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>The lack of buying interest or support from both insiders <
I don't think they can safely buy before the deal closes.
Additional terms await disclosure, and until closing the terms
are at least theoretically labile.
In other words, the cat's head may be out of the bag but
the tail is not.
>The chances are good that some of the shares you sold today were bought by me.
And sold by me (@ 1.25)!
Actually my premise is much more likely than yours, as the
deal went down in the after-session which encompassed about
one-tenth of today's volume so far.
Badminton can be just as much fun as backgammon!
>not unusual for a board to honor requests of such an indiviual<
True of small potatoes but the decision to rec an offer at
a dollar or below is of sufficient import that I would expect
the management seats to hold no more sway than their votes
afford.
Not sure where you are coming from with the "speed and
efficiency" stuff, don't see how that bears on my points
at all. I can see our partners fighting over our IP. That's
always been my article of faith of last resort, that if push
really came to shove there would be many buyers at the auction
of our IP so that we would come out ok.
I don't expect Ch11. How we muster the liquidity I know not,
but I don't discount the possibility of some swing funding
from our partners.
We are not merely free to let imagination "run wild": it
is part and parcel of due diligence to identify every
possible scenario. Risk management requires risk assessment
which in turn requires risk identification. Similarly a
reasoned approach to valuation requires the same
process, together with payoff estimation.
My point was that dismissing a bankruptcy event on grounds
that Ch7 risk is neglible is fallacy. I consider Ch11 a real
enough possibility to include it in my valuation picture.
If you don't that's fine--judgment is idiosyncratic and I
don't claim mine is somehow objectively better than yours.
Didn't mean to ruffle your personal feathers with the "sock
puppet" reference, not at all, sometimes I speak too soon and
too sharply.
>If GTC were to shut down operations, these dependents would be forced to abandon projects with very probable future profits in the billions of dollars<
Sure Ch7 isn't in the cards but that's a red herring/straw
dog. The material risk re bankruptcy is expropriation of IP
by the mentioned parties via Ch11 leaving those of us who got
in on the ground floor entombed in the rubble-filled foundation of a magnificent edifice.
Ad takeunder:
>it probably aint going to happen without Cox's blessing<
Are you suggesting the BOD is his private sock puppet collection?
It is their call, whether or not to recommend
an offer say of one dollar. My personal (financial) experience
with their stewardship informs me that they put my net worth
pretty far down on their list of priorities. To the extent
they lend weight to the views of Cox and Meade in this regard
I see no mitigating effect whatsoever.
>If Dew is trying to deny perceptional reasoning for the RS, then explain why the Nasdaq allows it or should I say demands it. It is strictly a matter of perception<
Yes, but not the perception of this or that firm, but of
the exchanges themselves. They show shark bait the door
out of self-interest:
"Why the Prerequisites?
Stock exchanges have these requirements because their reputations rest on the quality of the companies that trade on them. Not surprisingly, the exchanges want only the cream of the crop - in other words, the companies that have solid management and a good track record. Thus, the minimum standards imposed by major exchanges serve to restrict access to only those companies with a reasonably credible business and stable corporate structure. Any top university or college has strict entrance requirements; top exchanges work the same way.
Staying Listed
However, an exchange's duty to maintain its credibility isn't over once a company becomes successfully listed. To stay listed, a company must maintain certain ongoing standards imposed by the exchange. These requirements serve to reassure investors that any company listed on the exchange is a suitably credible firm, regardless of how much time has passed since the firm's initial listing. To fund their ongoing scrutiny, exchanges charge periodic maintenance fees to listed companies. On the Nasdaq, annual listing fees range from approximately $20,000 to $70,000 (higher fees are charged to companies with more shares outstanding). To extend the university analogy, these ongoing requirements are much like the minimum grade point averages students must maintain once admitted.
For stock exchanges, the ongoing minimum standards are similar to the initial listing standards, but they're generally a little less stringent. In the case of the Nasdaq, one ongoing standard that a listed company must meet is to maintain 750,000 public shares outstanding worth at least $5 million - anything less could result in a delisting from the Nasdaq.
In other words, if a company messes up, the exchange will kick the company out of its exclusive club. A stock that has experienced a steep price decline and is trading below $1 is very risky because a relatively small price movement could result in a huge percentage swing (just think - with a $1 stock, a difference of $0.10 means a change of 10%). In low volume penny stocks, the fraudsters flourish and stocks are much more easily manipulated; major exchanges don't want to be associated with this type of behavior, so they delist the companies that are liable to be affected by such manipulation."
http://www.investopedia.com/articles/02/032002.asp
Trusting this will all be deleted when "business as usual"
resumes, my submission:
>But this doesn’t mean that ease of financing is the only reason to have a Nasdaq listing.
Now I trust you refer to liquidity in our hands:
the same considerations I mentioned re financiers apply
to all owners--we are all financiers--so that impaired
liquidity/depth weighs on price.
>Can I take it from this post that you feel that listing (Which you opine would be the principal benefit of an RS) would not help the company obtain funds through stock placements (dilutions).<
I thought he meant just the opposite, at least I hope he
did--I don't like to disagree with him.
