Spinogenix has been awarded a research grant from the U.S. Department of Defense (DOD) to further test its lead compound as a potential treatment of amyotrophic lateral sclerosis (ALS), the company announced.

We are pleased that the DoD has recognized the potential of our novel drug candidate to change the course of disease progression in ALS, Stella Sarraf, PhD, founding CEO at Spinogenix, said in a press release. The grants amount and its duration were not disclosed in the release.

ALS is characterized by the progressive loss of motor neurons, or the nerve cells involved in the control of voluntary movement. Although some ALS treatments can slow nerve cell degeneration, they are not disease modifying and provide only a modest survival benefit. Spinogenix also noted in its release that not all patients tolerate these treatments well.

Spinogenixslead therapy candidate is a small, orally bioavailable, molecule designed to induce an increase in synapses the point of contact between two nerve cells that allows them to communicate. Its goal is to restore these neuronal connections and reverse patients decline in cognition and motor function, two faculties often affected in neurodegenerative diseases.

Spinogenix reports that the compounds mechanism is well understood, and believed to work across all the diseases where synapse loss occurs, regardless of the underlying disease mechanism.

With this grant from the DODs Congressionally Directed Medical Research Programs, Spinogenix aims to study the potential therapy using induced pluripotent stem cells (iPSCs) derived from both ALS patients and healthy controls.

iPSCs are stem cells generated from mature cells derived from the skin or blood that can give rise to different cell types, including nerve cells, depending on the particular chemical cues they are given. When these cells are derived directly from patients, they generate cellular models that mimic the diseases genetic and clinical diversity.

Additional experiments will also be conducted in ALS animal models.

Under the grant, Spinogenix will collaborate with researchers Rita Sattler, PhD, at the Barrow Neurological Institute, and Justin Ichida, PhD, at the Keck School of Medicine of the University of South Carolina.

Spinogenixs novel approach has the potential to demonstrate that replacing lost synapses may result in drugs that can provide a meaningful benefit for patients with ALS, said Merit Cudkowicz, MD, director of the Sean M. Healey and AMG Center for ALS at Mass General Hospital.

Diana holds a PhD in Biomedical Sciences, with specialization in genetics, from Universidade Nova de Lisboa, Portugal. Her work has been focused on enzyme function, human genetics and drug metabolism.

Total Posts: 45

Ins holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Cincias e Tecnologias and Instituto Gulbenkian de Cincia. Ins currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.

Read more here:
Spinogenix Wins Grant to Advance Testing of Potential Oral Therapy - ALS News Today

Stem Cell Assay Market: Snapshot

Stem cell assay refers to the procedure of measuring the potency of antineoplastic drugs, on the basis of their capability of retarding the growth of human tumor cells. The assay consists of qualitative or quantitative analysis or testing of affected tissues andtumors, wherein their toxicity, impurity, and other aspects are studied.

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With the growing number of successfulstem cell therapytreatment cases, the global market for stem cell assays will gain substantial momentum. A number of research and development projects are lending a hand to the growth of the market. For instance, the University of Washingtons Institute for Stem Cell and Regenerative Medicine (ISCRM) has attempted to manipulate stem cells to heal eye, kidney, and heart injuries. A number of diseases such as Alzheimers, spinal cord injury, Parkinsons, diabetes, stroke, retinal disease, cancer, rheumatoid arthritis, and neurological diseases can be successfully treated via stem cell therapy. Therefore, stem cell assays will exhibit growing demand.

Another key development in the stem cell assay market is the development of innovative stem cell therapies. In April 2017, for instance, the first participant in an innovative clinical trial at the University of Wisconsin School of Medicine and Public Health was successfully treated with stem cell therapy. CardiAMP, the investigational therapy, has been designed to direct a large dose of the patients own bone-marrow cells to the point of cardiac injury, stimulating the natural healing response of the body.

Newer areas of application in medicine are being explored constantly. Consequently, stem cell assays are likely to play a key role in the formulation of treatments of a number of diseases.

Global Stem Cell Assay Market: Overview

The increasing investment in research and development of novel therapeutics owing to the rising incidence of chronic diseases has led to immense growth in the global stem cell assay market. In the next couple of years, the market is expected to spawn into a multi-billion dollar industry as healthcare sector and governments around the world increase their research spending.

The report analyzes the prevalent opportunities for the markets growth and those that companies should capitalize in the near future to strengthen their position in the market. It presents insights into the growth drivers and lists down the major restraints. Additionally, the report gauges the effect of Porters five forces on the overall stem cell assay market.

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Global Stem Cell Assay Market: Key Market Segments

For the purpose of the study, the report segments the global stem cell assay market based on various parameters. For instance, in terms of assay type, the market can be segmented into isolation and purification, viability, cell identification, differentiation, proliferation, apoptosis, and function. By kit, the market can be bifurcated into human embryonic stem cell kits and adult stem cell kits. Based on instruments, flow cytometer, cell imaging systems, automated cell counter, and micro electrode arrays could be the key market segments.

In terms of application, the market can be segmented into drug discovery and development, clinical research, and regenerative medicine and therapy. The growth witnessed across the aforementioned application segments will be influenced by the increasing incidence of chronic ailments which will translate into the rising demand for regenerative medicines. Finally, based on end users, research institutes and industry research constitute the key market segments.

The report includes a detailed assessment of the various factors influencing the markets expansion across its key segments. The ones holding the most lucrative prospects are analyzed, and the factors restraining its trajectory across key segments are also discussed at length.

Global Stem Cell Assay Market: Regional Analysis

Regionally, the market is expected to witness heightened demand in the developed countries across Europe and North America. The increasing incidence of chronic ailments and the subsequently expanding patient population are the chief drivers of the stem cell assay market in North America. Besides this, the market is also expected to witness lucrative opportunities in Asia Pacific and Rest of the World.

Global Stem Cell Assay Market: Vendor Landscape

A major inclusion in the report is the detailed assessment of the markets vendor landscape. For the purpose of the study the report therefore profiles some of the leading players having influence on the overall market dynamics. It also conducts SWOT analysis to study the strengths and weaknesses of the companies profiled and identify threats and opportunities that these enterprises are forecast to witness over the course of the reports forecast period.

Some of the most prominent enterprises operating in the global stem cell assay market are Bio-Rad Laboratories, Inc (U.S.), Thermo Fisher Scientific Inc. (U.S.), GE Healthcare (U.K.), Hemogenix Inc. (U.S.), Promega Corporation (U.S.), Bio-Techne Corporation (U.S.), Merck KGaA (Germany), STEMCELL Technologies Inc. (CA), Cell Biolabs, Inc. (U.S.), and Cellular Dynamics International, Inc. (U.S.).

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TMR Research is a premier provider of customized market research and consulting services to business entities keen on succeeding in todays supercharged economic climate. Armed with an experienced, dedicated, and dynamic team of analysts, we are redefining the way our clients conduct business by providing them with authoritative and trusted research studies in tune with the latest methodologies and market trends.

Excerpt from:
Stem Cell Assay Market Competitive Landscape Analysis with Forecast by 2025 - SoccerNurds

A U.S. study has shown for the first time that enhancing signals from the nociceptive nervous system could provide new approaches to improve the collection of hematopoietic stem cells (HSCs) for treating cancers of the blood and bone marrow, the authors reported in the December 23, 2020, edition of Nature.

The findings may help cancer treatments, as "in a meaningful fraction of leukemia, multiple myeloma and lymphoma patients, particularly those who have received anticancer treatment, the HSC mobilization yield can be insufficient," said study leader Paul Frenette.

"Therefore, more efficient HSC mobilization methods would allow the harvest of sufficient HSCs for life-saving transplantation," said Frenette, a professor and director of the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research at Albert Einstein College of Medicine in New York.

HSCs characteristically migrate to different hematopoietic sites during embryonic development and continue to be released from the adult bone marrow.

Most hematopoiesis occurs in the bone marrow, where different types of blood cells are derived from limited numbers of HSCs, which are multipotent and capable of extensive renewal.

The HSC migratory properties have facilitated their collection from the blood and transplantation as regenerative cancer treatment, although the mechanisms by which HSCs migrate out of the bone marrow remain largely unknown.

In tissues exposed to the external environment, such as the skin, lung and gut, nociceptors enable the rapid detection of external insults, including pain, cold or heat, in order to avoid organ damage.

Nociceptor sensory neurons detect these harmful stimuli and can regulate the immune response to them by releasing neurotransmitters and other regulatory molecules.

However, other than for pain perception, the role of nociceptors in a deep tissue, such as the bone marrow, is poorly understood.

In bone marrow, HSCs are found in specialized microenvironments or niches, which are complex regulatory environments influenced by multiple cellular constituents, including nerves.

Although sympathetic nerves are known to regulate the HSC niche, the role of nociceptive neurons in the bone marrow in this regard remains unclear.

"We have previously shown that nerves from the sympathetic nervous system promoted HSC mobilization in bone marrow, so we were curious to see whether nociceptive neurons might also be involved," Frenette told BioWorld Science.

In their new Nature study, the Frenette and his team showed that nociceptive neurons are required for HSC mobilization and that they interact with sympathetic nerves to maintain HSCs in the bone marrow.

Notably, nociceptor neurons were demonstrated to drive granulocyte colony-stimulating factor (G-CSF)-induced HSC mobilization via secretion of calcitonin gene-related peptide (CGRP).

"Our findings may lead to more efficient mobilization methods in [blood and bone marrow cancer] patients in whom existing methods are insufficient," Frenette said.

For example, "we have shown that the CGRP pathway synergizes with G-CSF and plerixafor [(Mozobil, Genzyme), an immunostimulant used to mobilize HSCs into the bloodstream in cancer patients]." Unlike sympathetic nerves, which regulate HSCs indirectly via the bone marrow niche, CGRP was shown to act directly on HSCs via receptor activity modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor to promote HSC egress via Galphas/adenyl cyclase/cAMP signaling pathway activation.

This research identifies potential treatment targets for boosting HSC mobilization, since "we have shown that increasing the downstream signaling of the CGRP receptor RAMP1, by increasing cyclic AMP can enhance HSC mobilization," said Frenette.

Importantly, the Einstein researchers then showed that ingestion of food containing capsaicin, a natural component of chili peppers that can trigger the activation of nociceptive neurons, significantly enhanced HSC mobilization in mice.

"Capsaicin tablets are currently sold over-the-counter to 'help support cardiovascular and digestive function' at higher doses than that predicted by our studies in mice for stimulating HSC mobilization in humans," said Frenette.

"These relatively low concentrations of capsaicin have biological effects without seemingly causing obvious pain," he said.

Collectively, these findings therefore suggest that targeting the nociceptive nervous system could represent a novel strategy by which to improve the yield of HSCs for stem cell-based therapies. (Gao, X. et al. Nature 2020, Advanced publication).

See the rest here:
Nociceptive neurons shown to boost hematopoiesis | 2020-12-28 - BioWorld Online

Multiple chimeric antigen receptor (CAR) T-cell therapies for the treatment of lymphomas and multiple myeloma have moved forward in the regulatory process, with 1 new FDA approval in 2020 and others anticipated in the near future.

In July, brexucabtagene autoleucel (Tecartus; KTEX19) received accelerated approval for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) based on the results of the phase 2 ZUMA-2 trial (NCT02601313), bringing the treatment landscape of this hematologic malignancy into a new era.1

This approval is only the very beginning, and we are walking into a sophisticated CAR T-cell therapy era with many constructs being designed with [different mechanisms of action], Michael Wang, MD, said in an interview with Targeted Therapies in Oncology (TTO).

Additional actions by the FDA this year included granting priority review designations to lisocabtagene maraleucel (liso-cel) for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma, after at least 2 prior therapies,2 as well as to idecabtagene vicleucel (ide-cel; bb2121)as treatment of adult patients with multiple myeloma who have received at least 3 prior therapies, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody.3

The approval of brexucabtagene autoleucel, an antiCD19 CAR T-cell product, in MCL was based on objective response rate (ORR) data from patients treated on a single-arm trial who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody, and a Bruton tyrosine kinase inhibitor (n = 74).2,4 Eligible patients received leukapheresis and optional bridging therapy, followed by conditioning chemotherapy and a single infusion of brexucabtagene autoleucel 2 106CAR T cells/kg.

The results of ZUMA-2 were published in the New England Journal of Medicine in April and demonstrated a 93% (95% CI, 84%-98%) ORR in 60 response-evaluable patients, 67% (95% CI, 53%-78%) of whom had a complete response (CR). ORRs were consistent across key patient subgroups. Two patients (3%) each had stable and progressive disease.

Progression-free and overall survival (OS) rates at 12 months were 61% and 83%, respectively, and 57% of patients remained in remission at the 12.3-month median follow-up.4 Cytokine release syndrome (CRS) was the most concerning adverse event, occurring in 91% of patients; grade 3 or higher CRS occurred in 15%.

Notably, the patient cohort comprised patients with a median of 3 prior lines of therapy (range, 1-5) and more than half (56%) were considered to have intermediateor high-risk features by the simplified Mantle Cell Lymphoma International Prognostic Index at baseline.

Before CAR T-cell therapy, we did not have any effective means [of getting patients with high-risk MCL into remission]. We used allogeneic transplantation [and] were able to put some of the patients into a long-term remission, but at a heavy price of mortality, said Wang, a professor in the Department of Lymphoma & Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston. Overall, this brings hope to the high-risk patient population. It looks as though fewer patients are relapsing.

Lisocabtagene Maraleucel In February, the FDA granted liso-cel a priority review designation, an action supported by the safety and efficacy findings of the phase 1 TRANSCEND-NHL-001 trial (NCT02631044).2

Histologic subtypes eligible for treatment included diffuse large B-cell lymphoma (DLBCL); high-grade double- or triple-hit B-cell lymphoma; transformed DLBCL from indolent lymphoma; primary mediastinal B-cell lymphoma; and grade 3B follicular lymphoma. Patients were administered 2 sequential infusions of CD8+ and CD4+ CAR T cells following optional bridging therapy and lymphodepleting chemotherapy and were assigned to 1 of 3 target dose levels: 50 106 (1 or 2 doses), 100 106 , or 150 106 CAR-positive T cells. Investigators determined that the recommended target dose was 100 106 CAR-positive T cells.

In the 256 patients who received at least 1 dose of liso-cel and were included in the efficacy-evaluable group, the ORR was 73% (95% CI, 67%-78%), with 53% (95% CI, 47%-59%) achieving a CR. Investigators observed all-grade CRS (42%) and neurological events (30%), but most cases were grade 1 or 2 in severity.

Due to relatively low rates of CRS and neurological events, the administration of liso-cel has been explored in both the inpatient and outpatient settings. One that included a cohort of patients treated in the outpatient setting with proper monitoring versus the traditional inpatient setting demonstrated consistent safety.6

Based on these results, the indication is that you can deliver [liso-cel] in the outpatient setting and the outcomes are good compared with those treated in the inpatient setting, explained study author Carlos R. Bachier, MD, the director of cellular research at Sarah Cannon in Nashville, Tennessee, in an interview with TTO. Aside from that, they also showed that liso-cel could be safely administered outside of university programs and in more community-based programs, most of them being aligned [with] or part of stem cell and bone marrow transplant programs.

The target action date for a decision on the biologics license application (BLA) for liso-cel was extended twice in 2020 and remains under review. In May, the FDA moved the Prescription Drug User Fee Act (PDUFA) goal date out 3 months from its original August deadline.2,7 Bristol Myers Squibb, the company responsible for developing the product, submitted additional information to the agency following the initial BLA submission, which resulted in more review time. Once again, the target action date was pushed in November, this time due to incomplete manufacturing facility inspections resulting from ongoing travel restrictions due to COVID-19. The FDA provided no new action date.8

For patients with multiple myeloma, the B-cell maturation antigen (BCMA)-targeting CAR T-cell therapy idecel is currently under review for approval in patients who have received at least 3 prior therapiesincluding an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibodybased on results of the phase 2 KarMMa trial (NCT03361748).9

Updated trial results were presented at the American Society of Clinical Oncology 2020 Virtual Scientific Program, and showed that both the primary and key secondary end points of ORR and CR rate were 75% and 33%, respectively. The median duration of response was 10.7 months, and the median progression-free survival was 8.8 months in all patients receiving ide-cel. Corresponding medians were 19.0 and 20.2 months among those achieving a CR or stringent CR. The median OS was 19.4 months in all treated patients.

