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In two weeks in Tokyo - yet another interesting conference on lipidomics.
60th ICBL
I remember Dr. John Nelson at the NLA AMRN symposium in Portland essentially said to track Japan. I think it'd be cool to see a couple of these frontier-land ppts.
The Economist in April had this one on synthetic biology and mentioned a firm in Seattle working on designer proteins while steering to avoid the fate of all the algae biofuel companies that came and went quickly before. And I heart that the writer even mentions vanilla pods...
www.economist.com/technology-quarterly/2019/04/04/the-engineering-of-living-organisms-could-soon-start-changing-everything
FunnyGI2- Your first quote, I take as JT's subtle, dry humor. Suppliers supply. And catchers, catch. Plus, in your comment provided on the $1B, it's not specific to any suppliers - so & I mean this only rhetorically, how would I assign the $1B in revenue for those suppliers? (which? all mentioned in 10Qs? or from ocean to pill?)
Second quote, I take as some API suppliers are keeping busy not actually impressing AMRN with the timing of their current campaigns and overly rosy expansion talk. (b/c he used the word "trying") AMRN as a buyer can probably tell about how much is BS. That was how I read it. I put less weight on a second interpretation that API suppliers are saying "how high" when AMRN says "jump." He could have said the latter interpretation with less of an O. Henry twist.
KCSven - Excellent post. Risk is a buyer's tactic to tire kick.
You and Tasty both are crushing it this morning.
Dancing- Lots of brands/industries have limited capacity and allocate widgets between regions or customers to chase margin, market share or geopolitical risk reduction. Flip side to reducing costs and risk, by having more than one supplier. The biggest and best market will get the first and largest product allocation. Leveraging regions or internal sales allocation battles to various wholesalers and markets...normal business problems. AMRN wouldn’t only want CVS insurance coverage. They’d want Kaiser, too. EU and US— same idea.
HDG - yeah, we talked about that before on UAE, MEX and Canada in terms of market size. I also assume like you guys that generic Lovaza producers could be induced to make some plant upgrades to elute EPA >95%. Maybe when that time comes like HerbieRay says, in 2023 when sales rock and roll. ;-D
On Pronova - known for filing lots of patents, keeps R&D busy...anyway I posted earlier this year when they lost in court one of their patents for an acid wash step because it was obvious and known in the prior art. Interesting, didn’t know that back in 2014 BASF refunded AMRN 3 mil or as LarryBird said about Lars’ family connection.
Larry, I've always thought BASF would dovetail nicely with AMRN regarding API supply. But, not sure about the time & effort to get agreement between themselves. Could be a cultural mis-alignment that goes away for the right price?
True supply issues at some point are highly likely. The API price to AMRN, their wholesalers & consumers will adjust to accommodate the supply limitations when that day comes. At this early build stage, I would assume its more the API suppliers attempting to extract more concessions as AMRN demands more volume for an inventory build. That's still a "supply issue" right, but just a normal sort of one.
The more immediate issue IMO is the speed with which healthcare practitioners adopt IPE therapy for whatever the final label expansion reads (+ the off-label scripts) and by extension insurance paying for an add-on to statin therapy. As the board likes to discuss.
Tasty - I think, yes I did some *rough* estimates like you did in the several thousand ton range. Last October I started to make estimates of each plant and how much API they could produce but the public figures are sparse and could change with new technology and process efficiencies that don't get reported. It would be hard to get closer to actual since plant capacity could have changed - plus, everything is under NDAs. And what isn't - the plants would say, well what would you like the yield to be... based on what starting intermediate %? If you have a lower intermediate % of O-3, it will still use up capacity and time which means you would yield less EPA API for the same amount of inbound material. A plant could have a capacity of say 1200 mt of Omacor. But, the capacity could be lower when trying to get ONLY EPA based on what techniques a plant uses. Say supercritical fluid extraction is the best (using CO2 as the solvent to split all the fractions out), but the plants AMRN has chosen only have 1 line utilizing costly SFE and everything else is slower but less expensive HPGC (I'm making this up to illustrate a point). I've seen some rates in process patents. Not sure if I'm making any sense, but hopefully that gives an idea of why its difficult to calculate with any specificity unless somebody whispers all the #s in your ear or you've gotten a tour of the plants. AMRN as a customer would have a pretty decent idea of specific capacities available out there.
Dancing/Kev - No idea why your article says Sweden. All the articles I linked to are in Denmark. See Kalundborg on DM map below & BASF Comm Mgr quoted was in DM. Funny, how something I thought would be as uncontroversial as a location...only the AMRN Ihub board. :-/
But yes, I think something could be going on - the timing is a bit coincidental to out of the blue, 5 years after mothballing, to make this announcement that it's "permanent."
Agree Dancing. It could.
Dancing/Tasty - hi, was on the road a lot the last 3 months. So, was scanning these past 2 weeks for whether PR would be granted and yay, it was!
Peru's anchovy quota they are fishing on now was announced at 2.1 mil mt back in April (biomass estimated at 7 mil mt). About a mil mt off from the same period last year. However yields have been better even with a high juvenile presence. They are 50+% of the way through and should be done around June 22nd if current catch rates hold up which is pretty good considering many Peruvian ports were closed on/off due to rough seas in May. Overall, global crude marine oil volume will be down from last year (Northern Europe production has also been down as expected due to quota reductions + poor yields). Original forecast was for a world reduction of around 100,000 mt from last year's total, but due to better yields on some fisheries it will likely be much less down than that. Maybe only 60,000 mt down from LY?
I'd guess roughly as follows:
- days/weeks, fishing off coast of Chile or Peru for anchovy
- 1-2 months, anchovy crude oil from shore plant in Peru/Chile (heat raw mat to 95degC & screw press/decanter to separate oil from solids and water)
- 2-3 weeks, from Lima/Callao or Santiago to Norway via Panama Canal on an ED&F bulk ocean freighter
- 1-2 months, 1st rectification step (washing + to mid-concentration step)
- 1-3 days, by ferry/feeder vessel if to mainland EU for 2nd final refining stage to API
- 1-2 months, 2nd refining stage to API via HPGC, SMBGC or SFE, etc etc.
