Staff Writer

What began when serial entrepreneur Paul Schimmel founded Angiosyn Inc. - later sold to Pfizer Inc. for $527 million - is advancing to the next level in the hands of San Diego start-up aTyr Pharma Inc.

Schimmel, a scientist with The Scripps Research Institute (TSRI), had a hand in founding Alkermes Inc., Cubist Pharmaceuticals Inc., Repligen Corp., Alnylam Pharmaceuticals Inc. and Sirtris Pharmaceuticals Inc. (now part of GlaxoSmithKline plc), just to name a few.

Working with fellow TSRI scientist Martin Friedlander, Schimmel founded Angiosyn to develop a specific protein fragment derived from an aminoacyl tRNA synthetase. When the drug completed preclinical studies for macular degeneration, Pfizer snatched it up. (See BioWorld Today, Jan. 25, 2005.)

But Schimmel soon realized that Angiosyn's drug was "just the tip of the iceberg," according to aTyr CEO Jeffry Watkins. He explained that there are 20 aminoacyl tRNA synthetases - one for each amino acid. The molecules typically reside inside cells and play a critical role in protein synthesis. But Schimmel's "ah-ha moment" came when he realized the synthetases had unique signaling capabilities outside of the cell, Watkins said.

In fact, Schimmel found that certain fragments of the aminoacyl tRNA synthetases could impact hematopoiesis, metabolism, angiogenesis, immunomodulation and neuroprotection - offering a broad range of potential applications. And since each of the 20 aminoacyl tRNA synthetases might have five active fragments, Schimmel found himself looking at about 100 new biologics.

Schimmel teamed up with John Clarke, managing general partner at Cardinal Partners and a co-founder of Alnylam, to capitalize on the embarrassment of riches offered by the aminoacyl tRNA synthetase fragments. The two founded aTyr in 2005 with less than $1 million in Series A financing. They then raised another $10.5 million in a Series B round in 2006 thanks to the support of Alta Partners, Polaris Venture Partners, Cardinal Partners and Imagene.

Watkins said he is in the process of raising $18 million to $20 million more, which he hopes to complete in the first half of the year. The money will go toward both discovery and development efforts, Watkins told BioWorld Today.

About two-thirds of aTyr's employees focus on uncovering all of the possible aminoacyl tRNA synthetase fragments, creating active molecules and determining potential applications. Most of the work is done at the company's wet labs in San Diego, but aTyr also has seven employees based out of the Hong Kong University of Science and Technology, in China.

The employees in China function as aTyr's "intellectual property engine," Watkins explained. Their work is partially supported by the university and the Chinese government, yet aTyr keeps any resulting IP, making the arrangement a "highly leveraged use of our capital," he said.

The remainder of the aTyr team works on development, particularly process development prior to outsourcing, Watkins said. Preclinical work is under way with candidates for immunomodulation, angiogenesis and neuroprotection - but the most advanced program is in hematopoiesis.

ATyr hopes to begin clinical trials next year with an aminoacyl tRNA synthetase fragment for thrombocytopenia. The compound has been shown to increase platelet counts in preclinical studies, and its mechanism is distinct from Promacta (eltrombopag, Ligand Pharmaceuticals Inc. and GlaxoSmithKline plc) and Nplate (romiplostim, Amgen Inc.), both of which gained approval last year for idiopathic thrombocytopenic purpura (ITP). (See BioWorld Today, Aug. 25, 2008, and Nov. 24, 2008.)

Watkins also noted that ITP represents only a small portion of the total thrombocytopenia market, which has been estimated at $2.5 billion to $4.5 billion.

ATyr anticipates establishing proof of concept in a small, Phase I trial, since increasing platelet counts is "very straightforward," Watkins said.

He added that the clinical data should validate the entire platform and allow the company to begin partnering its other aminoacyl tRNA synthetase fragments at the preclinical proof-of-concept stage.

Watkins said aTyr plans to explore all of its partnering options, including licensing its assets by program and/or by geographic territory.