In-Silico Drugmaker Highlights Rapid Rx Development at BIO Investor Forum

 BIO Investor Forum meeting October 21, 2015, Parc 55 Hilton Hotel, San Francisco. Cyclica is an emerging biotech firm that invented a therapeutic platform based on technologies. It’s called the Ligand Express (TM). The company is now in a license deal with Johnson & Johnson . They repurposed a pharmaceutical product made in the US. The DoD asked them to weed out 2000 drugs down to 53 and eventually they selected one, Zoloft. It turns out that this drug works against Ebola. The Army’s recent deployment of 3000 people to Africa to set up field hospitals, used Zoloft to treat Ebola patients.

Another example, Procter & Gamble has a drug compound that was causing skin irritation in some people that use their Olay skin cream products. It caused a rash. The company isolated three compounds that cause the issue and then eliminated the compound. 

The company’s vision is to 

  •  Cut drug development costs in half
  •  FDA to approve their drugs and 
  • Be the best tech platform for every doc to do personalized medicine solution in the future. 

The goal is to create an automated platform compared to other in-Silico players. Other in Silico firms look for chemogenic compounds, but this company does it all via Ligands. The company’s business model is mainly to work with big pharmaceutical and nutraceutical projects. 

The platform is like the eBay platform. For example on a project basis they might get $10,000 $20,000 in revenue with this model. The second thing they would do is have a license model in which they would receive $25,000 or more per project. 

Their current prospects include Procter & Gamble, the Department of Defense or other similar types of firms. The CEO’s name is Paul Angelico. He said that they will need $20 million in cash by 2019. They currently seek $9.5 million from VC investors.

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British Tech Network and New Products at MacWorld/iWorld 2014

SAN FRANCISCO (HighTech Reports), Moscone North, March 27, 2014 – MacWorld/ iWorld 2014. We watched a panel discussion session at the Second Stage presented by the British Tech Network (BTN) with speaker Paul Wheatley, User Experience Consultant and Host at the BTN. Paul and the panelists talked about the pros and cons of a bigger screen on the current or future iPhone, among other topics. He said that consumers are buying bigger iPhones, but the panel still preferred iPhones with smaller screens because they fit better in men’s pants pockets.

The panelists also talked about two interesting new products that they saw at the expo, BearExtender Edge and the Ring. The BearExtender Edge is long range Wi-Fi repeater/ booster that works with Macs, iPad/iPhone, and other devices (PCs with Wi-FI, other phones or tablets with Wi-Fi). The one-piece Wi-Fi repeater block plugs into an AC outlet and has an antenna that repeats/ boosts the Wi-Fi signal in the area. It does not require software or USB connector.  BearExtender also makes a high power standalone USB Wi-Fi radio adapter with an external antenna that increases the range of a Mac’s Wi-Fi signal by nearly four times that of an internal AirPort card. It adds Wi-Fi to older Macs or Windows PCs that do not have a built-in Wi-Fi adapter.

Paul and the panel were very intrigued by a new product called the Ring from Logbar, Inc., a San Carlos, California-based company.  It is a wearable technology product that fits on a finger as a finger ring.  The new Kickstarter funded device transmits hand movements or gestures to an iPhone or other Bluetooth enabled devices. The Ring works as an in-the-air pointing device that drew a largish crowd around its booth. A spokesperson from the Asian firm that is making the device suggested that the Ring is still in beta-test.

MacWorld/iWorld 2014 Returns to Moscone North

SAN FRANCISCO (HighTech Reports), Moscone North, March 27, 2014 – MacWorld/ iWorld 2014. It was refreshing to see that MacWorld/ iWorld returned to Moscone North, MacWorld’s former location of years ago. There were around 30,000 attendees at this year’s MacWorld. The exhibit floor seemed bigger than last year and highlighted more booths that we visited. We spent some time in the MacIT room where companies that had booths gave presentations. While there, we learned about products from Printer Logic, Lantronix, Absolute Software, Parallels, and Crash Plan.

