bioscience (IMB). With hundreds of chemists and biologists working under the one roof, it was the perfect environment to create new pharmaceuticals.
Smythe saw an opportunity in a type of molecule called constrained peptides.
“When I arrived at IMB, there was a lot of constrained peptide work underway, which really inspired my thoughts,” Smythe says. “I realised there were numerous constrained peptides found in nature that impacted lots of different biology, but not many had been harnessed for human pharmaceuticals.
“So, I became interested in exploring this angle, which became a 20-year effort in making various constrained peptides to modulate human biology.”
Smythe took peptides from nature, including venomous animals, and engineered them into molecules suitable for drug development. To do this, he developed a complete computational drug design platform called Vectrix as well as a biological method for making millions of molecules using viral phages to discover the starting points of the peptide scaffolds that occur in natural molecules.
This led him to found Protagonist Therapeutics, a company focussed on exploiting constrained peptides as human pharmaceuticals, and Vast Bioscience, which is investigating the potential of carbohydrates as human pharmaceuticals.
Protagonist is now worth AUD5 billion after announcing the successful completion of three Phase 3 studies for treatments for plaque psoriasis and polycythaemia vera, a rare form of blood cancer.
Treating heart attack and stroke with help from a spider
With Protagonist going from success to success, why did Smythe leave?
“The company was in a really good position; it had a lot of money and was in late-stage clinical trials. It was a billion-dollar company with over 100 employees.
“I enjoy and have skills in building and growing companies from research. I really like this space, and that’s exactly what Infensa wanted. And I thought their discovery looked really interesting.”
There are some clear parallels between Protagonist and Infensa. Both companies are based on peptides found in venomous animals by researchers working at IMB. In Infensa’s case, the peptide that inspired the company’s lead molecule was discovered by Professor Glenn King in the venom of the K’gari funnel-web spider.
A key difference, however, is the diseases each company is targeting: Infensa’s peptide is a potential treatment for heart attack and stroke, rather than inflammatory diseases.
Coming full circle on his career journey
“If I think about it now, my journey has come full circle, with my current ventures reflecting the foundation of my early career,” Smythe says.
“My work has translated six peptides into clinical trials at Protagonist, while Infensa and Vast continue to push the boundaries of peptide- and carbohydrate-based discovery.
Recent accolades, including the 2023 Industry Excellence Award and Infensa's 2024 Emerging Innovators Award from Queensland’s peak life sciences body, underscore the industry's recognition of Smythe's contributions.
With $17.8 million in funding secured from the Australian Government's Medical Research Future Fund, Infensa is poised for further breakthroughs and is set to enter Phase 1 clinical trials in the second half of 2025.
A legacy of advancing healthcare through purpose-driven science
Smythe's career exemplifies the power of purpose-driven science. His unwavering commitment to creating transformative therapies has not only propelled him to personal success, but has also pushed the boundaries of drug discovery and development. He has two late-stage products on the cusp of revolutionising healthcare treatment, a feat that few other Australians can boast.
As Smythe continues to innovate and lead in the biotech industry, his work promises to improve countless lives, cementing his legacy as a scientist who truly makes a difference.