VentureBeat

TODAY’S HEADLINES:

• Surgical-device maker Aragon Surgical receives $25M (release)
• Tacere Therapeutics strikes RNAi deal with Pfizer for up to $145M (release)
• Benvenue Medical raises $15M for spine-repair devices (release)
• Genome-association co. Genizon BioSciences draws C$31M (release)
• Contract research organization Inclinix pulls in $10M (release)
• EPocrates, healthcare IT developer, gets strategic investment from Goldman Sachs (release)
• ZyGem closes first funding round (release)
• Onset Ventures names John Ryan partner (release)
• Retired Scripps immunologist Richard Ulevitch joins 5AM Ventures (release)
• SV Life Sciences promotes Darren Black to partner (release)
• Medical-software maker SafeMed appoints Richard Noffsinger CEO (release)
• Artromick, healthcare IT developer, names Williams Shields CEO (release)
• Stem-cell biotech BioE seeks $3.5M (VentureWire, sub req’d)
• Inovise raises $3.4M for heart diagnostics (VW)
• Fairway Medical pockets $1M for medical devices, aims for $10M (VW)
• Cancer-drug biotech Genspera pulls in $650K, looks for $5M more (VW)
• E-trolZ looks for $400K for electrophysiology devices (VW)

Tacere Therapeutics strikes RNAi deal with Pfizer for up to $145M — San Jose, Calif.-based Tacere Pharmaceuticals, a biotech developing new drugs based on the gene-silencing technique known as RNA interference, struck a partnership deal with Pfizer that could be worth up to $145 million. The company’s release is here.

The deal involves Tacere’s leading drug candidate for hepatitis C. Known as TT-033, the drug consists of short stretches of RNA designed to trigger cellular mechanisms that shut down the activity of specific genes — an exciting but so far still unproven approach. In this case, TT-033 aims to shut down three separate parts of the hepatitis C genome, theoretically not only inactivating the virus, but also preventing the development of resistant viral strains.

Tacere is already co-developing TT-033 with Oncolys BioPharma of Japan, and in fact has deep Japanese roots, as the company also received its founding capital from Hokkaido Venture Capital of Sapporo, Japan. (Our coverage of the Oncolys deal is here.) The Pfizer deal appears to be complementary to Tacere’s previous agreement, as the Big Pharma will receive worldwide rights to TT-033 excluding Asian nations. Pfizer will fund all future development of the drug, and will make milestone payments to Tacere as development proceeds. TT-033 has not yet entered human testing.

Surgical-device maker Aragon Surgical receives $25M — Aragon Surgical, a Palo Alto, Calif., developer of surgical instruments, raised $25 million in a second funding round. Investors included Bay City Capital, Integral Capital Partners, Delphi Ventures and Onset Ventures.

Founded in 2005, Aragon develops tools and instruments intended to speed surgical procedures and to improve their safety. The company is working on two major classes of devices — “electrosurgical” instruments, which use electric current to stop bleeding, remove growths and cut tissue, and tools that improve the speed and safety of minimally invasive surgeries known as laparoscopies. Last September, Aragon launched its first product, the LapCap, which guides a needle used to inflate a patient’s abdomen with gas in order to reduce the risk of inaccurate placement and injury.

Benvenue Medical raises $15M for spine-repair devices — Mountain View, Calif.-based Benvenue Medical, a developer of minimally invasive devices for spine surgery, raised $15 million in a second funding round. Investors included Three Arch Partners, Versant Ventures and De Novo Ventures.

Benvenue is developing spinal implants designed for the treatment of spinal compression fractures and degenerative disk disease via spinal fusion. The company’s Web site is a stub, and it doesn’t seem to have described its technology in much detail yet.

Stem-cell biotech BioE seeks $3.5M — St. Paul, Minn.-based BioE, a provider of stem-cell products for the drug and biotech industries, hopes to raise $3.5 million in a first funding round, VentureWire reports (subscription required). The company has so far raised $30 million from angel investors, and disclosed its plans in a regulatory filing. The funds will allow the company to commercialize lines of “multi-lineage” progenitor stem cells and a system for processing and freezing of umbilical-cord blood stem cells.

Inovise raises $3.4M for heart diagnostics — Inovise Medical, a Portland, Ore., developer of cardiac diagnostics, raised $3.4 million in convertible notes, VentureWire reports, citing a regulatory filing. The company is in the midst of fundraising for a sixth financing round. Inovise makes a non-invasive cardiac monitoring system called Audicor that records and analyzes sounds emitted by a beating heart.

