Agios Nikolaos, Crete http://bit.ly/uNaFMW
On November 17, 2011, Agios Pharmaceuticals (Cambridge, MA), arguably the leader in cancer metabolism R&D, secured $78 million in an oversubscribed Series C financing.
The company intends to use the proceeds of this financing to advance its preclinical cancer metabolism therapeutics into the clinic, and to expand its R&D efforts into inborn errors of metabolism (IEMs). IEMs comprise a large class of inherited disorders of metabolism, most of which are defects in single genes that code for metabolic enzymes. These conditions have a high level of unmet medical need.
Investors participating in this round included Agios’ existing strategic partner Celgene, existing investors ARCH Venture Partners, Flagship Ventures and Third Rock Ventures, and several new, undisclosed investors, including three leading large public investment funds. In conjunction with the new financing, Perry Karsen, COO of Celgene, joined Agios’ Board of Directors.
Despite being only a preclinical-stage biotech company, and despite the tough early-stage biotech venture capital market, Agios has done very well in fundraising. In April 2010, as discussed in a Biopharmconsortium Blog article, Agios secured a $130 million upfront payment in a strategic collaboration with Celgene. In October 2011, Celgene extended its collaboration with Agios from three to four years, including making an additional $20 million payment to Agios. According to a November 11, 2011 Fierce Biotech article, Agios has secured a total of over a quarter of a billion dollars in financing, beginning with its $33 million Series A round in July 2008.
Also according to Fierce Biotech, by bringing in public investors in its new financing round, Agios has taken a financing route that has enabled other biotechs to go public. For example, Ironwood Pharmaceuticals took this route. Agios’ CEO, David Schenkein, told Fierce Biotech that his management intends to build an independent company for the long term, including securing an investor base that could support a public offering.
The Biopharmconsortium Blog has been following Agios since December 2009. See our December 31, 2009 and April 23, 2010 articles. Also see our December 22, 2010 article on the reemergence of intermediary metabolism as an important field of biology, which highlighted the role of Agios in developing applications of this field to oncology therapeutics.
Recent research at Agios
More recently, Agios researchers and academic collaborators led by Agios Scientific Advisory Board member David Sabatini M.D., Ph.D (Whitehead Institute and Massachusetts Institute of Technology, Cambridge MA) published a study in the 18 August 2011 issue of Nature. In this study, the researchers demonstrated that 70% of estrogen receptor (ER)-negative human breast cancers exhibit amplification and elevated expression of the gene for phosphoglycerate dehydrogenase (PHGDH). PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased flux through this pathway. This in turn results in increased levels of α-ketoglutarate, which is a tricarboxylic acid (TCA) cycle intermediate. (The TCA cycle, the central pathway in intermediary metabolism, was illustrated in the figure at the top of our December 22, 2010 blog post).
Suppression of PHGDH [via RNA interference (RNAi)] in breast cancer cell lines with elevated PHGDH expression, but not in those without, causes a strong reduction in cell proliferation, a reduction in serine synthesis, and a reduction in levels of α-ketoglutarate. This result indicates that most ER-negative breast cancers are dependent on deregulation of the serine synthesis pathway, and that targeting this pathway may provide a novel therapeutic strategy for this subset of breast cancers.
In the September 2011 issue of Nature Genetics, Agios founder Lewis C. Cantley, Ph.D., and Agios advisor Matthew Vander Heiden, M.D., Ph.D., (Beth Israel Deaconess Medical Center/Harvard Medical School and MIT, respectively) published a report that provides further evidence that amplification of PHGDH and deregulated activity of the serine pathway are linked to the growth and survival of certain cancers, especially melanoma and subtypes of breast cancer. This study was carried out using a novel research method called metabolic flux analysis, which is an important component of Agios’s technology platform in cancer metabolism.
These studies provide additional validation for the field of cancer metabolism as a source of novel therapeutic strategies.
Pharmaceutical industry interest in cancer metabolism
Agios is not the only company that is active in the field of cancer metabolism. For example, Forma Therapeutics (Cambridge, MA) is also conducting R&D in this field. According to an article in XConomy Boston, Forma entered into a collaboration with Genentech in cancer metabolism on June 27, 2011. Under the agreement, Genentech will receive exclusive rights to acquire one of Forma’s early preclinical-stage cancer metabolism drugs. In return, Forma will receive an upfront payment, research support, R&D milestone payments, and development funding for that drug. If Genentech decides to acquire the drug after it has met its development goals, Forma will forgo any royalty payments. Instead, Genentech will make an asset buyout payment, which will be distributed to Forma’s investors. In addition, Forma will receive milestone payments on sales of the drug.
Thus Forma’s investors will receive a return on their investments, without the need for an acquisition or an initial public offering. Forma will thus remain an independent company, free to develop its other pipeline drugs, including any other of the approximately 8-10 cancer metabolism drugs that it has already discovered.
This deal, which is made possible by the industry’s keen interest in cancer metabolism-based therapeutics, suggests that Forma, like Agios, intends to remain an independent company over the long haul. Forma has raised over $50 million in venture capital so far, and has revenue-producing alliances with Novartis, Cubist, and the Leukemia & Lymphoma Society as well as Genentech.
Conclusions
Agios is leveraging the strong biotech/pharma industry interest in cancer metabolism, and its own leadership in the field, to build and to finance its R&D programs, and also its corporate development. However, as always, all will depend on the performance of the company’s compounds in the clinic. Dr. Schenkein is providing no information on the timeline for entry of Agios’ drugs into clinical trials. However, he says that the funding secured by Agios will provide the means to get its lead drugs through proof-of-concept studies in humans.
Interestingly, Agios Pharmaceuticals’ founders and management have a particular fondness for the Greek language. At the apex of Agios’ values is arete (ἀρετή), an ancient Greek word that connotes virtue, excellence, and courage and strength in the face of adversity. CEO Schenkein also adds another meaning, “living up to ones potential”.
“Agios” itself is a Greek word (Άγιος), which means “holy” or “Saint”. This is why I chose the figure at the top of this article. It is a photo of the town of Agios Nikolaos (Άγιος Νικόλαος), Crete, which is named for Saint Nicholas.
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