Have a Plan

Lately I've been thinking about the way in which ideas become accepted. The Cargo Cult natives saw the cargo emerging from the big metal birds and a desired outcome was born. Now all they needed was a plan. They watched the Allied forces carefully and began piecing together their plan. The desired outcome however was the most important piece of the plan. The ideas of how to acheive the outcome took a back seat while the leaders dreamed of the cargo.

We recently experienced the Republican and Democratic national conventions. The mission was to convince the majority of America that one party will provide a better future than the other. The melt down of wall street however is an excellent example of our political and corporate leaders ability to predict and shape the future. Our government is going to put up 700 billion dollars (this week!) to "fix" the problem.

But what about 2 weeks ago? Was anyone preparing for the bailout? What was being done 2 months ago? When did this government bailout start to take shape? We now have our desired outcome. We want the economy to be strong. That is our cargo. What is our plan? Bail out the banks so they can go back to making loans.

How did the ideas that went into the bail out plan gain acceptance?

The 700 billion dollar bailout does not guarentee success. It is a plan however. For the politicians, a plan is all that is needed. Even if the plans spells the end to the great American era. It doesn't occur to the Cargo Cults that there plan is not working. Simply carrying out any plan gives off the impression that work is being done.

Only a proper scientific method will bring about a proper change. Compare the actual outcome to the desired outcome. The ideas that were accepted may have lead you astray.

The Psychology of RNAi

This summers reading brought me in contact with a most beautiful book on the subject of randomness. The book is called "The Black Swan". In it you will find heretical discussions such as, "Academic success is partly (but significantly) a lottery. It's easy to test the effect of reputation. One way would be to find papers that were written by famous scientists, had their authors identities changed by mistake and got rejected. You could verify how many of these rejections were subsequently overturned after the true identities of the authors were established."

The painful truth about science is that it is run on the most non-scientific means of judging a persons work. Reputations rule. Good solid science will do you no good if you cannot convince the powers that be that they have missed something. This is not an easy task due to the arrogance of power. If you dare challenge someone like a David Baltimore or Craig Mello you had better have a powerful group of cohorts willing to back you in your battle.

The CCS knows this and is under no delusions that he is actually battling the powers that be. This is rather an exercise in psychology. What does any person have to do to affectively be heard? Write a blog? Ha! Have a great idea? Ha again. Great ideas can have just as hard of a time being sold as bad ones. In fact, the scientific merits of an idea is not as important as its presentation. Who is presenting the idea. Are they confident? Is the idea presented in peer reviewed journals, scientific meetings or books? Does the idea fly in the face of current thinking?

Billions of dollars have been spent and many more are on their way out the door for RNAi to be used as a drug. Beyond that, RNAi has been the bane of many a research associate whose job it is to use RNAi to knock out genes. It's like using a feather to hammer nails. But no one is going to listen to a guy who wears a white lab coat daily. No one is going to publish a paper stating that RNAi has yet again failed to produce knockout data. The idea that it doesn't work is no longer being accepted. Like gene therapy however, it will cease to impress and thus be put on the back burner. One day the real story behind what happened in the early studies of RNAi will be known. Until then we must accept that we are in the middle of a common situation in the history of human reasoning. We are convinced that we know the truth. We no longer require evidence to the contrary. Yet the planes are not landing.

http://www-tech.mit.edu/V125/N50/50van_parijs.html

This is an old story. This marks a new chapter in the CCS. We will now make it our mission to explain why this (RNAi) happened and how it will end. We have learned much from gene therapy and the demise of hundreds of biotech companies. Tens of billions of dollars are gone but there is something to be learned.

Just for fun, we start with a Harvard PhD who is fired from MIT after a rather successful beginning to his career. As you read about this story please think about the environment that make it possible. Harvard? MIT!!! But... but... PhDs? 461 citations. But there was a Nobel prize awarded for the RNAi story. Why would anyone in such a world have to cheat?

One Flame Out, One Flame Close Behind

http://seattlepi.nwsource.com/business/366495_nastech11.html
http://blog.seattlepi.nwsource.com/thelifesciencesblog/archives/141684.asp

Nastech is no more. Therapeutics will be done soon as well. Notice the name change at Nastech however. Cell Therapeutics may do the same thing. There is much to learn from companies like these who promise the cures. They take until they can no longer get away with it. Then they change their names and go back for more.

Sirna Sold For 1.1 Billion!!!

