Boz - we usually go to Squaw, Alpine Meadows, Homewood, Northstar, or Diamond Peak on the north shore. When I first started going to Tahoe 20+ years ago I always went to the south shore, which is fun if you want to gamble and party at night (I'm getting old now, so that's not my cup of tea anymore....although I do still like to hit the casino and sportsbook while I'm there). Heavenly is great obviously, but I always liked Sierra-at-Tahoe. I've usually gotten free lift tickets too w/ my military ID, or significantly reduced. That was always a reason we liked to go there. There's a small Coast Guard small-boat station on the north shore, they have two A-frame cabins (4 total units). We'd get a group of guys and stay there (for around $60/night) and free lift tickets. I've had some great trips out there.
Man..that sounds prefect. I loved Cal Neva back in the day.
It's going to be a rough few weeks in the market...I could see a lot of money coming outa this market shortly.
I haven't even read this one..So.
Global Market Comments
January 11, 2021
Fiat LuxFeatured Trade:(MARKET OUTLOOK FOR THE WEEK AHEAD, or A WEEK FOR THE HISTORY BOOKS),
($INDU), (TSLA), (TBT), (TLT), (JPM), (WFC)
January 11, 2021
Fiat LuxFeatured Trade:(MARKET OUTLOOK FOR THE WEEK AHEAD, or A WEEK FOR THE HISTORY BOOKS),
($INDU), (TSLA), (TBT), (TLT), (JPM), (WFC)
The Market Outlook for the Week Ahead, or A Week for the History Books
A man came at me with a crowbar last week.I drove into Reno to buy some used backpacks for my Boy Scout troop and parked my Tesla in a nice residential neighborhood. Out of nowhere, a man ran down the street at me screaming profanities, crowbar in hand.
He shouted that I was from Antifa and that I had hired people to invade the Capitol Building to make President Trump look bad.
I reached into my car for my own crowbar. Then the local residents interceded, separating us. The man turned around and walked away, fuming.
“Who the heck was that?” I asked.
“He has mental issues,” said a neighbor. “We’ve had many problems with him before.”
Another said “He’s a Trump supporter. He saw your Tesla and thought you were a liberal.”
Wow! Looks like the nation has a very long way to heal.
Last year, the US defense budget amounted to $622 billion. When the greatest threat to congress in the nation’s history presented itself, it was antique chairs piled against the door that provided the best defense. Maybe we should ditch some big-ticket nuclear missiles and buy more chairs.
Of course, once the insurrection started on Wednesday, I was inundated with international calls from investors asking if they should pull all their money out of the US. I answered “NO” and that it was in fact time to double down. Those who did made a killing.
Ask any professional money manager what his reaction to a coup d’état in Washington would be, their response definitely would NOT be to run out and buy a ton of Tesla (TSLA). Yet, that was exactly the perfect thing to do, the stock soaring an astonishing $135, or 18% in two days. I have many followers who did exactly that and they made millions.
All I can say is that if a market gets hit with an insurrection, and exploding pandemic, and a crashing economy and only goes down 400 points and then bounces back the next day, you want to buy the hell out of it.
I’m talking about going on margin and taking a second mortgage on your home and pouring it into stocks. You might even consider going to a loan shark and borrowing at 18% because you can easily make double that in the right stocks.
After the Biden win and the Georgia sweep, there is now more rocket fuel pouring into the stock market than ever. Call it the “Biden blank check”. Estimates of new spending and subsidies about to hit the market now go up to $10 trillion. Let me list some of them:
*$2 trillion in enforced savings by locked up American consumers.
*Credit card balances have collapsed to multi-year lows, making available hundreds of billions in spending power.
*Trillions of Money market balances sitting on the sidelines yielding zero
*$908 billion stimulus package passed in the closing days of 2020
*A further $2 trillion stimulus package to pass shortly, including $2,000 checks for all 150 million US taxpayers.
*Add another $2 trillion infrastructure budget
*$1 trillion in student loan forgiveness for 10 million borrowers at $10,000 each
*Enormous subsidies for any alternative energy companies and Tesla cars
*The return of the deductibility of $1 trillion worth of state and local real estate taxes (known as (SALT)).
MUCH OF THIS CASH MOUNTAIN IS GOING STRAIGHT INTO THE STOCK MARKET!
It all sets up a stock market that has the potential to have “extreme”moves to the upside, according to my friend, Fundstrat’s Tom Lee.
All you need to retire early is someone to point you in the right direction, into the right sectors and the right stocks. Actually, I happen to know just the right person who can do that and that would be me!
Storming of the Capital shut down markets. After the initial crash, markets flatlined as the entire country dropped what they were doing and glued themselves to a TV, their jaws hanging open. The Dow dove 400 points, bonds and the US dollar stabilized, Tesla and oil took big hits, and gold and silver took off. The electoral college vote has been suspended, gunfights broke out on the house floor, and several explosive devices placed. Trump incited his followers to attack the capitol and they did exactly that. Washington DC is now subject to a 6:00 PM curfew for two weeks. Is this the beginning of the 2024 presidential election? It’s the worst day in Washington since the British burned it in 1814.
Democrats took Georgia, giving them Senate control and a blank check on spending for at least two years. Trump clearly blew the election for his party. My 3X short in bonds soared as the market crashed. Banks rocketed on a 10-basis point leap in interest rates. Infrastructure plays went ballistic. The US dollar faded. Add another couple of percentage points of US GDP growth for 2021.
Tesla Shorts posted biggest loss in history, setting on fire a staggering $38 billion in short positions. Many of these were financed by big oil looking to put Tesla out of business. The short interest in the stock has plunged from 37% to 5%. Did I mention that Tesla was the biggest Mad Hedge long of 2020? I’ve been buying it since it was a split-adjusted $3.30 a share in 2010 against a Friday close of $880, a gain of 290X. Elon Musk is now the richest man in the world and he’s only just getting started!
Tesla met its 500,000-unit 2020 target, far in excess of analyst forecasts. Q4 came in at a surprise 180,570 units. The firm’s 2021 target is 1.1 million units. The market Cap is about to touch $1 trillion, more than all of the global car industry combined. The Model 3 is doing the heavy lifting. Model Y production in Shanghai is about to ramp up and Berlin is to follow. If Tesla can mass-produce their solid-state batteries, they’ll attain a global monopoly in the car industry with 25 million units a year and a share price of $10,000.
A Saudi surprise production cut, a million barrels a day, sent oil over $50. But with demand that weak, how long can the rally last? The market is entering short-selling territory. I bet you didn’t use much gas today commuting from your bedroom to your home office. Use the rally to unload what energy you have left. Sell the (XLE) on rallies.
Bitcoin topped $42,000, more than doubling in a month, and exceeded $1 trillion as an asset class. A Biden-run economy means more money creation which has to find a home. My friend’s pizza purchase for 8 Bitcoin a decade ago is now worth $320,000. I hope it was good!
The Nonfarm Payroll came in at a loss of 140,000, giving more credence to the Q1 double-dip scenario and far worse than expected. The headline Unemployment Rate came in unchanged at 6.7%, Leisure & Hospitalitylost a mind-blowing 498,000 and an incredible 3.9 million since January. Private Education lost 63,000 and Government 45,000. Professional & Business Services gained 161,000. The real U-6 Unemployment Rate is a very high 11.6%.
The bond crash has only just begun, with the (TLT) down $8 on the week. The risk/reward is the worst of any financial asset anywhere. I am maintaining my triple short position. Massive government borrowing will be a death knell for fixed income investors.
When we come out the other side of pandemic, we will be perfectly poised to launch into my new American Golden Age, or the next Roaring Twenties. With interest rates still at zero, oil cheap, there will be no reason not to. The Dow Average will rise by 400% to 120,000 or more in the coming decade. The American coming out the other side of the pandemic will be far more efficient and profitable than the old. Dow 120,000 here we come!
My Mad Hedge Global Trading Dispatch closed out a blockbuster 2020 with a blockbuster 10.20% in December, taking me up to an eye-popping 66.64% for the year. I’m up 81% since the March low. In 2021, I shot out of the gate with an immediate 5.93% profit for the first four trading days of the year.
That brings my eleven-year total return to 428.48% double the S&P 500 over the same period. My 11-year average annualized return now stands at a nosebleed new high of 38.51%. My trailing one-year return exploded to 72.57%, the highest in the 13-year history of the Mad Hedge Fund Trader. We have earned 89% since the March low.
