TOKYOand BOTHELL, Wash., Feb. 18, 2021 /PRNewswire/ --Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (Nasdaq:SGEN) today announced completion of submissions for two supplemental Biologics License Applications (sBLAs) to the U.S. Food and Drug Administration (FDA) for PADCEV (enfortumab vedotin-ejfv). One submission, based on the phase 3 EV-301 trial, seeks to convert PADCEV's accelerated approval to regular approval. The second submission, based on the pivotal trial EV-201's second cohort, requests an expansion of the current label to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and are ineligible for cisplatin.

The FDA is reviewing both applications under the Real-Time Oncology Review (RTOR) pilot program. The RTOR program aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible.

"The FDA's review of our applications under Real-Time Oncology Review supports our efforts to expand PADCEV's availability as a treatment option for more patients as quickly as possible," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "Locally advanced or metastatic urothelial cancer is an aggressive disease with limited treatment options."

The sBLA for regular approval of PADCEV in the U.S. is supported by data from the global EV-301 phase 3 confirmatory trial, which compared PADCEV to chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. The trial's primary endpoint was overall survival of patients treated with PADCEV vs. chemotherapy, and full results were presented at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) and published in the New England Journal of Medicine.[1]

The second submission, for a label expansion in the U.S., is based on results from the second cohort of EV-201, a pivotal phase 2 clinical trial evaluating PADCEV in patients with locally advanced or metastatic urothelial cancer who had received prior immunotherapy treatment but were not eligible for cisplatin. The trial's primary endpoint was objective response rate, and full results were presented at ASCO GU.[2]

"Advanced bladder cancer patients urgently need more treatment options," said Roger Dansey, M.D., Chief Medical Officer, Seagen. "Based on recently presented clinical trial results, PADCEV could address a significant unmet need for more patients with advanced urothelial cancer after initial immunotherapy treatment."

In 2019 PADCEV received accelerated approval in the U.S. for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery in a locally advanced or metastatic urothelial cancer setting. PADCEV is currently only approved for use in the U.S.

About the EV-301 TrialThe EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician's choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and platinum-based therapies. The primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters.

About the EV-201 TrialThe EV-201 trial (NCT03219333) is a single-arm, dual-cohort, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (cohort 2). The trial enrolled 128 patients in cohort 1 and 91 patients in cohort 2 at multiple centers internationally. The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability.

About Urothelial CancerUrothelial cancer is the most common type of bladder cancer (90 percent of cases) and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.[3] Globally, approximately 549,000 new cases of bladder cancer and 200,000 deaths are reported annually.[4]

About PADCEV (enfortumab vedotin-ejfv)PADCEV was approved by the U.S. Food and Drug Administration (FDA) in December 2019 and is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. PADCEV was approved under the FDA's Accelerated Approval Program based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.[5]

PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.5,[6] Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).5 PADCEV is co-developed by Astellas and Seagen.

PADCEV Important Safety Information

Warnings and Precautions

Adverse ReactionsSerious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

The most common adverse reactions (20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade 3 adverse reactions (5%) were rash (13%), diarrhea (6%) and fatigue (6%).

Lab AbnormalitiesIn one clinical trial, Grade 3-4 laboratory abnormalities reported in 5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%).

Drug Interactions

Specific Populations

For more information, please see the full Prescribing Information for PADCEV here.

About Astellas Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+ healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website athttps://www.astellas.com/en.

About Seagen Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit http://www.seagen.com and follow @SeagenGlobal on Twitter.

About the Astellas and Seagen CollaborationAstellas and Seagen are co-developing enfortumab vedotin under a collaboration that was entered into in 2007 and expanded in 2009.

Astellas Cautionary NotesIn this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.

Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.

Seagen Forward Looking StatementsCertain statements made in this press release are forward looking, such as those, among others, relating to the potential conversion of PADCEV's current accelerated approval in the U.S. to regular approval and the potential expansion of the current PADCEV label to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and are ineligible for cisplatin, and the therapeutic potential of PADCEV, including its efficacy, safety and therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include, without limitation, the possibility that the sBLA submissions based on the EV-301 and EV-201 second cohort clinical trials may not be accepted for filing by, or ultimately approved by, the FDA in a timely manner or at all; that the results of the EV-301 clinical trial may not be sufficient to convert PADCEV's accelerated approval in the U.S. to regular approval and that the results of the second cohort of the EV-201 clinical trial may not be sufficient to support the requested label expansion; that, even if PADCEV receives regular approval and even if the PADCEV label is expanded based on the results of the second cohort of the EV-201 clinical trial, the product labeling may not be as broad or desirable as requested or anticipated; and that setbacks in the development and commercialization of PADCEV could occur as a result of the difficulty and uncertainty of pharmaceutical product development, the risk of adverse events or safety signals, the failure of ongoing and subsequent clinical trials to establish sufficient efficacy, or as a result of adverse regulatory actions. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

[1]Powles T, Rosenberg J, Sonpavde G, et al. Primary Results of EV-301: A Phase 3 Trial of Enfortumab Vedotin vs Chemotherapy in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma. ASCO Meeting Library 2021. https://meetinglibrary.asco.org/record/194738/abstract. Accessed February 11, 2021.[2] Balar AV, McGregor B, Rosenberg J, et al. EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors. ASCO Meeting Library 2021. https://meetinglibrary.asco.org/record/194731/abstract. Accessed February 11, 2021.[3]American Society of Clinical Oncology. Bladder cancer: introduction (5-2019). https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed January 27, 2021.[4]Cancer today: data visualization tools for exploring the global cancer burden in 2020. https://gco.iarc.fr/today/home. Accessed January 27, 2021.[5]PADCEV [package insert] Northbrook, IL: Astellas Pharma Inc.[6]Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016;76(10):3003-13.

SOURCE Astellas Pharma Inc.

http://www.us.astellas.com

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Astellas and Seagen Announce Submission of Two Supplemental Biologics License Applications to the US FDA for PADCEV (enfortumab vedotin-ejfv) in...

Cardiac Stem Cells Comments Off on Astellas and Seagen Announce Submission of Two Supplemental Biologics License Applications to the US FDA for PADCEV (enfortumab vedotin-ejfv) in… | February 19th, 2021

A cross section of mouse small intestine, showing intestinal crypts and villi, is visualized with immunofluorescence microscopy (nuclei in red, and F-actin, which marks the cytoskeleton, in blue). Intestinal stem cells reside at the base of crypts, where they maintain cell turnover.

Tissues with high intrinsic turnover, such as the skin and intestinal lining, rely on resident stem cells, which generate all native cell types. Intestinal stem cells (ISCs) are highly sensitive to damage, although they recover quickly. It is unclear whether this recovery (i.e., regeneration) occurs from less sensitive pools of reserve stem cells (1) or whether ISC progeny undergo reverse differentiation into stem cells (2). Recent studies in diverse organs highlight that dedifferentiation of specified cell types is a pervasive and dominant means for tissue regeneration. The findings have broad implications because all tissues experience some cell attrition over a lifetime, and knowing how tissues replenish those losses may help in preventing or treating organ failure. Moreover, it remains unclear whether incomplete differentiation, a common feature of cancer, reflects normal tissue plasticity, and it is unclear whether stem cells that arise by dedifferentiation may spawn cancers.

ISCs expressing leucine-rich repeatcontaining G proteincoupled receptor 5 (Lgr5) lie at the bottom of small bowel crypts (3). In the course of homeostatic tissue turnover, their immediate progeny adopt alternative enterocyte or secretory fates, then fill the crypts with replicating progenitors that migrate away from ISCs. Cell division ceases at the crypt tops, where postmitotic cells begin a 3- to 5-day journey along intestinal villi. When ISCs sustain irreparable damage, some source in the crypt must regenerate new ISCs. Other adult epitheliasuch as airways, prostate, and liverare organized differently from the intestine and from each other (see the figure). These epithelia also restore cells lost by damage or attrition, even though at rest they turn over at least a hundred times more slowly than the intestinal lining.

Airway epithelial structure varies from trachea to small bronchioles, and distinct progenitors in different segments produce assorted secretory and ciliated cell types. In the lining of human and mouse upper airways, flat basal cells lie beneath a layer of columnar differentiated cells and adjacent to submucosal myoepithelial glands. Stem cell activity in normal tissue turnover maps to a subpopulation of keratin 5 (Krt5)expressing basal cells (4). The trachea and bronchi are vulnerable to diverse injuries, including targeted destruction of Krt5+ stem cells and pervasive mucosal damage from noxious inhalants or viruses.

