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
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
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.

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?

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.


The cannabis bubble is actionable. I’d short TLRY, WEED, ACB, and the rest, and be patient. If I were at a hedge fund with a big “central book” (Citadel, Bridgewater, Tiger, Soros, Goldman Sachs, Third Point), I’d ask senior management to just write upside volatility or short common stock from here to eternity. Can probably make $500m to $1B.

NASH is probably the last big pharma mass-market/GP indication. Makes me jealous but also annoyed I never took it too seriously.

Clinical Trials
An Investigational Immunotherapy Study of BMS-986310 Administered Alone and in Combination With Nivolumab in Patients With Advanced Solid Tumors.
I wonder what 986310 is…

Alzheimer’s Disease Treatment with Combination of 40Hz Light and Cognitive Therapy. Alzheimer’s Light LLC.
Who needs drugs when you have light?

Football season has been interesting.
Yard differential R^2 with point differential is about 0.70 (turnovers, 3rd down/4th down conversion limit R^2 from becoming 1.0). Yet, I see YF-YA as a better indicator of team strength. Turnovers and 3D/4D conversion are more random. I guess I could see which is more predictive of future point differential…
Vegas point spreads seem to have a R^2 of 0.50 to 0.70, which is a little less than what I can get without them.


Are there too many antibody-focused companies? There are only so many antibody targets by virtue of their limitations (no intracellular targets). You have JNJ-US, ROG-VX, NOVN-VX, LLY, BMY, SAN-FP, MRK-DE, AMGN, AZN-LN, REGN, GEN-DC, ALXN, SGEN, MOR-DE, MGNX, ANAB, XOMA, etc. Once a target is of interesting, everyone can make one relatively similar product and trial it. There are a lot of potential targets, so does that shift the game to disease biology where are there actually very few intelligent players? Clinical execution is obviously important as well. Maybe we can do an analysis of all new antibody candidates and see how long it took for a fast-follower/competitor to show up…?
Doing this analysis now. My preliminary conclusion after looking at about 200 antibodies is despite the expected chase of exciting targets, there is a lot of stalling and usually more than enough room for multiple entrants. Now, about that biologics capacity…

RIP $VTL, you will be missed.

Wow, BAYN.DE really falling apart.

It will definitely be interesting to see changes in Chinese drug revenue. If you try and look at Sino (1177), it kinda looks like there is a lot of revenue growth (30% y/y) but it’s hard to tell how much is organic. Jiangsu Hengrui is all in Mandarin 🙁 otherwise I’d really like to understand that megacap ($40bn!).

Cannabis-related stocks are or will be epic shorts soon.

I’ve been working on predictive scoring functions for NFL games. I like the Ravens!

Wishing Lil’ Wayne luck on a successful release of “THA CARTER V” — everyone go buy it!

Make sure you follow by official instagram @martinshkreli15 — which my friend Taylor is now managing (thank you, trap queen!)

Sorry I haven’t posted in a while. I was (and still am) busy reading about rare diseases.

I’ve decided to play the Scandinavian after 1. e4 after failing miserably at the French. 1…d5 seems dynamic and tricky, more well-suited to my personality. Wish me luck!


I had a dream MDGL stock was $2 and I said “who ever thought that was a good idea?”. That’s probably a premonition as well as a dream.

Book Review – Tesla: Inventor of the Modern by Richard Munson
I liked it. I’m reading “How to Change Your Mind” now. I don’t like it.

Papers I’ve Read
Discovery of Potent and Centrally Active 6-Substituted 5-Fluoro-1,3-dihydro-oxazine beta-Secretase (BACE1) Inhibitors via Active Conformation Stabilization. Nakahara et al. J Med Chem 2018, 61, 5525-5546.
These BACE inhibitors arise from a Shionogi/J&J collaboration. Recall the Shionogi scientists wrote a nice paper explaining semagacestat as a pseudo-gamma-secretase inhibitor. Here, I’m not sure they apply their learnings. They see potent CSF Abeta drop in beagles but don’t report on total brain Abeta. Maybe it is cumbersome to do a total beagle brain homogenate analysis? Otherwise its a classic pharma paper, optimize for Pgp and CYP inhibition. Some interesting perspectives on equatorial/axial conformation with Newman projections that you don’t see often in these papers.

HIV vaccine candidate activation of hypoxia and the inflammasome in CD14+ monocytes is associated with a decreased risk of SIV_mac251 acquisition. Vaccari et al. Nat Medicine 2018.
Not worth reading.

I mostly like prison and the people here. Yet, I do have one complaint. After midnight, the floor on which I stay is populated by some unruly inhabitants who insist on reciting rap song lyrics, quite audibly, in the hallway to which my room is adjoined. I must make it clear to all parties that this behavior will no longer be tolerated. It is rude to me, disruptive to all and unbecoming of the interloper. I might also add that these recitations fall short of honoring the original artist!

35 months to go on 9/13/18. I checked all the math. 84 months – 12 months in = 72 months. 12 months for “the program” makes 60. 12 months of re-entry/early-release yields 48 months. 13 months of good time, which the above do not diminish or factor into, brings the total remaining time to 35 months. Without appeal. In another year or so I will probably relocate to a “prison camp” where the aforementioned nuisance is unlikely to require my vigilance

Can’t wait for NFL season to begin!

Thank you to all the professors, postdocs and other math professionals who have reached out to help me. It has been great to communicate with you all. Bear with me as I order my thoughts and respond in the limited way I can.