According to an analysis of interim results from a randomized study of young patients with high- or intermediate risk B-cell precursor acute lymphoblastic leukemia (B-ALL) at first relapse, the overall efficacy and safety of post-reinduction therapy with the bispecific T-cell engager (BiTE) blinatumomab outperformed conventional chemotherapy. The findings from this study were presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition held in Orlando, Florida.

Disease relapse, particularly early relapse, following initialtreatment of children, adolescents, and young adults with B-ALL is a marker ofpoor prognosis. While allogeneic hematopoietic stem cell transplantation (HSCT) is typicallyconsidered the treatment of choice for these patients, barriers to itsimplementation can include concerns related to adverse events associated withreinduction and subsequent consolidation chemotherapy, and the presence ofminimal residual disease (MRD) following administration of second-remission reinductiontherapy. Those patients who experienceearly bone marrow relapse, and those with MRD greater than 0.1% in the settingof a prolonged CR, at the end of reinduction therapy are considered to have high-riskand intermediate-risk disease, respectively.

Blinatumomab is an artificial, bispecific monoclonal antibody-basedconstruct created from the fusion of single-chain variable fragments from 2different antibodies. In the case of blinatumomab, targets include the CD3receptor on T cells and CD19 on B cells, resulting in the formation of a link betweenthese 2 cell types.

Currently, blinatumomab is approved by the US Food and DrugAdministration (FDA) for the treatment of adult and pediatric patients with B-ALL in first or second CR,with minimal residual disease (MRD) greater than or equal to 0.1%, as well asfor patients with relapsed/refractory B-ALL.2

In this phase 3 Childrens Oncology Group study (AALL1331; ClinicalTrials.gov Identifier: NCT02101853), patients with B-ALL in first relapse between the ages of 1 and 30 years with bone marrow blasts less than 25% and/or failure to clear extramedullary disease following reinduction chemotherapy (UKALLR3 regimen3) were randomly assigned in a 1:1 ratio following risk assessment to receive either 2 blocks of intensive consolidation chemotherapy according to the UKALLR3 regimen3 or two 4-week cycles of otumumab separated by a 1-week break. Allogeneic HSCT was scheduled following these treatments.

The primary end point of the trial was intent-to-treat disease-freesurvival (DFS), with secondary study end points including MRDresponse, overall survival (OS), and ability to proceed to HSCT.

A planned interimanalysis of 208 patients, performed followingthe occurrence of approximately 60% of expected events,included only those with high- (67%) or intermediate-risk (33%) disease. Patientages ranged from 1 to 27 years, with a median age of 9 years.

At a medianfollow-up of 1.4 years, some of the key efficacy findings from this analysis includedrates of 2-year DFS in the intention-to-treat (ITT) population of 41.0% forpatients receiving chemotherapy and 59.3% for those treated with blinatumomab (P =.050). Rates of 2-year OS forpatients in these 2 study arms were 79.4% (blinatumomab) and 59.2% (chemotherapy),(P =.005).

The percentages ofthose achieving undetectable MRD after reinduction chemotherapy were only 22%and 18% in the chemotherapy and blinatumomab arms, respectively. Followingblock 2 of chemotherapy (ie, first cycle of consolidation chemotherapy) orcycle 1 of blinatumomab, rates of undetectable MRD increased to 29% in thechemotherapy arm and 76% in the blinatumomab arm (P <.0001).

Regarding resultsrelated to MRD response, all of the benefit of blinatumomab with respect to MRDclearance appeared to occur in the first cycle, commented PatrickA. Brown of the Sidney Kimmel ComprehensiveCancer Center, Johns Hopkins University, Baltimore, Maryland, who was thepresenting study author.

Furthermore, 45%of patients in the chemotherapy arm compared with 73% of those in the blinatumomabarm were able to proceed to HSCT (P<.0001).

Regarding patientsafety, 4 and 0 patients receiving blinatumomab or chemotherapy, respectively,experienced a postinduction, induction-related toxic death.

In addition, thefrequencies of specific adverse events were considerably higher in thechemotherapy vs the blinatumomab arm. For example, rates of grade 3 or higher febrileneutropenia were 44% and 46% for patients receiving the 2nd and 3rd blocks ofthe UKALLR3 regimen, respectively, but only 4% and 0% of patients receivingcycle 1 and cycle 2 of blinatumomab, respectively (P <.001). Similar differences between the 2 study arms wereobserved with respect to the rates of infections and sepsis.

For patientsreceiving blinatumomab, low-grade cytokine release syndrome (CRS), occurring in22% of patients, was generally limited to the to the first cycle. Seizuresoccurred in 4% and 0% of patients during cycles 1 and 2, respectively, and the incidenceof mostly low-grade encephalopathy was 14% in cycle 1 and 11% in cycle 2.

Accordingto the results of this scheduled interim analysis, the prespecified monitoring thresholdto the primary end point of DFS was not crossed. However, based on the overallresults of the study, the data monitoring committee recommended permanentclosure of study randomization for patients with high- or intermediate-riskdisease, with those in these risk groups immediately crossed over to theblinatumomab arm.

We believe that blinatumomab constitutes anew standard of care in this setting, concluded Dr Brown.

Disclosure:Some of the authors disclosed financial relationships with the pharmaceuticalindustry. For a full list of disclosures, please refer to the originalabstract.

Read more of Cancer Therapy Advisors coverage of ASHs annual meeting by visiting the conference page.

References

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Blinatumomab May Become New Standard of Care for Post-Reinduction Therapy in Young Patients With B-ALL - Cancer Therapy Advisor

Bone Marrow Stem Cells Comments Off on Blinatumomab May Become New Standard of Care for Post-Reinduction Therapy in Young Patients With B-ALL – Cancer Therapy Advisor | December 12th, 2019

LentiGlobin, Bluebird Bios investigational gene therapy for sickle cell disease (SCD), continues to show promising results in SCD patients participating in the companys Phase 1/2 HGB-206 clinical trial, according to the latest study data.

The new findings which included data from additional patients treated in the trial, updated data from those previously reported, and exploratory analyses were presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition, held Dec. 6-10 in Orlando, Fla.

LentiGlobinisa gene therapy that has been developed to increase the levels of hemoglobin the protein that transports oxygen in the blood in people with SCD.

The therapy works by delivering functional copies of a modified form of the beta-globin gene (A-T87Q-globin gene) into patients red blood cell precursors, known as hematopoietic stem cells, or HSCs. Once these precursors differentiate, their red blood cells start producing a modified version of hemoglobin, called HbAT87Q.

By boosting the production of this anti-sickling form of the protein, LentiGlobin reduces the proportion of defective hemoglobin in patients red blood cells. That, in turn, reduces the sickling and destruction of these red blood cells and other complications associated with SCD.

The safety and efficacy of LentiGlobin is currently being evaluated in three groups identified as A-C of SCD patients participating in Bluebirds ongoing open-label, Phase 1/2 HGB-206 trial (NCT02140554).

Those in group A were treated per the original trial protocol. Meanwhile, those in groups B and C received an enhanced treatment protocol, approved in 2016, that is designed to increase the therapys efficiency. In groups A and B, patients HSCs were extracted from the bone marrow, while in group C, they were extracted from the blood.

As of the data cutoff date of August 26, 2019, seven participants in group A, two in group B, and 17 in group C had been treated with LentiGlobin. According to new data presented at the meeting, only two patients from group A required regular blood transfusions after the treatment.

In addition, the updated findings revealed that the levels of anti-sickling HbAT87Q remained stable in all participants from groups A and B over a post-treatment follow-up period of three years. Similarly, levels of total hemoglobin also were found to have remained stable in both patient groups over a two-year follow-up.

At the trial participants last visit, the median levels of anti-sickling HbAT87Q were 0.9 g/dL among those from group A, and 3.6 g/dL and 7.1 g/dL in the two patients from group B. The median levels of total hemoglobin were 9.0 g/dL among patients from group A, and 11.3 g/dL and 13.0 g/dL among those from group B.

Normal levels of hemoglobin in the blood range from 12.5 to 17.5 g/dL.

Among 12 patients from group C who were followed for at least six months, the median levels of anti-sickling HbAT87Q made up at least 40% of their total hemoglobin. At their last visit, the levels of anti-sickling HbAT87Q ranged from 2.7 to 9.0 g/dL, and the levels of total hemoglobin from 9.3 to 15.2 g/dL.

In groups A and B, LentiGlobin reduced the frequency of painful vaso-occlusive crises (VOCs) and acute chest syndrome (ACS) in the two years following treatment.

Nine patients from group C who were followed for at least six months had experienced four or more VOCs or ACS episodes in the two years prior to receiving LentiGlobin. Treatment with the gene therapy led to a reduction of 99% in the frequency of annual VOCs and ACS. In this group, there were no reports of ACS or severe VOCs for up to 21 months following treatment.

Moreover, among those from group C, LentiGlobin reduced the levels of different markers of red blood cells destruction, including reticulocytes, lactate dehydrogenase (LDH), and bilirubin.

LentiGlobins safety profile was consistent with previous data. No serious adverse events related to treatment were reported during the study. Only one mild, non-serious event of hot flush was found to be related to LentiGlobin. That event was rapidly resolved and did not require treatment.

Exploratory analyses were performed in a sub-group of patients from all three groups. In 12 participants who had been followed for at least six months, more than 70% of the individuals red blood cells were found to contain the anti-sickling HbAT87Q at the last study visit, these analyses showed. Moreover, in four of these patients, nearly all their red blood cells (90%) were positive for HbAT87Q.

In addition, exploratory analyses revealed that participants red blood cells were less prone to sickling following treatment with LentiGlobin.

At ASH, the growing body of data from our clinical studies of LentiGlobin for SCD reflects results from 26 treated patients with up to four years of follow-up, David Davidson, MD, Bluebird Bios chief medical officer, said in a press release.

We continue to observe patients treated in Group C producing high levels of gene-therapy derived anti-sickling hemoglobin, HbAT87Q, accounting for at least 40% of total hemoglobin in those with six or more months of follow-up, and exploratory assays show that HbAT87Q is present in most red blood cells of treated patients, Davidson said.

The robust production of HbAT87Q was associated with substantial reductions of sickle hemoglobin, HbS, as well as improvement in key markers of hemolysis [red blood cells destruction]. Most importantly, patients in Group C have not experienced any episodes of acute chest syndrome or serious vaso-occlusive crises following LentiGlobin for SCD treatment, he added.

The company is recruiting participants with transfusion-dependent -thalassemia (TDT) for a Phase 3 trial (NCT03207009) testing LentiGlobin. Moreover, according to the companys pipeline, there is a Phase 2/3 trial planned in sickle cell disease for this gene therapy.

Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells cells that make up the lining of blood vessels found in the umbilical cord of newborns.

Total Posts: 94

Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Tcnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.

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LentiGlobin Gene Therapy Continues to Show Promising Results in SCD, Updated Trial Data Shows - Sickle Cell Anemia News

Bone Marrow Stem Cells Comments Off on LentiGlobin Gene Therapy Continues to Show Promising Results in SCD, Updated Trial Data Shows – Sickle Cell Anemia News | December 12th, 2019

by Tyler English | published Dec. 11th, 2019

illustration by Darius Serebrova

Ever wonder where those neon yellow, green, blue and pink fish came from? You know, the ones that have all the matching accessories: tanks, decorations, rocks and their own special ultraviolet light? Well, as it turns out, a team ofscientists in Singapore were the first ones to genetically modify fish to glow in such a way.

Genetic editing in small animals and plants has been aroundsince the 1970s, according to Synthego, a company that providesgeneticallyedited stem cells. Starting with plants and bacteria, scientists began to explore the realm of DNA and genetics. As their understanding of the proteins grew, so did their curiosity.

When scientists learned how to modify the genes of small, simple organisms, they began to wonder, "How could this be applied to humans?"

The scientific community is stirring with the emergence of CRISPR DNA,more specifically known as the CRISPR-Cas9 protein.CRISPR stands forClustered Regularly Interspaced Short Palindromic Repeats.CRISPR is a faster, cheaper and more accurate way of editing the genome, according to theNational Institute of Health.By sending in two different pieces of CRISPR DNA,scientists are able to modify genes. To do so, theycutout areas of genes that aren'tperforming how they should be or as they're expected to.

Dr. Sandi Connelly, a principallecturer in the Thomas H. Gosnell School of Life Sciences, explained how DNA works and what the CRISPRCas-9 protein actually does. Connelly compared DNA to a street of houses each person has different foundations that sprout out different and unique homes.

CRISPR is a piece of DNA, and we [scientists] attach to it an enzyme ...it cuts the DNA at a very specific place like a pair of scissors, Connelly said. When we look at CRISPR, typically we look at CRISPR Cas-9."

Whereas CRISPR is the DNA itself, Cas-9 is the enzyme, a specialized protein that splits the DNA.Connelly said that this allows for both the CRISPR DNA and the original DNA to stick together like magnets. However, due to the specificity of this technique, scientists need to know where in the DNA they'relooking.

Using those same enzymes, we can cut [and] place back inthe good gene, Connelly said.

Now, this technique would not be doneby injecting the CRISPR DNA directlyinto a fully grown adult. Instead,scientists would take a sample of a persons bone marrow and alter the genes of those cells. Since bone marrow is responsible for producing red blood cells, the new altered bone marrow will produce cells with the new DNA.

Connelly saidthechangeswouldnot be instantaneous.The human body replaces a majority of its cells within 13 days, soit would take around two weeks for the newly edited gene to be present in the human body.

The ability to now alter genes of morecomplexorganisms brings with it a variety of applications. Plants can be changed to increase nutritional value and pesticidal properties,whereas bacteria can be used to generate hormones and medicines.

Dr. David Holtzman,an adjunct professor in the College of Science, understands how gene editing is used and what it could be used for.

Most people are familiar with it [gene editing] for things like modifying plants ...[but] there is a lot of misunderstanding about gene editing, Holtzman said.

There is a lot of misunderstanding about gene editing.

CRISPR has begun to work its way into at-home kits, where those with some scientificexpertise can genetically modify their own plants to glow or be a different color. This is fairly simple in the world of gene editing as it is changing a simple expressed trait one that isbiologically shown.

Genes decide what traits a person has, but that persons environment and what happens to their body determines how those traits are expressed. As gene editing becomes more and more innovative, Holtzman said that there are limitations to what gene editing can and cannot do.

It turns out most traits are more than one gene, Holtzman said.

Holtzman used hair color as an example. Numerous genes and sections of DNA code for what an individual's hair colorwill be. Itcan behard and time-consuming to find the right area of the DNA to target for modification.

Connelly talked about the idea of changing hair coloras well,but took it a few steps further. Shesuggestedthat we may start wanting to create offspring that all have blonde hair and blue eyes, which realistically we could accomplish. This then opens parents up to the ideas of having all male children or all female children.

In recent years, science has progressed faster than we could have thought.What appeared to be science fiction in the past is inching ever closer to our scientific reality.

The ability to do [new]things happens a lot faster than our understanding of what we are doing, Holtzman said.

Regardless of the potential scientific progress that could be made, Holtzman, Connelly and other members of the scientific community are having conversations about what should be done with this technology. Where should the limits lie, and how far should humans gowith genetic technology?

"Where should the limits lie, and how far should humansgowith genetic technology?"

If our parents changed our genes, they would also be changing the genes of all of our descendants by extension. Did they consent to something like that?

Some might argue, whether we gene edit or not, we dont really have control over what our parents did, Holtzman said. There is the possibility that if we changed [certain genes]then we can change them back.

Reversal isn't a guarantee, though.

Holtzman mentioned ways in which gene editing could greatly improve the quality of life for all humankind, such as curing Alzheimers disease. Connelly brought up how easy it would be to reduce the effects of aging using genetic modification.

The consequences of the choices made nowmay not affect the generation making them. As the movement to improve the genetic composition of the human race pushes forward,plots in sci-finovelsmay no longer be abstract, distant futures. Rather, for better or worse, they could bethe reality we are setting up for generations to come.