As I mentioned in the last post, a company called PhaseRx boasted that they are an RNAi company. What's the big deal about that you ask? SIRNA SOLD FOR 1.1 BILLION DOLLARS! So let's give PhaseRx some money!

Do you think that is a silly thing to say? How can a bunch of grown men with PHDs and MDs get together and hoodwink investors so easily? Does PhaseRx not have to present the scientific merits of their RNAi company?

In more recent news, the notorious Dr. Quay of Nastech Pharmaceuticals discussed the ruins of his biotech company today. In an attempt to ease the suffering of his investors he spoke glowingly about his spin-off 'MDRNA' a new RNAi company. There wasn't much information about the last five years of RNAi research under the old banner of Nastech. But he did mention this interesting fact:

SIRNA SOLD FOR 1.1 BILLION DOLLARS!

Who will be the first to go? MDRNA or PhaseRx? Will Merck keep spending money on SIRNA projects? The CCS will be on the lookout. Our eyes cast to the skies, we look for the kind of cargo that only billions of dollars can summon.

Would You Work for This Company???

Seattle Biotech has a new management team that has been sued by their investors. http://seattletimes.nwsource.com/html/businesstechnology/2004127544_cellcyte16.html

Okay, so that is old news. We also have a new fire to light our runway. And they specialize in RNAi!!! They have the old Nastech CSO who was "resigned" recently after years of not making RNAi work there.
http://seattletimes.nwsource.com/html/businesstechnology/2004247523_biovc28.html

Welcome to the airport.

What's in the News

'In the South Seas there is a cargo cult of people. During the war they saw airplanes with lots of good materials, and they want the same thing to happen now. So they've arranged to make things like runways, to put fires along the sides of the runways..."


We here at the CCS look at each biotech hub as a cargo cult airport. Seatte, the bay area, San Diego, Boston, North Carolina are all airports. The fires along the runways are small biotech companies.

The seattle cargo cults had a bad week.

Cell Therapeutics throws a 30K$ party after laying off 31 employees to save money.
http://seattlepi.nwsource.com/business/351048_cti13.html?source=rss
Amgen lays off 130 employees... up from the 50 they anticipated. They found more useless people than they originally thought they had hired?
http://seattlepi.nwsource.com/business/351138_amgen14.html
Dendreon can't get a break!
http://seattlepi.nwsource.com/business/351210_dendreon14.html
Nastech is one step closer to the end.
http://seattlepi.nwsource.com/business/350985_nastech13.html
Zymogenetics has layoffs after finally getting a drug approved.
http://seattlepi.nwsource.com/business/351223_zymogenetics14.html
CellCyte is a ridiculous company!!!
http://seattlepi.nwsource.com/business/351230_cellcyte15.html
The CellCyte CEO did lied?
http://www.sequence-inc.com/fraudfiles/2008/01/13/usana-executives-arent-the-only-ones-lying-about-their-credentials/

Sheesh!!!

A Burning Flame Going Dim

We think of biotech companies as bright burning flames that illuminate the runway of our Cargo Cult airport. We think of technologies such as RNAi as the fuel for the flames. Today we are concerned about our Nastech flame.

On January 16, 2008, Novo Nordisk A/S ("Novo") advised Nastech Pharmaceutical Company Inc. that Novo intends to cease development under the feasibility study agreement that the parties entered into in March 2006.

Jan 22 (Reuters) - Nastech Pharmaceutical Company Inc (NSTK.O: Quote, Profile, Research) said it may periodically sell up to $50 million in debt securities, common and preferred stock, warrants and units.

The company said it intends to use the proceeds in part to fund its clinical research and development programs.

Is the end coming soon? How will it end? Will they rebound??? We are watching.

A New Set of Questions for Scientists

Merck and Schering Plough make a drug called Vytorin which combines Zocor, a cholesterol lowering statin, with Zetia, a drug that limits cholesterol's absorption into the body. The ran a trial that was hoped to show that this drug was more effective than Zocor alone in slowing the growth of arterial plaque, which can lead to heart attacks. It wasn't. Vytorin users did see a larger drop ini cholesterol than Zocor users. The decline however didn't result in a improved arterial health. http://www.revolutionhealth.com/news/?id=hd-611715&s_kwcid=vytorin934891494

Shocking news to the scientists and doctors working for the drug companies. They just had no clue this would happen.

