Researchersarepoised to makeunprecedentedbreakthroughsinhuman health thanks toadvancesin biomedical and computational sciencesthathave drivencritical tools and technologiessuch as genetic engineering,synthetic biology, andartificial intelligence.

Thats the messageDr. VictorDzau, president oftheU.S.National Academy ofMedicine, delivered to Medicine by Designs fifthannual symposium on Dec. 7 and 8.

Thevirtual event, whichattracted more than 500 registrants from across North America, focused on the theme of better science throughconvergence theintegration of approaches from engineering, science, medicine and other fields to expand knowledge and spark innovation.

I think for younger people, there is really not a more exciting time, in my opinion, to do research than now, because we can really see that some of the initial concepts that people have about health and medicinecan be realizedand truly transform the way we do health andmedicine.

In his talk, Dzau focused on the National Academy of MedicinesHealthy Longevity Global Challenge,an international competition that aims to catalyze transformative ideas and breakthroughs that will extend human healthand lifespan.

That program is one of the inspirations for Medicine by DesignsGrand Questions Program, which seeks to fund bold research that promises dramatically better health outcomes by changing the future of regenerative medicine.

Through our Grand Questions Program, we are thinking about what comes next and how to overcome fundamental problems in regenerative medicine,saidMichael Sefton, executive director of Medicine by Design andUniversity Professorin the department of chemical engineering and applied chemistry and theInstitute of Biomedical Engineeringat the University of Toronto.

We have a broad definition of regenerativemedicine, andpreventing degeneration can be as important as the next cell therapy.

Sefton pointed out that the symposium theme of better science through convergencefocusedon a key aspect of Medicine by Design:That we combine campus and hospital investigators, transformative science and translational elements, junior and senior investigators, and local and international collaborators, to address fundamental problems in regenerative medicine.

Thesymposium also featured a talk byRobert Langer, David H. KochInstitute Professorin the department of chemical engineeringat the Massachusetts Institute of Technology. The most highly cited engineer in history, he spoke about lessons helearnedfromhisscientific and business successes and how he decidedto be his own champion after facing criticism for his novel ideas early in his career.

If you try to do things whether its convergence, or things that a lot of people disagree with you have tohang in there, Langer said.Having good intellectual property has been key toraising the funds to do these things, and medicine is an incredibly expensive thing.

And finally, you really need teams that are super driven, and I think these startup companies have been a wonderful way to do this.

The symposium was organized around four sessions: translation, inflammation, biomaterials andimmunoengineering.Invited speakers from across North AmericaincludedKim Warren(AVROBIO),Kenneth Walsh(University of Virginia),Sarah Heilshorn(Stanford University)andMegan Levings(University of British Columbia).

All speakers fromU of T and its partnerhospitals were lead investigators on Medicine by Designs multi-disciplinary, multi-institution team projects. They included:John Dick,Clinton RobbinsandShaf Keshavjee(University Health Network (UHN));Molly Shoichet(department of chemical engineering and applied chemistry and Institute of Biomedical Engineering);Juan CarlosZiga-Pflcker(Sunnybrook Health Sciences Centre);andAndras Nagy(Sinai Health System).

Ted Sargent, vice-president of research and innovation, and strategic initiatives,and a University Professor in the Edward S. Rogers Sr. department of electrical and computer engineering,opened the symposium by congratulatingMedicine by Design on its successful mid-term review, which was conducted in early 2020 by a panel of international experts and theCanada First Research Excellence Fund(CFREF), which funds Medicine by Design.

Medicine by Design has amplified existing areas ofexcellenceatU of Tandour partner hospitals (Toronto Academic Health Sciences Network),and pushed the boundaries of regenerative medicine to tackle cell-based therapies, strategies for endogenous repair and the use of a stem cell lens to target the triggers of disease,Sargent said. In fact, Medicine by Design is such a compelling collaborative, cross-disciplinary initiative that itis a template fora new class of initiatives at the University ofToronto theInstitutional Strategic Initiativesportfolio whosepurpose is to mobilize ambitious,groundbreaking, collaborative, multi-institutional research networks that tackleimportantresearch problems, buildmajorexternal partnershipsboth with industry and emerging companies as well as with global academic peers;and foster societal impact.

They support the pursuit of grand challenges and bold ideas across disciplinary boundaries,further elevate U of Ts profile in high priority research areas of strategic importance,and enable us to realize transformational impacts on issues of major societal import.

The symposium also offered an opportunity for almost 45trainees to present their research during a poster session.KerstinKaufmann, a post-doctoral fellow in the laboratory ofJohn Dick(Princess Margaret Cancer Centre,UHN), won first place.JonathanLabriola, apost-doctoral fellowinSachdev Sidhuslab(Donnelly Centre for Cellular and Biomolecular Research, U of T), placed second, whileSabihaHacibekiroglu, a post-doctoral fellow in the lab ofAndras Nagy(Lunenfeld-Tanenbaum Research Institute, UHN)placed third.The awards were sponsored by STEMCELL Technologies.

YasamanAghazadeh,a post-doctoral fellow in the labsofCristina Nostro(McEwen Stem Cell Institute, UHN)andSara Nunes Vasconcelos(Toronto General Hospital Research Institute,UHN),won theCCRMTranslation Awardfor the poster with the greatest translational potential.AndAi Tian, a post-doctoral fellow fromJulien Muffatslab (The Hospital for Sick Children), won thePeoples Choice Award, a new award this year that wasdetermined byvotingby symposium attendeesand sponsored byBlueRockTherapeutics.

Funded by a $114-million grant from CFREF, Medicine by Design brings together more than 145principal investigators at the University of Toronto and its affiliated hospitals to work at the convergence of engineering,medicineand science. It 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 andErnest McCulloch.

Regenerative medicine uses stem cells to replace diseased tissues and organs, creating therapies in which cells are the biological product. Regenerative medicine 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.

(Photo of Robert Langer by Jason Alden)

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Medicine by Design symposium highlights importance of convergence in regenerative medicine and human health - News@UofT

The research report on NK Cell Therapy and Stem Cell Therapy Market gives thorough insights regarding various key trends that shape the industry expansion with regards to regional perspective and competitive spectrum. Furthermore, the document mentions the challenges and potential restrains along with latent opportunities which may positively impact the market outlook in existing and untapped business spaces. Moreover, it presents the case studies, including the ones related to COVID-19 pandemic, to convey better understanding of the industry to all the interested parties.

The recent market trend of increasingly using NK Cell Therapy and Stem Cell Therapy for understanding the development of a disease extensively fuel the growth of this market in the coming years. Another trend that will aid the growth of the global NK Cell Therapy and Stem Cell Therapy market is the escalating demand for personalized medicine. Extensive investments are being made by various organizations, pharmaceutical companies, and governments for the research and development of drugs, and this is another trend that is benefiting the growth of the global NK Cell Therapy and Stem Cell Therapy market. This is because NK Cell Therapy and Stem Cell Therapy techniques enable researchers to compare NK Cell Therapy and Stem Cell Therapy changes between disease samples and normal samples. Public health can thus be analyzed as the changes in NK Cell Therapy and Stem Cell Therapy are influenced by internal biological system and environment directly.

Request a sample of this premium research: https://www.bigmarketresearch.com/request-sample/3930448?utm_source=Nilesh-MCC

The report covers extensive analysis of the key market players in the market, along with their business overview, expansion plans, and strategies. The key players studied in the report include: Osiris Therapeutics, Chiesi Pharmaceuticals, Molmed, Takeda Pharmaceutical, Medi-post, Chipscreen Biosciences, Affimed NV, JCR Pharmaceutical, Pharmicell, Innate Pharma SA, NuVasive, Anterogen, Altor BioScience Corporation.

NK Cell Therapy and Stem Cell Therapy Market Segmentation:

In market segmentation by types of NK Cell Therapy and Stem Cell Therapy, the report covers-

NK Cell TherapyStem Cell Therapy

In market segmentation by applications of the NK Cell Therapy and Stem Cell Therapy, the report covers the following uses-

Hospital & clinicsRegenerative medicine centersDiagnostic centersResearch institutesOthers

Regional Analysis for NK Cell Therapy and Stem Cell Therapy Market-:

1) North America- (United States, Canada)

2) Europe- (Germany, France, UK, Italy, Russia, Spain, Netherlands, Switzerland, Belgium)

3) Asia Pacific- (China, Japan, Korea, India, Australia, Indonesia, Thailand, Philippines, Vietnam)

4) Middle East & Africa- (Turkey, Saudi Arabia, United Arab Emirates, South Africa, Israel, Egypt, Nigeria)

5) Latin America- (Brazil, Mexico, Argentina, Colombia, Chile, Peru)

The report provides insights on the following pointers :

Market Penetration: Comprehensive information on the product portfolios of the top players in the Supply Chain Analytics market.

Product Development/Innovation: Detailed insights on the upcoming technologies, R&D activities, and product launches in the market

Competitive Assessment: In-depth assessment of the market strategies, geographic and business segments of the leading players in the market

Market Development: Comprehensive information about emerging markets. This report analyzes the market for various segments across geographies

Market Diversification: Exhaustive information about new products, untapped geographies, recent developments, and investments in the Supply Chain Analytics market

NOTE: Our analysis involves the study of the market taking into consideration the impact of the COVID-19 pandemic. Please get in touch with us to get your hands on an exhaustive coverage of the impact of the current situation on the market. Our expert team of analysts will provide as per report customized to your requirement.

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Table of Content

Chapter 1 NK Cell Therapy and Stem Cell Therapy Introduction and Market Overview

Chapter 2 Executive Summary

Chapter 3 Industry Chain Analysis

Chapter 4 Global NK Cell Therapy and Stem Cell Therapy Market, by Type

Chapter 5 NK Cell Therapy and Stem Cell Therapy Market, by Application

Chapter 6 Global NK Cell Therapy and Stem Cell Therapy Market Analysis by Regions

Chapter 7 North America NK Cell Therapy and Stem Cell Therapy Market Analysis by Countries

Chapter 8 Europe NK Cell Therapy and Stem Cell Therapy Market Analysis by Countries

Chapter 9 Asia Pacific NK Cell Therapy and Stem Cell Therapy Market Analysis by Countries

Chapter 10 Middle East and Africa NK Cell Therapy and Stem Cell Therapy Market Analysis by Countries

Chapter 11 South America NK Cell Therapy and Stem Cell Therapy Market Analysis by Countries

Chapter 12 Competitive Landscape

Chapter 13 Industry Outlook

Chapter 14 Global NK Cell Therapy and Stem Cell Therapy Market Forecast

Chapter 15 New Project Feasibility Analysis

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Global NK Cell Therapy and Stem Cell Therapy Market: Development, Current Analysis and Estimated Forecast to 2025 - The Courier

GALWAY, Ireland, & SAN DIEGO, Calif.--(BUSINESS WIRE)--ONK Therapeutics Ltd, an innovative natural killer (NK) cell therapy company, today announced that it has secured three new exclusive option license agreements which strengthen its off-the-shelf, dual-targeted natural killer (NK) cell therapy platform and extend its pre-clinical pipeline to four programs across both hematological and solid tumors.

The first option agreement, with Cellerant Therapeutics, gives exclusive rights to a humanized CLEC12A scFv binder. CLEC12A is strongly expressed by blasts in the majority of AML patients. The option to license has enabled ONK to expand its pre-clinical product portfolio, launching a fourth program (ONKT104). This dual-targeted approach combines the CLEC12A CAR with a TNF-related apoptosis-inducing ligand variant (TRAILv) targeting death receptor 4 (DR4).

While expressed on leukemic stem cells, CLEC12A is absent from normal hematopoietic stem cells and we thus expect that our dual-targeted NK cell therapy approach should enable safe targeting, with a reduced risk of prolonged aplasia in AML, said Prof Michael ODwyer MD, ONK Therapeutics co-founder, and CSO.

The second agreement in-licenses a humanized, tumor-specific antibody targeting an aberrantly glycosylated tumor-associated form of MUC1 (TA-MUC1) from Glycotope GmbH. Multiple solid tumor types express the mucin MUC1, including non-small cell lung cancer, breast cancer, and ovarian cancer. This antibody will be integrated into ONKs pre-clinical program ONKT103, for solid tumors.

Non-selective targeting of MUC1 could be problematic since the target is also expressed by healthy tissues, but ODwyer explains how ONKs dual-targeted approach can be used to address this. We have designed a CAR tailored to the glycosylation pattern distinct to tumor-associated MUC1 with specific recognition of the carbohydrate antigens Tn and T on MUC1, the expression of which is restricted to cancer cells. Glycotope has identified the glycosylation pattern as a way to unlock the potential of TA-MUC1 as a solid tumor target. ONK is thus set to bring the natural benefits of NK cells over T cells to bear on TA-MUC1, in a tumor-specific fashion, while also further boosting efficacy and countering resistance through the use of our TRAIL variant targeting DR5, he said.

ONKs unique platform approach combines the expression of a chimeric antigen receptor (CAR) and a high affinity, membrane-bound TRAILv. The incorporation of these two humanized scFvs has the potential to minimize the risk of immunogenicity in the allogeneic setting.

ONK is also exploring several innovative strategies to improve the homing of NK cells. This is an important consideration as ex-vivo expansion can lead to changes in chemokine receptor expression. Through this new license agreement with the NIH, ONK plans to enforce the expression of CCR7, which is downregulated on NK cell expansion. This may improve the homing of NK cells to lymph nodes and is expected to be particularly useful for ONKs off-the-shelf CD19 program targeting B cell lymphoma, ONKT101, which is partnered with Avectas.

