9/27/18

Biopharma/Investing
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So much to say, so much I should keep to myself!

ALNY had some porphyria biochemical data. I think you have to show attack rate decline in this disease. They will.
ALXN acquisition is interesting. This was one of the hotter private companies.
Novartis job cuts are consistent with every drug company shifting to specialty. This means A LOT fewer jobs across the board (not just manufacturing and S&M).
GERN, TGTX should have been very anticlimactic.

Papers I’ve Read
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Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1-Mutant Cancers. Popovici-Muller et al. ACS Med Chem Lett.
A nice little paper from Agios demonstrating a classic example of overcoming metabolic instability to arrive at a lead. Fluorinate!

Optimization of 3-Pyrimidin-4-yl-oxazolidin-2-ones as Orally Bioavailable and Brain Penetrant Mutant IDH1 Inhibitors. ACS Med Chem Lett.
Novartis’ IDH1 inhibitor, with the same fluorination of alkyl groups to increase stability.

Chemical Approaches to Modulating Complement-Mediated Diseases. Iyet, et al. J Med Chem 2017.
Reasonable review of what should be a more exciting space for pharma than it currently is.

Glanced at a poorly written Italian paper on new, “selective” glucocorticoids, a new IDO inhibitor and a silly CRO-industry white paper masquerding as a journal paper. I think someone should try IDO for CNS given its clearly related mechanism (don’t steal my idea).

Clinical Trials I’ve Reviewed
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Birds and Bees Research Study. Behavioral: Web-based resource vs. alternate web-based resource on adolescent sexual health.
There were plenty of web-based resources in my 26.6k modem days.

Dose-response of Cannabis and Driving. Cannabis vs. placebo. Centre for Addiction and Mental Health.
Hmm. Wouldn’t want to be a participant.

Football
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What a week… How do you explain the Bills-Jaguars? There is a sort of unpredictability that strikes some games. Not quite sure how to model it… Personnel changes and personnel history is important to include in the data sets. The QB change there should simply widen a confidence interval. I’m starting to integrate a ELO approach into my other formulas.

How about Brady? Is it over?

Personal
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We had to move buildings here while our building is being repaired. The carbon-copy building temporarily housing us is fine. Jail is jail. Unfortunately, almost all of my papers and books had to be left in the old building. I’m reading Zimmer’s “She has her Mother’s Laugh” and a Medical Genetics textbook in the meantime.

28 thoughts on “9/27/18”

  1. Martin you are my hero, your resilience is inspirational, I hope one day to acomplish as much as you.
    Stay strong for the people that love you.

  2. Nice post man. I’d love to maybe see a long post on your experience as a semi-popular irl streamer. Example questions: What was your take on the whole thing? Why do you think people watched your stream? Did you do it to correct an image of you that you thought would influence your court case? Best of luck in there man. Let us know if you need outside help!

  3. Nice post man. I’d love to maybe see a long post on your experience as a semi-popular irl streamer. Example questions: What was your take on the whole thing? Why do you think people watched your stream? Did you do it to correct an image of you that you thought would influence your court case? Best of luck in there man. Let us know if you need outside help!

  4. Thank you so much for posting. Your natural tendency to share and care for others has always been evident. So much of your thoughts on important matters are greatly appreciated as you yourself have shown greatness in staying positive and not dwell on the negatives of the abundant imbalances and injustices found pretty much everywhere in this world. I hope you stay well and make it through this sentence. Best of luck and health.

  5. Great to hear from you again, we are all glad you are faring well, considering the circumstances. Best of luck to you in the future!

  6. I really like your spirit in there, regardless of your past. What’s more important is the present and the future. I sincerely hope you can get out early and reinvent yourself, in a good way. Use your gift in a more constructive way. Cheers!

  7. Martin, you called the company ALXN acquired, Syntimmune, one of the hotter private companies. Their CMO, formerly of Vertex, recently joined off the radar company BIOAF. He obviously got Syntimmune right. SHould we follow him to BIOAF? BIOAF’s President and CEO is also formerly of ALXN. BIOAF’s market cap is only $18 million but it is an elephant hunter and believes its technology can usher in a new era in neuroscience. They believe they have a best in class solution for delivering drugs, including FDA approved Herceptin, over the blood-brain barrier. Is this a 100-bagger? It’s preclinical but this is where the big money can be made.

  8. I don’t know if anyones updated you but man they banned Alex Jones from twitter, facebook, youtube, and even paypal. He’s still doing his show on his own site but its getting crazy out here bro lol (not that i was ever a huge fan of his, but interested from time to time about what he had to say). Elon Musk tweeted “funding secured at $420” as “a joke to impress his girlfriend” and now the SEC is after him for fraud/insider trading/who knows? They want him to step down as CEO from Tesla. Apparently being the cool billionaire bad boy smoking weed on the biggest podcast in the world (he did that if youre not aware i dont know how much they let you see in there), saving the world with his expensive inventions, and dating celebrity women is enough to get him sent to the principals office these days.

    just discovered your blog via reddit, cool stuff here.

