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AstraZeneca Launches Genomics Initiative to Drive Drug Discovery and Development

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NEW YORK (GenomeWeb) – AstraZeneca and its biologics research and development arm MedImmune plan to include genomics in drug development and discovery across its entire R&D pipeline, the company said today.

As part of the initiative, the firm will collaborate with Human Longevity, the Wellcome Trust Sanger Institute, and the Institute for Molecular Medicine in Finland. AstraZeneca will also establish an in-house Center for Genomics Research, which will develop a database that includes patients' genomic sequence data, as well as drug response and other clinical features.

Over the next 10 years, AstraZeneca plans to analyze the genomes of 2 million patient samples — including 500,000 samples patients have donated to AstraZeneca as part of clinical trials, 1 million samples from Human Longevity's database, and 500,000 other samples that are in the public domain and include comprehensive phenotypic data.

The "time is now right to immerse ourselves fully in the international genomics community," Menelas Pangalos, executive vice president of innovative medicines and early development at AstraZeneca, said in a statement. "Genomics will be fundamental to our laboratory research, our clinical trials, and the launch of our medicines for patients."

The company did not disclose financial details, but during a press conference that was webcast, Pangalos estimated AstraZeneca would invest in the range of hundreds of millions of dollars throughout the the program.

Human Longevity will sequence the genomes of up to 500,000 patients who have participated in AstraZeneca's clinical trials and consented to research, including patients from trials that have been conducted over the last 15 years and ones that will be conducted over the next 10 years.

In addition, Human Longevity will provide AstraZeneca access to its database — which is slated to include 1 million samples with genomic and clinical data by 2020.  AstraZeneca will be able to use Human Longevity's machine learning and computational tools in its research and development pipelines. Human Longevity will also add data from the 500,000 AstraZeneca samples it sequences into its database.

Currently, Human Longevity has around 26,000 sequenced whole genomes, along with corresponding clinical and phenotypic data, and is adding approximately one genome every 15 minutes to its database, Craig Venter, CEO of Human Longevity, said during the press conference.

The genome center that AstraZeneca plans to create at its headquarters in Cambridge, UK will focus on creating a database that will include donated patient samples from the last 15 years and samples collected over the next 10 years, all of which will have clinical health, phenotypic, and genomic data.

David Goldstein, director of Columbia University's Institute for Genomic Medicine, will chair AstraZeneca's genomics advisory board.

Mike Stratton, director of the Sanger Institute, said during the press conference that a team of scientists led by an AstraZeneca employee would work within the Sanger Institute to develop the overall research strategy for gleaning insights from the genomes and translating these into drug discovery and development pipelines.

Stratton said that the team would essentially have free reign to design the research portfolio and priorities under the overarching umbrella of genomics and disease, but one area he said might be particularly fruitful is cells. For instance, he said, the Sanger Institute has invested substantially in technologies that allow researchers to create induced pluripotent stem cells, which could be used to explore the impact of mutations. "It's at the level of cells that therapeutics work," he said, so "understanding how a DNA variant impacts cell biology, how the cells of a particular individual differ in their fundamental biology from a different person … will bring us central insights."

The third collaboration announced today is with Finland's Institute for Molecular Medicine, which launched its own sequencing initiative in 2014.

The project's most recent data release includes genomic data on over 10,000 Finnish samples from disease cohorts that include Alzheimer's, diabetes, metabolic disorders, and inflammatory bowel disease. Aarno Palotie, research director of genomics at the Institute for Molecular Medicine, said that the Finnish population would provide a unique contribution for studying rare variants. Due to it having been a relatively isolated population, variants that are very rare in the rest of the world are more frequent in Finnish individuals, he said. In addition, the country has a centralized clinical and phenotypic data collection system as well as a biobanking protocol that allows for recall.

In collaboration with AstraZeneca, Palotie said, the group has chosen a handful of drug target genes to try to find disease targets, comorbidities between diseases, and unexpected or potential safety concerns.

Aside from the collaborations announced today, AstraZeneca anticipates it will strike deals with other academic medical institutions for the project. For instance, Ruth March, vice president and head of personalized healthcare at AstraZeneca, said that the pharma company is currently negotiating with the Stratified Medicine Consortium in Scotland, and would announce collaborations with other institutions as they developed. It will be through these other collaborations and the public domain that it will gain access to genomic and clinical data from 500,000 additional individuals. "We're starting a network of academic partnerships," she said.

The company already has some existing collaborations, including with the Montreal Heart Institute and Genomics England. March said that these collaborations would continue and would help bolster the new initiative. For instance, AstraZeneca will be able to use data from Genomics England's 100,000 Genomes project. Those samples also have clinical data associated with them.

March added that the two projects would not be redundant or competitive since they have different aims. The Genomics England project, for instance, is focused primarily on cancer and rare disease and on the clinical application of the genomic data, as well as on medical education within the UK's National Health Service.

The initiative will be pre-competitive: AstraZeneca will not develop intellectual property around any of the data generated or even potential drug targets identified, but only on the drug compounds themselves, Pangalos said.

"Understanding the biology gives you a head start," Pangalos said, adding that it will be that head start that leads to patentable compounds, rather than patenting the biology. 

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