Biotech Experts Highlight Clinical Sequencing at Rx/Dx Summits

I recently attended the IBC Rx/Dx Summits held in San Francisco in the first week of August 2012.  The meeting was held at the Westin San Francisco Market Street Hotel.  I was attracted to this event because it gave me the opportunity to learn about some of the new emerging market dynamics in next generation sequencing (NGS) and other areas that I track for my firm.

I listened to a talk comparing desktop sequencing systems by Jason Lih, Ph.D., Principal Scientist, SAIC-Frederick.  His talk was called Assay Development for Detecting Somatic Mutations in Cancer by Targeted Amplicon Sequencing: A Technical Comparison between PGM  and MiSeq.

Dr. Lih’s talk compared two desktop NGS machines, the Life Technologies, Ion Torrent, PGM with the Illumina MiSeq. At the beginning of his discussion, he said that he would not say which NGS platform is better.

In his NGS application, he used targeted amplicon sequencing to develop assays to detect somatic mutations in cancer.  Jason said that the PGM used AmpliSeq  v. Illumina’s TruSeq Custom Amplicon  (TSCA) technology.  He said that Life’s PGM requires just 20 ng of DNA sample, whereas the Illumina MiSeq requires 250 ng of DNA sample.  The Life PGM uses a 4-plex #‘316’ chip which outputs 1×200 base pairs of bi-directional sequence in one day plus 4 hours. (or 28 hrs).  The MiSeq takes 27 hrs (or 1 hr. less).

Using a comparison concept that he called the “Cosmic” MOI (Molecule Of Interest), he created a comparison chart comparing 1160 Cosmic MOIs.  He compared both vendor’s reagents.  His results showed that the PGM produced slightly more MOIs.

Vendor Model	Reagents	MOIs	DNA Sample	Run Time	QScore
PGM	AmpliSeq	1148	20ng	28 hrs	30
MiSeq	TSCA	1108	250ng	27 hrs	30

The PGM variant caller was the Ampliseq Reporter.  He used a 3^rd party software from CLC Bio.  The CLC Bio Integrated Genome Viewer showed a Qscore of 30 for each NGS machine.

What is interesting to me is that at end of his talk during the Q&A, an attendee asked Jason for his opinion about which was the best of the two NGS machines that he compared.  He said that his comparison was not intended to find the “best” NGS machine. My take away from his answer was that as far as Jason’s application was concerned, one could use either NGS machine and get comparable/ usable research data.  Also of note is that Roche Applied Systems demonstrated their 454 GS Junior desktop sequencer at the exhibit hall.  I wonder how the 454 GS Junior would compare against the PGM and MiSeq machines.

During the lunch- networking break in the exhibit hall, I met Robert Klein, Ph.D., Chief Business Development Officer, Complete Genomics, Inc. who said that he was giving a talk later in the day.  I attended his talk called: Large-scale, Accurate Whole Genome Sequencing to Enable Genomic Medicine. 

Robert gave a update on the business direction or activities at Complete Genomics (CG).  He said that CG v.1 was about research sequencing and that CG v.2 is more about clinical sequencing.  Dr. Klein said that in 2006 CG developed its proprietary sequencing technology and service model.  By 2011 they had delivered 3,000 genomes to customers.  Robert said that CG now produces 1,000 genomes per month.  He explained that they have a DNA factory in Mountain View and sends the data to its data center in the nearby city of Santa Clara.  CG does this because Santa Clara offers a lower cost for electricity.  CG provides “research ready” data to the customer and the customer analyzes the data.

Robert highlighted CG’s goals as including: Setup a CLIA facility 2H’12, Scale-up quality, Scale down cost, Scale-up throughput and Offering ‘clinical use’ sequencing.  CG will be focusing on new apps. including Idiopathic kids, Refractory cancers, Replacing cytogenetic arrays and Replacing targeted panels.  Dr. Klein also added that CG is interested in Wellness/ concierge medicine and Reproductive genetics.  He mentioned that CG is exploring other market spaces such as Prenatal screening, Newborn screening, and Reproduction Issues.  Dr. Klein predicted that the first areas that whole genome (clinical) sequencing would show clinical utility would be in studies of copy number, neuroblastomas and translocations. Robert said that NGS will likely democratize genomic medicine.

