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Saved by @Alex1Powell

$ARPO Thread: Raz P2b glaucoma readout Dec 15 to Jan 15, assigning 90% POS, potential 3 to 5x, with (likely) partnership 1H21. Glaucoma dead for Big Pharma unless there’s a brand new MOA or pathway being targeted. Here we have both…a new MOA (Tie2) and a new location (SC)

 https://t.co/zsc2eBVI4e Tons of great preclinical work on TIE2 MOA showing clear correlation to SC integrity, adult-onset glaucoma, and disease-modifying effects. See mosaic if interested
What do KOL's think of the new MOA: Special session held at ARVO 2019 to discuss Tie2 for Glaucoma. $ARPO then completed a closely watched P1b with a topical formulation. Now, a P2b trial in 195 pts enrolled within 3 mos, a month ahead of schedule, in the middle of a pandemic.
SOC is PG (-7 mm Hg IOP) +/- adjunct (-1 to -1.5 mm delta). Best efficacy adjunct is Rocklatan (-1.5), but AE profile: hyperemia (60 vs 15%), pruritus (8 vs 2%) site pain (20 vs 7%) vs PG , + other AE’s not seen with PG: 10% conjunctival hemorrhage, 15% verticillata. Almost DOA
But, sells $80 to $100M/yr US (same as $ARPO MC ha!). Every 0.3 mm reduction critical towards delaying vision loss. Rocklatan MOA was projected to make it a $1B drug, until AE profile (& payor delays) killed launch. $ARPO thesis: Raz efficacy >/= Rocklatan, without AE baggage.
P1 trial: Difficult to draw conclusions from a 7 day trial, but clear dose response curve and nice -1.5 to -2.2 delta with QD/BID dosing in POAG/normotensive pts. 40 mg/ml QD dosing showed 35% pts with -3 delta in POAG pts. AE was stellar, limited to mild conjunctival hyperemia
What can we expect for P2b efficacy? P1 trial was 7 days, P2b is 28 days 40 mg/ml QD & BID dose + PG vs PG alone. If Tie2 is disease modifying (see preclinical studies), we can hope to see better efficacy with longer trials. BID dose & higher baseline IOP also -> higher delta
We actually have a clue from the subQ trial that $ARPO ran for Raz in normotensive NPDR pts. Increasing separation seen for IOP change. Notice separating curves from first 7 days to first 4 weeks, and also between QD and BID doses. P2b should win on efficacy, high POS.
However, the biggest risk for this trial was always safety since it’s a 4% w/w solution being tested with BID dosing now over 28 days instead of 7. https://t.co/kxvD8AMTEl. While we can be convinced of efficacy, how do we accommodate for safety?
This is where the 3Q earnings call gave us a huge clue. This trial recruited ~195 pts, of which 194 patients have completed the study! Even if they recruited a couple more than 195, that gives us a drop-out rate of 0.5 to 1%. If pts didn't drop out, AE profile likely to be clean.
Here's some Rocklatan drop-out data from their pivotal trial that @biosleuth pointed out. A 5% drop out at week 2, and a 10% dropout by week 6 for Rocklatan. Based on these data, very high POS that safety will be clean for Raz in the $ARPO P2 trial
Trial completed Nov 15 (LPI Sep 15 + 4 wk wash-out + 4 wk trial). Data out Dec 15 – Jan 15. Based on prior company comms: If -ve, expect a short PR early. If +ve, perhaps a top-line PR in Dec with data in Jan leading into JPM. 90% it's the latter:)
Interesting question 1: https://t.co/cOba1Wdcdd A very pertinent issue: Raz is not yet a FDC like Rocklatan. But Aerie initially developed the ROCK inhibitor by itself (Rhopressa) and then co-formulated. $ARPO is currently working on a FDC, and yes, an FDC is a must for P3/market
Interesting question 2: https://t.co/qNiJ6bTDyq Glaucoma market likely moving towards a 6 mo PG depot. It would be easy for a big pharma player to make a Raz+PG depot if needed. But these are all nice problems to have once you have a winning profile, which Raz will likely have.
A clean safety profile and -1.8 mean delta (with follow thru on -3 mm %). That’s my bar for this trial to be a big win (3 to 5x). If it hits -1.6 with clean safety, that’s still a win from a valuation standpoint (2-3x), and will still be attractive for partnership. The End.

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How position sizing can affect your trading performance-

Assuming that you are trading a Trend-following system with Big RR and low win-rate.