The 128 patients treated received 1 of 3 target dose levels: 150, 300, or 450 106 CAR-positive T cells. The investigators noted that the highest efficacy outcomes were seen in patients in the 450 106 CAR-positive T-cell group, with an ORR of 82% and a 39% CR rate.

The incidence of CRS was 84% across the treatment cohort and increased with higher target doses. Overall, less than 6% of patients have grade 3 or higher CRS and only 1 patient in the highest target dose cohort had a grade 5 event. Neurological toxicity was low across target doses, with no grade 4 or 5 events reported.

At baseline, the majority of patients (51%) had high tumor burden, 39% had extramedullary disease, and 35% had high-risk cytogenetics including deletion 17p or translocations in t(4;14) or t(14;16).

In May, the FDA issued a refusal letter regarding the BLA for ide-cel because the Chemistry, Manufacturing, and Control (CMC) module required more information before they could complete the review.10 In September, the resubmitted application received a priority review and the agency assigned a PDUFA action date of March 27, 2021.11

If approved, ide-cel would be the first CAR T-cell therapy available for the treatment of patients with multiple myeloma.

References:

1. FDA approves brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma. FDA. Updated July 27, 2020. Accessed November 18, 2020. https://bit. ly/3pEDQV5

2. US Food and Drug Administration (FDA) accepts for priority review Bristol-Myers Squibbs biologics license application (BLA) for lisocabtagene maraleucel (liso-cel) for adult patients with relapsed or refractory large B-cell lymphoma. Press release. Bristol Myers Squibb. February 13, 2020. Accessed November 18, 2020. https:// bit.ly/37ruQbs

3. US Food and Drug Administration (FDA) accepts for priority review Bristol Myers Squibb and bluebird bio application for anti-BCMA CAR T cell therapy idecabtagene vicleucel (ide-cel, bb2121). Press release. Bristol Myers Squibb. September 22, 2020. Accessed November 18, 2020. https://bit.ly/3kDhakH

4. Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382(14):1331-1342. doi:10.1056/ NEJMoa1914347

5. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396(10254):839-852. doi:10.1016/ S0140-6736(20)31366-0

6. Bachier CR, Palomba ML, Abramson JA, et al. Outpatient treatment with lisocabtagene maraleucel (liso-cel) in 3 ongoing clinical studies in relapsed/refractory (R/R) large B cell non-Hodgkin lymphoma (NHL), including second-line transplant noneligible (TNE) patients: Transcend NHL 001, Outreach, and PILOT. Paper presented at: 2020 Transplantation & Cellular Therapy Meetings; February 19-23, 2020; Orlando, FL. Abstract 29. Accessed November 18, 2020. bit.ly/37I7DC9

7. Bristol Myers Squibb provides update on biologics license application (BLA) for lisocabtagene maraleucel (liso-cel). Press release. Bristol Myers Squibb. May 6, 2020. Accessed November 18, 2020.https://bit.ly/2YFWAs8

8. Bristol Myers Squibb provides regulatory update on lisocabtagene maraleucel (liso-cel). News release. Business Wire. November 16, 2020. Accessed November 18, 2020. https://bwnews.pr/3pKQMZI

9. Bristol Myers Squibb and bluebird bio announce submission of biologics license application (BLA) for anti-BCMA CAR T cell therapy idecabtagene vicleucel (ide-cel, bb2121) to FDA. Press release. Bristol Myers Squibb. March 31, 2020. Accessed November 18, 2020. https://bit.ly/2JwKbxO

10. Bristol Myers Squibb and bluebird bio provide regulatory update on idecabtagene vicleucel (ide-cel, bb2121) for the treatment of patients with multiple myeloma. News release. Business Wire. May 13, 2020.Accessed November 18, 2020. https:// bwnews.pr/3cpgJa1

11. US Food and Drug Administration (FDA) accepts for priority review Bristol Myers Squibb and bluebird bio application for anti-BCMA CAR T cell therapy idecabtagene vicleucel (ide-cel, bb2121). Press release. Bristol Myers Squibb. September 22, 2020. Accessed November 18, 2020. https://bit.ly/3kDhakH

Originally posted here:
CAR T-Cell Therapies Are Set to Expand Into More Hematologic Malignancy Indications - Targeted Oncology

First gene therapy to receivefull EU marketing authorization for eligible MLD patients

One-time treatment with Libmeldy has been shown to preserve motor and cognitive function

Achievement shared with research alliance partners Fondazione Telethon and Ospedale San Raffaele

BOSTON and LONDON and MILAN, Italy, Dec. 21, 2020 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, and its research alliance partners Fondazione Telethon and Ospedale San Raffaele, today announced that the European Commission (EC) granted full (standard) market authorization for Libmeldy (autologous CD34+ cells encoding the ARSA gene), a lentiviral vector-based gene therapy approved for the treatment of metachromatic leukodystrophy (MLD), characterized by biallelic mutations in theARSAgene leading to a reduction of the ARSA enzymatic activity in children with i) late infantile or early juvenile forms, without clinical manifestations of the disease, or ii) the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline. Libmeldy is the first therapy approved for eligible patients with early-onset MLD.

MLD is a very rare, fatal genetic disorder caused by mutations in the ARSA gene which lead to neurological damage and developmental regression. In its most severe and common forms, young children rapidly lose the ability to walk, talk and interact with the world around them, and most pass away before adolescence. Libmeldy is designed as a one-time therapy that aims to correct the underlying genetic cause of MLD, offering eligible young patients the potential for long-term positive effects on cognitive development and maintenance of motor function at ages at which untreated patients show severe motor and cognitive impairments.

Todays EC approval of Libmeldy opens up tremendous new possibilities for eligible MLD children faced with this devastating disease where previously no approved treatment options existed, said Bobby Gaspar, M.D., Ph.D., chief executive officer of Orchard. Libmeldy is Orchards first product approval as a company, and I am extremely proud of the entire team who helped achieve this milestone. We are grateful for and humbled by the opportunity to bring this remarkable innovation to young eligible patients in the EU.

With Libmeldy, a patients own hematopoietic stem cells (HSCs) are selected, and functional copies of the ARSA gene are inserted into the genome of the HSCs using a self-inactivating (SIN) lentiviral vector before these genetically modified cells are infused back into the patient. The ability of the gene-corrected HSCs to migrate across the blood-brain barrier into the brain, engraft, and express the functional enzyme has the potential to persistently correct the underlying disease with a single treatment.

The EC approval of Libmeldy comes more than a decade after the first patient was treated in clinical trials performed at our Institute, and ushers in a remarkable and long-awaited shift in the treatment landscape for eligible MLD patients, said Luigi Naldini, M.D, Ph.D., director of the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy. Our team at SR-Tiget has been instrumental in advancing the discovery and early-stage research of this potentially transformative therapy to clinical trials in support of its registration through more than 15 years of studies supported by Fondazione Telethon and Ospedale San Raffaele, and we are extremely proud of this achievement and what it means for patients and the field of HSC gene therapy.

MLD is a heart-breaking disease that causes immeasurable suffering and robs children of the chance of life, said Georgina Morton, chairperson of ArchAngel MLD Trust. As a community, we have been desperate for a treatment for young MLD patients, and we are incredibly excited to now have such a ground-breaking option approved in the EU.

The marketing authorization for Libmeldy is valid in all 27 member states of the EU as well as the UK, Iceland, Liechtenstein and Norway. Orchard is currently undertaking EU launch preparations related to commercial drug manufacturing, treatment site qualification and market access.

Data Supporting the Clinical and Safety Profile of Libmeldy

The marketing authorization for Libmeldy is supported by clinical studies in both pre- and early- symptomatic, early-onset MLD patients performed at the SR-Tiget. Early-onset MLD encompasses the disease variants often referred to as late infantile (LI) and early juvenile (EJ). Clinical efficacy was based on the integrated data analysis from 29 patients with early-onset MLD who were treated with Libmeldy prepared as a fresh (non-cryopreserved) formulation. Results of this analysis indicate that a single-dose intravenous administration of Libmeldy is effective in modifying the disease course of early-onset MLD in most patients.

Clinical safety was evaluated in 35 patients with MLD (the 29 patients from the integrated efficacy analysis as well as six additional patients treated with the cryopreserved formulation of Libmeldy). Safety data indicate that Libmeldy was generally well-tolerated. The most common adverse reaction attributed to treatment with Libmeldy was the occurrence of anti-ARSA antibodies (AAA) reported in five out of 35 patients. Antibody titers in all five patients were generally low and no negative effects were observed in post-treatment ARSA activity in the peripheral blood or bone marrow cellular subpopulations, nor in the ARSA activity within the cerebrospinal fluid. In addition to the risks associated with the gene therapy, treatment with Libmeldy is preceded by other medical interventions, namely bone marrow harvest or peripheral blood mobilization and apheresis, followed by myeloablative conditioning, which carry their own risks. During the clinical studies, the safety profiles of these interventions were consistent with their known safety and tolerability.

For further details, please see the Summary of Product Characteristics (SmPC).

About MLD and Libmeldy

MLD is a rare and life-threatening inherited disease of the bodys metabolic system occurring in approximately one in every 100,000 live births. MLD is caused by a mutation in the arylsulfatase-A (ARSA) gene that results in the accumulation of sulfatides in the brain and other areas of the body, including the liver, gallbladder, kidneys, and/or spleen. Over time, the nervous system is damaged, leading to neurological problems such as motor, behavioral and cognitive regression, severe spasticity and seizures. Patients with MLD gradually lose the ability to move, talk, swallow, eat and see. In its late infantile form, mortality at five years from onset is estimated at 50% and 44% at 10 years for juvenile patients.1

Libmeldy (autologous CD34+ cell enriched population that contains hematopoietic stem and progenitor cells (HSPC) transduced ex vivo using a lentiviral vector encoding the human arylsulfatase-A (ARSA) gene), also known as OTL-200, is approved in the European Union for the treatment of MLD in eligible early-onset patients. In the U.S., OTL-200 is an investigational therapy which has not been approved by the U.S. Food and Drug Administration (FDA) for any use. Libmeldy was acquired from GSK in April 2018 and originated from a pioneering collaboration between GSK and the Hospital San Raffaele and Fondazione Telethon, acting through their joint San Raffaele-Telethon Institute for Gene Therapy in Milan, initiated in 2010.

About Orchard

Orchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through the development of innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. In 2018, Orchard acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Orchard now has one of the deepest and most advanced gene therapy product candidate pipelines in the industry spanning multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist.

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

Availability of Other Information About Orchard

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

About Fondazione Telethon, Ospedale San Raffaele and the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget)

Based in Milan, Italy, the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) is a joint venture between the Ospedale San Raffaele, a clinical-research-university hospital established in 1971 to provide international-level specialized care for the most complex and difficult health conditions, and Fondazione Telethon, an Italian biomedical charity born in 1990 and focused on rare genetic diseases. SR-Tiget was established in 1995 to perform research on gene transfer and cell transplantation and translate its results into clinical applications of gene and cell therapies for different genetic diseases. Over the years, the Institute hasgiven a pioneering contribution to the field with relevant discoveries in vector design, gene transfer strategies, stem cell biology, identity and mechanism of action of innate immune cells. SR-Tiget has also established the resources and framework for translating these advances into novel experimental therapies and has implemented several successful gene therapy clinical trials for inherited immunodeficiencies, blood and storage disorders, which have already treated >115 patients and have led through collaboration with industrial partners to the filing and approval of novel advanced gene therapy medicines.

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Forward-Looking Statements

This press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements may be identified by words such as anticipates, believes, expects, plans, intends, projects, and future or similar expressions that are intended to identify forward-looking statements. Forward-looking statements include express or implied statements relating to, among other things, Orchards business strategy and goals, including its plans and expectations for the commercialization of Libmeldy, and the therapeutic potential of Libmeldy, including the potential implications of clinical data for eligible patients. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, these risks and uncertainties include, without limitation:: the risk that prior results, such as signals of safety, activity or durability of effect, observed from clinical trials of Libmeldy will not continue or be repeated in our ongoing or planned clinical trials of Libmeldy, will be insufficient to support regulatory submissions or marketing approval in the US or to maintain marketing approval in the EU, or that long-term adverse safety findings may be discovered; the inability or risk of delays in Orchards ability to commercialize Libmeldy, including the risk that we may not secure adequate pricing or reimbursement to support continued development or commercialization of Libmeldy; the risk that the market opportunity for Libmeldy, or any of Orchards product candidates, may be lower than estimated; and the severity of the impact of the COVID-19 pandemic on Orchards business, including on clinical development, its supply chain and commercial programs. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.

Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchards quarterly report on Form 10-Q for the quarter endedSeptember 30, 2020, as filed with theU.S. Securities and Exchange Commission(SEC), as well as subsequent filings and reports filed with theSEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

Contacts

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

MediaChristine HarrisonVice President, Corporate Affairs+1 202-415-0137media@orchard-tx.com

1 Mahmood et al. Metachromatic Leukodystrophy: A Case of Triplets with the Late Infantile Variant and a Systematic Review of the Literature.Journal of Child Neurology2010, DOI:http://doi.org/10.1177/0883073809341669

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Orchard Therapeutics Receives EC Approval for Libmeldy for the Treatment of Early-Onset Metachromatic Leukodystrophy (MLD) - GlobeNewswire

Pune, Maharashtra, India, December 18 2020 (Wiredrelease) Brandessence Market Research and Consulting Pvt ltd :Global Cell Banking Outsourcing Market is valued at USD 7122.6 Million in 2019 and expected to reach USD 18489.6 Million by 2026 with the CAGR of 14.6% over the forecast period.

Rising prevalence of cancer and infectious chronic disorders couples with growing demand for research and development in therapy viral cell banking and viral cell banking safety testing are expected to propel the growth of the Global Cell Banking Outsourcing Market.

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Scope of Global Cell Banking Outsourcing Market Report

The cell banking outsourcing is an ability that stores cells of specific genome for the purpose of future use in a product or medicinal needs to use of gene therapy, stem cell therapy, biopharmaceutical production that target on novel active sites. They are frequently containing expansive amounts of base cell material that can be utilized for various projects. The cell banking outsourcing can be used to generate detailed characterizations of cell lines and can also help mitigate cross-contamination of a cell line. Hence, the cell banking outsourcing is commonly used within fields including stem cell research and pharmaceuticals with cryopreservation being the traditional method of keeping cellular material intact. However, the cell banking is most generally used in stem cell research and therapy. The similar types of cell banking include master cell banks and working cell banks. Although, the master cell banks are expanded to form working cell banks consist of pure cells from are replicated whereas working cell banks consist of thawed cells that are replicated in cell culture.

Additionally, it is a process of replicating and storing cells for the purpose of future use. This storage of these cell samples can be utilized for research purposes and for surgical reconstruction of damaged body structures. However, the bank storage in cell banking encompasses preservation of both master and working cell banking, and their respective safety testing. The cell banking outsourcing expected to witness lucrative growth over the forecast period owing to the presence of increased research in cell line development coupled with the presence of market players providing outsourcing services for cell banking and cell line storage to different hospitals and clinical research organizations.

Global Cell Banking Outsourcing Market report is segmented on the basis of type, application, and by regional & country level. Based on type, global cell banking outsourcing market is classified as the master cell banking, viral cell banking and working cell banking. Based upon application, global cell banking outsourcing is classified into bank storage, working cell bank storage, master cell bank storage cell storage stability testing, bank preparation, bank characterization & testing and others.

The regions covered in this cell banking outsourcing market report are North America, Europe, Asia-Pacific and Rest of the World. On the basis of country level, market of cell banking outsourcing is sub divided into U.S., Mexico, Canada, U.K., France, Germany, Italy, China, Japan, India, South East Asia, GCC, Africa, etc.

