Transparency Market Research (TMR) has published a new report titled, Autologous cell therapy Market Global Industry Analysis, Size, Share, Growth, Trends, and Forecast, 20192027. According to the report, the global autologous cell therapy market was valued at US$ 7.5 Bn in 2018 and is projected to expand at a CAGR of 18.1% from 2019 to 2027.

Overview

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Rise in Prevalence of Neurological Disorders & Cancer and Others to Drive Market

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Bone Marrow Segment to Dominate Market

Neurology Segment to be Highly Lucrative Segment

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Hospitals Segment to be Highly Lucrative Segment

North America to Dominate Global Market

Competitive Landscape

The global autologous cell therapy market is fragmented in terms of number of players. Key players in the global market include Pharmicell Co., Inc., Castle Creek Biosciences, Inc., Vericel Corporation, Lineage Cell Therapeutics, Inc., BrainStorm Cell Therapeutics, Caladrius Biosciences, Inc., Opexa Therapeutics, Inc., Regeneus Ltd., Takeda Pharmaceutical Company Limited., Sangamo Therapeutics, U.S. Stem Cell, Inc. and other prominent players.

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Autologous Cell Therapy Market is Anticipated to Expand at a CAGR of 18.1% from 2019 to 2027 - Eurowire

Skin Stem Cells Comments Off on Autologous Cell Therapy Market is Anticipated to Expand at a CAGR of 18.1% from 2019 to 2027 – Eurowire | October 19th, 2020

Skin is a complex, living organ made up of several structural components that (quite literally) touches a lot of different parts of us. When you look at the makeup, there's collagen, elastin, hyaluronic acid, ceramides, lipids, and so forth; from there, it's also affected by the muscle composition and bone underneath. This is all to say, when wrinkles formit's hardly ever due to a singular reason.

So to start, there is the fact that many components of our skin structure decline with age. "As we age, we lose collagen, fat, and start to resorb bone. These changeslead to volume loss, thin, saggy skin. As a result, our nasolabial folds become more pronounced," says Lolis.

It's also important to note that these lines are exacerbated with movement, the same way crow's feet can come from squinting and the "11's" can come from scrunching yourbrow. "Laugh lines are formed by constant use of the orbicularis orbis muscle which allows us the ability to speak," says Masur. "Over time as we age the skin protecting this muscle becomes stretched creating laxity increasing the appearance of these folds. The region around the mouth known as the peri-oral area is one of the thinnest-skinned on the face, making us more susceptible to fine lines or wrinkles forming the 'laugh lines.'"

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Laugh Lines Are Totally Normal How To Ease Them Sans Injections - mindbodygreen.com

Skin Stem Cells Comments Off on Laugh Lines Are Totally Normal How To Ease Them Sans Injections – mindbodygreen.com | October 17th, 2020

Market Report Summary

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The healthcare industry has been focusing on excessive research and development in the last couple of decades to ensure that the need to address issues related to the availability of drugs and treatments for certain chronic diseases is effectively met. Healthcare researchers and scientists at the Li Ka Shing Faculty of Medicine of the Hong Kong University have successfully demonstrated the utilization of human induced pluripotent stem cells or hiPSCs from the skin cells of the patient for testing therapeutic drugs.

The success of this research suggests that scientists have crossed one more hurdle towards using stem cells in precision medicine for the treatment of patients suffering from sporadic hereditary diseases. iPSCs are the new generation approach towards the prevention and treatment of diseases that takes into account patients on an individual basis considering their genetic makeup, lifestyle, and environment. Along with the capacity to transform into different body cell types and same genetic composition of the donors, hiPSCs have surfaced as a promising cell source to screen and test drugs.

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In the present research, hiPSC was synthesized from patients suffering from a rare form of hereditary cardiomyopathy owing to the mutations in Lamin A/C related cardiomyopathy in their distinct families. The affected individuals suffer from sudden death, stroke, and heart failure at a very young age. As on date, there is no exact treatment available for this condition.

This team in Hong Kong tested a drug named PTC124 to suppress specific genetic mutations in other genetic diseases into the iPSC transformed heart muscle cells. While this technology is being considered as a breakthrough in clinical stem cell research, the team at Hong Kong University is collaborating with drug companies regarding its clinical application.

The unique properties of iPS cells provides extensive potential to several biopharmaceutical applications. iPSCs are also used in toxicology testing, high throughput, disease modeling, and target identification. This type of stem cell has the potential to transform drug discovery by offering physiologically relevant cells for tool discovery, compound identification, and target validation.

A new report by Persistence Market Research (PMR) states that the globalinduced pluripotent stem or iPS cell marketis expected to witness a strong CAGR of 7.0% from 2018 to 2026. In 2017, the market was worth US$ 1,254.0 Mn and is expected to reach US$ 2,299.5 Mn by the end of the forecast period in 2026.

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Customization to be the Key Focus of Market Players

Due to the evolving needs of the research community, the demand for specialized cell lines have increased to a certain point where most vendors offering these products cannot depend solely on sales from catalog products. The quality of the products and lead time can determine the choices while requesting custom solutions at the same time. Companies usually focus on establishing a strong distribution network for enabling products to reach customers from the manufacturing units in a short time period.

Entry of Multiple Small Players to be Witnessed in the Coming Years

Several leading players have their presence in the global market; however, many specialized products and services are provided by small and regional vendors. By targeting their marketing strategies towards research institutes and small biotechnology companies, these new players have swiftly established their presence in the market.

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Persistence Market Research (PMR) is a third-platform research firm. Our research model is a unique collaboration of data analytics and market research methodology to help businesses achieve optimal performance.

To support companies in overcoming complex business challenges, we follow a multi-disciplinary approach. At PMR, we unite various data streams from multi-dimensional sources. By deploying real-time data collection, big data, and customer experience analytics, we deliver business intelligence for organizations of all sizes.

Our client success stories feature a range of clients from Fortune 500 companies to fast-growing startups. PMRs collaborative environment is committed to building industry-specific solutions by transforming data from multiple streams into a strategic asset.

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Induced Pluripotent Stem Cells Market To Grow At 7% YOY In Forecast Years 2026 - The Think Curiouser

Skin Stem Cells Comments Off on Induced Pluripotent Stem Cells Market To Grow At 7% YOY In Forecast Years 2026 – The Think Curiouser | October 17th, 2020

Switch up your regular makeup routine for a more naturally radiant look by switching to CC cream. Its perfect for days when you want lighter coverage, or you can use it as a primer. The benefit of CC cream is that it works both harder and smarter for you. Often, they contain extra nourishing ingredients to boost your hydration and sun protection to prevent damage from harmful UV rays. Plus, they use color-correcting technology and pigments to even out skin tone, cover blemishes, and diminish the look of fine lines and wrinkles. Its a great alternative or addition to your foundation for an easy, glowy, radiant look.

Put your best face forward with the Super CC Cream from Physicians Formula. It contains micro color-correcting pigments and anti-aging ingredients to even out skin tone and to reduce the appearance of fine lines, age spots, and dullness. Plus, youll get a good dose of moisturizing elements, as well as SPF 30 that protects your skin from additional sun damage. The formula is lightweight and blends easily, making application quick and straightforward, leaving your skin feeling smooth and youthful.

BUY

Chanels CC Cream packs a punch in correcting signs of aging and proving beautifully light coverage. It is infused with extracts from the murunga plum, a native Australian superfruit. This plant is rich in vitamin C and antioxidants for improving texture and glow while protecting the skin from free radicals. The broad-spectrum sunscreen component covers you for both UVA and UVB damage. Meanwhile, the addition of hyaluronic acid draws moisture to the skin for a plump, youthful look. With continual use, your skin will look younger, healthier, and more radiant.

BUY

Enjoy 24-hour hydration with this CC cream formula from Lancome. It contains SPF50 physical sunscreen, as well as mineral filters for full-coverage color correction. Improve your skin texture, minimize pores, balance uneven skin tone, and reduce the appearance of fine lines and wrinkles, all in one easy step. It also has an antioxidant complex, vitamin E, and mint-extract to add additional environmental protection, hydration, and an energizing feel.

BUY

Giorgio Armani brings cutting-edge technology and the expertise of makeup artist Linda Cantello together in this Prima Color Control Glow Moisturizer. Enjoy long-lasting hydration from vitamin E, moringa oleifera extract, and adenosine. When it comes to coverage, the five shades adapt to the skins color to enhance the natural luminosity while hiding blemishes and fine lines. Plus, added menthol-based ingredients leave you feeling refreshed and awake, ready to tackle the day ahead.

BUY

If youre looking for a CC cream that does more for you, the Bare Minerals Complexion Rescue is an excellent option. Youll not only get radiant coverage but sun protection and long-lasting skincare benefits. The oil-free, water-infused formula keeps the skin hydrated for up to 12 hours after application, and with continual use, can boost the skins overall hydration. Made with 97% naturally derived ingredients, the gel-cream texture feels light and smooth on the skin. Lastly, there are 20 flexible shades to choose from, which naturally adapts to your skin tone.

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Get glowing skin by using Cliniques Moisture Surge CC Cream. The oil-free formula provides a shot of hydration, so your skin looks good from the inside out. Next, it instantly color corrects to diminish any redness, dullness, or imperfections, giving you a healthy vibrance. A sun protection factor of 35 prevents additional damage from harmful UV rays, yet the formula is lightweight and feels beautiful on the skin. Use it on its own for an easy, glowy vibe, or add additional foundation for a full-coverage look.

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Youll be feeling and looking fresh as a daisy with Supergoops Daily Correcting CC Cream. It contains brightening ingredients such as apple extract and mica, which reflects the light to give you a youthful, glowy look. Vitamin C and alpha-hydroxy acids keep the skin smooth, while sodium hyaluronate is a humectant that draws moisture into the skin, keeping you hydrated. Wear this CC cream daily to minimize skin discoloration, dryness, fine lines, and blotchiness. Plus, the SPF 35 UV protection is mineral-based, rather than chemical, making it suitable for sensitive skin types.

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Nourish, hydrate, and protect your skin all in one step by using Olays lightweight Total Effects Tone Correcting CC Cream. It feels light on your skin while still providing a heavy dose of beneficial ingredients. There are seven vitamins and antioxidants for extra protection, including vitamin B3 and VitaNiacin Complex II, both of which improve the skins appearance and repairs the barrier. It also corrects your skin tone, diminishes fine lines, and minimizes the pores. You can use this product in place of both your moisturizer and foundation, as well as sunscreen, thanks to the SPF 15.

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Choose from eleven different shades in IT Cosmetics inclusive CC+ Cream range. This foundation replacement corrects any color imbalances and pigmentation issues, as well as hydrates and protects your face from the sun and environmental aggressors. It was developed in collaboration with plastic surgeons to ensure you get the most benefit. Its chock full of active ingredients, including niacin, peptides, hydrolyzed collagen, and hyaluronic acid, as well as antioxidants and minerals. Combined, these ingredients hydrate, reduce the appearance of acne scarring and wrinkles, evening out skin tone, tackling dark under-eye circles, and minimizing large pores. The result is a flawless, radiant complexion that wont crack or crease, leaving you feeling beautiful and confident.

BUY

Fruit stem cells and vitamin C come together in this lightweight CC cream. Youll enjoy beautiful tinted coverage that easily replaces your foundation when you feel like a more natural look. It also reduces the appearance of fine lines and wrinkles while evening out skin tone and texture. Plus, you need not worry about sun damage, with broad-spectrum SPF 30 protection from UVA and UVB rays. There are seven shades to choose from, ranging from Natural Glow to Deep Glow.