- 3-4 weeks, shipping containers of drums or flexis to encapsulator
- 3-12 weeks, encapsulator could be less if JIT delivery is perfect
- 1-2 weeks, shipment out to wherever, USA DCs
Switching gears,
Long ago history refresher on GSK/Pronova/Reliant. GSK promised a big ramp up in API fish oil demand and Denmark built a plant...GSK cancelled their agreement to buy API from the plant in Kalundborg and a lot of people were laid off.
That memory sticks partly because of the manner in which GSK made their demands with a lot of BP swagger. I've attached articles (use Danish to English translation), but interesting 2 days ago BASF decided NOT to resume production at this Kalundborg plant which has been mothballed since 2014.
new article this week on Pronova factory
https://sn.dk/Kalundborg/Helt-slut-med-Pronova-fabrik/artikel/844012
https://www.berlingske.dk/business/rig-nordmand-gaar-i-land-i-kalundborg
https://sn.dk/Kalundborg/Fabrik-skal-genopstaa/artikel/687303
https://www.tv2east.dk/artikler/100-nye-arbejdspladser-til-kalundborg
2014 article on plant closure
https://sn.dk/Kalundborg/Pronova-lukker-fabrik/artikel/437477
Yes, in a similar vein, WAPO did an article on health fitness trackers and employers last month. Bosses of especially family run companies are telling employees they need to get more sleep if devices show they don't get at least 8 hours or exercise more if they don't move or get their heart rate up for the minimums.
Companies, government, labor... - always a dance between competing interests.
More employers up here in Seattle are doing something similar to your Providence kind of experience, too. For $700-$1500 annual premium discounts on your employer-sponsored health insurance then you have mandatory health check-ins, reading material, etc etc.
I agree, it's inevitable and for some already here. We aren't into the penalty phase yet...still the behavior nudge stage.
Raf - Apples! or well, some species of our domestically grown foods seem to be on the mind of Scott Gottlieb today, too.
Frans de Waal, a Phd in primate Zoology - has a short TED video on his fairness studies in primates (his books are even better): www.ted.com/talks/frans_de_waal_do_animals_have_morals?language=en
Your apple example is a good one and it fits with the spirit of "cooperation" and or fairness that appears consistently across the animal world. Wash State produces close to 60% of our nation's apples. None of it would have been or continue to be possible without government developed irrigation and subsidies from tributaries of the Columbia River (an apple orchard needs 3 1/2 acre feet of water for a given growing season!!). The irrigation systems were originally built and maintained along with the dams by the US Bureau of Reclamation and the US Army Corps of Engineers. Now, extension agencies at universities like Wash State Univ in Pullman, WA help to further the horticultural knowledge necessary to yield more with less water for farmers due to lots of competing interests for the same water and water levels (outdoor recreation, NEPA, tribal rights). The US Dept of Agriculture (and APHIS), EPA, FDA, Bureau of Indian Affairs and Interior departments help coordinate (or hinder ;-D) efforts across all agricultural sectors to bring apples to market. I'm not even going to list the WA State or county agencies. An excellent introduction to the subject of dams and water policy in the Western US is a book entitled Cadillac Desert. It reads like a noire political thriller. The Hollywood version of some of California's water disputes back in the 70's was Chinatown.
If we didn't have laws and institutions powered as they currently are there would be no apples or at least any that you would trust to crunch into except if grown locally in NC by those in your social network or neighbors although they might be polluting your adjacent property with too much fertilizer and pesticide run-off or stealing your water and where would you turn to enforce your property rights in a peaceful sort of way? Government courts...
The apples we crunch into - exist because of a multi-partner dance between farmers, government, co-ops and universities. We all partially subsidize our apple growers, FWIW.
Flubber: Viet Le is handling the AMRN messaging regarding yes, that type of O-3 and dose matters.
Probably if people took 8-10g/day of combined EPA and DHA. But, then a patient's bathroom might smell like the seal or penguin exhibit at the zoo.
A centrifugal separation technology alone isn't going to purify to 95% EPA. Centrifuging is pretty much only the very first stage from fish to crude fish oil (separating water, proteins, any remaining fish tissue). Or you could consider centrifuging the second stage after the press cake (the fish mass left that goes into protein rich fishmeal for animal and aquaculture feed).
Afterwards, there are a number of strategies often used in combination available to chemical engineers to purify to various concentration levels - all have their pros & cons.
Here are some typical ones:
- urea adduction
- gas chromatography
- low temperature fractional crystallization
- super critical CO2 extraction
- short path distillation
- enzyme (like adding an amine) extraction
AQB up big today on FDA lifting import ban on GMO salmon & salmon eggs.
www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm632952.htm
I still think some of these US land-based farms end up like NGEY did or the catfish farmers in the south who have been limping along for more than 10 years (Alabama's SouthFresh Aquaculture (catfish) declared Chapter 11 recently)...unless they have the backing (subsidized or vertically integrated under a group umbrella) from a large Ag outfit or are niche going to high end restaurants/farmer's markets. They always have a lot of headwinds: volatile feed costs (although lower right now), expensive water systems, (relatively) long grow-out periods, fish diseases, high transport cost to market etc.
And if it's a salmon farm - they need O-3 in their diet. Fishoil inclusion rates in salmon diets were reduced too much over the last 6-7 years (now being admitted by the Europeans) so if Veramaris (DSM & Evonik) isn't over-promising and under-delivering then we should see their algae oil entering the feed markets this summer - volumes still TBD, but Veramaris vaguely claims their algae oil will be 15% of aquaculture demand.
A very few companies control the farmed salmon sector. The EU is investigating those big farmed salmon companies right now for "price-fixing." I doubt it will go anywhere.
Git 'em JL. Heart counts over head counts.
Keep movin', movin', movin'
Though they're disapprovin'
Keep them doggies movin', rawhide
Don't try to understand 'em
Just rope 'em, throw, and brand 'em
Soon we'll be livin' high and wide
My heart's calculatin'
Rawhide!
LB, I don't have a background in pharma or pharma plant construction - let alone the regs for those associated topics in Europe, and North Asia.
What I have seen with respect to FSMA (Food Safety Modernization Act) is that a food factory can be revamped to meet FDA requirements in about a year or so. It's done by a box-in-a-box, essentially that puts a new shell on the inside of a factory. Again, that's not accounting for with respect to pharma grade oils whatever new pipes, columns, evaporators, in-take areas to prevent contamination, etc for processes that would also need to be upgraded.
