11/7/2018

Biopharma/Investing
————————–
Earnings season is in full swing! Oh ALNY… probably a good long here…

Would readers prefer a “deep-dive” on CELG or AMGN?

Papers I’ve Read
———————
Will Courts Allow States to Regulate Drug Prices? Christopher Robertson, JD, PhD. NEJM 2018.
This isn’t a paper, just drivel the NEJM allowed published for some self-destructive reason. States can’t “regulate” drug prices. Countries that have ONE payor, that country’s government health body, cannot “regulate” drug prices, either. What happened when Greece couldn’t pay for Roche’s cancer drugs? Do you think Roche let Greece give them IOUs? No. They cut of supplies of life-saving medicines to a country that chose not to pay due to financial difficulty. The writer of the article seems to propose states should have the option to do the same. What this poor fellow confuses is regulation and access. Firms have a choice as to what they’ll supply at what price. If Maryland’s ill-fated attempt (reversed by Circuit Court) for drug price regulation were to somehow be found legal again, companies like mine would just stop selling to Maryland.

Maybe they can ask Greece for advice?

Clinical Trials I Noticed
—————————
CLN-0046: Treatment of AMD Subjects with OTX-TKI. Ocular Therapeutix, Inc.
I had no idea this was a public company. Pipeline is kind of neat. OCUL is the ticker.

Vaginal Elasticity Assessment Before and After Vaginal CO2 Laser Treatment.
You got me after vaginal elasticity assessment. How do I enroll?

Briefly Reviewed: Perfect English Grammar by Grant Barrett
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Initially, I bought this small (3/4th size, 200pgs) guide for my language-impaired roommates. Of course, not being a remotely adept writer myself, I had to go through it first before recommending it to others. Barrett writes for an audience somewhere between their needs and mine. “PEG” probably should not be read by someone who hasn’t finished high school, but I found it too incomplete and scattered for a scientific or financial professional looking to improve his knowledge of English.
Despite that, unless you’re familiar with copulas, gerunds, determiners and the myriad mind-numbing derivatives of various parts of speech that come with writing for a living, this is a nice refresher for the “too busy to care”. You should care, though.

Sports
——–
9/10 for my last ten football selections (some were ML). I don’t have a read on the Panthers/Steelers game, but if I make a decision before gametime, I’ll try and make a quick post. Basketball will be interesting tonight. I’m going with DEN -3 and ML, DAL+9.5 and ML, CHI+10.5 and ML, SAC+8 and ML and ATL+1 in order of conviction. I’m enjoying the NBA and predictions increase the edifying feeling.

Poker
——
Bummed over some bad luck. In a 1/2 unit 6-player game, I’m 3rd to act after the binds. UTG check, call of 2 to my right and with AdJh I raise to 6. All fold except our caller villian. Flop shows Jc 2d 3s. Pot has 15 in it. Villian checks, I bet 7. Villian calls. Turn card is a 7c. Pot has 29 in it. Vil checks I bet 15, Vil calls. River is a Kc. Villain checks, I bet only 10, Vil calls and turns over 8Jc. Did I play it right?

Also lost a frustrating AI hand with JJ vs AKo. My luck!

Personal
———–
Spoke with my attorneys today. Brafman is really a great fellow. Lawyers are generally despised, typically for good reason. Ben is not one of those. Several of my other attorneys are fantastic friends and great advisors. They all know who they are, but I have about 10 fantastic attorneys that have become friends. Hopefully it’s not just for the bills 🙂

11/5/2018

Biopharma/Investing
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So, I guess we’ll find out if the Pfizer/Glycomimetics drug for sickle cell works next year.

I still like SRPT and GBT.

Interesting to see VRTX’s early stage programs include FSGS (hey, that’s my disease!) and PKD. What’s up with that!

I think I will do a “deep-dive” for a stock, including a full DCF (done in my notebooks!). I’ll try and shoot for one stock a week. That’ll cover 52 stocks out of a universe of… 500? Not much coverage but I beg the reader’s forgiveness. Maybe I can do two some weeks.

