FeaturesKieran Khan6 Hrs AgoLicensed naturopathic physician Dr Anna Maria Pouchet says people don't realise how seemingly little things impact them and make them susceptible to cancer. Photo courtesy Dr Anna Maria Pouchet

The key approach to dealing with cancer will always be with prevention," explained Dr Anna-Maria Pouchet, a licensed naturopathic physician with the Hope and Wellness Clinic, "and it starts with the things that many women and men overlook in their everyday life. They dont realise how seemingly little things impact them and make them susceptible to cancer.

Turmeric is a natural herb that can be used in the fight against cancer. Image taken from cdn-prod.medicalnewstoday.com

We need to be more aware how our cell phones, the lotions containing parabens, nail polishes, birth control tablets, laundry detergent, fabric softeners, bleach, and even the plastic bottles we drink from every day are impacting on our life as much as the antibiotics and pesticides in our foods are too.

The cancer-environment connection

Pouchet's view of the world we live in is echoed by dozens of documentaries and hundreds of research papers. Human beings are destroying the planet in a way that it is also in turn destroying us.

We are aware of the oestrogen hormone, but what people fail to recognise is that the amount of hormones produced in our bodies is so minimal but we absorb additives to our beauty products and our food, (and) in particular oral contraceptives, that contain milligrams of synthetic hormones milligrams when our bodies dont even need these amounts, she pointed out.

The result is that our kidneys and liver are overburdened by the detoxification of all (these) toxic chemicals, including excess hormones, and eventually we become nutrient-depleted by the process of eliminating and begin to store many of these in our fatty tissue which for women often means in the breasts and other areas like the hips, butt and thighs.

"Toxins also cause damage to our DNA and as a result our cells are not able to regulate and eventually mutate and become malignant, she elaborated.

Pouchet focuses on helping the body to function in the right way with proper diet, nutrition, detoxification, and supplementation, as needed.

Our hormonal balances are dependent on having proper functioning of our liver, kidney and a good gut flora so that we process and eliminate toxins. To achieve that you want to ensure you have sufficient intake of fibre and basic nutrients such as zinc, B vitamins, magnesium, etc.

"I highly recommend flaxseed or chia seeds daily along with lots of water. When it comes to water you also want to filter your water as best as you can. Flaxseed contains Omega-3 fatty acids and is especially important, in that it binds to excess oestrogen in the GI tract and gets it out the body.

Oral contraceptives contain synthetic hormones. Image taken from flushinghospital.org

According to LiveStrong.com, lignan by-products are known to bind to the oestrogen receptors found in body tissues, shifting oestrogen production to weaker forms which do not enhance cancer cell growth. The lignans found in flax may also inhibit aromatase, an enzyme which produces oestrogen.

Pouchet also advises everyone to invest in their health with good quality daily vitamin and mineral supplements to avoid nutritional deficiencies, even if they think they eat well.

And what if you are diagnosed?

Depending on the stage of the cancer and the size of the tumour as well as the course of treatment chosen, there is a lot that you can do for yourself to help you beat cancer.

Pouchet says, Research shows that there are herbs that work with the chemotherapy synergistically, which help to protect your healthy cells while they go through the process. There are also natural herbs that fight cancer and should be used for prevention of tumours, like turmeric, green tea, aloes, ginger, for example.

People living with cancer also struggle to get the daily intake of nutrients needed to fight the disease. Pouchet suggested supplementing as needed, and avoiding sugar, refined carbohydrates and, as far as possible, to turn to steamed cruciferous vegetables and probiotics to fuel and feed the gut lining, which is damaged by chemotherapy.

The emotional connection

In addition to diet and exercise, there is one key area Ikeen to learn Pouchet insights on cancer and its emotional roots. There are areas of research that link the onset of cancer to emotional disturbances or upheavals in peoples lives.

Pouchet agrees.

There is absolutely a connection. Many natural oncologists point out that cancer starts with the collapse of the nervous system or the sympathetic and parasympathetic systems in our bodies. The autonomic nervous system regulates many bodily functions, and they have links to every organ, especially our digestion.

According to licensed naturopathic physician Dr Anna Maria Pouchet, flaxseed contains Omega-3 fatty acids and binds to excess oestrogen in the GI tract and gets it out the body. Image taken from cdn-prod.medicalnewstoday.com

"From my own work I have seen patients that point out that there was a divorce or some form of recent conflict in their lives prior to their diagnosis. Negative emotions are involved in the breaking down of how the body protects itself and can create openings for the emergence of cancer, she said.

Given the emotional disturbances brought on by the covid19 pandemic, keeping positive eating habits and healthy exercise regimens should be an area of focus for everyone.

Though covid19 dominates our headlines, lifestyle diseases are still the leading causes of preventable death in TT.

Dr Anna Maria Pouchet is a licensed as a naturopathic physician by the State of Washington who practises in Trinidad. Education and medical training was at Bastyr University, which is one of four accredited naturopathic programmes in the US and internationally recognised as a pioneer in the natural sciences. Always consult a medical doctor or nutritionist before starting major diet changes.

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Cancer, naturopathy and emotional roots - TT Newsday

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While antibody-drug conjugates (ADCs), such as fam-trastuzumab deruxtecan-nxki (Enhertu), may have shown efficacy in patients with HER2-low breast cancer in initial studies, according to Sara M.Tolaney, MD, MPH, investigators still need better methods for identifying this disease subtype to guide treatment decisions.

What we're learning is that we really need to improve our ability to detect very low levels of HER2 expression, said Tolaney. Testing will need to change so that we can potentially address all patients who are able to benefit from these therapies.

In an interview with OncLive, Tolaney, associate director of the Susan F. Smith Center for Womens Cancers; director of Clinical Trials, Breast Oncology;andsenior physician at Dana-Farber Cancer Institute, as well as anassistant professor of medicine at Harvard Medical School, discussed the challenges in treating patients with heterogenous HER2 expression and what treatments could potentially improve outcomes for this subgroup.

Tolaney: Some challenges that we face surround the patients who have heterogeneous expression for HER2. For example, it's not that the entire tumor is strongly HER2-positive. We've learned from a couple trials, 1 of them being the KRISTINE trial, and another that is exploring heterogeneity in the preoperative setting, that having heterogeneous HER2 expression can impact the efficacy of ado-trastuzumab emtansine [T-DM1; Kadcyla].

The other challenge is: What about patients who, for example, lose HER2 expression after preoperative therapy? Many of us are uncertain with what to do with those patients who have residual disease, but at the time of surgery are no longer HER2-positive. We did see some data from the KATHERINE study, which showed that even those patients who had HER2-negative disease at the time of surgery, despite being HER2-positive prior to preoperative therapy, still benefited from adjuvant T-DM1, which was quite interesting. There are all of these complexities that come up when caring for patients, but again, we're quite fortunate to have so many nice treatment options in this setting.

HER2-low is defined as tumors with a little bit of HER2 expression but aren't quite HER2-positive. What that means is that if a patient, for example, has a tumor that is 1+ by immunohistochemistry [IHC], we would consider them HER2-lowpositive. If they're HER2 2+ by IHC and is not amplified via fluorescence in situ hybridization [FISH], we would also consider them HER2-lowpositive.

We've seen from various datasets that about 55% of all breast cancers are actually HER2-low, which is a significant proportion of our patients with breast cancer. We do know that the prevalence is different by hormone receptor [HR] expression. [About 60% of] HR-positive tumors are more commonly HER2-lowpositive, as opposed to triple-negative breast cancers where only about one-third of those cases will end up being HER2-lowpositive. The prevalence is different based on breast cancer subtype.

We've seen some initial attempts looking to see if trastuzumab [Herceptin] would have any benefit in patients with a little bit of HER2 expression. We have seen data from a randomized phase 3 trial where, in fact, there was no benefit from trastuzumab added to chemotherapy in the early breast cancer setting for patients with HER2-lowpositive [disease].

What we have seen now is that some of the new ADCs do have activity in these tumors. For example, trastuzumab deruxtecan was explored in patients who were HER2-lowpositive. We saw that the objective response rates [ORRs] were almost 40% in this population; this response was similar for patients who had HER2 1+ disease compared with HER2 2+ disease; these data suggest very impressive efficacy in this subgroup.

Many of us have been a little bit perplexed about why some drugs work for HER2-lowpositive disease and others don't. For example, [when using] trastuzumab deruxtecan, we're seeing an almost 40% ORR, but we did not see significant responses with T-DM1 in subsets of HER2-lowpositive patients. Why is this? We truthfully don't have the answer, but it may be that you're delivering more chemotherapy with trastuzumab deruxtecan than you are with T-DM1. Perhaps that's why you need just a bit of HER2 expression to get that binding of the ADC and get the drug into the cancer cell.

We have also seen this with other novel ADCs, such as [vic-]trastuzumab duocarmazine [SYD985], where we've also seen ORRs between 25% and 30% in HER2-lowpositive disease. Again, this is very promising and there are lots of other drugs in development that are being studied in this setting, such as new bispecific antibodies. Were going to see many more [treatments] come in this space. There is even a registration trial ongoing with trastuzumab deruxtecan compared with standard chemotherapy for HER2-lowpositive patients.

Right now, testing for these breast cancers is really quite rudimentary and is via IHC. If a patient is HER2 1+, they would be HER2low-positive and if they are HER2 2+ but not FISH-amplified, they would be HER2low-positive. We need to see if there are better tests that can be done to detect very low levels of HER2 expression, because there may be some patients who have tumors [that dont show any positivity but have] low levels of expression that just don't quite meet criteria to be HER2 1+ that may benefit from some of these novel ADCs.

Right now, I'm very excited about the ongoing registration study for trastuzumab deruxtecan compared with physicians choice for patients who have received 1 or 2 prior chemotherapies for metastatic HER2-lowpositive breast cancer. Seeing ORRs that are near 40%, at least in the early single-arm studies, makes us quite excited about the potential to get this level of activity. This would be a nice opportunity for patients to get more personalized treatment that could improve their outcomes.

We've seen a lot of very interesting data come out about approaches to take for patients who have early-stage, HER2-positive disease. Prior to 2 or 3 years ago, we were predominantly treating patients in the adjuvant setting with HER2-directed therapy, but we have since learned that it's quite critical to give the majority of our patients preoperative therapy because we can adapt postoperative treatment to improve outcomes.

Data have evolved over the last year, and we've learned that giving adjuvant ado-trastuzumab emtansine [T-DM1; Kadcyla] can improve outcomes for patients with residual disease after neoadjuvant HER2-directed therapy.

Also, we can augment outcomes for patients by adding an additional biologic therapy, such as pertuzumab [Perjeta], to our patients who are getting chemotherapy and trastuzumab [Herceptin]. We certainly have a lot of tools added to our toolbox, but we've been trying to refine that even further. That's what the focus of a lot of the more recent developments have been on. Now that we have all of these very effective biologic therapies, can we potentially de-escalate therapy for patients who may be at lower risk? Can we potentially escalate therapy for those who may be of a higher clinical risk?

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Tolaney Touches on HER2+ -Low Breast Cancer Testing, Possibilities, and Challenges - OncLive

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Theres so much going on in the markets, that its hard to know where to start and what to look for. On the red side of the ledger, its clear that the headwinds are gathering. House Democrats are still rejecting the $1.8 trillion coronavirus aid and stimulus package put forth by the White House, saying that President Trumps proposal does not go far enough. The House Dems are pushing their own $2.2 trillion stimulus. At the same time, both Eli Lilly and Johnson & Johnson have paused their coronavirus vaccine programs, after the latter company reported an adverse event in early trials. This has more than just investors worried, as most hopes for a return to normal hang on development of a working vaccine for the novel virus.And earnings season is kicking off. Over the next several weeks, well see Q3 results from every publicly traded company, and investors will watch those results eagerly. The consensus is, that earnings will be down year-over-year somewhere between 20% and 30%. With this in mind, weve used theTipRanks databaseto pull up three dividend stocks yielding 6% or more. Thats not all they offer, however. Each of these stocks has a Strong Buy rating, and considerable upside potential.Philip Morris (PM)First on the list is tobacco company Philip Morris. The sin stocks, makers of tobacco and alcohol products, have long been known for their good dividends. PM has taken a different tack in recent year, with a turn toward smokeless tobacco products, marketed as cleaner and less dangerous for users health.One sign of this is the companys partnership with Altria to launch and market iQOS, a heated smokeless tobacco product that will allow users to get nicotine without the pollutants from tobacco smoke. PM has plowed over $6 billion into the product. Given the regulatory challenges and PR surrounding vaping products, PM believes that smokeless heated tobacco will prove to be the stronger alternative, with greater potential for growth.No matter what, for the moment PMs core product remains Marlboro cigarettes. The iconic brand remains a best seller, despite the long-term trend of public opinion turning against cigarettes.As for the dividend, PM has been, and remains, a true champ. The company has raised its dividend payment every year since 2008, and has reliably paid out ever quarter. Even corona couldnt derail that; PM kept up its $1.17 quarterly payment through 2020, and its most recent dividend, paid out earlier this month, saw an increase to $1.20 per common share. This annualizes to $4.80, and gives a yield of 6%.Covering PM for Piper Sandler, analyst Michael Lavery likes the move to smokeless products, writing, We remain bullish on PM's strong long-term outlook, and we believe recent iQOS momentum throughout the COVID-19 pandemic has been impressive. iQOS has had strong user growth and improving profitability, and store re-openings could further help drive adoption by new users.Lavery rates PM shares an Overweight (i.e. Buy), and his $98 price target implies a one-year upside of 24%. (To watch Laverys track record, click here)Overall, the Strong Buy consensus rating on PM is based on 9 reviews, breaking 8 to 1 in Buy versus Hold. The shares are priced at $79.10 and their $93.56 average price target suggests an 18% upside potential. (See PM stock analysis on TipRanks)Bank of N.T. Butterfield & Son (NTB)Butterfield is a small-cap banking firm based in Bermuda and providing a full range of services to customers on the island and on the Caymans, the Bahamas, and the Channel Islands, as well as Singapore, Switzerland, and the UK. Butterfields services include personal and business loans, savings accounts and credit cards, mortgages, insurance, and wealth management.Butterfield saw revenues and earnings slide in the first half of this year, in line with the general pattern of banking services globally the worldwide COVID-19 pandemic put a damper on business, and bankers felt the hit. Earnings in the last quarter of 2019 were 87 cents per share, and by 2Q20 were down to 67 cents. While a significant drop, that was still 21% better than the expectations. At the top line, revenues are down to $121 million. NTB reports Q3 earnings later this month, and the forecast is for 63 cents EPS. Along with beating earnings forecasts, Butterfield has been paying out a strong dividend this year. By the second quarter, the dividend payment was up to 44 cents per common share, making the yield a robust 7%. When the current low interest rate regime is considered the US Fed has set rates near zero, and Treasury bonds are yielding below 1% NTBs payment looks even better.Raymond James Donald Worthington, 4-star analyst with Raymond James, writes of Butterfield, robust capital levels [provide] more than sufficient loss absorption capacity in our view for whatever credit issues may arise. Its fee income stability has proven valuable given the impacts of declining rates on NII, where the bank has actively managed expenses to help support earnings. We continue to believe its dividend is safe for now given its low-risk loan portfolio, robust capital levels, and our forecast for a sub-100% dividend payout even under our stressed outlook.These comments support the analysts Outperform (i.e. Buy) rating, and his $29 price target suggests a 15% upside for the coming year. (To watch Worthingtons track record, click here)Overall, NTB has 4 recent reviews, which include 3 Buys and a single Hold, making the analyst consensus rating a Strong Buy. This stock has a $29 average price target, matching Worthingtons. (See NTB stock analysis on TipRanks)Enviva (EVA)Last on our list is an energy company, Enviva. This company holds an interesting niche in an essential sector, producing green energy. Specifically, Enviva is a manufacturer of processed biomass fuel, a wood pellet derivative sold to power generation plants. The fuel is cleaner burning than coal an important point in todays political climate and is made from recycled waste (woodchips and sawdust) from the lumber industry. The companys production facilities are located in the American Southeast, while its main customers are in the UK and mainland Europe.The economic shutdowns imposed during the corona pandemic reduced demand for power, and Envivas revenues fell in 1H20, mainly due to that reduced demand. Earnings remained positive, however, and the EPS outlook for Q3 predicts a surge back to 45 cents in line with the strong earnings seen in the second half of 2019.Enviva has shown a consistent commitment to paying out its dividend, and in last quarter the August payment the company raised the payment from 68 cents per common share to 77 cents. This brought the annualized value of the dividend to $3.08 per share, and makes the yield 7.3%. Even better, Enviva has been paying out regular dividends for the past 5 years.Covering this stock for Raymond James is analyst Pavel Molchanov, who rates EVA as Outperform (i.e. Buy) and sets a $44 price target. Recent share appreciation has brought the stock close to that target.Backing his stance, Molchanov writes, Enviva benefits from an increasingly broad customer base, and there is high-visibility growth via dropdowns. In the context of the power sector's massive coal retirements including (as of September 2020) 34 countries and 33 subnational jurisdictions with mandatory coal phase-outs (To watch Molchanovs track record, click here.)Envivas Strong Buy consensus rating is based on 4 Buys and 1 Hold. Its share price, which has gained in recent sessions, is $42.60, and as mentioned, it has closed in on the $44.80 average price target. (See EVA stock analysis at TipRanks)To find good ideas for dividend stocks trading at attractive valuations, visit TipRanks Best Stocks to Buy, a newly launched tool that unites all of TipRanks equity insights.Disclaimer: The opinions expressed in this article are solely those of the featured analysts. The content is intended to be used for informational purposes only. It is very important to do your own analysis before making any investment.

