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ZymoGenetics’ moves recall young Genentech
Jim Kling, Bellingham, Washington
NATURE BIOTECHNOLOGY VOLUME 25 NUMBER 9 SEPTEMBER 2007
In a move reminiscent of Genentech’s early days, Seattle-based ZymoGenetics signed an agreement with Leverkusen, Germany–based Bayer Healthcare in June to share marketing rights to Zymo’s
recombinant thrombin, a coagulation protein that potentially has wide application in controlling bleeding during surgical procedures. The deal calls for Bayer Healthcare to coordinate with ZymoGenetics to market recombinant thrombin in the US for three years after its expected approval in January. ZymoGenetics will pay a commission to Bayer for its commercialization
efforts, whereas Bayer will make milestone payments and pay
tiered royalties to ZymoGenetics. (Bayer will develop and commercialize the product outside the US.) ZymoGenetics received
$30 million up front and will receive an additional $40 million upon FDA approval. The current thrombin market is dominated
by bovine thrombin, sold by Bristol, Tennessee–based King Pharmaceuticals, with sales of $246 million in 2006. That market
is ripe for penetration, however, because bovine thrombin is associated with development of antibodies that may cross-react with human blood antibodies—a phenomenon that has been linked to serious bleeding complications. ZymoGenetics is betting that its deal with Bayer will take over that market and propel it
forward on the path to becoming a fully integrated
biotech company. Its stock has subsequently underperformed, partly because expectations are too high for recombinant
thrombin, notes analyst Kevin DeGeeter at New York–based Oppenheimer & Co. Investors will come around eventually, he believes, but it may take time because recombinant thrombin
is no more effective than bovine thrombin—and although it has a better safety profile, it isn’t clear what clinical significance that better profile will have. Another issue is competition
from Tel Aviv, Israel–based Omrix Biopharmaceuticals, which has a deal with New Brunswick, New Jersey–based Johnson & Johnson to commercialize a thrombin product derived from human plasma. “There’s a place in the market for both types of products,” says
DeGeeter. ZymoGenetics president and CEO Bruce Carter points out that no recombinant replacement proteins have failed in the clinic—nor have they failed in the market. “That’s the basic
model for ZymoGenetics,” adds DeGeeter. With something like thrombin, which isn’t extraordinary, you can get cash that can be
invested in mid-stage programs that are really pretty ntriguing.” He points to Atacicept, a soluble fusion protein that links part of the cytokine receptor TACI to the Fc portion of immunoglobulin, which ZymoGenetics is developing for rheumatoid arthritis and lupus, among other indications. In that sense, ZymoGenetics’ deal with Bayer evokes S. San Francisco–based Genentech’s development of human growth hormone, which it used to fund its earlier pipeline candidates that had greater economical potential but higher development risk. Recombinant thrombin is a safe bet that could pave the way for ZymoGenetics’ riskier pipeline products, which are being developed for indications
including autoimmune diseases, cancer and hepatitis C. And ZymoGenetics and Genentech have more in common than a portfolio management strategy, as both are affiliated with large
pharmaceutical companies that hold significant equity stakes, giving them some shelter from the vagaries of stock movements.
Basel-based Roche acquired a majority interest in Genentech in 1990, then exercised an option in 1999 to acquire the rest of the
shares it didn’t already own. But the pharma company sold 42% of Genentech’s common stock in three offerings on the open market,
keeping a controlling interest and pledging to allow Genentech to operate as an independent company. So far, Roche has kept its promise and Genentech has grown into a preeminent,
research-driven biotech. Genentech’s 1999 deal gave Roche an option to license non-US rights to products, eliminating Genentech’s sales and marketing forces outside the US and
allowing the company to focus more of its resources on R&D.
ZymoGenetics’ partner is Bagsværd, Denmark–based Novo Nordisk,
which bought ZymoGenetics in 1988. ZymoGenetics remained a subsidiary of Novo Nordisk before being spun out in 2000. Since then, the companies have maintained a close partnership, and
Novo owns about 31% of the company. Novo Nordisk also possesses a licensing arrangement with ZymoGenetics similar to Roche’s with Genentech. Until November 2006, for example, Novo maintained rights outside North America to a number of proteins in
ZymoGenetics’ pipeline, and it continues to collaborate on development of certain others, including Factor XIII, IL-20
and IL-21. In September, 2004, ZymoGenetics made another arrangement with Geneva-based Merck Serono (formerly Serono Labs), in which Serono gained access to a large portfolio
of ZymoGenetics’ genes and proteins for in-house evaluation. The deal also gave Serono the option to license up to 12 products from ZymoGenetics’ pipeline over the next five years. In an unusual twist, Serono’s rights to license proteins outside the US were subordinate to certain options maintained by Novo,
until its claim expired in November 2006. “I would say that ZymoGenetics has served as the protein discovery engine now for two companies,”says Edward Tenthoff, a senior research analyst at Minneapolis-based Piper Jaffray. Nevertheless, the shape of ZymoGenetics’ future may depend on recombinant thrombin’s
performance. If the launch is as successful as Zymo’s management
believes it will be, “the stock price should react accordingly,” says DeGeeter. If not, Novo Nordisk could swoop in and acquire
the firm. DeGeeter points out that it has an option coming in autumn to increase its equity stake in the firm. “Their first window to make a bid opens up this fall. On the one hand, it
may make sense—the stock is cheap and the pipeline has matured a bit. On the other hand, if you have to pay one-and-a-half billion for a company, you want to have an idea of what product you’re betting on. It will be much more clear 12 to 18 months from now where the rheumatoid arthritis program [atacicept] is. It’s tough for me to see anyone coming in and making a serious bid until we have a sense for what that data looks like.” Jim Kling, Bellingham, Washington
I was blind but now I an see :)
Enantiomer?
