Big Data and Precision Medicine Trending at CHI Tri-Con in SF

Moscone North Hall, Feb. 17, 2015. After walking the halls in the exhibit area at the recent annual CHI Tri-Con event in San Francisco, I discovered that a theme came together after I passed by various booths.

For one thing, the words “precision medicine” seemed to be resonating among those firms that were exhibiting and I asked some of them, “Is that the same thing as “personalized medicine” or “individualized medicine?”” I noted to that person that President Obama had recently made some kind of a speech that was promoting the idea of precision medicine so maybe the time has come for precision medicine to take the spotlight.

In any event I also found that there are other themes there such as big data. It is being used in a number of different biomedical research areas. I stopped by the Illumina booth spoke with the lady there whose name was Kathleen. She said that she had just joined the company about two months ago from Roche where she was involved in the clinical area. She said that her firm is moving into the data management side of their business with a focus on clinical diagnostics and take advantage of the fact that a lot of NexGen sequencing is now being used for clinical types of applications and will be generating lots and lots of data.  So big date is the theme here as well. They’re hoping to sell their systems into the clinic and hospital type settings so that they develop some very useful software systems to make sense of all that data. Data analytics is going to be a big deal.

I walked around and came across another booth that was also telling the story of powerful computer power and big data and that was the guy at Cray Computer that is famous for supercomputers in the past, but today they are using many many computers together as a cluster, a Hadoop and have another one they called SPARK. I’ll have to check out what “Spark” means. It seems to me that quite a lot is happening in the software.

CHI had other usual events that they have at the Exhibit Hall such as a raffle in which an attendee might win some kind of electronic gadget. This part of the event also featured a discussion tables. There were 40 tables that could handle as many as 8 to 10 people.  I noticed that just about every table was filled up in the hall and some of the tables had probably 10 to 15 people there, so they must have had some very popular topics to discuss. Traditionally, this part of the exhibit area has been very popular in past meetings that I’ve attended.

Simple Cancer Biomarkers are Inadequate to Enable Personalized Medicine

It seems that researchers are finding that using single cancer biomarkers to develop companion diagnostics (CDx’s) to be used with future targeted therapeutics is very challenging. An article in the November 15 issue of Genetic Engineering and Biotechnology News, called Traversing the Cancer Biomarker Labyrinth, by Kathy Liszewski, is a very interesting read.

Apparently progress in this field has slowed in finding clinically useful biomarkers for diagnostics and making other tests that guide doctors for disease prognosis and prediction. Researchers are using a variety of reductionist technical approaches that range from analysis of certain glycans, key microRNAs, and epigenetic changes, to big data analysis of massive data stores of genomic data to tease out more clues to what is going on in cancers.

Scientists seek to develop early detection blood tests that can detect cancers of interest.  Such a blood test could be considered a ‘liquid biopsy’ and might include a panel of a dozen or more miRNAs that represent a biomarker signature.  An oncologist might one day be enabled to quickly screen certain patients with a blood test that would help them diagnose, stage or predict the potential outcome of a cancer.

Acute Need for Early Warning Dx for “Silent Killer” Cancers

There is a need for early warning diagnostics to detect “silent killer” cancers such as pancreatic, liver, GI and lung cancers. Most of these cancers are discovered at the late stage when acute symptoms appear and no cure is possible.  Maybe an annual simple screening test could be developed that could accurately detect a molecular signature of these cancers.

It is a very sad situation indeed to see patients die just after two, four or six weeks post-diagnosis.  Just this past weekend, our co-writer and industry analyst for this blog and our market research firm succumbed to an aggressive cancer of unknown primary origin that spread to the liver.  She died in less than five weeks from diagnosis.  The FDG- PET CT scan showed active cancers in the liver, pancreas, uterus and breast. Ultimately the oncologist concluded that the cancer likely came from the pancreas. May she rest in peace.

Close relatives interested in getting a PET scan for themselves were advised that the Radiology Dept. would only offer a PET scan after a patient was already diagnosed to have cancer.  Whereas a PET scan is good at detecting cancer, it is a very expensive resource that hospitals choose to limit access to.