I hope you don't mind, that I'd rather not make up a loose number that there's so many thousands of tons of pharma grade underutilized capacity available and that capacity currently going to DS will convert to 95% pharma purity capacity at such and such a rate over the next 10 years. Do I think there is excess capacity currently - yes and that bodes well for AMRN for the next couple of years.
Suppliers are going to want to see sales of V continue to shine to justify plant conversions where necessary, but IMO that's several years away.
PS - you were spot on, regarding posting to Federal Register rule changes after comment period...
HDG, Absolutely! <chuckling> I had thought about putting a note in for an assumption relating to churn (compliance) rate of like 55% or whatever, but decided to go for clarity in a sense of physical scale as I said at the end. (prior to encapsulation)
Maybe it will have a better compliance rate than statins (b/c "natural source", etc) or worse because it's an add-on?! At any rate, it makes modelling fuzzier.
--------------
Duke - just to clarify for understanding, crude refers to what's rendered from the source material. Then you'd have intermediates from the crude. So-
source material (fish, algae, other) > crude > intermediate > refined
IPE/V - whatever you want to call AMR101 - would be refined and purified to a pharmaceutical standard (not crude, not intermediate).
Aumeoli, AMRN can meet its current demand with available refining capacity.
With JT speaking for his roadshows in terms of 40 million statin patients as a potential size of the market - that tends to dovetail conservatively with the 50-70 million patient range based off typical harvested EPA volumes in a given year, exclusive of actual refining capacity volumes in FDA approved pharma plants.
Maybe this visualization will help? Let's say AMRN has 50,000 patients on V in 2019. That's 72 metric tons (mt) of EPA or about 3 tanker trucks or intermodal containers going down the highway (18-20 mt allowed on a highway for weight restrictions, depends on gross weight of trucks which varies). Or almost one tanker railcar (about 80 mt +/- in a tanker railcar).
So, 40 million statin users = 57,600 mt of EPA or 2,880 trucks or 720 railcars.
I'm using these container types as examples to help in developing a sense of scale for the volumes involved, ie, the difference between 3 trucks and 2,880 trucks. If we were to start talking in terms of 1 gram capsules then we could probably describe in terms of length traveled in outer space if we lined up all the capsules end-to-end or how many capsules would fill a football field or something like that. Scale can use a dose of creativity to convey adequately.
I agree AllinFun - we all know Renee does a *great* service to the Ihub boards.
I cut Renee some slack on her hypothesis generating statements (aka opinions) . I think she was just trying to be helpful;she can't control the cackling mob that follows her around.
There are risks here - but most of us knew that we when put money into a ticker that had a skull and crossbones next to it. Back in college I used to race bicycles - USCF Category 4 aka Crash 4. It was called Crash 4 because of all the newbie guys once packed up in the peloton if they followed too closely or made a dumb mistake could cause several other guys to go down. I don't mind some mad money risk - its a bit of an adrenaline rush really just like racing or any other endeavor with a bit of risk attached to it (remember this was a theme in the movie directed by Kathryn Bigelow - The Hurt Locker). I once met and chatted with Lance Armstrong at the Tour DuPont where I was a happy spectator with a Cat 3 friend (he rode only Colnago frames with top of the line Campy parts) cheering him on. He had won the stage that day and was too young to accept the bottle of champagne that went with the stage win!!
Leane and Carter orchestrating justice through the courts for the 3 electrical engineers who had their patents STOLEN by Comcast...a $180B company told these three engineers to go pound sand. 12 other cable companies are also included although through mergers and acquisitions the original 13 have morphed from the original 2015 filings.
The electrical engineers called Leane and Carter to help them seek the monies they are due for the illegal misappropriation of their patent processes to packet electrical signals in such a way as to send more information down the same existing pipeline that made high speed internet possible through our cable modems.
Go Chanbond/UOIP!
Early April - late May or later, all good whenever it happens.
I had been planning on picking up a few more little cheapies in April or May. Looks like I better do it this month before we go private.
Nelly Furtado says it best - 'but after midnight, morning will come':
Turn off the lights
Nice K! Settlement discussions. I will assume still on going for the next several months even if nothing reached as of yesterday.
As we all knew - likely explains the volume action this past week and the usual types of FUDster drones being sent out as Justus said.
AJ - your customary greeting this morning made me laugh - too funny!
I need a bowl of popcorn.
Factual and succinct response BrokeAgent. Nice.
This article is a bit of a mish-mash. Atlantic cod populations crashed due to overfishing not warming oceans (Mark Kurlanksky's "Cod" is a good one - and AVI will surely feast, if you can call it that, on dried & salted cod in Portugal next month, called bacalhau). For those who have the time or inclination for a good fishing yarn I'd recommend - "Distant Water - The Fate of the North Atlantic Fisherman" by William W. Warner. He also wrote "Beautiful Swimmers" about blue crabs in the Chesapeake Bay. VIMS at the College of William & Mary in VA has done a lot of research on the bay (and the Potomac aquifer that all you Virginians rely on. The effects on the aquifer likely won't be pretty as salt water intrusion hits the piedmont and begins effecting the watershed hydrology) - Woods Hole tends to do more of the New England species. A professor, Dr. Deborah Steinberg at VIMS recently did some fascinating studies on (dare I say the word? ;-P) krill populations shrinking since they won't pass the wall where the temperature gradient shifts.
Oceans are warming, for whatever reason. And even small differences to a human mind, can cause massive shifts in ocean dynamics.
Fish are on the move. Some species will win. Others will lose.
The species relied upon for their EPA are as we all know, cold water fish. I spoke with a former Bunge director of oil seeds trading this week who goes to Asia frequently to the palm plantations (very old school which was perfect as I wasn't looking for the politically adroit opinion aka spin). Well, he brought up a good point I hadn't thought of with respect to GMO seed oils (as in Cargill's MT trial and if it will hit the big time in the next half a decade) - farmers only devote so much of their acreage to specialty crops because of higher costs in maintaining them...
These are complicated problems in the food supply to resolve.
A few items from last Friday which was very positive-
Portlandia
I didn't include anything from Dr. Mason or Viet Le because they were pretty much the same as what has been posted previously and talked about on board.
Dr Mason - HDL, APOB combined with EPA likely improves their AOX, reverse cholesterol transport & endothelial stabilization & anti-inflammatory effects with resolvins, etc. DHA does nothing for cardio. DS unregulated and not equivalent to RX.
