Friday, December 29, 2006
A similar form of flawed thinking takes place among pharmaceutical industry scientists. If we can make a molecule bind tighter to its target we say we have a better drug. How tight? They don't know, but they know it needs to be as tight as they can get it.
To me, true science and art are the same. Knowing just how much color to add, how long to hold a note, or how much sky to include in a landscape is part of it. When starting a war you should know what your objectives are so you'll know when you are done. President Bush is not a practicioner of true art and science. He is a cargo cult scientist! He started a war and made a list of 50 bad guys in Iraq that needed to die. Number one on the list will die this weekend. But that airplane carrying peace in the middle east isn't coming. Do we need to kill more leaders? More fighters? Maybe less killing would help.
Wednesday, December 27, 2006
BOTHELL, Wash., Dec. 21 /PRNewswire-FirstCall/ -- Nastech Pharmaceutical Company Inc. (Nasdaq: NSTK) today reported positive results from a dose ranging study designed to evaluate the pharmacokinetic parameters, appetite, food intake and safety of various doses of Nastech's proprietary PYY(3-36) nasal spray in obese subjects. The study identified doses for a long-term Phase 2 efficacy and safety clinical trial.
Now let's go back in time to see where PYY was in 2004.
86th Annual Meeting of The Endocrine Society (ENDO 2004), New Orleans, LA,
Nasal Peptide YY3-36: Phase 1 Dose Ranging & Safety Studies in Healthy Human Subjects. Download Poster (PDF)
13th European Congress on Obesity, Prague, Czech Republic, May, 2004
Nasal Peptide YY 3-36: Phase 1 Dose Ranging and Safety Study in Healthy Human Subjects. Download Poster (PDF)
So we are back to a point that seemed to be established back in 2004. At that time Nastech was partnered up with Merck to advance PYY. In March of 2006 Merck pulled out of the collaboration after it decided data from a "Preliminary Proof of Concept Study" of the intra-nasal formulation of PYY didn't demonstrate efficacy. Merck didn't want to play The Beer and Pizza Diet so Nastech went back to a happier time, 2004.
From the NSTK website: To date, Nastech has completed three Phase I trials of PYY. These trials have enrolled over 60 subjects and administered in excess of 900 doses in the Nastech PYY program. Results from the PYY Phase I clinical trials indicate the investigational product is safe, well-tolerated and shows evidence of reducing caloric intake, moderating appetite and demonstrating weight loss in human subjects. Unless you ask Merck
Steven C. Quay, M.D., Ph.D., Chairman, President and CEO of Nastech. "These results support a decision (#4 on The Five Dumbest Things On Wallstreet This Week by Colin Barr, 3/3/2006) to advance this program toward a long-term Phase 2 Weight Loss Clinical Trial. With obesity reaching epidemic levels worldwide, the need for a safe and effective product that promotes weight loss has become critically important."
Never ask a drug company CEO if there is a need for a safe and effective product that has become critically important. It's guarenteed that he/she's got one and it works.
Tuesday, December 26, 2006
and a spiked show in the corner,
a jigger of scotch, a blue necktie,
a small volume of poems by rimbuaud,
a horse running as if the devil
were twisting his tail
over bluegrass and screaming,
like a streetcar turning the corner
the city waiting,
the wine and the flowers,
the water walking across the lake
and summer and winter
and summer and summer
and winter again
--from the poem, " If We Take"
Written by Charles Bukowski
Wednesday, December 20, 2006
The Legal Services Corporation was set up to provide legal service to the poor. They run on tax money but they have a special status that allows them to operate as an independent non-profit corporation. That means they didn't have to follow government-wide expense guidelines. A recent audit uncovered some egregious expenditures. $13 per person high tea service, $12 bagel breaks, $70 dollar lunches, and $14 Death By Chocolate deserts at board meetings. Then there was the first class airline tickets and the limosine service. Meanwhile poor people in need of legal services were turned away from clinics that we underfunded. Who is helping who here?