Clinical Trials I’ve Noticed
——————————-
Compassionate Use Individual Request Program for GSK525762 in NUT Midline Carcinoma. Drug: molibresib. GlaxoSmithKline
This BET inhibitor must be working for GSK to take this action.

Lenalidomide in Anti-MAG Neuropathy. Phase Ib Study.
I’ve never heard of Anti-MAG Neuropathy. Seems like myasthenia gravis. Might be a good indication for would-be drug company builders.

A RETROspective Study of Patients with TK2d. Drug: dC/dT. Modis Therapeutics Inc.
This Orbimed-funded orphan drug company just announced a $30m Series A. I don’t know a lot about this disease or putative drug, but interested in learning more. Someone shoot me a paper or two on this, please.

Assess the Gluten Degradation Activity of PvP001 and PvP002 in Healthy Adult Volunteers. PvP Biologics, Inc.
This Celiac Disease-focused company is fairly quiet about what they do. I wonder what these drugs are… oral enzymes perhaps? Could be a big product but I thought Takeda had rights.

BHV-4157 in Adult Subjects with Spinocerebellar Ataxia. Troriluzole. Biohaven Pharmaceuticals Inc.
I know very little about BHVN but I do know a lot about riluzole. I suspect this riluzole derivative will do nothing, but who knows.

Daunorubicin and Cytarabine With or Without Uproleselan in Treating Older Adult Patients With Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy. NCI.
This is Glycomimetic’s E-selectin drug.

Pinometostat and 5-Azacitidine in Treating Patients With Relapsed, Refractory, or Newly Diagnosed Acute Myeloid Leukemia With 11q23 Rearrangement. NCI.
This is Epizyme’s DOT1L drug.

Brief Review – My Inventions – The Autobiography of Nikola Tesla
—————————————————————————–
I found this tiny volume confirmatory of the recent biography: Tesla is simultaneously delusional and brilliant. He’s a man of science but also of the supernatural. Truly one of the most bizarre individuals I’ve ever read about.

I’ll try to make a book “section” of the site. If anyone is a WordPress pro perhaps my people can reach out to you to coordinate this. A simple list of books I’ve read while I’ve been in my New Jersey office might be interesting to the reader.

Sports
———-
The Patriots, Steelers and Chiefs came through and my small token on the Bills did not (so much for their fearsome defense). I’m 8/9 in my last few football selections. My algorithm is a fairly simple relative-strength stochastic. I think the big question is how much “decay” one builds into memory. Does a team’s performance from last year matter? Two years ago? Is there a variable one could create to model individual player performance longitudinally and another variable to assess team roster identity? Lots of ways to improve an algorithm. Lots of ways to mess it up, too 🙂

So much for the Knicks as well. I forgot to include the “never bet on the Knicks” function that all NYers have come to appreciate. The Wizards have a pretty good roster but a bad start to the season. Hard to predict those things. I also flunked on the T’Wolves game but did pick up the Raptors/Lakers. Poor Lebron. My basketball look-back period is very short, unlike football, and a few other differences exist between formulae.

Personal
———-
I have to refill prescriptions here, just like in the real world. Go figure. No copay.

75% of the people here shouldn’t be here. I doubt our founding fathers wanted a prison state where most individuals are incarcerated for long periods of time for owning guns and peddling “illegal drugs”. Very sad. So often, jail is an expected outcome of a troubled, urban youth. The cost of incarceration is incredible and few lessons are learned. If anything, the inmate is set back further from potential redemption.

I fear the plethora of cats that cohabitate this compound will be very cold this winter. The tough guy persona the reader has come to love is betrayed by my love for these furry interlopers. The cats are well-fed, thanks to inmate willingness to share lunch. I sometimes wonder if while lounging about they ask each other what they’re in for. “Ate the dog’s treats.” “Catnip, possession and intent to sell.” “Dogslaughter. (gasp!)”.

11/4/2018

Biopharma/Investing
—————————
Poor PBYI. Hard to tell if its a ‘value stock’ now.

Innovent is public. $3b USD MC. Another PD1 player (and Beigene competitor).