Printer Logic sells an enterprise software app that attaches to Windows 2008R file server. The app replaces print server boxes in the enterprise. A license for up to 50 printers costs $5,000. The spokesperson said that most users have 25-30 printers. Each client driver for Mac/Windows PCs links to the printer app via Wi-Fi that scales very big in the enterprise. For example, the Department of Homeland Security used its service to reduce support calls for print servers that went down. The app solution was more efficient and saved the client money.

Absolute Software makes software that helps organizations manage all types of computer assets: PCs, laptops, tablets, phones, etc. It helps track the life cycle of all IT equipment assets to end-of-life. For example, the software helps Apple track iTunes content licensee IP assets. The firm’s solution helped the Columbine school track tablets, laptops, and thefts from intruders entering its campus. The company puts a special sticker on devices with a phone number to call if a child gets cyber bullied. The victimized child connects to a caring person to talk to and so forth. Absolute Software is also exploring other vertical markets.

 

iPhone 5 More Powerful than the Curiosity Mars Rover

SAN FRANCISCO (Takeda Pacific HighTech Reports), Moscone West, January 30, 2013 — MacWorld/iWorld 2013.  NASA experts spoke about NASA’s Curiosity Mars Rover and its connection to Apple products at a meeting here.  The session was titled “Software, Hardware, and Flying to Mars. How We Built, Programmed and Operate NASA’s Curiosity Mars Rover.”  David Oh, Lead Flight Director and Software Engineer at JPL/Caltech Mars Science Lab, asked the question, “Why are we at MacWorld?”  The answer was shown in a slide of the NASA control room at the JPL in Pasadena, California.  On the desk was a mixture of Apple products such as MacBook Pros, iPhones and iPads during the Rover’s Mars landing.  The Macs were running Mac OS X.

Ben Cichy, Chief Flight Software Engineer, compared the processing power of the iPhone 5 to Curiosity’s processing power.  The iPhone 5 has 1.3 GHz and the Curiosity has only 132 MHz.  In addition, the iPhone 5 has 1GB of memory and 64GB of storage and the Rover has 128MB of memory and 4GB of storage.  The cost of an iPhone 5 is $399 while the cost of the Curiosity was $1.8 billion.

During the session, the audience was shown a video of the landing of the Curiosity on Mars.  It only took 7 minutes, but a very tense 7 minutes.  It was very exciting watching the landing of the Mars Rover all over again.  “The Rover’s goal is to explore and see if Mars ever sustained life or is now,” Ben said.

David showed a slide that described the different parts that make up the Rover.  He added that the heart of the mission is the SAM (Sample Analysis at Mars).  The SAM analyzes the chemical and isotopic composition of the planet’s atmosphere and surface.  He said that the “Curiosity has two brains (computers) in its belly.  One is the primary computer and the other is the backup.”  This time social media plays a big part in providing people access to seeing what is happening with the Curiosity as it explores the surface of Mars.  The Curiosity has its own Facebook page and iPhone app.

Cegedim SA and Simcere Pharmaceutical Group Presented at 2013 J.P. Morgan Healthcare Meeting

SAN FRANCISCO, January 8, 2013 – Several emerging international healthcare firms presented their information to investors and potential partners at the 31st Annual J.P. Morgan Healthcare Conference held at the Westin St. Francis Hotel near Union Square in San Francisco.

Most of the smaller firms presented their talks at the conference’s smaller rooms.  This is where I found the Cegedim SA presentaiton.

Emerging European Firm

Jan Eryk Umiastowski, Chief Investment Officer gave a talk about his firm Cegedim SA, a private company that is located in France. He said that the company is a market research firm for pharmaceutical market development companies.  The company competes with companies like IMS Health.

He said that Cegedim collects prescribing information from pharmacies and doctors of what pharmaceuticals are being used by patients.  He said that they capture data that includes drug product name, quantity and so on to create databases.

Jan said that the company provides an IT application for claims transaction management.

He showed a bright green, credit card-like, card. He said that the patient goes to the pharmacy and presents the special green charge card, swipes the card and the IT application completes the transaction overnight.  Cegedim receives its revenues from pharmaceutical firms, doctors, doctors office groups, and others.