Adult human and mouse prostate glands also contain columnar luminal and flat KRT5+ basal cells. Distinct unipotent progenitors maintain both populations, and castration induces massive luminal cell loss. Androgen reexposure restores prostate mass within weeks, which implies the presence of castration-resistant progenitors. However, an unequivocal stem cell pool has not been identified. The liver also has notable regenerative abilities after chemical or surgical injury. The emerging consensus is that this organ lacks a dedicated stem cell compartment and recovers from damage through dedifferentiation of mature hepatocytes and biliary cells (5, 6).

Stem cell activity in vivo is demonstrated most persuasively by introducing into a tissue a permanent color or fluorescent label whose expression depends on Cre recombinasemediated excision of a STOP cassette. When Cre activity is restricted to stem cells, all the progeny of those cells exclusively carry the label. ISCs and tracheal stem cells were thus identified because targeted Cre activity in LGR5+ or KRT5+ mouse cells labeled the respective full lineages (3, 4). Investigation of tissue regeneration requires ablation of a stem cell compartment, followed by tracking of the restored ability to produce sufficient numbers of all native stem cell progeny. The canon of tissue repair rests heavily on such lineage-tracing experiments, but one limitation is that Cre recombinase is not often confined to a single defined cell type. This challenge lies at the heart of competing models for tissue recovery after lethal cell injuries.

Dividing cells take up labels such as [3H]thymidine or fluorescent histone 2B and shed these labels as they replicate further or their daughters die. In the intestine, however, rare cells located near the fourth tier from the crypt base retain [3H]thymidine for weeks. Given once-popular ideas that stem cells must be few in number and retain one immortal DNA strand when they replicate, +4 label-retaining cells (LRCs) were described as ISCs. In support of that idea, lineage tracing from Bmi1, a locus thought to be restricted to nonreplicating +4 LRCs, elicited an ISC-like response in vivo (7).

Physiologic cell turnover and recovery from injury occur from different cellular sources in diverse epithelia (intestine, upper airway, and prostate gland). Homeostatic turnover is driven by the stem cell pool, and tissue restoration from injury occurs through transient expansion and dedifferentiation of specified mature cells.

To reconcile the evidence for ISC properties in both LGR5+ crypt base columnar cells (CBCs) and +4 LRCs, researchers postulated that abundant CBCs serve as frontline ISCs, whereas the smaller +4 LRC population contains dedicated reserves. Indeed, intestinal turnover is unperturbed when LGR5+ CBCs are ablated because other crypt cells' progeny continue to repopulate villi and an LGR5+ ISC compartment is soon restored (1). Multiple candidate markers of +4 LRCs that regenerate ISCs after injury have been proposed (8). Although these cells are too few to explain the typical scale and speed of ISC restoration, the prospect of two stem cell pools carried the additional allure of a sound adaptive strategy in a tissue that requires continuous self-renewal.

ISC differentiation is, however, not strictly unidirectional. Cre expression in absorptive or secretory cell types tags those cells selectively, but upon ablation of LGR5+ CBCs, the label appears throughout (9). These observations imply that differentiated daughter cells have reverted into ISCs. Moreover, Bmi1 expression was found to mark differentiated crypt endocrine cells (10), and putative +4 markers are expressed in many crypt cells including LGR5+ CBCs. Accordingly, when Cre is expressed from these loci, the traced lineage might simply reflect CBC activity in resting animals and reverse differentiation of crypt cells after ISC ablation. But is dedifferentiation a rare and physiologically inconsequential event or the predominant mode of stem cell recovery? Dedifferentiation may obviate the need to invoke a dedicated reserve population, or it is possible that ISC recovery may reflect both dedifferentiation and contributions from a reserve stem cell population.

To investigate these issues, researchers activated a fluorescent label in LGR5+ CBCs and waited for this label to pass into progeny cells before ablating CBCs (11). Thus, only the CBCs that recover by dedifferentiation should be labeled, and any cells arising from reserve ISCs should not. Nearly every restored crypt and CBC was fluorescent, with substantial contributions from both enterocytes and secretory cells (11). Cells captured early in the restorative process coexpressed mature-cell and ISC genes, which is compatible with recovery by dedifferentiation. Another study found that damaged ISCs are reconstituted wholly by the progeny of LGR5+ CBCs (8). Thus, dedifferentiation would seem to be the principal mode of ISC regeneration, and prior conclusions about +4 ISCs likely reflect unselective Cre expression.

Different tissues might deploy distinct regenerative strategies, and recent studies in mouse airway, prostate, intestinal, and liver epithelia provide insightful lessons. After ablation of KRT5+ airway stem cells, specified secretory and club cell precursors were found to undergo clonal multilineage expansion and accounted for up to 10% of restored KRT5+ cells in vivo (12). Chemical or viral damage was subsequently reported to induce migration and dedifferentiation of submucosal gland myoepithelial cells into the basal layer to reconstitute the surface lining, including KRT5+ stem cells (13). Thus, dedifferentiation into native stem cells occurs upon injury to both airway and intestinal linings in mice.

Single-cell RNA sequencing (scRNA-seq) analysis of mouse prostate glands recently revealed distinct gene expression profiles in 3% of luminal cells, which are more clonogenic than others, express putative stem cell markers, and hence qualify as a pool enriched for native stem-like cells (14). After androgen reexposure following castration, however, the scale and distribution of cell replication and the location of restored clones were incompatible with an origin wholly within that small pool. Rather, the principal source of gland reconstitution in vivo, including new KRT5+ basal cells, was the dominant population of differentiated luminal cells (14). These observations parallel those in the liver, where recovery of organ mass after tissue injury occurs by renewed proliferation of mature resting hepatocytes (5), abetted by expansion of bile duct cells that transdifferentiate into hepatocytes (6). Cell plasticity is thus widespread, whether tissues have or lack native stem cell compartments.

Reverse differentiation in the intestine, airways, and prostate gland was generally observed after near-total elimination of resident stem or luminal cells, an extreme and artificial condition. However, several observations suggest that this dedifferentiation reflects a physiologic process designed to maintain a proper cell census. Contact with a single KRT5+ airway stem cell prevents secretory and club cell dedifferentiation in vitro (12), and tracheal submucosal glands exhibit limited stem cell activity even in the absence of injury (13). Live imaging of intestinal crypts reveals continuous and stochastic exit from and reentry into the ISC compartment (15), implying that barriers for differentiation or dedifferentiation are inherently low. However, the primary purpose of dedifferentiating airway, intestinal, liver, and prostate cells is not to enable tissue recovery. Therefore, they should be regarded as facultative stem cells; that is, they have other physiologic functions and realize a latent stem cell capacity only under duress.

This distinction from reserve stem cells is not merely semantic. Emphasis in regenerative therapy research belongs on any cell population with restorative potential; in vivo findings now direct attention away from putative reserve cells and toward dedifferentiation as a common means for tissue recovery. The absence of dedicated reserves and the inherent cellular ability to toggle between stem and differentiated states also inform cancer biology. Because mutations realize oncogenic potential only in longlived cells, both frontline and reserve stem cells represent candidate sources of cancer, in contrast to differentiated cells, which are generally short-lived. However, oncogenic mutations that arise in differentiated cells could become fixed upon dedifferentiation, thus enabling tumor development.

Notably, stem cell properties and interconversion with their progeny are not stereotypic. ISCs divide daily into two identical daughters, whereas hematopoietic stem cell replication is infrequent and asymmetric. Severe loss of blood stem cells does not elicit substantial dedifferentiation and is rescued only by adoptive stem cell transfer. Immature secretory precursors dedifferentiate more readily than terminally mature airway cells (12), whereas fully differentiated cells fuel liver and prostate regeneration. Cell plasticity in each case is determined by local signals. Unknown factors from KRT5+ tracheal stem cells, for example, suppress secretory cell dedifferentiation (12), and specific factors secreted from the prostate mesenchyme stimulate luminal cell dedifferentiation (14). The intestinal mesenchyme probably senses ISC attrition to trigger tissue recovery, but the spatial and molecular determinants remain unknown. Outstanding challenges are to identify the signaling pathways that ensure a stable cell census and to harness diverse regenerative responses to ameliorate acute tissue injuries or prevent organ failure. Knowing the cellular basis for stem cell recovery in different contexts brings us closer to those goals.

