Category Archives: Cell Medicine

EAST HANOVER, N.J., June 3, 2021 /PRNewswire/ -- Novartis today reported the final analysis from the NETTER-1 phase III study comparing treatment using Lutathera (INN: lutetium (177Lu) oxodotreotide / USAN: lutetium Lu 177 dotatate) plus 30 mg octreotide LAR to 60 mg of octreotide LAR in patients with midgut neuroendocrine tumors. The previously reported primary analysis of the trial demonstrated a statistically significant improvement in progression free survival (PFS) (HR: 0.18*, p < 0.0001)3. In the final analysis of overall survival, a secondary objective of the trial, treatment with Lutathera resulted in a clinically relevant prolongation in median overall survival of 11.7 months [48.0 months (95%CI: 37.4-55.2) compared to the control arm (36.3 months (95%CI: 25.9-51.7)]1.While this analysis did not reach statistical significance (Hazard ratio for OS (HR): 0.84 with 95% CI: (0.60, 1.17) (p=0.30, two-sided))1, the analyses of overall survival may have been impacted by multiple factors, including the crossover of patients from the control arm receiving subsequent radioligand therapy (36% of patients) as well as heterogenous subsequent anti-cancer treatments in both study arms1.No new safety signals emerged in the final analysis1. These results will be presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting on June 4.

Jonathan Strosberg, MD, Principal Investigator and Associate Professor, Section Head, Neuroendocrine Tumor Program at Moffitt Cancer Center, said, "Lutathera plus long-acting octreotide was associated with a nearly 12-month difference in median overall survival compared to high-dose long-acting octreotide in these difficult to treat patients with inoperable midgut NETs progressing under standard dose octreotide LAR treatment.While not statistically significant, I consider this difference to be clinically relevant for these patients. It is also important to emphasize that PFS was the primary endpoint of this study.Moreover, 36% of patients in the control arm crossed over to receive subsequent radioligand treatment, which may have impacted the comparison of survival between both study arms."

"We are proud of our 30-year legacy as an innovator for patients in the neuroendocrine tumor community," said John Tsai, Head of Global Drug Development and Chief Medical Officer for Novartis. "Since its approval by the European Commission in 2017 and the FDA in 2018, Lutathera has been administered to more than 9,000 gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients in Europe and the United States1. We believe in the potential of targeted radioligand therapy and are investing in new discovery and expansion of this important platform, including exploration of new radioisotopes and combinations with complementary mechanisms of action, such as immunotherapy and inhibitors of DNA damage response."

At this final analysis, no new safety signals emerged in the long-term safety follow-up with a median of 6.3 years. In terms of secondary hematological malignancies, no new cases of MDS or acute leukemia were reported in the long term follow up4.

Radioligand therapy combines a targeting compound that binds to receptors expressed by tumors and a radioactive isotope, causing DNA damage that inhibits tumor growth and replication and may lead to cell death5-7. In the case of Lutathera, it binds to somatostatin receptor type 2, which is over-expressed on certain types of cells, such as gastroenteropancreatic neuroendocrine tumor cells8,9.

Novartis has established global expertise and specialized supply chain and manufacturing capabilities across its network of four radioligand therapy production sites, and is further increasing capacity to ensure delivery of future targeted radioligand therapies to patients in need. Novartis is the only pharmaceutical company which is pursuing four different cancer treatment platforms. These include targeted radioligand therapy, cell and gene therapy, targeted therapy and immunotherapy, with an opportunity to combine these platforms for the best outcomes for each cancer patient.

Visithttps://www.hcp.novartis.com/virtual-congress/a-2021/for the latest information from Novartis, including our commitment to the Oncology community, and access to our ASCO21 Virtual Scientific Program data presentations (for registered participants).

* HR: 0.21 (0.13, 0.32) in the US Package Insert

About NETTER-1NETTER-1 is a Phase III international, multicenter, controlled, randomized study that compared treatment using Lutathera every eight weeks plus best standard of care (octreotide LAR 30 mg) to 60 mg of octreotide LAR (dosed every four weeks) in patients with inoperable midgut NETs progressing under standard dose octreotide LAR treatment and overexpressing somatostatin receptors3.

The primary endpoint was to compare the progression-free survival (PFS) after treatment with Lutathera plus octreotide LAR 30 mg versus octreotide LAR 60 mg using RECIST 1.1 criteria3. Secondary trial endpoints included comparing objective response rate, overall survival, time to tumor progression, duration of response and safety between the two study arms3.

About GEP-NETs Neuroendocrine tumors (NETs) are a type of cancer that originate in neuroendocrine cells throughout the body. NETs are commonly considered slow-growing malignancies. However, some NETs are associated with rapid progression and poor prognosis10-11. In many cases, NET diagnosis is delayed until patients have advanced disease12. Symptoms such as fatigue, diarrhea, and abdominal pain can occur on a daily basis13. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are subdivided into two categories: tumors of the gastrointestinal (GI) tract and pancreas14. There is a need for additional treatment options for inoperable or advanced GEP-NET, including those who have progressed while taking first-line somatostatin analogs.

The estimated age-adjusted incidence, or rate of new cases of NETs in the United States is approximately 6.98/100,000 per year (as of 2012), while the estimated 20-year limited-duration prevalence for 2014, based on the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, was 171,32111. Even though NETs have historically been considered to be rare (orphan disease), their incidence has grown over 500% over the last 3 decades 10,11,12,15.

