Regenerative Medicine: Overcoming The Supply Chain Challenges – Contract Pharma

Regenerative medicine is one of modern sciences most exciting developments. Defined by the Medical Research Council, regenerative medicine is an interdisciplinary field that seeks to develop the science and tools that can help repair or replace damaged or diseased human cells or tissues to restore normal function.

In the human body, the liver is the only organ capable of regenerating itself spontaneouslyeven after serious injurybut in the future, any part of the human body may be capable of doing so. Our own cells will also be able to treat and cure diseases and conditions of the blood and immune system, as well as restore the blood system after treatments for specific cancers.

Once only imaginable in science fiction, the latest applications include engineered skin tissue to treat burn victims, custom-grown bones for implants and joint replacements, personalized dietary treatments using gut bacteria and just recently, the worlds first 3D vascularized engineered heart was created using a patients own cells and biological materials.

As scientists understanding and the tools at their disposal become more advanced, the closer to the widespread commercialization of regenerative medicine the pharmaceutical industry finds itself.However, offering regenerative medicine therapies at scale requires one of the biggest shake-ups to the global pharmaceutical supply chain ever seen. Without it, the world risks missing out on the curative promises of this next-generation medical technology.

Regenerative medicine is one of, if not the most, exciting advancements in modern science which has far-reaching benefits for big pharma, healthcare systems and patient outcomes.

Regenerative medicine is a growth industry in more than one sense of the word; as a sector, its growing from strength to strength. In fact, last year the global regenerative medicine market was worth $28 billion and its expected to grow to $81 billion by 2023.

As a more efficient and less invasive alternative to transplanting cells or organs to replace damaged or lost tissue, established pharma companies alongside small biotech start-ups are racing to discover and bring to market medicine-based approaches that stimulate the bodys natural ability to repair itself.The cutting-edge innovations of regenerative medicine generally fall into three distinct categories:

Replenish Replace Rejuvenate

Stem cells can generate vital growth factors to naturally reduce inflammation, increase muscle mass, repair joints, grow hair and boost the immune system, replenishing the body. Organ regeneration and 3D printing are replacing the reliance on the failing donor system and overcoming the issue of organ rejection. The root causes of aging are being better understood and delayed by using stem cells to rejuvenate the body.

Marking a new era in healthcare and one which has the promise of addressing the needs of an aging population challenged by escalating chronic diseases, regenerative medicine is certainly a game-changer. Beyond more effective medical treatments that can be applied routinely despite age, comorbidities, or disease severity, it also has the potential to cure many of todays incurable diseases and support healthcare systems to move towards a preventative model.

Today, regenerative medicine is largely confined to a research environment. In fact, according to a recent report, there were 1,028 clinical trials for regenerative therapies taking place globally at the end of 2018.

Regenerative medicine is poised to transform healthcare as we know it, offering potential cures for deadly diseases which before would require long-term treatment to manage. However, while billions are being spent on regenerative medicine research and clinical studies, little resource has, so far, been allocated to the management and delivery of innovative medical therapies at scale.

Currently, the race appears to be on between smaller Medtech companies and large multi-national pharmaceutical companies to see who wins first-mover advantage in the regenerative medicine market. Today, many established pharmaceutical companies prefer to partner with Medtech startups to in-license products in early clinical development stages as opposed to conducting early development on their own which comes at a huge cost. This is a risk-reduction tactic, but it could mean big pharma misses the boat.

The question remains unanswered as to whether a peer-to-peer collaborative model will prosper where Medtech companieswho are in some instances one step ahead of big pharma in terms of drug developmentare happy to be a third-party provider to big pharma who have the budgets and networks to truly deliver the regenerative medicine revolution.

Regulation is, and will continue to, play a hugely important role in delivering regenerative medicines from a lab setting to a clinical setting. Only recently, the FDA announced a new policy framework for the development of regenerative medicine products, taking into account the dynamic and fast-moving nature of the field.

Ultimately, the governments aim is to protect patients from products that pose potential significant risks, while accelerating access to safe and effective new therapies according to Former FDA Commissioner Dr. Scott Gottlieb. The FDA plans to achieve this over the coming years by driving stakeholder engagement with the developing regulatory framework in order to efficiently advance access to safe and effective regenerative medicine advanced therapies.

However, so far, progress by the pharma industry in coming into compliance with FDAs regulations for regenerative medicines has been slow, despite the grace period set by the FDA before it fully exercises enforcement fast approaching (ending in November 2020).

In order to speed up the process of bringing novel medicines to market, the FDA is toying with the idea of fast-tracking products that are deemed low risk to patients if sponsors have engaged with the regulatory process and demonstrated responsibility by filing Investigational New Drug Applications (INDs).

The FDA has also promised to strengthen its enforcement action against drug developers who are marketing unapproved products, prioritizing cases where the threat to patient health and safety is largest.For example, last November the FDA stepped in where a Californian business was selling stem cell products using umbilical cord blood for the treatment of arthritis and other conditions, despite this form of treatment not having FDA approval for that particular use. Several patients (at least 12) undergoing this treatment were hospitalized after developing infections of the bloodstream and joints, as well as abscesses along the spine and skull.

In summary, one of the FDAs central aims over the coming years is to drive stakeholder engagement with the developing regulatory framework for regenerative medicine advanced therapies in order to efficiently advance access to safe and effective new products.

The promise of regenerative medicine requires an innovative look at the complete product lifecycle, including the development of an efficient distribution network.

Once these novel drugs become mainstream, the entire healthcare ecosystem will have to adapt. Regulatory approval for any drug relies on it safely and successfully fulfilling its medical intent. As such, information about supply chain management needs to be submitted to the regulator after the completion of phase three clinical trials, including packaging, labeling, storage and distribution.

