Adam Smith (1723-1790) was not who you think he was. I'm talking about the original Adam Smith who wrote The Wealth of Nations (1776) and spent most of his life in Edinburgh, Scotland. The more recent "Adam Smith" - nom de plume of the late George Goodman who wrote The Money Game (1967) - bears much more resemblance to the Adam Smith you think you know.

The first Adam Smith would have had little interest in stock market wisdom because he regarded himself as a moral philosopher rather than an analyst of markets. In fact, he was not even a capitalist. His works do not include the words "capitalist" or "capitalism" because neither came into use in his lifetime. The first mention of "capitalism" in print was in the 1854 novel The Newcomes by William Makepeace Thackeray, whose father had been involved with the East India Company. Karl Marx, oddly enough, helped popularize the term in his classic Das Kapital (1867). The irony is that if Marx did not quite invent the concept of capitalism, he certainly made the term popular in the process of opposing and bashing it.

No one can know what Adam Smith would have thought about free market capitalism as presently practiced, nor can we guess what he would have thought about the aftermarket in shares which we call "the stock market." The first stock exchanges came into being a couple of years after his death and shares were traded in only a small handful of companies including the still extant Bank of New York (NYSE:BK). Security trading over Smith's lifetime was concerned primarily with credit instruments, the exceptions being one-off exchanges organized by and for the British and Dutch East India Companies. So no capitalism, no market opinions from Adam Smith. Sorry to have to tell you.

The primary interest of Adam Smith was the goal which gave his book its full title - an inquiry into the nature and causes of the wealth of nations, in short, the well-being of the general populace. Counterintuitively paired with this was the self-interest which led tradesmen and the early industrialists to seek profit. He used the term "invisible hand" only three times in his writing and just once in The Wealth of Nations, to wit:

The rich consume little more than the poor, and in spite of their natural selfishness and rapacity, though they mean only their own conveniency, though the sole end which they propose from the labours of all the thousands whom they employ be the gratification of their own vain and insatiable desires, they divide with the poor the produce of all their improvements. They are led by an invisible hand to make nearly the same distribution of the necessaries of life which would have been made, had the earth been divided into equal portions among all its inhabitants, and thus without intending it, without knowing it, advance the interest of the society, and afford means to the multiplication of the species...the beggar, who suns himself by the side of the highway, possesses that security which kings are fighting for."

This is the central core of Adam Smith's thinking. It has always interested me that the ultimate goals of Adam Smith and Karl Marx did not differ greatly. The important difference is that Smith believed in freedom of the market while Marx believed that the solution was the top-down mandate of a command economy. We are familiar at this point with the general course of events in top down economies. The 20th Century resolved that question definitively in favor of Smith's view, which we now call capitalism.

Smith, however, never imagined a world with an after-market of securities measured by such things as price earnings ratios and discounted free cash flow. He would have been astonished at the use of these and other forms of analysis central to modern markets including shares of corporations with thousands of shareholders and many millions of shares. The few larger businesses in his day - a few early industrialists and the enormous East India Companies - did not lend themselves to that kind of analysis.

Does that mean that the thinking of Adam Smith is useless in trying to understand value in the modern financial markets? Not at all. Smith's model of the invisible hand contains a clue as to the way he might have valued companies and their shares. In fact, the view of Adam Smith may take us back to the primary purpose of capital markets which focus on start-ups, IPOs, unicorns, perhaps even SPACs, and all companies in their early stages. Such companies seek capital with which they aspire to bring innovations. They hope to profit by serving the unmet and often unrecognized needs of a body of potential customers.

What Smith saw was the intricate interplay between the needs and desires of customers and the self-interest of a risk-taking capitalist. That is the core transaction of the capitalist system. Without so much as a glance at discounted future cash flow, Smith implicitly understood that for a business the important thing was the population for which a business might add value. The issues for the entrepreneur involve the accuracy of their estimate of that market, the share of that market they might expect to win, the revenues they might expect to receive, and the profit margin they might expect to realize on those revenues.

In short, Adam Smith's thinking may not ordinarily be very helpful in the after-market we call "the stock market" but is central to the universe of young and innovative companies. It is directly connected with the way businesses and customers are conjoined. What a business does for its customers, he implies, provides an outline of its ultimate value. For this reason, I see the conjunction of businesses and customers as potentially useful in thinking about leading companies in the current market, especially for those companies which cannot be analyzed usefully by the standard market metrics of sales, margins, earnings, PE, and discounted cash flow.

In Adam Smith terms, a company should be worth a reasonable return for what it contributes to the greater good of the general populace. This single sentence is at the heart of what I am calling the "Adam Smith Model" of valuation. Does it actually work when trying to value innovative companies? Can one make decisions based on this model? To a large degree I think it is the only really helpful approach in valuing companies driven by new products and concepts.

To show how this sort of analysis might work, I will start with my daughter's portfolio of innovative biotech companies, which she put together in the early days of the pandemic. It is a pretty good model of the kind of thing I have always kept a careful distance from. Her surprising success with this portfolio prompted my own internal debate.

My daughter is a bright young woman who will soon turn 50. She has a doctorate in art history from Penn but retrained as a nurse in order to live in the woods in western Massachusetts and raise her children as a single mom close to nature and away from urban centers. Her life is modeled more on Thoreau's Walden than on Ben Graham's The Intelligent Investor. Despite sitting at my dinner table for seventeen years she remained almost entirely ignorant about financial markets until recently. The after-market in stocks seemed to her insufficiently serious to deserve her attention, which might well have been Adam Smith's view had he lived to see it. I confess to having had similar thoughts myself at times but have suppressed them.

In recent years, however, prompted by the realization that she may one day retire and need an income, she has begun to take an interest in markets. Around the beginning of the COVID-19 crisis (on which she had early insight and much sound advice), she put together without telling me a portfolio of biotech companies. She did this on a very small scale. Over four or five months she is up well over 200%, an amount I have never made in anything like that period. Here's an excerpt from an email she sent me on her portfolio:

Yes, that's why I like leronlimab - CytoDyn (OTCQB:CYDY). It has many uses, a high safety profile (I don't give a second glance to drugs with a low safety profile-anyone could have seen that with hydroxychloroquine, and now dexamethasone-which is a broad-target immunosuppressant, hence will never be a commonly used drug for Covid). Leronlimab has a great safety profile and works with a known mechanism vs. the cytokine storm. Anything good for Covid (or the other viruses that are still around: SARS, MERS and Ebola) must not suppress the immune system as a whole (as do all steroids such as dexamethasone). Leronlimab is targeted at the CCR5 receptor-which makes it effective for coronaviruses as well as cancers and autoimmune disease. Amazing for metastatic cancer, including prostate (though the recent studies are on a hard to treat breast cancer), and probably other untreatable but common cancers. It's going to be great for HIV. It's going to work for host vs graft disease (post-transplants, when we go back to doing them). It also appears to work for NASH (non-alchoholic fatty liver disease, which has increased dramatically in numbers, but is silent in most people until it is at a late stage.) It is the next diabetes.

Mesoblast (MESO):

The next wave of medical advances are going to come through better understanding of immunomodulation. Most if not all diseases-including cardiac disease and diabetes--will come to be understood as inflammatory diseases to be manipulated at the cellular level. We will see more and more of these diseases due to our inflammatory (sedentary, antioxidant-deprived) lifestyle and toxic environment. In any case, I'm interested in the companies who are leading the way in specialized research in immunomodulation. Mesoblast is using stem cell technologies to repair the immune system, and applying that technology to many untreatable diseases.

Avalon GloboCare (AVCO):

Same argument as Mesoblast: multiple technologies, targeted immunotherapy. I'm not so interested in any single technology, but they are partnering on several important technologies (stem cells, diagnostic technologies), with broad implications and clinical uses. They are partnering to develop a nasal vaccine for Covid, but again, I'm not as interested in that particular product, but the broader technology. Nasal vaccines are going to be a winner for many reasons-ease of use, global application, and the fact that we will run short on syringes for other vaccines).

Altimmune (ALT):

Same as above: leader in NASH (non-alcoholic fatty liver disease), nasal vaccine technology

Okay, those are my four picks. Amazing for metastatic cancer, including prostate (though the recent studies are on a hard to treat breast cancer). The others, JNJ, Becton Dickinson, and DaVita, you know."

I love the fact that my daughter comes at investing from an angle so different from mine and with a skill set that does not overlap mine at all. I also love that its method combines brains and a good heart - the assumption that a company is worth the sum of what it contributes to human well being. What I find most intriguing is that her natural way of coming at things aligns so closely with the Adam Smith view. Can growth investing possibly have such a simple foundation?

You will probably have guessed that I have never bought anything like these biotech companies nor used anything resembling this kind of analysis. I do not, and could not possibly, recommend any or all of them. They are well outside my areas of knowledge and expertise. The only counsel I was able to give my daughter included the fact that when buying companies like this you should probably buy a basket of them - something which she had already done, intuitively.

By early July she had tripled her money and was beginning to be worried about what felt to her like an overhyped sector of an overpriced market. This was where she thought my advice might be useful. I laughed and said that she should be giving me financial advice instead of vice versa, but if she was nervous she should probably sell down to her comfort level (she's in a low tax bracket so cap gains aren't a problem). Perhaps she should at least sell down to the point at which she was investing with house money. I added that it was okay to leave a few chips on the table and let her long term bet ride. She agreed and did something close to that.

Her insight had been pretty simple. The value of a company should correspond to the amount of value added via the "invisible hand" to the health, happiness, and well-being of its customers - perhaps even to the general populace. You would start by estimating the size of the market for which it provided a product or service. You would then adjust to take into account the competition for that market and finally the probability of your particular company capturing a major part of that market. Then, and only then, you might begin to make rough estimates as to potential revenues and profit margin. The key correlation is not revenue and profit margin, which are well out in the future, but the value the company is likely to add to society. The payoff in small biotechs like these, if it comes at all, is likely to come in a rush when a large pharma company sees the potential and buys them out, fulfilling the Adam Smith projection of appropriate reward for a large service.

When I started to formulate it this way, I realized that I have missed quite a lot in never owning stocks which might be best measured in this way. This includes not just small biotechs and niche technology startups but also giant current market leaders such as Amazon (AMZN), Netflix (NFLX), and Tesla (TSLA). At every point in the lives of these three companies, I have found that the methods by which I have always valued stocks - things like discounted earnings, dividends, and cash flow - made me unable to put together any reasonable argument for owning them.

Had I finally stumbled upon a valuation model that might provide a rationale for buying them? Up to this point, I have not seen a persuasive methodology for thinking about the value of these companies. Could this simple approach account for their unusually high valuations?

Adam Smith implied that the relationship between a business and the population it served was the invisible force behind what we call capitalism. It takes only a small further step to propose that the population served by a business can also be described as an "asset" owned by that business. In some cases, especially young or innovative companies, it is customers acquired that is the central asset. The idea of a business "owning" its customers is not new. I first read about it in a novel at least fifty years ago when a literary agent retires by essentially selling his customers to a rival - a practice that was apparently commonplace even then.

This customer-based approach seems to be the way the founders of these three market leaders looked at the opportunity. Customers weren't just part of the picture. They were the whole thing. Acquiring customers is what these companies set out to do. Everything else could come later. They were determined to do everything it takes to own the largest number of customers, including running their businesses with negative earnings and free cash flow for a long time. The market caught on to their goals and their prices shot up to the stratosphere.

Amazon, Netflix, and Tesla have always sold at ridiculous multiples of earnings and cash flow, if any, and are ridiculously expensive by pretty much every other traditional measure. When you look at them the way my daughter looks at biotechs, however, the picture changes. You set the standard ratios aside and instead ask: what is the value of these companies if measured by the sum of value they provide in service to their actual and potential customers? The transmission of that value to shareholders is initially as invisible as the invisible hand by which value is distributed to the populace. It is nevertheless reflected in the stock price.

Here's how one might do a broad estimate of value for the three companies:

Today, online commerce saves customers money and precious time," writes Bezos. "Tomorrow, through personalization, online commerce will accelerate the very process of discovery. Amazon.com uses the internet to create real value for its customers and, by doing so, hopes to create an enduring franchise, even in established and large markets.

We believe that a fundamental measure of our success will be the shareholder value we create over the long-term. This value will be a direct result of our ability to extend and solidify our current market leadership position. The stronger our market leadership, the more powerful our economic model.

Because of our emphasis on the long-term, we may make decisions and weigh tradeoffs differently than some companies... We will continue to make investment decisions in light of long-term market leadership considerations rather than short-term profitability considerations or short-term Wall Street reactions...We aren't so bold as to claim that the above is the 'right' investment philosophy, but it's ours, and we would be remiss if we weren't clear in the approach we have taken and will continue to take.

From the beginning, our focus has been on offering our customers compelling value," explained Bezos. "We brought [customers] much more selection than was possible in a physical store (our store would now occupy six football fields), and presented it in a useful, easy-to-search, and easy-to-browse format in a store open 365 days a year, 24 hours a day."

That's Amazon's mission statement summed up in a few paragraphs. The guiding purpose to this business model is positioning yourself to "own" more and more customers. This customer-obsession of Bezos amounts to is a manifesto for innovative companies. The second paragraph flows directly from the core principle of Adam Smith. Get first things first, Bezos is saying, meaning understanding the potential market and seizing it. Profitability and measurements commonly used by Wall Street come later.

Amazon is no longer a young company in chronological age, but the vision embedded in its mission statement is to remain a young company forever. A Day 1 company, as Bezos calls it, is always visionary and entrepreneurial in its thinking. What Bezos is saying to investors is: disregard the numbers used by Wall Street analysts. They are important measures only for Day 2 companies (slow-moving, mature companies in stasis, for which the next stage is death). Keep your eyes on the main thing - the growth of your customer base and a high level of customer satisfaction. Facebook (FB) and Alphabet (GOOG)(GOOGL) were like that in early stages but moved fairly quickly to address the question of how to monetize their users, eventually succeeding and becoming measurable by ordinary metrics. They are now ordinary growth companies with moderately high PEs, at least in context of the current market. Bezos rejected early monetization. Have faith, he said. We will monetize our customer base when we get around to it.