Clinical Trials I Noticed
—————————-
Neoadjuvant and Concurrent PD-1 Blockade Combined with Definitive Chemoradiation in Nasopharyngeal Carcinoma. Innovent.
Sintilimab is Innovent (and Lilly’s) PD1 mab. See above for brief comment on innovent.

Safety, Tolerability, Pharmacokinetics, and Antitumor Study of ADCT-601 to Treat Advanced Solid Tumors. ADC Therapeutics.
An AXL armed antibody. This is in addition to their CD19, CD25, CD22, PSMA and DLK1 ADCs. This company is probably worth a few billion.

A Study of Lobaplatin/Etoposide With or Without Anlotinib Maintenance Therapy in Patients with ES-SCLC.
Well, China is here. Between anlotinib and apatanib, you have two home-grown TKIs from China. Lobaplatin is a Chinese platinum as well. China is sort of like the new Japan for pharma.

Clinical Trial Using the Proteolytic Fraction P1G10 From V. Cundinamarcensis to Heal Diabetic Foot Ulcer. Federal University of Minas Gerais.
Not for me but possibly a good opportunity for would-be in-licensors out there.

Comparison of the Efficacy & Safety of Resusix with FP24 in Patients with Acquired Coagulopathy. Entegrion, Inc.
Pretty interesting alternative to FFP.

Sports
———–
Nothing too exciting this weekend. I think the Patriots -5 are fairly safe against the lowly Packers. It’s painfully clear Rodgers can’t carry them this season. Also trying the Knicks+ 7 tonight. We’ll see!

10/31/2018

Biopharma/Investing
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Celgene is going to have a rough next decade. With 12 of 15 billion in revenue disappearing in the form of generic Revlimid, Otezla and Abraxane, I’m not sure CART, JAK and S1P1 will do the trick. The company spent a lot of money on buybacks and finds itself in a potent net debt position. Novartis reported $20m in revenue in the second full quarter of their CART product Kymriah. You know what to do!

Papers I’ve Read
———————
Mutant APP and Amyloid Beta-induced defective autophagy, mitophagy, mitochondrial structural and functional changes and synaptic damage in hippocampal neurons from Alzheimer’s Disease. Reddy et al. Hum Mol Genet 2018.
Papers like this should not be published. The authors find impaired mitochondria in AD neurons. No shit. Things go wrong, horribly wrong in Alzheimer’s brains. Biological processes are upended and synaptic integrity collapses. Why? Well, we know that mAPP (mutated amyloid precursor protein) patients suffer early-onset AD, which certainly implicates A-beta. Despite this, all attempts to neutralize A-beta have not changed outcomes in AD. This is probably due to a temporal-treatment mismatch. But this paper tries to suggest impaired mitophagy and mitochondrial function as a direct consequence of AB. It certainly is an epiphenomenon, but that is about all that can be claimed. Eating fruit in my home and then throwing it in the garbage results in garbage. Not throwing that garbage into the incinerator or leaving it on the sidewalk results in garbage buildup. Garbage buildup will attract rats. Rats crowding my kitchen garbage can will scare wifey. Wifey punching me in the face will cause a black eye. Eating fruit does not cause black eyes.

Brief Review – Ship of Fools – Tucker Carlson
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Liberals and the bi-curious should read this. Carlson provides the best current thinking from the right. He does not genuflect to Trump (and even seems dismayed), which perhaps is a conscious effort to win credibility from the reader, so don’t think you’re picking up a propaganda pamphlet. With his television charisma transported to the page, Carlson runs through a dozen or so disparate subjects through his perceptive and historically-informed lens. How left-core issues have become right-core issues (labor) fascinated me. I’m not a keen politics observer but I really enjoyed this as Carlson lauds certain old-line liberal principles (which appeal to me) and have been lost in today’s demagoguery.

Football
———–
The Bills play remarkably well for their record. Their defense made the Patriots look silly and I “sweated” this game substantially. I took the Patriots ML, -13.5 and a tiny bit -21.5. So, I was 3-0 this weekend (Patriots, Panthers, Redskins)! Now if I can only get my poker game moving… I’ll try to post football picks BEFORE the games start. With the return of the old PCs, I am attracted to writing again. I’m still very busy, however! Despite this I am also going to try and pay attention to basketball.