The clinical supply chains required to deliver these therapies are arguably the most complex the industry has seen so far, even more so than for biologic medicine. Thats because, unlike many mass-market drugs, regenerative medicine is either personalized or matched to a unique donor-recipient.

The distribution of regenerative medicine therapies is further complicated by the fact they are also extremely sensitive to exogenous factors like time and temperature. Therefore, there are strict conditions under which these therapies must be transported and received.

Advanced IT solutions and monitoring systems are being developed and employed to ensure end-to-end traceability across the pharma supply chain. These are giving clinicians access to view the progress of therapies and their distribution in real-time and allow users to automatically schedule or amend material collections in line with manufacturing capacity, helping to keep the supply chain as agile as possible and avoid costly wastage.

The live tissues and cells which form the basis of regenerative medicine products are highly sensitive and some have a shelf life of no more than a few hours, making distribution a complex task. Therefore, materials need to be transported from the site of harvest to manufacturing facilities, and from manufacturing facilities to medical institutions under strictly controlled conditions, within certain time periods and temperatures, according to different cell and tissue requirements which can vary from product to product.

Temperature-controlled logistics solutions are vital to ensure a safe, effective and financially viable supply chain network for these high-value shipments. Cryopreservation is one technique increasingly being used to deliver medicines at optimum temperature using vapor phase nitrogen, however, many clinical settings remain ill-equipped to handle such equipment.

Onsite production is an alternative manufacturing arrangement, particularly for autologous products which are derived from a patients own cells. However, this throws up a number of compliance and infrastructure challenges, as the hospital would need to comply with a host of regulations including installing a licensed clean room which may not be possible given budget restrictions and limited space onsite.As a first-generation technology, stakeholders will have a greater tolerance for higher pricing, but only for a limited time period. By streamlining the currently very expensive manufacturing process and improving supply chain management, yields will automatically get larger and costs will slowly come down.

While there are many challenges in the road ahead, 2019 certainly appears to be the start of regenerative medicines move to the big time. Just like big data and artificial intelligence is transforming the practice of medicine, regenerative medicine holds the promise of extending the bodys natural ability to replenish, replace and rejuvenate itself.

If the global health industry can work collaboratively on overcoming the challenges presented by delivering safe and effective advanced therapies, a dramatic extension of the human healthspan is possible. We may even reach the point where no disease is considered incurable, transforming healthcare as we know it.

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Regenerative Medicine: Overcoming The Supply Chain Challenges - Contract Pharma

Scientists find promising drug combination against lethal childhood brain cancers – National Institutes of Health

News Release

Wednesday, November 20, 2019

Studies in cell and animal models reveal insights into cancer cells vulnerability that could lead to new strategies against brain cancers.

Researchers have devised a new plan of attack against a group of deadly childhood brain cancers collectively called diffuse midline gliomas (DMG), including diffuse intrinsic pontine glioma (DIPG), thalamic glioma and spinal cord glioma. Scientists at the National Institutes of Health, Stanford University, California, and Dana-Farber Cancer Institute, Boston, identified a drug pair that worked together to both kill cancer cells and counter the effects of a genetic mutation that causes the diseases.

The researchers showed that combining the two drugs panobinostat and marizomib was more effective than either drug by itself in killing DMG patient cells grown in the laboratory and in animal models. Their studies also uncovered a previously unrecognized vulnerability in the cancer cells that scientists may be able to exploit to develop new strategies against the cancer and related diseases. The results were published Nov. 20 in Science Translational Medicine.

DMGs are aggressive, hard-to-treat tumors that represent the leading cause of brain cancer-related death among U.S. children. DMGs typically affect a few hundred children a year between ages 4 to 12; most children die within a year of diagnosis. Most cases of DMG are caused by a specific mutation in histone genes. Histones are protein complexes in the cell nucleus. DNA wraps around histones to form chromatin, which packages DNA in the nucleus. How DNA winds and unwinds around histones is influenced by enzymes, including histone deacetylases. These enzymes add or remove chemical tags, which indirectly controls if genes are turned on or off.

In an earlier study, Stanford neuro-oncologist Michelle Monje. M.D., Ph.D., and her colleagues showed that panobinostat, which blocks key histone deacetylase enzymes, could restore the DIPG histone function to a more normal state. While panobinostat is already in early clinical testing in DIPG patients, its usefulness may be limited because cancer cells can learn to evade its effects. So Monjes team wanted to identify other possible drugs and combinations of them that could affect the cancer.

Very few cancers can be treated by a single drug, said Monje, a senior author of the study who treats children with DIPG and other diffuse midline gliomas. Weve known for a long time that we would need more than one treatment option for DIPG. The challenge is prioritizing the right ones when there are thousands of potential options. Were hopeful that this combination will help these children.

Monje and the National Cancer Institutes Katherine Warren, M.D., now at Dana-Farber Cancer Institute and Boston Childrens Hospital, collaborated with Craig Thomas, Ph.D., and his colleagues at the NIHs National Center for Advancing Translational Sciences (NCATS). Thomas and his team used NCATS drug screening expertise and matrix screening technology to examine drugs and drug combinations to see which ones were toxic to DIPG patient cells.

NCATS robotics-enabled, high-throughput screening technologies enable scientists to rapidly test thousands of different drugs and drug combinations in a variety of ways. Scientists can examine the most promising single drugs and combinations, determine the most effective doses of each drug and learn more about the possible mechanisms by which these drugs act.

