Editing DeCODE genetics (section)

== Business ==
Despite its pathbreaking science, or perhaps because it was often far ahead of the field, deCODE had a volatile history as a standalone business. In July 2000, it completed a $200 million IPO on Nasdaq, big for the time and the first listing by an Icelandic company on a US exchange. Its early pharmaceutical alliances, particularly that with Roche, further helped to fund the enrollment of most of the adults in the country in the first decade of its research, and the rapid expansion of both its discovery capabilities and its product development efforts in drugs, diagnostics and personal genomics.<ref>Matthew Herper, "Choppy IPO for deCODE genetics", ''[https://www.forbes.com/2000/07/19/mu5.html#63aee4d52d4e Forbes]'' 19 July 2000</ref>

From a scientific perspective, as the Broad Institute's David Altschuler told the MIT Tech Review in 2004, "This is a business in which critical mass is important, and they have achieved critical mass."<ref>Corie Lok, "Translating Iceland's Genes into Medicine," ''[https://www.technologyreview.com/s/403018/translating-icelands-genes-into-medicine/ MIT Technology Review]'', 1 September 2004</ref> But the business was also about money. Being an innovation enterprise pioneering new markets, the company had spent more than $500 million on R&D in its first decade and never been profitable. By 2006 it was borrowing more,<ref>On investment and business performance see for example [https://www.sec.gov/Archives/edgar/data/1022974/000110465907019321/a07-5795_110k.htm deCODE's 2006 10-K] filed with the SEC; Company press release, "deCODE genetics, Inc. Announces Placement Of $65 Million Of Convertible Notes," reprinted in ''Biospace'', 14 November 2006</ref> to fund drug development programs based on completely novel premises; to bring forward diagnostic tests in a market that even supporters termed "still embryonic"; and to market personal genomics, where it was being overshadowed by the Silicon Valley glamour and cash of 23andMe.<ref>Daniel Macarthur, "deCODE Genetics on the brink of insolvency," ''[https://www.wired.com/2009/08/decode-genetics-on-the-brink-of-insolvency/ Wired]'', 8 November 2009</ref>

By late 2008, the company was "between a rock and a hard place," in Stefansson's own words.<ref>Vermazis, ''[http://www.bio-itworld.com/2008/11/07/decode-genetics-q3.html BioIT World] {{Webarchive|url=https://web.archive.org/web/20200320142417/http://www.bio-itworld.com/2008/11/07/decode-genetics-q3.html |date=20 March 2020 }}'', Nov 2008</ref> Under threat of being delisted from Nasdaq for its flagging stock price, the company needed more capital just as the global markets were going into crisis.<ref>"DeCODE Genetics on the Ropes," ''[https://www.science.org/content/article/decode-genetics-ropes Science]'', 7 November 2008</ref> Although its scientists kept publishing breakthroughs at a remarkable rate, in late 2009, the company's listed US holding company, deCODE genetics, Inc., declared Chapter 11 bankruptcy.<ref>[https://www.marketscreener.com/DECODE-GEN-9014/news/DECODE-GEN-deCODE-genetics-Inc-Files-Voluntary-Chapter-11-Petition-to-Facilitate-Sale-of-Assets-13280827/ Company press release], "deCODE genetics, Inc. Files Voluntary Chapter 11 Petition to Facilitate Sale of Assets," 17 November 2009</ref> Its key assets - the heart of which was the Iceland genetics operation - were bought and kept running by a consortium of the company's two main original venture backers: [[ARCH Venture Partners]] and [[Polaris Partners|Polaris Ventures]], along with [[Illumina, Inc.]], the dominant maker of genotyping chips and sequencing equipment.<ref>Nicholas Wade, "Out of bankruptcy, genetics company drops drug efforts," ''[https://www.nytimes.com/2010/01/22/business/global/22gene.html?scp=2&sq=decode&st=cse New York Times]'', 21 January 2010</ref> It abandoned work on its drug development programs.<ref>Emily Singer, "deCODE ditches drug development," ''[https://www.technologyreview.com/s/417206/decode-ditches-drug-development/ MIT Technology Review]'', 22 January 2010</ref>

