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GSK's New Drug Concept, New HIV Protease-like Reyataz
 
 
  GlaxoSmithKline teams up with biotech company
2:00 a.m. June 3, 2009
 
GlaxoSmithKline signed a potential $1 billion deal with U.S. biotech company Concert Pharmaceuticals to develop drugs that use deuterium, a chemical that could improve how some medicines work. The collaboration will beef up GlaxoSmithKline's pipeline of early stage drugs.
 
Glaxo will gain the rights to three research programs by privately held Concert a protease inhibitor for HIV due to start Phase I clinical trials this year, a preclinical drug for chronic kidney disease and a third unspecified product. Deuterium is a safe, non-radioactive relative of hydrogen that can be isolated from sea water and has been used extensively in human metabolic and clinical studies.
 
LONDON (AP) - GlaxoSmithKline PLC signed a potential $1 billion deal with U.S. biotech company Concert Pharmaceuticals on Tuesday to access deuterium-containing medicines, a deal that will beef up its pipeline of early stage drugs.
 
Glaxo will gain the rights to three research programs by privately held Concert - a protease inhibitor for HIV due to start Phase I clinical trials this year, a preclinical drug for chronic kidney disease and a third unspecified product.
 
Deuterium is a safe, non-radioactive relative of hydrogen that can be isolated from sea water and has been used extensively in human metabolic and clinical studies.
 
As deuterium is heavier than hydrogen, it forms a stronger chemical bond to a carbon atom of a molecule, which may substantially improve a drug's metabolic properties, potentially resulting in better efficacy.
 
InVivoblog
 
Privately held Concert will have responsibility for research and development for each of its three drug programs. GSK has the option to license the drug candidates at any time in the process. GSK would then assume responsibility for development and commercialization of those drug targets. Concert will retain full rights to further develop and commercialize its product candidates in any program GSK chooses not to license.
 
GSK paid the biotech $35 million up-front (which includes $16.7 million for equity priced consistent with the price of the shares sold in its $37 million 2008 Series C) in exchange for options on three Concert projects: CTP-518 (a deuterated version of BMS's atazanavir HIV protease inhibitor that is scheduled to enter Phase I this year), a preclinical compound in chronic kidney disease, and a third undetermined compound. Like most of GSK's option-deals, the Big Pharma can choose to opt into a program at clinical proof-of-concept (generally post Phase IIa but in the case of '518 post Phase I).
 
Concert will also create deuterated versions of three additional molecules for GSK, and hand those off after lead optimization. The deal's milestones total more than $1 billion and are heavily weighted to the three option candidates, says Concert's chief business officer Steve Bernitz. What's more the majority of the payments are for clinical and regulatory accomplishment, as opposed to sales-based payments. Concert will get a double digit royalty on compounds from its pipeline and an undisclosed royalty on deuterium-containing molecules from GSK's pipeline.
 
Replacing hydrogen atoms with deuterium atoms (hydrogen atoms saddled with a neutron) essentially creates new NCEs, getting Concert around existing composition-of-matter IP. But "it does not change the physical characteristics of a drug," president and CEO Roger Tung, PhD, told us today. After leaving Vertex where he led that company's drug discovery efforts (and co-invented the successful HIV PIs Lexivaand Agenerase) Tung co-founded Concert with Richard Aldrich and Christoph Westphal in 2006, and has largely kept things under wraps until recently (though we were sufficiently intrigued back then to include them in our inaugural A-List of that year's top Series A financings). "So we're retaining the way a drug interacts with receptors and the pharmacology of a drug, with respect to its positive effects and selectivity profile, is unchanged."
 
But, says Tung, deuterium forms stronger bonds with other atoms in comparison with hydrogen, because of its greater mass. And that increase in bond strength can change the rate of a drug's metabolism and the relative ratio of its metabolites, which in turn can affect the safety and tolerability and even efficacy of certain drugs, he says.
 
All this remains to be seen in the clinic, but if it works out, Concert's deuteration approach (also embraced by biotechs like Auspex and Protia) seems to be the ultimate in life-cycle management. In an interview both Tung and Bernitz kept returning to the low-risk nature of the company's approach. "Generally we've been able to move from concept to the clinic in about two years," says Bernitz. And Concert doesn't take on "the risk of new biology" that many pharmaceutical companies are now embracing. "That lower risk-approach to drug discovery and development is recognized in this deal," given the substantial terms Concert has garnered for its preclinical programs, he says.
 
It seems logical that Concert's window for patenting deuterated versions of existing molecules is finite, perhaps now even closed since industry should be wise to deuterated drugs by now, though Tung doesn't see it that way. "Industry will take this up in the coming years, but we believe we have the poll position now and are the leaders in the use of deuterium."
 
And beyond deuterated versions of marketed drugs there are "tens of thousands" of compounds available that showed promise but for one reason or another did not become marketed therapies, he says. "I think we're going to be very busy for quite some time."
 
