Dec. 8, 2020 16:00 UTC

DUARTE, Calif.--(BUSINESS WIRE)-- City of Hope doctors participated in research presented at the American Society of Hematology (ASH) virtual meeting, Dec. 5 to 8, that are helping advance the treatment of blood cancers, including one study which demonstrated allogeneic stem cell transplants do have a survival benefit for older adults with myelodysplastic syndromes (MDS) compared with current standard of care.

The study is the largest and most definitive trial to demonstrate the benefits of an allogeneic stem cell transplantation for older adults with MDS, and is just one of numerous studies that City of Hope doctors help lead with the aim of finding more effective treatments of various blood cancers.

This years ASH conference truly showcases City of Hopes leadership in finding more effective treatments for blood cancers, said Stephen J. Forman, M.D., director of City of Hopes Hematologic Malignancies Research Institute. Whether its finding innovative treatments to make it possible for more older adults with cancer to receive stem cell transplants, or pursuing therapies that are more effective with fewer side effects, City of Hope doctors continue to lead innovative research in blood cancers and other hematological malignancies.

City of Hope doctors are leading novel clinical trials for patients with leukemia, lymphoma and other blood cancers.

Multicenter clinical trial led by City of Hope makes stem cell transplant possible for older adults with myelodysplastic syndromes

Allogeneic hematopoietic cell transplantation, or stem cell/bone marrow transplants, for blood cancers that have recurred or are difficult to treat can put the disease into long-term remission and provide a potential cure. The therapy establishes a new, disease-free blood and immune system by transplanting healthy blood stem cells from a donor into a cancer patient after destroying the patients unhealthy bone marrow.

City of Hope and other institutions started this therapy in 1976, primarily for younger patients with blood cancers. The therapy involves using high-dose chemotherapy and/or radiotherapy to make room for a person to receive new stem cells; serious side effects can also occur after transplant. Because of these and other considerations, for many years, older adults with blood cancers have not been considered for transplants.

City of Hope has been leading the way to make transplants possible for more older adults with various cancers.

A new study presented at ASH demonstrates transplants are now a possibility and beneficial for patients with myelodysplastic syndromes (MDS). Approximately 13,000 people in the United States each year are diagnosed with MDS, an umbrella term describing several blood disorders that begin in the bone marrow.

Co-led by City of Hopes Ryotaro Nakamura, M.D., director of City of Hopes Center for Stem Cell Transplantation, the study is the largest and first trial to demonstrate the benefits of an allogeneic stem cell transplantation for older adults with MDS as opposed to the standard of care currently provided to these patients. The multicenter trial for patients aged 50 to 75 with serious MDS compared how long transplant patients survived with those who didnt receive a transplant, as well as disease progression and quality of life. The transplant therapy used reduced-intensity conditioning, which delivers less chemotherapy and radiation before transplant and relies more on the anti-tumor effects of the therapy.

Between 2014 and 2018, the study enrolled 384 participants at 34 cancer centers nationwide. It included 260 patients who were able to find a donor for a transplant, as well as 124 patients who did not find a donor for a transplant.

After three years, nearly 48% of MDS patients who found a donor for transplant had survived compared with about 27% of those patients who didnt have a donor for transplant and received current hypomethylating therapy, a type of chemotherapy that is current standard of care for MDS. Leukemia-free survival which is relevant because myelodysplastic syndrome can develop into leukemia was also greater in transplant recipients after three years nearly 36% compared with about 21% for those who did not have a transplant.

There was a large and significant improvement in survival for patients who had a transplant, Nakamura said. The benefit margin in overall survival was over 20% (21.3%) for patients who had a transplant.

In addition, quality of life was the same for both transplant and nontransplant patients. There were no clinically significant differences when taking such measurements as physical and mental competency scores.

This is an extremely exciting study because it provides evidence that stem cell transplant is highly beneficial for older patients with serious MDS and will likely be practice-changing for this group, Nakamura said. Before, many doctors wouldnt even consider a transplant for this group of patients, but our study demonstrates that these patients should be evaluated for a transplant, which could potentially provide a cure for their disease.

The trial is part of Blood and Marrow Transplant Clinical Trials Network, which was established with support from the National Heart, Lung, and Blood Institute and National Cancer Institute, because of a critical need for multi-institutional clinical trials focused directly on improving survival for patients undergoing hematopoietic cell transplantation.

Updated results from a study of a potential new CAR T cell therapy, liso-cel, for relapsed/refractory chronic lymphocytic leukemia

Patients with relapsed or difficult-to-treat chronic lymphocytic leukemia/small lymphocytic leukemia continue to do well 24 months after receiving lisocabtagene maraleucel (liso-cel) chimeric antigen receptor (CAR) T cells, according to Tanya Siddiqi, M.D., director of City of Hopes Chronic Lymphocytic Leukemia (CLL) Program, which is part of the Toni Stephenson Lymphoma Center. She presented these findings during the 2020 ASH annual meeting virtual conference.

