Assistant Managing Editor

"Once a drug gets approved, the first thing other pharmaceutical companies do is try to make their version of the drug that's better," observed Mitchell Mutz, co-founder and chief scientific officer of Amplyx Pharmaceuticals Inc.

It's a strategy that's been working well for a number of firms, but Amplyx, a 2006 start-up, is hoping to put its own spin on that approach. The San Diego-based firm's platform stems from the lab of Gerald Crabtree, a Stanford University professor who previously founded Cambridge, Mass.-based Ariad Pharmaceuticals Inc., along with researcher Jason Gestwicki, who's now at the University of Michigan.

Their work involved the use of small molecules to improve the efficacy of existing drugs, and "after initial experiments, it looked like this was going to be a really productive approach," Mutz said.

The idea is to attach a small ligand to a drug to improve its targeting function - specifically by binding to the FKBP protein found inside cells. As a result, the improved drug has a higher concentration inside the cell and is metabolized more slowly than the original compound. Not only does that boost the efficacy, it also aims to limit the kind of off-target toxicity that plagues other firms well into late-stage clinical development.

Recently, for example, InterMune Inc., of Brisbane, Calif., had to pull the plug on the highest dose cohort for protease inhibitor ITMN-191 in a Phase IIb hepatitis C trial after reports of liver toxicity. (See BioWorld Today, Nov. 18, 2009.)

At Amplyx, "toxicity is actually the first problem we address," Mutz told BioWorld Today.

One of the firm's preclinical programs is tasked with designing a safer version of paclitaxel, a commonly used chemotherapy in breast and ovarian cancers but one that carries a severe dose-limiting toxicity: peripheral neuropathy. "It's extreme enough so that patients can't take the drug anymore," Mutz said.

Paclitaxel's widespread use makes it a large potential market for any firm that can come up with a safer drug. And Amplyx isn't alone. Lake Bluff, Ill.-based NeoPharm Inc. is in midstage testing with a liposome-entrapped version of paclitaxel, and Abraxis BioScience Inc., of Los Angeles, has had success with its albumin-bound nab-paclitaxel formulation Abraxane, which pulled in revenues of $314.5 million for 2009.

Both of those are designed to eliminate the need for the cremaphor component, which is toxic in itself. "But Abraxane still causes peripheral neuropathy just as severe, so that problem's not fixed," Mutz said.

Amplyx's taxane derivative so far has shown equivalent efficacy to paclitaxel in a xenograft mouse model of breast cancer, and a rat study that used mechanical allodynia as an indicator of peripheral neuropathy showed that the company's compound was significantly less toxic compared to paclitaxel.

That program is the most advanced at Amplyx and, with those proof-of-principle data in hand, the firm is positioned to start seeking some additional funding.

"We're going to partners and VCs now that we've shown the platform works," said CEO Elaine Heron, who came on board in February 2009 and helped the firm bring in some angel funding earlier this year.

To date, work at Amplyx has been funded by about $1.55 million from Life Science Angels and Tech Coast Angels, as well as from Golden Seeds, an angel group that invests in start-up companies led by women.

"We hope to raise a Series B in the $10 million range," Heron said.

Partnering also is an option. Amplyx already has partnered two programs: A preclinical antibacterial compound is part of collaboration with an undisclosed midsize pharma firm, and an early stage antifungal program is in development with Duke University.

In addition to the paclitaxel program, Amplyx also is working on its own in HIV.

While the technology also could be applied to development-stage drugs to resolve toxicity hurdles much earlier in the process, Amplyx has decided to limit its initial work to approved drugs, mostly because "we know a lot about their target and their toxicity profile," Mutz said, though he added that Amplyx might consider expanding the technology's use through additional collaborations.

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