The greatest single risk for Amazon is its increasing size, which makes it difficult to remain nimble and full of energy. At some point, it will face the horror which confronts history's great empires - running out of worlds to conquer. Political constraints may have something to do with that, but pure size is the major burden. Summing it up, I would buy Amazon at something like 50-60% of its present price if nothing had gone wrong in the business in the meantime.

2. Elon Musk somehow manages to top Bezos. His manifesto, much of which comes out in random statements and tweets, is that Tesla will one day produce pretty much every car sold in the US, maybe even the world. At the very least it will be the driving force in a new industry. His business has a powerful technological core, but the rational for it is the prospect of capturing much of the total customer base for vehicles. It currently appears to be priced on the assumption that Musk will succeed in this ambition to a large degree.

Musk is confident that Tesla's technology will become the universal standard and squeeze most of the current auto industry into terminal decline. Its panache stems from great aesthetics and the promise of enlisting his customers in the project of slowing climate change and helping save the world. Tesla, he implies, will almost incidentally become highly profitable, an outcome to which Musk himself seems to be personally indifferent but in which his investors might have some interest. If he is right, Tesla will probably look cheap if bought today or tomorrow at 160 times its current (and first annual) positive earnings.

Like Bezos, Musk would have us remember: we don't care about all that. That's the old valuation model. What we care about is a market of 17 million vehicles sold annually in the US and a number around five times that in the world. That's the scale of customers Elon wants to own. Once that happens, he will bite the bullet and monetize.

To own Tesla at anything like the current price you have to make a few audacious assumptions. You have to believe that vehicles will continue to be bought on very large scale and that the overwhelming number of vehicles sold will become electric within a short period of time. You then have to believe that Tesla will become the company that owns most of the customers and sells most of the vehicles. It's not impossible, but there are obstacles to overcome.

If Ford, GM, Toyota, Honda and others launch a modestly successful counterattack, or the whole market shrinks, you will see the earnings and cash flow multiples of Tesla shares contract in the general direction of the valuations of those "Day 2" companies. In other words, if you are an investor, you don't want Tesla to become just another car company, nor do you want it to be the last giant in an industry that is contracting and possibly dying. If one of those things happens, Tesla, as measured by the Adam Smith premise, is likely to be a disappointing investment. This is very broad brush analysis, but that's the only way to really deal with Tesla, a company quite similar to my daughter's biotechs. The risks for Tesla seem high and hard to calculate. These are the problems routinely faced by innovative companies in their early stages, and you must also pay attention to the risk that Tesla could run out of time to overthrow the industry while the industry still exists in its present form.

3. Netflix is a company I have looked at only recently. Until a few months ago I had never used their product - not once. Entertainment is OK - I'm being entertained by writing this, and I dare to hope that you readers are both entertained and stimulated to further thought by it - but I didn't experience Netflix until a millennial step child and her husband spent some time with us and promptly realized that they couldn't live without it. They put it on a couple of our TVs so that they would have some kiddie movies to bribe their 3-year-old to eat dinner plus an hour of decompressing entertainment for themselves before sleep.

A few months ago my wife and discovered that we still had it, linked somehow to their home two thousand miles away, and it turns out that the shows are pretty good. They turned out to be especially valuable during the lockdown. We had run out of old movies, so we started over with Netflix. I started paying attention to articles on Netflix and ultimately took a look at their numbers.

Egads! They have been unprofitable from day one and their negative cash flow has done nothing but increase. Their costs for content are going up and their competition is mounting. On the other hand, Stranger Things is the kind of nitwit escapism that I found that I like after a long hot day teaching tennis (my wife not so much).

How do I put the two views of Netflix together. In this case, the risks and uncertainties make the stock uninvestable for me. For one thing, I am used to having entertainment piped into me for free (I automatically tune out all ads.) The numbers needed are just too daunting for Netflix, the rising costs for content are worrisome, and ultimate limits in a market now sliced several ways implies limits to growth. I am doubtful that Netflix will ever morph into a company I can measure more conventionally. I'm pretty sure I wouldn't renew if our faraway relatives stopped providing it for free. That's the core of it: I'm a customer of sorts, but they don't really own me. I don't own them either, and am not likely to any time soon.

The outperformance of high growth companies over the last decade and most spectacularly over recent months has naturally invited vigorous debate. The catastrophic dot.com crackup exactly two decades ago has receded sufficiently that alt explanations of market behavior are once again beginning to be proposed in earnest. This article is perhaps one of them but exists within the frame of traditional methods.

The dot.com era which reached its peak in 2000 crashed amidst assertions that eyeballs and clicks were better measures of value than earnings or cash flow. I lived through it as a bystander, listening to fellow fitness enthusiasts in the workout room at my tennis club boast about their portfolios, then noticing their absences one by one as the crisis unfolded. I didn't feel schadenfreude, far from it, only relief that I myself had not been ruined.

Valuations are once again at a point which calls ordinary prudence into question. Are the traditional models of valuation no longer worth using? This was suggested recently by BlackRock quant Jeff Shen who argued here that traditional efforts to solve the "mystery" of value are worthless. The Shen view, by the way, derives from this article by another BlackRock analyst, Gerald T Garvey, published in the prestigious Journal of Portfolio Management. The Garvey article comes down firmly on the growth side of the growth/value debate arguing that "elevated percentage value spreads predict higher risk, not higher returns."

In more down to earth terms, Shen and Garvey are saying that companies whose shares haven't been able to grow in this environment are losing ground and possibly dying, and should be avoided. If a stock goes up a lot it is probably safe because the wisdom of crowds is behind its rise. This is the kind of statement that is true until it isn't. Shen goes on to argue that contemporary investors should look for alt indicators and models such as the happiness of a company's employees. That particular idea didn't exactly blow me away, and neither Bezos nor Musk seem to be proponents of using that principle to focus or drive their businesses.

On the other hand, an effort to measure a company's success in terms of the overall value it provides to its customers does seem to me an interesting way to think about growth companies. Most companies trading in the aftermarket for stocks - by now you know that when I use this awkward but accurate phrase I am referring to the "stock market" - are not high growth companies and are probably best analyzed by traditional measures. Ultimately some form of traditional value measurement must appear within the life-cycle of a successful company.

To Jeff Bezos, the moment when traditional cash measures become important to a company is the day that it wakes up as a Day 2 company, a company that does not attempt to reinvent the world afresh every morning. While such a company may still turn out to be a decent investment, it's important for value investors to pay careful attention to their risk of having their business disrupted by new technologies and methods. This is a fairly straightforward way of thinking about the world we now live in, and I have learned to ask the hard questions about everything I own - even companies with seemingly strong moats.

Disruption is a major theme of the contemporary world, and every thoughtful person would do well to put the world together afresh every morning. Even with an open mind, it's hard to anticipate what hidden risks might cause a company's current defenses to collapse. Because of the incredible speed of change and the prevalence of unsuspected collateral effects, this questioning is important in a way that it has never been in the past. That was the important lesson number two from the dot.com event. Buying the disruptors rarely made fortunes, but not being sufficiently cautious about potential disruptees was a good way to lose a fortune.

For these businesses the Adam Smith Model needs to be turned upside down so that it becomes a story about loss of customers. One of the great anecdotal examples was Bill Gates stunning a 1990s gathering of Buffett's value investor pals by using his knowledge of the digital world to inform them that Eastman Kodak (KODK), then a market stalwart, was "toast." The customer criterion proves its importance when inverted. I was unable to estimate the outcome for Amazon - haven't made a nickel directly by buying it - but it was obvious to me instantly that it was going to be the end of the road for many other retailers, as well as many malls and REITs. The history of Sears Roebuck and Walmart were powerful precedents. The only thing not entirely clear was the time frame, which is proving to be much faster than most people expected.

The astonishing thing was how eagerly investors jumped on the Amazon bandwagon, which has many uncertainties, and how slowly the investor mind adjusted to the knock-on effects, which were far more certain. The key to grasping this quickly, is to focus on customers "owned" but sure to slip away, as in the case of Kodak.

The Adam Smith Model is simply one of the ways of making an estimate concerning what the cumulative value should be somewhere down the road at whatever time the company decides to monetize the cash value of owning its customer base. At that point, it will begin to report profits and cash flow, pay dividends, and buy back shares. Apple (AAPL) may be the best current example of this model. It started paying dividends and buying back shares about a year before its growth began to level off. As the dream of perpetual growth disappeared, investors were rewarded by the cold cash that abundantly flowed.

This is the distant event that Bezos' mission statement grudgingly projects. For Bezos, earnings, dividends, and buybacks are Day 2 concerns, and you get the feeling that he would just as soon not live to see them. Being a Day 2 company, is like living a comfortable and happy life: the great second-best award for those who have given up their aspirations to greatness. So Apple was once an innovative company priced on the basis of the Adam Smith Model and has now normalized into a Day 2 company which can be valued by the traditional tools. Who knows, maybe it has a few positive tricks up its sleeve but relentless regular growth is a thing of the past.

Amazon seems to be on the same general course as Apple, but with ordinary shareholder gratification deferred into a less well defined and more distant future. You just have to wait for it, and at an incredibly low discount rate such as the current Treasury rates you are willing to pay up for the ultimate awards now and wait a long time. This is part of the current market infatuation with rapid and persistent growth. If you project very far into the future, the value may approach infinity, or since that concept no longer exists even in physics, you could approximate it by the difficulty Amazon would have if Amazon's business became the major part of the gross product of the planet.

High valuations in the current market can be partially explained by a number of factors including historically low interest rates and the appeal of the tech leaders during a broad public lockdown. It also true, however, that the most optimistic thinking stems from a gambling mentality which is supported by the famous Petersburg Paradox which has come to bear in their valuations. There are a number of recent articles with varied approaches to this subject, and you can sample them by googling Petersburg Paradox.

The Petersburg Paradox is generally credited to Daniel Bernoulli, who published an article on it in 1738, but is sometimes credited to his cousin Nicolaus Bernoulli who talked about it in a letter written in 1713. It is a simple gambling game that doubles your winnings with each successive throw of tails. Its expected return generates an infinite series of events the probability of which decline by the exponential 1/2 to the N power exactly offsetting the exponential increase in winnings (2 to the N power).

Each successive term is exactly 1. The mathematically expected return is the sum of that infinite number of ones. I suppose that this means you max out when the number in dollars is equal to the number of bits (or Planck units) in the universe.

This series, therefore, produces quite large expectation of winnings despite the fact that the probability of large winnings at any particular future point obviously diminishes enormously and becomes very slight after a few coin tosses. It is famous for the contradiction of the expected total return and the relatively small amount that any reasonable person would be willing to wager on that return. A number of mathematicians have attempted to resolve this contradiction - economist and quant Paul Samuelson having been one of them - but their efforts at refutation have been unsatisfying.

Recent articles have related the Petersburg Paradox to investor expectations for stocks with high and persistent earnings growth. An extremely smart and interesting article was published way back in 1957 by David Durand (The Journal of Finance, Vol 12, No 3, Sep 1957, pp 348-363). Durand explored the problem of valuation for growth stocks including the then relatively new approach of using multiple discount rates at various break points in time. The growth numbers are quaint - annual growth at numbers like 5 and 6.5% - chickenfeed compared to growth rates of modern high tech companies.

Durand related the question of pricing long growth periods to the Petersburg Paradox, addressing the infinity problem and the need to truncate the infinite series at some point. This has a parallel to the problem of valuing current growth companies where it is necessary to consider not only forecasts for future earnings growth rates but also the length of waiting time before cash flows and dividends appear. There's also the question of the interest rate used for discounting, which is now virtually nil but has been very significant at times in the past.

The Adam Smith Model happens to dovetail nicely with the distant outcomes of the Petersburg Paradox coin flip game. The further away the payout is from the present the larger the rewards become when you finally throw heads. It's just that in the case of fast growing but not yet profitable companies, you more or less defer the chance of hitting heads early in order to let the reward build exponentially and have the promise of hitting a very large summative outcome in the future. That's where the thinking of investors in Amazon, Tesla, and Netflix must come from, and it's more or less rational if their estimate of the payoff and the time necessary to achieve it are reasonably accurate. It has been pretty accurate in the case of Apple.

There's just one more thing, of course. What if the estimate of Adam Smith value proves to be outright wrong? What if a tough new competitor with a better technology or improved business model appears? What if competition already in place proves to be more formidable than assumed? Even with Amazon these risks must be taken into account, but with Tesla they should be major concerns, and with Netflix they should be very major concerns.

There could also be exogenous risks such as a major rise in interest rates which would wreck the denominator and greatly reduce the value of a distant payoff. That high denominator, by the way, was what drove price earnings ratios in the 1970s down to the single digits. Returns even a few out years were so heavily discounted that no one wanted to look that far into the future. This sort of thinking served to greatly diminish the appeal of growth stocks.

Innovative companies don't always work out. I thought about that a lot around the year 2000, when I attached a 95% probability to my belief that the investing world had lost its collective mind but reserved a 5% probability I was the one who just didn't get it. The odd thing is that some of the new model dot.coms did, in fact, contribute quite a bit to the general welfare. They made all sorts of businesses more efficient, and at the same time made basic communication for everyone cheaper, faster, and better. This is presumably a good thing. In the end, however, it didn't work out well for shareholders who held on long term.

But there's another question. Did their temporarily outrageous valuations represent a magical mechanism for pulling forward a proper reward for founders and the most nimble shareholders despite the fact that the companies themselves were destined to never ultimately earn any money? In a just version of Adam Smith's invisible handsome reward was certainly owed to the founders and early owners who contributed so much to human well being but the mechanism by which they received it is somewhat murky,

So what if that deferred payoff never comes?

Schopenhauer asked a similar question in his Studies in Pessimism, except that he asked it about death, not a sudden gush of cash flow. Calm down, Schopenhauer argued. Why fear death? If you knew it wasn't the end of things, that you would wake up tomorrow morning feeling fine, you wouldn't worry about it much. What about waking up next week? What about next year? What about five or ten years out? What about a thousand years before you wake up? Ten thousand? What about... never? Would it make a difference?

Schopenhauer's courage in the face of non-being is reflected in the large number of investors who seem unworried about the possible absence of cash returns many years into the future. Once you take the Schopenhauer premise, it doesn't matter if the payoff never arrives. The stock is going up today in anticipation of it. That's all that really matters. Shareholders are happy. You can always cash out at your convenience. What is the future anyway but a dwindling infinite series?

