Success rates in drug research for common diseases is low, and one reason for that could be perspective. Science has approached each common disorder as a single disease affecting a large population of patients. But John Mendlein, executive chairman and interim CEO of startup Vesalius Therapeutics, says a deeper look reveals that a single disease is actually many different diseases, each one with different biology that can be analyzed and potentially targeted with a novel medicine.
Vesalius is still early in its effort to change the R&D paradigm for common disease drugs, but its work now has some validation from the pharmaceutical industry. GSK has struck a multi-target alliance with Cambridge, Massachusetts-based Vesalius, a deal that secures global rights to a small molecule developed from the startup’s platform technology. The pharma giant is paying Vesalius $80 million up front.
Vesalius’s technology creates a molecular human avatar that represents a disease. The company also develops a digital human avatar based on patient data and patient samples. Using artificial intelligence, the technology helps scientists understand the differences within a common disease. It also matches a potential therapy to the patient who is most likely to respond to that medicine.
The platform technology was initially developed in the labs of startup creator Flagship Pioneering. Vesalius emerged from stealth in 2022, backed by $75 million from Flagship. But the young startup stumbled initially, reportedly implementing layoffs six months after its launch. The company had not specified which diseases it was pursuing. But with the GSK deal, Vesalius is now revealing Parkinson’s is one indication the company has been researching for the past two years.
Though many drugs are available for Parkinson’s, many of them do similar things. There is a need for newer and better approaches to the disease. But there’s another reason why Vesalius applied its technology to the neurological disorder. The current preclinical models for Parkinson’s aren’t regarded as strong models to inform R&D decisions, explained Mendlein, who is also executive partner at Flagship. Drug hunters need better ways to determine how and where to intervene in a disease, and they need to do so in ways that are more predictive of what could happen in humans.
“We thought this would be an area that would be amenable to this, and might offer the ability to inform preclinically the best way to intervene in Parkinson’s — the entire patient group or a subgroup of the Parkinson’s population,” Mendlein said. “We believe using human-based systems gives us a competitive edge in discovering drugs in this particular area, and over time it may eliminate the need for (animal) efficacy models as part of the R&D process.”
Mendlein said Vesalius’s research tried to discern whether Parkinson’s is actually multiple diseases that each have overlapping clinical manifestations. From there, the company tried to learn whether connecting one or more of those sub-populations of Parkinson’s to a particular intervention point could lead to a new treatment. As an example, Mendlein said that if a target has more than one function, it’s important to know which function to hit and how to hit it to change clinical outcomes. Beyond discovering novel targets and intervention points, the Vesalius technology could also help in patient recruitment for clinical trials, Mendlein said. The platform enables the company to look at subsegments of patient data to identify a biomarker that could be used for a companion diagnostic.
The Vesalius Parkinson’s research piqued GSK’s interest. Flagship hosts an annual R&D summit that’s attended by pharmaceutical companies. Mendlein said initial conversations with GSK began at one of these summits, paving the way for the collaboration now in place. The Vesalius small molecule addresses a novel target that the companies are not disclosing. But Mendlein said this Vesalius-discovered target represents a new way of intervening in the neurodegenerative disease.
GSK has global rights to the Vesalius small molecule and is responsible for advancing the asset’s development in Parkinson’s and another unspecified neurodegenerative condition. If this research leads to an approved product, the pharma giant is responsible for its commercialization. Vesalius could receive up to $570 million in milestone payments, plus royalties from sales. The deal also makes the startup eligible to receive preclinical, development, and commercial milestone payments and tiered royalties for each of the novel intervention points that result from the multitarget deal. The companies are not disclosing financial details related to novel intervention points.
As with any platform technology, Vesalius’s technology is applicable to a wide range of therapeutic areas. Besides Parkinson’s, Vesalius also has programs in immunological diseases. Mendlein is interested in pursuing additional partnerships while also continuing to develop some programs internally. He declined to specify Vesalius’s other therapeutic areas of interest, other than to say the startup will go where the science takes it. Vesalius Therapeutics is named for Andreas Vesalius, who was a physician and scientist during the Renaissance. His dissections of human bodies led to a series of books whose text and illustrations are considered groundbreaking in advancing medical understanding of anatomy.
“Vesalius created an atlas of human anatomy,” Mendlein said. “Vesalius the company is creating a modern-day atlas of diseases and redefining disease itself.”
Illustration: Dr_Microbe, Getty Images