The coming week will be a slow one on the data front after last week's fireworks. We also need to keep an eye on the number of US Coronavirus cases at 22 million and deaths 370,000, which you can find here.
When the market starts to focus on this, we may have a problem.
On Monday, January 11 at 11:00 AM EST, US Inflation Expectations are released, which will increasingly become an area of interest.
On Tuesday, January 12 at 4:30 PM, API Crude Inventories are published.
On Wednesday, January 13 at 8:30 AM, the US Inflation Rate for December is announced.
On Thursday, January 14 at 8:30 AM, the Weekly Jobless Claims are published. We also get November Housing Starts.
On Friday, December 15 at 8:30 AM, December Retail Sales are printed. Q4 earnings seasons starts, with JP Morgan Chase (JPM) and Wells Fargo (WFC) reporting. At 2:00 PM we learn the Baker-Hughes Rig Count.
As for me, I’ll be taking my old Toyota Highlander down to the dealer in Reno. Squirrels moved into the engine and ate the wiring, knocking out the heater and the fan. All part of the cost of living in a mountain paradise. However, you have to share it with the critters.
I’ll also be investing in some pepper spray.
Stay healthy.
John Thomas
CEO & Publisher
The Diary of a Mad Hedge Fund Trader
A man came at me with a crowbar last week.I drove into Reno to buy some used backpacks for my Boy Scout troop and parked my Tesla in a nice residential neighborhood. Out of nowhere, a man ran down the street at me screaming profanities, crowbar in hand.
He shouted that I was from Antifa and that I had hired people to invade the Capitol Building to make President Trump look bad.
I reached into my car for my own crowbar. Then the local residents interceded, separating us. The man turned around and walked away, fuming.
“Who the heck was that?” I asked.
“He has mental issues,” said a neighbor. “We’ve had many problems with him before.”
Another said “He’s a Trump supporter. He saw your Tesla and thought you were a liberal.”
Wow! Looks like the nation has a very long way to heal.
Last year, the US defense budget amounted to $622 billion. When the greatest threat to congress in the nation’s history presented itself, it was antique chairs piled against the door that provided the best defense. Maybe we should ditch some big-ticket nuclear missiles and buy more chairs.
Of course, once the insurrection started on Wednesday, I was inundated with international calls from investors asking if they should pull all their money out of the US. I answered “NO” and that it was in fact time to double down. Those who did made a killing.
Ask any professional money manager what his reaction to a coup d’état in Washington would be, their response definitely would NOT be to run out and buy a ton of Tesla (TSLA). Yet, that was exactly the perfect thing to do, the stock soaring an astonishing $135, or 18% in two days. I have many followers who did exactly that and they made millions.
All I can say is that if a market gets hit with an insurrection, and exploding pandemic, and a crashing economy and only goes down 400 points and then bounces back the next day, you want to buy the hell out of it.
I’m talking about going on margin and taking a second mortgage on your home and pouring it into stocks. You might even consider going to a loan shark and borrowing at 18% because you can easily make double that in the right stocks.
After the Biden win and the Georgia sweep, there is now more rocket fuel pouring into the stock market than ever. Call it the “Biden blank check”. Estimates of new spending and subsidies about to hit the market now go up to $10 trillion. Let me list some of them:
*$2 trillion in enforced savings by locked up American consumers.
*Credit card balances have collapsed to multi-year lows, making available hundreds of billions in spending power.
*Trillions of Money market balances sitting on the sidelines yielding zero
*$908 billion stimulus package passed in the closing days of 2020
*A further $2 trillion stimulus package to pass shortly, including $2,000 checks for all 150 million US taxpayers.
*Add another $2 trillion infrastructure budget
*$1 trillion in student loan forgiveness for 10 million borrowers at $10,000 each
*Enormous subsidies for any alternative energy companies and Tesla cars
*The return of the deductibility of $1 trillion worth of state and local real estate taxes (known as (SALT)).
MUCH OF THIS CASH MOUNTAIN IS GOING STRAIGHT INTO THE STOCK MARKET!
It all sets up a stock market that has the potential to have “extreme”moves to the upside, according to my friend, Fundstrat’s Tom Lee.
All you need to retire early is someone to point you in the right direction, into the right sectors and the right stocks. Actually, I happen to know just the right person who can do that and that would be me!
Storming of the Capital shut down markets. After the initial crash, markets flatlined as the entire country dropped what they were doing and glued themselves to a TV, their jaws hanging open. The Dow dove 400 points, bonds and the US dollar stabilized, Tesla and oil took big hits, and gold and silver took off. The electoral college vote has been suspended, gunfights broke out on the house floor, and several explosive devices placed. Trump incited his followers to attack the capitol and they did exactly that. Washington DC is now subject to a 6:00 PM curfew for two weeks. Is this the beginning of the 2024 presidential election? It’s the worst day in Washington since the British burned it in 1814.
Democrats took Georgia, giving them Senate control and a blank check on spending for at least two years. Trump clearly blew the election for his party. My 3X short in bonds soared as the market crashed. Banks rocketed on a 10-basis point leap in interest rates. Infrastructure plays went ballistic. The US dollar faded. Add another couple of percentage points of US GDP growth for 2021.
Tesla Shorts posted biggest loss in history, setting on fire a staggering $38 billion in short positions. Many of these were financed by big oil looking to put Tesla out of business. The short interest in the stock has plunged from 37% to 5%. Did I mention that Tesla was the biggest Mad Hedge long of 2020? I’ve been buying it since it was a split-adjusted $3.30 a share in 2010 against a Friday close of $880, a gain of 290X. Elon Musk is now the richest man in the world and he’s only just getting started!
Tesla met its 500,000-unit 2020 target, far in excess of analyst forecasts. Q4 came in at a surprise 180,570 units. The firm’s 2021 target is 1.1 million units. The market Cap is about to touch $1 trillion, more than all of the global car industry combined. The Model 3 is doing the heavy lifting. Model Y production in Shanghai is about to ramp up and Berlin is to follow. If Tesla can mass-produce their solid-state batteries, they’ll attain a global monopoly in the car industry with 25 million units a year and a share price of $10,000.
A Saudi surprise production cut, a million barrels a day, sent oil over $50. But with demand that weak, how long can the rally last? The market is entering short-selling territory. I bet you didn’t use much gas today commuting from your bedroom to your home office. Use the rally to unload what energy you have left. Sell the (XLE) on rallies.
Bitcoin topped $42,000, more than doubling in a month, and exceeded $1 trillion as an asset class. A Biden-run economy means more money creation which has to find a home. My friend’s pizza purchase for 8 Bitcoin a decade ago is now worth $320,000. I hope it was good!
The Nonfarm Payroll came in at a loss of 140,000, giving more credence to the Q1 double-dip scenario and far worse than expected. The headline Unemployment Rate came in unchanged at 6.7%, Leisure & Hospitalitylost a mind-blowing 498,000 and an incredible 3.9 million since January. Private Education lost 63,000 and Government 45,000. Professional & Business Services gained 161,000. The real U-6 Unemployment Rate is a very high 11.6%.
The bond crash has only just begun, with the (TLT) down $8 on the week. The risk/reward is the worst of any financial asset anywhere. I am maintaining my triple short position. Massive government borrowing will be a death knell for fixed income investors.
When we come out the other side of pandemic, we will be perfectly poised to launch into my new American Golden Age, or the next Roaring Twenties. With interest rates still at zero, oil cheap, there will be no reason not to. The Dow Average will rise by 400% to 120,000 or more in the coming decade. The American coming out the other side of the pandemic will be far more efficient and profitable than the old. Dow 120,000 here we come!
My Mad Hedge Global Trading Dispatch closed out a blockbuster 2020 with a blockbuster 10.20% in December, taking me up to an eye-popping 66.64% for the year. I’m up 81% since the March low. In 2021, I shot out of the gate with an immediate 5.93% profit for the first four trading days of the year.
That brings my eleven-year total return to 428.48% double the S&P 500 over the same period. My 11-year average annualized return now stands at a nosebleed new high of 38.51%. My trailing one-year return exploded to 72.57%, the highest in the 13-year history of the Mad Hedge Fund Trader. We have earned 89% since the March low.
The coming week will be a slow one on the data front after last week's fireworks. We also need to keep an eye on the number of US Coronavirus cases at 22 million and deaths 370,000, which you can find here.
When the market starts to focus on this, we may have a problem.
On Monday, January 11 at 11:00 AM EST, US Inflation Expectations are released, which will increasingly become an area of interest.
On Tuesday, January 12 at 4:30 PM, API Crude Inventories are published.
