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$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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So we had discussed a few pointers in the previous thread about options,its time now we discuss further implications and applicability in this thread which will help you in NEW YEAR.
Let’s go and dive into the world of options trading.

-The amount of decay can be measured by theta. This is why you can be right on stock price direction and still lose money. The time decay portion of the option price overpowers the directional move in the underlying stock price.

-During result days due to the heightened uncertainty, there is opportunity for options sellers because of the expensive premium. When entering into an earnings trade, it is optimal to initiate the trade as close in time to the event as possible.

-Keep some cash on sidelines. This would help in adjustments,margin expansion,face losses and also during new opportunities which suddenly arise. A lot of people do the mistake of going all in and regretting later.

-Everything in trading has a trade off.

Unlimited profit comes at the expense of low probability of profit. Give up some profit potential, and you gain a higher probability of profit.
-By using portfolio beta weighted delta, you can accurately gauge your overall portfolio risk. If your portfolio is leaning too far in..
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Cory Doctorow #BLM
Cory Doctorow #BLM
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There is no shortage of takes about what's going on with Gamestop (and other surging stocks), Robinhood and Reddit's r/wallstreetbets, many of them contradictory - at least on the face of them. But I think it's possible for most of these takes to be right. Here's how.

1/


First you need to understand the underlying mechanics of the story. Stock markets are fundamentally a way of making bets, including bets on the outcome of other peoples' bets, and bets on the outcomes of THOSE bets.

2/

All this complexity creates lots of exploitable opportunities. Some of these opportunities are considered legitimate and are given respectable names like "arbitrage." Others are considered illegitimate, and are called disreputable things like "stock manipulation."

3/

A hypothetical Martian observing all this through a telescope could not tell you which kinds of bets were honest and which were dishonest, because the difference isn't about any objective standard, but rather, about power.

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The strategies of powerful people are legit, while the strategies of their would-be dethroners are not legit. Sometimes, even outright frauds are OK if they're done by people with enough power.

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A thread on Risk and Returns


Trader X -

Net-worth - 5 Cr
Trading capital - 25 lakh

Trader Y -

Net-worth - 30 lakh
Trading capital - 25 lakh

Trader X take risk of 2% per trade and he makes about 30-40 % Return on trading capital per month,

Whereas Trader Y only risk 0.25% per trade and he makes about 3-4 % on Trading capital per month.

Trader Y saw how much trader X is making with the same amount of capital that he has.

He is frustrated with his mediocre results as compared to Trader X, though he don’t know the fact that Trader X Is only trading with 5 % of his total net worth.

Trader X has much more risk taking ability in Rupee terms as compared to the Trader Y because he has higher net-worth.

Trader X will not have much impact when he goes into deep Drawdowns , 40-50% where as if the Trader Y goes below 15% DD , it will have deep psychological impact on him.

Even if the Trader X makes 100% return on his trading capital , turns 25 lakh into 50 lakhs ,
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Nikita Poojary
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@niki_poojary
Thread: Free Options Trading Course for Beginners with small capital.

Reference: Option trading marathon series, part 1 from Mr. Subasish Pani ft. @PushkarRThakur

Collaborated with @AdityaTodmal

1/ Trading journey of Mr. Pani

• He has an experience of 7 years.

• He has made a profit of Rs. 20 cr. over these years with a capital of Rs. 2 cr.

• However, it's not easy to make such profits.

• More difficult, is to retain those profits and build more on it.

2/ How he ventured to options selling

• He started with futures and option buying however after a certain point when his capital grew, he faced scalability issues and hence he resorted to options selling.

3/ Investing becomes imp once the capital grows:

• Since his trading profits have grown well, he has started investing (investing is always for LT).

• For folks who dnt have much info regarding investing can simply buy Nifty 50 stocks & keep rebalancing as Nifty 50 does.

4/ Covered calls strategy for the portfolio:

• Pledge the portfolio and receive margin ~80% which he would then use to sell OTM CEs of the stocks which are in his portfolio.

• This helps in generating fixed income from the portfolio.
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Aditya Trivedi
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@itsAdityaT
Most of the successful traders here are option sellers.

Ever wondered why?

Why we have chosen option selling?

Find our below

1: Being wrong and still making money.

We as option sellers can be wrong with our market view and still end up making money because of the power of theta decay and adjustments to some extent.

Adjustments work better as get closer to expiry since decay is the highest.

2: Theta decay

The biggest reason and one of the prime reasons is the theta decay.

Option sellers always have an advantage because the as time passes, the option premium falls even if the underlying instrument doesn't move.

3:Playing directional view

Option selling also enables us to take a directional view. In fact, directional view along with theta decay makes it a solid combination.

Debit spreads and credit spreads works great for a directional view.

4: Playing Neutral view

We can make money in option selling even if the market doesn't move as the otm options will go to 0 with the help of theta decay. It's the most fascinating thing.

This is what attracted many into option selling.
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It was Ved Vyas who edited the eighteen thousand shlokas of Bhagwat. This book destroys all your sins. It has twelve parts which are like kalpvraksh.

In the first skandh, the importance of Vedvyas


and characters of Pandavas are described by the dialogues between Suutji and Shaunakji. Then there is the story of Parikshit.
Next there is a Brahm Narad dialogue describing the avtaar of Bhagwan. Then the characteristics of Puraan are mentioned.

It also discusses the evolution of universe.( https://t.co/2aK1AZSC79 )

Next is the portrayal of Vidur and his dialogue with Maitreyji. Then there is a mention of Creation of universe by Brahma and the preachings of Sankhya by Kapil Muni.


In the next section we find the portrayal of Sati, Dhruv, Pruthu, and the story of ancient King, Bahirshi.
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Charlie Hebdo doesn’t come up as a cautionary tale now but rather 'why cant we be like that'?
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