Whether you're still coming to terms with that earlier pre-commute wake-up call or being kept awake by the little ones on the nightly, it's likely you're feeling (and seeing) the results of disrupted sleep. According to a study from the University of Southampton, the number of people experiencing insomnia rose from one in six to one in four during the height of the pandemic and the majority are experiencing more of the same.

'The last 18 months have been turbulent, and we need to prioritise sleep more than ever', says Dr Anna Persaud, CEO of This Works. 'It is essential good health, well-being and quality of life.'

Nights spent tossing and turning have an impact on our energy levels and yes, our skin too.

Skin cells have their own schedule. Sleep paves the way for their 'repair and renew' phase, that's when stem cells work to replace old cells with bright, shiny, new fully-functioning ones. The less sleep we get, the less efficient this process is. Enter dull, lacklustre skin. So, how to combat it?

According to skincare and laser specialist Debbie Thomas, gentle exfoliation can mimic the glow you get from a great night's sleep. 'To brighten up the skin first of all address your exfoliation. Gentle and regular is best, I always recommend a liquid exfoliator over a scrub, think acids or enzymes.'

Work vitamin C into your morning skincare routine too. 'Vitamin C is known for its brightening qualities,' explains Thomas, 'and with consistent use it also helps boost collagen levels too.' Never underestimate a two-pronged approach.

Who doesn't wake up with a slightly puffy face in the morning? Puffiness comes from fluid retention and fluid retention can be eased with a gentle lymphatic drainage massage. 'De-puffing your face takes a little gentle arm work', says Thomas. 'While washing your face with a slippery cleanser, use the heel of your hand to firmly massage up and out in sweeping movements to push the fluid build-up towards your ears and the lymph nodes. The idea is to push up to lift then sweep out to drain. Just make sure that your skin is a little slippery so that you aren't tugging at it.'

'For puffy eyes specifically, reach for something cold,' advises Thomas. 'Holding something cold against your eye area helps to tone down inflammation and puffiness. If you don't own a cryo-massage tool then grab an ice cube with some tissue, let it warm enough to be slippery on your skin then sweep it around your eyes and over your skin for 1-2 minutes.'

It goes without saying, but routine is key says This Works sleep expert Dr Anna Persaud. 'On a practical level establishing and maintaining a nightly wind down or sleep routine helps to reset and rebalance our minds. Try dimming lights, limiting brain stimulation - for example turning off Netflix an hour earlier and disconnecting from our devices - can help to signal to our brain that it is time to sleep.'

And from a beauty perspective? Never knock the instant results of a decent under-eye concealer.

This new overnight mask is infused with kombucha to help combat irritation and redness, and niacinamide for super soft, supple skin. Simply pop on overnight and let it get to work whilst you sleep, leaving skin refreshed, energised and glowy with minimal work. A time saving treasure.

A one stop shop for refreshed and rejuvenated skin, the Essential Skin Grade treatment combines the necessary services for your skin concerns as recommended by consultation. Think mild peels, extractions, microdermabrasion, Byonik pulse triggered cold laser, photodynamic red and blue light therapy, lymphatic drainage, radiofrequency, and ultrasound product infusion, as well as an assortment of serums and masks

"Our collection of pillow sprays all contain a clinically proven Sleep Superblend to you fall asleep faster. A natural, aromatherapeutic fragrance with 100% natural essential oils including French Lavender, wild Camomile and Vetivert. The Sleep Plus, Love Sleep and Deep Sleep Pillow Sprays calm both the mind and body and target various sleep issues. Independent consumer studies found that after using the product, 97% reported less broken sleep and 89% said they fell asleep more quickly than usual. As a result of using Deep Sleep Pillow Spray, 98% felt more relaxed in the morning and 97% felt less tired the day after using. We've sold over 8 million pillow sprays thanks to ongoing scientific research and continuous product innovation so it's fair to say they really work." Dr Anna Persaud, CEO, This Works and VP Skincare & Topicals, Canopy Growth

Angela Caglia's ultra-luxurious Self Love Rose Quartz Eye Mask is garnering a cult following for its calming and soothing properties. If you're drawn to the energy in crystals, real rose quartz is woven together to create a pampering eye mask to release tension and focus the mind. Sign us up.

"You don't need us to tell you that sleeping is a fundamental part of a healthy lifestyle", says Becky O'Neill, Global Brand Manager of Sanctuary Spa. "It improves concentration levels, mood and ability to cope with stress. Getting a good night's rest also lowers the levels of cortisol in the body, promoting a healthy and stress-free mindset". So soak away the days stress with Sanctuary Spa's wellness bath salts. The rest of the range includes a CBD calming oil, de-stress balm and pillow spray to help you properly unwind from bath to bed.

To touch up dark circles on the go, this full coverage but easily blendable concealer has a smooth, buttery formula that blends seamlessly into skin for a brightening lift. The best part? It doesn't dry out and crack, so this second skin will last as long as your day does.

This lightweight but potent serum packs a punch to give fatigued skin a dose of Vitamin C for a brighter complexion, and perceptibly plumper and more even skin. Use before moisturiser for a shot of extra hydration.

According to Slip, 'by the time we are 60 we will have slept for an average of 20 years' so better make that time count. This pure silk eye mask (and accompanying range of pillowcases) are anti aging, anti sleep crease, anti bed head and can help to reduce friction and irritation on delicate facial skin. Perfect for blocking out the early morning light and getting you to sleep through to your alarm.

Ease tense and aching joints with this concentrated CBD balm that is a non-greasy and easily absorbed formula, to massage into localised areas and melt away stress.

Aromatherapy is great for unwinding, and this calming and tranquil scented candle has notes of Lavender and Ylang Ylang. to help you take a moment to ground yourself and reset.

READ MORE: The Best Body Scrubs To Soften Dry Winter Skin, Fast

READ MORE: November 2021 Beauty Edit: The Best New Beauty Buys Out This Month

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How To Look Less Tired According To Experts | Grazia - Grazia

Skin Stem Cells Comments Off on How To Look Less Tired According To Experts | Grazia – Grazia | November 8th, 2021

NEW YORK Tara Biosystems and Scipher Medicine said Wednesday that they have entered a collaboration to identify therapeutic targets for drug development in cardiac laminopathies.

Scipher aims to use its Spectra platform to identify potentially therapeutic targets from among proteins found both up- and downstream of LMNA for a stratified disease population, while incorporating data from Tara's Biowire II LMNA disease models.

These human cardiac tissue models derive from induced pluripotent stem cells and include a repertoire of healthy, gene-edited, patient-derived, and drug-induced phenotypes of human disease. "The TARA platform is highly versatile and can capture robust physiologic endpoints of human cardiac function, including contractility, electrophysiology, calcium signaling, [and] structure, as well as genomic, proteomic, and metabolic profiles," Robert Langer, a member of Tara Biosystems' board of directors, said in a statement.

Meanwhile, Scipher's Spectra platform "uniquely integrates AI with the protein network of human cells to identify novel targets in highly complex and debilitating diseases such as laminopathy," Slava Akmaev, chief technology officer and head of therapeutics at Scipher Medicine, said in a statement. "By interrogating the network neighborhood of LMNA and its relationship with the proteins appropriate for targeted therapeutics we are confident that we can identify several novel and relevant drug targets."

In this collaboration, Tara has the exclusive option to pursue drug discovery and clinical development of any identified targets and retains the rights to develop and commercialize any resulting therapeutics. Scipher is eligible for milestone payments and royalties.

"The ability to quickly validate novel targets identified by Spectra on Tara's human tissue model platform allows us to rapidly iterate to identify most effective target," Scipher CEO Alif Saleh said in a statement.

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Tara Biosystems, Scipher Medicine Partner to Find Therapies for Cardiac Laminopathies - GenomeWeb

Cardiac Stem Cells Comments Off on Tara Biosystems, Scipher Medicine Partner to Find Therapies for Cardiac Laminopathies – GenomeWeb | November 8th, 2021

Twenty years ago, cardiologist and stem-cell scientist Piero Anversa published an exciting paper. He was then a prominent researcher at New York Medical College in Valhalla, and his data in mice showed that injured hearts could regenerate with the help of stem cells taken from bone marrow1contrary to prevailing wisdom.

Myocardial infarction, commonly known as a heart attack, deprives cardiac muscle cells of oxygen, causing them to perish. The human heart responds by laying scar tissue over lost muscle. But these reconstituted areas dont pump blood as competently as before. In time, this can lead to heart failureparticularly if other heart attacks follow. The implications of Anversas work were clear: stem cells, through their growth and proliferation, had the potential to reverse the damage caused by heart attacks and thereby prevent heart failure.

But other researchers who attempted to replicate these mouse studies found themselves coming up short. Allegations of faked results eventually began to surface, and Anversa, who had since joined Harvard Medical School, and Brigham and Womens Hospital in Boston, Massachusetts, was forced to leave his posts in 2015. Two years later, Brigham and Womens Hospital paid the US government US$10 million to settle allegations that Anversa and his colleagues had used fraudulent data to apply for federal funding. And a 2018 investigation conducted by Harvard called for 31 of Anversas papers to be retracted.

This saga has dampened the enthusiasm that once surrounded research into stem-cell therapy, says Michael Schneider, a research cardiologist at Imperial College London. The controversy, overt scientific misconduct and evidence against Anversas claims has cast aspersions on the field more generally, he admits. Thats unfortunate, because many other stem-cell scientists are conducting legitimate research.

Meanwhile, another heart-healing strategy has emerged, drawing inspiration from species that, unlike humans, can regrow cardiac muscle after trauma. Researchers are seeking to learn more about the molecules produced by zebrafish (Danio rerio) hearts as they heal themselvesand are investigating whether injectable drugs containing the same substances could also yield reparative results.

The question is now whether it will be stem cells, small-molecule drugs or a combination of the two that achieve the goal of convincing the heart to heal instead of scar.

In the wake of the Anversa scandal, there has been an important evolution of thinking on the stem-cells front. A 2019 literature review pointed out that newer studies tend to show the most significant impact from stem-cell therapy comes from the substances the cells secrete, rather than their proliferation2. After many years of work, we find that when we deliver cells into the heart, the benefit of replaced damaged cells is only minor, says the reviews author Javaria Tehzeeb, an internal-medicine specialist at the Albany Medical Center in New York. The real work of regeneration happens, she explains, when the cells produce growth factors, which in turn affect heart repair by reducing inflammation and stimulating the development of new heart muscle.

That means stem-cell therapies share some similarities with the drug strategyessentially it comes down to molecules secreted by the stem cells versus molecules that are directly injected. But they also have important differences.

First, part of the stem-cell therapy benefits might still come from the cells proliferation, even if that bonus is relatively small. Second, theres little control over what substances the stem cells produce once theyre injected, whereas specific molecules can be administered at known doses. And finally, the logistics of scaling up and delivering these two therapies will be very different.

A study published in 2020 showcased the importance of stem-cell-produced molecules by looking at the structural integrity of proteins found in infarcted mouse hearts3. The scientists artificially induced heart attacks in eight adult mice. Four weeks later, they administered stem cells to half the rodents. After a further four weeks, their hearts were removed and washed with a series of buffer solutions and chemical reagents to extract the proteins, which were then analysed. We essentially did a massive scan of every single protein in the heart, says Andre Terzic, lead author of the study. The authors were able to identify almost 4,000 proteins, and showed that heart attacks distorted the structure of 450 of them. But with stem-cell therapy, that number fell to 283.

Proteins are the intimate components that make our hearts work properly, and when the heart is diseased, they become damaged, says Terzic, who is director of the Mayo Clinic Center for Regenerative Medicine in Rochester, Minnesota. The ability of these stem cells to secrete healing signals is probably a key element to what weve observed.

All cells and tissues are constantly telling each other what they need and whether theyre stressed through molecular signalling. When you lose a chunk of cells in a heart attack, you lose part of that conversation, explains Charles Murry, an experimental pathologist and director of the Institute for Stem Cell and Regenerative Medicine at the University of Washington in Seattle. Injected stem cells could be filling in the missing dialogue by secreting signalling and rescue molecules, he explains.

Although this sounds encouraging, there are still parts of the stem-cell-therapy approach that need to be finessed. In a 2018 study, Murry and colleagues transplanted approximately 750 million cardiomyocytes into macaque monkeys that had experienced major heart attacks4. One month after the intervention, the amount of blood pumped by their hearts had increased by 10.6% compared with just 2.5% in the control group. This advantage persisted three months later, but one out of the five stem-cell-treated monkeys suffered arrhythmias. The onset of arrhythmia wasnt previously observed in small-animal studies, but it is a known complication of heart attacks. Nevertheless, the researchers thought it could be a potential side effect of the stem-cell infusion. Obviously it isnt statistically significant, but common sense led us to classify this as a treatment complication, says Murry.

In addition to safety concerns, stem-cell therapies are also beset by questions of practicality. Think of a lab with all these cell culture flasks where you have to grow millions of cells just to create a single dose, says Terzic. Now imagine tens of thousands of patients. Its a formidable effort to be ready, especially if you want to intervene rapidly. You dont have the luxury of time to build up supplies.

Thats one reason why some people think the promise of cardiac rejuvenation lies elsewhere. Theres been an awful lot of time and money spent on stem-cell therapy, raising false hope in patientsand so far, the clinical outcomes have been largely disappointing, says Paul Riley, a cardiovascular scientist at the University of Oxford, UK. Riley is investigating whether inserting specific molecules into the heart might be more effective.

Human hearts cant regenerate on their own, but other animals do have such abilities. Zebrafish, for example, can regrow their hearts after as much as 20% is removed. Newborn mice can also regenerate heart tissue. Observing the molecular pathways in these animals might make similar results possible in humans.

Research has shown that following a myocardial infarction in zebrafish, the epicardiuma membrane surrounding the heart muscleproduces molecular signals that might kick-start muscle-cell regeneration5. The hope is that manipulating the human epicardium could elicit the same therapeutic results. There are probably approaches we can take to target the cells that exist in the heart with small molecules or drugs, that could invoke repair and regeneration, says Riley.

Back in 2011, Riley and colleagues showed that this is theoretically possible6. They pre-treated adult mice with a daily injection of a protein called thymosin 4 for one week before inducing an infarction, and found that these mice were able to produce new cardiac muscle. This offers a road map to a pre-emptive therapy. If an individual is at high risk of a heart attack, says Riley, then its conceivable they could be advised to take a priming or preventative therapeutic, which may counteract an event, but its not quite the holy grail of restoring lost tissue after a heart attack that were searching for. In other studies, Riley has since shown that other proteins besides thymosin 4 might also have a role in stimulating the epicardium to regenerate the heart7.

Its easier to see how the drug route offers clearer prospects for scaling upbut the science behind this approach is newer, and there havent been any clinical trials in humans yet. What goes in stem cells favour is the body of work behind them, says Tehzeeb.

It might be that stem-cell therapies achieve government approvals first, but then drugs overtake them once the science and research have had time to catch up. When we get to the end of the line with molecules, then maybe we can say stem cells are a thing of the past, Tehzeeb says. But until then, we should continue to pursue their potential.

Murry echoes that sentiment, arguing that findings from both camps could end up helping everyones research. We need an ecosystem with a competition of ideas, and as long as its all openly published then well figure it out, he says. Thats the better approach, rather than saying my idea is better than your idea.

This article is part ofNature Outlook: Heart health, an editorially independent supplement produced with the financial support of third parties.About this content.

Orlic, D.et al.Nature410, 701705 (2001).

Tehzeeb, J., Manzoor, A. & Ahmed, M. M.Cureus11, e5959 (2019).

Arrell, D. K., Rosenow, C. S., Yamada, S., Behfar, A. & Terzic, A.npj Regen. Med.5, 5 (2020).

Liu, Y.-W.et al.Nature Biotechnol.36, 597605 (2018).

Cao, J. & Poss, K. D.Nature Rev. Cardiol.15, 631647 (2018).

Smart, N.et al.Nature474, 640644 (2011).

McManus, S.et al.J. Mol. Cell. Cardiol.140, 3031 (2020).

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Cells or drugs? The race to regenerate the heart - Scientific American

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Our Need For Things Lab-Grown

What was once something of the movies objects forming themselves in thin air is real now. Various things can be grown in a laboratory setting, some even on a large scale for commercial distribution. This technology could be a big part of the solution to establish sustainable societies. At the moment, we harvest organs from the deceased, rear animals for meat and dairy, destroy forests by cutting down trees for wood, mine the earth for diamonds, and the list goes on. All these things can already be lab-made or are on the brink of reality.

Once these staples of society can be mass-made affordably, they could supply the world while minimally impacting the natural environment. Acres of land wouldnt need to be used for food and building materials, meaning deforestation can cease, for starters. Looking at lab-grown meats alone: they require 99% less land than traditionally farmed meats, generate up to 96% fewer emissions, use up to 96% less water, and no animals need to be slaughtered in the process.

Naturally, there will be short-term disruptions, particularly job-related. For example, eco-friendly agriculture will mean fewer farms and agriculture jobs. But new employment opportunities will emerge in the scientific and technical fields related to lab-grown foods.

