VentureBeat

Featured companies: AngioScore, Forsight Labs, Genoptix, Metastatix, Optherion, QLT

UPDATED: See below.

Artery opener AngioScore pulls in $30M — AngioScore, a Fremont, Calif., maker of balloon catheters used to open up clogged arteries, raised $30 million in a fifth funding round. Investors included Telegraph Hill Partners, Psilos Group Management, QuestMark Partners, L.P., UV Partners, California Technology Ventures and Innomed Ventures.

AngioScore’s balloon catheters, which inflate inside blocked blood vessels to restore blood flow, are designed to overcome problems that sometimes occur during traditional angioplasty procedures. Conventional angioplasty can lead to tears and splits in the plaque that lines blocked arteries and can damage arterial walls as well. AngioScore claims its new catheter overcomes this problem by making precise cuts, or “scores,” in the plaque, thereby reducing the chance that it will crack and split unpredictably.

Optherion raises $37M for macular degeneration — New Haven, Conn.-based Optherion, a biotech focused on new treatments for forms of the eye condition macular degeneration, raised $37 million in a first funding round. Investors included Quaker BioVentures, Domain Associates, Johnson & Johnson Development, Purdue Pharmaceutical Products, Pappas Ventures, Biogen Idec New Ventures and GE Healthcare Financial Services.

Optherion is developing drugs that affect the “alternative complement pathway,” an arm of the immune system that may be implicated in two forms of macular degeneration, an eye condition that can lead to partial blindness, and possibly other autoimmune disorders as well. The company was founded in 2005 following discoveries that linked the alternative-complement system to macular degeneration.

Metastatix draws $35M for low-side-effect drugs — Atlanta’s Metastatix, a biotech working on drugs for AIDS, cancer and inflammatory disease, raised $35 million in a second financing round. Investors included Frazier Healthcare, H.I.G. Ventures, the Aurora Funds, CM Capital, SR One, MedImmune Ventures, Georgia Venture Partners, Centrosome Ventures and the State of Georgia.

Metastatix is developing drugs that block a cellular receptor called CXCR4, which is best known as one of the two ways HIV can enter and infect cells. CXCR4 may also be involved in cancer and inflammation. Metastatix says it is particularly focused on drug candidates with the “fewest possible side effects.”

Optical-device incubator Forsight Labs sells unnamed “newco” to QLT for $42M+ — Forsight Labs, an incubator for optical-device companies backed by Morgenthaler Ventures, Split Rock Partners and Versant Ventures, agreed to sell its second, unnamed startup to QLT for $42 million plus milestone payments that could be worth $25 million or more. The startup, known only as ForSight NewCo II, has developed a new type of ocular drug-delivery system that could potentially be used to treat a variety of conditions including glaucoma. The release describing the deal is here.

Diagnostic-services company Genoptix sets IPO terms, aims for $92M — The Carlsbad, Calif., provider of cancer and blood-disease diagnostic services, said it plans to sell up to 5.75 million shares at a price of $14 to $16 apiece, for a maximum possible take of $92 million. The company’s SEC filing is here. We covered the company in some detail at the time of its IPO filing here.

UPDATE: Added items on Metastatix and Optherion.

(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.

Baltimore, Md.-based Profectus BioSciences, a biotech developing new strategies to attack HIV, received a $200,000 small-business innovation grant from the National Institutes of Health to improve the effectiveness of anti-HIV antibodies. Last month, the company received a similar $300,000 grant (PDF link), just a few days after the company raised $3 million in a private placement.

Profectus, which was spun out of the Institute for Human Virology in 2005, has so far rased a total of at least $6.5 million.

(UPDATED: See below.)

Seattle’s Koronis Pharmaceuticals, a biotech focused on antiviral drugs that cleverly attempt to to drive viruses into extinction, got some serious validation yesterday when it raised $20 million to fund a mid-stage “proof of principle” trial for its leading AIDS drug.

Koronis, which was founded in 1998 to commercialize the pioneering viral research of Larry Loeb, Jim Mullins and John Essigmann, is pursuing a novel and unusual path to defeating viral disease. Most antiviral drugs are designed to prevent viruses like HIV from reproducing themselves, often by gumming up enzymes or proteins that are key to viral replication. HIV protease inhibitors, for instance, are molecules that stick in the craw of a scissors-shaped molecule called HIV protease, which clips certain HIV proteins to an appropriate length. Other AIDS drugs muck up HIV by inhibiting the action of an another viral-replication enzyme called reverse transcriptase. The Achilles heel of all these antiviral strategies, however, is that many viruses reproduce and mutate so quickly that they can quickly grow resistant to any particular drug. That’s why AIDS treatment is typically delivered in a three-drug “cocktail,” because to survive, HIV has to become resistant to all three drugs at the same time — a generally unlikely event.

Koronis, by contrast, has designed drugs that don’t attack HIV directly — in fact, they aim to ensure that the virus will reproduce. The trick here is that the drugs actually amplify HIV’s natural mutation rate to an untenable level. If the drugs work as planned, HIV will mutate so quickly — in other words, producing an enormous number of errors in its genome each time it replicates — that succeeding generations of the virus will eventually be rendered inert. In other words, HIV’s mutations will eventually drive the virus into extinction. Koronis calls this process “viral decay acceleration,” and it’s unquestionably a very cool idea.

