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.

Cinders

In honor of Mr. Cinders:

"My relationship with cats has saved me from a deadly, pervasive ignorance." -William S. Burroughs

"Do you have a cat? Or cats? They sleep baby. They can sleep 20 hours a day and they look beautiful. They know there's nothing to get excited about. The next meal. And a little something to kill now and then. When I'm being torn by forces, I just look at one or more of my cats. There are 9 of them. I just look at one of them sleeping or half-sleeping and I relax." -Charles Bukowski 4/16/92 12:39 a.m.

Couldn't find a good quote but Jack loved his cats!

Cinders came to me on a rainy day in fall. He was hiding from the cruel world on the cold pavement underneath my truck. When I stepped out to go to work he came up to me. He seemed to be asking for help. I sat down and let him warm up on my lap. When I got up the next day he was there again. He eventually came into the house through the dog door. He had a good end to his life. We did not force him to live and die slowly like we do with humans. I said good-bye and went home without him. This was very hard but it reminded me to take more time with the people (and animals) that I love. Life is not about quantity it is about quality. Cinders added a certain quality to this life.

As Tough Times Loom...

SAN DIEGO--(BUSINESS WIRE)--Ligand Pharmaceuticals Incorporated (NASDAQ:LGND - News) announced today that it is restructuring its business, pursuant to its new business model, by reducing its workforce by about 267 positions or approximately 76 percent.

LONDON, Feb 1 (Reuters) - AstraZeneca Plc (AZN.L: Quote, Profile , Research) plans to cut some 3,000 jobs, or 4.6 percent of its global workforce, to ensure future profit growth as generic competition bites and some key drugs start to mature, the company said on Thursday.

ZURICH, Feb 5 (Reuters) - Swiss drug maker Roche (ROG.VX: Quote, Profile , Research) plans to restructure its research and development activities around therapeutic areas to speed up decisions and increase efficiency.

A hard rain is falling. The scientists that are chucked out of the universities are not getting the job done. They are failing time and time again. They are using their scientific credentials to become businessmen. They are leaving the hardest part up to underlings.

A new paradigm must take shape. Scientists must return to the laboratory. They must figure out how to run clinical trials. The age of scientists as businessmen must end. Science is the way. The old way has brought about a hard rain, as Bob Dylan would say. A weeding out process must take place. Those who survive must emerge as scientists.

If Only There Was A Way...

LONDON, Jan 29 (Reuters) - GlaxoSmithKline Plc (GSK.L: Quote, Profile , Research) was accused on Monday of distorting clinical trial results of its antidepressant Seroxat, or Paxil, and covering up a link with suicide in teenagers.

http://www.ahrp.org/cms/content/view/444/29/

A classic study in career survival in the wild kingdom of a global corporation.

E. Howard Hunt,

MIAMI -- E. Howard Hunt, who helped organize the Watergate break-in, leading to the greatest scandal in American political history and the downfall of Richard Nixon's presidency, has died. He was 88.

Hunt eventually spent 33 months in prison on a conspiracy charge, and said he was bitter that he was sent to jail while Nixon was allowed to resign.

Scooter Libby is still alive, awaiting his punishment for carefully following the orders of Karl Rove and Dick Cheney and leaking certain information to the press. Rove and Cheney hatched the idea of outing Valerie Plame as a punishment for her husband Joe Wilson. Wilson, you will recall, had the audacity to release information from his fact finding mission to Nigeria to determine if they sold yellowcake to Saddam Hussein.

It's about dishonesty. Supressing information can be as bad as lying. It all began with supressing Joe Wilsons information. He (Wilson) wrote an article that was published in the New York Times thus working against the white house efforts to start a war. They (the white house) made the decision to release information that we (the American people) need to supress, the identity of our CIA agents. Plame and Wilson and the press wanted to know who released this information to the public. Then Libby and Rove and Cheney and all the rest of them began lying.

It is indeed a tangled web. The lesson for the science minded person is that honesty is not just about fact and fiction. It's about selecting data that fits your bias. You may begin by ingoring a piece of data that doesn't fit your hypothesis. Next you may get more agressive and try to discredit people who disagree with you. If that fails you will end up lying. A true scientist must work very hard from the beginning to stay off of this path. At all points you must keep your eyes open to make sure you haven't strayed onto it. Otherwise you are no better than a politician.

RIP Howard Hunt. Libby will carry the torch of dirty rotten scoundrels like yourself who lie and cheat to protect our highest ranking politicians. Let's hope Scooter gets at least 33 months for his part in starting the Iraq war. At least you, Howard, didn't do as much harm as Scooter.

Dead Investors Walking

The CEO of Cell Therapeutics had a stipulation written into his contract stating that he had to put a drug onto the market prior to 2000 or he would not receive a huge bonus for his services. Just prior to that date Dr. Bianco bought Trisenox, which was destined to be approved but not destined to earn much money. It satisfied Dr. Biancos contract but did not earn the foolish investors of CTI any money.

Now CTI, a desperate company, is vying for DOR BioPharma, Inc.