Whats the difference between 3D printing (additive manufacturing) and lab-grown, you may be wondering? 3D printing uses material as ink anything from plastic to cellular material whereas lab-grown materials start off as a bit of material that multiplies on its own, replicating natural processes. Thus, lab-grown material has the same cellular structure as the naturally occurring material and mimics the natural formation process but within a much shorter period.

In the future, we are bound to see various lab-grown breakthroughs coming from the medical field. Eventually, there should be alternative sources for organs and blood cultured from stem cells. In addition, there will likely be lab-produced medicines (lotions, ointments, balms, nutraceuticals, energy drinks, etc.), breast milk, and more.

Scientists are well on the way to functioning full-sized organs, with several innovations in fully functional mini-organs, or organoids, making headlines in recent years. For now, these organoids are tools for testing new drugs and studying human diseases. But soon enough, these research teams will take the technology to the next level and develop organs that can be used for implantation when someone needs an organ replacement. So far, the brain, liver, lungs, thymus, heart, blood, and blood vessels are among the growing list of lab-grown medical accomplishments.

A team of scientists from the University of Pittsburgh managed to grow miniature human livers using induced pluripotent stem cells (IPSCs) made from human skin cells. Meaning, in the far future, someone needing a liver transplant could have the organ grown from their own skin cells! This method may even reduce the chances of a patients immune system rejecting the new tissue because it would recognize the cells as self. Whats more, their lab-grown livers matured in under a month compared to two years in a natural environment.

The scientists tested their fully-functional mini-livers by transplanting them into rats. In this proof-of-concept study, the lab-made organs survived for four days inside their animal hosts, secreting bile acids and urea like a healthy liver would.

A research team led by the University Hospital Dsseldorf induced pluripotent stem cells (iPSCs) to grow into pea-sized brain organoids with rudimentary eye structures that sense light and send signals to the rest of the brain. They used skin cells taken from adult donors, reverted them back into stem cells, and placed them into a culture mimicking a developing brains environment, which encourages them to form specific brain cells. Their mini-brains grew optic cups, vision structures of the eye found where the optic nerve and retina meet. The cups even grew symmetrically, as eyes would, and were functional!

Jay Gopalakrishnan, a senior author of the study, said:

Our work highlights the remarkable ability of brain organoids to generate primitive sensory structures that are light sensitive and harbor cell types similar to those found in the body. These organoids can help to study brain-eye interactions during embryo development, model congenital retinal disorders, and generate patient-specific retinal cell types for personalized drug testing and transplantation therapies.

This achievement is the first time an in vitro system shows nerve fibers of retinal ganglion cells reaching out to connect with their brain target an essential aspect of the mammalian brain.

Scientists from Michigan State University developed functional miniature human heart models grown from stem cells complete with all primary heart cell types and with functioning chambers and vascular tissue. The models could help researchers better understand how hearts develop and provide an ethical platform for treating disease and testing drugs or new treatments.

The teams lab-grown mini hearts follow the fetal development of a human heart, offering a new view into that process. The organoids start beating by day six, and they grow into spheres approximately 1 mm (0.4 in) wide, with all significant cardiac cell types and multiple internal chambers by day 15.

Aside from research purposes, full-sized lab-grown hearts could solve the shortage problem of hearts the world faces today. More than 25 million people suffer heart failure each year. In the United States, approximately 2,500 of the 4,000 people in line for heart transplants receive them. That means almost 50% of the people needing a new heart to keep them alive wont get it.

Unlimited supplies of blood for transfusions are possible with lab-growing technology. Blood has been challenging to grow in the lab. However, real breakthroughs in creating artificial blood have sprung up!

A couple of years ago, Japanese researchers developed universal artificial blood that worked for all blood types. It even has a shelf life of one year stored at room temperature, therefore eliminating the problem of identifying blood type and storage simultaneously.

Like that wasnt impressive enough, last year, a team of scientists from the South China University of Technology, the University of New Mexico, and Sandia National Laboratories created artificial red blood cells (RBCs) with more potential capabilities than real ones! The synthetic RBCs mimic the properties of natural ones such as oxygen transport, flexibility, and long circulation times with the addition of a few new tricks up their sleeves, such as toxin detection, magnetic targeting, and therapeutic drug delivery. In addition, blood contains platelets and red blood cells, so these new cells could be used to make superior artificial blood.

Researchers from the University of British Columbia successfully coaxed stem cells to grow into human blood vessels. The thing that is so remarkable about this study is that the system of blood vessels grown in the lab is virtually identical to the ones currently transporting blood throughout the body. They are using this now to generate new leads in diabetes treatment. They put the lab-grown blood vessels in a petri dish designed to mimic a diabetic environment.

The global demand for meat and dairy is expected to rise by almost 90% over the next 30 years, regardless of the need to cut back on meat consumption. The risk of environmental damage and the rising food demand itself is a problem many have recently addressed. Thats why companies worldwide are on the verge of scaling up all sorts of lab processes to produce various food items, including steaks, chicken, cheese, milk, ice cream, fruits, and more.

Thinktank RethinkX even published research suggesting that proteins from precision fermentation (lab-grown protein using microbes) will be about ten times cheaper than animal protein by 2035, resulting in a collapse of the livestock industry. It says the new food economy will subsequently:

replace an extravagantly inefficient system that requires enormous quantities of inputs and produces considerable amounts of waste with one that is precise, targeted, and tractable. [Using tiny land areas, with a massively reduced requirement for water and nutrients, it] presents the most significant opportunity for environmental restoration in human historyFarm-free food offers hope where hope is missing. We will soon be able to feed the world without devouring it.

The worlds pace of meat consumption is placing a significant strain on the environment. Many studies show that eating less meat is just as crucial to slowing down global warming as using solar panels and zero-emissions vehicles. Unfortunately, animal farming generates an obscene amount of greenhouse gas emissions. Yet again, scientists come to the rescue, working diligently to fix this situation.

Over a decade ago, researchers created something akin to ground beef, but the complex structure of steak didnt happen until recently, with Aleph Farms debuting its thick-cut rib-eye steak in 2018. Furthermore, that first burger cost around US$345,000, but now the price has dropped dramatically to the point that lab-grown chicken is to be commercially produced and hit grocery store shelves as of this year.

SuperMeat, Eat Just, and Aleph Farms are todays most prominent startups working on getting lab-grown meats to people looking to lower their carbon and environmental footprints. In addition, their products are made from actual animal cells, so theyre real meat, but no animals had to be hurt or killed.

Speaking of Aleph Farms, the company also grew meat in space to show that it can even be done in a zero-gravity environment with limited resources.

Aside from Aleph Farms figuring out how to make steak like an authentic steak, a group of Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) researchers also devised a solution to the texture challenge. First, they made edible gelatin scaffolds that have the texture and consistency of real meat. Then, they grew rabbit and cow muscle cells on this scaffolding. The research demonstrates how realistic meat products are possible!

Parker and his Disease Biophysics Group developed a technique to produce the scaffolding. Its a fiber-production system inspired by cotton candy known as immersion Rotary Jet-Spinning (iRJS). It enabled the team to spin long nanofibers of a specific shape and size using centrifugal force. So, they spun food-safe gelatin fibers, creating the base upon which cells could grow.

Natural muscle tissue is composed of an extracellular matrix, which is the glue that holds the tissue together. As a result, it contributes to the texture of the meat. The spun gelatin fibers mimicked this extracellular matrix and provided the texture to make the lab-grown meat realistic. When the team seeded the fibers with animal (rabbit and cow) muscle cells, they anchored to the gelatin scaffolding and grew in long, thin structures, similar to real meat.

Meanwhile, Boston College developed a new, even greener technology that uses the skeleton of spinach leaves to support bovine animal protein growth. However, animal products arent eliminated from the process entirely. For example, lab-grown steak and chicken are created by painlessly harvesting muscle cells from a living cow, subsequently fed and nurtured to multiply and develop muscle tissue. But for this to have the same texture as real meat, the cells need structural support to flourish and are therefore placed in a scaffold.

Singapore is leading the way, becoming the first country in the world to approve the sale of Eat Justs cultured chicken. The company will start by selling nuggets at a restaurant. Meanwhile, SuperMeat has been handing out lab-grown chicken burgers in Israel for free. Theyre aiming to gain public acceptance of the idea.

The cultured chicken starts as a tiny number of harvested cells. Those cells are put into a bioreactor and fed the same nutrients the living animal would consume to grow. The cells multiply and turn into an edible portion of cultured chicken meat. The meats composition is identical to that of real chicken and offers the same nutritional value. And its cleaner because its antibiotic-free!

Labs are manufacturing dairy products by utilizing the fermentation process of living microbes to produce dairy proteins like whey and casein. These proteins are then used to make dairy products like butter, cheese, and ice cream. Two leading companies in this category are Imagindairy and Perfect Day, which already have several products on supermarket shelves in the United States.

Researchers havent figured out how to make fruits and vegetables yet, but a team is perfecting a cell cultivation process that generates plant biomass. The stuff tastes like the natural-grown product from which the cells were obtained and even exceeded its nutritional properties. Although, the texture of the biomass is different. For example, an apple isnt a solid apple akin to one grown from a tree. Instead, its like applesauce.

Lab-produced materials Including wood, diamonds, leather, glass, clothing, crystals, gels, cardboard, and plastics for making objects are either under development or already available. Many materials need to be taken from nature mined from the earth or cut down from forests. If they can be made in a lab instead, then people could leave nature alone!

A recent project led by a Ph.D. student at MIT paves the way for lab-grown wood one of the worlds most vital resources used to make paper, build houses, heat buildings, and so much more. The process begins with live plant cells cultivated in a growth medium coaxed using plant hormones to become wood-like structures. Next, a gel matrix is used to guide the shape of the cellular growth, and controlling the levels of plant hormones regulates the structural characteristics. Therefore, the technology could grow anything from tables and chairs to doors to boats and so on.

The environmental and socio-economic impact of traditionally mined diamonds has been exposed in recent years, and as awareness grows, the rising popularity of lab-grown diamonds does too. Mined diamonds are linked to bloody conflicts, and their excavation produces carbon emissions, requires substantial water use, and causes severe land disturbances.

Research has found that 1,000 tons of earth have to be shifted, 3,890 liters or more of water is used, and 108kg of carbon is emitted per one-carat stone produced. In addition, the traditional diamond mining industry causes irreversible damage to the environment, hence why, a decade ago, researchers started experimenting with how to grow them in the lab. Its been a feat a long time in the making, but we finally have lab-grown diamonds available for eco-conscious consumers to buy.

Diamonds are made of pure carbon. It takes extreme heat and pressure for carbon to crystalize. In nature, this happens hundreds of miles beneath the Earths surface. The ones being mined were shot out by a volcano millions of years ago. So how have scientists managed to hack such an intense and time-consuming process?

They began by investigating the mechanisms behind the diamond formation, zooming in at the atomic level. This led to the invention of a novel technology that utilizes the process of HPHT (high pressure, high temperature) to mimic the natural atmospheric conditions of diamond formation. Labs can use it to replicate the process and turn pure carbon into diamonds in 2-6 weeks.

Lab-grown gems are eco-friendly rocks, especially when theyre made entirely from the sky, like SkyDiamonds. Even the electricity used to grow its stones is from renewables, so theyll indeed be the worlds first zero-impact diamonds.

But how are the diamonds created out of thin air? They are made of carbon from the sky and rainwater. The sky mining facility is in Stroud. Energy is sourced from wind and sunlight. The CO2 is sourced directly from the air. Hydrogen is produced by splitting rainwater molecules in an electrolysis machine using renewable energy. The captured carbon and hydrogen are then used to make methane, used to grow the diamonds. The final product is a diamond anatomically identical to those mined from the ground. It is even accredited, fully certified, and graded by the International Gemological Institute.

Another company, Climeworks, is also making diamonds using carbon sucked from the sky. However, SkyDiamonds takes it a step forward by using rainwater and sunshine in the process.

The last lab-grown object were going to discuss is not something in the works, but an idea a fantastic and outlandish one thats jumping far into the future but was thought up in 2010 by Mercedes Benz. The luxury car companys ambitious BIOME idea shows just how wild imagination can get with lab-grown technology. It envisions a day when it can grow an entire supercar from scratch.

Mercedes-Benz explained when launching the concept:

The interior of the BIOME grows from the DNA in the Mercedes star on the front of the vehicle, while the exterior grows from the star on the rear. The Mercedes star is genetically engineered in each case to accommodate specific customer requirements, and the vehicle grows when the genetic code is combined with the seed capsule. The wheels are grown from four separate seeds.

This list of lab-grown possibilities is just the tip of the iceberg! Other materials in the pipeline include leather, chocolate, and silk. This intelligent technology can make anything a scientist can dream up! The only limit is the imagination and dedication of brilliant people.

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Lab-Growing Everything Might Be The Only Way To Attain A Sustainable World - Intelligent Living

Cardiac Stem Cells Comments Off on Lab-Growing Everything Might Be The Only Way To Attain A Sustainable World – Intelligent Living | November 8th, 2021

A 51-year-old man presented with worsening fatigue on exertion and pallor, with an ECOG performance score of 1. He eventually received a diagnosis of stage II standard-risk multiple myeloma after testing and examination.

During a Targeted Oncology Case-Based Roundtable event, Kenneth Shain, MD, PhD, of Morsani College of Medicine at the University of South Florida in Tampa, FL, discussed a 51-year-old patients with newly-diagnosed multiple myeloma with a group of peers.

MANCHANDANI: For most of my patients I tell them theyre OK. [Although myeloma is incurable], depending upon if its stage II disease, the chances of their survival are good with the newer treatment options out there. Considering the young age [of this patient] andgood performance status, he will be a candidate for transplant.

KREM: I take people through the ISS and I explain the general life span estimates associated with [each stage]. I also explain that any patients prognosis can be different based upon the responsiveness of their disease and their willingness, and ability, to undergo transplant. While cytogenetics and other prognostic features such as ISSR give some prediction of how people will do, theyre not absolute predictors. Ive had people with stage III disease do wonderfully and people with stage I be almost refractory to treatment.

I always let them know theres some wiggle room in that, but I give them a general expectation that this is thought to be incurable, but we can manage it for a fairly good number of years with all the different therapies we have out there. I also explain that with transplant, we probably get the best duration of survival but we dont knowfor sure [how long that duration will last] and that Ive had some patients go 10 to 15 years with multiple myeloma. I also tell people to try to hang in there if they can, because the longer they hang in there, the newer agents well have to manage their disease down the road. But I leave a little bit of a glimmer of hope open while also telling them they have a chronic disease and [that] theyre likely to be seeing me or [some] of my colleagues for a prolonged period.

SHAIN: Does anybody else have a different way of approaching [their patient] or [an opinion] that would be a little counter to [that line of thinking]? Or are we all pretty much in agreement?

ATRASH: In terms of how I run that discussion with my patients, its one of the most challenging discussions, especially for patients with multiple myeloma. Since [2014 there have been a] lot of new drugs added to the market, and if you look at the overall survival for these patients its getting better and better. Still, its very difficult to predict survival for patients based on the ISSR, [although] its a helpful tool in the discussions about transplant or maintenance and [their long-term treatment plan]. But survival is changing [because of] newly approved drugs, so I try to avoid any discussions about survival, especially when we know that some data are showing numbers that are completely different from myeloma centers. It seems like multiple myeloma is a disease [from which], if you have access to novel treatments, you get better; but it depends, and there are a lot of variables there. I think in myeloma centers, where the research is ongoing, the survival almost doubled. It means the researched new drugs that are coming to the market are probably more powerful than the drugs that we have right now.

SHAIN: You kind of have to use the ISSR [scores] as guidelines or guide markersbut they are the only ways of categorizing patients. We all know their [ISSR scores] dont quite behave, and we also know that they were really based on very specific high-risk cytogenetic features. There are ones that have not been incorporated and there are thingsevolving along the way. Not all patients with myeloma read the book, [so to speak,] and their disease doesnt behave the way its supposed to or they cant tolerate drugs. [Getting patients] on the right path of therapy is probably the most important thing. Balancing that hope and that reality. I think hope is something they need to hold onto, because theres a lot more hope than theres ever been in the past with this disease. But it also leads into what is the most appropriate way to take care of these patientsa lot [of which concerns] this transplant-eligible case. I dont really [perform] transplants [in] individuals, but I have them all [receive] transplants when possible.

KREM: I say transplant eligibility is there until they prove theyre not eligible, so for patients 75 or younger, but Ive [performed transplants in] people up to [age] 76 or 77 if they look right, and they have to have a caregiver. They have to have adequate cardiac and pulmonary function and they have to demonstrate good treatment [adherence], and they cant have an active infection. Of course, their disease has to show some glimmer of chemotherapy response and you dont want to put someone through high-dose [treatment] if all the indications are theyre not going to get any mileage out of that. I would say that this patient has painted a picture of someone whos purely a transplant candidate butwho presents another difficult situation because hes not someone whos going to reach his expected life expectancy with standard therapies.

