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TODAY’S HEADLINES:

• Oxford NanoLabs takes in £10M for sequencing tech (PDF release)
• Alure Medical raises $4.5M for plastic-surgery implants (release)
• Bone-disease biotech Therosteon spins out of research institute, raises funds (PDF release)
• Genome-analysis toolmaker BioTrove files for $75M IPO (Edgar)
• RNAi developer Tekmira acquires Protiva, ends litigation (release)

Oxford NanoLabs takes in £10M for sequencing tech – U.K. based Oxford NanoLabs, yet another startup developing high-speed genome-sequencing technology, raised £10 million in a new funding round. The company said only that its backers included institutional and private investors.

Oxford is working on a so-called nanopore technique for DNA analysis, which typically involves chips laced with a lattice of tiny holes. The company says its process can identify the DNA “letters,” or bases, that compose the genetic code by passing DNA molecules through the pores. As each base slides past, it sticks temporarily to the side of the pore, interrupting electricity being conducted through the surface in a characteristic way that identifies whether the base is an A, C, G or T — the four letters of the DNA alphabet.

Of course, Oxford is entering a field crowded with established companies and other startups. In no particular order, we’ve recently covered fundraising and technology developments at BioNanomatrix, Intelligent Bio-Systems and Pacific Biosciences in recent months.

Alure Medical raises $4.5M for plastic-surgery implants – San Diego’s Alure Medical, a startup developing “soft-tissue” implants for cosmetic procedures, raised $4.5 million in a first funding round. Its backers include EDF Ventures and private investors.

The company is working on implants that lift sagging tissues in the breast, neck and elsewhere. Alure also named France Dixon Helfer, a former Medtronic executive and co-founder of Pegasus Biologics, as its new CEO.

BioNanomatrix, a Philadelphia developer of genome-analysis systems, raised $5.1 million in a first funding round. Investors included Battelle Ventures, Innovation Valley Partners, KT Venture Group, Ben Franklin Technology Partners and21Ventures.

BioNanomatrix is developing a single-molecule imaging and analysis system that the startup says is ideal for reading DNA sequences. The startup still isn’t divulging many details about its system, although the Philadelphia Inquirer suggested that the company’s “nanofluidics” technology could potentially read all three billion bases from a single DNA molecule without chopping it up first — a common step in most sequencing setups these days, albeit one that also increases the complexity of reassembling the fragmented sequences into a coherent whole.

According to that article, in fact, BioNanomatrix has produced a nanofabricated chip with more than a mile of tiny channels that can accomodate the full DNA molecules from all 46 chromosomes of 200 people at a time. That’s pretty spectacular if true, although of course the challenge with this sort of technology is always proving that it does what the company says it should.

We previously covered BioNanomatrix last October, when the company formed a joint venture with Complete Genomics of Menlo Park, Calif. The two companies, which shared an $8.8 million grant from the National Institute of Standards and Technology last year, are aiming to sequence an entire human genome in eight hours for $100, although they haven’t set a date by which they hope to accomplish that feat. It’s a nice bragging point, since that’s about an order of magnitude faster and cheaper than anyone else is predicting at the moment, but it’s also little more than an unsubstantiated claim for the moment.

For more coverage of the high-speed genomics race, see my previous posts onPacific Biosciences and its nanowell technique, Intelligent Bio-Systems’ $5,000 genome challenge, and VisiGen’s promise of a $1,000 genome by the end of 2009. Don’t miss my Q&A with MDV’s Bill Ericson about the medical promise of fast, cheap genome scans.

Bill Ericson doesn’t see much cause for pessimism about the dawning Genomic Age. The Mohr Davidow Ventures partner, who’s helped resuscitate the firm’s life-science practice since he came aboard in 2000, believes the widespread dissemination of genetic information will be a virtually unalloyed good, opening up a wealth of opportunities for more effective medicine, lower healthcare costs and individual empowerment — not to mention investment opportunities for those prescient enough to seize them. (See here and here for my own take on the subject.)

Ericson, of course, has plunked down some serious cash in service of his convictions. He played a significant role in funding the genome-sequencing startup Pacific Biosciences, which announced itself with a splash last weekend, and previously backed Tethys Bioscience, a biotech with a test it says will predict your diabetes risk with high precision. I spoke with him recently about the PacBio investment, and somewhat to my surprise soon found myself in a broader conversation about the impact genomic data will have on the world. (I’ve edited the transcript for clarity and brevity.)