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Enjoy medium coverage with the Ultra CC Cream from Pacific Store. This illuminating formula contains coconut water, kelp, and ginseng for a light, smooth finish that rehydrates your skin. The color correcting minerals even out your skin tone and hide any blemishes, while the SPF 17 physical sunscreen protects your skin from UV damage. Plus, its vegan, cruelty-free, and comes in a 100% recyclable container.

BUY

Cle Cosmetics adds an extra element to their CCC cream a color control and change cream. This product can replace both your primer and foundation, as well as sunscreen, thanks to the powerful SPF50. It offers more substantial coverage than regular CC creams and matches flawlessly to your skin using unique Micro Capsule Technology. Plus, it comes in ten different, inclusive colors, so no matter your skin tone, you can rock a dewy, moisturized complexion all day long.

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Protect and hydrate your skin while looking fabulous. The Honest Beauty Clean Corrective cream is a six-in-one formula that primes, perfects, protects, blurs, brightens, and moisturizes. It boasts vitamin C to improve skin tone, as well as an antioxidant blend to protect from environmental damage. Physical sunscreens also shield your skin from sun damage, with a sun protection factor of 30. Plus, it provides blue light defense and is vegan and cruelty-free.

BUY

Embrace smoother, beautiful skin with Alamys Smart Shade CC cream. It features color correction technology that reduces imperfections, discoloration, and dullness while providing a boost of hydration. It also adjusts to your natural skin tone. Meanwhile, the SPF35 protects your face from the suns damaging rays. Lastly, the hypoallergenic, fragrance-free formula also makes it great for anyone with more sensitive skin.

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This mattifying tinted moisturizer from black Up is designed specifically for black women and people of color with darker skin tones a segment of the beauty market often left out of CC cream shades. You can use it on its own as a lightweight foundation or put it to work as a primer. In one simple step, it evens out skin tone, targets dark spots and excess sebum, and improves the natural radiance of the skin. Plus, it adds a boost of hydration to keep your skin feeling smooth and supple.

BUY

The best CC cream will combine high levels of hydration and protection, as well as match your skin tone. You want both sun protection in the form of sunscreen and protection from environmental aggressors by including vitamins and antioxidants. Look for brands like Physicians Formula, Supergoop!, and IT Cosmetics. If you have darker skin, look for inclusive brands such as IT Cosmetics, black Up, and Cle Cosmetics.

The BB stands for beauty balm or blemish balm. It's very similar to CC cream in that it combines the benefits of skincare with makeup to give you light coverage for a simple, natural look, or as a primer. You'll enjoy hydrated, illuminated skin with regular use. This most significant difference is that it doesn't provide comprehensive coverage, so if you need more, then a CC cream or foundation will be the better option.

CC cream stands for color corrector or complexion corrector cream. It's a lightweight alternative to foundation or can be used in conjunction with it, as a primer. It often contains nourishing ingredients to boost hydration, sun protection elements, and color-correcting technology. It's the best of both worlds, combing skincare and makeup into one fantastic product.

You can use a primer in addition to CC cream, but it's not always necessary. Primer acts to fill in and smooth out imperfections but doesn't necessarily provide additional benefits such as moisturizing or sun protection. Meanwhile, CC cream corrects discoloration and smooths out the skin, while giving that extra protection. If you have heavy acne scarring or deeper wrinkles, a primer will still be beneficial. However, if you're looking to even out your complexion and increase hydration, the CC cream will be sufficient by itself.

CC cream stands for color corrector or complexion corrector cream. It's lighter weight than foundation but provides more coverage than BB cream. All you need to do is substitute it for your foundation in your makeup routine, or use it as a primer. Start with a cleansed, toned, and moisturized face. Then using a beauty blender or your fingertips, apply the liquid all over your face, ensuring you're fully smoothed out around the edges, building up the coverage as you desire.

You can use CC cream on the days where you're not vibing a full face of makeup but still want some coverage. It's great when you're running behind schedule or just a bit time-poor. You can also use it as a primer under your regular foundation. CC Cream eliminates steps in your makeup routine, such as using a separate sunscreen, color corrector, and foundation, which can save you time in the morning.

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15 Best CC Creams for a Flawless Complexion - The Trend Spotter

Skin Stem Cells Comments Off on 15 Best CC Creams for a Flawless Complexion – The Trend Spotter | October 17th, 2020

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An international team of researchers has published a study showing how the control of stem cell metabolism is critical to maintaining hair follicles. The study appeared in the high-impact journal Cell Metabolism.

University of Arkansas researchers included Kyle Quinn, associate professor of biomedical engineering, and Olivia Kolenc, a graduate student in Quinn's lab. The project was led by Sara Wickstrm, associate professor at the University of Helsinki, and included researchers from the research groups of Professor Sabine Eming at the University of Cologne and Martin Denzel at the Max Planck Institute for Biology of Ageing in Germany.

The team studied how the metabolism of stem cells in hair follicles is critical to the growth and long-term maintenance of hair. The follicles are unique in mammals because unlike most organs or tissues, they naturally regenerate and cycle through phases of rest, growth and degeneration. Those cycles are maintained by stem cells. Kolenc used advanced non-invasive skin imaging to monitor hair follicle metabolism in live mice.

Kolenc's work showed how the metabolism of stem cells changes as the follicle transitions to a growth phase, which provided a critical foundation to the study's larger goal of discovering the cell signaling pathways associated with the metabolic control of stem cell fate and hair follicle cycles.

The study provides insight into how our organs are maintained by stem cells and how aging can result in conditions such as hair loss. Kolenc said hair follicle stem cells aren't like some stem cells, which can transform into a wide variety of different cell types. Instead, she said, they can transform to match the surrounding area in the skin tissue.

"Hair follicle stem cells are able to differentiate into a subset of what's in their surrounding area," she said. "They can't just create any other cell, but they can contribute to regeneration and increasing the number of cells within the skin tissue."

Kolenc said hair follicle stem cells are unique among the cells in our skin because they can contribute to repair and regeneration of the skin.

"There are few populations of stem cells known to exist within the skin, so this is really a big target to help skin wound healing," she said.

Kolenc said the opportunity to contribute to such a large-scale project was special.

"It's a bit humbling," she said. "I contributed a small part to a large project that was conducted over many years. It's a cool feeling to see something like that with my name on it."

"Olivia played an important role in this study by monitoring hair follicle stem cells within their natural environment in live skin," Quinn said. "The insights she gained during this work will be very helpful as she continues studying how our metabolic imaging techniques can be applied to aging and wound healing research."

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Biomedical Engineering Team Contributes to High-impact Study on Metabolism - University of Arkansas Newswire

Skin Stem Cells Comments Off on Biomedical Engineering Team Contributes to High-impact Study on Metabolism – University of Arkansas Newswire | October 16th, 2020

Vanderbilt University researchers have reported the counterintuitive discovery that certain chemotherapeutic agents used to treat tumors can have the opposite effect of tissue overgrowth in normal, intact mammary glands, epidermis and hair follicles. The researchers also are the first to report the discovery of an innate immune signaling pathway in fibroblaststhe spindle-shaped cells responsible for wound healing and collagen productionthat causes cells to proliferate. Such signaling pathways previously were attributed only to immune cells.

The article describing the research, DNA Damage Promotes Epithelial Hyperplasia and Fate Mis-specification via Fibroblast Inflammasome Activation, was published in the journal Developmental Cell on Oct. 13.

The findings of this work, led by postdoctoral fellow Lindsey Seldin and Professor and Chair of the Department of Cell and Developmental Biology Ian Macara, have broad implications for diseases associated with the immune system like psoriasis, as well as cancer and stem cell research.

Understanding the functionality of stem cells and the way that their behavior is regulated has been a longstanding research interest for Seldin. Normal stem cells have an amazing ability to continuously divide to maintain tissue function without forming tumors, she explained. We wanted to understand what happens to these cells in their native environment when subjected to damage, and if the response was connected to a specific tissue.

By testing perturbations to the epidermis, mammary gland and hair follicles vis--vis mechanical damage or DNA damage through chemotherapeutic agents, the researchers saw a paradoxical response: Stem cells, which otherwise would divide slowly, instead divided rapidly, promoting tissue overgrowth.

When the tissues were subjected to DNA damage, their stem cells overly proliferated, giving rise to different cells than they normally would. This was a very perplexing result, said Seldin, the papers lead author. We were determined to figure out if this was a direct response by the stem cells themselves or by inductive signals within their environment. The key clue was that stem cells isolated from the body did not behave the same way as in intact tissuean indication that the response must be provoked from signals being sent to the stem cells from other surrounding cell types.

The investigators turned their attention to fibroblasts, the predominant component of the tissue microenvironment. When fibroblasts in the epidermis were removed, the stem cell responsiveness to DNA damage was diminished, indicating that they played an important role. RNA sequencing revealed that fibroblasts can signal by way of inflammasomescomplexes within cells that help tissues respond to stress by clearing damaged cells or pathogens, which also in this case caused stem cells to divide. This is an astounding discovery, said Macara. Inflammasome signaling has previously been attributed only to immune cells, but now it seems that fibroblasts can assume an immune-like nature.

Seldin intends to replicate this work in the mammary gland to determine whether fibroblasts initiate the same innate immune response as in the epidermis, and more broadly how fibroblasts contribute to the development of cancer and other diseases associated with the immune system.

This work was supported by NCI/NIH grants R35CA132898, F32CA213794 and T32CA119925, as well as American Cancer Society grant PF-18-007-01-CCG.

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Vanderbilt researchers make counterintuitive discoveries about immune-like characteristics of cells, chemotherapys impact on tissue growth -...

Skin Stem Cells Comments Off on Vanderbilt researchers make counterintuitive discoveries about immune-like characteristics of cells, chemotherapys impact on tissue growth -… | October 16th, 2020

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

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

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

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

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

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

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

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

Contact:

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

_________________________________

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

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

Skin Stem Cells Comments Off on Pluristem Announces Clearance to Move Forward with Enrollment for Cohort II in an Investigator-Led Phase I/II Chronic Graft vs Host Disease… | October 16th, 2020

Oct. 15, 2020 10:45 UTC

KENILWORTH, N.J.--(BUSINESS WIRE)-- Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved an expanded label for KEYTRUDA, Mercks anti-PD-1 therapy, as monotherapy for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL). The approval is based on results from the Phase 3 KEYNOTE-204 trial in which KEYTRUDA significantly reduced the risk of disease progression or death by 35% (HR=0.65 [95% CI, 0.48-0.88; p<0.0027]) compared to brentuximab vedotin (BV). Additionally, median progression-free survival (PFS) was 13.2 months (95% CI, 10.9-19.4) for patients treated with KEYTRUDA and 8.3 months (95% CI, 5.7-8.8) for patients treated with BV. The FDA also approved an updated pediatric indication for KEYTRUDA for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after two or more lines of therapy.

An estimated 8,500 patients in the U.S., many of them 40 years of age or younger, will be diagnosed with cHL this year. Now patients with cHL who progress after frontline therapy have a new option in KEYTRUDA, which has demonstrated a clinically meaningful improvement in progression-free survival compared to brentuximab vedotin, said Dr. Vicki Goodman, vice president, clinical research, Merck Research Laboratories. At Merck, we are committed to improving outcomes for patients with cancer. Todays FDA approval builds upon our growing range of options for people with blood cancers.

Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, KEYTRUDA should be withheld or discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see Selected Important Safety Information below.