It's really more like heaven than death. Both of my grandmothers believed strongly in its existence, although I can't imagine what they really thought it would be like. It probably didn't matter. In both cases, it sustained them over the course of long and productive lives which they lived with great confidence of a wonderful if not precisely defined eternity. Ignorance was bliss.

A business is its customers. Is it as simple as that? The value of a business is the value of the services provided to its present and prospective customers discounted for the distance in time to monetization of those customers but discounted to reflect the possibility of various things that could happen to reduce or wipe out that future payoff. Both new and rapid growth businesses generally defer that payout further into the future than most businesses, especially if the discounting factor is relatively low.

This model produces huge winners and abject losers. We marvel at the winners when we see them without considering survivor bias. We discard the losers even if they have played a major part in the evolution of the economic world and traded at high prices in optimistic moments along the way. In retrospect we wonder why they once traded at such high prices.

In very young industries such as biotechs, the outcome often leaves losers by the way side and rewards just one or two competitors. One way of thinking about this is that at the outset many such companies own a similar probability of surviving but one or two end up "owning" most of the customers and the cash flow bonanza that will eventually come with them. The probability of winning gradually shrinks for most but rises for the winners. For that reason, my daughter's approach of buying a basket of these companies is probably the best way for investors to participate.

This approach may also be very helpful in evaluating growth companies which are not new but remain at some distance from giving investors serious cash rewards. Here the method for selecting a basket of winners draws upon the kind of broad-brush estimates and calculations used in selecting a basket of small biotechs. If looking closely at Amazon, Tesla, and Netflix doesn't help much, it's important to make and constantly update estimates bearing upon the scale and strength of their "ownership" of customers as well as rough estimates of risks. This broad and approximate approach is how Adam Smith would probably have looked at valuation of companies if he was as interested in profits as we sometimes assume him to have been.

Disclosure: I am/we are long JNJ, BDX. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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How Adam Smith Might Have Valued Amazon, Netflix, Tesla, And Tiny Biotechs - Seeking Alpha

Cardiac Stem Cells Comments Off on How Adam Smith Might Have Valued Amazon, Netflix, Tesla, And Tiny Biotechs – Seeking Alpha | August 10th, 2020

August 4, 2020 - More than three years after a clinical trial was prematurely ended for failing to show progress in healing heart attack scars, the European Heart Journal publishing some surprising results showing that the heart cell treatment does benefit patients.[1]

Data from the ALLSTAR study published Tuesday by the European Heart Journal showed that although infusions of allogeneic cardiac cells (called cardiosphere-derived cells or CDCs) did not appear to shrink the infarct scar after a heart attack, other data from the study show a clear benefit.

Compared with patients who received placebo treatment, patients randomized to receive CDC infusions showed a decrease in the volume of blood in the heart before and after it beats, indicating that the heart had not dilated, as it does progressively in heart failure.

"As it develops heart failure, the heart gets bigger and bigger, like a swelling balloon," said the study's lead author, Raj Makkar, M.D., vice president of cardiovascular innovation and intervention for Cedars-Sinai and the Stephen R. Corday, M.D., chair in interventional cardiology. "One way we can measure the health of a heart is to measure the volume of blood it can hold. The bigger the volume, the more damaged the heart."

The newly analyzed data from the ALLSTAR study, which was sponsored by Capricor Therapeutics, showed that patients given a placebo had hearts that continued to swell, holding larger volumes of blood, while the patients who received CDC infusions had smaller hearts with lower volumes.

The new data results include:

The volume of blood held by the heart was essentially unchanged six months after CDC infusion, but increased by more than a teaspoonful in placebo patients.

A blood protein that measures heart failure severity was reduced in patients who had received CDCs, but not in placebo patients.

The chance that these findings were statistical flukes was only 2 percent.

"To me, these data are very reassuring that there really is therapeutic benefit," said Eduardo Marbn, M.D., Ph.D., executive director of the Smidt Heart Institute. "There is a growing body of evidence that this cell treatment does work."

Results from the earlier CADUCEUS trial, published in The Lancet in 2014, showed that injecting CDCs into the hearts of heart attack survivors significantly reduced infarct size. In 2017, however, the multicenter ALLSTAR study was prematurely halted after six months of data showed no decrease in heart attack scar size, but later analyses revealed the beneficial findings reported here.

"We think we may have chosen the wrong endpoint," said Marbn, the Mark S. Siegel Family Foundation Distinguished Professor, whose discoveries and technologies resulted in CDCs. "This happens in science because you have to design the trial a year or more before you begin, and sometimes you bet on the wrong hors... but that doesnt necessarily mean the therapy is ineffective."

The cells used in the study were CAP-1002, Capricor Therapeutics off-the-shelf, cardiosphere-derived cell (CDC) product candidate. Other clinical trials and case series, in which CDCs were used to treat advanced heart failure, Duchenne Muscular Dystrophy, and COVID-19, also demonstrated positive results. And new studies using CDCs are in the planning stages.

"California is known as the stem cell state, but few technologies being tested in California actually were developed here," said Shlomo Melmed, MB, ChB, executive vice president of Academic Affairs, dean of the Medical Faculty and professor of Medicine. "Increasing evidence-including the results of the large multicenter ALLSTAR trial-validates the potential utility of a cell product which was conceived by a faculty member at Cedars-Sinai, and first tested clinically here."

Read the complete study published by the European Heart Journal.

Disclosures: Except for the cells used in CADUCEUS, the cardiosphere-derived cells used in these studies were derived from donor hearts and provided by Capricor Therapeutics. Marbn developed the process to grow CDCs when he was on the faculty of Johns Hopkins University; the process was further developed at Cedars-Sinai. Capricor has licensed the process from Johns Hopkins and from Cedars-Sinai for clinical and commercial development. Capricor has licensed additional intellectual property from Cedars-Sinai and the University of Rome. Cedars-Sinai and Marbn have financial interests in Capricor.

Reference:

1. Raj R Makkar, Dean J Kereiakes, Frank Aguirre, et al. Intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR): a randomized, placebo-controlled, double-blinded trial. European Heart Journal, ehaa541, https://doi.org/10.1093/eurheartj/ehaa541.

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Three Years After Stem Cell Trial for Heart Failure was Abandoned New Evidence Shows it Works - Diagnostic and Interventional Cardiology

Cardiac Stem Cells Comments Off on Three Years After Stem Cell Trial for Heart Failure was Abandoned New Evidence Shows it Works – Diagnostic and Interventional Cardiology | August 10th, 2020

Aug. 9, 2020 / PRZen / SUZHOU, China -- Re-Stem Biotech (Re-Stem or the Company), a biotechnology firm engaged in the research and development of cell therapies targeting osteoarthritis, spinal cord injury and various cancers recently funded in part a study titled "Solid-phase inclusion as a mechanism for regulating unfolded proteins in the mitochondrial matrix". Researchers at The Johns Hopkins University School of Medicine, led by Rong Li, Ph.D., published their findings in the journal "Science Advances" (view full article here: https://advances.sciencemag.org/content/6/32/eabc7288) The study may provide mechanistic insights for mitochondrial dysfunction observed in aging and age-related diseases.

About Mitochondrial DysfunctionMitochondrial dysfunction is a hallmark of age-related diseases, such as cardiovascular diseases and neurodegenerative diseases. During aging, damaged/unfolded proteins in mitochondria that are failed to be degraded gradually accumulate. In addition, recent evidence suggests that non-mitochondrial proteins constituting pathological aggregates in neurodegenerative diseases also accumulate in mitochondria and cause mitochondrial dysfunction. However, it remains unclear how excessive damaged proteins are managed within mitochondria when known quality control mechanisms become inadequate, and how they contribute to mitochondrial dysfunction during the aging process.

About the StudyThe researchers discovered that excessive unfolded proteins in the mitochondrial matrix are consolidated into novel structures, which they named Deposits of Unfolded Mitochondrial Proteins (DUMP). DUMP formation is an age-dependent process, while accelerated DUMP formation causes mitochondrial dysfunction and premature aging. They found that DUMP formation was not random, but specific in mitochondria near endoplasmic reticulum (ER), another organelle in cells. The contact sites between mitochondria and ER regulate DUMP formation via transferring lipids between two organelles. Via a series of genetic and live-cell imaging studies, researchers identified key enzymes of mitochondrial lipid metabolism that control DUMP formation. Manipulation of these enzymes modulates DUMP formation, therefore, potentially they could be targets for anti-aging or treating age-related diseases.

About Re-Stem BiotechRe-Stem Biotech (Re-Stem) is a biotechnology firm engaged in the research and development of cell-based therapies and products. Backed by state of the art GMP facilities and an international team of world-leading scientists, doctors and management team, Re-Stem currently has a robust technology platform including four profitable therapies on the market and eight other therapies and products in the pipeline. Incorporated and headquartered in 2012 in Suzhou, China, Re-Stem is focused on the large and aging population of China. It also operates clinics and research and development laboratories in Shenzhen, Beijing, Kunming and Ganzhou. For more information visit Re-Stem Biotech website: https://www.restembio.com/

Forward-Looking StatementsStatements in this press release relating to plans, strategies, trends, specific activities or investments, and other statements that are not descriptions of historical facts and may be forward-looking statements are inherently subject to risks and uncertainties, and actual results could differ materially from those currently anticipated due to a number of factors, which include those regarding our ability to implement objective, plans and strategies for future operations. Forward-looking information may be identified by terms such as "will," "may," "expects," "plans," "intends," "estimates," "potential," or "continue," or similar terms or the negative of these terms. Although Re-Stem believes the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that future results, performance or achievements will be obtained. Re-Stem does not have any obligation to update these forward-looking statements other than as required by law.

Follow the full story here: https://przen.com/pr/33354426

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Re-Stem-Funded Study Targeting Mitochondrial Dysfunction in Aging and Age-Related Diseases Published in Science Advances Journal - Press Release -...

Spinal Cord Stem Cells Comments Off on Re-Stem-Funded Study Targeting Mitochondrial Dysfunction in Aging and Age-Related Diseases Published in Science Advances Journal – Press Release -… | August 10th, 2020

Brazilian researchers announced that a 36-year-old man in Brazil is HIV-free after receiving a cocktail of antiviral drugs.

If true, this unidentified case, detailed at the medical conference AIDS 2020, would be the first instance of long-term remission from HIV without a stem cell or bone marrow transplant.

But the researchers peers are sceptical, since anti-retroviral therapy, which is used to queel HIV and prevent it from developing into AIDS, has been the standard treatment for all HIV-positive people since the treatment was invented in 1995.

There will be a lot of buzz, a lot of controversy about this part everyones going to be sceptical, HIV researcher Dr. Steve Deeks told the New York Times. Am I sceptical? Of course. Am I intrigued? Absolutely.

According to the research team at the Federal University of So Paulo, the man was diagnosed with HIV in 2012 and began taking the typical antiretroviral drugs.

In 2016, he joined a clinical trial where he was given three additional drugs, including maraviroc and nicotinamide, for 11 months, in an aggressive treatment designed to flush the virus out of his body.

The man returned to the standard anti-retroviral therapy after the trial ended, and stopped taking all anti-retroviral drugs in March 2019. Every three weeks since March 2019, his blood has been tested.

The fact that he tested negative for HIV is not remarkable in itself anyone religiously taking anti-retroviral therapy for more than six months will reach an undetectable viral load.

But in this case, the researchers said they found no trace of dormant HIV-infected cells in his system.These latent cells can become active as soon as treatment stops, making people sick again.

The researchers announced that virus-detecting blood tests did not show any remaining traces of HIV in the mans blood. The man also did not show any signs of having antibodies to the virus.

Prior to this, just two people had been cured of HIV.

First was the Berlin Patient, an American man named Timothy Ray Brown, who received a bone marrow transplant in 2007 in Berlin, Germany.

Brown had leukemia, and required a bone marrow transplant to survive. His doctors sought bone marrow from someone with an HIV-resistant gene. Post-transplant, Brown suffered a series of health issues, he needed to be put in a medically induced coma, and nearly died. But not only was his cancer gone, so was his HIV. He is still alive today, with no HIV, and no need for the anti-retroviral therapy that HIV-positive people must take habitually.

In 2019, the London Patient, a man named Adam Castillejo, became the second person ever to enter long-term remission from HIV. Castillejo, who was treated in London, England, had two bone marrow transplants. His recovery process was less intense, assuaging scientists concerns that Brown had only been cured because of the massive destruction to his immune system, which also rid him of HIV.

Deeks said that independent lab results will be needed to confirm these results. The Brazilian research team has offered to send the mans blood samples to other labs.

When HIV enters the body, it inserts genetic material into the DNA of its hosts immune cells. This forces the cells to make copies of the virus. Some active HIV-infected cells are created, and some latent HIV-infected cells are created. These cells are infected with HIV but are not actively producing new HIV, according to the NIH.

But there is a difference between testing negative for HIV, as some people do after taking medication that makes their HIV undetectable, and having zero traces of HIV in your RNA or DNA. In the first instance the virus is controlled within the body, but in the second instance it is entirely removed from the body.

Many researchers have announced they have cured HIV in their patients, only for the disease to return a short while later.

A baby in Mississippi stopped taking antiretroviral medication at 18 months, researchers eagerly announced that the virus was gone, and then two years later, in 2014, researchers detected HIV in the child again. In 2013, two Boston patients received bone marrow transplants, and headlines declared that they had been cured, only for the virus to resurface again.

The So Paulo Patient has gone 66 weeks without showing signs of the virus.

Read more:

Case of HIV patient in remission raises hopes for future AIDS cure

Doctors say experimental treatment may have rid man of HIV

There is no virus there that we can measure. Second HIV patient in remission becomes new hope for a cure

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Scientists say a man with HIV is the first to reach long-term remission without a bone marrow transplant, but their peers are sceptical - Business...