That's the spirit :)
But I had a long day and early Tai-Chi practice tomorrow, so you'll have to wait for the next lesson.
Sweet dreams Dubi.
Right, we're back to square one,
wanna learn?
Apology accepted.
Sorry Roy, I don't have a clue.
Better post the quiz in your board where the hot shots will solve it :)
Why don't you check it now
Better Dubi?
Boy, you're a hard man to please...
Dubi this is not an attempt to drag you but to teach you how to upload a pic from a file (not from a link, you know this already)
Wanna learn?
[A bit OT but this post-KSR ruling in favor of the generic (Lupin) might be of importance for future cases and generics.]
Aventis' Altace Patent Invalidated by Circuit Court
By Aaron F. Barkoff September 12, 2007
On Tuesday, the Court of Appeals for the Federal Circuit reversed (pdf) a district court trial verdict that held the asserted claims of Aventis's (SNY) patent on Altace not invalid, finding instead that the claimed invention would have been obvious. The patent in suit was U.S. Patent No. 5,061,722, which covers ramipril, the active ingredient in Altace. Aventis owns the '722 patent and King Pharmaceuticals (KG) markets Altace under an exclusive license.
Ramipril is a stereoisomer belonging to a family of compounds that includes 25 stereoisomers. Additionally, ramipril is one of a family of drugs known as Angiotensin-Converting Enzyme inhibitors, or "ACE inhibitors," which are useful for treating high blood pressure. The prior art asserted by Lupin included structurally similar ACE inhibitors, including enalapril, as well as publications describing how to separate stereoisomers from each other.
The Supreme Court's recent decision in KSR v. Teleflex appears to have been a key to the Federal Circuit's decision on Tuesday:
The district court held that Lupin failed to meet its burden of proof by clear and convincing evidence that a person of ordinary skill in the art would have been motivated to purify 5(S) ramipril into a composition substantially free of other isomers. The district court saw this as a close case based principally on the absence of a clear and convincing showing of motivation. Since the date of that decision, however, the Supreme Court decided KSR Int'l Co. v. Teleflex Inc. . . . . Requiring an explicit teaching to purify the 5(S) stereoisomer from a mixture in which it is the active ingredient is precisely the sort of rigid application of the TSM test that was criticized in KSR.
Another interesting aspect of Tuesday's decision is that just six days ago, in Forest Labs v. Ivax Pharms., the Federal Circuit upheld the validity of another patent on a stereoisomer pharmaceutical compound: Lexapro (escitalopram). On Tuesday, the Federal Circuit held that ramipril is prima facie obvious (based, in part, on its structural similarity to prior art compounds), and that Aventis and King "failed to show unexpected results that would tend to rebut a prima facie case of obviousness." In contrast, according to Tuesday's opinion, in the Lexapro case "prima facie obviousness of a claim to a particular stereoisomer over a racemic mixture was rebutted where the particular stereoisomer showed unexpected benefits, and evidence indicated that the isomers would have been difficult for a person of ordinary skill in the art to separate."
Given the amount of revenue at stake (about $700 million in annual U.S. sales), I would expect Aventis and King to file a petition for rehearing or rehearing en banc with the Federal Circuit.
http://soundmoneytips.com/article/47049-aventis-altace-patent-invalidated-by-circuit-court
I was just trying to drag you out to play,
didn't realise you had this kind of problem:
As for your second concern, remember what Oscar said:
"To lose one parent, may be regarded as a misfortune; to lose both looks like carelessness."
One can not be too careful about this.
One more reason to avoid public jacuzzi- you can never tell what is really going on under all those baubles. What are those baubles anyway? I always had the suspicious they are the result of too much Tshulnt eaten by the people inside.
The smelly elements are all natural but like the salt and other minerals, in the water and mud there, they are found in high concentrations considered healthy for skin and rheumatic pain.