What is needed is an annual pre-symptomatic, accurate, low-cost multiple-molecular-marker, blood test that can screen for cancer at the earliest point – before a tumor is formed. The screening test would likely use a panel of biomarkers associated with the “silent cancers.”

Emerging Changes Coming to the Drug Development Ecosystem

At last, the face of the Affordable Care Act (ACA) has entered the public arena.  Last October at the launch of the web marketplace of the ACA, the public became keenly aware that major changes in the US healthcare system were underway.  Despite its rocky beginning, by January several million customers had successfully signed up for their new healthcare insurance plans for 2014.  The ACA will have an impact on many stakeholder groups including patients, health care providers, hospitals, insurance payers, government agencies, drug developers, and others.  In particular, one can expect to see changes of the drug development ecosystem emerge over the next few years.

On January 14th at the Parc 55 Hotel in San Francisco, the Biotech Showcase presented a plenary luncheon presentation, The Changing Dynamic of the Drug Development Ecosystem.  A panel of experts shared their insights and opinions of what might play out in the industry over the next few years.  Moderator, Ellen Corenswet, Partner at Covington & Burling LLP, posed key questions to the panelists.

The panelists included:  Karen Bernstein – Co-Founder, Chairman and Editor-In-Chief, BioCentury; Anton Gopka – Managing Partner, RMI Partners; Dan Mendelson – CEO, Avalere Health; Dennis Purcell – Sr. Managing Director, Aisling Capital; Evonne Sepsis – Managing Director, ESC Advisors.

Karen Bernstein opened the initial discussion about patients, what drugs they want, how they pay for healthcare insurance and so on.  She spoke about the ACA (aka: ObamaCare) in relation to patients and how they interact with drug companies.  Dan Mendelson seemed to know many detail data points about what to expect from the ACA since his firm has done some studies that model the potential impacts of the law.  Dan said “more and more, healthcare costs are being pushed to consumers.”  He said that many of the plans offered on the Exchanges cause consumers that need Tier-4 drugs “to pay 50% of the market price of the drugs.”  Tier-4 drugs are expensive targeted cancer drugs.

Berstein said that drug companies have offered discount coupons to consumers for some expensive drugs.  Mendelson said that there is a contradiction between ObamaCare and Medicare.  For example, Medicare does not accept discount coupons.  But, ObamaCare does accept discount coupons.

Dennis Percell said “In Boston, there are three hospitals within three miles of each other that do heart transplants. In New York City, there are hospitals that repair hips. There is one that charges $15,000.  At another place it costs $60,000.”  He asked, “What’s going to happen in pricing five years from now to the hospitals that do the heart transplants and the ones that do the hip repairs?”

Dan Mendelson  said he has “seen that consolidation is already happening either through acquisition or through contracts among organizations.“  “In many areas there is significant over capacity such as from teaching hospitals and academic centers.”  He said that “a lot of the teaching hospitals are being excluded from the networks that are fielded under the exchanges.”  Dan said that the exchanges will get up to about 6 million people and will represent just two percent of the health care system.

He said that “small businesses are calling the insurance companies and asking them to design new insurance plans for them.” He expects that “over the next five years, the benefit designs for the ACA will eventually spill over to whole healthcare insurance market.”  This scenario will have an impact on biotech’s future drug development plans.

Evonne Sepsis said “Reimbursement needs to be considered at the beginning of drug development process. She said “historically, most drug development companies considered reimbursement later.”  But not now.

Bernstein noted that companies say that their partner’s drug R&D costs need to be recovered through higher prices. However, high new drug prices are not sustainable. Dennis Purcell pointed out that “the last ten of twelve new cancer drugs cost $100,000 or more” for a course of treatment.

Evonne added “A few years ago, ten years ago, we saw the orphan drug market emerge. It needed just a patient population of 1000-5000.”  But now “with smaller patient populations in personalized medicine it is similar to the orphan drug market.”

Ellen asked  “What about the role of international going forward?”