Bone Marrow Stem Cells Comments Off on Scientists say a man with HIV is the first to reach long-term remission without a bone marrow transplant, but their peers are sceptical – Business… | July 10th, 2020

FT819 CAR T-cell Product Candidate Derived from Clonal Master iPSC Line with Novel CD19-specific 1XX CAR Integrated into TRAC Locus

Phase 1 Clinical Study will Evaluate FT819 for Patients with Advanced B-cell Leukemias and Lymphomas

SAN DIEGO, July 09, 2020 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, announced today that the U.S. Food and Drug Administration (FDA) has cleared the Companys Investigational New Drug (IND) application for FT819, an off-the-shelf allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD19+ malignancies. FT819 is the first-ever CAR T-cell therapy derived from a clonal master induced pluripotent stem cell (iPSC) line, and is engineered with several first-of-kind features designed to improve the safety and efficacy of CAR T-cell therapy. The Company plans to initiateclinical investigation of FT819for the treatment of patients with relapsed / refractory B-cell malignancies, including chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), and non-Hodgkin lymphoma (NHL).

The clearance of our IND application for FT819 is a ground-breaking milestone in the field of cell-based cancer immunotherapy. Our unique ability to produce CAR T cells from a clonal master engineered iPSC line creates a pathway for more patients to gain timely access to therapies with curative potential, said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. Four years ago, we first set out under our partnership with Memorial Sloan Kettering led by Dr. Michel Sadelain to improve on the revolutionary success of patient-derived CAR T-cell therapy and bring an off-the-shelf paradigm to patients, and we are very excited to advance FT819 into clinical development.

FT819 was designed to specifically address several limitations associated with the current generation of patient- and donor-derived CAR T-cell therapies. Under a collaboration with Memorial Sloan Kettering Cancer Center (MSK) led by Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering, and Head, Gene Expression and Gene Transfer Laboratory at MSK, the Company incorporated several first-of-kind features into FT819 including:

The multi-center Phase 1 clinical trial of FT819 is designed to determine the maximum tolerated dose of FT819 and assess its safety and clinical activity in up to 297 adult patients across three types of B-cell malignancies (CLL, ALL, and NHL). Each indication will enroll independently and evaluate three dose-escalating treatment regimens: Regimen A as a single dose of FT819; Regimen B as a single dose of FT819 with IL-2 cytokine support; and Regimen C as three fractionated doses of FT819. For each indication and regimen, dose-expansion cohorts of up to 15 patients may be enrolled to further evaluate the clinical activity of FT819.

At the American Association for Cancer Research (AACR) Virtual 2020 Meeting, the Company presented preclinical data demonstrating FT819 is comprised of CD8 T cells with uniform 1XX CAR expression and complete elimination of endogenous TCR expression. Additionally, data from functional assessments showed FT819 has antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines that is comparable to that of healthy donor-derived CAR T cells, and persists and maintains tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia.

Fate Therapeutics has an exclusive license for all human therapeutic use to U.S. Patent No. 10,370,452 pursuant to its license agreement with MSK1, which patent covers compositions and uses of effector T cells expressing a CAR, where such T cells are derived from a pluripotent stem cell including an iPSC. In addition to the patent rights licensed from MSK, the Company owns an extensive intellectual property portfolio that broadly covers compositions and methods for the genome editing of iPSCs using CRISPR and other nucleases, including the use of CRISPR to insert a CAR in the TRAC locus for endogenous transcriptional control.

1 Fate Therapeutics haslicensedintellectual propertyfrom MSK on which Dr. Sadelain is aninventor.As a result of the licensing arrangement, MSK has financial interests related to Fate Therapeutics.

About Fate Therapeutics iPSC Product PlatformThe Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with cycles of other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 300 issued patents and 150 pending patent applications.

About Fate Therapeutics, Inc.Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for cancer and immune disorders. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology product candidates include natural killer (NK) cell and T-cell cancer immunotherapies, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens with chimeric antigen receptors (CARs). The Companys immuno-regulatory product candidates include ProTmune, a pharmacologically modulated, donor cell graft that is currently being evaluated in a Phase 2 clinical trial for the prevention of graft-versus-host disease, and a myeloid-derived suppressor cell immunotherapy for promoting immune tolerance in patients with immune disorders. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

Forward-Looking StatementsThis release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the advancement of and plans related to the Company's product candidates and clinical studies, the Companys progress, plans and timelines for the clinical investigation of its product candidates, the therapeutic potential of the Companys product candidates including FT819, and the Companys clinical development strategy for FT819. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk of difficulties or delay in the initiation of any planned clinical studies, or in the enrollment or evaluation of subjects in any ongoing or future clinical studies, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials or to support regulatory approval, difficulties in manufacturing or supplying the Companys product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), the risk that results observed in preclinical studies of FT819 may not be replicated in ongoing or future clinical trials or studies, and the risk that FT819 may not produce therapeutic benefits or may cause other unanticipated adverse effects. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Companys periodic filings with the Securities and Exchange Commission, including but not limited to the Companys most recently filed periodic report, and from time to time in the Companys press releases and other investor communications.Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Contact:Christina TartagliaStern Investor Relations, Inc.212.362.1200christina@sternir.com

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Fate Therapeutics Announces FDA Clearance of IND Application for First-ever iPSC-derived CAR T-Cell Therapy - GlobeNewswire

Bone Marrow Stem Cells Comments Off on Fate Therapeutics Announces FDA Clearance of IND Application for First-ever iPSC-derived CAR T-Cell Therapy – GlobeNewswire | July 10th, 2020

By David Bautz, PhD

NASDAQ:BCLI

READ THE FULL BCLI RESEARCH REPORT

Business Update

KOL Event for Alzheimers Program

On July 8, 2020, BrainStorm Cell Therapeutics, Inc. (NASDAQ:BCLI) conducted a Key Opinion Leader (KOL) webinar to discuss the companys upcoming Phase 2a clinical trial of NurOwn in patients with Alzheimers Disease (AD). The event included presentations by two of the lead investigators for the upcoming trial, Dr. Philip Scheltens, Professor of Cognitive Neurology and Director of the Alzheimer Centre at VU University Medical Center in Amsterdam, Netherlands, and Dr. Bruno Dubois, Professor of Neurology at the Neurological Institute of the Salptrire University Hospital in Paris, France. The presentation can be found here.

The companys Phase 2a trial (BCT-201-EU) is expected to enroll approximately 40 patients with prodromal to mild AD. It will be taking place at medical centers in France and the Netherlands. To be eligible for the trial, patients must have been diagnosed with prodromal to mild dementia at least six months prior to enrollment. In addition, patients must score between 20-30 on the Mini-Mental State Exam (MMSE) and have a Clinical Dementia Rating (CDR) global score of 0.5-1.0. The MMSE is a series of questions that are designed to assess a patients mental skills, with the maximum score being 30 points and a score of 20-24 suggesting mild dementia. The CDR is a scale used to characterize six domains of cognitive and functional performance with a score of 0.5 suggesting very mild dementia and a score of 1.0 suggesting mild dementia.

The primary objective of the trial is to assess the safety and tolerability of three intrathecal injections of NurOwn in AD patients. Following bone marrow aspiration during a 10-week run-in period, patients will be treated three times with NurOwn, with eight weeks between treatments. Follow-up visits will occur 12 and 26 weeks following the final injection of NurOwn for a total trial length of 52 weeks. The following figure gives an overview of the trial design.

Cerebrospinal fluid (CSF) and serum will be collected prior to treatment and again at Weeks 0, 8, and 16 to assess changes in various neurotropic, neurodegenerative, and inflammatory factors (e.g., VEGF, HGF, NfL, NfH, MCP-1, IL-6), markers associated with amyloid deposition (e.g., a40, a42), and markers of tau protein levels (e.g., p-tau, t-tau). Additional clinical outcome measures will be analyzed through administration of the following tests:

Clinical Dementia Rating ScaledSum of Boxes (CDR-SB)

Free and Cued Selective Reminding Test (FCSRT)

Neuropsychological Test Battery (NTB)

Delis-Kaplan Executive Function System (D-KEFS) subtests

Mini Mental State Examination(MMSE)

AmsterdamInstrumentalActivitiesofDailyLivingQuestionnaire-ShortVersion(A-IADL-Q-SV)

Alzheimers Disease

Alzheimers disease (AD) is the most common form of dementia in older adults. The disease is named after Dr. Alois Alzheimer, who identified the first case in a 50-year-old woman named Auguste Deter in 1902. Dr. Alzheimer followed her case until her death in 1906, at which point he first publicly reported on it (Alzheimer, 1907).

After Ms. Deters death, Dr. Alzheimer examined her brain and found many abnormal clumps (now known as amyloid plaques) and tangled bundles of fibers (now known as neurofibrillary tangles). Over the next five years, 11 similar cases were reported in the medical literature, with some of them already using the term Alzheimers disease (Berchtold et al., 1998).

The most common early symptom of AD is a gradually worsening ability to remember new information. This is due to neurons associated with forming new memories dying off first. As neurons in other parts of the brain die, individuals experience different symptoms, which include:

Memory loss that disrupts daily life

Inability to plan or solve problems

Difficulty completing familiar tasks

Confusion with location and time

Difficulty with visual images and spatial relationships

Problems with words in speaking or writing

Withdrawal from social activities

Changes in mood, including apathy and depression

Each person progresses through AD at a different rate, and little is known about how or why there is such a marked variation, thus predicting how it will affect someone is quite difficult. One thing that is common to everyone diagnosed with AD is that his or her cognitive and functional abilities will gradually decline. As the disease progresses symptoms can include confusion, irritability, aggression, mood swings, and long-term memory loss. In the final advanced stage of the disease, people need help with the basic activities of living (e.g., bathing, dressing, eating, and using the restroom), they lose the ability to communicate, fail to recognize loved ones, and eventually become bed bound and reliant on round-the-clock care (Frstl et al., 1999). The inability to move makes them more prone to infections, including pneumonia, which are often a contributing factor to the death of those with AD.

Competing Theories for the Cause of Alzheimers

The root cause of Alzheimers is still unknown; however, it is likely to involve a number of different factors as opposed to being due to one single cause. These factors are likely a combination of genetic, environmental, and lifestyle. There are a number of hypotheses that exist to explain the cause of the disease, with the two dominant hypotheses focused on amyloid and tau.

Amyloid hypothesis: This hypothesis proposes that extracellular beta-amyloid deposits are the fundamental cause of the disease (Hardy et al., 1991). Beta-amyloid is a fragment of the larger protein amyloid precursor protein (APP), mutations of which are known to cause FAD. Several lines of evidence support the amyloid hypothesis: 1) the location of APP is on chromosome 21, while those with Down Syndrome (trisomy 21) almost all show signs of AD by 40 years of age (Lott et al., 2005); 2) APOE4 is a major genetic risk factor for AD, and while apolipoproteins enhance the breakdown of beta-amyloid, some isoforms are less capable of performing this task than others, leading to more beta-amyloid buildup on the brain (Polvikoski et al., 1995); 3) mice that harbor a mutant form of APP develop amyloid plaques and Alzheimers-like pathology (Games et al., 1995). Lastly, amyloid plaques are readily identifiable by microscopy in the brains of AD patients (Tiraboschi et al., 2004). While the brains of many older individuals develop some plaques, the brains of AD patients show severe pathological changes specifically within the temporal neocortex (Bouras et al., 1994).

Tau hypothesis: Tau is a protein located mainly within the axonal compartment of neurons and is an important element in microtubule stabilization and neurite outgrowth. In AD, a proportion of tau protein becomes abnormally phosphorylated, dissociates from axonal microtubules, and accumulates in paired helical filaments inside the neuron (Goedert et al., 1991). When this occurs, the microtubules disintegrate causing the collapse of the neurons transport system (Igbal et al., 2005). Just as with beta-amyloid plaques, tau tangles are readily observable in the brains of those affected by AD.

In addition to amyloid and tau, inflammation has been an underappreciated and often overlooked mediator in patients with AD (Akiyama et al., 2000). A multitude of inflammatory markers are found in AD patients brains and a number of studies have shown a link between chronic inflammation and an increased risk of developing AD (Walker et al., 2017; Tao et al., 2018). Thus, a treatment such as NurOwn that can decrease inflammatory mediators could prove beneficial in AD patients.

On Track to Repot Topline Data from Phase 3 ALS Trial in 4Q20

On July 2, 2020, BrainStorm announced that all doses have been administered in the pivotal Phase 3 trial ofrecen NurOwn in patients with amyotrophic lateral sclerosis (ALS) and that it remains on track to report topline data in the fourth quarter of 2020.

The ongoing randomized, double blind, placebo controlled, multi-dose Phase 3 clinical trial is testing the ability of NurOwn to alter disease progression as measured by the ALSFRS-R (NCT03280056). Cells were extracted once from each patient prior to treatment, with all administrations of NurOwn derived from the same extraction of cells due to a cryopreservation process the company developed for long-term storage of mesenchymal stem cells (MSC). Just as with the companys prior studies, there was a 3-month run-in period prior to the first treatment with two additional NurOwn treatments occurring two and four months following the first treatment. The company is focusing the trial on faster-progressing ALS patients since those patients demonstrated superior outcomes in the Phase 2 trial of NurOwn.

BrainStorm Joins Russell 2000 and Russell 3000; Granted SME Status by EMA

On June 23, 2020, BrainStorm announced that its shares would be included in the Russell 2000 Index and the Russell 3000 Index. The annual reconstitution of the Russell indexes is done to capture the 4,000 largest U.S. stocks by market capitalization.

On June 15, 2020, BrainStorm announced that the company has been granted Small and Medium-Sized Enterprise (SME) status by the European Medicines Agency (EMA). SME status allows the company to participate in a number of financial incentives including a 90-100% reduction in the EMA fee for scientific advice, clinical study protocol design, endpoints and statistical considerations, quality inspections of facilities, and fee waivers for selective EMA pre- and post-authorization regulatory filings, including Orphan Drug and PRIME designations.

Conclusion

Were excited about the potential for NurOwn in AD and we look forward to the initiation of the Phase 2a trial later in 2020. We have recently made a few changes to our model, including the inclusion of NurOwn in AD and lowering of the discount rate from 20% to 15% for all indications. We model for the company to file for approval of NurOwn in AD in 2026 and to be granted approval in 2027. We currently estimate peak sales of over $2 billion for NurOwn in AD in both the U.S. and E.U. Using a 25% probability of approval leads to an NPV of $113 million. Combined with the NPV for NurOwn in ALS ($700 million) and MS ($41 million) along with the companys current cash position and potential cash from warrants leads to a valuation for the company of a bit less than $900 million. Dividing by the companys current fully diluted share count of 35.7 million leads to a valuation of $25 per share.

