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Short Topics From All Over

(1) Bnet Pharma on “How Not to Write a Pharma Press Release“. Privately held Epeius is sending out bulletins loaded with phrases like “more stunning results” and “Epeius Biotechnologies draws the sword of targeted gene delivery from the stone of chemistry and physics”. If they were publicly traded, this would be fun to watch. . .
(2) The rise of Micropharma? We’ll come back to this subject:

The drug discovery pipelines of the major pharmaceutical companies have become shockingly depleted, foreshadowing a potential crisis in the ability of Big Pharma to meet the pharmaceutical demands created by the ever-changing spectrum of human disease. However, from this major crisis is emerging a major opportunity, namely micropharma – academia-originated biotech start-up companies that are efficient, innovative, product-focused, and small. In this Feature, we discuss a “new ecosystem” for drug development, with high-risk innovation in micropharma leading to Big Pharma clinical trials. . .

(3) Cleaving amyloid precursor protein into beta-amyloid has long been thought (by many) to be the key pathological event in Alzheimer’s. But what about the piece of APP that’s left inside the cell?
(4) A favorite post around here for some time has been “Sand Won’t Save You This Time“, about the wonderfulness of chlorine trifluoride. Well, here’s a method to produce very interesting-looking compounds that uses. . .bromine trifluoride. How much do you want these products, that’s what you have to ask yourself. To be sure, the authors do mention that “Although commercial, bromine trifluoride is not a common reagent in every organic laboratory, and many chemists do not feel at ease with it because of its high reactivity. . .”. You have to go to the Supporting Information file before you start hearing about freshly preparing the stuff from elemental fluorine.

35 comments on “Short Topics From All Over”

  1. Jose says:

    Oh wow, “biotech start-up companies that are efficient, innovative, product-focused, and small” !! is just too damn precious for words…. ’cause you know, macrobiotechs aren’t innovative *or* product-focused, right? And a staff of three that has to drive across town to get an LCMS or NMR is sure to be exceedingly efficient, right? Bwahhhhhhhh!!!

  2. They should have used the name “Excalibur”. It has a much more positive ring to it than the generic noun “sword”.
    “Epeius Biotechnologies draws the Excalibur of targeted gene delivery from the stone of chemistry and physics.” See? Much better.

  3. gyges says:

    @Jose – I’m in partial agreement with you except … often, micropharma doesn’t pay rent, wages, disposal and analytical costs. If the project goes pearshaped they can just continue with their day jobs (academics/post docs). Consequently, anyone wanting to compete against these parasites aren’t in a position to do so on a level playing field.

  4. CMCguy says:

    In terms of micropharm there may be two of the adjectives that do apply well in that likely will be small and very possibly offer innovative approaches. I do have doubts about gain in efficiency and product-focus aspects as most will not be aware of all the steps required or will not even be able to define what the ultimate product is. Of course pharma continuously struggles with all these and as gutting of organizations continue will seek “easy solutions” such a micropharm dependency as the next great paradigm shift.

  5. Rhenium says:

    From the SI…
    “BrF3 tends to react very exothermically with water and oxygenated organic solvents such as acetone or THF. Alkanes, like petroleum ether, cannot serve as a solvent either since they too react fast with BrF3. Solvents such as CHCl3, CH2Cl2, CFCl3 or, if solubility is not an issue, any perfluoroalkane or perfluoroether may be used. Any use of BrF3 should be conducted in a well-ventilated area, and caution and common sense should be exercised.”

  6. Sushila says:

    Speaking of chlorine trifluoride etc, would like to request more “things I won’t work with” posts!

  7. bad wolf says:

    Micropharma might be a great approach… to microproblems. Then, anything with broader applicability or passing Phase 2 or 3 can get snatched up by a macropharma that just fired its research division.

  8. reb56 says:

    1) Doesn’t micropharma depend on pharma people with jobs (so they don’t have to get paid) – you know, the people who are being outsourced/laid off at an alarming rate? Most people on unemployment are worried about spending their money on trivialities like rent and food, rather than doing the NMR of the brown mud they just made in someone’s basement?
    2) What happens in the future when potential drug chemists see that the only jobs in their field are in other countries (and at far lower wages)? Where will the pool of people to do micropharma be?
    3) If the FDA is (over)worried about drug safety, how is micropharma (who probably has fewer resources and less willingness to run trials than smaller pharma companies who were already uneager to run them) going to help matters?
    Other than as a rationalization for pharma to continue the outsourcing festival (because other people will be doing your discovery research for free!), and as a potential boon to unemployed VCs and universities selling equipment time and space to make ends meet, I don’t see how micropharma solves anything.
    As a bonus, if micropharma does get big, I wonder if states will have to include it in all those meth lab cleanup laws for home sales.