Viet Le - Went into all the known pleiotropic effects beyond TGs with special emphasis on supports plaque stabilization - increases fibrous cap thickness, decreases lipid volume (quizzed on it multiple times til audience didn't flunk).
Dr. Nelson - He described all the different imaging modalities and their applications. I think he was going at the speed of an OCT. He led off with a microbiology vignette about thiomargarita in microbiology class because it was the largest (.1-.3 micron) and easiest to remember - margaritas. One time he put a margarita next to a fruit fly. He was illustrating how to think of the sizes and that the human eye can see 100 microns. He listed a whole lot of micron size examples for reference. In Japan sadly since Jelis, their EPA is now down from 95 to 60 (slide 8) because they are eating more like us. Slide #11 was where Dr. Nelson started to tell everyone to buckle up for the integrated backscatter looks where EPA reduces the lipid volume and increases the fibrous volume. Slide 12 was where he talked a lot about Pentraxins and MCPs. All the following slides were important as they showed EPA reducing various markers of athero. Slide 18, he was ecstatic over Nishio's 2014 study which he said had been largely overlooked along with another one (I forget which one) (increased fibrous cap & macrophages going down) and then went on down the list of various other Japanese studies and stressed that they were way ahead of us and already figured it all out. He said he's working on a paper to get it reviewed, etc.
Then Dr. Nelson gave another presentation on Serum EPA and the EPA/AA ratio (I scanned it and the print is so tiny that I also took photos using phone to pdf - uploaded both copies since so hard to read). He said Moz study was really important, but then Kohashi looked at even more variables. I marked the ones he said were key on slide 15. On slide 18 he said as a cardio he wants to see ejection fraction. Slide 24 was where he said heart attack survival rates are worse for women. They don't get them as often, but when they do they are often deadlier? I think he said something like that. The top of slide 25 was a misprint. Slide 27 - "DHA didn't work out" - only clinical benefit for MACE was in EPA from these Japanese studies.
Other things Dr. Nelson said - Insurance companies are a problem. R-it results "striking" - lots of "biological plausability mechanisms" - "non-fish eating populations benefit more!"
Dr. Miller - steering committee for R-it, back in the day thought HDL was etiological, now TG rich lipoproteins. Goal of R-it was to evaluate patients who have traditionally been overlooked for hypertriglyceridemia since a high risk cohort seemed to benefit from past studies even when the CT failed. Low does O-3 mixtures show no sig. benefit. 1st signal was Jelis. Elevated TG, atherogenic. Before TG rich lipoproteins were thought to be causal (ProveIt trial). He talked about TRLs (trigylceride recycled proteins). CVD reduction is key (inc. ImproveIT) and hard to show. Shows it trending in that direction. He recapped all the charts in R-it. Dr. Miller also said something like "TG benefit not the whole story. It's really hard for us to say that IPE is achieving a pure TG lowering benefit. Just not there. It probably contributes" Late breaker @ ACC (later studies planned).
Dr. Peter Jones - He led off talking about the Copenhagen Heart Study. TGs are causative of CVD. Significant risk factor even if control for HDL, non-fasting levels, etc. TG & LDL -> causative, not HDL. APoC3, APoB. Jelis saw more dyslipidemic patient, high TG/LDL more benefit. It's expensive and complicated. TG 150, LDL + APoB patient +/- Ezetimbe...so do you add IPE therapy? Fibrates, Niacin....fibrates PPAR a... IPE - intriguing risk reduction. Optimize LDL treatment first (= max statin). Dr. Miller's approach is rational & reasonable. "Michael showed problem of MO not enough to give an additional benefit" (ie, non-issue) Difference between lowering TGs & magnitude of benefit? - not everything is lipid related - let's see what STRENGTH shows, etc. etc.
Just a few observations at the NLA this afternoon. There were about 60 or so people present for the satellite symposium. And about 250 people for Sessions I and II. (Grand ballroom was full with many standing in the back of the room). Somebody asked how many in the audience had been at the AHA and about 30 hands went up.
I caught the very end of the chat with Dr. Neil Stone. I also listened to the Reduce-It session II with Dr. Michael Miller and Dr. Peter Jones including the Q&A with a question on fat alleles already answered by Dr. Miller, and then there was another question from a person good naturedly trying to “put panelists on the spot” by getting them to make O-3 predictions on STRENGTH in light of Reduce-It. Dr. Jones took the bait. I visited the sponsor tables in another room afterwards which included some folks from Amarin here in the PNW, etc. I also briefly saw them at the bar with MD34 and his wife. All were very warm, gracious and upbeat.
I took some notes and also have a copy of Lipid Spin & an Amarin booklet of the satellite symposia ppts entitled “Everything You Need to Know About EPA - its effects on HDL Functionality and Plaque, Pleiotropic Effects and the Clinical Utility of the EPA/AA Ratio”. I can scan the booklet to a pdf form later - but b/c there are 3 slides to a page it will be hard to read.
The NLA is a forum for healthcare professionals - so there were many “quizzes” with patient cases. A lot of the conversation revolved around studies/science that support and extend the findings of Reduce-It along the lines of what would allow enhanced decision making with all the different treatment options for reducing CVD risk open to clinicians for various scenarios and how EPA, for example should be slotted in.
These were the only sessions I intended to attend.
I’ll try and find time to post more later next week, but now for some weekend skiing & tubing at Mt. Hood with 3 feet of fresh snow called for by Monday.
MD34- yes, here. blue blazer, scarf. Also can PM me and can text you back. Nice recap of EPA detail 2 hr ppt presentations—clinicians working hard on EPA/AA ratio becoming standard part of lipidology repertoire. At bar, may go back in at 5 for R-it results presentation. Started with a quiz. Dr Preston Mason’s presentation we are all familiar with. Viet Le, PA works a lot with Dr Nelson, etc. Dr John Nelson’s presentation was super high energy and helped me connect more dots on EVAPORATE. This is a very understated kind of crowd.
SocialBoom, FWIW, here's the TMI on TMA.
On the organoleptic qualities like smell - V would have gone through a deodorization processing step. The EPA EE inside the capsules was most likely completely fine with their extensive pharma level process controls. I don't think the deodorization step is perfect at removing the odors that Americans in particular find so objectionable. Smells are hard for all of us, I know!!
