Company Announcement

Copenhagen, Denmark; October 21, 2020 Genmab A/S (Nasdaq: GMAB) announced today positive topline results from the second part of the Phase 3 CASSIOPEIA (MMY3006) study of daratumumab monotherapy as maintenance treatment versus observation (no treatment) for patients with newly diagnosed multiple myeloma eligible for autologous stem cell transplant (ASCT). The second part of the study, which is being conducted by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen Research & Development, LLC (Janssen), met the primary endpoint of improving progression free survival (PFS) at a pre-planned interim analysis (Hazard Ratio (HR) = 0.53 (95% CI 0.42 0.68), p < 0.0001) resulting in a 47% reduction in the risk of progression or death in patients treated with daratumumab. The safety profile observed in this study was consistent with the known safety profile of daratumumab and no new safety signals were observed.

Based on the results at the pre-planned interim analysis conducted by an Independent Data Monitoring Committee (IDMC), it was recommended to unblind the study results. Janssen Biotech, Inc., which licensed daratumumab from Genmab in 2012, plans to discuss the potential for a regulatory submission for this indication with health authorities, and plans to submit the data to an upcoming medical conference and for publication in a peer-reviewed journal.

Following the positive data from the first part of the CASSIOPEIA study, we are very pleased to see this benefit. We are appreciative of the efforts of the IFM, of HOVON and of Janssen for their work on this study, said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the CASSIOPEIA (MMY3006) StudyThis Phase 3 study is a randomized, open-label, multicenter study, conducted by the IFM in collaboration with the HOVON and Janssen, which includes 1,085 newly diagnosed subjects with previously untreated symptomatic multiple myeloma who were eligible for high dose chemotherapy and ASCT. In the first part of the study, patients were randomized to receive induction and consolidation treatment with daratumumab combined with bortezomib, thalidomide and dexamethasone (VTd) or VTd alone. The primary endpoint was the number of patients that achieved a stringent complete response (sCR). In the second part of the study, patients that achieved a response underwent a second randomization to either receive maintenance treatment of daratumumab 16 mg/kg every 8 weeks for up to 2 years versus no further treatment (observation). The primary endpoint of this part of the study is progression free survival.

About Multiple MyelomaMultiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,000 new patients were expected to be diagnosed with multiple myeloma and approximately 13,650 people were expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5

About DARZALEX (daratumumab)DARZALEX (daratumumab) has become a backbone therapy in the treatment of multiple myeloma. DARZALEX intravenous infusion is indicated for the treatment of adult patients in the United States: in combination with carfilzomib and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma who have received one to three previous lines of therapy; in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma.

DARZALEX is indicated for the treatment of adult patients in Europe via intravenous infusion or subcutaneous administration: in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy7. Daratumumab is the first subcutaneous CD38 antibody approved in Europe for the treatment of multiple myeloma. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S.

In Japan, DARZALEX intravenous infusion is approved for the treatment of adult patients: in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United States, Europe and Japan. For more information, visit http://www.DARZALEX.com.

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj), a subcutaneous formulation of daratumumab, is approved in the United States for the treatment of adult patients with multiple myeloma: in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for ASCT; in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for ASCT and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy; in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy; and as monotherapy, in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.8 DARZALEX FASPRO is the first subcutaneous CD38 antibody approved in the U.S. for the treatment of multiple myeloma.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a persons own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).6,9,10,11,12

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase 3 studies in smoldering, relapsed and refractory and frontline multiple myeloma settings. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases in which CD38 is expressed, such as amyloidosis and T-cell acute lymphocytic leukemia (ALL). Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA for certain indications of multiple myeloma, including as a monotherapy for heavily pretreated multiple myeloma and in combination with certain other therapies for second-line treatment of multiple myeloma.

About Genmab Genmab is a publicly traded, international biotechnology company specializing in the creation and development of differentiated antibody therapeutics for the treatment of cancer. Founded in 1999, the company is the creator of the following approved antibodies: DARZALEX (daratumumab, under agreement with Janssen Biotech, Inc.) for the treatment of certain multiple myeloma indications in territories including the U.S., Europe and Japan, Kesimpta (subcutaneous ofatumumab, under agreement with Novartis AG), for the treatment of adults with relapsing forms of multiple sclerosis in the U.S. and TEPEZZA (teprotumumab, under agreement with Roche granting sublicense to Horizon Therapeutics plc) for the treatment of thyroid eye disease in the U.S. A subcutaneous formulation of daratumumab, known as DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) in the U.S., has been approved in the U.S. and Europe for the treatment of adult patients with certain multiple myeloma indications. The first approved Genmab created therapy, Arzerra (ofatumumab, under agreement with Novartis AG), approved for the treatment of certain chronic lymphocytic leukemia indications, is available in Japan and is also available in other territories via compassionate use or oncology access programs. Daratumumab is in clinical development by Janssen for the treatment of additional multiple myeloma indications, other blood cancers and amyloidosis. Genmab also has a broad clinical and pre-clinical product pipeline. Genmab's technology base consists of validated and proprietary next generation antibody technologies - the DuoBody platform for generation of bispecific antibodies, the HexaBody platform, which creates effector function enhanced antibodies, the HexElect platform, which combines two co-dependently acting HexaBody molecules to introduce selectivity while maximizing therapeutic potency and the DuoHexaBody platform, which enhances the potential potency of bispecific antibodies through hexamerization. The company intends to leverage these technologies to create opportunities for full or co-ownership of future products. Genmab has alliances with top tier pharmaceutical and biotechnology companies. Genmab is headquartered in Copenhagen, Denmark with sites in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan.

Contact: Marisol Peron, Corporate Vice President, Communications & Investor Relations T: +1 609 524 0065; E: mmp@genmab.com

For Investor Relations: Andrew Carlsen, Senior Director, Investor RelationsT: +45 3377 9558; E: acn@genmab.com

This Company Announcement contains forward looking statements. The words believe, expect, anticipate, intend and plan and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with pre-clinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmabs most recent financial reports, which are available on http://www.genmab.com and the risk factors included in Genmabs most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at http://www.sec.gov. Genmab does not undertake any obligation to update or revise forward looking statements in this Company Announcement nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law.

Genmab A/S and/or its subsidiaries own the following trademarks: Genmab; the Y-shaped Genmab logo; Genmab in combination with the Y-shaped Genmab logo; HuMax; DuoBody; DuoBody in combination with the DuoBody logo; HexaBody; HexaBody in combination with the HexaBody logo; DuoHexaBody; HexElect; and UniBody. Arzerra and Kesimpta are trademarks of Novartis AG or its affiliates. DARZALEX and DARZALEX FASPRO are trademarks of Janssen Pharmaceutica NV. TEPEZZA is a trademark of Horizon Therapeutics plc.

1 American Cancer Society. "Multiple Myeloma Overview." Available at http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma.Accessed June 2016.2 National Cancer Institute. "A Snapshot of Myeloma." Available at http://www.cancer.gov/research/progress/snapshots/myeloma. Accessed June 2016. 3 Globocan 2018. United States of America Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/840-united-states-of-america-fact-sheets.pdf.4 Globocan 2018. World Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed December 2018.5 American Cancer Society. "How is Multiple Myeloma Diagnosed?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed June 20166 DARZALEX Prescribing information, August 2020 https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761036s029lbl.pdf Last accessed August 20207 DARZALEX Summary of Product Characteristics, available at https://www.ema.europa.eu/en/medicines/human/EPAR/darzalex Last accessed June 20208 DARZALEX FASPRO Prescribing information, May 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761145s000lbl.pdf Last accessed May 20209 De Weers, M et al. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors. The Journal of Immunology. 2011; 186: 1840-1848.10 Overdijk, MB, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015; 7: 311-21.11 Krejcik, MD et al. Daratumumab Depletes CD38+ Immune-regulatory Cells, Promotes T-cell Expansion, and Skews T-cell Repertoire in Multiple Myeloma. Blood. 2016; 128: 384-94.12 Jansen, JH et al. Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking.Blood. 2012; 120(21): abstract 2974.

Company Announcement no. 45CVR no. 2102 3884LEI Code 529900MTJPDPE4MHJ122

Genmab A/SKalvebod Brygge 431560 Copenhagen VDenmark

View original post here:
Genmab Announces IFM, HOVON and Janssen Achieve Positive Topline Results in Second Part of Phase 3 CASSIOPEIA Study of Daratumumab in Multiple Myeloma...

Bone Marrow Stem Cells Comments Off on Genmab Announces IFM, HOVON and Janssen Achieve Positive Topline Results in Second Part of Phase 3 CASSIOPEIA Study of Daratumumab in Multiple Myeloma… | October 23rd, 2020

Careful, man, theres a beloved actor here.

Jeff Bridges revealed that he has lymphoma, which is the most common type of blood cancer. And this sobering news has spurred celebrities and fans to send their best wishes to the star best known for playing the Dude, the White Russiandrinking bowler and casual-wear icon from the Coen brothers 1998 cult classic, The Big Lebowski.

But the Dude abides, and Bridges suggested that his outlook looks just as promising.

As the Dude would say.. New S**T has come to light, tweeted Bridges, 70, on Monday. I have been diagnosed with Lymphoma. Although it is a serious disease, I feel fortunate that I have a great team of doctors and the prognosis is good.

Celebrities such as Cary Elwes, John Lithgow, Patricia Arquette and George Takei posted encouraging words and prayers to Bridges, who is the son of Lloyd and Dorothy Bridges, and has starred in more than 70 films including Starman, True Grit and The Last Picture Show. He won an Academy Award in 2010 for Crazy Heart, and was honored with the Cecil B. DeMille lifetime-achievement award during the 2019 Golden Globes.

And he is now one of the most high-profile cases of lymphoma, a cancer of the bodys infection-fighting lymphatic system that affects the blood and bone marrow. And more than 85,000 new cases of lymphoma are expected to be diagnosed in the U.S. this year, according to American Cancer Society data shared by the Leukemia & Lymphoma Society, with some 791,550 people currently living with lymphoma or in remission from the disease in the U.S.

Many different types of lymphoma exist, and Bridges did not share any more details about his diagnosis or treatment. But his disclosure is an opportunity to share more information about lymphoma, the risk factors and symptoms to be aware of, as well as treatment options.

What is lymphoma?

Lymphoma is a type of cancer that starts in cells that are part of the bodys immune system, specifically the lymphocytes, which are a type of white blood cell that fights germs. So these cancers can affect the blood and bone marrow, as well as the other tissues and organs that produce, store and carry white blood cells including the spleen.

Doctors still dont know what specifically causes lymphoma, but at some point a lymphocyte mutates and begins to reproduce rapidly. The mutated, abnormal cells live longer than the normal cells would, and in time, the diseased and ineffective lymphocytes outnumber the healthy cells, which causes the lymph nodes, liver and spleen to swell.

There are two main types of lymphoma, the CDC explains, including:

Hodgkin lymphoma (HL), which spreads in an orderly manner from one group of lymph nodes to another.

Non-Hodgkin lymphoma (NHL), which spreads through the lymphatic system in a non-orderly manner.

What are the symptoms?

Signs and symptoms of lymphoma may include:

These symptoms can be signs of other health conditions, of course, so its recommended that anyone experiencing them should see a doctor to determine the cause.

How is it treated?

There are many different types of lymphoma including 90 different types of non-Hodgkin lymphoma and treatment varies depending on the type and severity. Generally, lymphoma treatment involves chemotherapy, radiation therapy and immunotherapy medication. The Mayo Clinic, which is an international authority on lymphoma research, explains that the goal of treatment is to destroy as many cancer cells as possible to bring the disease into remission. A bone marrow or stem cell transplant may be performed in some cases to help rebuild healthy bone marrow after chemo and radiation has suppressed the diseased bone marrow.

Bridges didnt specify his own treatment, only saying that he is beginning treatment and will keep the public posted on his recovery.

Treatment can be very expensive, however, with almost 60% of patients covered by Medicare telling the Leukemia & Lymphoma Society in a 2019 study that they decided to delay or forego treatment, largely due to steep out-of-pocket costs. It noted that some traditional Medicare lymphoma patients getting anti-cancer therapy though infusions experienced out-of-pocket costs of more than $19,000 in their first year. And costs can extend two or three years beyond a blood cancer diagnosis.

Who is most at risk?

While children, teens and adults can all develop lymphoma, some types are more common in certain age groups. The CDC notes that rates of Hodgkin lymphoma are highest among teens and young adults (ages 15 to 39) as well as among older adults (ages 75 and older). But non-Hodgkin lymphoma becomes more common as people get older.

Men are also slightly more likely to develop lymphoma than women, the CDC adds, and white people are more likely than Black people to develop non-Hodgkin lymphoma.

Cases have also been more common in people who are immunocompromised, including those who take drugs to suppress their immune systems. And some infections such as HIV and the Epstein-Barr virus are also associated with an increased lymphoma risk.

And like many other cancers, family history has been linked with a higher risk of Hodgkin lymphoma.

What is the survival rate?

The good news is, Hodgkin lymphoma is now considered to be one of the most curable forms of cancer, according to the Leukemia & Lymphoma Society, with a five-year survival rate of 94.4% among patients younger than 45 at diagnosis. And the five-year relative survival rate for those with Hodgkin lymphoma more than doubled from 40% in whites in 1960 to 1963 (the only data available) to 88.5% for all races from 2009 to 2015.

And the five-year relative survival rate for people with non-Hodgkin lymphoma rose from 31% in whites from 1960 to 1963 (the only data available) to 74.7% for all races from 2009 to 2015.

Still, an estimated 20,910 Americans are expected to die from lymphoma this year, including 19,940 with non-Hodgkin lymphoma and 970 with Hodgkin lymphoma.

How does COVID-19 complicate things?

While the medical community is still learning about COVID-19, the general consensus is that people with cancer, who are in active cancer treatment or have previously been treated for cancer, may be at higher risk of severe illness and death if they get the coronavirus. So its important that these folks lower their risk of exposure to COVID-19 by avoiding large crowds and non-essential travel; working from home, if possible; staying at least six feet away from people outside their household; wearing a face mask when they cant socially distance; as well as washing their hands frequently, and not touching their eyes, nose or mouth.

Where can I find more information or support?

Visit the CDC and American Cancer Society pages on lymphoma.

The Mayo Clinic also outlines its lymphoma research and treatment strategies on its website.

The Leukemia & Lymphoma Society and the Lymphoma Research Foundation also provide valuable information and support.

Excerpt from:
Jeff Bridges is one of the 85,000-plus lymphoma cases expected in the U.S. this year - MarketWatch

Bone Marrow Stem Cells Comments Off on Jeff Bridges is one of the 85,000-plus lymphoma cases expected in the U.S. this year – MarketWatch | October 21st, 2020

Myelofibrosis or osteomyelofibrosis is a myeloproliferative disorder which is characterized by proliferation of abnormal clone of hematopoietic stem cells. Myelofibrosis is a rare type of chronic leukemia which affects the blood forming function of the bone marrow tissue. National Institute of Health (NIH) has listed it as a rare disease as the prevalence of myelofibrosis in UK is as low as 0.5 cases per 100,000 population. The cause of myelofibrosis is the genetic mutation in bone marrow stem cells. The disorder is found to occur mainly in the people of age 50 or more and shows no symptoms at an early stage. The common symptoms associated with myelofibrosis include weakness, fatigue, anemia, splenomegaly (spleen enlargement) and gout. However, the disease progresses very slowly and 10% of the patients eventually develop acute myeloid leukemia. Treatment options for myelofibrosis are mainly to prevent the complications associated with low blood count and splenomegaly.

