11/17/2018

Biopharma/Investing
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Celgene deep-dive is progressing smoothly. I’ve skimmed hundreds of papers (4000 Revlimid entries in Pubmed), docket entries and more in preparation. Thanks for the crazy amount of mail.

Fascinating, if not desperate, deal to save $UTHR with $ARNA.

Papers I’ve Read
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Computational antimicrobial peptide design and evaluation against multidrug-resistant clinical isolates of bacteria. Nagarajan et al. JBC 2017.
I had fun flipping through this “end-to-end” paper that astonishingly starts with computer/math concepts and ends with in vitro testing. It’s too bad antibiotic resistance isn’t the threat some are making it out to be. The piper cites that deaths due to antimicrobial resistance are expected to exceed 10 million by 2050. I am very suspicious of that number and if you consider deaths by all infectious microbes, I’m not sure what the apples-to-apples comparison is.

Metabolic enzyme PFKFB4 activates transcriptional coactivator SRC-3 to drive breast cancer. Dasgupta et al. Nature 2018.
This brick-by-brick/no-tricks paper is a good example of core biology informing pathogenesis. This Baylor group starts with SRC-3 and tries to determine its phosphorylation kinase. The group convincingly demonstrates PFKFB4, a glycolysis (read: Warburg) enzyme, is the culprit. A series of experiments demonstrates enzyme/TF hyperactivity in a high-glucose environment. The noting of SRC-3/estrogen receptor coactivation unfortunately is not followed up on beyond some transcriptional data. I would have included ER antagonists to determine the functional relevance of PFKFB4 blockade vis-a-vis ER redundancy. Nevertheless, the group proceeds to microarrays where they demonstrate purine synthesis as the downstream consequence of this axis. One wonders if we’ve returned to square one with chemotherapy that often targets nucleotide synthesis. Anyway, once xenografts are included, we see etremely convincing evidence o this axis driving metastasis and tumor growth. Finally, they even find human evidence that SRC3-PFKFB4 overactive TNBC patients have poorer outcomes. Truly a Nature-worthy paper. Would be drug-hunters may be interested in developing PFKFB4 inhibitors.

Clinical Trials I’ve Noticed
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Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Anti-tumor Activity of FN-1501 Monotherapy in Patients With Advanced Solid Tumors. Shanghai Fosun Pharmaceutical Development Co., Ltd.
SF is one of the bigger Chinese pharma companies. This is a FLT3/CDK2/4/6 inhibitor.

A Study Examining The Effect of eFT508 in Patients with Advanced Castrate-Resistant Prostate Cancer (CRPC). Effector Therapeutics.
This is a private company focused on MNK1/2 and eiF4A inhibitors. They raised $38 million in a Series C. Definitely one to watch.

Efficacy and Safety Evaluation of Glepaglutide in Treatment of SBS. Zealand Pharma.
Zealand is still alive and actually might be a decent investment.

REGN2810 in Pediatric Patients With Relapsed, Refractory Solid, or Central Nervous System Tumors and Safety and Efficacy of REGN2810 in Combination With Radiotherapy in Pediatric Patients with Newly Diagnosed or Recurrent Glioma.
If you’re Libtayo, this is the part of the cancer world not carved up by Opdivo and Keytruda. Cancer’s Australia, if you will.

VNRX-5133 With VNRX-5022 in Subjects With Varying Degrees of Renal Impairment. VenatoRx Pharmaceuticals.
VenatoRx is apparently an antibiotic private biotechnology company. Also known as a company that is unlikely to survive. See above comments.

Cell Therapy for High Risk T-Cell Malignancies Using CD7-Specific CAR Expressed on Autologous T Cells. Baylor College of Medicine.
Interesting…

Feasibility and Efficacy of the Ketogenic Diet in Alzheimer’s Disease. University of Kansas Medical Center.
Don’t hold your breath!

Study of Anti-CD19 CAR NK Cells in Relapsed and Refractory B Cell Lymphoma. Allife Medical Science and Technology Co., Ltd.
Another mysterious Chinese CART player.

Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease. Gold Coast Hospital and Health Service. CannaTrust Inc.
Smonk weed?! What can this miracle plant NOT do?

Adherence to Walking on an Alter-G Anti-Gravity Treadmill. Texas Tech University.
Sign me up!?