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Science Fiction Becoming Reality - Reporter Magazine

Bone Marrow Stem Cells Comments Off on Science Fiction Becoming Reality – Reporter Magazine | December 12th, 2019

DORVAL, QC, Dec. 12, 2019 /CNW/ - Novartis Pharmaceuticals Canada Inc. is pleased to announce that sites in Ontario have been certified in accordance with applicable requirements to treat eligible patients with Kymriah (tisagenlecleucel), the first chimeric antigen receptor T cell (CAR-T) therapy that received regulatory approval in Canada. Patients with relapsed/refractory (r/r) pediatric and young adult B-cell acute lymphoblastic leukemia (ALL) and adult r/r diffuse large B-cell lymphoma (DLBCL) may be eligible to be treated with Kymriah at one of the initially certified Canadian treatment sites. This news follows the recent decision by the Ontario government to fund Kymriah and publication of guidelines by Cancer Care Ontario regarding the enrolment process and criteria for patients to receive CAR-T cell therapy.ii

"Early results show that patients who receive CAR-T cell therapy are either seeing their cancer go into remission or can use CAR-T as a bridge to a stem cell transplant," said Christine Elliott, Deputy Premier and Minister of Health. "We are pleased that Ontario is among the first provinces in Canada to offer CAR-T cell therapy to eligible pediatric and adult patients."

Per the guidelines, eligible patients are now able to access Kymriah from The Hospital for Sick Children (SickKids) in Toronto and Hamilton Health Sciences. Princess Margaret Cancer Centre in Toronto and The Ottawa Hospital are working to complete the process to become certified treatment sites and join the network of qualified Ontario centres in 2020.

"Novartis would like to acknowledge and applaud the collaboration of all stakeholders involved, including Cancer Care Ontario, in helping to ensure patients have access to the first CAR-T therapy approved in Canada for patients with B-cell ALL and DLBCL who historically have poor outcomes. Having treatment sites certified in Ontario allows eligible patients to be treated with CAR-T therapy and is in line with our mission to provide rapid access to life-changing therapies to all Canadians," said Christian Macher, Country President & General Manager, Oncology, Novartis Pharmaceuticals Canada Inc. "Novartis is committed to bringing additional qualified Canadian treatment centres into the network to give patients the opportunity to be treated closer to home."

Due to the sophisticated and individualized nature of Kymriah, treatment sites that are part of the network are required to be FACT-accredited (Foundation for the Accreditation of Cellular Therapy). This means they are qualified to perform intravenous infusion of stem cells collected from the bone marrow of a donor, also referred to as allogeneic hematopoietic stem cell transplantation (alloSCT) and have experience with cell therapies and treating leukemia and lymphoma to facilitate safe and seamless delivery of Kymriah to eligible patients.

About KymriahKymriah (tisagenlecleucel), a CD19-directed genetically modified autologous T-cell immunocellular therapy, is approved to treat two life-threatening cancers that have limited treatment options and historically poor outcomes, demonstrating the critical need for new therapies for these patients.

Kymriah is approved by Health Canada for use in pediatric and young adult patients 3 to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) who are refractory, have relapsed after allogenic stem cell transplant (SCT) or are otherwise ineligible for SCT, or have experienced second or later relapse; and for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphomai.

Kymriah is a one-time treatment that uses a patient's own T cells to fight and kill cancer cells. Bringing this innovative therapy to Canadian patients requires collaboration among many health system stakeholders.

Kymriah (tisagenlecleucel) Important Safety InformationThe full prescribing information for Kymriah can be found at: http://www.novartis.ca

Novartis Leadership in Cell and Gene Therapy Novartis is at the forefront of investigational immunocellular therapy and was the first pharmaceutical company to significantly invest in CAR-T research, work with pioneers in CAR-T and initiate global CAR-T trials. Active research programs are underway targeting other hematologic malignancies and solid tumors, and include efforts focused on next generation CAR-Ts that involve simplified manufacturing schemes and gene edited cells.

About Novartis in CanadaNovartis Pharmaceuticals Canada Inc., a leader in the healthcare field, is committed to the discovery, development and marketing of innovative products to improve the well-being of all Canadians. In 2018, the company invested $52 million in research and development in Canada. Located in Dorval, Quebec, Novartis Pharmaceuticals Canada Inc. employs approximately 1,000 people in Canada and is an affiliate of Novartis AG, which provides innovative healthcare solutions that address the evolving needs of patients and societies. For further information, please consult http://www.novartis.ca.

About NovartisNovartis is reimagining medicine to improve and extend people's lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world's top companies investing in research and development. Novartis products reach more than 750 million people globally and we are finding innovative ways to expand access to our latest treatments. About 109,000 people of more than 140 nationalities work at Novartis around the world. Find out more at http://www.novartis.com.

Kymriah is a registered trademark.

SOURCE Novartis Pharmaceuticals Canada Inc.

For further information: Novartis Media Relations, Daphne Weatherby, Novartis Corporate Communications, +1 514 633 7873, E-mail: camlph.communications@novartis.com

http://www.novartis.ca

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Novartis completes certification of initial sites in Ontario for first approved Canadian CAR-T therapy, Kymriah (tisagenlecleucel)[i] - Canada...

Bone Marrow Stem Cells Comments Off on Novartis completes certification of initial sites in Ontario for first approved Canadian CAR-T therapy, Kymriah (tisagenlecleucel)[i] – Canada… | December 12th, 2019

Led by researchers at Baylor College of Medicine, a study published in the journal Cell Stem Cell reveals a new mechanism that contributes to adult bone maintenance and repair and opens the possibility of developing therapeutic strategies for improving bone healing.

Adult bone repair relies on the activation of bone stem cells, which still remain poorly characterized, said corresponding author Dr. Dongsu Park, assistant professor of molecular and human genetics and of pathology and immunology at Baylor. Bone stem cells have been found both in the bone marrow inside the bone and also in the periosteum the outer layer of tissue that envelopes the bone. Previous studies have shown that these two populations of stem cells, although they share many characteristics, also have unique functions and specific regulatory mechanisms.

Of the two, periosteum stem cells are the least understood. It is known that they comprise a heterogeneous population of cells that can contribute to bone thickness, shaping and fracture repair, but scientists had not been able to distinguish between different subtypes of bone stem cells to study how their different functions are regulated.

In the current study, Park and his colleagues developed a method to identify different subpopulations of periosteum stem cells, define their contribution to bone fracture repair in live mouse models and identify specific factors that regulate their migration and proliferation under physiological conditions.

Periosteal stem cells are major contributors to bone healing

The researchers discovered specific markers for periosteum stem cells in mouse models. The markers identified a distinct subset of stem cells that contributes to life-long adult bone regeneration.

We also found that periosteum stem cells respond to mechanical injury by engaging in bone healing, Park said. They are important for healing bone fractures in the adult mice and, interestingly, their contribution to bone regeneration is higher than that of bone marrow stem cells.

In addition, the researchers found that periosteal stem cells also respond to inflammatory molecules called chemokines, which are usually produced during bone injury. In particular, they responded to chemokine CCL5.

Periosteal stem cells have receptors molecules on their cell surface that bind to CCL5, which sends a signal to the cells to migrate toward the injured bone and repair it. Deleting the CCL5 gene in mouse models resulted in marked defects in bone repair or delayed healing. When the researchers supplied CCL5 to CCL5-deficient mice, bone healing was accelerated.

The findings suggested potential therapeutic applications. For instance, in individuals with diabetes or osteoporosis in which bone healing is slow and may lead to other complications resulting from limited mobility, accelerating bone healing may reduce hospital stay and improve prognosis.

Our findings contribute to a better understanding of how adult bones heal. We think this is one of the first studies to show that bone stem cells are heterogeneous and that different subtypes have unique properties regulated by specific mechanisms, Park said. We have identified markers that enable us to tell bone stem cell subtypes apart and studied what each subtype contributes to bone health. Understanding how bone stem cell functions are regulated offers the possibility to develop novel therapeutic strategies to treat adult bone injuries.

Reference

Ortinau et al. (2019) Identification of Functionally Distinct Mx1+SMA+ Periosteal Skeletal Stem Cells. Cell Stem Cell. DOI: https://doi.org/10.1016/j.stem.2019.11.003

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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New Mechanism of Bone Maintenance and Repair Discovered - Technology Networks

Bone Marrow Stem Cells Comments Off on New Mechanism of Bone Maintenance and Repair Discovered – Technology Networks | December 12th, 2019

Regardless of the advancements made in understanding the genetic and molecular landscapes of acute myeloid leukemia (AML) in young patients, bespoke treatment approaches are yet to be adopted. Based on the NCCN 2009 guidelines,2 AML risk stratification depends on genetic/cytogenetic abnormalities of AML cells and groups patients into favorable-risk" (FR), intermediate-risk (IR) or poor-risk (PR) categories. This will then determine the treatment pathway of whether they will receive allogeneic stem cell transplantation (allo-SCT). Currently, treatment of IR patients is less defined and often post-induction treatment with allo-SCT is adopted. Nevertheless, this approach does not appropriately take into account the heterogeneity in this group regarding the risk of disease relapse. Despite high complete remission (CR) rates in these patients, overall survival (OS) remains low due to the high rate of relapse incidence.3

Adriano Venditti et al., from the Gruppo Italiano Malattie EMatologiche dellAdulto (GIMEMA) Foundation investigated in a multicenter prospective clinical trial (NCT01452646) the benefit of risk-adapted, MRD-based therapy in young adults with AML. This study consisted of the integration of pre-treatment cytogenetics/genetics with post-treatment MRD assessment (detected using multiparametric flow cytometry [MFC]) to stratify patients to receive post-consolidation autologous stem cell transplantation (auto-SCT) or allo-SCT.1

In conclusion, the authors recognized that this study has intrinsic limitations due to scientific progression over time, such as better understanding of basic biology, new AML classification and increased MRD monitoring, which makes the historical control not wholly comparable. However, this is the first study that attempts to apply a prospective program of risk-adapted, MRD-driven treatment in patients with NCCN-IR AML, that integrates genetics and post-consolidation MRD status.

Patients that were in the NCCN-IR group demonstrated that allo-SCT can be avoided if patients are tested MRD-negative after induction therapy. In contrast, if patients are MRD-positive, allo-SCT improved OS and prolonged DFS to comparable levels as those of patients in the NCCN-FR group. Patients in the IR group, who could not be monitored for LAIP had an inferior 2-year OS of 50% when compared to the other risk groups. This suggests that, in this group, a number of patients could have benefited from an allo-SCT. Further studies that integrate baseline factors and monitor MRD are needed, as it could potentially be a promising tool to refine and customize outcome prediction in patients with AML.

Link:
GIMEMA AML1310 trial of risk-adapted, MRD-guided therapy for young patients with newly diagnosed AML - AML Global Portal

Bone Marrow Stem Cells Comments Off on GIMEMA AML1310 trial of risk-adapted, MRD-guided therapy for young patients with newly diagnosed AML – AML Global Portal | December 12th, 2019

By Aprille HansonAssociate Editor

Aprille Hanson

Deacon Butch King and his wife Debbie (left) stand with their daughter Paula Draeger (center) in front of the Seed of Hope garden at UAMS Winthrop P. Rockefeller Cancer Institute in Little Rock Dec. 4. Last month, King was able to place a seed of hope token into the garden, signifying he is cancer-free, thanks to a stem cell donation from his daughter.

Aprille Hanson

Deacon Butch King and his wife Debbie (left) stand with their daughter Paula Draeger (center) in front of the Seed of Hope garden at UAMS Winthrop P. Rockefeller Cancer Institute in Little Rock Dec. 4. Last month, King was able to place a seed of hope token into the garden, signifying he is cancer-free, thanks to a stem cell donation from his daughter.

Deacon Butch King was given a gift in 2017. He was diagnosed with a rare disease MDS/MPN, myelodysplastic/myeloproliferative neoplasm-unclassifiable to be exact.

The hybrid disease results when bone marrow overproduces unhealthy blood cells, according to University of Arkansas for Medical Sciences in Little Rock.

The diagnosis sent the family on a harrowing journey for the next two and a half years: four changes of insurance coverage and medical facilities, 19 rounds of chemotherapy, 430 lab results, 14 bone marrow biopsies, 11.25 gallons of donated blood and the disease progressing to Acute Myeloid Leukemia.

Looking at a deadly disease as a gift takes a radical faith in God, one that King and his wife Debbie have carried with grace to his cancer-free diagnosis Nov. 4.

It was given to us as a gift. And how do we manage gifts? We care for them, we nurture them, we polish them, show them off with pride and we give thanks to God. Those are his words, our words together. We had a gift and we had to manage it, we didnt get a choice, his wife said.

King was ordained a deacon in 2012, serving at Immaculate Conception Church in North Little Rock. The couple has four children, 12 grandchildren and six great-grandchildren, with another on the way in March. After 23 years of serving in the U.S. Air Force working in secure communications, he spent 22 years with the U.S. Postal Service.

In October 2016, he had a metal stent placed in his heart and could not have any surgeries for the following six months. In November of that year, he twisted his knee at work. When he was finally ready to have knee surgery in May, his lab work was irregular. In June they learned he had developed a rare blood disorder, MDS, which later in the year progressed to MPN. It required a stem cell transplant, with only a 30 percent chance of surviving a transplant.

I was kind of stunned at first, King said. As a deacon, he had been used to visiting the sick in nursing homes and hospitals.

This is one of the stories you can say, I know how you feel because Ive been there or were praying for you and really mean it, he said.

With every roadblock of insurance not covering the procedure or a hospital turning the transplant down because he was high risk, faith prevailed.

In December 2017, their youngest daughter Paula Draeger, 38, was a perfect match for a stem cell transplant, an extremely rare result.

OK, we can do this; were going to heal him. Weve got the perfect match. If this doesnt work, nothing will. So that was just kind of the reaction, lets do it, the married mother of two said.

Debbie King said, Shes a Spina bifida baby. We were told that she would be a vegetable when she had her spinal surgery. So shes a miracle to be here; long before this ever came God had a plan.

Once Medicare kicked in, insurance would cover a transplant if a clinical trial was available. It led the family to 13 visits to University of Oklahoma Stephenson Cancer Center in Oklahoma City, though they refused the transplant.

Debbie King said they specifically chose Oklahoma City because the family had been, and still are, praying daily for Blessed Stanley Rothers intercession.

The martyr, who grew up on a farm in Okarche, Okla., was declared blessed on Sept. 23, 2017, in Oklahoma City. He was killed in 1981 while serving his people in Guatemala.

He needed a miracle. And we said God provides miracles, Debbie King said.

Before we started any treatment we would place the entire illness and what would be happening at Blessed Stanley Rothers gravesite in Oklahoma City, visiting 11 times, she said.

Whats the miracle? The miracle is the faith. And thats what Butch has said, she said.

On March 13, the Kings were told they wouldnt be continuing the trial in Oklahoma.

We were ready to just be on maintenance and enjoy the days we had, she said. On March 14, our 44th wedding anniversary we were celebrating what we thought could be our last one.

But Dr. Appalanaidu Sasapu, hematologist oncologist with the UAMS Stem Cell Transplantation and Cellular Therapy Program, never gave up on them. Because Kings disease had progressed to leukemia in April, the stem cell procedure could now be done at UAMS and covered by insurance.

Draeger said the stem cell donations, done over a weekend via a port, were simple, with no side effects aside from building her energy up in the following week.

For what youre able to give somebody, what you have to endure pales in comparison to what hes been through and what you can give him, she said.

King no longer has the blood disease and is cancer free, though he will continue at least a years worth of chemotherapy treatments.

Since his diagnosis, they attend the smaller St. Patrick Church in North Little Rock for Mass, but he cannot yet return to ministry.