On Wednesday, January 13 at 8:30 AM, the US Inflation Rate for December is announced.
On Thursday, January 14 at 8:30 AM, the Weekly Jobless Claims are published. We also get November Housing Starts.
On Friday, December 15 at 8:30 AM, December Retail Sales are printed. Q4 earnings seasons starts, with JP Morgan Chase (JPM) and Wells Fargo (WFC) reporting. At 2:00 PM we learn the Baker-Hughes Rig Count.
As for me, I’ll be taking my old Toyota Highlander down to the dealer in Reno. Squirrels moved into the engine and ate the wiring, knocking out the heater and the fan. All part of the cost of living in a mountain paradise. However, you have to share it with the critters.
I’ll also be investing in some pepper spray.
Stay healthy.
John Thomas
CEO & Publisher
The Diary of a Mad Hedge Fund Trader
Quote of the Day“Getting rid of your great companies and adding to you bad companies is like cutting the flowers and watering the weeds,” said my former client and mentor, Magellan Fund’s Peter Lynch.
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Not bad but its thin on the top peaks..the crowds are super small No line waits
Storm skiing today with a few inches of new snow. I'm pretty abused today and may sit it out with the big winds.
The top peaks are awesome the south face inset is epic , great shoot skiing but the rocks right now are making it hard to go for it.
Big sky is worth the trip.
https://bigskyresort.com/trail-maps
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Nice CB....It's undervalued in a big way.It's one I don't worry about too much, I'll hold for years I think.
Yesterdays MH
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| Global Market Comments January 13, 2021 Fiat Lux Featured Trade: (MY RADICAL VIEW OF THE MARKETS), (INDU), (SPY), (AAPL), (FB), (AMZN), (ROKU) 
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My Radical View of the Markets What if the consensus is wrong?What if instead of being in the 12[SUP]th[/SUP] year of a bull market, we are actually in the first year, which has another decade to run? It’s not only possible but also probable. Personally, I give it a greater than 90% chance. There is a possibility that the bear market that everyone and his brother have been long predicting and that the talking heads assure you is imminent has already happened. It took place during the first quarter of 2020 when the Dow Average plunged a heart-rending 40%. How could this be a bear market when historical ursine moves down lasted anywhere from six months to two years, not six weeks? Blame it all on hyperactive algorithms, risk parity traders, Robin Hood traders, and hedge funds, which adjust portfolios with the speed of light. If this WAS a bear market and you blinked, then you missed it. It certainly felt like a bear market at the time. Lead stocks like Amazon (AMZN), Apple (AAPL), Facebook (FB), and Alphabet (GOOGL) were all down close to 40% during the period. High beta stocks like Roku (ROKU), one of our favorites, were down 60% at the low. It has since risen by 600%. It got so bad that I had to disconnect my phone at night to prevent nervous fellows from calling me all night. In my experience, if it walks like a duck and quacks like a duck, then it is a bear. If true, then the implications for all of us are enormous. If I’m right, then my 2030 target of a Dow Average of $120,000, an increase of 300% no longer looks like the mutterings of a mad man, nor the pie in the sky dreams of a permabull. It is in fact eminently doable, calling for a 15% annual gain until then, with dividends. What have we done over the last 11 years? How about 13.08% annually with dividends reinvested for a total 313% gain. For a start, from here on, we should be looking to buy every dip, not sell every rally. Institutional cash levels are way too high. Markets have gone up so fast, up 12,000 Dow points in eight months, that many slower investors were left on the sideline. Most waited for dips that never came. It all brings into play my Golden Age scenario of the 2020s, a repeat of the Roaring Twenties, which I have been predicting for the last ten years. This calls for a generation of 85 million big spending Millennials to supercharge the economy. Anything you touch will turn to gold, as they did during the 1980s, the 1950s, and well, the 1920s. Making money will be like falling off a log. If this is the case, you should be loading the boat with technology stocks, domestic recovery stocks, and biotech stocks at every opportunity. Although stocks look expensive now, they are still only at one fifth peak valuations of the 2000 market summit. Let me put out another radical, out of consensus idea. It has become fashionable to take the current red-hot stock market as proof of a Trump handling of the economy. I believe the opposite is true. I think stocks have traded at a 10%-20% discount to their true earnings potential for the past four years. Anti-business policies were announced and then reversed the next day. Companies were urged to reopen money-losing factories in the US. Capital investment plans were shelved. Yes, the cut in corporate earnings was nice, but that only had value to the 50% of S&P 500 companies that actually pay taxes. Now that Trump is gone, that burden and that discount are lifted from the shoulders of corporate America. It makes economic sense. We will see an immediate end to our trade war with the world, which is currently costing us 1% a year in GDP growth. Take Trump out of the picture and our economy gets that 1% back immediately, leaping from 2% to 3% growth a year and more. The last Roaring Twenties started with doubts and hand wringing similar to what we are seeing now. Everyone then was expecting a depression in the aftermath of WWI because big-time military spending was ending. After a year of hesitation, massive reconstruction spending in Europe and a shift from military to consumer spending won out, leading to the beginning of the Jazz Age, flappers, and bathtub gin. I know all this because my grandmother regaled me with these tales, an inveterate flapper herself, which she often demonstrated. This is the same grandmother who bought the land under the Bellagio Hotel in Las Vegas for $500 in 1945 and then sold it for $10 million in 1978. And you wonder where I got my seed capital. It all sets up another “Roaring Twenties” very nicely. You will all look like geniuses. I just thought you’d like to know. 
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Quote of the Day “We live in a world that is not described by classical economics,” said Oracle of Omaha Warren Buffet. 
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sweet action CB..300 bucks shortly..
TWST 200.00 today...WOW
MH today
Global Market Comments
January 19, 2021
Fiat Lux
January 19, 2021
Fiat Lux
Featured Trade:(WHY THERE’S ANOTHER DOUBLE IN CRISPR THEREPEUTICS)
(CRSP), (BLUE), (EDIT), (NVS), (GILD)
(CRSP), (BLUE), (EDIT), (NVS), (GILD)
Why There’s Another Double in CRISPR Therapeutics
Occasionally, I discover a piece of research from one of my other Mad Hedge publications that is so important that I send it out to everyone immediately.Recently, a piece from the Mad Hedge Biotech & Healthcare Letter is one of the instances. It makes the case and provides the numbers as to why Biotech & Healthcare will be one of two dominant sectors to follow for the next decade. It also is a key plank in my argument for a return of a new Golden Age and a second “Roaring Twenties.”
Here it is.
Biotech investors, take note: 2019 was a great year for the industry, but the best is yet to come.
In the final three months of 2019, the biotech sector grew by 32% -- notably outpacing the pharmaceutical industry, which only recorded a 9.5% gain.
However, the biotechnology sector is estimated to grow substantially in 2021 and reach over $775 billion in revenue by 2024 as more and more treatments for previously incurable diseases get discovered.
Looking at all the progress in the biotechnology space, this could even be the year we’d finally discover the cure to many life-threatening and debilitating conditions like cancer and Alzheimer’s disease.
With all these technological advancements, two revolutionary tools have been overhauling the entire biotechnology and healthcare industry from the ground up: precision medicine and CRISPR. Actually, the impressive growth of the biotechnology industry has been largely attributed to the excitement generated by the gene-editing sector.
While the majority of companies concentrating on the human genome are still in the research phase, the growth of this industry is undeniable.
Here’s tangible proof.
Just 20 years ago, reading all the DNA of a single person cost approximately $3 billion. Now, this price is down to only $1,000. In the future, this number will go even lower at $100. There are now gigantic factories in China sequencing DNA for companies like Ancestry.com and 23andMe.
This is just one example of how the biotechnology industry has grown by leaps and bounds. It’s also the reason behind the surge of CRISPR shares.
In effect, the specialists in this niche, including Crispr Therapeutics (CRSP), Bluebird Bio (BLUE), and Editas Medicine (EDIT), are amplifying their efforts.
Among the specialist companies, CRISPR Therapeutics is considered as one of the frontrunners -- if not the top stock. This is because compared to its rivals, which are still in preclinical phases of development, CRISPR Therapeutics already has two drugs going through Phase 1 trials: CTX001 and CTX110.
The promising results of the company’s research resulted in a 113% rise in shares last year, with the bulk of the surge starting in October. In fact, CRISPR Therapeutics’ performance had been so impressive that its market cap reached $3.4 billion.
CTX001 is created to target patients suffering from genetic blood disorders, specifically sickle-cell disease and transfusion-dependent beta-thalassemia.