Cargo Cult lesson: Work is done when poor people obtain the legal services that the agency was set up to provide. The leaders used the money to provide food services to themselves. Work was not done.
Now to Wall Street. Ah money. People love it but they don't care much for hard work. That's why they created wall street. Put your money into a stock that will turn a dollar into ten while you fly first class to your next LSC meeting! You haven't paid for the flight, your lunch or the ride to the meeting and your own money has made you more money. The rest of America is so dumb for not doing this. But wait, not everyone can do this. If they did there would be no products or services. You have to disallow the riff raff from reaching the highest level of success. Only allow a selected few into this world where work is for suckers.
Check out Goldman Sachs chasm. Investors gave Goldman Sachs boss Lloyd Blankfein a year-end bonus worth an estimated 53.4 million dollars, a record for a Wall Street executive. In all, the bank granted a total of 180 million dollars in bonuses to its top 11 executives. I guess the bank was primariy set up to enrich 11 guys.
Imagine if every construction worker got one square foot for every 1000 they contributed to building. Their own homes would be huge. They could start their own neighborhoods. With that kind of incentive they would work very hard. But they show up every day and earn an hourly salary. If they build a mansion or a shack, they make the same. Somehow they didn't get to write the rules the way the Wall Street bankers did.
Cargo Cult Lesson: Leaders know what people want.
Followers need to know what the leaders want.
This is a good metaphor for biotech. I've mentioned 1616 Eastlake in Seattle. This building is also a large empty space. They built laboratories with no scientists vying for them. No one, so far, has came along to rent them out. Then I've talked about Jeb Bush shelling out hundreds of millions to attract biotech to Florida. The people of Boca Raton authorized 20 million and ended up attracting biotechs golden boys who showed up in Brooks Brothers suits asking for more money. I've mentioned that by 2001 biotech had squandered 40 of the 100 billion invested. And that includes huge profits from Amgen and Genentech.
Biotech is that huge mall in China. Todays top stories from Biospace:
Altus Pharmaceuticals Inc. (ALTU) Enters Into Exclusive Strategic Collaboration With Genentech, Inc. (DNA) To Develop And Commercialize Products For Growth Hormone Deficient Patients; Altus To Receive $30M Upfront Payment And Equity Investment ... More
One of Genentechs first cloned proteins was human growth hormone. What is new here? No product, just a promise.
KOSAN Biosciences, Inc. (KOSN) Announces License Of Motilin Agonist Program To Pfizer Inc. (PFE); Kosan Will Receive Upfront Payment $12.5M; Additional Milestone Payments Up To $250M ... More
No product, just a promise.
Genta Incorporated (GNTA) Cuts More Than A Third Of Its Workforce ... More
No product, no promise.
Northfield Laboratories (NFLD) Blood Substitute Misses Trial Goal ... More
No product, no promise.
Panacos Pharmaceuticals Inc. (PANC) Bevirimat Study Falls Short ... More
No product, no promise.
Janssen, L.P.'s INVEGA(TM) Approved By FDA As New Treatment For Schizophrenia ... More
Eureka! A product. Let's hope it doesn't cause weight gain and diabetes like Zyprexa.
Orexigen Therapeutics, Inc. Files Registration Statement For Proposed Initial Public Offering ... More
No product, just a promise. 90% of all start-ups fail so the promise is weak. Plus their lead candidate is a fat pill. To not come across as a homeopathic type of drug company they throw in the promise of treating CNS disorders. Their research is driven by the obesity market. Some weak science connects their fat pill science with other conditions that can't be better treated with diet and exercise.
Gilead Sciences (Foster City, CA) (GILD) Drug Meets Goal; Company Announces Preliminary Results From Phase III Study of Aztreonam Lysine for Inhalation in Patients With Cystic Fibrosis ... More
No product, but they are getting closer to a product. This is a real product that will help people. Antibiotics work!