Cell Banking Outsourcing Manufacturers:

Some major key players for Global Cell Banking Outsourcing Market are,

BioReliance Covance Global Stem Inc BSL Disservice Clean cells Charles River Laboratories Lonza Toxikon Corporation Cryobanks International India Wuxi Apptec Reliance Life Sciences Life Cell International Pvt. Ltd BioOutsource (Sartorious) CordLife PXTherapeutics SA SGS Life Sciences Texcell Cryo-Cell International Inc. Others

Global Cell Banking Outsourcing Market Dynamics

The rapidly increasing awareness for stem cell banking in the developing countries, and increasing governments initiatives that promote awareness for stem cell isolation and related benefits are some of the major factors driving the market growth during the forecast period. In addition, increasing application of stem cells for developing personalized medicines to minimize the spread of various chronic diseases and also the association of aging with the inability of the body to maintain tissue turnover and hemostasis has helped researchers to focus on this target population for providing relative therapies that would act effectively on the damaged cells. These factors are also supplementing the market growth. According to the World Health Organization (WHO), estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 globes about 18.1 million new cancer cases about 17.0 million excluding no melanoma skin cancer and 9.6 million cancer deaths in 2018. Furthermore, the master cell banks are useful for the preparation of working cell banks and thus find applicability in various research and development perspectives for stem cell therapy and gene therapy thereby resulting to section growth. The occurrence of favorable government initiatives pertaining to the R&D for development of stable cell lines, the opening of new technology for storage and description of cell lines are among the critical factors predictable to advance market growth over the forecast period.

However, the high cost associated with storing these cells in cell banks is a major challenge faced by this market which may hamper the growth of cell banking outsourcing market. In addition, the various legal challenges associate with banking a variety of cells, especially considering stem cells banking, are expected to restrain market growth. The advanced technologically cryopreservation techniques are expected to fuel the growth of this market throughout the forecast period. In spite of that, the increase in the average life expectations due to advanced medical research and improved general lifestyle of the population and straightforward regulations for the stem cell researchers are expected to create significant potential for this market in coming few years. Increasing number of adipose tissue banking can offer various opportunities of the cell banking outsourcing market.

Global Cell Banking Outsourcing Market Regional Analysis

North America is expected to dominate the global cell banking outsourcing drug market due to the highest market share owing to the increasing number biopharmaceutical companies & manufacturers and increasing awareness for the use of stem cells as therapeutic proteins and antibiotics in this region. According to the World Health Organization (WHO), the American Cancer Society epidemiologists, at least 42% of newly diagnosed cancers in the U.S. about 729,000 cases are potentially avoidable, including 19% that are caused by smoking and 18% that are caused by a combination of excess body weight, physical inactivity, excess alcohol consumption, and poor nutrition. In addition, presence of regulatory authorities that promotes continuous R&D activities is also supplementing the market growth in North America.

The Asia Pacific is expected to witness significant growth in demand over the forecast period owing to increase in number of supportive government initiatives pertaining to investments in biotechnology sector in this region. In addition, the ongoing R&D activities for cancer treatment and fertility preservation facilitate the demand for cell banking services in this region.

Key Benefits for Global Cell Banking Outsourcing Market Report

Global Cell Banking Outsourcing Market report covers in depth historical and forecast analysis.

Global Cell Banking Outsourcing Market research report provides detail information about Market Introduction, Market Summary, Global market Revenue (Revenue USD), Market Drivers, Market Restraints, Market opportunities, Competitive Analysis, Regional and Country Level.

Global Cell Banking Outsourcing Market report helps to identify opportunities in market place.

Global Cell Banking Outsourcing Market report covers extensive analysis of emerging trends and competitive landscape.

Global Cell Banking Outsourcing Market Segmentation:

By Type:Master Cell Banking, Viral Cell Banking, Working Cell Banking

By Application:Bank Storage, Working Cell Bank Storage, Master Cell Bank Storage, Cell Storage Stability Testing, Bank Preparation, Bank Characterization & Testing

Regional & Country AnalysisNorth America, U.S., Mexico, Canada , Europe, UK, France, Germany, Italy , Asia Pacific, China, Japan, India, Southeast Asia, South America, Brazil, Argentina, Columbia, The Middle East and Africa, GCC, Africa, Rest of Middle East and Africa

Table of Content

1. Chapter Report Methodology1.1. Research Process1.2. Primary Research1.3. Secondary Research1.4. Market Size Estimates1.5. Data Triangulation1.6. Forecast Model1.7. USPs of Report1.8. Report Description

2. Chapter Global Cell Banking Outsourcing Market Overview: Qualitative Analysis2.1. Market Introduction2.2. Executive Summary2.3. Global Cell Banking Outsourcing Market Classification2.4. Market Drivers2.5. Market Restraints2.6. Market Opportunity2.7. Cell Banking Outsourcing Market: Trends2.8. Porters Five Forces Analysis2.9. Market Attractiveness Analysis

3. Chapter Global Cell Banking Outsourcing Market Overview: Quantitative Analysis

4. Chapter Global Cell Banking Outsourcing Market Analysis: Segmentation By Type

5. Chapter Global Cell Banking Outsourcing Market Analysis: Segmentation By Application

Continued.

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At 14.6% CAGR, Cell Banking Outsourcing Market 2020 Industry Analysis of Current Trends and Opportun - PharmiWeb.com

In this Article In this Article In this Article

Most treatment for heart failure can only slow it down or ease your symptoms. Soon, it may be possible to fix what causes it. Doctors are testing whether stem cells can repair or replace damaged heart cells.

Stem cells can grow into many different kinds of cells. You have them in organs and tissues all over your body. They divide to replace worn-out or damaged cells, and to become new stem cells.

In the lab, scientists have turned stem cells into ones that make up blood vessel walls and linings, and into actual beating heart cells. Now theyre trying to translate that into a treatment.

Scientists have zeroed in on a few specific kinds of cells that may be helpful:

Bone marrow mononuclear cells: A mixture of cells that comes from your own bone marrow.

Cardiac-derived stem cells: Ones found in heart tissue.

Mesenchymal stromal cells: They're usually taken from bone marrow, fat, or umbilical cord blood.

Proangiogenic progenitor cells: These are in blood and bone marrow.

It's not approved to treat heart failure, yet. You can get it through a clinical trial. Thats when the research moves from the lab to the hospital to see if a treatment is safe and if it works.

If you want to try stem cell therapy, ask your doctors if there are studies that may be a good fit for you. The National Library of Medicine has a website that helps you search for all kinds of clinical trials.

Not all experimental treatments are part of a clinical trial, so make sure you understand what youre signing up for. If its a legitimate study, you shouldnt have to pay for treatment or follow-ups.

Most people testing stem cell therapy for heart failure get one treatment. Then theyre checked every few months for a year or more.

Not everyone in a trial actually gets stem cells. Researchers need to compare the results of the new treatment against what happens with a group of people who dont get it.

Doctors are testing several different methods of giving people stem cells:

Intramyocardial injection: Cells go right into the heart muscle, usually during another procedure like open-heart surgery, bypass surgery, or implanting a pacemaker.

Intracoronary infusion: A catheter puts cells into your coronary artery. It goes into a large blood vessel in your groin and threaded through your heart.

Intravenously: Cells go right into the bloodstream through a needle placed in a vein.

With any of these methods, most stem cells leave the body quickly. Researchers are looking for better ways to make them stick. One possibility is growing them into a patch that goes directly to the damaged part of the heart.

Theres no way to fix heart damage that leads to heart failure. Stem cell therapy could change that. Still, its too early to call any treatment a success. The studies done so far have been too small. They've also used very different methods.

But it does look like stem cells could help repair heart tissue. In most studies, people who got them were less likely to die or go to the hospital during the study. Their hearts worked better and their quality of life was better than for people who didnt get them.

It isnt clear how stem cells help. Doctors hope clinical trials and research will help them discover that. They're also hoping to answer many other questions, including:

If you are interested in joining a trial, talk to your doctor.

SOURCES:

International Society for Stem Cell Research: Heart Disease, Types of Stem Cells, About Clinical Trials, Stem Cell Research: What to Ask.

National Institutes of Health: Mending a Broken Heart: Stem Cells and Cardiac Repair, Can Stem Cells Repair a Damaged Heart? Stem Cell Basics, NIH Clinical Research Trials and You.

Current Cardiology Reviews: Cellular Therapy for Heart Failure.

U.S. National Library of Medicine: ClinicalTrials.gov.

U.S. Food and Drug Administration: Consumer Information on Stem Cells.

Circulation Research: Cell Therapy for Heart Failure, Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial).

The Lancet: Ixmyelocel-T for patients with ischaemic heart failure: a prospective randomised double-blind trial.

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Stem Cell Therapy for Heart Failure Treatment

As interest in chimeric antigen receptor (CAR) T-cell therapy continues to grow with more promising data coming out and approvals from the FDA in various hematologic malignancies, the role of this cellular therapy has yet to be defined in multiple myeloma, but recent data have inspired hope for this therapy in the relapsed/refractory population.

The B-cell maturation antigen (BCMA)directed CAR T-cell therapy idecabtagene vicleucel (ide-cel; bb2121) has generated excitement in this population following the submission of a Biologics License Application (BLA) in March 2020, seeking approval of ide-cel in patients with multiple myeloma who have received at least 3 prior therapies, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody, and a Priority Review designation granted in September 2020. Following delays in the review due to coronavirus disease 2019, the Prescription Drug User Fee Act action date has been set as March 27, 2021.

Deep and durable responses were observed with ide-cel as treatment of heavily pretreated patients with relapsed/refractory multiple myeloma, according to updated results from the CRB-401 study presented by Yi Lin, MD, PhD, assistant professor of oncology and associate professor of medicine at Mayo Clinic, during the 2020 American Society of Hematology (ASH) Annual Meeting. The efficacy and safety findings were consistent with prior findings and supported a favorable clinical risk-benefit profile at target dose levels 150 x 106.1

The median overall survival with ide-cel was 34.2 months (95% CI, 19.2-not evaluable) among all patients in this triple-classexposed population, and half of the patients who had ongoing responses achieved a duration of response >2 years. The median progression-free survival (PFS) was 8.8 months (95% CI, 5.9-11.9). The objective response rate (ORR) overall was 75.8%, which included complete responses (CRs) in 38.7%.

These results from CRB-401 are comparable to the findings from the pivotal phase 2 KarMMa study (NCT03361748), which were presented earlier this year during the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program and support the Biologics License Application. The median OS for this study was 19.4 months, and the median PFS was 8.8 months. The ORR was 73%, which included a CR rate of 33%, and the median duration of response was 10.7 months.2

Ide-cel is being explored in several ongoing studies as well, including the phase 2 KarMMa-2 (NCT-3601078), phase 3 KarMMa-3 (NCT03651128), and phase 1 KarMMa-4 (NCT04196491) clinical trials. These phase 2 and 3 studies are evaluating ide-cel in patients with triple-classexposed disease, and the phase 1 study will explore the use of this CAR T-cell therapy in patients with high-risk newly diagnosed multiple myeloma.

These data have also set the stage for other BCMA-directed CAR T-cell therapies in development for the treatment of patients with multiple myeloma.

In an interview with Targeted Oncology, Lin discussed the updated findings from the CRB-401 study of ide-cel as treatment of patients with relapsed/refractory multiple myeloma.

TARGETED ONCOLOGY: What historical data have we seen with BCMA-directed CAR T-cell therapy in patients with relapsed/refractory multiple myeloma?

Lin: With the CAR T approach in multiple myeloma, the very first case report was actually with CD19-targeted CAR T because there was already experience with that particular antigen in leukemia and lymphomas. There's some ongoing effort in terms of dual targeting with CD19 and BCMA, but BCMA very quickly emerged as an ideal candidate for the myeloma space. This is an antigen that is more uniformly expressed on plasma cells, including myeloma cells, and maybe a small subset of mature B cells, but otherwise BCMA is not expressed on healthy tissues.

There have been some single-center clinical trials with the BCMA-targeted CAR T approach prior to the CRB-401 study, both with National Cancer Institute and the University of Pennsylvania with slightly different constructs. With those early phase 1 studies, there was a little bit more toxicity seen, although there was certainly some response, but the response wasn't particularly durable. CRB-401 is the first in a series of now industry-sponsored multicenter studies, in which we are now seeing a much more encouraging durable response rate and also a more favorable side effect profile as well. At ASH this year, I presented the longer follow-up on the phase 1 CRB-401 study. There is a pivotal phase 2 KarMMa study using the same CAR T construct that had been presented at ASCO earlier this year.

TARGETED ONCOLOGY: Please describe the design of the trial and what was different about the study.

Lin: The CRB-401 study has 2 parts. The first part is the dose-escalation part, and the second part is the dose expansion. The dose escalation is basically testing the range of a fixed dose of 50 million all the way up to 800 million of ide-cel CAR T cells in a relatively small number of patients, basically looking for signs of severe side effects to identify a safe dose. The dose expansion cohort is where we take the more promising doses in terms of response, and also safety profile, and test them in more patients to get a better safety signal, which is then moved forward for phase 2 testing in the KarMMa study.

In the dose-expansion portion of CRB-401, we required that each patient must have had exposure to an anti-CD38 antibody. That was allowed in a dose escalation but not required for everybody. [To be included in the study,] the patient must have had become refractory to the most recent line of treatment before they came on the study. The other thing that was different was that in the dose-escalation cohort, all patients had their myeloma cells in the bone marrow reviewed centrally by immunohistochemistry staining, and they were required to have at least 50% of these cells having BCMA expression in a dose-expansion cohort, to better understand the clinical efficacy and safety profiles of this treatment. We also included some patients that had BCMA expression below that to even levels that were not detectable by immunohistochemistry.

TARGETED ONCOLOGY: What were the results from this study?

Lin: The study [included] a total of 62 patients. The results from the first 33 patients were already published in the New England Journal of Medicine last year, and this year at ASH, data were presented for outcomes of the entire 62-patient cohort, with a median follow-up of now 18.1 months. What we have seen so far is in this entire treated patient cohort these are patients with very high-risk features of myeloma, and close to a third of these patients had high-risk cytogenetics, 37% of these patients had extra modularity plasma effect, and almost half of these patients needed some type of systemic therapy while their CAR T cells are being made. These patients, on average, had 6 lines of prior therapy, and in close to 70% or higher, these patients are either triple-refractory or were refractory to the most recent line of therapy.

For this group of patients that was treated overall, the safety signal was very tolerable, which is not surprising with CAR T therapy because these patients also do get lymphodepletion chemotherapy as part of the treatment with CAR T. We do see that low blood count is the most common side effect, including the more severe low blood counts, but on average, the recovery of these blood counts can be seen well under the first 3 months after CAR T infusion. The other most common side effects that we need to watch for with CAR T are cytokine release syndrome (CRS) and neurotoxicity. What we have seen in this study is that, on average, about 76% of these patients had some type of CRS. However, those that had grade 3 or higher, that is only [seen] in 6.5% of the patients, so much lower, and that's also reflected in the relative lower use of tocilizumab and steroids, as well, to manage the side effects. About 35% of these patients had some type of neurologic side effect, but again, only 1 patient had a more severe form of neurotoxicity. Compared to what we have seen with the CAR T experience in the lymphoma/leukemia space, this is a very, very encouraging safety profile.

We have also now seen that the ORR is quite high. It's 75.8% with a CR and stringent CR rate of about 38.7%. Many of these patients that had bone marrow that were evaluable for minimal residual disease (MRD) response were MRD-negative. We are seeing, since we tested many doses, that there is a dose-related increase in response with increasing [the] dose, and we have also seen that the duration of response is 10.3 months. When we look at the dose that was tested as well in those expansions [in] the 150 to 450 range, what we have seen is that the duration of response is comparable, so not significantly decreased, for patients with high-risk features like those with extramedullary disease for older patients, as well as patients who needed to get bridging therapy during treatment. The median PFS is 8.8 months, and the median OS is 34.2 months.