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BCLI: KOL Event Gives Overview of the use of NurOwn in Alzheimer's Disease; Raising Valuation to $25/Share - Zacks Small Cap Research

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BOSTON, July 09, 2020 (GLOBE NEWSWIRE) -- Ziopharm Oncology, Inc. (Ziopharm or the Company) (Nasdaq:ZIOP), today announced the initiation of a phase 1 clinical trial to evaluate CD19-specific CAR-T, using its Rapid Personalized Manufacturing (RPM) technology, as an investigational treatment for patients with relapsed CD19+ leukemias and lymphomas. The trial is now open for enrollment at The University of Texas MD Anderson Cancer Center.

In this trial, the Company utilizes its non-viral Sleeping Beauty genetic engineering technology to infuse CAR-T the day after electroporation. Ziopharms RPM CD19-specific CAR-T therapy results from the stable, non-viral insertion of DNA into the genome of resting T cells to co-express the chimeric antigen receptor (CAR), membrane-bound IL-15 (mbIL15) and a safety switch.

We are pleased to expand the scope of our clinical development with MD Anderson, as we seek to evaluate our RPM technology using CD19-specific CAR-T cells, said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of Ziopharm. RPM is a promising manufacturing solution, as T cells from the bloodstream are genetically reprogramed with DNA plasmids from the Sleeping Beauty system and then simply administered the next day.

Our CAR-T therapy can be administered at low cell doses, which may control cytokine release syndrome and is appealing for the treatment of patients including those with CD19-expressing malignancies that have relapsed after allogeneic bone marrow transplantation (BMT). There are limited effective treatment options for such patients as evidenced by the low rate of remission and poor long-term survival, Dr. Cooper added.

Up to 24 patients with advanced CD19+ leukemias and lymphomas who have relapsed after allogeneic BMT will be enrolled in this investigator-initiated trial (NCT03579888). The primary endpoint of the study is to determine the safety and maximum tolerated dose of donor-derived genetically modified CD19-specific T cells manufactured using the RPM process. An additional study is planned through Ziopharms joint venture with Eden BioCell to evaluate the RPM technology using patient-derived (autologous) CD19-specific CAR-T in Greater China.

Research reveals three-year survival for adults with CD19+ acute lymphoblastic leukemia after allogeneic BMT ranges from 30% to 65%.1 For patients with other CD19+ cancers, allogeneic BMT can provide three-year survival rates between 30% to 75%.1 Few patients experience a durable remission following allogeneic BMT, regardless of the treatment modality, with some having a median survival of only 2 to 3 months.2

About Ziopharm Oncology, Inc.Ziopharm is developing non-viral and cytokine-driven cell and gene therapies that weaponize the bodys immune system to treat the millions of people globally diagnosed with a solid tumor each year. With its multiplatform approach, Ziopharm is at the forefront of immuno-oncology with a goal to treat any type of solid tumor. Ziopharms pipeline is built for commercially scalable, cost effective T-cell receptor T-cell therapies based on its non-viral Sleeping Beauty gene transfer platform, a precisely controlled IL-12 gene therapy, and rapidly manufactured Sleeping Beauty-enabled CD19-specific CAR-T program. The Company has clinical and strategic collaborations with the National Cancer Institute, The University of Texas MD Anderson Cancer Center and Regeneron Pharmaceuticals. For more information, please visit http://www.ziopharm.com.

Forward-Looking Statements DisclaimerThis press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to, statements regarding the progress, design and timing of the Company's research and development programs, the potential benefits of the Companys therapies, and the Companys expectations regarding the number of patients in its clinical trials. Although Ziopharms management team believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Ziopharm, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, changes in our operating plans that may impact our cash expenditures, the uncertainties inherent in research and development, future clinical data and analysis, including whether any of Ziopharms product candidates will advance further in the preclinical research or clinical trial process, including receiving clearance from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies to conduct clinical trials and whether and when, if at all, they will receive final approval from the U.S. FDA or equivalent foreign regulatory agencies and for which indication; the strength and enforceability of Ziopharms intellectual property rights; competition from other pharmaceutical and biotechnology companies as well as risk factors discussed or identified in the public filings with the Securities and Exchange Commission made by Ziopharm, including those risks and uncertainties listed in Ziopharms Quarterly Report on Form 10-Q filed by Ziopharm with the Securities and Exchange Commission. We are providing this information as of the date of this press release, and Ziopharm does not undertake any obligation to update or revise the information contained in this press release whether as a result of new information, future events or any other reason.

Investor Relations Contacts:Ziopharm Oncology:Chris TaylorVP, Investor Relations and Corporate CommunicationsT: 617.502.1881E: ctaylor@ziopharm.com

LifeSci Advisors:Mike MoyerManaging DirectorT: 617.308.4306E: mmoyer@lifesciadvisors.com

Media Relations Contact:LifeSci Communications:Patrick BurseyT: 646.876.4932E: pbursey@lifescicomms.com

1 D'Souza A, Fretham C. Current Uses and Outcomes of Hematopoietic Cell Transplantation (HCT): CIBMTR Summary Slides, 2018. Available at https://www.cibmtr.org

2 Keil F, Prinz E, Kalhs P, et al. Treatment of leukemic relapse after allogeneic stem cell transplantation with cytotoreductive chemotherapy and/or immunotherapy or second transplants. Leukemia 2001; 15:355-361.

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Embryonic stem cells. The ethical issues associated with stem cell research could be resolved through the use of induced pluripotent stem cells, which are derived from fully committed and differentiated cells of the adult body

The almost miraculous benefits that stem cells may one day deliver have long been speculated on. Capable of becoming different types of cells, they offer huge promise in terms of transplant and regenerative medicine. It is, however, also a medical field that urges caution one that must constantly battle exaggeration. If stem cells do in fact hold the potential to reverse the ageing process, for example, then such breakthroughs remain many years away.

Recently, though, the field has had cause for excitement. In 2006, Japanese researcher Shinya Yamanaka discovered that mature cells could be reprogrammed to become pluripotent, meaning they can give rise to any cell type of the body. In 2012, the discovery of these induced pluripotent stem cells (iPSCs) saw Yamanaka and British biologist John Gurdon awarded the Nobel Prize in Physiology or Medicine. Since then, there has been much talk regarding the potential iPSCs possess, not only for the world of medicine, but for society more generally, too.

A big stepHistorically, one of the major hurdles preventing further research into stem cells has been an ethical one. Until the discovery of iPSCs, embryonic stem cells (ESCs) represented the predominant area of research, with cells being taken from preimplantation human embryos. This process, however, involves the destruction of the embryo and, therefore, prevents the development of human life. Due to differences in opinion over when life is said to begin during embryonic development, stem cell researchers face an ethical quandary.

The promise of significant health benefits and new revenue streams has led some clinics to offer unproven stem cell treatments to individuals

With iPSCs, though, no such dilemmas exist. IPSCs are almost identical to ESCs but are derived from fully committed and differentiated cells of the adult body, such as a skin cell. Like ESCs, iPSCs are pluripotent and, as they are stem cells, can self-renew and differentiate, remaining indefinitely propagated and retaining the ability to give rise to any human cell type over time.

One important distinction to make is that both ESCs and iPSCs do not exist in nature, Vittorio Sebastiano, Assistant Professor (Research) of Obstetrics and Gynaecology (Reproductive and Stem Cell Biology) at Stanford Universitys Institute for Stem Cell Biology and Regenerative Medicine, told The New Economy. They are both beautiful laboratory artefacts. This means that at any stage of development, you cannot find ESCs or iPSCs in the developing embryo, foetus or even in the postnatal or adult body. Both ESCs and iPSCs can only be established and propagated in the test tube.

The reason neither ESCs nor iPSCs can be found in the body is that they harbour the potential to be very dangerous. As Sebastiano explained, these cells could spontaneously differentiate into tumorigenic masses because of their intrinsic ability to give rise to any cell type of the body. Over many years of research, scientists have learned how to isolate parts of the embryo (in the case of ESCs) and apply certain culture conditions that can lock cells in their proliferative and stem conditions. The same is true for iPSCs.

To create iPSCs, scientists take adult cells and exogenously provide a cocktail of embryonic factors, known as Yamanaka factors, for a period of two to three weeks. If the expression of such factors is sustained for long enough, they can reset the programme of the adult cells and establish an embryonic-like programme.

Turning back the clockThere is already a significant body of research dedicated to how stem cells can be used to treat disease. For example, mesenchymal stem cells (usually taken from adult bone marrow) have been deployed to treat bone fractures or as treatments for autoimmune diseases. It is hoped that iPSCs could hold the key for many more treatments.

Global stem cell market:25.5%Expected compound annual growth rate (2018-24)$467bnExpected market value (2024)

IPSCs are currently utilised to model diseases in vitro for drug screening and to develop therapies that one day will be implemented in people, Sebastiano explained. Given their ability to differentiate into any cell type, iPSCs can be used to differentiate into, for example, neurons or cardiac cells, and study specific diseases. In addition, once differentiated they can be used to test drugs on the relevant cell type. Some groups and companies are developing platforms for cell therapy, and I am personally involved in two projects that will soon reach the clinical stage.

Perhaps the most exciting prospects draw on iPSCs regenerative properties. Over time, cells age for a variety of reasons namely, increased oxidative stress, inflammation and exposure to pollutants or sunlight, among others. All these inputs lead to an accumulation of epigenetic mistakes those that relate to gene expression rather than an alteration of the genetic code itself in the cells, which, over time, results in the aberrant expression of genes, dysfunctionality at different levels, reduced mitochondrial activity, senescence and more besides. Although the epigenetic changes that occur with time may not be the primary cause of ageing, the epigenetic landscape ultimately affects and controls cell functionality.

What we have shown is that, if instead of being expressed for two weeks we express the reprogramming factors for a very short time, then we see that the cells rejuvenate without changing their identity, Sebastiano said. In other words, if you take a skin cell and express the reprogramming genes for two to four days, what you get is a younger skin cell.

By reprogramming a cell into an iPSC, you end up with an embryonic-like cell the reprogramming erases any epigenetic errors. If expressed long enough, it erases the epigenetic information of cell identity, leaving embryonic-like cells that are also young.

Slow and steadyAs with any scientific advancement, financial matters are key. According to Market Research Engine, the global stem cell market is expected to grow at a compound annual growth rate of 25.5 percent between 2018 and 2024, eventually reaching a market value of $467bn. The emergence of iPSCs has played a significant role in shaping these predictions, with major bioscience players, such as Australias Mesoblast and the US Celgene, working on treatments involving this particular type of stem cell.

The business potential around stem cell research is huge, Sebastiano told The New Economy. [Particularly] when it comes to developing cell banks for which we have detailed genetic information and, for example, studying how different drugs are toxic or not on certain genetic backgrounds, or when specific susceptibility mutations are present.

Unfortunately, even as the business cases for iPSC treatments increase, a certain degree of caution must be maintained. The promise of significant health benefits and new revenue streams has led some clinics to offer unproven stem cell treatments to individuals. There have been numerous reports of complications emerging, including the formation of a tumour following experimental stem cell treatment in one particular patient, as recorded in the Canadian Medical Association Journal last year. Such failures risk setting the field back years.

The challenge for researchers now will be one of balance. The potential of iPSCs is huge both in terms of medical progress and business development but can easily be undermined by misuse. Medical advancements, particularly ones as profound as those associated with iPSCs, simply cannot be rushed.

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Could induced pluripotent stem cells be the breakthrough genetics has been waiting for? - The New Economy

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New HCPCS Code Enables Facility Reimbursement to Physician Offices Performing Skin Graft Substitute Procedures, Benefiting Wound Patients

RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)-- Merakris Therapeutics, LLC., a leader in innovative approaches for cutaneous wound healing, announces that the Centers for Medicare & Medicaid Services (CMS) has assigned a Healthcare Common Procedure Coding System (HCPCS) product code Q4248 for its topical skin graft substitute, Dermacyte Matrix. The new HCPCS code, effective July 1, 2020, enables physician office reimbursement under Medicare Part B. Dermacyte Matrix is a crosslinked amniotic membrane allograft designed for cutaneous wound applications, commonly used by outpatient surgical, podiatry and dermatology clinics. Dermacyte is available in dehydrated and hydrated configurations with 5 years of shelf stability at room temperature.

This is another milestone for Merakris Therapeutics that the largest healthcare payer, CMS, has recognized Dermacyte Matrix with a unique reimbursement code. This strengthens our position with broader payer coverage for Dermacyte Matrix, says Chris Broderick, CEO of Merakris. We are dedicated to continued leadership in cell-free biologics and have aligned with academic institutions to support its product development and commercial operations while retaining full rights to our intellectual property.

Merakris has developed a novel purification system yielding two separate amniotic biomolecule fractions, one capable of promoting early-stage cutaneous wound healing, and the second fraction promoting late stage wound healing, including epithelialization and re-keratinization. Dr. W. Sam Fagg, MSc., PhD says this technology distinguishes our value proposition to physicians and payers. Merakris has successfully combined these with Dermacyte Matrix to demonstrate improved healing outcomes in cutaneous ulcers. Pursuant to recent FDA guidance, Merakris has completed a pre-IND meeting with the FDA and is preparing an IND to further develop the use of this technology in combination with Dermacyte Matrix.

About Merakris Therapeutics, LLC

Merakris Therapeutics, based in Research Triangle Park, North Carolina, is focused on researching, developing, and actively marketing regenerative healthcare products for wound care, ophthalmology, pain management, and skin rejuvenation. Our vision is to improve global patient care by pioneering commercially scalable biotherapeutic technologies primarily derived from perinatal cells and tissues. The company has filed patents to protect its amniotic fractionation technology, and a novel stem cell co-culture technology that produces an amniotic fluid-like solution targeted for scalable manufacturing for various therapies.