The global market for myelofibrosis treatment is expected to grow moderately due to low incidence of a disease. However, increasing incidence of genetic disorders, lifestyle up-gradation and rise in smoking population are the factors which can boost the growth of global myelofibrosis treatment market. The high cost of therapy will the growth of global myelofibrosis treatment market.

To remain ahead of your competitors, request for a sample[emailprotected]

https://www.persistencemarketresearch.com/samples/11341

The global market for myelofibrosis treatment is segmented on basis of treatment type, end user and geography:

As myelofibrosis is considered as non-curable disease treatment options mainly depend on visible symptoms of a disease. Primary stages of the myelofibrosis are treated with supportive therapies such as chemotherapy and radiation therapy. However, there are serious unmet needs in myelofibrosis treatment market due to lack of disease modifying agents. Approval of JAK1/JAK2 inhibitor Ruxolitinib in 2011 is considered as a breakthrough in myelofibrosis treatment. Stem cell transplantation for the treatment of myelofibrosis also holds tremendous potential for market growth but high cost of therapy is foreseen to limits the growth of the segment.

To receive extensive list of important regions, Request Methodology here @

https://www.persistencemarketresearch.com/methodology/11341

On the basis of treatment type, the global myelofibrosis treatment market has been segmented into blood transfusion, chemotherapy, androgen therapy and stem cell or bone marrow transplantation. Chemotherapy segment is expected to contribute major share due to easy availability of chemotherapeutic agents. Ruxolitinib is the only chemotherapeutic agent approved by the USFDA specifically for the treatment of myelofibrosis, which will drive the global myelofibrosis treatment market over the forecast period.

Geographically, global myelofibrosis treatment market is segmented into five regions viz. North America, Latin America, Europe, Asia Pacific and Middle East & Africa. Northe America is anticipated to lead the global myelofibrosis treatment market due to comparatively high prevalence of the disease in the region.

Some of the key market players in the global myelofibrosis treatment market are Incyte Corporation, Novartis AG, Celgene Corporation, Mylan Pharmaceuticals Ulc., Bristol-Myers Squibb Company, Eli Lilly and Company, Taro Pharmaceuticals Inc., AllCells LLC, Lonza Group Ltd., ATCC Inc. and others.

You Can Request for TOC[emailprotected]

https://www.persistencemarketresearch.com/toc/11341

Explore Extensive Coverage of PMR`s

Life Sciences & Transformational HealthLandscape

About us:

Persistence Market Research (PMR) is a third-platform research firm. Our research model is a unique collaboration of data analytics andmarket research methodologyto help businesses achieve optimal performance.

To support companies in overcoming complex business challenges, we follow a multi-disciplinary approach. At PMR, we unite various data streams from multi-dimensional sources. By deploying real-time data collection, big data, and customer experience analytics, we deliver business intelligence for organizations of all sizes.

Our client success stories feature a range of clients from Fortune 500 companies to fast-growing startups. PMRs collaborative environment is committed to building industry-specific solutions by transforming data from multiple streams into a strategic asset.

Contact us:

Naved BegPersistence Market ResearchAddress 305 Broadway, 7th Floor, New York City,NY 10007 United StatesU.S. Ph. +1-646-568-7751USA-Canada Toll-free +1 800-961-0353Sales[emailprotected]Websitehttps://www.persistencemarketresearch.com

More:
The Myelofibrosis Treatment market to turn out to be Sublime between 2016 and 2022 - PRnews Leader

Bone Marrow Stem Cells Comments Off on The Myelofibrosis Treatment market to turn out to be Sublime between 2016 and 2022 – PRnews Leader | October 21st, 2020

Stem Cell Therapy Market report would come handy to understand the competitors in the market and give an insight into sales, volumes, revenues in the Stem Cell Therapy Industry & will also assists in making strategic decisions. The report also helps to decide corporate product & marketing strategies. It reduces the risks involved in making decisions as well as strategies for companies and individuals interested in the Stem Cell Therapy industry. Both established and new players in Stem Cell Therapy industries can use the report to understand the Stem Cell Therapy market.

In Global Market, the Following Companies Are Covered:

Get a Sample Copy of the Report @ https://www.360marketupdates.com/enquiry/request-sample/14849805

Analysis of the Market:

Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition. Bone marrow transplant is the most widely used stem-cell therapy, but some therapies derived from umbilical cord blood are also in use.

In the last several years, global stem cell therapy market developed fast at a average growth rate of 46.81%.

Market Analysis and Insights: Global Stem Cell Therapy Market

In 2019, the global Stem Cell Therapy market size was USD 403.6 million and it is expected to reach USD 1439.9 million by the end of 2026, with a CAGR of 19.7% during 2021-2026.

Global Stem Cell Therapy Scope and Market Size

Stem Cell Therapy market is segmented by Type, and by Application. Players, stakeholders, and other participants in the global Stem Cell Therapy market will be able to gain the upper hand as they use the report as a powerful resource. The segmental analysis focuses on revenue and forecast by Type and by Application in terms of revenue and forecast for the period 2015-2026.

Segment by Type, the Stem Cell Therapy market is segmented into Autologous, Allogeneic, etc.

Segment by Application, the Stem Cell Therapy market is segmented into Musculoskeletal Disorder, Wounds & Injuries, Cornea, Cardiovascular Diseases, Others, etc.

Regional and Country-level Analysis

The Stem Cell Therapy market is analysed and market size information is provided by regions (countries).

The key regions covered in the Stem Cell Therapy market report are North America, Europe, China, Japan, Southeast Asia, India and Central & South America, etc.

The report includes country-wise and region-wise market size for the period 2015-2026. It also includes market size and forecast by Type, and by Application segment in terms of revenue for the period 2015-2026.

Competitive Landscape and Stem Cell Therapy Market Share Analysis

Stem Cell Therapy market competitive landscape provides details and data information by vendors. The report offers comprehensive analysis and accurate statistics on revenue by the player for the period 2015-2020. It also offers detailed analysis supported by reliable statistics on revenue (global and regional level) by player for the period 2015-2020. Details included are company description, major business, company total revenue and the revenue generated in Stem Cell Therapy business, the date to enter into the Stem Cell Therapy market, Stem Cell Therapy product introduction, recent developments, etc.

The major vendors include Osiris Therapeutics, NuVasive, Chiesi Pharmaceuticals, JCR Pharmaceutical, Pharmicell, Medi-post, Anterogen, Molmed, Takeda (TiGenix), etc.

This report focuses on the global Stem Cell Therapy status, future forecast, growth opportunity, key market and key players. The study objectives are to present the Stem Cell Therapy development in North America, Europe, China, Japan, Southeast Asia, India and Central & South America.

Stem Cell Therapy Market Breakdown by Types:

Stem Cell Therapy Market Breakdown by Application:

Critical highlights covered in the Global Stem Cell Therapy market include:

The information available in the Stem Cell Therapy Market report is segmented for proper understanding. The Table of contents contains Market outline, Market characteristics, Market segmentation analysis, Market sizing, customer landscape & Regional landscape. For further improving the understand ability various exhibits (Tabular Data & Pie Charts) has also been used in the Stem Cell Therapy Market report.

Get a Sample Copy of the Report @ https://www.360marketupdates.com/enquiry/request-sample/14849805

Reasons for Buy Stem Cell Therapy Market Report:

In the end, Stem Cell Therapy Industry report provides the main region, market conditions with the product price,profit, capacity, production, supply, demand and market growth rateand forecast etc. This report also Present newproject SWOT analysis,investment feasibility analysis, andinvestment return analysis.

Contact Us:

Name: Mr. Ajay More

Email: [emailprotected]

Organization: 360 Market Updates

Phone: +14242530807 / + 44 20 3239 8187

Valencene Market Size Research Report 2020-2026,Comprehensive Study, Development Status, Opportunities, Future Plans, Competitive Landscape and Growth

Enhanced Fire Protection Systems Market Size 2020,Growth Factors, Business Opportunity,Segmentation and Forecast to 2026 Research Reportby implies of360 Market Updates

Antifungal Agents Market Size, Defination, Industry Trends, News andlargeGrowth With Regional Trends By Forecast 2026 Research Reportwith the aid of360 market updates

Rainboots Market Size 2020-2026 Industry Trends, Size, Segments, Competitors Classification, Growth, Up and Down Stream Industry Analysis and Forecast

Ku-Band LNB Market Size & Growth, Sales Revenue, Key Players Analysis, Development Status, Opportunity Assessment and Industry Expansion Strategies 2025 Research Reportwith the aid of360 market updates

ITO Glass Market Size 2020-2026 Research Report by Key Companies, Future Trend, Pipeline Projects, Product, Application, Growth and Regional Forecasts

Perfluoropolyethers Market Size 2020,Business Opportunity, SWOT Analysis, Applications, Trends and Forecast to 2026 Research Reportby360 Market Updates

Read the original here:
Stem Cell Therapy Market 2020-2026 | XX% CAGR Projection Over the Next Five Years, Predicts Market Research Future with Market Size & Growth Key...

Bone Marrow Stem Cells Comments Off on Stem Cell Therapy Market 2020-2026 | XX% CAGR Projection Over the Next Five Years, Predicts Market Research Future with Market Size & Growth Key… | October 21st, 2020

Stem Cell Assay Market: Snapshot

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

Get Exclusive PDF Sample Copy Of This Report:https://www.tmrresearch.com/sample/sample?flag=B&rep_id=40

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

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

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

Global Stem Cell Assay Market: Overview

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

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

Buy This Report @https://www.tmrresearch.com/checkout?rep_id=40<ype=S

Global Stem Cell Assay Market: Key Market Segments

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

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

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

Global Stem Cell Assay Market: Regional Analysis

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

Global Stem Cell Assay Market: Vendor Landscape

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

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

To know more about the table of contents, you can click @https://www.tmrresearch.com/sample/sample?flag=T&rep_id=40

About Us:

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

View original post here:
Stem Cell Assay Market In-Depth Analysis & Forecast 2017-2025 - The Think Curiouser

Bone Marrow Stem Cells Comments Off on Stem Cell Assay Market In-Depth Analysis & Forecast 2017-2025 – The Think Curiouser | October 21st, 2020

More than 2 million people have registered to become stem cell donors the UK, new figures released today reveal. The UK stem cell register had an immensely successful year in 2019/20, with 326,756 new donors added over 100,000 more than the previous year.

The UK stem cell register is known as the Anthony Nolan and NHS Stem Cell Registry and is made up of donors recruited by NHS Blood and Transplant, the Welsh Blood Service, DKMS and Anthony Nolan. The UK donor registers are urging young men, and people from black, Asian and minority ethnic backgrounds to register and ensure that all patients in need of a stem cell transplant can find a, potentially, lifesaving match.

If a patient has a condition that affects their bone marrow or blood, then a stem cell transplant may be their best chance of survival. Doctors will give new, healthy stem cells to the patient via their bloodstream, where they begin to grow and create healthy red blood cells, white blood cells and platelets.

In 2019/20 62 per cent of people who donated stem cells or bone marrow to patients in the UK were men under 30. They are the demographic most likely to be chosen to donate, but make up just 19 per cent of the UK stem cell register.

The percentage of all donors from minority ethnic backgrounds has remained steady at 13 per cent in 2019/20, highlighting the importance of raising awareness of their lifesaving potential amongst this group. Patients from Black, Asian or other minority backgrounds have a 20 per cent chance of finding the best possible stem cell match from an unrelated donor, compared to 69 per cent for northern European backgrounds.

Henny Braund, Chief Executive of Anthony Nolan, said:

Nobody could have foreseen the challenges this year would bring to building a healthy, diverse stem cell register. But weve adapted and weve innovated as patients cant wait and were thrilled that in 2020, weve collectively recruited two million donors onto the stem cell register. Each donor represents hope, a potential cure for blood cancer.

I thank colleagues and partners for their commitment helping us reach this point. I am also immensely grateful for the two million selfless individuals who signed up to the registry, making themselves available whenever they are needed.

The two million milestone means increased chances for many of finding an unrelated donor match. But were still far from our goal of finding a match for everyone who needs one.

I would urge anyone thinking of joining the stem cell register, especially young men, who are the most likely to be chosen, to do so today. You could be someones lifesaver, without you there is no cure.

Christopher Harvey, Head of the Welsh Bone Marrow Registry, said:

Its incredibly heart-warming to know there are two million people in the UK who are willing to donate stem cells should they be the match for someone in need of their potentially lifesaving donation.

We see in our roles the difference stem cells make, for lots of patients receiving stem cells is the final treatment option.

Despite this great news we still have more to do. Unfortunately, there are still patients who are unable to find a match. Thats why were committed to ensuring every patient has the best possible chance of finding that one lifesaving donor in their time of need.

Guy Parkes, Head of Stem Cell Donation & Transplantation at NHS Blood and Transplant, said:

We want all patients in need of a transplant to be able to find a lifesaving match. Each time a person joins this register it brings fresh hope to patients of a match.

This register is used by hospitals across the UK to find suitable matches for patients and it has helped to save and improve the lives of thousands of people since its creation 33 years ago its amazing that we now have over 2 million people on the register, putting the chances of matching donors to patients at a record high.

Donating stem cells is an altruistic, lifesaving act and its an amazing thing to do. We will continue to expand the UK register to help patients in need. We particularly need more young men to join.

Jonathan Pearce, CEO of DKMS UK said:

Were delighted to have reached such an amazing milestone and are grateful to those two million people who are actively registered and waiting to help give someone living with blood cancer or a blood disorder a second chance of life.

At any one time there are around 2,000 people in the UK in need of a blood stem cell transplant, so whilst we recognise this achievement it goes without saying that we need to continue to encourage everyone that can register to do so. This will help to grow the numbers and diversify the registry further in order to improve the odds for those who currently have less chance of finding a matching donor.

Visit link:
The Anthony Nolan and NHS Stem Cell Registry - The Hippocratic Post

Bone Marrow Stem Cells Comments Off on The Anthony Nolan and NHS Stem Cell Registry – The Hippocratic Post | October 19th, 2020

"Young people today are often drivers of social change movements and we look forward to engaging them."

South African youth aged 16 and 17 will be able to make history, alongside their peers in the UK, as the worlds youngest bone marrow donors.

The South African Bone Marrow Registry (SABMR) received the nod from its Clinical Governance Committee and board members, as well as the National Health Department to allow 16 and 17-year-old teens to become bone marrow, stem-cell donors.

Recent changes in legislation and advances in stem cell donation have allowed registries to reduce the age limit of donors. South Africa now joins the UK in this move. The latter became one of the first countries to do so.

Dr Charlotte Ingram, Medical Director of the SA Bone Marrow Registry (SABMR) the largest registry in the country says it's a landmark moment as the change in joining policy will contribute to saving more lives.

"In general, young people make better donors. Research shows that younger donors are associated with better survival rates for patients following a stem cell transplant."

"It's a step towards further enhancing the registry towards a younger and more ethnically diverse pool for blood cancer patients and others in need of a bone marrow transplant."

Previously, teenagers had to wait until they were 18 to join the SA Bone Marrow Registry. Now they can join by following the same procedure as others would.