VentureBeat Life Sciences: Makers of biological tools like gene-sequencing equipment have been out of favor with VCs for almost a decade. How did you get involved with a genome sequencer like PacBio?

Bill Ericson: Back in the mid-1990s, it became clear that we were entering a period in which we could measure biological functions and patterns in ways that we hadn’t previously been able to do. When I joined Mohr Davidow, I wanted to focus on where measuring biology in more systematic, quantitative ways would lead. It was just the beginning of a period of rapid technological advances and of rapidly improving understanding of fundamental biology. I was convinced that all sorts of goods and services would flow out of that.

One area we considered greatly underinvested was sequencing. Other nucleic-acid measurement techniques are surrogates for sequence information, which we thought was the gold standard. At the end of the day, if you could do fast, accurate sequencing, you’d probably end up dominating the field.

One technology that got us really excited was at a company then called Nanofluidics [now PacBio], where three Cornell postdocs were working on zero-mode waveguides and using them to do sequencing. We convinced them to move their group to the Palo Alto area, where they incubated with us for the better part of a year. We wanted to invest in people and technology that could really take you to the next, next level of sequencing — as close as possible to the end state of sequencing technology. These guys had at least the theoretical ability to do the full human genome for $1,000 or less.

VBLS: What consequences do you expect from the advent of such high-speed sequencing?

BE: This is an information-generating technology, one that’s faster, cheaper and more powerful than anything else. Any number of new applications could flow from that. For instance, everyone believes that genetics plays a role in predisposing you to various diseases. If we do the population studies [that reliably link genetic differences to disease], you can arm physicians, patients and consumers with a better way of looking at health. Human health turns into much more of an information system that can be understood and proactively addressed, in sharp contrast to medical practice today, which is tremendously reactive and wasteful.

Once you shine the spotlight of sequencing on large populations, you’ll identify patterns that are invisible today. I would love to see genetic studies show that only five percent of the population actually needs to go on a drug that today is prescribed for 40 percent to 50 percent. That’s a tremendous win — no drug has no side effects. Sequencing could also be very useful in an area that frankly ought to scare all of us to death, which is the emergence of drug-resistant infectious disease. You could see the mutations [that confer resistance] happening in real time. In real time, you could be measuring somatic mutations [that give rise to cancer].

I think all these tools are going to give rise to new applications. It’s a lot like watching the computer industry — once PCs were adopted to the point of being cheap and readily available, people created applications for them. I honestly wish I could tell you precisely what will be valuable and what won’t, but we’re still in the early innings.

(More after the jump.)

Read the rest of this entry »

TODAY’S HEADLINES:

• Metabolic-disease biotech NGM Biopharma raises $25M (peHUB)
• Heart, HIV drug maker Numerate acquires assets of Pharmix (release)
• Next-gen sequencer VisiGen promises $1,000 genome by late 2009 (Genome Technology)
• CalciMedica raises $5.5M for autoimmune drugs (VentureWire)
• Cancer-drug e-marketplace OneOncology raises funds (release)
• U.K. biotech Hunter-Fleming acquired by Newron for €8M (release)
• Intertek acquires Ireland’s Bioclin Labs, a contract research organization (release)

Metabolic-disease biotech NGM Biopharma raises $25M – South San Francisco-based NGM Biopharmaceuticals (Web site under construction), a biotech developing new drugs for heart and metabolic conditions, raised $25 million in a first funding round, peHUB reports. Investors included Column Group, Prospect Venture Partners and Rho Ventures.

NGM, currently helmed by Tularik founder David Goeddel on an acting basis, isn’t divulging much about its plans. According to VentureWire, the company is developing new treatments based on “post-genomic bioinformatics” (a virtually content-free buzzphrase if I’ve ever heard one) and “new approaches to human biology” (which isn’t much better). NGM plans to devote the funding to R&D spending over the next three years.

The company’s ties to the former Tularik — which was acquired by Amgen in 2004 — are worth noting. In addition to Goeddel, the company’s chief scientific officer, Jin-Long Chen, was formerly a VP of biology at Tularik, and then headed Amgen’s metabolic-disorders unit.

Heart, HIV drug maker Numerate acquires assets of Pharmix – I’ve updated this item and moved it into a standalone post here.