NY-ESO-1 TCR Engineered T Cell and HSC After Melphalan Conditioning Regimen in Treating Participants With Recurrent or Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. Roswell Park Cancer Institute.
Why not contact Roswell Park for a partnership here, if you believe in NY-ESO-1?

Study of SHR-1210 in Combination With Chemotherapy in Advanced Esophageal Cancer. Jiangsu HengRui Medicine Company.
This is a Phase 3 trial of camrelizumab in China, licensed to Incyte fo $25m. A PD-1 mab, and the… 5th? Chinese PD-1 mab (Innovent, Cstone, Beigene, Jiangsu and one other I’ve forgotten… not to mention PD-1s already approved in China: Keytruda, Opdivo and more coming…) Good luck to all.

A Prospective Study Evaluating the Effect of Ocrelizumab on Brain Innate Immune Microglial Cells Activation in Multiple Sclerosis Using PET-MRI With 18F-DPA14. Roche Pharma AG.
Ah. A Clue!

VX15/2503 in Combination With Ipilimumab or Nivolumab in Patients with Head and Neck Cancer. Vaccinex Inc.
Apparently, these guys are public: VCNX. This is an antibody to not such an exciting target (at first blush).

Investigating the Cardiovascular Toxicity Exposure of Electronic Hookah Smoking. NIH.

Brief Book Review – Chernobyl: The History of a Nuclear Catastrophe. Serhii Plokhy
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Plokhy takes you inside the control room as Unit 4 of the Chernobyl Power Plant explodes and threatens the viability of the Eurasian continent. The author can’t help but be riveting thanks to the subject matter. No film or novel could match the truth of April 26, 1986 and Plokhy does the moments before, during and after justice. Those expecting Patterson will be disappointed, however. Plokhy is still a plodding Harvard history professor and he admirably contextualizes Chernobyl in the appropriate Cold War milieu. Given a 10% meltdown of just one of four adjacent reactors more than thirty years ago threatened millions of people, one cannot help but be petrified of nuclear energy (or nuclear anything) today. I’m sure reactor design has improved substantially to the point where uncontrolled reactions are unlikely (if not impossible), but the risk of “unknown unknowns” (Fukushima comes to mind) would preclude my support for nuclear power. Anything where the option of wiping out the planet is on the table is a risk to great to bear. That’s just me.

Sports/Poker/Chess
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How about those Knicks?

I am so, so bad at poker. Can’t wait to play Ivey for $5 million when I get out.

What does everyone think of the Carlsen match so far? I bet he comes back strong in the back-to-back white games.

Personal
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Less than 33 months to go! There seems to be some incredulity here. 84 month sentence – 14 months in = 70 months – 13 months good time = 57 months – 12 months program referenced in sentencing = 45 months – indeterminate but no less than 9 month home confinement and no more than 12 month half-way house = 33 to 36 months. Read the statutes. Pending reform remove a month or two. Don’t forget my appeal and possible media exposure calling for my immediate release.

6 thoughts on “11/17/2018”

  1. Hi Martin,

    could you review any economic books?
    I’m really enjoying personal section of your blog posts. “A day in life” commentary would be interesting.

    Take care!

  2. I’m going to London for game 7 live today. Would be a bad idea for Carlsen to go into the Petrov again I think. White can’t get anywhere so far!

  3. Martin,

    The media and managers won’t stop talking about late cycle/ bear market talking points. I see more than half of stocks off their early 2018 highs. If I was a fund I might be shorting just about everything with high importance on cannabis, FANG, and high tech in general, riding the possible momentum down. I personally give it 80% chance right now. Do you see any shifts or think about it at all. And the other question is, do you make a move now, or wait for the beast to take form.

  4. Could you please give us a guide on how to conduct deep dives/analyses of pharmas? (Teach a man to fish!)

    Otherwise, our hearts are with you big chief x

    All the best,

    -Z

  5. He couldn’t capitalize on his two whites, both draws. It seems Fabi has the better opening preparation this match, even with some of his prep being leaked!

    I’m writing this in the 19th where Fabi currently has a nice advantage with white in an open Sicilian. Would be an interesting turn of events if he won a classical game, as it seems Magnus’ strategy is to steer the game into tie breaks where he has a significant rapid and blitz rating edge. For Magnus and Fabi respectively, their rapid ELO ratings are: 2880 to 2789 and blitz: 2939 to 2767.

    But like I said, Fabi has an excellent position and looks like he might win this 9th game! Time for an American champion?

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