New CEO to announce outcome of new restructuring plan in Jan Feb, what's he going to say?
In my experience most lab-based scientists knew the values and limitations of their in vivo models very well - but higher levels insisted on this that or the other animal model of whatever because it was the essential disease model.
So, not so much a counter argument as a cry for help. You would do well to remember that the vast majority of the top 50 blockbusters over the past 30 years were not derived from HTS. In fact, we obtained them employing low throughput screens and the tradtional animal models that you criticise from your lofty position of ignorance. If you are not even aware of the basic history of drug discovery then your contribution is neither valid, informed or relevant. So, given that you are a walking metaphor for HTS and no doubt always in need of the last word on any subject, you may have it.
Utter, utter nonsense. You are looking for a simple scapegoat outside your own scientific discipline, that’s all. You lost it - and your job.
Sorry but that is utter nonsense. It is near impossible to obtain good, predictive animal models of human disease. Their limitations have always been appreciated by clinicians. What we could have done without was any respect given to that layer of self-serving stupidity that gave us screening of mixtures of compounds of questionable chemical integrity that had been through multiple freeze-thaw cycles in physiologicaly irrelevant assays in over-expressed systems employing either forcibly coupled receptors or non-endogenous substrates and ovary cells from Chinese hamsters. Compound that with routinely compromised data analysis and what you end up with is development saturated with sub-standard chemical entities. Poor animal models my arse.
HTS and fragment screening are just tools, some companies know how to use them, some don’t. Main issue is the reliance on piss poor animal models. Have you ever asked yourself WHY drugs fail in Phase-II even if all the animal data looked good? This has nothing to do with HTS.
I remember witnessing HTS 'in-action' with it's associated compromised data analysis and just feeling relieved that Sir James Black was not around to see it. He would have cried. Every company copied each other so we all shared the same flawed approach. Sadly, that now means we will all share the same fate. The Pfizer collapse was big, and so is ours. But for christs sake, open your eyes and see that this is only the start. GSK, Novartis, Merck, Abbot, BMS, Lilly, J&J, Shire, Amgen etc, etc, all use the same approach and have equally weak pipelines with major patent expiries over the next five years. What a fecking mess. So to all those button-pushers, the pioneers of HTS and the retarded management who let it all happen, on behalf of patients everywhere, thanks for nothing.
Amen to that. And let us never forget the pile of managerial dross produced by the 'More-Is-Better' approach. The easiest way to get promoted was to hit an easily achieved target e.g compounds screened, screens run etc. After all, numbers were the only things understood by the guys at the top. They were sold the argument that if we screened more, we should obtain a proportionate increase in the number of clinical candidates and hence marketed products. Bullshit. And that's not said in hindsight. There was significant vocal criticism of this approach during its early 90s birth. But of course, we were accused of being negative or too academic. And it's clear that exactly the same scenario has occurred in all big pharma. It is interesting that one of the great proponents of HTS from its early days at Pfizer was recently sacked by Novartis in the USA. Novartis are clearly worried by their empty pipeline and are trying to avoid a Pfizer/AZ style collapse by eliminating the robot-loving, numbers-oriented, power-point scientists. I agree, scientists should be driving the process again with management taking a background role and HR just fu&*ing off completely. But I think its too late for us. Personally, I don't see the Cambridge thing happening. I think the headcount reductions will simply make it easier for GSK to assimilate what is left. And given what happened to the Pharmacia, Wyeth, Warner-Lambert and King Pharma staff who did move to Groton (most were sacked after they relocated), does anyone really want to take the risk of moving themselves and family to Cambridge?
HTS isn't a problem - it simply kickstarts a process. The issue is failure to invest in basic study further down the line to understand what the outcome is doing and then being realistic in stopping chemical aproaches that have substantial issues rather than sitting around constantly discussing how these problems can be managed - as a long gone senior at AZ omce said (yup, they weren't all bad) problems only ever get worse as they progress in clinical trials. This attitude was seen as negative but was actually realistic. So, NCEs were propped up until they made expensive and often public failures - leading to a media wit observing that "if AZ didn't have bad luck they would have no luck at all!"