SHAIN: Does anybody else have a different opinion about transplant or a similar [one]? How do you think about that and when do you introduce it?

EPNER: I sell it as, I would take care of them at all phases of their care and oversee them rather than having to refer them and then having communication with the transplanting doctor.There are several FDA-approved drugs, such as ibrutinib [Imbruvica] andpost transplant, cyclophosphamide [Cytoxan]. There are a lot of ways that we can probably make graft-vs-host disease more livable as opposed to giving them another disease thats worse than the disease they had to begin with. I will have that discussion with people and tell them they would have to do it under a clinical trial and have to go [to a bigger cancer center].

KREM: I think that also brings up the question of how you define young patients and what is young.Some people might say that young [patients] are patients under 65 years old, but I think theres especially young. Whos really young? Because there are some patients who are in their 50s or their 40s and you might want to bring that discussion up with them. Maybe you get them under control with the first [autologous stem cell transplant] and then you have a plan ready at first relapse of how youre going to handle them. I think for someone in their 40s or early 50s, just the standard cells for 2 transplants arent quite enough [for] planning and thinking about the future.

SHAIN: Allogeneic transplant is one of the things that I discuss much less than I did even 5 or 10 years ago. Thats because of therapies that exist. I have people that have [had] allogeneic transplant and theyve done very well, and I have people who have [had] allogeneic transplant and theyve done very poorly. So, its still a question we have to think about.

SHAIN: VRd [bortezomib (Velcade) plus lenalidomide (Revlimid) and dexamethasone] is the standard of care and has been the standard of care for a long time for [patients who are] transplant eligible.1 It looks like everybody recognizes that CyBorD or [daratumumab (Darzalex) plus] VRd is only effective in patients with renal failure and probably shouldnt be a standard of care based on data we have. No KRd [carfilzomib (Kyprolis) plus lenalidomide (Revlimid) and dexamethasone] individuals, thats reasonable, though there are some questions there. I would tell you that today Im a DRVd [daratumumab, lenalidomide, bortezomib, and dexamethasone] guy, and I think [that with] the data [from the GRIFFIN trial (NCT02874742)], and if you marry in a little bit of Cassiopeia [NCT02541383 data], theres really strong evidence for 4 drugs to drive the disease down.

KREM: I think its an important point to make that bortezomib is not in all the publications, but there are more and more data starting to come out about the efficacy of the bortezomib dosing schedule.

SHAIN: We know our question is really triplet vs quadruplet. So how are we doing bortezomib in those dosing regimens and what do you think about it?

KREM: With the bortezomib, [data have] suggested that giving bortezomib twice a week for more than a cycle really beats people up. Whether you do it subcutaneously or intravenously, 1.3 mg/m2 in that dose density of cycles 1, 4, 8, and 11 really isnt tolerated long.

PAUL: I also exclusively use weekly bortezomib with the GRIFFIN regimen. Ive had patients [whom] Ive converted to a 28-day regimen as opposed to the 21-day regimen thats currently being evaluated. If I do the 28-day regimen, I do not do weekly daratumumab for cycles 1 through 3, which is what is being evaluated for the current trial. I do that to minimize toxicities and also for patient convenience. We have a lot of patients who come from far away to get their treatments and its challenging to make them come twice a week or even weekly for 12 weeks in a row.

SHAIN: I [also think weekly treatment] makes life a lot easier. Whether it be 1 or 2 cycles of twice weekly [treatment] is probably not terrible, but Ive moved away from it. I was a stickler for a long time to get some dose-dense bortezomib in the beginning, but I think its an important point that we all really understand that keeping people on the drug is more important than getting them a little bit of dose-dense [drug] to begin with.

EPNER: I had a patient with [a recent] myeloma [diagnosis], a couple [of them], in the COVID-19 era, before the vaccines were available. I was concerned about bringing them into the infusion room and exposing them to the risk. What I did was start them on ixazomib [Ninlaro] until they could get vaccinated and then I switched it over to bortezomib. Now, I sent them for their transplants to Emory [Transplant Center] and talked to some of the members of the team there, and they didnt have a very strong opinion about the use of ixazomib in terms of its efficacy.

SHAIN: Ixazomib is a good drug but its not bortezomib. Its a very good drug for the right person who doesnt want to come in or who cant come in. Ive seen it work outstandingly for patients in combination. Ive used it multiple times, but it is not what I walk in thinking about and its not something I often pick forpatients [with a new diagnosis].

KREM: On the plus side for ixazomib, it has great tolerability. I have seen much [fewer] adverse eventscompared with the other therapies. I would politely say that Im not sure how good the single agent or the doublet efficacy is for that drug. It does reasonably well in combination with other agents, but I think it does have a specialized setting, and as you said, Dr Shain, I dont think it replaces bortezomib.

ATRASH: I dont think I had much luck with ixazomib 4 mg, but yes, some patients do get a lot of benefits from ixazomib. In [a phase 1/2 study (NCT01217957)] that showed us that [the] high-risk population did get benefits from ixazomib, all the new data are [indicating that] perhaps ixazomib is not as effective as bortezomib.2 At the beginning of COVID-19at the very beginningI did a similar approach where I tried to avoid infusion center visits, but later we figured out that perhaps going very aggressive, despite COVID-19, is the best approach.

References

1. Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936-945. doi:10.1182/blood.2020005288

2. Kumar SK, Berdeja JG, Niesvizky R, et al. Ixazomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma: long-term follow-up including ixazomib maintenance. Leukemia. 2019;33(7):1736-1746. doi:10.1038/s41375-019-0384-1

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Roundtable Discussion: Shain Looks at the Role of Transplant Eligibility in Patients With Newly Diagnosed Multiple Myeloma - Targeted Oncology

Cardiac Stem Cells Comments Off on Roundtable Discussion: Shain Looks at the Role of Transplant Eligibility in Patients With Newly Diagnosed Multiple Myeloma – Targeted Oncology | November 8th, 2021

About five years ago, UGBC President Jack Bracher joined the registry to become a potential stem cell donor. A few years later, Bracher found out that he had a match.

I got a call from the nonprofit that Id done it through saying that I was a match for a patient with leukemia, so I had started going through the process of being able to donate to him, Bracher, MCAS 22, said. Fortunately he went into remission, so my donation wasnt needed, but I wanted to find a way to bring back the stem cell drive to Boston Colleges campus and register more students to donate.

The Undergraduate Government of Boston College (UGBC), Student Athlete Advisory Committee (SAAC), and Project Life Movement teamed up on Thursday and Friday to encourage students to join the global registry of potential bone marrow and stem cell donors.

Project Life Movement ambassador Luke Kuechly, former linebacker for the Carolina Panthers and BC 11, returned to campus to encourage students to get swabbed.

The University last hosted a Project Life Movement bone marrow registration event when BC retired Kuechlys jersey in 2016. Over 800 people joined the registry. This year, 777 people registered, according to Bracher, with 480 students getting swabbed on the first day. Bracher said this was the most swabs Project Life Movement got on a single day at a college campus.

Steve Luquire, a co-chair of Project Life Movement, said the number of students swabbed at BC exceeds what it defines as a good number for most colleges.

On most college campuses where we go to do these drives, 200 is a good drive, Luquire said. Were gonna be here today because of SAAC and the student government, and weve already done I think close to 250 in less than two hours.

College campuses are the best place to find a healthy, diverse group willing to join the registry, according to Luquire.

My wife of 41 years died of myelodysplasia syndrome, Luquire said. Her only match was her brother, who was 60 years old, and frankly, it works so much better if you have a person who is 18 to 35. And theres no place better than a college campus to find people who are willing to look at the vision and mission and join us.

Kuechly, who met Luquire in 2013, said they have been hosting drives together since then to raise awareness and improve the chances of finding donor matches.

We just know this little bit of time that we spend today and tomorrow and having you guys come by, we can raise awareness to potentially have a match for somebody that needs it, Kuechly said.

Finding even a few donor matches, Kuechly said, is a huge deal.

You might have five to 500 to 1000 people here, but if you can get a couple donors that match, thats whats powerful, Kuechly said.

Students joining the registry, Kuechly said, is a perfect example of BC students being men and women for others.

The big pillar in the Jesuit community is how can you help other people by being selfless with your time, and this is a perfect example of it, he said.

The impact of becoming a donor goes beyond just saving a persons life, according to Ann Henegar, executive director of Project Life Movement.

When you donate your stem cells or your bone marrow to a patient, youre not only saving that persons life, youre affecting a community, youre affecting a family, you know, a workplace, a campus, Henegar said.

Henegar said she encourages people to think about the impact they can make by registering to be a donor.

This is what I tell everybody If it were your sister, your boyfriend, your girlfriend, your aunt, your child, wouldnt you want someone to say yes? she said.

For Lubens Benjamin, CSOM 23, joining the registry is a great way of fulfilling BCs mission.

I think part of being someone who goes to BC is being a person for others and, like, this is right along with that mission, Benjamin said. If I could be a match for someone, if I can help someone extend their life, thats just something great to be a part of and I dont see why Id say no to that.

Jostine Rozenich, MCAS 25, spoke to the importance of taking time out of the day to join the registry.

Its such a crucial and important thing, even if it only takes a few minutes and it can save lives, Rozenich said. I think thats all about finding ways to put service into your daily life.

Rozenich said she has family members who have needed various transplants that rely on others to donate, which has shaped her perspective on joining the registry.

Why not go ahead and do that and save the life of somebody? she said. That is such a scary feeling to not know whether or not youre going to get a match.

Ultimately, it is a privilege to be part of a drive like this, Bracher said, and hosting the event just before the Red Bandanna Gamean annual football game that commemorates Welles Crowther, the BC alumnus credited with saving the lives of about a dozen people during the Sept. 11 terrorist attacksis a great way of uniting the mission of Project Life Movement and Crowthers story.

I think its just a great privilege to be able to work with Project Life and Luke, as well as the Student Athlete Advisory Committee, who hosted the drive that I was a match for, and for all that to come full circle, Bracher said. And for us to of course be doing it on Red Bandanna weekend of all weekends means a lot.

Featured Image by Ikram Ali / Heights Editor

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Kuechly Returns to Campus for Stem Cell and Bone Marrow Registry Drive The Heights - The Heights

Bone Marrow Stem Cells Comments Off on Kuechly Returns to Campus for Stem Cell and Bone Marrow Registry Drive The Heights – The Heights | November 8th, 2021

PlateletBio, a company developing a new class of cell therapies based on the biology of platelets, has raised $75.5 million to advance its drug pipeline, including a lead candidate for a rare bleeding disorder on track to reach the clinic next year.

Platelets are components of blood best known for their role forming clots that stop bleeding. But Watertown, Massachusetts-based PlateletBio notes that platelets have other properties, including a role delivering growth factors and proteins throughout the body. PlateletBio is developing therapies that take advantage of these properties, but rather than using platelets from a patient or healthy donors, the startup makes them.

In the body, platelets are formed in bone marrow. PlateletBio produces its platelet-like cells, or PLCs, inside a bioreactor that mimics bone marrow conditions. The source material for its PLCs are stem cells, which have the ability to become almost any cell or tissue in the body.

Platelets are technically not cells. They dont have a nucleus, but thats an advantage for therapeutic applications. Since a PlateletBio therapy wont introduce DNA into a patients body, the potential risks that come from introducing foreign genetic material are avoided. PlateletBio says it can produce PLCs with new features and therapeutic payloads that include antibodies, signaling proteins, therapeutic proteins, and nucleic acids.

PlateletBios lead cell therapy candidate is being developed to treat immune thrombocytopenia, a blood disorder in which the immune system mistakenly sees a patients platelets as foreign and destroys them. Immune thrombocytopenia patients have dangerously low platelet counts that make them susceptible to bleeding.

There is no FDA-approved treatment for the underlying cause of immune thrombocytopenia, but corticosteroids are used to try to dampen the immune systems attack on platelets. Platelet transfusions are another option, but the National Organization for Rare Disorders notes that these treatments are usually reserved for emergencies because the platelets are likely to be destroyed by antibodies produced by the patient.

Patients who have not responded to earlier treatments have two FDA-approved small molecule options: Tavalisse, from Rigel Pharmaceuticals, and the Swedish Orphan Biovitrum drug Doptelet. Sanofi aims to treat the disease with a small molecule called rilzabrutinib. That drug is designed to block Brutons tyrosine kinase, a protein that plays a role in the development of a B cells, a type of immune cell. Sanofi acquired the molecule last year via its $3.7 billion acquisition of Principia Biopharma.

The lead disease target for the Principia drug was multiple sclerosis. In September, Sanofi reported that rilzabrutinib failed that Phase 3 study. A separate Phase 3 test in immune thrombocytopenia is ongoing, as is a mid-stage clinical trial in another autoimmune condition called IgG4-related disease.

PlateletBio isnt the only company trying to turn a component of the blood into a new type of cell therapy. Cambridge, Massachusetts-based Rubius Therapeutics is developing cell therapies based on red blood cells. After disappointing early clinical trial results in the rare disease phenylketonuria last year, Rubius shifted its focus to cancer and immune system disorders. PlateletBios PLCs would represent an entirely new approach to treating immune thrombocytopenia. According to PlateletBios website, the company plans to file an investigational new drug application for its therapeutic candidate in the first half of next year.

PlateletBio is based on the research of Harvard University scientist Joseph Italiano, who co-founded the company under the name Platelet BioGenesis. When the startup emerged in 2017, it was developing platelets that could address the platelet shortage problem facing blood donation centers. Two years ago, the startup expanded its Series A round with $26 million in additional financing and plans to make its platelets into cell therapies. Besides immune thrombocytopenia, other diseases the biotech aims to treat include osteoarthritis and liver fibrosis.

PlateletBios latest financing, a Series B round, adds new investors SymBiosis, K2 HealthVentures, and Oxford Finance. Earlier investors Ziff Capital Partners and Qiming Venture Partners also participated in the new round.

This is a major milestone for PlateletBio, adding capital and resources needed to advance our innovative platelet-like cell therapy science and manufacturing platform and support key corporate initiatives over the next 18 to 24 months, Sam Rasty, the startups president and CEO, said in a prepared statement.

Photo by Flickr user Marco Verch via a Creative Commons license

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Cell therapy biotech PlateletBio reels in $75M as it looks ahead to first clinical test - MedCity News

Bone Marrow Stem Cells Comments Off on Cell therapy biotech PlateletBio reels in $75M as it looks ahead to first clinical test – MedCity News | November 8th, 2021

TORONTO -- Owen Snider was given as little as three months to live. His blood cancer had returned and the prognosis was not good. The news, delivered over the phone during the height of the early pandemic lockdown in spring 2020, was devastating.

The Ottawa-area retiree began putting his affairs in order, preparing for what appeared to be inevitable.

It was terrible, his wife Judith Snider told CTV News. But we finally decided that what we had to do was to live each day not to look forward to the end, but to look forward to tomorrow.

And yet, a year later, Snider is alive -- transformed, even -- and his non-Hodgkins lymphoma is in remission. His second chance is all thanks to a promising, Canadian-run program for cancer treatment called CAR T-cell therapy.

Snider became one of the first patients to participate in a national research program that is assessing whether this experimental treatment can be done safely in Canada and cheaper than in the U.S., where costs can run upwards of half a million dollars per patient.

I think I am a pretty successful lab rat, Snider, who previously endured chemotherapy treatments and a stem cell transplant, said in an interview.

Thirty days after treatment, the lymphoma was gone. So how can you not be happy about that?

CAR T-cell therapy is a type of gene therapy that trains or engineers a patients own immune system to recognize cancerous cells. A type of white blood cell, called a T-cell, is a key component of a bodys immune system. They are developed from stem cells in the bone marrow and help fight infection and disease by searching and targeting specific foreign substances, known as antigens, in the body.

The protein receptors on T cells bind to the protein antigens on the surfaces of foreign particles that fit those receptors, like a lock and key. The foreign substance is eradicated once their antigens are bound to a T-cell. But blood cancer cells are normal cells that undergo mutations, so they are not recognized as a foreign threat to the body. In other words, T-cells generally do not have the right receptor key to fit with the antigens of a cancer cell.

CAR T-cell therapy modifies the cells so they are able to identify the cancer cells and destroy them. Its a labour-intensive process that involves taking blood from a patient and separating the T-cells. Then scientists add a gene to the cells that gives them instructions to develop an artificial receptor called a chimeric antigen receptor, or CAR.

We actually take the T-cells out and we modify them in the lab and put them back into the patient. So now they're able to recognize the cancer and kill it off, explained Dr. Kevin Hay, Medical Director for Clinical Cell Therapy with BC Cancer.

I think we're just at the cusp of really understanding what this is going to do for patients in the future.

The therapy is a labour-intensive process -- Snider's cells were shipped to Victoria, B.C to be processed in a special lab facility, then shipped back to Ottawa about a week later, where they were infused back into his body.

The treatment is still being studied, but is already available for some cancers in the U.S. and Canada at a steep price.

