What happens when you start a business, get tens of millions of dollars in funding, and discover shortly afterward that the market may have no interest in your product?
In the case of Prolexys Pharmaceuticals, it took its technology and recast the company into exactly the kind of end-market user that was supposed to be its customer.
Last week, Prolexys announced it had reached a milestone in its reinvention by raising $20 million in Series A-1 funding, the first capital infusion it has secured since it turned its focus from developing proteomic tools to developing drugs using those tools.
Prolexys said it will use the cash to perform additional clinical studies on its lead drug candidate, a treatment for a variety of cancers, and to develop other drugs.
‘The Pendulum Swung’
Prolexys was launched in 2001 in Salt Lake City as Myriad Proteomics with a business plan devoted to developing proteomic technologies with a yeast 2-hybrid platform for detecting binary protein interactions and a mass spectrometry-based protein complex “pull-down” technique. The following year the company set out to map the entire human proteome by 2004 [See PM 03/18/02].
But in 2003 in the midst of a collapse of the proteomics field, Myriad Proteomics was left wondering what to do with its technology, Sudhir Sahasrabudhe, Prolexys’ acting CEO and CSO, told ProteoMonitor this week.
When he joined the company during its vaporware stage in 2000, “there was great interest in … technology by which [someone] could identify massive numbers of protein-protein interactions using an automated robotic” system, Sahasrabudhe said.
Using its yeast 2-hybrid platform and mass spec-based protein complex-analysis technology, Myriad Proteomics developed a database of protein-protein interactions with the goal of selling the database on a subscription model.
And when its founders shopped their idea around, they found enough interest from investors to raise $85 million from Oracle, Hitachi, Myriad Genetics, and Swiss venture capital firm New Venturetec, and launched the firm.
But just two years later, interest in proteomics cratered and dragged along with it Myriad Proteomics’ business plan.
“From 1995 to 2001 technology was gold,” Sahasrabudhe said. “Pharma companies would sign multi-million-dollar deals.” But by 2003 “there was absolutely no appetite for that” as the initial exuberance embracing proteomics turned into the cold reality that proteomics technology may not be ready to solve the complexities of the science.
“The pendulum swung from one end where technology would be the answer to pharma productivity all the way to where [people were saying] technology is useless,” he said.
“The pendulum swung from one end where technology would be the answer to pharma productivity all the way to where [people were saying] technology is useless.”
So the company turned itself into a drug-discovery firm and changed its name to Prolexys [See PM 07/04/03]. Soon the firm found itself between a rock and a hard sell: There was not enough interest in the market for Myriad Proteomics’ proteomics technologies, and there was too much competition in drug development for Prolexys.
To differentiate itself, Prolexys did two things: It took advantage of its expertise in signal-transduction pathways, and it developed a chemiproteomics platform to look at drug targets that other firms appeared to be ignoring.
Its chemiproteomics workflow is based on immobilizing compounds to a solid support by special linkers, reducing steric hindrance. Bead technology is used to dangle the compound using different linker lengths. According to Sahasrabudhe, if an immobilized compound cannot be rotated to present itself, a protein will not be captured.
Prolexy’s method is to modify the compound so that it can be attached to the bead surface.
“We use carbon linkers of different lengths, so we can accommodate those compounds that have deep binding pockets, and we also dangle the compounds off different areas of the molecule, not just one, so that we can understand which moiety might be important in interacting with the protein itself,” he said.
Prolexys also runs experiments with up to 10 different analogs of a compound. The efficacy of each analog will vary, he said, but “with that compound scaffold, you can sort things out, because then you can discern [which] proteins bind to the compound scaffold that have nothing to do with the pharmacological transaction we’re interested in.”
According to Prolexys, its method identifies the primary targets of a drug and the proteins interacting with that target, providing pathway information and a broader context in which to view the primary target.
“This combination of target and pathway information can be used to prioritize targets for continued drug development,” according to Prolexys’ website.
Drug development has historically focused on selecting target drugs coming from differential gene analysis, Sahasrabudhe said. “However when you ask them to do the same thing with a small molecule, there is reluctance,” he said. Prolexys is seeking to exploit that reticence.
Prolexys continues to generate massive amounts of proteomics data, Sahasrabudhe said, and the company is trying to use that data in its drug-discovery research.
“We are good in proteomics and what we are going to do is … take those exquisitely well-designed phenotypic screens to identify compounds,” he said. “We will advance the compounds in the clinic while in parallel making a commitment to elucidate mechanism of action.”
Which brings it to its $20 million Series A-1 funding. The company is currently in clinical studies of a molecule called PRLX 93936, which in disease models has shown anti-tumor activity in colon, lung, pancreatic, and ovarian cancer, several sarcoma sub-types, and multiple myeloma.
It will use the capital to conduct additional tests to determine safe dosage levels for the molecule. The two things that need to be addressed, Sahasrabudhe said, are to understand PRLX 93936’s mechanism of action, and to reach dosing levels that will show “robust anti-tumor activity” in an in vivo model.
He said Prolexys hopes to be able to show by the end of the first quarter in 2009 that the molecule has therapeutic efficacy. Then it will begin seeking a partner to fully develop it and bring it to market.
Prolexys will also use part of the $20 million round to continue developing back-up molecules to PRLX 93936. The company plans to submit an investigational new drug application to the US Food and Drug Administration by the third quarter of 2009 for an analog to PRLX 93936, and file an IND for a molecule unrelated to PRLX 93936 directed at colon-= cancer by the fourth quarter of 2010, Sahasrabudhe said.
The company is now 180 degrees from what Myriad Proteomics had set out to be, Sahasrabudhe said. “The original intent was to hand off the technology and the data from the technology to disease-biology entities like pharmaceutical companies,” he said. “We would then stick to our core expertise in proteomics.
“Now we’ve come to the other end of the spectrum where we’re still able to use our technology, but the focus of the company really is to take small molecules and bring them into the clinic,” he said.