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New Comprehensive CBD Alternative from Life Extension, Introducing Endocannabinoid Support, without THC or Hemp - Yahoo Finance

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DetailsCategory: More NewsPublished on Friday, 16 October 2020 13:41Hits: 187

SAN DIEGO, CA, USA and FREISING, Germany I October 15, 2020 I Life Science Newswire Antlia Bioscience, Inc., a privately owned biopharmaceutical company located in San Diego, California, and XL-protein GmbH, a privately owned biopharmaceutical company located in Germany, are pleased to announce a strategic slliance using XL-protein's proprietary PASylation technology for plasma half-life extension to develop a novel, long-acting, peptide therapeutic treatment for chronic heart failure. Brian Johnson, Antlia Biosciences CEO commented, "chronic heart failure is a significantly unaddressed medical condition and a major public health concern. XL-protein's PASylation technology will allow us to safely and effectively translate our peptide into a meaningful therapeutic option for patients with chronic heart failure. "PASylation is an excellent biological solution for plasma-half extension of therapeutic peptides, and we believe that PASylation offers a simpler manufacturing process and superior pharmacological properties," commented Claus Schalper, CEO of XL-protein. "We are excited to work with Antlia Bioscience to further exploit the potential of our technology and to develop new therapeutic options for the treatment of chronic heart failure." Financial terms of the agreement have not been disclosed.

About PASylation Technology

'PASylation' involves the genetic fusion or chemical conjugation of a therapeutic protein or pharmaceutically active compound with a conformationally disordered polypeptide of defined sequence comprising the small natural amino acids Pro, Ala, and/or Ser. Due to the biophysical size effect, the typically rapid clearance via renal filtration of the original drug can be retarded by a factor 10-100, depending on the length of the PAS chain. PAS sequences are highly soluble while lacking charges, they are biochemically inert, non-toxic and non-immunogenic, they offer efficient recombinant protein production in a variety of biotechnological host organisms, and they show high stability in blood plasma but are biodegradable by intracellular proteases.

About XL-protein GmbH

XL-protein is a German biotech company commercializing its ground-breaking PASylation technology, which enables the design of biopharmaceuticals with extended plasma half-life and enhanced action. Based on a strong proprietary technology position, XL-protein focuses at the preclinical as well as clinical development of PASylated proteins in diverse disease areas. XL-protein is engaged in a growing number of partnerships with international pharmaceutical and biotech companies at various levels.

For more information, please visit: http://www.xl-protein.com

About Antlia Bioscience, Inc.

Antlia Bioscience is a San Diego-based biotech developing groundbreaking peptide-based therapies to treat cardiovascular and metabolic diseases. Using PASylation and other state-of-the-art techniques, we turn promising peptides into groundbreaking therapies. We are driven to make a profound difference in the treatment of cardiovascular and metabolic diseases and believe that our efforts will result in a paradigm shift in how cardiovascular and metabolic diseases will be treated in the future.

For more information, please visit: antliabio.com

SOURCE: Antlia Bioscience

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XL-protein and Antlia Bioscience Announce Collaboration to Develop Long-acting Peptide Therapy of Chronic Heart Failure using PASylation Technology |...

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If Im telling the truth, Ive been outside my apartment maybe three times this weekand thats a generous estimate.

Since I started strictly working from home, Ive accepted the fact that the inside of my not-so-spacious New York apartment is where youll find me for the foreseeable futurewhich also means my former Florida gal days of soaking up ample vitamin D are far, far behind me.

But it turns out Im not the only one lacking in vitamin D, and its not just a WFH-specific problem either. According to Michael A. Smith, MD, director of education at Life Extension, many people in the U.S. have insufficient vitamin D levels (more on the difference between deficient and insufficient below), and they have for some time.

These insufficiencies are nothing new to 2020, Dr. Smith says. Its more the product of an issue that were starting to recognize now.

In fact, a recent study showed that up to 30 percent of aging adults are actually vitamin D deficient, and sunlight alone is not likely enough to increase their vitamin blood levels to any significant degree, says Dr. Smith.

These insufficiencies are nothing new to 2020.

Lacking vitamin D isnt the only way I recognized spending more time at home might be affecting my health. Given the heightened stress of 2020 in general, I havent been totally feeling like myself. So, I decided to chat with Dr. Smith about what I can do about it.

Stress can zap your body of all vitamins and minerals, Dr. Smith says. Stress is an activator of your system. It turns on your drive for fight or flight. And, since theres a vitamin D receptor in every type of cell in the human body, he explains, its connected to many of those systems.

According to Dr. Smith, the easiest first step to get my well-being on track is supplementing, so after chatting with him, I picked up Life Extension Vitamin D3 to try for myself. Supplementation can bring you into optimal range quicker, and sustain you there over time, Dr. Smith adds. Sign. Me. Up.

Although somestudies suggest as much as 42 percent of the U.S. population is deficient in vitamin D, Dr. Smith says examining vitamin Dinsufficiencyis more useful for correcting the problem.

There are two words: deficiency and insufficiency, which are the two official medical words for low levels,' Dr. Smith says. Most people dont meet the medical definition of deficiency, instead, there is a widespread insufficiencyso were really just talking about people who are suboptimal. And suboptimal isnt your goal here.

My biggest question was: How can you tell when youre actually insufficient? According to Dr. Smith, the signs are different for different people, but they tend to show up during cold and flu season and can include cold symptoms, fatigue, and mood changes, among other things. People tend to be lower in mood in fall and winter months, but it might be even a little worse for someone who is insufficient, Dr. Smith says.

I didnt feel like I could pin-point my exact vitamin D insufficiency signals (my mood goes up and down all the time), but that doesnt mean there might not be consequences later on, according Dr. Smith. Its important to understand that vitamin D is such a key nutrient for so many body processes, he says. You need sufficient levels of it to support heart, immune, and bone health. Heres to taking measures now that my 50-year-old self will thank me for.

Now that I know the importance of vitamin D for both my immediate and long-term health, I recognized I needed to make a few changes. Off the bat, Dr. Smith suggested trying to reduce the stress in my life. Stress is a zapper of energy and micronutrients, he says. For people who deal with it, its not uncommon to truly be [vitamin D] insufficient because their body is just on all the time.

Some of the best ways to reduce stress, according to Dr. Smith, are going outside and exercisingtwo things that on their own also help to increase your vitamin D levels (and two things I could definitely do more of).

Another way to target stress is to use supplements to promote better relaxation. In addition to vitamin D (which can also help maintain healthy blood pressure), Dr. Smith suggested I take a multivitamin (for overall health), melatonin (to ensure Im getting high-quality zzzs), and Life Extension Enhanced Stress Relief, which helps to raise more relaxation hormones and battles that always-on feeling, Dr. Smith says.

Coming out of my chat with Dr. Smith, I have two main goals: Sticking to an easy-but-effective supplement routine (already on it), and spending at least 30 minutes a day outside. A walk around my city block might not be the same as a sunny stroll down the beach, but Im about to be well on my way to Florida-levels of vitamin D.

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These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.

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Im Definitely Getting Less Vitamin D Since Ive Been Cooped Up IndoorsBut What Does That Actually Mean? - Well+Good

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On-orbit service and logistics startup Astroscale has raised a $51 million Series E funding round, bringing its total raised to date to $191 million thus far. The Japan-based company has been focused on delivering new solutions for orbital end-of-life meaning ways to make orbital operations more sustainable by offering easy ways to safely de-orbit spacecraft after the end of their useful service life, clearing up some of the growing orbital debris problem thats emerging as more companies create satellites and constellations.

Astroscale has since expanded its mission to also include extending the life of geostationary satellites another key ingredient in making the orbital operating environment more sustainable as we look toward a projected exponential explosion in orbital activity. The startup announced earlier this year that it was acquiring the staff and IP of a company called Effective Space Solutions, which was in the process of developing a space drone that could launch to provide on-orbit servicing to large, existing geostationary satellite infrastructure, handling tasks like refueling and repairs.

ESS has formed the basis for Astroscale Israel, a new international office for the globe-spanning Astroscale that will be focused on geostationary life extension. Todays funding was led by aSTART, and will be used to help the company continue to establish its global offices and increase the team to more than 140 people.

Astroscales end-of-life orbital debris-removal technology is set to get its first demonstration mission sometime in the second half of this year, with a launch aboard a Russian Soyuz rocket. The system uses two spacecraft that find and latch on to target debris to be de-orbited.

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Astroscale raises $51 million in Series E funding to fuel its orbital sustainability ambitions - TechCrunch

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Even a casual observer of the contemporary global strategic environment will concur that nuclear weapons are very much back in the picture as several countries including the United States and China seek to modernize their arsenals and develop new capabilities. With many nuclear powers pushing their envelope and, in some cases, luck, and the future of arms control under stress, the current nuclear environment is defined by several challenges around proliferation and escalation risks.

To understand them better, The Diplomat spoke to Vipin Narang, associate professor of political science at the Massachusetts Institute of Technology (MIT) and member of MITs Security Studies Program. Narang, also a nonresident scholar in the Nuclear Policy Program at the Carnegie Endowment for International Peace, is author of Nuclear Strategy in the Modern Era (Princeton University Press, 2014).

In your opinion, what are the top three nuclear challenges the world faces today?

First, vertical proliferation, and specifically renewed great power nuclear competition and arms racing, threatens to upset decades of trends that enhanced strategic and crisis stability. Russian and Chinese modernization programs largely driven by Americas large conventional and nuclear counterforce capability and the unfulfilled fantasy of American national missile defenses aim to survive an American strike and penetrate defenses. That has led to a variety of programs, including hypersonic glide vehicles, nuclear-powered cruise missiles, and the oldie but goodie building up mobile capabilities. The US threatens to respond in kind with the withdrawal from the INF Treaty and the prospect that New START is not renewed with Russia. All of these developments threaten to disturb strategic stability.

Second, horizontal proliferation. However, we face not just the looming risk of adversarial proliferation states such as Iran but also of allied proliferation, in states such as South Korea, Germany and even Japan, due to concerns surfaced during the Trump administration that the United States may not indefinitely provide credible extended deterrence. In addition, a third class of states, frenemies like Saudi Arabia, who have promised to acquire nuclear weapons if their primary adversary (Iran in this case) does are also flirting with the idea and capabilities for at least a nuclear hedge. We may be on the cusp, in the next decade or two, of a cascade of new nuclear weapons powers.

Third, 75 years after the last wartime use of nuclear weapons, todays nuclear weapon states seem less chastened by the prospect of nuclear use and escalation and are increasingly pushing the line against other nuclear weapons powers, attempting to break free of the constraining effects of being deterred. The last year has seen some disturbing firsts: India bombing the undisputed territory of another nuclear weapons power at Balakot for the first time in history, and Turkey an American ally which hosts US nuclear weapons at Incirlik firing at American troops. The problem with the threat that leaves something to chance, is that it leaves something to chance. And as nuclear states push the line against other nuclear states, even if they do not want a war war may find them. That is, nuclear powers are increasingly running the risk that they may stumble into a war, and that would put us in uncharted territory.

You have warned against Trumps North Korea strategy (if one can call it that) and have been consistently pessimistic about the prospect of denuclearization there. As a new administration takes over in January, what advice would you give the new president about Kim Jong Un and his nukes?

I have long argued that Kim Jong Un will not voluntarily surrender his nuclear weapons program and taking it away by force as some like John Bolton [the former US national security advisor] continued to advocate even after North Korea tested an ICBM and purported thermonuclear weapon is exceptionally dicey. But that does not mean that we cannot try to slow down the growth of the program, seek caps on certain capabilities, and keep the rhetorical fiction of denuclearization of the Korean Peninsula as an end goal that we accept is unlikely to ever be achieved.

In fact, it appears that this deal Yongbyon in exchange for some sanctions relief was on the table at Hanoi. If verified and completed, that would have shut off North Koreas only known source of plutonium and tritium production, and a nontrivial proportion of its uranium enrichment. This could have slowed the growth of the nuclear program and shaped the future composition of the force by starving it of further plutonium and potentially tritium (for thermonuclear weapons). But Trump walked away, claiming it was too small a deal. Instead, we got no deal and Kim Jong Un continues to expand and improve his nuclear and missile force.

I suspect we will look back at Hanoi with regret, though it is possible a similar deal may resurface. If it does, I believe we should take it. Slow, cap, rollback, and eliminate (even if we never get there) for corresponding measures, in tandem, is a sensible formula to manage a nuclear North Korea.

We recently saw North Korea flash a new missile capability during its annual parade. Any thoughts on what the missile may portend in terms of where Kim sees his nuclear capabilities going in the future?

For a year, Kim Jong Un had been promising a new strategic system, and on October 10 we discovered that it was a new heavy transportable liquid fuel ICBM, based on its Hwasong-15 ICBM. This new missile is one of the worlds largest mobile liquid fuel missiles and the key feature is the large payload it can seemingly deliver, such as potentially penetration aids or multiple warheads, to defeat American national missile defenses which may not work well today, but which adversaries such as Russia, China and North Korea fear may work tomorrow.

This new missile was not a surprise, and largely represents a continuing evolution of North Koreas growing missile and nuclear capabilities. It is designed to solve one of two North Korean strategic problems: penetrating American missile defenses. There were questions about whether North Korea could develop warheads compact enough for MIRVs (multiple warheads on a single missile), but the size of this missile obviates some of that problem your cars can be bigger if you build a gigantic garage. However, the missile is so big and slow, and takes so long to potentially fuel, that it may exacerbate the other problem survivability but I think we should fully expect that North Korea is also working on capabilities to address that concern, such as a mobile solid fuel ICBM that is easier to hide and prompter to launch. In fact, we may have seen tantalizing hints of that capability as well in the parade, and that would represent a bigger leap for the program. In any event, these developments and improvements which are still away from being operational are precisely what normal nuclear powers do, and further suggests that Kim Jong Un has no intention of surrendering his nuclear weapons program.

We have heard a lot from the Trump administration of late about Chinas nuclear ambitions. How do you assess the trajectory of Chinas nuclear weapons and delivery platforms, as well as its doctrine?

Lets start with the facts: China has maybe 200 nuclear weapons that can range the continental United States, very few of which are deployed during peacetime. The United States, by contrast, has well over a 1,000, depending on your accounting, that are ready within minutes to range mainland China. This does not even account for the warheads in the stockpile that can be quickly uploaded to American ICBMs and SLBMs which are not fully MIRVd under New START. So even a doubling of Chinas strategic nuclear force still leaves it multiples lower than the United States and Russia.

My main reaction to Chinese nuclear modernization is: What took it so long to start? For decades, it lived with a posture of plausible retaliation with maybe two dozen ICBMs that could range the continental United States. With growing conventional and nuclear counterforce capabilities, and the unrelenting pursuit of national missile defenses which can in combination threaten to neutralize Chinas second strike capability, by eliminating a large portion of the ICBMs and relying on missile defenses to intercept the residuals the question is why China only started investing in mobility and numbers and penetration aids/hypersonics in the last decade or so. To me, all of these developments are Chinas delayed effort to guarantee assured retaliation. Chinas massive buildup in conventional short-range ballistic missile capabilities obviates the need for it to rely on nuclear weapons in a theater scenario, though scholars such as Caitlin Talmadge have pointed out that we cannot sleep on the risks of inadvertent Chinese nuclear escalation. But, I see continuity in overall strategy, and a delayed effort to develop the capabilities and deployment patterns mobility, penetration, SSBNs to implement that strategy with greater assurance.

What do you make of the hype around hypersonics? What about claims around artificial intelligence and nuclear command and control?

The pursuit of hypersonics is again driven by the unfulfilled fantasy of working national missile defenses. Presently, long range missile reentry vehicles, and certainly maneuverable reentry vehicles, which are decades-old technology, are perfectly sufficient to penetrate American missile defenses. And all of these reenter the atmosphere at hypersonic speeds. The advent of the new generation of hypersonics are actually slower than long range reentry vehicles. But some are air breathing and can maneuver and porpoise at very high altitudes in the event missile defenses ever work. So, at least in the medium term, Im a skeptic that these capabilities fundamentally alter the strategic balance. Russia and China do not face a penetration problem at the moment, so hypersonic glide vehicles only have marginal value at the moment.

Similarly, there is a lot of hype over AI and command and control, but a lot remains to be seen whether it affects a states ability to maintain command and control or disrupt it. AI may help solve some detection and ISR problems, but the general cat-and-mouse game of emerging technologies and counter-responses is a decades-old phenomenon.

What do you think about future arms control measures for emerging technologies?

Like all arms control measures, the empirical record suggests they will emerge and be adhered to when both states view them as being in their interests, which is unsatisfying and tautological but also the reality. States with an asymmetric advantage in a particular technology will oppose limits on it, while those that fear it will seek those limits. The zone of overlap generally emerges when both or all sides perceive a benefit in capping or limiting that capability either amongst themselves or collusively to prevent the diffusion of technology to other states. I am not an arms control skeptic so much as an arms control realist.

