BC SCIENCE
Saved by @Mollyycolllinss

#DDDD $LBPS $LOAC

A thread on the potential near term catalysts behind why I have increased my position in 4d Pharma @4dpharmaplc (LON: #DDDD):

 1) NASDAQ listing. This is the most obvious.

The idea behind this is that the huge pool of capital and institutional interest in the NASDAQ will enable a higher per-share valuation for #DDDD than was achievable in the UK.
Comparators to @4dpharmaplc #DDDD (market capitalisation £150m) on the NASDAQ and their market capitalisation:
Seres Therapeutics: $2.33bn = £1.72bn (has had a successful phase 3 C. difficile trial); from my previous research (below) the chance of #DDDD achieving this at least once is at least 90%.

https://t.co/O8Fd9uuR7f
Kaleido Biosciences: $347m = £256m. 4 products under consideration, compared to #DDDD's potential 16. When you view @4dpharmaplc's 1000+ patents and AI-driven MicroRx platform (not to mention their end-to-end manufacturing capability), 4d's undervaluation is clear.
Evelo Biosciences: $496m = £366m. 11 potential treatments under consideration compared to #DDDD's 16. 4d's IP, platform and manufacturing are superior. Very arguable that 4d should be comparably valued. @lramseu's content is excellent for comparisons.
This does not take into account the recent frenzy for IPOs/SPAC offerings, like #DDDD. In fact, however, without DraftKings and Nikola included, SPAC returns are negative - hence the case for 4d rests firmly on fundamentals.

https://t.co/EHvA8xVbep.
2) Potential Blautix Phase 3 trial. The below graphic taken from @AimHardy's excellent research shows #DDDD's Blautix was comparable to existing IBS-C and D offerings.
It offers a far superior safety profile however, making it the potential treatment of choice, especially for the $1.1bn-$1.65bn IBS-M market (patients whose symptoms fluctuate between IBS-C and D).
The fact that c. 60% of phase 3 trials are a success notwithstanding, comparing Blautix with Seres' C.difficile trial shows how selecting for specific biomarkers/genotype can yield a highly successful final stage trial.
Just the initiation of a trial netted Seres $20m from Nestlé Health Science, excluding the revenues from developing a safe live biotherapeutic. The potential for #DDDD to rerate, just based on precedent (Seres jumped c. 500% on their P3 success) is colossal.
It is likely that the announcement of a phase 3 trial and partner would lead to some of this movement being priced in, given the favourable chance of a success. Hence it is a potential near term (3-6 month) catalyst, and if not, a potential long term catalyst.
3) Potential FDA fast track for MRx0518. Interim analysis for the #DDDD treatment on its own yielded the following (from 17 individuals under trial):
"Following MRx0518 treatment, relative increases in cytotoxic cells, CD8+ T cells and other immune subsets associated with anti-tumor activity were observed in paired tumor samples.
Upregulation of key immuno-stimulatory anti-tumor cytokines and chemokines, such as IL-12 and CXCL10, was observed in post-treatment plasma samples."
Gene expression analysis identified significant expression changes in 98 genes (p<0.05) in paired samples as a result of MRx0518 treatment, including upregulation of pathways associated with antigen presentation, costimulatory signaling, cytokine and chemokine signaling, known
…to promote anti-tumor immune activity."

This is for #DDDD's treatment group who had exhausted many previous options and had metastatic cancer.
The fact that #DDDD's treatment is clearly having an effect without significant side effects is extremely important (as patients may forgo treatment due to side effects alone), and certainly presents the opportunity for fast-track approval.
To me, it belongs in this list of 2020 fast track approvals:

