The success rate of drug discovery research for common diseases is low, and one reason for this may be perspective. Science has approached each common disease as a single disease that affects a large number of patients. But John Mendline, executive chairman and interim CEO of startup Vesalius Therapeutics, says that upon closer inspection, a single disease is actually many different diseases. They say each has a different biology, which, when analyzed, will reveal potential targets for new drugs.
Vesalius is in the early stages of an effort to change the research and development paradigm for common disease drugs, and its results are gaining some validation from the pharmaceutical industry. GSK has entered into a multi-target collaboration with Cambridge, Mass.-based Vesalius, securing global rights to small molecules developed from the company’s platform technology. The pharmaceutical giant is paying Vesalius $80 million upfront.
Vesalius’ technology creates molecular human avatars that represent diseases. The company is also developing digital human avatars based on patient data and patient samples. This technology uses artificial intelligence to help scientists understand the differences between common diseases. It also matches potential treatments to patients most likely to respond to the drug.
The platform technology was originally developed in the lab of startup creator Flagship Pioneering. Vesalius emerged from stealth in 2022 with $75 million in support from Flagship. However, the young startup reportedly stumbled initially and cut jobs six months after launching. The company did not disclose which diseases it targets. However, in its deal with GSK, Vesalius revealed that Parkinson’s disease is one of the symptoms the company has been researching for the past two years.
Many drugs are available for Parkinson’s disease, many of which work in similar ways. We need newer and better approaches to this disease. But there was another reason why Vesalius applied his technique to neurological disorders. Current preclinical models of Parkinson’s disease are not considered strong enough to inform research and development decisions, explained Mendline, who is also an executive partner at Flagship. Drug hunters need better ways to decide where and how to intervene in disease. It also needs to be done in a way that is more predictive of what will happen to humans.
“We thought this was a good fit for the field and could potentially inform the best way to intervene in Parkinson’s disease in preclinical settings, either across patient groups or subgroups of the Parkinson’s disease population.” Mendlin said. “We believe that using human-based systems can give us a competitive edge in drug discovery in this particular field. As a result, (animal) efficacy models may become unnecessary.
Mendlin said Vesalius’ research sought to identify whether Parkinson’s disease is actually multiple diseases, each with overlapping clinical symptoms. From there, the company sought to learn whether linking one or more subpopulations of Parkinson’s disease to specific points of intervention could lead to new treatments. As an example, Mendlin said that when a target has multiple functions, it is important to know which function to attack and how to change the clinical outcome. In addition to discovering new targets and points of intervention, Vesalius technology could also help recruit patients to clinical trials, Mendlin said. The platform will allow the company to examine subsegments of patient data to identify biomarkers that can be used for companion diagnostics.
Vesalius’ research into Parkinson’s disease piqued GSK’s interest. Flagship hosts an annual research and development summit attended by pharmaceutical companies. Mendlin said the initial conversations with GSK began at one of these summits, paving the way for the cooperation that is currently taking place. Vesalius small molecules address new targets not disclosed by the companies. But Mendlein said the target discovered by Vesalius points to a new way to intervene in neurodegenerative diseases.
GSK holds worldwide rights to Vesalius small molecules and is responsible for advancing the development of the asset in Parkinson’s disease and other unspecified neurodegenerative diseases. If this research leads to approval of the product, the pharmaceutical giant will be responsible for its commercialization. In addition to milestone payments, Vesalius could receive up to $570 million in sales royalties. The agreement also entitles the startup to receive preclinical, development and commercial milestone payments, as well as tiered royalties on each new intervention point resulting from the multi-target agreement. The companies have not disclosed financial details related to the new intervention points.
Like other platform technologies, Vesalius’ technology can be applied to a wide range of therapeutic areas. In addition to Parkinson’s disease, Vesalius also has programs in immune diseases. Mendlein is interested in pursuing additional partnerships while continuing to develop some programs internally. He declined to specify other therapeutic areas that Vesalius is interested in, but said the startup will move in the direction that science leads. Vesalius Therapeutics is named after Renaissance physician and scientist Andreas Vesalius. His dissections of the human body led to a series of books considered groundbreaking in advancing medical understanding of anatomy.
“Vesalius created an atlas of human anatomy,” Mendline said. “Vesalius is creating an atlas of modern disease and redefining disease itself.”
Illustration: Dr_Microbe, Getty Images