While it is not required, it is important for the SABMR to involve parents and address any questions or concerns they may have re the procedure and what it entails.

Once youth have applied online, they will be contacted to discuss the easiest way of dispatching and collecting swab kits. The only initial sample that is required is a cheek swab.

Currently, 18-25-year olds only account for 6.8% of the SABMR registry but with increased awareness of bone marrow donation among young people, the figure should increase substantially.

Read:Knowledge is key: What you need to know about the most common childhood cancer in SA

"Studies tell us that generation WE (aged 14-20) and generation Z (21-25) are a lot more self-aware, socially-responsible and globally-minded than previous generations. They are more concerned about tackling social issues and want to roll up their sleeves and make a difference. Young people today are often drivers of social change movements and we look forward to engaging them."

She says there is no greater way to help another than to potentially save a life.

"So many lives are lost if there is a delay in finding a donor match. While we have 74 000 donors on our registry, we often discover that many older donors can no longer donate stem cells as they have developed hypertension, heart disease or diabetes."

"When this happens, we have to start the search process all over again, which prolongs the agonising wait for a patient, who doesn't have time to waste."

"By opening up the donor pool to a younger audience, means doctors and donors can choose the healthiest matches that substantially increases a patients chance of survival."

For now, social media will serve as the primary channel to create awareness among youth, but physical donor drives at schools and other initiatives, which encourage collaboration between learners, peers and patients are in the pipeline for 2021.

If you are between the ages of 16 and 45 and want to become a donor, contact the SABMR on 021 447 8638 or email: donors@sabmr.co.za.

Financial donations can also be made via http://www.sabmr.co.za/donate.

Submitted to Parent24 by theSA Bone Marrow Registry

Chatback:

Share your stories and questions with us via email at chatback@parent24.com. Anonymous contributions are welcome.

Don't miss a story!

For a weekly wrap of our latest parenting news and advice sign up to our free Friday Parent24 newsletter.

Follow us, and chat, on Facebook and Twitter.

Excerpt from:
SA becomes 2nd country to allow 16 and 17-year-olds to donate bone marrow - News24

Bone Marrow Stem Cells Comments Off on SA becomes 2nd country to allow 16 and 17-year-olds to donate bone marrow – News24 | October 19th, 2020

DENVER A baby broken.

Most doctors gave little unborn Payton Calvillo any hope she would survive.

But through strong faith and the help of a team of medical experts, she is thriving today.

"She's a complete miracle baby," said Payton's mother, Ahna Calvillo.

When Ahna was just five months pregnant, she was told her unborn baby would probably not survive birth.

"It was pretty much a death sentence from the beginning."

Payton's bones were breaking and bending inside the womb.

"She likely had a problem where she couldn't make alkaline phosphatase properly," explained Dr. Sunil Nayak, a pediatric endocrinologist at Rocky Mountain Hospital for Children.

Alkaline phosphatase is needed for bones to grow and strengthen.

There was little anyone could do.

19 different specialists were on hand for the C-section delivery

"They even asked us the question that morning, how far do you want us to go?" Ahna remembered.

"'Do you want a ventilator on her?', you know, 'How far do you want us to prolong her life?'"

"Our ultimate hope and goal was that she would come out and breathe on her own."

"She just came out screaming," said Ahna.

"She came out crying. She breathed on her own right away. She was perfect."

Payton was diagnosed with hypophosphatasia, a disorder that weakens bones.

She was immediately placed on a new FDA-approved medicine.

"Here we are just one year later at one year of age and you see a dramatic difference in the shape," said Dr. Jared Riley, a pediatric orthopedic surgeon at Rocky Mountain Hospital.

Before the medicine, 75% of all patients died by the age of five.

Now there is a 97% chance Payton will live a normal life.

"My baby was broken and that's what I needed God to do was a miracle," said Ahna.

One was also treated with bone fragments and cultured osteoblasts, which are bone-forming cells.

"Cultured" refers to cells that are grown under specific conditions outside of the natural environment (the body) and within a laboratory.

Both patients showed significant, but incomplete improvement, although no more formal studies have been conducted.

Then, the drug teriparatide (parathyroid hormone 1-34) has been given "off-label" to several adults with HPP with metatarsal stress fractures or femoral pseudo fractures, resulting in healing.

The drug is not permitted for use in children.

More research is necessary to determine the long-term safety and effectiveness of teriparatide in the treatment of HPP.

Every year eight million babies are born with genetic disorders passed down from generation to generation.

Payton will stay on the new medication for the next few years and then doctors will re-evaluate whether she needs to continue.

Payton's family didn't even know they carried the problematic HPP gene until an ultrasound revealed it in their unborn baby.

After being genetically tested, Payton's mother and grandfather are positive.

Neither one has ever suffered from weak or broken bones.

If this story has impacted your life or prompted you or someone you know to seek or change treatments, please let us know by contacting Jim Mertens at jim.mertens@wqad.com or Marjorie Bekaert Thomas atmthomas@ivanhoe.com.

Read the original:
YOUR HEALTH: Saving an unborn baby breaking apart in the womb - WQAD.com

Bone Marrow Stem Cells Comments Off on YOUR HEALTH: Saving an unborn baby breaking apart in the womb – WQAD.com | October 19th, 2020

Global Stem Cell Therapy Market was valued at USD 117.66 million in 2019 and is projected to reach USD 255.37 million by 2027, growing at a CAGR of 10.97% from 2020 to 2027.

For top companies in United States, European Union and China, this report investigates and analyzes the production, value, price, market share and growth rate for the top manufacturers, key data from 2020 to 2027.

The Stem Cell Therapy market report firstly introduced the basics: definitions, classifications, applications and market overview; product specifications; manufacturing processes; cost structures, raw materials and so on. Then it analyzed the worlds main region market conditions, including the product price, profit, capacity, production, supply, demand and market growth rate and forecast etc. In the end, the Stem Cell Therapy market report introduced new project SWOT analysis, investment feasibility analysis, and investment return analysis.

Get a Sample Copy of the Stem Cell Therapy Market Report with Latest Industry Trends @ https://www.verifiedmarketresearch.com/download-sample/?rid=24113

Competitive Analysis:

The competitive analysis covers key players and the innovations and business strategies undertaken by them. The report captures the best long term growth opportunities for the sector and includes the latest process and product developments. The report includes basic information of the companies along with their market position, historical background, and market capitalization and revenue. The report covers revenue figures, market growth rate, and gross profit margin of each player based on regional classification and overall market position. The report provides a separate analysis of the recent business strategies such as mergers, acquisitions, product launches, joint ventures, partnerships, and collaborations.

Key features of the Report:

Leading players of Stem Cell Therapy including:

You can Buy This Report from Here @ https://www.verifiedmarketresearch.com/select-licence/?rid=24113

Market Breakdown:

The market breakdown provides market segmentation data based on the availability of the data and information. The market is segmented on the basis of types and applications.

1.Stem Cell Therapy Market, By Cell Source:

Adipose Tissue-Derived Mesenchymal Stem Cells Bone Marrow-Derived Mesenchymal Stem Cells Cord Blood/Embryonic Stem Cells Other Cell Sources

2.Stem Cell Therapy Market, By Therapeutic Application:

Musculoskeletal Disorders Wounds and Injuries Cardiovascular Diseases Surgeries Gastrointestinal Diseases Other Applications

3.Stem Cell Therapy Market, By Type:

Allogeneic Stem Cell Therapy Market, By Application Musculoskeletal Disorders Wounds and Injuries Surgeries Acute Graft-Versus-Host Disease (AGVHD) Other Applications Autologous Stem Cell Therapy Market, By Application Cardiovascular Diseases Wounds and Injuries Gastrointestinal Diseases Other Applications

Request a discount on the report @ https://www.verifiedmarketresearch.com/ask-for-discount/?rid=24113

To understand the global Stem Cell Therapy market dynamics, the market is analyzed across major global regions and countries. Market Research Intellect provides customized specific regional and country-wise analysis of the key geographical regions as follows:

North America: USA, Canada, Mexico

Latin America: Argentina, Chile, Brazil, Peru, and Rest of Latin America

Europe:K., Germany, Spain, Italy, and Rest of EU

Asia-Pacific: India, China, Japan, South Korea, Australia, and Rest of APAC

Middle East & Africa: Saudi Arabia, South Africa, U.A.E., and Rest of MEA

The report considers:

Historical Years: 2017-2018

Base Year: 2019

Estimated Year: 2020

Forecast Years: 2020-2027

Benefits of Stem Cell Therapy Market Report:

Report Overview with TOC:

Browse the complete report Along with TOC @ https://www.verifiedmarketresearch.com/product/Stem-Cell-Therapy-Market/

Thank you for reading our report. Customization of the report is also available on the basis of region and countries. Kindly get in touch with us for more information regarding the report and its customization. Our team will ensure the report is best suited according to your needs.

About us:

Verified Market Research is a leading Global Research and Consulting firm servicing over 5000+ customers. Verified Market Research provides advanced analytical research solutions while offering information enriched research studies. We offer insight into strategic and growth analyses, Data necessary to achieve corporate goals, and critical revenue decisions.

Our 250 Analysts and SMEs offer a high level of expertise in data collection and governance use industrial techniques to collect and analyze data on more than 15,000 high impact and niche markets. Our analysts are trained to combine modern data collection techniques, superior research methodology, expertise, and years of collective experience to produce informative and accurate research.

Contact us:

Mr. Edwyne Fernandes

US: +1 (650)-781-4080UK: +44 (203)-411-9686APAC: +91 (902)-863-5784US Toll-Free: +1 (800)-7821768

Email: sales@verifiedmarketresearch.com

See the article here:
Stem Cell Therapy Market To Observe Exponential Growth By 2020-2027 | Verified Market Research - Stock Market Vista

Bone Marrow Stem Cells Comments Off on Stem Cell Therapy Market To Observe Exponential Growth By 2020-2027 | Verified Market Research – Stock Market Vista | October 19th, 2020

NEW YORK, Oct. 15, 2020 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of cellular therapies for neurodegenerative diseases, announced today financial results for the third quarter ended September 30, 2020, and provided a corporate update.

"The most important near-term event for BrainStorm will be the upcoming top-line data readout for the NurOwn Phase 3 trial in ALS, expected by the end of November. A successful outcome will set us on the path to filing a Biologic License Application (BLA) for what we believe will be a valuable new treatment for ALS," said Chaim Lebovits, Chief Executive Officer of BrainStorm Cell Therapeutics. "In parallel to our preparations for upcoming data read out, we are very busy planning and executing on other pre-BLA activities. On the management front, we appointed William K. White and Dr. Anthony Waclawski, adding valuable commercial and regulatory expertise to our leadership team. This expertise will be crucial as we work towards obtaining regulatory approval for NurOwn and ensuring that, if approved, it will be readily accessible to ALS patients in need of new treatment options for this devastating disease."

NurOwn has an innovative mechanism of action that is broadly applicable across neurodegenerative diseases and BrainStorm continues to invest in clinical trials evaluating the product in conditions beyond ALS to maximize value creation for its various stakeholders. The company remains on track to complete dosing in its Phase 2 clinical trial in progressive multiple sclerosis (PMS) by the end of 2020. In addition, the Company recently unveiled a clinical development program in Alzheimer's' disease (AD) and is planning a Phase 2 proof-of-concept clinical trial at several leading AD centers in the Netherlands and France.

Third Quarter 2020 and Recent Corporate Highlights:

Presented at the following Investor Conferences:

Cash and Liquidity as of October 14, 2020

Total available funding as of October 14, 2020, which includes cash, cash equivalents and short-term bank deposits of approximately $33.1 million as well as remaining non-dilutive funding from CIRM, IIA and other grants, amounts to approximately $36 million.

Financial Results for the Three Months Ended September 30, 2020

Conference Call & WebcastThursday, October 15, 2020 at 8 a.m. Eastern TimeFrom the US:877-407-9205International: 201-689-8054Webcast:https://www.webcaster4.com/Webcast/Page/2354/37811

Replays, available through October 29, 2020From the US:877-481-4010International: 919-882-2331Replay Passcode: 37811

About NurOwn

NurOwn (autologous MSC-NTF) cells represent a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. BrainStorm has fully enrolled a Phase 3 pivotal trial of autologous MSC-NTF cells for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm also recently received acceptance from theU.S. Food and Drug Administration(FDA) to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS) and completed enrollment inAugust 2020.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc.is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug status designation from theU.S. Food and Drug Administration(FDA) and theEuropean Medicines Agency(EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has fully enrolled a Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at sixU.S.sites supported by a grant from theCalifornia Institute for Regenerative Medicine(CIRM CLIN2-0989). The pivotal study is intended to support a filing forU.S.FDA approval of autologous MSC-NTF cells in ALS. BrainStorm also recently receivedU.S.FDA clearance to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS). The Phase 2 study of autologous MSC-NTF cells in patients with progressive MS (NCT03799718) completed enrollment inAugust 2020. For more information, visit the company's website atwww.brainstorm-cell.com.

Safe-Harbor Statement

Statements in this announcement other than historical data and information, including statements regarding future clinical trial enrollment and data, constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may", "should", "would", "could", "will", "expect", "likely", "believe", "plan", "estimate", "predict", "potential", and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorm's need to raise additional capital, BrainStorm's ability to continue as a going concern, regulatory approval of BrainStorm's NurOwn treatment candidate, the success of BrainStorm's product development programs and research, regulatory and personnel issues, development of a global market for our services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorm's NurOwn treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorm's ability to manufacture and commercialize the NurOwn treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorm's ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation,; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available athttp://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

ContactsInvestor Relations:Corey Davis, Ph.D.LifeSci Advisors, LLCPhone: +1 646-465-1138[emailprotected]

Media:Paul TyahlaSmithSolvePhone: + 1.973.713.3768[emailprotected]

BRAINSTORM CELL THERAPEUTICS INC. AND SUBSIDIARIESINTERIM CONDENSED CONSOLIDATED BALANCE SHEETSU.S. dollars in thousands(Except share data)

September30,

December31,

2020

2019

U.S.$ inthousands

Unaudited

Audited

ASSETS

Current Assets:

Cash and cash equivalents

$

24,770

$

536

Short-term deposit (Note 4)

4,038

33

Other accounts receivable

1,473

2,359

Prepaid expenses and other current assets (Note 5)

56

432

Total current assets

30,337

3,360

Long-Term Assets:

Prepaid expenses and other long-term assets

27

32

Operating lease right of use asset (Note 6)

1,377

2,182

Property and Equipment, Net

950

960

Total Long-Term Assets

2,354

3,174

Total assets

$

32,691

$

6,534

LIABILITIES AND STOCKHOLDERS' EQUITY (DEFICIT)

Current Liabilities:

Accounts payable

$

3,283

$

14,677

Accrued expenses

917

1,000

Operating lease liability (Note 6)

1,216

1,263

Other accounts payable

1,013

714

Total current liabilities

6,429

17,654

Long-Term Liabilities:

Operating lease liability (Note 6)

284

1,103

Total long-term liabilities

284

1,103

Total liabilities

$

6,713

$

18,757

Stockholders' Equity (deficit):

Stock capital: (Note 7)

12

11

Common Stock of $0.00005 par value - Authorized: 100,000,000 shares at September 30, 2020 and December 31, 2019 respectively; Issued and outstanding: 31,567,592 and 23,174,228 shares at September 30,2020 and December31,2019 respectively.