Fairway Medical pockets $1M for medical devices, aims for $10M — Fairway Medical Technologies, a Houston incubator that develops a variety of medical devices, raised $1 million from angel investors and is looking to draw another $5 million to $10 million in a first institutional round later this year, VentureWire reports. Founded in 1992, Fairway Medical in-licenses medical devices and ushers them through the development process.

Cancer-drug biotech Genspera pulls in $650K, looks for $5M more — Santa Monica, Calif.-based Genspera, a biotech focused on cancer drugs, raised $650,000 in a seed round and aims to close another $5 million in funding later this quarter, VentureWire reports. The company plans to list its shares on the Nasdaq over-the-counter bulletin board following the financing. Genspera is working on cancer drugs using technology licensed from Johns Hopkins University.

E-trolZ looks for $400K for electrophysiology devices — North Andover, Mass.-based E-trolZ, a developer of electrophysiology measurement devices, raised $400,000 in a follow-on to its first $1.2 million funding round, VentureWire reports. The company is developing components that measure various physiological signals and which can be integrated into other medical devices.

(UPDATED: See below.)

For at least a decade, biotech futurists have been predicting that the genomics revolution will lead to medical treatments tailored to the genetic quirks of individuals. And for at least as long, we’ve all been waiting for evidence that this “personalized medicine” revolution is coming to pass.

On Monday, the field took a baby step forward when the FDA approved Selzentry, a new AIDS drug from Pfizer. Selzentry is unique in a number of ways — for instance, it’s the first drug that tries to “lock down” T-cells to prevent HIV (that’s the culprit, above and to the left) from entering and infecting them. Fuzeon, a less-than-successful drug from Roche and Trimeris, does something similar, although it works to gum up HIV’s “landing gear,” not the T-cell’s docking port.

But the particularly interesting thing about Selzentry is that it only works against a particular sub-strain of HIV — those that dock to a T-cell surface protein called CCR5 in order to invade. (Most HIV strains use another protein called CXCR4 or a combination of the two.) That means would-be Selzentry users first have to be tested to ensure that their HIV strain will respond to the drug. And that, in turn, makes Selzentry one of the first drugs to be paired with a diagnostic test that limits the number of people who can try it, but which also greatly enhances the odds that it will work in those who do.

That test, offered by Monogram Biosciences, requires “amplifying” the HIV genome in the lab, producing scads of genetically identical viruses that are used to infect cultures of T-cells that lack either CCR5 or CXCR4. When infection occurs, a transplanted gene in the cell cultures begins to produce fluorescent proteins, making it easy to tell whether the viral strain is CCR5-specific. (There’s more info in this Monogram press release.)

Of course, Selzentry — generically known as maraviroc — most likely wouldn’t appear to work at all if tested in a general population, which helps explain why Pfizer was willing to pair it with a diagnostic. Genentech’s breast-cancer drug Herceptin — long the sole poster-child for the nascent field of personalized medicine — likely would have gone the same way had researchers not realized that it appeared to work particularly well in an identifiable subset of tumors.

So far, however, there aren’t too many other similar personalized treatments out there, or even in development. One exception is the beta blocker bucindolol being developed by Arca Discovery, which aims to test the drug in patients who have specific genetic variants; I wrote about them here.

Why aren’t there more? The simplest explanation is that most drug developers, whether pharma companies or biotechs, don’t want to risk circumscribing their patient population unless they have to, since doing so by definition limits the potential sales of a new drug. Up to now, drug makers haven’t really faced much economic pressure to embrace personalized medicine, or “pharmacogenomics,” as it’s technically known. With pipelines drying up and the patent environment getting a lot harsher for the me-too drugs drug giants have long relied on, however, they may soon have little choice.

(Brief aside: Pharmacogenomics, of course, is also the answer to the oft-touted assertion that me-too drugs — meaning a variety of drugs that all target the same biological mechanism, such as the half-dozen statins approved to lower cholesterol — aren’t the waste that drug-industry critics often assert. This argument holds that patients who, for instance, don’t respond to one statin might actually benefit from a different one. The short and simple response is, Where’s the proof? If the makers of statins, or of the depressants known as SSRIs, really want to know which patients their drugs work best in, it’s certainly within their ability to find out. The fact that no one is conducting such tests tells you quite a bit of what you need to know about decision-making in the drug industry.)

UPDATE: Apropos of nothing, I just stumbled across this Reuters story describing a Royal Society report on personalized medicine. The bottom line:

“Personalized medicines show promise but they have undoubtedly been over-hyped,” said David Weatherall, who chairs the working group that produced the report.

UPDATE REDUX: For more on the FDA’s big push behind personalized medicine, see this more recent post.

Conatus Pharmaceuticals, a San Diego developer of drugs for inflammation and liver disease, closed a $22 million private placement that brings its first round of funding to $27.5 million. Investors included Aberdare Ventures, Advent Venture Partners, Bay City Capital, and Gilde Healthcare Partners.