Next-gen sequencer VisiGen promises $1,000 genome by late 2009 – Does anyone else hear a bandwagon banging through town? Just three days after secretive Pacific Biosciences took the wraps off its high-speed sequencing effort, Houston-based VisiGen Biotechnologies laid down a new marker and said it plans to offer $1,000 sequencing of human genomes by the end of 2009 at the rate of roughly one genome a week.

The news, which comes courtesy of GenomeWeb, further turns up the pressure in the bragging-rights race to achieve the artificial “$1,000 genome” benchmark. More than a half-dozen companies have thrown their hats into the ring either explicitly or implicitly, each with its own complex approach to reading every one of the six billion DNA letters, or bases, in a human’s 23 pairs of chromosomes.

VisiGen was founded in 2000, and has received funding from Applied Biosystems and Houston’s SeqWright, as well as grants from the National Institutes of Health.

CalciMedica raises $5.5M for autoimmune drugs – San Diego’s CalciMedica, a biotech developing drugs for immune-related conditions, raised $5.5 million in a second funding round, VentureWire reports. Investors included Sanderling Ventures and SR One. We previously noted the startup’s first funding round here.

The company plans to attack autoimmune diseases such as rheumatoid arthritis and psoriasis by targeting a “calcium channel” — that is, a cellular mechanism that moves calcium in and out of cells — in immune-system components that govern the body’s adaptive immunity. That arm of the immune system sometimes goes haywire, producing autoimmune disease in which the body’s defenses attack normal tissue. CalciMedica acquired technology and drug candidates for targeting that calcium channel from TorreyPines Therapeutics in May.

More than a half-dozen startups and established companies are in hot pursuit of the “$1,000 genome,” a Holy Grail for those who believe fast, cheap genome sequencing will revolutionize medicine. The latest is Pacific Biosciences, a formerly secretive Menlo Park, Calif., company that just spilled its guts to the NYT over the weekend. We take a look at the company, its technology and the competitive landscape in this piece over at VentureBeat Life Sciences.

Competition to analyze human genomes faster and cheaper — a subject I’ve discussed at length here and here — keeps heating up. The latest shot came yesterday, when Menlo Park, Calif.-based Pacific Biosciences granted the NYT an exclusive look at technology it says should eventually make it possible to sequence a genome in just a few minutes for under $1,000.

Although the “$1,000 genome” is a purely arbitrary goal, it’s become a Holy Grail of sorts for the genomics field. (The startup Knome, which we covered here, currently offers full-genome sequencing for $350,000.) Cheap, fast sequencing of all six billion DNA “letters,” or bases, in humans could make it possible, for instance, for doctors to better tailor treatments to a patient’s own genetic quirks or to identify the specific weaknesses of tumor cells. More broadly, it would also vastly increase our understanding of the genome, which has turned out to be a much more mysterious realm than just about anyone expected only a decade ago, and illuminate the ways DNA varies between individuals, groups and even among cells and tissues within a single individual.

PacBio has long been secretive about its work, although it’s been clear that the company has some heavy hitters backing it, including Kleiner Perkins Caufield & Byers, Alloy Ventures and Mohr-Davidow Ventures. (Our earlier coverage of the company’s $50 million financing last year is here.) A research team including scientists from PacBio — then known as NanoFluidics — and Cornell did publish a 2003 paper in Science describing some of the company’s work, but it’s a fairly abstruse piece even by the standards of the scientific literature, unless ploughing through mathematical descriptions of zero-mode waveguides is your idea of fun.

Before getting into the PacBio technology, however, a word of caution. The high-speed sequencing race is pretty crowded, with more than a half-dozen companies pushing forward with new technological approachs and making grand claims for their speed, accuracy and ultimate utility. None of these claims are really possible to evaluate at the moment, and of course the companies involved have every incentive to play up their strengths. PacBio is no different in this respect, and while the NYT story focuses on this particular startup, reporter Andrew Pollack is careful to quote several skeptics who raise perfectly reasonable concerns about the company’s expansive claims.

According to a sidebar to the main NYT story, PacBio’s basic approach involves trapping individual DNA molecules in thousands of tiny holes, or “wells,” fabricated in a thin sheet of metal. These holes are only 70 nanometers wide, or about one-thousandth the width of a human hair — small enough to hold a single stretch of DNA, but large enough for various biochemical reactions to take place inside.

Once inside the wells, the double-helix structure of DNA “unzips” into two single strands, each of which then rebuilds a complementary strand from chemical bases floating in the wells with the help of an enzyme called DNA polymerase. Those bases are tagged with fluorescent molecules that make it possible to identify them under a microscope. PacBio’s system uses digital-camera technology to observe the process in real time, allowing it to analyze and “read” the order in which the bases are strung together.