Regardless of what it evidences listed paper is inherently
more attractive simply because it's more liquid. I suppose
some financiers take Buffett's view--that they are buying
a business--but I suppose more do not. They are buying those
shares with a view to someday selling them, and that task is
facilitated by listing.
So the same asset would suffer a markdown if not listed, which
would increase our cost of equity capital, ie more dilution
per dollar raised.
She had a short skirt (indicating, of couse, a higher range for GTC<
That's obviously "fuzzy thinking"--shame on you!
Staple is half the story, but the reference to wool barbs
is the other half. I thought I saw something in the nature
of a possible polymerization breakthrough that would support
the production of longer fibers. I couldn't find that but
I did find this and it is surely required reading for biosteel
geeks. We are trying to spin stuff which is nowhere close
to what comes out of a spider's butt, and have a long way to
go in understanding what does.
http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0000998
>I believe that that is the license now held by Pharmathene
No that was the Protexia stuff, Nexia continues to do biosteel.
http://www.nexiabiotech.com/en/00_home/index.php
Biosteel is fascinating stuff, but it takes some craft
to go from a manila fiber to a hawser fit for hauling
battleships. That's the hangup as I understand it.
My wife is a handspinner. The most important thing
is the average length of the individual filaments being
spun ("staple"). If the fibers have little barbs (eg wool)
then a good yarn can be had from short staple, but if they
are smooth as a baby's butt (eg silk) you need a long staple.
I think the biosteel fibers are smooth. There is another
poster here who knows more about it than I do, maybe he
can add some color.
Also, when I say "Nexia continues" understand that contrary
to "true story but the names have been changed to protect
the innocent" the name remains Nexia but different principals
are now behind it than when biosteel began.
There was a technical item in the news river a year or so
ago indicating that things may be looking up for biosteel
but a quick dredge didn't turn it up, maybe the other poster
knows what I'm remembering.
The biosteel wiki is terse but informative:
http://en.wikipedia.org/wiki/BioSteel
>You might try burning something other than incense<
Money?
JB I don't know where you're getting "16 million share you think are being bought by insiders"--if you follow the
nasdaq link I posted you will land on a page that says
in the last twelve months net insider buying (and yes that
includes LFB) amounted to 33,447,153 shares. Are you just
trying to cause trouble by making stuff up to get a rise
out of me? Show a little manhood if you can, sir.
>I still believe that about 70% more or less of the float is held by retail.
"still"?!? What's with that? You claimed the company was
70% owned by retail. Do try to bear in mind that
when you make public claims they enter the public record!
>this stock trades like it is retail
Sure, that's what I said, remember? Institutional volume
over the past year came to about three weeks volume, that
leaves 49 weeks for retail, duh!
I think you are a message board vandal with no heft, no clue,
and no character. Witness your oh so snarky post on Yahoo!
yesterday:
>It's only a stock, there are many around
It's not a religious experience.
Nor is it a life style choice.<
Now that's really freighted with substance, isn't it?
Something tells me you're nobody's rich uncle and always
will be. Be that as it may, I wash my hands of you: the
last word is yours, now and evermore.
I should think the average tween smart enough.
What you neglect is the risk that pps might trend
up (limiting profit) or down (eliminating profit).
If it doesn't, sure, piece of cake, guaranteed wealth.
However, said risk is non-negligible, especially the down part.
>The process has a 10 percent success rate, meaning over the last few decades there have been hundreds of modified goat babies that didn’t come out looking like goats.
Gosh how long has this been going on?
Reagan?
Carter?
TRUMAN???
>My point was that it is retail doing most of the trading most of the time
Claiming 70% of the firm is owned by retail is a peculiar
way to make that point.
12 month institutional turnover 3,228,506
about three weeks volume
so your point is well enough, if peculiarly, taken
I don't think of individual investors moving 100K blocks
as "retail" but I won't quibble about that.
According to nasdaq, net insider purchases over the last
twelve months amounted to 32.6% of outstanding, and present
institutional ownership amounts to 16% of outstanding.
http://www.nasdaq.com/asp/holdings.asp?symbol=GTCB&selected=GTCB
Yet 70% (then backing off to 60%) you say is retail!
Yes I'm pulling numbers from somewhere, and that makes
two of us.
One naked claim deserves another.
Clearly at most one of us is correct.
>about 70% of the stock is held by retail.
Public market float is less than 30% of outstanding issuance.
What I was getting at was the possibility it might move from
our back burner to Ovation's, which draws a bit more current.
I may be too optimistic but I assume absent a corporate
obit a la BioMarin's neutralase that ghosts like decorin
and tysabri might conceivably if improbably be again flesh.
Writing them off re valuation is appropriate though.
All these neuro-'s make me wonder if decorin might find
some interest. Recall this item from four years ago:
Reduced scarring helps nerves grow through spinal injuries
09.03.2004
Infusing a naturally occurring anti-scarring agent called decorin into the damaged spinal cords of rats suppresses key molecules that block nerve regeneration after spinal cord injury, said Baylor College of Medicine (BCM) researchers in a study published today in the European Journal of Neuroscience.