Overall, 23 and 22 patients were evaluated for safety and efficacy in this phase 1 trial, respectively. Their median age was 66 and they had received a median of four prior therapies; all patients had received prior ibrutinib, which is one of the standard of care drugs for CLL.

The overall response rate, or patients whose CLL diminished after liso-cel CAR T cell therapy, was 82%, and 45% of patients also had complete responses, or remissions.

After 15 months of treatment, 53% of patients maintained their responses to the therapy, and six patients continued to be in remission. After 18 months, 50% of patients maintained their response, and there were five remissions. All seven patients who completed the 24-month study maintained their response. Median progression-free survival, or the amount of time the cancer did not worsen during and after treatment, was 18 months.

As early as 30 days after receiving liso-cel, about 75% of 20 patients evaluated for the therapys efficacy had undetectable minimal residual disease (MRD, or no detectable traces of cancer) in the blood and 65% had undetectable MRD in the marrow.

These are remarkable results for a group of patients that prior to this CAR T treatment had no good treatment options if they had already progressed on novel targeted therapies like ibrutinib and venetoclax, Siddiqi said. Liso-cel is providing new hope for CLL patients, and the remissions are also long lasting with few serious side effects.

Because of its safety and effectiveness in clinical trials, liso-cel, which targets the CD19 protein on cancer cells, may soon receive approval from the Food and Drug Administration as a commercial therapy for relapsed or refractory B cell lymphoma. City of Hope is also taking part in the phase 2 trial of liso-cel in CLL patients.

Consolidation treatment with brentuximab vedotin/nivolumab after auto stem cell transplant for relapsed/refractory Hodgkin lymphoma patients leads to 18-month progression free-survival

Patients who have Hodgkin lymphoma that has not been cured by initial treatment will usually receive more chemotherapy and an autologous hematopoietic cell transplant. But even after a stem cell transplant, recurrence of the lymphoma is possible.

This multicenter phase 2 clinical trial, led by City of Hope, examined whether treating patients with brentuximab vedotin (BV), an antibody-based treatment that targets delivery of chemotherapy only to Hodgkin lymphoma cells, and nivolumab, which works by blocking the PD-1 immune checkpoint pathway that Hodgkin lymphoma hijacks to evade the immune system, was safe and effective as consolidation to prevent disease recurrence after transplant in patients with high-risk Hodgkin lymphoma.

Alex Herrera, M.D., assistant professor in City of Hope's Department of Hematology & Hematopoietic Cell Transplantation, discussed 19-month progression-free survival for trial participants, as well as overall survival, safety and response rates during ASH.

Fifty-nine patients were enrolled in the trial. Patients received the consolidation treatment starting a median of 54 days after transplant, and received a median of eight cycles of the therapy. The 19-month progression-free survival in patients was 92%, and overall survival in patients was 98%. Only three patients relapsed after receiving BV and nivolumab consolidation after transplant, and one patient passed away due to PCP pneumonia unrelated to the study treatment.

The most common sides effects related to the treatment were peripheral neuropathy (51%), neutropenia (42%), fatigue (37%) and diarrhea (29%).

Using brentuximab vedotin and nivolumab after transplant is a promising approach for preventing relapse of Hodgkin lymphoma after transplant that merits further study, Herrera said.

City of Hope doctors published research on innovative approaches against graft-versus-host-disease

Historically, a bone marrow/stem cell transplant is more likely to be effective if patients have a donor who is a 100% match, or as close to that as possible. Finding that perfect match is more difficult for African Americans, Latinos, Asian Americans and other ethnic groups as bone marrow donor registries are still trying to increase the number of non-white donors.

Transplant doctors are also looking for ways to make the transplant more effective if a perfect match cant be found; donors who are not a 100% or close match are referred to as mismatched unrelated. One major barrier to these transplants being effective is a condition known as graft-versus-host-disease (GVHD). The condition, which is more common in transplants involving mismatched donors, is caused by donated cells that recognize the recipient's cells as foreign and attack them, damaging the skin, eyes, lungs, liver and digestive tract.

In order to help prevent GVHD, therapies can be given to patients after transplant. A prospective clinical trial at City of Hope examined whether using cyclophosphamide after an infusion of stem cells could prevent GVHD.

Thirty-eight patients were enrolled in the trial, which is the first to examine the use of cyclophosphamide in transplants with a mismatched unrelated donor.

With a median follow-up period of 18 months, 87% of patients had survived, and the majority did not relapse or develop severe GVHD.

During the first 100 days post-transplant, acute GVHD incidence was around 50%; most cases were mild to moderate while severe GVHD was only 15%. A year after transplant, 52% of patients had some form of chronic GVHD, but only 3% had moderate or severe chronic GVHD.

The trial also examined toxicities, infections and immune system recovery after the transplant.