ONK is making rapid progress since it announced its most recent financing in October. Chris Nowers, ex Kite Pharma Head of Europe, who joined at that time as Chief Executive Officer, said: The recent American Society of Hematology meeting highlighted the NK cell therapy area as offering great hope as the next generation of advanced cell therapies. We believe our best-in-class off-the-shelf, dual-targeted NK cell therapy platform has the potential to improve performance and overcome some of the shortcomings seen with earlier approaches. These new licensing activities strengthen and expand our programs and illustrate our ambition and strategy to become a leader in this exciting field.

The company recently expanded its operations into the USA, moving into JLABS @ San Diego, Johnson & Johnson Innovations flagship facility, at the heart of San Diegos precision medicine and cell therapy cluster. This represents a second facility that complements its main R&D team and operations in Galway, Ireland. The companys recruitment drive across both facilities has been rapid and the company continues to expand its capability in key areas, including NK cell biology, construct design, gene editing, and process development.

-Ends-

ONK Therapeutics http://www.onktherapeutics.com ONK Therapeutics Ltd is an innovative cell therapy company dedicated to developing the next generation of off-the-shelf, dual-targeted NK cell therapies targeting solid and hematological cancers.

The company was founded in 2015, by Prof. ODwyer MD, of NUI Galway, an expert in translational multiple myeloma research, the tumor microenvironment, and exploitation of NK cells as cellular immunotherapy. Its core proprietary platform is based on a dual-targeted NK cell expressing both a chimeric antigen receptor (CAR) targeting a known tumor antigen and a TNF-related apoptosis-inducing ligand variant (TRAILv) targeting the death receptor pathway (i.e. DR4 or DR5). This unique approach has the potential to enhance efficacy by addressing both intrinsic (e.g. CAR engagement of a tumor-specific antigen) and extrinsic (e.g. signaling through the death receptor pathway) apoptotic pathways and to reduce the susceptibility to possible target antigen escape through the engagement of tumor antigen-independent TRAILv.

Its pre-clinical pipeline comprises four programs;

In addition to the unique dual-targeted NK cell therapy platform, the company has a strong research focus on strategies to enhance homing and persistence, and overcome exhaustion, including the exploration of proprietary gene edits, such as the deletion of checkpoint inhibitory receptors in NK cells.

ONK Therapeutics is headquartered in the med-tech hub of Galway, Ireland, with a wholly-owned US subsidiary, ONK Therapeutics, Inc. based at JLabs @ San Diego. Shareholders include Acorn Bioventures, ALSHC (principally Seamus Mulligan), and Enterprise Ireland.

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About Avectas - http://www.avectas.com Avectas is a cell engineering technology business that has developed a unique delivery platform, Solupore to enable the ex vivo manufacture of cell therapy products, which have high in-vivo functionality.

Glycotope http://www.glycotope.com Glycotope is a biotechnology company utilizing a proprietary technology platform to develop highly tumor-specific monoclonal antibodies called GlycoBodies. GlycoBodies bind to targets (GlycoTargets) tumor-specific carbohydrate structure dependent, enabling the development of highly-specific immunotherapies across a broad range of cancer indications. Glycotope has to date discovered in excess of 150 GlycoTargets with GlycoBodies against eight of these targets currently under development.

Each GlycoBody can be developed in an array of modalities with different modes of action providing a unique offering in the (immuno) oncology space. Currently, six clinical and pre-clinical programs based on the GlycoBody technology are under development by Glycotope or its licensing partners.

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ONK Therapeutics Announces Three Exclusive Option License Agreements, Which Extend and Strengthen its Dual-Targeted NK Cell Therapy Pipeline -...

Cancer cells pose an uncanny ability to make new cells and dodge drugs, "somewhat like would-be robbers hacking the bank's alarm code," one doctor explains. But researchers at Cincinnati Children's Hospital Medical Center have figured out how cancer cells rewire themselves and, in turn, how to possibly overcome drug resistance.

This drug resistance may explain why some acute myeloid leukemia (AML) and other cancer patients suffer fatal relapses despite many improvements in leukemia outcomes over the years, according to a Children's news release.

"Overcoming resistance to therapy remains a holy grail of leukemia treatment," says Yi Zheng, Ph.D., director, experimental hematology and cancer biology at Cincinnati Children's. Zheng and his colleagues have now discovered a way to boost the effectiveness ofmTOR inhibitors, which prohibit unwanted cell proliferation.

"While the latest study is based on mouse models, building upon the findingspublished Dec. 21, 2020, in PNASeventually could improve outcomes for people with AML, and possibly other forms of cancer," a release says.

What Happens When Treatments Target mTOR?

"Using a novel mouse model, we have learned that deleting the mTOR gene prompts blood stem cells to multiply rapidly to open other pathways to continue producing new blood cells," says Zheng, the study's senior author. "We also found that leukemia cells use a similar response to continue multiplying despite mTOR-inhibiting treatments."

He says attacking mTOR essentially sets off alarms among hemopoietic stem cells (HSCs), which act like blood cell factories deep in bone marrow. Then the cells themselves produce a flood of new, re-wired blood cells. These re-wired stem cells, treated with mTOR inhibitors, can begin multiplying, rendering mTOR inhibitor drugs useless.

The co-authors say mTOR treatment resistance can be counteracted by inhibiting activity of the MNK, CDK9 or c-Myc genes. So-called BET inhibitors can act against c-Myc activity. Other inhibitors that are in clinical trials can act against CDK9.

Next Steps

Scientists at Cincinnati Childrens have already launched some of the research needed to prepare the combination therapies for in vivo test leading to human clinical trials, the news release says. That process will take time, but since mTOR inhibitors have been widely tested in clinical trials, investigators have a head start on exploring combination therapies.

Longer term, the findings may extend beyond AML, Zheng says, because mTOR has been a recognized target in most human cancers, including solid tumors like brain tumors.

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New Combination Therapy Tested By Children's May Offer Hope For Leukemia Patients - WVXU

ASHLEY Cain has revealed more than 80,000 have people joined the stem cell register after he pleaded for the public's help to save his baby daughter's life.

Little Azaylia was diagnosed with one of the rarest forms of leukaemia, AML [Acute Myeloid Leukaemia] , last month and needs a stem cell transplant to beat the disease.

7

Ashley, 30, called upon his fans to help him and his partner Safiyya Vorajee find a donor - along with the charitable organisations DKMS and Anthony Nolan - for the four-month-old tot.

In a new interview, Ashley and Safiyya have spoken for the first time at their shock at the overwhelming amount of support they received and opened up about the turmoil they're going through as they watch their baby daughter fight for her life.

Former footballer Ashley said: "When Azaylia needed a donor the amount of people who came together straight away to order test kits, do the tests and then send them back, was crazy.

7

"The DKMS and Anthony Nolan probably get around 30,000 to 40,000 registers a year. We got 80,000 people in a single weekend.

"It's now topping 100,000. And not only are they helping Azaylia, they are helping the thousands of people who also need donors.

"Social media can be such a cruel and cynical place at times but this has made me realise how beautiful it can be and how beautiful the people using it can be.

"For that support we will be forever grateful."

Ashley and Safiyya are currently living in a hotel next to Birmingham Children's Hospital to ensure they can be with their daughter around the clock.

Because of Covid-19 restrictions the couple can not be with their baby daughter together so spend 24 hours a day with her on rotation so they can both spend equal amounts of time with her.

7

When they first discovered Azaylia was sick, Ashley said the couple were warned to expect the worst.

He explained: "When Azaylia first got diagnosed it looked really bleak.

"Me and you as normal people would have a white cell count of five. Someone with leukaemia, even an adult, would have a white cell count of 40.

"Azaylia had a white cell count of 200. Plus tumours in her lungs, kidneys and stomach.

"I am strong but having that news was something I never thought I would have to go through. It broke me. I was a broken man."

7

Azaylia has since undergone two rounds of chemotherapy and is responding well to treatment.

However she will need a life-saving transplant in order to beat the disease once and for all.

Ashley added: "Its very rare to have leukaemia in babys as young as Azaylia, she is the only baby on the ward.

7

"And she also has AML, the most aggressive type of leukaemia, which is even rarer.

"And what is even rarer again is the fact that she had tumours on her stomach, her lungs and her kidneys. And that her white blood cell count was so high.

"Realistically for her to have even got to this point is an absolute miracle."

Ashley and Safiyya also wanted to speak publicly to warn other parents about the signs to look out for after doctors repeatedly misdiagnosed Azaylia.

Ashley said: "We had back and forth to the doctors over the course of four weeks. She had cold type symptoms and we got told she had a blocked nose. At points we were pleading with the doctors to let us come in because we knew something wasnt right.

"Then we were told she had colic and then they told us she had constipation. We did all the things to treat that and then we noticed the mottling."

Going back to the beginning, Safiyya continued: There was an occasion four weeks after Azaylia was born when there was red spotting in her nappy.

7

I went to the doctors and they told me to keep an eye on it. Then a little while after she had a really bloated stomach. I called up the doctor and then I took them in for her first course of injections.

Prior to her having her six week injection the doctor gave her a once over. I told the doctor about her stomach and that her chest was really heavy, it sounded like her chest was rattling it was like she couldnt breathe properly.

Her eyes were gunking up too, to the point where they were really swollen. It was making her face then swollen.

The tummy was so hard, it was like a hard ball, obviously now that was all the tumours. They gave her laxatives to try and sort it out, they gave us colic mixture, they gave us a spray for her nose

To know a doctor has felt over all the symptoms that were there, and there were two-three-four-five doctors we saw. The doctor I sent the picture of the mottling to was an on call doctor and he was the one who said take her immediately to A and E.

7

The couple now credit Azaylia for giving them the strength to continue their appeal for donors.

Ashley added: We call Azaylia little lion, she has the face of an angel and the heart of a lion.

It is personally inspiring every day for us to see her sheer strength. Her waking up smiling every day, no matter what she is going through, gives us strength.

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We also have to thank Birmingham Childrens hospital. We heard a lot about them before and everything we had heard was right.

From the nurses to the cleaners to the doctors, everyone goes the extra mile. They do incredible work but they also make you feel so at home.

Its those little touches and the extra effort they put into helping you which they dont get paid for. They all go the extra mile. To everyone on ward 18, they are just incredible.

If you want to help, you can join the register here.

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Ashley Cain says over 80,000 people registered for stem cell donation in 48 hours after appeal to save baby - The Sun

WHIPPANY, N.J. & SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Bayer and Atara Biotherapeutics, Inc. (Nasdaq: ATRA) today announced an exclusive worldwide license agreement and research, development and manufacturing collaboration for mesothelin-directed CAR T-cell therapies for the treatment of solid tumors. The agreement includes the development candidate ATA3271, an armored allogeneic T-cell immunotherapy, and an autologous version, ATA2271, for high mesothelin-expressing tumors such as malignant pleural mesothelioma and non-small-cell lung cancer.

Atara is a pioneer in allogeneic T-cell immunotherapy with industry-leading allogeneic cell manufacturing processes and CAR T technologies. The licensed technology leverages Atara's novel, proprietary Epstein-Barr Virus (EBV) T-cell platform combined with CAR T technologies targeting mesothelin to improve efficacy, persistence, safety, and durability of response.

This transaction is a fundamental element of Bayers new Cell & Gene Therapy strategy. It strengthens our development portfolio through allogeneic cell therapies and consolidates our emerging leadership in the field, said Wolfram Carius, Head of Bayers Cell & Gene Therapy Unit. We look forward to collaborating with Atara to develop off-the-shelf CAR T-cell therapies for patients with difficult-to-treat cancers.

This exciting collaboration between Atara and Bayer will accelerate the development of mesothelin-targeted CAR T-cell therapies for multiple solid tumors and helps us advance the power of our allogeneic cell therapy platform to patients as quickly as possible, said Pascal Touchon, President and CEO Atara. Bayers proven track record in oncology global development and commercialization, and growing presence in cell and gene therapy, enhances Ataras capabilities and complements our leading allogeneic T-cell platform.

Under the terms of the agreement, Atara will lead IND (Investigational New Drug)-enabling studies and process development for ATA3271 while Bayer will be responsible for submitting the IND and subsequent clinical development and commercialization. Atara will continue to be responsible for the ongoing ATA2271 phase 1 study, for which an IND filing has been accepted and the clinical trial has been initiated. Atara will receive an upfront payment of USD 60 million and is eligible to receive payments from Bayer upon achievement of certain development, regulatory and commercialization milestones totaling USD 610 million, as well as tiered royalties up to low double-digit percentage of net sales.

As part of the transaction, Atara will also provide translational and clinical manufacturing services to be reimbursed by Bayer. In addition, for a limited period of time, Bayer has a non-exclusive right to negotiate a license for additional Atara CAR T product candidates.

Atara Conference Call and Webcast Information

Atara will hold a conference call at 8:30 a.m. ET. Analysts and investors can participate in the conference call by dialing (888) 540-6216 for domestic callers and (734) 385-2715 for international callers, using the conference ID 3995182.

A live audio webcast can be accessed by visiting the Investors & Media News & Events section of atarabio.com. An archived replay will be available on the Company's website for 30 days following the live webcast.