Meanwhile, CTX110 is a CAR-T treatment. The process involves the extraction of immune cells from the patient. These are then retrained and later re-introduced to the human body.
CRISPR Therapeutics’ CAR-T treatment is anticipated to be offered at a cheaper price compared to the other CAR-T therapies.
Both Novartis (NVS) and Gilead Sciences (GILD) are pursuing the same treatment. However, the cost of the therapy from the latter two is expected to reach as much as $475,000 for every patient annually.
Apart from CTX001 and CTX110, CRISPR Therapeutics has two more immunology candidates, currently dubbed CTX120 and CTX130.
If both phase trials succeed, these will bring massive home runs for CRISPR Therapeutics, especially since the cancer immunology market is expected to reach $127 billion by 2026. Over the next 10 years, this niche is estimated to reach $25 trillion in sales.
Among the gene-editing treatments under development today, CRISPR is projected to grow tenfold in the number of applications and potentially curing 89% of disease-causing genetic variations by 2026.
Taking this pace into consideration, the valuation for this market is expected to grow from $551 million in 2017 to reach roughly $3.1 billion by 2023 and $6 billion by 2025.
Meanwhile, precision medicine as a whole is estimated to show a significant jump from $48.6 billion in 2018 to $84.6 billion by 2024. In 2028, this market is expected to rake in $216 billion.
Hence, further success with CTX001 and CTX110 along with additional treatments in the drug pipeline would all but guarantee that Crispr Therapeutics could beat the market again in 2021.
To subscribe to the Mad Hedge Biotech & Healthcare Letter for a bargain $1,500 a year, please click here.
Occasionally, I discover a piece of research from one of my other Mad Hedge publications that is so important that I send it out to everyone immediately.Recently, a piece from the Mad Hedge Biotech & Healthcare Letter is one of the instances. It makes the case and provides the numbers as to why Biotech & Healthcare will be one of two dominant sectors to follow for the next decade. It also is a key plank in my argument for a return of a new Golden Age and a second “Roaring Twenties.”
Here it is.
Biotech investors, take note: 2019 was a great year for the industry, but the best is yet to come.
In the final three months of 2019, the biotech sector grew by 32% -- notably outpacing the pharmaceutical industry, which only recorded a 9.5% gain.
However, the biotechnology sector is estimated to grow substantially in 2021 and reach over $775 billion in revenue by 2024 as more and more treatments for previously incurable diseases get discovered.
Looking at all the progress in the biotechnology space, this could even be the year we’d finally discover the cure to many life-threatening and debilitating conditions like cancer and Alzheimer’s disease.
With all these technological advancements, two revolutionary tools have been overhauling the entire biotechnology and healthcare industry from the ground up: precision medicine and CRISPR. Actually, the impressive growth of the biotechnology industry has been largely attributed to the excitement generated by the gene-editing sector.
While the majority of companies concentrating on the human genome are still in the research phase, the growth of this industry is undeniable.
Here’s tangible proof.
Just 20 years ago, reading all the DNA of a single person cost approximately $3 billion. Now, this price is down to only $1,000. In the future, this number will go even lower at $100. There are now gigantic factories in China sequencing DNA for companies like Ancestry.com and 23andMe.
This is just one example of how the biotechnology industry has grown by leaps and bounds. It’s also the reason behind the surge of CRISPR shares.
In effect, the specialists in this niche, including Crispr Therapeutics (CRSP), Bluebird Bio (BLUE), and Editas Medicine (EDIT), are amplifying their efforts.
Among the specialist companies, CRISPR Therapeutics is considered as one of the frontrunners -- if not the top stock. This is because compared to its rivals, which are still in preclinical phases of development, CRISPR Therapeutics already has two drugs going through Phase 1 trials: CTX001 and CTX110.
The promising results of the company’s research resulted in a 113% rise in shares last year, with the bulk of the surge starting in October. In fact, CRISPR Therapeutics’ performance had been so impressive that its market cap reached $3.4 billion.
CTX001 is created to target patients suffering from genetic blood disorders, specifically sickle-cell disease and transfusion-dependent beta-thalassemia.
Meanwhile, CTX110 is a CAR-T treatment. The process involves the extraction of immune cells from the patient. These are then retrained and later re-introduced to the human body.
CRISPR Therapeutics’ CAR-T treatment is anticipated to be offered at a cheaper price compared to the other CAR-T therapies.
Both Novartis (NVS) and Gilead Sciences (GILD) are pursuing the same treatment. However, the cost of the therapy from the latter two is expected to reach as much as $475,000 for every patient annually.
Apart from CTX001 and CTX110, CRISPR Therapeutics has two more immunology candidates, currently dubbed CTX120 and CTX130.
If both phase trials succeed, these will bring massive home runs for CRISPR Therapeutics, especially since the cancer immunology market is expected to reach $127 billion by 2026. Over the next 10 years, this niche is estimated to reach $25 trillion in sales.
Among the gene-editing treatments under development today, CRISPR is projected to grow tenfold in the number of applications and potentially curing 89% of disease-causing genetic variations by 2026.
Taking this pace into consideration, the valuation for this market is expected to grow from $551 million in 2017 to reach roughly $3.1 billion by 2023 and $6 billion by 2025.
Meanwhile, precision medicine as a whole is estimated to show a significant jump from $48.6 billion in 2018 to $84.6 billion by 2024. In 2028, this market is expected to rake in $216 billion.
Hence, further success with CTX001 and CTX110 along with additional treatments in the drug pipeline would all but guarantee that Crispr Therapeutics could beat the market again in 2021.
To subscribe to the Mad Hedge Biotech & Healthcare Letter for a bargain $1,500 a year, please click here.
Quote of the Day"A pessimist sees the difficulty in every opportunity; an optimist sees the opportunity in every difficulty," said the late British Prime Minister, Winston Churchill.
Thanks as always Bozzie!
I bought CRSP earlier this year around $40, sold it around $80. So I am/was very happy with the trade, but as it keeps going up I'm kicking myself for not holding
Hope you had a good vaca! I'm not a big skier, but I vacationed in Jackson Hole and Big Sky a couple years ago in the early fall to do some hiking. It's beautiful.
I bought CRSP earlier this year around $40, sold it around $80. So I am/was very happy with the trade, but as it keeps going up I'm kicking myself for not holding
Hope you had a good vaca! I'm not a big skier, but I vacationed in Jackson Hole and Big Sky a couple years ago in the early fall to do some hiking. It's beautiful.
in hiding, got atta dodge!!!!!.......to live to see another day ....... China govt reminding him who's boss.
BABA has an economic moat, its a beast. Does the China govt give it a slap on the wrist or lay into it? (full disclosure i own it in two different etfs )some fun numbers comparing BABA vs AMZN
monthly active users : BABA - 845 million AMZN - 200 million
total revenue: BABA- $86 billion AMZN- $347 billion
revenue growth (5yr) - BABA- 46% AMZN- 28%
net profit margin - BABA - 22% AMZN - 5%
market cap - BABA - $692 billion AMZN- $1558 billion
BABA owns many subsidiaries and has their hands in seemingly everything-- b2c, c2c, b2b, digital media, cloud.
in hiding, got atta dodge!!!!!.......to live to see another day ....... China govt reminding him who's boss.
some fun numbers comparing BABA vs AMZN
monthly active users : BABA - 845 million AMZN - 200 million
total revenue: BABA- $86 billion AMZN- $347 billion
revenue growth (5yr) - BABA- 46% AMZN- 28%
net profit margin - BABA - 22% AMZN - 5%
market cap - BABA - $692 billion AMZN- $1558 billion
BABA owns many subsidiaries and has their hands in seemingly everything-- b2c, c2c, b2b, digital media, cloud.
Hands in everything is right.. Retail on the ground level as a driver in 4th 5th and 6ht tiered cities.
The CCP likes what BABA offers as a driver toward the reserve currency status it craves. The CCP needs BABA in a way, You're seeing them "take" partnership in BABA ventures..See what ANT might look like post Jack Ma's comments on the Chinese banking systems and it's officials...CCP party members.
You might as well sleep with the party in BABAs case the CCP isn't going away and I'd bet it leads to huge numbers price wise eventually..The CCP won't do Fintech but BABA will.
https://www.wsj.com/articles/jack-ma-makes-ant-offer-to-placate-chinese-regulators-11608479629
Thanks as always Bozzie!