Our study showed that patients who received a transplant from a mismatched unrelated donor using post-transplant cyclophosphamide had a comparable outcome to what we see in matched donor transplants with few cases of serious GVHD cases, said Monzr Al Malki, M.D., associate clinical professor of City of Hopes Department of Hematology & Hematopoietic Cell Transplantation and director of unrelated donor BMT and haploidentical transplant programs. Our data support further development of this therapy in transplant patients who would otherwise have no suitable donors and limited treatment options.

City of Hopes Anthony Stein, M.D., also led a pilot trial that examined whether a new treatment approach may reduce the rate of GVHD in patients with acute myelogenous leukemia (AML) who have received an allogeneic hematopoietic cell transplant. Although a transplant can put AML into remission, GVHD remains the main serious complication after transplant, impacting a patients quality of life and increasing health care costs.

Eighteen patients between the ages of 18 and 60 enrolled in the trial. Each patient received a novel conditioning regimen of total marrow and lymphoid irradiation, which targets a patients marrow and lymph nodes while reducing radiation to other parts of the body, and cyclophosphamide, a therapy that suppresses the immune system. Tacrolimus was also provided to patients.

Radiation was delivered twice daily on the fourth day before transplant and on the day of transplant without chemotherapy. Cyclophosphamide was given to patients on the third and fourth day after transplant.

There were mild to moderate toxicities. Acute GVHD developed in two patients and only one patient developed the most serious GVHD. Five patients developed mild chronic GVHD. Nearly 60% of patients had not developed GVHD or the condition had not worsened after a year.

After a year, all patients had survived, and 83% had not relapsed. After two years, nearly 86% of patients had survived, and the relapse number remained the same.

The therapeutic approach did not interfere with the transplant process as all patients engrafted, or the donors cells started to produce bone marrow and immune cells.

This is welcome news for AML patients who receive an allogeneic transplant and are concerned about developing GVHD, said Stein, associate director of City of Hope's Gehr Family Center for Leukemia Research. Our study demonstrated that using this new combination of therapies is safe and feasible and does not interfere with the engraftment process.

In addition, after a year, patients in this trial were no longer taking immunosuppressive therapy and had an improved quality of life, Stein said. He added that because many of the patients didnt have GVHD, health care costs after a year were also lower than if patients required treatment for the condition.

City of Hope now plans to start a larger phase 2 trial using this treatment approach.

Bispecific antibodies continue to show promise against blood cancers

Mosunetuzumab is a promising new immunotherapy for the treatment of relapsed/refractory non-Hodgkin lymphoma (NHL) that recently received breakthrough therapy designation from the Food and Drug Administration. The designation is intended to expedite the development and review of drugs for serious or life-threatening diseases.

Elizabeth Budde, M.D., Ph.D., assistant professor in City of Hope's Department of Hematology & Hematopoietic Cell Transplantation, is leading clinical trials that are showing how well mosunetuzumab works against NHL. At this years ASH, one trial discussed is how the therapy is working for patients with follicular lymphoma.

Mosunetuzumab is a bispecific antibody targeting both CD3 (a protein found on the surface on T cells) and CD20 on the surface of B cells. The therapy redirects T cells to engage and eliminate malignant B cells.

Sixty-two patients, ranging in age from 27 to 85 years old, were enrolled in the trial for follicular lymphoma. They received intravenous doses of mosunetuzumab.

Sixty-eight percent of the patients responded to the therapy, and 50% had a complete response, or went into remission. Consistent complete response rates occurred even in patients with double refractory disease and patients who received prior CAR T cell therapy. Median duration of response was approximately 20 months, and media progression free survival was nearly one year.

Side effects were reported in 60 patients with serious adverse effects in 22 patients. The most frequently reported serious side effects were hypophosphatemia, an electrolyte disorder, and neutropenia, a condition caused by low numbers of white blood cells. Fourteen patients experienced cytokine release syndrome, but none required extensive treatment for it.

Neurological side effects included headache, insomnia and dizziness.

Patients in this trial had high response rates and their disease remained in control for a year, Budde said. This is remarkable because many patients were no longer responding to other therapies.

About City of Hope

City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hopes translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope has been ranked among the nations Best Hospitals in cancer by U.S. News & World Report for 14 consecutive years. Its main campus is located near Los Angeles, with additional locations throughout Southern California. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.

View source version on businesswire.com: https://www.businesswire.com/news/home/20201208005458/en/

Read the original here:
City of Hope Doctors Present Innovative Therapies to Better Treat Blood Cancers at American Society of Hematology Virtual Conference - BioSpace

Older, male patients with more severe underlying conditions and a greater risk of death tended to be more accepting of new approaches such as stem cell research

A new review of research bringing together patient, carer and public views of cell and gene therapies has highlighted a need for appropriate education to better inform people including how clinical trials work and the risks and benefits of various treatments.