How do you assess the prospects of the New START treaty being extended, if Trump is reelected next month?

Ultimately, I do think New START will be extended no matter who wins the election. I think the Trump administration is attempting to play chicken with New START to try to pressure Russia into limiting, for example, its tactical nuclear weapons capability. But ultimately, a New START extension is in Americas interest: arms controllers love it because it is arms control and counter-forcers should love it because it provides a cap and accounting on the systems they have to eliminate. The only constituency that opposes New START are arms racers who believe that an arms race with Russia is good and easy to win. But in the current economic climate, there may be little appetite for a renewed arms race, or even persistent uploading of warheads from the stockpile. And Russia has an interest in New START for similar economic and management reasons. It is possible that a second Trump administration would only extend New START for one year and attempt to negotiate something stronger or multilateral in that year he may in fact try to do this before the election itself. I do not think there is any chance of China joining a multilateral equivalent of New START it would either be an invitation for it to build to parity with the US and Russia, or force it to agree to inequitable limits, which it will never do. But I do think we will see an extension of the bilateral New START at the end of the day. But whether it is for one or five years remains to be seen.

Would a Biden administration, come January, roll back some of Trumps nuke modernization plans?

The Democrats, in general, seek a safe, secure, and effective nuclear deterrent for the United States and Americas allies at an affordable cost. Although there was a loose bipartisan consensus for the modernization program, there are some components that may be revisited. For example, the ICBM replacement, the ground based strategic deterrent, could be forsook for another life extension of Minuteman III, which may save some cost. I do think certain capabilities, such as the low yield SLBM and the nuclear sea launch cruise missile, could be rolled back. But those are not so much part of the modernization program as particular capabilities that the Trump administration believed filled a deterrent gap, which I suspect many in a Biden administration remain unconvinced ever existed

To your mind, have India and Pakistan learnt the wrong lessons about escalation after Indias February 2019 Balakot air strikes and Pakistans retaliatory action?

I hesitate to judge what lessons either side may have privately taken away from Balakot, but at least publicly both sides seem to underestimate the role that pure luck played in keeping the crisis from further escalating. I think, for example, that if Indian fighter pilot Abhinandan Varthaman had been killed when his MiG-21 was shot down, or if he had died in Pakistani custody, or if there was a delay in his return and Prime Minister Narendra Modi carried out an alleged surface-to-surface missile strike, the crisis could have quickly escalated as domestic political pressure to hit back boiled over. Even in this case, where neither state wanted a broader war, both sides do seem to underestimate the risk that they came very close to stumbling into one. In general, Indias frustration with Pakistans continued use of terror against the Indian homeland is leading it to see how far it can push the line against another nuclear weapons power. That frustration is understandable, but it does not mean that pushing the line is risk-free.

I am disappointed you did not ask me about my hobby horse: the sanctity of Indias No First Use (NFU) declaration! At this point, no one believes the absoluteness of Indias NFU declaration though it sort of remains official doctrine including, most importantly, Indias government itself.

Read the article in The Diplomat.

See more here:
Vipin Narang on the global nuclear landscape: hype and reality | News - MIT News

Recommendation and review posted by Bethany Smith

Earlier this month, FoodBytes! Pitch announced that 45 companies will participate in the start-up discovery platform, which provides corporate leaders and investors exposure to a group of innovative start-ups, with opportunities for deeper interaction and networking throughout the year.

The FoodBytes! Pitch competition, which has been running for five years, will be staged virtually in 2020 due to COVID restrictions.

Participants were chosen from nearly 340 submissions from across the globe and six European applicants made the cut.

A predominant focus among start-ups based in Europe is digitising the supply chain, from farm to fork, Rabobank noted.

Greven said that this is reflective of the challenges faced by food corporates, who have had to evaluate their distribution strategies in recent years.

According to a report from Rabobanks supply chain experts, many US and European food companies have been ramping up discussions on distribution strategies in the past few years. The main reason for this is a rise in logistics costs due to an increasing variety of distribution channels and stricter fulfilment requirements set by customers. In Europe specifically, as corporates look to drive cost efficiency, the outsourcing of food logistics is once again growing, the investment expert told us.

Start-ups are bringing innovative solutions to the table, as reflected in the latest FoodBytes! cohort.

Switzerlands Koa, for instance, focuses on providing digital tools to smallholder farmers in order to create a transparent cocoa product. Meanwhile, Norwegian Farmforce is working to create a mobile platform to secure sustainable sourcing for farmers. At the consumer end of the chain, UK start-up Good Club aims to provide consumers with a go-to online market for sustainable food products.

As well as addressing efficiency and cost, supply chain technologies are helping to strengthen the food system and build a more resilient and sustainable supply chain, Greven continued. All of these technologies address various and important areas across the supply chain from loss mitigation (shelf-life extension and food safety), food e-commerce (accessibility and transparency), and connected marketplaces that help close the gap between farmers and consumers.

The ability of agile start-up innovators to develop new and pioneering approaches to the table has driven investment in the space. Indeed, Greven noted:Half of capital invested into European food and ag start-ups in 2020 has been to midstream technologies focused on supply chain efficiency and digitisation."

This figure is higher than the level seen in the US, where that number is closer to 40%, she added.

Biotechnology and cellular solutions also offer the opportunity to re-think how we produce food and source materials.

New understandings of the role biosciences can play in the food industry can help address major challenges from agricultural production to food quality and health and nutrition.

Were seeing excitement from our community of experts and corporates surrounding the development of next gen food technologies, Greven observed.

Greven said that the rapid development of this sector means that applications from biotech companies to FoodBytes! are also increasing.

Our biotech applications globally are on the rise in 2019 and 2020, biotech companies comprised of 10% of applications received, double that of the two years preceding.

This years FoodBytes! saw a total of three start-ups two of whom are European focused on cell-based meat and fermented protein.

CellulaREvolution has developed cell-culturing meat technology utilising a cell coating to facilitate the continuous production of proteins, rather than in batches, working with clients across the fields of cultured meat, cell therapy and biologics. NovoNutrients upcycles industrial carbon dioxide waste into food system ingredients. While Future Meat Technologies has developed a cell-culturing meat technology utilising the rapid growth of connective tissue cells to reach high densities before turning the cells into cultured muscle and healthy fats.

Elsewhere, innovators are looking at how fermentation technologies and bioreactors can be used to create ingredients without depleting natural resources. One of our selected start-ups for 2020, Michroma, is a perfect example this Argentinian based company produces next-generation natural ingredients in a sustainable, cost-effective and scalable way to brew food colorants, mycoprotein and more alternatives, Greven noted.

The 45 selected startups hail from 15 countries, including the US, Australia, Canada, the UK, Argentina, Brazil, Chile, India, Israel, Nigeria, Norway, Peru, Singapore, South Korea and Switzerland.

Consumer food and beverage (CPG):

Food and beverage products made with upcycled ingredients are a top trend among FoodBytes! 2020 CPG startups, who are also pioneering innovations including edible spoons to reduce plastic waste, a distilled spirit made from upcycled whey byproduct, and plant-based cheese and egg products.

Food tech:

The shortlisted food tech startups have developed technologies for cell-based meat production, natural coatings that extend produce shelf life, and sustainable, antimicrobial packaging made from crustacean shells to replace plastic. Food safety technologies, advanced nutrition products and online marketplaces also address relevant needs in the wake of COVID-19.

Ag tech:

The shortlisted ag tech startups have developed solutions that address soil and water sustainability, farm efficiency and labour needs. Their innovations include technology that transforms air pollution into fertilizer, animal feed that reduces methane emissions, a method of growing rice out of water and on-farm robotics to combat labour shortages and worker safety concerns.

Each of the three winners (CPG, food tech, and ag tech) will receive a $10,000 prize, while FoodBytes! Pitch corporate members will also offer additional consulting to support winning startups, including:

See the original post here:
Digitalisation, distribution and biotech: Rabobank talks next gen food tech innovation - FoodNavigator.com

Recommendation and review posted by Bethany Smith

Bruce Power and the Town of Saugeen Shores are working with researchers from the University of Guelph to learn more about the challenges and opportunities facing employers and people working or looking for work in Saugeen Shores.

As COVID-19 has added new difficulties to the challenges many were already facing in the local labour market, this research project will help provide critical considerations and recommendations to the Town of Saugeen Shores and local employers to support future investments and programming to support the local economy.

"Council looks forward to the results of this study as we explore evidence-based solutions to challenges faced by employers and job seekers," said Mayor Luke Charbonneau. "We encourage residents and non-residents to take part and share their experiences with the researchers."

"We are proud that our Life Extension Program is creating unprecedented opportunity in our community, however, opportunity and challenge often ride together and we want to ensure we are doing our part in seizing the opportunities and meeting the challenges and we believe this research will help to achieve that," said John Peevers, Bruce Power's Director of Community, Media Relations and Economic Development.

The research team is currently recruiting participants to share their experiences through interviews. People interested in participating in the project are encouraged to complete a pre-screening process by visiting http://bit.ly/GettingToWork2020.

The Getting to Work research initiative is part of a Mitacs Accelerate Internship being completed by Ashleigh Weeden (PhD Candidate, University of Guelph), funded by Bruce Power and the University of Guelph, and supported by the Town of Saugeen Shores. Mitacs-supported projects support partnerships between academics, industry, and communities to respond to critical challenges and foster a more innovative Canada.

The Getting to Work research initiative is supported by an Advisory Committee composed of local stakeholders and nationally recognized experts in rural research, including:

" Dr. Ryan Gibson - Associate Professor & Libro Professor in Regional Economic Development, School of Environmental Design & Rural Development, University of Guelph

" Heather Hyde - Economic Development Officer, Town of Saugeen Shores

" John Peevers - Director, Community Relations & Economic Development, Bruce Power

" Dr. Karen Foster - Associate Professor, Sociology & Social Anthropology, Canada Research Chair (Tier II) in Sustainable Rural Futures for Atlantic Canada, and Director, Rural Futures Research Centre, Dalhousie University

" Gemma Mendez-Smith - Executive Director, Four County Labour Market Planning Board

" Kimberley Inniss-Petersen - Executive Director, Saugeen Shores Chamber of Commerce

Read the original post:
Saugeen Shores, Bruce Power and University of Guelph teaming up for labour survey - 92.3 The Dock (iHeartRadio)

Recommendation and review posted by Bethany Smith

The spotlight remains on the potential of antibody therapies as a possible way out of the COVID-19 pandemic crisis, with the US government investing millions in a hopeful from AstraZeneca and president Donald Trump recovering from coronavirus after receiving a rival therapy from Regeneron.

Thanks to a drug cocktail including Regenerons antibody therapy, Trump says he is back on his feet after becoming infected with the virus around the end of last month.

Trump has hailed the Regeneron therapy as a cure for the virus, but the companys CEO Leonard Schleifer was quick to point out that the scientific evidence is not there to support the claim.

Regenerons therapy is based on two antibodies the company has developed to neutralise the virus.

The thinking is that by having a double therapy, the chances of the virus developing resistance to both parts of the drug are reduced.

Like rivals Eli Lilly, Regeneron is in talks with the FDA to get an Emergency Use Authorisation based on the data it has gathered so far.

But CEO Leonard Schleifer said in a TV interview that there is a long way to go before the drug is fully approved.

Schleifer told CBS News Face the Nation: So the presidents case is a case of one, and thats what we call a case report, and it is evidence of whats happening, but its kind of the weakest evidence that you can get.

The real evidence has to come about how good a drug is and what it will do on average has to come from these large clinical trials.

Its just low down on the evidence scale that we really need.

Regeneron CEO Leonard Schleifer

Antibody therapies could also be used prophylactically, to protect people at high risk of getting the disease such as healthcare workers, or vulnerable people in areas where there are large numbers of cases.

AstraZeneca is to begin phase 3 trials of a long-acting antibody therapy combination in the US and other countries, to prevent infection happening and as therapy for those already infected.

AZs long-acting antibody (LAAB) combination, AZD7442, will advance into two phase 3 clinical trials in more than 6,000 participants at sites in and outside the US in the next few weeks.

The LAABs have been engineered with AstraZenecas proprietary half-life extension technology to increase the durability of the therapy for six to 12 months following a single administration.

The combination of two LAABs is also designed to reduce the risk of resistance developed by the SARS-CoV-2 virus.

The LAABs have been engineered with AstraZenecas half-life extension technology to increase the durability of the therapy for six to 12 months following a single shot.

Like Regenerons therapy the combination of two LAABs is also designed to reduce the risk of resistance developed by the SARS-CoV-2 virus.

The US government agency, the Biomedical Advanced Research and Development Authority (BARDA) has invested $486 million in the project.

One trial will test whether AZD7442 can safely and effectively prevent infection in up to 5,000 people, and the second trial will test post-exposure prophylaxis and pre-emptive treatment in around 1,100 people.

AZ is planning additional trials to evaluate AZD7442 in approximately 4,000 patients for the treatment of COVID-19.

The company plans to supply up to 100,000 doses starting towards the end of 2020 and the US Government can acquire up to an additional one million doses in 2021 under a separate agreement.

Visit link:
Spotlight on COVID-19 antibody therapies after Trump's recovery - - pharmaphorum

Recommendation and review posted by Bethany Smith

Classification society DNV GL and FPSO specialist Bluewater are undertaking a pilot project to use hybrid digital twin technology to predict and analyse fatigue in the hull of an FPSO in the North Sea.

The project aims to validate and quantify the benefits of creating a virtual replica of the FPSO to optimise the structural safety of the vessel and enhance risk-based inspection (RBI), a decision-making methodology for optimising inspection regimes. The pilot underpins Bluewaters mission to take a proactive, responsible approach to safety and environmental care in its operations.

Bluewaters Aoka Mizu FPSO, currently in operation in the Lancaster field, west of Shetland, will be used. To date, the pilot test has shown encouraging results.

DNV GLs combination of domain experience, inspection capabilities and digital analytics and modelling, enables the monitoring of the assets hull structure during operation without dependence on costly routine inspection regimes. Termed Nerves of Steel, the underlying concept permits the use of various data sets (external environmental data or local sensor data) combined with digital models of the asset, to develop a hybrid replica model of the vessels structure. This can be used in real-time to monitor the assets condition, identify and monitor high risk locations, and plan targeted and cost-efficient maintenance and inspection activities.

Hybrid twin technology uses a combination of numerical design models and data from actively recorded strain gauge sensors on board the FPSO. These sensors allow for a full understanding of the accumulative loading and current state of the FPSO structure. The technology blends computer-simulated modelling with real-time data, which is then streamed to the operator via DNV GLs Veracity data platform or an existing data transfer solution.

By informing and enhancing the RBI process, operators can reduce operational costs and time, providing significant improvements in safety, thereby extending the lifespan and integrity of assets. With fluctuating oil price and the impact of Covid-19 on travel, delivering a mirror image of an asset from the safety of shore needs to be trusted and of value, said Koheila Molazemi, Technology and Innovation Director, DNV GL Oil & Gas.

DNV GLs visual dashboard presents data to Bluewater on stresses in the hulls structure, alongside information that can be used to identify areas with relative higher risk of cracks or deformities to occur. The information, which is constantly recorded, can be accessed and analysed to inform decision-making and implement inspection based on risk priority.

The trial will expand on traditional FPSO integrity management strategies, which are based on software-based assumptions made at the design stage as well as current inspection record to enhance RBI decision-making. The pilot with Bluewater is expected to provide new insight and smarter ways of managing risks and costs related to structural integrity management.

This is DNV GLs third pilot project evaluating the performance of hybrid digital twin technology. With global support from the advisors experts in Singapore, the UK and Norway, the first involved defining a repair procedure for a FPSO flare tower. Another trial, which is still ongoing, is being performed on a fixed offshore platform.

Like an insurance policy, the hybrid digital twin can potentially save millions by avoiding the costly and possibly catastrophic repercussions of ill-informed integrity management by pre-empting and preventing detrimental damage. For an asset operating in a harsh environment, where the loads play an important part in the possible degradations of the asset, using data from the site as a basis for optimised inspection planning, alarms for extreme events and asset suitability for life extension is crucial, added Francois-Xavier Sireta, Technical Lead for Naval Architecture and Principal Engineer, DNV GL Oil & Gas.

Peter van Sloten, Department Head Technology Management, Bluewater said, We decided to extend our digital twin programme to include our FPSO Aoka Mizu. Our ambition for the structures largely matched with the novel digitalisation services of DNV GL. We are therefore pleased to team up with DNV GL to develop a tool to monitor the structural integrity of this most versatile FPSO, designed and proven to operate in harsh environments with high uptimes and a maintained, strict regulatory and safety regime. This will enhance the safety and enables an optimised inspection regime.

Here is the original post:
DNV GL and Bluewater to use digital twin to analyse FPSO fatigue - ShipInsight

Recommendation and review posted by Bethany Smith

I am a clinical immunologist that happens to also be a stem cell scientist with 45 years of experience. The first CD34 bone marrow transplantation in 1978 was done at Roswell Park using FACS flow cytometry. We watch GvHD take hold to many leukemia patients to these brave patients trying to save their life with no way to treat them, until now with MSC (mesenchymal stem cells).

I watched many patients give their lives to science research for a chance of cures, which we had successes 40 years forward, if you get CML, CLL you have 98% of treatment or cure. CAR T and other treatments etc.