The rest is here:
BrainStorm Announces Financial Results for the Third Quarter of 2020 and Provides a Corporate Update - PRNewswire

Bone Marrow Stem Cells Comments Off on BrainStorm Announces Financial Results for the Third Quarter of 2020 and Provides a Corporate Update – PRNewswire | October 19th, 2020

India just conducted its first successful experiment with savior sibling therapy, in which a baby was conceived through in-vitro fertilization for the purposes of donating bone marrow to an older ailing brother struggling with thalassemia, a condition characterized by low levels of hemoglobin in the blood that requires frequent blood transfusions. While the doctors involved in the therapy celebrated their success this week, some on social media challenged the ethics of such a therapy, in which a baby was essentially birthed to save her sibling.

In this case, the child with the genetic disorder needed a bone marrow transplant to cure his disease, and the chances of a successful cure are higher if coming from a person whose proteins (human leukocyte antigens, or HLA) exactly match those of the child. None of the childs existing family members was a match, further complicating the process of getting a bone marrow transplant an already difficult process to execute. The parents, in an effort to create a perfect bone marrow match for their child, underwent three cycles of in-vitro fertilization, out of which 18 embryos were created, and one perfectly matched that of the child, and was disease-free, using a technique called pre-implantation genetic diagnosis (PGD). The embryo was then implanted in the mothers uterus, carried to term, and a baby girl was born.

We had to wait for the baby to grow. She had to weigh 10 kg before we could draw bone marrow, Deepa Trivedi, program director of Sankalp Bone Marrow Unit in Ahmedabad, told The Hindu. Its been approximately seven months since the transplant, and the older sibling has not needed any more blood transfusions, indicating he has been cured of his thalassemia, his doctors announced.

Savior sibling therapy has already been used in countries such as the United Kingdom, the U.S.A., New Zealand, and France. Its mainly used to cure genetic blood disorders in children, such as sickle cell anemia or as seen in the Indian case, thalassemia major. The main way this is done, which is a departure from the Indian case, is by harvesting stem cells from a newborns umbilical cord, which are then injected into the bone marrow of the sibling with the disease, a practice that works 90% of the time. In case it doesnt, doctors can take bone marrow from the savior sibling as they grow, in a process that is painful but not known to be dangerous.

Related on The Swaddle:

Designer Babies Are Far From Reality, Even After the Gene-Edited Babies in China

The first ethical concern with this practice is treating a baby as a source for spare parts, as a means to an end, as a commodity. A study of the bioethics of savior sibling therapy, published in the Journal of Medical Ethics, surmised that treating a baby as a means to an end was not by itself a concern that devalued the utility of savior sibling therapy, as long as theyre also treated as human beings. Bioethicists surmise that using cord blood, something that is frequently discarded after birth, cannot endanger a newborn, or prove to be an ethical quandary used against the therapy.

But what has happened in the most recent case in India actually complicates the issue, because its not the umbilical cord blood that was harvested from the savior sibling at birth, but bone marrow 10 months into her life, which makes her an organ donor. This traverses thorny territory, as governments strictly regulate organ donation by minors due to issues related to consent. Can a baby consent to donating bone marrow to their sibling, or a 10-year-old consent to donating a kidney to their parent? It depends on where the individual resides, and how old the person being asked to donate is. In India, for example, it was only recently that the Delhi High Court ruled that minors could donate organs or tissues, as long as the procedure didnt pose a danger to their lives, and only in exceptional circumstances. However, where minors are mostly dependent upon their families, an element of coercion can also manifest. Also, determining whether a child rationally consented to donate an organ to their parent, for example, becomes difficult when we factor in the emotional element of their relationship that can perhaps override their judgments about their own safety.

Another concern is the well-being of the savior sibling throughout their life, both physical and psychological. Whats to stop a parent from asking the savior sibling to be on standby for their entire lives for their siblings health, available to be tapped for tissues and organs at any point in their lives? This is the plot of Jodi Picoults My Sisters Keeper (also turned into a film of the same name starring Cameron Diaz), but it is an unlikely scenario in real life, ethics experts have said. The aforementioned organ donation rules can prevent such an exploitative situation from arising, they say, with governments around the world tasked with ensuring the consent of the donor remains at the forefront of organ donation.

The third issue with savior sibling therapy arises out of the process itself if a parent can select an embryo that perfectly matches their child, whats to stop them from selecting an embryo for intelligence, or athleticism? This wades into the territory of the production of designer babies, which is an ethical slippery slope that critics have said goes against the natural reproductive order. However, the bioethics study asserts that the connection between savior sibling therapy and the production of designer babies is less of a slippery slope and more of a reach, as the technology might be similar, but the utility of both poles apart the former is used to save childrens lives, while the latter is a superficial, hypothetical fantasy.

For now, the world of savior sibling therapy, and its perception, remains similar to when parents first selected an embryo to create a savior sibling in the U.S. in 2000. As appeared in a New York Times article at the time, It is the kind of talk heard with every scientific breakthrough, from the first heart transplant to the first cloned sheep. We talk like this because we are both exhilarated and terrified by what we can do, and we wonder, with each step, whether we have gone too far. But though society may ask, How could you? the only question patients and families ask is, How could we not? 20 years later, savior sibling therapy still centers the children that can be saved, while government stipulations around the world try to ensure the savior siblings are protected, cared for, and treated as human beings, like any other child.

While a few critics argue for a ban, the bioethics study sums up the dilemma, and perhaps a solution to this ethical debate given that a ban will be fatal for a section of the population, the onus of proof rests clearly with the prohibitionists who must demonstrate that these childrens deaths are less terrible than the consequences of allowing this particular use of PGD.

You have got to have a very powerful reason to resist the means by which a childs life can be saved.

Read more:
An Indian Baby 'Savior Sibling' Just Gave Her Brother Bone Marrow. But Is It Ethical? - The Swaddle

Bone Marrow Stem Cells Comments Off on An Indian Baby ‘Savior Sibling’ Just Gave Her Brother Bone Marrow. But Is It Ethical? – The Swaddle | October 17th, 2020

A one-year-old girl donated her bone marrow to her brother. (Representational)

A one-year-old girl, conceived by her parents through IVF technology specifically for the purpose of donating her bone marrow to their thalassemic son, has succeeded in saving her six-year-old brother's life.

Baby Kavya was born a year ago through In-Vitro Fertilisation (IVF) technique in Ahmedabad, under the concept known as "saviour sibling".

Her bone marrow was successfully transplanted to her brother Abhijeet Solanki in March this year and the boy is now "risk-free", doctors said on Thursday.

Abhijeet, the second child of Sahdev Singh Solanki and Alpa Solanki, was diagnosed with Thalassemia-major, a blood disorder, and was dependent on blood transfusion every month, they said.

Thalassemia-major patients require frequent blood transfusions and their life expectancy is also less.

His parents were advised bone marrow transplant as the last resort to treat the child, but they could not find the required HLA (human leukocyte antigen) match.

"Due to unavailability of matching HLA donors for the transplant, we opted for IVF with HLA matching," city-based Nova IVF Fertility's medical director Dr Manish Banker told PTI.

This process of HLA typing is an established method for conceiving a child, who may donate cord blood or hematopoietic stem cells for transplantation to save a sibling with a critical illness.

Abhijeet's father approached Mr Banker after he found that the bone marrow of his family members, including the boy's elder sister, was not matching.

"Bone marrow transplant from an HLA-identical donor is the best therapeutic option for thalassemia major patients. We took the challenge and created a healthy savior sibling to save her elder brother," Mr Banker said.

With the help of IVF, Abhijeet's mother delivered a healthy baby girl Kavya a year ago, who was found to be the HLA match for the sibling.

In March this year, after Kavya gained the required weight, a successful bone marrow transplant was done for Abhijeet at the CIMS Hospital, Mr Banker said.

"Now, Abhijeet is risk-free and doesn't require blood transfusion," Mr Banker said.

"This is the first case in India when an HLA matching baby was born through IVF specifically to save the thalassemia-major sibling," he said.

The siblings' father, who himself researched well about this technique, thanked Mr Banker and other expert doctorsfor saving his son.

Go here to read the rest:
Child Conceived To Donate Bone Marrow Saves 6-Year-Old Brother's Life - NDTV

Bone Marrow Stem Cells Comments Off on Child Conceived To Donate Bone Marrow Saves 6-Year-Old Brother’s Life – NDTV | October 17th, 2020

Cecelia Ahern, the author of P.S. I love you, once beautifully said: Moments are precious; sometimes they linger and other times theyre fleeting, and yet so much could be done in them; you could change a mind, you could save a life and you could even fall in love.

Helping save lives is what we decided to dedicate some of our lives to at Manchester Marrow.More specifically, we are the student-ran arm of the charity Anthony Nolan, which signs up students/young people (aged 16-30 years) to the stem cell register. This is required in finding matches for patients suffering from blood cancers and blood disorders who desperately need transplants. The more people we sign up for this register, the higher the chance of finding a blood stem cell or bone marrow match.

Anthony Nolan was initially founded by Shirley Nolan in 1974, realising the hardships associated with requiring an urgent bone marrow transplant. This was due to her three-year-old son suffering from a rare blood disorder known as Wiskott-Aldrich Syndrome. This inspired her to set up the worlds first register to match donors with people in desperate need. Today, there are over 800,000 people on Anthony Nolans UK register list, and each of these people could be a potential donor and save a life.

Although there are many resources at hand, without you, theres no cure! In Marrow, we have three important missions: raise awareness of Anthony Nolan and blood cancer within UK universities through our events, encourage every student to join stem cell register through our donor recruitment opportunities, and lastly, raise funds to help support this vital work.

As a student, in addition to signing up to the register, you have the amazing opportunity of volunteering for us and to save a life! One of our most outstanding achievements is signing up over 100,000 people to the Anthony Nolan register and raising over 92,000 in a year. Additionally, 1 in 4 people who go on to donate stem cells is recruited via Marrow!

Being a volunteer for us is no hard work. You could do many things, including spreading the word and talking to people about why they should sign up to the register. Furthermore, you need to inform them what the donation involves if they ever found a match, checking medical backgrounds for donor eligibility, assisting them with cheek swabs, and filling out an application form.

If youre interested in this opportunity, there will be several volunteer training sessions held throughout the year. Unfortunately, due to the current situation, all these events will be held online. We can assure you, however, that were doing our best to make the most of it.

To sign up to the register visit the Anthony Nolan website!

Make sure to follow Manchester Marrows social media accounts to keep updated with all the news and events:

Facebook: @ManchesterMarrow

Facebook: Manchester Marrow Volunteers Group

Instagram: @manchestermarrow

Original post:
Looking to save lives? Here's how - The Mancunion

Bone Marrow Stem Cells Comments Off on Looking to save lives? Here’s how – The Mancunion | October 17th, 2020

DetailsCategory: DNA RNA and CellsPublished on Friday, 16 October 2020 14:20Hits: 301

First therapy recommended for full marketing authorization in the EU for eligible patients with confirmed diagnosis of late infantile or early juvenile MLD variants

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

Libmeldy is backed by data across 35 patients with follow-up of up to 8 years post-treatment, demonstrating the potential durability of HSC gene therapy

BOSTON, MA, USA and LONDON, UK I October 16, 2020 I Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending full, or standard, marketing authorization for Libmeldy (cryopreserved autologous CD34+ cells encoding the arylsulfatase-A, or ARSA, gene), an investigational gene therapy for the treatment of metachromatic leukodystrophy (MLD), characterized by biallelic mutations in the ARSA gene leading to a reduction of the ARSA enzymatic activity in children with i) late infantile or early juvenile forms, without clinical manifestations of the disease, or ii) the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline.

The CHMPs positive opinion will now be reviewed by theEuropean Commission(EC), which has the authority to grant marketing authorization for Libmeldy in theEuropean Union(EU). A final decision by the EC for Libmeldy is anticipated before the end of 2020. If approved, Libmeldy would be the first commercial therapy and first gene therapy for eligible patients with early-onset MLD.

MLD is a very rare, severe genetic condition caused by mutations in the ARSA gene which lead to neurological damage and developmental regression. In its most severe and common forms, young children rapidly lose the ability to walk, talk and interact with the world around them. A majority of these patients pass away in childhood, with palliative care often as their only option.

Todays positive CHMP opinion for marketing authorization of Libmeldy is a remarkable achievement that we share with the MLD community, as it brings us closer to delivering a one-time, potentially transformative therapy for eligible children suffering from this devastating disease, said Bobby Gaspar, M.D., Ph.D., chief executive officer, Orchard Therapeutics. Data from the Libmeldy clinical program have demonstrated the potential for long-term positive effects on cognitive development and maintenance of motor function, translating to individual preservation of motor milestones such as the ability to sit, stand and/or walk without support, as well as attainment of cognitive skills like social interactions and school attendance, at ages at which untreated patients show severe motor and cognitive impairments.

Libmeldy is designed as a one-time gene therapy, developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy, in which the patients own hematopoietic stem cells (HSCs) are selected, and functional copies of the ARSA gene are inserted into the genome of the HSCs using a lentiviral vector before these genetically modified cells are infused back into the patient. The ability of the gene-corrected HSCs to migrate across the blood-brain barrier into the brain, engraft, and express the functional enzyme has the potential to persistently correct the underlying genetic condition with a single treatment.

This is an important milestone toward making the availability of HSC gene therapy a reality for more patients, and it also is extremely rewarding for our multi-disciplinary team at SR-Tiget who has worked relentlessly along this 15-year journey to move the seminal proof of principle studies to the first in-human testing of this therapy, said SR-Tiget director Luigi Naldini, M.D, Ph.D. The robust and durable clinical benefits observed in early-onset MLD patients who received HSC gene therapy are compelling, especially when compared to the natural history of the disease. These results also further illustrate our view that the HSC gene therapy approach has the potential to deliver transformative effects in other storage diseases as well, especially when the cells are designed to overexpress the functional enzyme and provide an enhanced supply of it to the affected tissues.

As a parent, watching your child start down a seemingly normal developmental path only to suddenly and rapidly lose some or all of his or her abilities is heart-wrenching, and the agony is even more acute knowing no approved therapies currently exist for MLD, said Georgina Morton, Chair of ArchAngel MLD Trust. Todays decision to advance Libmeldy to the final EC approval stage represents a huge step forward for the parents of these young children and for all of us in the MLD community.

We are extremely appreciative of the EMAs expedited and thorough review of Libmeldys marketing authorization application, considering the severity of MLD coupled with the limited treatment options available today for young patients, said Anne Dupraz, chief regulatory officer, Orchard Therapeutics. The Agencys collaboration on this assessment is a testament to their broader public health commitment to ensure timely evaluation of new medicines for diseases where a pressing unmet need exists.

Data Supporting the Clinical Profile of Libmeldy

The positive CHMP opinion is supported by clinical studies of Libmeldy in both pre- and early- symptomatic, early-onset MLD patients. Early-onset MLD encompasses the disease variants traditionally referred to as late infantile (LI) and early juvenile (EJ).