For the science-minded among you out there, here’s a base-pairing diagram that illustrates how a Koronis drug called KP-1212 encourages mutations:

The company’s description of the technology is here (warning: it’s pretty dense). The short explanation goes something like this. KP-1212 is structurally similar to a “nucleoside,” which is essentially one of the five DNA/RNA bases (adenine, guanine, cytosine, thymine and uracil) bound to a sugar. In this case, KP-1212 is a nucleoside analogue of cytidine and thymidine.

In ordinary circumstances, HIV — a retrovirus whose genome is encoded in RNA — hijacks cellular machinery to create new RNA versions of itself. When KP-1212 is present, however, it infiltrates HIV’s RNA genome by taking the place of cytidine and thymidine nucleosides. The next time the virus replicates, however, each molecule of KP-1212 will randomly pair with either guanosine, the complement of cytidine, or adenosine, the complement of thymidine.

In other words, each molecule of KP-1212 in HIV genome template has a 50 percent chance of introducing a genetic error into the replicated virus — and this will happen again and again, each time the virus replicates. When enough errors accumulate, the virus should essentially drop dead, an effect that should be mirrored throughout the entire HIV population in the body of an individual taking the drug.

Existing nucleoside-analogue drugs essentially aim to disable reverse transcriptase, although they do so in a way that the virus can eventually mutate to counter. By contrast, HIV should have much more difficulty resisting the viral-decay acceleration strategy, since it affects the virus randomly and continues mutating it as long as the drug is present.

So, the science is nifty, no question. Do the drugs work? That’s much harder to say. Preclinical studies have apparently shown that KP-1461, a cousin of sorts to KP-1212, can “extinguish” HIV — this according to Robert “Chip” Schooley, an eminent AIDS expert at UCSD. I haven’t yet figured out whether that refers to “in vitro” experiments — that is, work in cell cultures — or “in vivo” tests in laboratory animals; the latter would obviously be far more convincing. Koronis hasn’t said much more about its early-stage human trials except that KP-1461 appears to be safe and “well tolerated.”

So stay tuned — I’ll update if I learn more. (If you happen to know more, please let us know in comments.) The drug is now headed into mid-stage trials.

The financing round, Koronis’ fourth, was led by Pacific Horizon Ventures, joined by Asset Management Company.

UPDATE: I’ve rewritten the scientific explanation to make it a little clearer, although it’s still on the dense side if you’re not up on the mechanics of nucleic-acid replication. I also fixed a broken link to the company’s technology description.

Profectus BioSciences, a Baltimore, Md., developer of antiviral drugs and vaccines targeting HIV, raised $3 million in a private placement. Private investors, including Cross Atlantic Capital Partners and board member Stewart Greenebaum, contributed.

Profectus is developing ways to combine AIDS drugs with “immune modulators” that would render HIV more vulnerable to antiviral attack, and is also at work on an AIDS vaccine. The company was founded in 2003 by three eminent virologists who also co-founded the Institute for Human Virology in Baltimore: Robert Gallo, William Blattner and Robert Redfield.

I’m at work on a longer post that hasn’t yet come together, so I thought I’d pull an old dodge favored by daily newspaper columnists and respond to some reader comments instead. Fortunately for me, both comments left here in the past day or so have been thought-provoking — maybe there’s hope for the Internet after all.

With respect to the tussle over patents and drug pricing in Thailand, Gal Josefsberg wrote:

I’m not sure how they expect to get cheap HIV drugs if the destroy the company’s profits. I know we all think these sort of drugs should be cheap, but there’s an enormous cost to developing and testing them. Without some kind of profit motive, the R&D spent on these treatments will go down. I’m not saying the pharma companies should gouge HIV patients, but just saying “thanks for developing this drug, we’ll take it from here” is not the right answer.

Where AIDS drugs in the developing world are concerned, the arguments tend to be a little more complicated than I may have suggested. Some pharma and biotech companies — I’m most familiar with Gilead Sciences, although I believe others do this as well — explicitly acknowledge that it’s wrong to profit from the world’s poorest nations and set what they call “no-profit” prices for HIV drugs in almost 100 countries. Of course, they still plan to make out handsomely in the U.S., Europe and other industrialized parts of the world.

Things, however, get quite a bit murkier in “middle income” nations like Thailand, where the population as a whole is unquestionably getting richer, but where many of the people who need the drugs most are also still quite poor. Critics argue that it’s the responsibility of the Thai government to help its citizens afford drugs, and while they have a point, I’m not convinced the drug companies are wholly blameless. Many of them have only grudgingly begun efforts to cut poorer nations some slack on the price of life-saving drugs, following years of protest by AIDS activists and international organizations. Given that many activists still think companies like Abbott are trying to profiteer in developing-but-not-exactly-wealthy nations like Thailand, it’s no wonder that distrust of the pharmas still runs high in many quarters.

By the way, Brazil has apparently issued a similar threat to Merck over its HIV drug efavirenz (via Pharmalot).

In response to an item on the tactics drug reps use to push their product on doctors, RJ notes:

the first paper seems to be describing a phenomenon known as “sales”– truly a beauty to behold when it’s done well. No matter whether you’re selling drugs or enterprise software. That’s why the great sales people are paid so much. They’re artists.

That paper was written so vividly that I couldn’t help but wonder if Ahari, the former Lilly rep, doesn’t kind of miss his old job for exactly those reasons. There’s definitely something awe-inspiring about watching a professional salesperson at work, although I’d feel better about admiring it here if the sales job wasn’t specifically designed to override a physician’s best medical judgment — which is, after all, what the patient needs most and what insurers are supposed to be paying for.