So far, the response rate, duration of response, and PFS seem to be comparable to what we also now see in the KarMMa study, which has less follow-up, but we are seeing a very nice median OS for a treatment in which we're just giving a 1 dose infusion and no follow-up maintenance therapy.

TARGETED ONCOLOGY: In terms of CAR T-cell therapy, how do you see this strategy impacting this patient population in the future?

Lin: I think there's definitely a role for this in the practice. The BLA for ide-cel has been submitted to the FDA, so we're anticipating review sometime in early 2021. This is very exciting because this could very well be the first CAR T for multiple myeloma. I think this would definitely be a treatment option for these patients. Based on how KarMMa is designed, we anticipate that the FDA approval will be in the space of patients who [have] had at least 3 lines of prior therapy and have been exposed to the currently approved 3 main backbones of treatmenta PI, IMiD, and the CD38 antibody. The full detail is pending final FDA review and the label. However, in that space, certainly looking at the demographic of the patient that's been treated so far as CRB-401 and KarMMa, that's a wider group of patients. Based on the fact that this is a treatment that is a basically living active cells, I perceive that the earlier that patient could get this therapy in the earliest possible approved indication, there would likely be potentially more benefit for the patients.

TARGETED ONCOLOGY: Do you think there is hope for this treatment in other hematologic malignancies outside of lymphomas and leukemias as well?

Lin: That is actually a very interesting question because what we're seeing in terms of the severity of CRS and neurotoxicity is a reflection of our evolving learning about how to manage the toxicity, as well. There is a component to the CAR design, the disease, the nature of the disease, the kinetics of the CAR T actions, in the manifestation of these symptoms. What we are seeing now, with even the prior CAR and next-generation CAR coming on, we will likely see an ongoing improvement in terms of a reduction of severity of these symptoms and also in the ways that we could manage these symptoms.

The fact that myeloma would be the next disease that has an FDA-approved CAR T also relates to the fact that the BCMA antigen is more restricted on the cell type where the malignancy is involved, similar to CD19 for lymphoid malignancy. We are seeing that there are some challenges, for example with acute myeloid leukemia or myeloid neoplasms where a number of antigens could overlap with stem cells, which we wouldn't want to try to hurt. There are some novel CAR approaches to try to overcome that, and those are in very early phase testing, so we'll need to see how those results evolve.

References

1. Lin Y, Raje NS, Berdeja JG, et al. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in patients with relapsed and refractory multiple myeloma: updated results from phase 1 CRB-401 study. Presented at: 2020 ASH Annual Meeting & Exposition; December 5-8, 2020; Virtual. Abstract 131.

2. Munshi NC, Anderson Jr LD, Jagannath S, et al. Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): Initial KarMMa results.J Clin Oncol. 2020;38(suppl):8503. doi:10.1200/JCO.2020.38.15_suppl.8503

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Updated Findings Show Continued Efficacy for CAR T-Cell Therapy in Heavily Pretreated Myeloma - Targeted Oncology

NEW YORK, Dec. 14, 2020 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, will host a webcast today to provide a corporate update.

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Mesoblast Corporate Update

NEW YORK, Dec. 14, 2020 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today announced top-line results from the landmark DREAM-HF Phase 3 randomized controlled trial of its allogeneic cell therapy rexlemestrocel-L (REVASCOR®) in 537 patients with advanced chronic heart failure1.

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Mesoblast Provides Topline Results From Phase 3 Trial of Rexlemestrocel-L for Advanced Chronic Heart Failure

CAMBRIDGE, Mass.--(BUSINESS WIRE)--HighPassBio, an ElevateBio portfolio company dedicated to advancing novel targeted T cell immunotherapies, today discussed the ongoing Phase 1 trial of the companys lead product candidate, an engineered T cell receptor (TCR) T cell therapy targeting HA-1 expressing cancer cells in an oral presentation at the 62nd American Society of Hematology (ASH) Annual Meeting. The Phase 1 clinical trial, which is being conducted by researchers at Fred Hutchinson Cancer Research Center, is designed to assess the feasibility, safety, and efficacy of this novel cell therapy in the treatment of leukemia following hematopoietic stem cell transplant (HSCT).

The prognosis for leukemia patients whove relapsed or who have residual disease following allogeneic hematopoietic stem cell transplantation is often poor, but we believe that by targeting the minor H antigen, HA-1, through a novel T cell immunotherapy, we can potentially treat and prevent subsequent relapse, said Elizabeth Krakow, M.D., MSc., Assistant Professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, principal investigator of the study, and presenting author. We have observed early promising indicators of anti-leukemic activity following treatment in this trial. We are eager to expand the trial to additional patients as we continue to research the feasibility, safety, and efficacy of this approach.

The abstract for the presentation titled Phase 1 Study of Adoptive Immunotherapy with HA-1-Specific CD8+ and CD4+ Memory T Cells for Children and Adults with Relapsed Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation (HCT): Trial in Progress, can be found on the ASH website under the abstract number 137726.

To date, four patients, including one pediatric patient, have received a total of six infusions in the Phase 1 clinical trial. Patient characteristic data was shared in the oral presentation at ASH, including documented HA-1 TCR T cell persistence in blood and bone marrow up to 18 months. In some patients, clear in vivo anti-leukemic activity was observed at the first dose level, including a subject with aggressive, highly refractory T-ALL and early post-HCT relapse. No significant toxicities attributed to the T cells have been observed, including no infusion reactions or evidence of cytokine release syndrome or graft versus host disease.

The Phase 1 clinical trial is currently recruiting adult and pediatric patients who have residual disease or relapsed leukemia or related conditions following HSCT. As part of the trial, transplant patients and prospective donors may be recruited to participate in the genetic screening portion to determine eligibility. More details are available on clinicaltrials.gov under the study ID number NCT03326921.

About TCR-Engineered T Cell Therapy

A key role of the immune system is to detect tumor antigens, engage T cells, and eradicate the tumor. However, the immune response to tumor antigens varies and is often insufficient to prevent tumor growth and relapse. An approach known as adoptive T cell therapy, using T cell receptors, or TCRs, can overcome some of the obstacles to establishing an effective immune response to fight off the target tumor. TCRs are molecules found on surface of T cells that can recognize tumor antigens that are degraded to small protein fragments inside tumor cells. Unlike CAR T cells that recognize only surface antigens, TCRs can recognize small protein fragments derived from intracellular and surface antigens offering a more diverse way to attack tumors. These small protein fragments show up on the tumor cell surface, with another protein called major histocompatibility complex (MHC), that are recognized by the TCRs and consequently signal the bodys immune system to respond to fight off and kill the tumor cells.

Tumor-specific TCRs can be identified and then engineered into T cells that recognize and attack various types of cancers, representing a novel approach to treating and potentially preventing disease.

Adoptive T cell therapy can be applied to tackling relapse of leukemia post hematopoietic stem cell transplant (HSCT) by targeting the antigens expressed only by the patients native cells, and not by the cells from the stem cell transplant donor. HA-1, a known minor histocompatibility antigen, is expressed predominantly or exclusively on hematopoietic cells, including leukemic cells. There is evidence that T cells specific for HA-1 can induce a potent and selective antileukemic effect. HA-1 TCR T cell therapy is a new investigational immunotherapy for the management of post transplantation leukemia relapse.

About Leukemia post HSCT Treatment and the Risk of Relapse

Leukemia, a cancer of the blood or bone marrow characterized by an abnormal proliferation of blood cells, is the tenth most common type of cancer in the U.S. with an estimated 60,140 new cases and 24,400 deaths in 2016. Leukemia arises from uncontrolled proliferation of a specific type of hematopoietic (blood) cell that is critical for a functional immune system. As a result, when patients are given very high doses of chemotherapy to eradicate leukemic cells, most normal cells are killed as well, necessitating a transplant of hematopoietic stem cells from a donor to reconstitute the patients bone marrow and circulating hematopoietic cells. In some cases, the transplanted T cells from the donor can also recognize and eliminate the hematopoietic cells, including leukemia, from the recipient, thus preventing relapse. This can be described as a graft versus leukemia effect. Other hematologic disorders related to leukemia, like myelodysplastic syndrome (MDS), can also be treated in this way.

While HSCT can be curative, it is estimated that 25-50 percent of HSCT recipients relapse; leukemia relapse remains the major cause of allogeneic HSCT failure, and the prognosis for patients with post-HCT relapse is poor. Relapse occurs following allogeneic HSCT in approximately one-third of patients with acute leukemia who undergo the procedure, and most patients subsequently die of their disease.

About HighPassBio

HighPassBio, an ElevateBio portfolio company, is working to advance a novel approach to treating hematological malignancies by leveraging T cell receptor (TCR)-engineered T cells, known as TCR T cells. The companys lead program is designed to treat or potentially prevent relapse of leukemia in patients who have undergone hematopoietic stem cell transplant (HSCT). The technology was born out of research conducted at Fred Hutchinson Cancer Research Center by world renowned expert, Dr. Marie Bleakley.

About ElevateBio

ElevateBio, LLC, is a Cambridge-based creator and operator of a portfolio of innovative cell and gene therapy companies. It begins with an environment where scientific inventors can transform their visions for cell and gene therapies into reality for patients with devastating and life-threatening diseases. Working with leading academic researchers, medical centers, and corporate partners, ElevateBios team of scientists, drug developers, and company builders are creating a portfolio of therapeutics companies that are changing the face of cell and gene therapy and regenerative medicine. Core to ElevateBios vision is BaseCamp, a centralized state-of-the-art innovation and manufacturing center, providing fully integrated capabilities, including basic and translational research, process development, clinical development, cGMP manufacturing, and regulatory affairs across multiple cell and gene therapy and regenerative medicine technology platforms. ElevateBio portfolio companies, as well as select strategic partners, are supported by ElevateBio BaseCamp in the advancement of novel cell and gene therapies.

ElevateBios investors include F2 Ventures, MPM Capital, EcoR1 Capital, Redmile Group, Samsara BioCapital, The Invus Group, Surveyor Capital (A Citadel company), EDBI, and Vertex Ventures.

ElevateBio is headquartered in Cambridge, Mass, with ElevateBio BaseCamp located in Waltham, Mass. For more information, please visit http://www.elevate.bio.

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ElevateBio's HighPassBio Presents on Novel T Cell Receptor Cell Therapy for Leukemia Relapse at 62nd Annual ASH Meeting - Business Wire

As the second wave of the pandemic engulfs us and the world works at warp speed to develop vaccines and therapies to respond, the importance of regenerative medicine has never been higher. Since 2017, Goldman Sachs has touted the sector as one of the most compelling areas for venture capital investment. With billions of dollars of global government spending being poured into the search for vaccines and therapies to respond to the novel coronavirus, and with the FDA having now granted approval to the first vaccines based on CRISPR mRNA gene-editing technologies, business models based on regenerative medicines are commanding record values. Despite the flood of cash into regenerative medicine, legal and ethical considerations will continue to cause much controversy.

Regenerative medicine ultimately accelerates the human bodys healing process. It is an area of biomedical sciences that involves medical treatments to repair or replace damaged cells, tissues, or organs. Instead of merely focusing on the symptoms, regenerative medicine uses cellular therapies, tissue engineering, medical devices, and artificial organs to improve peoples health. For example, stem cell therapies, tissue grafts, and organ transplants are all part of regenerative medicine.

Today, cellular and acellular regenerative medicines are often used in clinical procedures such as cell, immunomodulation, and tissue engineering therapies. They have the potential to effectively treat many chronic diseases, including Alzheimers, Parkinsons and cardiovascular disorders, osteoporosis, and spinal cord injuries.

A small number of unscrupulous actors, according to the FDA, however, have seized on the clinical promise of regenerative medicine to offer patients unproven treatments. The FDA and other regulators are challenged to provide assurances of safety for these therapies without stifling development, as well as to approve treatments based on manipulation of stem cells derived from human and animal embryos given the ethical issues involved.

In the future, stem cell research will play an increasingly outsized role in regenerative medicine techniques. In November 2020, voters in California narrowly passed Proposition 14, a referendum to approve $5.5 billion in new government funding for stem cell research. Other governments around the world are doing the same.

Today, the growing prevalence of chronic medical ailments and genetic disorders across the globe is a primary factor driving the regenerative medicine industrys growth, according to the Regenerative Medicine Market: Global Industry Trends, Share, Size, Growth, Opportunity and Forecast 2020-2025. The increasing aging population, prone to various musculoskeletal, oncological, dermatological, and cardiological disorders, is a key growth driver. Widespread adoption of organ transplantation is another contributing factor to this growth in market share. The current pandemic that began in January 2020, however, has changed the paradigm for regenerative medicine.

Market applications are burgeoning. Regenerative medicine can prevent and cure disease through effective vaccines and efficacious therapies. It can minimize the risk of organ rejection post-transplant and speed recovery. Technological advancements in cell-based therapies, such as the development of 3-D bioprinting techniques and the adoption of artificial intelligence in the production of regenerative medicines, are also stimulating growth. These advancements also facilitate dermatological grafting procedures to treat burns, bone defects, and skin wounds. Other factors, including extensive research and development activities in medical sciences and improving healthcare infrastructure, are also predicted to drive the market even further.

According to the Alliance for Regenerative Medicine, there are approaching approximately 1,000 companies focusing on this evolving area worldwide. These new companies are focusing on gene therapy, cell therapy and tissue engineering therapeutic developers. More than half of these companies are in North America, followed by almost a quarter in Europe and Israel and approximately 20% in Asia. More than 50% of these companies are focusing on cell therapy and gene therapy.

From 2014 to 2019, the global regenerative medicine market experienced a nearly 16% CAGR. Companies involved in gene and cell therapies as well as other regenerative medicine areas raised $4.8 billion during the first half of 2019, including $2.6 billion in the second quarter. Meanwhile, companies in Europe and Israel saw an acceleration of fundraising, with $1.3 billion amassed in just the first half of 2019, representing a 17% increase over the same period in 2018. Project Warp Speed has attracted billions of dollars of U.S. government spending, and similar efforts are ongoing in China, Russia, the European Union and among other major powers. Consequently, regenerative medicine has never before benefited from such a combination of public and private investment.

Whenever the viability and quality of human life are at stake, ethical and legal considerations always arise.

The modern ethical controversy surrounding regenerative medicine began in 1998 when research scientists at the University of Wisconsin succeeded in deriving and growing stem cells from early-stage human embryos. Ethicists and right-to-life activists protested that scientists were taking away human life (embryos) to conduct scientific experiments. Left unchecked, so the argument went, doctors could usurp nature and play God by developing the power to create and terminate life. A society where human life could be fundamentally perverted by medicine conjured up comparisons to Nazi Germany and Frankenstein. In 2001, then-U.S. President George W. Bush cut off federal funding for any research involving newly created embryonic stem cell lines, but agreed to continue funding research on 60 existing stem cell lines, where the life and death decision ha[d] already been made. The State of California responded in 2004 and again in 2020 with voter-approved programs directing billions of funding into stem cell research, making the region the global hub of regenerative medicine.

The use of human-derived embryonic stem cells, or animal-derived stem cells, continues to cause much controversy among ethicists and society at large. Some fear the risks of enrolling humans in experimental stem cell studies. Others fear the use of organs from human-animal chimeras in transplantation.

While these techniques have the potential to cure disease and save lives, they also have the potential to forever alter the nature of life as we know it and fundamental aspects of our society.

In the United States, legal jurisdiction for regulating regenerative medicine on a federal level lies with the FDA and in a patchwork of state laws, R&D funding programs and non-binding, NGO-promulgated statements of policy. The main responsibility of the FDA is to protect the public from dangerous products and ensure its safety, including overseeing medications for humans and animals, vaccines, and more.

During the Trump Administration, the FDA has largely focused on enabling developers to gain product approvals through a less burdensome and costly process. In numerous policy statements, the FDA under President Trump has deferred questions about the efficacy of new regenerative health products to the free markets, so long as they posed no serious safety or toxicity concerns.

