Teaming up to interrogate genes about ADME

Roche and RainDance Technologies join forces in targeted sequencing to advance research into drug metabolism and response

Lloyd Dunlap
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BRANFORD, Conn.—To help scientists capture known and unknownfunctional mutations associated with core sets of pharmacokinetic andpharmacology genes, Roche subsidiary 454 Life Sciences and Lexington,Mass.-based RainDance Technologies Inc. have signed a deal for developing andcommercializing a targeted next-generation sequencing (NGS) solution for simpleand cost-effective investigation of drug absorption, distribution, metabolismand excretion (ADME).
As part of the collaboration, RainDance and 454 LifeSciences plan to commercially launch a core ADME gene screening research panelthat will be made available on both the 454 Life Sciences' GS Junior and GS FLXSystems. Financial terms of the deal were not disclosed.
"For the first time, researchers can look beyond themutations found on current genotyping panels and discover novel chromosomalchanges and rare mutations associated with drug metabolism and adverse drugevents," said Roopom Banerjee, president and CEO of RainDance Technologies, ina news release about the deal. "Through our collaboration, Rain Dance and 454 LifeSciences are combining the power of our microdroplet technology with 454 LifeSciences' proven next-generation sequencing platforms to provide a robust andeconomical ADME sequencing solution."
Current ADME research products are primarily limited to genotypingcommon alleles, the companies note, and therefore lack the sensitivity, breadthof genomic coverage and ability to identify previously unknown variants thatare important to drive scientific discovery and routine use.
RainDance and 454 Life Sciences maintain that theircollaboration will enable researchers to interrogate a set of corepharmacokinetic and pharmacology genes, while at the same time to detect knownand unknown functional mutations associated with drug metabolism and response.
"We started collaborating on a new ADME solution conceptabout a year ago," recalls James Brayer, RainDance's product manager fortargeted sequencing. "The idea was born out of a mutual desire to bring thepower of next-generation sequencing to ADME research. We have a number ofmutual customers who are interested in an easy-to-use solution that targets allof the core ADME-related genes in a high-throughput fashion."
The impetus to deal with that concern wasn't simply abusiness opportunity for the two companies, but a push they felt fromcustomers, adds Ulrich Schwoerer, 454 Life Sciences' head of global marketing,who tells ddn that "companies andresearch organizations involved in the discovery, development and manufactureof medicines are under increasing pressure to bring down costs and, moreimportantly, ensure the safety of products that are bound for, or already in,consumer markets."
In choosing 454 Life Sciences as a partner, RainDance wasremaining true to its commitment to work with best-in-class partners, Brayersays, "to enable a number of new targeted sequencing applications that wouldbenefit from the single-cell and single molecule resolution that is possiblewith our microdroplet-based platform. We also believe that our platform plays acentral role in further advancing the routine use of next-generation sequencingin research areas that have been difficult to examine using previoustechnologies."
Looking at his own company's strategic goals, Schwoerer saysthat 454 Life Sciences' vision is to enable researchers, particularly in thearea of medical research, to do their jobs far better and more efficiently.
"For the time being, targeted sequencing offers the mostcost-effective and tractable approach to translate the use of genomicinformation into a medically relevant result," he says. "Targeted resequencingtechnologies such as RainDance's provide an opportunity to focus on the genomicregions with the highest likelihood of impacting research in a cost- andtime-efficient manner."
The two men say their companies continue to evaluate otherpotential complementary applications and workflows, adding that they view thisnew ADME panel as a proof of principle illustrating the capability of couplingRainDance's targeting methods with 454 Sequencing Systems. RainDance's abilityto custom-design PCR amplicon panels that fit into the 454 Sequencing workflowwith minimal effort means that researchers can use this panel as a startingpoint, but also have the flexibility to target any region of the genome theyare interested in, they say.
RainDance's proprietary primer design method reportedlyenables highly accurate, consistent and reproducible next-generation sequencingin ADME research, which is required for large-scale drug metabolism studies.454 Life Sciences' GS Junior and GS FLX Systems are said to providehigh-quality, long-sequencing reads which enable higher levels of coverage,accuracy and quantitation with fewer dropouts, as well as detection of a widerange of genomic variations, including SNPs, insertions, deletions andmultinucleotide polymorphisms.
"Our collaboration with RainDance will result in solutionsthat better equip scientists to leverage the GS FLX and GS Junior Systems toeffectively predict and understand drug activity early in the drug developmentprocess," said Christopher McLeod, president and CEO of 454 Life Sciences, in anews release about the deal, adding that adverse drug events represent morethan two million hospitalizations and approximately $1 billion in healthcare costburden annually in the United States alone.

RainDance and Ambry Genetics ink ADME analysis deal
LEXINGTON, Mass.—RainDance Technologies Inc. also recentlyannounced that it will collaborate with Ambry Genetics on the development andcommercialization of a comprehensive drug absorption, distribution, metabolismand excretion (ADME) genetic screening panel for use on next-generationsequencing (NGS) systems.
The announcement was made at the Society of Toxicology's50th Annual Meeting in Washington, D.C. Financial terms of the collaborationwere not disclosed.
The new ADME panel will provide scientists with the capacityto perform sequence analysis of entire coding regions associated with more than220 key drug metabolism-linked genes, including transporters, receptors,regulators and all pharmacodynamic and pharmacogenetic genes, as well as allU.S. Federal Drug Administration (FDA)-identified pharmacogenomic biomarkergenes. The panel, provided as part of Ambry's ADME sequencing service, willleverage RainDance's primer design methods and microdroplet-based RDT 1000platform, which according to RainDance provides the highly accurate, consistentand reproducible results required in ADME research and for most FDA drugapplications.

"Scientists interested in analyzing ADME-linked genes cannow look far beyond what existing genotyping panels reveal and discover thenovel chromosomal changes and rare variants associated with drug metabolism andmolecular pharmacology," says Dr. Darren Link, RainDance's co-founder and vicepresident of research and development. "Through our collaboration with AmbryGenetics, we are providing a solution that puts the most advanced ADME researchtools within reach of the many research organizations focused on reducing thesignificant costs associated with failed drug trials and avoidablehospitalizations."

Lloyd Dunlap

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