The patients with cHL who do not achieve remission following initial treatment or who relapse after transplantation face a poor prognosis, reflecting the unmet need for improved therapies in the relapsed/refractory setting, said Dr. John Kuruvilla, hematologist and associate professor of medicine, Princess Margaret Cancer Centre and University of Toronto. With this approval, KEYTRUDA has the potential to change the current standard of care and help these patients achieve better outcomes.

KEYTRUDA was previously approved under the FDAs accelerated approval process for the treatment of adult and pediatric patients with refractory cHL, or who have relapsed after three or more prior lines of therapy based on data from the KEYNOTE-087 trial. In accordance with accelerated approval regulations, continued approval was contingent upon verification and description of clinical benefit; these accelerated approval requirements have been fulfilled with the data from KEYNOTE-204.

This approval was reviewed under the FDAs Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among its international partners. For this application, a modified Project Orbis was undertaken, and the FDA is collaborating with the Australian Therapeutic Goods Administration and Health Canada on their ongoing review of the application.

Data Supporting the Approval The approval was based on data from KEYNOTE-204 (NCT02684292), a randomized, open-label, active-controlled trial conducted in 304 patients with relapsed or refractory cHL. The trial enrolled adults with relapsed or refractory disease after at least one multi-agent chemotherapy regimen. Patients were randomized 1:1 to receive either KEYTRUDA 200 mg intravenously every three weeks or BV 1.8 mg/kg intravenously every three weeks.

Treatment was continued until unacceptable toxicity, documented disease progression or a maximum of 35 cycles (up to approximately two years). Disease assessment was performed every 12 weeks. Randomization was stratified by prior autologous HSCT (yes vs. no) and disease status after frontline therapy (primary refractory vs. relapse less than 12 months after completion vs. relapse 12 months or more after completion). The main efficacy measure was PFS as assessed by blinded independent central review (BICR) using 2007 revised International Working Group (IWG) criteria.

Patients were enrolled and randomized to KEYTRUDA (n=151) or BV (n=153). The study population characteristics were median age of 35 years (range, 18 to 84); 57% male; 77% white, 9% Asian and 3.9% Black. The median number of prior therapies was two (range, 1 to 10) in the KEYTRUDA arm and three (range, 1 to 11) in the BV arm, with 18% in both arms having one prior line. Forty-two percent of patients were refractory to the last prior therapy, 29% had primary refractory disease, 37% had prior autologous HSCT, 5% had received prior BV, and 39% had prior radiation therapy.

In KEYNOTE-204, KEYTRUDA reduced the risk of disease progression or death by 35% (HR=0.65 [95% CI, 0.48-0.88; p=0.0027]) and showed a median PFS of 13.2 months (95% CI, 10.9-19.4). Median PFS was 8.3 months (95% CI, 5.7-8.8) for patients treated with BV. For PFS, in the KEYTRUDA arm, there were 81 patients (54%) with an event versus 88 patients (58%) in the BV arm. For patients treated with KEYTRUDA, the objective response rate (ORR) was 66% (95% CI, 57-73), with a complete response rate of 25% and a partial response rate of 41%. For patients treated with BV, the ORR was 54% (95% CI, 46-62), with a complete response rate of 24% and a partial response rate of 30%. The difference in ORRs is not statistically significant. Among the responding patients, median duration of response (DOR) was 20.7 months (range, 0.0+ to 33.2+) with KEYTRUDA and 13.8 months (range, 0.0+ to 33.9+) with BV.

In KEYNOTE-204, the median duration of exposure to KEYTRUDA was 10 months (range, 1 day to 2.2 years), with 68% receiving at least six months of treatment and 48% receiving at least one year of treatment. Serious adverse reactions occurred in 30% of patients who received KEYTRUDA. Serious adverse reactions in those greater than or equal to 1% of patients included pneumonitis, pneumonia, pyrexia, myocarditis, acute kidney injury, febrile neutropenia and sepsis. Three patients (2%) died from causes other than disease progression: two from complications after allogeneic HSCT and one from an unknown cause.

Permanent discontinuation of KEYTRUDA due to an adverse reaction occurred in 14% of patients; 7% of patients discontinued treatment due to pneumonitis. Dosage interruption of KEYTRUDA due to an adverse reaction occurred in 30% of patients. Adverse reactions that required dosage interruption in greater than or equal to 3% of patients were upper respiratory tract infection, pneumonitis, transaminase increase and pneumonia. Thirty-eight percent of patients had an adverse reaction requiring systemic corticosteroid therapy. The most common adverse reactions (greater than or equal to 20%) were upper respiratory tract infection (41%), musculoskeletal pain (32%), diarrhea (22%), and pyrexia, fatigue, rash and cough (20% each).

About Hodgkin Lymphoma Hodgkin lymphoma is a type of lymphoma that develops in the white blood cells called lymphocytes, which are part of the immune system. Hodgkin lymphoma can start almost anywhere most often in lymph nodes in the upper part of the body, with the most common sites being in the chest, neck or under the arms. Worldwide, there were approximately 80,000 new cases of Hodgkin lymphoma, and more than 26,000 people died from the disease in 2018. In 2020, it is estimated nearly 8,500 people will be diagnosed with Hodgkin lymphoma in the United States. Classical Hodgkin lymphoma accounts for more than nine in 10 cases of Hodgkin lymphoma in developed countries.

About KEYTRUDA (pembrolizumab) Injection, 100 mg KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications Melanoma KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) 10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Tumor Mutational Burden-High KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Selected Important Safety Information for KEYTRUDA Immune-Mediated Pneumonitis KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients. Pneumonitis occurred in 8% (31/389) of patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib) Immune-Mediated Hepatitis KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barr syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and post-marketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risk of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT.

Increased Mortality in Patients With Multiple Myeloma In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-002, KEYTRUDA was permanently discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). The most common adverse reactions were fatigue (43%), pruritus (28%), rash (24%), constipation (22%), nausea (22%), diarrhea (20%), and decreased appetite (20%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

In KEYNOTE-204, KEYTRUDA was discontinued due to adverse reactions in 14% of 148 patients with cHL. Serious adverse reactions occurred in 30% of patients; those 1% included pneumonitis, pneumonia, pyrexia, myocarditis, acute kidney injury, febrile neutropenia, and sepsis. Three patients died from causes other than disease progression. The most common adverse reactions (20%) were upper respiratory tract infection (41%), musculoskeletal pain (32%), diarrhea (22%), and pyrexia, fatigue, and cough (20% each).

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those 1% included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment. The most common adverse reactions (20%) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. Serious adverse reactions occurred in 42% of patients; those 2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients; those 2% were urinary tract infection, pneumonia, anemia, and pneumonitis. The most common adverse reactions (20%) in patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

In KEYNOTE-057, KEYTRUDA was discontinued due to adverse reactions in 11% of 148 patients with high-risk NMIBC. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.4%). Serious adverse reactions occurred in 28% of patients; those 2% were pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract infection (2%). The most common adverse reactions (20%) were fatigue (29%), diarrhea (24%), and rash (24%).

Adverse reactions occurring in patients with MSI-H or dMMR CRC were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

Adverse reactions occurring in patients with gastric cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

Adverse reactions occurring in patients with esophageal cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients with recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

Adverse reactions occurring in patients with hepatocellular carcinoma (HCC) were generally similar to those in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of ascites (8% Grades 3-4) and immune-mediated hepatitis (2.9%). Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (20%), ALT (9%), and hyperbilirubinemia (10%).

Among the 50 patients with MCC enrolled in study KEYNOTE-017, adverse reactions occurring in patients with MCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy. Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (11%) and hyperglycemia (19%).

In KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse reactions occurred in 40% of patients, the most frequent (1%) were hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse reaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only (13%), and the combination (8%); the most common were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common adverse reactions (20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

Adverse reactions occurring in patients with TMB-H cancer were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

Adverse reactions occurring in patients with cSCC were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

Lactation Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the final dose.

Pediatric Use In KEYNOTE-051, 161 pediatric patients (62 pediatric patients aged 6 months to younger than 12 years and 99 pediatric patients aged 12 years to 17 years) were administered KEYTRUDA 2 mg/kg every 3 weeks. The median duration of exposure was 2.1 months (range: 1 day to 24 months).

Adverse reactions that occurred at a 10% higher rate in pediatric patients when compared to adults were pyrexia (33%), vomiting (30%), leukopenia (30%), upper respiratory tract infection (29%), neutropenia (26%), headache (25%), and Grade 3 anemia (17%).

Mercks Focus on Cancer Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit http://www.merck.com/clinicaltrials.

About the Merck Access Program for KEYTRUDA At Merck, we are committed to supporting accessibility to our cancer medicines. Merck provides multiple programs to help appropriate patients who are prescribed KEYTRUDA have access to our anti-PD-1 therapy. The Merck Access Program provides reimbursement support for patients receiving KEYTRUDA, including information to help with out-of-pocket costs and co-pay assistance for eligible patients. More information is available by calling 855-257-3932 or visiting http://www.merckaccessprogram-keytruda.com.

About Mercks Patient Support Program for KEYTRUDA Merck is committed to helping provide patients and their caregivers support throughout their treatment with KEYTRUDA. The KEY+YOU Patient Support Program provides a range of resources and support. For further information and to sign up, eligible patients may call 85-KEYTRUDA (855-398-7832) or visit http://www.keytruda.com.

About Merck For more than 125 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the worlds most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit http://www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the company) includes forward-looking statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the companys management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the companys ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the companys patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the companys 2019 Annual Report on Form 10-K and the companys other filings with the Securities and Exchange Commission (SEC) available at the SECs Internet site (www.sec.gov).

Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.

View source version on businesswire.com: https://www.businesswire.com/news/home/20201015005355/en/

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FDA Approves Expanded Indication for Merck's KEYTRUDA (pembrolizumab) in Adult Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (cHL) -...

Skin Stem Cells Comments Off on FDA Approves Expanded Indication for Merck’s KEYTRUDA (pembrolizumab) in Adult Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (cHL) -… | October 16th, 2020

Using a brush or comb, in the shower, passing your hand through your hair In a 2015 IFOP survey, three out of four French people (76%) without baldness declared that they lost their hair. In addition, after 65 years, three in ten men suffer from androgenetic alopecia (or baldness). In general, therefore, we often see a loss of density with age, both in men and in women. However, science has long looked into the phenomenon of age-related hair loss, both to understand its origin and to treat it. Focusing on stem cells seems to offer the best hope for a cure, based on numerous studies.

The hair transplant procedure is indeed a sometimes expensive and invasive procedure. As for drugs, finasteride used for androgenetic alopecia in men can induce side effects such as loss of libido and erectile dysfunction while minoxidil can cause hypertrichosis. Today, researchers therefore seem to be looking more at alternative solutions, and in particular by focusing on stem cells.

Stem cells, directly linked to hair lossFor decades, researchers have always focused on keratinocytes, cells that make up the epidermis and integuments (body hair, hair, etc.). However, as part of a study conducted by the University of Calgary (Canada), the team of researchers focused on a small cell group present in hair follicles and in skin stem cells. : fibroblasts. And according to them, these fibroblasts are the main cause of age-related hair loss.

By studying the sparse coat of elderly mice, they noticed that fibroblast stem cells had lost their regenerative function or were malfunctioning. There werent enough of them to regenerate fibroblasts. As a result, the fibroblasts and hair follicles began to miniaturize and were no longer able to produce hair, explains Biernaskie, head of the research team.

Remember that fibroblasts are important because they send messages to keratinocytes to force them to divide, and in so doing, orchestrate the growth cycles of hair follicles allowing the production of new hairs. When the fibroblasts become scarce, the signal then becomes too weak to reach the keratinocytes and maintain the process of capillary growth. For Jeff Biernaskie: if we want to one day succeed in preventing hair loss or re-grow those that are already falling, we must work to preserve the function of these stem cells which are found in the hair follicles.