And so for now, what about Bristol-Myers? The company's Reyataz(atazanavir) remains on-patent and according to Tung will likely still be on-patent by the time '518 should be hitting the market. Though Tung says Concert talked to BMS prior to the GSK deal it's unclear whether BMS was in the running for the compound. For Concert, finding a partner with strength in HIV was important.
 
A bonus? "The deal validates that [the originator] isn't the only company we can work with" when dealing deuterated compounds, says Bernitz.
 

Concert Pharmceuticals Inks Up To $1B Deal With Glaxo
 
By Jason Douglas
Of DOW JONES NEWSWIRES
 
LONDON (Dow Jones)--Pharmaceutical firm Concert Pharmaceuticals Inc. Tuesday said it inked a research deal potentially worth up to $1 billion with GlaxoSmithKline PLC (GSK.LN) to develop drugs which use deuterium, a chemical that could improve how some medicines work.
 
Lexington, Massachusetts-based Concert said GlaxoSmithKline will make a $16.7 million equity investment as part of a $35 million payment to fund research, which will focus around six experimental drugs in the early stages of development.
 
Including future payments for meeting development milestones and royalties from sales on any drugs that make it to market, the collaboration could be worth as much as $1 billion to Concert, the company said.
 
The deal covers three of Concert's compounds and three GlaxoSmithKline drugs. Roger Tung, Concert Chief Executive, told Dow Jones Newswires Concert's compounds are an experimental treatment for HIV called CTP-518, one for renal disease and a third, which the two companies haven't decided on yet. Concert's pipeline includes treatments for conditions like hypertension, hepatitis and pain, he said.
 
GlaxoSmithKline has asked Concert to modify three undisclosed drugs in its pipeline with deuterium, which Glaxo will develop itself, Concert said. Brentford, England-based GlaxoSmithKline has the option to take a worldwide license for any of the compounds.
 
Concert is focused on using deuterium chemistry to create new drugs. An isotope of hydrogen, deuterium could improve a drug's metabolic properties and enhance its effectiveness.
 
Tung said deuterium is heavier than hydrogen, so it makes stronger bonds with other elements, like carbon. That means drugs incorporating it can take longer to break down in the body.
 
"We can tune the effect of deuterium to favorably change the properties of a drug," said Tung.
 
Company Web site: www.gsk.com; www.concertpharma.com
 
-By Jason Douglas, Dow Jones Newswires; 44-20-7842-9272; jason.douglas@dowjones.com
 

Jun 2 2009, 10:15 am by Derek Lowe theatlantic
 
Heavy Atoms and Hard Times
 
There's a deal that was announced this morning in the pharmaceutical business that shows two (nearly contradictory) things at the same time. Concert Pharmaceuticals, a start-up company in Massachusetts, has partnered with behemoth GlaxoSmithKline to develop a series of compounds which might show improved blood levels and toxicity profiles compared to existing drugs. So far, so good - deals like this happen all the time. But there's an odd feature here.
 
Concert's whole business plan revolves around deuterium, a heavy isotope of hydrogen. Drug molecules, like all compounds in organic chemistry, tend to bristle with hydrogen atoms, and these are often the first things attacked by liver enzymes once a drug is dosed. Metabolism of this type can clear the drug out of the bloodstream more quickly than one would like, produce a new metabolite compound with side effects of its own, or interfere with the usual clearance of other drugs being taken at the same time. It's a big issue in the development of any new compound.
 
But if you substitute a deuterium for one of those hydrogens that gets chewed off, things change. Now that chemical bond to the hydrogen atom is harder to break, because it's attached to something weightier. (Thinking of two weights attached to ends of a spring is, for once, a pretty good model of what's going on). If you pick your D-for-H swaps carefully, you can batten down an existing drug molecule so it lasts longer in the bloodstream, makes fewer side products, and so on. Improved molecule, benefit to patients, new chemical entity, fresh patent rights: you've just absorbed Concert's business plan.
 
This is all fine - in fact, as I point out on my blog this morning, the company and its founders deserve a lot of credit for giving this idea a fair hearing. It may sound like an obvious winner the way I've presented it, but I'm just (ahem) unnaturally convincing. I can tell you that this is the sort of idea that has surely occurred to many other pharma researchers over the years, who've thought about it a bit and said "Nah...someone else must have tried that already".
 
One downside is that it's an idea with an expiration date. If this works (and it's already working to the tune of many tens of millions of dollars, at any rate), you can be sure that every other drug company will batten down its patent filings from here on out to make sure that they own the deuterium versions of their new drug candidates. For now, Concert (and their competitors in the deuteration business) have been filing patents on every existing drug they can think of where the technique might show a benefit. My guess, though, is that everything that's usable has been claimed by now.
 
So that's one side of the story - ingenuity and innovation. But the other side is that, well, this ingenious idea is mostly going to furnish new (and presumably better) versions of things that we already know about. It's no secret that drug discovery has gotten harder and harder over the years (well, it's no secret to those of us who do it, I can tell you!) And as the screws slowly tighten, all kinds of ideas start to sound reasonable. Perhaps this one was just waiting for the times to get tough enough.
 
 
 
 
 
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