Researchers began trials in Canada in 2019 to see if it could be done domestically at a lower cost, highlighting the importance of having key medical production and therapies available in Canada.

We knew we had to do domestic manufacturing and if we've learned anything from COVID-19, it's that domestic capability is really important when it comes to science and medicine, and this is a perfect example of that, said Dr. Natasha Kekre, a hematologist and lead researcher on the trail based at the Ottawa Hospital.

Progress was impacted slightly by the pandemic, but Snider was fortunate enough to participate and is the first patient to come forward to discuss their experience and why he hopes the program will expand across Canada to help others dealing with otherwise untreatable forms of cancer.

Scientists are hoping to release more data in the coming months -- more than 20 patients have been treated so far, according to Dr. Kekre.

This is hopefully just the beginning for us. So this first trial was a foundation to prove that we could actually manufacture T cells, that we could do this in a clinical trial. And so this trial will remain open for patients who are in need, she said.

So absolutely we feel like were opening a door.

Snider's first experience with cancer treatment was more than a decade ago, in 2010, when he underwent a powerful and aggressive chemotherapy regimen that helped him stay cancer-free for six years.

But the treatment was so harsh that when his cancer came back in 2016, doctors told him he could not go through that kind of chemotherapy again. Instead, Snider underwent a stem cell transplant, which gave him another four years without cancer, until April 2020.

This time the outlook was grim, so doctors decided to try and get him into the CAR T-cell trials that started just before the pandemic hit. The study was specifically for patients with acute lymphoblastic leukemia and non-Hodgkins lymphoma who were not responding to other treatments.

Snider said the entire process was a walk in the park compared to what he had gone through before. He was given a mild chemotherapy treatment for three days while his T-cells were being modified in a lab on the other side of the country.

[The T-cells] went to work right away. There's a period of time where there's a lot going on inside fighting each other and that sort of thing. You don't feel great or you don't really know how you feel, Snider described. The treatment was met with outstanding success.

And in 30 days, there was no lymphoma. I couldn't believe it.

For Dr. Kekre, the results bring hope. Snider has done quite well and does not have any evidence of lymphoma at the moment, she said.

I'm unfortunately in a business where I often have to give bad news, and it is really motivating and exciting to be able to offer therapies to patients who didn't have options and to make them better, she said.

The trial is currently at the stage where scientists are making sure the product remains safe. Side-effects can include neurotoxicity, which harms the nervous system, and cytokine release syndrome, which triggers an acute system-wide inflammatory response that can result in organs not functioning properly. But so far researchers have, for the most part, been able to manage and reverse any side effects.

With such promising outcomes for patients who otherwise had no options left, researchers are talking about expanding these studies across Canada and to other forms of cancer. For now, the lab in Victoria is the only facility equipped to make these cell modifications.

I think its really going to be revolutionary with how we treat cancer in the future, not just blood cancers, but all cancers, said Dr. Hay.

Today, Snider is healthy and strong, even able to chop wood at his home near Ottawa. He and his wife Judith, a retired federal judge, are enjoying life anew.

It certainly has given us a future that we didnt know we had, she said.

The treatment not only bought Snider extra time, but also significantly improved his quality of life.

What was given to me is practically a normal life, he added.

It's really just transformed, not just extended, but transformed my life.

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CAR T-cell therapy: Hear from a Canadian patient - CTV News

Bone Marrow Stem Cells Comments Off on CAR T-cell therapy: Hear from a Canadian patient – CTV News | November 8th, 2021

TEL AVIV, Israel, Nov. 4, 2021 /PRNewswire/ --BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a late clinical-stage biopharmaceutical Company focused on oncology, today announced an oral presentation and three poster presentations at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition, which is being held December 11-14, 2021 in Atlanta, GA, and virtually.

The oral presentation will elaborate on the successful results of the Company's GENESIS Phase 3 pivotal trial. The study showed highly significant and clinically meaningful results supporting the use of Motixafortide on top of G-CSF for mobilization of stem cells for subsequent collection and transplantation in patients with multiple myeloma. In addition, the poster presentations will show that extended inhibition of the CXCR4 receptor by Motixafortide results in the mobilization of high numbers of stem cells, including specific sub-populations, which were correlated with reduced time to engraftment when infused in high numbers.

The Company is also presenting findings from in-vivo and in-vitro pre-clinical studies demonstrating that Motixafortide acts as an immunomodulator by affecting the biology of regulatory T cells (Tregs), supporting biomarker findings from the Company's COMBAT Phase 2 study in pancreatic cancer patients.

"We are very pleased with the breadth of our oral and poster presentations at this year's ASH meeting, which reflect the versatility of Motixafortide as the potential backbone of promising new treatments for both hematological and solid tumor cancers," stated Philip Serlin, Chief Executive Officer of BioLineRx. "Of particular note is the oral presentation on the outstanding results from our GENESIS Phase 3 pivotal study in stem cell mobilization demonstrating that Motixafortide effectively mobilizes a high number of cells enabling ~90% of patients to undergo transplantation following a single administration of Motixafortide and a single apheresis session. In addition, the high number of cells mobilized by Motixafortide enables infusion of an optimal number of cells, which could result in faster time to engraftment, and also allows for cryopreservation for future transplantation(s). These results, together with our recently completed successful pharmacoeconomic study, strongly support our view that Motixafortide on top of G-CSF can become the new standard of care in SCM, if approved, to the benefit of patients and payers alike. We look forward to submitting an NDA in the first half of next year, as previously communicated."

Further details of the presentations are provided below.

Oral Presentation

Title: Motixafortide (BL-8040) and G-CSF Versus Placebo and G-CSF to Mobilize Hematopoietic Stem Cells for Autologous Stem Cell Transplantation in Patients with Multiple Myeloma: The GENESIS Trial

Date: Sunday, December 12, 2021

Time: 12:00 PM

Location: Georgia World Congress Center, Hall A1

This oral presentation describes the GENESIS Phase 3 pivotal trial design, endpoints and results. The GENESIS study was a double blind, placebo controlled, multicenter trial, in which 122 patients were randomized (2:1) to receive either Motixafortide + G-CSF or placebo + G-CSF for stem cell mobilization prior to stem cell transplant in multiple myeloma patients. Total CD34+ cells/kg were analyzed on site to determine if patients mobilized to the goal and all samples were subsequently sent for assessment by a central laboratory. The number of CD34+ cells infused was determined independently by each investigator according to local practice.

The study concluded that a single administration of Motixafortide on top of G-CSF significantly increased the proportion of patients mobilizing 6x106 CD34+ cells/kg for stem cell transplantation (92.5%) vs G-CSF alone (26.2%) in up to two apheresis days (p<0.0001), while enabling 88.8% to collect 6x106 CD34+ cells/kg in just one apheresis day (vs 9.5% with G-CSF alone; p<0.0001). In addition, the median number of hematopoietic stem cells mobilized in one apheresis day with Motixafortide + G-CSF was 10.8x106 CD34+cells/kg vs 2.1x106 CD34+ cells/kg with G-CSF alone.

Poster Presentations

Title:Autologous Hematopoietic Cell Transplantation with Higher Doses of CD34+ Cells and Specific CD34+ Subsets Mobilized with Motixafortide and/or G-CSF is Associated with Rapid Engraftment A Post-hoc Analysis of the GENESIS Trial

Date: Sunday, December 12, 2021

Time: 6:00 PM - 8:00 PM

The CD34+ hematopoietic stem and progenitor cell (HSPC) dose infused during stem cell transplantation remains one of the most reliable clinical parameters to predict quality of engraftment. A minimum stem cell dose of 2-2.5x106 CD34+ cells/kg is considered necessary for reliable engraftment, while optimal doses of 5-6x106 CD34+ cells/kg are associated with faster engraftment, as well as fewer transfusions, infections, and antibiotic days.

An analysis was performed using pooled data from all patients in the GENESIS trial to evaluate time to engraftment based on the total number of CD34+ cells/kg infused, as well as specific numbers of CD34+ cell sub-populations infused.

The addition of Motixafortide to G-CSF enabled significantly more CD34+ cells to be collected in one apheresis (median 10.8x106 CD34+ cells/kg) compared to G-CSF alone (2.1x106 CD34+ cells/kg), as well as 3.5-5.6 fold higher numbers of hematopoietic stem cells (HSCs), multipotent progenitors (MPPs), common myeloid progenitors (CMPs) and granulocyte and macrophage progenitors (GMPs) (all p-values <0.0004). A dose response was observed with a significant correlation between faster time to engraftment and infusion of higher number of total CD34+ HSPC doses (6x106 CD34+ cells/kg) and combined HSC, MPP, CMP and GMP subsets. The high number of CD34+ cells/kg mobilized with Motixafortide on top of G-CSF enables the potential infusion of 6x106 CD34+ cells/kg, as well as cryopreservation of cells for later use.

Title: Immunophenotypic and Single-Cell Transcriptional Profiling of CD34+ Hematopoietic Stem and Progenitor Cells Mobilized with Motixafortide (BL-8040) and G-CSF Versus Plerixafor and GCSF Versus Placebo and G-CSF: A Correlative Study of the GENESIS Trial

Date: Monday, December 13, 2021

Time: 6:00 PM - 8:00 PM

CD34 expression remains the most common immunophenotypic cell surface marker defining human hematopoietic stem and progenitor cells (HSPCs). The addition of CXCR4 inhibitors to G-CSF has increased mobilization of CD34+ HSPCs for stem cell transplantation; yet the effect of CXCR4 inhibition, with or without G-CSF, on mobilization of specific immunophenotypic and transcriptional CD34+ HSPC subsets is not well-characterized.

Motixafortide is a novel cyclic peptide CXCR4 inhibitor with a low receptor-off rate and extended in vivo action when compared to plerixafor. GENESIS Phase 3 trial patients were prospectively randomized (2:1) to receive either Motixafortide + G-CSF or placebo + G-CSF for HSPC mobilization. Demographically similar multiple myeloma patients undergoing mobilization with plerixafor + G-CSF prior to stem cell transplant were prospectively enrolled in a separate tissue banking protocol.

Extended CXCR4 inhibition with Motixafortide + G-CSF mobilized significantly higher numbers of combined CD34+ HSCs, MPPs and CMPs compared to plerixafor + G-CSF or G-CSF alone (p<0.05). Additionally, Motixafortide + G-CSF mobilized a 10.5 fold higher number of immunophenotypically primitive CD34+ HSCs capable of broad multilineage hematopoietic reconstitution compared to G-CSF alone (p<0.0001) and similar numbers compared to plerixafor + G-CSF. Furthermore, lack of CXCR4 inhibition resulted in mobilization of more-differentiated HCSs, whereas extended CXCR4 inhibition with Motixafortide + G-CSF (but not plerixafor + G-CSF) mobilized a unique MPP-III subset expressing genes specifically related to leukocyte differentiation.

Title: The High Affinity CXCR4 Inhibitor, BL-8040, Impairs the Infiltration, Migration, Viability and Differentiation of Regulatory T Cells

Date: Sunday, December 12, 2021

Time: 6:00 PM - 8:00 PM

This poster describes results of pre-clinical in-vivo and in-vitro studies demonstrating that Motixafortide potentially acts as an immunomodulator by affecting the biology of regulatory T cells. Motixafortide reduced the amount of infiltrating Tregs into the tumors, impaired the migration of Tregs toward CXCL12 and induced Tregs cell death. Furthermore, Motixafortide was found to inhibit the differentiation of nave CD4 T cells toward Tregs.

About BioLineRx

BioLineRx Ltd. (NASDAQ/TASE: BLRX) is a late clinical-stage biopharmaceutical company focused on oncology. The Company's business model is to in-license novel compounds, develop them through clinical stages, and then partner with pharmaceutical companies for further clinical development and/or commercialization.

The Company's lead program, Motixafortide (BL-8040), is a cancer therapy platform that was successfully evaluated in a Phase 3 study in stem cell mobilization for autologous bone-marrow transplantation, has reported positive results from a pre-planned pharmacoeconomic study, and is currently in preparations for an NDA submission. Motixafortide was also successfully evaluated in a Phase 2a study for the treatment of pancreatic cancer in combination with KEYTRUDA and chemotherapy under a clinical trial collaboration agreement with MSD (BioLineRx owns all rights to Motixafortide), and is currently being studied in combination with LIBTAYO and chemotherapy as a first-line PDAC therapy.

BioLineRx is also developing a second oncology program, AGI-134, an immunotherapy treatment for multiple solid tumors that is currently being investigated in a Phase 1/2a study.

For additional information on BioLineRx, please visit the Company's website at http://www.biolinerx.com, where you can review the Company's SEC filings, press releases, announcements and events.

Various statements in this release concerning BioLineRx's future expectations constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as "may," "expects," "anticipates," "believes," and "intends," and describe opinions about future events. These forward-looking statements involve known and unknown risks and uncertainties that may cause the actual results, performance or achievements of BioLineRx to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Factors that could cause BioLineRx's actual results to differ materially from those expressed or implied in such forward-looking statements include, but are not limited to: the initiation, timing, progress and results of BioLineRx's preclinical studies, clinical trials and other therapeutic candidate development efforts; BioLineRx's ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; BioLineRx's receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings and approvals; the clinical development, commercialization and market acceptance of BioLineRx's therapeutic candidates; BioLineRx's ability to establish and maintain corporate collaborations; BioLineRx's ability to integrate new therapeutic candidates and new personnel; the interpretation of the properties and characteristics of BioLineRx's therapeutic candidates and of the results obtained with its therapeutic candidates in preclinical studies or clinical trials; the implementation of BioLineRx's business model and strategic plans for its business and therapeutic candidates; the scope of protection BioLineRx is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; estimates of BioLineRx's expenses, future revenues, capital requirements and its needs for additional financing; risks related to changes in healthcare laws, rules and regulations in the United States or elsewhere; competitive companies, technologies and BioLineRx's industry; risks related to the COVID-19 pandemic; and statements as to the impact of the political and security situation in Israel on BioLineRx's business. These and other factors are more fully discussed in the "Risk Factors" section of BioLineRx's most recent annual report on Form 20-F filed with the Securities and Exchange Commission on February 23, 2021. In addition, any forward-looking statements represent BioLineRx's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. BioLineRx does not assume any obligation to update any forward-looking statements unless required by law.

Contact:

Tim McCarthyLifeSci Advisors, LLC+1-212-915-2564[emailprotected]

or

Moran MeirLifeSci Advisors, LLC+972-54-476-4945[emailprotected]

SOURCE BioLineRx Ltd.

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BioLineRx Announces an Oral Presentation and Three Poster Presentations at the 63rd American Society of Hematology (ASH) Annual Meeting &...

Bone Marrow Stem Cells Comments Off on BioLineRx Announces an Oral Presentation and Three Poster Presentations at the 63rd American Society of Hematology (ASH) Annual Meeting &… | November 8th, 2021

Two kidney transplant patients who received a stem cell therapy developed by Talaris Therapeutics were able to come off all immunosuppressant drugs within a year, without any evidence of graft rejection.

The first findings from Talaris phase 3 trial of the cell therapy called FCR001 suggest it may be possible to eliminate the need entirely for patients to take what may be dozens of tablets daily after organ transplants, according to the US biotech.

While still preliminary, the experience with the two patients back up Talaris hope that giving a one-shot dose of FCR001 the day after an organ transplant could stimulate immune tolerance in the recipient, and avoid the side effects of current drug treatments such as infections, heart disease, and some forms of cancer.

The companys approach relies on administering haematopoietic stem cells from the individual who donated the organ, in order to generate what Talaris refers to as chimerism, with both donor and recipient cells present in the bone marrow. That allows the immune system to see the transplanted organ as self rather than foreign.

The first two recipients in Talaris FREEDOM-1 phase 3 trial had received FCR001 at least 12 months earlier, and showed stable kidney function, according to Talaris.

A larger group of five patients who were at least three months from the cell therapy maintained more than 50% chimerism in their T cells, which the biotech said was a sign of long-term, immunosuppression-free tolerance to the donated kidney in its phase 2 trials.

The FREEDOM-1 results reported at the American Society of Nephrology (ASN) meeting this week were accompanied by updated results from Talaris phase 2 study, in which all 26 patients originally weaned off immunosuppressants have continued to remain off them without rejecting their donated kidney.

Some transplant patients treated with Talaris therapy in earlier trials have now been off all immunosuppression for more than 12 years without signs of kidney rejection.

Talaris intends to enrol 120 subjects into the phase 3 trial, which is scheduled to generate results in 2023.

Earlier this year, Talaris raised $150 million via a Nasdaq listing that will be used to take FCR001 through the phase 3 programme in organ transplantation and as a treatment for rare autoimmune disease scleroderma.

It also recently started a phase 2 trial of the cell therapy to see if it is able to induce immune tolerance to a transplanted kidney in patients who received the transplant from a living donor up to a year prior to administration of FCR001.