The researchers are the first to use decorin to suppress inflammation and scar formation in spinal cord injuries. "Scar tissue that develops at sites of injury stops the regeneration of connections in the adult central nervous system," said Dr. Stephen Davies, lead author on the study and an assistant professor of neurosurgery and neurosciences at BCM. "Infusion of decorin into spinal cord injuries prevents the formation of proteoglycan rich scar tissue by suppressing inflammation."
Misaligned scar tissue that forms at spinal cord injuries physically blocks nerve regeneration and contains molecules called chondroitin sulfate proteoglycans that inhibit nerve fiber growth. Decorin inhibits the action of pro - inflammatory molecules released in spinal cord injuries, called transforming growth factors, which are thought to promote the formation of scar tissue.
Researchers in the study infused decorin directly into the injury site in rats with a mini-pump system, which used silica cannulas 160 microns in diameter. Because the cannulas were so small, they did not contribute to the formation of scar tissue. Using a high-powered laser scanning microscope and protein chemistry to analyze tissue samples, Davies and co-workers were able to show that decorin infusion reduced inflammation, scar formation and the levels of some proteoglycans by 80-95 percent allowing nerve fibers (called axons) to grow across spinal cord injuries in just four days.
"We have found a promising new approach to control inflammation and scar formation, which will be an important part of future strategies to encourage axon regeneration and recovery after spinal cord injury," Davies said.
The work was supported by TIRR (The Institute for Rehabilitation and Research) Foundation’s Mission Connect and conducted in collaboration with scientists at Integra LifeSciences Holdings Corporation, The Burnham Institute and GTC Biotherapeutics Inc, who together developed the genetically engineered form of human decorin for use in the study.
http://www.innovations-report.com/html/reports/medicine_health/report-26667.html
Senate Committee Approves Follow-On Biologics Bill: Fear and Trepidation Follow
In a long-awaited — and some would say long-feared — update in the regulatory pathway for FDA approval of follow-on biologics, the Senate’s Senate Health, Education, Labor and Pensions HELP Committee
[ http://help.senate.gov/ ]
gave the thumbs up to the Biologics Price Competition and Innovation Act of 2007 (S. 1695),
[ http://www.patentbaristas.com/wp/wp-content/uploads/2007/06/biologics-act-2007.pdf ]
which will address the scientific, regulatory and legal issues involved in bringing generic biologics to the marketplace.
Senators Kennedy, Hatch, Clinton, and Enzi introduced the legislation authorizing the FDA to approve a follow-on version of biologic therapies. The legislation includes standards for the FDA to approve follow-on biologics as well as a period of exclusivity for the brand name drug company. The Act amends section 351 of the Public Health Service Act
[ http://www.fda.gov/opacom/laws/phsvcact/phsvcact.htm ]
to provide for an approval pathway for safe biosimilar and interchangeable biological products (relying in part on the previous approval of a brand product):
A biosimilar applicant is required to demonstrate that there are no clinically meaningful differences in safety, purity and potency between its product and the brand product. A demonstration of biosimilarity includes analytical data, animal testing and one or more clinical studies, unless such a requirement is determined by the FDA to be unnecessary.
The Act provides incentives for the development of both new life-saving biological products and interchangeable biosimilar products: 12 years of data exclusivity for the brand company during which a biosimilar product may not be approved, and 1 year of exclusivity for the first interchangeable biological product.
The biosimilar applicant must provide its application and information about its manufacturing process to the brand company. A series of informational exchanges then occur in which the biosimilar applicant and the brand company identify patents in question and explain their views as to their validity or infringement.
Senator Kennedy said the committee plans to attach the bill to the Prescription Drug User Fee Act (PDUFA)
[ http://www.fda.gov/oc/pdufa/ ]
reauthorization bill. Sen. Sherrod Brown (Go Ohio!) had drafted an amendment that would have shortened the exclusivity period to seven years but withdrew the amendment without a vote.
Biotechnology Industry Organization (BIO) president Jim Greenwood stated that:
Senators Kennedy, Enzi, Clinton and Hatch deserve credit for their hard work in crafting this complex legislation, and for the bipartisan support they have achieved for the bill. Biotechnology innovators share the goal of ensuring all patients have access to life-enhancing and life-saving biologics. We support the development of a pathway for the approval of follow-on biologics.
Toward that goal, we will continue to work with Congress to make certain the legislation is improved to ensure it supports the principles we have outlined for a pathway to follow-on products, namely providing better protections for patient safety and the patient-doctor relationship.
In addition, the patent litigation rules included in the bill must be revised to improve protections for the intellectual property rights of innovators, ensure timely resolution of all patent disputes and maintain incentives to develop future medical breakthroughs.
Earlier, BIO released a set of principles to guide the development of a pathway for the approval of follow-on biologics. BIO also developed a detailed rationale supporting the need for substantial data exclusivity. Meanwhile, generic manufacturers expressed concern that a 12 year exclusivity for the brand company is too long.