We do our prayer time in the mornings and evenings, we count our blessings every night before we go to bed and we just know, what was our blessing today? Did we see somebody that we havent seen before that God put in our path? Is it a new doctor who is going to take this on? King said.

But through this whole process weve been truly blessed, had no regrets. If I had to do it over, if thats the path of my life that God wants me to take, then Ill do it.

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Deacon Butch King learns to accept the 'gift' of cancer - Arkansas Catholic

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DUBLIN--(BUSINESS WIRE)--The "Global Blood and Bone Marrow Cancer Treatment Market Size, Market Share, Application Analysis, Regional Outlook, Growth Trends, Key Players, Competitive Strategies and Forecasts, 2019 to 2027" report has been added to ResearchAndMarkets.com's offering.

The global blood and bone marrow cancer treatment market was valued at US$ 38.8 Bn in 2018 and is expected to reach US$ 74.9 Bn by 2027, expanding at a CAGR of 7.7% from 2019 to 2027.

Market Insights

Blood cancer begins in the bone marrow which is the integral source of stem cells which later are differentiated in different types of blood cells in the human body. Researchers at Bristol Myers Squibb Company have stated that approximately 1.85 million new cases of blood cancer will be diagnosed by 2040 throughout the globe.

Lymphoma is the largest indication segment for blood and bone marrow cancer treatment market. It is prevalent in 2 types Hodgkin lymphoma and Non-Hodgkin lymphoma throughout the globe. The chief variables responsible for its rising prevalence worldwide are increasing prescription of immunosuppressant drugs for treating chronic infections and genetic mutations. Leukemia occurs when the DNA of immature white blood cells gets damaged due to exposure to ionizing radiation, hazardous chemicals, smoking, etc. The prevalence rate of leukemia is highly variable across different ethnic groups with men to women ratio of 1.4.

Chemotherapy is reigning the therapy segment for blood and bone marrow cancer treatment market. The key parameter hold responsible for its increasing demand is the availability of its generic version at affordable cost, drastically reducing the healthcare burden on ailing patients. Oncologists prefer to use them in combination therapy either with radiotherapy or immunotherapy to treat patients showing resistance to first-line drug therapy. Immunotherapy will be the fastest-growing segment during the forecast period owing to its promising drug pipeline for the treatment of blood cancer.

North America representing a market share of 34.6% is dominating the regional segment for blood and bone marrow cancer treatment market. The chief contributing factor for its market supremacy is a growing incidence of blood cancer. As per the research citings of the Leukemia and Lymphoma Society (CDC) figures after every 3 minutes, 1 person in the U.S. is diagnosed with blood cancer. In 2019, approximately 176,200 people in the U.S. are diagnosed with blood cancer in the United States. Europe holds a market share of 30.8% owing to the supportive regulatory framework provided by the European Medical Agency for the development and sale of medication for the treatment of blood cancer. The Asia Pacific accounts for 18.4% market share on account of rising public health awareness related to blood cancer & its treatment and developing healthcare infrastructure.

Key Market Movements:

Key Topics Covered:

Chapter 1. Preface

1.1. Report Scope and Description

1.1.1. Purpose of the Report

1.1.2. Target Audience

1.1.3. USP and Key Offerings

1.2. Research Scope

1.3. Research Methodology

1.3.1. Phase I-Secondary Research

1.3.2. Phase II-Primary Research

1.3.3. Approach Adopted

1.3.4. Top-down Approach

1.3.5. Bottom-up Approach

1.3.6. Phase III-Expert Panel Review

1.3.7. Assumptions

1.4. Market Segmentation

Chapter 2. Executive Summary

2.1. Global Blood and Bone Marrow Cancer Treatment Market Portraiture

2.2. Global Blood and Bone Marrow Cancer Treatment Market, by Indication, 2018 (US$ Bn)

2.3. Global Blood and Bone Marrow Cancer Treatment Market, by Therapy, 2018 (US$ Bn)

2.4. Global Blood and Bone Marrow Cancer Treatment Market, by Geography, 2018 (US$ Bn)

Chapter 3. Blood and Bone Marrow Cancer Treatment Market: Dynamics and Future Outlook

3.1. Market Overview

3.2. Drivers

3.3. Challenges

3.4. Opportunities

3.5. Attractive Investment Proposition, by Geography, 2018

3.6. Competitive Analysis: Global Blood and Bone Marrow Cancer Treatment Market, by Key Players, 2018

Chapter 4. Global Blood and Bone Marrow Cancer Treatment Market, by Indication

4.1. Overview

4.2. Multiple Myeloma

4.3. Leukemia

4.4. Lymphoma

4.5. Others

Chapter 5. Global Blood and Bone Marrow Cancer Treatment Market, by Therapy

5.1. Chemotherapy

5.2. Immunotherapy

5.3. Stem Cell Transplant

5.4. Radiotherapy

5.5. Pipeline Analysis

5.5.1. Phase III Drug

5.5.1.1. Eltrombopag

5.5.1.2. Avatrombopag

5.5.1.3. Hetrombopag

5.5.1.4. Omidubicel

5.5.1.5. Fedratinib

5.5.1.6. ATIR101

5.5.1.7. Pegylated Proline Interferon Alpha-2b

5.5.2. Tabular Representation of Phase II and I Pipeline Drugs

Chapter 6. Global Blood and Bone Marrow Cancer Treatment Market, by Geography

6.1. Overview

6.2. North America Blood and Bone Marrow Cancer Treatment Market Analysis, 2017- 2027

6.3. Europe Blood and Bone Marrow Cancer Treatment Market Analysis, 2017 - 2027

6.4. Asia Pacific Blood and Bone Marrow Cancer Treatment Market Analysis, 2017 - 2027

6.5. Latin America Blood and Bone Marrow Cancer Treatment Market Analysis, 2017 - 2027

6.6. Middle East and Africa Blood and Bone Marrow Cancer Treatment Market Analysis, 2017 - 2027

Chapter 7. Company Profiles

7.1. AstraZeneca, Plc.

7.1.1. Business Description

7.1.2. Financial Information (Subject to data availability)

7.1.3. Product Portfolio

7.1.4. News Coverage

7.2. Celgene, Inc.

7.3. Bristol Myers Squibb & Company

7.4. Eli Lilly & Company

7.5. Johnson & Johnson Company

7.6. F.Hoffman La-Roche Ltd.

7.7. Merck & Co., Inc.

7.8. Novartis AG

7.9. Pfizer, Inc.

7.10. Varian Medical Systems, Inc.

For more information about this report visit https://www.researchandmarkets.com/r/pi0qoz

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Global Blood and Bone Marrow Cancer Treatment Market Trends & Analysis During the Forecast Period, 2019-2027 - ResearchAndMarkets.com - Business...

Bone Marrow Stem Cells Comments Off on Global Blood and Bone Marrow Cancer Treatment Market Trends & Analysis During the Forecast Period, 2019-2027 – ResearchAndMarkets.com – Business… | December 10th, 2019

In the summer, a mother in Nashville with a seemingly incurable genetic disorder finally found an end to her suffering -- by editing her genome.

Victoria Gray's recovery from sickle cell disease, which had caused her painful seizures, came in a year of breakthroughs in one of the hottest areas of medical research -- gene therapy.

"I have hoped for a cure since I was about 11," the 34-year-old told AFP in an email. "Since I received the new cells, I have been able to enjoy more time with my family without worrying about pain or an out-of-the-blue emergency."

Over several weeks, Gray's blood was drawn so doctors could get to the cause of her illness -- stem cells from her bone marrow that were making deformed red blood cells.

The stem cells were sent to a Scottish laboratory, where their DNA was modified using Crispr/Cas9 -- pronounced "Crisper" -- a new tool informally known as molecular "scissors."

The genetically edited cells were transfused back into Gray's veins and bone marrow. A month later, she was producing normal blood cells.

Medics warn that caution is necessary but, theoretically, she has been cured.

"This is one patient. This is early results. We need to see how it works out in other patients," said her doctor, Haydar Frangoul, at the Sarah Cannon Research Institute in Nashville. "But these results are really exciting."

In Germany, a 19-year-old woman was treated with a similar method for a different blood disease, beta thalassemia. She had previously needed 16 blood transfusions per year.

Nine months later, she is completely free of that burden.

For decades, the DNA of living organisms such as corn and salmon has been modified.

But Crispr, invented in 2012, made gene editing more widely accessible. It is much simpler than preceding technology, cheaper and easy to use in small labs.

The technique has given new impetus to the perennial debate over the wisdom of humanity manipulating life itself.

"It's all developing very quickly," said French geneticist Emmanuelle Charpentier, one of Crispr's inventors and the cofounder of Crispr Therapeutics, the biotech company conducting the clinical trials involving Gray and the German patient.

Crispr is the latest breakthrough in a year of great strides in gene therapy, a medical adventure started three decades ago, when the first TV telethons were raising money for children with muscular dystrophy.

Scientists practising the technique insert a normal gene into cells containing a defective gene.

It does the work the original could not -- such as making normal red blood cells, in Victoria's case, or making tumor-killing super white blood cells for a cancer patient.

Crispr goes even further: instead of adding a gene, the tool edits the genome itself.

After decades of research and clinical trials on a genetic fix to genetic disorders, 2019 saw a historic milestone: approval to bring to market the first gene therapies for a neuromuscular disease in the U.S. and a blood disease in the European Union.

They join several other gene therapies -- bringing the total to eight -- approved in recent years to treat certain cancers and an inherited blindness.

Serge Braun, the scientific director of the French Muscular Dystrophy Association, sees 2019 as a turning point that will lead to a medical revolution.

"Twenty-five, 30 years, that's the time it had to take," he told AFP from Paris. "It took a generation for gene therapy to become a reality. Now, it's only going to go faster."

Just outside Washington, at the National Institutes of Health (NIH), researchers are also celebrating a "breakthrough period."

"We have hit an inflection point," said Carrie Wolinetz, NIH's associate director for science policy.

These therapies are exorbitantly expensive, however, costing up to $2 million -- meaning patients face grueling negotiations with their insurance companies.

They also involve a complex regimen of procedures that are only available in wealthy countries.

Gray spent months in hospital getting blood drawn, undergoing chemotherapy, having edited stem cells reintroduced via transfusion -- and fighting a general infection. "You cannot do this in a community hospital close to home," said her doctor.

However, the number of approved gene therapies will increase to about 40 by 2022, according to MIT researchers. They will mostly target cancers and diseases that affect muscles, the eyes and the nervous system.

Another problem with Crispr is that its relative simplicity has triggered the imaginations of rogue practitioners who don't necessarily share the medical ethics of Western medicine.

Last year in China, scientist He Jiankui triggered an international scandal -- and his excommunication from the scientific community -- when he used Crispr to create what he called the first gene-edited humans.

The biophysicist said he had altered the DNA of human embryos that became twin girls Lulu and Nana.

His goal was to create a mutation that would prevent the girls from contracting HIV, even though there was no specific reason to put them through the process.

"That technology is not safe," said Kiran Musunuru, a genetics professor at the University of Pennsylvania, explaining that the Crispr "scissors" often cut next to the targeted gene, causing unexpected mutations.

"It's very easy to do if you don't care about the consequences," Musunuru added.

Despite the ethical pitfalls, restraint seems mainly to have prevailed so far.

The community is keeping a close eye on Russia, where biologist Denis Rebrikov has said he wants to use Crispr to help deaf parents have children without the disability.

There is also the temptation to genetically edit entire animal species -- malaria-causing mosquitoes in Burkina Faso or mice hosting ticks that carry Lyme disease in the U.S.

The researchers in charge of those projects are advancing carefully, however, fully aware of the unpredictability of chain reactions on the ecosystem.

Charpentier doesn't believe in the more dystopian scenarios predicted for gene therapy, including American "biohackers" injecting themselves with Crispr technology bought online.

"Not everyone is a biologist or scientist," she said.

And the possibility of military hijacking to create soldier-killing viruses or bacteria that would ravage enemies' crops?

Charpentier thinks that technology generally tends to be used for the better.

"I'm a bacteriologist -- we've been talking about bioterrorism for years," she said. "Nothing has ever happened."

Link:
2019: the year gene therapy came of age - Japan Today

Bone Marrow Stem Cells Comments Off on 2019: the year gene therapy came of age – Japan Today | December 10th, 2019

DURHAM, N.C., Dec. 10, 2019 (GLOBE NEWSWIRE) -- Chimerix, Inc. (Nasdaq: CMRX), a biopharmaceutical company focused on accelerating the development of medicines to treat cancer and other serious diseases, today announced that data relating to its dociparstat sodium (DSTAT) program, formerly known as CX-01, were presented at the 61st American Society of Hematology Annual Meeting, in Orlando, FL.

The poster, titledUpdated Study Results for CX-01, an Inhibitor of CXCL12/CXCR4, With Azacitidine for the Treatment of Hypomethylating Agent Refractory AML and MDS, was presented byEric Huselton, M.D., Assistant Professor of Medicine at the University of Rochester on December 9, 2019.

As reported in the published study abstract, 20 patients with refractory myelodysplastic syndrome (MDS) (n = 9) or refractory acute myeloid leukemia (AML) (n = 11) were enrolled of which 15 were considered evaluable for response with a bone marrow biopsy after cycle 2. Patients received a 7-day continuous infusion of DSTAT (CX-01) at a dose of 0.25 mg/kg/hour, and azacitidine 75 mg/m2 daily days 1-7, in 28-day cycles. The primary objective of this trial was to assess the overall response rate. Half of the patients had high risk cytogenetic abnormalities and 3 had TP53 mutations. Patients had a median of 2 prior lines of therapy (range 1-3) with median of 6 prior cycles of hypomethylating agent (HMA) therapy (range 4-20). Only 4 patients had a confirmed response to prior HMA therapy.

The 15 evaluable patients received a median of 3 cycles of CX-01 and azacitidine (range 2-9). Of 15 evaluable patients, there was 1 CR (complete remission) and 3 bone marrow CRs (mCR, with incomplete peripheral blood count recovery), 9 stable disease, and 2 progressive disease for an overall response rate of 27%. Of the 3 patients with a mCR after cycle 2, two had hematologic improvement of their neutrophil and platelet counts, respectively, by the end of cycle 4. A patient with stable disease also had hematologic improvement in platelets.

The median overall survival of evaluable patients was 221 days. The median overall survival was not significantly different between AML patients at 221 days and MDS patients at 248 days.

Following a minimum of 4 cycles of prior HMA therapy, one would not expect to observe response to subsequent HMA therapy, said Dr. Huselton. These results demonstrate DSTATs potential to improve HMA therapy outcomes in terms of both response and overall survival.

"DSTATs mechanism of action is intended to enhance patient benefit when combined with an active agent, so to observe these results in HMA-refractory patients is promising. In addition to our planned Phase 3 pivotal trial in newly diagnosed AML, this study highlights the potential to develop DSTAT to enhance the benefit of multiple therapies such as azacitidine, in AML and MDS in both front-line and recurrent settings," said Mike Sherman, Chief Executive Officer of Chimerix.

AboutChimerix

Chimerixis a development-stage biopharmaceutical company dedicated to accelerating the advancement of innovative medicines that make a meaningful impact in the lives of patients living with cancer and other serious diseases. The two clinical-stage development programs are dociparstat sodium (DSTAT) and brincidofovir (BCV).

Dociparstat sodium is a potential first-in-class glycosaminoglycan biologic derived from porcine heparin that has low anticoagulant activity but retains the ability to inhibit activities of several key proteins implicated in the retention and viability of AML blasts and leukemic stem cells in the bone marrow during chemotherapy (e.g., CXCL12, selectins, HMGB1). Mobilization of AML blasts and leukemic stem cells from the bone marrow has been associated with enhanced chemosensitivity and may be a primary mechanism accounting for the observed increases in EFS and OS in Phase 2 with DSTAT versus placebo. Randomized Phase 2 data suggest that DSTAT may also accelerate platelet recovery post-chemotherapy via inhibition of platelet factor 4, a negative regulator of platelet production that impairs platelet recovery following chemotherapy. BCV is a lipid conjugate DNA polymerase inhibitor in development as a medical countermeasure for smallpox.For further information, please visit the Chimerix website,www.chimerix.com

CONTACT:

Investor Relations:Michelle LaSpaluto919-972-7115ir@chimerix.com

Will OConnorStern Investor Relations212-362-1200will@sternir.com

Link:
Chimerix Presents Updated Results from Phase 2 Clinical Trial of DSTAT in Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia at American...

