PMV Pharmaceuticals Inc., a company developing cancer therapies to restore p53, a protein commonly mutated in tumors, has landed a $74 million series B financing. Topspin Biotech Fund and Euclidean Capital led the round. Orbimed Advisors, Osage University Partners and founding investor Interwest Partners also chipped in after backing the company's $30 million series A financing in 2014.

The new financing will help PMV move its lead candidate into the clinic in 2018 for proof-of-concept studies, with a second candidate to follow in 2019. It will also support early studies to back applications to run clinical trials for further p53-focused cancer candidates.

The Cranbury, N.J.-based company was co-founded in mid-2013 by p53 pioneer Arnold Levine, virologist Tom Shenk and industry veteran David Mack, with seed funding from Interwest. Levine and Shenk are now scientific advisors to the company, while Mack, a general partner at Alta Partners from 2002 to 2013, is serving as its president and CEO. The company, which expects to double in size to 24 employees this year, takes its name from the "P" in p53, the "M" from Mdm2, a component of the p53 pathway, and "V" for its now-set-aside interest in applying p53 biology to viruses.

When functioning normally, p53 is considered the "guardian of the genome," directing cells that have endured an external insult and are going down a bad path to die. However, with a single nucleotide mutation that leads to a single amino acid substitution, p53 can lose its wild-type activity. "What we want to do is take small molecules and structurally correct that one amino acid kink, that mutation in p53, to restore its wild-type activity," Mack said.

That restoration, PMV is betting, can eliminate negative effects associated with mutant p53, putting it back on track to exert its wild-type benefits. Its approach, Mack said, is modulating molecules to "restore the structure of a mutant" to make it look and act like wild-type p53, a process that in animal models has killed cancer cells.

The p53 space is increasingly active. Earlier this month, Cellceutix Corp., of Beverly, Mass., initiated its main clinical site for a phase IIa trial of the p53 activator Kevetrin (thioureidobutyronitrile) in the treatment of platinum-resistant/refractory ovarian cancer. Another therapy in development is Aileron Therapeutics Inc.'s phase II-stage ALRN-6924.

In March 2016, Aprea AB raised €46 million (US$50.7 million) in a series B round that will fund a phase IIb trial in ovarian cancer of its p53 reactivator APR-246, as well as a series of exploratory trials in several other oncology indications in which p53 mutations are implicated. (See BioWorld Today, March 10, 2016.)

PMV's differentiator in the space, said Mack, is that its molecules only target the mutant allele in p53, leaving wild-type 53 alone. It also has molecules in development targeting each of the 10 major amino acid substitutions that stem from various mutations, something that will allow the company to approach cancer not necessary by tumor type, but rather by mutation, providing "the right drug for the right tumor with the right allele," Mack said.

With a global drug review and approval system built around specific indications, PMV or a potential future licensor will have to pick one cancer to get the ball rolling. High-grade, serious ovarian cancer, a tumor type driven entirely by mutant p53, is "an obvious place someone is going to go," Mack allowed.