  9. Martin what do you think of VK5211 (patients recovering from non-elective hip fracture surgery) and VK2809 (treatment of patients with hypercholesterolemia and fatty liver disease).

  10. Any _current_ trial recommendations for non-resectable GBM for a friend?

    He’s being offered a place in a CAR-T trial and I wonder if you have a view on the durability/success probability of targets (such as IL13Rα2, EGFRvIII, …) or combinations that make sense (besides aPD-1/L1 I’ve think of autophagy inhibitors and anything that solves the problem with Tregs). Or maybe he should just go to the jungle and try to catch some Zika (http://jem.rupress.org/content/214/10/2843.long
    http://stm.sciencemag.org/content/9/409/eaao6888). Or additionally/alternatively, ask Walter White to fabricate some D-1MT (“IDO-inhibitor”/actually signals Trp sufficiency) and secretly take it while on a trial? By the way, NLNK is doing a trial with SBRT + D-1MT for pediatric DIPG reading out next year.

    In the long term (= time he does not have), IMHO fighting against S1P1-receptor loss on T-cells could be worthwile (“T cell sequestration is accompanied by tumor-imposed loss of S1P1 [receptor] from the T cell surface … In murine models of GBM, hindering S1P1 internalization [by actually using a knock-out mouse] and reversing sequestration licenses T cell–activating therapies that were previously ineffective.”
    https://www.nature.com/articles/s41591-018-0135-2). Currently we do not know what causes this loss. If it’s just too much of S1P1 being produced by the glioma (leading to receptor internalisation as far away as in the bone marrow??), then maybe a Sphingosine Kinase 1+2 inhibitor might be a first idea (note: there is only a Sphingosine Kinase 2 inhibitor in a ph2 and this only for Cholangiocarcinoma).

    Also in the long-run some CAR-T/CAR-NK construct with “gas and brake”-pedals might be interesting. In case of brain swelling during a trial, obviously, somewhen steroids are given and IMHO this stops the immune reaction too harshly.

    Thx

  11. Hi I’m new to your blog. If you read this hope I can get your opinion on 2 companies…cprx and aveo. They are very interesting to me and I’m bullish on both. Thank you!

  12. ESPN recently wrote an article about “selling high” on QB’s that have emerged (using Goff from the Rams as a prime example). The thought is that by selling high and gaining draft picks, and maybe drafting a few QB’s (shooting ducks in a barrel), you would further add depth to your roster. I think this is trying to push that fact that the NFL is not a QB league. I am actually interested in this because it has been pushed for so long that it IS a QB league, but we are seeing now more than ever, inexperienced QB’s having a lot of success and many castoff QB’s getting in the right system and tearing it up. I do find talk that Brady is a product of his system and coaching interesting. I don’t have the Brady hate that some have; I think he is for sure talented. But there is something to be said about a well ran org, management, and putting people in a place to succeed… hate it or love it.

  13. I did want to ask for your comments regarding Q1 and Q2 sales of Sanofi’s hemophilia drugs (via Bioverative) Alprolix and Eloctate.

    ALPROLIX: Q1’18 21 Mill Eur ; Q2’18 81 Mill Eur
    ELOCTATE: Q1’18 43 Mill Eur ; Q2’18 176 Mill Eur

    Also do you find Sanofi being in a stronger position now?

  14. Investors are getting a bit concerned about SGMO recent clinical results. Can you comment on most recent findings? Thank you.

  15. Hey Martin,
    Have you looked at / considered microbiome companies such as 4d Pharma in the UK ?

    I’ve invested as I have oesophillic oesophagitis which is resolved by me taking probiotics – making me think there is something in this.

    Happy to post you stuff if you indicate interest.
    Rob

  16. Hey man, love the blog.

    Sorry if this is not the best place for this (comments) but unsure how to send a message to you directly. Curious as to your opinion on RNAi as a therapy in general. Ever look at ARWR, ABUS, PRQR, etc? Would love to see a post on this area in general.

    Cheers mate.

  17. You are a wonderful caring person. Prison sentence can be a blessing in disguise. One of those things that gives you more time to learn and grow. Please let us know if you run out of books or if you need any specific books, research articles, or peer reviewed studies so we can help you on your journey.

    Also, I would not want to be a cannabis driving participant either.

  18. Check out Spero. $190m cap. In 2017 they appear to have ass-raped some Japanese company. For $3m + single digit royalties they got an oral carbapenem, already de-risked.

    An Atlas Venture company staffed w/ lots of Cubist vets.

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