My concerns (are that) the media is presenting a perspective in vacuum of the stem cell world in California. Prop 71 put California in play and pushed embryonic research. The people of California need to protect their investment of $3.3 billion, or the industry leadership will be lost along with the clinical trials supported by CIRM. Please do not underestimate the RPE for blindness. #1 unmet medical need when the Japanese pharma Astellas bought Ocata in 2015 and put it on the shelf setting back embryonic research.

Lets look at say, Mesoblast, a Australian stem cell company and the leader in field with four studies. (They) had a setback recently of their BLA of SR aGvHD for kids under 12 years old (which is a death sentence) using MSC stem cells (approved for treatment in Japan for two years now) on the first stem cells for regenerative medicine to be approved the FDA, on Sept. 30, 2020. Mesoblast has 330 double blind studies for Covid19 treatment.

We will know before Christmas if FDA will approve these cells. MSC will be better than vaccinations, with super antigens stimulating the immune memory cells being develop by many companies and Federal government.

Two points: federal funding for embryonic research is not very well supported, and you cannot put a price tag on the patients who are willing to put their life on the line for hope and a chance.

Stay in the game California - do not be shortsighted.

See the original post here:
Yes on 14 | Mailbox | independentnews.com - Livermore Independent

Recommendation and review posted by Bethany Smith

Indias first saviour sibling experiment is a success, say doctors.

A one-year-old sibling has saved her brothers life by donating her bone marrow. Kavya was conceived by her parents through invitro fertilisation to save her brother, Abhijeet Solanki, who was born with Thalassemia.

Thalassemia is a disorder where the haemoglobin count is low in blood and such persons require frequent blood transfusions.

Abhijeet was born in November 2013 but unlike normal babies he did not achieve the growth milestones. The parents learned that Abhijeet had Thalassemia major. Abhijeet required blood transfusions every 25 days and the gap between two transfusions reduced as he grew. By the age of six Abhijeet had undergone 80 transfusions, recalled his father Sahdev Singh Solanki. The only way to save him was through a bone marrow transplant.

The family was willing to donate their bone marrow but the human leukocyte antigen (HLA) of the family, including that of his older sister, did not match.

The Solanki family consulted many doctors. Mr. Solankis research led him to the saviour sibling concept following which he sought out Manish Banker, medical director of Nova IVF Fertility in Ahmedabad.

Dr. Banker said Mr. Solankis research and the science behind it was known but nobody had approached him with such a request before.

Dr. Banker started the assisted reproductive therapy, called pre-implantation genetic testing, for monogenic disorder with HLA matching. The couple underwent three cycles of IVF and 18 embryos were created. Of this only one perfectly matched Abhijeets HLA. The embryo was implanted in Apla Solanki, who delivered a baby girl a year ago.

We had to wait for the baby to grow. She had to weigh 10 kg before we could draw bone marrow, said Deepa Trivedi, programme director of Sankalp Bone Marrow Unit, CIMS Hospital, Ahmedabad.

Pointing out that the best therapeutic option for Thalassemia major patients is bone marrow transplant from an HLA-identical donor, Dr. Banker said, We are extremely thrilled to be part of reproductive history in India to create the first-ever saviour-sibling through ART. We used pre-genetic diagnosis and screening test, an established method for conceiving a child who may donate cord blood or hematopoietic stem cells for transplantation to save a critically ill sibling.

Mr. Solanki said the transplant was done on March 17. Since then Abhijeet has not needed any blood transfusion, indicating that he had been cured of the disorder. His haemoglobin count was 11.3, Dr. Trivedi said.

See the article here:
A sister born to save ailing brother - The Hindu

Recommendation and review posted by Bethany Smith

Every 20 minutes someone in the UK is diagnosed with blood cancer and the register of stem cell donors who are needed to save thousands of patients lives does not currently meet the demand. Only 1 in 3 patients will find a donor match within their family and so every year over 2,000 people in the UK are left searching for a matching blood stem cell donor each year.

Blood cancer patients from Black, Asian or minority ethnicity groups face lower survival odds due to the lack ofdonordiversity. These patients have just a 20% chance of finding the best possible stem cell donor match, compared to 69% for northern European backgrounds.

This is due in part to the low numbers of donors registered from those Black, Asian or ethnic minority backgrounds. Donors from minority ethnic backgrounds make up just 13.1% of the UK stem cell register and because Black, Asian or ethnic minority patients tend to have more varied tissue meaning there is an even more specific biological requirement needed of a donor than for a white patient.

The global pandemic has made this situation even worse. Only 2% of stem cell registrations with DKMS came from black people during lockdown, falling by 20% compared to the same time the previous year.

Vaughn Scott is a patient who received a lifesaving donation from a stranger.

Vaughn Scott (34 years old) lives in Bristol and is grateful to the generous stranger who helped save his life. Theyve given him more time with his two children and the chance to marry his now wife last summer in a beautiful ceremony. Vaughn was incredibly fit and active, playing all kinds of sports and serving in the Navy. It was whilst on deployment across the world that he was urgently flown back to the UK and shockingly diagnosed with acute lymphoblastic leukaemia (ALL).

Vaughn said:

Hearing the diagnosis was the biggest blow Ive ever heard. My mind raced straight to my children and partner. When we learnt there was a way I could go into remission, I was excited that there was a way I could get better but very nervous too. With no family members as a match, all my faith was in a complete stranger that may have registered as a potential stem cell donor. Thankfully my match was found, Im now married and enjoying life with my family and Im so grateful. So many people arent as lucky as me. If you can, please register and give other people the second chance at life that I have been given.

To request a swab kit and register as a potential donor click HERE.

About blood cancer

Blood cancer is the third most common cause of cancer death in the UK but there is a lot of fear around stem cell donation of the process itself and of having a depleted supply of stem cells. This isnt the case. After donation, stem cells regenerate within 2 weeks so the donor wont lose anything. Blood stem cell donation is easy to do and similar to blood donation. Around 90% of all donations are made through a method called peripheral blood stem cell (PBSC). In this method, blood is taken from one of the donors arms and a machine extracts the blood stem cells from it. The donors blood is then returned to them through their other arm. This is an outpatient procedure that is usually completed in 4-6 hours. In just 10% of cases, donations are made through bone marrow collection. This is under general anaesthetic so that no pain is experienced.

See the article here:
Black History Month The struggle to find a lifesaving stem cell donor - Keep the Faith

Recommendation and review posted by Bethany Smith

Glancy Prongay & Murray LLP ("GPM") reminds investors of the upcoming December 7, 2020 deadline to file a lead plaintiff motion in the class action filed on behalf of investors who purchased or otherwise acquired Mesoblast Limited ("Mesoblast" or the "Company") (NASDAQ: MESO) securities between April 16, 2019 and October 1, 2020, inclusive (the "Class Period").

If you suffered a loss on your Mesoblast investments or would like to inquire about potentially pursuing claims to recover your loss under the federal securities laws, you can submit your contact information at https://www.glancylaw.com/cases/mesoblast-limited/. You can also contact Charles H. Linehan, of GPM at 310-201-9150, Toll-Free at 888-773-9224, or via email at shareholders@glancylaw.com to learn more about your rights.

Mesoblast develops allogeneic cellular medicines using its proprietary mesenchymal lineage cell therapy platform. Its lead product candidate, RYONCIL (remestemcel-L), is an investigational therapy comprising mesenchymal stem cells derived from bone marrow. In February 2018, the Company announced that remestemcel-L met its primary endpoint in a Phase 3 trial to treat children with steroid refractory acute graft versus host disease ("aGVHD").

In early 2020, Mesoblast completed its rolling submission of its Biologics License Application ("BLA") with the FDA to secure marketing authorization to commercialize remestemcel-L for children with steroid refractory aGVHD.

On August 11, 2020, the FDA released briefing materials for its Oncologic Drugs Advisory Committee ("ODAC") meeting to be held on August 13, 2020. Therein, the FDA stated that Mesoblast provided post hoc analyses of other studies "to further establish the appropriateness of 45% as the null Day-28 ORR" for its primary endpoint. The briefing materials stated that, due to design differences between these historical studies and Mesoblasts submitted study, "it is unclear that these study results are relevant to the proposed indication."

Story continues

On this news, the Companys share price fell $6.09, or approximately 35%, to close at $11.33 per share on August 11, 2020, on unusually heavy trading volume.

On October 1, 2020, Mesoblast disclosed that it had received a Complete Response Letter ("CRL") from the FDA regarding its marketing application for remestemcel-L for treatment of SR-aGVHD in pediatric patients. According to the CRL, the FDA recommended that the Company "conduct at least one additional randomized, controlled study in adults and/or children to provide further evidence of the effectiveness of remestemcel-L for SR-aGVHD." The CRL also "identified a need for further scientific rationale to demonstrate the relationship of potency measurements to the products biologic activity."

On this news, the Companys stock fell $6.56, or 35%, to close at $12.03 per share on October 2, 2020, on unusually heavy trading volume.

The complaint filed in this class action alleges that throughout the Class Period, Defendants made materially false and/or misleading statements, as well as failed to disclose material adverse facts about the Companys business, operations, and prospects. Specifically, Defendants failed to disclose to investors: (1) that comparative analyses between Mesoblasts Phase 3 trial and three historical studies did not support the effectiveness of remestemcel-L for steroid refractory aGVHD due to design differences between the four studies; (2) that, as a result, the FDA was reasonably likely to require further clinical studies; (3) that, as a result, the commercialization of remestemcel-L in the U.S. was likely to be delayed; and (4) that, as a result of the foregoing, Defendants positive statements about the Companys business, operations, and prospects were materially misleading and/or lacked a reasonable basis.

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If you purchased or otherwise acquired Mesoblast securities during the Class Period, you may move the Court no later than December 7, 2020 to ask the Court to appoint you as lead plaintiff. To be a member of the Class you need not take any action at this time; you may retain counsel of your choice or take no action and remain an absent member of the Class. If you wish to learn more about this action, or if you have any questions concerning this announcement or your rights or interests with respect to these matters, please contact Charles Linehan, Esquire, of GPM, 1925 Century Park East, Suite 2100, Los Angeles California 90067 at 310-201-9150, Toll-Free at 888-773-9224, by email to shareholders@glancylaw.com, or visit our website at http://www.glancylaw.com. If you inquire by email please include your mailing address, telephone number and number of shares purchased.

This press release may be considered Attorney Advertising in some jurisdictions under the applicable law and ethical rules.

View source version on businesswire.com: https://www.businesswire.com/news/home/20201015005282/en/

Contacts

Glancy Prongay & Murray LLP, Los AngelesCharles H. Linehan, 310-201-9150 or 888-773-92241925 Century Park East, Suite 2100Los Angeles, CA 90067www.glancylaw.com shareholders@glancylaw.com

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Glancy Prongay & Murray LLP Reminds Investors of Looming Deadline in the Class Action Lawsuit Against Mesoblast Limited (MESO) - Yahoo Finance

Recommendation and review posted by Bethany Smith

HAIFA, Israel, Oct. 13, 2020 (GLOBE NEWSWIRE) -- Pluristem Therapeutics Inc. (Nasdaq:PSTI) (TASE:PSTI), a leading regenerative medicine company developing a platform of novel biological products, today announced that it has received clearance from the safety committee of an investigator initiated Phase I/II study to move forward with patient enrollment for cohort II. The study will evaluate PLX-PAD cells in the treatment of steroid-refractory chronic graft vs. host disease (GvHD) and is led by Principal Investigator Prof. Ron Ram, Director of the Hematology Blood and Marrow Stem Cell Transplantation Unit at Tel Aviv Sourasky Medical Center, Ichilov Hospital, Israel. Prof. Ram and his research staff are responsible for the design and implementation of the study at Sourasky Medical Center.

GvHD is a severe complication in patients who have undergone an allogeneic hematopoietic cell transplantation (HCT) and is a major cause of morbidity and mortality in these patients in which the donated stem cells identify the recipient's body as foreign and attack it. The chronic form of GvHD (cGvHD) usually appears later than 100 days post-transplant.

Cohort I included 6 patients treated with 2 injections of 150 million cells, a week apart. At the 3-month follow up, interim safety results concluded that PLX-PAD cells were safe and that no treatment related side effects were reported. Efficacy results demonstrated that 4 out of the 6 patients reported improvement in symptoms that translated into a reduction in the severity of cGvHD with notable reduction in the required steroid doses for part of the patients. Based on these results, the study was approved to commence enrollment of 14 patients in cohort II to be treated with 4 injections of 150 million cells.

Prof. Ram of Ichilov Hospital commented, From our experience in having treated 6 patients in the study to date, we have so far found no negative side effects from the use of the PLX-PAD cells in the treatment of steroid-refractory cGvHD. Patients with significant GvHD skin disorders previously unresponsive to multiple types of therapy showed remarkable response. Responses were also observed for severe mouth ulcers which prevented patients from eating solid foods. This resulted in a major improvement of quality of life and tapering of steroid doses."

Pluristem is committed to contributing to the wellbeing and quality of life of our patients. cGvHD is an indication where we see a significant need to enhance the current course of treatment for this life-threatening condition among patients undergoing bone marrow transplants. The preliminary results from cohort I of this Phase I/II study, and prior preclinical data, both indicate that PLX-PAD cells may potentially treat cGvHD patients and mitigate symptoms. We are very pleased to cooperate with Prof. Ram and Sourasky Medical Center, and we place a high importance in examining PLX-PAD for this indication, stated Pluristem CEO and President, Yaky Yanay.

About cGvHDChronic graft-versus-host disease (cGvHD) remains a common and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HCT). The 2-year cumulative incidence of chronic GvHD requiring systemic treatment is 30% to 40% by National Institutes of Health criteria1. The hematopoietic stem cell transplants are used to treat bone marrow failure resulting from treatment of some blood or bone marrow cancers as well as other hematologic failures, such as aplastic anemia, which are not related to cancer. The donated cells identify the recipients body as foreign and attack it as a result. While acute GvHD usually appears in the first 100 days after a transplant, and in specific body systems, chronic GvHD can occur at any time (even several years) after a transplant, and may manifest in many parts of the body such as: skin, mouth, eyes, liver, intestines, lungs and joints. Long term immunosuppression is given to try to prevent or treat cGvHD. Since this treatment suppresses the immune system for a very long time, patients are at high risk of infections, and are prescribed multiple medications to try to address this major risk.

About Pluristem TherapeuticsPluristem Therapeutics Inc. is a leading regenerative medicine company developing novel placenta-based cell therapy product candidates. The Company has reported robust clinical trial data in multiple indications for its patented PLX cell product candidates and is currently conducting late stage clinical trials in several indications. PLX cell product candidates are believed to release a range of therapeutic proteins in response to inflammation, ischemia, muscle trauma, hematological disorders and radiation damage. The cells are grown using the Company's proprietary three-dimensional expansion technology and can be administered to patients off-the-shelf, without tissue matching. Pluristem has a strong intellectual property position; a Company-owned and operated GMP-certified manufacturing and research facility; strategic relationships with major research institutions; and a seasoned management team.

Safe Harbor StatementThis press release contains express or implied forward-looking statements within the Private Securities Litigation Reform Act of 1995 and other U.S. Federal securities laws. For example, Pluristem is using forward-looking statements when it discusses the patient enrollment for cohort II for its Phase I/II study of its PLX-PAD cells, the implication from the results of the first patient cohort in the study, the belief that GvHD is an indication that has a significant need for enhanced treatments among patients undergoing bone marrow transplants and that the preliminary results from cohort I of the study, and the prior preclinical data, indicate that PLX-PAD cells may potentially treat chronic GvHD patients and mitigate symptoms. These forward-looking statements and their implications are based on the current expectations of the management of Pluristem only, and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. The following factors, among others, could cause actual results to differ materially from those described in the forward-looking statements: changes in technology and market requirements; Pluristem may encounter delays or obstacles in launching and/or successfully completing its clinical trials; Pluristems products may not be approved by regulatory agencies, Pluristems technology may not be validated as it progresses further and its methods may not be accepted by the scientific community; Pluristem may be unable to retain or attract key employees whose knowledge is essential to the development of its products; unforeseen scientific difficulties may develop with Pluristems process; Pluristems products may wind up being more expensive than it anticipates; results in the laboratory may not translate to equally good results in real clinical settings; results of preclinical studies may not correlate with the results of human clinical trials; Pluristems patents may not be sufficient; Pluristems products may harm recipients; changes in legislation may adversely impact Pluristem; inability to timely develop and introduce new technologies, products and applications; loss of market share and pressure on pricing resulting from competition, which could cause the actual results or performance of Pluristem to differ materially from those contemplated in such forward-looking statements. Except as otherwise required by law, Pluristem undertakes no obligation to publicly release any revisions to these forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. For a more detailed description of the risks and uncertainties affecting Pluristem, reference is made to Pluristem's reports filed from time to time with the Securities and Exchange Commission.

Contact:

Dana RubinDirector of Investor Relations972-74-7107194danar@pluristem.com

_________________________________

1 Flowers ME, Martin PJ. How we treat chronic graft-versus-host disease. Blood. 2015 Jan 22;125(4):606-15. doi: 10.1182/blood-2014-08-551994. Epub 2014 Nov 14. PMID: 25398933; PMCID: PMC4304105., https://pubmed.ncbi.nlm.nih.gov/25398933/

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Pluristem Announces Clearance to Move Forward with Enrollment for Cohort II in an Investigator-Led Phase I/II Chronic Graft vs Host Disease...