I bought CRSP earlier this year around $40, sold it around $80. So I am/was very happy with the trade, but as it keeps going up I'm kicking myself for not holding
Hope you had a good vaca! I'm not a big skier, but I vacationed in Jackson Hole and Big Sky a couple years ago in the early fall to do some hiking. It's beautiful.
Nice....
CRSP..I've been watching ....I loveBios.
It was great, beautiful for sure... next time I'll bring a fly rod.
Waiting on a Ginkgo Bio IOP.....
Besides building momentum against COVID-19, biopharma will accelerate its progress in genome editing, gene and cell therapy, synthetic biology, and other crucial areas
By
Alex Philippidis -
January 8, 20210
Source: whyframestudio/Getty Image
Last year, when GEN prepared an editorial titled Eight Biopharma Trends to Watch in 2020, who could have foreseen COVID-19 and the deaths, illnesses, and economic disruption that the disease would wreak? And who could have foreseen how armies of industry and academic researchers would race to develop hundreds of new and repositioned vaccines and drugs? (GEN tracks more than 300 on its COVID-19 Drug and Vaccine Tracker webpage).
While biopharma was dominated by COVID-19, which prompted a surge of research and business activity, the industry also saw developments that will position it for further growth even after the virus is brought under control.
The pandemic and other hot therapy areas drove venture capital (VC) financing to new heights, while propelling a new wave of mergers and acquisitions (M&A) activity as well as an increase in initial public offerings (IPOs). Clinical and commercial activity increased in traditional drug discovery as well as in cell therapy and gene therapy—the latter withstanding the deaths of four participants in two clinical trials. Investors warmed to emerging technologies offering the potential for new therapies, including genome editing and synthetic biology.
Below are seven biopharma-related trends cited by experts and others with a stake in the industry, as articulated in interviews with GEN, or in reports and other public statements.
1. COVID-19: Seeing the finish line
Hope for an eventual end to the COVID-19 pandemic was raised in November when positive Phase III vaccine data emerged from Pfizer and BioNTech, which promptly sought emergency authorization (EUA) for their BNT162b2 vaccine candidate. This hope was strengthened when Moderna reported progress about its mRNA-1273 vaccine candidate.
Other encouraging developments included the FDA’s approval of the first COVID-19 therapy, Gilead Sciences’ repositioned antiviral remdesivir (marketed as Veklury®).
In December, two vaccines, Moderna’s mRNA-1273 and Pfizer/BioNTech’s BNT162b2, joined remdesivir in crossing the finish line of FDA approval. These vaccines will likely be joined by several others, including AZD1222 (AstraZeneca/University of Oxford), JNJ-78436735 (Johnson & Johnson’s Janssen Pharmaceutical), NVX-CoV2373 (Novavax), MRT5500 (Translate Bio and Sanofi), V591 (Merck & Co.), and an unnamed vaccine that is being developed by Sanofi and GlaxoSmithKline.
With the approval of multiple new vaccines, vaccination capacity is projected to grow nearly 150-fold, from 35 million people in the fourth quarter of this year to 5 billion people by the fourth quarter of 2021, according to a November 18 research note by Michael J. Yee, equity analyst with Jefferies, and three colleagues.
On the drug front, remdesivir will likely be joined on the market by two antibody therapies, bamlanivimab (Eli Lilly) and REGEN-COV2 (Regeneron Pharmaceuticals), for mild to moderate COVID-19. The FDA granted emergency use authorizations to Eli Lilly and to Regeneron in November, paving the way for their drugs’ eventual approvals. Also nearing approval is a combination therapy of remdesivir plus Eli Lilly’s Olumiant®(baricitinib), indicated for hospitalized COVID-19 patients. It received an EUA in November.
2. Gene therapy: Big pharma, big deals
Big pharma firms have truly warmed to gene therapy to expand their pipelines in 2021 and beyond. Bayer agreed to acquire Asklepios BioPharmaceutical (AskBio) for up to $4 billion in October, followed two days later by Novartis purchasing ocular gene therapy developer Vedere Bio for up to $280 million. Roche agreed to spend up to $1.8 billion to use Dyno Therapeutics’ CapsidMap™ platform to develop next-generation adeno-associated virus (AAV) vectors for gene therapies for central nervous system diseases and liver-directed therapies.
Pfizer invested $60 million in Homology Medicines three days after Homology presented positive data from a Phase I/II trial (NCT03952156) for pheNIX, a gene therapy for adults with phenylketonuria (PKU). Among biotech giants, Biogen and Sangamo Therapeutics are developing and commercializing Sangamo gene regulation therapy candidates through a collaboration that could generate $2.7 billion-plus for Sangamo.
A continuing challenge in 2021 will be preventing tragedies arising from gene therapy clinical trials. In October, Lysogene disclosed that a five-year-old girl with mucopolysaccharidosis type IIIA (MPS IIIA) died in a Phase II/III trial (NCT03612869) designed to evaluate the company’s LYS-SAF302.
Between May and July, Audentes Therapeutics, which was acquired by Astellas Pharma for $3 billion in January 2020, acknowledged the deaths of three patients in a Phase I/II trial (NCT03199469) assessing its X-linked myotubular myopathy (XLMTM) candidate AT-132. The 3 were among 17 patients who received AT132 at the trial’s high dose of 3 × 1014vg/kg. Audentes said all three patients who died showed notable features that included older age, heavier weight, and evidence of preexisting hepatobiliary disease.
“That is definitely a wake-up call for the field to really consider dose escalation more carefully, and to put much more emphasis on CMC [chemistry, manufacturing and control] than simply making a higher potency,” said Guangping Gao, PhD, the Penelope Booth Rockwell Professor in Biomedical Research at the University of Massachusetts Medical School, the director of the Horae Gene Therapy Center and Viral Vector Core, and the co-director of the Li Weibo Institute for Rare Diseases Research.
Despite the deaths, gene therapy did not see the disruption that followed the death of 17-year-old Jesse Gelsinger in 1999. According to the Alliance for Regenerative Medicine, gene therapy financing nearly tripled year over year, rising 178% to $3.5 billion in the third quarter of 2020. Between January and September 2020, financing jumped 114% to $12 billion.
The alliance recorded 373 gene therapy trials during the third quarter of 2020—up 4% from 359 in the second quarter but barely above the 370 reported in the third quarter of 2019. Of those trials, 115 were in Phase I, 223 in Phase II, and 32 in Phase III.
3. Genome editing: CRISPR and beyond
Genome editing showed in November that it, too, can spark big-money collaborations. Eli Lilly committed up to $2.7 billion toward using Precision BioSciences’ ARCUS® genome editing platform to research and develop potential in vivo therapies for genetic disorders, starting with Duchenne muscular dystrophy. Bayer’s investment arm Leaps by Bayer co-led a $65 million Series A financing for Metagenomi, a developer of CRISPR-based gene editing systems for developing cell and gene therapies.
CRISPR Therapeutics and Vertex Pharmaceuticals continue to study CTX001, the CRISPR-Cas9 gene edited therapy that in June showed proof of concept in two patients with transfusion-dependent β-thalassemia, and effectiveness in another patient with sickle-cell disease, in two Phase I/II trials that are the first clinical studies of a gene editing candidate sponsored by U.S. companies.
A market report issued November 20 by the Business Research Company projected the global CRISPR technology market will grow from $1.65 billion this year to $2.57 billion by 2023, then leap to $6.7 billion by 2030.
That market is expected to grow faster once the ongoing legal wrangle is resolved over who invented CRISPR-Cas9. The bitter dispute is at the center of a second interference proceeding winding its way through the Patent Trial and Appeal Board (PTAB).
In September, the PTAB redeclared the interference by designating the Broad Institute of MIT and Harvard the senior party, and according junior party status to the Regents of the University of California, CRISPR Nobel Laureate Emmanuelle Charpentier, PhD, and the University of Vienna, collectively called CVC. The PTAB also held off immediately deciding which party offered the strongest evidence of being first to show CRISPR’s effectiveness in eukaryotic cells.
4. Financing: Impressive VC, M&A, and IPO activity
Capital flowed into biopharma companies, as shown by record-high VC investment. That trend is expected to continue in 2021, as are strong if not equally impressive gains in M&A activity, IPOs, and the broader stock market.
The quarterly MoneyTree Report, issued by PwC and CB Insights, showed a record-high $5.9 billion invested during the third quarter of 2020 in biopharma-related industries, dominated by $3.9 billion in 104 deals invested in biotech alone—more than double the $1.9 billion in 74 deals reported for the third quarter of 2019.