About CAR-T cell therapy

T cells are a type of white blood cell that are critical in eliminating the body of abnormal and cancerous cells in healthy individuals. In cancer patients, these T cells frequently fail to either recognize or effectively engage cancer cells. CAR T-cell therapies involve engineering a human T cell to express a chimeric antigen receptor (CAR) that increases its ability to recognize cancer cells. These therapies use the immune system to fight cancer and have the potential to disrupt cancer care and potentially even provide a cure. Mesothelin is a tumor-specific antigen that is commonly expressed at high levels on the cell surface in many aggressive solid tumors and is an attractive target for immune-based therapies, including CAR T therapy.

About Bayers new Cell & Gene Therapy (C>) Unit

In order to build up its presence in C>, Bayer is strengthening its internal C> capabilities. At the same time, the company is pursuing external strategic collaborations, technology acquisitions and licensing. The goal is to build robust platforms with broad application across different therapeutic areas. Strategically, Bayer focuses on selected areas of C>, such as stem cell therapies (with focus on induced pluripotent cells or iPSCs), gene augmentation, gene editing and allogeneic cell therapies in different indications. Leveraging external innovation together with the expertise of the teams at Bayer represents a key value-driver, especially in the highly dynamic and competitive field of C>. Bayers operating model for C>, where partners operate autonomously and are fully accountable to develop and progress their portfolio and technology, is essential for preserving their entrepreneurial culture and positions Bayer as a partner of choice. The role of Bayers C> Platform is to steer strategically, ensuring the different parts of the organization complement each other and combining the best in Biotech and Pharma know-how. As part of the Pharmaceuticals Division, the C> Platform will combine multiple backbone functions providing support across the entire value chain for the research and development of cell and gene therapies. This includes expertise in Research and Preclinical Development, CMC (Chemistry, Manufacturing and Controls), Clinical Development, Commercial, Strategy Implementation and Project Management. With a high level of flexibility, it will orchestrate operations from science to launch in order to generate and maintain a sustainable pipeline, with the goal to bring new products to market as fast as possible.

About Ataras Mesothelin CAR-T Franchise

Two of Ataras investigational CAR T immunotherapy programs, developed in collaboration with Memorial Sloan Kettering Cancer Center (MSK), target mesothelinthe autologous ATA2271 program and allogeneic ATA3271 program. Mesothelin is a tumor-specific antigen that is commonly expressed at high levels on the cell surface in many aggressive solid tumors including mesothelioma, non-small cell lung cancer, ovarian cancer and pancreatic cancer.

Both ATA2271 and ATA3271 are engineered for use in solid tumors as they incorporate Ataras novel inclusion of both a PD-1 DNR construct to overcome checkpoint inhibition and a 1XX costimulatory domain on the CAR (chimeric antigen receptor) to enhance expansion and functional persistence of the CAR T cells. ATA3271, the allogeneic version of this CAR T, leverages Ataras EBV T-cell platform and is currently in IND-enabling studies. ATA2271, the autologous version has enrolled the first patient in an open-label, single-arm Phase 1 clinical study in November 2020.

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2019, the Group employed around 104,000 people and had sales of 43.5 billion euros. Capital expenditures amounted to 2.9 billion euros, R&D expenses to 5.3 billion euros. For more information, go to http://www.bayer.com

About Atara

Atara Biotherapeutics, Inc. is a pioneer in T-cell immunotherapy leveraging its novel allogeneic EBV T-cell platform to develop transformative therapies for patients with serious diseases including solid tumors, hematologic cancers and autoimmune disease. With our lead program in Phase 3 clinical development, Atara is the most advanced allogeneic T-cell immunotherapy company and intends to rapidly deliver off-the-shelf treatments to patients with high unmet medical need. Our platform leverages the unique biology of EBV T cells and has the capability to treat a wide range of EBV-associated diseases, or other serious diseases through incorporation of engineered CARs (chimeric antigen receptors) or TCRs (T-cell receptors). Atara is applying this one platform to create a robust pipeline including: tab-cel (tabelecleucel) in Phase 3 development for Epstein-Barr virus-driven post-transplant lymphoproliferative disease (EBV+ PTLD); ATA188, a T-cell immunotherapy targeting EBV antigens as a potential treatment for multiple sclerosis; and multiple chimeric antigen receptor T-cell (CAR T) immunotherapies for both solid tumors and hematologic malignancies. Improving patients lives is our mission and we will never stop working to bring transformative therapies to those in need. Atara is headquartered in South San Francisco and our leading-edge research, development and manufacturing facility is based in Thousand Oaks, California.

For additional information about the company, please visit atarabio.com and follow us on Twitter and LinkedIn.

Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayers public reports which are available on the Bayer website at http://www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

Forward-Looking Statements

This press release contains or may imply 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. For example, forward-looking statements include statements regarding: the development, timing and progress of ATA2271 or ATA3271, the potential characteristics and benefits of ATA2271 or ATA3271, and the progress and results of, and prospects for, any collaboration involving ATA2271 or ATA3271, including the potential financial benefits to Atara thereof. Because such statements deal with future events and are based on Ataras current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Atara could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including, without limitation, risks and uncertainties associated with the costly and time-consuming pharmaceutical product development process and the uncertainty of clinical success; the COVID-19 pandemic, which may significantly impact (i) our business, research, clinical development plans and operations, including our operations in South San Francisco and Southern California and at our clinical trial sites, as well as the business or operations of our third-party manufacturer, contract research organizations or other third parties with whom we conduct business, (ii) our ability to access capital, and (iii) the value of our common stock; the sufficiency of Ataras cash resources and need for additional capital; and other risks and uncertainties affecting Ataras and its development programs, including those discussed in Ataras filings with the Securities and Exchange Commission (SEC), including in the Risk Factors and Managements Discussion and Analysis of Financial Condition and Results of Operations sections of the Companys most recently filed periodic reports on Form 10-K and Form 10-Q and subsequent filings and in the documents incorporated by reference therein. Except as otherwise required by law, Atara disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date hereof, whether as a result of new information, future events or circumstances or otherwise.

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Bayer and Atara Biotherapeutics Enter Strategic Collaboration for Mesothelin-Targeted CAR T-cell Therapies for Solid Tumors - Business Wire

Newswise LOS ANGELES (Dec. 4, 2020) -- Cedars-Sinai has launched a center to manufacture the next generation of stem cell and gene therapies that will enable biomedical researchers, government medical programs, commercial entities and others to develop new biologic drugs and propel novel disease discoveries.

Biologic drugs are produced from living organisms or contain components of living organisms, such as cells, proteins or genes.

"TheCedars-Sinai Biomanufacturing Centerleverages our world-class stem-cell expertise, which already serves scores of clients, to provide a much-needed biomanufacturing facility in Southern California," saidClive Svendsen, PhD, executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute. "It is revolutionary by virtue of elevating regenerative medicine and its therapeutic possibilities to an entirely new level-repairing the human body."

Among the facility's initial clients is the Department of Defense, which has asked Cedars-Sinai scientists to manufacture banks of stem cells from multiple healthy volunteers for later use in repairing vascular injuries sustained by military personnel in combat.

The core technology of the Cedars-Sinai Biomanufacturing Center involves production of specialized cells known as induced pluripotent stem cells, or iPSCs. Scientists make iPSCs by genetically converting adult blood cells into cells that can self-renew indefinitely and differentiate into nearly any type of tissue. Each resulting cell carries the exact DNA of the person who donated the blood sample.

"IPSCs are powerful tools for understanding human disease and developing therapies," saidDhruv Sareen, PhD, executive director of the Biomanufacturing Center and director of the induced pluripotent stem cell facility at the Regenerative Medicine Institute. "These cells enable us to truly practiceprecision medicineby developing drug treatments tailored to the individual patient or groups of patients with similar genetic profiles."

The Biomanufacturing Center is designed to address a critical bottleneck in bringing cell- and gene-based therapies to the clinic. It will help relieve a nationwide shortage of facilities that can scale up production of cells for drug products that consistently meet current good manufacturing practice (cGMP) standards for strength, quality, and purity. These standards, set by the U.S. Food and Drug Administration, must be met when producing pharmaceuticals for use in humans.

To comply with the federal standards, the new Cedars-Sinai center features nine "clean rooms" that maintain rigorously aseptic conditions for handling of all biomaterials. These rooms are supported by staging areas, gowning rooms, quality control laboratories and storage rooms with ample freezers and liquid nitrogen tanks.

Other sections of the Biomanufacturing Center are devoted to research and production of iPSC cells, technology and development, training and collaboration laboratories, offices, and facilities maintenance equipment. Overall, the center occupies more than 28,000 square feet.

"Our expansive facilities provide complete, end-to-end support of biomedical research and development of cell therapies that are 'living medicines,'" said Sareen, assistant professor of Biomedical Sciences. "We enable our clients to explore and create new types of cells, use them to make discoveries about diseases and transform the resulting biomaterials into cGMP-compliant therapies for testing in clinical trials."

The recent grand opening of the Biomanufacturing Center, hosted on a virtual platform by Cedars-Sinai leadership, was attended by representatives of local and federal governments, biotechnology companies, funding organizations and other stakeholders. It was followed by another Cedars-Sinai virtual event, a "Symposium on Translational Medicine and Biomanufacturing," that drew world-renowned keynote speakers from academia and industry and hundreds of attendees to explore the latest developments in these fields.

"Our new Biomanufacturing Center reaffirms Cedars-Sinai's commitment to deliver the finest clinical care for our patients-and patients everywhere-by expanding the frontiers of medical science," said Svendsen, professor of Biomedical Sciences and Medicine.

Read more on the Cedars-Sinai Blog:What Are Induced Pluripotent Stem Cells?

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New Cedars-Sinai Biomanufacturing Center to Spur Cell Therapies - Newswise

Treatment with an off-the-shelf CAR T-cell therapy that targets B-cell maturation antigen (BCMA), ALLO-715, elicited responses in heavily pretreated patients with relapsed/refractory multiple myeloma in early findings from a first-in-human study presented at the 2020 ASH Meeting.1

The therapy generated responses in 6 of 10 patients (60%), including a very good partial-plus response (VGPR+) in 4 patients (40%), who were treated with ALLO-715 at a dose of 320 x 106 CAR cells plus a lymphodepleting regimen that included ALLO-647, an anti-CD52 monoclonal antibody, during the ongoing phase 1 UNIVERSAL study (NCT04093596).1

The findings mark the first results for an allogeneic CAR therapy directed at BCMA, said lead study author Sham Mailankody, MBBS, a medical oncologist and investigator in the Cellular Therapeutics Center at Memorial Sloan Kettering Cancer Center in New York, New York. BCMA, which is highly expressed on plasma and multiple myeloma cells, has sparked intensive research interest.2

These results demonstrate the feasibility and safety of an off-the-shelf CAR T cell therapy for multiple myeloma. In this first report of an allogeneic BCMA CAR T-cell therapy, we show that nearly 90% of patients were treated within 5 days of enrollment and without needing any bridging therapy, Mailankody said.

Allogeneic CAR therapy offers the potential for scalable manufacturing for on-demand treatment with shorter waiting times, which would overcome some of the logistical challenges posed by autologous CAR therapy, Mailankody said. The T cells needed for ALLO-715 are harvested from healthy donors and genetically engineered to express CARs aimed at specific cancer targets, according to Allogene Therapeutics, the company developing the therapy.3

ALLO-715 includes a human-derived single-chain variable fragment anti-BCMA cell with a 4-1BB costimulatory domain. Mailankody said the 2 key attributes of the construct are a knockout of CD52, which allows for selective lymphodepletion with ALLO-647 to prevent graft rejection without affecting the CAR T cells, and a knockout of the TRAC gene, which also minimizes the risk of graft-versus-host disease (GVHD).1

The UNIVERSAL study, which is being conducted at 11 cancer centers in the United States, is recruiting patients with multiple myeloma who have received 3 or more prior therapies, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 agent, and are refractory to their last treatment. Participants must have an ECOG performance status score of 0 or 1.

The dose escalation portion of the study is testing ALLO-715 as a single infusion across 4 doses: 40, 160, 320, or 480 x 106 CARs. Lymphodepletion regimens consist of fludarabine (F; 30 mg/m2/day) plus cyclophosphamide (C; 300 mg/m2/day) given on 3 days with ALLO-647 (A; 13-30 mg x 3 days; FCA) or cyclophosphamide plus ALLO-647 (CA).

Among the 35 patients enrolled at the time of the presentation, 4 became ineligible because of organ failure due to rapidly progressing disease. Of 31 patients in the safety population, the median age was 65 years (range, 46-76). Nearly half of the patients (48%) have high-risk cytogenetics and 23% had extramedullary disease. The efficacy population at data cutoff on October 30, 2020, comprised 26 patients across the 4 dosing levels, with a median follow-up of 3.2 months.1

The overall response rate (ORR) varied across dosing cohorts and lymphodepleting regimens. No responses were observed among 3 patients each who received CARs at 40 x 106 with FCA or 160 x 106 with CA, both with low-dose ALLO-647. The ORRs were 50% in 4 patients who received CARs at 160 x 106 with lowALLO-647 FCA; 33% in 3 at 480 x 106 with lowALLO-647 FCA; and 67% in 3 at 320 x 106 with lowALLO-647 CA.