For example, assume that you risk one percent per trade on a 100,000 account
and you have 20 straight losses.

That one percent is of your remaining equity and at the end of 20 losses, you would be down to 81,790.60.

Now if you got a 30R winner and you are risking one percent of your balance of 81,790.60, your new equity would be 106,327.9,


You’ve had 20 losses and one winner though you are still up 10Rplus your equity is up by 6.3R percent.

Now, let’s say you risk five percent per trade on your balance. At the end of 20 straight losses, you would be down to 35,772.89 or down 64 percent.


If you risk five percent on this amount and get a 30R winner, you would be up to 89,621.48. You are up 10R, but because of your position sizing, your equity is still down over 10 percent.

#positionsizing
#Trading
#nifty50

This is why position sizing is the most important factor in trading if you get it right and you have an edge, you will do good.

Thanks for reading till here.
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On this auspicious day of #GuruPurnima, happy to share an easy to read and an exceptionally worthwhile investment. I plan to make a thread that will hopefully help us invest and live better. Thank you @awealthofcs 🙏🏻


Experience has taught me that less is always more when making investment decisions. Simplicity trumps complexity. Conventional gives you much better odds than exotic. A long-term process is more important than short-term outcomes.

And perspective goes much further than tactics. Tactics are useless to investors in a matter of days—sometimes in a matter of hours. But perspective is something that stays with the investor for a lifetime. It allows you to adapt to the changing market and economic landscape.

While keeping it simple won’t make it any easier to predict the future—no one has a crystal ball—it can give you the necessary capacity to make rational decisions, no matter what happens next.

Perspective is so important because, without it, even the most intelligent of investors can be ruined from a lack of self-awareness in their own abilities. Investors that fail to put the news or market moves into the proper context....[1/2]
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Emperor\U0001f451
Emperor👑
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Technical Analysis Masterclass- Part 2

'Entering the trade'

Entering a trade without ascertaining a certain things is gambling.

In this masterclass we will learn the pre-requisites to enter a trade.

DON'T ENTER A TRADE WITHOUT DETERMINNG THE FOLLOWING.

Please share.

We understand what reward to risk (popularly called risk to reward) is.
It will be denoted by R:R.

We will also try to bust a few myths about R:R and how to avoid losing trades.

Before entering a trade, you need to determine 3 things.

1. Entry trigger
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3. Target

1. Entry trigger = Reasons for entering a trade. There could be multiple reasons or a single reason for entry.

Generally a set of reasons AKA confluence is a higher probability trade and a generally a safer entry.

Example of an entry trigger.


2. Stop Loss.

The price in the opposite direction of the trade where the trade is exited, at a loss.

At this level, the reason for the entry becomes invalidated according to TA and the price can then move in the opposite direction, probabilistically.


3. Target is the possible price level that the asset might touch based on previous trends or confluence AND where a possible reversal could occur.

Target is the next path of least resistance from where the price might reverse.

We will always ONLY use TA to determine all 3.
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Aditya Todmal
Aditya Todmal
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How to save tax when income is above 50 lakhs?

Here are 9 benefits of trading in a corporate account: 🧵

Collaborated with @niki_poojary

1. Make a Pvt Ltd Company.

Form a company with family members and trade under it. The family members should be directors of the company. Will explain why later.

Why form a company?
You will only need to pay 25% flat tax. Individuals have to pay 30% tax above 10 lakh profits.

2. Surcharge Benefits:

You will be charged a lower surcharge in a corporate account.

Check the picture below:


Total Tax Outlay:

The total tax outlay for individuals is 30% plus surcharge. If you really earn a lot (10 cr +) then you will be paying 42% tax.

Whereas in a company you'll be paying a maximum of 28% tax.

This is how rich people save a lot of their money by paying low taxes.

3. Expenses can be deducted.

All expenses can be deducted from a company account.

Companies:
1. First make a profit.
2. then deduct the expenses
3. & Pay tax on the remaining income

Individuals:
1. First Profit
2. Then Pay tax
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Full Technical Analysis in Single Thread🧵

This whole course is worth 40-50K-

1- Candle sticks and how to use

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Joey Tawadrous \U0001f1ee\U0001f1ea
Joey Tawadrous 🇮🇪...
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1) Core attributes of a promising founder worth following:
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We can easily pivot and vastly change a project of ours. We can change as we learn more about our users.

Big companies can take months/years for even the smallest of pivots.

3) Before you find a product market you can pivot your project as many times as necessary until you find something that works.