One of the principal reasons for the failure of Pharma to discover new drugs was the industrialisation of discovery ie the idea that the techniques to produce eg cars could be brought into pharma. Therefore HTS and associated chemistry with little real understanding of what was happening but what the hell the required number of hits and molecules were made so all was well with the world. Utter nonsense. We need to get back to letting scientists do the science, test the ideas and be allowed to think
Re Moderna deal
“I met with quite a number of companies, and nobody I’ve met understood it as deeply as Pascal [Soriot] does, in terms of what this technology can do,” Bancel [CEO of Moderna] says. At a breakfast meeting in December, the first meeting between Bancel and Soriot, they hit it off right away. “He got it in five minutes,” Bancel says. He adds: “Pascal was willing to pay what I was asking because he understands that this technology can do things in a profound way. It can treat disease in a way you can’t with other technology.”
$240MM - one of the biggest deals ever for an untested platform line and the CEO decided without any internal AZ help. Due diligence??? Well would you tell the new boss this is a really bad idea when he is already sacking so many???
A little look at Moderna - they only have 32 staff. And looking at the employee reviews on Glassdoor they are not a happy bunch - every last one of them. They raised $40MM last year so those VC's must be laughing all the way to the bank. Normally doubling your money in 2 years is what they are after. 8 fold increase in 1 year - Wow!!! The main thing Moderna have been doing is patenting, broad and deep. 100's of claims - this is often poor patent writing but hey, it is just marketing material. The whole area is a patent mess with everyone claiming everything and the attorneys getting rich filing. The only way to sort is out is to go to court but this won't happen because that only happens when someone gets a product and starts making money. Which ain't ever going to happen.
What 100% validated targets have AZ got for this expensive, untried platform technology that they couldn't do with the safer small molecule/biologic routes??? None??!!!
AZ is toast - 3 years max.
"The issue is not Big Pharma vs. CRO but more rational target selection vs. shots on target."
You make a valid point regarding the current strategy employed being flawed but then mess up your argument mixing it up with tactics (eg HTS - which is not as widely discredited as you make out. Its failures often go back to the flawed strategy above) and Ph3 failures which have more to do with safety/ differentiation/ commercial issues than target selection strategy.
I think we both agree that something needs to change or the whole industry (Big Pharma/Biotech/CRO) is gone. Personally I think AZ has run out of time/cash to turn around but would love to be proved wrong. Good luck.
AZs issue has been drugs failing in phase 3 clinical trials. These drugs have been developed inhouse AND bought from CROs.
The issue is not Big Pharma vs. CRO but more rational target selection vs. shots on target.
Big Pharma and CROs have, through the use of widely discredited technologies (HTS etc), applied the "if you shoot enough times, you're bound to score" philosophy to medicine development. Clearly this is wasteful - but in good times it was acceptable; to mis-quote Jurassic Park - the technology allowed them to do it but they didn't think "should we do it"
In more "enlightened times", we need to be focusing more on getting a single molecule through to the market, and that requires increased understanding of both the target and the molecule (and to some extent, the Market in to which you'll be launching).
Don't, by default, link the Big Pharma model with failure and CRO model with success. Both are equally dead if they continue with the old approach.
"I don't understand why big pharma cannot do R&D and everyone thinks bio tech and CROs can. Is it because they employ poor scientists in big pharma or poor management. Or is it CROs etc are just dressing up what they do/achieve"
I've worked in both biotechs, CROs and big pharma. Poor management has messed up big pharma. Biotechs & CROs massively big up what they can and have done. Nothing good will come out of the CROs. Perhaps something out of the biotechs, but probably an even less efficient model than in-house research. Question is, how long until the pendulum starts to swing back towards sanity.
"Pharma has to make less profits and needs to work for the common good"
Now here is a dilemna - Major pharma needs to keep its investors happy, they will move their cash unless the profits give the same returns they can get elsewhere. Drug R&D needs some philanthropy or altruism and big pharma can't provide it!
Get used to it. Pharma has to make less profits and needs to work for the common good. Making a profit of 20 percent is pretty fantastic compared to 33 percent
So you are saying management.
