San Diego’s aTyr Pharma says today it has closed on $59 million in a Series D financing to advance its development of a new class of protein-based drugs for treating rare immune diseases.
The $59 million deal includes $49 million in venture funding raised in recent months from an unnamed “global public investment fund” and aTyr’s existing venture investors—Alta Partners, Cardinal Partners, Domain Associates, and Polaris Partners. Silicon Valley Bank provided an additional $10 million in debt financing.
The Series D deal is bigger than the $47 million in total venture capital funding that aTyr raised through three previous rounds, aTyr CEO John Mendlein told me in a recent telephone interview (and brings total funding to $108 million since aTyr was founded eight years ago). The latest round is intended to enable aTyr to bring its first therapeutic program into the clinic and to continue to build out the company’s pipeline of additional therapies, Mendlein said.
The funding should enable aTyr, (pronounced A-tire), to stage multiple human proof-of-concept trials of drugs derived from a new class of natural proteins called “physiocrines” that represent a promising new area of biology. Research led by Dr. Paul Schimmel of The Scripps Research Institute and others showed that physiocrines are naturally occurring proteins (derived from tRNA synthetases) that regulate immune response and help maintain homeostasis, or equilibrium. Schimmel is a scientific founder of aTyr, and continues to serve on the company’s board.
“These new proteins are associated with an ancient gene family previously associated with protein synthesis,” Mendlein said. “We’ve discovered new pathways in modulating the immune system that were previously unknown.” Instead of blocking or inhibiting target molecules, however, Mendlein said physiocrines act sort of like a carburetor, by revving up or throttling back an immune response rather than turning it off completely.
The company maintains that physiocrines offer potential therapeutic advantages to existing anti-inflammatory drugs through improved selectivity, efficacy, and reduced side effects.
Since Mendlein stepped in as aTyr’s CEO at the end of 2011 (he retained his executive chairman title), the company has narrowed its strategic focus. It is more specifically focused now on developing drugs for immune disorders that are very severe, “and in which existing therapies are old and unproven, and from our standpoint, not very effective,” Mendlein says. “Our fundamental thesis is that almost everyone in the industry is working on the big signals in inflammation. But obviously, your body has ways of modulating the immune system on its own. We’re trying to leverage what nature has done over millions of years of evolution in primates.”
In the statement scheduled for release today, Mendlein adds, “The aTyr team believes these mechanisms [of modulating inflammation] will benefit patients with grave outcomes in ways that antibody and small molecule approaches can not because physiocrines evolved to naturally balance the immune system to resolve inflammation rather than being a designed inhibitor of pro-inflammatory pathways.”
Mendlein would not identify the immune disorder targeted by aTyr’s lead drug candidate. But he acknowledged that sarcoidosis could serve as an example of the type of disease aTyr is targeting, in which the immune system becomes “deranged.” He also mentioned that Lupus was “too big” for the company—indicating that aTyr is focused, at least initially, on addressing more niche markets.
Another clue to the company’s likely targets lies in a presentation that aTyr’s Kyle Chiang delivered in November at the American College of Rheumatology’s annual meeting in Washington D.C. on the “Characterization of Jo-1 Autoantibodies in Patients with Inflammatory Myopathy and Interstitial Lung Disease.”
Inflammatory myopathy and interstitial lung disease are progressive and debilitating immune disorders characterized by antibodies that attack tRNA synthetase—in most cases by Jo-1 autoantibodies. While corticosteroids and other immunosuppressive drugs are often used to treat these diseases, no specific drugs are approved, and the disease progression is often fatal.