The bill will still need to be passed by the full Senate and the House and then signed by the President.
Read the draft legislation here:
http://www.patentbaristas.com/wp/wp-content/uploads/2007/06/biologics-act-2007.pdf
See lawmakers pat themselves on the back here:
http://kennedy.senate.gov/newsroom/press_release.cfm?id=f669f22b-dfae-4341-827f-4624ceb8d291
http://patentbaristas.com/archives/2007/06/28/senate-committee-approves-follow-on-biologics-bill-fear-and-trepidation-follow/
>the half life to answer questions seems to be about 2 or 3 decades<
Mathematicians should be so lucky: the necessary and sufficient
conditions for commutation of differentiation and integration
were not obtained until 1938. My point is that some life
questions may well remain open a very long time, perhaps
longer than we exist.
Myriad Genetics Begins Phase 1 Trial of Anti-Thrombin Drug MPC-0920.
Publication Date: 02-MAY-06
SALT LAKE CITY, May 2 /PRNewswire-FirstCall/ -- Myriad Genetics, Inc. has initiated a Phase 1 human clinical trial of MPC-0920, an orally available, direct thrombin inhibitor. The trial will enroll healthy volunteers in a single, escalating dose format. The Phase 1 is designed to determine the safety, dose range and pharmacokinetics of the drug candidate. The market to treat thrombosis is large, totaling over $6.5 billion in the United States last year, and there is an urgent need for improved drugs, particularly those that can be taken orally.
MPC-0920 is designed to address these pressing medical needs for rapid and predictable anticoagulant action, an improved therapeutic window, predictable patient response and increased efficacy. The Phase 1 trial will be administered in a single ascending dose format, in which there are eight volunteers per cohort, six of whom are given the drug and two are given placebo. The dose escalation will continue until a blood clotting time that is several times higher than normal and sufficient to ensure clinical utility in thrombotic conditions is reached. The primary objective is to examine the safety of MPC-0920 and a secondary objective will be to study the biological activity of MPC-0920. Because MPC-0920 demonstrated an effect on blood clotting time in animal studies, even at very low dose, we expect the Phase 1 trial to show it to have an effect at low dose in humans as well. This may allow us to determine a biological effect in the volunteers, which is unlike the situation in most Phase 1 studies.
MPC-0920 has been the subject of 27 preclinical studies to date, comprising safety, toxicity, pharmacokinetics and formulation. MPC-0920 is covered by four issued patents, two U.S. and two foreign.
"We are excited to study MPC-0920 in the clinic due to appealing preclinical data that indicate significant benefits are possible compared to currently used drugs in thrombosis," said Adrian Hobden, Ph.D., President of Myriad Pharmaceuticals, Inc. "Thrombosis is a large problem and we believe MPC-0920, if approved, has the potential to make a significant impact for patients."
Thrombosis, the formation of a clot within a blood vessel, is one of the most common causes of death in the Western World. Approximately two million individuals in the United States die each year from an arterial or venous thrombosis or its consequences. In addition, thrombosis results in significant morbidity, particularly in the elderly. The most common form of thrombosis is deep-vein thrombosis (DVT) in the leg. This type of clot can break apart, travel up the leg and through the heart, lodging in the lungs and causing blockage of an artery. Known as pulmonary embolism, this condition causes lung tissue death and is an often-fatal complication of DVT. Major indications for MPC-0920 in anti-thrombosis include DVT, atrial fibrillation, artificial heart valves and in major open surgery such as hip replacement, which is increasingly common in older patients.
The drugs currently used to treat this condition are the anticoagulants heparin and warfarin (tradename Coumadin(R)). These drugs are widely used. One-third of hospitalized patients in the United States, approximately 12 million in total, receive heparin. However, both drugs have major drawbacks. Heparin requires intravenous administration and blood-level monitoring. Heparin-induced thrombocytopenia -- low platelet count -- is the most common serious drug reaction in hospitals. Warfarin is the only orally-available anti-thrombotic currently approved for use in the U.S. The use of warfarin is complicated by the fact that it has serious interactions with many commonly used drugs, causing unwanted side effects. It also interacts with compounds found in food. Warfarin can be highly toxic and has a very narrow therapeutic window. Because of the risk of serious side effects, patients are typically monitored twice weekly when they are first put on warfarin. Accordingly, there is a large and urgent unmet medical need for new therapies.
Myriad is developing a suite of drugs that are designed to address large markets with unmet medical needs. Many of these drugs are designed to treat diseases that are expected to increase as the U.S. population ages over the next generation. They include Flurizan(TM) for Alzheimer's disease, MPC-6827 for prostate cancer, Azixa(TM) for brain cancer and MPC-0920 for thrombosis.
Myriad, Flurizan and Azixa are trademarks of Myriad Genetics, Inc. Other marks are the property of their respective owners.
Myriad Genetics, Inc. is a biopharmaceutical company focused on the development of novel healthcare products. The Company develops and markets predictive medicine products, and is developing and intends to market therapeutic products. Myriad's news and other information are available on the Company's Web site at http://www.myriad.com/.