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Talaris therapy ends need for immune drugs in transplant patients - - pharmaphorum

Bone Marrow Stem Cells Comments Off on Talaris therapy ends need for immune drugs in transplant patients – – pharmaphorum | November 8th, 2021

Rachel B. Salit, MD, discussed the case of a 48-year-old patient with graft-versus-host-disease.

Rachel B. Salit, MD, associate professor, Clinical Research Division, Fred Hutchinson Cancer Research Center at the University of Washington School of Medicine in Seattle, WA, discussed the case of a 48-year-old patient with graft-versus-host-disease.

Targeted OncologyTM: What are your thoughts on the currently accepted options for acute GVHD (aGVHD) prophylaxis?

SALIT: Between calcineurin inhibitors, if we have a choice, my preference is usually tacrolimus. Tacrolimus is better tolerated [than cyclosporin] in terms of adverse events [AEs], blood pressure, kidney function, and [even] the smell.

Methotrexate is a tried-and-true prophylaxis, especially in the myeloablative or high-intensity transplant setting. [In contrast], mycophenolate mofetil [MMF]; [CellCept] is usually used in the nonmyeloablative or reduced-intensity setting. When calcineurin inhibitors were used with MMF as prophylaxis for GVHD, the GVHD was higher. Thats why we [use] methotrexate [instead of MMF].1

Sirolimus [Rapamune] is often combined with a calcineurin inhibitor and MMF, or with a calcineurin inhibitor and methotrexate. Sirolimus is very well tolerated, except for some triglyceride AEs. Additionally, the combination of sirolimus plus MMF and a calcineurin inhibitor has been shown to significantly decrease GVHD in the reduced-intensity setting compared with [the effect observed with] MMF and a calcineurin inhibitor alone.2

CAR [chimeric antigen receptor] T-cellantibody therapy plus antithymocyte globulin [ATG] and alemtuzumab [Lemtrada] are more frequently used in Europe [than in the United States]. There have been mixed results, and there is some concern of increased relapse with [anti-thymocyte globulin (ATG) therapy]. Ex vivo T-cell depletion and CD34-positive cell selection [are] also uncommon in the United States.

Posttransplant cyclophosphamide [Cytoxan] [is becoming more common], and it was originally [used in the setting of] haploidentical transplants. Now it is increasingly used in the unrelated donor setting, and Im sure it will be translated to the sibling setting, too. [This regimen] has been shown to decrease effector T cells.3 Moreover, chronic GVHD is [reduced by this regimen], but aGVHD is not changed.

A recent study retrospectively compared many patients [with haploidentical donors] to a smaller number of patients [who had] unrelated donors and who received posttransplant cyclophosphamide. The data showed that the patients with unrelated donors and posttransplant cyclophosphamide had better overall survival [OS] and decreased relapse compared with the patients with haploidentical donors.4

For a long time, [most trials that compared GVHD and OS between patients with haploidentical] vs unrelated or sibling donors have shown that posttransplant [cyclophosphamide in the setting of haploidentical] transplants is associated with reduced chronic GVHD, but the other outcomes were the same. Is this result attributable to the fact that the transplant is haploidentical, or is it attributable to the posttransplant cyclophosphamide? I think that question will be answered within the next [few] years.

What risk factors for GVHD do you notice in the case described?

There are multiple risk factors. The fact that the donor is multiparous puts the recipient at higher risk for GVHD. The patients high intensity, myeloablative conditioning regimen increases the risk for GVHD, as do the donors CMV seropositivity and the fact that the patient and donor are not sex matched. The risk of GVHD also increases with donor age.

Risk for GVHD is also increased by major human leukocyte antigen [HLA] disparity. We look at class I [HLA-A, -B, and -E] and class II [HLA-DR and -DQ] antigens, with a 10 out of 10 score constituting a match. There are data coming out that show that the class II antigen HLA-DP also matters in certain cases5; a match that includes this antigen [a 12 out of 12 (score)] is better than a 10 out of 10 [score]. [This patients donor was HLA-matched, but] minor HLA mismatches can increase the risk of GVHD [in patients like this one whose donor is unrelated].

Stem cell source and graft composition are other considerations, but this patient received peripheral blood, which confers a higher risk of GVHD than does bone marrow. Peripheral blood has a higher CD34-positive cell count, therefore a higher T-cell dose; both factors increase GVHD risk. At our center, we dont often cap CD34-positive cell count or T-cell dose, except in the haploidentical setting.

I would not include ABO blood type as a risk factor. There are mixed data regarding whether major and minor ABO mismatches lead to increased GVHD.6

What standardized guidelines exist for organ staging and grading in the context of aGVHD?

[According to Mount Sinai Acute GVHD International Consortium], the skin, the liver, and gastrointestinal [GI] tract are the 3 organs included in aGVHD staging. The skin is [described in terms of] the percentage of body surface area [BSA] affected. Stage 0 is no rash, stage 1 is a rash covering less than 25% of the BSA, stage 2 is a rash covering 25% to 50% of the BSA, stage 3 is a rash covering greater than 50% of the BSA, and stage 4 is generalized erythroderma.7

According to the liver status [bilirubin level], staging starts at stage 0 [less than 2 mg/dL] and progresses through stage 1 [2-3 mg/dL], stage 2 [3.1-6 mg/dL], and stage 3 [6.1-15 mg/dL] to a final stage of 4 [greater than 15 mg/dL]. The lower GI staging system [counts] the number of episodes per day of liquid stool output. Stage 0 is fewer than 3 episodes [of stool output], stage 1 is 3 to 4 episodes, stage 2 is 5 to 7 episodes, and stage 3 is greater than 7 episodes. If you have an inpatient, then you can use these exact quantities. If you have an outpatient, you can use these values as rough markers. Regarding the upper GI staging system, in stage 0, nausea, vomiting, or anorexia are absent or intermittent, but in stage 1, they are persistent.

The other thing I often look at [to judge] severity [of GI involvement] is the electrolytes. For example, if the patient says they are having 5 episodes of stool a day, but their potassium and magnesium are normal and theyre not becoming acidemic, then you [might consider that] these stools are only of small volume. If the patient starts to have electrolyte abnormalities or starts to become acidemic, then you [should consider that] maybe theyre having more diarrhea than theyre [telling you].

When we grade according to most severe target organ involvement, grade I reflects the presence only of stage 1 to 2 skin involvement. Any GI or liver involvement is automatically [at least grade] II, the point at which you would consider treating symptoms topically. Grade IIA indicates upper GI involvement, and grade IIB indicates lower GI involvement.8 Once the patient gets to grade III, they almost always [require] systemic therapy.7

What stage and grade would you give this patient?

With 60% skin involvement, he would have a skin stage of 3, and with 4 episodes of diarrhea per day, he would have a lower GI stage of 1. [He would have an overall clinical grade of IIB.]

What are GVHD and aGVHD biomarkers, and how are they used?

Biomarkers of GVHD are markers of inflammation found in the blood that will tell you the patient is at a higher risk for developing GVHD. These biomarkers include elafin, IL-2 receptor-, IL-8, tumor necrosis factor receptor-1, hepatocyte growth factor, and regenerating islet-derived 3- [NCT00224874].9 The use of biomarkers [to predict patients risk of developing GVHD could guide physicians as they choose] a starting steroid dosage, eg, 2 mg/kg vs 1 mg/kg.

What data guide your decisions about steroid therapy in GVHD?

Although the concept of GVHD and aGVHD risk stratification is not generally used in practice, high-risk GVHD vs standard-risk GVHD has been shown to be associated with a lower rate of complete response to steroids [27% vs 48%, respectively; P < .001] and higher treatment-related mortality [incidence at 6 months after steroid therapy onset, 44% vs 22%, respectively; P < .001].10 If a patient has a higher grade of GVHD, they are more likely to be steroid refractory.

The steroid response of GVHD is classified as steroid refractory or resistant if GVHD progresses within the first 3 to 5 days of prednisone therapy onset [ 2 mg/kg per day], fails to improve within 5 to 7 days of treatment initiation at 1 mg/kg or shows an incomplete response after more than 28 days [of immunosuppressive treatment including steroids]. Steroid dependence [means that either] the prednisone cannot be tapered below 2 mg/kg daily or the GVHD recurs during the steroid taper.11

You cant really [know] who is going to respond to steroids without [trying]. Our initial treatment for any patient with GVHD is steroids. There are no data to suggest that we [should] add something other than steroids as the first line or that we [should] add double therapy for the first line. Its going to be different for every individual.

Also, regarding steroid therapy, the question has been raised: If patients receive higher doses sooner, will that result in a lower [total] exposure to steroids? In the study we did at our institution, we found that when patients with skin GVHD were randomly assigned [to receive] 1 mg/kg vs 0.5 mg/kg, patients [who received the lower dose] had a longer and higher overall exposure to steroids.12 [In cases of skin GVHD], we tend to undertreat patients, and it may help to give them at least 1 mg/kg, but for GI GVHD, we usually give 1 mg/kg. It may not help to give 2 mg/kg unless the GVHD is severe.

Other than steroids, what therapy options exist for aGVHD, according to the National Comprehensive Cancer Network (NCCN)?

Ruxolitinib [Jakafi] is the only approved therapy, and it is supported by category 1 evidence. Some other therapies, such as MMF and sirolimus, are [relatively] benign. Other treatments, like ATG, are more toxic, whereas extracorporeal photopheresis [ECP] doesnt have a lot of data [to support it]. However, we do use a lot of ECP, [primarily for] steroid-dependent GVHD of the skin.13

What data support the use of ruxolitinib for aGVHD?

In the REACH1 study [NCT02953678], patients with steroid refractory grade 2 to 4 aGVHD received ruxolitinib, 5 mg twice a day. Later, patients could increase to 10 mg twice a day.14,15

The overall response rate [ORR] at day 28 was about 55%. The best ORR at any time during treatment was 73%. Time to response was about 7 days [range, 6-49]. The median duration of response was almost a year. Death from causes other than malignancy relapse was found in about 50% of patients. The median OS was about 5 months, whereas median OS for steroid refractory GVHD was 1 month, [but median OS for day 28 responders was not reached].16,17 The overall response rate [ORR] at day 28 was about 55%. The best ORR at any time during treatment was 73%. Time to response was about 7 days [range, 6-49]. The median duration of response was almost a year. Death from causes other than malignancy relapse was found in about 50% of patients. The median OS was about 5 months, whereas median OS for steroid-refractory GVHD was 1 month, [but median OS for day 28 responders was not reached].15

The ORR at day 28 was 62% in the ruxolitinib group vs 39% in the control group [odds ratio (OR), 2.64; 95% CI, 1.65-4.22; P < .001]; the durable ORR at day 56 was 40% in the ruxolitinib group vs 22% in the control group [OR, 2.38; 95% CI, 1.43-3.94; P < .001].18 These results led to the FDA approval of ruxolitinib for second-line therapy for steroid-refractory aGVHD.19

[Separate analyses were conducted of] GI and skin GVHD. In the ruxolitinib group, aGVHD staging of the lower GI was stage 3 and 4 for most patients at baseline. This was reduced in most patients to stage 0, 1, and 2 by day 28. In contrast, most patients treated with BAT still presented with stage 2 to 4 GVHD by day 28. Likewise for the skin, the GVHD stage was more likely to decrease following treatment with ruxolitinib than with BAT.19

Median failure-free survival was 5 months in the ruxolitinib group vs 1 month in the BAT group [HR, 0.46; 95% CI, 0.35-0.60]; 5 months was a big achievement compared with our previous standard. After 1 year, 40% of the patients in the experimental group were still alive. Regarding AEs associated with ruxolitinib, the most difficult [AE to manage] is thrombocytopenia [in REACH2, affecting 33% of the ruxolitinib group vs 18% of the BAT group]. Infections with ruxolitinib [in the context of GVHD] probably are equivalent to [those observed with] any other immune suppression drug [for cytomegalovirus, 26% in the ruxolitinib group, 21% in the BAT group].19

REFERENCES:

1. Yoshida S, Ohno Y, Nagafuji K, et al. Comparison of calcineurin inhibitors in combination with conventional methotrexate, reduced methotrexate, or mycophenolate mofetil for prophylaxis of graft-versus-host disease after umbilical cord blood transplantation. Ann Hematol. 2019;98(11):2579-2591. doi:10.1007/s00277-019-03801-z

2. Bejanyan N, Rogosheske J, DeFor TE, et al. Sirolimus and mycophenolate mofetil as calcineurin inhibitor-free graft-versus-host disease prophylaxis for reduced-intensity conditioning umbilical cord blood transplantation. Biol Blood Marrow Transplant. 2016;22(11):2025-2030. doi:10.1016/j. bbmt.2016.08.005

3. Wodarczyk M, Ograczyk E, Kowalewicz-Kulbat M, Druszczyska M, Rudnicka W, Fol M. Effect of cyclophosphamide treatment on central and effector memory T cells in mice. Int J Toxicol. 2018;37(5):373-382.

4. Shaw BE. Related haploidentical donors are a better choice than matched unrelated donors: counterpoint. Blood Adv. 2017;1(6):401-406. doi:10.1182/bloodadvances.2016002188

5. Zachary AA, Leffell MS. HLA mismatching strategies for solid organ transplantation - a balancing act. Front Immunol. 2016;7:575. doi:10.3389/ fimmu.2016.00575

6. Brierley CK, Littlewood TJ, Peniket AJ, et al. Impact of ABO blood group mismatch in alemtuzumab-based reduced-intensity conditioned haematopoietic SCT. Bone Marrow Transplant. 2015;50(7):931-938. doi:10.1038/bmt.2015.51

7. Harris AC, Young R, Devine S, et al. International, multicenter standardization of acute graft-vs-host disease clinical data collection: a report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant. 2016;22(1):4-10. doi:10.1016/j.bbmt.2015.09.001

8. Lee SJ. Classification systems for chronic graft-versus-host disease. Blood. 2017;129(1):30-37. doi:10.1182/blood-2016-07-686642

9. Levine JE, Logan BR, Wu J, et al. Acute graft-vs-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study. Blood. 2012;119(16):3854-3860. doi:10.1182/blood-2012-01-403063

10. MacMillan ML, Robin M, Harris AC, et al. A refined risk score for acute graft-vs-host disease that predicts response to initial therapy, survival, and transplant-related mortality. Biol Blood Marrow Transplant. 2015;21(4):761-767. doi:10.1016/j.bbmt.2015.01.001

11. Schoemans HM, Lee SJ, Ferrara JL, et al; European Society for Blood and Marrow Transplantation [EBMT] Transplant Complications Working Party; EBMT-National Institutes of Health [NIH]-Center for International Blood and Marrow Transplant Research [CIBMTR] GVHD Task Force. EBMT-NIH-CIBMTR Task Force position statement on standardized terminology & guidance for graft-vs-host disease assessment. Bone Marrow Transplant. 2018;53(11):1401-1415. doi:10.1038/s41409-018-0204-7

12. Mielcarek M, Furlong T, Storer BE, et al. Effectiveness and safety of lower dose prednisone for initial treatment of acute graft-versus-host disease: a randomized controlled trial. Haematologica. 2015;100(6):842-848. doi:10.3324/haematol.2014.118471

13. NCCN. Clinical Practice Guidelines in Oncology. Hematopoietic cell transplantation, version 5.2021. Accessed October 13, 2021. https://www.nccn.org/professionals/physician_gls/pdf/hct.pdf

14. Chao N. Finally, a successful randomized trial for GVHD. N Engl J Med. 2020;382(19):1853-1854. doi:10.1056/NEJMe2003331

15. Jagasia M, Zeiser R, Arbushites M, Delaite P, Gadbaw B, von Bubnoff N. Ruxolitinib for the treatment of patients with steroid-refractory GVHD: an introduction to the REACH trials. Immunotherapy. 2018;10(5):391-402. doi:10.2217/ imt-2017-0156

16. Jagasia M, Perales MA, Schroeder MA, et al. Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial. Blood. 2020;135(20):1739-1749. doi:10.1182/blood.2020004823

17. Jagasia M, Ali H, Schroeder MA, et al. Ruxolitinib in combination with corticosteroids for the treatment of steroid-refractory acute graft-vs-host disease: results from the phase 2 REACH1 trial. Biol Blood Marrow Transplant. 2019;25(suppl 3):S52. doi:10.1016/j.bbmt.2018.12.130

18. Zeiser R, von Bubnoff N, Butler J, et al; REACH2 Trial Group. Ruxolitinib for glucocorticoid-refractory acute graft-vs-host disease. N Engl J Med. 2020;382(19):1800-1810. doi:10.1056/NEJMoa1917635

19. Przepiorka D, Luo L, Subramaniam S, et al. FDA approval summary: ruxolitinib for treatment of steroid-refractory acute graft-versus-host disease. Oncologist. 2020;25(2):e328-e334. doi:10.1634/theoncologist.2019-0627

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Salit Discusses the Use of Staging and Grading for Patients With GVHD to Choose Appropriate Treatment - Targeted Oncology

Bone Marrow Stem Cells Comments Off on Salit Discusses the Use of Staging and Grading for Patients With GVHD to Choose Appropriate Treatment – Targeted Oncology | November 8th, 2021

Updates from OTL-201 Clinical Proof-of-Concept Study in MPS-IIIA and OTL-204 Preclinical Study for GRN-FTD at ESGCT Showcase Potential for HSC Gene Therapy in Multiple Neurodegenerative Disorders

Launch Activities for Libmeldy Across Key European Countries, including Reimbursement Discussions, Progressing in Anticipation of Treating Commercial Patients

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Cash and Investments of Approximately $254M Provide Runway into First Half 2023

BOSTONandLONDON, Nov. 04, 2021 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today reported financial results for the quarter ended September 30, 2021, as well as recent business updates and upcoming milestones.