Against hair loss, but not only!This finding may help guide future research on hair loss more precisely. Scientists at the University of Calgary are particularly hoping to find a way to prevent this degeneration by blocking certain genetic mutations that occur directly in stem cells in fibroblasts.

They also believe that this will have wider implications. Indeed, Wisoo Shin, lead author of the study, points out that similar fibroblasts are found in most of our organs, maintaining their integrity and promoting tissue regeneration. Finding a way to promote self-renewal to produce new functional fibroblasts into old age therefore also offers the hope of being able to treat certain injuries and help the skin to regenerate.

Lamia spent a couple of years interning at an organization that offered medical consultation before joining the editorial team at FLWL News. An enthusiastic fitness freak in the room, she offers the best amounts of insights and craft-based writing style to keep us up to date about the medicine industry, health and science.

Email:lamia@flwl.orgPhone: +1 512-845-8162

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Stem cells are believed to play a key role in hair loss - FLWL News

Skin Stem Cells Comments Off on Stem cells are believed to play a key role in hair loss – FLWL News | October 14th, 2020

Electric organoid: Neurons derived from people with 22q11.2 syndrome are hyperexcitable and show calcium-signaling deficits.

Courtesy of Pasca lab

Neurons derived from people with 22q11.2 deletion syndrome, a genetic condition linked to autism, show deficits in electrical activity and calcium signaling, according to a new study1. A single gene appears to be largely responsible for these defects, the study shows.

Up to 20 percent of people who lack part or all of the chromosomal region 22q11.2 have autism. Individuals with the deletion may also have schizophrenia, seizures, heart defects, immune dysfunction or learning problems.

The new findings uncover factors that may contribute to the development of psychiatric conditions associated with 22q11.2 deletion syndrome. They could also help researchers identify new therapeutic targets, says lead author Sergiu Pasca, associate professor of psychiatry and behavioral sciences at Stanford University in California.

The syndrome is relatively common, occurring in up to 1 in 4,000 newborns, Pasca says. But researchers do not fully understand how genes in the 22q11.2 region contribute to autism or other conditions, he adds.

To solve this molecular puzzle, Pasca and his team reprogrammed skin cells from 15 people with the deletion and 15 controls into induced pluripotent stem cells. Using a technique they developed in 2015, they coaxed these cells to turn into neurons, which self-organize in a dish into spherical clusters called organoids. The organoids show some key features of the developing cerebral cortex, a brain region implicated in autism.

The neurons derived from people with 22q11.2 syndrome spontaneously fire four times as frequently as neurons derived from controls, the researchers found. And the electrical activity of the 22q cells does not set off the usual spike in calcium levels, which is crucial for neurons to exchange messages.

In some other syndromes tied to schizophrenia and autism, calcium-channel genes are mutated. But the number of channels and the speed at which they work in 22q neurons is the same as in control neurons. Instead, the 22q cells show an unusually low voltage difference across the cell membrane when they arent firing, causing the signaling defects and hyperexcitability, the researchers found.

The researchers suspected that a gene called DGCR8 might be responsible for the neuronal deficits in the organoids because it lies within 22q11.2 and is linked to abnormal electrical activity in the neurons of mice2. DGCR8 is essential for the synthesis of short RNA fragments, called microRNAs, that regulate gene expression.

Lowering DGCR8s expression levels in control neurons reproduced the abnormalities seen in 22q neurons. In contrast, boosting the genes activity in 22q neurons or treating them with antipsychotic drugs prevented them from being overly excitable and reversed their calcium-signaling defects. The study was published 28 September in Nature Medicine.

Previous studies have analyzed lab-grown neurons derived from people with schizophrenia or autism-related disorders such as Rett and fragile X syndromes. But most used only a few human-derived cell lines, says Guo-li Ming, professor of neuroscience at the University of Pennsylvania in Philadelphia. The new study, Ming says, has a total of 30 human lines thats a huge effort.

By studying brain organoids derived from so many people, the researchers were able to identify the gene that might be involved in the psychiatric conditions associated with 22q11.2 syndrome, says Sally Temple, scientific director of the Neural Stem Cell Institute in Rensselaer, New York. Whenever we have a light shining ahead, saying, This is what you should really be looking at, it means that were making progress, she says.

The study participants with 22q11.2 syndrome vary in their psychiatric diagnoses, and yet all the brain organoids derived from their cells show the same neuronal abnormalities. Thats somewhat surprising, because we know there are a lot of differences in the genetic background of different people, Ming says.

The deletion might conspire with other factors to ultimately determine which psychiatric conditions a person has, Pasca says. It could be that the deletion causes cellular defects, and once there is a stressor such as social stress, disease develops. Its also unclear whether these cellular defects are related to the high prevalence of seizures in people with 22q11.2 syndrome, he says.

The hallmarks of most neuropsychiatric conditions can change over time, says Giuseppe Testa, director of the stem cell epigenetics unit at the European Institute of Oncology in Milan, Italy. Studies that look at a larger number of people with 22q11.2 deletion syndrome or other neurodevelopmental conditions could help to elucidate the relationship between the neuronal defects observed in the lab and the psychiatric manifestations of the conditions, Testa says. The new study, however, is a great resource for understanding how the 22q11.2 deletion contributes to schizophrenia and autism, he says.

Pascas team is trying to pinpoint molecules that could open new therapeutic avenues for 22q11.2 deletion syndrome. The antipsychotics they tested restore the unusual voltage differences in the 22q neurons, but they dont address the core mechanisms responsible for psychiatric conditions linked to the syndrome, Pasca says.

Whats more, antipsychotics have many side effects, and not all individuals respond to them, he says. We need better therapies we need to identify what the key molecular players are and target those.

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Brain organoids reveal neuronal flaws in syndrome tied to autism - Spectrum

Skin Stem Cells Comments Off on Brain organoids reveal neuronal flaws in syndrome tied to autism – Spectrum | October 14th, 2020

Patients with cystic fibrosis experience recurrent lung infections that eventually destroy their airways, shortening their average life expectancy to 50 years in Canada. Current drug treatments, which target a malfunctioning pathway in cells that causes the infections, are costly and have varying effectiveness.

Now, with funding from Medicine by Design, a researcher at the Hospital for Sick Children (SickKids) is combining stem cells, gene editing and computational modelling to try to hijack an alternative cell pathway in the hopes of restoring lung function in these patients.

If successful, our study will be the first to provide proof-of-concept that this alternative approach to treating cystic fibrosis is effective, saysAmy Wong, a scientist working in developmental and stem cell biology at SickKids who is also an assistant professor in the department of laboratory medicine and pathobiology in the University of Torontos Temerty Faculty of Medicine.

Wongs project is one of seven across U of T and its affiliated hospitals that have been awarded 2020New Ideas AwardsandSeed Fundawards from Medicine by Design. Through a $1 million investment, Medicine by Design is supporting research aimed at advancing new concepts expected to be important to regenerative medicine in the coming years. The funded projects will have potential impacts in diseases and conditions such as vision loss, amyotrophic lateral sclerosis (ALS), intestinal disease in premature babies and more.

Supporting novel strategies and approaches is crucial to moving regenerative medicine into the future, saysMichael Sefton, executive director of Medicine by Designand a University Professor at U of Ts Institute of Biomedical Engineeringand thedepartment of chemical engineering & applied chemistry in the Faculty of Applied Science & Engineering.

Our 2020 New Ideas project portfolio integrates mathematical modelling, physics and computational biology with stem cell biology and biomedical engineering, and strengthens engagement with clinicians who are key to translating our research into patient impact. We are particularly delighted this year to support so many outstanding early-career researchers, who will ensure Toronto remains a global leader in regenerative medicine for years to come.

Wong is one of three investigators to receive a 2020 New Ideas Award, which is valued at $100,000 per year for up to two years. Four additional projects were selected for Seed Fund Awards of $100,000 each for one year to further develop their potential.

Medicine by Design selected the funded projects from among 36 short-listed proposals, which were evaluated and ranked through an external peer review process. Applications were submitted by clinicians and researchers at U of T and its affiliated hospitals from a wide range of disciplines including biochemistry, biomedical engineering, developmental and stem cell biology, immunology, neuroscience and surgery.

Medicine by Design builds on decades of made-in-Canada excellence in regenerative medicine dating back to the discovery of stem cells in the early 1960s by Toronto researchers James Till and Ernest McCulloch. Regenerative medicine uses stem cells to replace diseased tissues and organs, creating therapies in which cells are the biological product. It can also mean triggering stem cells that are already present in the human body to repair damaged tissues or to modulate immune responses. Increasingly, regenerative medicine researchers are using a stem cell lens to identify critical interactions or defects that prepare the ground for disease, paving the way for new approaches to preventing disease before it starts. Medicine by Design is made possible thanks in part to a $114-million grant from theCanada First Research Excellence Fund.

Current cystic fibrosis drug treatments target a genetic mutation that causes epithelial cells, which line the airway and act as a barrier against viruses, to function improperly. The mutation affects the function of an important ion channel in cells, called CFTR, which helps to maintain the right balance of fluid in the airways. Poor function causes mucosal obstructions in the airways and prevents clearance of foreign pathogens, which leads to chronic infections and ultimately destroys airway tissue.

In her project, Wong will explore an alternative ion channel in the epithelial cells to determine if it can be hijacked and used to compensate for the lack of function caused by the mutant CFTR. The research will be conducted using a combination of stem cell-derived lung models, gene editing and computational modelling.

Wongs project builds on decades of cystic fibrosis research at SickKids, where the cystic fibrosis gene was first identified 30 years ago.

To date, more than 2,000 mutations in the cystic fibrosis gene have been identified, says Wong. SickKids scientists and U of T researchers have become the epicentre of incredible cystic fibrosis research to understand how this disease works at the genetic and molecular level.

Wong says that, while the idea of targeting an alternative pathway is not necessarily ground-breaking on its own, its the array of tools now available that makes the idea a potential game changer.

We have access to an incredible resource of primary cells and stem cells from more than 100 individuals with cystic fibrosis harbouring various mutations. Wong says.Our lab has developed human lung models from stem cells that can be used to model lung disease such as cystic fibrosis. And with new advanced tools in single-cell genomics and gene-editing, coupled with key collaborations for computational modelling, we are poised to find new therapeutic targets for cystic fibrosis.

Leo Chou, an assistant professor at the Institute of Biomedical Engineering, andHyun Kate Lee, an assistant professor in the department of biochemistry in the Temerty Faculty of Medicineboth Medicine by Design New Investigators are also leading 2020 New Ideas projects.

Chou, along with co-investigatorsJulie Lefebvre, a scientist at SickKids and U of T assistant professor of molecular genetics, andValerie Wallace, a senior scientist at the Krembil Research Institute, University Health Network and a U of T professor of laboratory medicine and pathobiology and ophthalmology, will focus on cell transplantation in the retina, a process that has demonstrated encouraging pre-clinical results such as partial vision restoration in several animal disease models.

Recent research had demonstrated that this restoration is a result of the transfer of proteins complex molecules required for the structure, function and regulation of the bodys tissues between host tissue and donor cells. But the scope of that transfer process is not well understood. Chous project will develop an imaging approach to detect the transfer of mRNA molecules between host and donor cells. The outcomes from this project will inform the future design of cell transplantation therapies and lead to novel methods to deliver therapeutics. This project could improve therapies for retinal diseases and visual impairments, and inform strategies for other degenerative disorders.