Anton Gopka said that international pharmas are doing clinical trials in Russia for proof of concept studies.  This business model might work.  After the trials they can commercialize the new drug in U.S. Dan Mendelson said “Well maybe not so, because most U.S. payers or regulators prefer drug trials to be done in U.S.”  Dennis Purcell said  “If it were a country, the U.S. healthcare system would be the 5th biggest country in world.”

The discussion turned toward disease foundations and patient groups.

Dennis Purcell said “I believe that we will see lot of disease foundations that will open a VC arm.  So VC groups should work together with them to bring their projects forward.  Dan Mendelson offered that disease groups would work as clients. That is. A diabetes group would test the glucose value of products.

Ellen asked how to engage with the patients.

Dan Mendelson said that we need to understand and look at the quality measures. “We can’t expect the payer to give you a guarantee. Its not possible.” “We need to show an advantage vs. other drug competitors.  We need payer buy-in — each payer wants something different.  Small companies need to be competitive.  This situation has ham-stringed the FDA — They are not up to speed with the leading technologies.”

Karen Bernstein wrapped up their discussion by saying that the FDA is good in certain areas.  They are the only government agency that is under funded.  She noted that Janet Woodcock is expected to return soon, others, key people are expected to leave or retire by 2016.  She said “I see the next five years as tough for the FDA.”

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 3rd 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.

Circulating Tumor Cells Emerging as a Hot Topic In Cancer Research

While visiting CHI’s Molecular Medicine Tri-Conference back on February 20th at the Moscone Convention Center, in  San Francisco, I had a chance to walk around the exhibit hall and talk with some of the people working at their trade show booths.

I spoke with Sally Hall, who was working at the Transgenomic, Inc. booth, and asked her, “What are some of the hot topics at the show?.” She said that it seems that this year, a hot topic at the CHI MMTC is about circulating tumor cells (CTCs).  Sally said that “this year there are about twenty companies working in this field.”

I mentioned that I noticed that the number of conference talks about CTCs at the CHI MMTC had grown over the last three years.  She agreed that she had seen increased research activity in the CTC field.

As I understand it, when cancer tumors reach a certain size or age, some of the cells break off and migrate through pores in the walls of  blood vessels and circulate in the blood stream as CTCs. The CTCs may remain dormant for months or years in the circulatory system before migrating through pores in the blood vessels to spread to other organs or tissues.

Scientists are using CTCs as a new type of biomarker.  Several research tools and technology companies have developed technology platforms to identify, isolate or characterize CTCs.

Some companies are working to develop a platform that utilizes CTCs as basis for a future personalized diagnostic.  Researchers might someday develop blood  tests that can accurately identify specific kinds of cancer tumors long before they spread to other organs.  Blood test based companion diagnostics might be developed using CTCs in concert with targeted medicines to kill tumor cells before a cancer tumor has a chance to spread.

On the other side of the exhibit hall, I spent a few moments to see a talk from the founder of Rarecells, Inc.who discussed their progress in developing a CTC-based diagnostic method that they called ISET.  I was impressed by their concept. The table below lists a few of the commercial companies working in CTCs.  Whereas the CTC field is an emerging niche market today, it may be too soon to tell what the size and shape that this market might take.

Selected companies working in CTCs

Application Company Comment
Clinical Use of CTCs Fluxion Biosciences, Inc. IsoFlux system for  analyzing CTCs
Clinical Use of CTCs On-Q-ity, Inc. Microfluidic system for selecting CTCs
Clinical Use of CTCs BioCept, Inc. OncoCEE™ Platform for capture and detecting CTCs for molecular analysis
Clinical Use of CTCs Rarecells, Inc. ISET, a diagnostic method for isolation and immuno-molecular characterization of CTCs
CTCs in Clinical Trials Johnson and Johnson, Oncology Biomarkers Liquid biopsy – the use of CTCs in clinical trials as prognostic and predictive markers.
Novel Technologies ScreenCell, Inc. A mini device to isolate rare circulating tumor cells (CTCs).
Novel Technologies Advanced Cell Diagnostics, Inc. The CTCscope platform for detection and character-ization of CTCs
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