I've attached 7 articles & reference pages regarding smells (fish VOCs). The "Is fish smelly?" article is a quick one minute read even if you skip all the more bookish attachments - ocean fish have different amino acids and amines to counter the saltiness of the oceans. we.tl/t-MaRDjyKt47
TMAO converts to TMA - trimethyl amine. Maybe a mnemonic to remember it is Too Much Ass-kicking smell.
And the fish can have different compositions based on species and depth as well as different combinations of proteases and lipases that upon dying start to cause chain reactions leading to TMA smells even if they haven't gone "bad."
Keeping fish chilled upon catch helps to slow the growth of the VOCs by delaying the amount of time before the reactions get going but in a lot of fisheries they don't have that kind of vessel infrastructure to support RSW tanks on board (Refrigerated Sea Water) or even ice slurries.
Also, it's not just fish. Texas has a problem with TMAs from cattle... www.researchgate.net/publication/269402783_Diel_VOC_Emissions_from_a_Beef_Cattle_Feedyard
Well, that was the TMI on TMA, trimethyl amines!
jmhill: Thanks for posting that profile.
Cards: Heroic effort!
JT/BioB - algal oil in the news this week with pricing, etc and the "we need to scale" bit once more...although tempered by familiar story of an ethanol plant using wheat in the UK shut down b/c couldn't make the economics work (FeedNavigator today). www.undercurrentnews.com/2019/02/12/algal-oil-in-salmon-a-hit-only-needs-scale-to-go-mainstream/
Here's a link to a decent 2016 ppt by a Peruvian consultancy that has some of the #s as I graphed earlier to the board but with more color. we.tl/t-zR05RlAJjw
For some Friday funnies: in 1972 the NYT reported that the CIA (did the Soviets not only take our grain, but also our access to anchovy?) was looking into the crop drop in Peru www.nytimes.com/1972/11/18/archives/c-i-a-mystery-perus-anchovies-agency-takes-up-difficulty-of-sea.html
And some Scandinavian opinion this week on where Peru goes for the next April - July quota period - crude oil supplies forecasts look good for the balance of 2019 & look who is mentioned:
Hi ----
Thanks for this email and the very best wishes for the new year –
Quota: 2.5-3.0 millions in Peru – yes agree, pretty realistic estimate
Market: Given that mother nature provides us with more or less same biomass worldwide in 2019/2020 as we had in 2018 :
We shall see a rather firm and steady market. It is difficult to find strong bearish arguments.
With the predicted growth in aquamarkets – steady go steady in petfoods (continuously showing a positive trend/growth/demand) – the Omega 3 markets worldwide will take their share of the
crude oils becoming available worldwide! Omega 3 processing companies had a good year in 2018 as the Peruvians were back on the stage with ample supply ---------------
30% oils – perfect match for the refineries etc.
New markets in new areas (Asia) as well as Amarin breakthru in the States – make the future pretty promising unless the producers in Peru get too greedy and killing the spirit by trying to squeeze out a last cent of the crude
CBB: If you or Mapman can, I'd highly recommend you visit India. I visited India once as a tourist a few years ago and vowed I need to go back and spend 3-6 months all over the country from Kerala to Darjeeling - if I could safely visit Kashmir, I would. Incredible India!
India is known as having a "license Raj" state - so much red tape to get anything done that nothing does get done. The other problem is the grinding poverty and a lack of jobs - have you heard about their glut of MBAs, engineers, etc? This is why so many try so hard to get H1-Bs or L1-As in the tech industry here in the US - there are a lot of Indian people in the Seattle area. economictimes.indiatimes.com/jobs/indias-mba-crisis-why-fresh-graduates-are-not-getting-jobs/articleshow/61794456.cms
They have to pay out-of-pocket for medicine. thewire.in/health/who-is-paying-for-indias-healthcare
I think your average person would be hard pressed to afford V in India at our prices, but as with China the middle class could better afford it if prices were kept super low - that might make a complicated sense to pursue for broad global health goals. I like it!
Yeah, Tasty, I wonder if CMM3rd has an opinion?
Good questions on the patents for V and do they get extensions for "new" indications which you're right the board has debated. LOL, along with everything else.
BerryFit: I'll second Cards and say I'm glad we have a RD publicly posting, too.
I agree that RD's can make a difference with V.
Most people just can't do this in the modern food system that exists, it's too complicated. My patients would say to me "isn't there just a pill I can take"?
MrMain: Be glad you live in Bellevue! Viadoom was super bad on Friday with the Stanford track team's bus catching on fire. Gummed up everything in Seattle for the commute home.
Anything is possible with respect to off-patent sales, but is it likely? Probably not. Someone is always willing to sell for a nickel cheaper and you'll see in Japan EPADEL sales have been falling off post patent cliff. About half of the market was generic as of 2015/16. I think Tasty did a scenario back in Oct or Nov that seemed reasonable for what a drop in V sales after 2029 could look like.
Regrettably, I don't know what you mean by locking up inventory channels - V's volume in the overall O-3 market is currently minuscule.
Tasty: 10 million patients should be doable from a gross EPA supply viewpoint - but I don't think industry can refine anywhere near that much 95% pure EPA today. Here's where you'd have to start watching large order equipment sales. (My WAG for the patent life they likely could if all things go well max out at around 5-7 million patients) As far as pricing...yes, I agree. Limited natural resource and a tight supply with increasing demand will cause the price to spike quickly, but V sales growth should be gradual enough to accommodate the shift both from aquaculture and nutraceuticals - that's what I'm going with anyway. I did post the EPADEL sales growth pie charts previously and sales growth was slow in Japan - blamed on doctors not prescribing despite the 1990s evidence, but after Jelis it picked up. I figure R-it is similar.
In Peru, as far as pricing, from feed grade to min O-3 unrefined fish oil = 25-30% price difference. From feed grade fish oil to high/max O-3 unrefined fish oil = about a 40% premium. Between min O-3 and max O-3 unrefined fish oil = 10% price difference. Let's say then a 30% O-3 crude fish oil was hypothetically $3500/mt FOB Peru. Maybe that goes to $4000-$6000/mt? Does the refiner want to be compensated not just for standard manufacturing costs, but also the hit to DHA prices as that gets "oversupplied" and has longer holding costs if they don't adjust the price downwards. Refiners will pump as much of the other fatty acid by-products into the nutraceutical and cosmetics industries before sending the soaps to bio-fuels, but still they will adjust their yields and manufacturing costs to keep their margin intact of I'm guessing 40-55%. (And algae oil as an input is still about 2-3x more expensive than marine based fish oil.)