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Tissue regeneration: Reserve or reverse? - Science Magazine

Skin Stem Cells Comments Off on Tissue regeneration: Reserve or reverse? – Science Magazine | February 19th, 2021

Heres a fun fact about rosehip oil: it does not smell like roses. It does, however, heal. Known as the Himalayan musk rose, this wild flowering plant has only five petals, says Roshni Laura George, who discovered the elusive bloom during her honeymoon in Kashmir, as she was researching medicinal plants through the country in the remotest parts of the valley. Every May, the musk rose bushes burst into bloom, covering trees, tumbling over cliffs and blanketing the earth with their heady scent. The hip, a powerhouse of essential nutrients, is what is left once the petals fall. Thats where the oil is extracted from, explains George, who preserved this juice in Timekeeper, a vivid amber face oil that launched her skincare brand, Rasula. We do not bleach, colour or deodorise our rosehip oil as this would deplete its natural goodness. The oil is hardly oily, the red lingers for just a few seconds before your skin drinks it up, and its nutty smell is so distinct that you can only assume it came from the roses hip. George promised it would become my one-step skincare routine (followed by sunscreen in the day, of course) and my combination-dehydrated- acne-prone-moody skin might agree.

Rosehip oil can handle the fussiest skin types. Two reasons: vitamin F and beta carotene. Vitamin F is an essential fatty acid, rich in omega-6, which produces ceramide 1, a key part of a healthy skin barrier. Beta carotene is an antioxidant that gives the oil its rich orange hue. It can neutralise free radicals from the environment, protect against UVA damage, reduce oxidative stress, and enhance the appearance of skin. Essential fatty acids in the rosehip oil are absorbed by the skin to regenerate collagen and elastin fibres that keep the skin firm and youthful, explains George. In short, it helps your skin fight for itself.

George aimed to create category-defining natural skincare for photo-aged skin. Three years of research working closely with leading institutions like IIM Jammu and the Council of Scientific and Industrial Research in Bengaluru, led to Rasula, a clean beauty brand that comes without parabens, SLS, and artificial fragrance, among other nasties. Rasulas products are handcrafted and packed by hand in recyclable glassware, and its rosehip is hand-picked from the Himalayan Range by the local women of Kashmir. While common extraction practices include cold-pressing, George took a more expensive, environmentally friendly approach to ensure her oil was more concentrated, cleaner and superior, with a longer shelf life. We flush supercritical CO2 under high pressure through the seeds, which gently removes the oil, explains George. And if youre still not convinced, know this: rosehip oil is the most inclusive ingredient in skincare. Suitable for all skin types and age groups, including pregnant women and children, the oil helps eradicate a host of skin issuesscars, burns, fine lines, stretch marks, acne, dryness, sensitivity, sun damage, uneven skin tone, age spots, eczema and more. Most importantly, it is gender-neutral, says George.

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Heres why natural ingredients and science-backed formulations are the perfect combination - Vogue India

Skin Stem Cells Comments Off on Heres why natural ingredients and science-backed formulations are the perfect combination – Vogue India | February 19th, 2021

CLEVELAND, Feb. 19, 2021 /PRNewswire/ -- Paulette Kaplan noticed something different as she entered into her 50s. Her skin was now dryer, and looked older than just a couple years earlier. Looking at her cabinet full of products that were supposed to work, she thought, "Nothing really works well."

As a skincare advocate, she began to consider creating her own line exclusively for the needs of the 50-plus.

In an industry obsessed with youth, Paulette found there to be a tremendous lack of skincare products made for this market.

According to an AARP national survey, "Women over age 50 make a big investment of time and money on beauty and personal grooming products, spending a whopping $22 billion annually, yet they still think that the beauty industry ignores them as they age."

Paulette was determined and began her search and discovered that some ingredients could be damaging to how skin looks and cause inflammation that works against the skin's ability to heal.

She did not want to make more 'anti-aging' potions. Or use unhealthy ingredients but to offer a clean and nourishing age perfect skincare line that would strengthen mature skin.

Trupure Organics was born with the help of scientists, chemists, and multiple formulas. A100% natural plant-based line using stem cells, bio-retinol, extracts, peptides, oils and juices. Their TruPurity promise excludes ingredients like chemicals, fragrances, dyes, parabens, GMOs, and phthalates.

What are the key goals? Provide continuous moisture, soothe, firm, protect, lift, strengthen, plump, smooth, and nourish with specific delivery systems.

Paulette explains her 50-plus line, "The focus isn't to put yourself under a magnifying glass, but actually celebrate your age by focusing on healthier radiant skin. Because when skin is healthy, it naturally looks beautiful."

Retinol is a common ingredient in skincare products because of how well it can promote collagen production. Trupure Organics No More Crepe Neck and Dcolletage Cream ($65) uses a different approach through a plant-based bio-retinol. Itwon't cause peeling, irritation, itching, or make skin considerably more sensitive to sunlight like standard retinol.

This same kind of approach is used in formulating all their plant-based products for mature skin. Visit trupureorganics.com to view the full collection of serums and creams.

References

Women 50 and Older Feel Overlooked by the Beauty Industry

Contact:

Paulette Kaplan Founder and CEO, Trupure Organics216.702.0345[emailprotected]http://www.trupureorganics.com

SOURCE Trupure Organics

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Trupure Organics Is First 50-Plus Brand Devoted to That Market's Distinct Needs - PRNewswire

Skin Stem Cells Comments Off on Trupure Organics Is First 50-Plus Brand Devoted to That Market’s Distinct Needs – PRNewswire | February 19th, 2021

MANILA, Philippines Breach. Reanimate. Create. This is the mantra behind La Prairies Platinum Rare Haute Rejuvenation Protocol, a new anti-aging product that is the Swiss luxury skincare brands most groundbreaking innovation yet.

La Prairie sought to go beyond skin renewal, and for the first time, we will create new skin tissue, says Dr. Daniel Stangl, La Prairies director of innovation.

This ultimate path to rejuvenation has been designed to work in three steps: breach the skin barrier, reanimate cells, and create new skin tissue.

As the first step, and in analogy to (La Prairie founder) Dr. Paul Niehans cellular therapy, the formula temporarily softens the skin barrier in order to optimally deliver the active ingredients into the skin and enhance the full potential, Stangl says.

In the second step, Platinum Rare Haute Rejuvenation Protocol reanimates cells in all skin layers, specifically stem cells and differentiated cells, which make up the majority of skin cells.

To reanimate these cells, the formula of the serum contains an exclusive platinum multi-peptide combined with two essential growth factors and La Prairies exclusive Cellular Complex. These highly potent active ingredients reanimate stem cells to produce new cells and differentiated cells to synthesize a new extracellular matrix, including fibers of collagen and elastin, as well as the hyaluronic acid, Stangl continues.

Thirdly, as a result of breaching the skins barrier and reanimating cells, La Prairie creates new skin tissue. The creation of new skin tissue in all skin layers is the fundamental process of rejuvenation, Stangl says. It literally infuses the skin with youth, improving all signs of aging as never seen before.

The product is designed as a month-long protocol, consisting of three vials. One vial is used for 10 days, day and night. After this month-long phase of intense rejuvenation, the skin needs time to re-equilibrate, notes Stangl. We therefore recommend using it for one month, four times a year.

The unique packaging includes a mini pedestal on which you put the jewel-toned vial and twist it, releasing clouds of product that you then shake to mix into a fresh serum. It displays La Prairies merging of art and science at its finest, giving its clientele the most luxurious, magical experience.

La Prairies Platinum Rare Haute Rejuvenation Protocol will be on counter at Rustans The Beauty Source on Feb. 25.

Light and cooling: Kiehls Ultra Facial Oil-free Gel Cream

One of Kiehls hero products has always been its Ultra Facial moisturizer, which can hydrate even the driest of skins. In the tropical Philippines, however, that formula might be too rich, especially for people with oily, acne-prone skin.

So now Kiehls has formulated Ultra Facial as an oil-free gel cream, a lightweight, cooling moisturizer thats perfect for our humid weather, especially in the coming summer months. Glacial glycoprotein Antarcticine hydrates skin for 24 hours, while Micronized Amino Acid helps regulate excess oil for shine control, so its suited to those with oily and combination skin who have a tendency to break out with maskne, like I do. I also love that its fragrance-, alcohol- and paraben-free.

