Looking to reactivate p53 by structurally correcting it
CEO: David Mack
Based: Cranbury, New Jersey
Clinical focus: p53-targeted small molecules for treating cancer
The scoop: In 1979, biologist Arnold Levine, Ph.D., was one of the scientists to discover the protein p53, which came to be known as the guardian of the genome because of its ability to kill damaged cells before they become cancerous. Mutations in the gene that makes this vital protein are at the center of many cancer types, and Levine—now professor emeritus at Princeton University—was one of the many scientists laboring to develop drugs to correct those genetic abnormalities.
Nearly 40 years later, Levine was confident that advances in genomics and chemistry would make it possible to realize that dream. So, he teamed up with Princeton virologist Thomas Shenk, Ph.D., and biotech entrepreneur David Mack, Ph.D., to launch PMV Pharma.
What makes PMV Fierce: The company’s main challenge has been figuring out how to correct the mutated p53 protein without negatively affecting normal versions of it—and to accomplish that with small molecules. “This is a hard challenge. What we’re asking is to correct a single amino acid,” says Mack, who is also well-schooled in biotech, holding a Ph.D. in molecular genetics and cell biology. “Thirty-eight years of biology, tools and chemistry got us to the point where we can actually pursue the strategy of reactivating p53 by structurally correcting it.”
PMV has recruited an impressive slate of investors to help it reach that goal. In 2014, it raised $38 million in a series A round led by OrbiMed. Then, three years later, it reeled in $74 million in a series B led by Topspin Biotech Fund.
Mack says the company is using the funding to develop drugs targeting the top nine cancers that are most frequently characterized by mutant p53. One area of interest for the company is hybrid serous ovarian tumors, 96% of which are characterized by mutant p53, he says. The company expects to launch its first human trials at the end of 2018, Mack says.
But more than half of tumors contain mutant p53, so PMV is considering a unique trial design that focuses not on the location of the cancer but rather the type of mutated p53 that its drugs are able to target. A single variety of mutant p53 may exist in one patient with a breast tumor, and another with a prostate tumor, Mack says.
“So what we would do is screen a patient population that has that mutant, irrespective of their tumor type,” he says. “When you screen by the genomic status of the patient, you could be looking at a trial design with many different tumor types.”
Investors: InterWest Partners, OrbiMed, Osage University Partners, Topspin Biotech Fund