About LutatheraLutathera (lutetium Lu 177 dotatate) is an Advanced Accelerator Applications product approved in the United States for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut and hindgut neuroendocrine tumors in adults16.

Lutathera (lutetium (177Lu) oxodotreotide) is also approved in Europe for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults3.

Important Safety InformationLUTATHERA(lutetium Lu 177 dotatate) is a prescription medicine used to treat adults with a type of cancer known as gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that are positive for the hormone receptor somatostatin, including GEP-NETs in the foregut, midgut, and hindgut.

LUTATHERA is associated with some serious safety considerations, and in some cases these may require a healthcare provider to adjust or stop treatment. Treatment with LUTATHERA will expose patients to radiation which can contribute to long-term radiation exposure. Overall radiation exposure is associated with an increased risk for cancer. The radiation will be detectable in urine for up to 30 days following administration of the drug. It is important to minimize radiation exposure to household contacts consistent with good radiation safety practices as advised by your healthcare provider. Treatment with LUTATHERA increases the risk of myelosuppression, a condition in which bone marrow activity is decreased, resulting in a drop in blood cell counts. You may experience blood-related side effects such as low red blood cells (anemia), low numbers of cells that are responsible for blood clotting (thrombocytopenia), and low numbers of white blood cells (neutropenia). Speak with your healthcare provider if you experience any signs or symptoms of infection, fever, chills, dizziness, shortness of breath or increased bleeding or bruising. Other serious conditions that you may develop as a direct result of treatment with LUTATHERA include blood and bone marrow disorders known as secondary myelodysplastic syndrome and cancer known as acute leukemia. Your healthcare provider will routinely check your blood cell counts and tell you if they are too low or too high. Treatment with LUTATHERA will expose kidneys to radiation and may impair their ability to work as normal. You may be at an increased risk for kidney problems after LUTATHERA treatment if you already have kidney impairment before treatment. In some cases, patients have experienced kidney failure after treatment with LUTATHERA. Your healthcare provider will provide you with an amino acid solution before, during, and after LUTATHERA to help protect your kidneys. You should stay well hydrated before, during, and after your treatment. You should urinate frequently during and after administration of LUTATHERA. Your doctor will monitor your kidney function and may withhold, reduce, or stop your LUTATHERA treatment accordingly. In clinical studies of LUTATHERA, less than 1% of patients were reported to have tumor bleeding (hemorrhage), swelling (edema) or tissue damage (necrosis) to the liver. If you have tumors in your liver, you may be more likely to experience these side effects. Signs that you may be experiencing liver damage include increases in blood markers called ALT, AST and GGT. Your healthcare provider will monitor your liver using blood tests and may need to withhold, reduce, or stop your LUTATHERA treatment accordingly. During your treatment you may experience certain symptoms that are related to hormones released from your cancer. These symptoms may include flushing, diarrhea, difficulty breathing (bronchospasm), and low blood pressure (hypotension), and may occur during or within the 24 hours after your first LUTATHERA treatment. Your healthcare provider will monitor you closely. Speak with your healthcare provider if you experience any of these signs or symptoms. Tell your healthcare provider if you are pregnant. LUTATHERA can harm your unborn baby. Females should use an effective method of birth control during treatment and for 7 months after the final dose of LUTATHERA. Males with female partners should use an effective method of birth control during treatment and for 4 months after the final dose of LUTATHERA. You should not breastfeed during treatment with LUTATHERA and for 2.5 months after your final dose of LUTATHERA. Treatment with LUTATHERA may cause infertility. This is because radiation absorbed by your testes or ovaries over the treatment period falls in the range of exposure where temporary or permanent infertility may occur.

The most common and most serious side effects of LUTATHERA include: vomiting, nausea, decreased blood cell counts, increased liver enzymes, decreased blood potassium levels, and increased blood glucose. Talk to your doctor if you experience any of these, or any other side effects.

Tell your healthcare provider if you are taking any other medications. Somatostatin analogs and corticosteroids may affect how your LUTATHERA treatment works. You should stop taking your long-acting somatostatin analog at least 4 weeks before LUTATHERA treatment. You may continue taking short-acting somatostatin analogs up to 24 hours before your LUTATHERA treatment. Avoid repeated high doses of glucocorticosteroids during treatment with LUTATHERA.

Please see fullPrescribing Informationfor LUTATHERA.

Disclaimer

This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "may," "could," "would," "expect," "anticipate," "seek," "look forward," "believe," "committed," "investigational," "pipeline," "launch," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Advanced Accelerator Applications S.A. Advanced Accelerator Applications, S.A. (AAA), a Novartis company, is developing targeted radioligand therapies and precision imaging radioligands for oncology indications. We are committed to transforming patients' lives by leading innovation in nuclear medicine. AAA has a legacy as a leader in radiopharmaceutical drugs for Positron Emission Tomography (PET) and Single-Photon Emission Computed Tomography (SPECT) diagnostic imaging. For more information, please visit: https://www.adacap.com

About NovartisNovartis is reimagining medicine to improve and extend people's lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world's top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 110,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com

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Novartis reports clinically relevant improvement in median overall survival data in final analysis of pivotal NETTER-1 study with targeted radioligand...

Feb. 9, 2021 13:00 UTC

PHILADELPHIA--(BUSINESS WIRE)-- Tmunity Therapeutics, Inc., a clinical-stage biotherapeutics company specifically designed to deliver on the bold promise to uncancer the world by creating the best T cell medicines for solid tumor patients, today announced the expansion of its T cell engineered therapy collaboration with the Center for Cellular Immunotherapies (CCI) at the Perelman School of Medicine at the University of Pennsylvania (Penn).

