A research collaboration signed in 2003 has led Prolexys Pharmaceuticals Inc. to in-license a cancer compound with cytotoxic properties.
The company got worldwide rights to the selective antitumor compound from Brent Stockwell and the Whitehead Institute for Biomedical Research in Cambridge, Mass. Stockwell, who previously worked at the institute, now serves as an assistant professor at Columbia University in New York, which also holds some of the joint intellectual property rights.
The Massachusetts Institute of Technology is acting as the licensing agent for the transaction. Financial terms were not disclosed.
The relationship originated as a research collaboration signed in December 2003 between Prolexys and Stockwell, said Kimberly Rogers, vice president of business development for Prolexys.
Stockwell "discovered a very interesting molecule that had selective cytotoxicity for cells with RAS mutation." That molecule also demonstrated "cytotoxicity in certain cancers, but without the side effects you get from general cytotoxic compounds," Rogers said. Prolexys used its chemiproteomics technology to discover the compound's mechanism of action and molecular targets.
"We're excited because it seems to have a nontraditional method of action, which causes non-apoptopic cell death and is specific for cells with RAS mutation," she said, adding that the compound, designated PRLX82845, was not cytotoxic to normal cells.
The compound is in preclinical work. Rogers said PRLX82845 will be investigated in several cancers that feature a high rate of mutated RAS oncoprotein, such as sarcoma, pancreatic, thyroid, colon and lung cancers.
Privately held Prolexys, which focuses on therapeutics for oncology and cardiovascular indications, originally was established as a proteomics-based company and has "a strong platform to discover new targets." It has two complementary proteomic platforms: HyNet and HySpec. HyNet is a yeast two-hybrid-based technology, which the company has used to build a database of human protein-protein interactions.
HySpec, a mass spectrometry-based platform, directs the process of protein expression, purification and high-throughput analysis.
"HyNet asks questions about binary protein-protein interaction on a 1-to-1 basis, while HySpec looks at the larger protein complexes," she said, adding that the company has a third platform, HyScreen, which validates the biological relevance of targets.
Although the company's technology lends itself to collaborations - such as the agreement Prolexys signed with Novartis Institutes for Biomedical Research, to map protein interactions for three therapeutic targets - Prolexys also uses the proteomics technology to advance its own drug candidates.
Rogers estimated that it takes between three to nine months to identify a target, validate its biological relevance and set up high-throughput screening for the compound. She told BioWorld Today that it provides Prolexys with a "sustainable machine that keeps pumping new products into the pipeline."
In addition to PRLX82845, the Salt Lake City-based company is developing PRLX2113 to disrupt a protein-protein interaction linked to colon cancer by inhibiting the activity of the beta catenin signaling pathway. Prolexys used both the HyNet and HySpec platforms to "fully flesh out beta catenin," Rogers said. In vivo animal efficacy testing is expected to begin soon, and the company hopes to have results by the end of the year.
A third program in development is aimed at the HSP20 signal, which affects vasorelaxation and bronchodilation. Possible clinical indications for the program include acute asthma, congestive heart failure, pulmonary hypertension and erectile dysfunction.
For HSP20, the company has "hits and now we need chemical optimization before we move them into in vivo testing," Rogers said.
As those products advance to the clinic, Prolexys likely would begin looking for marketing partners. Prolexys has 48 employees and does not intend to develop a marketing presence.
Prolexys was founded in 2001 as Myriad Proteomics, but changed its name in September 2003 to avoid confusion with one of its initial investors, Myriad Genetics Inc., also of Salt Lake City. Other investors included Tokyo-based Hitachi Ltd.; Oracle Corp., of Redwood City, Calif.; and Friedli Corporate Finance AG, of Zurich, Switzerland.
The company was founded with $80 million, and Rogers said Prolexys has "plenty of cash in the bank right now, though we'll probably be looking at a new round of financing sometime within next year," as the products get closer to clinical trials.