The most robust responses were seen among those who received ALLO-647 at 320 x106. For this cohort, the ORR was 60% among 10 patients, including 3 of 6 who received CARs with lowALLO-647 FCA and 3 of 4 who had the therapy with highALLO-647 FCA. Overall, 6 patients had a VGPR+, defined as stringent complete response, complete response, or VGPR. These included 1 at 160, 4 at 320, and 1 at 480 10 x 106 CARs. Of the VGPR+ patients, 5 were negative for measurable residual disease. Additionally, 6 of 9 patients treated at the 320 or 480 x 106 dose levels remain in response.

Mailankody highlighted the experience of 1 participant, a 71-year-old man whose myeloma had progressed after undergoing 9 prior lines of therapy including autologous stem cell transplant and an experimental BCMA-targeted therapy. The patient received a conditioning regimen of FCA with low-dose ALLO-647 and ALLO-715 at 320 x 106. He reached a VGPR on day 14 that deepened to a stringent complete response by day 28 that remains in effect at 6 months, while experiencing grade 1 cytokine release syndrome (CRS).

The patient is clinically doing very well and is back at work, Mailankody said.

Among 31 patients in the safety population, most adverse effects were of grade 1 or 2 severity. These included CRS in 14 patients (45%) and infusion-related reactions to ALLO-647 in 7 patients (23%). The use of drugs to manage CRS also was low, at 19% for tocilizumab and 10% for steroids.

All-grade infections were reported in 13 patients (42%), including grade 3 events in 4 (13%). One patient (3%) died from a presumed fungal pneumonia related to progressive disease and the CA conditioning regimen but unrelated to ALLO-715. There were no instances of neurotoxicity or GVHD.

Notably, the fact that we did not see any GVHD is encouraging for an off-the-shelf allogeneic product, Mailankody said.

In response to a question from a conference attendee, Mailankody said it is too soon to compare efficacy levels seen with this allogeneic CAR therapy with those observed with investigational autologous CARs, which have been under study for several years.

Moving forward, investigators are continuing to evaluate dosing levels for ALLO-715. UNIVERSAL is enrolling patients to the 480 x 106 cohort, Mailankody said, adding that the appropriate dose likely would land between 320 and 480 x 106.

References

1. Mailankody S, Matous JV, Liedtke M, et al. Universal: an allogeneic first-in-human study of the anti-Bcma ALLO-715 and the Anti-CD52 ALLO-647 in relapsed/refractory multiple myeloma. Presented at: 2020 American Society of Hematology Annual Meeting and Exposition. December 5-8, 2020; Virtual. Abstract 129. Accessed December 5, 2020. https://ash.confex.com/ash/2020/webprogram/Paper140641.html

2. Cho SF, Anderson KC, Tai YT. Targeting B cell maturation antigen (BCMA) in multiple myeloma: potential uses of BCMA-based immunotherapy. Front Immunol. 2019;9:1821. doi:10.3389/fimmu.2018.01821

3. AlloCAR T Therapy. Allogene Therapeutics. Accessed December 5, 2020. https://www.allogene.com/allocar-t-therapy

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ALLO-715, Off-the-Shelf CAR T-Cell Therapy, Produces Early Promise in Multiple Myeloma - Cancer Network

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Magenta Therapeutics (NASDAQ: MGTA) and bluebird bio, Inc. (NASDAQ: BLUE) today announced an exclusive clinical trial collaboration to evaluate the utility of MGTA-145, in combination with plerixafor, for mobilization and collection of stem cells in adults and adolescents with sickle cell disease (SCD). The data from this clinical trial could provide proof-of-concept for MGTA-145, in combination with plerixafor, as the preferred mobilization regimen for patients with SCD. bluebird bios experience with plerixafor as a mobilization agent in sickle cell disease aligns with Magentas combination therapy approach, utilizing MGTA-145 plus plerixafor with potential to achieve safe, rapid and reliable mobilization of sufficient quantities of high-quality stem cells to improve outcomes associated with stem cell transplantation. Under the collaboration, the stem cells will be fully characterized, and Magenta will undertake preclinical studies to evaluate the ability of these cells to be gene corrected and engrafted in mouse models. The companies will co-fund the clinical trial and Magenta will retain all rights to its product candidate.

We are excited to build upon our leading position in the field of ex-vivo gene therapy and the promising clinical data with LentiGlobin in SCD with a collaboration focused on achieving improved stem cell mobilization, said Dave Davidson, M.D., chief medical officer, bluebird bio. In this initial study, we hope to establish whether the combination of plerixafor with MGTA-145 can generate appropriate CD34+ stem cells with a single round of mobilization. If successful, we hope to evaluate this novel mobilization regimen with LentiGlobin to make another step forward in the treatment of patients with SCD.

Achieving reliable and rapid stem cell mobilization and a simplified collection process can ensure the entire patient experience is optimal with respect to therapeutic outcome. The incorporation of bluebird bios experience in this area of treatment will be immensely valuable in further developing MGTA-145 plus plerixafor to address the remaining unmet needs in gene therapy approaches for diseases like sickle cell disease, said John Davis Jr., M.D., M.P.H., M.S., Head of Research & Development and Chief Medical Officer, Magenta Therapeutics. We look forward to collaborating with bluebird bio to evaluate MGTA-145 as the preferred mobilization option for people with sickle cell disease.

SCD is a serious, progressive and debilitating genetic disease caused by a mutation in the -globin gene that leads to the production of abnormal sickle hemoglobin (HbS), causing red blood cells (RBCs) to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and painful vaso-occlusive events (VOEs). For adults and children living with SCD, this means unpredictable episodes of excruciating pain due to vaso-occlusion as well as other acute complicationssuch as acute chest syndrome (ACS), stroke, and infections, which can contribute to early mortality in these patients.

Currently available mobilization drugs, including granulocyte-colony stimulating factor (G-CSF), a commonly used mobilization agent administered over the course of five to seven days in other transplant settings, is not used in sickle cell disease because it can trigger vaso-occlusive crises and even death in adults and adolescents. Plerixafor is used to mobilize a patients stem cells for collection prior to transplant and while an available treatment option, multiple cycles of apheresis and collection may sometimes be required to generate sufficient stem cells for gene therapy. Magenta is developing MGTA-145, in combination with plerixafor, to be the preferred mobilization regimen for rapid and reliable mobilization and collection of hematopoietic stem cells (HSCs) to improve stem cell transplantation outcomes in multiple disease areas, including genetic diseases such as sickle cell disease, as well as blood cancers and autoimmune diseases.

About Magenta Therapeutics MGTA-145

MGTA-145, in combination with plerixafor, has demonstrated, in a recently completed Phase 1 study in healthy volunteers, it can rapidly and reliably mobilize high numbers of functional stem cells in a single day, without the need for G-CSF. MGTA-145 works in combination with plerixafor to harness a physiological mechanism of stem cell mobilization to rapidly and reliably mobilize HSCs for collection and transplant across multiple indications.

Additionally, as shown in preclinical studies, stem cells mobilized with MGTA-145 can be efficiently gene-modified and are able to engraft, potentially allowing for safer and more efficient mobilization for gene therapy approaches to treat sickle cell disease and other genetic diseases.

Magenta completed its Phase 1 trial of MGTA-145 in healthy volunteers, demonstrating MGTA-145 was well tolerated and enables same-day dosing, mobilization and simplified collection of sufficient stem cells for transplant, meeting all primary and secondary endpoints.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, were developing gene and cell therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, were working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. Were putting our care and expertise to work across a spectrum of disorders: cerebral adrenoleukodystrophy, sickle cell disease, -thalassemia and multiple myeloma, using gene and cell therapy technologies including gene addition, and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

LentiGlobin and bluebird bio are trademarks of bluebird bio, Inc.

About Magenta Therapeutics

Magenta Therapeutics is a clinical-stage biotechnology company developing medicines to bring the curative power of immune system reset through stem cell transplant to more patients with autoimmune diseases, genetic diseases and blood cancers. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant world to revolutionize immune reset for more patients.

Magenta is based in Cambridge, Mass. For more information, please visit http://www.magentatx.com.

Follow Magenta on Twitter: @magentatx.

Forward-Looking Statement

This press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavour, potential, continue or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation risks set forth under the caption Risk Factors in Magentas Annual Report on Form 10-K filed on March 3, 2020, and in bluebird bios Annual Report on Form 10-K filed on February 18, 2020, as updated by each companys most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta and bluebird bio believe that the expectations reflected in the forward-looking statements are reasonable, neither Magenta nor bluebird bio can guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta or bluebird bio, nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. Neither Magenta nor bluebird undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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Magenta Therapeutics and bluebird bio Announce a Phase 2 Clinical Trial Collaboration to Evaluate Magenta's MGTA-145 for Mobilizing and Collecting...

This article was originally published here

Cytotherapy. 2020 Nov 9:S1465-3249(20)30932-4. doi: 10.1016/j.jcyt.2020.11.001. Online ahead of print.

ABSTRACT

The end of 2019 saw the beginning of the coronavirus disease 2019 (COVID-19) pandemic that soared in 2020, affecting 215 countries worldwide, with no signs of abating. In an effort to contain the spread of the disease and treat the infected, researchers are racing against several odds to find an effective solution. The unavailability of timely and affordable or definitive treatment has caused significant morbidity and mortality. Acute respiratory distress syndrome (ARDS) caused by an unregulated host inflammatory response toward the viral infection, followed by multi-organ dysfunction or failure, is one of the primary causes of death in severe cases of COVID-19 infection. Currently, empirical management of respiratory and hematological manifestations along with anti-viral agents is being used to treat the infection. The quest is on for both a vaccine and a more definitive management protocol to curtail the spread. Researchers and clinicians are also exploring the possibility of using cell therapy for severe cases of COVID-19 with ARDS. Mesenchymal stromal cells are known to have immunomodulatory properties and have previously been used to treat viral infections. This review explores the potential of mesenchymal stromal cells as cell therapy for ARDS.

PMID:33257213 | DOI:10.1016/j.jcyt.2020.11.001

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Stem cell therapy in coronavirus disease 2019: current evidence and future potential - DocWire News

An effective new treatment to restore vision is on the horizon that works by injecting genetically modified stem cells into the eye to mend the damaged retina.

Researchers found that the cells of damaged retinas send out a rescue signal to attract the stem cells that repair eye damage.

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They identified two of these cell signals known as Ccr5 and Cxcr6 and then genetically engineered the stem cells to make them more sensitive to those signals.

When these modified stem cells were transplanted back into mice and human tissue samples in the lab they flocked to the retina cells in much greater numbers, keeping the tissue of the damaged retina alive and functioning.

The technique holds promise for improving sight in people with poor vision and potentially even to cure blindness altogether but the researchers cautioned that any such development was some years away and required much bigger studies to confirm their findings.

One of the main hurdles in using stem cells to treat damaged eyesight is low cell migration and integration in the retina, says Pia Cosma, at the Centre for Genomic Regulation in Barcelona.

After the cells are transplanted they need to reach the retina and integrate through its layers. Here we have found a way to enhance this process using stem cells commonly found in the bone marrow, but in principle can be used with any transplanted cells, Dr Cosma said.

There is still considerable work to be done, but our findings could make stem cell transplants a feasible and realistic option for treating visual impairment and restoring eyesight, she said.

Retinal damage, which is currently incurable, inevitably leads to visual disabilities and in most cases blindness. With a growing and ageing population, the number of people affected by retinal damage is estimated to increase dramatically over the next few decades.

Stem cell therapies have been touted as one way of treating degenerative retinal conditions. Stem cells can be transplanted into the eye, releasing therapeutic molecules with neuroprotective and anti-inflammatory properties that promote the survival, proliferation and self-repair of retinal cells. The stem cells can also generate new retinal cells, replacing lost or damaged ones.

The researchers used mesenchymal stem cells, which are found in bone marrow and can differentiate into lots of types of cells, including retinal cells that respond to light.

Mesenchymal stem cells can also be easily grown outside an organism, providing abundant starting material for transplantation compared to other cell sources such as hematopoietic stem cells.

The study is published in the journal Molecular Therapy.

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Treatment to restore vision by injecting stem cells into the eye could help people with damaged eyesight - iNews

Bayer has created a cell and gene therapy platform to support its growing pipeline of advanced therapy medicinal products. The platform is intended to enable Bayer to make its expertise and resources available to its partners while preserving their autonomy and culture.

Germanys Bayer has moved into cell and gene therapies on multiple fronts in recent years, buying up induced pluripotent stem cell specialist BlueRock Therapeutics and adeno-associated virus (AAV) gene therapy player Asklepios BioPharmaceutical while investing in a clutch of other biotechs. The deals have given Bayer a pipeline of five advanced assets and more than 15 preclinical prospects.

Rather than subsume BlueRock and AskBio, Bayer opted to allow the businesses to operate as independent companies in an attempt to preserve their cultures. Yet, Bayer also wants to enable the companies to realize the benefits that can come from being part of a larger organization.

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The cell and gene therapy platform is the result of that effort to get the best of both worlds. Bayer will use the platform to provide support to its cell and gene therapy businesses and orchestrate its operations in the area across the product life cycle. Specific areas of support offered by the platform span preclinical through to commercial, strategy implementation and project management.

Bayer is investing in its internal capabilities to strengthen the platform as well as looking to enter into strategic collaborations, acquire technologies and strike licensing deals. The deals entered into so far have given Bayer infrastructure as well as product candidates.