The NCATS researchers first studied the effects of single approved drugs and investigative compounds on DIPG cell models grown in the laboratory from patient cells. They focused on agents that could both kill DIPG cells and cross the brains protective blood-brain barrier, a necessity for a drug to be effective against DIPG in patients. The team then tested the most effective single agents in various combinations.

Such large, complex drug screens take a tremendous collaborative effort, said Thomas, also a senior study author. NCATS was designed to bring together biologists, chemists, engineers and data scientists in a way that enables these technically challenging studies.

While there were multiple, promising outcomes from these screens, the team focused on the combination of histone deacetylase inhibitors (like panobinostat) with drugs called proteasome inhibitors (such as marizomib). Proteasome inhibitors block cells normal protein recycling processes. The panobinostat-marizomib combination was highly toxic to DIPG cells in several models, including DIPG tumor cell cultures that represented the main genetic subtypes of the disease and mice with cells transplanted from patient tumors. The combination also reduced tumor size in mice and increased their survival. A similar response was found in spinal cord and thalamic DMG models developed from cells grown in culture from patient cells.

The screening studies also provided important clues to the ways the drugs were working. Building on these data, the collaborative team subsequently conducted a series of experiments that showed the DIPG cells responded to these drugs by turning off a biochemical process in the cells mitochondria that is partly responsible for creating ATP, which provides energy to cells. The drug combination essentially shuts down tumor cell ATP production.

The panobinostat-marizomib drug combination exposed an unknown metabolic vulnerability in DIPG cells, said first author Grant Lin, Ph.D., at Stanford University School of Medicine. We didnt expect to find this, and it represents an exciting new avenue to explore in the development of future treatment strategies for diffuse midline gliomas.

Plans are underway for clinical trials of the drug combination and of marizomib alone.

Many drugs that we test have multiple effects on DIPG cells, said Warren, a senior study author. Panobinostat, for example, inhibits a specific enzyme, but it has other mechanisms working in tumor cells that may contribute to its effectiveness. Were still trying to understand the various Achilles heels in these cancer cells. This work is an important step in translating our preclinical data into patients.

Monje stressed the panobinostat-marizomib combination might be an important component of a multitherapy strategy, including approaches that harness the immune system and those that disrupt factors in the tumor microenvironment that the glioma cells depend on to grow. Like Warren, Monje emphasized the need to better understand how drugs target and impact the DIPG cells vulnerabilities.

Our work with NCATS showed the need to gather more preclinical data in a systematic, high-throughput way to understand and prioritize the strategies and agents to combine, Monje said. Otherwise were testing things one or two drugs at a time and designing clinical trials without preclinical data based on hypothesized mechanisms of action. We want to move past this guesswork and provide preclinical evidence to guide clinical decisions and research directions.

Lin added, The idea is to get as many effective tools as possible to work with that can have an impact on patients.

The research was funded by Alexs Lemonade Stand Foundation, Izzys Infantry Foundation, McKenna Claire Foundation, Unravel Pediatric Cancer, Defeat DIPG Foundation, ChadTough Foundation, N8 Foundation, Kortney Rose Foundation, Cure Starts Now Foundation and the DIPG Collaborative, Sam Jeffers Foundation, Lyla Nsouli Foundation, Abbies Army Foundation, Waxman Family Research Fund, Virginia and D.K. Ludwig Fund for Cancer Research, National Institute for Neurological Disorders and Stroke (R01NS092597) and NIH Directors Common Fund (DP1NS111132), Maternal and Child Health Research Institute at Stanford, the Anne T. and Robert M. Bass Endowed Faculty Scholarship in Pediatric Cancer and Blood Diseases, The DIPG All-In Initiative and the NCATS and NCI intramural programs.

About the National Center for Advancing Translational Sciences (NCATS):NCATS conducts and supports research on the science and operation of translation the process by which interventions to improve health are developed and implemented to allow more treatments to get to more patients more quickly. For more information about how NCATS is improving health through smarter science, visithttps://ncats.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

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Scientists find promising drug combination against lethal childhood brain cancers - National Institutes of Health

Exclusive: Humans placed in suspended animation for the first time – New Scientist News

By Helen Thomson

shapecharge/Getty

Doctors have placed humans in suspended animation for the first time, as part of a trial in the US that aims to make it possible to fix traumatic injuries that would otherwise cause death.

Samuel Tisherman, at the University of Maryland School of Medicine, told New Scientist that his team of medics had placed at least one patient in suspended animation, calling it a little surreal when they first did it. He wouldnt reveal how many people had survived as a result.

The technique, officially called emergency preservation and resuscitation (EPR), is being carried out on people who arrive at the University of Maryland Medical Centre in Baltimore with an acute trauma such as a gunshot or stab wound and have had a cardiac arrest. Their heart will have stopped beating and they will have lost more than half their blood. There are only minutes to operate, with a less than 5 per cent chance that they would normally survive.

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EPR involves rapidly cooling a person to around 10 to 15C by replacing all of their blood with ice-cold saline. The patients brain activity almost completely stops. They are then disconnected from the cooling system and their body which would otherwise be classified as dead is moved to the operating theatre.

A surgical team then has 2 hours to fix the persons injuries before they are warmed up and their heart restarted. Tisherman says he hopes to be able to announce the full results of the trial by the end of 2020.

At normal body temperature about 37C our cells need a constant supply of oxygen to produce energy. When our heart stops beating, blood no longer carries oxygen to cells. Without oxygen, our brain can only survive for about 5 minutes before irreversible damage occurs. However, lowering the temperature of the body and brain slows or stops all the chemical reactions in our cells, which need less oxygen as a consequence.