Over the last decade, new cell, gene and tissue-engineered therapies have been developed to treat various cancers, inherited diseases and some chronic conditions. They offer opportunities for the treatment of disease and injury, to restore function, and in some cases offer cures. In response the NHS Advanced Therapies Treatment Centres (ATTCs) were set up to bring together the health service, academia and industry to address the unique and complex challenges of bringing these therapies to patients.

Led by experts from the Centre for Patient Reported Outcome Research (CPROR) at the University of Birmingham and the Midlands and Wales ATTC (MW-ATTC), the review, funded by a MW-ATTC grant from UK Research and Innovation is the first of its kind and the first to consider both patient and public opinions of cell and gene therapies. Examining 35 studies, the majority of which were published between 2015 and 2020, analysis showed that a lack of understanding of the aims of clinical trials and overestimation of the potential benefits of cell and gene therapy were common among both patients and the general public. Patients were generally of the opinion that more information about participating in clinical trials is vital to enable them to make informed assessment of potential risks and benefits.

Older, male patients with more severe underlying conditions and a greater risk of death tended to be more accepting of new approaches such as stem cell research and generally, while views of therapies varied among patients, the provision of adequate information increased acceptance.

Interestingly the review also found that patients considered their clinicians to be the most trustworthy source of information which would suggest that patients would approach and discuss these treatments with their physicians. However, researchers found that this might not always be the case due to a number of reasons including the perception that clinicians do not always approve of cell and gene therapies and may try to discourage them from pursuing treatment and may not have enough knowledge of the field to provide adequate advice.

Lead author Dr Olalekan Lee Aiyegbusi, Co-Deputy Director of the Centre for Patient Reported Outcomes Research (CPROR) said: The findings from this research are intended to inform the patient engagement work of the ATTCs. We hope that by highlighting various issues, efforts will be made to correct misconceptions, and improve the awareness of patients and the public about the potential benefits and risks associated with cell and gene therapies.

It is important that the public and patients are aware of these therapies, understand the issues involved, and can contribute to the ongoing debates. A high level of awareness will also enhance patients ability to make informed decisions about participating in clinical trials and routine administration of cell and gene therapies.

The full paper Patient and public perspectives on cell and gene therapies: a systematic review was published today (Tuesday 8 December 2020) in Nature Communications.

ENDS

For more information please contact Sophie Belcher, Communications Manager, University of Birmingham, on +44 7815607157. Alternatively, contact the Press Office out of hours on +44 (0)7789 921165.

DOI: 10.1038/s41467-020-20096-1.Full paper: http://www.nature.com/ncomms

The University of Birmingham is ranked amongst the worlds top 100 institutions, and its work brings people from across the world to Birmingham, including researchers and teachers and more than 6,500 international students from nearly 150 countries.

About the Midlands and Wales ATTC (MW-ATTC)

The 9M Midlands and Wales Advanced Therapy Treatment Centre (MW-ATTC) is one of three national Innovate UK funded centres whose goal is to accelerate the delivery of advanced therapies.

It is a regional network spanning the Midlands & Wales comprising a large consortium of industry, healthcare and university partners with expertise in advanced therapy manufacturing including academic and commercial partners, logistics companies, specialists in clinical trial delivery and teams focussed on IT logistics solutions and health economics.

The aim of the MW-ATTC is to enable UK advanced therapy companies to reach the clinical market, whilst simultaneously building clinical capacity regionally to deliver these breakthrough therapies to patients.

Continue reading here:
Better education needed to give patients improved understanding of gene therapies, new review highlights - University of Birmingham

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of stem cell transplant to more patients, today announced final clinical results from its earlier completed Phase 1 clinical trial as well as development updates for its MGTA-145 stem cell mobilization therapy, including commencement of enrollment in a Phase 2 clinical trial in multiple myeloma, and its plans for a Phase 2 clinical trial in allogeneic stem cell transplant for patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndrome (MDS). The company also previously announced a clinical collaboration with bluebird bio to evaluate MGTA-145 for mobilizing and collecting stem cells in adults and adolescents with sickle cell disease (SCD). Additional preclinical results were also presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually from December 5-8, 2020, on the Magenta conditioning platform, including MGTA-117 program, which is a targeted antibody-drug conjugate (ADC) to prepare patients for stem cell transplant.

MGTA-145 Advancement to Phase 2 Development in Blood Cancers

The company announced that enrollment has started and is ongoing in a Phase 2 clinical trial of MGTA-145, used in combination with plerixafor, to mobilize and collect stem cells for autologous stem cell transplantation of multiple myeloma patients at Stanford University. Magenta expects that this trial will provide patient-level data on stem cell mobilization and collection, characteristics of the mobilized graft and engraftment in patients with multiple myeloma.