For more information contact Matt Murray at mmurray@merakris.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200709005591/en/

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Plasma transfers exercise benefit in mice

Exercise has a broad range of beneficial healthful effects. Horowitz et al. tested whether the beneficial effects of exercise on neurogenesis in the brain and improved cognition in aged mice could be transferred in plasma (blood without its cellular components) from one mouse to another (see the Perspective by Ansere and Freeman). Indeed, aged mice that received plasma from young or old mice that had exercised showed beneficial effects in their brains without hitting the treadmill. The authors identified glycosylphosphatidylinositol-specific phospholipase D1 as a factor in plasma that might, in part, mediate this favorable effect.

Science, this issue p. 167; see also p. 144

Reversing brain aging may be possible through systemic interventions such as exercise. We found that administration of circulating blood factors in plasma from exercised aged mice transferred the effects of exercise on adult neurogenesis and cognition to sedentary aged mice. Plasma concentrations of glycosylphosphatidylinositol (GPI)specific phospholipase D1 (Gpld1), a GPI-degrading enzyme derived from liver, were found to increase after exercise and to correlate with improved cognitive function in aged mice, and concentrations of Gpld1 in blood were increased in active, healthy elderly humans. Increasing systemic concentrations of Gpld1 in aged mice ameliorated age-related regenerative and cognitive impairments by altering signaling cascades downstream of GPI-anchored substrate cleavage. We thus identify a liver-to-brain axis by which blood factors can transfer the benefits of exercise in old age.

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Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain - Science Magazine

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Remember Owen Buell of Joliet, the toddler who was diagnosed with a neuroblastoma right before the COVID-19 pandemic began?

His abdomen had doubled in size and his eye looked bruised and was drooping, the story also said.

Since his diagnosis, Owen's had chemotherapy and abdominal surgery to remove a large tumor that had wrapped itself around major blood vessels.

And Tuesday night, Owen, who wont even turn 2 until Aug. 10, had the first of two stem cell treatments.

His health care team is hoping will help to address the hot spots in some of his bones his shoulders and one of his shins places chemo struggles to reach, according to his great-grandmother Jackie Moore of Florida.

The big thing yesterday is that he had very high blood pressure, Moore said. But sometimes thats from too much hydrationonce they put that IV in, he had tons of fluid.

But the family, which includes his parents Brian Buell and Valerie Mitchell, along with his brothers Elliott, age 8, and Bentley, age 5, still needs financial help.

Although the GoFundMe account has raised $20,000 of its $30,000 goal, donations have stalled, Moore said, but the familys needs are still so high.

Brian and Val are exhausted," Moore wrote on the Help for Baby Owen Buell Facebook page. "Val has the weight of the world on her shoulders and it shows on her face. Brian has done so much.

"Now after almost 5 months he is able to give Val a day off from the hospital. Otherwise, they have been there 24/7 with Owen. There are no volunteers right now because of the Covid virus."

No one is working right now and the familys van has taken a toll with the continual trips to Ann & Robert H. Lurie Children's Hospital of Chicago.

The medical bills for all this care has gone over a million dollars, Moore wrote on the Help for Baby Owen Buell Facebook page. Just one of Owen's shots is $6,000.

On top of the financial worries, Owens chemotherapy treatments have been very rough, Jackie said. When his platelet count would plummet, he went to the hospital for transfusions, she added.

Owen requires frequent diaper changes because the chemotherapy is so acid it can burn his skin, Moore said, so his parents have a special cream to use, too.

Doctors could not remove the part of Owens tumor that had wrapped itself around his major blood vessels, Moore said.

They literally would have scraped them off the blood vessels. It was too risky, Moore said. They could have nicked one of those blood vessels and he could have had a major bleed.

Owen required a special chemotherapy before the stem cell transplant. And then he had to be submerged in water every six hours to reduce the likelihood of welts, a reaction from this type of chemo, Moore said.

Sometimes he complains his leg is hurting, Moore said. But he never says his head hurts from the chemotherapy or that he is going to throw up because he doesnt have enough vocabulary for it yet, she added.

He simply throws up.

A nasogastric tube makes it difficult for Owen to eat.

And still he smiles, Moore said. Sometimes not the biggest of smiles.

But about 2 million stem cells were harvested from Owens body. He will stay in the hospital for a month and a parent can remain with him. Then Owen will go to a Ronald McDonald House for two weeks because he will need to stay close to the hospital, Moore said.

And then Owen will repeat the process: two rounds of potent chemo, a second stem cell transplant, a month-long stay in the hospital and two weeks at Ronald McDonald House, Moore said.

Hes at the point where he knows something is wrong, Jackie said. But you cant sit him down like you could to even an 8-year-old and say, Youve got this thing that wants to hurt your body.

People can donate to the GoFundMe page at bit.ly/2S7sPN7 or visit the Help for Baby Owen Buell and His Family Facebook page for updates and detailed instructions on other ways to help the family.

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Written by Jayashree Narayanan | Pune | Updated: July 9, 2020 6:38:55 pm Lifestyle coach Luke Coutinho on dry fasting and why it matters for your body. (Source: PR Handout)

Dry fasting for good health has raised eyebrows for its complete abstinence from food and water for an extended period, but the trend has been presented as a superior form of fasting and cleansing by Luke Coutinho in his book The Dry Fasting Miracle: From Deprive to Thrive, published by Penguin Random House India.

Coutinho, a holistic lifestyle coach-integrative medicine, who has co-authored the book with Sheikh Abdul Aziz Nuaimi aka Green Sheikh, from UAEs Ajman royal family, advocates dry fasting and intermittent fasting for healthy living. He talks to indianexpress.com on the book, why fasting is for everyone, and how it could be a way to build immunity given the pandemic concerns.

Excerpts:

Why do you think fasting is important?

Fasting in earlier times was built into ones lifestyle; people ate early because there was hardly any light after sunset and their next meal would only be after sunrise. This practice spread to all religions as a discipline due to its health and spiritual benefits. Sickness too was followed by fasting, because it allowed the body to redirect its energy towards healing and repairing. So, fasting is very natural to us, however, we have moved too far away from this concept because of the habit of constant nibbling, an abundance of food and storage options, etc. Our bodies were never designed to eat the amount of food we actually eat today. Overeating turns out to be one of the most common causes of sickness, more so when the quality of food is bad and inappropriate.

Today, science is proving how necessary fasting is for the immune system, digestive system, energy, spirituality, cardiovascular health, obesity, mental health and so much more.

Fasting draws up an image of no food, no water, and basically starving. How is dry fasting different?

Fasting is not starvation. Fasting is not deprivation. Fasting is a discipline where one willingly gives their body and digestive system a break, redirecting the energy towards rejuvenation and detoxification. Fasting is way more disciplined and planned. Skipping meals is not fasting.

Fasting must be practiced around the same time, so our body builds a memory around when it can expect food. Starvation can lead to nutritional deficiencies and acidity, whereas a well-planned fasting schedule eradicates acidity.

Isnt it dangerous for the body to go without food and, more importantly, water for more than 12 hours?

Dry fasting is a cleansing practice that involves complete abstinence from food and water (in any form) for a brief period of time, which could range from 10 hours to 16, 18, 20 hours, depending upon an individuals comfort level.

Our digestive system utilises almost 80 per cent of the energy into digestion, absorption and assimilation with 20 per cent of the energy towards healing, repair, recovery, growth, rejuvenation, detoxification and building the immune system. Too much eating, eating at the wrong timings, overeating can all drain energy, leaving little or no energy for repair and recovery. Fasting gives the digestive system a temporary shutdown, boosting the immune system, stem cell regeneration, hormonal balance, etc.

Dry fasting also sends our body into the autophagy mode (prolonged fasting) wherein its intelligence sacrifices the sickest cells and activates stem cell regeneration. All of this and more can be achieved through fasting, provided its done the right way.

Of course, if someone has a medical condition and cannot fast, they must refrain or modify it according to what their health experts recommend. For example, dry fasting may not suit someone with recurrent UTI infection, so he/she may adopt intermittent fasting. Or someone on water restriction may not be able to do intermittent fasting and can take short fasts under expert guidance only.

Interestingly, the book also mentions hard dry fasting, which means absolutely no contact with water, not just consumption of it but also bathing, washing or cleaning. Is it possible?

Yes, for a brief period of time. Also, hard dry fasting is intense, so its a personal choice whether one is comfortable with fasting by not washing hands, bathing, brushing, or handling water. Not many people are because they go to offices and travel or work and that is absolutely fine. Soft dry fasting (which includes brushing, bathing, etc) if done the right way is powerful in itself.

Fasting is viewed from a religious angle. But in the book, you mention, it is more than that. Can you elaborate?

Fasting does have religious and spiritual significance but its benefits extend beyond that. In fact, it improves the health of an individual from all dimensions physical, mental, emotional, intellectual as well as spiritual.

Fasting is also turning into another fad simply because it is used as a quick fix to achieve health goals, especially losing weight and belly fat.

Fasting is not a solution for weight gain. Use it to instill discipline with reference to eating and constant nibbling, start listening to your body.

Secondly, individuals try to complete with each other on fasting and the number of hours fasted. If someone is doing a 16-hour fast, everyone wants to do a 16 hour fast. Fasting is not a competition. Its what suits you. There is no magic number of hours one should fast.

Lastly, some people claim to be fasting but still have tea/coffee/juices, etc. Such an approach can be detrimental to ones health. Fasting is not a fad.

You mention that the human body is designed for fasting and the simplest way to begin is to have an early dinner. But, people rarely follow that and tend to even eat at odd hours. Is it healthy?

Times may have changed, but not the way the human body functions.While the wisdom of early dinner comes through our grandparents, today, science is proving how late-night meals mess up our digestion, immunity, blood sugar levels, weight, etc. The very fact that the pancreatic cells have melatonin receptors on them proves that our pancreas is meant to shut down when our body starts to secrete melatonin which is when the sun sets. A person who has had a late-night dinner would be able to answer how heavy and uncomfortable it could make one feel the next day and even during the course of the night. Even worse, if the dinner is heavy, because our body is just not designed to digest it at night.

By far, eating an early dinner which is as close to sunset is a powerful lifestyle change. It can result in better immunity, digestion, energy levels, better skin and hair, etc.

Considering each and everyones body systems are different, do you think dry fasting is everyone?

Absolutely. What do you lose by trying? Most people do not fear fasting, they resist moving out of their comfort zones. There are so many people who report literally magical benefits from fasting. If someone is in a dilemma, read about these inspiring stories.At the same time, fasting doesnt have to suit all. Also, if one form of fasting doesnt suit a person, for e.g. dry fasting, in case of a health condition like recurrent UTI, they can adopt intermittent fasting. In the end, its about what suits a person.

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Fasting is not starvation or a fad, it is a discipline: Luke Coutinho - The Indian Express

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Global Stem Cell-Derived Cells market Research presents a Comprehensive scenario Which can be segmented according to producers, product type, applications, and areas. This segmentation will provide deep-dive analysis of the Stem Cell-Derived Cells business for identifying the growth opportunities, development tendencies and factors limiting the development of the marketplace. This report features forecast market information based on previous and present Stem Cell-Derived Cells industry scenarios and growth facets. Each of the Essential regions coated in Stem Cell-Derived Cells report are North America, Europe, Asia-Pacific, South America, Middle East and Africa. The Stem Cell-Derived Cells market share and market prognosis of every region from 2020-2027 are presented within this report. A deep study of Stem Cell-Derived Cells marketplace dynamics will help the market aspirants in identifying the business opportunities that will lead to accumulation of earnings. This segment can efficiently determine the Stem Cell-Derived Cells hazard and key market driving forces.

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The Stem Cell-Derived Cells report is segmented to provide a clear and Precise view of this international Stem Cell-Derived Cells market statistics and market quotes. Stem Cell-Derived Cells report Information represented in the form of graphs, charts, and statistics will show the Stem Cell-Derived Cells growth rate, volume, goal customer analysis. This report presents the significant data to all Stem Cell-Derived Cells business aspirants which will facilitate useful business decisions.

key players in stem cell-derived cells market are focused on generating high-end quality cardiomyocytes as well as hepatocytes that enables end use facilities to easily obtain ready-made iPSC-derived cells. As the stem cell-derived cells market registers a robust growth due to rapid adoption in stem cellderived cells therapy products, there is a relative need for regulatory guidelines that need to be maintained to assist designing of scientifically comprehensive preclinical studies. The stem cell-derived cells obtained from human induced pluripotent stem cells (iPS) are initially dissociated into a single-cell suspension and later frozen in vials. The commercially available stem cell-derived cell kits contain a vial of stem cell-derived cells, a bottle of thawing base and culture base.

The increasing approval for new stem cell-derived cells by the FDA across the globe is projected to propel stem cell-derived cells market revenue growth over the forecast years. With low entry barriers, a rise in number of companies has been registered that specializes in offering high end quality human tissue for research purpose to obtain human induced pluripotent stem cells (iPS) derived cells. The increase in product commercialization activities for stem cell-derived cells by leading manufacturers such as Takara Bio Inc. With the increasing rise in development of stem cell based therapies, the number of stem cell-derived cells under development or due for FDA approval is anticipated to increase, thereby estimating to be the most prominent factor driving the growth of stem cell-derived cells market. However, high costs associated with the development of stem cell-derived cells using complete culture systems is restraining the revenue growth in stem cell-derived cells market.

The global Stem cell-derived cells market is segmented on basis of product type, material type, application type, end user and geographic region:

Segmentation by Product Type

Segmentation by End User

The stem cell-derived cells market is categorized based on product type and end user. Based on product type, the stem cell-derived cells are classified into two major types stem cell-derived cell kits and accessories. Among these stem cell-derived cell kits, stem cell-derived hepatocytes kits are the most preferred stem cell-derived cells product type. On the basis of product type, stem cell-derived cardiomyocytes kits segment is projected to expand its growth at a significant CAGR over the forecast years on the account of more demand from the end use segments. However, the stem cell-derived definitive endoderm cell kits segment is projected to remain the second most lucrative revenue share segment in stem cell-derived cells market. Biotechnology and pharmaceutical companies followed by research and academic institutions is expected to register substantial revenue growth rate during the forecast period.