Under the terms of the expanded collaboration, Tmunity receives further access and rights to certain platform and manufacturing technologies, as well as the exclusive licensing of a Penn-developed clinical stage asset, a Mesothelin CAR T-cell therapy product. Tmunity has also committed to further funding of T cell engineering research programs at Penn and will receive exclusive rights, subject to certain limitations, to products and technologies resulting from those programs. Tmunity will continue to have certain rights to intellectual property originating from the laboratories of its scientific founders at Penn including: Carl June, MD, Bruce Levine, PhD, and James Riley, PhD.

We are delighted to see the further expansion of our existing scientific and clinical partnership with Penn to bring leading edge T cell engineered medicines to patients with solid tumors. This partnership with Dr. June and the Penn CCI team further expands our access and certain rights to discoveries, clinical programs, cell engineering, and manufacturing at the cutting edge of T cell engineering, including platform technologies in the field, such as safety switches, signaling domains, payload delivery, and novel approaches for cell persistence and durability, said Usman Oz Azam, President and Chief Executive Officer of Tmunity Therapeutics.

We formed Tmunity to deliver the promise of T cell medicine to patients, bringing together all the essential expertise, technology, and scientific insight to make the next great leap, said Carl H. June, M.D., Director of the Center for Cellular Immunotherapies at Penns Perelman School of Medicine, and Director of the Parker Institute for Cancer Immunotherapy at the University of Pennsylvania. I am tremendously proud of the progress we have accomplished to date and look forward to building on this success in the future.

Tmunity has licensed 4 clinical stage solid tumor CAR-T programs created at Penn and is supporting the further development of several more pipeline candidates through sponsored research agreements with Penn. Drs. June, Levine, Riley, and Chew are all individual equity holders in Tmunity. Penn receives sponsored research funding from Tmunity, and as inventors of some of the licensed technology, Drs. June, Levine, Riley, and Chew, along with Penn, may receive additional financial benefits under the license in the future. Penn is also an investor in the company and holds equity interests.

About Tmunity Therapeutics

Tmunity is a private clinical-stage biotherapeutics company focused on saving and improving lives by delivering the full potential of next-generation T-cell immunotherapy to patients with devastating diseases. Integrating a foundational collaboration with the University of Pennsylvania (Penn) with the groundbreaking scientific, clinical, and manufacturing expertise, and the demonstrated track record of its founders (Carl June, MD; Bruce Levine, PhD; Yangbing Zhao, MD, PhD; Jim Riley, PhD; and Anne Chew, PhD), Tmunity represents a new center of gravity in translational T-cell medicine. Through the University of Pennsylvania, the Parker Institute for Cancer Immunotherapy and other collaborations, the company is developing a diversified portfolio of novel treatments that exhibit best-in-class control over T-cell activation and direction in the body, with a focus in cancer and four programs currently in clinic development. With headquarters in Philadelphia, Tmunity utilizes laboratories and production facilities at Penn and its own dedicated cGMP manufacturing facility in East Norriton, PA, to pursue process improvement and production scale-up in support of clinical development of its T-cell therapies. For more information, visit http://www.tmunity.com and connect with us on social media at @TmunityTx and LinkedIn.

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Tmunity Therapeutics Announces Expansion of T Cell Engineered Therapy Collaboration - BioSpace

DUBLIN, Feb. 9, 2021 /PRNewswire/ -- The "Cell Therapy Market by Cell Type, Therapy Type, Therapeutic Area, and End User: Global Opportunity Analysis and Industry Forecast, 2020-2027" report has been added to ResearchAndMarkets.com's offering.

The global cell therapy market accounted for $7,754. 89 million in 2019, and is expected to reach $48,115. 40 million by 2027, registering a CAGR of 25. 6% from 2020 to 2027.

Cell therapy involves administration of somatic cell preparations for treatment of diseases or traumatic damages. Cell therapy aims to introduce new, healthy cells into a patient's body to replace diseased or missing ones.

This is attributed to the fact that specialized cells, such as brain cells, are difficult to obtain from human body. In addition, specialized cells typically have a limited ability to multiply, making it difficult to produce sufficient number of cells required for certain cell therapies. Some of these issues can be overcome through the use of stem cells. In addition, cells such as blood and bone marrow cells, mature, immature & solid tissue cells, adult stem cells, and embryonic stem cells are widely used in cell therapy procedures.

Moreover, transplanted cells including induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), neural stem cells (NSCs), and mesenchymal stem cells (MSCs) are divided broadly into two main groups including autologous cells and non-autologous cells. Development of precision medicine and advancements in Advanced Therapies Medicinal Products (ATMPS) in context to their efficiency and manufacturing are expected to be the major drivers for the market. Furthermore, automation in adult stem cells and cord blood processing and storage are the key technological advancements that fuel growth of the market for cell therapy.

In addition, growth in aging patient population, The rise in cell therapy transplantations globally, and surge in disease awareness drive growth of the global cell therapy market. Furthermore, The rise in adoption of human cells over animal cells for cell therapeutics research, technological advancements in field of cell therapy, and increase in incidences of diseases such as cancer, cardiac abnormalities, and organ failure are the key factors that drive growth of the global market.

Moreover, implementation of stringent government regulations regarding the use of cell therapy is anticipated to restrict growth of the market. On the contrary, surge in number of regulations to promote stem cell therapy and increase in funds for research in developing countries are expected to offer lucrative opportunities to the market in the future.