Then you only have one thing to do: scale, scale, scale.

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In the early stages of a company just;
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Kaspars Ozolins
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THREAD: Meditations on marriage metaphors in Ruth

The book of Ruth is, of course, a story about a beautiful marriage. But even before the courtship and the wedding and the important genealogy at the end, we find interesting language that is strikingly reminiscent of Genesis 2:24


That important verse reads:

'Therefore a man shall leave [יַֽעֲזָב] his father and his mother and hold fast [וְדָבַ֣ק] to his wife, and they shall become one flesh.'

The verb עזב can be quite strong in force. For example, Joseph leaves behind [וַיַּעֲזֹ֤ב] his garment as he flees from Pharaoh's wife's sexual advances. Countless times, Israel is depicted abandoning the LORD, for example in Judg 2:12 [וַיַּעַזְב֞וּ], and going after other gods.

Likewise, the verb דבק is rather striking. Lot is mortified of disaster overtaking him [תִּדְבָּקַ֥נִי] as he flees from Sodom. Israel is commanded in Deut 10:20 to cling fast [תִדְבָּ֔ק] to the LORD and serve him and swear by his name.

Together they illustrate how radical God designed marriage to be. Marriage is a real severing of family relations in order to form a new, permanent bond with another human being.

Something very similar to this takes places in Ruth's life.
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Jaya_Upadhyaya
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SRI LALITHAMBIGAI, THIRUMEYACHUR (TN)
#bharatmandir #navratri2021

Kshetram where Shiva is worshipped as Meghanatha and his consort is Lalithambigai seen in Abhay mudra.
Once, a demon Pandasura was harassing the Devas who went to Devi Parashakti for protection. 
@GunduHuDuGa


Devi rose from a Yaga Gunda, mounted on the Sri Chakra Rath with the name Lalithambika, waged a war against Pandasura and destroyed him.  When her fury did not subside, Shiva asked her to go to Earth, assume the name Manonmani, perform penance and shed her fury.


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Hayagriva taught the greatness of Lalitha Sahasranama to Rishi Agasthya. Pleased with his devotion, Ma Lalithambikai appeared before Agastya. He is believed to have then sung Lalita Navaratnamala in praise of Devi. He has also composed a hymn named Rahasyanamasahasram.
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1. I was walking in the woods yesterday and I had an epiphany. It wasn’t one I wanted to have. I was thinking about today’s class, where we are reading Kimmerer’s ‘Gathering Moss’. I’ve taught Braiding Sweetgrass in multiple classes every year since 2016. It’s eminently teachable

2. Both books are beautifully written. Students uniformly enjoy them as assigned reading. They do a great job communicating to non-Indigenous folks the contours of basic Indigenous relationships to more-than-human beings. They’re wildly popular with white readers.

3. I’ve found Braiding Sweetgrass to be a great entry point for non-Indigenous folks to Indigenous scholarship. But this is where yesterday’s epiphany comes in. Neither Braiding Sweetgrass or Gathering Moss tends to the deep deep lineages of Indigenous scholarship in Canada or US

4. As the popularity of ‘Braiding Sweetgrass’ has soared, I’ve seen more and more white folks wax on about ‘braiding knowledge’. But they often don’t know any of the lineages of these concepts beyond what is presented in this one book. They confidently run with this.

5. Kimmerer does a commendable job of weaving in her own experiences, her family stories+nods to some very important knowledge keepers who deserve to be celebrated for their work. But Braiding Sweetgrass does not tend to the citational politics Sara Ahmed & others teach us about
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STEALTH JEFF
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Ok I was wrong about theHouse. 2 years of legislative gridlock = not fun. Few bills passing.

Control of the House is useless when it comes to keeping Trump from declassifying all the SpyGate docs. Or stopping an Inspector General from releasing a report.

Trump still gets control of judicial appointments so we can expect another 100 judges over the next two years. This time there’ll be no McCain or Flake playing the Maverick role with their swing vote.

That new margin in the Senate is huge if another Supreme Court seat comes open.

So from the responses I’m getting, people seem to think if Trump declassifies the Spygate stuff now, nothing happens.

Are you under the impression federal prosecutors have to wait until CONGRESS finishes an investigation and makes criminal referrals before the DOJ can act?

There’s a federal grand jury on McCabe right now. Did Congress ever finish it’s investigation and make a referral to the DOJ against him?

No.

BUT INSPECTOR GENERAL HOROWITZ DID. On finishing his McCabe leak report.

Funny how nobody remembers that.
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