Folkmans Delivery Problems

Dr. Judah Folkman was a rising star with several publications and patents on anti-angiogenisis factors. The problem was that no one was able to reproduce his results. From his book "Dr. Folkmans War":

Soon after he began shipping endostatin to researchers around the country, Folkman heard that the drug had become inactive by the time it got to some of the laboratories... The recipients reported that the drugs were having little or no effect on cancer-bearing animals. Folkman was alarmed, needless to say. Any such report carries with it the suggestion that somehow the original research was wrong, or worse, that the results had been embellished.

Folkman and his colleagues soon noticed that the problem seemed to be only with batches that were shipped to distant places. The endostatin being tested in local labs was fine. So the problem, in all likelihood, was in the shipping.Like many drugs or biomedical compounds, the endostatin was being frozen in small plastic vials, packed in dry ice, and was sent out via Fed Ex. Folkman began doing experiments to figure out what might be going wrong. First, they found that the problem was not caused by freezing. When they froze a vial of endostatin, then thawed it, the drug worked normally. So how could transportation hurt it? Hoping to find clues they packed a sample in dry ice, stowed it in the trunk of a car, and drove around Boston with it. Sure enough, when they brought it back into the lab and thawed it, the endostatin didn't work. But why?"

The answer they later came up with was that the dry ice that the drug was packed in bathed the solution in carbon dioxide that had seeped through the vials. The result was the lowering of the pH that inactivated the drug. The solution to the problem was to put the drug into glass vials for shipping. The results of this experiment were not covered in the book.

Judah Folkman Is Dead

No sacred cows here. Dr. Juday Folkman died of a heart attack this past week at the airport in Denver. He had a great career in medicine. He was an MD surgeon who had a second career as a PI in a laboratory that explored the involvement of blood vessel in tumor growth.

The CCS does respect Dr. Folkman for offering up a new idea to the establishment and proving that tumors need blood. But then all cells need blood for oxygen and to carry away their waste. This should have been less heresy than it was. The real issue we have with Dr. Folkman however is his role in bringing corporate america into academia.

Dr. Folkman had spent a long time looking for a tumor angiogenesis factor that he decided had to be secreted by the tumor. What he needed was money to grow up large amounts of tumor cells to increase the odds of finding the factor. Monsanto was eager to give him what he wanted. The grant he was given and the terms of the deal swung the academic doors wide open for the corporate world. Their money could now buy access to the usefulness of our university system.

What they wanted of course were patents. They wanted to lay claim to the good work being done, not in their laboratories, but in the superior labs of university scientists. In my next post I will recount a humorous ending to one of Dr. Folkmans corporate sponsored R&D projects. For now I will end with the moral of this story:

The introduction of corporate minds and money into the world of science has been a disaster. In many ways, it began with Dr. Folkmans desire to become a scientist.

Is It Dishonest?

Nastech Pharmaceutical Company Inc. (Nasdaq: NSTK) announced today that the U.S. Patent and Trademark Office (USPTO) has issued a Notice of Allowance for U.S. patent application No. 10/976,942, entitled "Phage Displayed Trp Cage Ligands." The patent application has claims that relate to a novel, high-throughput method for identifying peptides which can bind to specific cell types.

"A major obstacle in the development of safe and effective medicines today is the inability to target the therapeutic directly to the cells of interest," stated Steven C. Quay, M.D., Ph.D., Chairman and CEO of Nastech. "The technology of this allowed patent provides Nastech with a process for rapidly identifying peptides that target specific cells. These targeting peptides can then be combined with therapeutics to enhance overall delivery and overcome this key challenge in drug development."

Why then did Nastech sack the Phage Display group in 2006. The Cargo Cult Scientist knew members of this team and the reason they were given was contrary to the above quote from the CEO. It just wasn't working. The question then is simple. Is this dishonest?

In Cargo Cult terms, yes this is dishonest. They stood at the airport and employed their technology. They looked to the sky and no planes came. They sent the staff home. A couple of years later they still talk about the technology. Their government has given them a nod of approval but no planes have come.

FDA Science

Does Dendreons cancer drug Provenge really work? After hundreds of millions of dollars spent on research and careful analysis from the MDs and PhDs of the medical science community, it's now up to the United States Congress to analyze the analyzers.