The global cell therapy market is categorized on the basis of therapy type, therapeutic area, cell type, end user, and region. On the basis of therapy type, the market is segregated into autologous and allogenic. By therapeutics, it is classified into malignancies, musculoskeletal disorders, autoimmune disorders, dermatology, and others.

The global cell therapy market is categorized on the basis of therapy type, therapeutic, cell type, end user and region. On the basis of therapy type, the market is segregated into autologous and allogenic. By therapeutic area, it is classified into malignancies, musculoskeletal disorders, autoimmune disorders, dermatology, and others. On the basis of cell type, it is segregated into stem cell therapy and non-stem cell type. On the basis of end user, it is segregated into hospital & clinics and academic & research institutes. On the basis of region, the market is studied across North America, Europe, Asia-Pacific, and LAMEA.

Key Benefits

Key Topics Covered:

Chapter 1: Introduction1.1. Report Description1.2. Key Benefits for Stakeholders1.3. Key Market Segments1.4. Research Methodology1.4.1. Secondary Research1.4.2. Primary Research1.4.3. Analyst Tools & Models

Chapter 2: Executive Summary2.1. Key Findings of the Study2.2. Cxo Perspective

Chapter 3: Market Overview3.1. Market Definition and Scope3.2. Key Findings3.2.1. Top Player Positioning3.2.2. Top Investment Pockets3.2.3. Top Winning Strategies3.3. Porter's Five Forces Analysis3.4. Impact Analysis3.4.1. Drivers3.4.1.1. Technological Advancements in the Field of Cell Therapy3.4.1.2. The Rise in Number of Cell Therapy Clinical Studies3.4.1.3. The Rise in Adoption of Regenerative Medicine3.4.2. Restraint3.4.2.1. Developing Stage and Pricing3.4.3. Opportunity3.4.3.1. High Growth Potential in Emerging Markets3.5. Impact of Covid-19 on Cell Therapy Market

Chapter 4: Cell Therapy Market, by Cell Type4.1. Overview4.1.1. Market Size and Forecast4.2. Stem Cell4.2.1. Key Market Trends and Opportunities4.2.2. Market Size and Forecast, by Region4.2.3. Market Size and Forecast, by Type4.2.3.1. Bone Marrow, Market Size and Forecast4.2.3.2. Blood, Market Size and Forecast4.2.3.3. Umbilical Cord-Derived, Market Size and Forecast4.2.3.4. Adipose-Derived Stem Cell, Market Size and Forecast4.2.3.5. Others (Placenta, and Nonspecific Cells), Market Size and Forecast4.3. Non-Stem Cell4.3.1. Key Market Trends and Opportunities4.3.2. Market Size and Forecast, by Region

Chapter 5: Cell Therapy Market, by Therapy Type5.1. Overview5.1.1. Market Size and Forecast5.2. Autologous5.2.1. Key Market Trends and Opportunities5.2.2. Market Size and Forecast, by Region5.2.3. Market Analysis, by Country5.3. Allogeneic5.3.1. Key Market Trends and Opportunities5.3.2. Market Size and Forecast, by Region5.3.3. Market Analysis, by Country

Chapter 6: Cell Therapy Market, by Therapeutic Area6.1. Overview6.1.1. Market Size and Forecast6.2. Malignancies6.2.1. Market Size and Forecast, by Region6.2.2. Market Analysis, by Country6.3. Musculoskeletal Disorders6.3.1. Market Size and Forecast, by Region6.3.2. Market Analysis, by Country6.4. Autoimmune Disorders6.4.1. Market Size and Forecast, by Region6.4.2. Market Analysis, by Country6.5. Dermatology6.5.1. Market Size and Forecast, by Region6.5.2. Market Analysis, by Country6.6. Others6.6.1. Market Size and Forecast, by Region6.6.2. Market Analysis, by Country

Chapter 7: Cell Therapy Market, by End-user7.1. Overview7.1.1. Market Size and Forecast7.2. Hospitals & Clinics7.2.1. Key Market Trends and Opportunities7.2.2. Market Size and Forecast, by Region7.2.3. Market Analysis, by Country7.3. Academic & Research Institutes7.3.1. Key Market Trends and Opportunities7.3.2. Market Size and Forecast, by Region7.3.3. Market Analysis, by Country

Chapter 8: Cell Therapy Market, by Region8.1. Overview8.2. North America8.3. Europe8.4. Asia-Pacific8.5. LAMEA

Chapter 9: Company Profiles9.1. Allosource9.1.1. Company Overview9.1.2. Company Snapshot9.1.3. Operating Business Segments9.1.4. Product Portfolio9.1.5. Key Strategic Moves and Developments9.2. Cells for Cells9.2.1. Company Overview9.2.2. Company Snapshot9.2.3. Operating Business Segments9.2.4. Product Portfolio9.3. Holostem Terapie Avanzate Srl9.3.1. Company Overview9.3.2. Company Snapshot9.3.3. Operating Business Segments9.3.4. Product Portfolio9.4. Jcr Pharmaceuticals Co. Ltd.9.4.1. Company Overview9.4.2. Company Snapshot9.4.3. Operating Business Segments9.4.4. Product Portfolio9.4.5. Business Performance9.4.6. Key Strategic Moves and Developments9.5. Kolon Tissuegene, Inc.9.5.1. Company Overview9.5.2. Company Snapshot9.5.3. Operating Business Segments9.5.4. Product Portfolio9.5.5. Key Strategic Moves and Developments9.6. Medipost Co. Ltd.9.6.1. Company Overview9.6.2. Company Snapshot9.6.3. Operating Business Segments9.6.4. Product Portfolio9.6.5. Business Performance9.7. Mesoblast Ltd9.7.1. Company Overview9.7.2. Company Snapshot9.7.3. Operating Business Segments9.7.4. Product Portfolio9.7.5. Business Performance9.8. Nuvasive, Inc.9.8.1. Company Overview9.8.2. Company Snapshot9.8.3. Operating Business Segments9.8.4. Product Portfolio9.8.5. Business Performance9.9. Osiris Therapeutics, Inc.9.9.1. Company Overview9.9.2. Company Snapshot9.9.3. Operating Business Segments9.9.4. Product Portfolio9.10. Stemedica Cell Technologies, Inc.9.10.1. Company Overview9.10.2. Company Snapshot9.10.3. Operating Business Segments9.10.4. Product Portfolio