50 million patients, if you could get all the EPA for V, based on the below supply regions totaling 74,500 mt of EPA would be limited by the lack of pharma grade refining plant capacity causing V production bottlenecks ($80-$100 million for a new plant? $15-$20 million to upgrade an existing one to pharma standards?).
I think these regions have the most accessible EPA from marine fish oil:
South America: 59,700 mt
North America: 9,600 mt
Africa: 5,200 mt
Total: 74,500 mt
Dancing in the Dark posted the iffo supply reference report back in 2016. DancingDark Post #89853 The thing to keep in mind about this report is that iffo had it done because of increasing pressure due to the Lenfest report commissioned by the Pew Charitable Trust. Lenfest Report There were some major problems with this study in the population modeling. For example, the authors used a model where all the predators are assumed to feed on the next trophic level below - as in they only eat one species. So, if you take out that species then the predator is assumed to have no food - in other words their model doesn't account for mid-level fish having a varied diet and maybe switching food sources if one preferred species is not available. Not to mention all the assumptions in models on how that would affect fecundity. I remember talking to Dr. Ray Hilborn about it a few years back and this is my recollection in addition to him telling me that NOAA adopted & uses among a few others the Lenfest model because it is an improvement over previous models which didn't take into account enough of the entire ecosystem. Also, from a moral imperative, for decades the UNDP has focused on trying to get Peru and Chile to directly eat more of these "forage fish" species rather than have them directed into the rendering industry. It worked with jack mackerel - they did increase the amount of that species that was frozen or canned for DHC. But, it hasn't worked for anchovy as well.
Regardless, other major philanthropic foundations have latched onto the Lenfest report and use it to attack marine derived ingredients by getting retailers to implement percentages of feed that must be from trimmings or max amount of (whole) forage fish. So, aquaculture producers have been on the defensive trying to show that they utilize trimmings not just whole fish in the feed ingredients. It's like GMO issues - different marketing stories for retailers to differentiate themselves as having more "higher-end" or more "transparency in the supply chain" than more value oriented chains. Here's Whole Foods values smt
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Peru Fishing Update: They should be done with the 2.1 million mt quota any day now and are pleased - remember in January 2018 they only caught 44% of their anchovy quota (left uncaught 828,291 mt). Fish oil yields are low for a second year in a row at about 1.5+% (should be at least 3-5%). Peruvian fish oil prices are up slightly, but basically stable for now and expected to moderate the second half of this year once the next quota season gets announced (and especially if it is announced at 3 million mt or so). Nobody is sure why. I wonder if its water temps? There was a good article in the WSJ last month on the Alaska Pollock fishery in the Bering Sea (the largest fishery in the US) and what's happening due to rising ocean temps.
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Well, and speaking of refiners Nissui won at the US PTAB versus Pronova (BASF) on a patent challenge on Jan 16, 2019. The PTAB agreed with Nissui that Pronova's '360 patent was mostly and variously depending on the claim, either obvious or indeterminate (in its use of terms) to those skilled in the art regarding a processing step to remove undesirable components from crude marine oil. Japan shoots & scores!
BioB: Unfortunately, I view it as VERY difficult for AMRN to enjoy a COGS advantage by dominating the supply chain like a John Paul Getty of EPA. Industry reports still cite the 2016 iffo/UN FAOSTAT commissioned report (posted by DiTD here in 2016) for about 115,000 mt +/- depending on annual quota allocations of total of EPA (lower than my back-of-the-napkin estimate in Oct to JL). Realistically then, that's about 50-80 million patients per year at current dosages. 80 million assumes a Getty of EPA could get all marine sourced oil to make V. 50 million assumes from the sources with the most EPA (= cheaper to produce the EPA since less concentrating)
It would be nice to improve the bio-availability of V and maybe only require half the dose. Like Rosemount and others here have said (and also Dr. Matthew Budoff in the July STAT interview)- compliance can be difficult for those who don't personally compare it to injection, but rather large V capsules to a smaller statin pill.
What's your opinion - should we expect 55% compliance which is about what I saw cited in a few adherence studies between different drug classes when I last searched it (and what I'm using in my valuation scenario)?
Anyway, so I think COGS stays the same or trends up a little in the range of up to 5 to 10 million patients treated and likely would go up beyond that because its a finite natural resource (tight supply = higher prices). Also in 2020 there are going to be new fuel rules going into effect for ocean vessels which will raise ocean freight costs which already are increasing this year ahead of the rule change:
www.exxonmobil.com/en/marine/technicalresource/news-resources/imo-sulphur-cap-and-mgo-hfo
IMO 2020
I view it as-
1) if EPA from harvested marine sourced oils = sprawling global supply chain (political, regulatory, and transportation risks and costs)
2) if from alt-sources (SCOs) = still would need to be build FDA pharma grade level plants next to the SCO production sites or you'll still have high logistics costs and regardless you have substantially higher energy costs to grow out the algae
Also, new rules went into effect last year in the US making truckers harder to come by as many have gotten out of trucking since they have to report electronically all their hours (forcing them to take mandated rest breaks which reduces their profit from lower turnover rates).
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Synthetic epoxides of EPA/DHA molecules - that'll be a different chapter for potential domination a decade or more from now.
North: Isn't copyright law complex and often judged on a case-by-case basis - I found surprising the monkey-selfie/PETA vs photographer case? I remember once a university librarian unprompted telling me while helping me copy a few pages in a book that I could copy up to some X% under the fair use doctrine.
I'm 100% supportive of the fourth estate being supported by subscribers (Ihub, too for that matter) with many friends in journalism many of whom have had to find other careers after being laid off. It's a financially rough way to "make a living." They get to live their values however. Hoo-rah.
I do find the history between AMRN and AH kind of curious - Stat's free hit/sensational/click-bait piece article the weekend of 11/10 that didn't include actual coverage of the crowd in attendance reaction at all?...and once I learned from this board the slanted history of coverage with AMRN went back to 2013 it's caused me to question the motives I initially assumed were only to be an internet provocateur.
I'm not sure what ADVFN does if anything about all the news and analyst reports that get posted to their servers to educate investors, but it is an interesting question. Maybe the mods are familiar?