This press release contains "forward-looking statements"...
http://www.accessmylibrary.com/coms2/summary_0286-15077662_ITM
Myriad shows this in P1:
http://www.myriad.com/research/
Right, they had to timely disclose at least a precis.
It was not completely uninformative--I think the 20 year
term and the non-compete part were new. That's a nice
long time, and a material concession, respectively.
And TN did say "this week".
It's not new, was up Thursday, but we were so busy talking
about weighty matters like the timing of the reverse split that
it didn't get any notice here.
The 8-K is up.
1.01 Entry into a Material Definitive Agreement.
On June 22, 2008 we entered into an Acquisition, Licensing, Development and Supply Agreement by and among us, ATIII LLC, our direct wholly-owned subsidiary, and Ovation Pharmaceuticals, Inc. The agreement, which is scheduled to close in thirty days, provides for a collaboration in which Ovation will develop and market ATryn®, our recombinant form of human antithrombin, in the U.S. The collaboration includes final development and commercialization of ATryn® in the hereditary antithrombin deficiency, or HD, indication. The collaboration also plans for further development in acquired antithrombin deficiencies, such as the treatment of heparin resistance in patients undergoing surgery requiring cardiopulmonary bypass and the treatment of disseminated intravascular coagulation associated with severe sepsis.
Under the agreement we will be responsible for production of ATryn® and Ovation will be responsible for sales and marketing of ATryn® in the U.S., including all launch activities. As the collaboration proceeds with the acquired deficiencies, Ovation will fund our anticipated costs of clinical development for the heparin resistance indication.
The agreement provides for potential payments to us for meeting clinical, regulatory, and sales milestones. The milestone payments include a total of $9 million through approval of ATryn® for HD in the U.S., including $3 million paid upon closing and an additional $2 million expected to be received in 2008. Additionally, we will receive a transfer price on commercial product, a royalty on net sales, and a payment for product used in clinical trials.
The agreement provides that a joint steering committee of our representatives and Ovation’s representatives will determine product development, manufacturing and commercialization of ATryn® in the U.S. The agreement provides that we will enter into a supply agreement with Ovation prior to closing which will govern our manufacture and supply of the ATryn® product to Ovation as well as a quality agreement with Ovation which will govern the quality standards of the ATryn® product that we deliver to Ovation.
The agreement is for a term of twenty years, subject to earlier termination under certain circumstances. Ovation has agreed not to market any product that competes with the ATryn® product during the term of the agreement.
The agreement between us and Ovation, which is expected to close within 30 days, is subject to certain closing conditions, including consents of third parties and termination of the Hart-Scott-Rodino waiting period.
http://www.sec.gov/Archives/edgar/data/904973/000119312508141452/d8k.htm
I think a crossed market is treated as a fault condition,
something that requires some back-channel attention
to straighten out. Given the gale that passed through
Wall St today there might not have been much attention
to spare.
"Those suffering the most are Nasdaq market makers who execute retail order flow and retail investors who may not receive the best price. This can cause auto-execution systems used by market makers to halt. If the bid and offer are the same, these systems assume the quote is stale or incorrect. If Nasdaq market makers auto-execution systems shut down, the market makers have to manually execute the orders which significantly slows trading"
http://www.financetech.com/featured/showArticle.jhtml?articleID=14702074
This long article holds that the root of the problem is we
have now competing pools of liquidity that are not as closely
coupled as they might be. It's five years old but I suppose
the color added still applies.
Human Coagulation factor VII in Fish
Human Coagulation factor VII in Fish A human blood-clotting factor used to treat some people with haemophilia and accident victims suffering serious bleeding has been produced using genetically modified fish. There is still a long way to go before any product reaches the market, but if the fish project is a commercial success many other proteins might be made in this way. "We have a list of 20 other human therapeutic proteins that could be produced via fish to treat lung disease, liver problems, even tumours," says Norman Maclean of the University of Southampton in the UK.
http://medicalhemostat.blogspot.com/2008/02/human-coagulation-factor-vii-in-fish.html
116 days ago
Tagged: Novoseven, Fish, Aquagene Medical Hemostat
http://medicalhemostat.blogspot.com
pretty good blog
>Yann Echelard, Ph.D.
HM's rock star status might lead us to forget that if he
keeled over tonight we would still rock in technical depth.
It's much the same thing with Atryn, it's easy to become
transfixed by the largest object in view, but the rest of
the picture is imo the greater part.
>quite possible that the role that GE played in IMAT's case is currently being played By GENZ in GTCB's case<
Or for that matter, by GE. As our financiers they obviously
know our story very well. Offered in good faith, in the
spirit of paranoia vs sarcasm.
Music is the only language in which you cannot say a mean or sarcastic thing. — John Erskine
The Biosimilar Pathway Is Filled With Obstacles
So many obstacles that one wag speculates the road to biosimilars - or follow-on biologics or biogenerics - may not be paved until 2010, or even 2012. What’s standing in the way? All sorts of things, writes Ramsey Baghdadi in The RPM Report.