Additionally, through a collaboration with the National Marrow Donor Program/Be The Match, a global leader in facilitating allogeneic hematopoietic stem cell transplantation, Magenta plans to initiate a Phase 2 clinical trial in early 2021 using MGTA-145 to mobilize and collect stem cells from allogeneic donors for transplant in patients with AML, ALL and MDS. Allogeneic stem cell transplant provides a potentially curative therapeutic option for patients with these diseases. This clinical trial will evaluate stem cell mobilization, collection, cell quality, engraftment and the potential for reduced Graft-versus-Host Disease (GvHD), which is of particular importance in the allogeneic transplant setting.

MGTA-145 in Sickle Cell Disease

Magenta Therapeutics recently announced an exclusive clinical collaboration with bluebird bio to evaluate the utility of MGTA-145, in combination with plerixafor, for the mobilization and collection of stem cells in adults and adolescents with SCD.

The data from this clinical trial could provide proof-of-concept for MGTA-145, in combination with plerixafor, as the preferred mobilization regimen for patients with SCD. bluebird bios experience with plerixafor as a mobilization agent in SCD aligns with Magentas combination therapy approach, utilizing MGTA-145 plus plerixafor with potential for safe, rapid and reliable mobilization of sufficient quantities of high-quality stem cells to improve outcomes associated with stem cell transplantation.

MGTA-145 Presentations at ASH

Magenta presented final clinical data from its MGTA-145 stem cell mobilization Phase 1 clinical trial in healthy volunteers at the ASH Annual Meeting. All primary and secondary endpoints were met in the study completed earlier this year.

The results demonstrate that a single dose of MGTA-145, in combination with plerixafor, rapidly and reliably mobilized high numbers of stem cells in a single day without the need for G-CSF for potential use in diseases that can benefit from autologous and/or allogeneic stem cell transplantation. The additional data also offer further confirmation that MGTA-145, in combination with plerixafor, was well tolerated and provides a rapid and reliable method to obtain large numbers of hematopoietic stem cells. Transplant of these cells in preclinical models resulted in enhanced, durable engraftment, in addition to highly immunosuppressive properties, leading to reduced GvHD.

Results from this study provide a robust dataset and proof of concept that MGTA-145, in combination with plerixafor, provides rapid and robust mobilization of stem cells and that these cells have better engraftment potential, are able to be gene modified and engraft and reduce GvHD in preclinical models compared to cells mobilized with other available agents. The data reinforce the availability of compelling opportunities for development in both the autologous and allogeneic transplant settings, said John Davis Jr., M.D., M.P.H., M.S., Head of Research & Development and Chief Medical Officer, Magenta Therapeutics.

The data were presented by Steven M. Devine, MD, Chief Medical Officer of the National Marrow Donor Program/Be The Match and Associate Scientific Director of the CIBMTR (Center for International Blood and Marrow Transplant Research).

Conditioning Program (MGTA-117 and CD45-ADC) Presentations at ASH

Magenta also provided updates on its conditioning platform at the ASH Annual Meeting, including MGTA-117 and CD45-ADC programs. Preclinical data from a study of MGTA-117 demonstrate that it is an effective, potent conditioning agent for transplant with anti-leukemic activity, significantly decreasing tumor burdens, leading to delayed tumor growth and increased median survival rates in animal models of AML. Ongoing GLP toxicology and GMP manufacturing progress continue to be supportive of advancing MGTA-117 towards an IND filing in AML and MDS.

Additionally, preclinical data from a study of Magentas CD45-ADC, a CD45-targeted conditioning agent designed to remove the cells that cause autoimmune diseases to enable curative immune reset, demonstrated the ability to achieve successful outcomes as a single agent in the most challenging disease model through fully mismatched allogeneic hematopoietic stem cell transplant, where only radiation or combinations of toxic chemotherapies are available, potentially providing patients the option of a reduced toxicity conditioning regimen. The company continues to evaluate this program preclinically.

About MGTA-145

MGTA-145 is being developed in combination with plerixafor to harness complementary chemokine mechanisms to mobilize hematopoietic stem cells for collection and transplantation. This new combination has the potential to be the preferred mobilization regimen for rapid and reliable mobilization and collection of hematopoietic stem cells to improve outcomes in autologous and allogeneic stem cell transplantation, which can rebuild a healthy immune system for patients with blood cancers, genetic diseases and autoimmune disorders.

MGTA-145 has the potential to replace the current standard of care for patients and allogeneic donors who currently rely on the use of granulocyte-colony stimulating factor (G-CSF) alone or in combination with plerixafor, which can take up to five days or longer to mobilize sufficient numbers of stem cells, often resulting in significant bone pain and other side effects.

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 blood cancer, genetic diseases and autoimmune diseases. 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 Annual Report on Form 10-K filed on March 3, 2020, 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.

More here:
Magenta Therapeutics Announces Commencement of First Phase 2 Clinical Trial of MGTA-145 for Stem Cell Mobilization, Oral Presentation of MGTA-145...