  9. Lucifer says:

    Innovation and big top-down byzantine bureaucracies do not mix.

  10. milkshake says:

    I was curious about that BrF3 paper myself last weekend because CF3 N-substituted amides could be useful way of busting patents (notwithstanding the horrid way they made them). Apparently BrF3 can be handled in Freon solution in glassware. But I have seen a geology lab that used a similar reagent (I think it was BrF5) to liberate elementary OXYGEN from silicate sample for oxygen isotopic analysis

  11. Lucifer says:

    Micropharma makes sense only if it funded through the government, in a Keynesian manner.
    If the government gives a grant to cover wages of a few people + CRO work for 4-5 years + reasonable access to instrumentation- it could work. However grants would have to be given liberally and be not based on peer review. Funding innovation requires support of non-peer approved ideas.
    The catholic church is an excellent example of where peer review takes you..
    However in the current bureaucracy heavy, innovation averse, BS saturated environment- it will not succeed.

  12. Mercury says:

    There is nothing magical about being small, but just think of the numerous errors that a micro-sized organization cannot make. Bloated projects teams, deeply nested hierarchical structures, cumbersome bureaucratic procedures, clueless ‘support’ departments… There thing you cannot have by default, if you are small enough.
    But yes, there are disadvantages as well. Therefore the real art of R&D management is not to think small in a small organization, for that is easy. It is to think small in a big organization. And very few of our managers have mastered it.
    In der Beschrankung zeigt sich erst der Meister.

  13. Ed says:

    Would an alternative not be syndicates of micropharmas loosely tied together by groups of universities, charities or VCs? You’d have the benefits of being small as individual units, but hopefully capture some of the advantages of being a little bit bigger.

  14. From the abstract for the paper using BrF3:
    “The reaction is performed under mild conditions ”
    Excuse me? Can they get away with calling it mild conditions just because they don’t heat it?

  15. metaphysician says:

    No kidding. I did a double take on reading that, and wondered on what planet any reaction involving reactive halogens could be called “mild conditions.”
    And even if it starts mild, it sure isn’t going to stay that way!

  16. Hap says:

    According to Cotton and Wilkinson, BrF3 isn’t as reactive as ClF3. That’s good to know. How much less reactive, though, it doesn’t say – it’s apparently fairly high up the reactivity hierarchy of fluorinating agents.
    This just seems like the chemistry stanza of “How Bad Do You Want It?” – I’d have to have a pretty good idea that trifluoromethyl amides will do something good to go through this to get them (and even then, to find someone who can work this out on big scale if they work really well). If you could generate BrF3 in situ, maybe this would be OK, but I don’t think too many people will be making trifluoromethyl amides if the day making them starts with BrF3.

  17. Cellbio says:

    I am currently working in a “micropharm”. I can share that having academic colleagues that can return to their day jobs is not a good thing (they will never actually leave them anyway). Small companies are supposed to be adaptable and efficient, but not so if they work at the pace of academic labs, and as a second priority to grant deadlines, publications, lecture tours and summer downtime. I believe, for many reasons, that the VC model is flawed, but one thing they got right was removing control from the academics. Not slamming academics, but commercialization of ideas is a very different world than idea generation.
    As for having the knowledge and resources for clinical trials etc, the idea is to partner early, relying on the infrastructure and capital of megapharma to handle these large tasks.
    What gets me about the topic is the idea that this is new. It is biotech. It is biotech in an era that can no longer provide capital to become a fully integrated company. For many years before the meltdown, almost no ventures were started with the belief that the company would carry the asset to market. That era ended long ago, replaced by the hope of having megapharma buy your company, perhaps because it was the only free standing antibody/RNAi/Longevity play left after previous foolish acquisitions. Not the same market today. The main thing new about today’s “ecosystem” is the price you can expect for the sale of your asset. That part is clearly closer to the “micro” side of the scale.

  18. Jack Daniels says:

    You forgot Astrazeneca is buying out its entire salesforce. Chinese replacements (pod people) will be springing up at a local hospital near you!

  19. Hap says:

    If you have nothing to sell and no one to sell it, how do you make money? Magic?
    Does the placebo effect work for stock?

  20. Lucifer says:

    Shhh.. Don’t give them any more ideas.
    On the other hand, Goldman-Sachs might be already working on that idea.

