8/6/18

Investing/Biopharma
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Ovid’s data look flimsy.

Opdivo and Keytruda are approved in China. CStone and countless others are in pivotal trials. AstraZeneca has a long history in China and you can bet will register Imfinzi there. I’m not sure what Roche’s or Pfizer’s ambitions are, but they also do strong business in China and have globally registered PD-1s. So there are at least 6 PD-1 mabs I can name off the top of my head that are China-approved or likely to be that do not come from Beigene. But Beigene has a very large market capitalization. This will not persist. I have not seen something like this in a long time.

Lots of interesting companies to look at. Constellation, Summit, Fibrogen and so many more. Not enough hours in the day!

Is the world ready for biosimilar orphan drugs? Cerezyme and Myozyme aren’t tiny. I guess we have a few “me-toos” but they’re not cheaper.

Interesting article in JAMA my father sent me on body dysmorphic disorder and social media photo editing software as a trigger for this disorder. BDD is real: if you’ve ever seen someone with large amounts of plastic surgery, they likely suffer from BDD. But there are plenty of people who suffer quietly. Most people are probably unconsciously affected by societal progression of beauty standards. There’s a reason I’m attracted to Lindsay Pelas and Jen Selter–it’s mostly because I’m a man and they largely embody deeply inherited/evolutionary desires of man. So what if they understand that and have perfected it? We’ve reached the singularity of female desirability and the technology-enabled enhancement (both photographical and biological) of it. What’s next? I don’t know.

Always study the history of the industry you’re following. For biopharma, be familiar with companies like Cetus, Chiron, MedImmune, Centocor, Immunex, HGS, Genentech, Genzyme, Idec, Millennium, ICOS, Vicuron, Athena, Genta, Sugen, Warner-Lambert, Pharmacia, Syntex, Abgenix, Triangle, CV Therapeutics, Pharmion, Sandoz, Ciba-Geigy, RPR, ICI, Aventis, Parke-Davis, Scios, COR, Imclone, Medarex, Atherogenics, Telik, Tularik, Intermune, Elan, Northfield, Vion, GenVec, Cell Genesys, Pharmasset, Idenix, ViroPharma, NPS, Myogen, MGI, OSI, Synta, Trimeris, TKT, Aviron, GI, Tanox, and so many more. There is some wisdom in history. You have to mine for it, distill it.

Papers I’ve Read
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Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. Dovey et al. J Neurochem 2001.
I guess this Elan/Lilly paper started the whole semagacestat/gamma-secretase mess. They go up to 200mg/kg (!!!) dosing in these experiments with their putative GS inhibitor DPAT. Its very hard to trust any of the data given what we know now about APP processing and intracellular retention. Still, you can see the errors in judgment with the high-powered lens of hindsight. It’s also funny to see what passed for a screen in 2001.

The gamma-secretase inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester Reduces AB Levels in Vivo in Plasma and Cerebrospinal Fluid in Young (Plaque-Free) and Aged (Plaque-Bearing) Tg2576 Mice. Lanz et al. JPET 2003, 305:864-871.
Pharmacia workers “replicate” Dovey. Same issues. I think everyone was okay with the 100-200mg/kg dose given low brain partitioning and a cell-based assay affinity of ~100nM. It’s really hard to tell what these ELISAs are picking up and what species are relevant for aggregation.

Personal
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I’ve received around 500 books by mail since I entered the prison system. There is a Twilight Zone episode, “Time Enough At Last” (I think that’s what it is called!), that summarizes my feelings on having a lot of time to read. It’s a joy, but I don’t exactly have the shelf space. I probably have around 50 books here at Fort Dix. This is still far too many. So, please don’t send me any books without my knowledge! They will probably end up donated or thrown away. Also, if you mail me, it must be in a plain white envelope with plain white paper. No stickers, glitter, or contents other than paper. No stamps.

Sarah Jeong joining the New York Times is a disgrace. This woman is not a satirist, she has truly backward and painful racial beliefs. We should ask her some simple questions to clear up her “satire”. If you did the same to me, it would look like this:

Q. What do you really think of Hillary Clinton?
A. I think she is an untrustworthy parasite of politics. She should not hold office and represents what is wrong with the American political system.

Q. But why?
A. Just look at how much money her family has made through “speeches”. That’s basic influence peddling. I don’t expect Bill Clinton to become a store clerk after being President, but to become a high-paid lobbyist is a bit disgusting. They’re certainly allowed to be capitalists, but the irony of HRC railing against the rich is not unnoticed.

Q. Do you wish harm on the Clintons?
A. No. I admire all Presidents, once elected. As someone who has achieved a lot, the Presidency is the ultimate achievement and I respect the winner of such an arduous contest. I haven’t yet seen a President so contemptuous to break this ingrained respect. I also begin my analysis of a candidate with a “clean slate”, once elected. I would have done the same for Hillary.

If you did that with Sarah Jeong I think she’d have a hard time disavowing some fairly extreme views. I’d like to see the demographics of the New York Times staff and its readership. I wonder if “white people” are high on that list. I also want to remind Ms. Jeong that Asian Americans are now the highest earners in the United States. There are a lot of poor, uneducated and very, very non-privileged white people. Racism is painful and shameful, but society must grow and move on. Never forget, but learn and grow. What is Jeong adding to the conversation?

Glossary
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strabismus – crossed eyes

29 thoughts on “8/6/18”

  1. You do know you can be procapitalist and still think we should help the poor right? All Hillary wants to do is have people pay taxes for the same things as people in other first world countries. We have the largest amount of poverty, crime, and people who die from not being able to afford healthcare. There’s also a way bigger homeless population in U.S. than than any other country. You know why? Because they learned you can’t have 100% unregulated capitalism, nor did they want to be full on socialist/communist. That’s just as bad if not worse to believe a country can run on either.