Tishermans plan for the trial was that 10 people who receive EPR will be compared with 10 people who would have been eligible for the treatment but for the fact that the correct team wasnt in the hospital at the time of admittance.

The trial was given the go-ahead by the US Food and Drug Administration. The FDA made it exempt from needing patient consent as the participants injuries are likely to be fatal and there is no alternative treatment. The team had discussions with the local community and placed ads in newspapers describing the trial, pointing people to a website where they can opt out.

Tishermans interest in trauma research was ignited by an early incident in his career in which a young man was stabbed in the heart after an altercation over bowling shoes. He was a healthy young man just minutes before, then suddenly he was dead. We could have saved him if wed had enough time, he says. This led him to start investigating ways in which cooling might allow surgeons more time to do their job.

Animal studies showed that pigs with acute trauma could be cooled for 3 hours, stitched up and resuscitated. We felt it was time to take it to our patients, says Tisherman. Now we are doing it and we are learning a lot as we move forward with the trial. Once we can prove it works here, we can expand the utility of this technique to help patients survive that otherwise would not.

I want to make clear that were not trying to send people off to Saturn, he says. Were trying to buy ourselves more time to save lives.

In fact, how long you can extend the time in which someone is in suspended animation isnt clear. When a persons cells are warmed up, they can experience reperfusion injuries, in which a series of chemical reactions damage the cell and the longer they are without oxygen, the more damage occurs.

It may be possible to give people a cocktail of drugs to help minimise these injuries and extend the time in which they are suspended, says Tisherman, but we havent identified all the causes of reperfusion injuries yet.

Tisherman described the teams progress on Monday at a symposium at the New York Academy of Sciences. Ariane Lewis, director of the division of neuro-critical care at NYU Langone Health, said she thought it was important work, but that it was just first steps. We have to see whether it works and then we can start to think about how and where we can use it.

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Exclusive: Humans placed in suspended animation for the first time - New Scientist News

Induction of Activated T Follicular Helper Cells is Critical for Anti-FVIII Inhibitor Development: Study – DocWire News

A new study published in Blood Advances suggests that inhibiting FVIII protein-specific T follicular helper (TFH) cells may be a viable strategy for preventing anti-FVIII inhibitor formation in hemophilia A (HA).

To conduct this study, FVIII-deficient (FVIIInull) mice with a targeted disruption of exon 17 of the FVIII gene27were obtained and crossed onto a C57BL/6J background. Subsequently, VWFnullFVIIInullmice, which are deficient in FVIII as well as VWF, were generated by crossing FVIIInullonto VWFnull.28Wild-type (WT) C57BL/6J mice, CD4-deficient (CD4/) mice,29and CXCR5-deficient (CXCR5/) mice30were purchased, and all study mice on the C57BL/6J background, except VWFnullFVIIInullmice, were on a B6/129S mixed genetic background.

The mice were kept in pathogen-free microisolator cages at the animal facilities before being immunized with recombinant human B-domaindeleted FVIII at a dose of 50 to 100 U/kg weekly for a duration of five to six weeks. The researchers collected blood samples five to seven days after the last immunization. The researchers immunizedC57BL/6J WT and mixed bone marrow (BM) chimeric mice with recombinant human full-length FVIII at a dose of 200 U/kg weekly over the duration of four weeks, followed by blood samples collected for assays after one week. In some experiments, CD4 T cells were depleted by the administration of anti-CD4 antibody GK1.5 on days 4 and 1 before the first immunization and 1 day before every other immunization.

BM chimeric mice were generated by transplantation of mixed BM cells from lethally irradiated mice, and BM cells were collected from the femurs, tibia, and humeri of donor mice, with red blood cells broken down. The lymphoid nodes (LNs) were isolated from immunized, FVIIInullmice. The spleens or lymphoid nodes (LNs) were isolated from rhF8-immunized, FVIIInullmice, and cells were stained for different proteins. The researchers used a 2-tailed Studentttest if data distribution passed the normality test, or the Mann-WhitneyUtest for comparing that failed the normality test.

FVIII inhibitor-producing mice showed increased germinal center (GC) formation and increased GC TFH cells in response to FVIII immunization. Emergence of TFH cells correlated with titers of anti-FVIII inhibitors. Re-challenge with FVIII antigen elicited recall responses of TFH cells, and in vitro FVIII re-stimulation resulted in antigen-specific proliferation of splenic CD4+T cells from FVIII-primed FVIIInullmice, and the proliferating cells expressed the TFH hallmark transcription factor BCL6. CXCR5+/+TFH-cellspecific deletion impaired anti-FVIII inhibitor production, confirming the essential role of CXCR5+/+TFH cells for the generation of FVIII-neutralizing antibodies.

Our results demonstrate that the induction of activated TFH cells in FVIIInullmice is critical for FVIII inhibitor development, suggesting that inhibition of FVIII-specific TFH-cell activation may be a promising strategy for preventing anti-FVIII inhibitor formation in patients with HA, the researchers wrote.

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Induction of Activated T Follicular Helper Cells is Critical for Anti-FVIII Inhibitor Development: Study - DocWire News

Global CAR T-Cell Therapy Market Analysis Report, 2019 – Market Anticipated to Record a CAGR of 56.2% During 2018-2026 – ResearchAndMarkets.com -…

DUBLIN--(BUSINESS WIRE)--The "Global CAR T-Cell Therapy Market Analysis 2019" report has been added to ResearchAndMarkets.com's offering.

The CAR T-Cell Therapy market is expected to reach $13,617.1 million by 2026 growing at a CAGR of 56.2% from 2018 to 2026.