Notably, AskBio has a CDMO unit, Viralgen, specializing in AAV gene therapy production. As limited access to manufacturing capacity has been a barrier to speedy gene therapy development, buying the CDMO could help Bayer remove a constraint on the progress of its programs and become a more attractive partner for startups. Bayer thinks allowing acquired startups autonomy makes it attractive, too.

Wolfram Carius, who joined Bayer from Sanofi in 2016, is heading up the new cell and gene therapy platform. Carius said the platform is vital to accelerate innovation at its source, and to ensure its translation into tangible therapies for patients who have no time to wait in a statement.

Bayers platform is a twist on strategies being pursued by many of its peers, which have identified cell and gene therapies as growth areas and bought in assets but sought to avoid smothering the startups. Kite, for example, operates as its own business unit within Gilead Sciences, and Spark Therapeutics is an independent company within the Roche group.

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Bayer creates cell and gene therapy platform to support partners - FierceBiotech

Trusted Business Insights answers what are the scenarios for growth and recovery and whether there will be any lasting structural impact from the unfolding crisis for the Stem Cell Therapy market.

Trusted Business Insights presents an updated and Latest Study on Stem Cell Therapy Market 2020-2029. The report contains market predictions related to market size, revenue, production, CAGR, Consumption, gross margin, price, and other substantial factors. While emphasizing the key driving and restraining forces for this market, the report also offers a complete study of the future trends and developments of the market.The report further elaborates on the micro and macroeconomic aspects including the socio-political landscape that is anticipated to shape the demand of the Stem Cell Therapy market during the forecast period (2020-2029).It also examines the role of the leading market players involved in the industry including their corporate overview, financial summary, and SWOT analysis.

Get Sample Copy of this Report @ Stem Cell Therapy Market Research Report Forecast to 2029 (Includes Business Impact of COVID-19)

Abstract, Snapshot, Market Analysis & Market Definition: Stem Cell Therapy MarketIndustry / Sector Trends

Stem Cell Therapy Market size was valued at USD 7.8 billion in 2018 and is expected to witness 10.2% CAGR from 2019 to 2025.

U.S. Stem Cell Therapy Market Size, By Type, 2018 & 2025 (USD Million)

Rising prevalence of chronic diseases will positively impact the stem cell therapy market growth. Cardiovascular diseases, neurological disorders and other chronic conditions have resulted in high mortality over past few years. Conventional therapeutic methods and treatments are currently replaced due to lack of efficiency and efficacy. Recently developed stem cell therapies are capable of replacing defective cells to treat diseases that has reduced morbidity drastically. Therefore, people have now started relying on stem cell therapy that has long term positive effects.

Advancements in stem cell therapy in developed regions such as North America and Europe have boosted the industry growth. Since past few years, there have been several researches carried out for stem cell therapy. Currently developed stem cell therapies have shown positive outcomes in treatment of leukemia. Similarly, due to advancements in regenerative medicine, several other chronic conditions such as muscular dystrophy and cardiovascular diseases also have been cured. Aforementioned factors have surged the industry growth. However, high cost of allogenic stem cell therapy may hamper the industry growth to some extent.

Market Segmentation, Outlook & Regional Insights: Stem Cell Therapy Market

Stem Cell Therapy Market, By Type

Allogenic stem cell therapy segment held around 39% revenue share in 2018 and it is anticipated to grow substantially during the analysis timeframe. Allogenic stem cell is available as off the shelf therapy and it is easily scalable that helps in providing treatment without delay. Moreover, the procedure includes culturing donor-derived immunocompetent cells that are highly effective in treatment of several diseases. Stem cells obtained in allogenic therapy are free of contaminating tumor cells. This reduces risk for disease recurrence that will surge its demand thereby, stimulating segment growth.

Autologous stem cell therapy segment is estimated to witness 10.1% growth over the forthcoming years. People usually prefer autologous stem cell therapy as it has minimum risk of immunological rejection. However, on introduction of allogenic stem cell therapy, demand for autologous stem cell therapy has declined as it is difficult to scale up. However, there are concerns regarding risk of cross contamination during large scale manufacturing of autologous stem cell lines that will impede segmental growth to some extent.

Stem Cell Therapy Market, By Application

The neurology segment was valued at around USD 1.6 billion in 2018 and it is estimated that it will witness significant growth over the forthcoming years. Stem cells are used to replenish the disrupted neurological cells that help in quick patient recovery. Pluripotent stem cells provide a replacement for cells and tissues to treat Alzheimers, Parkinsons disease, cerebral palsy, amyotrophic lateral sclerosis, and other neurodegenerative diseases. Thus, the pivotal role of stem cells in treating the life-threatening neurological condition will escalate segment growth.

The cardiovascular segment will witness 10% growth over the analysis timeframe. Considerable segmental growth can be attributed to development in stem cell therapies that have enhanced recovery pace in patients suffering from cardiovascular diseases. Recently developed allogeneic stem cell therapies are efficient and easily available that have reduced the mortality rates in cardiovascular patients. Above mentioned factors will propel cardiovascular segment growth in near future.

Stem Cell Therapy Market, By End-users

The hospital segment held over 56% revenue share in 2018 and it is anticipated to grow significantly in near future. The rising preference for stem cell therapies offered by hospitals proves beneficial for business growth. Hospitals have affiliations with research laboratories and academic institutes that carry out research activities for developing stem cell therapies. On the introduction and approval of any novel stem therapy, hospitals implement it immediately. Associations with research and academic institutes further help hospitals to upgrade its stem cell treatment offerings that positively impact the segmental growth.

The clinics segment is expected to grow at around 10% during the forecast timeframe. Clinics specializing in providing stem cell therapies are well-equipped with advanced medical devices and superior quality reagents required for imparting stem cell therapies. However, as clinics offer specialized stem cell therapies, their treatment cost is much higher as compared to hospitals that may reduce its preference.

Stem Cell Therapy Market, By Region

North America stem cell therapy market held around 41.5% revenue share in 2018 and it is estimated to grow substantially in near future. Increasing the adoption of novel stem cell therapies will prove beneficial for regional market growth. Moreover, favorable government initiatives have a positive impact on regional market growth. For instance, the government of Canada has initiated Strategic Innovation Fund Program that invests in research activities carried out for stem cell therapies enabling development in stem cell therapy. Above mentioned factors are expected to drive the North America market growth.

Asia Pacific stem cell therapy market is anticipated to witness 10.8% growth in the near future owing to increasing awareness amongst people pertaining to the benefits of advanced stem cell therapies. Additionally, favorable initiatives undertaken by several organizations will promote industry players to come up with innovative solutions. For instance, according to Pharma Focus Asia, members of the Asia-Pacific Economic Cooperation collaborated with Life Sciences Innovation Forum to involve professionals having expertise in stem cell therapies from academia and research centers to promote developments in stem cell research. Thus, growing initiatives by organizations ensuring the availability of new stem cell therapies will foster regional market growth.

Latin America Stem Cell Therapy Market Size, By Country, 2025 (USD Million)

Key Players, Recent Developments & Sector Viewpoints: Stem Cell Therapy Market

Key industry players in the stem cell therapy market include Astellas Pharma Inc, Cellectis, Celyad, Novadip Biosciences, Gamida Cell, Capricor Therapeutics, Cellular Dynamics, CESCA Therapeutics, DiscGenics, OxStem, Mesoblast Ltd, ReNeuron Group, and Takeda Pharmaceuticals. Chief industry players implement several initiatives such as mergers and acquisitions to sustain market competition. Also, receiving approvals for stem cell therapy products from regulatory authorities fosters the companys growth. For instance, in March 2018, the European Commission approved Takedas Alofisel that is off-the-shelf stem cell therapy. Product approval will help the company to gain a competitive advantage and capture market share.

Stem Cell Therapy Industry Viewpoint

The stem cells industry can be traced back to the 1950s. In 1959 first animals were made by in-vitro fertilization by preserving the stem cells. Till 2000, research was being carried out on stem cells to study its therapeutic effect. In 2000, fund allocations were made to research on cells derived from aborted human fetuses. In the same year, scientists derived human embryonic stem cells from the inner cell mass of blastocytes. Later, in 2010, clinical trials for human embryonic stem cell-based therapy were initiated. As technology progressed, stem cell therapy for treating cancer was developed. However, due to ethical issues, the use of stem cells for curing diseases witnessed slow growth for a few years. But as the regulatory scenario changed, people started preferring stem cell therapies due to its better efficacy. Stem cell therapy is in the developing stage and has numerous growth opportunities in developing economies with a high prevalence of chronic diseases.

Key Industry Development

In September 2020, Takeda Pharmaceutical Company Limited announced the expansion of its cell therapy manufacturing capabilities with the opening of a new 24,000 square-foot R&D cell therapy manufacturing facility at its R&D headquarters in Boston, Massachusetts. The facility provides end-to-end research and development capabilities and will accelerate Takedas efforts to develop next-generation cell therapies, initially focused on oncology with the potential to expand into other therapeutic areas.

The R&D cell therapy manufacturing facility will produce cell therapies for clinical evaluation from discovery through pivotal Phase 2b trials. The current Good Manufacturing Practices (cGMP) facility is designed to meet all U.S., E.U., and Japanese regulatory requirements for cell therapy manufacturing to support Takeda clinical trials around the world.

The proximity and structure of Takedas cell therapy teams allow them to quickly apply what they learn across a diverse portfolio of next-generation cell therapies including CAR NKs, armored CAR-Ts, and gamma delta T cells. Insights gained in manufacturing and clinical development can be quickly shared across global research, manufacturing, and quality teams, a critical ability in their effort to deliver potentially transformative treatments to patients as fast as possible.

Takeda and MD Anderson are developing a potential best-in-class allogeneic cell therapy product (TAK-007), a Phase 1/2 CD19-targeted chimeric antigen receptor-directed natural killer (CAR-NK) cell therapy with the potential for off-the-shelf use being studied in patients with relapsed or refractory non-Hodgkins lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Two additional Phase 1 studies of Takeda cell therapy programs were also recently initiated: 19(T2)28z1xx CAR T cells (TAK-940), a next-generation CAR-T signaling domain developed in partnership with Memorial Sloan Kettering Cancer Center (MSK) to treat relapsed/refractory B-cell cancers, and a cytokine and chemokine armored CAR-T (TAK-102) developed in partnership with Noile-Immune Biotech to treat GPC3-expressing previously treated solid tumors.

Takedas Cell Therapy Translational Engine (CTTE) connects clinical translational science, product design, development, and manufacturing through each phase of research, development, and commercialization. It provides bioengineering, chemistry, manufacturing, and control (CMC), data management, analytical, and clinical and translational capabilities in a single footprint to overcome many of the manufacturing challenges experienced in cell therapy development.

Key Insights Covered: Exhaustive Stem Cell Therapy Market

1. Market size (sales, revenue and growth rate) of Stem Cell Therapy industry.

2. Global major manufacturers operating situation (sales, revenue, growth rate and gross margin) of Stem Cell Therapy industry.

3. SWOT analysis, New Project Investment Feasibility Analysis, Upstream raw materials and manufacturing equipment & Industry chain analysis of Stem Cell Therapy industry.

4. Market size (sales, revenue) forecast by regions and countries from 2019 to 2025 of Stem Cell Therapy industry.

Research Methodology: Stem Cell Therapy Market

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Quick Read Table of Contents of this Report @ Stem Cell Therapy Market Research Report Forecast to 2029 (Includes Business Impact of COVID-19)

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Stem Cell Therapy Market Research Report Forecast to 2029 (Includes Business Impact of COVID-19) - Cheshire Media

Updated data for a second anti-BCMA therapy, idecabtagene vicleucel (ide-cel) from Bristol Myers Squibb/bluebird bio, will be presented, including health-related quality of life results from the KarMMA study in patients with heavily pretreated R/R multiple myeloma. FDA has assigned a March 27, 2021, target date for action on this therapy.

Also anticipated are results from the APOLLO study in relapsed multiple myeloma, which will show that adding daratumumab and hyaluronidase-finj, called Darzalex Faspro by Janssen, to pomalidomide and dexamethasone reduces the risk of disease progression or death by 37% compared with pomalidomide and dexamethasone alone.

Notably, this phase 3 study involves subcutaneous administration of daratumumab, which offers significantly reduced treatment time and burden for patients. Janssen has submitted results from APOLLO to FDA and the European regulators.

The subcutaneous formulation of daratumumab offers patients and physicians a 3- to 5-minute administration experience and the potential to reduce systemic administration-related reactions compared to intravenous administration of daratumumab, said Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Athens, Greece, who is the studys principal investigator.

The REACH3 study, a phase 3 randomized study of ruxolitinib (Jakavi) vs best-available-therapy, will have important implications in chronic graft-vs-host-disease (GvHD). This condition occurs when new T cells from a stem cell transplant identify the patients cells as foreign and attack them, creating reactions from rashes to gastrointestinal issues to harm to the liver.

Results involving transplant in myelodysplatic syndromes (MDS) could have important implications for reimbursement. Corey Cutler, MD, MPH, FRCPC, of Dana-Farber Cancer Institute will present results that show transplantation of hematopoietic stem cells from compatible donors nearly doubled the survival rate of patients aged 50 to 75 years.

Even though transplant is frequently used in younger patients, it has not been widely used among older patients. Lack of Medicare coverage is a major barrier, Cutler explained. This study adds to a growing body of evidence that suggests its time to revisit the reimbursement question.