A biotech company often starts as a result of an idea that shows promise and once they have projects mature enough for Phase I/II/III chances are moderately good that it will succeed. Big Pharma R&D forces people to try to come up with ideas within areas that may not work and pour loads of resources into projects that will fail before FTiM. Internal projects that make it past this point have a history of investment into them and there is a reluctance to drop them and they are pushed too far before they are dropped. A good idea born in a Big Pharma is not pursued if it's not within the box that management has described...
I don't understand why big pharma cannot do R&D and everyone thinks bio tech and CROs can. Is it because they employ poor scientists in big pharma or poor management. Or is it CROs etc are just dressing up what they do/achieve
"Welp, I reckon R&D has 18 months before AZ bails out. Soon we follow the standard R&D model, buy small biotechs and get rid of internal R&D. AZ to focus on clinical development, only we're 4 years too late, compared to the rest
4 Years behind who? Which other big Pharma have completely pulled out of R&D? Novartis? GSK? Pfizer? Sanofi? Talk about ridiculous scaremongering for no reason"
I agree with both of you.
1) This should've been done five years ago.
2) All other "Big Pharma" are also in similar positions and need to make drastic changes too...
"Welp, I reckon R&D has 18 months before AZ bails out. Soon we follow the standard R&D model, buy small biotechs and get rid of internal R&D. AZ to focus on clinical development, only we're 4 years too late, compared to the rest"
4 Years behind who? Which other big Pharma have completely pulled out of R&D? Novartis? GSK? Pfizer? Sanofi? Talk about ridiculous scaremongering for no reason
Welp, I reckon R&D has 18 months before AZ bails out. Soon we follow the standard R&D model, buy small biotechs and get rid of internal R&D. AZ to focus on clinical development, only we're 4 years too late, compared to the rest.
Purchase of CAT was largely funded by cutting inflammation research at AP, now a deal for RNA-based products is costing the rest of their research.
Name one product currently sold by AstraZeneca/MedImmune that originated by the CAT team in Cambridge - there isn't one - yes they made products for Abbott and HGSI - no they have not made a single product that is currently sold by the company.
The reason AZ failed to produce the goods is down to management - from senior management to middle management. Its that simple. Firstly you have stupid metrics and appraisal systems designed to hack off scientists and prevent them from doing research. You cannot have section managers who haven't been in the labs for 20 years telling research chemists they are not allowed to submit compounds containing nitro, aromatic amino or cyano groups for starters. You cannot have "modellers" telling chemists what to make based on whether it fits the modellers virtual site. Its lunacy. Proper research wasn't allowed at AZ and that's why it failed. If the same style of management appears in Cambridge its doomed from the start.
Alderley and Charnwood were botrh like that. Difficult to move on from, cheaper places to live than Cambridge & south east etc. So people stayed on (& on, & on) when the firm was overall shrinking. Meant many staff were promoted to fairly irrelevant, unneccessary project leader, senior scientist, etc roles on a more-or-less time served basis. Which stuffed up the company with relatively non-productive quite senior (costly) mid-managers'. Hence much of the poor morale low productivity.
In case anyone failed to notice, several sites have closed to R&D over the last few years and Alderley is just the latest. The new site at Cambridge could be a great place to work - free of the risk-averse culture and over-management, with better IT, more cash to invest maybe. I hope so.
Which is the point. The AP culture is not so much risk-averse as self-congratulatory. Sorry - but there are so, so many people there - and not just managers - who should have "moved on" or been "moved on" years ago. But why didn't they? Nowhere to go! By relocating to Cambridge you get - more than anything else - a unit that is more diverse, more open to change and capable of vibrancy and self-renewal. I am all for it.
"2013 is the expiry date for the lucrative redundancy T & C's put in place 20 years ago to stop the aggressive takeover of Zeneca by Hanson"
This is a half-truth - there was no 'expiry date'. AZ would have changed T&C's already if they could.
AP in Cambridge will never open as R&D. Promise. In a year we will hear: "Ops there is no money for that".
apparently there are no changes to the redunancy packages till 2016. Not bad if you are pre 2006 then eh?