He hearts her: Nars Claudette Collection was inspired by Francois Nars mother and first muse.

Nars limited-edition Claudette Collection is Francois Nars tribute to his mother and very first muse, Claudette, and the bohemian spirit of Paris Rive Gauche (Left Bank) in the 70s. The prints on the packaging were inspired by the prints on the dresses his mom used to wear.

Claudettes eyeshadow palette, St. Germain Des Prs, is filled with six warm, neutral shades in matte, satin and shimmer finishes. You cant go wrong with the neutrals in this palette, which are so subtle and wearable youll always end up with an elegant look, no matter which color or combination you use.

Nars cult-favorite satin Audacious lipstick comes in four shades named after his mom Claudette is a striking rust red and the other inspiring women in his life, grandmothers La and Ginette.

New to Audacious is a Sheer Matte formula with a soft-focus finish and medium-sheer coverage: Sandrine is a scarlet red; Sylvie is a berry red, and they feel so comfy and soft on the lips.

The Claudette Collection is available at Nars boutiques and Rustans The Beauty Source.

Dress your lips: Rouge Dior comes in 75 shades and new, refillable logo cases.

Christian Diors most iconic lipsticks have been released in modern, refillable packaging, and ultra-flattering finishes.

Rouge Dior 999 Velvet is a crimson-red born from the first two lipsticks launched by Christian Dior 9 and 99 and 100 Nude Look, a reinterpretation of the greige new look of 1947. (The other two icons are 080 Red Smile, one of the first reds Dior created in 1950 thats been reinvented as an intensely luminous red; and 525 Chrie, a rosewood nude whose name conveys Diors love of women and his muses.)

The legendary fashion designer not only wanted to dress women but also their smiles, so he created his first couture lipstick in 1953, eventually releasing it in over a thousand shades. Ever the visionary, Rouge Dior was already sustainable back then, as the lipsticks came in refillable cases.

Today, Peter Philips, the creative and image director for Dior Makeup, has resurrected 75 shades in new, refillable logo cases, and satin, matte, velvet and metallic finishes to flatter all skin tones.

Flowers always inspired Dior, so the formula has been enriched with floral, lip-care ingredients like red peony and pomegranate blossom extract.

Rouge Dior is available at Dior boutiques and SM Makati.

Beauty bargains: Get discounts on beloved brands at Shopee Beauty.

I love Shopee for its amazing deals and steals, so I was really excited to learn that the e-tailer has launched Shopee Beauty, a one-stop online destination for the best deals from top makeup and skincare brands.

You can find well-established, beloved brands such as Dove, TRESemm, and Cream Silk, as well as exciting finds from up-and-coming brands like Face Republic, Beauty Avenue, Teviant, and Seoul White Korea.

Brands will curate based on the latest makeup trends, and recommend products based on your needs. Youll also get fun tutorials from their favorite Shopee KOLs, product reviews, makeup tips, and giveaways on Shopee Live.

But face it: we love the bargains, right? Aside from free shipping vouchers, limited-time deals and exclusive product launches, until March 24 theyre giving discounts of up to 90 percent off on their go-to lippies, mascaras, and skincare brands.

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The ultimate path to skin rejuvenation - Philstar.com

Skin Stem Cells Comments Off on The ultimate path to skin rejuvenation – Philstar.com | February 19th, 2021

While youre receiving treatment for cancer, some of the drugs you take can cause painful sores to develop inside your mouth. You can also get them if youve had a bone marrow (stem cell) transplant as part of your cancer care.

Although they often heal on their own, these mouth sores can make it uncomfortable to eat and talk. Well discuss what you can do to relieve the pain and prevent them from getting worse.

Mouth sores can be a common side effect of cancer treatment. The condition, known as stomatitis or mucositis, is an inflammation of the tissues inside your mouth.

Whitish, ulcer-like sores can form on your cheeks, gums, lips, tongue, or on the roof or floor of your mouth. Even if you dont develop mouth ulcers, you may have patches that feel inflamed and painful, as if theyve been burned.

Anyone who is receiving chemotherapy, radiation therapy, or a bone marrow (stem cell) transplant can develop mouth sores as a side effect of these treatments.

If you have dry mouth or gum disease, or if your teeth and gums are not well taken care of, you may be at a higher risk of getting mouth sores during your treatment. Women and people who smoke or drink alcohol are also at a higher risk, according to the Oral Cancer Foundation.

If youre receiving chemotherapy, the sores could begin forming anywhere from 5 days to 2 weeks after your treatment. Depending on the specific cause, the sores could go away on their own in a few weeks, or they could last longer.

Its important to find ways to manage your pain and to watch for signs of an infection. Cancer-related mouth sores can lead to weight loss, dehydration, and other serious complications.

Cancer cells can grow very quickly. The aim of cancer treatment is to stop or slow down that growth. The cells in the mucous membranes lining your mouth are also fast-growing cells, so cancer treatments affect them, too.

Cancer treatments also keep the cells in your mouth from being able to repair themselves efficiently when theyre damaged.

Radiation therapy can also damage the glands in your mouth that make saliva. A dry mouth is more susceptible to infections that cause mouth sores.

Chemotherapy and radiation can both change the microbiome in your mouth, upsetting the balance between good and bad bacteria. The growth of harmful bacteria in your mouth can also lead to mouth sores.

Sometimes cancer treatments suppress your immune system, which may make it more likely that youll get a bacterial, viral, or fungal infection that causes mouth sores. An older infection (such as the herpes simplex virus) can also suddenly flare up again.

If youve had a bone marrow (stem cell) transplant, sores may be a sign that youve developed a condition known as graft-versus-host disease (GVHD).

When this happens, the cells in your body are attacking the transplanted cells as though they were an unhealthy invader. According to research published in Journal of Clinical and Experimental Dentistry, short-term (acute) GVHD occurs in 50 to 70 percent of stem cell transplant cases and longer-term (chronic) GVHD is seen in 30 to 50 percent of cases.

The form of GVHD that causes mouth sores is usually mild, and doctors often treat it with corticosteroid medications.

Its important to talk with your doctor if you develop mouth sores after a stem cell transplant, as some kinds of GVHD can turn serious if left untreated.

There is a good chance that youll experience mouth sores at some point during your cancer treatment. Researchers estimate that 20 to 40 percent of those who have chemotherapy and 80 percent of those who have high-dose chemotherapy will develop mucositis afterward.

Still, there are steps you and your cancer care team can take to lower your risk, reduce the severity of the sores, and promote faster healing.

About a month before your cancer treatment begins, schedule an appointment with your dentist to make sure your teeth and gums are healthy. If you have cavities, broken teeth, or gum disease, its important to come up with a dental treatment plan to take care of these conditions so they dont lead to infections later, when your immune system may be vulnerable.

If you wear braces or dentures, ask your dentist to check the fit and remove any part of the device you dont need during your treatment.

Its very important to maintain good oral hygiene practices throughout your treatment to lower your risk of infection. Brush and floss gently but regularly, avoiding any painful areas. You can also ask your dentist whether a mouth rinse with fluoride is advisable in your case.

For certain kinds of chemotherapy (bolus 5fluorouracil chemotherapy and some high-dose therapies), your healthcare team may give you ice chips to chew for 30 minutes before your treatment. This type of cold therapy can lower your risk of getting mouth sores later.

During treatment of some blood cancers, doctors may give you injections of palifermin, also known as human keratinocyte growth factor-1 (KGF-1), to prevent mouth sores.

If youre scheduled to receive high-dose chemotherapy or radiotherapy, your cancer care team may prepare your mouth using low-level laser therapy beforehand to keep you from getting mouth sores.

For people who have radiation therapy for head and neck cancers, doctors may prescribe this medicated mouthwash to minimize mouth sores.

The length of time your mouth sores may last depends on the specific cancer treatment youve had. Here are some estimates broken down by treatment:

You may notice symptoms anywhere between a few days and a few weeks after your cancer treatment. Heres what you may see and feel as mucositis develops:

You may notice that the sores become slightly crusty as they heal. Its important to keep track of your symptoms and let your oncologist know if the sores arent healing on their own.

Contact your doctor right away if you:

Untreated mouth sores can lead to malnutrition, dehydration, and life-threatening infections.