For more information about this report visit https://www.researchandmarkets.com/r/shw12n

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Worldwide Cell Therapy Industry to 2027 - Profiling Allosource, Medipost and Mesoblast Among Others - PRNewswire

For Immediate Release: February 05, 2021

Today, the U.S. Food and Drug Administration approved Breyanzi (lisocabtagene maraleucel), a cell-based gene therapy to treat adult patients with certain types of large B-cell lymphoma who have not responded to, or who have relapsed after, at least two other types of systemic treatment. Breyanzi, a chimeric antigen receptor (CAR) T cell therapy, is the third gene therapy approved by the FDA for certain types of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.

Todays approval represents another milestone in the rapidly progressing field of gene therapy by providing an additional treatment option for adults with certain types of cancer affecting the blood, bone marrow, and lymph nodes, said Peter Marks, M.D., Ph.D., director of the FDAs Center for Biologics Evaluation and Research. Gene and cell therapies have evolved from promising concepts to practical cancer treatment regimens.

DLBCL is the most common type of non-Hodgkin lymphoma in adults. Non-Hodgkin lymphomas are cancers that begin in certain cells of the immune system and can be either fast-growing (aggressive) or slow-growing. Approximately 77,000 new cases of non-Hodgkin lymphoma are diagnosed in the U.S. each year and DLBCL represents approximately one in three newly diagnosed cases.

Each dose of Breyanzi is a customized treatment created using a patients own T-cells, a type of white blood cell, to help fight the lymphoma. The patients T-cells are collected and genetically modified to include a new gene that facilitates targeting and killing of the lymphoma cells. Once the cells are modified, they are infused back into the patient.

The safety and efficacy of Breyanzi were established in a multicenter clinical trial of more than 250 adults with refractory or relapsed large B-cell lymphoma. The complete remission rate after treatment with Breyanzi was 54%.

Treatment with Breyanzi has the potential to cause severe side effects. The labeling carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T cells, causing high fever and flu-like symptoms and neurologic toxicities. Both CRS and neurological events can be life-threatening. Other side effects include hypersensitivity reactions, serious infections, low blood cell counts and a weakened immune system. Side effects generally appear within the first one to two weeks following treatment, but some side effects may occur later.

Because of the risk of CRS and neurologic toxicities, Breyanzi is being approved with a risk evaluation and mitigation strategy (REMS) which includes elements to assure safe use (ETASU). The FDA is requiring, among other things, that healthcare facilities that dispense Breyanzi be specially certified. As part of that certification, staff involved in the prescribing, dispensing or administering of Breyanzi are required to be trained to recognize and manage the risks of CRS and neurologic toxicities. The REMS program specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with Breyanzi.

To further evaluate the long-term safety, the FDA is also requiring the manufacturer to conduct a post-marketing observational study involving patients treated with Breyanzi.

The FDA granted Breyanzi Orphan Drug, Regenerative Medicine Advanced Therapy (RMAT) and Breakthrough Therapy designations. The RMAT designation program was created under the 21st Century Cures Act to help facilitate the expeditious development of regenerative medicine therapies intended for serious conditions. Breyanzi is the first regenerative medicine therapy with RMAT designation to be licensed by the FDA. Orphan Drug designation provides incentives to assist and encourage the development of drugs for rare diseases. The Breyanzi application was reviewed using a coordinated, cross-agency approach, including both the Center for Biologics Evaluation and Research and FDAs Oncology Center of Excellence.

The FDA granted approval of Breyanzi to Juno Therapeutics Inc., a Bristol-Myers Squibb Company.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nations food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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FDA Approves New Treatment For Adults With Relapsed Or Refractory Large-B-Cell Lymphoma - FDA.gov

PHOENIX, Feb. 8, 2021 /PRNewswire/ --(OTC-CELZ) Creative Medical Technology Holdings Inc. announced today recruitment of Dr. Caigan Du, Associate Professor at the University of British Columbia to the Company's Scientific Advisory Board.

Dr. Du is a top researcher in the area of molecular and immunological understanding of kidney failure and transplant rejection. Dr. Du is funded by numerous national and international organizations including the Kidney Foundation and the Canadian Institutes of Health Research.

"I am honored to work with Creative Medical Technology Holdings in this fascinating field of leveraging reprogrammed immune cells for regenerating injured kidneys." Said Dr. Du. "To date people think about regenerative medicine and immunology as separate fields. It is very exciting to consider the possibility that immune cells can act as a catalyst for regenerative processes: this is the basis of the ImmCelz product."