For one, Ted Kennedy may not be around to push legislation while he seeks cancer treatment. The Medicare compromise bill, Baghdadi speculates, is the most likely piece of health legislation to make it through Congress this year, but biosimilars aren’t in either Democratic or Republic versions. The election year is slowing everything down. Biotechs and generics are still far apart on such key issues as data exclusivity. And satisfying two key congressmen - Henry Waxman and John Dingell - is a must.
So Baghdadi suggests circling PDUFA V, or the next version of the Prescription Drug User Fee Act, on your calendars.
“We expect a compromise to be hammered out over the next year or two and attached to the user fee bill when it comes up for reauthorization in 2012,” he writes, noting that the first negotiations over PDUFA V will start in 2010. “It will be much easier to attach a ready-made piece of legislation to the next user fee iteration then than to try and rush something through Congress that doesn’t meet everyone’s threshold for satisfaction.
Meanwhile, the House Energy and Commerce Committee, which Dingell chairs, has just released responses from 35 companies and organizations to an April 3 request for input on creating a biosimilar pathway. Here are the replies.
http://energycommerce.house.gov/Press_110/040308.FOB.Responses.shtml
http://www.pharmalot.com/2008/06/the-biosimilar-pathway-is-filled-with-obstacles/
(cited item follows)
Scoring Follow-On Biologics
By Ramsey Baghdadi
Rumor has it that 2008 will be a lost year for follow-on biologics. But CBO is still in the process of scoring savings from the potential biosimilars. The PDUFA V reauthorization year increasingly looks like the safe bet for a FOBs law to finally become a reality.
When it comes to follow-on biologics, time keeps on slipping. There was a lot of optimism that legislation creating an abbreviated pathway for approving FOBs could slip in by the end of 2007. Not so much. Talk turned to 2008 as the year when a bill gets passed through Congress.
Well, there’s good news and bad news on that prediction depending on where you stand on the issue. Word on the street is the staff of Sen. Ted Kennedy (D-Mass.), who serves as Chairman of the Senate Health, Education, Labor & Pensions, doesn’t expect legislation to move in 2008 because of the high number of other high-profile legislative priorities ahead in the queue and the fact that Kennedy was diagnosed with a malignant brain tumor.
The good news is the Congressional Budget Office appears to be moving forward in scoring the 10-year savings presented by having follow-on biologics in place. Specifically, CBO is reaching out to stakeholders to determine what impact, if any, the issue of “evergreening” could have in scoring savings over 10 years. The appropriate definition of a “new” biologic threw a monkey wrench into negotiations during the last days when the bill was being considered as part of the drug reform legislation in 2007. In other words, where is the line drawn between a new, innovative product and one that is incrementally improved, but not “new” per se? The concern among generic hopefuls is that a product that is slightly changed would get another 10 to 12 years of data/market exclusivity (meaning FDA wouldn’t allow a FOBs maker to reference that product in an application to the agency seeking approval).
If the Hatch/Waxman experience serves as a benchmark, you can bet the farm, the car and whatever else you own that whatever lines the legislation draws between “innovative” changes to biologics that merit additional exclusivity and non-protected changes will be the source of controversy and legal actions for many, many years.
CBO officials are understood to be of the opinion that “evergreening” would not wipe out savings during the 10-year scoring period because approvals couldn’t happen that quickly during the study timeframe. Biogenerics stakeholders, however, point to the relatively quick development and approval of Roche’s “next-generation” EPO Mircera as evidence that those types of products can impact savings analyses. It will be difficult, however, for CBO to identify significant savings over such a short period of time, primarily because follow-ons will be deemed interchangeable on a case-by-case basis and new FOBs entrants will be few and far between.
The law firm Engel & Novitt on behalf of the Pharmaceutical Care Management Association estimated cost-savings from FOBs for the top 200 Medicare Part B-reimbursed therapies would be approximately $14 billion over 10 years. Two other studies, conducted by Howrey/CapAnalysis Group and Avalere Health, estimated considerably smaller savings in the range of $2 billion to $4 billion over 10 years.
We’ve said all along that if CBO comes out with numbers closer to the Howrey and Avalere analyses, that won’t do much to motivate lawmakers to push for the legislation.
There are a number of challenges to getting a bill done in 2008 and beyond that fall outside of the trenches separating the innovators and the biosimilars proponents:
1) Kennedy’s health: Kennedy took the lead on trying to get a compromise bill into the FDA Amendments Act, signed into law in September 2007, but the Senate Biologics Price Competition and Innovation Act (BPCIA) just missed getting through. With Kennedy out of the day-to-day operations in Washington while he receives treatment, it’s unlikely there will be someone to take his place in championing new legislation. Still, most with chips in the pot agree that any law will have the BPCIA provisions at its core.