Asked his thoughts on whether CMS might change its policy, Cutler said, I cant speak for the agency, but I will tell you there are several studies that do suggest it should be covered.We are, of course, reaching out to CMS.

Fridays press briefing ahead of the opening of ASH highlighted the results for MDS and daratumumab and others that are expected to be practice changing. To know that older patients do well with transplant is a really important message, said Lisa Hicks, MD, MSc, a hematologist from St. Michaels Hospital in Canada, who moderated the briefing.

Ian Flinn, MD, of Tennessee Oncology, who is an author on several studies being presented at ASH involving venetoclax (Venclexta) and Brutons tyrosine kinase (BTK) inhibitors in chronic lymphocytic leukemia, said he was interested to see the results of the CAPTIVATE trial.

He said that right now, venetoclax is a fixed-duration therapy. Now, we need to figure out whether thats a good idea or not, Flinn said. CAPTIVATE will help clinicians understand whether they should keep patients on venetoclax plus ibrutinib after they have reached the point of minimal residual disease.

The ASH meeting will also highlight research examining disparities in care, as well as the effects of COVID-19 on outcomes. On Saturday, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), will discuss the latest information on COVID-19 and its impact on hematologic conditions in a fireside chat with ASH President Stephanie J. Lee, MD, MPH.

This week, President-elect Joe Biden announced that Fauci will be a chief medical adviser, in addition to retaining his longtime role at NIAID during the new administration.

Maggie L. Shaw contributed to this report.

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ASH Goes Remote as CAR T-Cell Therapy Competition Heats Up - AJMC.com Managed Markets Network

Ankit Kansagra, MD, an assistant professor in theDepartment of Internal Medicineat UT Southwestern Medical Center and assistant director of theOutpatient Stem Cell Transplant Program, discusses chimeric antigen receptor T-cell agents in the pipeline for multiple myeloma (MM) and how these therapies may impact the treatment landscape pending future approvals.

In part two of this interview with Dr. Kansagra, available December 8, he discusses potential new combination therapy options for MM.

DocWire News: Dr. Kansagra, can you discuss some of the CAR T-cell therapies in development for multiple myeloma, including their targets, clinical trial data that weve seen, and your expectations for any future FDA approvals?

Dr. Kansagra: In multiple myeloma, a few of the CAR T-cell therapy targets, which in the most developments, have been the BCMA-targeted CAR T-cell therapies. Those have been most exciting because they have made it to the phase I to phase II trials, especially the registrational studies from Celgene or Bluebird, BMS, the bb2121 compound or the Janssen compound 4538, being farthest out in the clinical development for CAR T-cell therapy. There are certainly a few other CAR T-cell therapies for multiple myeloma, which have grown, and theyre probably in the earlier development of therapy. An example being the CD38 CAR T-cell therapy, the SLAMF CAR T-cell therapy, and GPR5CD CAR T-cell therapy. Those are the three different targets which are being evaluated as T-cell targets.

DocWire News: How do you see the approval of these CAR T-cell therapy impacting the treatment landscape for multiple myeloma?

Dr. Kansagra: I think its going to be a huge improvement in our momentum of our treatment options. We have already seen cell therapy in myeloma have impressive results in terms of the response rates. I think the first important step is you have these patients who have got six or seven different lines of treatment, and now they are getting a novel product or a novel mechanism of action and also novel target and seeing an impressive response rate. That was amazing. Thats step number one.

Step number two is, as we have got further into the clinical development of CAR T-cell therapy, we have seen the safety of these products because that is extremely important that our products are safer.

Then the third thing which we have seen is that long-term follow-ups are not there, but what we have started seeing is that our responses, which could last up to a year or a year and a half for the population, where we would have usually seen maybe barely a response in a matter of months.

I think those are exciting times for our patients with multiple myeloma, where they have failed a lot of therapies. I think the more exciting times are going to come when we will start seeing these CAR T-cell therapies, potentially even in earlier lines of treatment options, where they could use maybe as a second-line treatment or as a first-line treatment after stem cell transplant or in lieu of stem cell transplant, maybe we can have deeper and longer remission rates.

DocWire News: With some of these agents potentially coming to market, do you foresee any challenges, either associated with adverse events or the ability to make these treatments widely available to patients?

Dr. Kansagra: Access to care is certainly near and dear to me, and thinking about those challenges is extremely, extremely important. I think were going to probably face challenges in a lot of different ways.

The first thing is, obviously, how can we get our patients to the centers who are giving CAR T-cell therapy? How are we going to bring them? We know from our autologous stem cell transplant over the last three to four decades, that still not every eligible transplant patient is referred to a transplant center, for whatever reasons. There are multiple reasons; there are socioeconomic reasons; there are distance reasons. But a lot of them are fixable reasons. There are some which are unfixable, but there are some fixable. I think the first and the foremost important thing is going to be to get our patients to a place who is delivering CAR T-cell therapy. Thats the challenge number one.

Challenge number two is, once they are in there, making sure that they are able to get that thing. So it means theyre not coming too late in their game, so trying to make sure theyre referred in earlier points, so that processes in place, that insurance approval has got started, if we need to work on the sociodemographic issues, how are they going to stay in a particular area? What is the social help, what is the family help theyre going to need? If they had referred earlier on, thats another, I call it, bottleneck that we need to think of that. Thats where we need to act on it.

The hard thing is obviously the cost. We dont know what is going to be the cost of the myeloma CAR T-cell therapy, or what is the price of those things. We can certainly estimate that its not going to be as cheap given the three CAR-Ts, which are not FDA-approved. I think its going to be expensive. You will have to think of the cost of care model of how we are going to work with this.

Last but not least of the challenges are the CAR-T itself. These are in the logistical challenge bucket. Then there are the challenges in the CAR-T landscape or the product itself. We still know that these are second-generation CAR T-cell therapies. They dont work for everybody. They have a high response rates, but they dont last that long. We hope to see longer remissions. An example I give, in comparison to large-cell lymphoma, we had 50% of the people who plateaued out, now coming up to about three years. In myeloma, we havent obviously made it to three years since the CAR T-cell therapy have started, but we do worry that there is a tail end of the curve that people are already relapsing to it. Obviously, that goes to the product itself or the construct itself, which needs to be developed in multiple different ways. I think of them as two major challenges ahead of us.

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Hematologist Discusses the Impact a Myeloma CAR T-Cell Approval Would Have on the Treatment Landscape - DocWire News

Ciltacabtagene autoleucel (cilta-cel; JNJ-68284528) demonstrated a significant response rate and showed a manageable safety profile at the recommended phase 2 dose in patients with relapsed or refractory multiple myeloma, according to combined results from the CARTITUDE-1 trial (NCT03548207).1

The objective response rate (ORR) was 96.9%, consisting of stringent complete responses (sCRs) in 67.0% of patients, very good partial responses in 25.8%, and partial responses in 4.1%.

We saw how heavily pretreated these patients were, and to see a one-time treatment give these kinds of response rates is quite exceptional, said Deepu Madduri, MD, in a presentation during the 2020 American Society of Hematology (ASH) Annual Meeting. Whats even more impressive is that 72% of these patients are still maintaining their response at the time of data cut off.

Cilta-cel is a second-generation chimeric antigen receptor (CAR) T-cell therapy consisting of a CD3 signaling domain, a 4-1BB costimulatory domain, and 2 B-cell maturation antigen (BCMA) binding domains.

CARTITUDE-1 is a phase 1b/2 study exploring the safety and efficacy of cilta-cel in patients with progressive multiple myeloma per IMWG criteria who have received at least 3 prior therapiesincluding a proteasome inhibitor, immunomodulatory drug, and anti-CD38 therapyor who are double refractory, and have an ECOG performance status of 0 or 1.

Once patients were screened and enrolled in the study, they underwent apheresis and bridging therapy, if necessary, followed by lymphodepleting chemotherapy of cyclophosphamide at 300 mg/m2 and fludarabine at 30 mg/m2 on days 5 to 3 prior to CAR T-cell infusion. The target dose was 0.75 x 106 viable CAR-positive T cells/kg, but the median dose administered was 0.71 x 106 (range, 0.51-0.95 x 106).

Primary objectives for the phase 1b portion of the study were to characterize the safety of the agent and set the recommended phase 2 dose; and in phase 2, the primary end point was to evaluate efficacy by ORR.

Previously, results of the phase 1b portion of the study were presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program showing responses in all 29 patients, including a very good partial response or higher rate of 97%.2

The presentation at ASH covered findings for all patients treated with cilta-cel in the phase 1b and 2 portions of the study (N = 97). Of these patients, 86% are still on the trial.

Median turnaround time for cilta-cel manufacturing was 29 days, and no patients discontinued from the study due to manufacturing failure.

At baseline, the median age of all patients was 61 (range, 43-78), 58.8% were male, and 13.4% had extramedullary disease. Almost one-fourth of patients (23.7%) had a high-risk cytogenetic profile, most often including del(17p), and 91.9% had tumor BCMA expression of at least 50%. The median number of prior therapies was 6 (range, 3-18), indicating a heavily pretreated population, with 87.6% being triple-class refractory and 42.3% being penta-refractory. Ninety-nine percent of patients were refractory to their last line of therapy, which was not required for inclusion in this study, noted Madduri. Additionally, 89.7% previously underwent autologous stem cell transplant and 8.2% received allogenic transplant.

Responses were ongoing at cutoff in 72.2% of patients and the median time to first response was 1 month (range, 0.9-8.5). Of 57 patients evaluable for minimal residual disease (MRD), the negativity rate at 10-5 was 93.0%, accounting for 54.6% of the overall population. A total of 33 patients (34.0%) achieved both sCR and MRD negativity. The median time to MRD negativity was also 1 month (range, 0.8-7.7).

Early, deep, and durable responses are observed in this heavily pretreated population, said Madduri, who is an assistant professor of medicine, hematology, and medical oncology at Mount Sinai Medical Center in New York.

The median progression-free survival (PFS) was not reached in responders but at 12 months, the PFS rate was 76.6% (95% CI, 66.0%-84.3%). In those who achieved an sCR, the 12-month PFS rate was 84.5% (95% CI, 72.0%-91.8%) and was 68.0% (95% CI, 46.1%-82.5%) in patients who had a very good partial response.

Patients with relapsed/refractory myeloma have a median overall survival of only 9.2 months in triple-refractory [disease] and only 5.6 months in penta-refractory. In this study, we know that the median PFS is at least a full year and we still haven't even reached a median PFS after a median duration of follow-up of 12.4 months, Madduri commented.

At 1 year, the overall survival rate was 88.5% (95% CI, 80.2%-93.5%). The median overall survival was also not yet reached.

The most common grade 3/4 adverse events (AEs) were hematologic and observed in 99.0% of all patients, consisting of neutropenia in 94.8%, anemia in 68.0%, leukopenia in 60.8%, and thrombocytopenia in 59.8%. The median time to recovery of these grade 3/4 cytopenias was 2 weeks for neutropenia and 4 weeks for thrombocytopenia. The rate of any-grade infections was 57.7%, and the most common grade 3/4 infections were pneumonia (8.2%) and sepsis (4.1%).

Grade 3/4 non-hematologic toxicities were not common in the study, including hypophosphatemia at 7.2%, fatigue at 5.2%, aspartate aminotransferase increase at 5.2%, and hyponatremia at 4.1%.

Additionally, cytokine release syndrome (CRS), a common CAR T-cell therapyrelated AE, was reported in 94.8% of patients at any grade, but only 4.1% were grade 3/4 in severity.

One distinguishing aspect of this study is the median time to onset of CRS, which is 7 days, with 89% of these patients having CRS at day 4 or later and 74% of these patients having CRS at day 6 or later, opening the possibility of outpatient administration. This may be explained by the fact that the maximum peripheral expansion of cilta-cel occurred generally around a median of 13 days, Madduri said.

Tocilizumab and corticosteroid support were required in 69.1% and 21.6% of patients, respectively. CRS resolved in 98.9% of all patients within 14 days of onset.

Neurotoxicity, another known complication of CAR T-cell therapies, was reported in 20.6% of patients at any grade and of grade 3 or higher in 10.3%. Specifically, immune effector cellassociated neurotoxicity syndrome (ICANS) cases were reported in 16.5% at any grade and of grade 3 or higher in 2.1%. All ICANS occurred within a median of 8 days (range, 3-12) and resolved within a median of 4 days (range, 1-12).

Other neurotoxicities, which were reported in 12 patients (12.4%), occurred after resolution of CRS or ICANS and included 5 patients with movement and/or neurocognitive changes and 7 with nerve palsy or peripheral motor neuropathy; 6 of these resolved. In the other 6 patients, 1 patient died from complications of the AE, 4 died of other causes, and 1 has ongoing neurotoxicity. The median time to onset for these toxicities was 27 days (range, 11-108) with recovery in a median of 75 days (range, 2-160).

We saw no clear etiology in the other neurotoxicities, but we saw that maybe there could be some mild associations with high tumor burden, prior CRS, ICANS, or even the higher expansion and persistence of these CAR T cells. So we did implement some mitigation strategies in our subsequent CARTITUDE development program allowing patients to have more chemotherapy, having more aggressive steroids for ICANS, like early intervention and extensive monitoring, Madduri said in the question-and-answer portion of the session following her presentation.