I would be more concerned about fungi in the jacuzzi (hehe) than from contagious disease in the dead sea.
I do give my parents a full physical examination before and after and so far, they have passed them all cum laude!
My folks like the place because it nice to lie in the black mud, have a foot massage and relax. The smell of sulphur and bromine never bothered them, after all it's healthy.
You don't feel the low pressure but the very salty water of the dead sea will be a real torture if you have an open wound or even a scratch.
There are great hiking tracks nearby, these are more my cup of tea.
>Is it worth a visit?<
Sure thing, It will give you a great reply when asked:
How low can you get?
Don't know about noone (hehe), I've been there several times, it is a great place if you have psoriasis...
Seriously, my folks like to go there at winter, I personally don't like the smell.
Are you considering a visit or what?
Avastin for metastatic breast cancer-
I think the panel will first have to determine whether PFS is an appropriate endpoint for approval.
I believe they will approve.
Who did you say the black-foot, floating, stunner in the photo is?
"Was it ever a live lake?"
Lake Lisan, the Pleistocene precursor of the Dead Sea probably was, but that was a little while before Dubi.
"Have you or anyone else been to The Dead Sea?"
It was already dead when I got there.
Do you think Dubi had anything to do with its death?
I know, but it was fun taking the balls away ;)
If we take testosterone out from the game, castrated men don't grow boobs but they do become fat.
>There’s no good reason to expect testosterone to increase the risk of breast cancer>
I did not expect a link to breast cancer risk either, but found a bunch of papers from recent years regarding potential adverse effects of testosterone therapy in women: including hirsutism, acne and deepening of the voice along with changes in lipid profiles. While less well understood, concern after increased risks for breast cancer and cardiovascular events has been raised about this therapy. Testosterone might promote breast cancer indirectly via its conversion to oestrogen or directly via androgen receptors.
BPA- > What might concern me if I were long BPA is that the incidence of breast cancer will be monitored in this study.<
Was the breast cancer risk not mentioned back in Procter Gamble's Intrinsa study?
"Why is BPA presenting this as new news if it was already disclosed?"
Maybe they thought no one was listening to the ARCH Small Cap Investment Conference on September 6, 2007 :)
A more serious explanation could be that they did not give the hole story (big safety study - cardiovascular events driven study of between 2,400 and 3,100 women exposed to LibiGel or placebo for 12 months and 4 years follow up) at the ARCH Conference (I didn't listen to the conf, just got the update by email).
Biocell (which is by far my largest holding) announced yesterday at TASE, that it will sell 10% of its PLX holding (They own 22% of PLX's shares so they will sell 2.2% of the total offering).
Marathon (holds 10% of PLX) will also try to sell what they are allowed to.
It’s been rumored that PLX will do the offering with value of about $1B.
They did talk about it already (and about the rest of their pipeline) at the ARCH Small Cap Investment Conference on September 6, 2007
http://origin.vcall.com/CustomEvent/conferences/arch_investment/090607/webcast.htm
Regarding LibiGel, they said that have understanding with the FDA
about the requirements:
A 12 months safety trial and one more 6 months efficacy trial. They intend starting those trials by late 2007 or begging of 2008.
I have read the Nature Medicine publication and some points bugs me:
Drop out rates were: placebo (58.7%), LY2140023 (33.7%) and olanzapine (20.6%). The placebo group was significantly worse. However, if the adverse events with the new drug were better than why the higher drop out rate? Moreover, the paper does not specify the reason for discontinuation in the LY2140023 group.
Also noted a significant increase in emotional lability in the LY2140023 group, Not a desired outcome in psychotic patients.
Last note is the trial was only 4 weeks long, makes me wonder if Lilly knew that a 6 weeks trial will show significant drop out rates for their compound.
Maybe I'm more suspicious with Lilly after the Zyprexa case but those points are disturbing.
P.S If anyone wants the full article, I still have it.
Not really a biggie but a very quick one (NVS's lawyers must be from a very fast model):
NVS got a court order that temporarily blocks Teva's sales of generic Famvir. TEVA probably have marketed as much as they could before this court order like they did with Loteral. To be continued on Tuesday.
http://www.marketwatch.com/news/story/court-temporarily-blocks-tevas-sales/story.aspx?guid=%7b6938F7...
That's fine but breakfast comes first and if you'll survive the day, you'll get dinner too.
Good night Dubi and have a nice weekend.
I thought that your breakfast is coffee...
CIBC raised PT to $54 from $44.
I'll take you to dinner sometime.
Thanks Dubi, you are a real pal but then I won't be able to say - I did it my way.
TEVA is in a good position to make a deal with Wyeth IMO.
But don't think that I have wasted the precious happy hour dancing with some prince. I've been searching Roy's board instead...
I hate it when the pumpkin stains my dress.