Lee and co-investigatorPenney Gilbert,an associate professor at the Institute of Biomedical Engineering, will look at a common but not well-understood structure called the neuromuscular junction (NMJ), which mediates communication between neurons and muscles throughout the body. Defects in NMJ integrity and function underlie fatal diseases such as ALS. NMJ diseases, which affect more than 500,000 people globally, lack effective treatments. This project will use stem cells derived from reprogrammed skin cells of healthy people to develop NMJs in culture. Through high-resolution imaging, the healthy human NMJs will be studied both on their own and along with NMJs built from ALS patient cells. Through this work, the research team aims to identify genes to target to improve the health of NMJs, which could eventually help prevent or delay NMJ degeneration and even promote regeneration.

Michael Garton, an assistant professor at the Institute of Biomedical Engineering, has received a Seed Fund award to tackle the challenge of translating the genetic tools of synthetic biology an area of research that aims to create or redesign biological components using engineering methods into effective medical therapies against a number of diseases.

But they are difficult to translate into human therapies, Garton says, because the bodys T-cells immune cells that detect and destroy cells containing foreign material will identify these tools as foreign and destroy them.

Instead of switching off the T-cells, Gartons goal is to use computational modelling and high-throughput screening to selectively turn off the bodys foreign antigen display system so the immune system will still respond to foreign invaders when necessary, but allow cells containing synthetic tools to survive. If successful, this approach could enable a new generation of synthetic biology-enhanced cell therapies for a range of diseases.

Medicine by Design funding will help to facilitate the integration of synthetic biology and regenerative medicine and aid the development of cell-based therapies that perform better than nature, says Garton.

Other Seed Fund projects will encompass research in repairing the heart after paediatric cardiac surgery, treating an intestinal emergency in premature babies and creating a database for cell lineage paths.

John Parkinson, a senior scientist at SickKids and a U of T professor of biochemistry and molecular genetics, along with co-investigatorsJason Maynes, Wasser Chair in Anesthesia and Pain Medicine at SickKids and a U of Tassociate professor of anesthesiology and biochemistry, andWilliam Navarre, an associate professor in the department of molecular genetics, will investigate manipulating the microbiome, or community of microorganisms in the gut, to improve cardiac repair in post-operative treatment of a congenital heart disorder. Through a process that will identify prebiotics in breast milk that help enhance the production of molecules that research has shown can aid cardiac repair, the team will organize both observational (how disease alters the microbiome) and interventional (how the microbiome alters the disease) multi-site trials, which will provide the opportunity to immediately translate findings into changes in patient care regimens and improve outcomes.

CliniciansAgostino Pierro, a surgeon at the Division of General and Thoracic Surgery at SickKids and a U of T professor of surgery and physiology, and Philip Sherman, a senior scientist and gastroenterologist at the Division of Gastroenterology, Hepatology and Nutrition at SickKids and U of T professor of dentistry, pediatrics and laboratory medicine and pathobiology, have proposed a novel way of enhancing gut repair for a common intestinal emergency in premature babies, called necrotizing enterocolitis (NEC). A leading cause of death for these infants, NEC causes complications such as blindness, intellectual disability, repeat hospitalizations and gut damage even in those that survive. This project will look at whether intestinal organoids organ-like structures grown in the laboratory from stem cells that mimic some of the functions of native intestines can potentially stimulate repair of the gut and recovery from NEC. The project will define how to best transplant organoids, identify how the organoids protect the intestine from injury and assess if organoid transplantation is a valid new treatment for NEC.

Lincoln Stein, who is head of adaptive oncology at the Ontario Institute for Cancer Research and a professor in the department of molecular genetics at U of T, has received seed funding to build a database called Cytomics Reactome, which will be freely available to Canadian and international researchers. The database will build on recent technologies that open the door to the possibility of deciphering cell lineage paths the series of steps that lead a young, undifferentiated cell into a specialized one at single-cell resolution. To accelerate the path from basic research to clinical application, the database will systematically organize pre-existing knowledge of cell lineage paths into a comprehensive, interactive and easily accessible map that can serve as a framework for interpretation and integration of the latest experimental findings.

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U of T's Medicine by Design invests $1 million to advance new ideas in regenerative medicine - News@UofT

Skin Stem Cells Comments Off on U of T’s Medicine by Design invests $1 million to advance new ideas in regenerative medicine – News@UofT | October 10th, 2020

IRVINE, Calif., Oct. 9, 2020 /PRNewswire/ --AIVITA Biomedical, Inc., a private biotechnology company developing personalized vaccines for the treatment of cancer and COVID-19, announced today the publication of the peer-reviewed manuscript, "Retina organoid transplants develop photoreceptors and improve visual function in RCS rats with RPE dysfunction,"in the journal Investigative Ophthalmology & Visual Science. The study, led by researchers at AIVITA Biomedical and the Sue & Bill Gross Stem Cell Research Center of the University of California, Irvine, used 3D-retina organoids generated from human stem cells developed by AIVITA to provide insight into the potential use of transplanted retina organoids as a therapeutic option for blinding diseases.

In the study, transplanted retina organoid sheets were examined to determine if human stem cell-derived photoreceptors coulddevelop, survive and function in vivo without the support of healthy retina pigment epithelium (RPE). Visual function was examined through a variety of tests, including optokinetic testing (OKT), electroretinogram (ERG), and superior colliculus (SC) brain recording. These tests concluded that retina organoid transplantations demonstrated significant improvement in visual function compared to non-surgery and sham surgery controls, supporting the application of AIVITA's stem cell technologies in visual disease therapeutics.

"Leveraging our expertise in stem cell growth and differentiation, I'm excited to see the promise of our technology platform in potential therapeutics for vision loss," said Hans Keirstead, Ph.D., chief executive officer of AIVITA and a contributing author to the paper. "To our knowledge, this study is the first to show that it's possible for photoreceptors derived from stem cells to survive and function after transplantation when a host has a dysfunctional RPE."

This work is supported by funding from the California Institute for Regenerative Medicine (CIRM) and National Institutes of Health (NIH).

About AIVITA Biomedical AIVITA Biomedical is a privately held company engaged in the advancement of commercial and clinical-stage programs utilizing curative and regenerative medicines. Founded in 2016 by pioneers in the stem cell industry, AIVITA Biomedical utilizes its expertise in stem cell growth and directed, high-purity differentiation to enable safe, efficient and economical manufacturing systems which support its therapeutic pipeline and commercial line of skin care products. All proceeds from the sale of AIVITA's skin care products support the treatment of people with cancer.

SOURCE AIVITA Biomedical, Inc.

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AIVITA Biomedical's Stem Cell Therapeutic in Vision Loss Published in Investigative Ophthalmology & Vision Science - PRNewswire

Skin Stem Cells Comments Off on AIVITA Biomedical’s Stem Cell Therapeutic in Vision Loss Published in Investigative Ophthalmology & Vision Science – PRNewswire | October 10th, 2020

Two years ago I received an Augustinus Bader cream in a goody bag. I hadnt heard of it at the time, so paid little attention, although it looked nice enough a sleek, big blue bottle with rose gold accents. Shortly after, having just run out of my current moisturiser, I dug it out to give it a go. A few days later, forensically inspecting my skin in the mirror as I am wont to do in my more idle moments, I thought this stuff is actually really great. This was swiftly followed by another thought oh dear when I discovered it costs a whopping 205 a pop (for 50ml, you can get 15ml for 65). But it was too late, I was hooked. And that is how I became a woman who drops 205 on a moisturiser.

I am probably the least glamorous and definitely least well-known member of the Augustinus Bader fan club, which has swiftly reached legendary status in the beauty world and beyond. Kim Kardashian West, Naomi Campbell, Kate Bosworth, Priyanka Chopra and Diane Kruger all love the cult brand. Victoria Beckham invited Professor Bader to sit front row at her AW20 show; she also tapped his talents to collaborate with her on her debut skincare line (from seeing VB up close I can testify that this is a woman who knows good skincare, and the Cell Rejuvenating Power Serum is indeed excellent).

Professor Augustinus Bader and Victoria Beckham Getty

The latest addition to the Bader fan club is Emma Corrin. Prepping the new Diana for The Crowns Zoom press junket this week, her makeup artist Florrie White revealed she used The Cream and The Face Oil on the young actress. I use The Cream on everyone; me and my clients, White tells me. It instantly plumps and smooths the skin with three perfect pumps and creates a calm and luxurious base for every make-up look. Everyone always comments on how lovely it feels on their skin.

Today Augustinus Bader is a cult phenomenon but the founder is a man who seems to be more at home in a laboratory than on a red carpet. A leader in stem cell biology, and head of stem cell research at the University of Leipzig, Professor Bader has spent over 30 years focusing on how reawakening these cells can aid the healing process in particular embarking on a mission to help burns victims. In 2008, Bader formulated a groundbreaking wound gel that could help heal third-degree burns without the aid of surgery or skin grafts.

It was this breakthrough that led to the founding of the skincare line. After all, if it could have this effect on serious injuries, imagine what the technology could do for those of us lucky enough to have run-of-the-mill skin niggles? The brand launched with two hero products: The Cream and The Rich Cream which, according to the brand literature, contain patented TFC8 (Trigger Factor Complex) technology, which supports the skins natural processes, leaving all skin types mature, dry, oily, or sensitive looking restored, renewed and regenerated.

I was useless at science at school and all this technical talk is pure gobbledygook to me. What I can tell you is what its done for me. My skin is super sensitive, I have eczema, and have found that Augustinus Bader creams genuinely help to soothe it when it is aggravated. I have found that since using it, my complexion appears clearer, more even and the Holy Grail of beauty dewy (despite drinking gallons of water a day, I have never achieved that before). My mum, who observes me with the scrutiny that only mothers do, confirms that my skin looks great (I am privvy only to this information because she thought it was a result of finally listening to her by stopping smoking and making the hours before midnight count). Is it expensive? Well, yes, theres no way around that. However, in much the same way that I think that an impeccably cut designer jacket earns its value back in cost per wear, I have found that since using The Cream and The Rich Cream my skincare regime has simplified.

Sure, theres an element of hype involved. I still find it thrilling to be In The Know about something. But, for me and my skin, Augustinus Bader lives up to it. Believe me, I wish it wasnt true (I am not snobby with beauty products, and would happily wax lyrical about a 5 wonder find if Id discovered one), but thats the 205 price I have to pay and Id say its worth it.

READ MORE: 'I Just Love The Way A Polished Lipstick Completes A Look': Victoria Beckham's New Posh Lipsticks Explained In Her Own Words

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Discover The Augustinus Bader Wonder Cream Loved By The A List - Grazia

Skin Stem Cells Comments Off on Discover The Augustinus Bader Wonder Cream Loved By The A List – Grazia | October 10th, 2020

The biotech industry has been soaring this year, with the SPDR S&P Biotech ETF (XBI) up 26.6% year to date so far. The race for a COVID vaccine has primarily driven this performance, but what if there was another segment of the biotech industry that top hedge fund managers are all going after right now? While many managers are known to take risks, its certainly worth looking into if there is a consensus between them.

The AlphaClone Alternative Alpha ETF (ALFA) tracks an index of equity securities that hedge funds have significant exposure to. The ETFs top three holdings are all biotech firms working on cancer drugs. While many investors have their attention on biotech and pharmaceutical companies working on a COVID vaccine, big money has been focused on the next big thing in biotech, the future oncology drug boom.