A total of 14 patients died during the study within 45 to 694 days of infusion. Five patient deaths were due to progressive disease, 3 were due to AEs that were not related to treatment, and 6 were due to AEs considered to be related to treatment with cilta-cel. These AEs included sepsis and/or septic shock in 2 patients, and CRS or hemophagocytic lymphohistiocytosis, lung abscess, respiratory failure, and neurotoxicity in 1 patient each.

Cilta-cel is continuing to be studied in patients with multiple myeloma in other clinical trials, including in earlier-line settings. Additionally, both the CARTITUDE-2 (NCT04133636) and CARTITUDE-4 (NCT04181827) studies are considering whether cilta-cel can safely be given in an outpatient setting.

In December 2019, cilta-cel was granted an FDA breakthrough therapy designation for the treatment of patients with previously treated multiple myeloma based on earlier results of the CARTITUDE-1 trial.3

References

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Cilta-Cel CAR T-cell Therapy Impresses With High ORR in R/R Multiple Myeloma - Targeted Oncology

The publication, based on data generated from a questionnaire with 150 industry representatives, explores the challenges and solutions facing cell and gene therapy (CGT) companies over the next few years.

The top six trends identified in the CRB survey were:

We got the inside track from Noel Maestre, director of SlateXpace, a CRB solution focused on suite-based manufacturing platforms for the Advanced Therapy Medicinal Products (ATMP) and Peter Walters, CRBs director of ATMP, on how the CGT landscape is likely to develop in the short-term.

In a recent report, the MITs Center for Biomedical Innovationprojected that around 500,000 patients will have been treated with 40-60 approved gene therapies by 2030.

Going from the current scenario whereby only a few gene therapies are approved to 60 launches in a decade would represent an extraordinary leap forward and would dramatically change how medicine is actually perceived, said Maestre.

But as regards CGT production today, especially autologous cell therapy (ACT) work, he said that while the science exists the technology - process equipment, facility design and automation platforms - is really still trying to catch up, endeavoring to address a sector that has exploded in the past five years, he commented.

Looking ahead at the CGT landscape over the next few years, he expects a significant amount of change. The science is evolving we see the industry moving away from old cell lines to new cell lines or moving away from viral vectors altogether and using cleavage enzymes as a gene editing tool.

A new host cell line stable producer lines is gaining momentum, he said.

We are seeing the industry moving towards suspension cell culture from less than optimal cell lines, and then further going into producer cell lines.

A full 65% of respondents to the CRB poll said they are developing or intend to develop this type of vector host cell, drawn by the potential for a less expensive, more scalable process.

CRB: Our survey findings provide a data-driven snapshot of an industry whose intellectual capital and cutting-edge science is too often betrayed by outdated technology and applications ill-suited for commercial scale at a time when demand for urgent therapies is rising.

Once the industry gets to the point where producer cell lines are more like a name brand, easier to pull off the shelf and use, it will be a much more cost-effective way to produce viral vectors.

But we are right on the cusp - a lot of companies are recognizing the opportunity and are investing the time and money into producing these. And we also see a lot of contract development and manufacturing organizations (CDMOs) producing their own cell lines in house and using those as a lure to [attract the clinical material work] of their clients, said Walters.

According to Maestre, and the CRB survey data backs him up, the product pipelines of companies operating in the CGT space are going to get more complex, for the next five years at least.

More than half of those polled indicated they expect to adopt a multimodal solution within the next two years, with flexibility, scalability, operational efficiency, and speed to market as the top drivers.

Every company is going to be dealing with this dilemma of whether they build dedicated spaces for each of their different modalities, or whether they build highly flexible facilities that can allow them to accommodate whatever is coming next, said Maestre.

He also sees a lot more companies wanting to integrate their supply chain, bringing a lot of manufacturing in-house whereas before they would have been reliant on a whole set of different CDMOs and manufacturers.

Project delivery is also where change is occurring.

We are seeing the industry really moving away from the way projects were executed in the past into a much more integrated model; they are looking for turnkey facility delivery and they want turnaround to be faster. COVID-19 has only accentuated that, with project timelines compressed by 30-40%, and I dont think that it is ever going back to the way it was I think that is going to become the standard, commented Maestre.

And another major trend over the next few years will be around the cost of therapies. As they become more commonplace and there are more and more CGT licensed products, the costs will come down.

Projecting forward, Walters sees an eventual shift away from autologous to allogeneic cell therapy.

As the technology continues to develop and the science continues to improve and new and better ways are found to use and leverage cells, we will see companies moving to a scalable allogeneic model, getting away from having to do that point-of-care, personalized tracking and more towards a classic manufacturing model that allows them to produce cells in advance in a way that they can be scaled up.

The idea, evidently, is to process cells for not one but dozens of patients at a time.

We see the industry moving towards donated cells for allogeneic therapy and we are also seeing the beginnings of a shift to using stem cells that can be genetically modified and scaled up and differentiated to become T-Cells or NK cells. I dont think industry has settled on a course yet but there are a lot of companies trying to find that pathway, trying to find the edge to move their manufacturing platform that way, remarked Walters.

Right now, though, all facets of CGT manufacturing are under pressure from COVID-19 vaccine production, they said.

There is significant shortage of cleanroom manufacturing space to manufacture and develop the almost 1,200 CGT products in clinical trials currently.

What we are seeing is that CDMOs have so much demand - they have 12-18 months of backlog in terms of contracts for product development so they are building [new facilities] very rapidly.

As owner operator companies are stuck with that delay in getting their products into development, they are also developing a significant amount of manufacturing space on their own. But while both branches are building as fast as they can, it still isnt enough.

We are constantly hearing from our clients that they are concerned about their supply chains and being able to secure their material. Right now, a lot of companies are moving towards a combination of using CDMOs and manufacturing in-house, said Maestre.

CRB is a provider of engineering, architecture, construction and consulting solutions to the global life sciences and advanced technology industries, with over 1,300 employees.

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Are stable producer cells the future of viral vector manufacturing and when will allogeneic cell therapy take hold? - BioPharma-Reporter.com

Coherent Market Insights Presents GlobalStem Cell Therapy MarketSize, Status and Forecast 2020-2027 New Document to its Studies Database

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Competitive Landscape and Stem Cell Therapy Market Share Analysis

Stem Cell Therapy market competitive landscape provides details and data information by players. The report offers comprehensive analysis and accurate statistics on revenue by the player for the period 2016-2020. It also offers detailed analysis supported by reliable statistics on revenue (global and regional level) by players for the period 2016-2020. Details included are company description, major business, company total revenue and the sales, revenue generated in Stem Cell Therapy business, the date to enter into the Stem Cell Therapy market, Stem Cell Therapy product introduction, recent developments, etc.

Some of the key players/Manufacturers involved in the Stem Cell Therapy MarketMagellan, Medipost Co., Ltd, Osiris Therapeutics, Inc., Kolon TissueGene, Inc., JCR Pharmaceuticals Co., Ltd., Anterogen Co. Ltd., Pharmicell Co., Inc., and Stemedica Cell Technologies, Inc.

Research and Methodology

For the research, the Stem Cell Therapy markets research teams are adopted various high-end techniques. Industry best analysts are worked on this report. They collected data from various reliable sources and have taken samples of different market segments. They utilize both qualitative and quantitative data in this report. All data are based on primary sources, which are focused on the assessment year 2020-2027. For wise decision-making, they have also done SWOT analysis, which can also help them know their predicted future results. This report also helps to develop Stem Cell Therapy market growth by improvising its strategic models.

Detailed Segmentation:

By Cell Source:

By Application:

If opting for the Global version of Stem Cell Therapy Market analysis is provided for major regions as follows:

North America (The US, Canada, and Mexico)

Europe (the UK, Germany, France, and Rest of Europe)

Asia Pacific (China, India, and Rest of Asia Pacific)

Latin America (Brazil and Rest of Latin America)

Middle East & Africa (Saudi Arabia, the UAE, South Africa, and Rest of Middle East & Africa)

Key Benefits:

This study gives a detailed analysis of drivers and factors limiting the market expansion of Stem Cell Therapy

The micro-level analysis is conducted based on its product types, end-user applications, and geographies

Porters five forces model gives an in-depth analysis of buyers and suppliers, threats of new entrants & substitutes and competition amongst the key market players

By understanding the value chain analysis, the stakeholders can get a clear and detailed picture of this Stem Cell Therapy market

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Reasons to Buy a Full Report In depth analysis by industry experts Use of data triangulation method for examining the various aspects of the market Detailed profiling of the major competitors in the market A complete overview of the market landscape Computed Annual Growth Rate is calculated for period, 2020-2027

Table of Contents

Report Overview: It includes the Stem Cell Therapy market study scope, players covered, key market segments, market analysis by application, market analysis by type, and other chapters that give an overview of the research study.

Executive Summary: This section of the report gives information about Stem Cell Therapy market trends and shares, market size analysis by region and analysis of global market size. Under market size analysis by region, analysis of market share and growth rate by region is provided.

Profiles of International Players: Here, key players of the Stem Cell Therapy market are studied on the basis of gross margin, price, revenue, corporate sales, and production. This section gives a business overview of the players and shares their important company details.

Regional Study: All of the regions and countries analyzed in the Stem Cell Therapy market report is studied on the basis of market size by application, the market size by product, key players, and market forecast.

Actual Numbers & In-Depth Analysis, Business opportunities, Market Size Estimation Available in Full Report.

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Global Stem Cell Therapy Market Detailed Analysis Of Current Industry Figures With Forecasts Growth By 2027 - The Haitian-Caribbean News Network

Hematologists and oncologists working in the community setting encounter multiple obstacles when prescribing chimeric antigen receptor (CAR) T-cell therapy to patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The challenges involve matters of processes, treatment cost, and access to treatment.

To further understand the issues and the solutions needed for physicians who treat relapsed/refractory DLBCL, researchers at Cardinal Health conducted 2 live survey sessions to collect information from clinicians. A total of 114 oncologists and hematologists from community practices and hospital settings participated in the survey. The population of hematologists/oncologists see roughly 20 patients per day, and the majority have been in practice for 11 to 20 years. Overall, 46% of the clinicians who attended the first live survey session, and 26% of those who attended the second reported that they had not referrer any patient for CAR T-cell therapy, and of those who did refer patients 32% and 22% of patients, respectively had not yet been infused with CAR T cells.1

The results of the survey revealed that while the use of CAR T-cell therapy increased in community practices over the past year, there remain issues with high cost and toxicity of treatment. It was also reported that the processing of insurance was a barrier to getting patients treated. These challenges continue to limit the number of clinicians who recommend CAR T-cell therapy to their patients.

In an interview withTargeted Oncology, Ajeet Gajra, MD, FACP, vice president, Cardinal Health, discussed the ongoing challenges community oncologists face with prescribing CAR T-cell therapy to patients with relapsed/refractory DLBCL.

TARGETED ONCOLOGY: Can you explain the overall prognosis for patients with DLBCL? What are outcomes generally like with existing standard of care therapy?

Gajra: The outlook for DLBCL improved with the advent of chemoimmunotherapy, better risk stratification, and improved supportive care. Recent studies demonstrate that despite aggressive biology, over 60% of patients with DLBCL treated with chemoimmunotherapy achieve long-term remissions and cures. However, the improvements reached a plateau in the past decade, especially for patients who relapse after initial chemoimmunotherapy. These patients typically have poor prognostic features as defined by the International Prognostic Index (IPI) with high likelihood of relapse and death. Patients with relapsed or refractory disease are typically treated with salvage immunochemotherapy such as rituximab, ifosfamide, carboplatin and etoposide (RICE) or rituximab, cisplatin high dose Ara-C and dexamethasone (RDHAP), and those with chemotherapy-sensitive disease receive autologous stem cell transplant (ASCT). Using this approach, complete response (CR) rates are 35% to 40%, and in a recent study the 3-year event-free survival (EFS) and overall survival (OS) were 31% and 50%, respectively. Outcomes with ASCT are much worse for patients with refractory DLBCL as demonstrated in the SCHOLAR trial wherein the objective response rate was 26% (CR rate, 7%) with a median OS of 6.3 months and only 20% of patients were alive at 2 years.

Thus, prior to 2017 when the first CAR T therapy was approved in DLBCL with progression after 2 prior lines of therapy, there had been a significant unmet need for patients with relapsed DLBCL. The approval of 2 CAR-T therapies, axicabtagene ciloleucel (axi-cel) in October of 2017 and tisagenlecleucel (Kymriah; tisa-cel) in May 2018, in the treatment of large-cell lymphoma (LBCL), has ushered in a new mode of treatment which offers the potential of long-term remission in what was essentially a fatal disease.

TARGETED ONCOLOGY: What has been your observation experience with using CAR T cell therapy in patients with DLBCL by US community oncologists?

Gajra: Axi-cel and tisa-cel are both CD19-directed, genetically modified autologous T cell immunotherapy agents. Since the process of obtaining CAR T therapy for an individual patient is quite complex, we sought to assess the uptake of these agents among United States community oncologists. We conducted a study of community oncologists at two time points to assess perceptions and use of approved CAR T therapies in relapsed DLBCL. At each time point over 50 distinct oncologists participated. At the early timepoint, 46% of participants indicated that they had not referred any patients for CAR T therapy but at the later timepoint, this number decreased to 29% suggesting increasing use over the course of the 10-month interval. Of those participants who had referred patients for CAR T therapy, 32% at the early timepoint reported that none of their patients had yet received the CAR T infusion but the percentage of non-receipt decreased to 22% at the later timepoint again suggesting improved uptake and utilization.