There are a few different ways that you can help mouth sores heal and avoid prolonger pain or an infection.

While the sores are healing, its very important to keep the inside of your mouth clean to prevent an infection from developing.

The National Cancer Institute recommends that you gently clean your teeth every 4 hours and just before you go to sleep at night. Here are a few tips to consider:

If the pain from mouth sores is interfering with your ability to eat and drink, your doctor may treat the condition with a opioid mouthwash or one containing doxepin or lidocaine.

To ease discomfort and keep your mouth from feeling dry, you may want to try rinsing with a mild saltwater or baking soda solution. Heres how to make each of them:

Your cancer care team may recommend that you use a lubricating liquid (artificial saliva) to moisten the inside of your mouth if dryness is a problem. These liquids are usually gel-like. They coat your mouth with a thin film to help ease discomfort and promote healing.

Some people have found it useful to rinse with a blend of medications called the magic mouthwash. Formulas for this mouthwash vary, but most of them include a combination of medications to treat different symptoms, including:

Magic or miracle mouthwash solutions usually have to be prescribed by a doctor and prepared by a pharmacist, although some people mix up an over-the-counter version at home.

There isnt enough research to say for sure whether magic mouthwash works. If you think youd like to try it, talk with your oncologist or a healthcare professional about whether its a good idea for you.

Here are a few more things you can try at home that may help ease pain from mouth sores:

Mouth sores are one of the most common side effects of cancer treatment. Shortly after chemotherapy, radiation, or transplant treatments, painful, ulcer-like sores can form on the inside of your mouth.

These sores may go away on their own. If they dont, its important to seek medical treatment for them because they can lead to very serious complications.

Before you start cancer treatments, visit a dentist to make sure your teeth and gums are healthy. Keeping up good dental hygiene practices during and after cancer treatment will help limit mouth sores.

If the sores are keeping you from eating and drinking, talk with your oncologist about medications could relieve the pain and speed up the healing process, so you can enjoy a better quality of life during treatment.

Its really important to keep track of any sores in your mouth so you can reach out to your healthcare team if they dont improve. Sores that deepen or worsen can lead to serious even life-threatening complications.

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Mouth Sores from Chemo: Symptoms, Causes, and Treatments - Healthline

Skin Stem Cells Comments Off on Mouth Sores from Chemo: Symptoms, Causes, and Treatments – Healthline | February 19th, 2021

This article was originally published here

Front Immunol. 2021 Jan 21;11:594572. doi: 10.3389/fimmu.2020.594572. eCollection 2020.

ABSTRACT

Mycobacterium tuberculosis (Mtb), the causative organism of pulmonary tuberculosis (PTB) now infects more than half of the world population. The efficient transmission strategy of the pathogen includes first remaining dormant inside the infected host, next undergoing reactivation to cause post-primary tuberculosis of the lungs (PPTBL) and then transmit via aerosol to the community. In this review, we are exploring recent findings on the role of bone marrow (BM) stem cell niche in Mtb dormancy and reactivation that may underlie the mechanisms of PPTBL development. We suggest that pathogens interaction with the stem cell niche may be relevant in potential inflammation induced PPTBL reactivation, which need significant research attention for the future development of novel preventive and therapeutic strategies for PPTBL, especially in a post COVID-19 pandemic world. Finally, we put forward potential animal models to study the stem cell basis of Mtb dormancy and reactivation.

PMID:33584661 | PMC:PMC7873989 | DOI:10.3389/fimmu.2020.594572

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Initiation of Post-Primary Tuberculosis of the Lungs: Exploring the Secret Role of Bone Marrow Derived Stem Cells - DocWire News

Bone Marrow Stem Cells Comments Off on Initiation of Post-Primary Tuberculosis of the Lungs: Exploring the Secret Role of Bone Marrow Derived Stem Cells – DocWire News | February 17th, 2021

Transparency Market Research (TMR) has published a new report titled, Cord Blood Banking Services Market Global Industry Analysis, Size, Share, Growth, Trends, and Forecast, 20192027. According to the report, the globalcord blood banking services marketwas valued atUS$ 25.8 Mnin2018and is projected to expand at a CAGR of10.9%from2019to2027.

Overview

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High Incidence of genetic disorders and rise in hematopoietic stem cell transplantation rates to Drive Market

Request for Analysis of COVID19 Impact on Cord Blood Banking Services Market https://www.transparencymarketresearch.com/sample/sample.php?flag=covid19&rep_id=1741

Private Cord Blood Bank Segment to Dominate Market

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North America to Dominate Global Market

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Cord Blood Banking Services Market projected to expand at a CAGR of 10.9% from 2019 to 2027 KSU | The Sentinel Newspaper - KSU | The Sentinel...

Bone Marrow Stem Cells Comments Off on Cord Blood Banking Services Market projected to expand at a CAGR of 10.9% from 2019 to 2027 KSU | The Sentinel Newspaper – KSU | The Sentinel… | February 17th, 2021

REDWOOD CITY, Calif.--(BUSINESS WIRE)--Jasper Therapeutics, Inc., a biotechnology company focused on hematopoietic cell transplant therapies, today announced the launch of a Phase 1/2 clinical trial to evaluate JSP191, Jaspers first-in-class anti-CD117 monoclonal antibody, as a targeted, non-toxic conditioning regimen prior to allogeneic transplant for sickle cell disease (SCD). Jasper Therapeutics and the National Heart, Lung, and Blood Institute (NHLBI) have entered into a clinical trial agreement in which NHLBI will serve as the Investigational New Drug (IND) sponsor for this study.

SCD is a lifelong inherited blood disorder that affects hemoglobin, a protein in red blood cells that delivers oxygen to tissues and organs throughout the body. Approximately 300,000 infants are born with SCD annually worldwide, and the number of cases is expected to significantly increase. Currently, hematopoietic stem cell transplantation (HSCT) is the only cure available for SCD.

"This clinical trial agreement with the NHLBI expands the development of JSP191 for transplant conditioning and could bring curative transplants to more patients in need," said Kevin N. Heller, M.D., Executive Vice President, Research and Development, of Jasper Therapeutics. "We look forward to collaborating with the NHLBI and learning more about the potential for JSP191 in patients living with sickle cell disease."

About JSP191

JSP191 (formerly AMG 191) is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from the bone marrow. JSP191 binds to human CD117, a receptor for stem cell factor (SCF) that is expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required for stem cells to survive. JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals in stem cells leading to cell death. This creates space in the bone marrow for engraftment of donor or gene-corrected transplanted stem cells.

Preclinical studies have shown that JSP191, as a single agent, safely depletes normal and diseased hematopoietic stem cells, including in animal models of severe combined immunodeficiency (SCID), myelodysplastic syndromes (MDS), and sickle cell disease (SCD). Treatment with JSP191 creates the space needed for transplanted normal donor or gene-corrected hematopoietic stem cells to successfully engraft in the host bone marrow. To date, JSP191 has been evaluated in more than 90 healthy volunteers and patients.

JSP191 is currently being evaluated in two separate Jasper Therapeutics-sponsored clinical studies in hematopoietic cell transplant. The first clinical study is evaluating JSP191 as a sole conditioning agent in a Phase 1/2 dose-escalation and expansion trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplant for SCID. Blood stem cell transplantation offers the only potentially curative therapy for SCID. JSP191 is also being evaluated in combination with another conditioning regimen in a Phase 1 study in patients with MDS or acute myeloid leukemia (AML) who are receiving hematopoietic cell transplant. For more information about the design of these clinical trials, visit http://www.clinicaltrials.gov (NCT02963064 and NCT04429191).

Additional studies are planned to advance JSP191 as a conditioning agent for patients with other rare and ultra-rare monogenic disorders and autoimmune diseases.

About Jasper Therapeutics

Jasper Therapeutics is a biotechnology company focused on the development of novel curative therapies based on the biology of the hematopoietic stem cell. The companys lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a hematopoietic cell transplant. This first-in-class conditioning antibody is designed to enable safer and more effective curative hematopoietic cell transplants and gene therapies. For more information, please visit us at jaspertherapeutics.com.

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Jasper Therapeutics Announces Launch of New Clinical Trial with National Heart, Lung, and Blood Institute to Evaluate JSP191 in Sickle Cell Disease -...