Cancer is the second leading cause of death in the U.S. behind heart disease. Almost everyone knows someone that has been affected by one of the many vicious types of cancer. There are now numerous companies focused on ways to treat and cure the various forms. While COVID is at the forefront, cancer is a long-term play. There is even an ETF that covers the cancer industry, the Loncar Cancer Immunotherapy ETF (CNCR), which is up over 39% over the last six months.

As the oncology drug market is expected to reach $394 billion by 2027, here are the three top cancer stocks based on a consensus of hedge fund managers: Seattle Genetics (SGEN), Fate Therapeutics (FATE), and Blueprint Medicines (BPMC).

Seattle Genetics (SGEN)

SGEN is a biotech firm focused on developing antibody-drug conjugates. Its lead lymphoma drug, Adcetris, has been performing quite well since it launched, and it is the primary growth driver for the company. The drugs label was also expanded, providing more revenue for the company. SGEN has been collaborating with Takeda (OTCMKTS:TKPHF), a Japanese pharmaceutical company, for the global development and commercialization of Adcetris.

In addition to Adcetris, the company has a promising pipeline of drug candidates for its antibody-drug conjugate (ADC) technology. In December, the FDA granted accelerated approval to Padcev to treat patients with metastatic bladder cancer, who were previously treated with a checkpoint inhibitor and platinum-based chemotherapy. This drug was created in collaboration with Astellas Pharma (OTCMKTS:ALPMF), another pharmaceutical company.

In April, the FDA approved Tukysa for the treatment of metastatic HER2-positive breast cancer. Investors should also be happy with the news Merck (MRK) plans to buy a 2.9% stake in SGEN. The companies are co-developing and selling SGENs breast cancer therapy, ladiratuzumab vedotin.

The company is rated a Strong Buy in our POWR Ratings system, with a grade of A in Trade Grade, Buy & Hold Grade, and Peer Grade. Those are three out of the four components that make up the POWR Ratings. The stock is also ranked #2 out of 377 Biotech stocks.

Fate Therapeutics (FATE)

FATE is a clinical-stage biopharmaceutical company engaged in the development of programmed cellular immunotherapies for cancer and immune disorders. The company has been building up its pipeline of immuno-oncology product candidates. These treatments are designed to elicit an immune response in patients with cancer.

The companys progress with FT596 is encouraging. FT596 is cell cancer immunotherapy derived from its iPSC line. The induced pluripotent stem cell (iPSC) platform provides a competitive advantage for the company as iPSC cells are stem cells that can become almost any cell type. They are grown from the same cell instead of a patients donated cells. This means that one engineered cell line can be manufactured for many patients, creating what is known as off the shelf immunotherapy.

If the development of this type of therapy is successful, this would reduce the cost of manufacturing and provide a potential cash cow for the company. FATE has entered into collaborations with other companies for fund and research expertise. It is currently working with Ono Pharmaceutical (OTCMKTS:OPHLY) for two off-the-shelf iPSC-derived CAR T-cell product candidates, and Janssen Biotech develop iPSC-derived CAR NK and CAR T-cell product candidates.

FATE is rated a Strong Buy in our POWR Ratings system. It holds a grade of A in Trade Grade, Buy & Hold Grade, and Peer Grade. It is also ranked #24 out of 377 stocks in the Biotech industry. The stock is up a whopping 145.3% after finishing the day up 6.7%.

Blueprint Medicines (BPMC)

BPMC is a biopharmaceutical company focused on improving patients lives with diseases driven by abnormal kinase activation. The company has developed a small molecule drug pipeline in cancer. The firms lead product, Ayvakit, was approved by the FDA in January to treat metastatic gastrointestinal stromal tumor. The drug generated $5.7 million in the second quarter, so its off to a good start.

The company is also looking to expand its label as it is being studied for advanced and smoldering forms of systemic mastocytosis, a condition where certain immune cells, called mast cells, build up under the skin and, or in the bones, intestines, and other organs. If approved for other labels, that should help drive further growth.

Last month, the FDA approved the companys second drug, Gavreto, for the treatment of RET fusion-positive NSCLC or non-small lung cancer. BPMC worked on the drug with Roche (OTCMKTS:RHHBY). Lung cancer is responsible for more cancer deaths than any other in men and women. If Gavreto can become a standard treatment, it could become a goldmine for the company. The drug can also treat medullary thyroid cancers.

BPMC is rated a Strong Buy in our POWR Ratings system. It has grades of A in Trade Grade, Buy & Hold Grade, and Peer Grade. It is also the #9 ranked stock in the Biotech industry. The stock is up over 27% for the past three months and 8.5% over the past week.

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SGEN shares were unchanged in after-hours trading Friday. Year-to-date, SGEN has gained 75.72%, versus a 9.31% rise in the benchmark S&P 500 index during the same period.

David Cohne has 20 years of experience as an investment analyst and writer. Prior to StockNews, David spent eleven years as a Consultant providing outsourced investment research and content to financial services companies, hedge funds, and online publications. David enjoys researching and writing about stocks and the markets. He takes a fundamental quantitative approach in evaluating stocks for readers. More...

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SGEN: The 3 Top Biotech Stocks That Hedge Fund Managers LOVE - StockNews.com

Skin Stem Cells Comments Off on SGEN: The 3 Top Biotech Stocks That Hedge Fund Managers LOVE – StockNews.com | October 10th, 2020

Find out what the pros had to say.

You never forget your first. Grey hair, that is. Maybe you pluck it? Heck, its just oneout of sight, out of mind, right? Yeah, we know, you pluck one and five more grow back in its place, and then those five turn into tenyou get the idea. Nothing that a good dye job cant fix. That is, until a pandemic forces you into quarantine with no access to your colorist, and it becomes brutally apparent just how grey your hair actually is these days. This standoff between my stealthy foe and I got me thinking: We know we cant reverse grey hair, but can we slow its progression or delay its initial onset? I called on the pros to find out, but first, some basic hair biology.

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A protein called melanin is responsible for the color of our hair, and the cells in the hair follicles that make melanin are called melanocytes. Melanocytes are made by stem cells in the root of the hair, says Dr. Morgan Rabach, board-certified dermatologist, assistant professor at Mount Sinai School of Medicine, and co-founder of LM Medical NYC, and over time the stem cells die out and stop making melanocytes, leaving us with no cells to color the hair.

The age at which we start to go grey varies and depends on many factors. Dr. Caroline Robinson, MD, FAAD, and dermatologist and founder of Tone Dermatology, believes there is likely a genetic tendency at play in most cases of greying hair, but, like many genetic tendencies, there are environmental factors that influence how these changes show up in each of us. Dr. Rabach concurs, adding that grey hair is a combination of genetics and lifestyle.

Premature greying is generally considered less than 20 years old and it is thought to be an inherited predisposition. However, premature greying can also be attributed to certain illnesses and deficiencies. Dr. Robinson notes the importance of annual physicals and doctor visits when it comes to premature greying, as it could be an early sign of metabolic abnormalities in a select population.

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Search results for grey hair yield a slew of information centered around the notion that going grey is a result of an accumulation of hydrogen peroxide in the follicle, and that it could be eradicated by a topical pseudocatalase cream. This claim seems to have originated from a segment of research on vitiligo, which then appeared to have been manipulated for headlines. Dr. Robinson weighed in with her thoughts on the claim, saying, There are no double-blinded, controlled clinical studies to support the use of topical pseudocatalase-based creams for loss of pigmentation in hair.

Similarly, some products have appeared on the market claiming to re-pigment the hair, but the consensus among experts is that the claims are unfounded. I havent seen any convincing evidence for products that claim to reverse or prevent greying of the hair, says Holden.

We know all too well the havoc that stress wreaks on our overall health, but the type of stress were referring to here is oxidative stressthe imbalance of free radicals and antioxidants in the body, which leads to cell and tissue damage. In oxidative stress, free radicals damage our cells and tissues when our body doesnt have enough antioxidants to combat them, and in our hair, this oxidative stress can damage the cells that produce melanin, says Kate Holden, consultant trichologist.

The pros agree that oxidative stress plays a key role in the loss of hair pigmentation. From recent research we know that oxidative stress, the same type of stress that our skin faces in response to UV rays and pollution, can be an important factor in the loss of hair pigmentation, says Dr. Robinson. While oxidative stress occurs naturally in our bodies, environmental factors can increase its effects, such as alcohol, smoking, sugar and processed foods, cortisol levels, etc.

In addition, a recent study conducted by a group of Harvard researchers looked at the impact of stress (like, say, the kind you feel during a worldwide pandemic) on pigment-producing cells and found that the hyper-activation of the sympathetic nerves caused the depletion of melanocyte stem cells. Trichologist Leata A. Williams explains, When we are under stress, our bodies signal the fight-or-flight response, and it is the nerves that send the response to our hair follicles, causing the hair to grey.

Just think of how many world leaders have gone grey while in officethats the sympathetic nervous system depleting their hair follicles of melanocytes. And although most of us will never feel the stress of running a country, were still susceptible to the same greying effect from our everyday lives.

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Unfortunately for us, the pros agree that there is no real evidence to suggest that we can turn back the clock and re-pigment or slow the greying of hair in any tangible way. What we can do, however, is engage in healthy lifestyle behaviors that promote our overall health, and increase our intake of antioxidants. Increasing antioxidant intake through foods in our diet (leafy veggies, fruit) has not directly been shown to impact greying hair, but it can help to decrease overall oxidative stress levels in the body, says Dr. Robinson, which is something she discusses with her patients.

Dr. Rabach agrees and adds that she believes that a stress-free and healthy lifestyle makes your whole body healthier, and this would be reflected in the youthfulness of your hair. While we may not be able to reverse or halt grey hairs from popping up, what is encouraging is Dr. Rabachs belief that through good hair health, nutritious diet, and stress management, we might be able to delay their initial appearance. Increasing your antioxidant intake, whether it be from your diet, a multivitamin, or even a product formulated for hair health, will be beneficial in reducing oxidative stress and may help delay the initial onset of grey hair, says Dr. Rabach, who also encourages the use of hair products with antioxidants.

According to Dr. Robinson, there are some reports that Platelet Rich Plasma (PRP) therapy an in-office procedure that involves scalp injection of a processed form of ones own bloodcan promote hair re-pigmentation or slow greying because of its ability to deliver growth factors to the the hair follicle. While it sounds promising, more data needs to be gathered to determine its efficacy as a hair treatment.

Bottom line: Dont waste your money on products that claim to turn back the clock on grey hair, and focus instead on increasing your antioxidant intake and mitigating the effects of oxidative stress. Here are a couple products to get you started.

$17

Dr. Rabach promotes the use of antioxidant-rich hair products to help protect against the effects of oxidative stress. Look for one that is formulated with powerful superfruits like goji, acai, and pomegranate, and includes biotin for the added hair-nurturing benefits.

Buy

$65

This ingestible powder is chock-full of antioxidant-rich superfoods, adaptogens, and a probiotic blend to help your body resist stress, support detoxification, and support immunity. Add a teaspoon to water or a cold beverage of your choice, and reap the benefits of this all-natural, whole-food blend and help fend off the effects of oxidative stress.

Buy

Original post:
Gray Hair: What You Need to Know about Causes and Possible Prevention - Coveteur

Skin Stem Cells Comments Off on Gray Hair: What You Need to Know about Causes and Possible Prevention – Coveteur | October 9th, 2020

CRANFORD, N.J., Oct. 7, 2020 /PRNewswire/ -- Citius Pharmaceuticals, Inc. ("Citius" or the "Company") (Nasdaq: CTXR), a specialty pharmaceutical company developing and commercializing critical care drug products, announced that it has signed an exclusive agreement with Novellus Therapeutics Limited ("Novellus") to license iPSC-derived mesenchymal stem cells (iMSCs), and has created a new subsidiary, NoveCite, that will be focused on developing cellular therapies.