Recommendation and review posted by Bethany Smith

Gosselies, Belgium, 14 October 2020, 7am CEST BONE THERAPEUTICS(Euronext Brussels and Paris: BOTHE), the cell therapy company addressing unmet medical needs in orthopedics and other diseases, today announces positive 24-month follow-up results for the Phase IIa study with the allogeneic cell therapy product, ALLOB, in patients undergoing lumbar spinal fusion procedures.

The 24-month data show a high percentage of successful lumbar vertebrae fusion of 90%. Patients also continue to experience important clinical improvements in function and pain, from as early as six months after treatment, up to the 24-month follow-up period.

Degenerative spine disorders have a major impact on the quality of life of patients. These impacts include decreases in the stability of the spine and pain in motion,said Dr. Alphonse Lubansu, M.D., Head of the Spinal Clinic, Erasme University Hospital, Universit libre de Bruxelles. The 24 month follow-up data of this Phase IIa clinical trial have demonstrated that patients treated with ALLOB in spinal fusion procedure show a high incidence in fusion, and benefit from a sustained, clinically meaningful improvement in function and pain throughout the 24 months following treatment together with a good safety profile. These results show that ALLOB in combination with the standard spine fusion surgery could be a promising treatment option to address the currently unmet needs of these patients.

This positive data forlumbar spinal fusion complementsthe strong Phase I/IIa results from ALLOB in patients with delayed union fractures,said Miguel Forte, MD, PhD, Chief Executive Officer of Bone Therapeutics. These studies provide promising clinical evidence for the potential ofBone Therapeuticsunique allogeneic cell therapy platform to address high unmet medical needs in orthopaedics and bone related disorders. We will now hold discussions with global regulators and our partners to explore a variety of options for the next stages of clinical development for ALLOB in different orthopedic indications, while pursuing the phase IIb study of ALLOB in difficult tibial fractures.In addition, theclinical results provide further evidence for the expansion of ALLOB and our platform of differentiated MSCs to other indications.

The multi-center, open-label proof-of-concept Phase IIa study was designed to evaluate the safety and efficacy of ALLOB administered, procedure in which an interbody cage with bioceramic granules mixed with ALLOB is implanted into the spine to achieve fusion of the lumbar vertebrae. The main endpoints of the 24-month follow-up analysis included safety and radiological assessments to evaluate vertebrae fusion (continuous bone bridges) and clinical assessments to evaluate improvement in patients functional disability as well as reduction in back and leg pain. The study evaluated 30 patients treated with ALLOB, 29 patients attended the 24-month visit.

Radiological data was collected from CT-scans at 24 months and assessed by three external readers. It showed a successful fusion of the lumbar vertebrae in 27 out of 30 patients (90%). In addition, the remaining 3 patients showed radiological evidence of bone formation. Treatment with ALLOB also resulted in a clear and statistically significant clinical improvement in function and reduction in pain over the 24-month follow-up period. Functional disability improved from the pre-treatment baseline to 24-month by a mean score of 60% (p<0.001) on the Oswestry Disability Index(1). Back and leg pain were strongly reduced by 57 to 62% (p<0.001) and 68 to 70% (p<0.001) respectively compared to pre-treatment baseline. Treatment with ALLOB was generally well-tolerated by the patients, consistent with previous reported results.

(1)The Oswestry Disability Index (ODI) is an index derived from the Oswestry Low Back Pain Questionnaire used by clinicians and researchers to measure a patients permanent functional disability. This validated questionnaire was first published by Jeremy Fairbank et al. in Physiotherapy in 1980. ODI score of 0%-20%: minimal disability; 21%-40%: moderate disability; 41%-60%: severe disability; 61%-80%: crippled; 81%-100%: bed bound.

About Spinal Fusion

Due to ageing populations and sedentary lifestyles, the number of people suffering from degenerative spine disorders continues to increase. Today, spinal fusion procedures are performed to relieve pain and improve patient daily functioning in a broad spectrum of degenerative spine disorders. Spinal fusion consists of bridging two or more vertebrae with the use of a cage and graft material, traditionally autologous bone graft or demineralised bone matrix placed into the intervertebral space for fusing an unstable portion of the spine and immobilizing a painful intervertebral motion segment. Over 1,000,000 spinal fusion procedures are performed annually in the US and EU, of which half at lumbar level and the market is growing at a rate of 5% per year. Although spinal fusion surgery is routine, non-fusion, slow progression to fusion and failure to eliminate pain are still frequent with up to 35% of patients not being satisfied with their surgery.

About ALLOB

ALLOB is the Companys off-the-shelf allogeneic cell therapy platform consisting of human allogeneic bone-forming cells derived from cultured bone marrow mesenchymal stem cells (MSC) from healthy adult donors, offering numerous advantages in product quality, injectable quantity, production, logistics and cost as compared to an autologous approach. To address critical factors for the development and commercialisation of cell therapy products, Bone Therapeutics has established a proprietary, optimised production process that improves consistency, scalability, cost effectiveness and ease of use of ALLOB. This optimized production process significantly increases the production yield, generating 100,000 of doses of ALLOB per bone marrow donation. Additionally, the final ALLOB product will be cryopreserved, enabling easy shipment and the capability to be stored in a frozen form at the hospital level. The process will therefore substantially reduce overall production costs, simplify supply chain logistics, improve patient accessibility and facilitate global commercialisation. The Company will implement the optimized production process for all future clinical trials with ALLOB.

About Bone Therapeutics

Bone Therapeutics is a leading biotech company focused on the development of innovative products to address high unmet needs in orthopedics and other diseases. The Company has a, diversified portfolio of cell and biologic therapies at different stages ranging from pre-clinical programs in immunomodulation to mid-to-late stage clinical development for orthopedic conditions, targeting markets with large unmet medical needs and limited innovation.

Bone Therapeutics is developing an off-the-shelf next-generation improved viscosupplement, JTA-004, which is currently in phase III development for the treatment of pain in knee osteoarthritis. Consisting of a unique combination of plasma proteins, hyaluronic acid a natural component of knee synovial fluid, and a fast-acting analgesic, JTA-004 intends to provide added lubrication and protection to the cartilage of the arthritic joint and to alleviate osteoarthritic pain and inflammation. Positive phase IIb efficacy results in patients with knee osteoarthritis showed a statistically significant improvement in pain relief compared to a leading viscosupplement.

Bone Therapeutics core technology is based on its cutting-edge allogeneic cell therapy platform with differentiated bone marrow sourced Mesenchymal Stromal Cells (MSCs) which can be stored at the point of use in the hospital. Currently in pre-clinical development, BT-20, the most recent product candidate from this technology, targets inflammatory conditions, while the leading investigational medicinal product, ALLOB, represents a unique, proprietary approach to bone regeneration, which turns undifferentiated stromal cells from healthy donors into bone-forming cells. These cells are produced via the Bone Therapeutics scalable manufacturing process. Following the CTA approval by regulatory authorities in Europe, the Company is ready to start the phase IIb clinical trial with ALLOB in patients with difficult tibial fractures, using its optimized production process. ALLOB continues to be evaluated for other orthopedic indications including spinal fusion, osteotomy, maxillofacial and dental.

Bone Therapeutics cell therapy products are manufactured to the highest GMP standards and are protected by a broad IP (Intellectual Property) portfolio covering ten patent families as well as knowhow. The Company is based in the BioPark in Gosselies, Belgium. Further information is available atwww.bonetherapeutics.com.

For further information, please contact:

Bone Therapeutics SAMiguel Forte, MD, PhD, Chief Executive OfficerJean-Luc Vandebroek, Chief Financial OfficerTel: +32 (0)71 12 10 00investorrelations@bonetherapeutics.com

For Belgian Media and Investor Enquiries:BepublicCatherine HaquenneTel: +32 (0)497 75 63 56catherine@bepublic.be

International Media Enquiries:Image Box CommunicationsNeil Hunter / Michelle BoxallTel: +44 (0)20 8943 4685neil.hunter@ibcomms.agency / michelle@ibcomms.agency

For French Media and Investor Enquiries:NewCap Investor Relations & Financial CommunicationsPierre Laurent, Louis-Victor Delouvrier and Arthur RouillTel: +33 (0)1 44 71 94 94bone@newcap.eu

For US Media and Investor Enquiries:LHA Investor RelationsYvonne BriggsTel: +1 310 691 7100ybriggs@lhai.com

Certain statements, beliefs and opinions in this press release are forward-looking, which reflect the Company or, as appropriate, the Company directors current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its subsidiary undertakings or any such persons officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.

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Bone Therapeutics' allogeneic cell therapy product, ALLOB, shows 90% fusion rate at 24 months in Phase IIa study in lumbar spinal fusion -...

Recommendation and review posted by Bethany Smith

Building on the transformative impetus from the first Food and Drug Administration (FDA)-approved Janus kinase (JAK) 1/2 inhibitor, ruxolitinib (Jakafi), in the clinical landscape of myeloproliferative neoplasms (MPNs), we are entering a new era of multiple JAK inhibitors and other diverse classes of drugs in rapid clinical development. Advancements in elucidating the pathophysiology of MPNs have spurred significant progress in developing novel promising agents or combination regimens with ruxolitinib to treat patients who are unresponsive to standard treatments or have specific clinical needs.

In myelofibrosis (MF), the most aggressive MPN, with an average survival of 5 to 7 years, abnormal clonal hematopoietic stem cell proliferation in the bone marrow (BM) leads to liberation of pro-inflammatory cytokines and extensive fibrosis, causing progressive pancytopenia, especially anemia and thrombocytopenia, along with splenomegaly and other symptoms, compromising quality of life.1

For nearly a decade, ruxolitinib has been the centerpiece therapy for patients with MF, markedly improving splenomegaly and constitutional symptoms and providing survival benefit.2 The second FDA-approved JAK2 inhibitor, fedratinib (Inrebic), may actually be a good second-line option for patients who are ruxolitinib-resistant with intermediate-2 and high-risk MF (primarily thrombocytopenic and characterized by platelet counts 50100 109/L).3 At present, 2 ongoing phase 3 clinical trials, the single-arm FREEDOM trial (NCT03755518) and the double-arm FREEDOM 2 trial (NCT03952039), are assessing the efficacy and safety of fedratinib in patients with MF who are resistant/refractory/intolerant to ruxolitinib. The FREEDOM trials are important because the previous JAKARTA studies (NCT01523171, NCT01437787) were placed on hold or terminated given concerns for the development of Wernicke encephalopathy. Pacritinib is a potent inhibitor of both JAK2 and fms-related receptor tyrosine kinase

3, or FLT3, but does not affect JAK1. Pacritinib is being evaluated in comparison with the physicians choice in an ongoing phase 3 trial (PACIFICA; NCT03165734) in patients with MF and severe thrombocytopenia (baseline platelet count < 50 109/L) at the optimal dose determined in the PAC203 study (200 mg twice daily; NCT03165734).3 Successful clinical development of pacritinib will provide a non-myelosuppressive JAK2 inhibitor for frontline treatment of patients with MF who have severe thrombocytopenia, a setting currently lacking approved drugs. Another JAK1/2 inhibitor that is in advanced clinical development and complements its predecessors is momelotinib, possessing the exclusive attribute to improve anemia, which becomes severe in patients with MF.3 At present, momelotinib is undergoing evaluation in patients who are symptomatic and anemic with advanced MF, previously treated with a JAK inhibitor, in a phase 3 trial (MOMENTUM; NCT04173494); the comparator drug is danazol.

Targeting anemia and thrombocytopenia. Given that patients with MF experience disease-associated and JAK inhibitor-induced anemia, several clinical trials have been evaluating drugs counteracting anemia, as monotherapies or in combination with ruxolitinib, in patients with MF-associated anemia.4 Currently, a global, multicenter phase 2 trial is under way to evaluate the safety and efficacy of luspatercept-aamt (Reblozyl), an activin receptor ligand trap that enhances late-stage erythropoiesis in patients with anemia and MF, including ruxolitinib-treated, transfusion-dependent individuals; a phase 3 trial (INDEPENDENCE) is planned for 2020. Interim results of the phase 2 study demonstrated significant efficacy of luspatercept-aamt, achieving reduction in red blood cell transfusion burden in ruxolitinib-treated patients with MF. Thalidomide (Thalomid), an immunomodulatory agent, significantly improved anemia and thrombocytopenia (platelet counts increased in 60% of patients) in a phase 2 trial evaluating ruxolitinib-treated patients with MF and baseline thrombocytopenia (NCT03069326).5

Synergistic combinations with ruxolitinib targeting epigenetics and JAK2 (TABLE). CPI-0610 is a selective bromodomain and extraterminal protein inhibitor that improved spleen volume, anemia, BM fibrosis, total symptom score, and transfusion dependence (alone or with ruxolitinib) in patients with MF who are enrolled in the global phase 2 MANIFEST study (NCT02158858).3 Furthermore, a phase 1 clinical trial combining an inhibitor of heat shock protein 90 (JAK2 is its chaperone protein), PU-H71, with ruxolitinib in patients with primary/secondary MF is under way (NCT03935555).3 The previous 2 trials are supported by preclinical data showing drug synergism. In a phase 2 trial of ruxolitinib/azacitidine (hypomethylating agent) in patients with MF, synergism was demonstrated in spleen length reduction and BM fibrosis improvement compared with ruxolitinib monotherapy (NCT01787487).5

Synergistic combinations with ruxolitinib targeting antiapoptotic proteins and JAK2. Navitoclax is an orally bioavailable inhibitor of the antiapoptotic B-cell lymphoma 2 (BCL2) family of proteins (primarily BCL extra-large [XL]). In preclinical studies, the nonclinical analogue of navitoclax, ABT-737, in combination with ruxolitinib showed synergism in inducing apoptosis of JAK2 V617F-driven MPN cell lines. Interim data from an ongoing phase 2 clinical trial evaluating navitoclax in combination with ruxolitinib in ruxolitinib-treated patients with MF (with baseline platelet count 100 109/L) showed reduction in spleen volume and BM fibrosis (1 grade) and improvement in total symptom score in a proportion of the patients (NCT03222609).3

Imetelstat is a short oligonucleotide telomerase inhibitor that possibly prolonged median overall survival in patients with MF in the higher-dose (9.4-mg/kg) arm of the phase 2 IMbark study (NCT02426086).3 A phase 3 trial comparing imetelstat to best available therapy in patients with refractory MF is planned for early 2021.

PRM-151, a plasma-derived analogue of the human antifibrotic protein pentraxin 2, improved BM fibrosis in mice models and patients with MF in preclinical and phase 1/2 clinical studies, respectively.3 The promising results merit a phase 3 trial, especially given the scarcity of antifibrotic agents.

The two relatively indolent MPN subtypes, polycythemia vera (PV) and essential thrombocythemia (ET), are characterized by abnorabnormal proliferation of myeloid cells, resulting in elevated blood counts (erythrocytosis and thrombocytosis in PV and ET, respectively), considerable risk of thrombosis and hemorrhage, and progression to secondary MF and acute myeloid leukemia (more common in PV than ET).6 In PV and ET, therapies are aimed at reducing risk of thrombosis, which is higher in patients over 60 years old or with a history of thrombosis, and in ET, when the calreticulin gene, CALR, is absent. A particularly promising agent for the two indolent MPNs is the long-acting ropeginterferon -2b, which was approved in Europe for frontline treatment of high-risk patients with PV and without symptomatic splenomegaly on the basis of the PROUD/CONTINUATION-PV studies [EudraCT, 2012-005259-18 (PROUD-PV) and 2014-001357- 17 (CONTINUATION-PV)].7 The previous investigations demonstrated superiority of ropeginterferon -2b versus hydroxyurea after 3 years of therapy. Besides awaiting possible approval of ropeginterferon -2b to treat patients with PV in the United States, a phase 3 trial of ropeginterferon -2b versus anagrelide in hydroxyurea-resistant/intolerant patients with ET has been planned to start in 2020. Givinostat, an inhibitor of histone deacetylases, demonstrated promising clinical responses (reduction in pruritus and thrombosis, and normalization of hematological parameters) in phase 1/2 studies in patients with JAK2 V617F positive PV and is entering a phase 3 trial in 2021.7 Currently, hydroxyurea and ruxolitinib are the first- and second-line treatments for high-risk patients with PV, respectively, and hydroxyurea is the first-line treatment for ET.

Herein we highlighted an array of drugs ranging from new JAK inhibitors to an antifibrotic agent, epigenetic modifiers, and telomerase and BCL-XL/BCL2 inhibitorsthat are in early or advanced clinical development in MPN. We are looking forward to enrichment of the MPN arsenal with new disease-modifying agents complementing the clinical benefits of ruxolitinib and fulfilling unmet needs in this population.