"two members of the FDA's advisory committee who opposed the drug's approval -- Howard Scher of the Memorial Sloan-Kettering Cancer Center and Maha Hussain of the University of Michigan -- had conflicts of interest.
"There is reason to believe that serious ethics rules were violated by two FDA advisory panel members in their decision, and that these violations played a role in the subsequent FDA decision to not approve Provenge at this time," said the letter, signed by Reps. Mike Michaud, D-Maine; Dan Burton, R-Ind.; and Tim Ryan, D-Ohio.
The congressmen said Scher was a lead investigator for a competing cancer drug..."

http://seattlepi.nwsource.com/business/343479_dendreon14.html

CTI Kicks Off a New Cargo Cult Season

Viewpoint #1

SEATTLE, Nov 21, 2007 /PRNewswire-FirstCall via COMTEX/ -- Systems Medicine, LLC (SM), a wholly-owned subsidiary of Cell Therapeutics, Inc. (CTI) , announced that cumulative preliminary results of a phase I trial combining cisplatin with brostallicin in patients with solid tumors that had relapsed or were resistant to front-line treatment were presented at the Highlights in Oncology meeting in Naples, Italy, on Tuesday, November 20, 2007. Cristina Geroni, Ph.D. of Nerviano Medical Sciences (NMS), which developed brostallicin, summarized the basis for the phase I trial design. The trial is based on data demonstrating tumors with high levels of GSH/GST, common in platinum-resistant disease, are more susceptible to the killing effects of brostallicin. High levels of GSH and GST are associated with resistance to most standard chemotherapy drugs
"Our phase I and II experience with brostallicin in over 160 patients demonstrates encouraging anti-tumor activity in a variety of solid tumors, with more than 50% of the patients experiencing at least disease stabilization," said Steven Weitman, M.D., of Systems Medicine.
The preliminary results from the first 21 patients treated in the phase I combination trial with cisplatin showed similar results, with 14 of the patients experiencing stable disease and half (50%) of those 14 patients having durable stable disease for more than six cycles of therapy. Toxicities were mainly hematological and were manageable and reversible in this heavily pretreated patient population

Viewpoint #2

Cell Therapeutics stock falls on treatment study results

Seattle's Cell Therapeutics Inc. reported the results of an early-stage study of a cancer treatment, which combines two drugs, brostallicin and cisplatin, Wednesday. Of the 21 patients with tumors treated in the study, 14 did not show any changes -- positive or negative -- in the progression of their cancer. Cell Therapeutics said side effects were manageable and the company expected to advance its studies. The company's stock fell about 17 cents, or about 6 percent, to close at $2.38 on the Nasdaq stock market.

I believe it was John Allen Paulos who pointed out the medical science can be easily corrupted by psuedoscience. Sick people can either get better, stay the same or get worse. The first 2 situations can be attributed to your drug. Once you apply statistics you have protected yourself with "science". Two thirds of the patients in the Cell Therapeutics study stayed the same. They did not get better. Is this positive news?

More on CTI

http://seattletimes.nwsource.com/html/businesstechnology/2003670653_cell18.html

The Year Gone By

I'll let the Seattle Times lay it all out for you. They are so much nicer than me.

http://archives.seattletimes.nwsource.com/cgi-bin/texis.cgi/web/vortex/display?slug=biotech12&date=20071112&query=biotech

I've been silent for so long waiting for one big write-up and here the Seattle Times has done it for me. But I will make a few comments regarding the future of Seattle Biotech. The Accelerator companies will soon be facing tougher customers now that they have obtained multi-million dollar payoffs. Of course their investors assume they are just taking off. Cargo Culters know that the main goal is to get paid. The secondary goal is to get out before the S hits the fan. 2008 will be a critical time for VLST and Spaltudaq. Homestead may have already disappeared without any official notice. No thoughts on the others.

So I raise a glass and toast the Cargo Cult Airport otherwise known as Seattle Biotechnology. Many a flight was cancelled or delayed this year. But we'll keep looking up. The Cargo Cult Scientist is always on the lookout.

Video - CNBC.com

Video - CNBC.com

Nastech

RNAi has finally been mentioned in a Nastech press release. They are spinning of the RNAi research into a subsidiary company called MDRNA. And the stock went up on this news!

While Nastech themselves had 5 years to create an RNAi drug, they are now claiming that the new company, MDRNA, will be seeking funding in the near future. Nastech screwed up the rest of their company so badly that they must now cut out RNAi research in order to survive. In the process they intend to send out their business people to ask for more money.

We here at the CCS would like to meet the people who intend to invest in MDRNA. We got a nice bridge we'd like to sell them.