Poker
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Someone tried to play a constant all-in/rebuy game against me. That didn’t work. Taking blinds here and there and then getting slammed on AI calls was a quick lesson for villain.

Personal
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Thanks to my new friend who sent me works on Real Analysis, Topology and other fields. Math sits at the throne of the mind.

10/29/2018

Biopharma/Investing
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ABBV looking attractive at these prices.

Papers I’ve Read
——————–
A mutation-led search for novel functional domains in MeCP2. Guy et al. Hum Mol Genet 2018.
Nothing too exciting, seems to confirm C-terminus deletions in MeCP2 don’t result in functional deficiency but more quality-control/protein-stability problems. Authors speculate on a drug helping but I think when you’re missing most of the translation product due to transcription truncation there isn’t much hope for small molecule approaches.

Impaired Mitochondrial Dynamics Underlie Axonal Defects in Hereditary Spastic Paraplegias. Denton et al. Hum Mol Genet 2018.
I don’t know much about this family of diseases, so this was a helpful paper to catch up with.

Football / Poker
——————–
Took the Redskins -1 and the Panthers ML. 2/2 this weekend. Staying away from Patriots -14 although that rises to the level of actionable. It’ll be a game-time decision.

I am truly awful at poker. One recent hand was J10 (mine) vs QQ (his). J 10 Q flop. I bet, he calls. Q hits. I check he bets heavy, I call. J hits. I’m already mostly all-in. Villain was very tight player but often doesn’t understand preflop hand-strength (noticed he’d raise preflop with K10o J8o etc).

Personal
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End of the year is approaching! 33.5 months until home. Everything is mostly good here. My bestie is leaving for prison camp.

Glossary
———-
I will be trying to improve this section with sequentially more complete definitions of terms/concepts, hosted on a separate page on my domain. Some of these concepts are very simple but get very complex quickly with more digging.

autophagy – The process of recycling (death) of cellular components.
mitochondria – Cellular organelles that are the main source of ATP. The shape and size of mitochondria are regulated by enzymatic fusion and fission processes. The mitochondria is membrane-enclosed and membrane potential is a measurement of mitochondrial health.
mitophagy – Mitochondrial degradation/autophagy.
negative/purifying selection – The removal of a gene or allele from a species’ gene pool due to disadvantageous properties via natural selection.
Southern Blot – laboratory technique used to detect nucleic acids via hybridization
transcription – The process of transcribing mRNA from a DNA template (gene).
translation – The process of building a protein from a mRNA template.

10/25/2018

Biopharma/Investing
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Poor SELB. Can’t win them all.

Still like GBT.

BGNE has come in a lot, appropriately. Hard to beat Imbruvica and I think you might need an ionic (standard) binder to change things here. Covalent is covalent, amirite?

Big Revlimid, Soliris, Keytruda and Opdivo numbers. Cancer/Rare disease is eating pharmaceuticals. All the basic necessities of statins, metformin, ARBs, antibiotics have been handled. The pharma industry basically exists to manage the 1%-10% of maladies that create 25-50% of healthcare costs. This is a good place to be. No one wants to die of these nasty illnesses and “greed” can’t come into play when you’ve created the first ever treatment for some rare tumor as opposed to improved dry eye symptoms by 30%.

Maybe VKTX is a long in comparison to MDGL. I remember when VKTX couldn’t find a dollar underneath a couch cushion, but that’s life!