References:

1. Verstovsek S, Gotlib J, Mesa RA, et al. Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses. J Hematol Oncol. 2017;10(1):156. doi:10.1186/s13045-017-0527-7

2. Bose P, Verstovsek S. Management of myelofibrosis after ruxolitinib failure. Leuk Lymphoma. Published online April 16, 2020. doi:10.1080/1 0428194.2020.1749606

3. Bose P, Verstovsek S. Management of myelofibrosis-related cytopenias. Curr Hematol Malig Rep. 2018;13(3):164-172. doi:10.1007/s11899- 018-0447-9

3. Bose P, Alfayez M, Verstovsek S. New concepts of treatment for patients with myelofibrosis. Curr Treat Options Oncol. 2019;20(1):5. doi:10.1007/s11864-019-0604-y

4. Bose P, Verstovsek S. Updates in the management of polycythemia vera and essential thrombocythemia. Ther Adv Hematol. 2019;10:2040620719870052. doi:10.1177/2040620719870052

5. Gisslinger H, Klade C, Georgiev P, et al. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020;7(3):e196-e208. doi:10.1016/S2352- 3026(19)30236-4

6. Chifotides HT, Bose P, Verstovsek S. Givinostat: an emerging treatment for polycythemia vera. Expert Opin Investig Drugs. 2020;29(6):525- 536. doi:10.1080/13543784.2020.1761323

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New Therapies in Development for Myelofibrosis - Targeted Oncology

Recommendation and review posted by Bethany Smith

NEW YORK, Oct. 15, 2020 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of cellular therapies for neurodegenerative diseases, announced today financial results for the third quarter ended September 30, 2020, and provided a corporate update.

"The most important near-term event for BrainStorm will be the upcoming top-line data readout for the NurOwn Phase 3 trial in ALS, expected by the end of November. A successful outcome will set us on the path to filing a Biologic License Application (BLA) for what we believe will be a valuable new treatment for ALS," said Chaim Lebovits, Chief Executive Officer of BrainStorm Cell Therapeutics. "In parallel to our preparations for upcoming data read out, we are very busy planning and executing on other pre-BLA activities. On the management front, we appointed William K. White and Dr. Anthony Waclawski, adding valuable commercial and regulatory expertise to our leadership team. This expertise will be crucial as we work towards obtaining regulatory approval for NurOwn and ensuring that, if approved, it will be readily accessible to ALS patients in need of new treatment options for this devastating disease."

NurOwn has an innovative mechanism of action that is broadly applicable across neurodegenerative diseases and BrainStorm continues to invest in clinical trials evaluating the product in conditions beyond ALS to maximize value creation for its various stakeholders. The company remains on track to complete dosing in its Phase 2 clinical trial in progressive multiple sclerosis (PMS) by the end of 2020. In addition, the Company recently unveiled a clinical development program in Alzheimer's' disease (AD) and is planning a Phase 2 proof-of-concept clinical trial at several leading AD centers in the Netherlands and France.

Third Quarter 2020 and Recent Corporate Highlights:

Presented at the following Investor Conferences:

Cash and Liquidity as of October 14, 2020

Total available funding as of October 14, 2020, which includes cash, cash equivalents and short-term bank deposits of approximately $33.1 million as well as remaining non-dilutive funding from CIRM, IIA and other grants, amounts to approximately $36 million.

Financial Results for the Three Months Ended September 30, 2020

Conference Call & WebcastThursday, October 15, 2020 at 8 a.m. Eastern TimeFrom the US: 877-407-9205International: 201-689-8054Webcast: https://www.webcaster4.com/Webcast/Page/2354/37811

Replays, available through October 29, 2020From the US: 877-481-4010International: 919-882-2331Replay Passcode: 37811

About NurOwn

NurOwn (autologous MSC-NTF) cells represent a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. BrainStorm has fully enrolled a Phase 3 pivotal trial of autologous MSC-NTF cells for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm also recently received acceptance from the U.S. Food and Drug Administration (FDA) to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS) and completed enrollment in August 2020.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug status designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has fully enrolled a Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six U.S. sites supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). The pivotal study is intended to support a filing for U.S. FDA approval of autologous MSC-NTF cells in ALS. BrainStorm also recently received U.S. FDA clearance to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS). The Phase 2 study of autologous MSC-NTF cells in patients with progressive MS (NCT03799718) completed enrollment in August 2020. For more information, visit the company's website at http://www.brainstorm-cell.com.

Safe-Harbor Statement

Statements in this announcement other than historical data and information, including statements regarding future clinical trial enrollment and data, constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may", "should", "would", "could", "will", "expect", "likely", "believe", "plan", "estimate", "predict", "potential", and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorm's need to raise additional capital, BrainStorm's ability to continue as a going concern, regulatory approval of BrainStorm's NurOwn treatment candidate, the success of BrainStorm's product development programs and research, regulatory and personnel issues, development of a global market for our services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorm's NurOwn treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorm's ability to manufacture and commercialize the NurOwn treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorm's ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation,; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at http://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

ContactsInvestor Relations:Corey Davis, Ph.D.LifeSci Advisors, LLCPhone: +1 646-465-1138cdavis@lifesciadvisors.com

Media:Paul TyahlaSmithSolvePhone: + 1.973.713.3768Paul.tyahla@smithsolve.com

BRAINSTORM CELL THERAPEUTICS INC. AND SUBSIDIARIESINTERIM CONDENSED CONSOLIDATED BALANCE SHEETSU.S. dollars in thousands(Except share data)

September 30,

December 31,

2020

2019

U.S. $ in thousands

Unaudited

Audited

ASSETS

Current Assets:

Cash and cash equivalents

$

24,770

$

536

Short-term deposit (Note 4)

4,038

33

Other accounts receivable

1,473

2,359

Prepaid expenses and other current assets (Note 5)

56

432

Total current assets

30,337

3,360

Long-Term Assets:

Prepaid expenses and other long-term assets

27

32

Operating lease right of use asset (Note 6)

1,377

2,182

Property and Equipment, Net

950

960

Total Long-Term Assets

2,354

3,174

Total assets

$

32,691

$

6,534

LIABILITIES AND STOCKHOLDERS' EQUITY (DEFICIT)

Current Liabilities:

Accounts payable

$

3,283

$

14,677

Accrued expenses

917

1,000

Operating lease liability (Note 6)

1,216

1,263

Other accounts payable

1,013

714

Total current liabilities

6,429

17,654

Long-Term Liabilities:

Operating lease liability (Note 6)

284

1,103

Total long-term liabilities

284

1,103

Total liabilities

$

6,713

$

18,757

Stockholders' Equity (deficit):

Stock capital: (Note 7)

12

11

Common Stock of $0.00005 par value - Authorized: 100,000,000 shares at September 30, 2020 and December 31, 2019 respectively; Issued and outstanding: 31,567,592 and 23,174,228 shares at September 30, 2020 and December 31, 2019 respectively.

Additional paid-in-capital

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BrainStorm Announces Financial Results for the Third Quarter of 2020 and Provides a Corporate Update - BioSpace

Recommendation and review posted by Bethany Smith

SAN DIEGO--(BUSINESS WIRE)--Robbins Geller Rudman & Dowd LLP announces that a class action lawsuit has been filed in the Southern District of New York on behalf of purchasers or acquirers of Mesoblast Limited (NASDAQ:MESO) securities between April 16, 2019 and October 1, 2020, inclusive (the Class Period). The case is captioned Kristal v. Mesoblast Limited, No. 20-cv-08430, and is assigned to Judge Philip M. Halpern. The Mesoblast class action lawsuit charges Mesoblast and certain of its executives with violations of the Securities Exchange Act of 1934.

The Private Securities Litigation Reform Act of 1995 permits any investor who purchased Mesoblast securities during the Class Period to seek appointment as lead plaintiff in the Mesoblast class action lawsuit. A lead plaintiff will act on behalf of all other class members in directing the Mesoblast class action lawsuit. The lead plaintiff can select a law firm of its choice to litigate the Mesoblast class action lawsuit. An investors ability to share in any potential future recovery of the Mesoblast class action lawsuit is not dependent upon serving as lead plaintiff. If you wish to serve as lead plaintiff of the Mesoblast class action lawsuit or have questions concerning your rights regarding the Mesoblast class action lawsuit, please provide your information here or contact counsel, J.C. Sanchez of Robbins Geller, at 800/449-4900 or 619/231-1058 or via e-mail at jsanchez@rgrdlaw.com. Lead plaintiff motions for the Mesoblast class action lawsuit must be filed with the court no later than December 7, 2020.

Mesoblast develops allogeneic cellular medicines using its mesenchymal lineage cell therapy platform. Mesoblasts lead product candidate, RYONCIL (remestemcel-L), is an investigational therapy comprising mesenchymal stem cells derived from bone marrow. In February 2018, Mesoblast announced that remestemcel-L met its primary endpoint in a Phase 3 trial to treat children with steroid refractory acute graft versus host disease (SR-aGVHD). In early 2020, Mesoblast completed its rolling submission of its Biologics License Application with the U.S. Food and Drug Administration (FDA) to secure marketing authorization to commercialize remestemcel-L for children with SR-aGVHD.

The Mesoblast class action lawsuit alleges that during the Class Period defendants made false and/or misleading statements and/or failed to disclose that: (1) comparative analyses between Mesoblasts Phase 3 trial and three historical studies did not support the effectiveness of remestemcel-L for SR-aGVHD due to design differences between the four studies; (2) thus, the FDA was reasonably likely to require Mesoblast to conduct further clinical studies; (3) as such, Mesoblasts commercialization of remestemcel-L in the United States was likely to be delayed; and (4) as a result of the foregoing, defendants positive statements about Mesoblasts business, operations, and prospects were materially misleading and/or lacked a reasonable basis.

On August 11, 2020, the FDA released briefing materials for its Oncologic Drugs Advisory Committee meeting revealing that Mesoblast provided post hoc analyses of other studies to further establish the appropriateness of 45% as the null Day-28 overall response rate for its primary endpoint. The briefing materials further stated that, due to design differences between these historical studies and Mesoblasts submitted study, it is unclear that these study results are relevant to the proposed indication. On this news, Mesoblasts share price fell by nearly 35%.

Then, on October 1, 2020, Mesoblast disclosed that it had received a Complete Response Letter (CRL) from the FDA regarding its marketing application for remestemcel-L for treatment of SR-aGVHD in pediatric patients. According to the CRL, the FDA recommended that Mesoblast conduct at least one additional randomized, controlled study in adults and/or children to provide further evidence of the effectiveness of remestemcel-L for SR-aGVHD. The CRL also identified a need for further scientific rationale to demonstrate the relationship of potency measurements to the products biologic activity. On this news, Mesoblasts share price fell an additional 35%, further damaging investors.

Robbins Geller Rudman & Dowd LLP is one of the worlds leading law firms representing investors in securities class action litigation. With 200 lawyers in 9 offices, Robbins Geller has obtained many of the largest securities class action recoveries in history. For seven consecutive years, ISS Securities Class Action Services has ranked the Firm in its annual SCAS Top 50 Report as one of the top law firms in the world in both amount recovered for shareholders and total number of class action settlements. Robbins Geller attorneys have helped shape the securities laws and have recovered tens of billions of dollars on behalf of aggrieved victims. Beyond securing financial recoveries for defrauded investors, Robbins Geller also specializes in implementing corporate governance reforms, helping to improve the financial markets for investors worldwide. Robbins Geller attorneys are consistently recognized by courts, professional organizations, and the media as leading lawyers in the industry. Please visit http://www.rgrdlaw.com for more information.

Continue reading here:
Notice of Lead Plaintiff Deadline for Shareholders in the Mesoblast Limited Class Action Lawsuit - Business Wire

Recommendation and review posted by Bethany Smith

Acute Lymphoblastic Leukemia (AML), also called acute myeloblastic leukemia, acute myelogenous leukemia, acute myeloid leukemia, or acute nonlymphocytic leukemia, is an aggressive, fast-growing, heterogenous group of blood cancers that arise as a result of clonal expansion of myeloid hematopoietic precursors in the bone marrow. Not only are circulating leukemia (blast) cells seen in the peripheral blood, but granulocytopenia, anemia, and thrombocytopenia are also common as proliferating leukemia cells interfere with normal hematopoiesis.

Approximately 40-45% of younger and 10-20% of older adults diagnosed with AML are cured with current standard chemotherapy. However, the outlook for patients with relapsed and/or refractory disease is gloomy. Relapse following conventional chemotherapy remains is a major cause of death.

The process of manufacturing chimeric antigen receptor (CAR) T-cell therapies. [1] T-cells (represented by objects labeled as t) are removed from the patients blood. [2] Then in a lab setting the gene that encodes for the specific antigen receptors is incorporated into the T-cells. [3] Thus producing the CAR receptors (labeled as c) on the surface of the cells. [4] The newly modified T-cells are then further harvested and grown in the lab. [5]. After a certain time period, the engineered T-cells are infused back into the patient. This file is licensed by Reyasingh56 under the Creative Commons Attribution-Share Alike 4.0 International license.Today, the only curative treatment option for patients with AML is allogeneic hematopoietic stem cell transplantation or allo-HSCT, which through its graft-vs.-leukemia effects has the ability to eliminate residual leukemia cells. But it is an ption for only a minority. And despite a long history of success, relapse following allo-HSCT is still a major challenge and is associated with poor prognosis.

In recent years, rresearchers learned a lot about the genomic and epigenomic landscapes of AML. This understanding has paved the way for rational drug development as new drugable targets, resulting in treatments including the antibody-drug conjugate (ADC) gemtuzumab ozogamycin (Mylotarg; Pfizer/Wyeth-Ayerst Laboratories).

CAR T-cell TherapiesChimeric antigen receptor (CAR) T-cells therapies, using a patients own genetically modified T-cells to find and kill cancer, are one of the most exciting recent developments in cancer research and treatment.

Traditional CAR T-cell therapies are an autologous, highly personalised, approach in which T-cells are collected from the patient by leukopheresis and engineered in the laboratory to express a receptor directed at a cancer antigen such as CD19. The cells are then infused back into the patient after administration of a lymphodepletion regimen, most commonly a combination of fludarabine and cyclophosphamide. Durable remissions have been observed in pediatric patients with B-ALL and adults with NHL.

CD19-targeted CAR T-cell therapies, have, over the last decade, yielded remarkable clinical success in certain types of B-cell malignancies, and researchers have made substantial efforts aimed at translating this success to myeloid malignancies.

While complete ablation of CD19-expressing B cells, both cancerous and healthy, is clinically tolerated, the primary challenge limiting the use of CAR T-cells in myeloid malignancies is the absence of a dispensable antigen, as myeloid antigens are often co-expressed on normal hematopoietic stem/progenitor cells (HSPCs), depletion of which would lead to intolerable myeloablation.

A different approachBecause autologous CAR T-cell therapies are patient-specific, each treatment can only be used for that one patient. Furthermore, because CAR T-cells are derived from a single disease-specific antibody, they are, by design, only recognized by one specific antigen. As a consequence, only a small subset of patients with any given cancer may be suited for the treatment.

This specificity means that following leukopheresis, a lot of work needs to be done to create this hyper personalised treatment option, resulting in 3 5 weeks of manufacturing time.

The manufacturing process of CAR T-cell therapies, from a single academic center to a large-scale multi-site manufacturing center further creates challenges. Scaling out production means developing processes consistent across many collection, manufacturing, and treatment sites. This complexity results in a the realitively high cost of currently available CAR T-cell therapies.

To solve some of the concerns with currently available CAR T-cell therapies, researchers are investigating the option to develop allogenic, off-the-shelf Universal CAR T-cell (UCARTs) treatments that can be mass manufactured and be used for multiple patients.

Allogeneic CAR T-cell therapy are generally created from T-cells from healthy donors, not patients. Similar to the autologous approach, donor-derived cells are shipped to a manufacturing facility to be genetically engineered to express the antibody or CAR, however, in contrast to autologous CAR T-cells, allogeneic CAR T-cells are also engineered with an additional technology used to limit the potential for a graft versus host reaction when administered to patients different from the donor.

One unique benefit ofn this approach is that because these therapies hey are premade and available for infusion, there is no requirement to leukopheresis or a need to wait for the CAR T-cells to be manufactured. This strategy also will benefit patients who are cytopenic (which is not an uncommon scenario for leukemia patients) and from whom autologous T-cell collection is not possible.

PioneersAmong the pioneers of developing allogeneic CAR-T therapies are companies including Celyad Oncology, Cellectis, Allogene Therapeutics, and researchers at University of California, Los Angeles (UCLA) in colaboration with Kite/Gilead.

Researchers at UCLA were, for example, able to turn pluripotent stem cells into T-cells through structures called artificial thymic organoids. These organoids mimic the thymus, the organ where T-cells are made from blood stem cells in the body.

Celyad OncologyBelgium-based Celyad Oncology is advancing a number of both autologous and allogeneic CAR T-cell therapies, including proprietary, non-gene edited allogeneic CAR T-cell candidates underpinned by the companys shRNA technology platform. The shRNA platform coupled with Celyads all-in-one vector approach provides flexibility, versatility, and efficiency to the design of novel, off-the-shelf CAR T-cell candidates through a single step engineering process.

In July 2020, the company announced the start of Phase I trials with CYAD-211, Celyads first-in-class short hairpin RNA (shRNA)-based allogeneic CAR T candidate and second non-gene edited off-the-shelf program. CYAD-211 targets B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma and is engineered to co-express a BCMA-targeting chimeric antigen receptor and a single shRNA, which interferes with the expression of the CD3 component of the T-cell receptor (TCR) complex.