“It seems like the biotech and life sciences industry has been pretty much agnostic to COVID-19,” Ousmane Caba, partner, U.S. Pharmaceuticals and Life Sciences, PwC US, told GEN. “COVID hasn’t stopped IPOs, transactions, and M&A. The industry hasn’t been that impacted by the pandemic.”
Two factors have been driving financing in recent months, Caba said. One is the ability to apply data to biology. The third quarter’s largest VC recipient was Recursion, a digital biology company that completed a $239 million oversubscribed Series D financing led by Leaps by Bayer. The other is the longtime interest by drug developers and investors in fighting cancer, especially through technologies applicable to multiple forms of the disease.
Caba observed that the targeting of cancer helped drive a series of big-dollar M&A deals during 2020. Gilead Sciences in October completed its $21 billion acquisition of Immunomedics, which bolstered the buyer’s oncology portfolio with a first-in-class breast cancer treatment that received an accelerated approval from the FDA in April. Illumina plans to buy cancer blood test developer Grail for $8 billion, a deal set to close in 2021. Grail’s ability to apply data also made the company attractive, Caba said.
Also showing strength in 2020 was the market for first-time public stocks. During the first three quarters of 2020, biopharma firms raised a combined $9.32 billion in 51 IPOs, more than double the $3.6 billion garnered in 41 IPOs during the first three quarters of 2019, according to EvaluatePharma.
Overall, biotech stocks enjoyed healthy gains during 2020. As of November 20, the NASDAQ Biotechnology Index stood at $4,364.15, up 22% from $3,581.05 the same date a year ago.
“We do see pharma and biotech as undervalued as we approach the end of 2020,” said Karen Andersen, a healthcare strategist at Morningstar. “Overall, we’re seeing progress with several therapeutic areas. In neurology, even beyond aducanumab, we could see data in 2021–2022 to support new drugs against Huntington’s, amyotrophic lateral sclerosis, Parkinson’s, and Alzheimer’s.”
5. Drug development: Alzheimer’s and more
One of the most closely watched drug development stories in 2021 will be whether the FDA approves aducanumab, the Alzheimer’s disease candidate that Biogen is co-developing with Eisai. Aducanumab is being evaluated under priority review, with a target action date of March 7, 2021.
In November, aducanumab ran into an unexpected obstacle on the road to FDA approval after an advisory panel recommended against approving the drug. The FDA’s Peripheral and Central Nervous System Drugs Advisory Committee balked at endorsing aducanumab. In March, Biogen halted EMERGE and ENGAGE, each a Phase III trial of the drug, after analyses indicated that the trials were unlikely to meet their primary endpoints. Then, in October, Biogen reported that a larger dataset for the EMERGE trial had become available, and that analysis of this dataset had showed a significant reduction in clinical decline. Biogen also indicated that in the ENGAGE trial, data from a subset of patients supported the new conclusions about the EMERGE trial.
“We think aducanumab will get a complete response letter in early 2021 requesting another large trial ahead of approval. We assume a 40% probability of approval in 2024,” Andersen said. “If Biogen gets a complete response letter, they will have to decide if they want to continue investing in aducanumab, or focus efforts on a similar antibody, BAN2401, that is already in a couple of Phase III studies with partner Eisai.”
Andersen added that aducanumab will either lead to more attention and higher valuations for Alzheimer’s programs, such as the programs at Roche and Eli Lilly, or dampen the enthusiasm for therapies that are based on clearing amyloid plaques: “Either way, we expect continued investment in other mechanisms of action, especially tau, and other modalities that can better cross the blood-brain barrier, like Denali’s small molecule inhibitors of leucine-rich repeat kinase 2 (licensed by Biogen), or RNA-based therapies, like those of Ionis Pharmaceuticals partnered with Biogen.”
According to Andersen, drug developers also continue to see progress in oncology. She cited antibody-drug conjugates, like those of Seagen (formerly Seattle Genetics), and two therapies with breast cancer indications—AstraZeneca’s Enhertu® (fam-trastuzumab deruxtecan-nxki) and Trodelvy™ (sacituzumab govitecan-hziy), which Gilead Sciences will inherit when it finishes acquiring Immunomedics. She added, “We expect more combination data with PD-1/PD-L1 antibodies for multiple bispecific antibody programs and other antibodies as well.”
6. Cell therapy: Buyers large and small
Developers are expected to extend last year’s cell therapy developments into 2021. Last November, PerkinElmer agreed to acquire Horizon Discovery Group for approximately $383 million, in a deal intended to add gene editing and gene modulation tools to the buyer’s portfolio of automated life sciences discovery and applied genomics solutions. Sanofi in November shelled out about $364 million to acquire Kiadis Pharma, a developer of natural killer cell therapies. Most of these therapies are focused on cancer, but one therapy in preclinical development is targeting COVID-19.
Two pharma giants completed facilities focused on cell therapy development. In September, Takeda Pharmaceutical opened a new R&D cell therapy manufacturing facility within its research headquarters in Boston. In October, Astellas Pharma opened a $120 million facility to be occupied by the Astellas Institute for Regenerative Medicine (AIRM). The new facility, which is located in Westborough, MA, is to focus on cell therapy manufacturing as much as on R&D.
Cell therapy financing grew at an impressive rate. According to the Alliance for Regenerative Medicine, cell therapy financing as of November 2020 reached $3 billion in the third quarter and $11 billion year to date, up 97% and 242%, respectively. The number of Phase I trials assessing cell therapies increased from 41 to 50 (for the first three quarters of 2019 and for the first three quarters of 2020, respectively) but dipped in Phases II and III. Overall, the number of clinical trials decreased from 218 to 202 trials as of the third quarter.
7. Synthetic biology: In the money
SynBioBeta recently shared some numbers illustrating the increasing allure of synthetic biology to investors. During the first half of 2020, total financing in the sector reached $3.041 billion (among 56 companies). During the first half of 2019, it was $1.9 billion (among 65 companies). The largest financing, $700 million, was raised by Sana Biotechnology, a developer of therapies that are based on engineering cells.
The synthetic biology money train continued into the second half. In September, Zymergen raised $300 million intended to propel its expansion into the $3 trillion chemical and materials industries; accelerate the manufacture of its biofabricated Hyaline film for electronics applications; and commercialize additional products with applications in electronics, agriculture, consumer care, and healthcare.
“The takeaway: coronavirus is not hampering the estimated $4 trillion bioeconomy being driven by synthetic biology,” SynBioBeta founder John Cumbers, PhD, commented recently in Forbes.
If anything, COVID-19 is helping to drive synthetic biology activity and will continue to do so in 2021. Ginkgo Bioworks raised $70 million in May toward developing large-scale testing infrastructure. In July, the company announced an approximately $40 million award from the NIH Rapid Acceleration of Diagnostics Advanced Technology Platforms (RADx-ATP) program to scale its automated technology for SARS-CoV-2 testing using next-generation sequencing.
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Besides building momentum against COVID-19, biopharma will accelerate its progress in genome editing, gene and cell therapy, synthetic biology, and other crucial areas
By
Alex Philippidis -
January 8, 20210
Source: whyframestudio/Getty Image
Last year, when GEN prepared an editorial titled Eight Biopharma Trends to Watch in 2020, who could have foreseen COVID-19 and the deaths, illnesses, and economic disruption that the disease would wreak? And who could have foreseen how armies of industry and academic researchers would race to develop hundreds of new and repositioned vaccines and drugs? (GEN tracks more than 300 on its COVID-19 Drug and Vaccine Tracker webpage).
While biopharma was dominated by COVID-19, which prompted a surge of research and business activity, the industry also saw developments that will position it for further growth even after the virus is brought under control.
The pandemic and other hot therapy areas drove venture capital (VC) financing to new heights, while propelling a new wave of mergers and acquisitions (M&A) activity as well as an increase in initial public offerings (IPOs). Clinical and commercial activity increased in traditional drug discovery as well as in cell therapy and gene therapy—the latter withstanding the deaths of four participants in two clinical trials. Investors warmed to emerging technologies offering the potential for new therapies, including genome editing and synthetic biology.
Below are seven biopharma-related trends cited by experts and others with a stake in the industry, as articulated in interviews with GEN, or in reports and other public statements.
1. COVID-19: Seeing the finish line
Hope for an eventual end to the COVID-19 pandemic was raised in November when positive Phase III vaccine data emerged from Pfizer and BioNTech, which promptly sought emergency authorization (EUA) for their BNT162b2 vaccine candidate. This hope was strengthened when Moderna reported progress about its mRNA-1273 vaccine candidate.