Jan said that the business model is subscription-based and there is a high switching cost to its business clients.  Jan said that the Cegedim works with Walgreens and is Number One in the countries that they operate in.  Their IT application runs on Windows 8. Their main clients are pharmaceutical companies in North America, Europe, and emerging countries.  In the future, the firm is looking for a 20% margin.  2012/Q3 was the first time that they were receiving pharmaceutical company business.

Emerging Chinese Firm

I learned that another group of emerging international firms was part of the Asia and China Forums. These meetings were located in the Victor’s room on the 32nd floor. The China meeting hosted fifteen or so presentations from China-based healthcare companies such as Simcere Pharmaceutical Group.

A woman executive gave the presentation about Simcere Pharmaceutical Group (NYSE: SCR).  The firm is located in Nanjing, China.  This young pharmaceutical firm started life as a pharmaceutical distributor.  The firm later became a fully integrated pharmaceutical company and currently has about 4,000 employees. The company recently changed its CEO and its business strategy.  Its disease focus is in oncology, strokes, cardiovascular disease, infectious diseases and pain.

According to the executive, the firm is doing cost cutting of its SG&A, and plans to grow its R&D operations.  She said that the company has partnerships with Merck and Bristol Myers Squibb.  Its pharmaceutical portfolio includes Endostar and others including branded generics.

She highlighted the financial performance and said that 2012/Q3 revenues were RMB 526 million and the first nine months revenues were RMB 1,543 million.  R&D investment has grown RMB 2009 to 2012Q1-Q3 as listed in this table:

Table: R&D Investment

Year 2009 2010 2011 2012/Q1-Q3
R&D SpendingRMB, millions 133 126 199 168

The executive said that market uptake of pharmaceuticals in China is gradual.  The company has eleven drug candidates in the pipeline.

Simcere Pharmaceuticals has several partnerships including:

  1. Merck J-V, Signed in 2011, 630 sales reps sell six products.
  2. Bristol Myers Squibb, Dev. metatinib, IND 09/2012
  3. Apexigen, antibody deal, BD0801 IND, 10/2012

Simcere Pharmaceuticals is looking for manufacturing partnerships to expand its manufacturing base. The company’s listing status in the US is part of its strategy to play in the US-based style of business to attract more US partners

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.

Next Gen. Sequencing for Dx – Exome v. Whole Genome?

While I was at CHI’s Molecular Medicine Tri-Con in San Francisco last week (Feb 23rd), I had a chance to sit in at a discussion table at the end of the day.  The topic at Table 6 was about diagnostic applications that used next generation sequencing (NGS).  About 16 people discussed the pros and cons of targeted resequencing versus whole genome sequencing. Karl Voelkerding M.D.,(Assoc. Professor, Pathology, Univ. of Utah; Medical Director, Advanced Technology and Bioinformatics, ARUP Laboratories), moderated the discussion. Karl said that NGS is being applied to multi-gene panels, exomes and whole genomes in clinical research and diagnostics. Each approach has different costs and complexity of data analysis and interpretation.

NGS for Multi-gene Panels v. Whole Genome
Karl started off by talking about multi-gene panels and NGS. Karl briefly talked about using multi-gene panels and Marfan Syndrome.  He said that the challenge involves sample preparation and noted that Fluidigm has a workable solution for this.

He asked the group “What’s being seen in Europe?” A person from Europe said that he has seen targeted NGS vs. whole genome NGS used by a fee-for-service company in Europe.  A person from Genomic Health said that, “if cost is not an issue, it’s OK to use whole genome.  But otherwise it’s better to use targeted resequencing.”  Karl said that at his lab, it takes over a year to do a CE- based multi-gene sequence [ vs. NGS].

Others at the table asked about costs.  The person from RainDance said that they have an in-solution capture method that could reduce costs.  Karl said that even there, there are non-trivial labor costs.  He said that “Some commercial companies do use robatic liquid handlers to reduce cost.”

Scenarios, Approaches, Costs
He said that this area is a moving target.  Amplified appproaches in multi-gene panels increase specificity for up to ten genes.  Otherwise if over ten genes, it takes many months of CE sequencing work. Researchers need to develop a special workflow for this type of CE- sequencing.  Karl said “An elusive goal is to make sequencing work like PCR.”  They are not there yet.