Factors such as technological advancement for advanced & reliable treatment for cancer, growing pharmaceutical industry, high prevalence of acute lymphoblastic lymphoma (ALL) and increase in the number of cell therapy clinical studies are fuelling the market growth. However, side-effects of CAR T-cell therapy and high cost of treatment are likely to hamper the market growth.

Based on the application, diffuse large B-cell lymphoma is a cancer of B cells, a type of white blood cell responsible for producing antibodies. It is the most common type of non-Hodgkin lymphoma among adults. This cancer occurs primarily in older individuals, with a median age of diagnosis at approximately 70 years of age, though it can also occur in children and young adults in rare cases. DLBCL is an aggressive tumour which can arise in virtually any part of the body, and the first sign of this illness is typically the observation of a rapidly growing mass, sometimes associated with B symptoms of fever, weight loss, and night sweats.

The key vendors mentioned are Mustang Bio, Inc., Celgene Corporation, Bluebird Bio, Inc., CARsgen Therapeutics, Ltd., Novartis International AG, Legend Biotech, Sorrento Therapeutics Inc., Kite Pharma, Inc., Immune Therapeutics, Bellicum Pharmaceuticals, Inc., Pfizer, Inc., Juno Therapeutics, Atara Biotherapeutics, Aurora Biopharma Inc., Eureka Therapeutics, Autolus, TILT Biotherapeutics, and Fortress Biotech.

Key Questions Answered in this Report

Key Topics Covered

1 Market Synopsis

2 Research Outline

2.1 Research Snapshot

2.2 Research Methodology

2.3 Research Sources

2.3.1 Primary Research Sources

2.3.2 Secondary Research Sources

3 Market Dynamics

3.1 Drivers

3.2 Restraints

4 Market Environment

4.1 Bargaining power of suppliers

4.2 Bargaining power of buyers

4.3 Threat of substitutes

4.4 Threat of new entrants

4.5 Competitive rivalry

5 Global CAR T-Cell Therapy Market, By Target Antigen

5.1 Introduction

5.2 CD20

5.3 EGFRV III

5.4 CD19

5.5 HER2

5.6 MESO

5.7 CD22

5.8 BCMA

5.9 GD2

5.10 CD30

5.11 HER1

5.12 CD33

6 Global CAR T-Cell Therapy Market, By Product

6.1 Introduction

6.2 Allogeneic

6.3 Autologous

7 Global CAR T-Cell Therapy Market, By Therapy

7.1 Introduction

7.2 Axicabtagene Ciloleucel (Yescarta)

7.3 Tisagenlecleucel (Kymriah)

8 Global CAR T-Cell Therapy Market, By Application

8.1 Introduction

8.2 Chronic Lymphocytic Leukemia

8.3 Diffuse Large B-Cell Lymphoma

8.4 Multiple Myeloma

8.5 Acute Lymphoblastic Leukemia

8.6 Follicular Lymphoma

8.7 Mantle Cell Lymphoma

8.8 Glioblastoma

8.9 Neuroblastoma

8.10 Breast Cancer

8.11 Sarcoma

8.12 Acute Myeloid Leukemia

8.13 Colorectal Cancer

8.14 Pancreatic Cancer

8.15 Hepatocellular Carcinoma

8.16 Non-Hodgkin Leukemia

8.17 Carcinoma

9 Global CAR T-Cell Therapy Market, By End User

9.1 Introduction

9.2 Cancer Research Centers

9.3 Hospitals

9.4 Academic and Research Institutes

9.5 Pharmaceutical Companies

9.6 Biotechnology Companies

9.7 Contract Research Organizations

10 Global CAR T-Cell Therapy Market, By Geography

10.1 Introduction

10.2 North America

10.3 Europe

10.4 Asia Pacific

10.5 South America

10.6 Middle East & Africa

11 Strategic Benchmarking

12 Vendors Landscape

12.1 Mustang Bio, Inc.

12.2 Celgene Corporation

12.3 Bluebird Bio, Inc.

12.4 CARsgen Therapeutics, Ltd.

12.5 Novartis International AG

12.6 Legend Biotech

12.7 Sorrento Therapeutics Inc.

12.8 Kite Pharma, Inc.

12.9 Immune Therapeutics

12.10 Bellicum Pharmaceuticals, Inc.

12.11 Pfizer, Inc.

12.12 Juno Therapeutics

12.13 Atara Biotherapeutics

12.14 Aurora Biopharma Inc.

12.15 Eureka Therapeutics

12.16 Autolus

12.17 TILT Biotherapeutics

12.18 Fortress Biotech

For more information about this report visit https://www.researchandmarkets.com/r/q389el

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Global CAR T-Cell Therapy Market Analysis Report, 2019 - Market Anticipated to Record a CAGR of 56.2% During 2018-2026 - ResearchAndMarkets.com -...

First Myeloma Patient Dosed With UCARTCS1 CAR T-cell Therapy in Phase 1 Trial, Cellectis Announces – Myeloma Research News

The donor-derived, or allogeneic CAR T-cell therapy candidate UCARTCS1 has been administrated to the first patient in an ongoing Phase 1 trial for relapsed/refractory multiple myeloma.

The study (NCT04142619), called MELANI-01, plans to enroll up to 18 adults whose multiple myeloma relapsed after prior treatment. It is currently recruiting at MD Anderson Cancer Center, in Houston, and at Hackensack Meridian Health, in New Jersey. Another testing site at Weill Cornell Medicine, in New York, is expected to open soon. More information on clinical sites and contacts is available here.