The U.S. federal government is now transitioning to an administration led by President-elect Biden. The president-elect has spent many years advocating for increased R&D funding and going for moonshots. With a new mandate from the U.S. electorate to address the coronavirus, more money will be earmarked for regenerative medicines and stem cell research. How this will affect the release of new products into the market remains to be seen.

Regenerative medicine is poised to change the way we live, work and interact like never before. The fourth industrial revolution is upon us. CRISPR gene-editing technologies, facilitated by quantum-computing capabilities at the edge of a computer network powered by 5G telecommunications bandwidths, artificial intelligence and machine learning, have changed the game for regenerative medicine. We can foresee a day when those suffering from paralysis regain movement, when a damaged heart reverses course through regeneration, and when a diagnosis of Alzheimers Disease no longer means neurodegeneration. What a wonderful day that will be.

Changing the traditional healthcare model and moving from cure to prevention will take time.

The rise in chronic disease and the effort to reduce healthcare costs presents a large opportunity for the field of regenerative medicine.

As the continent becomes a bigger player, western companies should explore the potential prospects.

Topics from regenerative medicine to artificial intelligence to cannabis will be discussed.

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Regenerative Medicine: Market Trends and Legal Developments on the Horizon for 2021 - MedTech Intelligence

Cell therapies involve the transfer of live cells into a patient to help treat, prevent or potentially cure diseases. One category of cell therapy focuses specifically on the use of stem cells, or cells within the body that have the potential to replace those that are lost through injury or disease. Their versatility and ability to transform allow them to replace problematic or deactivated cells with new, healthy ones is giving patients around the world a second chance at life.Stem cells are found all throughout the human bodyincluding the skin, muscle tissue and even deep inside bone marrow.

Bone marrow, the spongy substance that fills the inner cavities of our bones, is a rich source ofhematopoietic stem cells. These cells are particularly valuable for their ability to develop into all types of blood cells, including white blood cells, red blood cells and platelets. Due to their unique ability,hematopoietic cells can be used to treat certain types of cancer, such as leukemia and lymphomaand have become a staple in the field of regenerative medicine.

Bone marrow aspirate concentrate(BMAC) is a procedure that collects bone marrow from a patient's body and then concentrates it to create the optimal level of stem cells and other crucial growth factors, which can offer a variety of health benefits that traditional surgical methods simply can't offer. Stem cells and their descendants, known as progenitor cells, combined with other bone marrow cells and platelets, have the potential to restore function when injected directly into the patient's damaged tissue. The BMAC procedure is popularly used by physicians who practice orthopedic surgery, pain management and sports medicine. It has been shown torepair tissue damage, preserving function and strengthand in some cases has even beenused as an alternative for more intensive procedures such as joint and hip replacements.

Bone Marrow Aspirate Concentrate is currently being used to:

While there are many bone marrow concentrate technologies currently out on the market, there are none quite like theThermoGenesis PXPSystem. The PXPSystem is an automated, closed system designed for sterile bone marrow separation and concentration. The automated system utilizes highly sensitive sensors to reduce the amount of red blood cells (RBCs) from the initial bone marrow aspirate, providing physicians with a high-quality final product.Red blood cell contaminationis, by far, the biggest issue physicians encounter when using open, non-automated bone marrow processing systems. When high RBC contamination occurs in the bone marrow concentrate, it can impair cell function and diminish the overall effectiveness of the cell treatments. The PXPSystem is specifically designed to eliminate RBCs contamination head-on, boasting aRBC reduction of over 99 percent.

[Link]

The PXPSystem obtains bone marrow concentrates easily, consistently, and reliably, setting itself apart from any other competitors on the market today. The automated nature of the system eliminates factors created by human error and allows for increased precision and control. It gives its user the ability to harvest a precise volume of cell concentrate from the bone marrow aspirate, while producing consistently high mononuclear cells (MNCs) and CD34+ progenitor cell recoveries.

[Link][Link]

Bone marrow aspirate is collected from the patient through a minimally invasive procedure, usually done under local or general anesthesia. After extraction, the aspirate is transferred into the PXP System and processed in a centrifuge to compartmentalize the aspirate into three separate chambers within the Disposable Cartridge - the central processing chamber, the red blood cell depletion chamber and the harvest chamber. The plasma, nucleated cells and RBCs are all sorted by density to create maximum separation of components. The RBCs are then removed and transferred to the depletion chamber, leaving users with a 6 ml harvest of enriched bone marrow concentrate (containing stem cells, platelets, growth factors) ready to be reintroduced into the patient.

The entire process only takes about twenty minutes from the moment the bone marrow aspirate is placed in the system to the point where it can be reinjected. For added convenience, the automated control module provides users with accurate data tracking and serves as a record for the entire process.

The PXPSystem is a tool for physicians looking for a quick, easy and efficient system for processing bone marrow. It is one of the most innovative systems available on the market and our mission is to make it even better. We are currently working with our partners in the field and evolving our products based on their feedback. Based on their response, we've begun designing a stripped-down version of the PXPSystem that requires less accessories and generates a smaller footprint, while still delivering a high-quality final product. Our applications are being developed with the needs of laboratories and physicians in mind, giving them the resources, they need to better serve their patients.

ThermoGenesis Holdings, Inc. (formerly Cesca Therapeutics Inc.), is a pioneer and market leader in the development and commercialization of automated cell processing technologies for the cell and gene therapy fields. We market a full suite of solutions for automated clinical biobanking, COVID-19 testing, point-of-care applications and large-scale cell processing and manufacturing with a special emphasis on the emerging CAR-T immunotherapy market. We are committed to making the world a healthier place by creating innovative solutions for those in need.

To see our full suiteof automated solutions,please visit the shop portion of our website today.

Disclaimer

Thermogenesis Holdings Inc. published this content on 08 December 2020 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 09 December 2020 18:24:01 UTC

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The Technology Behind Bone Marrow Cellular Processing: The PXP System - marketscreener.com

HAMBURG, GERMANY / ACCESSWIRE / December 9, 2020 / Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) and the life science company Sartorius announced today that they have entered into a partnership with the recently established Curexsys GmbH, a Goettingen, Germany-based technology leader specialising in the emerging field of therapeutic exosomes.

Curexsys delivers a proprietary isolation technology for exosomes based on a traceless immune-affinity process. This process is different from commonly used antibody-based processes and enables the company to overcome a key hurdle in exosome preparation, i.e. remaining antibodies in the final preparation. Curexsys is founded by Herbert Stadler, a serial biotech entrepreneur, and Jens Gruber, a former group leader of Medical RNA Biology who is going to lead Curexsys as Chief Scientific Officer.

Under the terms of the agreement, Evotec and Curexsys will collaborate with the production of Human Mesenchymal Stem Cells ("MSCs"), which serve as a source for exosomes. These are small vesicles that are naturally released from a cell. They contain proteins, nucleic acids and metabolites, which carry information from secreting to receiving cells. Exosomes have immunomodulatory and anti-inflammatory effects, which makes them a promising novel approach for innovative regenerative therapies, as therapeutics in age-related conditions, but also for diagnostic purposes. Curexsys aims to develop targeted approaches for a variety of diseases, initially focusing on Sicca Syndrome, commonly known as "dry eye", an inflammatory condition affecting 14% to 17% of the adult population for whom there is currently no effective treatment available.

The collaboration combines Evotec's industry-leading induced Pluripotent Stem Cell ("iPSC") platform with Curexsys' proprietary technology to selectively isolate exosomes. Sartorius will support Curexsys to set up a GMP-compliant and scalable manufacturing platform.

Furthermore, Evotec and Sartorius have formed a consortium to jointly invest in Curexsys' 8.2 m seed financing round with Evotec acquiring an equity stake of approx. 37% in Curexsys and Sartorius of approx. 21%.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, commented: "Therapeutic exosomes hold significant promise for regenerative medicine and beyond. Steadily increasing evidence suggests that exosomes derived from stem cells can aid tissue repair and engineering vesicles could carry drugs to diseased tissues. These efforts have been held back by a dearth of standardised methods to isolate and study vesicles. Combining Evotec's industrial-grade iPSC and PanOmics platforms with Curexsys' proprietary exosome isolation technology and Sartorius' ability to translate these into a fully GMP-compliant process is a unique opportunity to build the leading exosome company in the industry."

Dr Ren Faber, Head of Sartorius' Bioprocess Solutions Division, said: "With our integrated portfolio of manufacturing solutions Sartorius is the 'go-to' partner for developers of such new modalities when it comes to implementing GMP-compliant, flexible production processes. We are very much looking forward to contributing our proven and scalable technology platform to Curexsys process and help them achieve their next milestones faster."

Dr Jens Gruber, Chief Scientific Officer of Curexsys, added: "We are very happy that we were able to form such a consortium with industry leaders in their field. This unique constellation gives Curexsys an optimal starting position to advance our technologies for highly specific isolation of exosomes and to rapidly approach therapeutic applications."

About Exosomes and CurexsysExosomes are extracellular, nanoscale vesicles that are actively secreted from cells to transfer information to neighbouring cells and distant tissues. Exosomes carry information of secreting to receiving cells utilising proteins, nucleic acids and metabolites. MSC-derived exosomes function as paracrine mediators that limit inflammation, reprogram immune cells, and activate endogenous repair pathways, recapitulating to a large extent the therapeutic effects of parental MSCs. Exosomes hold potential as diagnostics, as therapeutics and cosmeceuticals. More than 100 clinical trials involving exosomes are currently ongoing, demonstrating their broad therapeutic potential.

Curexsys is a Goettingen, Germany-based start-up company founded by molecular biologist Dr Jens Gruber and the biochemist and serial entrepreneur Dr Herbert Stadler. With a scalable and semi-automated proprietary system for traceless immune-affinity cell sorting, Curexsys aims to become the leading supplier for clinical grade exosomes in regenerative medicine and anti-aging therapies.

About Evotec and iPSCInduced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from adult cells. Pluripotent stem cells hold great promise in the field of regenerative medicine. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease.

Evotec has built an industrialised iPSC infrastructure that represents one of the largest and most sophisticated iPSC platforms in the industry. Evotec's iPSC platform has been developed over the last years with the goal to industrialise iPSC-based drug screening in terms of throughput, reproducibility and robustness to reach the highest industrial standards, and to use iPSC-based cells in cell therapy approaches via the Company's proprietary EVOcells platform.

ABOUT SARTORIUSThe Sartorius Group is a leading international partner of life science research and the biopharmaceutical industry. With innovative laboratory instruments and consumables, the Group's Lab Products & Services Division concentrates on serving the needs of laboratories performing research and quality control at pharma and biopharma companies and those of academic research institutes. The Bioprocess Solutions Division with its broad product portfolio focusing on single-use solutions helps customers to manufacture biotech medications and vaccines safely and efficiently. The Group has been annually growing by double digits on average and has been regularly expanding its portfolio by acquisitions of complementary technologies. In fiscal 2019, the company earned sales revenue of some 1.83 billion euros. At the end of 2019, more than 9,000 people were employed at the Group's approximately 60 manufacturing and sales sites, serving customers around the globe.

SARTORIUS CONTACTPetra KirchhoffHead of Corporate Communications and Investor Relations+49 (0)551.308.3684 petra.kirchhoff@sartorius.comwww.sartorius.com

ABOUT EVOTEC SEEvotec is a drug discovery alliance and development partnership company focused on rapidly progressing innovative product approaches with leading pharmaceutical and biotechnology companies, academics, patient advocacy groups and venture capitalists. We operate worldwide and our more than 3,400 employees provide the highest quality stand-alone and integrated drug discovery and development solutions. We cover all activities from target-to-clinic to meet the industry's need for innovation and efficiency in drug discovery and development (EVT Execute). The Company has established a unique position by assembling top-class scientific experts and integrating state-of-the-art technologies as well as substantial experience and expertise in key therapeutic areas including neuronal diseases, diabetes and complications of diabetes, pain and inflammation, oncology, infectious diseases, respiratory diseases, fibrosis, rare diseases and women's health. On this basis, Evotec has built a broad and deep pipeline of more than 100 co-owned product opportunities at clinical, pre-clinical and discovery stages (EVT Innovate). Evotec has established multiple long-term alliances with partners including Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CHDI, Novartis, Novo Nordisk, Pfizer, Sanofi, Takeda, UCB and others. For additional information please go to http://www.evotec.com and follow us on Twitter @Evotec.

FORWARD LOOKING STATEMENTSInformation set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. The forward-looking statements contained herein represent the judgement of Evotec as of the date of this press release. Such forward-looking statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.

SOURCE: Evotec AG via EQS Newswire

View source version on accesswire.com:https://www.accesswire.com/620112/Evotec-and-Sartorius-Partner-with-Start-Up-Curexsys-on-IPSC-Based-Therapeutic-Exosome-Approach

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Evotec and Sartorius Partner with Start-Up Curexsys on IPSC-Based Therapeutic Exosome Approach - BioSpace

CAMBRIDGE, Mass.--(BUSINESS WIRE)--bluebird bio, Inc. (Nasdaq: BLUE) announced that new data from Group C of its ongoing Phase 1/2 HGB-206 study of investigational LentiGlobin gene therapy (bb1111) for adult and adolescent patients with sickle cell disease (SCD) show a complete elimination of severe VOEs and VOEs between six and 24 months of follow-up. These data are being presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually from December 5-8, 2020.

Now with more than two years of data, we continue to observe promising results in our studies of LentiGlobin for SCD that further illustrate its potential to eliminate the symptoms and devastating complications of sickle cell disease. Consistently achieving the complete resolution of severe vaso-occlusive events (VOEs) and VOEs between Month 6 and Month 24 follow-up is unprecedented other than with allogeneic stem cell transplantation. Importantly, our data show the potential for LentiGlobin for SCD to produce fundamentally disease-modifying effects with sustained pancellular distribution of gene therapy-derived anti-sickling HbAT87Q and improvement of key markers of hemolysis that approach normal levels, said David Davidson, M.D., chief medical officer, bluebird bio. In addition to these clinical outcomes, for the first time with a gene therapy we now have patient-reported outcomes through the validated PROMIS-57 tool, showing reduction in pain intensity at 12 months after treatment with LentiGlobin for SCD. These results provide insight into the potential real-life impact LentiGlobin for SCD may offer patients.

SCD is a serious, progressive and debilitating genetic disease. In the U.S., the median age of death for someone with sickle cell disease is 43 46 years. SCD is caused by a mutation in the -globin gene that leads to the production of abnormal sickle hemoglobin (HbS). HbS causes red blood cells to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and unpredictable, painful VOEs.

In the HGB-206 study of LentiGlobin for SCD, VOEs are defined as episodes of acute pain with no medically determined cause other than a vaso-occlusion, lasting more than two hours and severe enough to require care at a medical facility. This includes acute episodes of pain, acute chest syndrome (ACS), acute hepatic sequestration and acute splenic sequestration. A severe VOE requires a 24-hour hospital stay or emergency room visit or at least two visits to a hospital or emergency room over a 72-hour period, with both visits requiring intravenous treatment.

LentiGlobin for SCD was designed to add functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). Once patients have the A-T87Q-globin gene, their red blood cells can produce anti-sickling hemoglobin (HbAT87Q) that decreases the proportion of HbS, with the goal of reducing sickled red blood cells, hemolysis and other complications.

As a hematologist, I regularly see the debilitating effects of pain events caused by sickle cell disease. Pain has an overwhelmingly negative impact on many facets of my patients lives and can lead to prolonged hospitalizations, said presenting study author Alexis A. Thompson, M.D., professor of pediatrics at Northwestern University Feinberg School of Medicine and head of hematology at Ann and Robert H. Lurie Childrens Hospital of Chicago. The results observed with LentiGlobin gene therapy for SCD include the complete elimination of severe vaso-occlusive pain episodes, which is certainly clinically meaningful, but also for the first time, we have documented patients reporting that they are experiencing improved quality of life. This degree of early clinical benefit is extraordinarily rewarding to observe as a provider."