Bone Marrow Stem Cells Comments Off on Chimerix Presents Updated Results from Phase 2 Clinical Trial of DSTAT in Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia at American… | December 10th, 2019

The global bone marrow aspirate concentrates market was valued around US$ 130.0 Mn in 2016 is anticipated to register a stable CAGR of over 5.0% during forecast period of 2017 to 2025, according to a new report published by Transparency Market Research (TMR) titled Bone Marrow Aspirate Concentrates Market Global Industry Analysis, Size, Share, Growth, Trends, and Forecast, 20172025.

Growth of the global bone marrow aspirate concentrates market is driven by increased prevalence of and incidences of orthopedic diseases, and sports injuries, along with high growth of the cosmetic surgery industry and increasing applications of the BMAC products in the cosmetic and orthopedic surgeries. The bone marrow aspirate concentrates market in Asia Pacific is expanding with a high potential to grow registering a CAGR above 6.0% on the backdrop of unmet clinical needs, rising geriatric population, large patient pool, favorable government regulations, development in health care sector, and increased focus on research and developmental activities.

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Increase in incidences of Osteoarthritis on the backdrop of rising geriatric population to drive market growth

According to a collaborative survey conducted by the United Nations and the World Health Organization, 1.2 billion people in China are suffering from OA, of which more than 55% are aged 60 years or above. On the backdrop of such a huge patient base, there has been several developments in the field orthopedic surgery. Bone marrow-derived stem cell treatment is considered a promising and advanced therapy. It reduces the injury healing time in orthopedic diseases to five to six weeks from four to six months in case of surgery.

Reduction in the healing time is a factor likely to propel the Bone Marrow Aspirate Concentrates market during the forecast period. However, pain associated with the treatment, lack of product approval, and preference for alternative treatments are negatively affecting the market growth. Moreover, high investments in R&D and clinical trials, slow approval processes entailing sunken costs, and marginal returns on investment (RoI) for stakeholders are primary concerns faced by manufacturer further hampering growth of the market.

Rise in the Number of BMAC Assisted Procedures to Boost Growth of Bone Marrow Aspirate Concentrates Accessories Segment

The product type segment is fragmented into bone marrow aspirate concentrates systems and bone marrow aspirate concentrates accessories. The bone marrow aspirate concentrates accessories segment is anticipated to carry major share of the market on the backdrop of rise in number of BMAC assisted procedures. Cell therapies have been used extensively over the past decade for a variety of medical applications to restore cellular function and enhance quality of life. Owing to the differentiation property, stem cells are being used for repair and regeneration of bone. Moreover, increase in awareness about hygiene and risk of cross-contamination in developing countries such as Brazil, China and India are expected to increase the use of single-use Jamshidi needles for bone marrow stem cell procedures. This is likely to fuel the growth of the accessories segment in the near future.

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Orthopedic Surgery Application to Dominate the Global Bone Marrow Aspirate Concentrates Market

The application segment of global bone marrow aspirate concentrates market is divided into orthopedic surgery, wound healing, chronic pain, peripheral vascular disease, dermatology, and others applications. Of which, orthopedic surgery segment is anticipated to dominate the market owing to rising geriatric population, and surge in incidences of osteoarthritis around the globe.

The dermatology segment is anticipated to expand at the highest CAGR of over 6.0% during forecast period of 2017 to 2025 owing to current boom in the industry, increase in disposable income, and technological advancements in the market. The utilization of the regenerative ability of fibroblasts and keratinocytes from human skin has formed new ways to develop cell-based therapies for patients. Moreover, capacity of bone marrow derived extra-cutaneous cells is being researched for its plasticity in regenerating skin; it is likely to lead to the future growth of cell therapies in dermatology.

Rise in Healthcare Expenditure to Fuel Growth of Hospitals & Clinics End-user Segment

In terms of end-users, market is divided into hospitals & clinics, pharmaceutical & biotechnology companies, Contract Research Organizations (CROs) & Contract Manufacturing Organizations (CMOs), and academic & research institutes. The hospitals & clinics segment dominated the bone marrow aspirate concentrates market in 2016. The trend is expected to continue during the forecast period. The hospitals & clinics segment is likely to be followed by the biotechnology & biopharmaceutical companies segment in terms of market share during the forecast period. The segment is anticipated to hold more than 8.0% of market share in 2016. Growth of the segment is attributed to increasing number of biotechnology companies and rising partnerships among the market players to expand global presence.

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Transparency Market Research is a next-generation market intelligence provider, offering fact-based solutions to business leaders, consultants, and strategy professionals.

Our reports are single-point solutions for businesses to grow, evolve, and mature. Our real-time data collection methods along with ability to track more than one million high growth niche products are aligned with your aims. The detailed and proprietary statistical models used by our analysts offer insights for making right decision in the shortest span of time. For organizations that require specific but comprehensive information we offer customized solutions through adhoc reports. These requests are delivered with the perfect combination of right sense of fact-oriented problem solving method-ologies and leveraging existing data repositories.TMR believes that unison of solutions for clients-specific problems with right methodology of re-search is the key to help enterprises reach right decision.

ContactMr. Rohit BhiseyTransparency Market ResearchState Tower,90 State Street,Suite 700,Albany NY 12207United StatesTel: +1-518-618-1030USA Canada Toll Free: 866-552-3453Email: [emailprotected]Website: http://www.transparencymarketresearch.comBlog: https://theglobalhealthnews.com/

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Bone Marrow Aspirate Concentrates Market to Expand at an Outstanding CAGR of 5% from 2017 to 2025 - VaporBlash

Bone Marrow Stem Cells Comments Off on Bone Marrow Aspirate Concentrates Market to Expand at an Outstanding CAGR of 5% from 2017 to 2025 – VaporBlash | December 10th, 2019

BOSTON--(BUSINESS WIRE)--Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to finding cures for blood cancers and serious blood diseases, today announced updated results from a Phase 1 clinical study of GDA-201, an investigational, natural killer (NK) cell-based cancer immunotherapy for the treatment of patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), at the 61st Annual Meeting of the American Society of Hematology (ASH), which is being held December 710 in Orlando, FL. Data from 22 patients in the ongoing study showed GDA-201 in combination with monoclonal antibodies was generally well tolerated and demonstrated early evidence of clinical activity in heavily pre-treated patients, including five complete responses observed among nine patients with NHL. Gamida Cell plans to initiate a Phase 1/2 multi-dose, multi-center study of GDA-201 in patients with NHL in 2020.

NK cells are increasingly recognized as a potential breakthrough approach in immunotherapy, and the data reported today provide early evidence that GDA-201 has the potential to be an important new treatment option, said Veronica Bachanova, M.D., Ph.D., Associate Professor of Medicine in the Division of Hematology, Oncology and Transplantation at the University of Minnesota and principal investigator of the study through the Masonic Cancer Center. Given the population of heavily pre-treated patients with advanced disease, its particularly encouraging to witness multiple complete responses. I look forward to the continued development of this investigational therapy.

New research was also presented today on the mechanism of action of Gamida Cells NAM-based cell expansion platform, which is designed to enhance the number and functionality of allogeneic donor cells. These data provide further scientific rationale for the favorable stem cell engraftment and patient outcomes observed in the Phase 1/2 clinical study of omidubicel, the companys advanced cell therapy currently in Phase 3 clinical development as a potential life-saving treatment option for patients in need of an allogeneic bone marrow transplant.

These mechanism of action data reinforce the transformative potential of our NAM therapeutic platform, which can be used to expand multiple cell types. Specifically for omidubicel, this research suggests that NAM modulates certain gene expression pathways that, collectively, mimic the hypoxic environment of the bone marrow to help preserve stem cell function and long-term engraftment ability, said Tracey Lodie, Ph.D., chief scientific officer of Gamida Cell. We expect to build on our findings by characterizing the metabolites produced when we expand stem cells to make omidubicel, and we are also beginning to conduct similar mechanism of action studies with GDA-201.

GDA-201 Phase 1 Clinical Data Presented at ASH

The oral presentation, Results of a Phase 1 Trial of GDA-201, Nicotinamide-Expanded Allogeneic Natural Killer Cells (NAM-NK) in Patients with Refractory Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma (MM) (Abstract #777), described data from the Phase 1 clinical study of GDA-201 in heavily pre-treated patients with advanced NHL and MM. Twenty-two patients were enrolled in the study, including nine patients with NHL and 13 patients with MM. Of these 22 patients, all were evaluable for safety and 21 were evaluable for response (NHL = 9; MM = 12).

In the study, cell therapy using GDA-201 with monoclonal antibodies was generally well tolerated and demonstrated early evidence of clinical activity. Of the nine patients with NHL, five achieved a complete response and one achieved a partial response. Among the patients with MM, one patient achieved a complete response, and five patients achieved stable disease.

GDA-201 was generally well tolerated, with no graft vs. host disease (GvHD), no tumor lysis syndrome, no neurotoxicity and no marrow aplasia observed. No dose limiting toxicities were observed. Hypertension and hematologic events were the most common Grade 3/4 adverse events observed. Most non-hematologic toxicities were attributed to cyclophosphamide/fludarabine, which was used as a pre-conditioning treatment.

NAM Therapeutic Platform Mechanism of Action Data Presented at ASH

The poster presentation, Nicotinamide (NAM) Modulates Transcriptional Signature of Ex Vivo Cultured UCB CD34+ Cells (Omidubicel) and Preserves Their Stemness and Engraftment Potential (Abstract #3718), included transcriptome, transcription factor, and pathway analysis to elucidate the pathways leading to the preservation of engraftment after ex vivo expansion of CD34+ hematopoietic stem cells derived from umbilical cord blood (the starting point for omidubicel) compared to CD34+ cells grown in the absence of NAM.

Analyses showed that the presence of NAM reduced the expression of genes involved in the production of reactive oxygen and nitrogen species, suggesting that cell stress was minimized during expansion. In addition, NAM also decreased growth factor pathways responsible for activation and differentiation of hematopoietic stem cells, suggesting NAM expanded cells while keeping them in an undifferentiated state. The presence of NAM also led to a decrease in the expression of genes responsible for matrix-metallo proteinase secretion, simulating the microenvironment of the bone marrow. Additionally, NAM led to an increased expression of telomerase genes, which is believed to enable cells to remain in a more quiescent, stem-like state. These data provide further scientific rationale for the favorable stem cell engraftment and patient outcomes that were observed in the Phase 1/2 clinical study of omidubicel.

About GDA-201GDA-201 (formerly known as NAM-NK) is being developed as an innate natural killer (NK) cell immunotherapy for the treatment of hematologic and solid tumors in combination with standard-of-care antibody therapies. NK cells have the ability to kill tumor cells, representing a novel immunotherapeutic approach to cancer treatment. GDA-201 is designed to address key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs of NK cells expanded in culture. GDA-201 is in Phase 1 development in patients with refractory non-Hodgkin lymphoma and multiple myeloma.1 For more information on the clinical study of GDA-201, please visit http://www.clinicaltrials.gov.

About OmidubicelOmidubicel (formerly known as NiCord), the companys lead clinical program, is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant solution for patients with hematologic malignancies (blood cancers). Omidubicel is the first bone marrow transplant product to receive Breakthrough Therapy Designation from the U.S. Food and Drug Administration and has also received Orphan Drug Designation in the U.S. and EU. In a Phase 1/2 clinical study, omidubicel demonstrated rapid and durable time to engraftment and was generally well tolerated.2 A Phase 3 study evaluating omidubicel in patients with leukemia and lymphoma is ongoing in the U.S., Latin America, Europe and Asia.3 Omidubicel is also being evaluated in a Phase 1/2 clinical study in patients with severe aplastic anemia.4 The aplastic anemia investigational new drug application is currently filed with the FDA under the brand name CordIn, which is the same investigational development candidate as omidubicel. For more information on clinical trials of omidubicel, please visit http://www.clinicaltrials.gov.

GDA-201 and omidubicel are investigational therapies, and their safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.

About the NAM Therapeutic PlatformGamida Cells proprietary NAM-based cell expansion platform is designed to enhance the number and functionality of donor cells in culture, enabling the creation of potentially transformative therapies that move beyond what is possible with existing approaches. The NAM therapeutic platform leverages the unique properties of nicotinamide to enable the expansion of multiple cell types including stem cells and natural killer (NK) cells with appropriate growth factors to maintain the cells original phenotype and potency. This can enable the administration of a therapeutic dose of cells with the potential to improve patient outcomes.

About Gamida CellGamida Cell is an advanced cell therapy company committed to finding cures for patients with blood cancers and serious blood diseases. We harness our cell expansion platform to create therapies with the potential to redefine standards of care in areas of serious medical need. For additional information, please visit http://www.gamida-cell.com.

Cautionary Note Regarding Forward Looking StatementsThis press release contains forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, including with respect to the initiation of new clinical trials and the continuation of the Companys clinical development program, which statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to the scope and progress of Gamida Cells clinical trials and other clinical, scientific, regulatory and technical developments. In light of these risks and uncertainties, and other risks and uncertainties that are described in the Risk Factors section of Gamida Cells public filing on Form 20-F, filed with the SEC on February 25, 2019, and other filings that Gamida Cell makes with the SEC from time to time (which are available at http://www.sec.gov), the events and circumstances discussed in such forward-looking statements may not occur, and Gamida Cells actual results could differ materially and adversely from those anticipated or implied thereby. Any forward-looking statements speak only as of the date of this press release and are based on information available to Gamida Cell as of the date of this release.

1ClinicalTrials.gov identifier NCT03019666.2 Horwitz M.E., Wease S., Blackwell B., Valcarcel D. et al. Phase I/II study of stem-cell transplantation using a single cord blood unit expanded ex vivo with nicotinamide. J Clin Oncol. 2019 Feb 10;37(5):367-374.3 ClinicalTrials.gov identifier NCT027302994 ClinicalTrials.gov identifier NCT03173937

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Gamida Cell Announces Results from Phase 1 Study of GDA-201 and New Mechanism of Action Data at ASH 2019 Annual Meeting - Business Wire

Bone Marrow Stem Cells Comments Off on Gamida Cell Announces Results from Phase 1 Study of GDA-201 and New Mechanism of Action Data at ASH 2019 Annual Meeting – Business Wire | December 9th, 2019

NEW ORLEANS, Dec. 9, 2019 /PRNewswire/ --Autoimmune Technologies LLC, a biotechnology company developing diagnostics and therapies for non-infectious and infectious disease, has established a new subsidiary, Stadius Biopharma LLC, to focus on proprietary anti-infective antibody therapeutics for diseases that are inadequately addressed by current standard-of-care medicines.

"Within this standalone entity we'll concentrate on our unique fully human antibodies and our stem cell antibody delivery platform to treat opportunistic viral, bacterial, and fungal infections," said Michael Charbonnet, who will serve as CEO of the newly formed business unit in addition to his continuing responsibilities for the parent company. Current Stadius antibody targets include invasive candidiasis and cytomegalovirus (CMV) infection.

"Ourantibodies bind and disrupt the function of conserved sequences of novel virulence factors associated with pathology of various species of Candida," said CSO Russell Wilson. "Candida aurisis an emerging fungus that presents a serious global health threat, and we'reencouraged by our initial preclinical data that indicates activity against C. auris as well as C. albicans, which is prevalent in high risk patients," he said.