Bone Marrow Stem Cells Comments Off on Jasper Therapeutics Announces Launch of New Clinical Trial with National Heart, Lung, and Blood Institute to Evaluate JSP191 in Sickle Cell Disease -… | February 17th, 2021

Novartis and the Bill and Melinda Gates Foundation are joining forces to discover and develop a gene therapy to cure sickle cell disease with a one-step, one-time treatment that is affordable and simple enough to treat patients anywhere in the world, especially in sub-Saharan Africa where resources may be scarce but disease prevalence is high.

The three-year collaboration, announced Wednesday, has initial funding of $7.28 million.

Current gene therapy approaches being developed for sickle cell disease are complex, enormously expensive, and bespoke, crafting treatments for individual patients one at a time. The collaboration aims to instead create an off-the-shelf treatment that bypasses many of the steps of current approaches, in which cells are removed and processed outside the body before being returned to patients.

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Sickle cells cause is understood. The people it affects are known. But its cure has been elusive, Jay Bradner, president of the Novartis Institutes for BioMedical Research, told STAT.

We understand perfectly the disease pathway and the patient, but we dont know what it would take to have a single-administration, in vivo gene therapy for sickle cell disease that you could deploy in a low-resource setting with the requisite safety and data to support its use, he said. Im a hematologist and can assure you that in my experience in the clinic, it was extremely frustrating to understand a disease so perfectly but have so little to offer.

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Sickle cell disease is a life-threatening inherited blood disorder that affects millions around the world, with about 80% of affected people in sub-Saharan Africa and more than 100,000 in the U.S. The mutation that causes the disease emerged in Africa, where it protects against malaria. While most patients with sickle cell share African ancestry, those with ancestry from South America, Central America, and India, as well as Italy and Turkey, can also have the hereditary disease.

The genetic mutation does its damage by changing the structure of hemoglobin, hampering the ability of red blood cells to carry oxygen and damaging blood vessels when the misshapen cells get stuck and block blood flow. Patients frequently suffer painful crises that can be fatal if not promptly treated with fluids, medication, and oxygen. Longer term, organs starved of oxygen eventually give out. In the U.S., that pain and suffering is amplified when systemic and individual instances of racism deny Black people the care they need.

Delivering gene therapy for other diseases has been costly and difficult even in the best financed, most sophisticated medical settings. Challenges include removing patients cells so they can be altered in a lab, manufacturing the new cells in high volume, reinfusing them, and managing sometimes severe responses to the corrected cells. Patients also are given chemotherapy to clear space in their bone marrow for the new cells.

Ideally, many of those steps could be skipped if there were an off-the-shelf gene therapy. That means, among other challenges, inventing a way to eliminate the step where each patients cells are manipulated outside the body and given back the in vivo part of the plan to correct the genetic mutation.

Thats not the only obstacle. For a sickle cell therapy to be successful, Bradner said, it must be delivered only to its targets, which are blood stem cells. The genetic material carrying corrected DNA must be safely transferred so it does not become randomly inserted into the genome and create the risk of cancer, a possibility that halted a Bluebird Bio clinical trial on Tuesday. The payload itself mustnt cause such problems as the cytokine storm of immune overreaction. And the intended response has to be both durable and corrective.

In a way, the gene delivery is the easy part because we know that expressing a normal hemoglobin, correcting the mutated hemoglobin, or reengineering the switches that once turned off normal fetal hemoglobin to turn it back on, all can work, Bradner said. The payload is less a concern to me than the safe, specific, and durable delivery of that payload.

For each of these four challenges delivery, gene transfer, tolerability, durability there could be a bespoke technical solution, Bradner said. The goal is to create an ensemble form of gene therapy.

Novartis has an existing sickle-cell project using CRISPR with the genome-editing company Intellia, now in early human trials, whose lessons may inform this new project. CRISPR may not be the method used; all choices are still on the table, Bradner said.

Vertex Pharmaceuticals has seen encouraging early signs with its candidate therapy developed with CRISPR Therapeutics. Other companies, including Beam Therapeutics, have also embarked on gene therapy development.

The Novartis-Gates collaboration is different in its ambition to create a cure that does not rely on an expensive, complicated framework. Novartis has worked with the Gates Foundation on making malaria treatment accessible in Africa. And in October 2019, the Gates Foundation and the National Institutes of Health said together they would invest at least $200 million over the next four years to develop gene-based cures for sickle cell disease and HIV that would be affordable and available in the resource-poor countries hit hardest by the two diseases, particularly in Africa.

Gene therapies might help end the threat of diseases like sickle cell, but only if we can make them far more affordable and practical for low-resource settings, Trevor Mundel, president of global health at the Gates Foundation, said in a statement about the Novartis collaboration. Its about treating the needs of people in lower-income countries as a driver of scientific and medical progress, not an afterthought.

Asked which is the harder problem to solve: one-time, in vivo gene therapy, or making it accessible around the world, David Williams, chief of hematology/oncology at Boston Childrens Hospital, said: Both are going to be difficult to solve. The first will likely occur before the therapy is practically accessible to the large number of patients suffering the disease around the world.

Williams is also working with the Gates Foundation, as well as the Koch Institute for Integrative Cancer Research at MIT, Dana-Farber Cancer Institute, and Massachusetts General Hospital, on another approach in which a single injection of a reagent changes the DNA of blood stem cells. But there are obstacles to overcome there, too, that may be solved by advances in both the technology to modify genes and the biological understanding of blood cells.

Bradner expects further funding to come to reach patients around the world, once the science progresses more.

There is no plug-and-play solution for this project in the way that mRNA vaccines were perfectly set up for SARS-CoV-2. We have no such technology to immediately redeploy here, he said. Were going to have to reimagine what it means to be a gene therapy for this project.

Excerpt from:
Novartis, Gates Foundation pursue a simpler gene therapy for sickle cell - STAT

Bone Marrow Stem Cells Comments Off on Novartis, Gates Foundation pursue a simpler gene therapy for sickle cell – STAT | February 17th, 2021

RESEARCH TRIANGLE PARK After 13 years as a clinical-stage oncology company,G1 Therapeuticsof Research Triangle Park transformed into a commercial-stage company overnight upon the approval of its first drug by the U.S. Food and Drug Administration.

The FDA on Feb. 12 approved G1s trilaciclib, to be marketed as Cosela, for protecting bone marrow from chemotherapy damage in adult patients with extensive-stage small cell lung cancer (ES-SCLC).

Cosela will help change the chemotherapy experience for people who are battling ES-SCLC, said Jack Bailey, the companys chief executive officer. G1 is proud to deliver Cosela to patients and their families as the first and only therapy to help protect against chemotherapy-induced myelosuppression.

Myelosuppression, or damage to the bone marrow, is the most serious and life-threatening side effect of chemotherapy. Chemotherapy-induced myelosuppression reduces the bodys essential supply of white blood cells, red blood cells and platelets, and can lead to increased risks of infection, severe anemia and bleeding.

RTP drug firm G1 secures FDA approval for treatment to prevent chemo damage to bone marrow

These complications impact patients quality of life and may also result in chemotherapy dose reductions and delays, said Jeffrey Crawford,M.D., Geller Professorfor Research in Cancer in theDepartment of MedicineandDuke Cancer Institute. In clinical trials, the addition of trilaciclib to extensive-stage small cell lung cancer chemotherapy treatment regimens reduced myelosuppression and improved clinical outcomes.The good news is that these benefits of trilaciclib will now be available for our patients in clinical practice.

Cosela is expected to be commercially available through G1s specialty distributor partner network in early March, the company said.

G1 is committed to helping patients with in theU.S.gain access to treatment with Cosela through access and affordability programs. Patients and healthcare can call the companys support center at 833-418-6663 for information.

Cosela is intended to be given as a 30-minute infusion four hours prior to chemotherapy treatments containing platinum/etoposide or topotecan. About 90 percent of all patients with ES-SCLC receive at least one of these chemotherapy regimens during their treatment, according to G1.

The approval of Cosela is based on data from three randomized, placebo-controlled trials. Data showed that patients receiving Cosela before the start of chemotherapy had less neutropenia, an abnormally low number of neutrophils, white blood cells that fight bacterial and fungal infection.

Data also showed a positive impact on red blood cell transfusions and other myeloprotective measures.

Chemotherapy is the most effective and widely used approach to treating people diagnosed with extensive-stage small cell lung cancer, Bailey said. However, standard-of-care chemotherapy regimens are highly myelosuppressive and can lead to costly hospitalizations and rescue interventions.