As of the data cut-off date of August 20, 2020, a total of 44 patients have been treated with LentiGlobin for SCD in the HGB-205 (n=3) and HGB-206 (n=41) clinical studies. The HGB-206 total includes: Groups A (n=7), B (n=2) and C (n=32).

HGB-206: Group C Updated Efficacy Results

The 32 patients treated with LentiGlobin for SCD gene therapy in Group C of HGB-206 had up to 30.9 months of follow-up (median of 13.0; min-max: 1.1 30.9 months).

In patients with six or more months of follow-up whose hemoglobin fractions were available (n=22), median levels of gene therapy-derived anti-sickling hemoglobin, HbAT87Q, were maintained with HbAT87Q contributing at least 40% of total hemoglobin at Month 6. At last visit reported, total hemoglobin ranged from 9.6 15.1 g/dL and HbAT87Q levels ranged from 2.7 8.9 g/dL. At Month 6, the production of HbAT87Q was associated with a reduction in the proportion of HbS in total hemoglobin; median HbS was 50% and remained less than 60% at all follow-up timepoints. All patients in Group C were able to stop regular blood transfusions by three months post-treatment and remain off transfusions as of the data cut-off.

Nineteen patients treated in Group C had a history of severe VOEs, defined as at least four severe VOEs in the 24 months prior to informed consent (annualized rate of severe VOE min-max: 2.0 10.5 events) and at least six months follow-up after treatment with LentiGlobin for SCD. There have been no reports of severe VOEs in these Group C patients following treatment with LentiGlobin for SCD. In addition, all 19 patients had a complete resolution of VOEs after Month 6.

Hemolysis Markers

In SCD, red blood cells become sickled and fragile, rupturing more easily than healthy red blood cells. The breakdown of red blood cells, called hemolysis, occurs normally in the body. However, in sickle cell disease, hemolysis happens too quickly due to the fragility of the red blood cells, which results in hemolytic anemia.

Patients treated with LentiGlobin for SCD in Group C demonstrated near-normal levels in key markers of hemolysis, which are indicators of the health of red blood cells. Lab results assessing these indicators were available for the majority of the 25 patients with 6 months of follow-up.

The medians for reticulocyte counts (n=23), lactate dehydrogenase (LDH) levels (n=21) and total bilirubin (n=24) continued to improve compared to screening values and stabilized by Month 6. In patients with Month 24 data (n=7), these values approached the upper limit of normal by Month 24. These results continue to suggest that treatment with LentiGlobin for SCD may improve biological markers to near-normal levels for SCD.

Pancellularity

As previously reported, assays were developed by bluebird bio to enable the detection of HbAT87Q and HbS protein in individual red blood cells, as well as to assess if HbAT87Q was pancellular, or present throughout all of a patients red blood cells. In 25 patients with at least six months of follow-up, on average, more than 80% of red blood cells contained HbAT87Q, suggesting near-complete pancellularity of HbAT87Q distribution and with pancellularity further increasing over time.

HGB-206: Improvements in Health-Related Quality of Life

Health-related quality of life (HRQoL) findings in Group C patients treated with LentiGlobin for SCD in the HGB-206 study were generated using the Patient Reported Outcomes Measurement Information System 57 (PROMIS-57), a validated instrument in SCD.

Data assessing pain intensity experienced by nine Group C patients were analyzed according to baseline pain intensity scores relative to the general population normative value: 2.6 on a scale of 0-10, where 10 equals the most intense pain. Data were assessed at baseline, Month 6 and Month 12.

Of the five patients with baseline scores worse than the population normative value average, four demonstrated clinically meaningful reductions in pain intensity at Month 12; the group had a mean score of 6.0 at baseline and a mean score of 2.4 at Month 12. Of the four patients with better than or near population normative values at baseline, two reported improvement and two remained stable with a mean score of 2.3 at baseline and 0.8 at Month 12.

HGB-206: Group C Safety Results

As of August 20, 2020, the safety data from Group C patients in HGB-206 remain generally consistent with the known side effects of hematopoietic stem cell collection and myeloablative single-agent busulfan conditioning, as well as underlying SCD. One non-serious, Grade 2 adverse event (AE) of febrile neutropenia was considered related to LentiGlobin for SCD. There were no serious AEs related to LentiGlobin for SCD.

One patient with significant baseline SCD-related and cardiopulmonary disease died 20 months post-treatment; the treating physician and an independent monitoring committee agreed his death was unlikely related to LentiGlobin for SCD and that SCD-related cardiac and pulmonary disease contributed.

LentiGlobin for SCD Data at ASH

The presentation of HGB-206 Group C results and patient reported outcomes research are now available on demand on the ASH conference website:

About HGB-206

HGB-206 is an ongoing, Phase 1/2 open-label study designed to evaluate the efficacy and safety of LentiGlobin gene therapy for sickle cell disease (SCD) that includes three treatment cohorts: Groups A (n=7), B (n=2) and C (n=32). A refined manufacturing process designed to increase vector copy number (VCN) and further protocol refinements made to improve engraftment potential of gene-modified stem cells were used for Group C. Group C patients also received LentiGlobin for SCD made from HSCs collected from peripheral blood after mobilization with plerixafor, rather than via bone marrow harvest, which was used in Groups A and B of HGB-206.

About LentiGlobin for SCD (bb1111)

LentiGlobin gene therapy for sickle cell disease (bb1111) is an investigational treatment being studied as a potential treatment for SCD. bluebird bios clinical development program for LentiGlobin for SCD includes the completed Phase 1/2 HGB-205 study, the ongoing Phase 1/2 HGB-206 study, and the ongoing Phase 3 HGB-210 study.

The U.S. Food and Drug Administration granted orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation for LentiGlobin for SCD.

LentiGlobin for SCD received orphan medicinal product designation from the European Commission for the treatment of SCD, and Priority Medicines (PRIME) eligibility by the European Medicines Agency (EMA) in September 2020.

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-307) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for SCD. For more information visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT04628585 for LTF-307.

LentiGlobin for SCD is investigational and has not been approved in any geography.

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.

Forward-Looking Statements

This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Any forward-looking statements are based on managements current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: regarding the potential for LentiGlobin for Sickle Cell Disease to treat SCD; the risk that the efficacy and safety results from our prior and ongoing clinical trials will not continue or be repeated in our ongoing or planned clinical trials; the risk that the current or planned clinical trials of our product candidates will be insufficient to support regulatory submissions or marketing approval in the United States and European Union; the risk that regulatory authorities will require additional information regarding our product candidates, resulting in delay to our anticipated timelines for regulatory submissions, including our applications for marketing approval; and the risk that any one or more of our product candidates, will not be successfully developed, approved or commercialized. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in our most recent Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and bluebird bio undertakes no duty to update this information unless required by law.

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Treatment with Investigational LentiGlobin Gene Therapy for Sickle Cell Disease (bb1111) Results in Complete Elimination of SCD-Related Severe...

It sounds too good to be true - and it is. But Jose Bianco Moreira and the CERG research group at the Norwegian University of Science and Technology (NTNU) are convinced that some of the positive health effects of physical exercise can be achieved using gene therapy and medication.

"We're not talking about healthy people and everyone who can exercise. They still have to train, of course," says Moreira. He and his colleagues at NTNU's Department of Circulation and Medical Imaging are studying the effect of exercise on our cells.

"But some people can't train, or only in a limited way. This could include individuals who've been in accidents, who are in wheelchairs, or who have diseases that prevent the possibility of physical expression. We want to create hope for these folks."

"A small group of healthy people out there also obtain very little effect from physical exercise - so-called low responders - and would benefit from a method that worked at the cellular level," says Moreira.

A lot of research confirms the health benefits of physical exercise, but we know far less about what happens in the cells that provides the positive effects.

"International research in this field is brand new. We've barely scratched the surface," says the researcher.

"We think increasing our knowledge about what happens at the cellular level will be important for discovering medications and treatments for heart disease. My group studies genes, proteins and mitochondria that produce energy and are key for chemical processes in the cells."

Moreira believes that gene therapy is the most effective method for reproducing the health benefits we normally get through physical exercise.

A medicine that uses gene therapy is already in use for spinal muscle atrophy, a serious disease that leads to muscle wasting. The drug uses a harmless virus to deliver a copy that replaces the damaged motor neuron network in patients.

This form of therapy can inhibit or enhance the expression of a gene. This is a very expensive medicine and has not been tried for heart disease, for example.

Moreira believes CRISPR will be the future go-to gene therapy method. He believes this method of editing the genes will revolutionize a lot of disease treatments.

"CRISPR is easier to use, faster and cheaper than today's gene therapy, which only attenuates or enhances the expression of a gene. CRISPR's potential is almost limitless. It can alter the gene itself. The parts of the gene that don't work properly are replaced with well-functioning parts."

Experiments on rats and mice have shown that the method works. Experiments have also been performed on human cells in the laboratory to confirm CRISPR's effectiveness, but it has not yet been tested on humans.

"CRISPR still has to be tested in large clinical studies. I'd be optimistic if I say gene editing will come into regular use in 10-15 years," says Moreira.

Moreira's research group has used CRISPR in its research, but the results are not yet ready for publication.

"We believe gene therapy is the most powerful method because patients don't have to take a pill every day. Usually, gene therapy changes the gene forever, perhaps with an injection or two. The challenge is to find the right gene that needs change, and an effective method to repair it," he says.

NTNU researchers are focusing on the heart. They have identified a protein that heart-diseased rats are deficit in, but which increases when the rats go through training.

"By increasing the amount of this protein through gene therapy, we've managed to strengthen the muscle cells and have replicated some of the positive effects of physical exercise," says Moreira.

Medications are another possible method of mimicking the effects of exercise. Some existing medicines might even be able to recreate some of the positive effect on the heart.

"The research now has powerful technology platforms to find possible other uses for medicines we already have. One problem, of course, is that medicine is chemistry that affects the whole body, not just the organ you want to help. Something that's good for the heart could be detrimental for the liver, for example. Compared to gene therapy, though, the potential for medications is much more limited," Moreira says.

When the research group at NTNU started their study, they had no idea which genes were affected by exercise. They performed experiments where rats with heart defects underwent training. Afterwards, the hearts were removed and examined. Then these hearts were compared with those from untrained rats with heart disease. Afterwards, the hearts of the trained and untrained rats with heart disease were compared to healthy rat hearts.

"We observed that genes were altered in the diseased hearts, but discovered that some of them were repaired in the rats that had trained. This way, we find genes that we can target. Through our measurements, we can find out exactly what training changes at the cellular level," says Moreira.

Reference: Moreira, J.B.N., Wohlwend, M. & Wislff, U. Exercise and cardiac health: physiological and molecular insights. Nat Metab. 2020;2,829839. doi:10.1038/s42255-020-0262-1

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Could Gene Therapy Be Used To Mimic the Positive Effects of Exercise? - Technology Networks

Editor's note: SpaceX has successfully launched the Dragon CRS-21 cargo mission for NASA and landed its Falcon 9 rocket. Read our launch wrap story here.

CAPE CANAVERAL, Fla. The next SpaceX resupply launch to the International Space Station, scheduled for Sunday (Dec. 6), will carry a host of science gear to the astronauts living and working on the orbiting laboratory.

The robotic flight, called CRS-21, marks the 21st mission for SpaceX under its commercial cargo resupply services contract with NASA. Launch is scheduled for 11:17 a.m. EST (1617 GMT) on Sunday from NASA's Kennedy Space Center in Florida, and you can watch the action live here at Space.com, courtesy of NASA. You can also watch directly via NASA TV or SpaceX.

SpaceX initially aimed to launch the CRS-21 cargo mission for NASA on Saturday (Dec. 5), but foul weather prompted a delay. "Due to poor weather in the recovery area for todays attempt, now targeting Sunday, December 6 at 11:17 a.m. EST for launch of CRS-21," SpaceX wrote in an update early Saturday morning. SpaceX plans to recover the mission's Falcon 9 booster for later reuse.

The upgraded Dragon cargo capsule that will launch atop a veteran SpaceX Falcon 9 rocket is filled with 6,400 lbs. (2,903 kilograms) of supplies and science investigations. The research gear will support a variety of experiments in the life sciences, regenerative medicine and many other fields.

Related: How SpaceX's Dragon space capsule works (infographic)

Saturday's flight will mark the first time SpaceXs upgraded Dragon spacecraft will carry cargo. (Up until now, the advanced Dragon variant has solely carried astronauts.) The vehicle is a modified version of the Crew Dragon spacecraft that lacks the systems necessary for human missions, such as seats, cockpit controls and a life-support system, as well as the SuperDraco thrusters that provide a special emergency escape system that's only used if a problem occurs during launch.

This new Dragon allows more science to ride skyward. Costello explained that the interior of Dragon can now support more powered payloads, which is a huge benefit for the life sciences as it allows for more cold storage and other types of investigations. It also allows for the crew to store some of the powered payloads onboard Dragon while the craft is on orbit.

Several of the payloads on Dragon feature a unique piece of hardware called a tissue chip. Human cells and tissue grow on the chip scaffold, creating a 3D structure in microgravity that researchers can observe to learn more about how fundamental processes work in space, including aging and bone and muscle loss.

One such investigation, run by the University of Florida, will study how muscles atrophy in space. Sixteen samples of skeletal muscle will be sent to the space station, where the bundles of muscle tissue will be observed in microgravity. Half of the muscle samples were donated by younger, active individuals while the other half are from older, more sedentary volunteers.

Half of the samples in each group will be subjected to electric stimuli to see how the muscles contract in the absence of gravity. Researchers will use this experiment as a starting point for future research that will eventually test therapies to see if muscle degradation can be prevented.

Another payload will look at brain organoids created using stem cell technology. This investigation seeks to understand how microgravity affects the survival and function of brain cells, which could lead to advances in treatments for autism and Alzheimers disease, researchers said.

"Space travel mimics the effects of aging we see on Earth, only in a much shorter time span, making it easier to examine the processes that are taking place," Bill McLamb, chief scientist at Kentucky-based company Space Tango, told Space.com. "Its hard to study human brains in space, which is why these types of experiments are so beneficial."

The investigation will take stem cells and convert them into brain cells that will form three-dimensional structures called brain organoids. Stored in a special container called a well, these types of mini organs are able to mimic both the cellular variety and the function of the developing human brain.

This type of research could help NASA and its partners prepare for crewed missions to distant destinations such as Mars, which will expose astronauts to the rigors of space for long stretches, and also help combat degenerative brain disease here on Earth, researchers said.

A team of researchers from Stanford University will be looking at how engineered heart tissue behaves in microgravity. The Cardinal Heart investigation will send tissue samples that consist of cardiomyocytes, endothelial cells and cardiac fibroblasts to study how changes in gravity affect the heart at the cellular level.

Researchers know that microgravity causes changes in the workload and shape of the human heart, but it's still unknown if these changes could become permanent if a person lived for long periods of time in space.

The project's tissue bundles will be affixed to tissue chips. The experiment's results could help identify new treatments and support development of screening measures to predict cardiovascular risk prior to spaceflight, team members said. Follow-on investigations will include therapies that could treat heart disease.

The HemoCue investigation will look at how white blood cells react in space. Here on Earth, doctors use the total number of white blood cells, as well as the various types observed, to diagnose illness. HemoCue will debut a new type of technology that will allow users to do white blood cell counts on orbit.

The goal is to test how well the device works in microgravity. If effective, it could be a valuable tool in an astronauts medical kit, researchers said.

Another payload called Micro-14 looks at how yeast, in particular Candida albicans, responds to the space environment. C. albicans is an opportunistic pathogen, capable of causing severe and even life-threatening illness in immunocompromised hosts. Micro-14 will evaluate how the yeast responds to microgravity, looking for changes at the cellular and molecular levels.

Since astronauts can become immunocompromised during spaceflight, researchers are especially interested in how best to predict the health risks from this organism. Previous research has shown that many microbes exhibit increased virulence in a microgravity environment, but more research is needed on this particular pathogen.