The CDC is monitoring the spread of C. auris colonization and infection in the United States.C. aurisis associated with a high rate of morbidity and mortality and is resistant to current standard of care antifungal treatments. Healthy individualsunknowingly colonized with C. aurisor other Candida species and can spread the fungal cells to surfaces in hospitals, long-term-care facilities, and other healthcare environments, where they pose a threat to people with weakened immune systems.

Also under development are antibody therapeutics to CMV infection. More than 50% of individuals in the U.S. over 40 years of age have been exposed to CMV and carry it without symptoms. It can re-activate in patients with subpar immune systems with the potential for multi-organ involvement, and it can be transmitted through body fluids such as breast milk and saliva. Over time, individuals can become re-infected with different strains of CMV, further complicating prophylaxis and treatment. CMV is the most frequent infectious complication following both solid organ transplantation and bone marrow transplantation.

The company is also developing its proprietary non-viral gene modified allogeneic stem cell platform for delivering antibodies in chronically immune compromised patients. The somatic adipose-derived mesenchymal stem cells, which have unique properties to allow prevention of rejection, are transfected with the genetic information needed to enable the implanted stem cells to produce inside the patient the antibodies needed to prevent or treat infection. Antibody delivery to patients via this platform is intended to provide continuous protection while reducing the requirement for more frequent dosing.

Follow Stadius Biopharma on http://www.stadiusbio.com.

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Autoimmune Technologies Announces New Subsidiary to Develop Novel Antibody and Allogeneic Somatic Stem Cell Therapeutics For the Treatment of Invasive...

Bone Marrow Stem Cells Comments Off on Autoimmune Technologies Announces New Subsidiary to Develop Novel Antibody and Allogeneic Somatic Stem Cell Therapeutics For the Treatment of Invasive… | December 9th, 2019

ORLANDO, Fla.--(BUSINESS WIRE)--Jasper Therapeutics, Inc., a new biotechnology company focused on enabling safer conditioning and therapeutic agents that expand the application of curative hematopoietic stem cell transplants and gene therapies, today announced that initial results from an ongoing Phase 1 dose-escalation study of its lead product candidate, JSP191 (formerly AMG191), will be presented today in an oral session at the American Society of Hematology (ASH) Annual Meeting & Exposition.

JSP191, a humanized antibody targeting CD117, is designed to replace or reduce the toxicity of chemotherapy and radiation therapy as a conditioning regimen to prepare patients for hematopoietic cell transplantation. The Phase 1 clinical trial is evaluating JSP191 as a conditioning agent to enable stem cell transplantation in patients with severe combined immunodeficiency (SCID) who received a prior stem cell transplant that had poor outcomes.

Life-threatening disorders such as SCID, and other conditions including autoimmune diseases and hematologic cancers, can be cured by hematopoietic cell transplantation, and those with certain genetic diseases can be cured with stem cell-directed gene therapies. However, the number of patients who can benefit from these approaches is limited because of the severe toxicity of the chemotherapy used for pre-transplant conditioning that is needed to allow room in the bone marrow for the stem cells to engraft, said Judith Shizuru, M.D., Ph.D., co-founder and member of the Board of Directors of Jasper Therapeutics. We are encouraged by the initial Phase 1 study results of JSP191 in these fragile patients with SCID and plan to expand clinical development of this antibody beyond patients with SCID. We expect to initiate clinical trials of JSP191 in 2020 to evaluate it as a conditioning agent in patients undergoing hematopoietic cell therapy for acute myeloid leukemia, myelodysplastic syndrome and Fanconi anemia, and IND-enabling studies for sickle cell disease and autoimmune indications.

Details of the oral presentation follow:

Abstract Title: Non-Genotoxic Anti-CD117 Antibody Conditioning Results in Successful Hematopoietic Stem Cell Engraftment in Patients with Severe Combined Immunodeficiency (abstract #800) Session Name: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Innovative Approaches in Allogeneic Transplantation for Pediatric or Nonmalignant DisordersPresenter: Rajni Agarwal, M.D., Associate Professor of Pediatrics and Stem Cell Transplantation, the Stanford University School of MedicineTime: 3:00 p.m. ETLocation: W311EFGH, Level 3, Orange County Convention Center

About Stem Cell Transplantation

Blood-forming, or hematopoietic, stem cells are cells that reside in the bone marrow and are responsible for the generation and maintenance of all blood and immune cells. These stem cells can harbor inherited or acquired abnormalities that lead to a variety of disease states, including immune deficiencies, blood disorders or hematologic cancers. Successful transplantation of hematopoietic stem cells is the only cure for most of these life-threatening conditions. Replacement of the defective or malignant hematopoietic stem cells in the patients bone marrow is currently achieved by subjecting patients to toxic treatment with radiation and/or chemotherapy that cause DNA damage and lead to short- and long-term toxicities, including immune suppression and prolonged hospitalization. As a result, many patients who could benefit from a stem cell transplant are not eligible. New approaches that are effective but have minimal to no toxicity are urgently needed so more patients who could benefit from a curative stem cell transplant could receive the procedure.

Safer and more effective hematopoietic cell transplantation regimens could overcome these limitations and enable the broader application of hematopoietic cell transplants in the cure of many disorders. These disorders include hematologic cancers (e.g., myelodysplastic syndrome [MDS] and acute myeloid leukemia [AML]), autoimmune diseases (e.g., lupus, rheumatoid arthritis, multiple sclerosis and Type 1 diabetes), and genetic diseases that could be cured with genetically-corrected autologous stem cells (e.g., severe combined immunodeficiency syndrome [SCID], sickle cell disease, beta thalassemia, Fanconi anemia and other monogenic diseases).

About JSP191

JSP191 (formerly AMG191) is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow. JSP191 binds to human CD117, a receptor for stem cell factor (SCF) that is expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required for stem cells to survive. JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals, causing the stem cells to undergo cell death and creating an empty space in the bone marrow for donor or gene-corrected transplanted cells to engraft.

Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in an animal model of MDS. This creates the space needed for transplanted normal donor or gene-corrected hematopoietic stem cells to successfully engraft in the host bone marrow. To date, JSP191 has been evaluated in more than 80 healthy volunteers and patients. It is currently being evaluated as a sole conditioning agent in a Phase 1 dose-escalation trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplant for SCID, which is curable only by this type of treatment. For more information about the design of the clinical trial, visit http://www.clinicaltrials.gov (NCT02963064). Clinical development of JSP191 will be expanded to also study patients with AML or MDS who are receiving hematopoietic cell transplant.

About Jasper Therapeutics

Jasper Therapeutics is a biotechnology company focused on enabling safer conditioning and therapeutic agents that expand the application of curative hematopoietic stem cell transplants and gene therapies. Jasper Therapeutics lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a stem cell transplant. For more information, please visit us at http://www.jaspertherapeutics.com.

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Jasper Therapeutics Announces Upcoming Data Presentation on Lead Program, JSP191, at 61st American Society of Hematology (ASH) Annual Meeting &...

Bone Marrow Stem Cells Comments Off on Jasper Therapeutics Announces Upcoming Data Presentation on Lead Program, JSP191, at 61st American Society of Hematology (ASH) Annual Meeting &… | December 9th, 2019

PALO ALTO, Calif.--(BUSINESS WIRE)--Jasper Therapeutics, Inc., a new biotechnology company focused on enabling safer conditioning and therapeutic agents that expand the application of curative hematopoietic stem cell transplants and gene therapies, today announced the launch of the company with a $35 million total Series A financing. Abingworth LLP and Qiming Venture Partners USA served as lead investors, with further investment from Surveyor Capital (a Citadel company) and participation from Alexandria Venture Investments, LLC. The proceeds will be used to advance the clinical development of the companys lead product candidate, JSP191, which is designed to replace or reduce the toxicity of chemotherapy and radiation therapy as a conditioning regimen to prepare patients for hematopoietic cell transplant.

Jaspers development of JSP191 is also supported by a collaboration with the California Institute for Regenerative Medicine (CIRM), which has been funding the program and is committed to providing a total of $23 million in grant support. As part of the Series A financing, Amgen, which discovered JSP191 (formerly AMG191), has licensed worldwide rights to Jasper that also include translational science and materials from Stanford University.

Jasper was co-founded by Judith Shizuru, M.D., Ph.D., a hematopoietic stem cell transplant expert at Stanford University, and Susan Prohaska, Ph.D., a Stanford University-trained immunologist, stem cell biologist and early-stage drug development professional. Dr Shizurus CIRM-funded lab advanced the understanding of the ability of anti-CD117 to impact hematopoietic stem cells and, together with the Lucile Packard Childrens Hospital Stanford and University of California, San Francisco (UCSF) pediatric transplant teams, was the first to study an anti-CD117 antibody in the clinic as a conditioning agent. That humanized antibody, now called JSP191, was first studied for conditioning for transplant in immune-deficient patients in collaboration with Amgen, UCSF and CIRM.

Stem cell transplantation is a potential curative therapy for people with hematologic cancers, autoimmune diseases, and debilitating genetic diseases. However, the pre-transplant conditioning required to prepare patients for transplant involves highly toxic chemotherapy, which can be life-threatening and limits the number of people who are able to benefit, said Dr. Shizuru, co-founder and member of the Board of Directors of Jasper Therapeutics. JSP191 is the only anti-CD117 antibody to demonstrate safety and efficacy in severely ill patients receiving stem cell transplant in the clinic. We plan to expand clinical development to patients receiving transplants for acute myeloid leukemia/ myelodysplastic syndrome or autoimmune diseases and to patients receiving stem cell-directed gene therapies.

Dr. Shizuru added, With an experienced executive team of biotech veterans and a strong syndicate of healthcare-focused investors, Jasper Therapeutics is well positioned to achieve our vision of building a leading biotech company starting with JSP191 and expanding to other novel therapies for immune modulation, graft engineering and cell and gene therapies.

JSP191 is currently being evaluated in an ongoing Phase 1 clinical trial as a conditioning agent to enable stem cell transplantation in patients with severe combined immunodeficiency (SCID) who received a prior stem cell transplant that failed. This severe genetic immune disorder leaves patients without a functioning immune system. Interim results of the study will be presented in an oral presentation (abstract #800) on Monday, December 9, at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Fla. Clinical studies to evaluate the safety and efficacy of JSP191 as a conditioning agent in patients undergoing hematopoietic cell therapy for hematologic cancers are planned for 2020.

Founding Management Team

Dr. Shizuru and Mr. Lis are joined on the Jasper Therapeutics Board of Directors by Kurt von Emster, Managing Partner of Abingworth LLP, and Anna French, Ph.D., Principal at Qiming Venture Partners USA. Dr. Prohaska is a Board observer.

With our investment in this program, were able to realize our mission of fast-tracking stem cell treatments by helping academic researchers rapidly advance the most promising discoveries in the lab into the clinics and to drug development with commercialization partners, said Maria T. Millan, M.D., President and CEO of CIRM. Jaspers two co-founders took a novel antibody with unique properties and moved it from the bench to the bedside relatively quickly, and were thrilled to partner with this talented team to potentially impact a broad group of people who could benefit from stem cell therapy.

About Stem Cell Transplantation

Blood-forming, or hematopoietic, stem cells are cells that reside in the bone marrow and are responsible for the generation and maintenance of all blood and immune cells. These stem cells can harbor inherited or acquired abnormalities that lead to a variety of disease states, including immune deficiencies, blood disorders or hematologic cancers. Successful transplantation of hematopoietic stem cells is the only cure for most of these life-threatening conditions. Replacement of the defective or malignant hematopoietic stem cells in the patients bone marrow is currently achieved by subjecting patients to toxic doses of radiation and/or chemotherapy that cause DNA damage and lead to short- and long-term toxicities, including immune suppression and prolonged hospitalization. As a result, many patients who could benefit from a stem cell transplant are not eligible. New approaches that are effective but have minimal to no toxicity are urgently needed so more patients who could benefit from a curative stem cell transplant could receive the procedure.

Safer and more effective hematopoietic cell transplantation regimens could overcome these limitations and enable the broader application of hematopoietic cell transplants in the cure of many disorders. These disorders include hematologic cancers (e.g., myelodysplastic syndrome [MDS] and acute myeloid leukemia [AML]), autoimmune diseases (e.g., lupus, rheumatoid arthritis, multiple sclerosis and Type 1 diabetes), and genetic diseases that could be cured with genetically-corrected autologous stem cells (e.g., severe combined immunodeficiency syndrome [SCID], sickle cell disease, beta thalassemia, Fanconi anemia and other monogenic diseases).

About JSP191

JSP191 (formerly AMG191) is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow. JSP191 binds to human CD117, a receptor for stem cell factor (SCF) that is expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required for stem cells to survive. JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals, causing the stem cells to undergo cell death and creating an empty space in the bone marrow for donor or gene-corrected transplanted cells to engraft.

Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in an animal model of MDS. This creates the space needed for transplanted normal donor or gene-corrected hematopoietic stem cells to successfully engraft in the host bone marrow. To date, JSP191 has been evaluated in more than 80 healthy volunteers and patients. It is currently being evaluated as a sole conditioning agent in a Phase 1 dose-escalation trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplant for SCID, which is curable only by this type of treatment. For more information about the design of the clinical trial, visit http://www.clinicaltrials.gov (NCT02963064). Clinical development of JSP191 will be expanded to also study patients with AML or MDS who are receiving hematopoietic cell transplant.

About Jasper Therapeutics

Jasper Therapeutics is a biotechnology company focused on enabling safer conditioning and therapeutic agents that expand the application of curative hematopoietic stem cell transplants and gene therapies. Jasper Therapeutics lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a stem cell transplant. For more information, please visit us at http://www.jaspertherapeutics.com.

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Jasper Therapeutics Launches with $35 Million Series A Financing to Develop and Commercialize Innovative Conditioning Agents and Therapies to...

Bone Marrow Stem Cells Comments Off on Jasper Therapeutics Launches with $35 Million Series A Financing to Develop and Commercialize Innovative Conditioning Agents and Therapies to… | December 9th, 2019

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of immune reset to more patients, today announced that new results from its CD117-ADC patient preparation program were presented at the 61st Annual Meeting of the American Society of Hematology (ASH). These results, which were highlighted in an oral presentation at ASH by John Tisdale, M.D., Director, Molecular and Clinical Hematology Section, National Institutes of Health, showed the first-ever successful transplant of gene-modified cells in non-human primates using a targeted, single-agent antibody-drug conjugate (ADC), without the use of chemotherapy or radiation.

Todays conditioning regimens involve high doses of chemotherapy, often paired with radiation, to remove the disease-causing cells. As a result, patients undergoing gene therapy or stem cell transplant are all faced with a difficult choice: whether to endure severe toxicity and risk infertility and cancer for the chance for a cure. Magentas portfolio of targeted ADCs represents an extremely promising new option to prepare patients for gene therapy or transplant with no need for toxic chemotherapy or radiation, said Dr. Tisdale. The results presented today show that a single dose of single agent CD117-ADC achieves the same level of depletion as four doses of busulfan chemotherapy to enable successful engraftment and persistence of stem cells modified with the -globin gene, the gene that causes sickle cell disease and -thalassemia when mutated. Importantly, the animals undergoing preparation with CD117-ADC showed none of the damaging toxicities associated with busulfan conditioning.

Magenta is the only company with the people, platforms and a product engine committed to comprehensively transforming immune and blood system reset, which includes revolutionizing the toxic methods that are used to prepare patients for gene therapy and transplant today. said Jason Gardner, D.Phil., Chief Executive Officer and President, Magenta Therapeutics. The gene therapy field has learned that higher levels of stem cell depletion, which meant higher doses of busulfan, were needed to ensure long-term engraftment of the gene-modified cells and persistence of gene therapy. Across all the modalities we have tested, we have seen that ADCs are most effective at achieving these high levels of stem cell depletion without chemotherapy to enable engraftment and long-term durability of the transplant. Todays impressive results provide important validation of the ADC approach as well as the CD117 target for patient preparation and underscore Magentas leadership in the field of conditioning.