During the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program in May 2020, the company presented updates from its allogeneic programs, including additional data from the alloSHRINK study, an open-label, dose-escalation Phase I trial assessing the safety and clinical activity of three consecutive administrations of CYAD-101, an investigational, non-gene edited, allogeneic CAR T-cell candidate engineered to co-express a chimeric antigen receptor based on NKG2D (a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands and the novel inhibitory peptide TIM TCR Inhibitory Molecule), for the treatment of metastatic colorectal cancer (mCRC).

The expression of TIM reduces signalling of the TCR complex, which is responsible for graft-versus host disease.every two weeks administered concurrently with FOLFOX (combination of 5-fluorouracil, leucovorin and oxaliplatin) in patients with refractory metastatic colorectal cancer (mCRC).

The safety and clinical activity data from the alloSHRINK trial in patients with mCRC demonstrated CYAD-101s differentiated profile as an allogeneic CAR T-cell candidate. Furthermore, the absence of clinical evidence of graft-versus-host-disease (GvHD) for CYAD-101 confirms the potential of non-gene edited approaches for the development of allogeneic CAR-T candidates.

Interim data from the alloSHRINK trial showed encouraging anti-tumor activity, with two patients achieving a confirmed partial response (cPR) according to RECIST 1.1 criteria, including one patient with a KRAS-mutation, the most common oncogenic alteration found in all human cancers. In addition, nine patients achieved stable disease (SD), with seven patients demonstrating disease stabilization lasting more than or equal to three months of duration.

Based on these results, clinical trials were broadened to include evaluating CYAD-101 following FOLFIRI (combination of 5-fluorouracil, leucovorin and irinotecan) preconditioning chemotherapy in refractory mCRC patients, at the recommended dose of one billion cells per infusion as an expansion cohort of the alloSHRINK trial. Enrollment in the expansion cohort of the trial is expected to begin during the fourth quarter of 2020.

CellectisCellectis is developping a universal CAR T-cell (UCART) platform in an attempy to create off-the-shelf CAR T-cell therapies. The companys pipeline includes UCART123, a CAR T-cell therapy designed to targets CD123+ leukemic cells in acute myeloid leukemia (AML). The investigational agent is being studied in two open-label Phase I trials: AML123 studying the therapys safety and efficacy in an estimated 156 AML patients, and ABC123 studying the therapys safety and activity in an estimated 72 patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

UCART22Another investigational agent in clinical trials is UCART22 which is designed to treat both CD22+ B-cell acute lymphoblastic leukemia (B-ALL) and CD22+ B-cell non-Hodgkin lymphoma (NHL). Cellectis reported that UCART22 is included in an open-label, dose-escalating Phase I trial to study its safety and activity in relapsed or refractory CD22+ B-ALL patients.

UCART22 harbors a surface expression of an anti-CD22 CAR (CD22 scFv-41BB-CD3z) and the RQR8 ligand, a safety feature rendering the T-cells sensitive to the antibody rituximab. Further, to reduce the potential for alloreactivity, the cell surface expression of the T-cell receptor is abrogated through the inactivation of the TCR constant (TRAC) gene using Cellectis TALEN gene-editing technology.[1]

Preclinical data supporting the development of UCART22 was presented by Marina Konopleva, M.D., Ph.D. and her vteam during the 2017 annual meeting of the American Society of Hematology (ASH) meeting. [1]

Cellectis is also developing UCARTCS1 which is developed to treat CS1-expressing hematologic malignancies, such as multiple myeloma (MM). UCARTCLL1 is in preclinical development for treating CLL1-expressing hematologic malignancies, such as AML.

Cellectis and Allogene Therapeutics, another biotech company involved in the developmen t of CAR T-cell therapies, are developing ALLO-501, another CAR T-cell therapy which targets CD19 and is being developed for the the treatment of patients with relapsed or refractory NHL. Allogene Therapeutics is also developing ALLO-715, an investigational CAR T-cell therapy targeting the B-cell maturation antigen (BCMA) for treating relapsed or refractory multiple myeloma and ALLO-819, which targets CD135 (also called FLT3), for treating relapsed or refractory AML.

Allogene, in collaboration with both Cellectis, Pfizer (which has a 25% stake in Allogene) and Servier have numerous active open-label, single-arm Phase I trials for an off-the-shelf allogeneic CAR-T therapy UCART19* in patients with relapsed or refractory CD19+ B-ALL. Participating patients receive lymphodepletion with fludarabine and cyclophosphamide with alemtuzumab, followed by UCART19 infusion. Adults patients with R/R B-ALL are eligible.

The PALL aims to evaluate the safety and feasibility of UCART19 to induce molecular remission in pediatric patients with relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) in 18 pediatric patients.

The CALM trial is a dose-escalating study evaluating the therapys safety and tolerability in 40 adult patients; and a long-term safety and efficacy follow-up study in 200 patients with advanced lymphoid malignancies.

Allogene reported preliminary proof-of-concept results during the annual meeting of the American Society of Hematology (ASH) in December 2018.

Data from the first 21 patients from both the PALL (n=7) and CALM (n=14) Phase I studies were pooled. The median age of the participating patients was 22 years (range, 0.8-62 years) and the median number of prior therapies was 4 (range, 1-6). Sixty-two percent of the patients (13/21) had a prior allogeneic stem cell transplant.

Of the 17 patients who received treatment with UCART19 and who received lymphodepletion with fludarabine, cyclophosphamide and alemtuzumab, an anti-CD52 monoclonal antibody, 14 patients (82%) achieved CR/CRi, and 59% of them (10/17) achieved MRD-negative remission.

In stark contrast, the four patients who only received UCART19 and fludarabine and cyclophosphamide without alemtuzumab did not see a response and minimal UCART19 expansion.

Based on these results, researchers noted that apparent importance of an anti-CD52 antibody for the efficacy of allogeneic CAR-T therapies. In addition, safety data also looked promising. The trial results did not include grade 3 or 4 neurotoxicity and only 2 cases of grade 1 graft-versus-host disease (10%), 3 cases of grade 3 or 4 cytokine release syndrome which were considered manageable (14%), 5 cases of grade 3 or 4 viral infections (24%), and 6 cases of grade 4 prolonged cytopenia (29%).

Precision BiosciencesPrecision Biosciences is developing PBCAR0191, an off-the-shelf investigational allogeneic CAR T-cell candidate targeting CD19. The drug candidate is being investigated in a Phase I/IIa multicenter, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study for the treatment of patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) or R/R B-cell precursor acute lymphoblastic leukemia (B-ALL).

The NHL cohort includes patients with mantle cell lymphoma (MCL), an aggressive subtype of NHL, for which Precision has received both Orphan Drug and Fast Track Designations from the U.S. Food and Drug Administration (FDA).

A clinical trial with PBCAR0191 Precision Biosciences is exploring some novel lymphodepletion strategies in addition to fludarabine and cyclophosphamide. Patients with R/R ALL, R/R CLL, R/R Richter transformation, and R/R NHL are eligible. Patients with MRD+ B-ALL are eligible as well. This trial is enrolling patients.

In late September 2020, Precision BioSciences, a clinical stage biotechnology amd Servier, announced the companies have added two additional hematological cancer targets beyond CD19 and two solid tumor targets to its CAR T-cell development and commercial license agreement.

PBCAR20APBCAR20A is an investigational allogeneic anti-CD20 CAR T-cell therapy being developed by Precision Biosciences for the treartment of patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) and patients with R/R chronic lymphocytic leukemia (CLL) or R/R small lymphocytic lymphoma (SLL). The NHL cohort will include patients with mantle cell lymphoma (MCL), an aggressive subtype of NHL, for which Precision BioSciences has received orphan drug designation from the United States Food and Drug Administration (FDA).

PBCAR20A is being evaluated in a Phase I/IIa multicenter, nonrandomized, open-label, dose-escalation and dose-expansion clinical trial in adult NHL and CLL/SLL patients. The trial will be conducted at multiple U.S. sites.

PBCAR269APrecision Biosciences is, in collaboration with Springworks Therapeutics, also developing PBCAR269A, an allogeneic BCMA-targeted CAR T-cell therapy candidate being evaluated for the safety and preliminary clinical activity in a Phase I/IIa multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study of adults with relapsed or refractory multiple myeloma. In this trial, the starting dose of PBCAR269A is 6 x 105 CAR T cells/kg body weight with subsequent cohorts receiving escalating doses to a maximum dose of 6 x 106 CAR T cells/kg body weight.

PBCAR269A is Precision Biosciencess third CAR T-cell candidate to advance to the clinic and is part of a pipeline of cell-phenotype optimized allogeneic CAR T-cell therapies derived from healthy donors and then modified via a simultaneous TCR knock-out and CAR T-cell knock-in step with the =companys proprietary ARCUS genome editing technology.

The FDA recently granted Fast Track Designation to PBCAR269A for the treatment of relapsed or refractory multiple myeloma for which the FDA previously granted Orphan Drug Designation.

TCR2 TherapeuticsTCR2 Therapeutics is developing a proprietary TRuC (TCR Fusion Construct) T-cells designed to harness the natural T cell receptor complex to recognize and kill cancer cells using the full power of T-cell signaling pathways independent of the human leukocyte antigen (HLA).

While succesful in hematological malignancies, CAR T-cells therapies have generally struggled to show efficacy against solid tumors. Researchers at TCR2 Therapeutics believe this is is caused by the fact that CAR T-cell therapies only utilize a single TCR subunit, and, as a result, do not benefit from all of the activation and regulatory elements of the natural TCR complex. By engineering TCR T-cells, which are designed to utilize the complete TCR, they have demonstrated clinical activity in solid tumors. However, this approach has also shown major limitations. TCR T-cells require tumors to express HLA to bind tumor antigens. HLA is often downregulated in cancers, preventing T-cell detection. In addition, each specific TCR-T cell therapy can only be used in patients with one of several specific HLA subtypes, limiting universal applicability of this approach and increasing the time and cost of patient enrollment in clinical trials.

In an attempt to solve this problem, researchers at TCR2 Therapeutics have developped a proprieatarry TRuC-T Cells which are designed to incorporate the best features of CAR-T and TCR-T cell therapies and overcome the limitations. The TRuC platform is a novel T cell therapy platform, which uses the complete TCR complex without the need for HLA matching.

By conjugating the tumor antigen binder to the TCR complex, the TRuC construct recognizes highly expressed surface antigens on tumor cells without the need for HLA and engage the complete TCR machinery to drive the totality of T-cell functions required for potent, modulated and durable tumor killing.

In preclinical studies, TCR2 Therapeutics TRuC T-cells technology has demonstrated superior anti-tumor activity in vivo compared to CAR T-cells therapies, while, at the same time, releasing lower levels of cytokines. These data are encouraging for the treatment of solid tumors where CAR T-cells have not shown significant clinical activity due to very short persistence and for hematologic tumors where a high incidence of severe cytokine release syndrome remains a major concern.

TCR2 Therapeutics product candidates include TC-210 and TC-110.

TC-210 is designed to targets mesothelin-positive solid tumors. While its expression in normal tissues is low, mesothelin is highly expressed in many solid tumors. Mesothelin overexpression has also been correlated with poorer prognosis in certain cancer types and plays a role in tumorigenesis. TC-210 is being developed for the treatment of non-small cell lung cancer, ovarian cancer, malignant pleural/peritoneal mesothelioma and cholangiocarcinoma.

The companys TRuC-T cell targeting CD19-positive B-cell hematological malignancies, TC-110, is being developed to improve upon and address the unmet needs of current CD19-directed CAR T-cell therapies. The clinical development TC-110 focus on the treatment of adult acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Preclinical data demonstrates that TC-110 is superior to CD19-CAR-T cells (carrying either 4-1BB or CD28 co-stimulatory domains) both in anti-tumor activity as well as the level of cytokine release which may translate into lower rates of adverse events. The development of TC-110 starts with autologous T-cells collection by leukopheresis. These T-cells undergo genetic engineering to create TRuC-T cells targeting CD19.

This strategy combines the best features of CAR T-cells and the native T-cell receptor. It is open for R/R NHL and R/R B-ALL.

AUTO1Auto1 is an autologous CD19 CAR T-cell investigational therapyis being developped by Autolus Therapeutics. The investigational drug uses a single-chain variable fragment (scFv) called CAT with a lower affinity for CD19 and a faster off-rate compared to the FMC63 scFv used in other approved CD19 CAR T-cell therapies. The investigational therapy is designed to overcome the limitations in safety while maintaining similar levels of efficacy compared to current CD19 CAR T-cell therapies.

Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T-cells, AUTO1 may reduce toxicity and be less prone to T-cell exhaustion, which could enhance persistence and improve the T-cells abilities to engage in serial killing of target cancer cells.

In 2018, Autolus signed a license agreement UCL Business plc (UCLB), the technology-transfer company of UCL, to develop and commercialize AUTO1 for the treatment of B cell malignancies. AUTO1 is currently being evaluated in two Phase I studies, one in pediatric ALL and one in adult ALL.

CARPALL trialInitial results from the ongoing Phase I CARPALL trial of AUTO1 were presented during European Hematology Association 1st European CAR T Cell Meeting held in Paris, France, February 14-16, 2019.

Enrolled patients had a median age of 9 years with a median of 4 lines of prior treatment. Seventeen patients were enrolled, and 14 patients received an infusion of CAR T cells. Ten of 14 patients had relapsed post allogeneic stem cell transplant. Eight patients were treated in second relapse, 5 in > second relapse and 3 had relapsed after prior blinatumomab or inotuzumab therapy. Two patients had ongoing CNS disease at enrollment.

This data confirmed that AUTO1 did not induces severe cytokine release syndrome (CRS) (Grade 3-5). Nine patients experienced Grade 1 CRS, and 4 patients experienced Grade 2 CRS. No patients required tociluzumab or steroids. As previously reported, one patient experienced Grade 4 neurotoxicity; there were no other reports of severe neurotoxicity (Grade 3-5). The mean cumulative exposure to AUTO1 CAR T-cells in the first 28 days as assessed by AUC was 1,721,355 copies/g DNA. Eleven patients experienced cytopenia that was not resolved by day 28 or recurring after day 28: 3 patients Grades 1-3 and 8 patients Grade 4. Two patients developed significant infections, and 1 patient died from sepsis while in molecular complete response (CR).

With a single dose of CAR T cells at 1 million cells/kg dose, 12/14 (86%) achieved molecular CR. Five patients relapsed with CD19 negative disease. Event free survival (EFS) based on morphological relapse was 67% (CI 34-86%) and 46% (CI 16-72%) and overall survival (OS) was 84% (CI 50-96%) and 63% (CI 27-85%) at 6 and 12 months, respectively.

CAR T cell expansion was observed in all responding patients (N=12), with CAR T cells comprising up to 84% of circulating T cells at the point of maximal expansion. The median persistence of CAR T-cells was 215 days.

The median duration of remission in responding patients was 7.3 months with a median follow-up of 14 months. Five of 14 patients (37%) remain in CR with ongoing persistence of CAR T-cells and associated B cell aplasia.

Fate TherapeuticsFT819 is an off-the-shelf CAR T-cell therapy targeting CD19 being developed by Fate Therapeutics. The T-cells are derived from a clonal engineered master induced pluripotent stem cell line (iPSCs) with a novel 1XX CAR targeting CD19 inserted into the T-cell receptor alpha constant (TRAC) locus and edited for elimination of T-cell receptor (TCR) expression.

Patients participating in the companys clinbical trial will receive lymphodepletion with fludarabine and cyclophosphamide. Some patients will also receive IL-2. Patients with R/R ALL, R/R CLL, R/R Richter transformation, and R/R NHL are eligible. Patients with MRD+ B-ALL are eligible as well.

At the Annual Meeting of the American Societ of Hematology held in December 2019, researchers from Fate Therapeutics presented new in vivo preclinical data demonstrating that FT819 exhibits durable tumor control and extended survival. In a stringent xenograft model of disseminated lymphoblastic leukemia, FT819 demonstrated enhanced tumor clearance and control of leukemia as compared to primary CAR19 T-cells. At Day 35 following administration, a bone marrow assessment showed that FT819 persisted and continued to demonstrate tumor clearance, whereas primary CAR T cells, while persisting, were not able to control tumor growth. [2]

CAR-NK CD19Allogeneic cord blood-derived Natural Killer (NK) cells are another off-the-shelf product that does not require the collection of cells from each patient.

Unlike T-cells, NK-cells do not cause GVHD and can be given safely in the allogeneic setting. At MD Anderson Cancer Center, Katy Rezvani, M.D., Ph.D, Professor, Stem Cell Transplantation and Cellular Therapy, and her team broadly focuses their research on the role of natural killer (NK) cells in mediating protection against hematologic malignancies and solid tumors and strategies to enhance killing function against various cancer.

As part of their research, the team has developed a novel cord blood-derived NK-CAR product that expresses a CAR against CD19; ectopically produces IL-15 to support NK-cell proliferation and persistence in vivo; and expresses a suicide gene, inducible caspase 9, to address any potential safety concerns.

In this phase I and II trial researchers administered HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood to 11 patients with relapsed or refractory CD19-positive cancers (non-Hodgkins lymphoma or chronic lymphocytic leukemia [CLL]). NK cells were transduced with a retroviral vector expressing genes that encode anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch. The cells were expanded ex vivo and administered in a single infusion at one of three doses (1105, 1106, or 1107 CAR-NK cells per kilogram of body weight) after lymphodepleting chemotherapy. The preliminarry resilts of the trials confirmed that administration of CAR-NK cells was not associated with the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, and there was no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline.