NASAs Jet Propulsion Laboratory in Southern California is spearheading a project that will take swab samples from various locations within the station to look at the relationship between bacteria and their metabolites (chemicals produced by bacterial growth). The project will help researchers better understand the distribution of microbes and metabolites within closed environments and how this distribution affects human health. The research could aid administrators of hospitals and nursing homes, where residents are often immunocompromised.

Related: SpaceX rocket launches for record 7th time, nails landing at sea

Sunday's launch marks the 101st flight overall for SpaceXs workhorse two-stage Falcon 9 rocket. The liftoff is expected to feature a veteran Falcon 9 first stage, designated B1058, that already has three flights under its belt. This frequent flyer previously launched SpaceX's Demo-2 mission, which sent two NASA astronauts to the space station this past summer, well as a communications satellite for the South Korean military and a batch of the companys own Starlink satellites.

Flying previously flown boosters has become commonplace for SpaceX, as the company continues to prove the Falcon 9's reliability. In fact, CRS-21 marks the 24th flight of 2020 for SpaceX, with the majority of those missions having flown on veteran rockets rather than brand-new ones.

To date, SpaceX has successfully landed its first-stage boosters 67 times. Now that the company has two fully operational drone-ship landing platforms "Of Course I Still Love You" and "Just Read the Instructions" in Florida, its able to launch (and land) more rockets. "Of Course I Still Love You" is already at the recovery zone waiting for its turn to catch B1058 when it returns to Earth shortly after liftoff.

Weather was a concern for SpaceX going into the weekend. Forecasts predicted iffy weather for a Saturday launch attempt, with the 45th Weather Squadron predicting a 50% chance of favorable conditions for liftoff. The primary concerns were thick clouds and cumulus clouds. The backup attempt on Sunday looks much better, with the forecast improving to 70% favorable on that day.

If all goes as planned, the Dragon will arrive at the station and dock at the Harmony modules space-facing port just over 24 hours after it blasts off.

Editor's note: This story was updated at 8:22 a.m. EST to include SpaceX's launch delay to Sunday, Dec. 6, due to bad weather.

Follow Amy Thompson on Twitter @astrogingersnap. Follow us on Twitter @Spacedotcom or Facebook.

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Tissue chips and organoids: SpaceX is launching lots of science to space for NASA on Sunday - Space.com

BERGEN, Norway, Dec. 6, 2020 /PRNewswire/ --BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical need, will present updated clinical data from two Phase II studies of bemcentinib in acute myeloid leukemia and high-risk myelodysplastic syndrome, in two poster sessions at the American Society of Hematology (ASH) Annual Meeting being held virtually from 5-8 December 2020.

Dr Sonja Loges will provide an update from the Company's Phase II study of bemcentinib (BGBC003) in combination with low dose cytarabine (LDAC) in elderly previously treated, relapsed and refractory AML patients.

The data indicates that treatment with the bemcentinib-LDAC combination shows promising efficacy in relapsed patients who are unfit for intensive chemotherapy. Of 11 evaluable relapsed patients a response rate of 45% to date has observed. CR/CRi rate was 36% with durable responses observed, and clinical benefit observed in eight patients (73%) to date.Although the study is ongoing, patients remain on drug, with median treatment of 6.2 months in CR patients.

The Company is currently undertaking an in-depth translational research program aiming to identify predictive molecular and biological factors associated with response.

Dr Sonja Loges, Principal Investigator on the trial commented"The current prognosis for relapsed AML patients is very bleak, so we are pleased to see such a positive clinical benefit rate in relapsed second line patients with many patients remaining on drug for extended durations. We are currently undertaking an analysis to identify the suspected immune based factors that potentiate the effects of the drug in certain patients. We hope that this will enable us to identify specific biomarkers that will help us decide which patients may benefit most from treatment with bemcentinib."

Details of this Poster presentation as follows:

Title:The Combination of AXL Inhibitor Bemcentinib and Low Dose Cytarabine Is Well Tolerated and Efficacious in Elderly Relapsed AML Patients: Update from the Ongoing BGBC003 Phase II Trial (NCT02488408)

Date:Sunday, December 6, 2020

Session name:613. Acute Myeloid Leukemia: Clinical Studies: Poster II

Time:7.00am - 3.30pm (Pacific Time) / 4.00pm - 12.30am (CET)

Abstract: https://ash.confex.com/ash/2020/webprogram/Paper136566.html

An update will also be presented from the fully recruited investigator sponsored BERGAMO Phase II Trial investigating bemcentinib monotherapy in patients having relapsed treatment with hypomethelating agents (HMAs) with High Risk Myelodysplastic Syndromes (HR-MDS) or Acute Myeloid Leukemia (AML).

The primary endpoint of overall response rate (ORR) was met, with the MDS cohort achieving a 36% response rate, while 8.3% of patients with AML achieved stable disease. Three patients remain on drug, with median treatment exceeding 8 months. A comprehensive translational research program is ongoing to identify and verify soluble plasma biomarkers, including sAXL, that continue to be predictive of response.

Richard Godfrey, Chief Executive Officer of BerGenBio, said: "We are pleased to continue sharing updates from our phase II clinical studies assessing bemcentinib with the scientific and medical community. Data from both of the studies being presented at ASH continue to show encouraging results in patients with a very poor prognosis with current treatment options. We believe these data provide further validation for our clinical development strategy in these indications as we prepare to progress bemcentinib into late stage randomised trials."

Details of this Poster presentations as follows:

Title:Efficacy and Safety of Bemcentinib in Patients with Myelodysplastic Syndromes or Acute Myeloid Leukemia Failing Hypomethylating Agents

Date:Saturday, December 5, 2020

Session name:637 Myelodysplastic Syndromes - Clinical Studies: Poster IHematology Disease Topics & Pathways: Diseases, Therapies, MDS, MyeloidMalignancies, Clinically relevant

Time:7.00am - 3.30pm (Pacific Time) / 4.00pm - 12.30am (CET)

Abstract:https://ash.confex.com/ash/2020/webprogram/Paper140240.html

Presentations will be made available at our website http://www.bergenbio.comunder Investors/Presentations at the date of the conference.

-End-

About AML and the BGBC003 trial

Acute myeloid leukaemia (AML) is a rapidly progressing blood cancer. AML is the most common form of acute leukaemia in adults, where malignant AML blasts interfere with the normal functioning of the bone marrow leading to a multitude of complications like anaemia, infections and bleeding. AML is diagnosed in over 20,000 patients in the US annually and is rapidly lethal if left untreated. Successful treatment typically requires intensive chemotherapy or bone marrow transplantation, and relapse and resistance are common. Consequently, there is an urgent need for effective novel therapies in relapsed/refractory patients, particularly those that are ineligible for intensive therapy or bone marrow transplant.

The BGBC003 trial is a phase Ib/II multi-centre open label study of bemcentinib in combination with cytarabine (part B2) and low dose decitabine (part B3 & B5) in patients with AML who are unsuitable for intensive chemotherapy as a result of advanced age or existing-co-morbidities.

For more information please access trial NCT02488408 at http://www.clinicaltrials.gov.

About MDS

Myelodysplastic syndromes (MDS) are stem cell disorders characterised by a decreased ability of the bone marrow to produce normal blood cells and platelets. MDS is associated with increased risk of developing AML and immune dysfunctions are seen in patients both with lower and higher-risk MDS. Hypomethylating agents (HMAs) are the standard of care for patients with higher-risk myelodysplastic syndrome not eligible for intensive chemotherapy or allogeneic stem cell transplantation. However, the majority of patients do not respond to these agents or relapse, and face a dismal outcome with very limited treatment options available. Hence, there is an urgent need for novel therapies to treat MDS

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases. In cancer, AXL suppresses the body's immune response to tumours and drives cancer treatment failure across many indications.AXL inhibitors, therefore, have potential high value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases.

About Bemcentinib

Bemcentinib (formerly known as BGB324), is a potentially first-in-class selective AXL inhibitor in a broad phase II clinical development programme. Ongoing clinical trials are investigating bemcentinib in multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent. Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity. Increase in AXL function has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers.

About BerGenBio ASA

BerGenBio is a clinical-stage biopharmaceutical company focused on developing transformative drugs targeting AXL as a potential cornerstone of therapy for aggressive diseases, including immune-evasive, drug resistant cancers. The company's proprietary lead candidate, bemcentinib, is a potentially first-in-class selective AXL inhibitor in a broad Phase II oncology clinical development programme focused on combination and single agent therapy in lung cancer and leukaemia. A first-in-class functional blocking anti-AXL antibody is undergoing Phase I clinical testing. In parallel, BerGenBio is developing a companion diagnostic test to identify those patient populations most likely to benefit from bemcentinib: this is expected to facilitate more efficient registration trials supporting a precision medicine-based commercialisation strategy. BerGenBio is based in Bergen, Norway with a subsidiary in Oxford, UK. The company is listed on the Oslo Stock Exchange (ticker: BGBIO). For more information, visit http://www.bergenbio.com

Contacts

Richard Godfrey CEO, BerGenBio ASA+47 917 86 304

Rune Skeie, CFO, BerGenBio ASA[emailprotected]+47 917 86 513

International Media Relations

Mary-Jane Elliott, Chris Welsh, Lucy Featherstone, Carina Jurs

Consilium Strategic Communications[emailprotected]+44 20 3709 5700

Media Relations in Norway

Jan Petter Stiff, Crux Advisers

[emailprotected]+47 995 13891

Forward looking statements

This announcement may contain forward-looking statements, which as such are not historical facts, but are based upon various assumptions, many of which are based, in turn, upon further assumptions. These assumptions are inherently subject to significant known and unknown risks, uncertainties and other important factors. Such risks, uncertainties, contingencies and other important factors could cause actual events to differ materially from the expectations expressed or implied in this announcement by such forward-looking statements.

This information is subject to the disclosure requirements pursuant to section 5-12 of the Norwegian Securities Trading Act.

This information was brought to you by Cision http://news.cision.com

https://news.cision.com/bergenbio-asa/r/bergenbio-presents-updated-clinical-data-from-two-phase-ii-studies-of-bemcentinib-in-aml-and-mds-pat,c3249801

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BerGenBio Presents Updated Clinical Data From Two Phase II Studies Of Bemcentinib in AML and MDS Patients At Ash 2020 - PRNewswire

WASHINGTON, Dec. 4, 2020 /PRNewswire/ --Four studies being presented during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition present opportunities to improve care for patients with a variety of blood disorders. Together, the studies provide support for new clinical approaches such as alternate treatment delivery methods, updated uses for existing therapies, and earlier referrals to specialty care.

"These are very practical trials with real-world implications," said press briefing moderator Lisa Hicks, MD, of St. Michael's Hospital and the University of Toronto. "They address important questions relevant to everyday practice in the clinic."

The first study supports administering the monoclonal antibody daratumumab for multiple myeloma via a quick injection instead of an intravenous infusion, an approach that could save significant time for patients and clinics.

The second study found that, despite being routinely used in practice, the clot stabilizer tranexamic acid does not prevent bleeding when used prophylactically for patients undergoing treatment for blood cancers, although it leaves open the possibility that the drug may be an effective treatment for these patients when bleeding occurs.

The third study reports the drug ruxolitinib can offer relief for patients with chronic graft-versus-host disease (GVHD) after a stem cell transplant, suggesting ruxolitinib is a viable second-line treatment for patients whose symptoms are not fully resolved with corticosteroids.

Finally, the fourth study supports referring older patients with myelodysplastic syndromes to transplant centers for allogeneic hematopoietic cell transplantation, an important shift from current practice that could offer many more patients the potential for a cure.

This press briefing will take place on Friday, December 4, at 9:30 a.m. Pacific time on the ASH annual meeting virtual platform.

Study Bolsters Case for Delivering Daratumumab Subcutaneously for Multiple Myeloma412: Apollo: Phase 3 Randomized Study of Subcutaneous Daratumumab Plus Pomalidomide and Dexamethasone (D-Pd) Versus Pomalidomide and Dexamethasone (Pd) Alone in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM)

A new study suggests the monoclonal antibody daratumumab has similar benefits when delivered via subcutaneous injection as it does when delivered intravenously to individuals with multiple myeloma which persists or recurs after first-line treatments. Patients given subcutaneous daratumumab along with the immunomodulator pomalidomide and the anti-inflammatory steroid dexamethasone were 37% less likely to die or have their disease worsen compared to patients who received pomalidomide and dexamethasone alone in the phase III trial.

"This is an effective combination with a predictable safety profile that allows for the use of subcutaneous daratumumab along with oral pomalidomide and dexamethasone for patients who have received at least one prior line of therapy that included lenalidomide and a proteasome inhibitor," said senior study authorMeletios A. Dimopoulos, MD,of National and Kapodistrian University of Athens in Athens, Greece. "Subcutaneous daratumumab is much easier for the patient and reduces the time they need to spend at the outpatient chemotherapy unit."

The combination of intravenous daratumumab and pomalidomide with dexamethasone has been widely adopted in the U.S. as a second-line therapy for patients whose multiple myeloma does not respond durably to lenalidomide and proteasome inhibitors. However, delivering daratumumab intravenously typically requires patients to spend a full day at the clinic for each infusion. Administering the therapy via a five-minute subcutaneous injection can substantially reduce the burden for patients and clinics, Dr. Dimopoulos said.

The researchers enrolled 304 patients in 12 European countries. Half were randomly assigned to receive daratumumab plus pomalidomide with dexamethasone and half only received pomalidomide with dexamethasone. Patients underwent 28-day treatment cycles until their disease worsened or they experienced unacceptable side effects.

About one-third of patients died during the trial's median follow-up period of about 17 months. The study met its primary endpoint, showing a significantly higher rate of progression-free survival at 12 months among patients receiving the combination therapy. Participants receiving the daratumumab-pomalidomide combination were treated for a median of nearly 12 months, substantially longer than the median treatment duration of less than seven months among those receiving pomalidomide alone.

Patients receiving daratumumab experienced adverse events at a rate consistent with previous studies, raising no new safety concerns. Dr. Dimopoulos said the findings suggest the combination therapy can be a good option for patients who have not experienced lasting benefits from lenalidomide and proteasome inhibitors, particularly those whose cancer is resistant to lenalidomide. He noted that the study suggested a slight trend toward increased survival in the daratumumab arm, but additional follow-up is necessary to assess any survival benefit.

Meletios A. Dimopoulos, MD,National and Kapodistrian University of Athens, will present this study in an oral presentation on Sunday, December 6, at 12:00 noon Pacific time on the ASH annual meeting virtual platform.

Tranexamic Acid Not Found to Prevent Bleeding in Patients with Blood Cancers 2: Effects of Tranexamic Acid Prophylaxis on Bleeding Outcomes in Hematologic Malignancy: The A-TREAT Trial

The clot stabilizer tranexamic acid performed no better than placebo when administered prophylactically to prevent bleeding in patients with blood cancers who also received routine prophylactic platelet transfusions. Researchers cautioned that the study's focus is different from other situations in which tranexamic acid has been found effective, such as its use in treating bleeding related to childbirth, surgery, or inherited blood disorders.

"Clearly patients with low platelet counts and blood cancers have a different kind of bleeding than the bleeding experienced by patients who have suffered some kind of trauma or surgery," said senior study author Terry B. Gernsheimer, MD, of the University of Washington School of Medicine. "Their bleeding likely is due to endothelial damage damage to the lining of blood vessels that tranexamic acid would not treat. To prevent bleeding in these patients, we may need to look at ways to speed the healing of the endothelium that occurs with chemotherapy, radiation, and graft-versus-host disease in patients receiving a transplant."

Between 48% and 70% of patients undergoing treatment for blood cancers experience bleeding complications of World Health Organization grade 2 or higher. Though not life-threatening, grade 2 bleeding for example, a nosebleed lasting more than 30 minutes can be concerning. Bleeding of grade 3 or 4 can be life-threatening and warrant blood transfusions. Most patients undergoing treatment for blood cancers are routinely given platelet transfusions to prevent bleeding, but many continue to experience bleeding episodes, nevertheless.