Other encouraging developments included the FDA’s approval of the first COVID-19 therapy, Gilead Sciences’ repositioned antiviral remdesivir (marketed as Veklury®).
In December, two vaccines, Moderna’s mRNA-1273 and Pfizer/BioNTech’s BNT162b2, joined remdesivir in crossing the finish line of FDA approval. These vaccines will likely be joined by several others, including AZD1222 (AstraZeneca/University of Oxford), JNJ-78436735 (Johnson & Johnson’s Janssen Pharmaceutical), NVX-CoV2373 (Novavax), MRT5500 (Translate Bio and Sanofi), V591 (Merck & Co.), and an unnamed vaccine that is being developed by Sanofi and GlaxoSmithKline.
With the approval of multiple new vaccines, vaccination capacity is projected to grow nearly 150-fold, from 35 million people in the fourth quarter of this year to 5 billion people by the fourth quarter of 2021, according to a November 18 research note by Michael J. Yee, equity analyst with Jefferies, and three colleagues.
On the drug front, remdesivir will likely be joined on the market by two antibody therapies, bamlanivimab (Eli Lilly) and REGEN-COV2 (Regeneron Pharmaceuticals), for mild to moderate COVID-19. The FDA granted emergency use authorizations to Eli Lilly and to Regeneron in November, paving the way for their drugs’ eventual approvals. Also nearing approval is a combination therapy of remdesivir plus Eli Lilly’s Olumiant®(baricitinib), indicated for hospitalized COVID-19 patients. It received an EUA in November.
2. Gene therapy: Big pharma, big deals
Big pharma firms have truly warmed to gene therapy to expand their pipelines in 2021 and beyond. Bayer agreed to acquire Asklepios BioPharmaceutical (AskBio) for up to $4 billion in October, followed two days later by Novartis purchasing ocular gene therapy developer Vedere Bio for up to $280 million. Roche agreed to spend up to $1.8 billion to use Dyno Therapeutics’ CapsidMap™ platform to develop next-generation adeno-associated virus (AAV) vectors for gene therapies for central nervous system diseases and liver-directed therapies.
Pfizer invested $60 million in Homology Medicines three days after Homology presented positive data from a Phase I/II trial (NCT03952156) for pheNIX, a gene therapy for adults with phenylketonuria (PKU). Among biotech giants, Biogen and Sangamo Therapeutics are developing and commercializing Sangamo gene regulation therapy candidates through a collaboration that could generate $2.7 billion-plus for Sangamo.
A continuing challenge in 2021 will be preventing tragedies arising from gene therapy clinical trials. In October, Lysogene disclosed that a five-year-old girl with mucopolysaccharidosis type IIIA (MPS IIIA) died in a Phase II/III trial (NCT03612869) designed to evaluate the company’s LYS-SAF302.
Between May and July, Audentes Therapeutics, which was acquired by Astellas Pharma for $3 billion in January 2020, acknowledged the deaths of three patients in a Phase I/II trial (NCT03199469) assessing its X-linked myotubular myopathy (XLMTM) candidate AT-132. The 3 were among 17 patients who received AT132 at the trial’s high dose of 3 × 1014vg/kg. Audentes said all three patients who died showed notable features that included older age, heavier weight, and evidence of preexisting hepatobiliary disease.
“That is definitely a wake-up call for the field to really consider dose escalation more carefully, and to put much more emphasis on CMC [chemistry, manufacturing and control] than simply making a higher potency,” said Guangping Gao, PhD, the Penelope Booth Rockwell Professor in Biomedical Research at the University of Massachusetts Medical School, the director of the Horae Gene Therapy Center and Viral Vector Core, and the co-director of the Li Weibo Institute for Rare Diseases Research.
Despite the deaths, gene therapy did not see the disruption that followed the death of 17-year-old Jesse Gelsinger in 1999. According to the Alliance for Regenerative Medicine, gene therapy financing nearly tripled year over year, rising 178% to $3.5 billion in the third quarter of 2020. Between January and September 2020, financing jumped 114% to $12 billion.
The alliance recorded 373 gene therapy trials during the third quarter of 2020—up 4% from 359 in the second quarter but barely above the 370 reported in the third quarter of 2019. Of those trials, 115 were in Phase I, 223 in Phase II, and 32 in Phase III.
3. Genome editing: CRISPR and beyond
Genome editing showed in November that it, too, can spark big-money collaborations. Eli Lilly committed up to $2.7 billion toward using Precision BioSciences’ ARCUS® genome editing platform to research and develop potential in vivo therapies for genetic disorders, starting with Duchenne muscular dystrophy. Bayer’s investment arm Leaps by Bayer co-led a $65 million Series A financing for Metagenomi, a developer of CRISPR-based gene editing systems for developing cell and gene therapies.
CRISPR Therapeutics and Vertex Pharmaceuticals continue to study CTX001, the CRISPR-Cas9 gene edited therapy that in June showed proof of concept in two patients with transfusion-dependent β-thalassemia, and effectiveness in another patient with sickle-cell disease, in two Phase I/II trials that are the first clinical studies of a gene editing candidate sponsored by U.S. companies.
A market report issued November 20 by the Business Research Company projected the global CRISPR technology market will grow from $1.65 billion this year to $2.57 billion by 2023, then leap to $6.7 billion by 2030.
That market is expected to grow faster once the ongoing legal wrangle is resolved over who invented CRISPR-Cas9. The bitter dispute is at the center of a second interference proceeding winding its way through the Patent Trial and Appeal Board (PTAB).
In September, the PTAB redeclared the interference by designating the Broad Institute of MIT and Harvard the senior party, and according junior party status to the Regents of the University of California, CRISPR Nobel Laureate Emmanuelle Charpentier, PhD, and the University of Vienna, collectively called CVC. The PTAB also held off immediately deciding which party offered the strongest evidence of being first to show CRISPR’s effectiveness in eukaryotic cells.
4. Financing: Impressive VC, M&A, and IPO activity
Capital flowed into biopharma companies, as shown by record-high VC investment. That trend is expected to continue in 2021, as are strong if not equally impressive gains in M&A activity, IPOs, and the broader stock market.
The quarterly MoneyTree Report, issued by PwC and CB Insights, showed a record-high $5.9 billion invested during the third quarter of 2020 in biopharma-related industries, dominated by $3.9 billion in 104 deals invested in biotech alone—more than double the $1.9 billion in 74 deals reported for the third quarter of 2019.
“It seems like the biotech and life sciences industry has been pretty much agnostic to COVID-19,” Ousmane Caba, partner, U.S. Pharmaceuticals and Life Sciences, PwC US, told GEN. “COVID hasn’t stopped IPOs, transactions, and M&A. The industry hasn’t been that impacted by the pandemic.”
Two factors have been driving financing in recent months, Caba said. One is the ability to apply data to biology. The third quarter’s largest VC recipient was Recursion, a digital biology company that completed a $239 million oversubscribed Series D financing led by Leaps by Bayer. The other is the longtime interest by drug developers and investors in fighting cancer, especially through technologies applicable to multiple forms of the disease.
Caba observed that the targeting of cancer helped drive a series of big-dollar M&A deals during 2020. Gilead Sciences in October completed its $21 billion acquisition of Immunomedics, which bolstered the buyer’s oncology portfolio with a first-in-class breast cancer treatment that received an accelerated approval from the FDA in April. Illumina plans to buy cancer blood test developer Grail for $8 billion, a deal set to close in 2021. Grail’s ability to apply data also made the company attractive, Caba said.
Also showing strength in 2020 was the market for first-time public stocks. During the first three quarters of 2020, biopharma firms raised a combined $9.32 billion in 51 IPOs, more than double the $3.6 billion garnered in 41 IPOs during the first three quarters of 2019, according to EvaluatePharma.
Overall, biotech stocks enjoyed healthy gains during 2020. As of November 20, the NASDAQ Biotechnology Index stood at $4,364.15, up 22% from $3,581.05 the same date a year ago.
“We do see pharma and biotech as undervalued as we approach the end of 2020,” said Karen Andersen, a healthcare strategist at Morningstar. “Overall, we’re seeing progress with several therapeutic areas. In neurology, even beyond aducanumab, we could see data in 2021–2022 to support new drugs against Huntington’s, amyotrophic lateral sclerosis, Parkinson’s, and Alzheimer’s.”
5. Drug development: Alzheimer’s and more
One of the most closely watched drug development stories in 2021 will be whether the FDA approves aducanumab, the Alzheimer’s disease candidate that Biogen is co-developing with Eisai. Aducanumab is being evaluated under priority review, with a target action date of March 7, 2021.