  21. MTK says:

    Jack Daniels,
    They’re not buying out their entire sales force. They offered packages to the entire force. They know darn well that not everyone is going to take it. In fact, they’ll probably have less than they want take it, which will then lead to layoffs.
    I actually think this is a better approach than just laying off the target number. At least they’re giving people a chance to get out before being shoved out.
    I think your Chinese pod people comment speaks for itself.

  22. Hap says:

    I guess if you have less stuff to sell, having fewer salespeople makes sense – it’s probably better in the long run, given that overselling of products has given pharma many recent headaches and bad returns. Of course, where are you going to go as a pharma salesperson at the moment? It doesn’t seem like there’s a lot of jobs here, and I don’t know how much job mobility drug salespeople actually have.
    Does getting rid of salespeople mean worse things for A-Z’s impression of its long-term business than getting rid of R+D?

  23. InfMP says:

    Note that one of the author’s current address is at the hospital…

  24. Anonymous BMS Researcher says:

    Hap on October 19, 2009 5:48 PM wrote…
    > Does the placebo effect work for stock?
    As best I can tell, a good chunk of the stock market IS the placebo effect, alternating with the nocibo effect.

  25. doctorpat says:

    The chinese companies I work with are swapping out their chinese sales force and replacing it with westerners. The pay is higher but the extra sales make up for it. (If I abandon my technical job and take a sales position, my after tax income will probably increase. Mmmm…)
    As far as pharma is concerned… you could be excused for thinking that in the future, a lot of “sales activity” will be banned. So downsize now while the poor schmucks think they’ve got other jobs to go to. The future will depend on political lobbying, which is a smaller, but much higher paid sales team.
    And was I the only one who noticed a recent episode of the spy thriller “Burn Notice” mention ClF3 as a suitable chemical for making bombs?

  26. cliffintokyo says:

    How about inviting suggestions for suitable nicknames for ‘reagents I would not work with’?
    My suggestion for BrF3: Brute Force 3

  27. metaphysician says:

    That brings to mind the idea that BrF3 is third most brute force way to react stuff. Presumably, this means ClF3 is Brute Force 2.
    I can scarcely imagine what “Brute Force 1” would be. . .
    ( FF3? I imagine if someone figured out a bizarre thermodynamic alchemy to formulate the stuff, it’d make ClF3 look cute and cuddly. . . )

  28. cliffintokyo says:

    Good thought.
    A strong candidate for ‘Brute Force 1’ would surely be hydrofluoric acid (ouch!)
    Actually, I was anticipating more out-of-the-box ideas for names; how about ‘Hyper Flu’ for HF?
    This name would also have the merit of being satisfyingly confusing and mystifying to chemistry *non*-cognocenti…in the sense they would not know W-T-H you are talking about…. [influenza perhaps?!] ;-))

  29. Reactive Species says:

    Hmmm… The N-CF3 group seems like a unsavory functional group. I bet it is just waiting for you to turn your back so it can eliminate F- to form N=F2 and then react with any number of nucleophiles. Anyone ever see a group like this make headway in a lead compound?

  30. metaphysician says:

    . . .
    . . .you know, I never would have thought I’d see a molecule that scares me more than CF3. But an N-ClF3? Universal solvent/oxidizer/halogen poison is bad enough, but US/O/HP that *wants to explode*?
    *notices its N-CF3, not N-ClF3* Oh. Nevermind.

  31. cliffintokyo says:

    Observing the lack of cognocenti skills…. reacts by exploding, with mirth
    [ClF3: Cool Freak, perhaps?]

  32. Hap says:

    F3C-amides might not be so bad – the CF3 should be more hindered than a standard Me group, and the fluorines should pull electron density out of the N so that the N is less likely to simply push out fluoride and generate a heinous iminium ion. The amide is also borrowing the lone pair. I don’t have any actual experience, though, and I still wouldn’t be eager to experience BrF3 to make one. Can one couple CF3 halides with amides instead?
    Someone here mentioned NF2 compounds though – those would make me nervous. SF5 isosteres wouldn’t thrill me, either, but I think they’re not so reactive as one might think at first.

  33. Anonymous says:

    Interesting discussion.
    Yes, fluorine substitution provides all kinds of surprising changes.
    Organic acid fluorides (RCOF) are fairly stable, often crystalline solids, not very reactive, unlike acid chlorides (e.g. acetyl chloride).
    I only know from once having made one accidentally.
    (I did not lose my job for being *inefficient*, so you can guess which companies I was *not* working for at the time)

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