Results from the CD117-ADC Patient Preparation Program

Title: A Single Dose of CD117 Antibody Drug Conjugate Enables Autologous Gene-Modified Hematopoietic Stem Cell Transplant (Gene Therapy) in Nonhuman Primates (Abstract #610)Presenter: John Tisdale, M.D., Director, Molecular and Clinical Hematology Section, National Institutes of Health, Bethesda, Md.

Magentas most advanced patient preparation program, CD117-ADC, targets CD117, a protein expressed on hematopoietic stem cells. CD117-ADC is designed to remove the genetically mutated cells in the bone marrow that cause certain genetic diseases, such as sickle cell disease, enabling curative stem cell transplant or gene therapy.

Results presented by Dr. Tisdale showed:

About Magenta Therapeutics

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

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

Follow Magenta on Twitter: @magentatx.

Forward-Looking Statement

This press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavor, potential, continue or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation risks set forth under the caption Risk Factors in Magentas Registration Statement on Form S-1, as updated by Magentas most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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Magenta Therapeutics Demonstrates First-ever Successful Gene Therapy Transplant Without Chemotherapy in Primates Using a Single Dose of Antibody-drug...

Bone Marrow Stem Cells Comments Off on Magenta Therapeutics Demonstrates First-ever Successful Gene Therapy Transplant Without Chemotherapy in Primates Using a Single Dose of Antibody-drug… | December 9th, 2019

SUZHOU, Chinaand SHANGHAI, Dec. 9, 2019 /PRNewswire/ -- Gracell Biotechnologies Co., Ltd ("Gracell"), a clinical-stage immune cell therapy company, today announced the progressive clinical outcomes for leading product candidates FasTCAR-19, Dual CAR-19-22, and Dual CAR-BCMA-19 at the American Society of Hematology (ASH) Annual Meeting in Orlando, Florida, held from December 7-10. Multiple pilot studies intend to evaluate the safety and efficacy of Gracell's first-in-class FasTCAR-19 (GC007F), Dual CAR-19-22 (GC012F) and Dual CAR-BCMA-19 (GC022F) cell therapy.

FasTCAR-19FasTCAR-19 or GC007F uses Gracell's patented FasTCARTM solution, which genetically modifies a patient's T-cells to express CD19-specific chimeric antigen receptor (CAR) for the treatment of B-cell acute lymphoblastic leukemia (B-ALL).

Utilizing the unique bioprocessing, FasTCAR-19 cells can be produced overnight through viral transfection in use of Gracell's proprietary fully-closed manufacturing system (from apheresis to filling). These cells are considered far more potent and durable in comparison to current market alternatives. To date, all 37 patient samples have been successfully manufactured. The process has been proven efficient, stable and duplicable, with a median 36.8% (range 13.1%-70.3%) transfection success and a median copies of 0.95 (range 0.2-4.21).

As of November, this investigational study enrolled 37 adult and adolescent patients aged from 14 to 70 years, who suffered from r/r B-ALL and had failed to respond to multiple prior lines of therapy, from eight clinical centers. All patients received a single infusion of FasTCAR-19 at one of the three-dose level (low: 0.6*10^5/kg; mid: 1.0*10^5/kg, and high: 1.6*10^5/kg), followed by prior conditioning regimen of fludarabine-cyclophosphamide (FC).

The treatment efficacy was assessed in 35 patients over 28 days of follow-up, of which:

During the over six month-durable remission period, FasTCAR-19 demonstrated a good level of persistence in line with previous clinical trials. In terms of safety, all 37 patients tolerated the single infusion of FasTCAR-19 at different dose levels, with no dose-limiting toxicities observed. The most common safety concerns were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) where mild to moderate side effects were observed. Across 30 patients in the low to mid doses group, only 5 (16.7%) manageable Grade 3 CRS and 5 (16.7%) manageable Grade 3 ICANS were reported; while the remaining 23 (76.7%) had Grade 1-2 CRS. The low to mid doses group will likely be selected for extensive study in future clinical trials.

Beyond single-antigen CAR, Dual CAR-T cells can deliver promising clinical outcomesSingle-antigen CAR-T cells have demonstrated considerable efficacy; however, antigen loss and high relapse rate have been observed in a significant number of patients. To combat this, treatments containing two separate CARs and dual transduction (GC022 targeting CD19 and CD22, GC012 targeting BCMA and CD19) were developed. Following positive results from in vitro and in vivo studies, human clinical trials have commenced testing the safety and feasibility of Dual CAR-19-22 and Dual CAR-BCMA-19 to treat B-ALL and MM, respectively.

Dual CAR-19-22

Dual CAR-19-22 or GC022 has achieved a manufacturing success rate of 20/20, without any patient loss due to manufacturing failure. Enrolled patients aged from 4-45 years old who has B-ALL, received a single infusion of Dual CAR-19-22 at one of the three-dose levels (low: 0.5*10^6/kg; mid: 2.0*10^6/kg, and high: 3.0*10^6/kg), under conventional bioprocessing. The study demonstrated a very good safety profile and high efficacy at mid to high doses.

The treatment efficacy was assessed in 20 patients with a 28-day follow-up, of which:

Dual CAR-19-22 proved effective on patients who had previously been treated with CD19 CAR-T cells and/or received allogeneic hematopoietic stem cell transplantation (allo-HSCT) for r/r B-ALL but failed to benefit from prior treatments. Among these five patients, four (80%) patients achieved MRD-CR with a 28-day follow-up. Surpassing the 3-month durable remission period, fifteenpatients still retain ongoing response.

Furthermore, Dual CAR-19-22 demonstrated an excellent safety profile, with 6/20 (30%) patients indicating no CRS, 14/20 (70%) reporting Grade 1 CRS. No ICANS events were reported.

Dual CAR-BCMA-19Dual CAR-BCMA-19 or GC012 has been demonstrated effective in eliminating multiple myeloma (MM) tumor cells both in vitro and in vivo. The first-in-human study showed a good safety profile and effectiveness. Beyond, FasTCARTM has successfully been applied to Dual CAR-BCMA-19, expected to enhance proliferation, potency, and migration in the human body.

"We are delighted to see that patients with relapsed/refractory B-ALL continue to gain substantial clinical benefit from FasTCAR-19. Furthermore, Dual CAR-19-22 with conventional bioprocess can generate promising clinical data. This marks our confidence to utilize FasTCAR technology to both Dual CAR programs for various indications," said Dr. William Cao, CEO of Gracell. "The results from our latest clinical trials reveal the immense potential of FasTCAR technology, and we are eager to see Gracell's highly efficacious, yet affordable therapies benefit more patients in China and worldwide."

About B-ALLAcute lymphoblastic leukemia (ALL), although rare, is one of the most common forms of cancer in children between the ages of two and five and adults over the age of 501. In 2015, ALL affected around 837,000 people globally and resulted in 110,000 deaths worldwide2. It is also the most common cause of cancer and death from cancer among children. ALL is typically treated initially with chemotherapy aimed at bringing about remission. This is then followed by further chemotherapy carried out over several years.

About MMMultiple myeloma (MM) is a cancer that forms in a type of white blood cell known as a plasma cell. MM cells are abnormal plasma cells (a type of white blood cell) that build up in the bone marrow and form tumors in many bones of the body. Healthy plasma cells make antibodies to help the body fight infection and disease. As the number of MM cells increases, more antibodies are produced. This can cause the blood to thicken and keep the bone marrow from making enough healthy blood cells. MM cells can also damage and weaken the bone. In 2018, MM affected around 160,000 people globally and resulted in 106,000 deaths worldwide3. Different types of treatments are available for patients with plasma cell neoplasms. Chemotherapy and targeted therapy are typical treatments; while stem cell transplant, biologic therapy, and radiation therapy, even surgery are also adopted.

About GracellGracell Biotechnologies Co., Ltd. ("Gracell") is a clinical-stage biopharma company, committed to developing highly reliable and affordable cell gene therapies for cancer. Gracell is dedicated to resolving the remaining challenges in CAR-T, such as high production costs, lengthy manufacturing process, lack of off-the-shelf products, and inefficacy against solid tumors. Led by a group of world-class scientists, Gracell is advancing FasTCARTM, TruUCARTM (off-the-shelf CAR), Dual CAR and Enhanced CAR-T cell therapies for leukemia, lymphoma, myeloma, and solid tumors.

CONTACT:

1https://www.cancer.org/cancer/acute-lymphocytic-leukemia/about/key-statistics.html2https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055577/3https://gco.iarc.fr/today/fact-sheets-cancers

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Gracell Announces Progressive Outcomes from Multiple Human Clinical Trials to Investigate FasTCAR and Dual CAR Cell Platform Technologies - PRNewswire

Bone Marrow Stem Cells Comments Off on Gracell Announces Progressive Outcomes from Multiple Human Clinical Trials to Investigate FasTCAR and Dual CAR Cell Platform Technologies – PRNewswire | December 9th, 2019

MB-107 preceded by low-dose busulfan conditioning continues to be well tolerated and results in development of functional immune system in newly diagnosed infants with XSCID

Enhanced transduction procedure is demonstrating improvements in older patients with XSCID who received prior hematopoietic stem cell transplantation

Data presented by St. Jude Childrens Research Hospital and National Institutes of Health at 61st American Society of Hematology Annual Meeting

NEW YORK, Dec. 09, 2019 (GLOBE NEWSWIRE) -- Mustang Bio, Inc. (Mustang) (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, announced today that updated Phase 1/2 clinical data for MB-107 lentiviral gene therapy for X-linked severe combined immunodeficiency (XSCID) were presented on Saturday by St. Jude Childrens Research Hospital (St. Jude) and today by the National Institutes of Health at the 61st American Society of Hematology (ASH) Annual Meeting.

MB-107 is currently being assessed in two Phase 1/2 clinical trials for XSCID: the first in newly diagnosed infants under the age of two at St. Jude, and the second in patients over the age of two who have received prior hematopoietic stem cell transplantation at the National Institutes of Health. Under a licensing partnership with St. Jude, Mustang intends to develop the lentiviral gene therapy for commercial use as MB-107. The U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to MB-107 for the treatment of XSCID in August 2019.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, The updated clinical data presented at the 2019 ASH Annual Meeting underscore the curative potential of MB-107 for newly diagnosed infants with XSCID, as well as its meaningful impact on older XSCID patients who received prior hematopoietic stem cell transplantation. St. Jude recently received the 2019 Smithsonian Magazine American Ingenuity Award for development of the lentiviral gene therapy, highlighting its potential to have an impact on this devastating disease. We are excited to be working with St. Jude and NIH to advance MB-107 and look forward to transferring the IND from St. Jude to Mustang in the first quarter of 2020.

Lentiviral Gene Therapy with Low Dose Busulfan for Infants with X-SCID Results in the Development of a Functional Normal Immune System: Interim Results of an Ongoing Phase I/II Clinical Study (Abstract Number: 2058)Poster presentation: Ewelina Mamcarz, M.D., Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Childrens Research Hospital, Memphis, TN, USA

Interim data from the multicenter Phase 1/2 clinical trial for infants under the age of two treated with the lentiviral gene therapy preceded by low exposure-targeted busulfan conditioning were published in the New England Journal of Medicine. Updated data presented at the 2019 ASH Annual Meeting include three more patients (n=11), 8 months additional median follow up (23.6 months; range: 1.5 to 33.9 months), more extensive analysis of T and B cell functional recovery, and detailed vector integration site studies.

Data Highlights:

The results from treatment with low-dose busulfan conditioning and the novel lentiviral gene therapy in newly diagnosed infants with XSCID continue to be very promising, said Dr. Mamcarz. We are pleased that the therapy has been well tolerated and all patients with a follow up of more than 3 months recovered from pre-existing infections, are off protective isolation and prophylactic antimicrobials, and have normal growth in respect to height and weight. This reinforces our belief that the lentiviral gene therapy has the potential to be an attractive alternative to current XSCID therapies.

Enhanced Transduction Lentivector Gene Therapy for Treatment of Older Patients with X-Linked Severe Combined Immunodeficiency (Abstract Number: 608)Oral presentation: Harry Malech, M.D., Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, USA

Early outcome data for five older children and young adults with XSCID who received the lentivector (also known as lentiviral) gene therapy as salvage therapy after having previously received haplo-identical hematopoietic stem cell transplantation (HSCT) as infants without chemotherapy-based conditioning were previously reported and published in Science Translational Medicine. By 2016, three additional patients were treated, and the cohort of eight patients (referred to as Cohort A) has now been followed for 3 to 7 years. Among Cohort A, gradual clinical benefit in the clearance of chronic norovirus and associated improved abdominal complaints, malabsorption, growth and IgG production were observed, and four patients were able to cease immunoglobulin replacement therapy.

While the results were positive, the relatively inefficient transduction of hematopoietic stem/progenitor cells (HSPCs) required large quantities of vector. This resulted in relatively low VCN in myeloid cells in some patients, with delayed immune cell recovery and persistent clinical disease, especially in the last patient treated (patient 8). To address this, NIH developed a refined enhanced transduction (ET) procedure consisting of a single overnight transduction after 48 hours pre-stimulation in cytokines (Stem cell factor, Thrombopoietin, Flt3-ligand; 100ng/mL) and incorporated transduction enhancers LentiBoost 1:100 and dimethyl prostaglandin 2 (dmPGE2; 1uM).

The presentation at the 2019 ASH Annual Meeting included data from six patients (referred to as Cohort B) treated by NIH, including re-treatment of patient 8. The patients, who were aged 12 to 36, had significant problems with donor T cell infiltration of liver, bone marrow and kidneys, and were nearly absent of B and NK cells. The enhanced transduction procedure achieved much greater transduction efficiencies than were observed in Cohort A, with greater than 10-fold less vector, and resulted in faster immune reconstitution and more significant clinical benefit by 3 months.

We are encouraged by the significantly improved measures of early clinical outcomes from lentivector gene therapy in older children and young adults with XSCID using an enhanced transduction procedure with the addition of LentiBoost and dmPGE2, said Dr. Malech. Notably, we have seen an early appearance of B and NK cells at much higher levels in Cohort B than we previously observed in Cohort A, even at years after treatment. We look forward to continuing to closely monitor patients and report outcomes.

About Mustang BioMustang Bio, Inc. (Mustang) is a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases. Mustang aims to acquire rights to these technologies by licensing or otherwise acquiring an ownership interest, to fund research and development, and to outlicense or bring the technologies to market. Mustang has partnered with top medical institutions to advance the development of CAR T and CRISPR/Cas9-enhanced CAR T therapies across multiple cancers, as well as a lentiviral gene therapy for XSCID. Mustang is registered under the Securities Exchange Act of 1934, as amended, and files periodic reports with the U.S. Securities and Exchange Commission. Mustang was founded by Fortress Biotech, Inc. (NASDAQ: FBIO). For more information, visit http://www.mustangbio.com.

ForwardLooking Statements This press release may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. Such statements include, but are not limited to, any statements relating to our growth strategy and product development programs and any other statements that are not historical facts. Forward-looking statements are based on managements current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; risks relating to the timing of starting and completing clinical trials; uncertainties relating to preclinical and clinical testing; our dependence on third-party suppliers; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law.

Company Contacts:Jaclyn Jaffe and William BegienMustang Bio, Inc.(781) 652-4500ir@mustangbio.com

Investor Relations Contact:Daniel FerryLifeSci Advisors, LLC(617) 430-7576daniel@lifesciadvisors.com

Media Relations Contact:Tony Plohoros6 Degrees(908) 591-2839tplohoros@6degreespr.com

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Mustang Bio Announces Updated Clinical Data on MB-107 Lentiviral Gene Therapy for Patients with X-Linked Severe Combined Immunodeficiency -...