Conatus was founded by former executives of Idun Pharmaceuticals in mid-2005 after Pfizer acquired their company. The funding will support mid-stage clinical trials of its lead compound, CTS-1027, for liver disease. The first trial, in hepatitis C patients, is expected to begin by the end of this year. Conatus licensed CTS-1027 from Roche last November.

Two fascinating papers in the open-access journal PLoS Medicine turn a spotlight on the practice of “detailing” — the office visits that drug-industry salespeople use to flatter and manipulate their way into the good graces of the doctors they want to influence.

The first and most eye-opening paper is co-authored by Shahram Ahari, a former Eli Lilly sales rep, and Adriane Fugh-Berman, a Georgetown University professor who researches drug marketing. Together, the two outline a variety of tactics that sales reps use on detail visits to disarm doctors and to indirectly — sometimes all but imperceptibly — nudge them into prescribing their company’s drugs more freely. This is one of those papers that best speaks for itself, so I’ve excerpted some key passages below. For the full effect, though, read the whole paper; Table 1 alone is worth the price of admission.

Good details are dynamic; the best reps tailor their messages constantly according to their client’s reaction. A friendly physician makes the rep’s job easy, because the rep can use the “friendship” to request favors, in the form of prescriptions. Physicians who view the relationship as a straightforward goods-for-prescriptions exchange are dealt with in a businesslike manner. Skeptical doctors who favor evidence over charm are approached respectfully, supplied with reprints from the medical literature, and wooed as teachers. Physicians who refuse to see reps are detailed by proxy; their staff is dined and flattered in hopes that they will act as emissaries for a rep’s messages. (See Table 1 for specific tactics used to manipulate physicians.) [...]

The purpose of supplying drug samples is to gain entry into doctors’ offices, and to habituate physicians to prescribing targeted drugs. Physicians appreciate samples, which can be used to start therapy immediately, test tolerance to a new drug, or reduce the total cost of a prescription. Even physicians who refuse to see drug reps usually want samples (these docs are denigrated as “samplegrabbers”). Patients like samples too; it’s nice to get a little present from the doctor. Samples also double as unacknowledged gifts to physicians and their staff. The convenience of an in-house pharmacy increases loyalty to both the reps and the drugs they represent….

Pharmaceutical companies spend billions of dollars annually to ensure that physicians most susceptible to marketing prescribe the most expensive, most promoted drugs to the most people possible. The foundation of this influence is a sales force of 100,000 drug reps that
provides rationed doses of samples, gifts, services, and flattery to a subset of physicians. If detailing were an educational service, it would be provided to all physicians, not just those who affect market share…. Physicians are susceptible to corporate influence because they are overworked, overwhelmed with information and paperwork, and feel underappreciated. Cheerful and charming, bearing food and gifts, drug reps provide respite and sympathy; they appreciate how hard doctor’s lives are, and seem only to want to ease their burdens.

The second paper isn’t anywhere near so colorful, but compensates with depth of analysis. A research team at the University of California, San Francisco, studied market-research forms for the anti-seizure drug Neurontin (generically known as gabapentin), which became public as the result of a whistleblower lawsuit against Neurontin’s maker, Pfizer. That lawsuit contended that the former Parke-Davis — later acquired by Pfizer — had violated federal rules by promoting Neurontin outside its FDA-approved uses, and concluded with a $430 million out-of-court settlement.

By studying 116 of the market-research forms filled out by selected doctors following a sales rep visit — here’s an example:

– the researchers built a detailed picture of the way Neurontin detailing worked. In 44 percent of the visits, physicians reported at least one “off-label” message related to Neurontin use in an unapproved fashion — exactly the sort of thing sales reps are forbidden to introduce in such conversations. Almost a full quarter of the visits involved only discussion of unapproved uses of the drug. (The researchers acknowledge that they have no way to know if the sales reps initiated such conversations.) Ultimately, almost half of the doctors involved said they planned to increase their prescription of the drug following the visits, while none reported plans to decrease Neurontin use.

Interestingly enough, former Pfizer exec Peter Rost is now closely tracking what may be a similar scandal related to AstraZeneca’s promotion of its chemotherapy drug Arimidex. The story, which began with the firing of an AstraZeneca regional sales manager who compared doctors’ offices to “a big bucket of money” in an internal newsletter, then mushoomed to include a cabal of alleged whisteblowers and leaked audio recordings — supposedly of AstraZeneca sales-rep training sessions — is detailed at his sometimes quirky blog Question Authority. If you don’t mind working backward, start here and keep scrolling down. Way, way down if you want to get all the way to the beginning — Rost is nothing if not prolific.