2013 is the expiry date for the lucrative redundancy T & C's put in place 20 years ago to stop the aggressive takeover of Zeneca by Hanson - is this coincidence ? Whatever the reality, having worked at several AZ R&D sites before leaving of my own accord, I can tell you AP was the worst by far - weird anachronistic place. The announcement this does not surprise me
AP will continue R&D for another couple of years. 2013 was the year the redundancy T&Cs were going to be reviewed. Does this mean that by the time people are leaving their jobs they will be getting the reduced payment?
To all ex-colleagues still at Alderley, just accept the reality that Astrazeneca don't want you anymore, thats why they are exiting.Take the redundancy money and run.To those at Macclesfield you have been spared for now but are living on borrowed time. its a question of when they close you and not if.
In the webpage accessible via this link is another link to the presentation given to investors yesterday.
Its just frustration
the beatings will continue until morale improves......
Rank and file can only screw up if managemebt system is inept - anywhere, not just AZ
2 years on and the same BS.
....real scientists, the workers, the soldiers.... blah blah. You are the cynics that kill off any spark of innovation and now you have killed of your jobs.
Hear hear! The last few days has been my worst ever at AP. Not because of what was announced but by all of the BS moaning by the ground down scientists that would bring the company back to its former glory if only someone would have let them. Take a hard look in the mirror people!! - YOU SCREWED IT UP FOR THE REST OF US!!
All towns close to Cambridge
Related to the just announced $420M-plus deal just announced by AstraZeneca, perhaps someone should tell the CEO at AstraZeneca about U.S. Patent No. 8,278,036 entitled “RNA containing modified nucleosides and methods of use thereof,” which issued on October 2, 2012. As will be clear from reading the patent, that the use of modified mRNA comprising any of the various recited naturally occurring modified nucleosides to express a protein in human and other mammalian cells was invented and demonstrated for a variety of therapeutic and other uses by Drs Katalin Kariko and Drew Weissman of the University of Pennsylvania. As is well known by Moderna, this technology is exclusively licensed to CELLSCRIPT, INC.
"MITP, Leadership Capabilities, Lean Sigma, Knower/Learner etc .."
Has this BS ever been applied successfully in the pharma. industry? Ever considered that the creativity and innovation required by scientists is stifled by this crap hence its lack of success? Wonder what have happened if these initiatives had never been introduced and we'd just been allowed to continue with our 'haphazard approach' - certainly no less unsuccessful and a darn sight happier and ironically probably more 'productive'. What's more we might have lost all of the morons who championed all this, as once promoted to their level of incompetence there would have been no place to hide.
I did over 17yrs, the last 12 were under middle/senior management increasingly believing in this BS. Some became different people in their pursuit of greatness.
"MITP, Leadership Capabilities, Lean Sigma, Knower/Learner etc ..
I was with AZ for 15 years. In my humble opinion all the initiatives above were sound if people had/took time to understand and learn from them."
I was with AZ for 12 years, and in MY humble opinion the whole "Culture" movement, including Knower/Learner, is about the sickest I have ever experienced. A colleague who knew something about the old Soviet union found striking similarities between the communist brain wash and the AZ Knower/Learner concept. The idea that all people should fit into the same mould and behave exactly the same is a huge joke. AZ paid vast sums of money to a US consultant company to introduce this BS, which poisoned our lives during the period 2010-2011.
"Middle management appeared to be obsesed with doing everything according to the correct procedure, which involved a multitude of boring meetings with people who there was really no rationale to involve..."
Same when I was with O-CD. My US manager more concerned with the process of running the meeting (and scoring it for various irrelavent critiria) than the outcome.
Where are the new products, guys?
All quiet at Macc?
Don’t fool yourself.
I came to the UK 15 years ago - the UK, land of milk and honey, paradise island, Oxbridge, the city, a new economy, no more boom and bust, house prices always go up, the new Jerusalem, bla bla.
So, what’s left?
Traditional drug R&D certainly gone fron UK for, what, 10 years. AP will be running on empty untilb it closes, slowly leaking its staff away and the new site will take years to fully build, staff & establish any sort of project portfolio. For several years projects will be old favorites of new staff from past company or academic interests.
Boston, Bay Area, Basel left over.
R+D in UK: gone.
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