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

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

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

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

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

About TCR-Engineered T Cell Therapy

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

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

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

About Leukemia post HSCT Treatment and the Risk of Relapse

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

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

About HighPassBio

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

About ElevateBio

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

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

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

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

LONDON--(BUSINESS WIRE)--The stem cell therapy market is expected to grow by USD 588.22 mn, progressing at a CAGR of almost 7% during the forecast period.

Click & Get Free Sample Report in Minutes

The increase in awareness of stem cell therapy is one of the major factors propelling market growth. However, factors such as the high cost of clinical trials will hamper the market growth.

More details: https://www.technavio.com/report/stem-cell-therapy-market-industry-analysis

Stem Cell Therapy Market: Type Landscape

Based on the type, the allogeneic transplants segment is expected to witness lucrative growth during the forecast period.

Stem Cell Therapy Market: Geographic Landscape

By geography, North America is going to have a lucrative growth during the forecast period. About 51% of the markets overall growth is expected to originate from North America. The US and Canada are the key markets for the stem cell therapy market in North America.

Buy 1 Technavio report and get the second for 50% off. Buy 2 Technavio reports and get the third for free.

View market snapshot before purchasing

Related Reports on Health Care Include:

Companies Covered:

What our reports offer:

Technavio suggests three forecast scenarios (optimistic, probable, and pessimistic) considering the impact of COVID-19. Technavios in-depth research has direct and indirect COVID-19 impacted market research reports.

Register for a free trial today and gain instant access to 17,000+ market research reports.

Technavio's SUBSCRIPTION platform

Key Topics Covered:

Executive Summary

Market Landscape

Market Sizing

Five Forces Analysis

Market Segmentation by Type

Customer landscape

Geographic Landscape

Vendor Landscape

Vendor Analysis

Appendix

About Us

Technavio is a leading global technology research and advisory company. Their research and analysis focuses on emerging market trends and provides actionable insights to help businesses identify market opportunities and develop effective strategies to optimize their market positions. With over 500 specialized analysts, Technavios report library consists of more than 17,000 reports and counting, covering 800 technologies, spanning across 50 countries. Their client base consists of enterprises of all sizes, including more than 100 Fortune 500 companies. This growing client base relies on Technavios comprehensive coverage, extensive research, and actionable market insights to identify opportunities in existing and potential markets and assess their competitive positions within changing market scenarios.

Read the original post:
Insights on the Global Stem Cell Therapy Market 2020-2024: COVID-19 Analysis, Drivers, Restraints, Opportunities, and Threats - Technavio - Business...

The lab of KrisSaha at the University of WisconsinMadison has developed an innovative combination of gene-editing tools and computational simulations that can be used to develop new strategies for editing genes associated with genetic disorders.

In proof-of-concept experiments, the labs researchers efficiently corrected multiple mutations responsible for a rare metabolic disorder, known as Pompe disease, in cells containing the disease-causing errors. They also used computer simulations to design the ideal gene-editing approach for treating human patients, a boon for rare disorders like Pompe disease that lack useful animal models.

Their promising platform advances the CRISPR genome-editing field and could lead to effective treatments for many diseases, not just Pompe disease.

The exact mutations seen in the Pompe patients are not in an existing animal model, so we cannot do all of the preclinical studies that we would like to do in order to evaluate the safety and efficacy of different genome editing strategies, says Saha, a professor of biomedical engineering at UWMadisons Wisconsin Institute for Discovery. We need a way to think about how we go from patient material to a therapy without having to build an animal model, a process that takes months to years and hundreds of thousands of dollars.

The lab of Kris Saha (standing) has developed an innovative combination of gene-editing tools and computational simulations that can be used to develop new strategies for editing genes associated with genetic disorders. Photo: Stephanie Precourt

Sahas team published its findings Dec. 8 in the journal Nature Communications.

In the first few months of life, an infant with Pompe disease becomes weaker and weaker as glycogen builds up in their muscles, their cells unable to break the complex sugar down. Multiple mutations in a gene calledGAAprevent their cells from correctly producing the proteins needed to make lysosomes, which turn glycogen into glucose, the fuel that powers cells. Left untreated, most patients with Pompe die within a year.

Developing effective therapies for such diseases can be difficult for a number of reasons. First, diseases like Pompe have no animal models in which to test treatments, a typical step in therapy development. And diseases like Pompe and many other inherited diseases are autosomal recessive, which means that mutations are present on both copies of a chromosome. Two sets of mutations require two successful gene-repair events for maximum effect. Further complicating the matter is the fact that many diseases are polygenic, resulting from mutations in two or more genes or multiple mutations spread across a single gene, as is the case for Pompe disease.

The Saha labs new approach uses precise gene-editing tools to edit both faulty alleles simultaneously within individual cells to restore function. In its new report, the research team used induced pluripotent stem cells derived from Pompe patients to reproduce the exactGAAmutations that cause the disease and to approximate the resulting tissue pathology.