ImmCelz is a personalized cell therapy generated by incubation of patient cells with allogeneic JadiCell stem cells under proprietary conditions. The JadiCell possess potent ability to reprogram the immune system, as exemplified in part by their ability to significantly extend survival of COVID patients in an FDA double blind, placebo controlled, clinical trial1. ImmCelz has been demonstrated effective in animal models of rheumatoid arthritis2, liver failure3, stroke4, type 1 diabetes5 and kidney failure6. Scientific studies suggest ImmCelz functions through secretion of a fundamentally important molecule called Hepatocyte Growth Factor7, as well as stimulation of T regulatory cells, a type of immune system cell that suppresses pathological immunity8.

"As a clinical-stage biotechnology company, having already commercialized other stem cell products, we understand the key to any success is based on the ability to attract scientific key opinion leaders." Said Timothy Warbington, President and CEO of Creative Medical Technology Holdings. "Dr. Du is a visionary and pioneer in understanding of kidney diseases and we wholeheartedly look forward to him joining our scientific advisory board."

The Advisory Board of Creative Medical Technology Holdings includes internationally renowned neurologist Santosh Kesari MD, Ph.D, the former head of cardiology at Cedar Sinai Medical Center Timothy Henry, MD and our Director Dr. Amit Patel, inventor of the JadiCell and the first physician to have implanted stem cells into the human heart.

About Creative Medical Technology HoldingsCreative Medical Technology Holdings, Inc. is a commercial stage biotechnology company specializing in regenerative medicine/stem cell technology in the fields of immunotherapy, urology, neurology and orthopedics and is listed on the OTC under the ticker symbol CELZ. For further information about the company, please visitwww.creativemedicaltechnology.com.

Forward Looking StatementsOTC Markets has not reviewed and does not accept responsibility for the adequacy or accuracy of this release. This news release may contain forward-looking statements including but not limited to comments regarding the timing and content of upcoming clinical trials and laboratory results, marketing efforts, funding, etc. Forward-looking statements address future events and conditions and, therefore, involve inherent risks and uncertainties. Actual results may differ materially from those currently anticipated in such statements. See the periodic and other reports filed by Creative Medical Technology Holdings, Inc. with the Securities and Exchange Commission and available on the Commission's website atwww.sec.gov.

Creativemedicaltechnology.comwww.StemSpine.comwww.Caverstem.comwww.Femcelz.com ImmCelz.com

1 Umbilical cord mesenchymal stem cells for COVID19 acute respiratory distress syndrome: A doubleblind, phase 1/2a, randomized controlled trial - Lanzoni - - STEM CELLS Translational Medicine - Wiley Online Library2 Creative Medical Technology Holdings Reports Positive Preclinical Data on ImmCelz Immunotherapy Product in Rheumatoid Arthritis Model | BioSpace3 Creative Medical Technology Holdings Announces Reversion of Liver Failure Using ImmCelz Personalized Cellular Immunotherapy in Preclinical Model | Nasdaq4 Creative Medical Technology Holdings Identifies Mechanism of Action of ImmCelz Stroke Regenerative Activity (prnewswire.com)5 Creative Medical Technology Holdings Announces Positive Data and Patent Filing Using ImmCelz to Treat Type 1 Diabetes (prnewswire.com)6 Creative Medical Technology Holdings Files Patent based on Positive Data on Renal Failure using ImmCelz Regenerative Immunotherapy (prnewswire.com)7 Creative Medical Technology Holdings Identifies and Files Patent on Novel Mechanism of ImmCelz Therapeutic Activity (apnews.com)8 Creative Medical Technology Holdings Identifies Mechanism of Action of ImmCelz Stroke Regenerative Activity (prnewswire.com)

SOURCE Creative Medical Technology Holdings, Inc.

http://creativemedicaltechnology.com

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Creative Medical Technology Holdings Recruits Internationally Renowned Kidney Expert to Scientific Advisory Board - PRNewswire

mRNA has been a game-changer for the development of a COVID-19 vaccine. It has allowed researchers to more efficiently engineer a less intrusive vaccine as it instructs your body to produce certain proteins rather than have your immune adjust to small bits of the virus it is trying to combat.

The mRNA technology has been used, in theory, since the 1990s, but the Pfizer and Moderna COVID-19 vaccines are the first time the technology has been put into practice for human use.

Its really fun to be part of this development, said Sven Even Borgos, a researcher with SINTEF, one of Northern Europes largest research institutes. The basic principle of mRNA is that when you deliver this code, you actually instruct the body to make its own medicine and thats partly why its so fascinating.

With the COVID-19 vaccines, the mRNA that is injected into the body instructs it to produce small bits spike protein, the main way through which the coronavirus injects itself into our cells. This way, the body recognizes the spike protein and attacks any cells that have it, such as COVID-19.

Researchers say that same mRNA technology has been a game-changer for a slew of other viruses and disorder such as cancer, sports recovery, and preexisting conditions.

There are certain things that we could never do before without being able to use DNA, or mRNA, to put new proteins into cells, said Bruce Zetter, the head researcher at Boston Childrens Hospital and a professor of cancer biology at Harvard Medical School.

He says mRNA is not a silver bullet, but it is a monumental step in accelerating cancer research.

Lets say we had a cancer cell in someones body and we knew it made a particular protein that normal cells dont make, he said. Ill call [that particular protein] Cancer Protein 1. So we have CP-1, and now, what I would do is I would get mRNA to specify CP1. Id inject it into the muscle in the arm and those cells in the muscle would make CP1 and theyd stimulate my immune system to fight any cell that had that protein.