Clinical efficacy was based on the integrated analysis of results from 29 patients with early-onset MLD who were all treated with Libmeldy prepared as a fresh (non-cryopreserved) formulation:

Clinical safety was evaluated in 35 patients with early-onset MLD:

Co-primary endpointsThe co-primary endpoints of the integrated efficacy analysis were Gross Motor Function Measure (GMFM) total score and ARSA activity, both evaluated at 2 years post-treatment. Results of this analysis indicate that a single-dose intravenous administration of Libmeldy is effective in modifying the disease course of early-onset MLD in most patients.

Pre-symptomatic LI and EJ patients treated with Libmeldy experienced significantly less deterioration in motor function at 2 years and 3 years post-treatment, as measured by GMFM total score, compared to age and disease subtype-matched untreated patients (p0.008). The mean difference between treated pre-symptomatic LI patients and age-matched untreated LI patients was 71.0% at year 2 and 79.8% at year 3. Similarly, the mean difference between treated pre-symptomatic EJ patients and age-matched untreated EJ patients was 52.4% at year 2 and 74.9% at year 3. Although not statistically significant, a clear difference in GMFM total score was also noted between treated early-symptomatic EJ patients and age-matched untreated EJ patients (28.7% at year 2; p=0.350 and 43.9% at year 3; p=0.054).

A statistically significant increase in ARSA activity in peripheral blood mononuclear cells was observed at 2 years post-treatment compared to pre-treatment in both pre-symptomatic patients (20.0-fold increase; p<0.001) and early-symptomatic patients (4.2-fold increase; p=0.004).

At the time of the integrated data analysis, all treated LI patients were alive with a follow-up post-treatment up to 7.5 years and 10 out of 13 treated EJ patients were alive with a follow-up post-treatment of up to 6.5 years. No treatment-related mortality has been reported in patients treated with Libmeldy.

Key secondary endpointsFor EJ patients who were early-symptomatic when treated with Libmeldy, meaningful effects on motor development were demonstrated when these patients were treated before entering the rapidly progressive phase of the disease (IQ85 and Gross Motor Function Classification (GMFC)1). By 4 years post-disease onset, an estimated 62.5% of treated, early-symptomatic EJ MLD patients survived and maintained locomotion and ability to sit without support compared with 26.3% of untreated early-symptomatic EJ MLD patients, representing a delay in disease progression following treatment with Libmeldy.

A secondary efficacy endpoint that measured cognitive and language abilities as quantified by Intelligence Quotient/Development Quotient (IQ/DQ) found:

Clinical safetySafety data indicate that Libmeldy was generally well-tolerated. The most common adverse reaction attributed to treatment with Libmeldy was the occurrence of anti-ARSA antibodies (AAA) reported in 5 out of 35 patients. Antibody titers in all 5 patients were generally low and no negative effects were observed in post-treatment ARSA activity in the peripheral blood or bone marrow cellular subpopulations, nor in the ARSA activity within the cerebrospinal fluid. Treatment with Libmeldy is preceded by other medical interventions, namely bone marrow harvest or peripheral blood mobilization and apheresis, followed by myeloablative conditioning, which carry their own risks. During the clinical studies, the safety profiles of these interventions were consistent with their known safety and tolerability.

About MLD and Investigational Libmeldy

Metachromatic leukodystrophy (MLD) is a rare and life-threatening inherited disease of the bodys metabolic system occurring in approximately one in every 100,000 live births. MLD is caused by a mutation in thearylsulfatase-A(ARSA) gene that results in the accumulation of sulfatides in the brain and other areas of the body, including the liver, gallbladder, kidneys, and/or spleen. Over time, the nervous system is damaged, leading to neurological problems such as motor, behavioral and cognitive regression, severe spasticity and seizures. Patients with MLD gradually lose the ability to move, talk, swallow, eat and see. Currently, there are no approved treatments for MLD. In its late infantile form, mortality at 5 years from onset is estimated at 50% and 44% at 10 years for juvenile patients.1Libmeldy (autologous CD34+ cell enriched population that contains hematopoietic stem and progenitor cells (HSPC) transduced ex vivo using a lentiviral vector encoding the human arylsulfatase-A (ARSA) gene), formerly OTL-200, is being studied for the treatment of MLD in certain patients. Libmeldy was acquired from GSK inApril 2018and originated from a pioneering collaboration between GSK and the Hospital San Raffaele and Fondazione Telethon, acting through their jointSan Raffaele-Telethon Institute for Gene TherapyinMilan, initiated in 2010.

About Orchard

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

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

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

SOURCE: Orchard Therapeutics

Originally posted here:
Orchard Therapeutics Receives Positive CHMP Opinion for Libmeldy for the Treatment of Early-Onset Metachromatic Leukodystrophy (MLD) | DNA RNA and...

Bone Marrow Stem Cells Comments Off on Orchard Therapeutics Receives Positive CHMP Opinion for Libmeldy for the Treatment of Early-Onset Metachromatic Leukodystrophy (MLD) | DNA RNA and… | October 17th, 2020

Gosselies, Belgium, 14 October 2020, 7am CEST BONE THERAPEUTICS(Euronext Brussels and Paris: BOTHE), the cell therapy company addressing unmet medical needs in orthopedics and other diseases, today announces positive 24-month follow-up results for the Phase IIa study with the allogeneic cell therapy product, ALLOB, in patients undergoing lumbar spinal fusion procedures.

The 24-month data show a high percentage of successful lumbar vertebrae fusion of 90%. Patients also continue to experience important clinical improvements in function and pain, from as early as six months after treatment, up to the 24-month follow-up period.

Degenerative spine disorders have a major impact on the quality of life of patients. These impacts include decreases in the stability of the spine and pain in motion,said Dr. Alphonse Lubansu, M.D., Head of the Spinal Clinic, Erasme University Hospital, Universit libre de Bruxelles. The 24 month follow-up data of this Phase IIa clinical trial have demonstrated that patients treated with ALLOB in spinal fusion procedure show a high incidence in fusion, and benefit from a sustained, clinically meaningful improvement in function and pain throughout the 24 months following treatment together with a good safety profile. These results show that ALLOB in combination with the standard spine fusion surgery could be a promising treatment option to address the currently unmet needs of these patients.

This positive data forlumbar spinal fusion complementsthe strong Phase I/IIa results from ALLOB in patients with delayed union fractures,said Miguel Forte, MD, PhD, Chief Executive Officer of Bone Therapeutics. These studies provide promising clinical evidence for the potential ofBone Therapeuticsunique allogeneic cell therapy platform to address high unmet medical needs in orthopaedics and bone related disorders. We will now hold discussions with global regulators and our partners to explore a variety of options for the next stages of clinical development for ALLOB in different orthopedic indications, while pursuing the phase IIb study of ALLOB in difficult tibial fractures.In addition, theclinical results provide further evidence for the expansion of ALLOB and our platform of differentiated MSCs to other indications.

The multi-center, open-label proof-of-concept Phase IIa study was designed to evaluate the safety and efficacy of ALLOB administered, procedure in which an interbody cage with bioceramic granules mixed with ALLOB is implanted into the spine to achieve fusion of the lumbar vertebrae. The main endpoints of the 24-month follow-up analysis included safety and radiological assessments to evaluate vertebrae fusion (continuous bone bridges) and clinical assessments to evaluate improvement in patients functional disability as well as reduction in back and leg pain. The study evaluated 30 patients treated with ALLOB, 29 patients attended the 24-month visit.

Radiological data was collected from CT-scans at 24 months and assessed by three external readers. It showed a successful fusion of the lumbar vertebrae in 27 out of 30 patients (90%). In addition, the remaining 3 patients showed radiological evidence of bone formation. Treatment with ALLOB also resulted in a clear and statistically significant clinical improvement in function and reduction in pain over the 24-month follow-up period. Functional disability improved from the pre-treatment baseline to 24-month by a mean score of 60% (p<0.001) on the Oswestry Disability Index(1). Back and leg pain were strongly reduced by 57 to 62% (p<0.001) and 68 to 70% (p<0.001) respectively compared to pre-treatment baseline. Treatment with ALLOB was generally well-tolerated by the patients, consistent with previous reported results.

(1)The Oswestry Disability Index (ODI) is an index derived from the Oswestry Low Back Pain Questionnaire used by clinicians and researchers to measure a patients permanent functional disability. This validated questionnaire was first published by Jeremy Fairbank et al. in Physiotherapy in 1980. ODI score of 0%-20%: minimal disability; 21%-40%: moderate disability; 41%-60%: severe disability; 61%-80%: crippled; 81%-100%: bed bound.

About Spinal Fusion

Due to ageing populations and sedentary lifestyles, the number of people suffering from degenerative spine disorders continues to increase. Today, spinal fusion procedures are performed to relieve pain and improve patient daily functioning in a broad spectrum of degenerative spine disorders. Spinal fusion consists of bridging two or more vertebrae with the use of a cage and graft material, traditionally autologous bone graft or demineralised bone matrix placed into the intervertebral space for fusing an unstable portion of the spine and immobilizing a painful intervertebral motion segment. Over 1,000,000 spinal fusion procedures are performed annually in the US and EU, of which half at lumbar level and the market is growing at a rate of 5% per year. Although spinal fusion surgery is routine, non-fusion, slow progression to fusion and failure to eliminate pain are still frequent with up to 35% of patients not being satisfied with their surgery.

About ALLOB

ALLOB is the Companys off-the-shelf allogeneic cell therapy platform consisting of human allogeneic bone-forming cells derived from cultured bone marrow mesenchymal stem cells (MSC) from healthy adult donors, offering numerous advantages in product quality, injectable quantity, production, logistics and cost as compared to an autologous approach. To address critical factors for the development and commercialisation of cell therapy products, Bone Therapeutics has established a proprietary, optimised production process that improves consistency, scalability, cost effectiveness and ease of use of ALLOB. This optimized production process significantly increases the production yield, generating 100,000 of doses of ALLOB per bone marrow donation. Additionally, the final ALLOB product will be cryopreserved, enabling easy shipment and the capability to be stored in a frozen form at the hospital level. The process will therefore substantially reduce overall production costs, simplify supply chain logistics, improve patient accessibility and facilitate global commercialisation. The Company will implement the optimized production process for all future clinical trials with ALLOB.

About Bone Therapeutics

Bone Therapeutics is a leading biotech company focused on the development of innovative products to address high unmet needs in orthopedics and other diseases. The Company has a, diversified portfolio of cell and biologic therapies at different stages ranging from pre-clinical programs in immunomodulation to mid-to-late stage clinical development for orthopedic conditions, targeting markets with large unmet medical needs and limited innovation.

Bone Therapeutics is developing an off-the-shelf next-generation improved viscosupplement, JTA-004, which is currently in phase III development for the treatment of pain in knee osteoarthritis. Consisting of a unique combination of plasma proteins, hyaluronic acid a natural component of knee synovial fluid, and a fast-acting analgesic, JTA-004 intends to provide added lubrication and protection to the cartilage of the arthritic joint and to alleviate osteoarthritic pain and inflammation. Positive phase IIb efficacy results in patients with knee osteoarthritis showed a statistically significant improvement in pain relief compared to a leading viscosupplement.

Bone Therapeutics core technology is based on its cutting-edge allogeneic cell therapy platform with differentiated bone marrow sourced Mesenchymal Stromal Cells (MSCs) which can be stored at the point of use in the hospital. Currently in pre-clinical development, BT-20, the most recent product candidate from this technology, targets inflammatory conditions, while the leading investigational medicinal product, ALLOB, represents a unique, proprietary approach to bone regeneration, which turns undifferentiated stromal cells from healthy donors into bone-forming cells. These cells are produced via the Bone Therapeutics scalable manufacturing process. Following the CTA approval by regulatory authorities in Europe, the Company is ready to start the phase IIb clinical trial with ALLOB in patients with difficult tibial fractures, using its optimized production process. ALLOB continues to be evaluated for other orthopedic indications including spinal fusion, osteotomy, maxillofacial and dental.

Bone Therapeutics cell therapy products are manufactured to the highest GMP standards and are protected by a broad IP (Intellectual Property) portfolio covering ten patent families as well as knowhow. The Company is based in the BioPark in Gosselies, Belgium. Further information is available atwww.bonetherapeutics.com.

For further information, please contact:

Bone Therapeutics SAMiguel Forte, MD, PhD, Chief Executive OfficerJean-Luc Vandebroek, Chief Financial OfficerTel: +32 (0)71 12 10 00investorrelations@bonetherapeutics.com

For Belgian Media and Investor Enquiries:BepublicCatherine HaquenneTel: +32 (0)497 75 63 56catherine@bepublic.be

International Media Enquiries:Image Box CommunicationsNeil Hunter / Michelle BoxallTel: +44 (0)20 8943 4685neil.hunter@ibcomms.agency / michelle@ibcomms.agency

For French Media and Investor Enquiries:NewCap Investor Relations & Financial CommunicationsPierre Laurent, Louis-Victor Delouvrier and Arthur RouillTel: +33 (0)1 44 71 94 94bone@newcap.eu

For US Media and Investor Enquiries:LHA Investor RelationsYvonne BriggsTel: +1 310 691 7100ybriggs@lhai.com

Certain statements, beliefs and opinions in this press release are forward-looking, which reflect the Company or, as appropriate, the Company directors current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its subsidiary undertakings or any such persons officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.

Originally posted here:
Bone Therapeutics' allogeneic cell therapy product, ALLOB, shows 90% fusion rate at 24 months in Phase IIa study in lumbar spinal fusion -...

Bone Marrow Stem Cells Comments Off on Bone Therapeutics’ allogeneic cell therapy product, ALLOB, shows 90% fusion rate at 24 months in Phase IIa study in lumbar spinal fusion -… | October 16th, 2020

Every 20 minutes someone in the UK is diagnosed with blood cancer and the register of stem cell donors who are needed to save thousands of patients lives does not currently meet the demand. Only 1 in 3 patients will find a donor match within their family and so every year over 2,000 people in the UK are left searching for a matching blood stem cell donor each year.

Blood cancer patients from Black, Asian or minority ethnicity groups face lower survival odds due to the lack ofdonordiversity. These patients have just a 20% chance of finding the best possible stem cell donor match, compared to 69% for northern European backgrounds.

This is due in part to the low numbers of donors registered from those Black, Asian or ethnic minority backgrounds. Donors from minority ethnic backgrounds make up just 13.1% of the UK stem cell register and because Black, Asian or ethnic minority patients tend to have more varied tissue meaning there is an even more specific biological requirement needed of a donor than for a white patient.

The global pandemic has made this situation even worse. Only 2% of stem cell registrations with DKMS came from black people during lockdown, falling by 20% compared to the same time the previous year.

Vaughn Scott is a patient who received a lifesaving donation from a stranger.

Vaughn Scott (34 years old) lives in Bristol and is grateful to the generous stranger who helped save his life. Theyve given him more time with his two children and the chance to marry his now wife last summer in a beautiful ceremony. Vaughn was incredibly fit and active, playing all kinds of sports and serving in the Navy. It was whilst on deployment across the world that he was urgently flown back to the UK and shockingly diagnosed with acute lymphoblastic leukaemia (ALL).

Vaughn said:

Hearing the diagnosis was the biggest blow Ive ever heard. My mind raced straight to my children and partner. When we learnt there was a way I could go into remission, I was excited that there was a way I could get better but very nervous too. With no family members as a match, all my faith was in a complete stranger that may have registered as a potential stem cell donor. Thankfully my match was found, Im now married and enjoying life with my family and Im so grateful. So many people arent as lucky as me. If you can, please register and give other people the second chance at life that I have been given.