To date, oncologists have relied on rescue therapy, a mix of growth factor agents, antibiotics and red blood cell transfusions, to restore bone marrow after it has been damaged by chemotherapy.

By contrast, trilaciclib provides the first proactive approach to myelosuppression through a unique mechanism of action that helps protect the bone marrow from damage by chemotherapy, Crawford said.

Cosela helps protect bone marrow cells from chemotherapy damage by inhibiting cyclin- dependent kinase 4 and 6, two enzymes involved in cancer cell growth. Inhibiting these enzymes temporarily stops hematopoietic stem cells and progenitor cells in the bone marrow from dividing, making them resistant to damage from chemotherapy drugs that target dividing cells.

Bonnie J. Addario, lung cancer survivor, co-founder and board chair of theGo2 Foundation for Lung Cancer, said many people with extensive-stage small cell lung cancerrely on chemotherapy to extend their lives and alleviate their symptoms.

Unfortunately, the vast majority will experience chemotherapy-induced side effects, resulting in dose delays and reductions, and increased utilization of healthcare services, she said.

G1 shares our organizations goal to improve the quality of life of those diagnosed with lung cancer and to transform survivorship among people living with this insidious disease. We are thrilled to see new advancements that can help improve the lives of those living with small cell lung cancer.

About 30,000 small cell lung cancer patients are treated inthe United Statesannually. SCLC, one of the two main types of lung cancer, accounts for about 10 to 15 percent of all lung cancers but is the more aggressive disease, tending to grow and spread faster than the other type, non-small cell lung cancer.

InJune 2020, G1 announced a three-yearco-promotion agreementwithBoehringer Ingelheimfor Cosela in small cell lung cancer in theU.S.andPuerto Rico. G1 will lead marketing, market access and medical engagement initiatives for Cosela whileBoehringer Ingelheimsoncology commercial team will lead sales force engagement initiatives.

G1 will book revenue and retain development and commercialization rights to Cosela and payBoehringer Ingelheima promotional fee based on net sales.

The three-year agreement does not extend to additional indications that G1 is evaluating for trilaciclib: breast, colorectal, bladder and non-small cell lung cancers.

G1 is a 2008 spin-out of the University of North Carolina at Chapel Hill.

The company raised $108 million in an initial public offering of stock in 2017 after receiving more than $95 million in three rounds of venture capital funding. The North Carolina Biotechnology Center provided two early-stage loans totaling $500,000.

G1s stock is traded on the Nasdaq Global Select Market under the ticker symbol GTHX.

(C) N.C. Biotech Center

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After 13 years of trials and tribulations RTP firm G1 wins first FDA approval for cancer drug - WRAL Tech Wire

Bone Marrow Stem Cells Comments Off on After 13 years of trials and tribulations RTP firm G1 wins first FDA approval for cancer drug – WRAL Tech Wire | February 17th, 2021

Job descriptionThe Centre for Stem Cells & Regenerative Medicine is located in Guys Hospital.It is internationally recognized for research on adult and pluripotent stem cells and is a focus for cutting-edge stem cell research currently taking place across the College and its partner NHS trusts, as part of Kings Health Partners. Through the Centre, Kings aims to drive collaboration between scientists and clinicians to translate the potential of stem cells into clinical reality for patients.Applications are invited for a postdoctoral researcher funded as part of the PIs Wellcome Clinical Fellowship, and will work with a dynamic group of scientists focussed on reproductive biology, early embryonic development and the causes of infertility. The post holder will contribute to the regenerative medicine theme and will be involved in the generation and processing of single cell experiments using a variety of techniques.This is an exciting opportunity following our recent work (Sangrithi et al. 2017, Dev Cell & Lau et al. 2020, Dev Cell). The project aims to discover the function of genes on the X-chromosome in male germline stem cells (spermatogonia) and their role in idiopathic and sex chromosome aneuploidy associated infertility. We aim to understand physiological gene regulatory networks functional in spermatogonial stem cells using a combination of single-cell methods, to explain how perturbation in X-gene dosage in SSCs may cause infertility. The postholder will also identify and validate candidate disease bio-markers.This post will be offered on an a fixed-term contract until 05/04/2026This is a full-time post - 100% full time equivalent

Key responsibilities Carry out world class research. Are adept at working in a wet lab setting with experience in designing and executing experiments. Familiarity in single cell work nucleic acid manipulation is desirable Communicate results effectively in writing and orally Contribute to publications arising from the research projects Keep clear and up-to-date records of work Attend and present at seminars, journal clubs and conferences Contribute to collaborative atmosphere of the department Share skills by training others Comply with all relevant safety legislation to ensure a safe working environment Take part in public engagement activities To support grant writing, for maintaining the continual research in this domain, e.g. Fellowships Post holder will be expected to plan and prioritise their own workload, with competing and shifting priorities under pressure of deadlinesThe above list of responsibilities may not be exhaustive, and the post holder will be required to undertake such tasks and responsibilities as may reasonably be expected within the scope and grading of the post.

Skills, knowledge, and experience

Essential criteria PhD awarded in the biological sciences Excellent general knowledge of molecular biology Knowledge of cell biology Knowledge of flow cytometry Relevant postdoctoral experience Experience in a molecular biology research lab Excellent record keeping / attention to detail Organized and systematic approach to research Pro-active, enthusiastic, positive attitude Self-motivated, with the ability to work under pressure & to meet deadlines Keen interest in infertility and regenerative medicine Ability to think strategically

Desirable criteria Understanding of the biology of germ cells and embryo development Previous experience in working with the laboratory mouse ES cell culture experience General knowledge of computational tools for single cell RNAseq Ability to make collaborative and independent decisions*Please note that this is a PhD level role but candidates who have submitted their thesis and are awaiting award of their PhDs will be considered. In these circumstances the appointment will be made at Grade 5, spine point 30 with the title of Research Assistant. Upon confirmation of the award of the PhD, the job title will become Research Associate and the salary will increase to Grade 6.Further informationABOUT THE SCHOOLThe School of Basic & Medical Biosciences is led by Professor Mathias Gautel and comprises five departments with a wide range of expertise and interests. Using a bench to bedside approach, the School aims to answer fundamental questions about biology in health and disease and apply this to the development of new and innovative clinical practise, alongside providing a rigorous academic programme for students.DepartmentsThe Centre for Human & Applied Physiological Sciences (CHAPS) uses an integrative and translational research approach focusing on fundamental questions about human physiological function in health and disease to explore 3 research themes: skeletal muscle & aging, sensory-motor control & pain and aerospace & extreme environment adaptation.The Centre for Stem Cells & Regenerative Medicine focuses on cutting-edge stem cell research, how stem cells interact with their local environment and how these interactions are important for developing effective cell therapies in the clinic.The Department of Medical & Molecular Genetics uses cutting-edge technologies and analysis techniques to explore the mechanistic basis of disease, improve diagnostics and understand the epigenetic mechanisms of gene regulation and RNA processing, working from whole population level to complex and rare disease genomesThe Randall Centre of Cell & Molecular Biophysics takes a multi-disciplinary approach at the interface of Biological and Physical Sciences to explore the underlying mechanisms behind common diseases.St Johns Institute of Dermatology seeks to improve the diagnosis and management of severe skin diseases, through a better understanding of the basic pathogenetic mechanisms that cause and sustain these conditions focussing on cutaneous oncology, genetic skin disorders, inflammatory & autoimmune skin disorders, and photomedicine.About the Department of Centre for Stem Cells & Regenerative MedicineThe Centre for Stem Cells & Regenerative Medicine is led by Professor Fiona Watt, whos laboratory comprises approximately 30 research staff and visiting scientists and is internationally recognised for research on adult and pluripotent stem cells. Along with Professor Watts group there are nine other research groups operating at the Centre, bringing the total number of staff to approximately 80 people.Research at the Centre is focused on how stem cells interact with their local environment, or niche. We believe that an understanding of these interactions is important for developing effective cell therapies in the clinic. Located on the Guys Hospital campus, the Centre acts as a focus for cutting-edge stem cell research taking place across the College and its partner NHS Trusts, as part of Kings Health Partners. To facilitate collaborations within Kings and with external partners, we have opened a Stem Cell Hotel where researchers can access specialist equipment and technical support to study stem cell behaviour at single cell resolution. We also host an international seminar series and run the Stem Cells @ Lunch seminar series to share ideas and unpublished data. Our researchers are committed to public engagement and take part in diverse outreach events.Detailed information about the Centre for Stem Cells & Regenerative medicine can be found in the link below:http://www.kcl.ac.uk/lsm/research/divisions/gmm/departments/stemcells/index.aspx

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Research Associate in Stem Cells and Regenerative Medicine job with KINGS COLLEGE LONDON | 246711 - Times Higher Education (THE)

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Usama Gergis, MD, MBA Professor of Oncology Director, Bone Marrow Transplant and Immune Cellular Therapy Sidney Kimmel Cancer Center Thomas Jefferson University Hospital Philadelphia, PA, reviewed that difference in acute and chronic graft-versus-host disease (GVHD) and the treatment available for each.