NoveCite has a worldwide exclusive license from Novellus, an engineered cellular medicines company, to develop and commercialize NoveCite mesenchymal stem cells ("NC-iMSCs") to treat acute respiratory conditions with a near term focus on Acute Respiratory Distress Syndrome ("ARDS") associated with COVID-19. Several cell therapy companies using donor-derived MSC therapies in treating ARDS have demonstrated that MSCs reduce inflammation, enhance clearance of pathogens and stimulate tissue repair in the lungs. Almost all these positive results are from early clinical trials or under the emergency authorization program.

NC-iMSCs are the next generation mesenchymal stem cell therapy. They are believed to be differentiated and superior to donor-derived MSCs. Human donor-derived MSCs are sourced from human bone marrow, adipose tissue, placenta, umbilical tissue, etc. and have significant challenges (e.g., variable donor and tissue sources, limited supply, low potency, inefficient and expensive manufacturing). iMSCs overcome these challenges because they:

Globally, there are 3 million cases of ARDS every year out of which approximately 200,000 cases are in the United States. The COVID-19 pandemic has added significantly to the number of ARDS cases. Once the COVID patients advance to ARDS, they are put on mechanical ventilators. Death rate among patients on ventilators can be as high as 50% depending on associated co-morbidities. There are no approved treatments for ARDS, and the current standard of care only attempts to provide symptomatic relief.

"NoveCite iMSCs have the potential to be a breakthrough in the field of cellular therapy for acute respiratory conditions because of the high potency seen in Novellus' pre-clinical studies, and because iMSCs are iPSC-derived, and therefore overcome the manufacturing challenges associated with donor derived cells," said Myron Holubiak, Chief Executive Officer of Citius.

"We are excited to be part of this effort because of the promise to save lives and reduce long term sequelae in patients with devastating respiratory diseases such as ARDS caused by COVID-19," said Dr. Matthew Angel, Chief Science Officer of Novellus. "Our iMSC technology has multimodal immunomodulatory mechanisms of action that make it potentially promising therapy to treat acute respiratory diseases."

About Citius Pharmaceuticals, Inc.

Citius is a late-stage specialty pharmaceutical company dedicated to the development and commercialization of critical care products, with a focus on anti-infectives and cancer care. For more information, please visit http://www.citiuspharma.com.

About Novellus, Therapeutics, Limited

Novellus is a pre-clinical stage biotechnology company developing engineered cellular medicines using its patented non-immunogenic mRNA high specificity gene editing, mutation-free & footprint-free cell reprogramming and serum insensitive mRNA lipid delivery technologies. Novellus is privately held and is headquartered in Cambridge, MA. For more information, please visit http://www.novellus-inc.com.

About NoveCite iMSC (NC-iMSC)

NoveCite's mesenchymal stem cell therapy product is derived from a human induced pluripotent stem cell (iPSC) line generated using a proprietary mRNA-based (non-viral) reprogramming process. The NC-iMSCs produced from this clonal technique are differentiated from human donor-derived MSCs (bone marrow, placenta, umbilical cord, adipose tissue, or dental pulp) by providing genetic homogeneity. In in-vitro studies, NC-iMSCs exhibit superior potency and high cell viability. NC-iMSCs secrete immunomodulatory proteins that may reduce or prevent pulmonary symptoms associated with acute respiratory distress syndrome (ARDS) in patients with COVID-19. NC-iMSC is an allogeneic (unrelated donor) mesenchymal stem-cell product manufactured by expanding material from a master cell bank.

First generation (human donor-derived) MSCs are isolated from donated tissue followed by "culture expansion". Since only a relatively small number of cells are isolated from each donation, first generation MSCs are increased by growing the cells in culture. Unfortunately, these type of MSCs start to lose potency, and ultimately become senescent. Each donation produces a limited number of MSCs, so a continuous supply of new donors is needed to produce commercial scale. The number and quality of MSCs that can be isolated from different donors can vary substantially.

About Acute Respiratory Distress Syndrome (ARDS)

ARDS is an inflammatory process leading to build-up of fluid in the lungs and respiratory failure. It can occur due to infection, trauma and inhalation of noxious substances. ARDS accounts for approximately 10% of all ICU admissions and almost 25% of patients requiring mechanical ventilation. Survivors of ARDS are often left with severe long-term illness and disability. ARDS is a frequent complication of patients with COVID-19. ARDS is sometimes initially diagnosed as pneumonia or pulmonary edema (fluid in the lungs from heart disease). Symptoms of ARDS include shortness of breath, rapid breathing and heart rate, chest pain (particularly while inhaling), and bluish skin coloration. Among those who survive ARDS, a decreased quality of life is relatively common.

Safe Harbor

This press release may contain "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements are made based on our expectations and beliefs concerning future events impacting Citius. You can identify these statements by the fact that they use words such as "will," "anticipate," "estimate," "expect," "should," and "may" and other words and terms of similar meaning or use of future dates. Forward-looking statements are based on management's current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated are: the risks associated with developing the NoveCite technology as a treatment for ARDS; risks associated with developing any of our product candidates, including any licensed from Novellus, Inc., including that preclinical results may not be predictive of clinical results and our ability to file an IND for such candidates; our need for substantial additional funds; the estimated markets for our product candidates, including those for ARDS, and the acceptance thereof by any market; risks relating to the results of research and development activities; uncertainties relating to preclinical and clinical testing; the early stage of products under development, including the NoveCite technology; our ability to obtain, perform under and maintain licensing, financing and strategic agreements and relationships; our ability to attract, integrate, and retain key personnel; risks related to our growth strategy; our ability to identify, acquire, close and integrate product candidates and companies successfully and on a timely basis; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law.

Contact:Andrew ScottVice President, Corporate Development(O) 908-967-6677 x105(M) 646-522-8410ascott@citiuspharma.com

View original content:http://www.prnewswire.com/news-releases/citius-pharmaceuticals-signs-an-exclusive-worldwide-licensing-agreement-with-novellus-therapeutics-for-unique-imsc-therapy-for-acute-inflammatory-respiratory-conditions-including-covid-19-related-acute-respiratory-distress-syndrom-301147409.html

SOURCE Citius Pharmaceuticals, Inc.

Company Codes: NASDAQ-SMALL:CTXR

Original post:
Citius Pharmaceuticals Signs an Exclusive Worldwide Licensing Agreement with Novellus Therapeutics for Unique iMSC-Therapy for Acute Inflammatory...

Skin Stem Cells Comments Off on Citius Pharmaceuticals Signs an Exclusive Worldwide Licensing Agreement with Novellus Therapeutics for Unique iMSC-Therapy for Acute Inflammatory… | October 7th, 2020

Essentially, graying hair is just natural, whether you have a full head of silver or patches of gray throughout. Loss of pigmentation in hair is something out of our control, agrees celebrity colorist and Redken brand ambassadorMatt Rez. Its largely due to genetics and aging in general, and unfortunately there arent any existing treatments to reverse those grays to their natural vigor.

Specifically, your pigment-producing cells (called melanocytes) start to deteriorate, leading to sprouted grays. The melanocytes are pigment producing cells located near the bulb of the hair and their stem cells, explains hair transplant surgeon James S. Calder, M.D., medical director of Ziering Medical. When your hair ages, those melanocytes dont function as well or start to migrate away from the hair bulb, which causes a sprinkling of grays. And according to Calder, no supplement, nor diet, can successfully prevent the process forever.

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Can You Prevent Gray Hair? The Answer Isn't Black & White, Experts Say - mindbodygreen.com

Skin Stem Cells Comments Off on Can You Prevent Gray Hair? The Answer Isn’t Black & White, Experts Say – mindbodygreen.com | October 7th, 2020

Despite the challenges brought about by Covid-19, leading cosmetic manufacturers, including Mibelle Biochemistry, Cargill Beauty, Givaudan Active Beauty and Lucas Meyer, put forward their most creative innovations for consideration by the in-cosmetics Global Awards jury.

Judged across three categories - Best Active Ingredient, Best Functional Ingredient and Best Green Ingredient - by some of the industrys foremost experts, the awards recognise the cosmetic ingredient manufacturers who are helping to push the boundaries of innovation, while responding to evolving consumer demands.

The winners were announced yesterday during a virtual ceremony from a list of finalists dominated by skin care ingredients.

Scooping both the Gold and Silver awards in the Best Active Ingredient category, Vytrus Biotech was recognised for its Kannabia Sense and Deobiome Noni ingredients.

Kannabia Sense took the top accolade. This probiotic treatment stimulates the skin microbiota to produce an in-situ postbiotic cocktail that promotes the synthesis of cutaneous oxytocin. Recommended for use in sensitive skin treatments, anti-ageing cosmetic products and delicate facial treatments, it is made from plant stem cells of Cannabis sativa.

Deobiome Noni is a prebiotic deodorant treatment that reduces the generation of body odour while allowing the skin to breathe and respecting the skin microbiota.

Closing the category, Mibelle Biochemistry and Clariant Active were announced as this years joint Bronze Award winners.

Alpine Rose Active, Mibelle Biochemistrys novel senolytics concept, was chosen for its ability to eliminate senescent skin cells and protect skin proteins from oxidative stress.

Clariant Active was applauded for Prenylium. Thanks to Clariants Plant Milking technology, Prenylium is extracted from the root of the mulberry tree (Morus Alba) without causing any damage. This innovative and sustainable approach to sourcing helps to stimulate root growth and results in a concentration of prenylated flavonoids 2000% higher than what is typically found in mulberry root extracts.

German cosmetic manufacturer Symrise took the top award in the Best Functional Ingredient category for its Symrise SymEffect Sun. Based entirely on renewable raw materials from responsible sources, the new ingredient combines the advantages of conventional sunscreen products with the increasing sustainability requirements of consumers.

Also demonstrating a sustainable approach to sun protection, Dow Chemical was awarded the Silver award for its SunSpheres BIO SPF Booster, a bio-based and readily biodegradable SPF boost that enables greater SPF efficiency in suncare and daily skincare products.

The category also honoured two bronze award winners: Clariant and Gattefoss. The former was awarded for Velsan Flex which, thanks to its high water solubility and Renewable Carbon Index (RCI) of 93%, offers preservation boosting powers together with broad formulation flexibility. Gattefosss Emulium Dolcea MB a natural origin O/W emulsifier - has the ability to create a wider range of textures, from fluid serum to thick butter in a wide range of applications, such as skincare, suncare, make up and haircare.

As sustainability continues to drive cosmetic manufacturers to assess the ingredients used in their formulations, this years Green Ingredient Award - in partnership with Ecovia Intelligence - recognises the ingredients championing sustainability in the personal care and beauty market.

Henry Lamotte Oils Paradise Nut Oil/Magdalena River Nut Oil scooped the Gold Award for its ability to support the regeneration of the skins lipid film, while improving the water retention capability of the skin, reducing trans-epidermal water loss.

Unveiled as the Silver Award winner, Cargill Beautys FiberDesign Sensation was praised for its approach to sustainability and upcycling. Derived from 100% natural origins, the texturiser and emulsion stabiliser, designed specifically for skincare, is based on citrus peel fibres from the pectin production side stream.

Joining the line-up of award winners, Minasolve SAS scooped the Bronze Award for its A-Leen Aroma-3, a nature-derived perfuming agent that also offers a broad-spectrum antimicrobial effect. It is a 100% natural version of phenylpropanol, it is produced from cassia essential oil.