This quarter, we are pleased by the progress demonstrated by our investigational neurometabolic HSC gene therapy programs with promising preclinical and clinical updates at ESGCT, said Bobby Gaspar, M.D., Ph.D., chief executive officer of Orchard. With follow-up in OTL-201 for MPS-IIIA patients now ranging between 6 and 12 months, biomarker data remain highly encouraging, showing supraphysiological enzyme activity and corresponding substrate reductions in the CSF and urine. The launch strategy for Libmeldy is also advancing in Europe with momentum building on reimbursement discussions and patient finding activities.

Recent Presentations and Business Updates

Data presentations at ESGCT

Clinical and pre-clinical data from across the companys investigational hematopoietic stem cell (HSC) gene therapy portfolio were featured in two oral and seven poster presentations at the European Society of Gene & Cell Therapy Congress (ESGCT) on October 19-22. Highlights from key presentations are summarized below:

OTL-201 for Mucopolysaccharidosis type IIIA (MPS-IIIA): A poster presentation featured supportive biomarker data from the first four patients with evaluable results, with duration of follow-up ranging from 6 to 12 months. The treatment has been generally well-tolerated in all enrolled patients (n=5) with no treatment-related serious adverse events (SAEs). Supraphysiological N-sulphoglucosamine sulphohydrolase ( SGSH) enzyme activity above the normal range was seen in leukocytes and plasma within one to three months in all evaluable patients (n=4).A greater than 90% reduction in urinary glycosaminoglycans (GAGs) was seen within three months in all evaluable patients (n=4).SGSH activity in the cerebrospinal fluid (CSF) increased from undetectable at baseline to within or above the normal range by six months in all patients with available data (n=3).CSF GAGs decreased from baseline in patients with available data (n=3).OTL-204 for Progranulin-mutated Frontotemporal Dementia (GRN-FTD): Preliminary in vivo data from the preclinical proof-of-concept study showed that murine GRN -/- HSPCs, transduced with an LV expressing progranulin under the control of a novel promoter, are able to engraft and repopulate the brain myeloid compartment of FTD mice and to locally deliver the GRN enzyme.

R&D Investor Event Summary

In September, Orchard hosted an R&D investor event highlighting its discovery and research engine in HSC gene therapy, including an update on the OTL-104 program in development for NOD2 Crohns disease (NOD2-CD) and potential new applications in HSC-generated antigen-specific regulatory T-cells (Tregs) and HSC-vectorization of monoclonal antibodies (mAbs).

The discussion also covered the differentiated profile of Orchards HSC gene therapy approach, which has exhibited favorable safety, long-term durability and broad treatment applicability.

In particular, Orchards lentiviral vector-based HSC gene therapy programs have shown no indication of insertional oncogenesis and no evidence of clonal dominance due to integration into oncogenes. Importantly, the promoters and regulatory elements of Orchard vectors are derived from human (not viral) sequences and are specifically designed to have limited enhancer activity on neighboring genes thereby mitigating the potential for safety concerns.In addition, because of the fundamental biological differences between the HSC and adeno-associated virus (AAV) gene therapy approaches, Orchards programs have not, to date, seen the safety and durability concerns experienced by the AAV gene therapy field.

Libmeldy (atidarsagene autotemcel) launch in Europe

Orchard is providing an update on the following key launch activities for Libmeldy in Europe:

Discussions with health authorities and payors are underway across Europe in key markets including Germany, the UK, France and Italy.Qualification of treatment centers is progressing with The University of Tbingen in Germany ready to treat commercial patients and other centers in the final stages of qualification and treatment readiness.Disease awareness and patient identification activities continue and have supported patient referrals in major European centers. Orchards partnerships in the Middle East and Turkey allow for opportunities to treat eligible patients from these territories at qualified European centers.Orchard is providing sponsorship for an ongoing newborn screening pilot in Germany and is working with laboratories to implement pilots in Italy, the UK, France and Spain.

Executive organizational update

The company also announced that Frank Thomas will step down from his role as president and chief operating officer, following a transition in 2022. A search for a chief financial officer is underway. Mr. Thomas other responsibilities will be assumed by existing members of the leadership team in commercial and corporate affairs. Orchard recently strengthened the executive team with the appointments of Nicoletta Loggia as chief technical officer and Fulvio Mavilio as chief scientific officer and the promotion of Leslie Meltzer to chief medical officer.

I want to extend my gratitude to Frank Thomas for his immense contributions to Orchard, said Gaspar. During his tenure, Frank oversaw the transition of the organization to a publicly traded company and has managed operations with a focus on cross-company innovation, including his role as a key architect in creating and executing the focused business plan we rolled out in 2020. Along with the entire board of directors and leadership team, I appreciate Franks commitment to facilitate a smooth transition during this time.

Gaspar continued, Our search is focused on a CFO to lead the broad strategic planning efforts necessary to capitalize on the full potential of our hematopoietic stem cell gene therapy platform. We have a strong team in place to aid Orchards success in this next phase of growth and are well capitalized through the anticipated completion of several value-creating milestones.

Upcoming Milestones

In June 2021, Orchard announced several portfolio updates following recent regulatory interactions for the companys investigational programs in metachromatic leukodystrophy (MLD), Mucopolysaccharidosis type I Hurler syndrome (MPS-IH) and Wiskott-Aldrich syndrome (WAS).

OTL-200 for MLD in the U.S: Based on feedback received from the U.S. Food and Drug Administration (FDA), the company is preparing for a Biologics License Application (BLA) filing for OTL-200 in pre-symptomatic, early-onset MLD in late 2022 or early 2023, using data from existing OTL-200 patients. This approach and timeline are subject to the successful completion of activities remaining in advance of an expected pre-BLA meeting with FDA, including future CMC regulatory interactions and demonstration of the natural history data as a representative comparator for the treated population.OTL-203 for MPS-IH: Orchard is incorporating feedback from FDA and the European Medicines Agency (EMA) into a revised global registrational study protocol, with study initiation expected to occur in 2022.OTL-201 for MPS-IIIA: Additional interim data from this proof-of-concept study are expected to be presented at medical meetings in 2022, including early clinical outcomes of cognitive function.OTL-103 for WAS: The company expects a MAA submission with EMA for OTL-103 in WAS in 2022, subject to the completion of work remaining on potency assay validation and further dialogue with EMA. The company will provide updated guidance for a BLA submission in the U.S. following additional FDA regulatory interactions.

Third Quarter 2021 Financial Results

Revenue from product sales of Strimvelis were $0.7 million for the third quarter of 2021 compared to $2.0 million in the same period in 2020, and cost of product sales were $0.2 million for the third quarter of 2021 compared to $0.7 million in the same period in 2020. Collaboration revenue was $0.5 million for the third quarter of 2021, resulting from the collaboration with Pharming Group N.V. entered into in July 2021. This revenue represents expected reimbursements for preclinical studies and a portion of the $17.5 million upfront consideration received by Orchard under the collaboration, which will be amortized over the expected duration of the agreement.

Research and development (R&D) expenses were $20.8 million for the third quarter of 2021, compared to $14.7 million in the same period in 2020. The increase was primarily due to higher manufacturing and process development costs for the companys neurometabolic programs and lower R&D tax credits as compared to the same period in 2020. R&D expenses include the costs of clinical trials and preclinical work on the companys portfolio of investigational gene therapies, as well as costs related to regulatory, manufacturing, license fees and development milestone payments under the companys agreements with third parties, and personnel costs to support these activities.

Selling, general and administrative (SG&A) expenses were $13.0 million for the third quarter of 2021, compared to $13.0 million in the same period in 2020. SG&A expenses are expected to increase in future periods as the company builds out its commercial infrastructure globally to support additional product launches following regulatory approvals.

Net loss was $36.4 million for the third quarter of 2021, compared to $20.3 million in the same period in 2020. The increase in net loss as compared to the prior year was primarily due to higher R&D expenses as well as the impact of foreign currency transaction gains and losses. The company had approximately 125.5 million ordinary shares outstanding as of September 30, 2021.

Cash, cash equivalents and investments as of September 30, 2021, were $254.1 million compared to $191.9 million as of December 31, 2020. The increase was primarily driven by net proceeds of $143.6 million from the February 2021 private placement and $17.5 million in upfront payments from the July 2021 collaboration with Pharming Group N.V., offset by cash used for operating activities and capital expenditures. The company expects that its cash, cash equivalents and investments as of September 30, 2021 will support its currently anticipated operating expenses and capital expenditure requirements into the first half of 2023. This cash runway excludes an additional $67 million that could become available under the companys credit facility and any non-dilutive capital received from potential future partnerships or priority review vouchers granted by the FDA following future U.S. approvals.

About Libmeldy / OTL-200 Libmeldy (atidarsagene autotemcel), also known as OTL-200, has been approved by the European Commission for the treatment of MLD in eligible early-onset patients characterized by biallelic mutations in the ARSA gene leading to a reduction of the ARSA enzymatic activity in children with i) late infantile or early juvenile forms, without clinical manifestations of the disease, or ii) the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline. Libmeldy is the first therapy approved for eligible patients with early-onset MLD. The most common adverse reaction attributed to treatment with Libmeldy was the occurrence of anti-ARSA antibodies. In addition to the risks associated with the gene therapy, treatment with Libmeldy is preceded by other medical interventions, namely bone marrow harvest or peripheral blood mobilization and apheresis, followed by myeloablative conditioning, which carry their own risks. During the clinical studies, the safety profiles of these interventions were consistent with their known safety and tolerability. For more information about Libmeldy, please see the Summary of Product Characteristics (SmPC) available on the EMA website. Libmeldy is approved in the European Union, UK, Iceland, Liechtenstein and Norway. OTL-200 is an investigational therapy in the US.

Libmeldy was developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy. About Orchard

At Orchard Therapeutics, our vision is to end the devastation caused by genetic and other severe diseases. We aim to do this by discovering, developing and commercializing new treatments that tap into the curative potential of hematopoietic stem cell (HSC) gene therapy. In this approach, a patients own blood stem cells are genetically modified outside of the body and then reinserted, with the goal of correcting the underlying cause of disease in a single treatment.

In 2018, the company acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Today, Orchard has a deep pipeline spanning pre-clinical, clinical and commercial stage HSC gene therapies designed to address serious diseases where the burden is immense for patients, families and society and current treatment options are limited or do not exist.

Orchard has its global headquarters inLondonandU.S. headquarters inBoston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

Availability of Other Information About Orchard

Investors and others should note that Orchard communicates with its investors and the public using the company website ( http://www.orchard-tx.com ), the investor relations website ( ir.orchard-tx.com ), and on social media ( Twitter and LinkedIn ), including but not limited to investor presentations and investor fact sheets,U.S. Securities and Exchange Commissionfilings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchards investor relations website and may include additional social media channels. The contents of Orchards website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Forward-Looking Statements

This press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include express or implied statements relating to, among other things, Orchards business strategy and goals, including its plans and expectations for the commercialization of Libmeldy, the therapeutic potential of Libmeldy (OTL-200) and Orchards product candidates, including the product candidates referred to in this release, Orchards expectations regarding its ongoing preclinical and clinical trials, including the timing of enrollment for clinical trials and release of additional preclinical and clinical data, the likelihood that data from clinical trials will be positive and support further clinical development and regulatory approval of Orchard's product candidates, and Orchards financial condition and cash runway into the first half of 2023. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, these risks and uncertainties include, without limitation: the risk that prior results, such as signals of safety, activity or durability of effect, observed from clinical trials of Libmeldy will not continue or be repeated in our ongoing or planned clinical trials of Libmeldy, will be insufficient to support regulatory submissions or marketing approval in the US or to maintain marketing approval in the EU, or that long-term adverse safety findings may be discovered; the risk that any one or more of Orchards product candidates, including the product candidates referred to in this release, will not be approved, successfully developed or commercialized; the risk of cessation or delay of any of Orchards ongoing or planned clinical trials; the risk that Orchard may not successfully recruit or enroll a sufficient number of patients for its clinical trials; the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials will not be replicated or will not continue in ongoing or future studies or trials involving Orchards product candidates; the delay of any of Orchards regulatory submissions; the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchards product candidates or the receipt of restricted marketing approvals; the inability or risk of delays in Orchards ability to commercialize its product candidates, if approved, or Libmeldy, including the risk that Orchard may not secure adequate pricing or reimbursement to support continued development or commercialization of Libmeldy; the risk that the market opportunity for Libmeldy, or any of Orchards product candidates, may be lower than estimated; and the severity of the impact of the COVID-19 pandemic on Orchards business, including on clinical development, its supply chain and commercial programs. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.

Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchards quarterly report on Form 10-Q for the quarter endedSeptember 30, 2021, as filed with theU.S. Securities and Exchange Commission(SEC), as well as subsequent filings and reports filed with theSEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

Contacts

Investors Renee Leck Director, Investor Relations +1 862-242-0764 Renee.Leck@orchard-tx.com

Media Benjamin Navon Director, Corporate Communications +1 857-248-9454 Benjamin.Navon@orchard-tx.com

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Orchard Therapeutics Reports Third Quarter 2021 Financial Results and Highlights Recent ... - KULR-TV

Bone Marrow Stem Cells Comments Off on Orchard Therapeutics Reports Third Quarter 2021 Financial Results and Highlights Recent … – KULR-TV | November 8th, 2021

TAZEWELL, Va. (WVVA) - Gabe is a seventeen year old who has battled and beat HLH, however recently he was diagnosed with leukemia and is in need of a blood stem cell and bone marrow transplant. Community members of Gabe's family are holding a bake sale, pumpkin contest and raffles to fund Gabe's cost of medical bills and travel expenses.

A DKMS drive was set up along with the bake sale at the Crab Orchard Veterinarians Services today to help find donors to give the gift of life to families just like Gabe's. All of the proceeds of the bake sale, contest and raffles will be given to Gabe's family.

'It's been a very stressful time for us but it's also been a very blessed time for us and I'm grateful for the outpouring from my community. My church family has been real big. My pastor and his wife and everybody involved at City on a Hill, I love you guys.

"I'm just grateful for everybody at Crab Orchard Vet Services and Honaker Animal Health for doing this for us and stepping up in a big way."

The process of becoming a potential donor for DKMS is simple. You get a swab kit and swab the inside of your cheeks. You fill out a paper with your contact info and from there you are registered into a database to see if you are a match with someone who needs stem cells or bone marrow.

"It means that we can not only help a family in the community but one of our own. Clifford works for our sister office in Honaker and it just means a lot to be able to reach out and help a family."

If you are interested in becoming a potential donor you can go to the DKMS website found here to get a donor kit: Register as a Stem Cell and Bone Marrow Donor | DKMS | DKMS

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Our bone marrow harbors thousandsof rare hematopoietic stem cells tiny shape shifters that can morph into red or white blood cells. But conditions like sickle cell anemia or immune deficiency can damage these cells, and treatments for blood cancers may destroy them altogether.

To rebuild bone marrow, researchers have perfected the art of transplanting stem cells either those belonging to the patient or ones that have been donated.

You only have so many of these cells, says Jennifer Gillette, PhD, associate professor inThe University of New Mexico Department of Pathology. These are cells that are with us our entire life. They stay turned off when youre healthy and things are moving along. But in a stress condition, these are cells that get turned on and rev up and then go quiescent again.

Gillette has been devising ways to trick donors bone marrow into releasing more stem cells into the bloodstream so they can be harvested and transfused.

Ina new paper published onlinein the journalStem Cell Reports, Gillette and her colleagues describe manipulating a protein called CD82 that sits on the surface of each stem cell and helps them migrate into and out of the bone marrow.

Gillettes team found that when CD82 disruption is coupled with existing medications used to stimulate stem cell release into the bloodstream, the process is significantly amplified, causing more stem cells to find their way into circulation.

One of those medications AMD3100 costs $10,000 for a single dose, she says, and it is hoped that treatment with antibodies might be less expensive.

Patients diagnosed with leukemia or lymphoma may be treated with chemotherapy and/or radiation, which destroy cancerous cells in the bone marrow along with stem cells.

It wipes out everything, Gillette says. For leukemia or blood cancers youre trying to get rid of that malignant population and replace it with healthy cells.

Patients may bank some of their stem cells beforehand for autologous transplants, or they could receive allograft transplants from suitable donors.