My very basic view of fair use: www.copyright.gov/fair-use/more-info.html
Fair use is a legal doctrine that promotes freedom of expression by permitting the unlicensed use of copyright-protected works in certain circumstances. Section 107 of the Copyright Act provides the statutory framework for determining whether something is a fair use and identifies certain types of uses—such as criticism, comment, news reporting, teaching, scholarship, and research—as examples of activities that may qualify as fair use. Section 107 calls for consideration of the following four factors in evaluating a question of fair use:
Interesting, thanks Zomby. Nice DD effort on the various patents final expiration dates.
Afish: Yes, I think so. Not ready for a divorce just yet then? ;-D
Kiwi: I did speak with Dr Decker. This is a super short version of the convo-
It's unrealistically difficult to check with any specificity for oxidation from a particular oil. The science is not settled and is controversial depending on who's opinion you are quoting.
Healthy populations - our bodies handle rancid oils pretty well except if a person has a specific allergic condition in the gut (think about all the fried foods people consume daily... with fry oils re-used 10+x)
Patient populations - rancid oils add to the inflammation burden especially in the GI tract
One could check isoprostanes in a urine sample and that would give an approximation of hydroperoxides.
He also said there are some interesting studies in Massachusetts going on with cranberries and the bennies their natural AOX confer as they pass through the GI tract unabsorbed (how they affect the GI microbiome).
He reiterated what I've said - these long chain PUFAs derived from coldwater fish in whatever forms EE, rTGs, etc should be kept in the fridge at a minimum, preferably your freezer.
Edwin Frankel (now retired) was his advisor and he mentioned this book for more in depth information-
Lipid oxidation
Afish: here you go
Amarin’s CEO drops enough JPM19 hints to know Vascepa sales driving higher
By ADAM FEUERSTEIN @adamfeuerstein JANUARY 9, 2019
ALEX HOGAN/STAT
SAN FRANCISCO — Amarin (AMRN) CEO John Thero used his Wednesday breakout session at the J.P. Morgan Healthcare Conference to not-so-subtly telegraph a stronger 2019 sales outlook for Vascepa than the company’s official guidance offered last week.
Thero, of course, can’t come out directly and say that Vascepa, Amarin’s heart drug derived from fish oil, will deliver significantly more than a 50 percent year-over-year increase to $350 million in 2019 sales. Like Fight Club, the first rule of sandbagging revenue guidance is not talking about sandbagging revenue guidance.
But during meetings with investors over three days here, and then on Wednesday during the breakout session, Thero dropped plenty of hints.
Vascepa sales in the fourth quarter were approximately $74 million, growing 35 percent sequentially. That puts the drug on a $300 million annual run rate already, without any expanded marketing push.
The company’s Vascepa salesforce, increased from 135 to 400 reps, just started to make doctor calls on Monday.
The New England Journal of Medicine is publishing print copies of the Vascepa REDUCE-IT study this week. Under Amarin’s First-Amendment, off-label drug marketing settlement with the FDA, the company’s sales reps will be able to use the NEJM paper to promote the cardiovascular benefits of Vascepa well before the FDA expands the label officially.
Amarin is purchasing enough Vascepa inventory in 2019 to support sales of up to “at least” $700 million this year.
The first (current) quarter is historically the weakest for Vascepa sales, Thero cautioned, because patients with insurance have to work through their renewed insurance deductibles. Growth re-accelerates in the second quarter and throughout the rest of the year, he said.
Thero’s bullish message is getting out there. While Amarin’s stock price dipped last Friday when Vascepa guidance was announced, shares have since risen more than 20 percent. On Wednesday alone, Amarin is up 9 percent to $15.23.
Merc21: Good post. To yours and XBL's points, I got a chuckle from this article below from the other day in Stat because it rings true whether the "commodity" is a bio-tech company, drug, equities, bushel of corn, a new app, real estate, star BBer, or whatever. That's why I figure it's important for me to at least >80% believe in some important aspect of executive mgt's mission being achievable if I'm buying into the long story - without that it's a lot of razzle-dazzle, schmazmatazzle.
What not to say at J.P. Morgan, according to a conference veteran
By REBECCA ROBBINS @rebeccadrobbins, ADAM FEUERSTEIN @adamfeuerstein, and DAMIAN GARDE @damiangarde JANUARY 4, 2019
Mike Huckman, a global practice leader at the PR firm W20
W2O GROUP
We are a few days away from the start of the biggest and most important biotech business meeting of the year — the J.P. Morgan Healthcare Conference in San Francisco. If you sit through enough presentations at J.P. Morgan, you start to get buzz-phrase fatigue. Seemingly everything is a “transformational” “holy grail” of a “game-changer,” endorsed by “key opinion leaders” with “clinically meaningful” “optionality.”
But it doesn’t have to be that way.
Mike Huckman is a global practice leader at the PR firm W20, and he’s experienced J.P. Morgan from both sides of the podium, first as a biopharma reporter at CNBC and now in his career advising drug companies on how not to be boring.
That means he’s seen the industry’s addiction to jargon up close. Keeping in mind the many executives polishing up their J.P. Morgan speeches this week, STAT asked Huckman to share some tips on how to keep your audience’s eyes from rolling deep into their heads.
You put together a David Letterman-style hit list of corporate clichés that should be avoided at all costs in a J.P. Morgan Healthcare Conference podium presentation. Walk us through it.
10. This has the potential to be or this is a real game changer.
9. We’re really excited about ________.
8. Blockbuster potential
7. We have a robust pipeline with multiple shots on goal.
6. We have several value-creating milestones in front of us.
5. Innovative
4. Novel, proprietary, unique MOA (That’s short for mechanism or mode of action.)
3. Sorry, but this slide is a bit of an eye chart/This is a busy slide.
2. Our goal is to become/We are a fully integrated, commercial-stage biopharmaceutical company.
1. Unmet medical need
Tell us about your No. 10 (“This has the potential to be or this is a real game changer”).
How many times do you hear “This is going to be a blockbuster” or “This has blockbuster potential”? Company executives put expectations way up there at that blockbuster threshold, and then what happens? Either it doesn’t get across the finish line or it never comes anywhere close to that level.
On behalf of those many executives now looking over their PowerPoint decks, what should you say if you want to convey that your number crunchers packed away in whatever basement have determined that you know there’s a multibillion dollar potential attached to some asset?
It’s not just the cliché but the the outsized expectation. We all know that this is an inherently risky business it’s an inherently risky but noble pursuit. My advice to our clients is to caveat wherever and whenever appropriate. So for example: Should the data continue to be positive, should we continue to generate results that showed that this experimental therapy is potentially safe and effective and we were to secure regulatory approval, all of the medical experts in this particular field are telling this telling us this could be a really important treatment option for the people they treat.”