To request a swab kit and register as a potential donor click HERE.

About blood cancer

Blood cancer is the third most common cause of cancer death in the UK but there is a lot of fear around stem cell donation of the process itself and of having a depleted supply of stem cells. This isnt the case. After donation, stem cells regenerate within 2 weeks so the donor wont lose anything. Blood stem cell donation is easy to do and similar to blood donation. Around 90% of all donations are made through a method called peripheral blood stem cell (PBSC). In this method, blood is taken from one of the donors arms and a machine extracts the blood stem cells from it. The donors blood is then returned to them through their other arm. This is an outpatient procedure that is usually completed in 4-6 hours. In just 10% of cases, donations are made through bone marrow collection. This is under general anaesthetic so that no pain is experienced.

More:
Black History Month The struggle to find a lifesaving stem cell donor - Keep the Faith

Bone Marrow Stem Cells Comments Off on Black History Month The struggle to find a lifesaving stem cell donor – Keep the Faith | October 16th, 2020

Indias first saviour sibling experiment is a success, say doctors.

A one-year-old sibling has saved her brothers life by donating her bone marrow. Kavya was conceived by her parents through invitro fertilisation to save her brother, Abhijeet Solanki, who was born with Thalassemia.

Thalassemia is a disorder where the haemoglobin count is low in blood and such persons require frequent blood transfusions.

Abhijeet was born in November 2013 but unlike normal babies he did not achieve the growth milestones. The parents learned that Abhijeet had Thalassemia major. Abhijeet required blood transfusions every 25 days and the gap between two transfusions reduced as he grew. By the age of six Abhijeet had undergone 80 transfusions, recalled his father Sahdev Singh Solanki. The only way to save him was through a bone marrow transplant.

The family was willing to donate their bone marrow but the human leukocyte antigen (HLA) of the family, including that of his older sister, did not match.

The Solanki family consulted many doctors. Mr. Solankis research led him to the saviour sibling concept following which he sought out Manish Banker, medical director of Nova IVF Fertility in Ahmedabad.

Dr. Banker said Mr. Solankis research and the science behind it was known but nobody had approached him with such a request before.

Dr. Banker started the assisted reproductive therapy, called pre-implantation genetic testing, for monogenic disorder with HLA matching. The couple underwent three cycles of IVF and 18 embryos were created. Of this only one perfectly matched Abhijeets HLA. The embryo was implanted in Apla Solanki, who delivered a baby girl a year ago.

We had to wait for the baby to grow. She had to weigh 10 kg before we could draw bone marrow, said Deepa Trivedi, programme director of Sankalp Bone Marrow Unit, CIMS Hospital, Ahmedabad.

Pointing out that the best therapeutic option for Thalassemia major patients is bone marrow transplant from an HLA-identical donor, Dr. Banker said, We are extremely thrilled to be part of reproductive history in India to create the first-ever saviour-sibling through ART. We used pre-genetic diagnosis and screening test, an established method for conceiving a child who may donate cord blood or hematopoietic stem cells for transplantation to save a critically ill sibling.

Mr. Solanki said the transplant was done on March 17. Since then Abhijeet has not needed any blood transfusion, indicating that he had been cured of the disorder. His haemoglobin count was 11.3, Dr. Trivedi said.

Read more:
A sister born to save ailing brother - The Hindu

Bone Marrow Stem Cells Comments Off on A sister born to save ailing brother – The Hindu | October 16th, 2020

Building on the transformative impetus from the first Food and Drug Administration (FDA)-approved Janus kinase (JAK) 1/2 inhibitor, ruxolitinib (Jakafi), in the clinical landscape of myeloproliferative neoplasms (MPNs), we are entering a new era of multiple JAK inhibitors and other diverse classes of drugs in rapid clinical development. Advancements in elucidating the pathophysiology of MPNs have spurred significant progress in developing novel promising agents or combination regimens with ruxolitinib to treat patients who are unresponsive to standard treatments or have specific clinical needs.

In myelofibrosis (MF), the most aggressive MPN, with an average survival of 5 to 7 years, abnormal clonal hematopoietic stem cell proliferation in the bone marrow (BM) leads to liberation of pro-inflammatory cytokines and extensive fibrosis, causing progressive pancytopenia, especially anemia and thrombocytopenia, along with splenomegaly and other symptoms, compromising quality of life.1

For nearly a decade, ruxolitinib has been the centerpiece therapy for patients with MF, markedly improving splenomegaly and constitutional symptoms and providing survival benefit.2 The second FDA-approved JAK2 inhibitor, fedratinib (Inrebic), may actually be a good second-line option for patients who are ruxolitinib-resistant with intermediate-2 and high-risk MF (primarily thrombocytopenic and characterized by platelet counts 50100 109/L).3 At present, 2 ongoing phase 3 clinical trials, the single-arm FREEDOM trial (NCT03755518) and the double-arm FREEDOM 2 trial (NCT03952039), are assessing the efficacy and safety of fedratinib in patients with MF who are resistant/refractory/intolerant to ruxolitinib. The FREEDOM trials are important because the previous JAKARTA studies (NCT01523171, NCT01437787) were placed on hold or terminated given concerns for the development of Wernicke encephalopathy. Pacritinib is a potent inhibitor of both JAK2 and fms-related receptor tyrosine kinase

3, or FLT3, but does not affect JAK1. Pacritinib is being evaluated in comparison with the physicians choice in an ongoing phase 3 trial (PACIFICA; NCT03165734) in patients with MF and severe thrombocytopenia (baseline platelet count < 50 109/L) at the optimal dose determined in the PAC203 study (200 mg twice daily; NCT03165734).3 Successful clinical development of pacritinib will provide a non-myelosuppressive JAK2 inhibitor for frontline treatment of patients with MF who have severe thrombocytopenia, a setting currently lacking approved drugs. Another JAK1/2 inhibitor that is in advanced clinical development and complements its predecessors is momelotinib, possessing the exclusive attribute to improve anemia, which becomes severe in patients with MF.3 At present, momelotinib is undergoing evaluation in patients who are symptomatic and anemic with advanced MF, previously treated with a JAK inhibitor, in a phase 3 trial (MOMENTUM; NCT04173494); the comparator drug is danazol.

Targeting anemia and thrombocytopenia. Given that patients with MF experience disease-associated and JAK inhibitor-induced anemia, several clinical trials have been evaluating drugs counteracting anemia, as monotherapies or in combination with ruxolitinib, in patients with MF-associated anemia.4 Currently, a global, multicenter phase 2 trial is under way to evaluate the safety and efficacy of luspatercept-aamt (Reblozyl), an activin receptor ligand trap that enhances late-stage erythropoiesis in patients with anemia and MF, including ruxolitinib-treated, transfusion-dependent individuals; a phase 3 trial (INDEPENDENCE) is planned for 2020. Interim results of the phase 2 study demonstrated significant efficacy of luspatercept-aamt, achieving reduction in red blood cell transfusion burden in ruxolitinib-treated patients with MF. Thalidomide (Thalomid), an immunomodulatory agent, significantly improved anemia and thrombocytopenia (platelet counts increased in 60% of patients) in a phase 2 trial evaluating ruxolitinib-treated patients with MF and baseline thrombocytopenia (NCT03069326).5

Synergistic combinations with ruxolitinib targeting epigenetics and JAK2 (TABLE). CPI-0610 is a selective bromodomain and extraterminal protein inhibitor that improved spleen volume, anemia, BM fibrosis, total symptom score, and transfusion dependence (alone or with ruxolitinib) in patients with MF who are enrolled in the global phase 2 MANIFEST study (NCT02158858).3 Furthermore, a phase 1 clinical trial combining an inhibitor of heat shock protein 90 (JAK2 is its chaperone protein), PU-H71, with ruxolitinib in patients with primary/secondary MF is under way (NCT03935555).3 The previous 2 trials are supported by preclinical data showing drug synergism. In a phase 2 trial of ruxolitinib/azacitidine (hypomethylating agent) in patients with MF, synergism was demonstrated in spleen length reduction and BM fibrosis improvement compared with ruxolitinib monotherapy (NCT01787487).5

Synergistic combinations with ruxolitinib targeting antiapoptotic proteins and JAK2. Navitoclax is an orally bioavailable inhibitor of the antiapoptotic B-cell lymphoma 2 (BCL2) family of proteins (primarily BCL extra-large [XL]). In preclinical studies, the nonclinical analogue of navitoclax, ABT-737, in combination with ruxolitinib showed synergism in inducing apoptosis of JAK2 V617F-driven MPN cell lines. Interim data from an ongoing phase 2 clinical trial evaluating navitoclax in combination with ruxolitinib in ruxolitinib-treated patients with MF (with baseline platelet count 100 109/L) showed reduction in spleen volume and BM fibrosis (1 grade) and improvement in total symptom score in a proportion of the patients (NCT03222609).3

Imetelstat is a short oligonucleotide telomerase inhibitor that possibly prolonged median overall survival in patients with MF in the higher-dose (9.4-mg/kg) arm of the phase 2 IMbark study (NCT02426086).3 A phase 3 trial comparing imetelstat to best available therapy in patients with refractory MF is planned for early 2021.

PRM-151, a plasma-derived analogue of the human antifibrotic protein pentraxin 2, improved BM fibrosis in mice models and patients with MF in preclinical and phase 1/2 clinical studies, respectively.3 The promising results merit a phase 3 trial, especially given the scarcity of antifibrotic agents.

The two relatively indolent MPN subtypes, polycythemia vera (PV) and essential thrombocythemia (ET), are characterized by abnorabnormal proliferation of myeloid cells, resulting in elevated blood counts (erythrocytosis and thrombocytosis in PV and ET, respectively), considerable risk of thrombosis and hemorrhage, and progression to secondary MF and acute myeloid leukemia (more common in PV than ET).6 In PV and ET, therapies are aimed at reducing risk of thrombosis, which is higher in patients over 60 years old or with a history of thrombosis, and in ET, when the calreticulin gene, CALR, is absent. A particularly promising agent for the two indolent MPNs is the long-acting ropeginterferon -2b, which was approved in Europe for frontline treatment of high-risk patients with PV and without symptomatic splenomegaly on the basis of the PROUD/CONTINUATION-PV studies [EudraCT, 2012-005259-18 (PROUD-PV) and 2014-001357- 17 (CONTINUATION-PV)].7 The previous investigations demonstrated superiority of ropeginterferon -2b versus hydroxyurea after 3 years of therapy. Besides awaiting possible approval of ropeginterferon -2b to treat patients with PV in the United States, a phase 3 trial of ropeginterferon -2b versus anagrelide in hydroxyurea-resistant/intolerant patients with ET has been planned to start in 2020. Givinostat, an inhibitor of histone deacetylases, demonstrated promising clinical responses (reduction in pruritus and thrombosis, and normalization of hematological parameters) in phase 1/2 studies in patients with JAK2 V617F positive PV and is entering a phase 3 trial in 2021.7 Currently, hydroxyurea and ruxolitinib are the first- and second-line treatments for high-risk patients with PV, respectively, and hydroxyurea is the first-line treatment for ET.

Herein we highlighted an array of drugs ranging from new JAK inhibitors to an antifibrotic agent, epigenetic modifiers, and telomerase and BCL-XL/BCL2 inhibitorsthat are in early or advanced clinical development in MPN. We are looking forward to enrichment of the MPN arsenal with new disease-modifying agents complementing the clinical benefits of ruxolitinib and fulfilling unmet needs in this population.

References:

1. Verstovsek S, Gotlib J, Mesa RA, et al. Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses. J Hematol Oncol. 2017;10(1):156. doi:10.1186/s13045-017-0527-7

2. Bose P, Verstovsek S. Management of myelofibrosis after ruxolitinib failure. Leuk Lymphoma. Published online April 16, 2020. doi:10.1080/1 0428194.2020.1749606

3. Bose P, Verstovsek S. Management of myelofibrosis-related cytopenias. Curr Hematol Malig Rep. 2018;13(3):164-172. doi:10.1007/s11899- 018-0447-9

3. Bose P, Alfayez M, Verstovsek S. New concepts of treatment for patients with myelofibrosis. Curr Treat Options Oncol. 2019;20(1):5. doi:10.1007/s11864-019-0604-y

4. Bose P, Verstovsek S. Updates in the management of polycythemia vera and essential thrombocythemia. Ther Adv Hematol. 2019;10:2040620719870052. doi:10.1177/2040620719870052

5. Gisslinger H, Klade C, Georgiev P, et al. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020;7(3):e196-e208. doi:10.1016/S2352- 3026(19)30236-4

6. Chifotides HT, Bose P, Verstovsek S. Givinostat: an emerging treatment for polycythemia vera. Expert Opin Investig Drugs. 2020;29(6):525- 536. doi:10.1080/13543784.2020.1761323

Read more from the original source:
New Therapies in Development for Myelofibrosis - Targeted Oncology

Bone Marrow Stem Cells Comments Off on New Therapies in Development for Myelofibrosis – Targeted Oncology | October 16th, 2020

Acute Lymphoblastic Leukemia (AML), also called acute myeloblastic leukemia, acute myelogenous leukemia, acute myeloid leukemia, or acute nonlymphocytic leukemia, is an aggressive, fast-growing, heterogenous group of blood cancers that arise as a result of clonal expansion of myeloid hematopoietic precursors in the bone marrow. Not only are circulating leukemia (blast) cells seen in the peripheral blood, but granulocytopenia, anemia, and thrombocytopenia are also common as proliferating leukemia cells interfere with normal hematopoiesis.

Approximately 40-45% of younger and 10-20% of older adults diagnosed with AML are cured with current standard chemotherapy. However, the outlook for patients with relapsed and/or refractory disease is gloomy. Relapse following conventional chemotherapy remains is a major cause of death.

The process of manufacturing chimeric antigen receptor (CAR) T-cell therapies. [1] T-cells (represented by objects labeled as t) are removed from the patients blood. [2] Then in a lab setting the gene that encodes for the specific antigen receptors is incorporated into the T-cells. [3] Thus producing the CAR receptors (labeled as c) on the surface of the cells. [4] The newly modified T-cells are then further harvested and grown in the lab. [5]. After a certain time period, the engineered T-cells are infused back into the patient. This file is licensed by Reyasingh56 under the Creative Commons Attribution-Share Alike 4.0 International license.Today, the only curative treatment option for patients with AML is allogeneic hematopoietic stem cell transplantation or allo-HSCT, which through its graft-vs.-leukemia effects has the ability to eliminate residual leukemia cells. But it is an ption for only a minority. And despite a long history of success, relapse following allo-HSCT is still a major challenge and is associated with poor prognosis.

In recent years, rresearchers learned a lot about the genomic and epigenomic landscapes of AML. This understanding has paved the way for rational drug development as new drugable targets, resulting in treatments including the antibody-drug conjugate (ADC) gemtuzumab ozogamycin (Mylotarg; Pfizer/Wyeth-Ayerst Laboratories).

CAR T-cell TherapiesChimeric antigen receptor (CAR) T-cells therapies, using a patients own genetically modified T-cells to find and kill cancer, are one of the most exciting recent developments in cancer research and treatment.