To fix these Pompe mutations, the lab turned to a specially designed, ultra-precise genome-editing system described in aprevious studyled by Jared Carlson-Stevermer, who was at the time a graduate student in Sahas group. That report established an up to 18-fold increase in precision of gene edits by combining a DNA repair template with the cutting machinery of CRISPR in one particle.

In the current study, the researchers used the method to fix two mutations at once in Pompe-derived cells. By doing so, the researchers improved cell function dramatically, bringing lysosome protein production up to the level of healthy cells without any major adverse effects, which sometimes emerge from gene editing.

The research advances the CRISPR genome-editing field and could lead to effective treatments for many diseases.

But treating cells in the laboratory, while providing crucial insight, is not the same as creating a therapy for patients. A critical step in developing treatments usually involves testing on animal models to evaluate efficacy and safety, a major obstacle for Pompe disease and other genetic conditions that lack viable animal models.

To determine the best therapeutic strategy for polygenic diseases evaluating different doses, delivery mechanisms and timing, risks and other factors the research team instead built a computational model that allows it to predict the outcomes of various conditions.

This allows us to survey a wider scope of many different gene therapies during the design of a strategy, says coauthor Amritava Das, a postdoctoral associate at the Morgridge Institute for Research. The computational approach is critical when you dont have an animal model that resembles the human disease.

After pumping close to a million simulation conditions through the computational model, Das, Carlson-Stevermer and Saha have gained key insights about the delivery of gene editors into the livers of human infants with Pompe disease without having to subject a single patient to experimental treatments. And those insights establish that the multiple-correction genome-editing approach tested in stem cells may be an effective treatment for Pompe and other polygenic recessive disorders.

The computational model, which can be easily adapted for other polygenic conditions, is a big step for the development of therapies for diseases like Pompe and lays the groundwork for a bridge from laboratory studies to the clinic. And as more measurements are added to the model, it will gain more predictive power.

Its a very broad, adaptable platform, Das says about the combined stem cell model and computational tool, and a very different way of thinking about gene therapy.

This work was supported by the National Science Foundation (CBET-1350178, CBET-1645123), the National Institutes of Health (1R35GM119644-01), the Environmental Protection Agency (EPA-G2013 STAR-L1), the University of Wisconsin Carbone Cancer Center (P30 CA014520), the Wisconsin Alumni Research Foundation, and the Wisconsin Institute for Discovery.

Follow this link:
Multiple gene edits and computer simulations could help treat rare genetic diseases - University of Wisconsin-Madison

ByHub staff report

Five Johns Hopkins faculty members have been elected as fellows of the National Academy of Inventors, a prestigious distinction that recognizes and honors the creators or co-developers of outstanding inventions that have made a difference in society. These professors join the more than 4,000 current fellows of the academy, which features members of more than 250 institutions worldwide.

The honorees from Johns Hopkins are:

Ramalingam Chellappa, who joined the Hopkins Department of Biomedical Engineering and the Department of Electrical and Computer Engineering as a Bloomberg Distinguished Professor earlier this year. Chellappa's work has shaped the field of facial recognition technology, and he is known as an expert in machine learning. At Hopkins he contributes to the Mathematical Institute for Data Science and the Center for Imaging Science.

Valina Dawson, a professor of neurology, neuroscience, and physiology in the School of Medicine, and co-director of the Neuroregeneration and Stem Cell Programs in the Institute for Cell Engineering. The lab aims to discover and describe the cell signaling pathways that contribute to neuron survival and death in Parkinson's disease and strokes. In her work, Dawson has discovered new therapies to treat neurological disorders, and established new neurological targets for patients' recovery processes.

Sharon Gerecht, professor of chemical and biomolecular engineering, and director of the Johns Hopkins Institute for NanoBioTechnology. Gerecht is an internationally recognized expert in vascular and stem cell biology and a member of the National Academy of Medicine. Together with her research group, she studies the interactions between stem cells and their microenvironments with the long-term goal of engineering artificial cell microenvironments.

Carol Greider, a professor in the Department of Molecular Biology and Genetics. In 2009, Grieder shared the Nobel Prize in Physiology or Medicine with Elizabeth Blackburn and Jack Szostak for their work on telomeres and telomerase, an enzyme that maintains protective "caps" on the ends of chromosomes. She studies the roles these enzymes play in cancer and age-related degenerative disease.

Nitish Thakor, a professor in the Department of Biomedical Engineering. Thakor conducts research on neurological instrumentation, biomedical signal processing, micro and nanotechnologies, neural prosthesis, and neural and rehabilitation techniques. Director of the Laboratory for Neuroengineering, Thakor also serves as director of the NIH Training Grant on Neuroengineering. Currently, he is developing a next-generation neurally controlled upper limb prosthesis alongside a multi-university consortium funded by DARPA.