One person asked about simplifying the data content in a database by choosing some data as benign.  Karl said that academics are randomly updating their data by using a grad student or even an undergrad student.  But this approach gives inconsistant data quality.  He said that some commercial-based databases use more regularly scheduled updating.

He said that you need to ask the question “Are the genes associated with pathology?  Some genes are benign, some others are linked to disease.  We need to know, over time, what data items get classified as a changed data set.”
Some companies do targeted resequencing as a business and make IP from the database content. The database tells what is benign or what is something else.

A consultant asked “It would be interesting to see what in the database is predictive.”  Karl said “Extract the DNA, do PCR, do CE-seq, and analyze.”
The consultant also asked “What if you do NGS, then find genes, then pass data on to CE-seq to verify for Dx accuracy?” Karl said “Some research corelabs do exome sequencing for genome sequencing.  NHGRI is good with that approach.  He does 30x coverage at his lab.

Another person asked “What is the control level for false positives?
Karl said that, downstream, it depends on technologies used such as mass spec, v. NGS v. CE sequencing v. PCR.  Karl mentioned that the American College of Cardiology considered testing for hypertrophic cardiomyopathy (HCM)  and asked “Should we do multi-gene testing”  They test by using using echocardiograms.  Karl give the statitics for WW incidence.

So with the exome v. whole genome question. Karl asked, “When can you use gDNA for Illumina. The workflow is to do DNA sonograph, do Agilent Bioanalyzer 2100 to get total DNA, do qPCR to get fragment library which can go to the SOLiD or to the Illumina cluster [for HiSeq2000].

The sequencing workflow is:

  • Day 1 do gDNA
  • Day 2 do qPCR,  then transfer to Cbot
  • Day 3 run the HiSeq2000 at 2×100 for 8 days
  • Then run SeqTest, run QSeqTest, then output in Qfile format

Karl said it takes 105 days from start to end.

He said that, if you do exome sequencing, you need to do a purification step at the beginning, which adds 3-4 days to the workflow, but the exome sequencing is at a lower cost. Karl said the his lab is hooked up to the Univ. of Utah’s cluster computer and can do a data alignment in 1-day.  The cluster computer at the Univ. of Utah is also HIPPA compliant for privacy.

So cost drives exome sequencing. Karl said that “When doing exome sequencing you are doing a lot less sequencing, but you do more sample preparation.  You sequence on 2 lanes v. on 8 lanes [on Illumina].

Some List Prices
Karl gave some cost numbers.

  • For whole genome sequencing it costs $10K  with all reagents, including for library preparation.
  • For exome sequencing, it costs $1,200-$1,300 at 200X to 900X coverage.

So an answer for supporting multi-gene sequencing is to use exome sequencing of all genes in a panel.  e.g. Broad can sequence 2000 exomes per week. They streamlined a special workflow for this. Anyway, at the end of the day, you need to do down stream validation.

Consent Approaches that Should be Considered
A woman asked, “But in the clinical environment, what if you find other genetic information?, Some other genetic information?, Do you not tell the clinician?”
Karl said that “the key is informed consent.”  He said “ARUP is developing a tiered consent process — its mostly used for pediatrics now. So if they set out looking for one genetic area, but what if they find something else?  They age-level at age-14 for consent.”

Karl gave an example about the rare disease area at the NIH..  The NIH does exome sequencing.  Their success rate is 20% to identify a suspicious gene.  “So why just 20% with de novo mutations?”  He said that they are using exome sequencing and they just use a small population.  He mentioned a paper in Nature Genetics involving a group in the Netherlands  that saw a lot of power in NGS of a child that is an alternative to use laborious CE sequencing.

Karl said that the items not covered in the consented area are marked off.  He said that this is usually done in laboratory medicine.  When it comes to a recessive gene, the answer is often guided by family history.  Therefore “consent with tiering” is the way to be able to manage what diagnostic information is delivered to clinicians.  Karl wrapped up the discussion by saying that “NGS is pushing the envelope!”

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