You see, I'm not so negative. I ended on a positive note. There is a part of the mall in China that is bustling with people. There is also a part of biotech that has produced useful drugs that help people. My criticisms of the industry come from those who use the good name acquired by honest men and women and use it to line their pockets. People like Jeff Kindler at Pfizer who was an executive at McDonalds prior to his current gig. The era began with scientists but soon became the domain of businessmen. Scientists who couldn't compete in academia hung up their lab coats and started companies. But they didn't have a product, service or a way of obtaining either. To this day they continue to start very expensive companies and/or clinical trials that have no chance of suceeding. They don't know what is needed to succeed. You start with basic science. When it becomes something, you raise the money to advance the drug.
Monday, December 18, 2006
Take Malaria for example. It infects between 300 and 500 million people every year and causes between one and three million deaths annually, mostly among young children in Sub-Saharan Africa. Malaria is not just a disease commonly associated with poverty, but is also a cause of poverty and a major hindrance to economic developmentt.
Sounds like a real problem. The Cargo Cult Scientist has the opportunity to join one of the SBRI groups. Top pay? $37,000.
House payment $2500 split two ways Average house in Seattle 430,000K
= 1250 x 12 months = $15,000
I've got $22,000 left over. But wait, I have to pay taxes. Let's assume 25% 22,000 - 9,300 = $12,700.
Student loan $1800
I'm down to $7,800 and I haven't bought food yet. No car payments or kids thankfully. Gas? Luckily SBRI offers free bus passes. Let's eat conservatively at $75 per week. Okay, I've got $3,900 left. That's $325 per month for gas, haircuts, eating out, baseball games, home improvement and maintainance, car insurance, and on and on..
I'm carving out quite a life here. What will I have to do in return for this opportunity? This job uses molecular biology and functional genomics to investigate the function of the apicoplast in malaria parasites. Working with mice and malaria sounds glamorous.
The guy who works on your car has more experience than most of the researchers working on curing disease. It just doesn't pay and that's why the research doesn't pay off. It's very noble to donate money to non-profit research organizations. Just be aware of how much of it reaches those who work in the laboratories. They ride home on the bus to their studio apartments contemplating new careers. Maybe finding cures for Malaria was a bad idea. Maybe being a school teacher would pay better.
Friday, December 15, 2006
He's at Creighton Hospital now. He'll be taken off of life support tomorrow. December 16, 2006.
Thursday, December 14, 2006
That's all you'll get from the news agencies. The Cargo Cult Scientist will go a little further. They were subpoena'd because they _____ and now they have to explain themselves or they will be ______ by the Feds. You heard it here first!
What I really want to do is start a journal. Instead of the usual assortment of unrelated articles I specialize in measuring the measurements. My team of skeptical researchers, who have an admitted bias against the upper echelons of science, devour the journals as they come out. They seek out trends in research tools and they come up with a topic for each new issue of our journal. We begin by trying to reproduce certain experiments. We ultimately make conclusions on the method or methods that are being applied. How hard is the science on a scale of 1 to 100? What pieces of information would be useful to know? Who is using the best equipment and who is taking a short cut? Oh it would be so much fun.
I guess my perfect job would be a thorn in the side of mainstream medical science. At the end of my career there will be a whole new science. The science of method. The study of method. If a scientist does on experiment 3 times and averages the results we'll break down the averages. We'll apply statistics, biology, chemistry, physics and the whole kitchen sink. If you think we are setting ourselves up as the judge and jury of other people without the proper authority you are wrong. The authority is reality. Your credentials won't help you here. You're affiliations will not trump honesty like Imanish Karis did. It's Gonzo science and anything goes.
That is my dream. To start the science of method. The science of negativity will be a subset. A new paradigm is needed for alternative voices to be heard. Modern scientist have made some rather egregious offenses against the good name of science and they need a parody journal to take on their work. I want the job!