    This is an extreme view of capitalism from 20-30 years of Republican propaganda that makes people think they only have a choice between extreme capitalism and socialism. That’s obviously not true when you realize that America, Canada, Australia, and all of modern Europe have mixed capitalism for a reason.

    That’s okay. You just have a very Americanized view of politics and economic systems. People just need to learn that you can have better than capitalism vs socialism. Just saying that’s a bad reason to choose a shit head like Trump that see’s life in only extreme views, vs Hillary.

      1. Maybe learn something or pick up a fucking book and someone wouldn’t have to type large paragraphs to teach you what something means.

        God, this is exactly why the country is under fire right now with both sides. You just want to plug your ears and never learn anything, but then will wake up and vote for someone like Trump because you don’t understand how you’re being fucked by propaganda.

  2. Very accurate statement on Sarah! Truly scary what the NYT is doing.

    I don’t know if you have heard about this yet but ANOTHER play has been written about you! The lead actor playing as you wrote this charming tweet. “You have another chance to see me play a monster in “Shkreli! Portrait of a Pharma Bro” THIS WEDNESDAY at @ucbtny!” Quite the monster you are lol. Even on the website selling the tickets they wrote this little piece, “Shkreli! Portrait of a Pharma Bro is the origin story of the one, the only (thank god), Martin Shkreli. In this new sketch show, Shkreli regales us from prison with tales of his terrible life — from childhood to his infamous run-in with the Wu Tang Clan. Buy your tickets now before prices are raised by 5,000%!” Quite slimy of them for saying shit like “tales of his terrible life”. I didn’t know untalented play-writers had the knowledge of what constitutes an amazing or terrible life. Maybe it’s their more than fortune upbringing in a rich family where they didn’t have to work a day in their life until they were throw into the real world.

    I see you’ve also amassed quite the collection of books as well. I sure hope you have a book on computer sciences and coding correct? You wouldn’t want to relearn all of that again (I once stopped for a year and I fell way behind).

    Until next time.

    By the way, I’m writing all of these words down. Striambus will make quite the addition to it!

  3. I saw an interview of you in which you said that it wouldn’t be such a bad idea if the normal rules of capitalism didn’t apply to the pharma industry. You also mentioned that you’d like the government to run its own drug company. Do you think it’d be a good for the healthcare industry if the government also ran it’s own health insurance company?

  4. Martin

    Can you recommend some of the books that have helped you in building your pharmaceutical knowledge e.g Zumdahl and Rosenbaum? Thanks

  5. In response to this portion of an earlier post:

    “I haven’t learned anything profound from this experience, other than doing what most prisoners do, which is to stew and grow more resentful of our overreaching and corrupt law enforcement. I’m innocent and was narrowly convicted with the assistance of witness coercion…[End Count of Monte Crisco rant.]”

    Across the line of bars and barbs,
    you curse your Judge and strike your Guard,
    “I’m not to answer for this charge,
    and seek to make my clear name whole!”
    What keeps a lie abay your soul?
    What scorn partake a destined role?
    Never public pity went
    to men unwilling to repent.
    And you, without holed hands, now tried,
    cannot pose as crucified.
    Each man shares another’s sin:
    The Count of Monte Crisco, fiction.

  6. How dare you credit nature for your love of booty. Sir Mix a Lot deserves more, Martin. I should have sent you The Beauty Myth before you stopped accepting unsolicited bullshit. Nothing like a little post 2nd wave feminist theory to pass the time, lmao. Hope all is well. Great blog. Think about you often, and always hope you’re doing okay.

  7. what if my desire for a boob job is less of some form BDD and more of an evolutionary response to my lack of (I believe this is the scientific term) “tig ol bitties”

    Men like tig ol bitties and therefore, if I can fool them into thinking I *have* them, does that not make me much more evolved than a simple man after the titties?
    Something to ponder.

    jk tbh I, too, am just after the titties.

    Ps: release despacito 2

  8. Thanks for these ongoing posts Martin, I’ve missed hearing your thoughts and ideas so to stumble upon this blog has been a blessing. I look forward to your freedom and I hope you are not suffering too much.

  9. Martin,
    I’d reframe from talking politics. Jail is about read, sleep, and eat. Thanks to you, I bought the merck manuals for humans and animals, less than 10 bucks invested as i purchased used. I’m reading the veterinary manual first. Good beach reading. : )

    1. And I voted for trump. My ex-wife voted for trump and it was the first time she had ever voted and she is 40. When i asked, what brought you out to vote, she said to vote against hillary and almost every person in that line had the same thoughts, people were too quiet. People were going to vote against what they had been told on tv. It really boils down to people are tired of the same old shit. You see the same response happening all over the world. That said, I question trump. What scares the hell out of me is what come after trump, at low tide.

          1. More like Trump won and is actually making bills that are fucking his own supporters over. He’s already causing jobs to be shut down and farmers are getting hit the most.

            But yeah spoopy Hillary conspiracy theories are what we should be worried about.

      1. People claim to be tired of the same old shit and want to be told the truth, but they mostly don’t. You and many other supporters voted for a guy that scapegoated immigrants, refers to anyone against him as an enemy, incites violence at his rallies, whines on Twitter, and he’s been caught in over 1,000 fact checked lies.

        It’s okay I can forgive if you’re questioning him, but what took you so long to see what he is? He’s always been as terrible as he is now. He literally told people he’d do things to fuck his supporters over, and they still voted for him.

  10. Martin,
    It makes me happy to read your blog. You’re such a talented dude and I like to see that you are still putting those talents to good use.
    Regards,
    James

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