Bone Marrow Stem Cells Comments Off on Mustang Bio Announces Updated Clinical Data on MB-107 Lentiviral Gene Therapy for Patients with X-Linked Severe Combined Immunodeficiency -… | December 9th, 2019

Investor call to be held December 9 at 8:30 am ET / 1:30 pm GMT to review data

LONDON, Dec. 07, 2019 (GLOBE NEWSWIRE) -- Autolus Therapeutics plc (Nasdaq: AUTL) announced today new data highlighting progress on its next-generation programmed T cell therapies to treat patients with acute lymphoblastic leukemia (ALL) and adults with relapsed/refractory diffuse large B cell lymphoma (DLBCL). The data were presented in oral presentations at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, FL. Additional data on pediatric patients with ALL will be presented on December 8.

The data on AUTO1 presented at this years ASH meeting demonstrate the favorable safety profile and high level of clinical activity of AUTO1 in both adults and pediatric patients with ALL, and we look forward to initiation of the pivotal program in adult ALL in the first half of 2020, said Dr. Christian Itin, chairman and chief executive officer of Autolus.

Acute Lymphoblastic Leukemia Data Presented

Title: AUTO1 A novel fast off CD19CAR delivers durable remissions and prolonged CAR T cell persistence with low CRS or neurotoxicity in adult ALL (Abstract # 226)

Updated results for ALLCAR19, the Phase 1 trial evaluating AUTO1 in adults with recurrent/refractory ALL, were presented by Dr. Claire Roddie MB, PhD, FRCPath, honorary senior lecturer, Cancer Institute, University College London (UCL), in an oral presentation. The trial is designed to assess the primary endpoints of safety ( Grade 3 toxicity) and feasibility of product generation, as well as other secondary endpoints, including efficacy. The trial enrolled patients with a high tumor burden (44% had 50% BM blasts), who were considered high-risk for experiencing cytokine release syndrome (CRS). Product was manufactured for 19 patients; product for 13 of those patients was manufactured using a semi-automated closed process, which will be used for commercial supply.

As of the data cut-off date of November 25, 16 patients had received at least one dose of AUTO1. AUTO1 was well tolerated, with no patients experiencing Grade 3 CRS, and 3 of 16 patients (19%), who had high leukemia burden, experiencing Grade 3 neurotoxicity that resolved swiftly with steroids.

Of 15 patients evaluable for efficacy, 13 (87%) achieved MRD negative CR at 1 month and all patients had ongoing CAR T cell persistence at last follow up. CD19-negative relapse occurred in 22% (2 of 15) patients. In the patients dosed with AUTO1 manufactured in the closed process, 9 of 9 (100%) achieved MRD negative CR at 1 month and 6 months event free survival, and overall survival in this cohort was 100%.

Adult ALL patients, who face a median survival of less than one year after their ALL recurs or relapses, have a significant need for a CAR T cell therapy that is highly active, safe and is a standalone therapy not requiring a stem cell transplant, said Dr. Hagop M. Kantarjian, Chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center.

The novel CD 19 CAR-T therapy, AUTO1, is potentially transformative as a standalone curative option for patients with r/r ALL, especially in adults, given its favorable safety profile, said Dr. Max Topp associate professor of Internal Medicine, Hematology and Oncology at the University of Wuerzburg.

Title: Therapy of pediatric B-ALL with a lower affinity CD19 CAR leads to enhanced expansion and prolonged CAR T cell persistence in patients with low bone marrow tumor burden, and is associated with a favorable toxicity profile (Abstract # 225)

Dr. Sara Ghorashian, honorary senior lecturer, Great Ormond Street Institute of Child Health, University College London, presented updated data from the phase 1 CARPALL study of AUTO1 in pediatric ALL patients with low bone marrow tumor burden. The trial is intended to assess the primary endpoints of safety and proportion of patients in molecular complete remission at 1 month. The study recruited a total of 25 patients and stratified them into 2 cohorts. Fourteen patients were treated in cohort 1, which utilized a manual manufacturing process; product was unable to be generated in 3 patients. Median follow-up was 27 months in cohort 1. Seven patients were treated in cohort 2, which utilized the semi-automated closed manufacturing process, which will be used for commercial supply. The aim of cohort 2 was to demonstrate feasibility of manufacture at scale. Product was generated for 100% of patients. Median follow-up was 7 months in cohort 2.

AUTO1 was well-tolerated overall, with no patients experiencing Grade 3 CRS and 1 of 21 (5%) experiencing Grade 4 neurotoxicity, which was considered unrelated to CAR T therapy.

Nineteen of 21 treated patients (90%) achieved molecular complete remission at 1 month post infusion. Consistent with pre-clinical data, CAR T cell expansion was excellent and detectable by flow in a number of patients up to 36 months. Persistence was noted in 15 of 21 patients at last follow-up, up to 36 months. In cohort 2, 100% of patients achieved molecular complete remission at 1 month post infusion.

In the 14 patients in cohort 1, the overall survival at 6 months was 86% and at 12 months was 71%; event free survival (EFS) at 6 months was 71% and at 12 months was 54%. The patients in cohort 2 are not yet evaluable for these parameters. Overall, nine patients relapsed; 5 of 8 evaluable relapses were due to loss of CD19 antigen on the tumor cells.

Title: Clonal dynamics of early responder and long-term surviving CAR-T cells in humans (Abstract # 52)

Dr. Luca Biasco, senior research associate at University College London, presented a detailed analysis of CAR T products, and insertion site analysis from the CARPALL phase 1 patients. This analysis revealed highly polyclonal engraftment, even at very late time-points. Dr. Biasco hypothesized that the propensity for high level polyclonal long-term engraftment was due to favorable phenotype of the CAR T product and the binding kinetic of the receptor.

Diffuse Large B-cell Lymphoma Data Presented

Title: Phase 1/2 study of AUTO3, the first bicistronic chimeric antigen receptor (CAR) targeting CD19 and CD22 followed by an anti-PD1 in patients with relapsed/refractory (r/r) Diffuse Large B Cell Lymphoma (DLBCL): Results of cohort 1 and 2 of the ALEXANDER study (Abstract # 246)

Dr. Kirit Ardeshna, consultant hematologist, Department of Hematology, University College London Hospital NHS Foundation Trust, presented updated data from the ALEXANDER Phase 1/2 study of AUTO3, the first bicistronic CAR T targeting CD19 and CD22 followed by an anti-PD1, in diffuse large B cell lymphoma (DLBCL). 16 patients were treated, and fourteen patients were evaluable at one month. AUTO3 was well-tolerated, with no patients experiencing Grade 3 CRS with primary treatment, and 1 of 14 experiencing Grade 3 neurotoxicity that resolved swiftly with steroids. Five of 14 had a complete response, with 4 of 5 complete responses ongoing, the longest at 18 months.

DLBCL is an aggressive and rapidly progressing cancer, and early response is critical to ensuring positive outcomes for these patients. These early data show the promise of AUTO3 in DLBCL, and we expect to advance AUTO3 to a decision point in relapsed/refractory DLBCL by the middle of next year, said Dr. Christian Itin, chairman and chief executive officer of Autolus. In addition, we look forward to presenting the data from the AMELIA trial of AUTO3 in pediatric ALL during poster sessions on Sunday, December 8, 6:00 8:00 PM ET.

Investor call to review data on Monday, December 9

Autolus management will host an investor conference call on Monday, December 9, at 8:30 a.m. EDT/ 1:30pm GMT, to review the data presented at ASH.

To listen to the webcast and view the accompanying slide presentation, please go to: https://www.autolus.com/investor-relations/news-and-events/events.

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID 9796038. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID 9796038.

About AUTO1

AUTO1 is a CD19 CAR T cell investigational therapy designed to overcome the limitations in safety - while maintaining similar levels of efficacy - compared to current CD19 CAR T cell therapies. Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, AUTO1 may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the T cells' abilities to engage in serial killing of target cancer cells. In 2018, Autolus signed a license agreement under which Autolus acquired global rights from UCL Business plc (UCLB), the technology-transfer company of UCL, to develop and commercialize AUTO1 for the treatment of B cell malignancies. AUTO1 is currently being evaluated in two Phase 1 studies, one in pediatric ALL and one in adult ALL.

About AUTO3

AUTO3 is a programmed T cell therapy containing two independent chimeric antigen receptors targeting CD19 and CD22 that have each been independently optimized for single target activity. By simultaneously targeting two B cell antigens, AUTO3 is designed to minimize relapse due to single antigen loss in patients with B cell malignancies. AUTO3 is currently being tested in pediatric ALL in the AMELIA clinical trial and in diffuse large B cell lymphoma in the ALEXANDER clinical trial.

About Autolus Therapeutics plc

Autolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T cell programming technologies, the company is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of hematological malignancies and solid tumors. For more information please visit http://www.autolus.com.

Forward-Looking Statement

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to, statements regarding Autolus financial condition and results of operations, as well as statements regarding the anticipated development of Autolus product candidates, including its intentions regarding the timing for providing further updates on the development of its product candidates, and the sufficiency of its cash resources. Any forward-looking statements are based on management's current views and assumptions and involve risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied in such statements. 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 titled "Risk Factors" in Autolus' Annual Report on Form 20-F filed on November 23, 2018 as well as discussions of potential risks, uncertainties, and other important factors in Autolus' future filings with the Securities and Exchange Commission from time to time. All information in this press release is as of the date of the release, and the company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required by law.

Investor and media contact: Silvia TaylorVice President, Corporate Affairs and CommunicationsAutolus+1-240-801-3850s.taylor@autolus.com

UK:Julia Wilson+44 (0) 7818 430877j.wilson@autolus.com

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Autolus Therapeutics Announces New Data Showcasing Clinical Progress of Programmed T Cell Therapy Pipeline in Blood Cancers - BioSpace

Bone Marrow Stem Cells Comments Off on Autolus Therapeutics Announces New Data Showcasing Clinical Progress of Programmed T Cell Therapy Pipeline in Blood Cancers – BioSpace | December 9th, 2019

Using immunotherapy with genetically modified T cells that express chimeric antigen receptors or CARs designed to target tumor-associated molecules, have impressive efficacy in the treatment hematological malignancies.

A CAR is a synthetic construct that, when expressed in T cells, mimics T cell receptor activation and redirects specificity and effector function toward a specified antigen.[1]

In the treatment of cancer, this process is accomplished by linking an extracellular ligand-binding domain specific for a tumor cell surface antigen to an intracellular signaling module that activates T cells upon antigen binding.[1]

The presented studies include results from emerging second-generation cellular immunotherapy products that strive to overcome the limitations of existing products such as resistance and reduce toxicity and simplify treatment.

Cellular immunotherapy uses genetic engineering to enhance the ability of the immune system the bodys defense system against infection and disease to kill malignant cells in the blood, the bone marrow, and other sites, in order to keep cancer from coming back.

CAR T-cell TherapyChimeric antigen receptor T-cell therapies, better known as CAR T-cell therapies, are developed by harvesting a patients own T-cells, the immune systems primary cancer-killing cells, engineering them to target proteins specific to the surface of cancer cells, and reintroducing these modified T-cells back into the patients immune system to kill the cancer cells.

First generationFirst-generation CAR T-cell therapies primarily target CD-19, a protein found on the surface of most normal and malignant B cells in B cell cancers such as lymphoma. These therapies have been shown to produce long-term remissions in about one-third of patients with B-cell lymphomas that have not responded to prior therapies.

We are now seeing efforts to enhance the effectiveness of CAR T-cell therapy by designing products capable of attacking multiple targets, expand the availability of cellular immunotherapy to other blood cancers such as multiple myeloma and replace the complex manufacturing process required for CAR T-cell therapy with a uniform off-the-shelf product, noted Gary Schiller, MD, UCLA Health, an academic medical center which includes a number of hospitals and an extensive primary care network in the Los Angeles, California, region.

One of the phase I studies evaluates an off-the-shelf cellular immunotherapy product that targets two proteins found on the surface of lymphoma cells, including its potential to revive previously administered CAR T-cells that have stopped working.

Another study presents preclinical results for one of the first cellular immunotherapies to be based on off-the-shelf natural killer (NK) cells and the first, according to its manufacturer, to be genetically engineered to contain three active anti-tumor components.

The other two studies, also phase I studies, assess novel CAR T-cell therapies for multiple myeloma that test different dual-target strategies.

One investigational agent is genetically engineered to contain two proteins that attach to BCMA, a protein found almost exclusively on the surface of plasma cells, the immune-system cells that become cancerous in multiple myeloma.

The other is designed to target both BCMA and CD-38, another protein found on the surface of plasma cells. In both studies, many patients achieved minimal residual disease (MRD) negativity, which means that using highly sensitive testing fewer than one myeloma cell per 100,000 cells was identified in the bone marrow. Previous studies have shown that patients who achieve this milestone have a lower risk of relapse after more than three years of follow-up.

Dual-targeted CAR T-cell therapiesThe three phase I studies also hint at the possibility that dual-targeted CAR T-cell therapies might result in fewer patients experiencing moderate to severe cytokine release syndrome (CRS), a known adverse effect caused by an immune response in the body to the activated T cells that are attacking the cancer. CRS causes flu-like symptoms such as fever, body aches, and fatigue, and in severe cases can be life-threatening. Treatment with the drug tocilizumab can reduce CRS symptoms.

Dual-Targeted Antibody Elicits Durable ResponsesPatients with B-cell Non-Hodgkin Lymphoma (NHL) that had returned after or failed to respond to a median of three prior therapies showed complete responses (CR) and durable remissions after being treated with an investigational drug called mosunetuzumab (RG7828; Genentech/Roche). [2]

This investigational agent is a humanized, T-cell bispecific antibody designed to engage T cells and redirect their cytotoxic activity against malignant B cells. The drug works by activating the patients own T-cells, stimulating them to attack and kill cancerous B cells to which they have been introduced by the novel antibody.

Mosunetuzumab simultaneously binds to CD3 epsilon (CD3), a component of the T-cell receptor (TCR) complex, and to CD20, a B-cell surface protein expressed in a majority of B-cell malignancies. This results in crosslinking of the TCR, inducing downstream signaling events that leads to B-cell killing.

Among patients whose lymphoma progressed after treatment with CAR T-cell therapy, 22% had complete remissions when treated with mosunetuzumab. This new drug targets two proteins, one on the surface of tumor cells and the other on the surface of the recipients Tcells.

Unlike CAR T-cell therapy, mosunetuzumab is an off-the-shelf immunotherapy product that can be given to patients without having to genetically modify their T cells, noted lead author Stephen J. Schuster, MD, of Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor. Of particular interest, we are seeing durable complete remissions in patients whose lymphomas progressed after CAR T-cell therapy, he added.

The researchers observed many remissions continue after patients stop receiving the drug.

I have stopped therapy in some patients after six months and they have remained in remission. Some patients have remained in remission without additional therapy for more than a year, Schuster said.

New treatment options are needed not only for patients in whom CAR T-cell therapy has failed, but also for those patients whose lymphomas are getting worse so quickly that they cannot wait for CAR T-cell manufacturing, which takes several weeks, Schuster explained.

The data presented during the annual meeting of the American Society of Hematology included 270 patients (median age 62, 172 men) enrolled in the phase I trial in seven countries (the United States, Australia, Canada, Germany, South Korea, Spain, and the United Kingdom). All participating patients had B-cell lymphomas that had come back or not responded to a median of three prior therapies. Two-thirds of patients (67%) had fast-growing lymphomas; 85 (31%) patients had more slow-growing forms of the disease. In 30 patients (11%), the cancer was resistant to or returned after an initial response to CAR T-cell therapy; in 77 patients (29%), the disease had progressed after a stem cell transplant.

All patients were treated with mosunetuzumab by intravenous infusion. They had an imaging test at either six weeks or three months after starting therapy to assess the initial response to treatment, and responses continued to be followed every three months thereafter.

Forty-six of 124 patients with fast-growing lymphomas (37%) had measurable decreases in the extent of their cancer (objective response); 24 of 124 patients (19%) saw all detectable tumors disappear (complete response). A higher response rate was observed in patients with higher exposure to mosunetuzumab. Among patients with slow-growing lymphomas, 42 of 67 (63%) had objective responses and 29 of 67 (43%) had complete responses. Both objective response rate and complete response rate were maintained in subgroups of patients at high risk for relapse.