Tuesday, December 12, 2006
Monday, December 11, 2006
WAUKEGAN, Ill.--(BUSINESS WIRE)--NEOPHARM, Inc. (Nasdaq: NEOL - News) today announced that the pivotal Phase 3 PRECISE trial evaluating cintredekin besudotox (IL13-PE38QQR) for the treatment of recurrent glioblastoma multiforme (GBM) did not meet the efficacy endpoint at 215 deaths, which was a statistically significant difference, or separation, in the overall survival curves versus Gliadel Wafer®. "Topline data suggests that cintredekin besudotox, while comparable, was not statistically superior to Gliadel," said Guillermo A. Herrera, President and Chief Executive Officer of NEOPHARM. "We will continue to work with our Scientific Advisory Board and the FDA to determine the best path forward."
Median Survival CB = 36.4 weeks
Median Survival Gliadel = 35.3 weeks
Damn! You take a slice of the population that has 9 months to live and you try to make a profit by extending the worst year of their life. There has got to be some chemical out there that can make this happen.
Good riddance NeoPharm.
Friday, December 08, 2006
Genta Incorporated (GNTA) Provides Update On Genasense(R) Phase 3 Trial; Leukemia Drug Misses Key Goal, Stock Drops
DOV Pharmaceutical Announces Termination Of License Agreement With Merck & Co., Inc. (MRK)
Coley Pharmaceutical Group Amends Strategic Alliance License Agreement With GlaxoSmithKline (GSK) For VaxImmune(TM) Vaccine Adjuvant ... More
Novacea (NOVC) Says CEO Resigns, Names Interim CEO ... More
Nastech Pharmaceutical Company Inc. (NSTK) Says $15 Million Payment From Procter & Gamble (PG) Deferred
Pfizer Chief Medical Officer Joe Feczko announced that the company was immediately canceling all trials of torcetrapib because it had sharply boosted the death rate of patients in a 15,000 patient trial.
Bayer Pharmaceuticals Corporation (CT) And Onyx Pharmaceuticals, Inc. (ONXX) Release: Phase III Trial Of Nexavar In Patients With Advanced Melanoma Does Not Meet Primary Endpoint
3M Company (MMM) To Cut 400 Headquarters Jobs, Outsource Support Work; 3M Pharmaceuticals (MMM) To Change Name
ImaRx Therapeutics Cancels IPO Due To Market Conditions
ProMetic Life Sciences Inc. (PFSCF.PK) Cancels UK Unit IPO, Says Price Could Rise
Forbes Medi-Tech Inc., a maker of drugs for lowering high cholesterol, said Monday preliminary results from a mid-stage clinical trial of drug candidate FM-VP4 fell short of the company's goals.
ImClone Systems Inc. chief scientific officer Philip Frost resigned Friday, according to a Monday filing with the Securities and Exchange Commission.
Evolutec Ltd Release: Primary Endpoint Not Met In Phase IIb rEV131 Trial In Allergic Rhinitis
Somaxon Pharmaceuticals, Inc. Reports Results From A Clinical Trial Of Oral Nalmefene in Pathological Gambling; Drug Fails In Study
Next week will bring more failure, job cuts, and reduced investment. The times are changing and biotech needs to start working smarter. The big pharmaceutical companies need to buy up well established drug programs. The place to be is somewhere near phase III trials in the lucrative disease areas, cholesterol control, type II diabetes, osteoporosis and pain management.
The message is clear. As a smaller company you must not set out to save the human race from disease. You must save the pharmaceutical giants from their own pending doom. The industry is sick and they need the next Lipitor or Viagra. Americans live very unhealthy lives. You must give them pills to offset their inability to take care of their health. If your drug falls too close to the margin of error you might just miss your clinical trial endpoints or even worse, end up killing people like Pfizer. Think carefully when choosing your pipeline. Do not create new drug classes. Cox-2 inhibitors and CETL inhibitors, although proven dangerous, can still become big sellers. It's tough to decide with so much conflicting data but that is what will keep you going for years to come. Even if you fail, you will have made a buck or two.