Read the rest here:
Five Johns Hopkins faculty named to National Academy of Inventors - The Hub at Johns Hopkins

DUBLIN--(BUSINESS WIRE)--The "Europe Tissue Engineering Market Forecast to 2027 - COVID-19 Impact and Regional Analysis by Material Type, Applications, and Country" report has been added to ResearchAndMarkets.com's offering.

The Europe tissue engineering market is expected to reach US$ 7,368.93 million by 2027 from US$ 2,798.86 million in 2019; it is estimated to grow at a CAGR of 13.2% during 2020-2027.

The market growth is primarily attributed to the increasing incidences of chronic diseases, road accidents, and trauma injuries, and technological advancements in 3D tissue engineering techniques. High cost associated to the tissue engineering process is one of the major factors restraining the growth of the market. Additionally, increasing financial contributions by government and private sector are likely to fuel the growth of the Europe tissue engineering market during the forecast period.

Tissue engineering is a blend of material methods and cellular activities. This approach involves the use of physicochemical and biochemical attributes of humans to replace the biological tissues and strengthen them. It is an innovative technology that works either separately or in conjunction with scaffolds, stem cells, regenerative medicine, and growth factors or negotiators. The process utilizes molecular and cellular processes in combination with the principles of material engineering to surgically repair and restore tissue.

The tissue engineering market in Europe is estimated to grow at a significant CAGR during the forecast period, and the growth is driven by the increase in research activities, growing demand for organ transplants, escalating number of initiatives by market players for expanding their presence in the region, and higher adoption of stem cell research in several European countries.

In the Europe, due to an increasing number of COVID-19 patients, healthcare professionals and leading organizations are rechanneling the flow of healthcare resources from R&D to primary care, which is slowing down the process of innovation. Further, the pandemic is also hindering the conduct of clinical trials and drug development, and the operations of diagnostic industry in Europe.

For instance, Stryker Corporation, a well-known player in the tissue engineering industry, has diverted operations to manufacture COVID-19 diagnostics and PPE kits. Moreover, according to a recent survey published by Medscape in July 2020, substantial disruption has been witnessed in routine research activities that include tissue engineering and regenerative medicines as a result of the COVID-19 pandemic. The rapid increase in the number of the infected patients in the Italy and Spain is likely to result in the slowdown of the market growth in the near future.

In 2019, the biologically derived material segment accounted for the largest share of the Europe tissue engineering market. The growth of the market for this segment is attributed to the rising adoption of biomaterials due to their natural regenerative potential to restore tissue functioning and ability to facilitate the on demand release of chemokines with the procedure. Further, the synthetic material segment is likely to register the highest CAGR in the market during the forecast period.

Key Topics Covered:

1. Introduction

1.1 Scope of the Study

1.2 Report Guidance

1.3 Market Segmentation

2. Europe Tissue engineering Market - Key Takeaways

3. Research Methodology

4. Europe Tissue engineering Market - Market Landscape

4.1 Overview

4.2 PEST Analysis

4.3 Expert Opinion

5. Europe Tissue engineering Market - Key Market Dynamics

5.1 Key Market Drivers

5.1.1 Increasing Number of Road Accidents and Trauma Injuries, and Elevating Incidence of Chronic Diseases

5.1.2 Technological Advancements in the Field of 3D Tissue engineering

5.1.3 Government and Private sector funding

5.2 Key Market Restraints

5.2.1 High Cost associated with tissue engineering

5.3 Impact Analysis

6. Tissue engineering Market - Europe Analysis

6.1 Europe Tissue engineering Market Revenue Forecasts and Analysis

7. Europe Tissue engineering Market Analysis - By Material Type

7.1 Overview

7.2 Europe Tissue engineering Market, By Material Type 2019-2027 (%)

7.2.1 Europe Tissue engineering Market Material Type Segment Revenue and Forecasts to 2027, By Material Type (US$ Mn)

7.3 Biologically Derived Material

7.4 Synthetic Material

7.5 Other

8. Europe Tissue engineering Market Analysis - By Application

8.1 Overview

8.2 Europe Tissue engineering Market, By Application 2019-2027 (%)

8.2.1 Europe Tissue engineering Market Revenue and Forecasts to 2027, By Application (US$ Mn)

8.3 Orthopedic, Musculoskeletal and Spine

8.3.1 Overview

8.3.2 Europe Orthopedic, Musculoskeletal and Spine Market Revenue and Forecasts to 2027 (US$ Mn)

8.4 Skin

8.5 Cardiology and Vascular

8.6 Neurology

8.7 Others

9. Europe Tissue engineering Market Revenue and Forecasts To 2027 - Regional Analysis

10. Impact of COVID-19 Pandemic on Europe Tissue Engineering Market

10.1 Europe: Impact Assessment of COVID-19 Pandemic

11. Company Profiles

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

Read the original post:
Europe Tissue Engineering Market Forecast to 2027 - COVID-19 Impact and Regional Analysis by Material Type, Applications, and Country -...