Currently, many cancer treatments rely on radiation to kill cancer cells. Through mRNA, however, Zetter says we are training our immune systems to act as the primary fighter.

Its almost like you could treat virtually any disease with it because almost all diseases in your body have a connection to a protein of some kind, said Borgos.

Researchers say mRNA could tell the body to produce proteins to make ligaments, helping patients recovering from a torn ACL.

It could also help autoimmune disorders like hemophilia, which can causes excessive bleeding, as it instructs the body to produce a protein that allows blood to clot properly.

Just a few weeks ago, researchers in Germany injected mice with mRNA, which reduced the activity of multiple sclerosis in those mice. Currently, there is no cure for the disease.

Researchers say we are still years from any type of vaccines for these diseases but say mRNA has sped up their development considerably.

Its really a revolution in vaccine technology, said Borgos.

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COVID-19 vaccine paves the way for new types of medication - The Denver Channel

WALTHAM, Mass.--(BUSINESS WIRE)--BostonGene Corporation, a biomedical software company committed to defining optimal precision medicine-based therapies for cancer patients, and Weill Cornell Medicine, today announced a publication in Cancer Discovery, a journal of the American Association for Cancer Research. The manuscript Clinical and biological subtypes of B-cell lymphoma revealed by microenvironmental signatures highlights the tumor microenvironment as a critical component of B-cell lymphoma biology and the effects of different microenvironments on diffuse large B-cell lymphoma (DLBCL) clinical behavior, establishing a significant opportunity for the development of novel and personalized therapeutic strategies for this disease.

In this research study, the microenvironment subtypes of over 4,600 DLBCL patients were classified using curated and refined transcriptional signatures encompassing key microenvironment and cancer cells activities and processes. This analysis revealed four distinct DLBCL microenvironments (LMEs), each with its own set of unique biological and clinical properties. The LMEs were also found to correlate with different clinical outcomes and prognoses, and downstream preclinical mechanistic studies demonstrated that the LMEs could be applied in clinical decision-making for DLBCL patients.

This study was designed to evaluate the role of the tumor microenvironment in DLBCL biology, said Leandro Cerchietti, M.D., Associate Professor of Medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. The results revealed distinct DLBCL microenvironments with unique therapeutic vulnerabilities that can be utilized for optimization of DLBCL treatment strategies.

The data demonstrate that this novel classification platform provides a roadmap for the therapeutic exploitation of the tumor microenvironment in DLBCL patients, said Nathan Fowler, MD, Chief Medical Officer at BostonGene. Together with Weill Cornell Medicine, we look forward to identifying new treatment strategies to ultimately improve the clinical outcomes of these patients.

About BostonGene Corporation

BostonGene Corporation is pioneering the use of biomedical software for advanced patient analysis and personalized therapy decision making in the fight against cancer. BostonGenes unique solution performs sophisticated analytics to aid clinicians in their evaluation of viable treatment options for each patient's individual genetics, tumor and tumor microenvironment, clinical characteristics and disease profile. BostonGenes mission is to enable physicians to provide every patient with the highest probability of survival through optimal cancer treatments using advanced, personalized therapies. For more information, visit BostonGene at http://www.BostonGene.com.

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BostonGene and Weill Cornell Medicine Announce Publication in Cancer Discovery Revealing the Role of the Tumor Microenvironment in the Clinical...

REDWOOD CITY, Calif.--(BUSINESS WIRE)--Jasper Therapeutics, Inc., a biotechnology company focused on hematopoietic cell transplant therapies, today announced positive preliminary findings from its ongoing multicenter Phase 1 clinical trial of JSP191, a first-in-class anti-CD117 (stem cell factor receptor) monoclonal antibody, as a conditioning agent in older patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) undergoing hematopoietic (blood) cell transplantation.

Data from the first six patients who received a single dose of JSP191 prior to transplantation showed successful engraftment in all six patients. Complete donor myeloid chimerism (equal or greater than 95%) was observed in five of six evaluable patients at 28 days, and all three evaluable patients had total donor chimerism equal or greater than 95% observed at day 90. In addition, at 28 days, three of five evaluable patients showed complete eradication of measurable residual disease (MRD) as measured by next-generation sequencing. Two of the five evaluable patients showed substantial reductions in MRD. No treatment-related serious adverse events were reported.

The findings were presented by lead investigator Lori Muffly, M.D., M.S., Assistant Professor of Medicine (Blood and Bone Marrow Transplantation) at Stanford Medicine, as a late-breaking abstract at the 2021 Transplantation & Cellular Therapy (TCT) Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR).

These early clinical results are the first to demonstrate that JSP191 administered in combination with a standard non-myeloablative regimen of low-dose radiation and fludarabine is well tolerated and can clear measurable residual disease in older adults with MDS or AML undergoing hematopoietic cell transplantation a patient population with historically few options, said Kevin N. Heller, M.D., Executive Vice President, Research and Development, of Jasper Therapeutics. These patients could be cured by hematopoietic cell transplantation, but the standard-of-care myeloablative conditioning regimens used today are highly toxic and associated with high rates of morbidity and mortality particularly in older adults. Traditional lower intensity transplant conditioning regimens are better tolerated in older adults, but are associated with higher rates of relapse in MDS/AML patients with measurable residual disease. JSP191, a well-tolerated biologic conditioning agent that targets and depletes both normal hematopoietic stem cells and those that initiate MDS and AML, has the potential to be a curative option for these patients.