There are some patients that just dont mobilize well, she says. Were looking for any way that we can enhance cell release, because the number and quality of cells going in really enhance the response of the patients.

Gillette has applied for a provisional patent to repurpose the antibodies originally developed to study CD82 functioning as a clinical treatment. The next step is to see exactly how that antibody is working, she says.

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UNM Scientist Jennifer Gillette Tricks the Bone Marrow ...

Bone Marrow Stem Cells Comments Off on UNM Scientist Jennifer Gillette Tricks the Bone Marrow … | October 28th, 2021

-- Biohaven initiates a clinical trial of the novel antibody recruiting molecule BHV-1100 to assess safety, tolerability, and exploratory clinical activity in Multiple Myeloma

Published: Oct. 27, 2021 at 7:30 AM EDT|Updated: 18 hours ago

NEW HAVEN, Conn., Oct. 27, 2021 /PRNewswire/ --Biohaven Pharmaceutical Holding Company Ltd. (NYSE: BHVN), announced the enrollment of the first patient in a Phase 1a/1b trial in Multiple Myeloma using the ARM, BHV-1100, in combination with autologous cytokine induced memory-like (CIML) natural killer (NK) cells and immunoglobulin (Ig) to target and kill multiple myeloma cells expressing the cell surface protein CD38 (Figure 1). BHV-1100 is the lead clinical asset from Biohaven's ARM Platform, developed from a strategic alliance with PeptiDream Inc. This clinical trial will assess the safety and tolerability, as well as exploratory efficacy endpoints, in newly diagnosed multiple myeloma patients who have tested positive for minimal residual disease (MRD+) in first remission prior to autologous stem cell transplant (ASCT).

NK cells are part of the innate immune system, which is designed to recognize and destroy "non-self" or diseased cells in the body. However, tumor cells can evade detection by immune effector cells, allowing the tumor to advance. BHV-1100 targets a cell-surface protein, CD38, that is heavily overexpressed on multiple myeloma and binds to it, recruiting primed autologous cytokine induced memory-like (CIML) natural killer (NK) cells to destroy the tumor.

Charlie Conway, Ph.D., Chief Scientific Officer at Biohaven commented, "While many recent advances have been made to benefit multiple myeloma patients, most patients will unfortunately still relapse. We are excited to investigate BHV-1100 for its ability to recruit autologous CIML NK cells to the site of the tumor. Based on preclinical data from Biohaven Labs, we anticipate that our CD38 targeting ARM-enabled NK cells will kill CD38-positive multiple myeloma cells, and recruit other immune effector cells to assist in reducing the tumor burden."

Biohaven has initiated enrollment in the clinical trial and plans to enroll 25 patients for this single-center, open-label study (ClinicalTrials.gov Identifier: NCT04634435; https://clinicaltrials.gov/ct2/show/NCT04634435). The study will enroll newly diagnosed multiple myeloma patients who have minimal residual disease (MRD+) in first remission prior to an autologous stem cell transplant (ASCT).

David Spiegel M.D., PhD, inventor of the ARM technology and Professor of Chemistry and Pharmacology at Yale University, commented, "This is an important milestone in the development of the ARM therapeutic platform taking a novel technology from 'benchtop to bedside'. It also highlights Biohaven's commitment to benefit patients in need."

About ARMs: Antibody Recruiting Molecules

ARMs,antibody recruiting molecules, are engineered with modular components that are readily interchangeable, giving the platform tremendous flexibility and rapid development timelines. ARM compounds are being developed at Biohaven Labs to redirect a patient's own antibodies for therapeutic effect with multiple benefits over traditional monoclonal antibody therapies, including the potential for oral dosing. For BHV

1100, the ARM platform is being used to provide antigen targeting to NK cell-based therapies without genetic engineering. This NK cell targeting approach is also being investigated with allogeneic, or 'off-the-shelf', immune cell-based therapies.

About Multiple Myeloma Multiple myeloma is a type of blood cancer of the plasma cell that develops in the bone marrow, the soft tissue inside our bones. Healthy plasma cells produce antibodies, which are critical for the immune system's ability to recognize disease-causing entities, such as bacteria, viruses and tumor cells. In multiple myeloma, however, genetic abnormalities in a single plasma cell cause it to divide uncontrollably. This leads to the over-production of a single (monoclonal) antibody protein, referred to as an "M protein". Also, these cancerous cells divide to the point of crowding out normal, healthy cells that reside in the bone marrow. Many patients are diagnosed due to symptoms such as bone pain or fractures, kidney failure (thirst, dehydration, confusion), nerve pain, fever, and weakness. The American Cancer Society estimates that approximately 34,920 new cases will be diagnosed, and 12,410 deaths will occur in 2021 from multiple myeloma.

About BiohavenBiohaven is a commercial-stage biopharmaceutical company with a portfolio of innovative, best-in-class therapies to improve the lives of patients with debilitating neurological and neuropsychiatric diseases, including rare disorders and areas of unmet need. Biohaven's neuro-innovation portfolio includes FDA-approved NURTEC ODT (rimegepant) for the acute and preventive treatment of migraine and a broad pipeline of late-stage product candidates across three distinct mechanistic platforms: CGRP receptor antagonism for the acute and preventive treatment of migraine; glutamate modulation for obsessive-compulsive disorder, Alzheimer's disease, and spinocerebellar ataxia; and MPO inhibition for amyotrophic lateral sclerosis. More information about Biohaven is available atwww.biohavenpharma.com.

About PeptiDream PeptiDream Inc. is a public(Tokyo Stock Exchange 1st Section 4587) biopharmaceutical company founded in 2006 employing their proprietary Peptide Discovery Platform System (PDPS), a state-of-the-art highly versatile discovery platform which enables the production of highly diverse (trillions) non-standard peptide libraries with high efficiency, for the identification of highly potent and selective hit candidates, which then can be developed into peptide-based, small molecule-based, or peptide-drug-conjugate-based therapeutics. PeptiDream aspires to be a world leader in drug discovery and development to address unmet medical needs and improve the quality of life of patients worldwide. Further information regarding PeptiDream can be found at: http://www.peptidream.com.

Forward-looking Statement This news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements involve substantial risks and uncertainties, including statements that are based on the current expectations and assumptions of Biohaven's management about BHV-1100 as a treatment for multiple myeloma. Forward-looking statements include those related to: Biohaven's ability to effectively develop and commercialize BHV-1100, delays or problems in the supply or manufacture of BHV-1100, complying with applicableU.S.regulatory requirements, the expected timing, commencement and outcomes of Biohaven's planned and ongoing clinical trials, the timing of planned interactions and filings with the FDA, the timing and outcome of expected regulatory filings, the potential commercialization of Biohaven's product candidates, the potential for Biohaven's product candidates to be firstin class or best in class therapies and the effectiveness and safety of Biohaven's product candidates. Various important factors could cause actual results or events to differ materially from those that may be expressed or implied by our forward-looking statements. Additional important factors to be considered in connection with forward-looking statements are described in the "Risk Factors" section of Biohaven's Annual Report on Form 10-K for the year ended December 31, 2020, filed with the Securities and Exchange Commission onMarch 1, 2021, and Biohaven's subsequent filings with the Securities and Exchange Commission. The forward-looking statements are made as of this date and Biohaven does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

NURTEC and NURTEC ODT are registered trademarks of Biohaven Pharmaceutical Ireland DAC.Neuroinnovation is a trademark of Biohaven Pharmaceutical Holding Company Ltd.

ARM is a trademark of Kleo Pharmaceuticals, Inc.

Biohaven ContactDr. Vlad CoricChief Executive OfficerVlad.Coric@biohavenpharma.com

Media ContactMike BeyerSam Brown Inc.mikebeyer@sambrown.com312-961-2502

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SOURCE Biohaven Pharmaceutical Holding Company Ltd.

The above press release was provided courtesy of PRNewswire. The views, opinions and statements in the press release are not endorsed by Gray Media Group nor do they necessarily state or reflect those of Gray Media Group, Inc.

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Biohaven Enrolls Phase 1a/1b Clinical Trial of BHV-1100, Lead Asset from its ARM (Antibody Recruiting Molecule) Platform, in Combination with NK Cell...

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DUBLIN--(BUSINESS WIRE)--The "Global Cell Therapy Market Size, Share & Trends Analysis Report by Use-type, by Therapy Type (Autologous, Allogenic), by Region (North America, Europe, Asia Pacific, Latin America, MEA), and Segment Forecasts, 2021-2028" report has been added to ResearchAndMarkets.com's offering.

The global cell therapy market size is expected to reach USD 23.0 billion by 2028 and is expected to expand at a CAGR of 14.5% from 2021 to 2028.

The emergence of new technologies to support the development of advanced cellular therapies has aided in market growth. Companies are leveraging new technologies not only for the expansion of their product portfolio but also for establishing out-licensing or co-development agreements with other entities to support their product development programs.

Cell-based therapies hold great potential for replacing, repairing, restoring, or regenerating damaged tissues, and organs. Researchers are making huge investments in the development of such effective and safe treatments as an alternative to conventional treatment strategies which can be further attributed to the market growth.

Out of all therapeutic areas, oncology has the highest number of ongoing clinical trials. T cells, CD34+ and/or CD133+ stem cells, mesenchymal stem/stromal cells are predominantly employed for clinical investigation.

The majority of biopharmaceutical entities have been affected by the COVID-19 pandemic, while several cellular therapy development companies have witnessed a strongly negative impact, which can be attributed to complications in logistics as well as the manufacturing models employed in this industry. In addition, substantial and stable funding is imperative to ensure successful commercial translation of cell-based therapeutics, a factor that was negatively affected in 2020, further affecting the market growth.

A survey conducted recently among executives of more than 15 European and U.S. cellular therapy companies indicated that disruption caused by the pandemic was significant, which demanded market entities to create strategies to sustain themselves and plan the next wave of innovative therapies.

Key issues faced by companies operating in the market include on-time delivery of therapies to patients at required clinical sites. In addition, the administration of these therapeutics poses several post-pandemic challenges. Hospitals are hesitant in offering services, owing to concerns over transmission of SARS-CoV-2, particularly to vulnerable individuals. Moreover, patients have not been able to visit cellular therapy centers either, owing to the lockdowns and travel bans.

Cell Therapy Market Report Highlights

Market Dynamics

Market driver analysis

Market restraint analysis

Market opportunity analysis

COVID-19 Impact Analysis

Challenges analysis

Opportunities analysis

Challenges in manufacturing cell therapies against COVID-19

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/n1u89x

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Global Cell Therapy Market Research Report 2021: Opportunities with the Approval of Kymriah and Yescarta Across Various Countries -...

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Did you know that every three minutes someone receives a diagnosis of a blood cancer? According to the National Foundation for Cancer Research, blood cancers account for nearly 10% of new cancer diagnoses in the United States annually. That means that approximately 178,520 people will receive a diagnosis this year most commonly with leukemia, lymphoma or myeloma. And although survival rates have increased dramatically over the past 20 years, theres still a long way to go when it comes to this patient population.

In this special issue of CURE, youll read about some of the research going on in blood cancer right now, including new treatment options for acute myeloid leukemia and a novel therapy using BK virus-specific T cells to treat BK virus-associated hemorrhagic cystitis (a painful side effect of stem cell transplants).

Dive into the issue for two patient stories, one about a three-time acute lymphoblastic leukemia survivor who now works as a nurse on the bone marrow transplant floor at Barnes-Jewish Hospital in St. Louis. This year also marks the 20th anniversary of the Food and Drug Administrations approval of Gleevec (imatinib mesylate), the tyrosine kinase inhibitor that saved Mel Mann. Who is Mel Mann? He is the longest-living survivor who was treated with the drug as a part of a clinical trial for chronic myeloid leukemia.

And because cancer is not a disease one should have to face alone, our cover story looks at the responsibilities and experiences of caregivers to patients with blood cancer. Not only will you read about what theyve gone through, but youll also find extra resources and tips for navigating the patient-caregiver relationship.

As always, thank you for reading.

For more news on cancer updates, research and education, dont forget tosubscribe to CUREs newsletters here.

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Bone Marrow Stem Cells Comments Off on New Treatments and Tips for Dealing With Blood Cancer – Curetoday.com | October 28th, 2021

Oncology drugs are therapeutics used to treat cancer, a group of diseases caused by uncontrolled growth and division of abnormal cells. Oncology drugs include a range of different types of medications, such as chemotherapy agents, targeted therapies, immunotherapies, and hormone therapies. There are also different types of drugs available to help treat the side effects from oncology drugs.

If you have cancer, its likely youll have a few options when it comes to treatment. Cancer treatment is constantly evolving and progressing. You now have more drug options to choose from than ever before.

A doctor may recommend that you treat your cancer with one or more of the following types of oncology drugs:

Chemotherapy drugs are chemical agents that work by destroying fast-growing cells in the body. Cancer cells grow and divide more rapidly than other cells. The goal of chemotherapy is to lower the total number of cancer cells in your body and reduce the chances that the cancer will spread to other parts of the body (metastasize).

There are at least 61 chemotherapy drugs approved in the United States. Your doctor may decide to treat your cancer with a a single chemotherapy drug or a combination of chemotherapy drugs.

Hormone therapy is used to treat cancers that rely on hormones to grow. This may include certain types of breast cancer and prostate cancer. Breast cancers may be fed by estrogen or progesterone, while prostate cancers often depend on the hormone androgen.

Some examples of hormone therapies include:

Targeted therapies are part of a new approach known as personalized medicine or precision medicine. Targeted therapies are able to seek out and kill cancerous cells without harming the normal cells in your body. These drugs work by blocking the molecular pathways that are critical to tumor growth.

To see if youre eligible for a particular targeted therapy, a doctor will first perform genetic or biomarker testing. The results of this testing will allow your doctor to make an informed decision about which drug is more likely to work for your type of cancer, based on the genetic mutations or other molecular characteristics of your tumor.

Examples of targeted oncology drugs include:

Immunotherapy is a type of targeted therapy that uses the bodys own immune system to attack cancer cells. Cancer cells sometimes have strategic ways of hiding from your immune system, but immunotherapies work by blocking these mechanisms.

Immunotherapies are approved to treat a variety of cancers. Examples include:

To counter the side effects of oncology drugs, your oncologist may prescribe additional medications. Examples include:

Oncology drugs have many benefits. Depending on your individual cancer, these drugs may:

On the other hand, oncology drugs often have side effects and risks. Chemotherapy, for example, can attack some of the normal cells in your body especially blood cells, skin, hair, and the cells lining the intestine and mouth. This can cause serious side effects that can negatively impact your quality of life.

Common side effects of chemotherapy include:

Targeted therapies and immunotherapies often have fewer side effects compared to chemotherapy since they only attack cancer cells while sparing healthy cells from harm, but they can still cause side effects. These may include:

Hormone therapies can block your bodys ability to make hormones, and can interfere with how hormones act in your body. Some common side effects of hormone therapies include:

Apart from oncology drugs, there are other treatments available for cancer, including:

Other therapies such as acupuncture, meditation, and herbal supplements may help with side effects of cancer treatment, but are ineffective at treating the cancer itself.

Yes, you can have a say in your cancer treatment, including making the decision to delay treatment or not have treatment at all. You can also seek a second opinion from another qualified doctor. Dont hesitate to ask your doctor for resources so you can do your own research on available treatments before you make a decision.

Ask your doctor about clinical trials taking place in your area. The National Institutes of Health (NIH) maintains a large database of clinical trials at clinicaltrials.gov. You can also search the National Cancer Institute (NCI)s online tool or contact them for help at 800-4-CANCER.

There are over 100 types of cancer, according to the National Cancer Institute (NCI). Your oncologist will formulate a recommended treatment plan based on the type of cancer you have, the stage or grade of the cancer, the characteristics of your tumor, your age, overall health, and several other considerations.

To determine the best treatment for you, your oncologist may perform molecular testing on your tumor among other imaging and blood tests. He or she will also likely consult with medical guidelines, such as those set forth by the National Comprehensive Cancer Network (NCCN).

To treat cancer, your doctor may recommend one type of oncology drug or a combination of drugs alongside surgery, radiation, or other types of treatment.

Before deciding to move forward with a cancer drug, learn as much as you can about the recommended treatment. Ask your doctor about benefits and risks of your recommended treatment plan and work together to make an informed decision.

Excerpt from:
Types of Oncology Drugs - Healthline

Bone Marrow Stem Cells Comments Off on Types of Oncology Drugs – Healthline | October 28th, 2021

The COVID-19 pandemic has created a sense of urgency to generate new drugs and vaccines. In many cases, this urgency became a regulatory opportunity to bypass established regulatory pathways for new drugs.

While this has led to the fast emergence of many useful drugs and vaccines for COVID-19, it has also led to a general reduction in the quality of medical research from which to derive conclusions.

For example, according to Janet Woodcock, former director of the Food and Drug Administrations (FDA) Center for Drug Evaluation and Research, an FDA analysis found that 6% of clinical trials are yielding results the agency deems actionable.