PacBio claims several advantages over other high-speed sequencing techniques, all of which involve chopping up DNA into short pieces that can be read more easily and then reassembled into a full genome. PacBio says it can read 1,000 bases of DNA in one go — several times greater than other high-speed techniques, which are capable of analyzing stretches of only 30 to 450 bases at once.

By observing the same reaction across thousands of wells, the PacBio sequencing system should read genomes with great speed. The company is currently able to read about 10 bases a second in any given well, so if 1,000 wells all worked at once — itself something of a tall order — the system should run about twice as fast as existing sequencers.

The company certainly doesn’t lack self-confidence. “If we ever make this work, there would be no other technology applicable in the sequencing field,” Hugh Martin, the company’s CEO, told the NYT. Martin went on to discuss the Archon X Prize for Genomics, which offers $10 million to anyone who can sequence 100 genomes in ten days. “When we’re ready,” Martin said, “we’re just going to win the X Prize.” (PacBio hasn’t even officially entered the contest yet.)

PacBio, however, doesn’t plan to release a commercial version of its system until early 2010, and won’t have a model capable of sequencing a full genome until 2013. Some of its competitors could leapfrog it in the meantime — Intelligent BioSystems, for instance, claims it will have a machine that can sequence a full genome in 24 hours for $5,000 by the end of this year. (The NYT says it will cost $10,000, presumably reflecting the difference between the full six billion bases in our 23 pairs of chromosomes and the three billion bases that make up just one set of chromosomes.) Complete Genomics and BioNanomatrix, who haven’t disclosed details of their technological approach except to say they plan to read a stunning 100,000 bases at a time, assert they’ll be able to decode a full genome in eight hours for $100, although it’s not clear by when.

As I noted earlier, however, it’s best to take all such projections with a grain of salt. Hitting goals like these are best-case scenarios that could be tripped up by any number of unexpected wrinkles in the engineering and technology-development process. Still, it’s a heck of a lot of fun to watch.

PacBio has raised a total of $78 million to date, and will probably need another $80 million to bring its systems to market, the company’s CEO told the NYT.

The cost of sequencing human genomes is dropping steadily, from several hundred million dollars a decade ago to $100,000 or so today, thanks to a bevy of entrepreneurial companies that have attacked the problem of making the process faster and cheaper with gusto. We’ve looked at several of the newer upstarts in the field, most recently Complete Genomics and Bionanomatrix, Genome Corp. (seventh item), and Genomic Diagnostics (fourth item).

Now another startup is preparing to establish a new benchmark in the fast, cheap and out-of-control gene-sequencing race. Intelligent Bio-Systems, a Waltham, Mass., sequencer, says that by late next year, its new technology should make it possible to sequence a full genome in 24 hours at a cost of just $5,000, according to this VentureWire story (subscription required). Not only is that a jaw-dropping reduction compared to today’s costs, it potentially brings the Holy Grail of the $1,000 genome far closer than than even many optimistic forecasts.

Of course, talk is cheap. IBS, however, says it’s already placed one of its sequencing systems with an undisclosed institution as part of its beta testing, and plans to distribute three more systems next year, with a full launch by the end of 2008. The company’s CEO, Steven Gordon, says the system should be able to sequence five billion DNA “letters” — technically, DNA base pairs — in a day. A full human genome consisting of 23 pairs of chromosomes — such as Craig Venter’s new high-resolution genome — contains six billion base pairs, although many sequencing efforts to date have settled for only one set of chromosomes, or three billion base pairs.

The details of sequencing technology are generally of interest only to experts, so anyone interested in the guts of the IBS approach is welcome to check out the company’s description here. This GenomeWeb story from late last year offers some additional technical analysis.

Assuming that IBS isn’t being wildly over-optimistic, which wouldn’t exactly come as a stunning surprise in this field, the new technology raises the possibility that a sufficiently motivated group might capture the Archon X Prize for Genomics within the next year or so. The $10 million award, offered by the X Prize Foundation, will go to anyone who can sequence 100 genomes in ten days.

Since that challenge amounts to sequencing 60 billion base pairs in 240 hours, anyone who ponies up for a dozen IBS sequencing systems could just barely knock off the requisite 100 genomes in that time period — assuming nothing goes wrong. In actuality, though, this strategy probably wouldn’t qualify for the prize, since the rules require the use of a single “device” in the challenge.

