Biopharma & Investing

I like Global Blood Therapies’ (GBT) drug. I’m still not through with my work but I suspect this is a real disease-modifying drug that treats the underlying cause of sickle cell anemia. A real breakthrough. This company may become as large as an Alexion or Onyx (pre-takeover) in due time.

CAR-T looks like a commercial dud. Sorry, Celgene and Gilead. Those billions are unlikely to come back. Who knows, though. Antibodies had slow uptake at first. What I’ve heard from various sources is institutions don’t want to do CAR-T. The side effects are tough and the reimbursement is difficult. This is good for companies like Morphosys and Seattle Genetics who are using traditional antibodies for CAR-T targets and some are seeing good results. Bad news for the 200 private CAR-Ts, ADAP, CLLS and everyone else who wants to be JUNO and KITE.

The flu market is heating up with new drugs from Roche, Shionogi and Vertex and some promise of a universal vaccine.

Idorsia is chugging along with their rHTN (resistant hypertension) ERA (endothelin receptor antagonist). Guess who also bought an ERA way back when 😉

Starting to watch the vaccine space very closely. One of the few areas of pharmaceuticals that is truly cost-effective, hard to replicate/genericize, etc. Every new vaccine company seems to get acquired (IDBE, CRXL for you old timers).

Papers I’ve Read
I’ve been reading some proprietary materials, so excuse the lack of commentary.

GBT440 increases haemoglobin oxygen affinity, reduces sickling and prolongs RBC half-life in a murine model of sickle cell disease. Oksenberg et al. Br J Haematology 2016.
Tremendous work from the GBT team here. This panel of preclinical data is comprehensive. Almost every question I would have asked is asked and answered here. The murine transgenic model was a bit of a flop, which was interesting. Nevertheless, GBT440 certainly works as advertised, increasing Hb-O2 affinity, thereby raising the question of whether these HbS-GBT440 complexes are TOO oxygen-hungry and will never release this oxygen to tissues. It would still (or should still) stop polymerization of the aggregation-prone HbS species. One question I would have answered is trying to determine binding kinetics here, especially Koff. Km wouldn’t hurt, we see some EC50s in the micro molar range. The engineering of a compound devoid of plasma binding is somewhat surprising. If I had to decide on buying this whole company, I’d probably run that assay independently to be really sure as it is not often compounds have close to zero albumin affinity.

Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. McDermott et al. Nature Medicine 2018.
The IMmotion150 Phase 2 results. Nothing exciting here. Gene expression-guided treatment is a pretty neat concept and shows were Sutent actually does rather well.

New Developments in Anti-Sickling Agents: Can Drugs Directly Prevent the Polymerization of Sickle Haemoglobin in Vivo? Oder, et al. Br J Haematol 2016.
Decent review. Somewhat stunning that there are 20T (trillion!) red blood cells, which are most of your cells (!!!). Each RBC has 250 million (!) hemoglobin proteins. so that is … 2*10^13 X 2.5*10^8 = 5.0*10^21. You need 20% of that hemoglobin ‘fixed’ according to various in vitro studies, so 1.0*10^21. The MW of GBT440 is 337, so the weight of the drug you need is 3.37*10^23. Avogadro’s # is 6.022*10^23. So you need 500mg of GBT440, but the bioavailability of the drug is something like 50%, so you need 1g/day. That’s roughly what they dosed in Phase 3. Incredible!

I received a rather ineluctable haircut after “looking like Harry Potter” (at least to various other convicts) for far too long. One barber agreed to “give me the Brad Pitt” after discussing various style options. Consequently, I have very little hair left. No longer hirsute, life goes on! Just like the memes, barbers here also insist on reciting “say no more, fam” prior to destroying your appearance.

Why does Bill Gates review EVERY trash book and think they’re good? Poor guy. Bridge & reading psychosocial commentary is one helluva retirement. At least his healthcare stuff seems well done. I’ll probably learn how to play bridge soon.

hemolysis (medicine, basic concept) – destruction of a red blood cell (RBC) that lyses the cell membrane and releases its contents
hemolytic anemia (medicine, basic concept) – anemia due to hemolysis
hematocrit (medicine, basic concept) – RBCs as a % of blood
aromatic (chemistry, basic concept) – adj – a compound with the presence of cyclic sigma bonds and non-localized pi bond
pi bond (chemistry, elementary concept) – delocalized bond present in a double bond (in addition to a sigma bond)
sigma bond (chemistry, elementary concept) – overlapping bond present in a single bond
aldehyde (chemistry, basic concept) – a functional group featuring a C=O bond with a R-C and H-C bond.
thiol (chemistry, basic concept) – a functional group consisting of R-S-H

25 thoughts on “7/24/18”

  1. I’m curious to read your thoughts on some of the more tech driven biotech plays, specifically Invitae, CryoPort, Veeya systems and biolife solutions thanks for writing the blog.

  2. Haha the at the hair story. I guess it’s a good thing that hair grows back. I don’t think most people will notice because they don’t see you.

    Love ya though no matter what!

  3. You can you upload a picture of your new hairdo? That be sick. I currently rockin’ your old hairdo and listening to Brand New on your spotify using my Audeze LCD-4.

  4. GILD was one of MS favorites. This is pretty significant folks. GBT is also significant. GBT is just a molecule, that’s it. No genetic modifying. Waiting to hear on SGMO and CURE? If MS says those are to go than it might mean the end of everything short of a complete economic collapse via the 2008 financial crisis. Or World War III, or significant earthquakes and volcanoes.

  5. GBT is already 2B. All of biotech has been so speculative a la CART. Even if it’s a great drug, what about revenues and therefore valuation.

  6. Martin,
    I miss the glossary portion of the blog that you were providing but the current format is cleaner looking. Do you have a recommended book list? The biotech/medical must have reading list for the layman? Maybe you can list a few on the next update.

  7. Thank you for the update. Good thing you posted a Glossary… Congratulations on your haircut. I don’t like your floppy “Harry Potter” bangs, anyway 🙂

  8. thank you. i understand the chemistry portion, its the other part i have a hard time understanding. The nomenclature.

  9. I believe martin can’t reply to comments. I think he’s only allowed to comment about stocks , pharma, and a short personal experience section. Otherwise he would have written a lot more.

  10. Just a comment to show appreciation from UK.
    Keep it up.
    Not sure if you can get access to music, but Nappeux by Romeo Elvis et Le Motel is an amazing Belgian hip-hop track, you might enjoy.

  11. Weird. I’ve always liked Harry Potter to the point of wanting kids with British accents, and I’ve always hated Brad Pitt because he ruined se7en. It’ll grow back. Keep up the good work.

  12. Ever heard of Babylon zoo – spaceman? Man you got to find that song right now from someone’s Mp3 player. You got to listen.

  13. Nonsense. I’m sure no one destroyed your physical appearance, but very likely improved it! I always thought shorter hair suited you.

  14. I think we can all relate to the hair story lol. Do you have any recommendations for books Martin? I remember in a previous post about you having read Snowball, anything else?

  15. The hair story left me laughing for a good five minutes. Much respect Martin! Thanks for keeping these going 🙂

  16. Martin, do you have any recommendations for books/articles/material on learning about healthcare reimbursement for physician-administered drugs at a high-level? Trying to get a better foundation of the parties involved, their motivations, pains, etc.

  17. I wish you’d play Magic again instead of bridge. This game needs some new leadership and brainpower as it’s overrun by herds of neckbeards and omega males :/ Guess bridge must do for the next 3 years.

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