2) The Medicare bill: The Medicare compromise, which includes the physician payment fix, looks to be the major piece of health legislation that will make it through Congress in 2008. So if FOBs has a chance, then it most likely has to be attached to that legislative vehicle. Well, as of right now, FOBs isn’t in either the Democratic legislation (sponsored by Senate Finance Committee Chairman Max Baucus) or the Republican counter-bill (sponsored by Iowa Republican Charles Grassley). And that means FOBs are almost assured to be left out of any final bill the two sides hash out. No one is going to be interested in tacking on a controversial piece of legislation to a must-pass bill.
3) The Election: As summer comes to an end, the election will heat up quickly, with many key Congressional leaders out campaigning for the Presidential candidates or otherwise indisposed. That pretty much knocks out 2008. Then much of the first half of 2009 will be focused on setting up the new administration. Good luck getting FOBs through in that environment. More on this in my next post.
4) General hatred and disdain between biotech and generic drugmakers: This is a half joke. But like all half jokes, half of it’s true. Both sides appear to be coming around, but the amount of rhetoric put forth by both sides leading up to final negotiations in 2007 clearly damaged their positions. The RPM Report has heard this from numerous staffers and stakeholders. Whether it was extending data exclusivity or how easily understood the science is for developing and approving follow-ons without clinical burden, Senate and House leadership staff, as well as senior FDA officials, were put off by the rhetoric.
5) Making Dingell and Waxman happy: One of the major reasons FOBs didn’t make it into FDAAA was the Senate and House schedules and views of the compromise didn’t match up. House Committee on Oversight and Government Reform Chairman Henry Waxman (D-Ca.) was and still is a key player in the follow-on biologics game, and any compromise will most likely have to have his sign-off as well as that of House Energy & Commerce Chairman John Dingell (D-Mich.); Dingell has expressed interest in getting legislation passed. But there is a lot of ground to cover between the Waxman proposal (the Access to Life-Saving Medicines Act) and the Kennedy bill in the Senate. Most importantly, the issue of data exclusivity.
So when will FOBs happen? We recommend targeting PDUFA V as the vehicle for follow-on biologics.
We expect a compromise to be hammered out over the next year or two and attached to the user fee bill when it comes up for reauthorization in 2012. Sound far away? It really isn’t. The first negotiations to gear up for PDUFA V will start taking place in 2010, and it will be much easier to attach a ready-made piece of legislation to the next user fee iteration then than to try and rush something through Congress that doesn’t meet everyone’s threshold for satisfaction.
It’s possible the follow-on biologics debate could accelerate due to some unforeseen catalyst—anything’s possible in Washington—but the safest bet is that the legislation will move in 2010, with 2012 as the finish line. Is that too safe? I would love to hear your thoughts.
http://therpmreport.com/Free/e3a5e24d-4c16-452a-bdc8-a980dc9a9f56.aspx?utm_source=SmartBrief
>if immunogenicity of milk-produced proteins turns out to be a
generic problem, then a whole class of transgenic production methods may
turn out to have a limited future.<
That will remain undeniable, and vacuous, forever.
No amount of clinical evidence can refute such a claim.
But yeah, maybe goat stuff is lethal, you never know...
Concur. It's one thing to fall in love with a firm and
another a CEO. He has reached the Peter Principle point,
the level of manifest incompetence, and ought be replaced.
Unless a damn big rabbit gets pulled from the hat immediately.
>looking over the entire history of GTCB as some kind of predictor of what will happen in the near future. That is clearly wrong<
Up and down sir: the goat process is NON-ERGODIC.
OK there you go again:
"Past performance of GTC has been a steady decline over it's entire history."
So "same as it ever was", nothing ever changes, H Ford and
JD Rocker took a different view and did ok.
I don't post macro stuff (at least not here) but just this once I make exception:
http://www.telegraph.co.uk/money/main.jhtml?xml=/money/2008/06/18/cnrbs118.xml
What part of "static scoring" don't you understand?
> Following FDA approval of rATIII, the metric for deals will once again shift<
Agreed. I related on Y!, that I once speculated in Kroger,
they were deemed trash and shortly wallpaper, but I saw that
operating cash flow was more than enough to dig them out of
the hole they were in, and as it did their perceived prospects
would move my way. I think this a parallel case: the least
bit of good news here alters the gauge function to radically
advance the bull case.
I'll ask God for an inch of onionskin and get back to you
(provided He delivers).
> guess the definition is clear but the question is: what is really the "efficient" market cap value of GTCB?
I think you are missing his point, which I take to be that
the market cap reflects a lack of insight--because most
owners lack both the industry and the information to obtain
it--whereas a suitor would have made a more thorough study
of the matter, being better resourced and more highly
motivated to weigh our prospects with sober care and in detail.
>For a surgeon, he was making his case as a hell of a salesman
Agreed.
MAbs in Development: Cardiovascular Diseases
Below is an excerpt from the new CHI Insight Pharma Report Monoclonal Antibodies: Pipeline Analysis and Competitive Assessment, by Mark C. Via. Monoclonal Antibodies: Pipeline Analysis and Competitive Assessment reviews the broad drug development effort that is focused on bringing improved mAbs-based products to the market, focusing on those used for therapeutic applications.