Philosophy

Oh what a tangled web we weave...

Annonymous qoute from an annomymous boss at my annonymouse biotech job.

"We can't use that control because it might not work out how we want it to. If it casts a shadow over our drug candidate we're screwed."

Ah the joy of science.

And now for a countdown of some of the consequences for leaving out proper controls.

Point Therapeutics (POTP) Cuts 76% of Work Force. Recent interim clinical results led the Company's Independent Monitoring Committee to recommend stopping the Company's two Phase 3 talabostat studies as a potential treatment for patients in advanced non-small cell lung cancer, and the talabostat clinical development program was subsequently put on clinical hold by the FDA.

ImClone Systems Incorporated (IMCL) Says Erbitux Fails in Lung Cancer Trial More...
Endo Pharmaceuticals (ENDP) Says Patch Fails 2 Late-Stage Trials; Shares Fall More...
Antisoma PLC (ASM.L) and Novartis Corporation (NVS) Drug Fails in Ovarian Cancer More...
Amgen (AMGN) (Jobs) and Daiichi Sankyo, Inc. Reach Deal on Bone Antibody More...

I threw in the Amgen story because I used to work with RANK ligand and one of the lead scientists at Amgen on the RANK ligand project. Amgen sent this scientist packing back in 2001. They didn't believe in the drug. This would never stop them from making a deal however. Good people.

Controls in the early stages of research would only put us out of work faster. Sorry cancer patients but we're going to keep trying to make these old drugs work. We don't have the time nor money to find new ones. Keep your fingers crossed. We do the same things when working without proper controls.

Cargo Cult Promotions

I mentioned the unusual deal between Zymogenetics and Bayer.

ZymoGenetics Establishes Global Collaboration With Bayer HealthCare for Development and Commercialization of Recombinant Human Thrombin6/19/2007
ZymoGenetics to receive up to $198 million plus royalties, including up to $70 million in 2007
Bayer HealthCare acquires product rights in all markets outside the U.S..

Not a very good deal considering Zymogenetics reported net losses of 130 million in 2006, 78 million in 2005 and 88 million in 2004. I mentioned a possible Cargo Cult connection of creating the illusion of a company on the move. The executives thus position themselves for rewards.

SEATTLE, July 2 /PRNewswire-FirstCall/ -- ZymoGenetics, Inc. today announced that Douglas E. Williams, Ph.D. has been named President of the company. Bruce L.A. Carter, Ph.D. will continue as ZymoGenetics' Chief Executive Officer and Chairman of the Board. James A. Johnson has been promoted to Executive Vice President and will remain Chief Financial Officer and Treasurer. Darren R. Hamby has been promoted to Senior Vice President, Human Resources. All three promotions were made effective July 1, 2007.

Promoted into jobs that didn't exist yesterday? Pay increases? When will Zymogenetics turn a profit? Now that senior management is now more... um... successful, perhaps the company will follow in their footsteps.

Back

I took some time off after starting my latest job in the biotech industry. A lot has gone on. Dendreon received a favorable evaluation from an advisory panel evaluating their Provenge drug. The stock from 7 bucks a share to over 20. Then the FDA asked decided more trials were in order sending the stock back down to 7 bucks again. Later a grass roots effort was put in motion where investors and prostate cancer advocacy groups started lobbying to get the FDA to change their minds. Hmm. Cramer (Mad Money) has stopped touting Nastech now that the stock has been sinking slowly but surely for the past month. Luckily Cramer picks stocks left and right and never has to discuss the ones that tank. He reminds the one of John Edwards amazing ability to speak with dead people. I'm seeing a hot company. Nazzzzzz... a nasal spray company... anyone??? Zymogenetics signed a deal with Bayer to market their Thrombin drug which will be competing with the already approved Thrombin drug from King Pharmaceutical. The deal was amazingly underwhelming financially leading one to wonder if the executive staff has a clause in their contracts to bring a drug to market or else. In general, nothing scientifically interesting has happened, just the same old tricks.

The real excitement for the Cargo Cult Scientist is to be around industry insiders who have their own stories to tell. Forging data, hoodwinking investors, and all of the usual subjects are alive and well. In the future I will try to get a few good stories. We have the GE Healthcare sales staff who point out the lack of activity coming from Amgen. We have the ex-Icos employees struggling to find new work. We have the re-structuring of R&D at a couple companies. We have plenty to work out.