Traditional CAR T-cell therapies are an autologous, highly personalised, approach in which T-cells are collected from the patient by leukopheresis and engineered in the laboratory to express a receptor directed at a cancer antigen such as CD19. The cells are then infused back into the patient after administration of a lymphodepletion regimen, most commonly a combination of fludarabine and cyclophosphamide. Durable remissions have been observed in pediatric patients with B-ALL and adults with NHL.

CD19-targeted CAR T-cell therapies, have, over the last decade, yielded remarkable clinical success in certain types of B-cell malignancies, and researchers have made substantial efforts aimed at translating this success to myeloid malignancies.

While complete ablation of CD19-expressing B cells, both cancerous and healthy, is clinically tolerated, the primary challenge limiting the use of CAR T-cells in myeloid malignancies is the absence of a dispensable antigen, as myeloid antigens are often co-expressed on normal hematopoietic stem/progenitor cells (HSPCs), depletion of which would lead to intolerable myeloablation.

A different approachBecause autologous CAR T-cell therapies are patient-specific, each treatment can only be used for that one patient. Furthermore, because CAR T-cells are derived from a single disease-specific antibody, they are, by design, only recognized by one specific antigen. As a consequence, only a small subset of patients with any given cancer may be suited for the treatment.

This specificity means that following leukopheresis, a lot of work needs to be done to create this hyper personalised treatment option, resulting in 3 5 weeks of manufacturing time.

The manufacturing process of CAR T-cell therapies, from a single academic center to a large-scale multi-site manufacturing center further creates challenges. Scaling out production means developing processes consistent across many collection, manufacturing, and treatment sites. This complexity results in a the realitively high cost of currently available CAR T-cell therapies.

To solve some of the concerns with currently available CAR T-cell therapies, researchers are investigating the option to develop allogenic, off-the-shelf Universal CAR T-cell (UCARTs) treatments that can be mass manufactured and be used for multiple patients.

Allogeneic CAR T-cell therapy are generally created from T-cells from healthy donors, not patients. Similar to the autologous approach, donor-derived cells are shipped to a manufacturing facility to be genetically engineered to express the antibody or CAR, however, in contrast to autologous CAR T-cells, allogeneic CAR T-cells are also engineered with an additional technology used to limit the potential for a graft versus host reaction when administered to patients different from the donor.

One unique benefit ofn this approach is that because these therapies hey are premade and available for infusion, there is no requirement to leukopheresis or a need to wait for the CAR T-cells to be manufactured. This strategy also will benefit patients who are cytopenic (which is not an uncommon scenario for leukemia patients) and from whom autologous T-cell collection is not possible.

PioneersAmong the pioneers of developing allogeneic CAR-T therapies are companies including Celyad Oncology, Cellectis, Allogene Therapeutics, and researchers at University of California, Los Angeles (UCLA) in colaboration with Kite/Gilead.

Researchers at UCLA were, for example, able to turn pluripotent stem cells into T-cells through structures called artificial thymic organoids. These organoids mimic the thymus, the organ where T-cells are made from blood stem cells in the body.

Celyad OncologyBelgium-based Celyad Oncology is advancing a number of both autologous and allogeneic CAR T-cell therapies, including proprietary, non-gene edited allogeneic CAR T-cell candidates underpinned by the companys shRNA technology platform. The shRNA platform coupled with Celyads all-in-one vector approach provides flexibility, versatility, and efficiency to the design of novel, off-the-shelf CAR T-cell candidates through a single step engineering process.

In July 2020, the company announced the start of Phase I trials with CYAD-211, Celyads first-in-class short hairpin RNA (shRNA)-based allogeneic CAR T candidate and second non-gene edited off-the-shelf program. CYAD-211 targets B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma and is engineered to co-express a BCMA-targeting chimeric antigen receptor and a single shRNA, which interferes with the expression of the CD3 component of the T-cell receptor (TCR) complex.

During the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program in May 2020, the company presented updates from its allogeneic programs, including additional data from the alloSHRINK study, an open-label, dose-escalation Phase I trial assessing the safety and clinical activity of three consecutive administrations of CYAD-101, an investigational, non-gene edited, allogeneic CAR T-cell candidate engineered to co-express a chimeric antigen receptor based on NKG2D (a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands and the novel inhibitory peptide TIM TCR Inhibitory Molecule), for the treatment of metastatic colorectal cancer (mCRC).

The expression of TIM reduces signalling of the TCR complex, which is responsible for graft-versus host disease.every two weeks administered concurrently with FOLFOX (combination of 5-fluorouracil, leucovorin and oxaliplatin) in patients with refractory metastatic colorectal cancer (mCRC).

The safety and clinical activity data from the alloSHRINK trial in patients with mCRC demonstrated CYAD-101s differentiated profile as an allogeneic CAR T-cell candidate. Furthermore, the absence of clinical evidence of graft-versus-host-disease (GvHD) for CYAD-101 confirms the potential of non-gene edited approaches for the development of allogeneic CAR-T candidates.

Interim data from the alloSHRINK trial showed encouraging anti-tumor activity, with two patients achieving a confirmed partial response (cPR) according to RECIST 1.1 criteria, including one patient with a KRAS-mutation, the most common oncogenic alteration found in all human cancers. In addition, nine patients achieved stable disease (SD), with seven patients demonstrating disease stabilization lasting more than or equal to three months of duration.

Based on these results, clinical trials were broadened to include evaluating CYAD-101 following FOLFIRI (combination of 5-fluorouracil, leucovorin and irinotecan) preconditioning chemotherapy in refractory mCRC patients, at the recommended dose of one billion cells per infusion as an expansion cohort of the alloSHRINK trial. Enrollment in the expansion cohort of the trial is expected to begin during the fourth quarter of 2020.

CellectisCellectis is developping a universal CAR T-cell (UCART) platform in an attempy to create off-the-shelf CAR T-cell therapies. The companys pipeline includes UCART123, a CAR T-cell therapy designed to targets CD123+ leukemic cells in acute myeloid leukemia (AML). The investigational agent is being studied in two open-label Phase I trials: AML123 studying the therapys safety and efficacy in an estimated 156 AML patients, and ABC123 studying the therapys safety and activity in an estimated 72 patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

UCART22Another investigational agent in clinical trials is UCART22 which is designed to treat both CD22+ B-cell acute lymphoblastic leukemia (B-ALL) and CD22+ B-cell non-Hodgkin lymphoma (NHL). Cellectis reported that UCART22 is included in an open-label, dose-escalating Phase I trial to study its safety and activity in relapsed or refractory CD22+ B-ALL patients.

UCART22 harbors a surface expression of an anti-CD22 CAR (CD22 scFv-41BB-CD3z) and the RQR8 ligand, a safety feature rendering the T-cells sensitive to the antibody rituximab. Further, to reduce the potential for alloreactivity, the cell surface expression of the T-cell receptor is abrogated through the inactivation of the TCR constant (TRAC) gene using Cellectis TALEN gene-editing technology.[1]

Preclinical data supporting the development of UCART22 was presented by Marina Konopleva, M.D., Ph.D. and her vteam during the 2017 annual meeting of the American Society of Hematology (ASH) meeting. [1]

Cellectis is also developing UCARTCS1 which is developed to treat CS1-expressing hematologic malignancies, such as multiple myeloma (MM). UCARTCLL1 is in preclinical development for treating CLL1-expressing hematologic malignancies, such as AML.

Cellectis and Allogene Therapeutics, another biotech company involved in the developmen t of CAR T-cell therapies, are developing ALLO-501, another CAR T-cell therapy which targets CD19 and is being developed for the the treatment of patients with relapsed or refractory NHL. Allogene Therapeutics is also developing ALLO-715, an investigational CAR T-cell therapy targeting the B-cell maturation antigen (BCMA) for treating relapsed or refractory multiple myeloma and ALLO-819, which targets CD135 (also called FLT3), for treating relapsed or refractory AML.

Allogene, in collaboration with both Cellectis, Pfizer (which has a 25% stake in Allogene) and Servier have numerous active open-label, single-arm Phase I trials for an off-the-shelf allogeneic CAR-T therapy UCART19* in patients with relapsed or refractory CD19+ B-ALL. Participating patients receive lymphodepletion with fludarabine and cyclophosphamide with alemtuzumab, followed by UCART19 infusion. Adults patients with R/R B-ALL are eligible.

The PALL aims to evaluate the safety and feasibility of UCART19 to induce molecular remission in pediatric patients with relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) in 18 pediatric patients.

The CALM trial is a dose-escalating study evaluating the therapys safety and tolerability in 40 adult patients; and a long-term safety and efficacy follow-up study in 200 patients with advanced lymphoid malignancies.

Allogene reported preliminary proof-of-concept results during the annual meeting of the American Society of Hematology (ASH) in December 2018.

Data from the first 21 patients from both the PALL (n=7) and CALM (n=14) Phase I studies were pooled. The median age of the participating patients was 22 years (range, 0.8-62 years) and the median number of prior therapies was 4 (range, 1-6). Sixty-two percent of the patients (13/21) had a prior allogeneic stem cell transplant.

Of the 17 patients who received treatment with UCART19 and who received lymphodepletion with fludarabine, cyclophosphamide and alemtuzumab, an anti-CD52 monoclonal antibody, 14 patients (82%) achieved CR/CRi, and 59% of them (10/17) achieved MRD-negative remission.

In stark contrast, the four patients who only received UCART19 and fludarabine and cyclophosphamide without alemtuzumab did not see a response and minimal UCART19 expansion.

Based on these results, researchers noted that apparent importance of an anti-CD52 antibody for the efficacy of allogeneic CAR-T therapies. In addition, safety data also looked promising. The trial results did not include grade 3 or 4 neurotoxicity and only 2 cases of grade 1 graft-versus-host disease (10%), 3 cases of grade 3 or 4 cytokine release syndrome which were considered manageable (14%), 5 cases of grade 3 or 4 viral infections (24%), and 6 cases of grade 4 prolonged cytopenia (29%).

Precision BiosciencesPrecision Biosciences is developing PBCAR0191, an off-the-shelf investigational allogeneic CAR T-cell candidate targeting CD19. The drug candidate is being investigated in a Phase I/IIa multicenter, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study for the treatment of patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) or R/R B-cell precursor acute lymphoblastic leukemia (B-ALL).

The NHL cohort includes patients with mantle cell lymphoma (MCL), an aggressive subtype of NHL, for which Precision has received both Orphan Drug and Fast Track Designations from the U.S. Food and Drug Administration (FDA).

A clinical trial with PBCAR0191 Precision Biosciences is exploring some novel lymphodepletion strategies in addition to fludarabine and cyclophosphamide. Patients with R/R ALL, R/R CLL, R/R Richter transformation, and R/R NHL are eligible. Patients with MRD+ B-ALL are eligible as well. This trial is enrolling patients.

In late September 2020, Precision BioSciences, a clinical stage biotechnology amd Servier, announced the companies have added two additional hematological cancer targets beyond CD19 and two solid tumor targets to its CAR T-cell development and commercial license agreement.

PBCAR20APBCAR20A is an investigational allogeneic anti-CD20 CAR T-cell therapy being developed by Precision Biosciences for the treartment of patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) and patients with R/R chronic lymphocytic leukemia (CLL) or R/R small lymphocytic lymphoma (SLL). The NHL cohort will include patients with mantle cell lymphoma (MCL), an aggressive subtype of NHL, for which Precision BioSciences has received orphan drug designation from the United States Food and Drug Administration (FDA).

PBCAR20A is being evaluated in a Phase I/IIa multicenter, nonrandomized, open-label, dose-escalation and dose-expansion clinical trial in adult NHL and CLL/SLL patients. The trial will be conducted at multiple U.S. sites.

PBCAR269APrecision Biosciences is, in collaboration with Springworks Therapeutics, also developing PBCAR269A, an allogeneic BCMA-targeted CAR T-cell therapy candidate being evaluated for the safety and preliminary clinical activity in a Phase I/IIa multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study of adults with relapsed or refractory multiple myeloma. In this trial, the starting dose of PBCAR269A is 6 x 105 CAR T cells/kg body weight with subsequent cohorts receiving escalating doses to a maximum dose of 6 x 106 CAR T cells/kg body weight.

PBCAR269A is Precision Biosciencess third CAR T-cell candidate to advance to the clinic and is part of a pipeline of cell-phenotype optimized allogeneic CAR T-cell therapies derived from healthy donors and then modified via a simultaneous TCR knock-out and CAR T-cell knock-in step with the =companys proprietary ARCUS genome editing technology.

The FDA recently granted Fast Track Designation to PBCAR269A for the treatment of relapsed or refractory multiple myeloma for which the FDA previously granted Orphan Drug Designation.

TCR2 TherapeuticsTCR2 Therapeutics is developing a proprietary TRuC (TCR Fusion Construct) T-cells designed to harness the natural T cell receptor complex to recognize and kill cancer cells using the full power of T-cell signaling pathways independent of the human leukocyte antigen (HLA).

While succesful in hematological malignancies, CAR T-cells therapies have generally struggled to show efficacy against solid tumors. Researchers at TCR2 Therapeutics believe this is is caused by the fact that CAR T-cell therapies only utilize a single TCR subunit, and, as a result, do not benefit from all of the activation and regulatory elements of the natural TCR complex. By engineering TCR T-cells, which are designed to utilize the complete TCR, they have demonstrated clinical activity in solid tumors. However, this approach has also shown major limitations. TCR T-cells require tumors to express HLA to bind tumor antigens. HLA is often downregulated in cancers, preventing T-cell detection. In addition, each specific TCR-T cell therapy can only be used in patients with one of several specific HLA subtypes, limiting universal applicability of this approach and increasing the time and cost of patient enrollment in clinical trials.

In an attempt to solve this problem, researchers at TCR2 Therapeutics have developped a proprieatarry TRuC-T Cells which are designed to incorporate the best features of CAR-T and TCR-T cell therapies and overcome the limitations. The TRuC platform is a novel T cell therapy platform, which uses the complete TCR complex without the need for HLA matching.

By conjugating the tumor antigen binder to the TCR complex, the TRuC construct recognizes highly expressed surface antigens on tumor cells without the need for HLA and engage the complete TCR machinery to drive the totality of T-cell functions required for potent, modulated and durable tumor killing.

In preclinical studies, TCR2 Therapeutics TRuC T-cells technology has demonstrated superior anti-tumor activity in vivo compared to CAR T-cells therapies, while, at the same time, releasing lower levels of cytokines. These data are encouraging for the treatment of solid tumors where CAR T-cells have not shown significant clinical activity due to very short persistence and for hematologic tumors where a high incidence of severe cytokine release syndrome remains a major concern.

TCR2 Therapeutics product candidates include TC-210 and TC-110.

TC-210 is designed to targets mesothelin-positive solid tumors. While its expression in normal tissues is low, mesothelin is highly expressed in many solid tumors. Mesothelin overexpression has also been correlated with poorer prognosis in certain cancer types and plays a role in tumorigenesis. TC-210 is being developed for the treatment of non-small cell lung cancer, ovarian cancer, malignant pleural/peritoneal mesothelioma and cholangiocarcinoma.

The companys TRuC-T cell targeting CD19-positive B-cell hematological malignancies, TC-110, is being developed to improve upon and address the unmet needs of current CD19-directed CAR T-cell therapies. The clinical development TC-110 focus on the treatment of adult acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Preclinical data demonstrates that TC-110 is superior to CD19-CAR-T cells (carrying either 4-1BB or CD28 co-stimulatory domains) both in anti-tumor activity as well as the level of cytokine release which may translate into lower rates of adverse events. The development of TC-110 starts with autologous T-cells collection by leukopheresis. These T-cells undergo genetic engineering to create TRuC-T cells targeting CD19.