The lack of regulation coupled with a sense of urgency has also led to overhype and rushed development of certain treatments, including cell-based therapies often sold as stem cell treatments.

While some of these products have undergone well-designed, adequately controlled trials, most are in the early stages. Some clinics are nevertheless offering these unproven and unlicensed treatments to people, promising to boost their immune system or overall health to protect against COVID-19.

Promoting and selling unproven and unlicensed treatments can harm public health and could lead many to undergo untested and potentially harmful treatments.

Recently, a group of researchers from the University of California, Irvine, the Georgia Institute of Technology, the University at Buffalo, NY, and the University of Melbourne in Australia, published a report outlining misinformation around cell-based treatments for COVID-19, calling for their stronger regulation.

Efforts to rapidly develop therapeutic interventions should never occur at the expense of the ethical and scientific standards that are at the heart of responsible clinical research and innovation, said Dr. Laertis Ikonomou, assistant professor of Oral Biology at the University at Buffalo, and co-author of the study.

Scientists, regulators, and policymakers must guard against the proliferation of poorly designed, underpowered, and duplicative studies that are launched with undue haste because of the pandemic, but are unlikely to provide convincing, clinically meaningful safety and efficacy data, said co-author Dr. Leigh Turner, professor of Health, Society and Behavior at the University of California, Irvine.

The researchers published their report in Stem Cell Reports.

Researchers conducted a study in August 2020 of 70 clinical trials involving cell-based treatments for COVID-19. They found that most were small, with an average of 51.8 participants, and only 22.8% were randomized, double-blinded, and controlled experiments.

The authors concluded that the cell-based interventions for COVID-19 were likely to have a relatively small collective clinical impact.

Cell-based treatments for COVID-19 are still at an experimental stage, Dr. Ikonomou told Medical News Today. There are tens of clinical trials, of varied complexity and rigor, that evaluate various cell types, such as mesenchymal stromal cells, for COVID-19 treatment.

Expanded or compassionate use of cell-based interventions has also been reported, but these individual cases are unlikely to tell us whether and how cell therapies could help with COVID-19 and do not substitute for the systematic clinical evaluation of cell-based products, he added.

A few completed phase 1/2 trials have shown a favorable safety profile, but larger size trials are required. Eventually, properly-powered, controlled, randomized, double-blinded clinical trials will help determine whether cell-based treatments are a viable therapeutic option for COVID-19 and its complications, he explained.

The urgency of the pandemic has made it easy to exaggerate early-stage research. The scientists highlight this is especially the case in press releases, where media professionals can over-hype findings and understate or omit limitations to gain more media coverage.

The researchers also say that even when online media include limitations and key aspects of studies, other communication channels can strip these away easily. What is left then gets amplified, as the public is desperate to see positive news.

To address this, the researchers say science communicators should ensure they have an accurate understanding of the information they report and highlight the required steps for the science to advance without exaggerating its speed.

The researchers also say that simply feeding the public more information in what is known as the information deficit model alone is insufficient. They also suggest science communicators should strive for an engaged or dialogue-based communication approach.

Over-hyping of promising treatments and in particular cell-based treatments has been a longstanding problem, and it did not first emerge with the COVID-19 pandemic, said Dr. Ikonomou. It has become a salient issue during these times due to the global nature of this health emergency and the resulting devastation and health toll.

Therefore, it is even more important to communicate promising developments in COVID-19-related science and clinical management [responsibly]. Key features of good communication are an accurate understanding of new findings, including study limitations and avoidance of sensationalist language, he explained.

Realistic timeframes for clinical translation are equally important as is the realization that promising interventions at preliminary stages may not always translate to proven treatments following rigorous testing, he added.

The researchers say that commercial investments by biotechnology companies to develop cell-based therapies for COVID-19 have led to well-designed and rigorous clinical trials.

However, some other businesses have overlooked the demanding process of pre-marketing authorization of their products. Instead, they made unsubstantiated and inaccurate claims about their stem cell products for COVID-19 based on hyperbolic reporting of cell-based therapies in early testing.

Some clinics advertise unproven and unlicensed mesenchymal stem cell treatments or exosome therapies as immune boosters that prevent COVID-19 and repair and regenerate lungs.

Often, these businesses make their treatments available via infusion or injection. However, one anti-aging clinic in California shipped its kits to clients, where they were to self-administer with a nebulizer and mask.

Such companies often market stem cell treatments via online and social media. In an initial review of many of these brands, the researchers could not find published findings from preclinical studies and clinical trials to support their commercial activities.

Instead, they found that these companies drew from uncritical news media reports, preliminary clinical studies, or case reports in which those diagnosed with COVID-19 received stem cell interventions.

Promoting such therapies that have not undergone proper tests for safety and efficacy have the potential for significant physical and financial harm.

Health experts have documented adverse events due to unlicensed stem cell products, including vision loss and autoimmune, infectious, neurological, and cardiovascular complications.

Early in the pandemic, scientific and professional societies, including the Alliance for Regenerative Medicine and the International Society for Stem Cell Research, have warned the public against businesses engaged in the marketing of cell-based treatments that have not undergone adequate testing.

The researchers highlight that it is unclear whether these warnings reached individuals and their loved ones or significantly affected public understanding of the risks of receiving unlicensed and unproven stem cell treatments for COVID-19.

They also indicate that it is unclear whether these societies and organizations have an important role in convincing regulatory bodies to increase enforcement in this space. Nevertheless, at the time of writing, the FDA and Federal Trade Commission have issued 22 letters to businesses selling unproven and unlicensed cell-based therapies.

And while many of these companies have ceased market activity, the presence of other companies continuing to pedal the same claims makes it clear that regulatory bodies must increase their enforcement.

Additionally, the researchers question whether warning letters are sufficient to disincentivize clinicians and others to sell unlicensed products. They write:

If companies and affiliated clinicians are not fined, forced to return to patients whatever profits they have made, confronted with criminal charges, subject to revocation of medical licensure, or otherwise subject to serious legal and financial consequences, it is possible that more businesses will be drawn to this space because of the profits that can be generated from selling unlicensed and unproven cell-based products in the midst of a pandemic.

The researchers conclude that regulators should increase enforcement against unproven and unlicensed therapies for COVID-19.

They also say that science communicators should report on scientific claims more realistically and include the public in more discourse.

In the U.S. and elsewhere, there are regulations and enforcement mechanisms that deal with harms caused by unproven and unlicensed cell-based interventions and false advertising claims, said Dr. Ikonomou. It may be preferable to implement existing regulations more vigorously than introduce new ones.

Stakeholders, such as scientific, professional, and medical associations, can contribute towards this goal with reporting and monitoring of cell therapy misinformation. There is a shared responsibility to combat cell-therapy related misinformation and disinformation that undercuts legitimate research and clinical efforts and portrays unproven interventions as silver bullets for COVID-19, he concluded.

For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.

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COVID-19: Researchers warn against overhyping early-stage therapies - Medical News Today

Skin Stem Cells Comments Off on COVID-19: Researchers warn against overhyping early-stage therapies – Medical News Today | October 28th, 2021

Phovia is highly effective for treating superficial and deep skin infections.

This article is sponsored by Vetoquinol.

Superficial bacterial folliculitis, also called superficial pyoderma, is a commonly diagnosed dermatological condition in dogs.1,2 These infections are secondary to primary conditions affecting normal skin barrier function (eg, allergic skin disease, trauma, burns), keratinization (eg, nutritional deficiency, liver disease), and immune regulation (eg, neoplasia, autoimmunity, endocrinopathy).2 Cats less commonly develop superficial pyoderma perhaps because of decreased adhesion of staphylococci to feline corneocytes, but the primary issues causing infection are similar to those seen in dogs.3-8

The primary pathogen associated with superficial pyoderma in dogs and cats is a normal resident of the skin, Staphylococcus pseudintermedius, but other flora may be involved.2,8-12 As the normal homeostasis of this organism is disrupted from a primary disease, these gram-positive cocci invade deeper regions of the epidermis and hair follicle epithelium, increase in number, and enhance inflammation.

Classical clinical lesions of superficial pyoderma include papules and pustules that may eventually progress to alopecia, epidermal collarettes, scales, and crusts. Often the skin is erythematous and pruritic. Chronic cases may demonstrate lichenification, hyperpigmentation, and scarring alopecia from long-standing inflammation and infection.2 Cats may develop even more unique cutaneous reaction patterns and skin lesionsespecially when allergic skin disease is presentincluding miliary dermatitis, eosinophilic plaques, rodent ulcers, and eosinophilic granulomas.5

Identifying and addressing the primary disease is paramount in achieving complete, permanent resolution of the superficial pyoderma. Therefore, treatment is multifactorial and aimed at addressing the primary disease, reducing skin inflammation, and treating the infection directly. Current guidelines for the treatment of superficial pyoderma in dogs recommend the use of topical antimicrobials as sole therapy whenever possible; however, overuse of systemic antibiotics remains common.2,13-16

Topical therapy has many benefits including direct antimicrobial effects without use of an antibiotic, reduction in antibiotic-resistant bacterial populations, restoration of the normal skin barrier, enhancement of skin hydration, physical removal of keratinous debris, and removal of offending allergens from the haircoat.2,14 However, topical therapy is met with challenges that impede clinical application. Adherence is the biggest concern when recommending topical therapy to pet owners. Frequent bathing or application of medicated solutions to the skin can be difficult when busy owner lifestyles combine with a nonadherent patient. Skin inflammation can be painful and animals may be resistant to topical therapy. Cats are fastidious groomers and may lick away a medicated topical therapy before it can achieve appropriate contact time. Additionally, some topical agents can cause oral erosions and ulcerations or even gastrointestinal disturbance when groomed off. For these reasons, systemic antibiotics continue to be a common prescribing practice for superficial pyoderma.

All antibiotic use, despite duration or frequency, contributes to the development of antibiotic-resistant bacterial populations on the animal and in the environment.17-19 From that very first dose, bacteria are constantly evolving to implement inherent and acquired resistance mechanisms necessary for survival. One well-recognized mechanism is oxacillin resistance through the mecA gene, which produces a penicillin-binding protein receptor with poor affinity for -lactam antibiotics.2,14,15,20-23 Even more concerning than these oxacillin-resistant strains are those that develop multidrug resistance, which is defined as resistance to 3 or more antibiotic drug classes. This may happen over time with repeated antibiotic exposure or after a single dose of certain antibiotics such as fluorinated quinolones.2,20,23-25 The continued emergence of antibiotic-resistant bacteria inhibits the successful treatment of bacterial infections in pets and humans. As veterinarians consider how their antibiotic use contributes to this growing pandemic, they must look for alternative, safe, effective, affordable, and convenient antibacterial treatment modalities.

Phovia as a solution

Investigation into the photobiological effects of light therapy has been ongoing for the past 50 years. Photobiomodulation (PBM) therapy is a type of light treatment that uses visible or near infrared light to promote therapeutic benefits including induction of tissue healing and regeneration and inhibition of biological responses that induce pain or inflammation. The treatment distance, wavelength, fluence, pulse parameters, spot size, and irradiation time influence the effects of light energy on tissue. Visible light with wavelengths ranging from 400 to 700 nm can stimulate positive photobiomodulatory effects that promote wound healing, reduce inflammation and pain, modulate stem cell populations, and reduce bacterial contamination of wounds.26,27

Once visible light enters the skin, it is absorbed by the cells and initiates chemical changes dependent on the wavelength (or color) of light and the chromophore within the skin.27 Within each cell, membrane-bound organelles called mitochondria contain chromophores that absorb the light energy and begin making energy (adenosine triphosphate; ATP) via activation of cytochrome c oxidase. Outcomes of the mitochondrial respiratory pathway activation include stimulation of secondary messenger pathways, production of transcription factors and growth factors, and increased ATP production. However, excessive light energy exposure will overstimulate mitochondrial respiration and cause expenditure of all ATP reserves, which creates oxidative stress resulting in damaging elevations of nitric oxide, production of harmful free radicals, and activation of cytotoxic mitochondrial-signaling pathways leading to apoptosis.27,28 This is why creating PBM therapy protocols is important for targeting the beneficial effects while avoiding unintended harm.

Specific benefits of light energy within the visible light spectrum can be broken down into each color of light. Blue light (400-500 nm) has a lower penetration depth and primarily interacts with keratinocytes, reduces bacterial adhesion and growth, and increases intracellular calcium and osteoblast differentiation.29-31 Green light (495-570 nm) affects the superficial tissue and alters melanogenesis, reduces hyperpigmentation of the skin, and reduces tissue swelling.29,30 Red light (600-750 nm) penetrates deeper into the dermis and subcutis where it acts on cellular mitochondria to reduce inflammation and promote collagen synthesis through fibroblast proliferation and production of transforming growth factor-, fibroblast growth factor, platelet derived growth factor, and others.26-28,32,33 Red light has proliferative effects on mesenchymal stem cells and induces proliferation of epithelial colony forming units important for tissue repair and regeneration.34,35

Phovia, sold by Vetoquinol, is a form of fluorescent PBM therapy utilizing a blue light emitting diode (LED lamp, 400-460 nm) and topical photoconverter gel that emits low-energy fluorescent light (510-600 nm) when illuminated by the LED lamp.36,37 This interaction results in the formation of multiple wavelengths of visible light, each with a unique depth of penetration and effect on the tissue as described above. Application is fast and simple. The affected skin may be clipped free of hair and cellular debris removed with gentle cleaning. The skin is allowed to dry before application of the photoconverter gel. Just prior to application, 1 ampule of fluorescence chromophore gel is added to 1 container of photoconverter carrier gel and mixed thoroughly. The mixture is applied in a 2-mm layer to the affected skin, and the LED lamp is held 5 cm above the lesion and used to illuminate the area for 2 minutes. The gel is wiped away using saline-soaked gauze. The application can be repeated immediately after 5 to 10 minutes of rest or a second application can occur a few days later. Twice-weekly applications are continued until the wound is healed. Appropriate eyewear is required to protect the operator from the intensely bright light. Application is pain free and stress free for the patient, so sedation is not typically required.

Benefits of Phovia

Phovia shows great promise as a safe, effective therapy for treatment of numerous inflammatory dermatoses in dogs including superficial pyoderma,38 deep pyoderma,39 perianal fistula,40 interdigital dermatitis,41 calcinosis cutis,42 acute traumatic wounds,43 chronic wounds,37 surgical wounds,44 and otitis externa.45 Phovia as a sole therapy speeds time to healing by 36% in canine superficial pyoderma as compared with dogs receiving oral antibiotics alone.38 In one study, dogs with superficial pyoderma were treated with Phovia alone or with an oral antibiotic alone. Dogs treated twice weekly with Phovia demonstrated complete clinical healing in about 2.3 weeks (P < .05)whereas dogs receiving oral antibiotic healed in about 3.75 weeks.38 Additionally, Phovia speeds time to healing by nearly 50% in deep pyoderma when used with an oral antibiotic (5.7 weeks of treatment) compared with dogs receiving only oral antibiotic (11.7 weeks of treatment).39 The ability of this fluorescent PBM therapy to eliminate or significantly reduce duration of exposure to antibiotics will decrease the spread of antibiotic-resistant bacterial strains within pets and humans.

Phovias high safety profile makes it a beneficial tool to implement in everyday practice. Training the veterinary team to communicate therapy benefits with clients as well as to perform treatments is fast and easy. Training the veterinary technicians to perform treatments will give the veterinarian time to examine other patients. A single back-to-back application takes about 15 minutes, so pet owners can be in and out of the clinic quickly; however, the 2 weekly treatments can be separated by a few days if the veterinarian prefers to evaluate the patient more frequently. Additionally, when used as a sole therapy, clients are not required to administer oral or topical medications at home. This greatly improves treatment adherence and success. Instruct clients to use once-daily smartphone photos to document improvement at home. This can be useful when deciding how many treatments to perform. Most cases of superficial pyoderma will resolve completely by the third treatment.38 It is a good idea to communicate to clients that 3 to 4 weekly treatments may be required.

Conclusion

Phovia is a versatile, innovative therapeutic approach to numerous types of dermatitis.36 It is easy to implement in general practice, and is safe, pain free, and affordable. Phovia is highly effective for superficial and deep skin infections and eliminates the need for clients to administer numerous at-home treatments. This greatly improves the pet-owner bond and treatment outcomes by promoting adherence. Phovia accelerates time to wound healing, which decreases duration of antibiotic exposure and may reduce risk of antibiotic resistance development in these cases.2,13,36-39 Phovias efficacy against antibiotic-susceptible and antibiotic-resistant bacteria shows promise as an alternative therapeutic approach that promotes the principles of antimicrobial stewardship.36 If you are interested in purchasing this medical device for your practice, contact your Vetoquinol service representative.

Amelia G. White, DVM, MS, DACVD is an associate clinical professor of dermatology at Auburn University College of Veterinary Medicine.

REFERENCES

Original post:
Managing superficial pyoderma with light therapy - DVM 360

Skin Stem Cells Comments Off on Managing superficial pyoderma with light therapy – DVM 360 | October 28th, 2021