https://t.co/GFsF6ZYraA

This is without taking into account #DDDD's trial of MRx0518 with Merck $MRK's Keytruda, which is likely to yield as high if not greater efficacy than MRx0518 alone.
4) Potential Merck takeover. This is more dubious so can be listed as a fringe point.
#DDDD's bacterial vaccine partnership with Merck yields a potential $347.5m in milestone payments, and if other treatments show further efficacy then, given Merck's interest in the MicroRx platform and live biotherapeutics (they own 6% of 4d) they may well consider a takeover,…
…which typically occur at a substantial premium to the current share price. Takoevers of Rebiotix and Epibiome in recent history offer validation of this theory.
The key here is if #DDDD become attractive enough to be taken over, their share price would have likely enjoyed a substantial re rate from today's levels already.
To summarise, I believe #DDDD offers substantial long-term value. However there are a number of potential near term catalysts, chiefly a NASDAQ listing, which have prompted me to increase my position in the short term from its historical average.
I believe a #DDDD rerate (and a subsequent SP multiplying of 2-3x given 4d have cash till Q4) could well happen in the coming 3-6 months, and I have positioned accordingly.

Merry Christmas and Happy Holidays!

#DDDD $LBPS $LOAC

More from Science

Prof. Gavin Yamey MD MPH
Prof. Gavin Yamey MD M...
@GYamey
I want to share my thoughts, as someone who has been so alarmed by the so-called "dissident" scientists like Gupta, Heneghan, Kuldorff, Bhattacharya, & Ioannidis who consider themselves brave Galileos unfairly treated by "establishment scientists." I will try not to swear. 1/n


I want to talk about 3 things:
‼️Their fringe views are inhumane, unethical junk science that promotes harm
‼️They complain that they've been marginalized but this is simply untrue
‼️I am sick of people telling me we have to "listen to both sides." There aren't 2 sides here 2/n

These 'dissident' scientists have consistently downplayed COVID-19, urging policymakers not to take aggressive control measures. They claim it is not a serious threat. Gupta even went on TV saying people under 65 shouldn't worry about it!

RECEIPTS

They have consistently argued that policymakers should just let the virus rip, in an attempt to reach herd immunity by natural infection. Kuldorff *continues* to argue for this even now that we have many highly effective, safe vaccines.


We've never controlled a deadly, contagious pandemic before by just letting the virus spread, as this approach kills & disables too many people. In Manaus, Brazil, 66% of the city was infected & an astonishing *1 in 500* people died of COVID-19
SCIENCE
Thomas A. Fine \U0001f1fa\U0001f1f8
Thomas A. Fine 🇺🇸...
@thomasafine
Let's talk about Avi Loeb and his theory about alien

First, I should disclose that I work at the fame research facility as Dr. Loeb, though I work in a different department and to my recollection we've never met.

He's a scientist; I'm in computer support.

With that out of the way...
The interview above is worth a read, and a lot of serious thought, because there's an idea there that's really critical to science, and it isn't whether or not aliens have visited (exactly).

It's about how fashion and culture and taboo have an unfortunately strong effect on science.

In particular he compares his theory on alien visitation with the multiverse theory.

Which of these is more deserving of ridicule?

Science is fundamentally a structure for forming hypotheses and then (critically) testing these hypotheses to see if they should be kept, rejected, or modified.
SCIENCE
Advertisement
Jason Hickel
Jason Hickel
@jasonhickel
Here's more on the new mitigation scenario for 1.5C. How does it work? What would society look like? Are we willing to do what's required to stop climate breakdown? See thread.


1. Most models assume we need to keep growing the economy indefinitely. The problem is this makes it impossible to transition to zero emissions quickly enough; so they speculate on geoengineering and negative-emissions technologies to save us. Scientists reject this as too risky.

2. By contrast, this scenario proposes that high-income countries don't *need* more growth, and can scale down unnecessary production and consumption. This reduces energy demand (from 140 EJ in 2020 to 40 EJ in 2050), and enables a rapid transition to renewable energy.

3. What does it require? In the global North (Annex 1 countries)
•a shift from private cars to public transportation
•reduction in flights
•smaller average house size

Meanwhile, consumption in the global South (non-Annex 1 countries) rises to converge.