Complete remissions appear to be long lasting, Schuster said.

With a median follow-up of six months since first complete remission, 24 of 29 patients (83%) who achieved complete remissions of their slow-growing lymphomas and 17 of 24 patients (71%) who achieved complete remissions of their fast-growing lymphomas remain free of disease. In some patients whose cancers progressed after receiving CAR T-cell therapy, highly sensitive molecular testing showed that the previously administered CAR T cells increased in number.

This suggests that, in addition to its ability to kill cancerous B cells, mosunetuzumab may also help augment the effect of the prior CAR-T treatment, Schuster noted.

Cytokine-release syndromeIn this study, 29% of patients treated with mosunetuzumab experienced cytokine-release syndrome that was mostly mild.

Cytokine release syndrome or CRS is caused by a large, rapid release of cytokines into the blood from immune cells affected by the immunotherapy. While most patients have a mild reaction, sometimes patients may have a severe, life threatening, reaction.

In 3% of patients, CRS was treated with tocilizumab (Actemra; Genentech/Roche). Four percent of patients experienced moderately severe neurologic side effects. Patients who received higher doses of mosunetuzumab were no more likely to have CRS or neurologic side effects than patients treated at lower doses.

A study of a higher dose of mosunetuzumab is now enrolling patients and long-term follow-up of these patients will ultimately help to better evaluate the durability of response data.

Larger, randomized trials are needed to further confirm these promising data and determine whether the treatment benefit of mosunetuzumab is enhanced when it is used earlier in the course of lymphoma therapy or in combination with other agents, Schuster concluded.

Novel Off-the-Shelf CARPreclinical studies provide the first evidence that cellular immunotherapy for B cell cancers could ultimately become an off-the-shelf product, capable of being uniformly manufactured in large quantities as prescription drugs are.

We have taken the concept of traditional pharmaceutical drug development and applied it to cellular therapy, explained senior author Bob Valamehr, Ph.D, of Fate Therapeutics, a San Diego biopharmaceutical company.

The product called FT596, is among the first cellular immunotherapies to be based on off-the-shelf NK cells the first line of defense of the immune system and is the first cellular immunotherapy to be genetically engineered to contain three active anti-tumor components, Valamehr explained.

Comparable with standard CAR T-cell therapyFT596 demonstrated comparable ability to kill cancerous white blood cells as standard CAR T-cells and, when combined with the drug rituximab (Rituxan; Genentech/Roche), killed cancerous white blood cells that were no longer responding to standard CAR T-cell therapy due to loss of the CD19 antigen target.

The U.S. Food and Drug Administration (FDA) approved Fate Therapeutics Investigational New Drug Application for FT596 in September 2019 and the company hopes to begin a first-in-human phase I clinical trial for the treatment of B-cell lymphoma and chronic lymphocytic leukemia in the first quarter of 2020.

The primary purpose of this trial will be to assess the safety and activity of FT596 in patients.

ManufacturingThe development and manufacturing of FT596 begins with human induced pluripotent stem cells (iPSCs) that are uniquely capable of unlimited self-renewal and can differentiate into more than 200 types of human cells. These iPSCs are genetically engineered, after which a single genetically engineered cell or clone is selected and multiplied in the laboratory to create a master engineered cell line that can be repeatedly used to generate cancer-fighting immune-system cells such as NK and T cells.

Natural Kiler Cells or NK cells are a type of lymphocyte and a component of innate immune system, the bodys first line of defense against infection and disease. Unlike T-cells, which have to be trained to recognize their target and can kill only cells that display that target on their surface, NK cells do not need special preparation before going on the attack and can kill many different types of transformed or infected cells.

NK cells are multifaceted and can be viewed as a jack-of-all-trades when it comes to protecting the host, whereas T cells can act in only one way, Valamehr explained.

But NK cells are also different in other ways. They are inherently limited in their capacity to multiply and expand when infused into patients, and they have a shorter lifespan.

Valamehr and his colleagues used genetic engineering to address these shortcomings. In addition to engineering FT596 to carry a CAR targeting the CD19 protein, which is produced by nearly all B-cell lymphomas and leukemias, they inserted two other novel proteins: CD16, which boosts and broadens the NK cells ability to kill cancer cells, and IL15, which stimulates FT596 to proliferate and persist.

Valamehr explained that FT596 has been designed to address two more limitations of CAR T-cell therapy .

The investigational agent is an off-the-shelf product. As a result, it significantly improves the current patient-by-patient CAR T-cell treatment paradigm by eliminating the time-consuming and costly process that is currently required to treat a patient with CAR T-cells.

The addition of the CD16 protein gives FT596 broader therapeutic activity and versatility. In combination with rituximab, FT596 has the potential to lead to deeper and more durable responses and overcome resistance that hampers the long-term efficacy of CAR T-cell therapy.

Eliminating the high production cost, weeks of manufacturing time, and complex manufacturing process required for CAR T-cell therapy and replacing it with a mass-produced, off-the-shelf product, promises to expand access to effective cell-based cancer immunotherapy to many more patients who may benefit from it, Valamehr concluded.

Results from CARTITUDE-1 in R/R Multiple MyelomaPatients with multiple myeloma who had received a median of five prior therapies, and for whom standard-of-care treatments were no longer working, had a high response rate when treated with the investigational CAR T-cell therapy JNJ-68284528 (JNJ-4528), which targets BCMA, a protein commonly found on the surface of multiple myeloma cancer cells.

These patients participated in a clinical trials (NCT03548207), supported by Janssen Research & Development, designed to characterize safety of and establish the recommended Phase II dose (RP2D) (Phase Ib) and to evaluate the efficacy of JNJ-68284528 (Phase II).

We are seeing a high response rate, with most patients achieving MRD negativity, noted lead study author Deepu Madduri, MD, of The Tisch Cancer Institute at Mount Sinai in New York.

Considering these patients have all received multiple prior therapies, these results are extremely encouraging, Madduri added.

All evaluable patients receiving this CAR T-cell therapy have achieved MRD-negative disease state and 27 of 29 patients are progression free at a median follow-up of six months, Madduri said.

Multiple myeloma is a cancer of plasma cells, which are found in the bone marrow and are part of the immune system, the bodys defense system against infection. Typical signs and symptoms of multiple myeloma may be bone pain or fractures, high levels of calcium in the blood, kidney damage, and anemia. Multiple myeloma affects an estimated 160,000 people each year, occurs most often in people over 60. The disease is slightly more common in men than in women.

Although new therapies for multiple myeloma have recently become available that can extend patients life expectancy, a cure for the disease remains elusive.

We can get the disease into remission, but most patients unfortunately relapse, and outcomes are very poor for patients who have relapsed multiple times, she said.

Researchers explained that JNJ-4528 is a novel CAR T-cell therapy featuring two molecules that bind to BCMA, a protein found on the surface of multiple myeloma cells.

We are learning that every CAR T-cell therapy is different, Madduri said.

JNJ-4528 has a unique CAR T-cell composition in patients, preferentially enriched in CD8 T cells, which are believed to be one of the most important T cells in killing cancer cells, she noted.

This phase Ib/II trial is continuing to enroll patients.

During the 2019 annual meeting of the American Society of Hematology, Madduri reported results for the first 29 patients enrolled.

Patients T-cells were collected and sent to a laboratory where they were genetically engineered to express JNJ-4528. Prior to re-infusing these CAR T-cells, the patients received three days of chemotherapy to make room in their immune systems for the engineered T-cells.

Following chemotherapy, each patient received a single infusion of the JNJ-4528 CAR T-cells.

After a minimum of 28 days, these patients had blood and bone marrow exams, which was followed by exams at six months, and one year after treatment to assess their response. The primary aims of the trial are to assess the therapys safety and to confirm the dose to be tested in a larger, phase II trial.

The median follow-up time in the current analysis is six months. Overall, 100% of patients had a clinical response to JNJ-4528. Moreover, 66% had a stringent complete response, meaning that sensitive laboratory and microscopic tests found no evidence for myeloma proteins or cells in blood, urine, or bone marrow.

Most patients (93%) experienced some form of CRS. One patient had severe (grade 3) CRS, and one patient died from its complications 99 days after the CAR T-cell infusion. In 76% of patients, CRS was treated with tocilizumab.

To see some patients in this heavily pretreated population surviving for a year or more with a one-time treatment and a manageable safety profile is remarkable, Madduri explained.

These patients feel that they have their quality of life back. They no longer have to come into the clinic for weekly treatments and some are well enough to travel, Madduri concluded.

The phase II portion of this study is ongoing to evaluate the overall response rate of patients treated with JNJ-68284528 (JNJ-4528). Additional clinical studies are evaluating the safety and efficacy of JNJ-4528 in different multiple myeloma treatment settings.

BreakthroughEarlier this week the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for JNJ-68284528 (JNJ-4528).

The granting of Breakthrough Therapy Designation for JNJ-68284528 (JNJ-4528) is a significant milestone as we continue to accelerate the global development of this innovative CAR-T therapy in collaboration with Legend Biotech, noted Sen Zhuang, MD, Ph.D., Vice President, Oncology Clinical Development, Janssen Research & Development.

We look forward to continuing to work closely with the U.S. Food and Drug Administration to advance the clinical development program for JNJ-68284528 (JNJ-4528) and ultimately bring this BCMA-targeted immunotherapy to patients living with multiple myeloma who are in need of a new therapeutic option, Zhuang concluded.

Encouraging Results for Dual-Targeted CAR T-Cell TherapyMore than three out of four patients with multiple myeloma that returned or did not respond to at least two therapies remained in remission seven months after treatment with a novel CAR T-cell therapy targeting two proteins that are frequently found on myeloma cells.

Nine patients experiencing sustained remissions in this study, which ws supported by the National Natural Science Foundation of China, the Major Technological Innovation Special Project fund of Hubei Province of China, and Cellyan Therapeutics, were diagnosed with a difficult-to-treat form of multiple myeloma in which the disease has spread beyond the bone marrow.

Roughly one in 10 patients with multiple myeloma develop tumors in the organs or soft tissues such as the blood vessels, muscles, and nerves. These so-called extramedullary tumors respond poorly to treatment, and patients who develop them have a poor outlook and poor health related quality of life (hrQoL)

Our results show that this CAR T-cell product can effectively achieve elimination of extramedullary tumors, said study author Yu Hu, MD, Ph.D, of Union Hospital, Huazhong University of Science and Technology in Wuhan, China.

Although these are preliminary data, they are encouraging for patients with multiple myeloma who have not responded to other therapies, Hu added.

Hu and his colleagues are developing the first CAR T-cell therapy to be genetically engineered to target BCMA and CD38, two proteins found on the surface of plasma cells. Multiple myeloma is a cancer of plasma cells, which are found in the bone marrow and are part of the immune system, the bodys defense system against infection and disease.

Our thinking was that targeting both of these proteins would improve treatment efficacy without increasing toxicity, and induce deeper, more durable remissions, Hu noted.

The first-in-humans phase I trial enrolled 22 patients whose average age was 59, of whom 11 were men. All had multiple myeloma that had returned or not responded to at least three therapies. Nine of the 22 patients had extramedullary tumors. The study aims were to determine the safest and most effective dose of the CAR T-cell therapy as well as to initially evaluate its effectiveness.

Just like in other trials with CAR T-cell therapies, the participating patients received three days of chemotherapy to make room in their immune systems for the engineered T-cells. Then each patient was infused with the dual-targeted CAR T cells. Patients were divided into five groups, with each group receiving a higher dose than the previous one. Depending on the cell dose, patients received either one or two infusions.

At a median of 36 weeks of follow-up, 18 patients (90.9%) had MRD-negative disease. Twelve patients (54.5%) had a stringent complete response, meaning that no plasma cells were detected in the bone marrow. Seven patients (31.8%) had a good or very good partial response, meaning that the level of M-protein (an abnormal protein produced by cancerous plasma cells) in the blood or urine was reduced but still detectable. In eight of the nine patients with extramedullary lesions, these tumors were undetectable on their computed tomography scans. For the 17 patients who remained in remission at seven months after treatment, the median duration of response was 28.8 weeks.

The adverse events observed included 20 patients who experienced CRS, of whom six needed treatment. No serious adverse neurologic effects such as seizures, movement impairment, difficulty speaking or understanding speech, or fatal swelling in the brain were reported.

With this dual-targeted CAR T-cell therapy, we have demonstrated a high response rate, especially a higher rate and longer duration of stringent complete response, compared with other therapies, as well as effective elimination of extramedullary lesions, with no serious neurologic adverse effects and manageable levels of other adverse effects, Hu concluded.

The investigators continue to follow the patients for the next two years. They are also planning to conduct a phase II trial in both China and the United States to test the treatments effectiveness in a larger number of patients.

Clinical trialsA Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1) NCT03548207

References[1] Srivastava S, Riddell SR. Chimeric Antigen Receptor T Cell Therapy: Challenges to Bench-to-Bedside Efficacy. J Immunol. 2018;200(2):459468. doi:10.4049/jimmunol.1701155 [Abstract][2] Schuster SJ, Bartlett NL, Assouline S, Yoon SS, Bosch F, Sehn LH, Cheah CY, Shadman M, et al. Mosunetuzumab Induces Complete Remissions in Poor Prognosis Non-Hodgkin Lymphoma Patients, Including Those Who Are Resistant to or Relapsing After Chimeric Antigen Receptor T-Cell (CAR-T) Therapies, and Is Active in Treatment through Multiple Lines. 61st annual meeting of the American Society of Hematology. Program: General Sessions. Session: Plenary Scientific Session. Hematology Disease Topics & Pathways: antibodies, Follicular Lymphoma, CRS, Diseases, Biological, Therapies, neurotoxicity, Adverse Events, CAR-Ts, Non-Hodgkin Lymphoma, DLBCL, immunotherapy, Lymphoid Malignancies. [Abstract][3] Goodridge JP, Mahmood S, Zhu H, Gaidarova S, Blum R, Bjordahl R, Cichocki F, et al. FT596: Translation of First-of-Kind Multi-Antigen Targeted Off-the-Shelf CAR-NK Cell with Engineered Persistence for the Treatment of B Cell Malignancies. 61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral. Session: 625. Lymphoma: Pre-ClinicalChemotherapy and Biologic Agents: Targeting Apoptosis Pathways in Lymphoma.[Abstract][4] Madduri D, Usmani SZ, Jagannath S, Singh I, Zudaire E, Yeh TM, Allred AJ, Banerjee A, et al. Results from CARTITUDE-1: A Phase 1b/2 Study of JNJ-4528, a CAR-T Cell Therapy Directed Against B-Cell Maturation Antigen (BCMA), in Patients with Relapsed and/or Refractory Multiple Myeloma (R/R MM). 61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral Session: 653. Myeloma: Therapy, excluding Transplantation: Novelty in CAR T in Relapsed/Refractory Multiple Myeloma. [Abstract][5] Li C, Mei H, Hu Y, Guo T, Liu L, Jiang H, Tang L, Wu Y, et al. A Bispecific CAR-T Cell Therapy Targeting Bcma and CD38 for Relapsed/Refractory Multiple Myeloma: Updated Results from a Phase 1 Dose-Climbing Trial61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral. Session: 653. Myeloma: Therapy, excluding Transplantation: Novel Therapy for Relapsed Myeloma. Hematology Disease Topics & Pathways: Biological, Diseases, Adult, Therapies, Lymphoma (any), Adverse Events, CAR-Ts, Elderly, Biological Processes, Technology and Procedures, Cell Lineage, Study Population, Clinically relevant, Lymphoid Malignancies.

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ASH 2019: Second-gen CAR T-Cell Therapy Overcome Resistance, Reduce Toxicity and Simplify Treatment - OncoZine

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