Book Review – She Has Her Mother’s Laugh – Carl Zimmer
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What do we make of “She Has Her Mother’s Laugh”, Carl Zimmer’s latest, and at 600 pages, plumpest work? While ordinarily, I’d say you can skip the theatrics and read Korf’s genetics textbook and keep up with Am J Hum Genet, I still recommend “SHHML” to the layperson and scientist alike.
Zimmer takes disperate fields and has mostly positive results in annealing a reasonable and cohesive narrative that leaves you satisfied. From the history of heredity, which is mostly an exercise in anthropology, and perhaps zoology, Zimmer then tackles the Darwin-Mendel-Lamarck-Galton pre-genetics era with the air of a historian. The problem is that half of this volume is retelling what Gould, Dawkisn and others have already done, and better. There’s far too much “gemmule” and far too little exon.
So why pay attention? First, Zimmer is a tremendous writer. While it took time to finish and synthesize SHHML, there are few moments when the story drugs or is unreadable. Second, Gould is dated: epigenetics, let alone CRISPR, didn’t exist when he was alive. Zimmer impressively weaves bleeding edge advances without temporal distinction. In general, the book moves from the past to the future, but Zimmer prevents SHHML from becoming an encyclopedia by dragging the future backwards and vice versa when appropriate, and by bringing his personal genetics journey into the story to illuminate the science. Unfortunately, this works only to break monotony of what would be a reasonable textbook on the history of genetics–Zimmer feels impersonal and detached. She may have her mother’s laugh, but we never hear the joke.
Another shortcoming is the substantial body of recent advances and basic facets of the subject which are completely left out. We can forgive Zimmer for excising topics like synthetic biology, alternative splicing, vaccines, CART and more, as he’s approaching the limit for a reasonable printing of a somewhat technical subject. This is not Principia Genetica.
Despite this amnesty, Zimmer comes up short when we ventures into a few places, including alternative modes of inheritance. Nodding to the meme, Zimmer nonetheless biopasses prions or any discussion at all of computer science and bioinformatics. Recent papers on algorithms imitating nature and vice versa would have been a nice addition to admittedly already myriad vignettes.
So, occassionally long-winded Zimmer does a great job of explaining sometimes abstract, sometimes concrete and always dense science. We’re left with an awfully preachy and bizarrely placed ending rant on the environment and politics. It would not be a modern mass-market published work without some social justice plea, I suppose. As someone who has made his living off of the subject matter in question, I can’t help but love SHHML. If you’re looking for a modern, up-to-date and reasonably comprehensive history of heredity and genetrics, Zimmer delivers.

Brief Book Review — Molly’s Game – Molly whoever
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This vapid scrawl outlining a classic tail of Hollywood failure never leaves the reader feeling sorry for its protagonist. Molly is a preeminent putative overacheiver who doesn’t realize she’s achieved nothing and is a product of parents who haven’t pushed her hard enough despite believing the opposite. Naive Molly doesn’t understand that going from her demeaning cocktail waitress job to “running the poker game” is not a graduation. The wealth of the men leering at you like a delicious pastry does not change the fact you are objectified. Still, she’s the proud poker princess pushing herself to the pinnacle of … party planning? Inevitably poor Molly involves herself (or vice versa) with organized crime and it all comes crashing down. Fuck Molly and the three hours it took to read this sorry chick flick.

Personal
———-
Is it okay to have a crush on Chelsea Clinton?

One life goal is to get served with a lawsuit every day. I probably average around one a month. Gotta step it up.

Wealth is massively increasing again. What to do? Sports teams have gotten stupid expensive for assets that do not produce income (unless I’m not in the know). Paintings seem like better investments–sports is eternal in some ways but shifts quite a bit within 50-100 years.

I am reading a lot on and playing a lot of poker.

I’m going to learn Java.

10/22/2018

Biopharma/Investing
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There are many diseases amenable to substrate replacement. I’ve designed some molecules recently.

Papers I’ve Read
——————–
It’s good to be back to my locker(s)-full of journals. Unfortunately I really am in a conflict position on a lot of what I read.There’s very little I’m reading these days that I’m not actively pursuing or have an interest in, so it’s a little unfair to share it here. Just keep that in mind if I seem quiet.

Caliphalaxis. NEJM.
Bad disease, weak paper.

Evidance that Leonardo da Vinci Had Strabismus. JAMA.
They ran a p-value on paintings, LMAO!

Personal
———–
Good news! We’re back in our building after a 3 week relocation. The computers have real keyboards again, perfectly destructible. Sorry I was away–those keyboards were really awful. I’ll try and write more!!! I am amazingly busy as I’ve mentioned. And without reader feedback it’s hard to stay too engaged. If someone wants to step up and actually send me comments so that I can respond, I would definitely do that! If you are on the “CORRLINKS/TRULINCS” system with me, that would work easily. Perhaps my Dad will do it!? It would require not only reading the comments but then posting them to the WordPress site. That’s probably too much for the old man.