TARGETED ONCLOGY: How do patient characteristics factor into how oncologists select patients to administer CAR T cells to? What are the barriers to CAR-T use?

Gajra: CAR T therapies approved in DLBCL have limitations as defined by the FDA approval and are to be used in adult patients with relapsed or refractory large B-cell lymphoma, including DLBCL, after 2 or more lines of systemic therapy. Neither agent is approved for the use of CNS lymphoma. As with the pivotal trials for the 2 agents, patients must have good ECOG performance status, adequate organ function including marrow, hepatic, cardiac and renal function, no active infection and no CNS involvement. Both agents carry black box warnings for neurotoxicity and cytokine release syndrome (CRS) which can be potentially fatal. Thus, the patients selected need to have good physiologic reserve and be willing to accept risks associated with the therapies. With the approval of a new CD19-directed monoclonal antibody, tafasitamab, it is not clear if patients exposed to that agent can still benefit from CAR T therapies.

In addition to patient specific factors, CAR T therapy represents a complex manufacturing process that is unlike traditional drug therapy or stem cell transplant. After identification of a potential patient with relapsed LBCL who has received at least two prior systemic therapies, a benefits verification and referral to a designated CAR T-cell therapy center is required. If deemed appropriate by the CAR T center, the patient undergoes apheresis for T-cell collection. The cells are then transported to the manufacturers facility where they are isolated, activated and undergo gene transfer, creating the chimeric cells which go through a process of expansion to generate the numbers needed for therapeutic effect. This process takes from 10 days to a few weeks. The CAR T cells are then cryopreserved and transferred back to the CAR T facility and reinfused into the patient. Thus, it is critical to maintain vein to vein integrity. Thus, unlike traditional cytotoxic or monoclonal antibody products, these agents are patient specific, living cell products that have a complex process for their manufacture, storage and shipping, leading to high costs to the healthcare system and the patient.

Given this information, not surprisingly, the oncologists surveyed identified the high cost of therapy as a major barrier to uptake and utilization at both time points respectively. Over half the participants identified cumbersome logistics of administering therapy and following patients as another major barrier. Further exploration of logistical issues identified barriers encountered during the referral process could be attributed to the payer or the CAR T center.

The payer specific challenges identified include slow approval process by 27% of payers (and high rates of denials by in 13% of payers. The challenges specific to the CAR-T center include slow intake process by 23% of CAR T centers lack of a CAR T center in geographic vicinity in 13%. CAR T center choosing stem cell transplant rather than CAR T for the patient was also seen 10% of the time. Other commonly encountered clinical challenges reported by the participants included deterioration of the patient prior to CAR T administration, and the need to administer bridging chemotherapy while awaiting manufacture of CAR T therapy. The lack of communication from the CAR T center during the process was identified by a minority as an impediment to recommending CAR T therapies, including lack of instructions to the primary oncologist and the patient.

TARGETED ONCOLOGY: Can you discuss the toxicities observed with CAR T cell therapy in this patient population? Do you haveany insight into toxicities observed in the real-world setting?

Gajra: As stated, both approved products carry black box warnings for CRS and neurotoxicity, now called Immune Effector Cell Associated Neurologic Syndrome (ICANS). CRS is an acute systemic inflammatory syndrome characterized by fever, hypotension, tachycardia, hypoxia and multiple organ dysfunction. ICANS is a neuropsychiatric complex manifested by encephalopathy, headache, tremor, dizziness, aphasia, delirium, insomnia and anxiety. The treating team needs to maintain a high index of suspicion for these potentially life-threatening agents and patients need to have access to facilities with advanced critical care. Tumor debulking ahead of CAR T infusion and prophylactic use of tocilizumab may reduce the risk of CRS. Use of corticosteroids early can alleviate the severity and duration of ICANS.

The scientific team at Cardinal Health has studied the real-world adverse events (AEs) to CAR T agents in DLBCL.2 We analyzed the postmarketing case reports from the FDA, AEs reporting system involving axicel and tisa-cel for large B-cell lymphomas were analyzed. Of 804 AE cases identified 67% of axi-cel cases and 26% of tisa-cel cases reported neurological AEs. Compared with cases without neurological AEs, significant associations were observed between neurological AEs and use of axi-cel, age 65 years, CRS and the outcome of hospitalization. These findings and those of other investigators suggest that there may be differences in neurological toxicity based on the agent used.

TARGETED ONCOLOGY: Can you provide background on how this web-based survey can about at Cardinal Health Specialty Solutions? What is the overall goal with it?

Gajra: We are continuously engaged in research with healthcare providers, including medical oncologists/hematologists, to assess their perspectives on issues they face in their day-to-day practice, including the impact of new therapies on patient care. We share our research findings with healthcare stakeholders through peer-reviewed manuscripts and abstracts, as well as through our Oncology Insights report, which is published twice a year.

TARGETED ONCOLOGY:How can the information obtained from this survey impact practice? Where are you in the process of response collect and obtaining results?

Gajra: Our research on CAR-T therapy, collected via web-based and in-person surveys, has helped us identify the challenges to the use of these therapies encountered by community oncologists. Given that over 50% of cancer care is rendered in the community setting, it is important to identify these barriers with a goal of mitigating them and facilitating timely access to these potentially life-saving therapies for patients. With a new CAR-T approval in mantle cell lymphoma this year and other potential approvals in newer indications on the horizon, streamlining access to CAR-T therapies will continue to be a priority.

We have a follow-up to this paper that will be presented at ASH 2020 where additional research with community oncologists in early 2020 has revealed that the rate of non-receipt of CAR-T therapies in DLBCL is relatively constant at around 30%. In addition, we are exploring interest and uptake of CAR-T therapies in the outpatient setting as oncologists gain more confidence in preventing, minimizing and managing the toxicity of CAR-T therapies.

References:

1. Gajra A, Jeune-Smith Y, Yeh T, et al. Perceptions of community hematologists/oncologists on barriers to chimeric antigen receptor T-celltherapy for the treatment of diffuse large B-cell lymphoma. Immunotherapy. 202012(10);725-732. doi: 10.2217/imt-2020-0118

2. Gajra A, Zettler ME, Phillips EG Jr, Klink AJ, Jonathan K Kish, Fortier S, Mehta S, Feinberg BA. Neurological adverse events following CAR T-cell therapy: a real-world analysis. Immunotherapy. 2020 Oct;12(14):1077-1082. doi: 10.2217/imt-2020-0161

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Not All Patients With Relapsed DLBCL Referred for CAR T in Community Setting - Targeted Oncology

Victoria Gray (right), shown with researcher Haydar Frangoul, was the first patient to be treated with the gene-editing tool CRISPR for sickle cell disease.

By Jocelyn KaiserDec. 5, 2020 , 12:30 PM

It is a double milestone: new evidence that cures are possible for many people born with sickle cell disease and another serious blood disorder, beta-thalassemia, and a first for the genome editor CRISPR.

In todays issue of The New England Journal of Medicine (NEJM) and tomorrow at the American Society of Hematology (ASH) meeting, teams report that two strategies for directly fixing malfunctioning blood cells have dramatically improved the health of a handful of people with these genetic diseases. One relies on CRISPR, marking the first inherited disease treated with the powerful tool created just 8 years ago. And both treatments are among a wave of genetic strategies poised to widely expand who can be freed of the two conditions. The only current cure, a bone marrow transplant, is risky, and appropriately matched donors are often scarce.

The novel genetic treatments still need longer folllow up, have the same safety issues as bone marrow transplants for now, and may also be extraordinarily expensive, but there is hope those risks can be eliminated and the costs pared down. This is an amazing time, and its exciting because its happening all at once, says hematologist Alexis Thompson of Northwestern University, who with a company called Bluebird Bio continues to test yet another genetic strategy that first demonstrated a sickle cell fix several years ago.

People born with sickle cell disease have mutations in their two copies of a gene for hemoglobin, the oxygen-carrying protein in red blood cells. The altered proteins stiffen normally flexible red blood cells into a sicklelike shape. The cells can clog blood vessels, triggering severe pain and raising the risk of organ damage and strokes. Sickle cell disease is among the most common inherited diseases, affecting 100,000 Black people in the United States alone. (The sickling mutations became widespread in African people, as one copy protects blood cells from malaria parasites.)

People with beta-thalassemia make little or no functioning hemoglobin, because of other mutations that affect the same subunit of the protein. About 60,000 babies are born each year globally with symptoms of the disease, largely of Mediterranean, Middle Eastern, and South Asian ancestry. Blood transfusions are standard treatment for both diseases, relieving the severe anemia they can cause, and drugs can somewhat reduce the debilitating crises that often send sickle cell patients to the hospital.

In the two new treatments, investigators have tinkered with genes to counter the malfunctioning hemoglobin. They remove a patients blood stem cells and, in the lab, disable a genetic switch called BCL11A that, early in life, shuts off the gene for a fetal form of hemoglobin. The patient then receives chemotherapy to wipe out their diseased cells, and the altered stem cells are infused. With the fetal gene now active, the fetal proteinrestores missing hemoglobin in thalassemia.In sickle cell disease it replaces some of the flawed adult sickling hemoglobin, and also blocks any remaining from forming sticky polymers.

Its enough to dilute the effect, says Samarth Kulkarni, CEO of CRISPR Therapeutics, which partnered with Vertex Pharmaceuticals on using the genome editor.

They engineered CRISPRs DNA-cutting enzyme and guide RNA to home in on and break the BCL11A gene. In a more traditional gene therapy effort, a team led by gene therapy researcher David Williams of Boston Childrens Hospital achieved the same goal. They used a harmless virus to paste into the blood stem cells genome a stretch of DNA coding for a strand of RNA that silences the fetal hemoglobin off switch.

Patients treated in both trials have begun to make sufficiently high levels of fetal hemoglobin and no longer have sickle cell crises or, in all but a single case, a need for transfusions. In one NEJM paper today, the Boston Childrens team reports on the success of its virus gene therapy in six sickle cell patients treated for at least 6 months. They include a teenager who can now go swimming without pain, and a young man who once needed transfusions but has gone without them nearly 2.5 years, says Erica Esrick of Boston Childrens. He feels perfectly normal.

CRISPR appears to have done at least as well. The first sickle cell patient to receive CRISPR 17 months ago, a Mississippi mother of four named Victoria Gray, has called the results wonderful. We have amelioratedthe symptoms, says Haydar Frangoul, a hematologist at the Sarah Cannon Research Institute who treated Gray as part of the CRISPR trial. Every time I call her on the phone or see her in the clinic, she feels great.

CRISPR Therapeutics and Vertex describe the results for Gray and one beta-thalassemia patient treated 22 months ago today in another NEJM paper, and Frangoul will report on seven beta-thalassemia and three sickle cell patients tomorrow at the online ASH meeting. The CRISPR results are really very impressive, says Boston Children's stem cell biologist Stuart Orkin, whose lab discovered the BCL11A switch that led to both trials. (He is not directly involved with either.)

The results are comparable to the older strategy from Bluebird that relies on a different genetic alteration: adding a gene for an adult hemoglobin that has been tweaked so it reduces polymerization of the sickling form. At the ASH meeting, Thompson will give an update on about two dozen sickle cell disease patients who received the treatment within the past 3 years. As of March, the 14 with a follow-up of 6 months or more had experienced just a single mild pain crisis overall.

The Bluebird treatment was approved in Europe in 2019 for certain beta-thalassemia patients, and the company expects to seek Food and Drug Administration approval in the United States for its products for both diseases within the next few years. Bluebird chief scientific officer Philip Gregory says the long-term data for the firm's treatment give it an advantage over the newer approaches. Weve set a very high bar, he says.

Others who treat these diseases say its too early to crown a specific genetic treatment the winner. For example, reversing the fetal hemoglobin off switch, as the new CRISPR and RNA-based gene therapy strategies do, allows blood cells to make natural levels of the protein. But so far there are no signs that Bluebirds treatment results in excess adult hemoglobin that causes problems, Williams says. And although a virus-carrying gene can land in the wrong place and trigger cancer, CRISPR could similarly make harmful off-target edits. There has been no sign of that. Still, We need long-term follow-up for all the strategies, says the National Institutes of Healths (NIHs) John Tisdale, a coleader of the Bluebird study.

None of these genetic treatments seems likely to immediately help the many patients in places like Africa and India who dont have access to sophisticated health care. Itswonderful, but it wont solve the global health problem, Orkin says. Bluebird expects to charge $1.8 million for LentiGlobin in Europea sum it derived from looking at a patients gains in life span and quality of lifeand the other genetic treatments are likely to be similarly expensive. Costs will also include the chemotherapy needed to eliminate patients diseased blood stem cells, and the attendant hospital stay.

Bluebird and other groups are exploring whether antibodies, instead of harsh chemotherapy, can wipe out a patients diseased cells. In a bolder effort, NIH and the Bill & Melinda Gates Foundation last year announced a plan to put at least $100 million into developing technologies that would modify blood stem cells in a patients bone marrow by injecting the gene-editing tools themselves into the body. Its a big hairy goal, but its an engineering challenge, says gene therapy researcher Donald Kohn of the University of California, Los Angeles, who leads another sickle cell treatment trial. Well get there.

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CRISPR and another genetic strategy fix cell defects in two common blood disorders - Science Magazine