Still, it’s fun to play with the numbers, since this approach — were it legal — could even be profitable. IBS estimates that each system will cost $250,000 to $275,000, or just $3.4 million for the dozen. It’s a fascinating indication of just how fast the whole genomics revolution is moving.

On the far more mundane business front, VentureWire reports that IBS raised an undisclosed amount of first-round venture funding in June from angels and angel groups. The company will be looking for another $10 million to $20 million for commercial launch unless it finds a distribution partner.

Things are starting to get crowded in the race to sequence entire human genomes quickly and relatively cheaply — usually meaning somewhere in the territory of $1,000 per genome, compared to the $100,000+ it costs with current technology. At least four startups have taken on the $1,000 genome challenge, two of which have already been acquired by larger companies. (See details at the end of the first item here.)

Last week, two relatively new venture-backed startups — Complete Genomics, of Menlo Park, Calif., and Philadelphia’s BioNanomatrix — considerably upped the ante in what I’ve started to think of as the “fast, cheap and out-of-control” genome race when they announced a joint venture that aims to sequence an entire human genome in eight hours for less than $100. (Technically, it appears that this figure applies only to a single set of the 23 paired chromosomes every individual carries, so a spiffy new high-resolution “diploid” genome like Craig Venter’s would presumably take more like 16 hours and cost somewhere around $200. That’s still dirt cheap, of course.)

This is, of course, some mighty big talk from companies that virtually no one had heard of until recently. (See our coverage of Complete Genomics here.) The companies still aren’t saying exactly how they hope to pull off this feat, although they’ve disclosed a bit more detail in their latest announcement. Apparently they plan to adapt a “novel DNA sequencing chemistry” (presumably from Complete Genomics) and combine it with a “linearized nanoscale DNA imaging” scheme (BioNanomatrix’s technology, it appears) in a way that allows them to read up to long DNA stretches of up to 100,000 nucleotide bases — those DNA “letters” we’re always carrying on about — at a time.

What, exactly, that means and whether it’s possible is something the experts will have to hash out. The best I can figure at the moment is that since BioNanomatrix specializes in “nanofluidics” systems — little gizmos that are essentially labs-on-a-chip at near-atomic dimensions — it might somehow be possible to snake long stretches of DNA into a tiny channel on a chip, where having the molecule laid out end-to-end might make it easier to tag and read out the bases in one fell swoop. But that’s just a guess at this point.

Another interesting element here is that these companies bluntly acknowledge the direct threat they pose to today’s genetic-testing industry. Existing genetic tests usually rely on antibodies or other probes that identify a single gene variant; newer varieties examine a handful of single-base variations that have been correlated with something like your risk of heart disease. The ability to read out an individual’s entire genome, however, would effectively demolish the need for such tests, as any the information the tests could turn up would be right there in your genome. (The same issue arises, albeit in somewhat less-dramatic form, with the SNP genome “outlines” that startups like 23andMe and Navigenics would like to provide — our coverage is here, here and here.) This is a potentially huge problem for companies like DNA Direct, one of the first consumer-oriented genetic-testing startups. Expect to see some fireworks on this front before it’s all settled.

The joint venture recently received an $8.8 million grant from the National Institute of Standards and Technology, which for some reason got virtually no attention at the time but for the noble exception of the Philadelphia Business Journal.

Here’s some additional detail from the press release:

“We tried to approach this project from the perspective of the clinician, looking at the requirements and opportunities associated with incorporating genetics into routine clinical diagnostics,” said Dr. Radoje (Rade) Drmanac, chief science officer and co-founder of Complete Genomics. “Accuracy, speed and low cost were paramount considerations. While there are a number of powerful and elegant sequencing strategies available or under development, we determined that we needed a completely novel approach to overcome their inherent limitations and achieve our $100 cost objective. We are optimistic that the combination of our two highly innovative approaches has a good chance of success. ”

The joint venture has proposed adapting a novel DNA sequencing chemistry combined with linearized nanoscale DNA imaging to create a system that can “read” very long DNA sequences of greater than 100,000 bases at high speed and with accuracy exceeding the current industry standard. By condensing a wide range of genetic tests into a single, cost-effective platform, the proposed technology has the potential to enable improvements in the diagnosis and personalized treatment of a wide variety of health conditions, as well as the ability to deliver individually tailored preventive medicine. The $100 genome would also have important applications in medical research and drug development.