The study results also demonstrated that of the 11 patients who were treated, 8 patients (73%) had a response. Of these patients, 7 (4 with lymphoma and 3 with CLL) had a complete remission ICR), and 1 had remission of the Richters transformation component but had persistent CLL. Noteworthy was that responses were rapid and seen within 30 days after infusion at all dose levels. The infused CAR-NK cells expanded and persisted at low levels for at least 12 months. The researchers also noted that a majority of the 11 participating patients with relapsed or refractory CD19-positive cancers had a response to treatment with CAR-NK cells without the development of major toxic effects.[3]

Note* Servier will hold ex-US commercial rights. Servier is the sponsor of the UCART19 trials.

Clinical trialsalloSHRINK Standard cHemotherapy Regimen and Immunotherapy With Allogeneic NKG2D-based CYAD-101 Chimeric Antigen Receptor T-cells NCT03692429Study Evaluating Safety and Efficacy of UCART123 in Patients With Relapsed/ Refractory Acute Myeloid Leukemia (AMELI-01) NCT03190278Study to Evaluate the Safety and Clinical Activity of UCART123 in Patients With BPDCN (ABC123) NCT03203369Study of UCART19 in Pediatric Patients With Relapsed/Refractory B Acute Lymphoblastic Leukemia (PALL) NCT02808442Dose Escalation Study of UCART19 in Adult Patients With Relapsed / Refractory B-cell Acute Lymphoblastic Leukaemia (CALM) NCT02746952Dose-escalation Study of Safety of PBCAR0191 in Patients With r/r NHL and r/r B-cell ALL NCT03666000.Dose-escalation Study of Safety of PBCAR20A in Subjects With r/r NHL or r/r CLL/SLL NCT04030195A Dose-escalation Study to Evaluate the Safety and Clinical Activity of PBCAR269A in Study Participants With Relapsed/Refractory Multiple Myeloma NCT04171843TC-110 T Cells in Adults With Relapsed or Refractory Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia NCT04323657Phase 1/2 Trial of TC-210 T Cells in Patients With Advanced Mesothelin-Expressing Cancer NCT03907852CARPALL: Immunotherapy With CD19 CAR T-cells for CD19+ Haematological Malignancies NCT02443831Umbilical & Cord Blood (CB) Derived CAR-Engineered NK Cells for B Lymphoid Malignancies NCT03056339

Reference[1] Petti F. Broadening the Applicability of CAR-T Immunotherapy to Treat the Untreatable. OncoZine. October 24, 2019 [Article][2] Wells J, Cai T, Schiffer-Manniou C, Filipe S, Gouble A, Galetto R, Jain N, Jabbour EJ, Smith J, Konopleva M. Pre-Clinical Activity of Allogeneic Anti-CD22 CAR-T Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia Blood (2017) 130 (Supplement 1): 808. https://doi.org/10.1182/blood.V130.Suppl_1.808.808%5B3%5D Chang C, Van Der Stegen S, Mili M, Clarke R, Lai YS, Witty A, Lindenbergh P, Yang BH, et al. FT819: Translation of Off-the-Shelf TCR-Less Trac-1XX CAR-T Cells in Support of First-of-Kind Phase I Clinical Trial. Blood (2019) 134 (Supplement_1): 4434.https://doi.org/10.1182/blood-2019-130584%5B4%5D Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, Nassif Kerbauy L, Overman B, Thall P, Kaplan M, Nandivada V, Kaur I, Nunez Cortes A, Cao K, Daher M, Hosing C, Cohen EN, Kebriaei P, Mehta R, Neelapu S, Nieto Y, Wang M, Wierda W, Keating M, Champlin R, Shpall EJ, Rezvani K. Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors. N Engl J Med. 2020 Feb 6;382(6):545-553. doi: 10.1056/NEJMoa1910607. PMID: 32023374; PMCID: PMC7101242.

Featured image: T-cells attacking a cancer cell. Photo courtesy: Fotolia/Adobe 2016 2020. Used with permission.

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CAR T-cell Therapies for the Treatment of Patients with Acute Lymphoblastic Leukemia - OncoZine

Recommendation and review posted by Bethany Smith

BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of cellular therapies for neurodegenerative diseases, announced today financial results for the third quarter ended September 30, 2020, and provided a corporate update.

"The most important near-term event for BrainStorm will be the upcoming top-line data readout for the NurOwn Phase 3 trial in ALS, expected by the end of November. A successful outcome will set us on the path to filing a Biologic License Application (BLA) for what we believe will be a valuable new treatment for ALS," said Chaim Lebovits, Chief Executive Officer of BrainStorm Cell Therapeutics. "In parallel to our preparations for upcoming data read out, we are very busy planning and executing on other pre-BLA activities. On the management front, we appointed William K. White and Dr. Anthony Waclawski, adding valuable commercial and regulatory expertise to our leadership team. This expertise will be crucial as we work towards obtaining regulatory approval for NurOwn and ensuring that, if approved, it will be readily accessible to ALS patients in need of new treatment options for this devastating disease."

NurOwn has an innovative mechanism of action that is broadly applicable across neurodegenerative diseases and BrainStorm continues to invest in clinical trials evaluating the product in conditions beyond ALS to maximize value creation for its various stakeholders. The company remains on track to complete dosing in its Phase 2 clinical trial in progressive multiple sclerosis (PMS) by the end of 2020. In addition, the Company recently unveiled a clinical development program in Alzheimer's' disease (AD) and is planning a Phase 2 proof-of-concept clinical trial at several leading AD centers in the Netherlands and France.

Third Quarter 2020 and Recent Corporate Highlights:

Presented at the following Investor Conferences:

Cash and Liquidity as of October 14, 2020

Total available funding as of October 14, 2020, which includes cash, cash equivalents and short-term bank deposits of approximately $33.1 million as well as remaining non-dilutive funding from CIRM, IIA and other grants, amounts to approximately $36 million.

Financial Results for the Three Months Ended September 30, 2020

About NurOwn

NurOwn (autologous MSC-NTF) cells represent a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. BrainStorm has fully enrolled a Phase 3 pivotal trial of autologous MSC-NTF cells for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm also recently received acceptance from the U.S. Food and Drug Administration (FDA) to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS) and completed enrollment in August 2020.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug status designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has fully enrolled a Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six U.S. sites supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). The pivotal study is intended to support a filing for U.S. FDA approval of autologous MSC-NTF cells in ALS. BrainStorm also recently received U.S. FDA clearance to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS). The Phase 2 study of autologous MSC-NTF cells in patients with progressive MS (NCT03799718) completed enrollment in August 2020. For more information, visit the company's website at http://www.brainstorm-cell.com.

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BrainStorm Announces Financial Results for the Third Quarter 2020 - Citybizlist

Recommendation and review posted by Bethany Smith

An international team of scientists from China, Taiwan and the United States has successfully sequenced and analyzed the genomes of the Chinese banyan tree (Ficus microcarpa), which is famous for its extraordinary aerial roots; Ficus hispida, a related fig species lacking aerial roots; and Eupristina verticillata, a wasp coevolving with the banyan tree. Theyve identified regions in the banyan trees genome that promote the development of its unusual aerial roots and enhance its ability to signal its wasp pollinator, and found a sex-determining region in Ficus hispida.

Zhang et al. reveal the genomic changes that allow the Chinese banyan tree (Ficus microcarpa) to produce roots that spring from its branches. Image credit: Gang Wang.

Understanding the evolutionary history of Ficus species and their wasp pollinators is important because their ability to produce large fruits in a variety of habitats makes them a keystone species in most tropical forests, said Professor Ray Ming, a researcher at the University of Illinois, Urbana-Champaign.

To better understand their evolutionary developments, Professor Ming and colleagues analyzed the genomes of the two fig species, Ficus microcarpa and Ficus hispida, along with that of Eupristina verticillata, a wasp that pollinates Ficus microcarpa.

When we sequenced the trees genomes, we found more segmental duplications in the genome of the banyan tree than in Ficus hispida, the fig without the aerial roots, Professor Ming said.

Those duplicated regions account for about 27% of the genome.

The duplications increased the number of genes involved in the synthesis and transport of auxins, a class of hormones that promote plant growth.

The duplicated regions also contained genes involved in plant immunity, nutrition and the production of volatile organic compounds that signal pollinators.

The levels of auxin in the aerial roots are five times higher than in the leaves of trees with or without aerial roots, Professor Ming said.

The elevated auxin levels appear to have triggered aerial root production. The duplicated regions also include genes that code for a light receptor that accelerates auxin production.

When the researchers studied the genome of the Eupristina verticillata wasp and compared it with those of other related wasps, they observed that the wasps were retaining and preserving genes for odorant receptors that detect the same smelly compounds the fig trees produce.

These genomic signatures are a signal of coevolution between the fig trees and the wasps.

The authors also discovered a Y chromosome-specific gene that is expressed only in male plants of Ficus hispida and three other fig species that produce separate male and female plants, a condition known as dioecy.

This gene had been duplicated twice in the dioecious genomes, giving the plants three copies of the gene, Professor Ming said.

But Ficus species that have male and female flowers together on one plant have only one copy of this gene.

This strongly suggests that this gene is a dominant factor affecting sex determination.

The results were published in the journal Cell.

_____

Xingtan Zhang et al. Genomes of the Banyan Tree and Pollinator Wasp Provide Insights into Fig-Wasp Coevolution. Cell, published online October 8, 2020; doi: 10.1016/j.cell.2020.09.043

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Researchers Sequence Genomes of Two Fig Species and Pollinator Wasp | Genetics - Sci-News.com

Recommendation and review posted by Bethany Smith

Norman Swan: One of the mysteries surrounding COVID-19, the disease that is caused by SARS-CoV-2, is why some people experience severe life-threatening disease and others don't. Age, male gender and having other problems like diabetes, heart and lung disease and probably obesity, are risk factors. But what about individual differences in people's immune systems? Well, two recent studies have found that to be the case in a significant percentage of people with serious COVID-19 disease. One study looked for genetic patterns and found an effect on immune messages called interferons. There are about 18 interferons in the body and they act like volume controls and orchestra conductors in the immune system once it has been alerted to an attack by a virus. The second study found antibodies against interferon in some people. This has huge implications for a better understanding of the immune system, not to mention more targeted therapies for people with COVID-19. Professor Paul Hertzog is one of Australia's leading experts on interferons. Paul is head of the Centre for Innate Immunity and Infectious Disease at the Hudson Institute in Melbourne.

Paul Hertzog: This study, initiated by Jean-Laurent Casanova who is based at the Rockefeller, and Helen Su at NIH, they've set up actually a global network looking for patients who might have genetic predispositions to getting extremely ill with the Covid SARS-CoV-2 virus. And it is really the first output of that global network of people who are doing the searches.

So firstly it's really the first substantial report that there is a genetic susceptibility of this disease. It's something that we always suspected but this really proves it. And more particularly what is unusual and fascinating is that most of the culprits they found were actually lying in different components of the interferon signalling system.

Norman Swan: They found a relatively consistent genetic problem in people when they looked at their genes, and these genes seem to code for the interferons in some shape or form.

Paul Hertzog: Yes, they identified 12 genes that we knew were involved in susceptibility to infections, particularly respiratory infections, and they happen to be in the interferon pathway, but involved in the production of it, or the response to it. And so they really looked where the light was and they said, well, can we find deficiency in any of these 12 genes? They actually found deficiencies in quite a high proportion of patients, about 3% of them. So I'm sure there are many more to cover because this was really just a very targeted look.

Norman Swan: So 3% doesn't sound too high.

Paul Hertzog: With a million people dying, I think it's a lot of human beings. And I think it is just the tip of the iceberg.

Norman Swan: People have been talking about interferons now for a while, and in fact interferons have been trialled as a treatment for people with COVID-19 disease even prior to these studies coming out. What's the net effect of these genetic abnormalities or these genetic differences?

Paul Hertzog: I suppose what they might enable us to do, Norman, is to use what you would call a precision medicine approach where we can identify people who would benefit and who would not benefit from this. So, for example, if a person has a defect which means they are unable to respond to interferon, and some of these genes are involved in that, it's absolutely pointless giving them interferon therapeutically because they just would not be able to respond. On the flipside, if we identify patients who can't make it and some of the genes are involved in the making of the interferon, then they are more likely to benefit from therapeutic administration of interferon.

Norman Swan: So where does this research go next? Presumably it's a simple test or what?

Paul Hertzog: I think that's a simple test. As I said, I think it might enable us to identify groups of patients who are likely to respond to interferon than those who don't. And if we can talk for a minute about the other paper which involves the identification of autoantibodies to interferon, that's probably in fact a far more fascinating study because autoantibodies, some of your listeners might recognise, are usually associated with autoimmune diseases like lupus where something goes wrong with the immune system, instead of recognising a foreign antigen it turns on itself, and these rogue antibodies can cause disease. So what they found in their second study was that 10% of the patients they looked at, which is a staggering number really, produced antibodies to these type I interferons and would negate its effect. That population of patients won't be able to respond. That has a number of implications. Secondly,

Norman Swan: Before you get to the implications, is the assumption that the autoantibodies pre-existed the infection or were created by the virus?

Paul Hertzog: Their study was nearly 1,000 patients, so there were probably about 100 of them and that they found these autoantibodies. I think in about 10 or 12 of them that they had the opportunity in the samples there to look before they had obvious signs of disease, and some of them did have pre-existing antibodies, but that's just a small proportion of those patients, I think it needs a much bigger study but it tells us that some of them certainly can predate. And that's interesting for a number of reasons because it identifies an underlying condition that we never would have thought of. And the other thing is those patients have no previous signs of other respiratory or susceptibility to viral infections, which raises the question whether this is fairly specific to COVID-19.

Norman Swan: And it also raises a question which a lot of people, at least to my Coronacast podcast ask, if I've got rheumatoid arthritis or Multiple Sclerosis or scleroderma or SLE, one of the other autoimmune diseases, doesn't make me more susceptible to COVID-19? Do any of the other autoantibodies that are around in the community affect interferons in this way?

Paul Hertzog: A really interesting question that has complicated answers, and the answers are yes and no. There are some autoimmune conditions where similar autoantibodies to interferons have been seen. But there are others like lupus where the opposite seems to happen. In lupus it seems a large part of the disease is driven by interferon, and in fact there was a large trial headed by an Australian clinician from Monash, Eric Morand last year that identified blocking antibodies to interferon that actually look like they will have beneficial effects in lupus, so that's quite the opposite effect.

Norman Swan: So this discovery of autoantibodies which might actually be quite significant in a reasonable percentage of people, is there a therapy there?

Paul Hertzog: Good question. Not obviously. It's probably may lieagain, if you're thinking interferon therapy it clearly wouldn't work and less there is some specificity in the antibodies that you could get around. I think there are ways of screening it out. For example, you wouldn't want the samples of those serum in your convalescent serum preparation, so I think there are practical outcomes like that.

Norman Swan: Oh yes, that's right, so if you're taking serum from these people to give to other people and you give them autoantibodies you can make them worse.

Paul Hertzog: Right, so it's another screening test for that. There are B cell and antibody depletion therapies that are used in other autoimmune diseases, and that might be in the area that could be looked at in these patients.

Norman Swan: So what's next for your research, given all this?

Paul Hertzog: Well, it provides us with an opportunity. For us it's yet another example of the importance of the interferon system. We are currently collaborating with Jean-Laurent Casanova in a number of these mutations prior to Covid and we will continue that. What we'll do is drill down to try and find out the mechanism whereby some of these mutations in the interferon system are working, and in fact whether some of them that haven't yet been identified as loss of function and disease contributing might in fact be so.

Norman Swan: Paul, thanks for joining us.

Paul Hertzog: My pleasure, thanks a lot.

Norman Swan: Professor Paul Hertzog is head of the Centre for Immunity and Infectious Disease at the Hudson Institute in Melbourne.

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Could genetics explain the mystery of severe coronavirus? - ABC News

Recommendation and review posted by Bethany Smith

How can you make this type of research information into news you can use? Thats a real challenge.

About a year ago, I thought I saw a path to greater use of genetic information by consumers. An ambitious company named Veritas Genetics was offering full genome sequencing to U.S. customers for $599 US. They told me they were planning to expand to Canada. Veritas is backed by considerable brainpower, including its co-founder, Harvard professor George Church, often called the father of synthetic biology.

A full human genome sequence is about three billion base pairs, containing your complete genetic blueprint. By contrast, companies like Ancestry and 23andme only look at certain parts of the genome that provide information about ancestral roots and common medical conditions.

What Veritas seemed to lack is financial backing. This was complicated by the fact that many of its investors were from China, which raised red flags because of possible U.S. regulations. Privacy experts have also told us to be very careful about where our genetic data goes once it leaves our mouth as a bit of spittle. Veritas has suspended their U.S. whole genome testing, laid off some staff, and is currently focusing on COVID-19 tests.

Competitors are cropping up, and theres no doubt you will eventually be able to download your complete gene sequence and scan it for interesting findings. There are already tools out there like OpenSNP that can work with the information you can download from 23andme, deCODEme or FamilyTreeDNA. It can answer questions like am I a fast metabolizer of caffeine?

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Keenan: Thinking well beyond COVID-19 - Calgary Herald

Recommendation and review posted by Bethany Smith