As a business, deCODE had in some sense gone back to the future: it was a 13-year-old company with a global reputation, again backed by its original VCs, which ''[[Newsweek]]'' called "the world's most successful failure."<ref>A good summary of the challenges and thinking for deCODE's revival post-bankruptcy, Mary Carmichael, "The world's most successful failure," ''[https://www.newsweek.com/can-decode-biotech-star-gone-bust-come-back-75021 Newsweek]'', 11 February 2010</ref> During the following period Stefansson mused publicly that deCODE had been founded between six and ten years too early.<ref>Stefansson said six years too early to Kevin Davies, in ''[https://web.archive.org/web/20081211150712/http://www.bio-itworld.com/issues/2008/nov-dec/first-base.html BioIT]'' in 2008; Kevin Davies, ''The $1,000 Genome: The Revolution in DNA Sequencing and the New Era of Personalized Medicine'' (New York: The Free Press, 2010), p. 148</ref> The technology for accurately reading DNA with sufficient detail, he reasoned, had not arrived until the mid-2000s, leaving deCODE in debt for years of R&D but based on findings that didn't provide a detailed enough insight into the biology of disease to swiftly create commercially compelling diagnostics and developmental drugs.<ref>Stefansson said company founded ten years too early and outlined his reasons to Victor McIlhenny in ''Drawing the Map of Life: Inside the Human Genome Project'' (London: Hachette UK, 2012)</ref> What might provide that insight was population-scale WGS data. By 2010 Stefansson was outlining how to sequence a few thousand individuals and then use imputation - powered again by the genealogies - to ensure that deCODE would be the first in the world to have anything like it.<ref>"For Kari Stefansson and deCODE, the diagnostics looks promising," ''[http://archive.sciencewatch.com/inter/aut/2010/10-sep/10sepStef/ Sciencewatch]'', September/October 2010</ref>

In spite of its straitened circumstances, with Illumina as one of its owners the company could still receive the latest sequencing machines and reagents. In 2011, deCODE and Illumina collaborated on a paper that gave an early hint at the power of WGS imputation, turning 500 sequences into 40,000 whole genomes of data. This was enough to begin to discover rare variants, validated through replication in several other populations.<ref>[https://www.decode.com/decode-genetics-in-collaboration-with-academic-colleagues-and-illumina-discovers-mutations-conferring-high-risk-of-ovarian-cancer/ Company press release] on the paper, "deCODE Genetics, in Collaboration with Academic Colleagues and Illumina, Discovers Mutations Conferring High Risk of Ovarian Cancer," 2 October 2011</ref> Unlike common variants, mutations causing rare diseases tend to be in the regions of genes that encode proteins, providing both a direct window on disease biology and so more direct utility as drug targets. In December 2012, the American pharmaceutical company Amgen acquired deCODE for $415 million.{{citation needed|date=December 2023}}

A key rationale for the acquisition was deCODE's unique ability to use WGS data to discover rare coding variants and cause extreme versions of more common diseases. As Sean Harper, then Amgen's head of R&D told Forbes, "It was really working on targets like PCSK9 [for heart disease]...that really drove home the immense value of having targets that have either been discovered or validated by the kind of human genetic analysis that Decode is a world expert in."<ref>Matt Herper, "With DeCode Deal, Amgen Aims To Discover Drugs Like We Meant To In 1999," ''[https://www.forbes.com/sites/matthewherper/2012/12/10/with-decode-deal-amgen-aims-to-discover-drugs-like-we-meant-to-1999/#4132be88130f Forbes]'', 12 December 2012</ref> More broadly, these capabilities could be applied to evaluate current programs as well, and within month of the acquisition deCODE had reviewed Amgen's entire pipeline. In 2018, Harper estimated that "just [by] having strong genetic support for half your pipeline you can improve your rate of return on R&D investments by approximately 50%."<ref>Quoted in Asher Mullard, "An audience with...Sean Harper," ''[https://www.nature.com/articles/nrd.2017.262 Nature Reviews Drug Discovery]'' (subscription required), vol 17, pp 10-11 (January 2018)</ref> By 2020, Amgen had brought two new cardiovascular drugs into clinical trials based directly on deCODE discoveries, which continue to be published in leading scientific journals.<ref>One targets lipoprotein (a), based on a [https://www.sciencedirect.com/science/article/pii/S0735109719380386?via%3Dihub deCODE discovery published in 2019]; another targets non-HDL cholesterol building on [https://www.nejm.org/doi/10.1056/NEJMoa1508419 deCODE's discovery of variants in the ASGR1 gene] in 2016. See Amgen's [https://www.amgenpipeline.com/ pipeline] and M. Janiszewski ''et al.'', ''[http://www.onlinejacc.org/content/73/9_Supplement_1/1755 Journal of the American College of Cardiology]'', Volume 73, Issue 9, Supplement 1 (March 2019)</ref>