Agios Pharmaceuticals Inc., of Cambridge, Mass., filed for an initial public offering (IPO) to raise up to $86 million to fund development of its pipeline in cancer and inborn errors of metabolism (IEMs), a subset of orphan genetic metabolic diseases.

Agios's partner, Celgene Corp., of Summit, N.J., agreed to concurrently purchase an as-yet undetermined amount of common stock at the public offering price.

Agios' two lead cancer programs target mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2). The drug candidates target mutated forms of the enzymes that are found in cancer cells. Agios expects to begin clinical trials by the middle of 2013 for its IDH2 candidate, AG-221, and in early 2014 for its IDH1 candidate, AG-120.

William G. Kaelin Jr., of the Dana-Farber Cancer Institute, Brigham and Women's Hospital, published a paper in Science demonstrating that the cancer-causing effects of oncometabolite 2-hydroxyglutarate could be reversed when treated with an IDH1 inhibitor developed by Agios, which is designed to block the production of 2-HG.

To additionally support its IDH1 and IDH2 programs, Agios has signed a multiyear diagnostic partnership for those programs with Foundation Medicine Inc., of Cambridge, Mass. The companies will collaborate to find tumor genomic alterations that can be used to identify which patients are most likely to respond to the drug candidates and to develop and commercialize diagnostics for those programs.

For its program in IEMs, Agios' most advanced candidate is AG-348, a small-molecule activator of PKR, an isoform of pyruvate kinase that leads to a deficiency in that enzyme.

Pyruvate kinase deficiency causes a rare form of hereditary hemolytic anemia. Supportive care such as splenectomy, transfusion support and chelation therapy are the only available treatments. Agios plans to begin trials of AG-348 in patients with PK deficiency in 2014.

Agios has had a stellar track record for fundraising and partnerships. It scored an early partnership with Celgene Corp. for $130 million, plus $120 million in potential milestones and royalties. (See BioWorld Today, April 16, 2010.)

Under that agreement, Agios takes the lead in discovery, preclinical and early clinical development for all cancer metabolism programs, and Celgene has the option to obtain exclusive rights for further development and commercialization of some of the programs, while Agios retains the rights to others.

Celgene extended the exclusivity period of that partnership from three to four years, triggering a $20 million milestone payment, in 2011. Agios has received $141.2 million in payments from Celgene through March 31 and $37.5 million in equity investments.

The discovery phase of the collaboration expires in April 2014.

Agios has racked up $241 million in venture funding. Its most recent financing, a Series C worth $78 million, closed in 2011. The financing syndicate included Celgene, Arch Venture Partners, Flagship Ventures and Third Rock Ventures, plus some undisclosed new investors.

Agios's technology is based on cellular metabolism. IEMs are a class of genetic diseases caused by mutations of single metabolic genes, which cause either a deficit or an accumulation of substances that interfere with normal cellular metabolism. With limited treatment options available for those disorders, Agios is working to develop therapies by targeting the specific metabolic pathways affected.

It uses its capability to monitor numerous metabolic pathways in cells or tissues in a high-throughput fashion, then analyzes the results mathematically to develop its product candidates. Agios has said it may also be possible to use metabolites as biomarkers eventually for purposes such as identifying appropriate patients for clinical trials.

Agios had about 10.4 million shares outstanding, as of April 30. It reported $115 million in cash, cash equivalents and marketable securities at the end of the second quarter.

Agios is classified as an emerging growth company according to the Jumpstart Our Business Startups Act of 2012, and will benefit from some reduced public reporting requirements.