North America and Europe cumulatively are projected to remain most lucrative regions and register significant market revenue share in global stem cell-derived cells market due to the increased patient pool in the regions with increasing adoption for stem cell based therapies. The launch of new stem cell-derived cells kits and accessories on FDA approval for the U.S. market allows North America to capture significant revenue share in stem cell-derived cells market. Asian countries due to strong funding in research and development are entirely focused on production of stem cell-derived cells thereby aiding South Asian and East Asian countries to grow at a robust CAGR over the forecast period.

Some of the major key manufacturers involved in global stem cell-derived cells market are Takara Bio Inc., Viacyte, Inc. and others.

The report covers exhaustive analysis on:

Regional analysis includes

Report Highlights:

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The Stem Cell-Derived Cells report cover following data points:

Part 1: This part enlists the global Stem Cell-Derived Cells marketplace Overview, covering the simple market debut, market analysis by kind, applications, and areas. Stem Cell-Derived Cells industry states and prognosis (2020-2027) is presented in this part. Additionally, Stem Cell-Derived Cells market dynamics saying the chances, market risk, and key driving forces are studied.

Part 2: This part covers Stem Cell-Derived Cells manufacturers profile based On their small business overview, product type, and application. Additionally, the sales volume, Stem Cell-Derived Cells product price, gross margin analysis, and Stem Cell-Derived Cells market share of every player is profiled in this report.

Part 3 and Part 4: This part presents the Stem Cell-Derived Cells competition Based on earnings, earnings, and market share of each producer. Part 4 covers the Stem Cell-Derived Cells market scenario based on regions. Region-wise Stem Cell-Derived Cells sales and growth (2015-2019) is studied in this report.

America and Europes Stem Cell-Derived Cells industry by countries. Under this Stem Cell-Derived Cells revenue, market share of those nations like USA, Canada, and Mexico is provided. Under Europe Stem Cell-Derived Cells report contains, the countries such as Germany, UK, France, Russia, Italy, Russia and their sales and growth is coated.

Part 7, Part 8 and Part 9: These 3 sections covers Stem Cell-Derived Cells The earnings and expansion in these regions are presented in this Stem Cell-Derived Cells industry report.

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Part 10 and Part 11: This component depicts the Stem Cell-Derived Cells marketplace Share, earnings, sales by product type and application. The Stem Cell-Derived Cells sales growth seen during 2012-2020 is covered in this report.

Related to Stem Cell-Derived Cells market (2020-2027) for every region. The sales channels including indirect and direct Stem Cell-Derived Cells advertising, traders, distributors, and future trends are presented in this report.

Part 14 and Part 15: These components present Stem Cell-Derived Cells market key Research findings and judgment, research methodology, and data sources are covered.

Therefore, Global Stem Cell-Derived Cells report is a complete blend covering all The very important market aspects.

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Stem Cell-Derived Cells Market is Projected to Reach US$XX by the end of 2019 2029 - 3rd Watch News

IPS Cell Therapy Comments Off on Stem Cell-Derived Cells Market is Projected to Reach US$XX by the end of 2019 2029 – 3rd Watch News | July 10th, 2020

The Skin Care Cosmetic market revenue was xx.xx Million USD in 2014, grew to xx.xx Million USD in 2018, and will reach xx.xx Million USD in 2024, with a CAGR of x.x% during 2019-2024. Based on the Skin Care Cosmetic industrial chain, this report mainly elaborates the definition, types, applications and major players of Skin Care Cosmetic market in details. Deep analysis about market status (2014-2019), enterprise competition pattern, advantages and disadvantages of enterprise products, industry development trends (2019-2024), regional industrial layout characteristics and macroeconomic policies, industrial policy has also be included. From raw materials to downstream buyers of this industry will be analyzed scientifically, the feature of product circulation and sales channel will be presented as well. In a word, this report will help you to establish a panorama of industrial development and characteristics of the Skin Care Cosmetic market., The Skin Care Cosmetic market can be split based on product types, major applications, and important regions.

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Major Players in Skin Care Cosmetic market are:, Avon Products Inc, Kao Corporation, Procter & Gamble, The Estee Lauder Companies Inc, Beiersdorf AG, Unilever PLC, The Body Shop International PLC, Johnson & Johnson, LOreal S.A.

Major Regions that plays a vital role in Skin Care Cosmetic market are:, North America, Europe, China, Japan, Middle East & Africa, India, South America, Others

Brief about Skin Care Cosmetic Market Report with [emailprotected] https://arcognizance.com/report/global-skin-care-cosmetic-industry-market-research-report

Most important types of Skin Care Cosmetic products covered in this report are:, Sensitive Skin Care, Dry Skin Care, Infants Skin Care, Others

Most widely used downstream fields of Skin Care Cosmetic market covered in this report are:, Stem Cells Protection Against UV, Flakiness Reduction, Rehydrate the Skin Surface, Minimize wrinkles, Increase the viscosity of Aqueous

There are 13 Chapters to thoroughly display the Skin Care Cosmetic market. This report included the analysis of market overview, market characteristics, industry chain, competition landscape, historical and future data by types, applications and regions.

Chapter 1: Skin Care Cosmetic Market Overview, Product Overview, Market Segmentation, Market Overview of Regions, Market Dynamics, Limitations, Opportunities and Industry News and Policies.

Chapter 2: Skin Care Cosmetic Industry Chain Analysis, Upstream Raw Material Suppliers, Major Players, Production Process Analysis, Cost Analysis, Market Channels and Major Downstream Buyers.

Chapter 3: Value Analysis, Production, Growth Rate and Price Analysis by Type of Skin Care Cosmetic.

Chapter 4: Downstream Characteristics, Consumption and Market Share by Application of Skin Care Cosmetic.

Chapter 5: Production Volume, Price, Gross Margin, and Revenue ($) of Skin Care Cosmetic by Regions (2014-2019).

Chapter 6: Skin Care Cosmetic Production, Consumption, Export and Import by Regions (2014-2019).

Chapter 7: Skin Care Cosmetic Market Status and SWOT Analysis by Regions.

Chapter 8: Competitive Landscape, Product Introduction, Company Profiles, Market Distribution Status by Players of Skin Care Cosmetic.

Chapter 9: Skin Care Cosmetic Market Analysis and Forecast by Type and Application (2019-2024).

Chapter 10: Market Analysis and Forecast by Regions (2019-2024).

Chapter 11: Industry Characteristics, Key Factors, New Entrants SWOT Analysis, Investment Feasibility Analysis.

Chapter 12: Market Conclusion of the Whole Report.

Chapter 13: Appendix Such as Methodology and Data Resources of This Research.

Some Point of Table of Content:

Chapter One: Skin Care Cosmetic Introduction and Market Overview

Chapter Two: Industry Chain Analysis

Chapter Three: Global Skin Care Cosmetic Market, by Type

Chapter Four: Skin Care Cosmetic Market, by Application

Chapter Five: Global Skin Care Cosmetic Production, Value ($) by Region (2014-2019)

Chapter Six: Global Skin Care Cosmetic Production, Consumption, Export, Import by Regions (2014-2019)

Chapter Seven: Global Skin Care Cosmetic Market Status and SWOT Analysis by Regions

Chapter Eight: Competitive Landscape

Chapter Nine: Global Skin Care Cosmetic Market Analysis and Forecast by Type and Application

Chapter Ten: Skin Care Cosmetic Market Analysis and Forecast by Region

Chapter Eleven: New Project Feasibility Analysis

Chapter Twelve: Research Finding and Conclusion

Chapter Thirteen: Appendix continued

List of tablesList of Tables and FiguresFigure Product Picture of Skin Care CosmeticTable Product Specification of Skin Care CosmeticFigure Market Concentration Ratio and Market Maturity Analysis of Skin Care CosmeticFigure Global Skin Care Cosmetic Value ($) and Growth Rate from 2014-2024Table Different Types of Skin Care CosmeticFigure Global Skin Care Cosmetic Value ($) Segment by Type from 2014-2019Figure Sensitive Skin Care PictureFigure Dry Skin Care PictureFigure Infants Skin Care PictureFigure Others PictureTable Different Applications of Skin Care CosmeticFigure Global Skin Care Cosmetic Value ($) Segment by Applications from 2014-2019Figure Stem Cells Protection Against UV PictureFigure Flakiness Reduction PictureFigure Rehydrate the Skin Surface PictureFigure Minimize wrinkles PictureFigure Increase the viscosity of Aqueous PictureTable Research Regions of Skin Care CosmeticFigure North America Skin Care Cosmetic Production Value ($) and Growth Rate (2014-2019)Figure Europe Skin Care Cosmetic Production Value ($) and Growth Rate (2014-2019)Table China Skin Care Cosmetic Production Value ($) and Growth Rate (2014-2019)Table Japan Skin Care Cosmetic Production Value ($) and Growth Rate (2014-2019)continued

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NOTE: Our report does take into account the impact of coronavirus pandemic and dedicates qualitative as well as quantitative sections of information within the report that emphasizes the impact of COVID-19.

As this pandemic is ongoing and leading to dynamic shifts in stocks and businesses worldwide, we take into account the current condition and forecast the market data taking into consideration the micro and macroeconomic factors that will be affected by the pandemic.

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Impact Of COVID-19 On Skin Care Cosmetic Market 2020 Industry Challenges, Business Overview And Forecast Research Study 2024 - Owned

Skin Stem Cells Comments Off on Impact Of COVID-19 On Skin Care Cosmetic Market 2020 Industry Challenges, Business Overview And Forecast Research Study 2024 – Owned | July 8th, 2020

The studies show that JAK inhibitors and other small molecules are capable of reawakening dormant hair follicles and stem cell therapies that can develop new follicles.

The first study was led by Angela Christiano, whos a professor of Dermatology at Columbia University Vagelos College of Physicians and Surgeons. The researchers discovered some previously unknown cells that ensure that mouse hair follicles dont leave a resting state. If the activities of these cells are inhibited, dormant follicles can be reawakened.

In the second research, the team of Christiano found a method for growing human hair in a dish. This method could make more men and women start exploring the idea of hair restoration surgery. It could also enhance the method that pharmaceutical companies consider when looking for new hair-growth medications.

In pattern baldness, lots of hair follicles are still in existence. However, they are dormant. The focus of researchers on getting drugs that function effectively in the same pathways as minoxidil and finasteride has affected their quest to find new drugs that can reawaken follicles and inhibit hair growth. Notably, minoxidil and finasteride are the only two medications that can be used by men suffering from male pattern baldness.

The researchers had previously found a new pathway, known as JAK-STAT, which is active in the stem cells of resting hair follicles and makes them remain in a state of dormancy. Christiano and other researchers in his team showed that JAK inhibitors used on mouse skin are good for reawakening resting follicles in mice.

Their second study was targeted at knowing more about the natural processes of making sure that the follicles remain dormant. Therefore, the researchers searched for factors that managed the activity of the JAK pathway in the hair follicle.

During the search, the Colombian researchers found a formerly unknown immune-related cell type that is capable of creating a substance called Oncostatin M. This substance makes sure that the follicle doesnt leave a dormant state. One of the authors of the study, Etienne Wang, Ph.D., notes Rare subsets of immune cells were previously difficult to identify in a whole skin, but this work was facilitated by our ability to sequence individual cells and pinpoint the ones making Oncostatin M.

There are some resemblances between these cells and macrophages, which are regarded as the immune systems scavenger cells. The researchers discovered that these cells are close to resting hair follicles.

These cells have been named trichophages. It should be noted that this name is taken from tricho, which is a Greek word for hair.

Besides, the hair cycle could be turned on when the trichophages are being targeted. By utilizing antibodies and small molecular inhibitors for inhibiting Csf1R, which is a receptor that is found on the trichophages, the flow of Oncostatin M could be blocked so that the hair cycle can start once again.

The second study involved the creation of a means of growing human hair in a dish. This method could lead to hair restoration surgery for an increased number of individuals including women. This new development could also enhance the method through which pharmaceutical companies find new hair growth medications.

It is worthwhile to note that this study brings a novel idea of growing human hair follicles in a dish without using any implantation in the skin.

Notably, researchers have been generating new rat or mouse hairs by culturing cells that were extracted from the end of existing follicles.

To find a way around human hair cells resistance, the Colombian researchers have been looking for ways to build conditions that look like the 3D environment that is the habitat of human hair cells. Although they failed at the beginning, they are making progress now as they have found a way to grow new human hair follicles in a dish in a lab.

In a nutshell, these new approaches can bring a significant change to the process of dealing with hair loss in both men and women. While studies are still going on, you can cope with your hair loss by picking the right products at Lilyhair.co.uk to improve your overall look.

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Studies uncover new approaches to combat hair loss in men and women - Business MattersBusiness Matters

Skin Stem Cells Comments Off on Studies uncover new approaches to combat hair loss in men and women – Business MattersBusiness Matters | July 8th, 2020

Stem cells have been holding great promise for regenerative medicine for ages. In the last decade, many studies have revealed this form of cell, which in Spanish is calledmother cell due to its ability to contribute to various different cell types, may be applied in regenerative medicine to diseases such as muscle and nervous system disorders, among others.

Scientists and stem cell leaders Sir John B. Gurdon and Shinya Yamanaka received the Nobel Prize in Physiology and Medicine in 2012 for this idea.

However, one of the key constraints in the application of these herbal remedies is the caliber of the stem cells that may be made in the lab, which impedes their use for curative purposes.

Currently, a team in the Cell Division and Cancer Group of the Spanish National Cancer Research Centre (CNIO), headed by researcher Marcos Malumbres, has recently developed a fresh, easy and fast technology that enhances in vitro and in vivo the possibility of stem cells to differentiate into adult cells. The study results will be released this week in The EMBO Journal.

In recent years, several protocols have been proposed to obtain reprogrammed stem cells in the laboratory from adult cells, but very few to improve the cells we already have.The method we developed is able to significantly increase the quality of stem cells obtained by any other protocol, thus favouring the efficiency of the production of specialised cell types.Mara Salazar-Roa, Study First Author and Researcher, Centro Nacional de Investigaciones Oncolgicas

Roa is likewise the co-corresponding author of this analysis.

Within this study, the researchers identified an RNA sequence, called microRNA 203, that can be found at the earliest embryonic stages before the embryo implants in the uterus and when stem cells have their highest ability to generate all the different cells.When they added this molecule to stem cells from the laboratory, they discovered that the cells ability to convert into other cell types improved appreciably.