4. Significant reduction of aggregate material use. How? Longer product lifespans; regionalization of production and consumption; ban on advertising; a shift in taxes from labour to resources. All of this allows us to reduce ground freight, which cuts energy use.
SCIENCE
Navin Kabra
Navin Kabra
@NGKabra
Did you know that all the nuclear bombs we exploded in the '40s-50s-60s have permanently contaminated all the steel the world has produced since then? All steel in the world is divided into two categories: pre-1945 non-contaminated steel, and post-1945 contaminated steel.

How?

Nuclear bombs (including the tests) create a lot of radioisotopes that are not found in nature. For example Cobalt-60 (a radioactive version of Cobalt-59). And since the 1945 Trinity test, these have all dispersed in the atmosphere.

What does this have to do with steel?

The process of manufacturing steel uses atmospheric air (or atmospheric oxygen). Some of the radioisotopes like Cobalt-60 get pulled in too, and as a result, any steel produced after 1945 has embedded in it some of these radioisotopes, sitting there emitting gamma rays.

Why do we care about traces of radioisotopes in steel? When making Geiger counters, or medical devices to check for radioactive contamination, or astronomical instruments, the emissions from the contaminated steel would interfere with the measurements.

So we need pre-1945 steel

Pre-1945 non-contaminated steel is called "low background steel". And when we need it, where do we get it from?

We go, find pre-World-War-II sunken shipwrecks, and then salvage the steel (and lead) from those to build our instruments which need heavy radiation shielding.
SCIENCE
Amy Maxmen, PhD
Amy Maxmen, PhD
@amymaxmen
Azar just released a delusional, alternative history of Covid testing in the US. I’m mad because our testing failures allowed this outbreak to blow-up. We can’t fix our system if we ignore where it is broken. I suspect @PublicHealth agrees.

My fact-check on remarks @HHSGov 🧵

“It is indisputable that the United States has built the most extensive testing system and strategy of any major country,” says Azar.

False. Several countries have had percent positivity ~1% whereas US has never been below 5% and is >10% today. Refs KCDC & USA @JohnsHopkins


"The federal government got out of the way of test development in safe and sensible ways,” says Azar.

False. In Feb, CDC & FDA blocked labs from testing as the disease spread exponentially. I broke this story👇🏼& wrote more like it as the year wore on.

Azar defends questions about why the CDC refused an early German test vetted & distributed by WHO, by saying it was ‘unapproved’ & beneath us.

False. Top US researchers in my stories vetted several tests as early as Feb,& found that the one recommended by WHO was ideal.


Azar refuses to concede that other countries handled Covid better. He attributes Koreas success to less travel, invasiveness & private sector.

False. Korea's gov't marshaled the private sector & tracing success was largely from hiring tons of tracers.
SCIENCE

You May Also Like

Greg Olear
Greg Olear
@gregolear
Strange things are afoot at the Circle K. Let’s sort it out.

[THREAD]


1/ Two nights ago, Rupert Murdoch called on Mitch McConnell, after hours. Since then, two Fox News-related Twitter accounts have not tweeted.

2/ Trump fired Sessions on Wednesday, replacing him with human dildo/Putin collaborator Matt Whitaker. Sessions had asked to stay until Friday and was told to leave immediately. So there was clearly some urgency to install the dildo...er, puppet.

3/ The Democrats won the SHIT out of the Midterms. Come January, the House check on Trump will leave him so hobbled, he’ll be like the dude from Misery.

4/ Trump went to Paris, ostensibly for an Armistice Day centennial event. He skipped the event, and much of the dinner tonight, because of “weather,” which everyone seems to agree is a bullshit excuse.
POLITICS
Raman Shalupau
Raman Shalupau
@ksaitor
Maker movement is doing to startups what startups did to corporations.

Here is why 👇

Startups fixed the problem of innovation, that corporations lack.

In big, slow corporations, innovation is a RISK and distraction from the core $$$ profitable business.

Agile startups could launch, iterate fast and eventually stumble upon new growing market opportunities.

However,

When a startup reaches product-market-fit, it has to 🚀 "grow at all costs" and reach market dominance before some giant corporation can replicate their new product and distribute it to their existing giant customer base.