Tranexamic acid works by slowing the process by which blood clots naturally break down. To determine whether tranexamic acid could help to further reduce bleeding in these patients, the researchers enrolled 327 patients undergoing treatment for blood cancers at three U.S. medical centers. Half were randomly assigned to receive tranexamic acid and half received a placebo, administered either orally or intravenously three times a day until they recovered their platelet count, or for up to 30 days. Researchers regularly followed up with participants to assess bleeding events both in and outside of the hospital.

The results revealed no significant differences among the study groups in terms of the number of bleeding events, the number of red blood cell transfusions, or the number of platelet transfusions patients required during the treatment period and for up to 14 days afterward. Patients receiving tranexamic acid had a significantly higher rate of occlusions in their central venous line (a catheter placed in a large vein commonly used for delivering cancer drugs) which required clearing with a clot-dissolving drug, but there was no difference in the occurrence of clots in patients' veins or arteries.

Dr. Gernsheimer noted that other studies could help elucidate whether the drug may be helpful for specific subgroups of patients with blood cancers or as a treatment for bleeding, rather than as a preventive measure in these patients. It may also be useful to prevent or treat bleeding in patients with other causes of low platelet counts.

Terry B. Gernsheimer, MD, University of Washington School of Medicine, will present this study in a plenary presentation on Sunday, December 6, 2020 at 7:00 a.m. Pacific time on the ASH annual meeting virtual platform.

Researchers Report First Successful Second-Line Treatment for Chronic Graft-Versus-Host Disease77: Ruxolitinib (RUX) Vs Best Available Therapy (BAT) in Patients with Steroid- Refractory/Steroid-Dependent Chronic Graft-Vs-Host Disease (cGVHD): Primary Findings from the Phase 3, Randomized REACH3 Study

The drug ruxolitinib brought relief from the debilitating effects of chronic graft-versus-host disease (GVHD) at twice the rate of the best available therapy in a phase III trial. The findings represent a major step forward for patients with chronic GVHD that is not resolved by taking corticosteroids, said researchers. There is currently no approved second-line therapy for chronic forms of the disease.

"This is the first multicenter randomized controlled trial for chronic, steroid-refractory or steroid-dependent GVHD that is positive," said senior study authorRobert Zeiser, PhD,of University Medical Center, Freiburg Im Breisgau, Germany. "It shows a significant advantage for ruxolitinib. It is likely that this trial will lead to approval for this indication and change the guidelines for the treatment of this disease."

GVHD is a complication of allogeneic hematopoietic (stem) cell transplantation, a therapy used to treat blood cancers. It occurs when T cells (the graft) received from a donor through the transplant see the patient's healthy cells and tissue (the host) as foreign and start to attack them. Roughly half of patients undergoing a stem cell transplant develop GVHD. About half of these patients are able to resolve their symptoms with a temporary course of corticosteroids, a class of drugs that lower inflammation in the body. The remaining patients either do not respond to steroids, cannot take them, or must take them continuously to stave off symptoms.

Ruxolitinib is designed to block a molecular signal involved in triggering inflammation. A previous trial, REACH2, found that ruxolitinib offered benefits for patients with acute GVHD, a severe form of GVHD with a mortality rate of 80%. The new trial, REACH3, aimed to determine whether the drug could bring similar benefits for the much larger number of patients affected by chronic GVHD. While chronic GVHD is not nearly as deadly as acute GVHD, its symptoms, which include weight loss, skin stiffness, and multiple disabilities, can severely and permanently affect patients' quality of life.

Researchers enrolled 329 patients with moderate-to-severe chronic GVHD. Half were randomly assigned to receive ruxolitinib for six 28-day cycles. The other half received one of nine alternative treatments, representing the best available therapy, at the discretion of their physician. At the end of the six treatment cycles, researchers assessed symptoms of 125 patients who had completed the full course of treatment to which they were assigned.

The trial met its primary endpoint, showing a clear and substantial improvement in the overall response to treatment among patients taking ruxolitinib. Of the 125 patients assessed, 50% of those receiving ruxolitinib had at least some reduction in symptoms, compared to only 25% among those receiving best available therapy. Seven percent of those taking ruxolitinib saw their symptoms resolve completely, compared to only 3% among those receiving best available therapy.

Participants in both arms of the study experienced similar rates of adverse events, which aligned with the health challenges commonly faced by patients with chronic GVHD, suggesting ruxolitinib has an acceptable safety profile in these patients, according to Dr. Zeiser.

Robert Zeiser, PhD, University Medical Center, Freiburg Im Breisgau, Germany, will present this study in an oral presentation on Saturday, December 5, at 8:00 a.m. Pacific time on the ASH annual meeting virtual platform.

Curative Transplant Improves Survival for Older Adults with Myelodysplastic Syndrome75: A Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplantation to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome: Blood and Marrow Transplant Clinical Trials Network Study 1102

Allogeneic hematopoietic cell transplantation nearly doubled the rate of survival among patients 50 to 75 years old with myelodysplastic syndrome (MDS) in a trial conducted by the Blood and Marrow Transplant Clinical Trials Network. Despite being the only known cure for MDS, this therapy is typically only offered to younger patients because its benefits for older adults have not previously been proven. Researchers say the study offers the most definitive evidence to date that this type of stem cell transplantation significantly improves the outlook for older adults who would otherwise face a high likelihood of dying.

"Transplantation has been underutilized, historically, in this patient group," said senior study author Corey Cutler, MD, MPH,of Dana-Farber Cancer Institute. "Based on our findings, all patients should at least be referred to a transplant center so that those who are eligible and who have a suitable donor can undergo transplant and have better survival. It is important to refer these patients early so that the transplant center can work on finding an optimal donor right from the get-go."

Allogeneic hematopoietic (stem) cell transplantation is a process to replace a recipient's stem cells and immune system with cells from a healthy donor. It is the only known method to cure patients with MDS. The Centers for Medicare and Medicaid Services (CMS) covers transplantation for MDS as part of a Coverage with Evidence Development program. CMS approved the design of the trial and is expected to consider the findings when determining future payment policies.

Researchers from the Blood and Marrow Transplant Clinical Trials Network enrolled 384 patients treated for MDS at 34 U.S. medical centers. Patients were referred to transplant centers, which searched for suitable stem cell donors. The 260 patients who were matched with a donor within 90 days were assigned to receive a stem cell transplant; the other 124 patients with no suitable donor received standard supportive care. Participants were followed for roughly three years from their date of enrollment.

Overall survival was much higher in patients assigned to receive a stem cell transplant (47.9%) compared to those who were not (26.6%) at three years from treatment assignment. Leukemia-free survival was also higher in those assigned to receive a transplant (35.8%) than those who were not (20.6%). The researchers observed no significant differences among subgroups and no differences in quality of life between the two study arms.

Dr. Cutler noted that starting the transplantation process as early as possible can increase a patient's chance of finding a suitable donor and successfully proceeding with a transplant.

This study was co-funded by the National, Heart, Lung and Blood Institute (NHLBI) and the National Cancer Institute (NCI), both part of the National Institutes of Health.

Corey Cutler, MD, MPH, Dana-Farber Cancer Institute, will present this study in an oral presentation on Saturday, December 5, at 7:30 a.m. Pacific time on the ASH annual meeting virtual platform.

Additional press briefings will take place throughout the meeting on health disparities, genome editing and cellular therapy, COVID-19, and late-breaking abstracts. For the complete annual meeting program and abstracts, visit http://www.hematology.org/annual-meeting. Follow ASH and #ASH20 on Twitter, Instagram, LinkedIn, and Facebook for the most up-to-date information about the 2020 ASH Annual Meeting.

The American Society of Hematology (ASH) (www.hematology.org) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH publishes Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, and Blood Advances (www.bloodadvances.org), an online, peer-reviewed open-access journal.

SOURCE American Society of Hematology

http://www.hematology.org

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Clinical Trials Offer Opportunities to Change Practice to Improve Prevention and Treatment of Blood Disorders - PRNewswire

(TNS) - Scientists at Bay Area universities, laboratories, biotechnology companies and drug manufacturers are fashioning drug concoctions out of blood plasma, chimpanzee viruses and cells taken from bone marrow in the race to rid the world of COVID-19.

The microbial treasure hunt is not just to find a cure which may not be possible but to control the debilitating health problems caused by the coronavirus.

Major progress has been made this year. The antiviral drug remdesivir, produced in Foster City, has improved recovery times, and the steroid dexamethasone has cut the number of deaths in severely ill patients.

What follows is a list of some of the most promising medications and vaccines with ties to the Bay Area:

Antibodies

and Immunity

Mesenchymal stem cells / UCSF and UC Davis Medical Center:

UCSF Dr. Michael Matthay is leading a study of whether a kind of stem cell found in bone marrow can help critically ill patients with severe respiratory failure, known as ARDS. Matthay hopes the stem cells can help reduce the inflammation associated with some of ARDS' most dire respiratory symptoms, and help patients' lungs recover.

In all, 120 patients are being enrolled at UCSF Medical Center, Zuckerberg San Francisco General Hospital, the UC Davis Medical Center in Sacramento and hospitals in Oregon and Texas. He said the trial, which includes a small number of ARDS patients who don't have COVID-19, should have results by summer or fall 2021. So far, 28 patients are enrolled in San Francisco.

Lambda-interferon / Stanford University:

Lambda-interferon is a manufactured version of a naturally occurring protein that had been used to treat hepatitis, and researchers hoped it would help patients in the early stages of COVID-19.

Stanford researchers completed their trial of lambda-interferon and found that it did not boost the immune system response to coronavirus infections.

"That trial did not find any difference in outcomes between the treatment and placebo," said Yvonne Maldonado, chief of pediatric infectious diseases at Lucile Packard Children's Hospital at Stanford, where 120 patients were enrolled in the trial. "It didn't work."

Antiviral drugs

Remdesivir / Gilead Sciences ( Foster City):

Remdesivir, once conceived as a potential treatment for Ebola, was approved by the Food and Drug Administration in October for use on hospitalized COVID-19 patients.

Trademarked under the name Veklury, the drug interferes with the process through which the virus replicates itself. It was one of the drugs given to President Trump and has been used regularly in hospitals under what is known as an emergency use authorization.

It was approved after three clinical trials showed hospitalized coronavirus patients who received remdesivir recovered five days faster on average than those who received a placebo. Patients who required oxygen recovered seven days faster, according to the studies.

Gilead now plans to conduct clinical trials to see how remdesivir works on pediatric patients, from newborns to teenagers, with moderate to severe COVID-19 symptoms. Remdesivir is also being studied with steroids and other drugs to see if it works better as part of a medicinal cocktail. An inhalable form of the drug is also being developed.

Favipiravir / Fujifilm Toyama Chemical ( Stanford University):

This antiviral drug, developed in 2014 by a subsidiary of the Japanese film company to treat influenza, is undergoing numerous clinical studies worldwide, including a trial involving 180 patients at Stanford University.

Stanford epidemiologists are testing favipiravir to see if it prevents the coronavirus from replicating in human cells, halts the shedding of the virus and reduces the severity of infection. Unlike remdesivir, it can be administered orally, so it can be used to treat patients early in the disease, before hospitalization is necessary.

The Stanford study has so far enrolled about 90 patients, who are given the drug within 72 hours of when they were first diagnosed with COVID-19. Half of them get a placebo. People can enroll by emailing treatcovid@stanford.edu.

Monoclonal antibodies

REGN-COV2 / Regeneron Pharmaceuticals / Stanford School of Medicine:

The REGN-COV2 cocktail is the same one Trump received, and Stanford is one of dozens of locations nationwide where clinical trials are being held. Two separate trials are under way at Stanford one for hospitalized patients, the other for outpatients. A third trial is about to begin for people who aren't sick but are in contact with carriers of the virus.

Regeneron halted testing on severely ill patients requiring high-flow oxygen or mechanical ventilation after the independent Data and Safety Monitoring Board determined that the drug was unlikely to help them.

The drug is a combination of two monoclonal antibodies lab-made clones of the antibodies produced naturally in people who have recovered from COVID-19. The antibodies bind to the virus' spike protein and block the virus' ability to enter cells.

Dr. Aruna Subramanian, professor of infectious diseases at Stanford and lead investigator for the inpatient trial, said the 21 hospitalized patients in the study receive a high dose like Trump, a lower dose or a placebo. Subramanian plans to expand the inpatient trial to 45 patients. The outpatient study has enrolled a little more than 40 of the 60 patients researchers intend to sign up.

"There's enough promising evidence that it helps people early in the infection," Subramanian said. "What we don't know is whether it helps people who are pretty sick but not critically ill."

Bamlanivimab / Eli Lilly / Stanford and UCSF:

Stanford and UCSF are testing the Eli Lilly monoclonal antibodies on outpatients after the pharmaceutical company halted trials on hospitalized COVID-19 patients because of adverse results.

Dr. Andra Blomkalns, chair of emergency medicine at Stanford and the lead in the Eli Lilly outpatient trial, said she is now enrolling older people with comorbidities like heart disease, chronic lung disease, a history of strokes and severe obesity shortly after they test positive.

The hypothesis is that the bamlanivimab monotherapy, which is very similar to the Regeneron monoclonals, might work best early in the infection. Although about 400 patients have been enrolled in the Lilly phase 3 trials nationwide, to date fewer than 10 have been enrolled at Stanford and UCSF.

Matthay, who headed up the Lilly monoclonal study with LY-CoV555 at UCSF, said the cancellation of this inpatient trial was disappointing, but "just because this one did not work, doesn't mean another one won't work for hospitalized patients."

Blomkalns said the testing criteria has been changing. She expects the outpatient trial to open soon to adolescents ages 12 and up to determine whether the drug can be used as a preventive.

Designer monoclonal antibodies / Vir Biotechnology, San Francisco:

Scientists at Vir are studying several types of monoclonal antibodies, including a type engineered to activate T cells, which can search out and destroy cells infected with the coronavirus. A study published in the journal Nature in October found that monoclonals, modified to bind with certain receptors, stimulated T cells and improved the human immune response.

"By observing and learning from our body's powerful natural defenses, we have discovered how to maximize the capacity of antibodies through the amplification of key characteristics that may enable more effective treatments for viral diseases," said Herbert Virgin, the chief scientific officer at Vir and co-author of the study.

A similarly modified monoclonal antibody, leronlimab, is being studied in coronavirus clinical trials by its Washington state drugmaker, CytoDyn, which has developed drugs to treat HIV. The company's chief medical officer is in San Francisco, and the company that does laboratory tests of leronlimab is in San Carlos.

Anti-inflammatory drugs

Colchicine / UCSF ( San Francisco and New York):

The anti-inflammatory drug commonly used to treat gout flare-ups is being studied by scientists at UCSF and New York University. The drug short-circuits inflammation by decreasing the body's production of certain proteins, and researchers hope that it will reduce lung complications and prevent deaths from COVID-19.

Preliminary results from a clinical trial found that "Colchicine can be effective in reducing systemic symptoms of COVID-19 by inhibiting inflammatory biomarkers."

Selinexor / Kaiser Permanente:

Kaiser hospitals in San Francisco, Oakland and Sacramento are studying selinexor, an anticancer drug that blocks a key protein in the cellular machinery for DNA processing. Preliminary findings during the trials indicated that low doses of selinexor helped hospitalized patients with severe COVID-19. The drug has both antiviral and anti-inflammatory properties, and it's administered orally, according to Kaiser's Dr. Jacek Skarbinski.

Vaccines

VXA-COV2-1 / Vaxart, South San Francisco:

The biotechnology company Vaxart is testing VXA-COV2-1, the only potential vaccine in pill form. It uses the genetic code of the coronavirus to trigger a defensive response in mucous membranes. The hope is that the newly fortified membranes will prevent the virus from entering the body.

"It's the only vaccine (candidate) that activates the first line of defense, which is the mucosa," said Andrei Floroiu, Vaxart's chief executive. He said intravenous vaccines kill the virus after it is inside the body, but this one stops it beforehand.

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Coronavirus Updates: The Latest Treatments and Vaccines - GovTech