Several speakers echoed TGEN’s David Craig, Ph.D., Deputy Director for Bioinformatics and Professor of Neurogenomics,  comment that “the cost of NGS went up in 2011 because the analysis bottleneck is the culprit.”  My take on that is that in clinical NGS, the all-in $1,000 genome might be postponed to beyond 2014 by perhaps a few more years.

Diagnostic Companies Speak About Challenges With Pharma Partners at IBC Event

On August 6, 2012, I attended the IBC Life Sciences’ Drug & Diagnostic Development Conference at the Westin San Francisco Market Street Hotel.  The three-day conference consisted of four ‘summits’ that included the Future of Rx/Dx Summit, the Clinical Biomarkers and New Frontiers in Cancer Summit, the Next-Gen Sequencing Summit, and the Antibody-Drug Conjugates, Bispecfics and Empowered Antibodies Summit.  I decided to focus on the Future of Rx/Dx Summit business track.  A number of the presentations discussed the many challenges and success factors that go into developing companion diagnostics (CDx), which companies need to consider when developing a CDx.

Tips to Navigate Rx/Dx Co-Development

Patrick Goody, Divisional Vice President, R&D at Abbott Molecular brought up a number of important guidelines during his case study presentation, “Co-development of Diagnostics and Therapeutics: Abbott/Pfizer Crizotinib.”  Crizotinib (Xalkori) is Pfizer’s personalized medicine that targets a type of late stage non-small cell lung cancer (NSCLC).  Abbott Molecular developed the FDA required EML4-ALK fusion companion molecular test that enables physicians to select the sub-group of patients that would benefit from using crizotinib.

He said in order to be successful, the partners need to “capitalize on their collective strengths and establish good chemistry.”  He believes that good “communication is key.”  Other important factors include “coordination of drug/IVD submissions as well as commercial execution and worldwide distribution.”  Goody emphasized that pharmas should get involved with a diagnostic partner early. This point was mentioned in other presentations as well.  He also said that there must be business incentives for both partners.

Ron Mazumber, Global Head, Research and Product Development, at Janssen Diagnostics spoke of the “Challenges and Opportunities/Solutions of CDx in Pharma” during his presentation.  Some of the main challenges include the “complex regulatory landscape, PMA process/expectations, and variability of testing.”  He offered some solutions such as “repurposing an existing 510 (k) cleared product, bridging studies, use of CTCs (circulating tumor cells), and multiple partners/platforms.”  Mazumber said the “ideal scenario is to start at Phase 3 with an IUO (investigational use only).”

Panel Discusses Rx/Dx Business Ideas

I also attended the panel discussion about “Emerging Commercialization, Collaboration and Business Models for Rx and Dx.”  One of the major themes of the discussion was that diagnostic companies need to continue to drive the value of their product.  Panelist Michael Pellini, President and CEO, at Foundation Medicine, said, “it’s all about education.”  Another panelist, Ron Andrews, President, Medical Sciences, at Life Technologies said, “We are venturing into a more complex world.”  He said “a lot more goes into a diagnostic nowadays than even five years ago.”  To the question posed by moderator Alexis Borisy, Partner, at Third Rock Ventures, “Do Pharmas ever pay diagnostic companies big fat royalties?”  “No, pharmas are not paying diagnostic companies big fat royalties,” said panelist Ron Mazumder at Janssen.”  However he did say, “pharmas are starting to recognize value but it is still a sticky issue.”  Andrews said “there are tons of therapeutics that have been shelved that might have value if the right diagnostic is developed.”  Panelist Pellini said that he “dreams of a fat royalty if they enter into a relationship with a pharma company and salvage a drug with a diagnostic.”  “They should share revenue downstream if they add enough value,” he added.