3.5. Monoclonal Antibodies in Development for Cardiovascular Diseases
Centocor (now part of Johnson & Johnson) was the developer of ReoPro (abciximab), a Fab fragment of the chimeric mAb 7E3, which was the second therapeutic mAb approved in the United States, in 1994. It is an anti-integrin antibody that targets the αvβ3 GP IIb/IIIa receptor on platelets, the vitronectin receptor on platelets and on vessel wall endothelial and smooth muscle cells, and the Mac-1 (CD11b/CD18) receptor on leukocytes. It is indicated for prevention of ischemic cardiac complications in high-risk patients who are undergoing percutaneous coronary intervention.
The targets that have been pursued in developing mAbs for cardiovascular indications are typically expressed on leukocytes, neutrophils, and other immune cells, and influence the inflammatory response that characterizes some forms of cardiac disease (Table 3.6). Reperfusion injury, for instance, the death of cells that is induced on the resumption of blood flow following prolonged ischemia, such as myocardial infarction, is essentially a severe inflammatory reaction. Experimental monoclonal antibodies to mediate this type of damage have targeted such receptors as activated complement 5 (C5) to inhibit leukotaxis; P-selectin, P-selectin glycoprotein ligand-1 (PSGL-1), L-selectin, and E-selectin to inhibit leukocyte rolling; and Mac-1 and intercellular adhesion molecule-1 (ICAM-1) to prevent adhesion of leukocytes to endothelial cells. Despite success in animal studies, however, these efforts have been generally unrewarding in the clinic, due to the complexity of the pathogenesis.39 For example, LeukArrest (rovelizumab; Hu23F2G), ICOS’ humanized anti-CD11/CD18 mAb, was discontinued for myocardial infarction after Phase II in 1999. Genentech’s rhuMAb CD18 (erlizumab), a humanized anti-CD18 F(ab΄)2 fragment, did not meet its primary objectives in Phase II trials in myocardial infarction patients in 2000. Wyeth discontinued PSGL-Ig, a recombinant version of PSGL-1 linked to the Fc portion of a human antibody, for myocardial infarction in 2002 after disappointing efficacy results in Phase II. Most recently, in 2006, Alexion Pharmaceuticals and Procter & Gamble Pharmaceuticals terminated development of pexelizumab, a C5-inhibiting humanized scFv, after it failed to demonstrate sufficient efficacy in a series of Phase III studies in patients undergoing coronary artery bypass graft surgery and in individuals undergoing percutaneous intervention following acute myocardial infarction.
Table 3.6. Monoclonal Antibodies in Clinical Trials for Cardiovascular Diseases
Company
Product
Antigen
Antibody Type
Indication
Status
Ablynx
ALX-0081
vWF
Nanobody
Thrombosis
Phase I
Millennium Pharmaceuticals
MLN1202
CCR2
Humanized
Atherosclerosis
Phase II
ThromboGenics; BioInvent International
TB-402
Factor VIII
Human
Deep vein thrombosis, atrial fibrillation
Phase I
vWF, von Willebrand factor.
Source: CHI Insight Pharma Reports
Ablynx
ALX-0081 is Ablynx’s lead Nanobody—Nanobodies are the company’s patented single-domain antibody fragments (see "Synthetic Antibodies" in Section 2.4)—targeting von Willebrand factor (vWF), intended to reduce the risk of thrombosis in patients with acute coronary syndromes. Preclinical studies indicated that it was safe and potent, and had a rapid onset of action. It entered Phase I trials in 2007; interim results released in July 2007 showed that ALX-0081 was well tolerated and had the desired pharmacodymamic effect.
ThromboGenics/BioInvent International
ThromboGenics’ TB-402 is a fully human antibody to factor VIII, a blood clotting factor. It is being developed as an anticoagulant for treating deep vein thrombosis (as a single postoperative injection) and atrial fibrillation (as a monthly injection). The compound interfered with clot formation in preclinical studies and entered a Phase I trial in February 2007. BioInvent International is codeveloping TB-402. The same 2 companies are also collaborating on TB-403, a humanized mAb against placental growth factor with potential in the treatment of cancer, age-related macular degeneration, and diabetic retinopathy. Phase I trials are scheduled for the second half of 2007. BioInvent, in collaboration with Genentech, is carrying out toxicology studies on BI-204, a fully human antibody that targets oxidized forms of low-density lipoprotein (LDL) cholesterol, specifically apoB100. The candidate has potential in the prevention of atherosclerosis.
Affimed Therapeutics
In December 2006, Affimed published in vivo preclinical data showing that AFM14, its fully human scFv targeting the activated form of the GP IIb/IIIa receptor (α2bβ3 integrin), had antithrombotic activity without prolonging bleeding times.40 The company is seeking a partner for further development of the compound.
Lexicon Pharmaceuticals
In July 2007, scientists at Lexicon Pharmaceuticals published research showing that antibodies against angiopoietin-like protein-4 (ANGPTL4) can rapidly lower triglycerides and cholesterol.41 Lexicon has chosen the target for internal development and has several mAbs in preclinical evaluation.
http://www.insightpharmareports.com/Reports_Content.aspx?id=12210