As for the investor... we have plenty new drugs for you to invest in. Good ones. Maybe some day you could visit our labs down in the swamps of Georgia. It won't be hard to get around down there. We're purchasing the Brooklyn Bridge and having it shipped down. By the way, could you help us offset the cost of that?
Thursday, December 07, 2006
All of our efforts in Iraq, military and civilian, are handicapped by Americans' lack of language and cultural understanding. Our embassy of 1000 has 33 Arabic speakers, just six of whom are at the level of fluency.
The report was 84 pages long. If the Cargo Cult Scientist could add one more recommendation it would be that the staff who wrote this report write another 20 pages on the work being done at the embassy. Who were these arabic speakers? Did they also speak English? Did they work as janitors or translators? Does the work being done at the embassy require a lot of Arabic language interpretation?
This would be a "wax on wax off" type of endeavor. When pursuing something that may seem trivial, you might just stumble upon a big problem. Perhaps the embassador doesn't do anything besides hold dinners and talk about how everyone in the room is going to get rich off of this scuffle. Perhaps we change the embassy mission to have them help us learn more from people in Iraq. How do they feel about the ideas being tossed around in this 84 page solution.
Old men start wars and young men die in them. The old men in this case cannot put an end to this struggle. The enemy is not known. When they get close to a real issue such as the lack of language and cultural understanding, they follow it up with a recommendation that we train people in the language. Languages are not learned that easily, especially when mixing with the locals is a life and death situation.
The war in Iraq suffers from too many old men who do not know their enemy. Too many people on the American side are making decisions for the young people who have to fight an enemy willing to die for their cause. Our leaders are only willing to sacrifice the lives of our young, not their own lives. They don't even take the time to learn from the young men who are dying.
Tuesday, December 05, 2006
Eden Bioscience, a 12 year old plant biotech company in Bothell Washington has sold the assets of its agricultural-products business to Plant Helath Care for $2.5 million. Eden will retain the right to the technology for sale in the home and garden market.
The company will also be "substantially reducing" its work force from the current number of 35 employees. CEO Rhett Atkens will resign as of Dec. 15, 2006. In the 12 years of their existance they have accumulated a deficit of $116 million. Another net loss of approximately $8 million will be recorded for the first 9 months of 2006.
The Cargo Cult Scientist can remember going to Eden Bioscience in 2004 to look at possible equipment to purchase. From that day on I saw the same scientist who was selling off his equipment walk the trail behind their building. I wondered why he was still there. What were they waiting for? When they held the auction at Encyte Inc. for their final clearance, I saw the scientist again. "Will they be buying new equipment for Eden", I wondered. Now I see that they are tapping out. This is the end.
We do not celebrate the demise of any company here at the Cargo Cult Scientist. We lament their inability to use their science effectively. When a company dies like Eden or Encyte, which was just up the street, more people are left to vie for the handful of jobs that remain. It is not a joyful occasion to see these failures, but it is what we predict based on our understanding of how science is looked at by the industry. They do not know what matters, and they fail. So rest in peace, when in fact you, Eden, do close up the doors and sell off your equipment and your phones. The scavengers will decend upon your old building and place their bids for your stuff. The place will empty and that will be the end. $124 million dollars and counting and that will be the end of it. Another airplane that did not land.
Monday, December 04, 2006
NEW YORK, Dec. 2 /PRNewswire-FirstCall/ -- Pfizer Inc said that in the interests of patient safety it is stopping all torcetrapib clinical trials and that it has informed the Food and Drug Administration. The Company was informed today that the independent Data Safety Monitoring Board (DSMB) monitoring the ILLUMINATE morbidity and mortality study for torcetrapib recommended terminating the study because of an imbalance of mortality and cardiovascular events."
Dr. Philip Barter, Director of the Heart Research Institute in Australia and Chairman of the Steering Committee overseeing the ILLUMINATE study, said, "Based on all the evidence we have seen regarding torcetrapib and in light of prior study results, we were very surprised by the information received from the DSMB, the only body with access to the unblinded safety data. We believed that the study was coming along as expected, and this new information was totally unexpected and disappointing, given the potential benefits of this drug."