This strategy combines the best features of CAR T-cells and the native T-cell receptor. It is open for R/R NHL and R/R B-ALL.

AUTO1Auto1 is an autologous CD19 CAR T-cell investigational therapyis being developped by Autolus Therapeutics. The investigational drug uses a single-chain variable fragment (scFv) called CAT with a lower affinity for CD19 and a faster off-rate compared to the FMC63 scFv used in other approved CD19 CAR T-cell therapies. The investigational therapy is 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 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 I studies, one in pediatric ALL and one in adult ALL.

CARPALL trialInitial results from the ongoing Phase I CARPALL trial of AUTO1 were presented during European Hematology Association 1st European CAR T Cell Meeting held in Paris, France, February 14-16, 2019.

Enrolled patients had a median age of 9 years with a median of 4 lines of prior treatment. Seventeen patients were enrolled, and 14 patients received an infusion of CAR T cells. Ten of 14 patients had relapsed post allogeneic stem cell transplant. Eight patients were treated in second relapse, 5 in > second relapse and 3 had relapsed after prior blinatumomab or inotuzumab therapy. Two patients had ongoing CNS disease at enrollment.

This data confirmed that AUTO1 did not induces severe cytokine release syndrome (CRS) (Grade 3-5). Nine patients experienced Grade 1 CRS, and 4 patients experienced Grade 2 CRS. No patients required tociluzumab or steroids. As previously reported, one patient experienced Grade 4 neurotoxicity; there were no other reports of severe neurotoxicity (Grade 3-5). The mean cumulative exposure to AUTO1 CAR T-cells in the first 28 days as assessed by AUC was 1,721,355 copies/g DNA. Eleven patients experienced cytopenia that was not resolved by day 28 or recurring after day 28: 3 patients Grades 1-3 and 8 patients Grade 4. Two patients developed significant infections, and 1 patient died from sepsis while in molecular complete response (CR).

With a single dose of CAR T cells at 1 million cells/kg dose, 12/14 (86%) achieved molecular CR. Five patients relapsed with CD19 negative disease. Event free survival (EFS) based on morphological relapse was 67% (CI 34-86%) and 46% (CI 16-72%) and overall survival (OS) was 84% (CI 50-96%) and 63% (CI 27-85%) at 6 and 12 months, respectively.

CAR T cell expansion was observed in all responding patients (N=12), with CAR T cells comprising up to 84% of circulating T cells at the point of maximal expansion. The median persistence of CAR T-cells was 215 days.

The median duration of remission in responding patients was 7.3 months with a median follow-up of 14 months. Five of 14 patients (37%) remain in CR with ongoing persistence of CAR T-cells and associated B cell aplasia.

Fate TherapeuticsFT819 is an off-the-shelf CAR T-cell therapy targeting CD19 being developed by Fate Therapeutics. The T-cells are derived from a clonal engineered master induced pluripotent stem cell line (iPSCs) with a novel 1XX CAR targeting CD19 inserted into the T-cell receptor alpha constant (TRAC) locus and edited for elimination of T-cell receptor (TCR) expression.

Patients participating in the companys clinbical trial will receive lymphodepletion with fludarabine and cyclophosphamide. Some patients will also receive IL-2. Patients with R/R ALL, R/R CLL, R/R Richter transformation, and R/R NHL are eligible. Patients with MRD+ B-ALL are eligible as well.

At the Annual Meeting of the American Societ of Hematology held in December 2019, researchers from Fate Therapeutics presented new in vivo preclinical data demonstrating that FT819 exhibits durable tumor control and extended survival. In a stringent xenograft model of disseminated lymphoblastic leukemia, FT819 demonstrated enhanced tumor clearance and control of leukemia as compared to primary CAR19 T-cells. At Day 35 following administration, a bone marrow assessment showed that FT819 persisted and continued to demonstrate tumor clearance, whereas primary CAR T cells, while persisting, were not able to control tumor growth. [2]

CAR-NK CD19Allogeneic cord blood-derived Natural Killer (NK) cells are another off-the-shelf product that does not require the collection of cells from each patient.

Unlike T-cells, NK-cells do not cause GVHD and can be given safely in the allogeneic setting. At MD Anderson Cancer Center, Katy Rezvani, M.D., Ph.D, Professor, Stem Cell Transplantation and Cellular Therapy, and her team broadly focuses their research on the role of natural killer (NK) cells in mediating protection against hematologic malignancies and solid tumors and strategies to enhance killing function against various cancer.

As part of their research, the team has developed a novel cord blood-derived NK-CAR product that expresses a CAR against CD19; ectopically produces IL-15 to support NK-cell proliferation and persistence in vivo; and expresses a suicide gene, inducible caspase 9, to address any potential safety concerns.

In this phase I and II trial researchers administered HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood to 11 patients with relapsed or refractory CD19-positive cancers (non-Hodgkins lymphoma or chronic lymphocytic leukemia [CLL]). NK cells were transduced with a retroviral vector expressing genes that encode anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch. The cells were expanded ex vivo and administered in a single infusion at one of three doses (1105, 1106, or 1107 CAR-NK cells per kilogram of body weight) after lymphodepleting chemotherapy. The preliminarry resilts of the trials confirmed that administration of CAR-NK cells was not associated with the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, and there was no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline.

The study results also demonstrated that of the 11 patients who were treated, 8 patients (73%) had a response. Of these patients, 7 (4 with lymphoma and 3 with CLL) had a complete remission ICR), and 1 had remission of the Richters transformation component but had persistent CLL. Noteworthy was that responses were rapid and seen within 30 days after infusion at all dose levels. The infused CAR-NK cells expanded and persisted at low levels for at least 12 months. The researchers also noted that a majority of the 11 participating patients with relapsed or refractory CD19-positive cancers had a response to treatment with CAR-NK cells without the development of major toxic effects.[3]

Note* Servier will hold ex-US commercial rights. Servier is the sponsor of the UCART19 trials.

Clinical trialsalloSHRINK Standard cHemotherapy Regimen and Immunotherapy With Allogeneic NKG2D-based CYAD-101 Chimeric Antigen Receptor T-cells NCT03692429Study Evaluating Safety and Efficacy of UCART123 in Patients With Relapsed/ Refractory Acute Myeloid Leukemia (AMELI-01) NCT03190278Study to Evaluate the Safety and Clinical Activity of UCART123 in Patients With BPDCN (ABC123) NCT03203369Study of UCART19 in Pediatric Patients With Relapsed/Refractory B Acute Lymphoblastic Leukemia (PALL) NCT02808442Dose Escalation Study of UCART19 in Adult Patients With Relapsed / Refractory B-cell Acute Lymphoblastic Leukaemia (CALM) NCT02746952Dose-escalation Study of Safety of PBCAR0191 in Patients With r/r NHL and r/r B-cell ALL NCT03666000.Dose-escalation Study of Safety of PBCAR20A in Subjects With r/r NHL or r/r CLL/SLL NCT04030195A Dose-escalation Study to Evaluate the Safety and Clinical Activity of PBCAR269A in Study Participants With Relapsed/Refractory Multiple Myeloma NCT04171843TC-110 T Cells in Adults With Relapsed or Refractory Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia NCT04323657Phase 1/2 Trial of TC-210 T Cells in Patients With Advanced Mesothelin-Expressing Cancer NCT03907852CARPALL: Immunotherapy With CD19 CAR T-cells for CD19+ Haematological Malignancies NCT02443831Umbilical & Cord Blood (CB) Derived CAR-Engineered NK Cells for B Lymphoid Malignancies NCT03056339

Reference[1] Petti F. Broadening the Applicability of CAR-T Immunotherapy to Treat the Untreatable. OncoZine. October 24, 2019 [Article][2] Wells J, Cai T, Schiffer-Manniou C, Filipe S, Gouble A, Galetto R, Jain N, Jabbour EJ, Smith J, Konopleva M. Pre-Clinical Activity of Allogeneic Anti-CD22 CAR-T Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia Blood (2017) 130 (Supplement 1): 808. https://doi.org/10.1182/blood.V130.Suppl_1.808.808%5B3%5D Chang C, Van Der Stegen S, Mili M, Clarke R, Lai YS, Witty A, Lindenbergh P, Yang BH, et al. FT819: Translation of Off-the-Shelf TCR-Less Trac-1XX CAR-T Cells in Support of First-of-Kind Phase I Clinical Trial. Blood (2019) 134 (Supplement_1): 4434.https://doi.org/10.1182/blood-2019-130584%5B4%5D Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, Nassif Kerbauy L, Overman B, Thall P, Kaplan M, Nandivada V, Kaur I, Nunez Cortes A, Cao K, Daher M, Hosing C, Cohen EN, Kebriaei P, Mehta R, Neelapu S, Nieto Y, Wang M, Wierda W, Keating M, Champlin R, Shpall EJ, Rezvani K. Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors. N Engl J Med. 2020 Feb 6;382(6):545-553. doi: 10.1056/NEJMoa1910607. PMID: 32023374; PMCID: PMC7101242.

Featured image: T-cells attacking a cancer cell. Photo courtesy: Fotolia/Adobe 2016 2020. Used with permission.

Link:
CAR T-cell Therapies for the Treatment of Patients with Acute Lymphoblastic Leukemia - OncoZine

Bone Marrow Stem Cells Comments Off on CAR T-cell Therapies for the Treatment of Patients with Acute Lymphoblastic Leukemia – OncoZine | October 16th, 2020

NEW YORK, Oct. 15, 2020 /PRNewswire/ -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of cellular therapies for neurodegenerative diseases, announced today financial results for the third quarter ended September 30, 2020, and provided a corporate update.

"The most important near-term event for BrainStorm will be the upcoming top-line data readout for the NurOwn Phase 3 trial in ALS, expected by the end of November. A successful outcome will set us on the path to filing a Biologic License Application (BLA) for what we believe will be a valuable new treatment for ALS," said Chaim Lebovits, Chief Executive Officer of BrainStorm Cell Therapeutics. "In parallel to our preparations for upcoming data read out, we are very busy planning and executing on other pre-BLA activities. On the management front, we appointed William K. White and Dr. Anthony Waclawski, adding valuable commercial and regulatory expertise to our leadership team. This expertise will be crucial as we work towards obtaining regulatory approval for NurOwn and ensuring that, if approved, it will be readily accessible to ALS patients in need of new treatment options for this devastating disease."

NurOwn has an innovative mechanism of action that is broadly applicable across neurodegenerative diseases and BrainStorm continues to invest in clinical trials evaluating the product in conditions beyond ALS to maximize value creation for its various stakeholders. The company remains on track to complete dosing in its Phase 2 clinical trial in progressive multiple sclerosis (PMS) by the end of 2020. In addition, the Company recently unveiled a clinical development program in Alzheimer's' disease (AD) and is planning a Phase 2 proof-of-concept clinical trial at several leading AD centers in the Netherlands and France.

Third Quarter 2020 and Recent Corporate Highlights:

Presented at the following Investor Conferences:

Cash and Liquidity as of October 14, 2020

Total available funding as of October 14, 2020, which includes cash, cash equivalents and short-term bank deposits of approximately $33.1 million as well as remaining non-dilutive funding from CIRM, IIA and other grants, amounts to approximately $36 million.

Financial Results for the Three Months Ended September 30, 2020

Conference Call & WebcastThursday, October 15, 2020 at 8 a.m. Eastern TimeFrom the US: 877-407-9205International: 201-689-8054Webcast: https://www.webcaster4.com/Webcast/Page/2354/37811

Replays, available through October 29, 2020From the US: 877-481-4010International: 919-882-2331Replay Passcode: 37811

About NurOwn

NurOwn (autologous MSC-NTF) cells represent a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. BrainStorm has fully enrolled a Phase 3 pivotal trial of autologous MSC-NTF cells for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm also recently received acceptance from the U.S. Food and Drug Administration (FDA) to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS) and completed enrollment in August 2020.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug status designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has fully enrolled a Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six U.S. sites supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). The pivotal study is intended to support a filing for U.S. FDA approval of autologous MSC-NTF cells in ALS. BrainStorm also recently received U.S. FDA clearance to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS). The Phase 2 study of autologous MSC-NTF cells in patients with progressive MS (NCT03799718) completed enrollment in August 2020. For more information, visit the company's website at http://www.brainstorm-cell.com.

Safe-Harbor Statement

Statements in this announcement other than historical data and information, including statements regarding future clinical trial enrollment and data, constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may", "should", "would", "could", "will", "expect", "likely", "believe", "plan", "estimate", "predict", "potential", and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorm's need to raise additional capital, BrainStorm's ability to continue as a going concern, regulatory approval of BrainStorm's NurOwn treatment candidate, the success of BrainStorm's product development programs and research, regulatory and personnel issues, development of a global market for our services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorm's NurOwn treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorm's ability to manufacture and commercialize the NurOwn treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorm's ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation,; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at http://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

ContactsInvestor Relations:Corey Davis, Ph.D.LifeSci Advisors, LLCPhone: +1 646-465-1138cdavis@lifesciadvisors.com

Media:Paul TyahlaSmithSolvePhone: + 1.973.713.3768Paul.tyahla@smithsolve.com

BRAINSTORM CELL THERAPEUTICS INC. AND SUBSIDIARIESINTERIM CONDENSED CONSOLIDATED BALANCE SHEETSU.S. dollars in thousands(Except share data)

September 30,

December 31,

2020

2019

U.S. $ in thousands

Unaudited

Audited

ASSETS

Current Assets:

Cash and cash equivalents

$

24,770

$

536

Short-term deposit (Note 4)

4,038

33

Other accounts receivable

1,473

2,359

Prepaid expenses and other current assets (Note 5)

56

432

Total current assets

30,337

3,360

Long-Term Assets:

Prepaid expenses and other long-term assets

27

32

Operating lease right of use asset (Note 6)

1,377

2,182

Property and Equipment, Net

950

960

Total Long-Term Assets

2,354

3,174

Total assets

$

32,691

$

6,534

LIABILITIES AND STOCKHOLDERS' EQUITY (DEFICIT)

Current Liabilities:

Accounts payable

$

3,283

$

14,677

Accrued expenses

917

1,000

Operating lease liability (Note 6)

1,216

1,263

Other accounts payable

1,013

714

Total current liabilities

6,429

17,654

Long-Term Liabilities:

Operating lease liability (Note 6)

284

1,103

Total long-term liabilities

284

1,103

Total liabilities

$

6,713

$

18,757

Stockholders' Equity (deficit):

Stock capital: (Note 7)

12

11

Common Stock of $0.00005 par value - Authorized: 100,000,000 shares at September 30, 2020 and December 31, 2019 respectively; Issued and outstanding: 31,567,592 and 23,174,228 shares at September 30, 2020 and December 31, 2019 respectively.

Additional paid-in-capital

View post:
BrainStorm Announces Financial Results for the Third Quarter of 2020 and Provides a Corporate Update - BioSpace

Bone Marrow Stem Cells Comments Off on BrainStorm Announces Financial Results for the Third Quarter of 2020 and Provides a Corporate Update – BioSpace | October 16th, 2020