Basketball season has started–very exciting. The NFL action this week was fairly predicatable. I stayed away from the Eagles game and thankfully avoided the fate of others who favored the team. The Bills are humorously bad without Allen. The Patriots were the “lock” and delivered. The Vikings were in a similar situation against the woeful Jets. The Browns surprised me, yet again. What an improvement from last year.

Helping inmates here is a challenge. One fellow adds a superfluous -ed to verbs already conjugated with an -ed. When you say that you likeded that album, a part of me dies. Others make small improvements but in general time is spent here entertaining oneself. Whatever TV shows, music, etc. we can be exposed to trumps any self-help. It’s hard to change everyone. Social justice is even harder. I reprimand anyone who utters homophobic slurs but I sense this negative feedback is not always welcome.

10/10/18

Biopharma/Investing
————————-
I like SRPT. Smart management, huge opportunities. Could 10x over the next 5-10 years. Think VRTX or BMRN but bigger and better.

New PFE management. Let’s see what they do with it. Big effort on the alopecia drug. I’d like to see smarter deals. MDVN and ANAC were embarrassing.

ASCO Fall (ESMO) shouldn’t bring much new.

Papers I’ve Read
——————–
Reminder that most of my mail is still in our “old building” which we’ve vacated for repairs.

Sweet Binders: Carbonic Anhydrase IX in Complex with Sucralose. Lomelino et al. ACS Med Chem Lett 2018.
CAIX is of interest to Warburg effect fans (not sure where I stand on that, not very positive at least). I’m sure the authors understand that carbohydrate-based drugs are mostly cell impermeable, but who knows what the carb uptake receptors will pull in…

Clinical Trials I Noticed
—————————-
Dose Escalation and Expansion Study of FLX475 Monotherapy and in Combination with Pembrolizumab. FLX Bio.
This a CCR4 antagonist from the people that brought you the Bristol-Flexus acquisition.

A Study of JNJ-63733657 in Healthy Japanese Participants. Janssen (JNJ).
This is a tau antibody for Alzheimer’s.

A Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of TAK-981 in Adult Participants With Metastatic Solid Tumors or Lymphomas. Takeda.
Mechanism unknown.

Arginase-1 Peptide Vaccine in Patients With Metastatic Solid Tumors. Heriev Hospital.
Interesting.

EBV-TCR-T (YT-E001) for Patients with EBV-positive Recurrenct or Metastatic NPC. China Immunotech Co., Ltd.
I’m not current on EBV-driven tumors but this looks interesting. China IO in general is fascinating.

Phase 2 Study to Assess Dystrophin Levels in Subjects with Nonsense Mutation Duchenne Muscular Dystrophy. Drug: Ataluren. PTC Therapeutics.
Give up, already.

BI 655130 Long-Term Treatment in Patients With Moderate-to-Severe Ulcerative Colitis. Boehringer Ingelheim.
This IL-36 antibody had very good results in pustular psoriasis (80% disease activity reduction). No other IL-36 mabs as far as I know…

Researching an Effect of GLP-1 Agonist on Liver STeasosis (REALIST). Trulicity (dulaglutide). Lilly.
I don’t think this trial is very realistic.

Dual mTORc Inhibition in advanced/recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer. Takeda.
This drug, TAK228 aka MLN0128 aka INK128 was acquired from Intellikine. Generic name is sapanisertib. Not sure on how more isoform activity will help.

Anhidrotic Area and Safety of MEDITOXIN in Healthy Male Volunteers. Meditoxin vs Botox. Medy-Tox.
Korea Botox.

Intestinal Microbiota Transplantation or Nonalcoholic Fatty Liver Disease. Zhongshan Hospital, Xiamen University.
Bizarre!