If only there were some way of predicting what a drug will do. Even "prior study results" cannot predict this Hindenburg-esque demise of a drug. Our science is incomplete. Studies cannot be trusted to predict the future. If only there were a way around this.
For the families of those who died, I hope they get more information on the prior studies and how this happened. It was a mistake. Now is the time to learn. The final word comes from the Pfizer CEO:
Pfizer's Chief Executive Officer Jeffrey B. Kindler said, "While the DSMB information we received today was both surprising and disappointing, our focus is on the best interests of patients and making sure all this information is communicated to appropriate medical and regulatory authorities as quickly as possible.
"With regard to our business, we understand the challenge that this represents and we will respond quickly and aggressively to it. It is important to put this information in the context of both our commitment to transform Pfizer and our overall product and financial strength," Mr. Kindler added.
Sunday, December 03, 2006
Companies begin when a PhD or MD doctor has an idea. He or she will pump up the idea much like George W. Bush pumped up the war in Iraq. A picture is painted. As we begin to lift the curtain on reality we only expose the things that look like the picture. Those who understand this process will be rewarded and given speaking roles in the company. That means no lab coats. The lab coat people are to be young and easily manipulated. None of them should stick around for long due to the obvious wool being pulled over the eyes of the investors.
PhDs learn how to write grants. They learn how to talk in meetings. It is imperative that a PhD contributes to conversations that are started by those above them. To remain silent would mean that you are not understanding the genius of the higher ranking person. You need that person to advance your career. You must always agree with the higher ranking person but in subtle ways. If they say the earth is flat, you must suggest ways of not driving off the edge. Thus, agreement can be assumed and a suggested advancement of the idea is duely noted. If you are concerned that the false assumption will bite you in the ass further down the road, you are not thinking clearly. You, and all other important people will not be around for the fallout. That's the genius of PhD advancement. You must take on more and more responsibility. When a project destined to fail enters its final stage you make sure it is not high on your list of priorities. You've delegated and your people failed. They may need to be let go. That is the courage of leadership. Some might call it audacity but it does take courage to set up people and convince them that only they can save a project.
When a company fails, the leadership takes what is left over and move on. This is not failure. This is called learning. It takes courage to put yourself at the top of a company chain of command. People expect great profits. You have learned a thing or two when a company goes down. The next company might fail but it won't be your fault. They are expected to fail. You must convince investors that you are the only thing in between certain failure and the big bucks. You'll do everything you can, but there is risk in investments.
And that is the lesson of becoming a successful PhD. You must get where there is no risk. You can make a fortune and never produce one single drug. You can work for one sinking ship after another. Never put yourself in a position where failure can be attributed to something you thought up. Rule number one: Stay out of the lab. Them cells and that DNA can't be told what to do. They are leading all of us and our future as a species. Nevermind that and get yourself into a position of as little risk as possible.
Friday, December 01, 2006
small conversation in the afternoon with John Fante
"but when he left Hollywood, I stayed on, and while I didn't drink like that maybe I should have, I might have had the guts then to follow him and get the hell out of there."
I told him, "you write as well as Faulkner.:
"you mean that?" he asked from the hospital bed, smiling.
They found that the best researchers are right here in the good o'l U.S.A. God bless them for that.
Eli Lilly seems to be eliminating R&D as a way of pumping up their pipeline. Recently they bought ICOS for 1.2 billion dollars to have full control of the drug Cialis. That's one drug in the bag. The R&D efforts at ICOS are not expected to continue. And there is more.
NEW YORK, Nov 30 (Reuters) - Eli Lilly and Co. (LLY.N: Quote, Profile , Research) said on Thursday it will take a restructuring charge of $100 million to $110 million primarily in the fourth quarter related to its previously announced closing of a research facility in Belgium.