In November, aducanumab ran into an unexpected obstacle on the road to FDA approval after an advisory panel recommended against approving the drug. The FDA’s Peripheral and Central Nervous System Drugs Advisory Committee balked at endorsing aducanumab. In March, Biogen halted EMERGE and ENGAGE, each a Phase III trial of the drug, after analyses indicated that the trials were unlikely to meet their primary endpoints. Then, in October, Biogen reported that a larger dataset for the EMERGE trial had become available, and that analysis of this dataset had showed a significant reduction in clinical decline. Biogen also indicated that in the ENGAGE trial, data from a subset of patients supported the new conclusions about the EMERGE trial.
“We think aducanumab will get a complete response letter in early 2021 requesting another large trial ahead of approval. We assume a 40% probability of approval in 2024,” Andersen said. “If Biogen gets a complete response letter, they will have to decide if they want to continue investing in aducanumab, or focus efforts on a similar antibody, BAN2401, that is already in a couple of Phase III studies with partner Eisai.”
Andersen added that aducanumab will either lead to more attention and higher valuations for Alzheimer’s programs, such as the programs at Roche and Eli Lilly, or dampen the enthusiasm for therapies that are based on clearing amyloid plaques: “Either way, we expect continued investment in other mechanisms of action, especially tau, and other modalities that can better cross the blood-brain barrier, like Denali’s small molecule inhibitors of leucine-rich repeat kinase 2 (licensed by Biogen), or RNA-based therapies, like those of Ionis Pharmaceuticals partnered with Biogen.”
According to Andersen, drug developers also continue to see progress in oncology. She cited antibody-drug conjugates, like those of Seagen (formerly Seattle Genetics), and two therapies with breast cancer indications—AstraZeneca’s Enhertu® (fam-trastuzumab deruxtecan-nxki) and Trodelvy™ (sacituzumab govitecan-hziy), which Gilead Sciences will inherit when it finishes acquiring Immunomedics. She added, “We expect more combination data with PD-1/PD-L1 antibodies for multiple bispecific antibody programs and other antibodies as well.”
6. Cell therapy: Buyers large and small
Developers are expected to extend last year’s cell therapy developments into 2021. Last November, PerkinElmer agreed to acquire Horizon Discovery Group for approximately $383 million, in a deal intended to add gene editing and gene modulation tools to the buyer’s portfolio of automated life sciences discovery and applied genomics solutions. Sanofi in November shelled out about $364 million to acquire Kiadis Pharma, a developer of natural killer cell therapies. Most of these therapies are focused on cancer, but one therapy in preclinical development is targeting COVID-19.
Two pharma giants completed facilities focused on cell therapy development. In September, Takeda Pharmaceutical opened a new R&D cell therapy manufacturing facility within its research headquarters in Boston. In October, Astellas Pharma opened a $120 million facility to be occupied by the Astellas Institute for Regenerative Medicine (AIRM). The new facility, which is located in Westborough, MA, is to focus on cell therapy manufacturing as much as on R&D.
Cell therapy financing grew at an impressive rate. According to the Alliance for Regenerative Medicine, cell therapy financing as of November 2020 reached $3 billion in the third quarter and $11 billion year to date, up 97% and 242%, respectively. The number of Phase I trials assessing cell therapies increased from 41 to 50 (for the first three quarters of 2019 and for the first three quarters of 2020, respectively) but dipped in Phases II and III. Overall, the number of clinical trials decreased from 218 to 202 trials as of the third quarter.
7. Synthetic biology: In the money
SynBioBeta recently shared some numbers illustrating the increasing allure of synthetic biology to investors. During the first half of 2020, total financing in the sector reached $3.041 billion (among 56 companies). During the first half of 2019, it was $1.9 billion (among 65 companies). The largest financing, $700 million, was raised by Sana Biotechnology, a developer of therapies that are based on engineering cells.
The synthetic biology money train continued into the second half. In September, Zymergen raised $300 million intended to propel its expansion into the $3 trillion chemical and materials industries; accelerate the manufacture of its biofabricated Hyaline film for electronics applications; and commercialize additional products with applications in electronics, agriculture, consumer care, and healthcare.
“The takeaway: coronavirus is not hampering the estimated $4 trillion bioeconomy being driven by synthetic biology,” SynBioBeta founder John Cumbers, PhD, commented recently in Forbes.
If anything, COVID-19 is helping to drive synthetic biology activity and will continue to do so in 2021. Ginkgo Bioworks raised $70 million in May toward developing large-scale testing infrastructure. In July, the company announced an approximately $40 million award from the NIH Rapid Acceleration of Diagnostics Advanced Technology Platforms (RADx-ATP) program to scale its automated technology for SARS-CoV-2 testing using next-generation sequencing.
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| Global Market Comments January 20, 2021 Fiat Lux Featured Trade: (I HAVE AN OPENING FOR THE MAD HEDGE FUND TRADER CONCIERGE SERVICE), (SOME SAGE ADVICE ON ASSET ALLOCATION) 
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I have an Opening for the Mad Hedge Fund Trader Concierge Service It’s happened again.Another long term follower of the Mad Hedge Fund Trader has informed me that he is hanging up his trading spurs and retiring from the game. After turning $3 million into $43 million since March solely on my trade alerts, he never has to work again. He is 50 years old. Ten baggers he earned over the past year in my calls on Tesla (TSLA), Nvidia (NVDA), Moderna (MRNA), and Zoom (ZM) were the final clincher. Thanks to the millions he has made following my trade alerts, he now has more time to spend working on his golf swing, cycling, pursuing hobbies, and coaching his kids' sports team. He confided in me that my service enabled him to retire 15 years ahead of schedule. As a result, he has created an opening Mad Hedge Fund Trader Concierge Service, a program that is aimed at our most valuable clients where I limit the service to only ten clients at any one time. The goal is to provide high net worth individuals with the extra degree of assistance they may require in managing diversified portfolios. Tax, political, and economic issues will all be covered. It is also the ideal service for the small and medium-sized hedge fund that lacks the resources to support their own in-house global strategist full time. The service includes the following: 1) A risk analysis of your own personal portfolio with the goal of focusing your investment in the highest return sectors for the long term. 2) A monthly phone call from John Thomas to update you on the current state of play in the global financial markets. 3) Personal meetings with John Thomas anywhere in the world once a year to continue our in-depth discussions. 4) You get my personal cell phone number so I can act as your investment 911. 5) Early releases of strategy letters and urgent trading information. The cost for this highly personalized, bespoke service is $10,000 a year. To best take advantage of this Mad Hedge Fund Trader Executive Service, you should possess the following: 1) Be an existing subscriber to the Mad Hedge Fund Trader Pro who is already well aware of our strengths and limitations. 2) Have a liquid net worth of over $500,000. 3) Possess a degree of knowledge and sophistication of financial markets. This is NOT for beginners. To subscribe to Mad Hedge Fund Trader Concierge Service Please email Filomena at support@madhedgefundtrader.com. Please put “Concierge Candidate” in the subject line. I look forward to hearing from you. 
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Some Sage Advice About Asset Allocation Asset allocation is the one question that I get every day, which I absolutely cannot answer.The reason is simple: no two investors are alike. The answer varies whether you are young or old, have $1,000 in the bank or $1 billion, are a sophisticated investor or an average Joe, in the top or the bottom tax bracket, and so on. This is something you should ask your financial advisor, if you haven’t fired him already, which you probably should. Having said all that, there is one old hard and fast rule, which you should probably dump. It used to be prudent to own your age in bonds. So, if you were 70, you should have had 70% of your assets in fixed income instruments and 30% in equities. Given the extreme overvaluation of all bonds today, I would completely ignore this rule and own no bonds whatsoever. This is especially true of long-term government bonds, which are yielding negative interest rates in Europe and Japan, and only 1.10% in the US. Instead, you should substitute high dividend-paying stocks for bonds. You can get 5% a year or more in yields these days, and get a great inflation hedge, to boot. You will also own what everyone else in the world is trying to buy right now, high yield US stocks. You will get this higher return at the expense of higher volatility. So just turn the TV off on the down days so you won’t get panicked out at the bottom. That is, until we hit the next recession. Then all bets are off. That may be next year, or not. I hope this helps. John Thomas The Diary of a Mad Hedge Fund Trader 
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Quote of the Day “The bubble is in the bond market, not the stock market,” said Leon Cooperman, CEO of Omega Advisors, an original investor in my 1990’s hedge fund. 
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