Cosmetic Ingredients - October 2020

For more information on the latest cosmetic ingredients launches, also read our special issue:

How far will clean beauty go?

Interest in upcycled ingredients expected to rise in the cosmetics industry

Driven by new consumer preferences, demand for cupuau butter is on the rise

in-cosmetics Awards 2020

Ingredient news: Akott, BASF, Berkem, Clariant, Codif, Covestro, DSM, Firmenich, Givaudaun, Grolman, Imerys, Inter Actifs, Lubrizol, Mibelle, Sederma, Seppic, Silab, Symrise

Read online for free or download the pdf version here.

Read more here:
Who are the winners of the in-cosmetics Global Awards 2020? - Premium beauty

Skin Stem Cells Comments Off on Who are the winners of the in-cosmetics Global Awards 2020? – Premium beauty | October 7th, 2020

Alex Peters is Dazed Beautys news writer. She picked up the phrase Its all happening from Almost Famous as a teen and it now exclusively makes up her vocabulary. Although in theory she likes the idea of a queer mullet, she is currently rocking the latest lockdown trend: Kajillionaire hair. Here, she shares her choice for Product of the Week a weekly round-up of the Dazed Beauty team and wider communitys must-have buys.

Brand: Augustinus Bader

Product: The Cream

Price: 205

As head of stem cell research at the University of Leipzig, Professor Augustinus Bader spent 30 years working with burns victims, developing a groundbreaking gel in 2008 that could heal third-degree burns without the need for skin grafts. Its this revolutionary stem cell technology the patented Trigger Factor Complex (TFC8) which lies at the heart of his skincare label and its hero product The Cream.

Powered by this technology, with consistent use (the Cream asks that you remain devoted to it for 27 days, using nothing else), the products activate and orchestrate the body's innate regenerative processes which basically means that when you use them your skin cells repair themselves. This helps with reducing the signs of ageing and environmental damage, reducing scarring and redness, and improving tone and texture.

Thats all very scientific, but the most important question is does it actually work? And for me it does. My skin is on the oily side as well as being sensitive and acne-prone so I use the Cream, rather than the Rich Cream which is better suited to dry skin types. The cream itself has a light texture that absorbs quickly and doesnt feel sticky. Two pumps is enough to cover your face and it goes on very smoothly. It has quite a distinctive scent, so if you are nose-sensitive be prepared. Its hard to describe clinical rather than artificial. It comes in a weighty blue and copper tube that feels fancy when youre using it.

I am not always great at using it consistently, particularly since we test out so many products as part of our job, but I have found that when I do, my skin looks noticeably better. My tone is more even and less red, the texture is better, scars look more faded, and I would tentatively say that it seems like I get fewer spots.

I would like to say, however, that the product is definitely on the higher end of the spectrum price-wise, and if you cannot afford it, please do not worry. There are a lot of great options out there that are more affordable and also very effective. If this is something that you can afford, I would highly recommend.

If I were communicating to an alien only using hand gestures, I would describe it with... Just a solid thumbs up. Or through elaborately miming the process of cell renewal.

It sounds like... A reassuring older German professor telling you efferyzing vill be alright and in the background the sound of a fire crackling.

If it was a meme it would be... Sorry to this man. Totally unrelated but its my favourite meme.

The fictional character who would use it is... Bette Porter from The L Word.

Alex Peters's Product of the Week

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The luxury skincare splurge that will help repair your skin cells - Dazed

Skin Stem Cells Comments Off on The luxury skincare splurge that will help repair your skin cells – Dazed | October 6th, 2020

DetailsCategory: AntibodiesPublished on Saturday, 03 October 2020 15:56Hits: 667

Opdivo + Yervoy is the first new systemic therapy in over 15 years to be approved by the FDA in this setting1,2

Approval is based on CheckMate -743 in which Opdivo + Yervoy demonstrated superior overall survival vs. standard of care chemotherapy1

Approval marks third indication for Opdivo + Yervoy-based treatments in thoracic cancers and seventh indication overall

PRINCETON, NJ, UA I October 2, 2020 IBristol Myers Squibb (NYSE: BMY) today announced that Opdivo (nivolumab) 360 mg every three weeks plus Yervoy (ipilimumab) 1 mg/kg every six weeks (injections for intravenous use) was approved by the U.S. Food and Drug Administration (FDA) for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).1 This approval is based on a pre-specified interim analysis from the Phase 3 CheckMate -743 trial in which Opdivo + Yervoy (n=303) demonstrated superior overall survival (OS) versus the platinum-based standard of care chemotherapy (n=302) (Hazard Ratio [HR]: 0.74 [95% Confidence Interval [CI]: 0.61 to 0.89]; P=0.002), with a median OS (mOS) of 18.1 months (95% CI: 16.8 to 21.5) versus 14.1 months (95% CI: 12.5 to 16.2), respectively.1 These results were observed after 22.1 months of minimum follow-up.3 At two years, 41% of patients treated with Opdivo + Yervoy were alive and 27% with chemotherapy.1,3

Malignant pleural mesothelioma is a rare cancer with limited treatment options. When it is diagnosed in advanced stages, the five-year survival rate is approximately 10 percent, said study investigator Anne S. Tsao, M.D., professor and Section Chief Thoracic Medical Oncology and Director of the Mesothelioma Program at The University of Texas M.D. Anderson Cancer Center.2,4 The survival results from the CheckMate -743 trial show that the combination of nivolumab and ipilimumab could become a new front-line standard of care option. This is exciting news, instilling hope for patients with this devastating disease and for the healthcare providers who care for them.1,3

Opdivo and Yervoy are associated with Warnings and Precautions including immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions; infusion reactions; complications of stem-cell transplant that uses donor stem cells (allogeneic); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.1Yervoy is associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplant after Yervoy, embryo-fetal toxicity and risks associated when administered in combination with Opdivo.5 Please see the Important Safety Information section below.

This is the third indication for an Opdivo + Yervoy-based combination in the first-line treatment of a form of thoracic cancer.1Opdivo + Yervoy is approved by the FDA as a first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L11% as determined by an FDA-approved test, and without EGFR or ALK genomic tumor aberrations.1 It is also approved in combination with limited chemotherapy for the first-line treatment of adult patients with metastatic or recurrent NSCLC with no EGFR or ALK genomic tumor aberrations regardless of PD-L1 expression.1

Thoracic cancers can be complex and difficult to treat, and we are focused on developing immunotherapy options that may have the potential to extend patients lives, said Adam Lenkowsky, general manager and head, U.S., Oncology, Immunology, Cardiovascular, Bristol Myers Squibb.2,6 Just a few months ago, Opdivo + Yervoy-based combinations received two first-line indications for certain patients with non-small cell lung cancer. Now, Opdivo + Yervoy is approved for use in another type of thoracic cancer, previously untreated unresectable MPM. With todays announcement, Opdivo + Yervoy becomes the first new systemic therapy approved in more than 15 years in this setting, and may offer these patients a chance for a longer life. 1

Opdivo + Yervoy is a unique combination of two immune checkpoint inhibitors that features a potentially synergistic mechanism of action, targeting two different checkpoints (PD-1 and CTLA-4) to help destroy tumor cells: Yervoy helps activate and proliferate T cells, while Opdivo helps existing T cells discover the tumor.1,7 Some of the T cells stimulated by Yervoy can become memory T cells, which may allow for a long-term immune response.7,8,9,10,11,12 Targeting of normal cells can also occur and result in immune-mediated adverse reactions, which can be severe and potentially fatal.1 Please see the Important Safety Information section below.

This approval was granted less than six weeks following the submission of a new supplemental Biologics License Application (sBLA), which was reviewed under the FDAs Real-Time Oncology Review (RTOR) pilot program. The RTOR program aims to ensure that safe and effective treatments are available to patients as early as possible.13 The review was also conducted under the FDAs Project Orbis initiative, enabling concurrent review by the health authorities in Australia, Brazil, Canada and Switzerland.

About CheckMate -743

CheckMate -743 is an open-label, multi-center, randomized Phase 3 trial evaluating Opdivo plus Yervoy compared to chemotherapy (pemetrexed and cisplatin or carboplatin) in patients with histologically confirmed unresectable malignant pleural mesothelioma and no prior systemic therapy or palliative radiotherapy within 14 days of initiation of therapy (n=605).1 Patients with interstitial lung disease, active autoimmune disease, medical conditions requiring systemic immunosuppression, or active brain metastasis were excluded from the trial.1In the trial, 303 patients were randomized to receive Opdivo 3 mg/kg every two weeks and Yervoy 1 mg/kg every six weeks; 302 patients were randomized to receive cisplatin 75 mg/m2 or carboplatin AUC 5 plus pemetrexed 500 mg/m2 in 3-week cycles for six cycles.1 Treatment in both arms continued until disease progression or unacceptable toxicity or, in the Opdivo + Yervoy arm, up to 24 months.1 The primary endpoint of the trial was OS in all randomized patients.1 Additional efficacy outcome measures included progression-free survival (PFS), objective response rate (ORR) and duration of response (DOR), as assessed by BICR utilizing modified RECIST criteria.1

Select Safety Profile from CheckMate -743 Study

Treatment was permanently discontinued for adverse reactions in 23% of patients treated with Opdivo + Yervoy, and 52% had at least one dose withheld for an adverse reaction.1 An additional 4.7% of patients permanently discontinued Yervoy alone due to adverse reactions. Serious adverse reactions occurred in 54% of patients receiving Opdivo + Yervoy.1 The most frequent (2%) serious adverse reactions in patients receiving Opdivo + Yervoy were pneumonia, pyrexia, diarrhea, pneumonitis, pleural effusion, dyspnea, acute kidney injury, infusion-related reaction, musculoskeletal pain, and pulmonary embolism.1 Fatal adverse reactions occurred in 4 (1.3%) patients and included pneumonitis, acute heart failure, sepsis, and encephalitis.1 The most common (20%) adverse reactions were fatigue (43%), musculoskeletal pain (38%), rash (34%), diarrhea (32%), dyspnea (27%), nausea (24%), decreased appetite (24%), cough (23%) and pruritus (21%).1 The median number of doses was 12 for Opdivo and 4 for Yervoy.3

About Malignant Pleural Mesothelioma

Mesothelioma is a rare but aggressive form of cancer that often forms in the lining of the lungs.2,14 There are approximately 3,000 cases diagnosed in the United States each year.14 Malignant pleural mesothelioma is the most common type of the disease.2 It is most frequently caused by exposure to asbestosand diagnosis is often delayed, with the majority of patients presenting with advanced disease.2,15 Prognosis is generally poor: in patients with advanced malignant pleural mesothelioma, median survival is approximately one year and the five-year survival rate is approximately 10%.2

INDICATIONS

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma (RCC).

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Bristol Myers Squibb: Advancing Cancer Research

At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase patients quality of life, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational CAR T cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early- to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering potential new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

About Bristol Myers Squibbs Patient Access Support

Bristol Myers Squibb remains committed to providing assistance so that cancer patients who need our medicines can access them and expedite time to therapy.

BMS Access Support, the Bristol Myers Squibb patient access and reimbursement program, is designed to help appropriate patients initiate and maintain access to BMS medicines during their treatment journey. BMS Access Support offers benefit investigation, prior authorization assistance, as well as co-pay assistance for eligible, commercially insured patients. More information about our access and reimbursement support can be obtained by calling BMS Access Supportat 1-800-861-0048 or by visiting http://www.bmsaccesssupport.com.

About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies as single agents and combination regimens for patients with cancer in Japan, South Korea and Taiwan.

About Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.

References

SOURCE: Bristol-Myers Squibb

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