Under the proposed terms, Cell Therapeutics would issue the Company's shareholders 29,000,000 shares of Cell Therapeutics' common stock, representing 19.9% of Cell Therapeutics' outstanding shares of common stock. Warrant and option holders would receive shares of Cell Therapeutics' common stock in an amount determined using the Black Scholes pricing model. Cell Therapeutics has reserved the right to offer cash as consideration for the warrants instead of Cell Therapeutics' common stock. In addition, Cell Therapeutics is also offering the potential for an additional $15 million payment (in stock or cash at the Company's option) upon receipt of the approval of the U.S. Food & Drug Administration of the Company's new drug application for orBec®. The proposal from Cell Therapeutics is subject to, among other things, the completion of satisfactory due diligence regarding clinical, regulatory, manufacturing and proprietary positioning for orBec®.

What is Dr. Bianco up to now? DOR is trading for less than a dollar a share. They are currently at 40 cents a share, down 27% on the news of being taken over by the esteemed Dr. Bianco. They could make a movie out of CTI. As boring as science is, you could create the greatest film noir out of the life lead by Dr. Bianco. Just don't try to create a profitable investment from this person.

Pfizer Falls

Pfizer came up with a new plan. Take ten percent of the work force and get rid of them. Ten thousand human beings working on the Cargo Cult Airport known as Pfizer are going to be set free.

Pfizer, the world’s largest pharmaceutical company, said it would cut manufacturing sites in Brooklyn and in Omaha and would seek to sell a third site in Germany. It would close three research sites in Michigan and said it hopes to close one in Japan and another France.

Pharmaceutical industry analysts have generally been welcoming cutbacks by Pfizer but have said that while cost-cutting is beneficial, the company needs to resume growth by bringing new products to market. Still, Pfizer’s shares were trading down about 1 percent this afternoon.

Pfizer has been suffering from the loss of patent protection on key drugs like the antidepressant Zoloft and the antibiotic Zithromax. Sales of both drugs plummeted more than 70 percent in the fourth quarter of 2006, the company reported today.

At the same time its laboratories have had difficulty coming up with new hits. The company suffered a huge blow in December when safety concerns prompted it to halt development of torcetrapib, a cardiovascular drug that it considered the most promising experimental drug in its pipeline.

The number one drug company in the world today, with billions and billions of dollars cannot come up with new useful drugs. With all of the advances in biological science over the past few decades you would think it would be easier.

The truth about drug science is that scientists all work in cubicles, attend meetings and write reports. They do not go into the lab. After obtaining their PhDs they go out and do what they do best; they talk. They are trained to write grant proposals. They are trained to defend popular notions that they most likely did not think of themselves. They learn to take a certain tone of voice that makes people think they know what they're talking about.

The Cargo Cult Scientist spent a year interpreting DNA data to PhD scientists in the drug industry. These "experts" were too old to have learned molecular biology software. If, for example, they wanted to know if there was a mutation in a clone they had to ask me. The only way they could know the truth was if I told them. And then they had to trust me. Others, less important, could easily bring up the files in Vector NTI software and compare for themselves. They would be able to come up with the mutation if there was one. It's easy if you take the time to learn new things.

Senior scientists have put themselves in positions where they do not need white lab coats. This disconnect between how data is obtained and how it is talked about has created a lull in the productivity of new drugs. Arrogance is a factor. There is also a culture of accepting failure as the norm. So ten thousand people are losing their jobs at Pfizer. This is perhaps a good thing for the industry. Some of us need to find more productive careers. If that means putting on a Home Depot apron and helping people with home impovement projects, then so be it. Society needs helpers more than they do useless scientists desperately clinging on to their jobs. The receptionists, lawyers, accountants and all of the other "carpet walkers" did their jobs. The scientists did not. They failed and Pfizer has fallen.

Ironically, it will be scientists who help Pfizer get back on its feet. Can Jeff Kindler find the right people? Getting rid of the wrong people is a good start.

Give Til It Hurts

BOTHELL, Wash., Jan. 18 /PRNewswire-FirstCall/ -- Nastech Pharmaceutical Company Inc. (Nasdaq: NSTK) today announced the pricing of an underwritten public offering of 3.25 million shares of its common stock at an estimated total public offering price of up to approximately $42.9 million.

On this news Nastechs stock plunged 94 cents (down 6.69%) to finish the day at 13.12. I'm no stock market genius but offering a stock currently valued at 13.12 for 13.20 might be a hard sell. Time to learn about the old stock market and how it works. Lets keep an eye on this deal.

Think of Nastech as a Cargo Cult airline that carries piles of cash for the investors who are waiting in the Cargo Cult airport lobby. Each of their flights, PYY, PTH, calcitonin, have been delayed. The siRNA airplane is still waiting for take off at an undisclosed location (does this plane really exist?). The investors see someone making their way to the information booth. What could it be? Positive clinical trial results? A new break through in siRNA research? Ewww the anticipation!!!

They want more money? Son of a...

The 6 months stock chart tells the story of investor patience.

P.S. Nastech seems to be good at raising the stock price when it's desparately needed. Day traders should take a risk and buy in the morning and sell by the end of the day.