A Multi-center, Prospective, Single-Blind, Controlled Trial Comparing Diagnostic Value of Different EUS-FNA Techniques.
Procedure: Standard suction, slow-pull, wet-suction.
Procedure: Standard suction, wet suction, slow-pull.
Procedure: Slow-pull, standard suction, wet suction.
Shanghai Zhongshan Hospital.
Now, I’m no expert, but I have received this therapeutic intervention dozens of times. You definitely want standard suction, wet suction, and FAST pull. Cuts procedure times meaningfully.

The Effect of Light Therapy on Post-Surgical Pain. Green LED vs. White LED light therapy. University of Arizona.

The Effect of Experimentally Increasing Sedentary Behaviour on Subjective Well-Being. Western University, Canada.

Influence of Dental Occlusion on the Performance of High-Level Rowers. Rennes University Hospital.

Personal
———-
34 months to go in a few days. At worst.

I haven’t seen such a mispriced line in the NFL this year until PHI -3 vs. NYG. The Giants are bad.

Anyone think Pinkerton is overrated in this 2018 #metoo environment? Geek misogyny?

Glossary
———–
myeloid. The bone marrow lineage which differentiates to granulocytes, monocytes, erythrocytes and platelets. Contrast with lymphoid.
ontogeny. Development of the organism from birth to death. Contrast with phylogeny.
phylogeny. Evolutionary development of a species, throughout time. Contrast with ontogeny.

10/3/18

Biopharma/Investing
————————-
So many distressed generics companies. ACET, LCI, TEVA, AKRX, CXR. There has been a bunch of consolidation: Sandoz/Aurobindo, Teva/Actavis, Amneal/Impax, Aceto/Citron, Lannet/Kremers, Stada/PE, . I think you have to see some more Indian consolidation. Perhaps Sun, Cipla, Lupin or Dr. Reddy’s will flex their muscles.

What do y’all think of the PTCT data?

Boston Pharmaceuticals didn’t get the memo that you can’t have a successful antibiotic company in 2018.

Clinical Trials I Noticed
—————————–
A Clinical Trial to Evaluate the Reversibility of Abacavir/Lamivudine/Dolutegravir CNS-Related Neurotoxicity After Switching to Tenofovir Alafenamide/Emtricitabine/Darunavir/Cobicistat
J&J funded.

Safety and Antitumor Activity Study of Loncastuximab Tesirine and Durvalumab in DLBCL, MCL or FL. ADC Therapeutics.
Safety and Antitumor Activity Study of Loncastuximab Tesirine + Ibrutinib in DLBCL or MCL.
ADC is one of the most exciting private companies. Target here is CD19.

PF-06952229 Treatment in Adult Patients with Advanced Solid Tumors. Pfizer.
Despite the title, this study is enrolling only breast and prostate cancer. My guess is its some androgen/steroid synthesis inhibitor. MOA unknown/unpublished.

A Study of FT2102 in Participants With Advanced Solid Tumors and Gliomas With an IDH1 Mutation. Forma Therapeutics.
Another IDH competitor–this drug, olutasidenib, makes me wonder if AGIO is a short. CELG has a bunch of weird options on Forma’s programs (and company).

Intratumoral AST-008 Combined With Pembrolizumab in Patients with Advanced Solid Tumors. Exicure.
I never understood the whole “stab the tumor with a drug” thing. I suppose there are non-resectable lesions that are still accessible by injection? Anyway, DVAX is doing this, too.

Effect of Shortening the Palatal Extension of the Mouthguard on the Degree of Satisfaction of Water Polo Players. University of Barcelona.
I hope these brave scientists conducting this ground-breaking research are successful.

Psychoeduc Interv. Through Meta-universes on Condom’s Use Self-Efficacy and Sexual Behavior in Students of UAChile.
Speaks for itself, really

Personal
————-
The computers here have new keyboards which are horrible. “The Virtually Indestructible Keyboard” does seem indestructible but it also virtually unusable. I’m an expert typist–I feel bad for the two-finger typers here.

Closing in on 34 months to go. This bid is about how much time I spent in college, not studying.

Football
———-
How good are the Chiefs?!!
My formula says Patriots have an 86% chance of beating the Colts. My other formula says they win by 15 points with R^2=0.5. Line is -10.5 with ML implying 75% win odds.

 

9/27/18

Biopharma/Investing
————————-
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
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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.