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aTyr Pharma's John Mendlein Keeps His Sights on New Biology

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By Jennifer Boggs
Managing Editor

CHICAGO – John Mendlein may not look like the typical biotech exec – the long hair and laid-back manner suggest he might be more at home catching a few waves rather than moderating a panel on orphan and rare diseases, as he did Tuesday morning at the BIO 2013 International Convention.

But looks belie a long list of credentials and experience. As one session attendee was overheard explaining to another as they left the orphan drug session, Mendlein is a rare combination of PhD and JD.

And insights gleaned over the years from his roles as scientist and entrepreneur landed the executive chairman and CEO of aTyr Pharma Inc. on the roster for two other sessions at this year's BIO.

Mendlein's roles in biotech include both start-up firms such as aTyr and Fate Therapeutics Inc., and he's also had experience joining established firms such as Adnexus Inc. (then named Compound Therapeutics Inc.), which he led through the acquisition by Bristol-Myers Squibb Co. (See BioWorld Today, Sept. 25, 2007.)

"I want to work wherever it makes sense," he said, adding that he looks for opportunities that are "productive, fun and exciting."

Most of all, he wants to work on new biology. His latest firm aTyr, for instance, founded in 2005 by serial entrepreneur Paul Schimmel, is based on research on physiocrines, a class of endogenous proteins that help rebalance the immune system for use in treating autoimmune diseases. The idea is that aTyr's candidates could "trigger a resetting of the immune system," Mendlein told BioWorld Today. (See BioWorld Today, Oct. 26, 2010.)

The lead program is heading to the clinic late this year or early next year, he said, with a focus on orphan autoimmune indications.

So many biotechs have pipelines full of drugs hitting familiar-sounding targets, but the lowered risk is offset by becoming fourth, fifth or sixth to market. "So why not work on a brand new novel mechanism?" he asked.

Mendlein actually started his biotech career on a new mechanism: He worked on the first protein pump inhibitor, omeprazole. At the time, the drug has its share of skeptics. It was directed to a brand new target and looking to go up against well-established drugs for acid secretion, Tagamet (cimetidine) and Zantac (ranitidine). "No one thought there was room for improvement."

Still, omeprazole ended up being a leader in acid reduction medicines, besting initial sales estimates by billions.

Similar skepticism surrounded a cystic fibrosis program being developed by Aurora Biosciences Inc., which Mendlein joined in 1998. Aurora later was acquired by Cambridge, Mass.-based Vertex Pharmaceuticals Inc. and the drug, a cystic fibrosis transmembrane conductance regulator potentiator, went on to gain approval as Kalydeco last year for patients whose disease is caused by the G551D gene mutation. (See BioWorld Today, Feb. 1 , 2012.)

"If 98 percent of the people aren't telling you you're wrong, you're probably not that innovative," Mendlein said.

Succeeding in development of innovative products takes much the same skill as running a biotech: good judgment. On the science front, that means choosing the right compounds and clinical path, decisions that are rarely cut and dry. Data are "a lot softer and fuzzier than you think," he said. "It's not always hard and precise."

On the business side, it means running multiple strategies – "even if it's a single-asset program" – to stay flexible in the chance of changes in clinical or regulatory pathways. "You want to find the best-fitted, almost in a Darwinian sense," he said.

And if a drug succeeds, it's a win for everyone, from the shareholders to the patients who now have new – sometimes the first – treatment option for their disease. That and the prospect of new science is what keeps Mendlein – and probably most others – in the biotech industry, despite the risks of drug development. "It's a very meaningful purpose, and it's an interesting job," he said. "It makes it worth it, getting up at 5:30."

Of course, it's possible he could be getting up early to go surfing, an activity he admitted to doing "sometimes." But the long-haired surfer look comes and goes.

"I grow out my hair for a cancer patient," he said, cutting it every two years or so. It's almost time to shear it off again, he added.