Startup's "growth at all costs" often means growth at the expense of charging customers $$$ money.

Hence, to be sustainable, startups have to constantly chase investor money.

Startup teams spend more time finding and pleasing investors, than finding and pleasing customers.

95% of startups die because they run out of (investor) money + no business model + crazy investor expectations.

Same way corporations die, when unable to adjust to new technology and market shifts.
MAKERS
Advertisement
Brian Cates
Brian Cates
@drawandstrike
A lot of people don't understand that Trump & his incoming team didn't face a normal transition period, like it was over a in a matter of a few weeks or months.

The DOJ transition period JUST ENDED when Sessions left. Almost 2 exact years to get it there.

Pompeo at the CIA took over a year before he was done and ready to shift over to the State Department.

All kinds of stuff has been going on behind the scenes nobody leaks or talks about.

We only had the barest mention of the fact the Clinton Email investigation restarted

Nobody leaked in a year that Huber was deep diving into the Clinton Foundation.
Keep that in mind as all the usual suspects continue to INSIST nothing is happening/going to happen.
POLITICS
Nicolas Cole
Nicolas Cole
@Nicolascole77
🚢 Atomic Essays Republishing Framework 🚢

1. Write Atomic Essay
2. Post image on Twitter
3. (Bonus) Copy/paste text as thread
4. Find relevant Question on Quora. Copy/paste Atomic Essay + image.
5. Copy/paste again on Medium.
6. Again on LinkedIn
7. Win

Guide below ✍️🚢👇

Step 1: Write Atomic Essay

I really enjoy writing right inside the Figma template. It helps give me a good sense of exactly how much "real estate" I have/have left before my time us up and I'm out of space.

Once finished, I export the image and send to my phone on Slack.


Step 2: Post image on Twitter

Before I publish my Atomic Essay on Twitter, I use the Edit/Photo Markup function on the iPhone to highlight standout sentences.

These are usually power-phrases: things the reader skims and thinks, "That's interesting," prompting them to read more.


Step 3: For the Ship 30 for 30 challenge, I only turn Atomic Essays into threads if...

1. The piece is SUPER actionable and lends itself well to the thread format (lots of bullets, quick points, lists, etc.)

or...

2. I'm referencing research and want to link to the pieces.

Step 4: Find relevant Question on Quora. Copy/paste Atomic Essay + image.

Search on Quora around the topic you wrote about. Find a related Question. Copy/paste the whole Atomic Essay as your "answer" (& fix formatting). Then include image so it appears in the thumbnail.
WRITING
GunduHuduga| \u0c97\u0cc1\u0c82\u0ca1\u0cc1 \u0cb9\u0cc1\u0ca1\u0cc1\u0c97|\U0001f549
GunduHuduga| ಗುಂಡು ಹುಡ...
@GunduHuDuGa
#SatiSavitri #RealLifeExperiences #BharatDarshana

Bharat Darshana publishes a small monthly magazine which has some very interesting puranic anecdotes and snippets.

When I picked up this month's magazine, I was intrigued by a story which I want to share as below

1/

This is a real-life incident as narrated by Prof. Krishna Bihari Pandey titled "Sati Savitri"

Sati Savitri is a well known puranic figure from Srimad DeviBhagwatham and Mahabharatha as one of those who fought with Yama to save her husband.

2/

This story is a modern real-life experience which mimics the puranic account in it's own unique way.

The story occurs in 1975 with Prof and his wife in Delhi with professor working as a researcher in university. Prof's family is in Allahabad in a large joint family

3/

Once Prof gets to know that his mother is not keeping well. He goes to his native and brings his mother. With dedicated care of his wife, his mother recovers quite remarkably and regains full stamina and strength

Mother-in-law & Daughter-in-law go out for shopping frequently

4/

Life's going smooth until one day when they receive a telegram that Prof's father is not keeping well.

His mother is distressed about the situation and requests her son to take her to the native. Prof is a little angry due to frequent travels and turns it down

5/
RELIGION , ALL