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Sunday, February 17, 2013

Covx, The Cult of Barbas

The last posts title was, 150,000 Jobs Lost Since 2009. Add another 100 or so losses from the ranks of Pfizer. Covx is going away. Started in 2002, Covx used phage display to make peptide-antibodies. Improving on natures invention of the antibody, Covx selected peptides that bound to target proteins (like an antibody) then they attached the peptides to a stealth antibody. The antibody protein is there only to stabilize the peptide and increase its bioavailability.

No one will talk about the demise of Covx like the Cargo Cult Scientist. The question we have is, and always has been, regarding the sustainability of the single target - single drug paradigm. We humans have thrown billions and billions into the paradigm and we haven't come up with much. Humans can still get rich in our current health/sick care system investing in this drug development approach. But are we really making any progress in treating disease? Do we understand how one protein can make us sick? How does one protein spin out of control, unregulated by the controls built into our DNA over billions of years, then suddenly become properly regulated by a single molecule that humans design in a few years tested at a few dosages? It seems highly unlikely that this actually works.

The CCS once worked with the laboratory that spun out Covx. Their phage displayed antibodies were sent to us in vials of various consistencies of goop. Our job was to take the goop and run western blots to verify binding to our target. Down in San Diego that merely had their technicians select candidate based on an arbitrarily selected ELISA signal. Anything above X was sent up to us at UCSF. Every single ding blasted frigg'n candidate was selected due to high background. We learned that they were panning their phage against completely denatured proteins. No structure! The day they started using non-denatured proteins to pan against was the day they started getting actual target binding antibodies. Those of us running the western blots were put through a humiliating few months of heavy criticism on our western blot skills.

Covx however was no different than most. They begin with the single target - single drug molecule paradigm. They have a technology to obtain the single drug molecule. A technology is a practical application of a science. That technology was not theirs originally. Phage display was developed by Dr.
George P. Smith at the University of Missouri. The folks at Scripps got ahold of a sexy new technology and ran with it. They made the Herculean leap from phage display technology to medical science. My personal knowledge that comes from experience indicated to me that they were lacking wealth in their technology system. How might they fare in the upper realms of science?

How can a group like this go on to form a multi-million dollar partnership? Some say the founder was awarded a couple hundred million dollars from Pfizer. Well of course the founder and a few at the top were the winners. The laboratory people are the ones who are suppose to  add those pesky details like having an actual test for target interactions. The leaders offer up the sexy narrative that attracts the investments. In our case, we were attracted to them by the narrative of getting antibodies quickly and for less money. In the end, we received ordinary antibodies that anyone with phage display skills could have provided. Ordinary...

Was Covx an ordinary phage display group that had an influential leader, Carlos Barbas, who excelled at the narrative? According to Pfizer, upon the acquisition of Covx:


CovXs biotherapeutic platform is a technology that links therapeutic peptides to an antibodyscaffold. The peptide targets the disease while the antibody scaffold allows the peptide to remain in the body long enough to achieve therapeutic benefit. The technology thereby allows half-life extension and bioavailability to support optimal dosing regimens for peptide therapeutics.
As validation of this technology, CovX has generated three early- stage compounds, one diabetes and two oncology compounds, that are expected to further strengthen Pfizers biologic pipeline portfolio.
Is it fair to say then, that "as validation" that this technology is just phage display, smoke and mirrors, Pfizer is sacking the entire staff of Covx? 
"We are pleased to transition the CovX technology to Pfizer's Biotherapeutic and Bioinnovation group and are confident they have the vision and resources to scale the platform and realize the opportunity to make efficacious drugs which will make a difference in peoples' lives," stated Shehan Dissanayake, Chairman of CovX and CEO of Tavistock Life Sciences.
I talked about a former gambler who decided it would be best to sell his picks rather than bet on them. For a fee he would let the gambler in on who he thought would be covering the spread that day. In a sense this is what Jeff Kindler and Corey Goodman did back in 2007 when they acquired Covx:
The acquisition of CovX is a further step in Pfizers strategy to acquire and identify new product candidates that we can put into development, leveraging both Pfizers expertise and that of world-class scientists charged with discovering and bringing in new compounds, said Jeffrey Kindler, chairman and chief executive officer of Pfizer. With this deal, we are building on our recent announcement of a new Biotherapeutic and Bioinnovation Center based in California and led by Dr. Corey Goodman. We are looking for the best science wherever we can find it, with a special focus in our priority areas, such as biotherapeutics.
 The ceremonial beginnings of Cargo Cult projects are always followed up by the rather unceremonious  announcement of their demise. It is sad to see so many people out of work. But we have to wonder if they were actually doing work, or were they focusing on the narrative offered by their leadership.

My friends you are getting tired of hearing it from me, but the cargo didn't come. Covx did not fail because the guys with the white lab coats were no good at phage display. They failed because the narrative was cargo cult. Phage display is real. We can select peptides that bind to targets. We can't make the binding lead to the outcomes described in the narratives.

Farewell Covx. Good luck to those who invested years of their professional lives on the Covx promise.

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Amusing and cultish but the venture capitalists make all the big money in deals like this. Certainly Barbas did not make hundreds of millions of dollars, that's silly yet cultish. I worked at CovX and the technology works! Several drugs (4) are now progressing in the clinic. Let's hope patients ultimately see the benefit.

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I think you use Phage Display as a synonym for everything and anything.....and by saying that Phage Display does not work you do know that Humira one of the worlds best selling drugs was developed using Phage Display?? And on top of that the COVX approach was not about Phage Display at all....it was about keeping peptides in the blood for longer and equipping them with antibody Fc effector functions.

But keep your conspiracy theories, no prob.
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