Targeted OncologyTM: How would you treat a patient with GvHD in the second line?

GERGIS: If you [have a patient with] second-line acute GVHD, your answer should be ruxolitinib [Jakafi] because its the only drug that has been tried in phase 3 trials. If you get a [case of] chronic GVHD, your answer should be ibrutinib [Imbruvica].

What is the efficacy of peripheral blood stem cells (PBSC) versus bone marrow from unrelated donors in patients with acute and chronic GvHD?

[Results from] a phase 3 study of bone marrow versus stem cells for unrelated donors [showed] the acute GVHD population [cumulative incidence] was the same between both.1 For the chronic population, the bone marrow did better [PBSC 53% vs bone marrow 41%; P = .01]. This was published almost 8 years ago, [and it] was reported almost 10 years ago, but we still use stem cells.

This has not changed practices, and the reasons are, number 1, there was more primary graft failure on the bone marrow than the PBSC, and number 2, its pretty involved to do bone marrow harvest, although I have done it for 15 years, at least a few every month.

The benefit of bone marrow versus PBSCand this benefit was only studied in unrelated donors, not in matched related donorswas seen across all organs affected with chronic GVHD except lungs, [gut, and serosa].2 So, there was no real benefit in the lungs.

Can you explain the difference between acute and chronic GvHD?

Chronic GVHD is more complicated and involved than acute GVHD. In acute, you have the skin, gastrointestinal organs, and the liver [that may be affected]. Thats it. In chronic, all the patients other organs can be affected. The patients weight can be affected. [Chronic GVHD is] more debilitating over a long time and [can] go unrecognized for a while. [If a patient is] experiencing acute GVHD, you see them twice a week, whereas if the patient has chronic GVHD, you probably see them once a month. So you can see a very stark change in your patients within that month if they lose 10% of their body weight and they already lost a lot of weight in the period right after [transplantation], so that can be obvious to you.

[In my institution], we have the GVHD clinic where we [grade the patient based on] studying the degree of fibrosis, how many organs are affected, the patients range of motion, and the degrees in range of motion. We do frequent pulmonary function tests and various [other] testing. By looking at all the affected organs, you reach a grade, and that can be mild, moderate, or severe [chronic GVHD].

How do you treat moderate-to-severe chronic GVHD at initial presentation and in the second line?

First-line treatment for chronic GVHD are steroids. For second line, there are many agents [to consider]. Ive tried most of them. I like photopheresis because its not pharmacological, but its pretty involved. Your patient will need a permanent catheter, and they will need to come to the transplant center twice a week, and you see a response after a long time. It takes an average of 50 photopheresis sessions for a response. But the beauty of photopheresis [is that] you could try it with other agents, so its not mutually exclusive. You could use it with ruxolitinib, ibrutinib, or any other agents.

The answer will be ibrutinib [for chronic GVHD], and thats based on the [results of a] phase 2 clinical trial that treated 42 patients with steroid-refractory chronic GVHD, and the efficacy was 69% [best overall response rate], and 31% complete response rate.3

What do you think of these poll results?

Everybody agrees on giving ibrutinib. When I gave this talk a couple months ago, lenalidomide [Revlimid] was not included in the poll. I added it because [recently], a nice study in Blood came out from the National Institutes of Health where they tried lenalidomide at a small dose, 2 mg, in steroid-refractory chronic GVHD. Its a large trial; I think its about 100 patients. Theyve seen responses that are comparable with ibrutinib....I treated a patient for multiple myeloma; he received a transplant for multiple myeloma, and now, 6 months later, he has chronic GVHD and some clonal plasma cells. So for him, I was comforted to know the results of the lenalidomide trial.

How does ruxolitinib play a role in this setting?

Ruxolitinib was reported in the REACH3 trial [NCT03112603] with very good responses in chronic GVHD.4 I think it probably will get approved for that indication. Looking at this study about 2 years ago, nothing was studied well in this indication, and ibrutinib was approved.

REACH3 was a large trial, almost 300 patients, and everybody was randomized to ruxolitinib 10 mg twice a day versus best available treatment. They looked at everybody about 6 months later for response.

What should physicians keep in mind when treating?

Chronic GvHD is pretty involved. Your patients will need a multidisciplinary approach. You need to pay attention to their bones. In the first 100 days post transplant, the average bone aging is 17 years.

So although were trying to treat acute GVHD, viruses, and prevent relapses, [by putting] your patients on some steroids, you are aging your patients bones by 17 years only in the first 100 days. No matter what you do, give your patients vitamin D, calcium, and Fosamax [alendronate sodium].

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Gergis Explains the Differences Between Acute and Chronic GVHD - Targeted Oncology

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First Investigational New Drug (IND) application cleared for NX-2127 in patients with relapsed and refractory B-cell malignancies

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Nurix Therapeutics Reports Fourth Quarter and Fiscal Year 2020 Financial Results and Provides a Corporate Update

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Lumos Pharma appoints new Board member, An van Es-Johansson, M.D., with wealth of experience in rare diseases Lumos Pharma appoints new Board member, An van Es-Johansson, M.D., with wealth of experience in rare diseases

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Lumos Pharma Announces Changes to its Board of Directors

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- More than 20 patients have been dosed with CTX001™ across CLIMB-Thal-111 and CLIMB-SCD-121 to date; completion of enrollment in both trials is expected in 2021 -

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CRISPR Therapeutics Provides Business Update and Reports Fourth Quarter and Full Year 2020 Financial Results

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Major teaching hospital in Grenoble, France demonstrates that ePlex BCID results could have modified antimicrobial treatment in 45% of patients Major teaching hospital in Grenoble, France demonstrates that ePlex BCID results could have modified antimicrobial treatment in 45% of patients

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Study Highlights Potential Clinical Value of ePlex® Blood Culture ID Panels

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WESTLAKE VILLAGE, Calif., Feb. 16, 2021 (GLOBE NEWSWIRE) -- Arcutis Biotherapeutics, Inc. (Nasdaq: ARQT), a late-stage biopharmaceutical company focused on developing and commercializing treatments for unmet needs in immune-mediated dermatological diseases and conditions, or immuno-dermatology, today reported financial results for the quarter and year ended December 31, 2020, and provided a business update.

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Arcutis Announces Fourth Quarter and Full Year 2020 Financial Results and Provides Business Update

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WALTHAM, Mass., Feb. 16, 2021 (GLOBE NEWSWIRE) -- Morphic Therapeutic (Nasdaq: MORF), a biopharmaceutical company developing a new generation of oral integrin therapies for the treatment of serious chronic diseases, today announced that Praveen Tipirneni, M.D., president and chief executive officer of Morphic Therapeutic, is scheduled to participate in a panel discussion on the gastrointestinal microbiome at the 41st Annual Cowen Health Care Conference. The panel discussion will take place at 11:10 AM ET on Tuesday, March 2, 2021.

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Morphic Therapeutic to Participate in GI/Microbiome Panel Discussion at the 41st Annual Cowen Health Care Conference

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DEER PARK, Ill., Feb. 16, 2021 (GLOBE NEWSWIRE) -- Eton Pharmaceuticals, Inc. (Nasdaq: ETON), a specialty pharmaceutical company focused on developing and commercializing innovative treatments for rare pediatric diseases, today announced that company management will be participating in the 10th Annual SVB Leerink Global Healthcare Conference from February 24th through February 26th.

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Eton Pharmaceuticals to Participate in 10th Annual SVB Leerink Global Healthcare Conference

Global News Feed Comments Off on Eton Pharmaceuticals to Participate in 10th Annual SVB Leerink Global Healthcare Conference | February 17th, 2021