The researchers will evaluate the safety and efficacy of multiple doses of UCARTCS1, being developed by Cellectis. The trial also will assess the transplanted cells ability to expand and survive inside the body.

After determining an optimal dose to be used in Phase 2, participants will be invited to continue treatment with this investigational treatment in an expansion study. MELANI-01 is expected to conclude in November 2022.

According to Cellectis, UCARTCS1 is the first allogeneic CAR-T cell therapy candidate cleared by the U.S. Food and Drug Administration to enter clinical trials for relapsed/refractory multiple myeloma.

In taking this next clinical step, we look forward to deepening our understanding of UCARTCS1 as a potential new treatment option for relapsed/refractory multiple myeloma patients in the future, Andr Choulika, PhD, chairman and CEO of Cellectis, said in a press release.

CAR T-cell therapies commonly use a patients own immune cells, which are harvested and modified in the lab to recognize and kill tumor cells. These cells are then expanded to several million and injected back into the patient to fight the cancer. This is called autologous, or patient-derived therapy.

Although such therapies have had positive results against multiple cancer types, scientists are not always able to collect enough cells from a patient to create the therapy. In addition, development and expansion of CAR T-cells requires time, which is in opposition to the prompt treatment needed for multiple myeloma.

To overcome these issues, Cellectis has been developing its off-the-shelf CAR T-cell products for diverse blood cancers including UCARTCS1 for multiple myeloma.

Instead of using a patients own cells, it uses immune T-cells from healthy donors. These donor cells must first be modified to avoid potential damage due to graft versus host disease the attack of the hosts cells by transplanted cells.

UCARTCS1 was specifically designed to target SLAMF7, or CS1 called signaling lymphocyte activation molecule family member 7 a protein found on the surface of myeloma cells. But as T-cells also produce SLAMF7, Cellectis used the TALEN gene editing technology to knock out or remove the protein from the surface of engineered T-cells.

This approach is intended to eliminate the patients T-cells to avoid cross reaction and create room for the transplanted cells to fight cancer.

This first patient dosing for our MELANI-01 clinical trial is an important advancement, as our team has worked tirelessly to develop and take the CS1 target from the lab to the clinic, Choulika said.

Total Posts: 34

Jos is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimers disease.

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First Myeloma Patient Dosed With UCARTCS1 CAR T-cell Therapy in Phase 1 Trial, Cellectis Announces - Myeloma Research News

Takeda sees cell, gene therapy in its future. Is it too late? – BioPharma Dive

Thanks to a $62 billion acquisition of Shire, Takeda is one of the world's largest developers of rare disease drugs.

Despite that, the 238-year-old Japanese pharmaceutical company lacks any mid- or late-stage cell or gene therapies, two technologies that figure to play a large role in how many rare cancers and inherited diseases will eventually be treated.

It's a mismatch Takedais putting substantial effort into addressing. Last week, executives made cell and gene therapy a notable focus of the company's first R&D day since closing its Shire deal.

"We have a world-class gene therapy platform," Dan Curran, head of Takeda's rare disease therapeutic area unit, told investors and Wall Street analysts gathered in New York city.

"We intend to build on that over the next five years. Because as we look to lead in the second half of [next]decade, we believe patients will demand and we can deliver transformative and curative therapies to patients globally."

But right now that's just an ambition. While Takedahas begun to explore how it can improve on current gene therapies, its candidates are early stage and lag their would-be competitors.

"Our heme A program we're behind. Our heme B program we're behind," admitted Curran in an interview. "But we're behind the first generation and when has there only been one generation of anything?"

Takeda's hemophilia A program is currently in Phase 1, with the hemophilia B candidate about to join it in human testing well back from leaders BioMarin Pharmaceutical, Spark Therapeutics and SangamoTherapeutics in hemophilia A and UniQure in hemophilia B.

Curran laid out three priorities for Takeda'spush: exploring whether gene therapy, typically pitched as a one-time treatment, can be re-dosed; lowering the doses currently used for first-generation therapies; and developing alternative gene delivery vehicles than the adeno-associatedand lentiviralvectors that are predominant today.

"We need to figure out how to re-dose AAVvectors if we want to provide functional cures for patients for the rest of their lives."

How long a gene therapy's benefit lasts is a critical question. In theory, it could last decades or potentially for life, depending on the treatment's target.

But clinical evidence presented to date suggests that benefit for some therapies could wane over time. BioMarin, for example, presented data this year that it argued is proof its gene therapy could raise Factor VIII expression levels in patients with hemophilia A above the threshold for mild disease for at least eight years a long time, to be sure, but not life-long.

Still, it's an unusual objective. Much of gene therapy's promise lies in the potential for it to be given just once and still deliver lasting benefits. And the therapies that have reached market most notably Spark Therapeutics' Luxturna, Novartis' Zolgensma and Bluebird bio's Zynteglo are among the most expensive drugs to ever reach market. Were a gene therapy to be re-dosed, the current value proposition those drugmakers describe would need to be re-evaluated.

Curran recognizes that bringing down costs substantially will be essential to any attempt to advance a multi-use gene therapy. But Takeda might have an advantage. In buying Shire, the pharma inherited a viral vector manufacturing plant, originally built by Baxalta, that Curran calls the company's "best kept secret."

"It's an enormous competitive advantage," he said, adding that Takeda believes it's among the industry's top three facilities by production capacity. "Roche trying to acquire Spark, Novartis and AveXis a significant component of value of those transactions was that these companies had actually invested in manufacturing capabilities."

Curran emphasized that Takeda's ambitions in gene therapy will require it to partner with academic leaders in the field, a playbook that it's followed over the past three years as it's worked to expand into cell therapy.