Let’s break down your No. 7 (“We have a robust pipeline with multiple shots on goal.”). What’s with that cliché? Why do we use that?
I have no idea why we use that one. It’s like saying, hey, if this doesn’t work, don’t worry about it because we’ve got lots of other stuff that we could try to make work. It’s become ubiquitous and instead we should just be saying, We’re working on a number of different diseases or disorders using similar approaches or maybe completely different approaches. And our goal is to hopefully develop these medicines to treat the people who need them.
If you had your way, would we eliminate all sports clichés from biopharma jargon?
No. I think they’re appropriate in certain places and times, but they just get overused. There is a sea of boring sameness at J.P. Morgan. And what we’re trying to do is to help clients stand out in that sea of sameness by telling stories in a much more compelling, interesting, intriguing way.
Tell us about your No. 5 (“Innovative.”)
It’s the most overused, devalued word in corporate-speak and in life sciences-speak. Everybody says they’re innovative, and because of that, it’s completely washed out.
Break down for us your No. 3 (“This slide is a bit of an eye chart/This is a busy slide.”)
How many Kaplan–Meier curves and forest plots and waterfall plots and bar charts and spider plots have you shoved onto that one slide? The pushback that we often get from clients is well, that means I’m going to have four more slides. And I tell them it doesn’t matter. The slide count doesn’t matter. What matters is, can the audience in the room or on the webcast— and at J.P. Morgan— comprehend and digest what you’re saying? So let’s limit it to one chart per slide and eliminate the clutter and get rid of that phrase. If it’s busy, un-busy it.
Then there’s your No. 2 (“Our goal is to become/We are a fully integrated, commercial-stage biopharmaceutical company.”)? That hits so many bingo words right there.
It suggests the possibility that some companies would go on stage and say our goal is to really just sell this to whoever is willing to pay us right now.
Exactly — as if this phrase were the actual measuring stick that all investors use to determine whether they’re going to buy and/or hold a stock. Oh, are you a fully integrated commercial-stage biopharmaceutical company? Oh, good. Then you check our box and we’re going to buy your stock.
“By definition if there’s a need, it’s unmet.”
MIKE HUCKMAN
Now let’s break down your No. 1 (“Unmet medical need”). What’s so wrong with that phrase?
So much is wrong with that phrase. It is an FDA-invented phrase. No one in the outside world says that. For example, I have an unmet need to take down our Christmas tree. I have an unmet need to get to the airport to get my flight to J.P. Morgan in San Francisco. I have an unmet need to get a new iPhone. Nobody says this in the outside world. We simply say, I need a new pair of shoes. I need to eat. I need a drink. So it is pure industry FDA jargon. By definition if there’s a need, it’s unmet.
Why can’t we just say there is a big need in this patient community that we’re hoping to fill?
You probably counsel your CEO clients to not use these phrases. How successful are you in stopping them?
It is a big hill to climb. These phrases are ubiquitous, they are pervasive, but I think at an anecdotal level we’re making progress little by little. We’re trying to shift the conversation and here’s why. It’s not just CEOs who are guilty of this. I’m guilty of it. I think certain journalists who will go unnamed are guilty of it.
We’re probably all to some extent guilty. So which large pharma biotech company CEOs do you think consistently put on the best JPM presentation?
I don’t think it’s fair to single somebody out. This is pervasive. I think if we were all to sit in on as many presentations as we could possibly go to next week, we will see evidence of people who are trying to step outside the box and to approach this differently. We’re in a world now where audiences are super distracted. Attention spans are getting shorter and shorter and shorter and there’s competition from our tablets and our laptops and our iPhones. So the onus is on presenters, whether you’re the CEO of a biopharmaceutical company or you’re the CEO of a technology company or an automobile company — it makes no difference. We have to work harder as presenters to grab audiences’ attention and to keep people’s attention.
Between large-cap pharma and the army of people they have preparing their presentations and small cap biotech, which side do you think is doing a better job?
At the risk of being pejorative here, I think that it’s at the smaller emerging company level. And at the risk of bucketing people into a category or class, it is primarily the younger generation of executives that I think are doing a better job, who understand that it’s a new world and we have to communicate in new and different ways to command people’s attention. That’s where I think you see the most, if you will, experimentation going on in presentations: you see them using more videos, using more patient vignettes, using slides that look more like an infographic than they do like an eye chart.
I do think that broadly speaking, at the Big Pharma level there is a template. There is a mold that in my experience they are afraid perhaps to break out of. But at the younger company level, we’re seeing more willingness to take on that task of approaching a presentation differently and more interestingly and more compellingly.
There’s an abundance of research showing that when women speak on the same stages and platforms as their male counterparts, they’re often judged differently and oftentimes more harshly based on superficial factors like the tone or the pitch of their voice and what they’re wearing. So when you work with female biopharma executives to prep them for J.P. Morgan, how do you think about gender and the way that audiences perceive women?
To me, gender doesn’t matter. What needs to happen is a presenter has to speak with passion, with gravitas, with authority, and credibility. And to me it makes no difference whether you’re a man or a woman. I’ve worked with people who are men who also do uptalk, which some people might say is primarily a younger female problem. So there are patterns and behaviors that are really gender agnostic. It’s all about coming across with authority, like I’m in command of this stage and I’m in command of this room and I’m in command of this subject matter. But I agree with you that there is a greater onus for better or for worse that is put on women executives more than men.
This is a lightly edited transcript from a recent episode of STAT’s biotech podcast, “The Readout LOUD.” Like it? Consider subscribing to hear every episode.
BioB: Yes, the ick factor is certainly there-
duck manure.
I read an article in WAPO yesterday where a consultant was quoted as saying he's afraid of the backlog that FDA will have to push through whenever the shutdown is lifted. A quick search of the consultancies does show past experience, post-shutdowns with CDER-regulated products is to build the new backlog delay into a timeline. Should I assume then by the time AMRN is ready to file in 60ish days? that we can add another 3 weeks and counting to original forecasts for either an expedited or regular approval process due to the shutdown imposed backlog?
Meanwhile Scott Gottlieb is tweeting that he's not leaving the FDA.
My wild guess is that the shutdown is lifted by Sunday night.