To corroborate them, they used stem cells of both human and murine origin, and of genetically altered mice. The results were so spectacular, both in mouse cells and in human cells

Application of the microRNA for just 5 days boosts the potential of stem cells in most situations we tested and improves their ability to become other specialised cells, even months after being connected with the microRNA. Says Salazar-Roa.

According to the research, cells modified by this new protocol are more efficient in generating functional cardiac cells, opening the doorway to a better generation of different cell types essential for the cure of degenerative disorders.

Malumbres, mind of the CNIO Cell and Cancer Division Group, states:To deliver this asset to the clinic, cooperation with labs or companies that are looking to exploit that technology is now essential in each particular case.

In this circumstance, Salazar-Roa recently participated, in close collaboration with all the CNIOs Innovation group, in prestigious creation programs like IDEA2 International of the Massachusetts Institute of Technology (MIT) and also CaixaImpulse of thisLa Caixa Foundation, where they also obtained funding to start the maturation of the technology.

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New technology May Raise the quality of stem cells Found in regenerative medicine - Microbioz India

Cardiac Stem Cells Comments Off on New technology May Raise the quality of stem cells Found in regenerative medicine – Microbioz India | July 8th, 2020

New Jersey, United States,- Market Research Intellect sheds light on the market scope, potential, and performance perspective of the Global Medicinal Fungi Market by carrying out an extensive market analysis. Pivotal market aspects like market trends, the shift in customer preferences, fluctuating consumption, cost volatility, the product range available in the market, growth rate, drivers and constraints, financial standing, and challenges existing in the market are comprehensively evaluated to deduce their impact on the growth of the market in the coming years. The report also gives an industry-wide competitive analysis, highlighting the different market segments, individual market share of leading players, and the contemporary market scenario and the most vital elements to study while assessing the global Medicinal Fungi market.

The research study includes the latest updates about the COVID-19 impact on the Medicinal Fungi sector. The outbreak has broadly influenced the global economic landscape. The report contains a complete breakdown of the current situation in the ever-evolving business sector and estimates the aftereffects of the outbreak on the overall economy.

Leading Medicinal Fungi manufacturers/companies operating at both regional and global levels:

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The Medicinal Fungi market report provides successfully marked contemplated policy changes, favorable circumstances, industry news, developments, and trends. This information can help readers fortify their market position. It packs various parts of information gathered from secondary sources, including press releases, web, magazines, and journals as numbers, tables, pie-charts, and graphs. The information is verified and validated through primary interviews and questionnaires. The data on growth and trends focuses on new technologies, market capacities, raw materials, CAPEX cycle, and the dynamic structure of the Medicinal Fungi market.

This study analyzes the growth of Medicinal Fungi based on the present, past and futuristic data and will render complete information about the Medicinal Fungi industry to the market-leading industry players that will guide the direction of the Medicinal Fungi market through the forecast period. All of these players are analyzed in detail so as to get details concerning their recent announcements and partnerships, product/services, and investment strategies, among others.

Sales Forecast:

The report contains historical revenue and volume that backing information about the market capacity, and it helps to evaluate conjecture numbers for key areas in the Medicinal Fungi market. Additionally, it includes a share of each segment of the Medicinal Fungi market, giving methodical information about types and applications of the market.

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This report gives a forward-looking prospect of various factors driving or restraining market growth.

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It presents a detailed analysis of changing competition dynamics and puts you ahead of competitors.

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This report helps the readers understand key product segments and their future.

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In the end, the Medicinal Fungi market is analyzed for revenue, sales, price, and gross margin. These points are examined for companies, types, applications, and regions.

To summarize, the global Medicinal Fungi market report studies the contemporary market to forecast the growth prospects, challenges, opportunities, risks, threats, and the trends observed in the market that can either propel or curtail the growth rate of the industry. The market factors impacting the global sector also include provincial trade policies, international trade disputes, entry barriers, and other regulatory restrictions.

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Medicinal Fungi Market Growth By Manufacturers, Type And Application, Forecast To 2026 - 3rd Watch News

Cardiac Stem Cells Comments Off on Medicinal Fungi Market Growth By Manufacturers, Type And Application, Forecast To 2026 – 3rd Watch News | July 8th, 2020

Due to the pandemic, we have included a special section on the Impact of COVID 19 on the Hematopoietic Stem Cells Transplantation Market which would mention How the Covid-19 is affecting the Hematopoietic Stem Cells Transplantation Industry, Market Trends and Potential Opportunities in the COVID-19 Landscape, Covid-19 Impact on Key Regions and Proposal for Hematopoietic Stem Cells Transplantation Players to Combat Covid-19 Impact.

Hematopoietic stem cell transplantation (HSCT) includes the intravenous infusion of autologous or allogeneic stem cells composed from bone marrow, or umbilical cord blood, peripheral blood to reestablish hematopoietic purpose in patients whose bone marrow or immune system is dented or flawed.

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Report Consultant has recently added a new Report on Hematopoietic Stem Cells Transplantation Market into its largest Database. It gives the complete report on trends, growth, and opportunity, restraint. Along with this, it delivers a comprehensive description of the key players of different regions.

Leading Players Hematopoietic Stem Cells Transplantation Market:

Escape Therapeutics, Lonza Group, Regen BioPharma Inc, Cesca Therapeutics Inc., Cryo-Save AG, CBR Systems, Inc., Pluristem Therapeutics Inc., China Cord Blood Corporation, and ViaCord Inc.

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Market Segmentation: The market is segmented on the basis of type, application, and region.

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Thriving Growth of Hematopoietic Stem Cells Transplantation Market Forecast 2020 with leading players Escape Therapeutics, Lonza Group, Regen...

Bone Marrow Stem Cells Comments Off on Thriving Growth of Hematopoietic Stem Cells Transplantation Market Forecast 2020 with leading players Escape Therapeutics, Lonza Group, Regen… | July 8th, 2020

LONDON, July 6, 2020 /PRNewswire/ -- IVIRMA, a global network of fertility clinics and world-leading pioneer in fertility research, are presenting a breakthrough study at the 36th Congress of the European Society of Human Reproduction and Embryology (ESHRE) today, demonstrating the possibility of 're-awakening' the ovaries in women under 40 (38 years and below) with the lowest reproductive reserve at the ovarian level.1 The ASCOT technique (involving infusion of stem cells in the ovarian artery), which has recently been shown to be successful in low-responder patients, has now shown it can achieve pregnancy in a woman with premature ovarian failure (POF).1

The study, 'Bone marrow derived stem cells restore ovarian function and fertility in premature ovarian insufficiency women. Interim report of a randomized trial: mobilization versus ovarian injection',1 which is still ongoing, includes two study arms: one using the ASCOT technique, that is, the infusion of stem cells in the ovarian artery* and, second, a less invasive option consisting of mobilising the stem cells, and allowing them to reach the ovaries through the bloodstream directly. The preliminary results have shown that ovarian follicle development was achieved in both groups, with some patients re-starting menstruation, and a decrease in menopausal symptoms. As a result of this procedure, embryos were obtained in 2 out of the 10 participants, and even one pregnancy through the ASCOT technique was achieved.

Dr. Diaz, Medical Director, IVI London, a leading fertility specialist and co-pioneer of the world's first womb transplant, commented, "We are truly excited by these very promising results achieving ovary re-awakening and pregnancy using stem cells in a woman who previously may not have had the option to conceive using her own eggs. We continually strive to pioneer on the cutting-edge of fertility research, as we know how harrowing it can be for every person struggling to conceive. These new techniques may give us potential new options for women with premature ovarian failure, in addition to those with low ovarian reserve."

It is estimated that 1 in 100 women under 40 years of age suffer from premature ovarian failure (POF) in the UK. 2.5% of all patients with POF are adolescents.2 This premature cessation of ovarian activity is one of the most challenging scenarios in terms of reproduction and can be devastating. Now, thanks to the findings of this study, led by Dr. Sonia Herraiz, researcher at the IVI Foundation-IIS la Fe, Spain and Dr. Nuria Pellicer, gynaecologist at Hospital la Fe in Valencia, Spain, there might be hope for women suffering from this fertility issue.

Dr. Nuria Pellicer, Gynaecologist, Hospital la Fe, Valencia, Spain added, "So far, we obtained embryos in 2 of the 10 patients included and one 37-week pregnancy in the ASCOT arm, in patients with almost no chance of successful pregnancy with classic in vitro fertilisation procedures. We found that both arms promoted the development of follicles, and some patients have even recovered their menstruation, thus reducing menopausal symptoms However, these are preliminary results of an ongoing study, so we remain cautious until the study is complete. We aim to develop a technique that is as minimally invasive as possible over time and standardise it so that it can be implemented in all our clinics. We would like to make it possible to offer any woman who wishes to become a mother the possibility of doing so, even when her reproductive circumstances are unfavourable."

"This is a very encouraging line of research in which we will continue to work with a single goal: to improve assisted reproduction techniques and treatments in order to obtain the best results, however difficult the reproductive prognosis may seem," concluded Dr. Herraiz, researcher at the IVI Foundation-IIS, la Fe, Spain.

More About the Study1

In addition to this research, IVI are presenting three more studies at the ESHRE Congress:

These new techniques and other research conducted by IVI is translated and applied to the treatments available in their clinics across the world, which is in turn reflected in the achieved results. The London clinic has achieved 71.4% clinical pregnancy rates per embryos transferred in women under the age of 386 and recent data shows that with PGT-A genetic screening the evolutive pregnancy rate is 57% in women undergoing treatment at IVI London as compared to the national average of 42%.7 Furthermore, 100% of these pregnancies have been achieved through single embryo transfer, eliminating chances of multiple pregnancy and the complications that arise with it.7

More about the ASCOT technique development: 3 babies and 6 pregnancies achieved so far in low-responder patients

To date, 3 babies and 6 pregnancies have been achieved using the ASCOT technique for ovarian rejuvenation in low-responder patients with low ovarian reserve, pioneered by IVIRMA Global. The technique involves transplanting bone marrow-derived stem cells (BMDSC) into the ovarian artery, achieving a partial reversal of ageing of the ovary, the organ responsible for ovulation, and activating the dormant follicles that would otherwise remain arrested in the ovary. After its first phase in animal models to test the effectiveness of the technique with stem cells, this study went to its second phase in low-responder patients. A total of 20 patients had their stem cells mobilized, extracted from peripheral blood and implanted back into the ovary in order to reverse the ageing process and activate the dormant follicles. This technique has improved ovarian function biomarkers in 81% of low responder patients. In addition, spontaneous pregnancies occurred. In view of the success of this phase, the next stage was undertaken, which consisted of recruiting women under 38 years of age, this time with early ovarian failure (a situation with a worse reproductive prognosis that of low responders). From here the above-mentioned study arose.

IVIRMA Global and IVI London, UK

IVI was founded in 1990, as the first medical institution in Spain fully dedicated to Assisted Reproduction. Since then it has helped with the birth of more than 200,000 babies thanks to the application of the latest Assisted Reproduction technologies. In early 2017, IVI merged with RMANJ, becoming the largest Assisted Reproduction group in the world. It currently has more than 65 clinics in 9 countries and is the leading centre for Reproductive Medicine. In 2016 IVI opened its doors in London, located in the heart of the medical district.www.rmanetwork.comhttps://ivi-fertility.co.uk/

References

Logo - https://mma.prnewswire.com/media/1200377/IVI_Logo.jpg

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Breakthrough study demonstrates the 're-awakening' of the ovaries and achieves pregnancy in woman with premature ovarian failure using stem cells -...

Bone Marrow Stem Cells Comments Off on Breakthrough study demonstrates the ‘re-awakening’ of the ovaries and achieves pregnancy in woman with premature ovarian failure using stem cells -… | July 8th, 2020

One cancer survivor looks at all the ways they might have gotten cancer, and wonders if any of those risk factors will factor into recurrence.

William Ramshaw resides in the expansive Pacific Northwest. He is a six-year survivor of pancreatic cancer and has written a memoir Gut Punched! Facing Pancreatic Cancer.

So, what would someone do to get cancer?

Use tobacco. Both my parents smoked packs a day. My brother chews. One of my best friends chain-smoked. I used to tell him, Dennis, this is going to kill you. He laughed. It did. Lost to esophageal cancer. Given those ominous Surgeon Generals Warnings, all caps and bolded, along with horrendous TV infomercials, I am mystified why people still use tobacco, but they do. Nicotine addiction is an awful thing.

Being overweight. Ok, this one is closer to home. Before getting pancreatic cancer, I had been a big guy. Not blimp-sized mind you but carrying pounds I didnt need. Post-surgery, I lost a third of my body weight, about 100 pounds. I have no butt. Yes, I can now wear those skinny jeans. Also, due to being replumbed, I cant even gain weight. Still, I wouldnt recommend my weight loss program to anyone. Its barbaric.

Getting too much sun. Growing up I plowed our orchard in my cutoffs with no shirt. By the end of summer, I was toasted brown. Looking back, I hope the layer of dirt shielded me from getting too many rays. Excess UV light is known to cause skin cancer. So far so good. I dont have any skin lesions yet.

Exposure to bad stuff. It seems everything I buy anymore comes with a warning such-and-such may cause cancer. I do pay attention but find myself unable to avoid exposure to everything that might be bad for me. At this point, I think breathing causes cancer. Should I stop breathing?

Breathing asbestos. Im a goner here too. As a former Navy-guy, I worked down in the boiler room. Hot as hell right there among gigantic steam pipes all encased in asbestos. Thankfully, so far, I have nothing other than a persistent cough and no lung cancer.

Worse draw an inside straight. (Also known as a gutshot or belly buster draw, where you have a straight but are missing the card in the middle.) While I dont play poker, getting cancer is a lot like drawing an inside straight. Our genes get messed up. Maybe we got them from a long-dead ancestor. One clicks over and we find ourselves with a losing cancer hand. Im not sure what happened in my case. My tumor was not genetically profiled. I wish it had been so I would better understand my odds at this point. Will I get another shot at a losing hand?

I know this in jest as no one tries or wants to get cancer. But its interesting to think about everything that causes cancer. Sadly, there are dozens of things. Cancer aside, I am indeed fortunate (and thankful) to be here.

Read more:
Seven 'Sure' Ways to Get Cancer - Curetoday.com

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