"In the cell space, there's more innovation you can bring up into proof of principle milestones in academia," said Andy Plump,Takeda'shead of R&D, in an interview.

"An academic can manipulate a cell, but it's very hard in an academic setting to optimize a small molecule," he added. "This is a space where Novartis, and now we, have been quite successful in creating those relationships."

Takeda has put partnerships in place with Japan's Center for iPS Cell Research and Application, GammaDelta, Noile-Immune Biotech, Memorial Sloan Kettering Cancer Center and, just this month, The University of Texas MD Anderson Cancer Center.

That last collaboration gives Takeda access to a chimeric antigen receptor-directed natural killer, or NK, cell therapy.The drugmaker believes NK cells could offer advantages over the T cells modified to create the currently available cell therapies Kymriah and Yescarta.

Most notably, MD Anderson's approach uses NK cells isolated from umbilical cord blood, rather than extracting T cells from each individual patient a time-consuming and expensive process that has complicated the market launch of Kymriah and Yescarta. Cord blood-derived NK cells are designed to be allogeneic, or administered "off the shelf."

Additionally, CAR NK cells haven't been associated (yet) with cytokine release syndrome or neurotoxicity, two significant side effects often associated with CAR-T cell therapies. That could help Takeda position its cell therapies as an outpatient option.

"Even if we were a company that entered a little bit later into the immuno-oncology space, we've very much tried to turn this into an advantage," said Chris Arendt, head of Takeda's oncology drug discovery unit, at the company's event.

"We believe we have a chance to establish a leadership position rather than jumping on the bandwagon and being a follower."

While Takeda's choice to pursue NK cell therapy stands out, its choice of target does not. TAK-007, a drug candidate from MD Anderson that is now Takeda's lead cell therapy program, is aimed at a cell surface protein called CD19 that's found in leukemias and lymphomas.

Both Yescarta and Kymriah target CD19, and a recent count by the Cancer Research Institute tracked 181 cell therapy projects aimed at the antigen.

Takeda is planning to advance TAK-007 into pivotal studies in two types of lymphoma and chronic lymphocytic leukemia by 2021, with a potential filing for approval in 2023.

By then, Kymriah and Yescarta will have been on the market for six years and current bottlenecks in cell therapy treatment could be solved, helping both Takeda's potential entry as well as the host of competitors it will likely face.

Next year will be a test of how productive Takeda'scell therapy unit can be. In addition to TAK-007, the pharmaexpects to have four other CAR-T and gamma delta cell therapies in the clinic, two of which will target solid tumors.

Cell and gene therapy are part of what Takeda calls its "second wave" of R&D projects, a group of early-stage drugs and programs that it sees as progressing to regulatory stages by 2025 or later.

In the nearer term, the drugmakeris advancing a "first wave" of clinical candidates that it told investors will deliver 14 new molecular entities by 2024. Five of those will come in rare disease, with the others spread across oncology, neuroscience, gastro-enterology and vaccines.

"We think the cascade of news coming forward on these programs will transform how people view Takeda," Curran said.

More importantly to the investors gathered in New York, Takeda expects these experimental drugs will eventually earn $10 billion in peak annual sales, which would represent a sizable addition to a business that generated $30 billion in sales last year.

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Takeda sees cell, gene therapy in its future. Is it too late? - BioPharma Dive

Global Cell & Gene Therapy Market Outlook and Forecast 2019-2024 – Robust Pipeline Products & Increasing Funding for R&D Activities Trigger Massive…

DUBLIN--(BUSINESS WIRE)--The "Cell and Gene Therapy Market - Global Outlook and Forecast 2019-2024" report has been added to ResearchAndMarkets.com's offering.

The global cell and gene therapy market is growing at a CAGR of over 24% during the forecast period 2018-2024.

Key Market Insights

The major drivers contributing to the growth of the global cell and gene therapy market are the growing incidence of several chronic and terminal diseases, including cancer, the launch of new products, the increasing availability in clinical evidences of these products in terms of safety and efficacy, the rapid adoption of CAR T-cell therapy, favorable regulatory support in the development of these treatment, and improved manufacturing expertise in these products.

Market Dynamics

Market Growth Enablers

Market Growth Restraints

Market Opportunities and Trends

Cell and Gene Therapy Market: Segmentation

This research report includes detailed market segmentation by product, application, end-user, and geography.

The global cell therapy market is growing at a steady rate, and this trend is expected to continue during the forecast period due to the increased patient base with a wide range of diseases/ailments. The segment is likely to witness upward growth on account of expanded expertise in the manufacturing of stem cell-based products.

The gene therapy segment is expected to witness faster growth as the penetration of these products is increasing at a significant rate, especially in developed economies. The market is expected to grow during the forecast period due to the increased patient base for the existing gene remedy products, expected the launch of other gene therapy-based products for several indications, and expanded indication approvals for existing commercially available products.

The oncology segment accounts for the highest share of the global market. The growth of the oncology segment is increasing at a fast rate on account of the growing prevalence of several types of cancers. Currently, the available products not only modify the disease but also improve the quality of the patient's life, thereby decreasing the mortality rate. The market in the dermatology segment is increasing at a steady rate. This segment owns its growth to the increasing incidence and prevalence rate of several types of wounds, which are difficult to treat under normal conditions and the launch of innovative products. The dermatology segment is likely to showcase growth due to the high product availability of wound care products in the market.

Hospitals are the leading end-user segment. The segment is growing mainly due to the increasing incidence/prevalence of chronic diseases such as cancer, cardiovascular diseases, diabetes, and chronic wound on account of diabetes feet, pressure ulcers, and other injuries.

Market Segmentation by Products

Market Segmentation by Distribution Channel Type

Market Segmentation by End-users

Geographical Insights

The US market dominates the cell and gene therapy market in North America due to the high prevalence of chronic diseases and other conditions, which require these treatment methods. There is also comparably high utilization and wide accessibility of these therapies. The oncology segment is likely to witness significant growth in North America.

The market in Europe is expected to witness upward growth in the near future on account of the growing prevalence of chronic diseases and rising elderly population. In Europe, cell and gene therapy products are considered to be part of the Advanced Therapy Medicinal Products (ATMPs), which are commonly known as regenerative medicine globally.

Key Vendor Analysis

The global market is characterized by the presence of a few global, large-scale companies and several small to medium-scale companies offering one or two cell and gene therapy products. Global players are majorly offering innovative products with the potential of disease-modifying characteristics that are generating significant revenues, especially in Europe and US regions. Most innovative and breakthrough products are approved in the European countries and the US.

Vendors are targeting mostly developed economies such as the US, Germany, France, the UK, Spain, and Japan as the uptake of these products is higher in these countries than low and middle-income countries. However, the market in these regions is at the nascent stage.

Key Vendors

Other Prominent Vendors

For more information about this report visit https://www.researchandmarkets.com/r/n758z0

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Global Cell & Gene Therapy Market Outlook and Forecast 2019-2024 - Robust Pipeline Products & Increasing Funding for R&D Activities Trigger Massive...

CAR-T therapies should be made by academic medical centers – STAT

Draw blood from someone with cancer. Engineer their blood cells to seek and destroy cancer. Reinfuse the cells and watch the cancer melt away. Chimeric antigen receptor T cell therapy (CAR-T) sounds like science fiction. But its the next frontier in cancer therapy.

Were weaponizing individuals immune systems to destroy cancer and add years to their lives. Its incredibly exciting. But at hundreds of thousands of dollars per dose, insurance companies and the U.S. government are struggling to figure out how to pay for these breakthrough treatments.

High prices not only pose a challenge to patient access, but they also raise a fundamental question: Are we creating these therapies the wrong way?

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CAR-T immunotherapy is being tested for a range of cancers, and now holds the potential to benefit more than 1 million Americans who live with or are in remission from blood cancers. A single dose typically costs around $400,000. What makes the price so high? Having drug corporations make the cells.

Under the current system, a hospital extracts blood cells from a patient and sends them to a drug companys manufacturing plant to be genetically engineered. It takes the company two to six weeks to engineer the cells, increase their number, perform quality and safety tests, and ship them back to the hospital to be reinfused into the patient. Under this system, there have been well-documented problems with the engineering process, as well as with shipping and handling.

Theres a better way, one that will lower the price, enable more precise and individualized targeting for specific patients, and allow for a faster process: Let medical centers do this.

Long before pharmaceutical companies took control of CAR-T, medical centers made these treatments. Cancer centers like the University of Pennsylvania, the National Cancer Institute, Memorial Sloan Kettering Cancer Center, Fred Hutchinson Cancer Center, Baylor University, and others figured out how to engineer CAR-T cells and ran the initial trials to test them. Drug companies were later involved mainly as a means to scale up production.

There are clear advantages to keeping CAR-T treatment in medical centers, closer to patients.

First, academic medical centers are well-equipped to make these therapies. They already safely handle stem cells every day. They also routinely perform autologous stem cell transplants (these use a patients own stem cells), which require in-house doctors and specialists to preserve and protect stored blood cells, wash and radiate them if needed, and sometimes select cell populations for clinical use.

Hospitals and academic medical centers can accomplish the CAR-T process more quickly because they do not need to ship cells to and from a drug company plant. This is a critical issue, because most patients currently treated with CAR-T have not responded to other treatments and their health is seriously compromised; some patients die between the time stem cells are removed from them and the time theyre supposed to come back to the hospital for re-infusion.

Second, there are different regulations around stem cells than there are for drugs. That means CAR-T therapies created at hospitals and academic medical centers would not have to go through the yearslong FDA regulatory process. And the treatments developed would allow hospitals to target more effectively and quickly each individuals specific cancer, which is off the table in the current system. Patients with advanced cancer do not have the luxury of time. Although this paradigm shift would require greater regulatory flexibility from the FDA, it would make CAR-T therapy far more effective.

Experience making CAR-T in leading medical centers show that locally engineered CAR-T cells can be made for less than half of what they are currently priced by pharmaceutical companies. We know this is possible because Switzerland is already doing it this way, and pricing CAR-T therapy between $150,000 and $200,000. Multiply that by the 10,000 individuals in the U.S. with the types of cancer for which CAR-T therapy is currently approved and we would save almost $2 billion a year. Factor in future CAR-T approvals and we will save many times that amount.

Making this change requires bucking the system. It means the FDA must redefine CAR-T from a drug to the autologous blood product it is. Its a move that would save not only money but lives because it can target cancer better and destroy it faster.

We took a fork in the CAR-T road a few years back and went the wrong way. There is still time to change course for the good of the many Americans who need this lifesaving treatment.

David Mitchell, who is living with incurable blood cancer, is the founder of Patients for Affordable Drugs. Saad Kenderian, M.D., is a physician-scientist and assistant professor of medicine and immunology at the Mayo Clinic in Rochester, Minn. S. Vincent Rajkumar, M.D., is a hematologist and professor of medicine at the Mayo Clinic. The views expressed are the authors personal views and do not necessarily reflect the policy or position of the Mayo Clinic.

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CAR-T therapies should be made by academic medical centers - STAT