The open-label, multicenter Phase 1 study (JSP-CP-003) is evaluating the safety, tolerability and efficacy of adding JSP191 to the standard conditioning regimen of low-dose radiation and fludarabine among patients age 65 to 74 years with MDS or AML undergoing hematopoietic cell transplantation. Patients were ineligible for full myeloablative conditioning. The primary outcome measure of the study is the safety and tolerability of JSP191 as a conditioning regimen up to one year following a donor cell transplant.

We designed JSP191 to be given as outpatient conditioning and to have both the efficacy and safety profile required for use in newborn patients and older patients for successful outcomes, said Wendy Pang, M.D., Ph.D. Executive Director, Research and Translational Medicine, of Jasper Therapeutics. We are enthusiastic about the reduction of measurable residual disease seen in these patients, especially given that it is associated with improved relapse-free survival. We are excited to continue our research in MDS/AML, with plans for an expanded study. We are evaluating JSP191, the only antibody of its kind, in two ongoing clinical studies and are encouraged by the positive clinical data seen to date.

About MDS and AML

Myelodysplastic syndromes (MDS) are a group of disorders in which immature blood-forming cells in the bone marrow become abnormal and do not make new blood cells or make defective blood cells, leading to low numbers of normal blood cells, especially red blood cells.1 In about one in three patients, MDS can progress to acute myeloid leukemia (AML), a rapidly progressing cancer of the bone marrow cells.1 Both are diseases of the elderly with high mortality. Each year, about 5,000 patients with MDS and 8,000 people with AML in the G7 countries receive hematopoietic cell transplants. These transplants are curative but are underused due to the toxicity of the current high-intensity conditioning regimen, which includes the chemotherapy agents busulfan and fludarabine.

About JSP191

JSP191 (formerly AMG 191) is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow. JSP191 binds to human CD117, a receptor for stem cell factor (SCF) that is expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required for stem cells to survive. JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals, causing the stem cells to undergo cell death and creating an empty space in the bone marrow for donor or gene-corrected transplanted stem cells to engraft.

Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in animal models of SCID, myelodysplastic syndromes (MDS) and sickle cell disease (SCD). Treatment with JSP191 creates the space needed for transplanted normal donor or gene-corrected hematopoietic stem cells to successfully engraft in the host bone marrow. To date, JSP191 has been evaluated in more than 90 healthy volunteers and patients.

JSP191 is currently being evaluated in two separate clinical studies in hematopoietic cell transplantation. A Phase 1/2 dose-escalation and expansion trial is evaluating JSP191 as a sole conditioning agent to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplantation for severe combined immunodeficiency (SCID), which is potentially curable only by this type of treatment. Data presented at the 62nd American Society of Hematology (ASH) Annual Meeting showed that a single dose of JSP191 administered prior to stem cell transplantation in a 6-month-old infant was effective in establishing sustained donor chimerism followed by development of B, T and NK immune cells. No treatment-related adverse events were reported. A Phase 1 clinical study is evaluating JSP191 in combination with another low-intensity conditioning regimen in patients with MDS or AML undergoing hematopoietic cell transplantation. For more information about the design of these two ongoing clinical trials, visit http://www.clinicaltrials.gov (NCT02963064 and NCT04429191).

Additional studies are planned to advance JSP191 as a conditioning agent for patients with other rare and ultra-rare monogenic disorders and autoimmune diseases.

About Jasper Therapeutics

Jasper Therapeutics is a biotechnology company focused on the development of novel curative therapies based on the biology of the hematopoietic stem cell. The companys lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a hematopoietic cell transplant. This first-in-class conditioning antibody is designed to enable safer and more effective curative hematopoietic cell transplants and gene therapies. For more information, please visit us at jaspertherapeutics.com.

1 https://www.cancer.org/cancer/myelodysplastic-syndrome/about/what-is-mds.html

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Jasper Therapeutics Announces Positive Data from Phase 1 Clinical Trial of JSP191 as Targeted Stem Cell Conditioning Agent in Patients with...

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of immune and blood systems reset via stem cell transplant to more patients, today announced data presentations across its stem cell mobilization and targeted conditioning programs at the Transplantation and Cellular Therapy (TCT) Annual Meeting, to be held virtually on February 8-12, 2021.

Magenta continues to generate encouraging data across our pipeline, furthering our commitment to patients to expand eligibility and improve the clinical outcomes with stem cell transplant, said John Davis Jr., M.D., M.P.H., M.S., Magentas Head of Research & Development and Chief Medical Officer. Our presentations this year at TCT highlight the potential wide-ranging utility of our portfolio, and we are particularly excited to share these results, and to continue our progress in the year ahead.

Oral Presentations Showcasing Clinical Data of MGTA-145 Stem Cell Mobilization Program

Magenta is developing MGTA-145 in combination with plerixafor utilizing complementary mechanisms to mobilize hematopoietic stem cells (HSCs) for collection and transplantation. This combination has the potential to be the preferred mobilization regimen for rapid, reliable, predictable and safe collection of high numbers of functional blood stem cells to improve outcomes across autologous and allogeneic stem cell transplantation, which also includes stem cells necessary for all HSC-based gene therapies.

Title: MGTA-145 / Plerixafor-Mediated HSC Mobilization and Intravenous HDAd5/35++ Vector Injection into Mice Allows for Efficient in vivo HSC Transduction and Stable Gene Marking in Peripheral Blood Cells (Oral Abstract, #16)Presenting Author: Chang Li, Ph.D., Division of Medical Genetics, Department of Medicine, University of WashingtonDate and Time of Presentation: Session B Transplantation for Non-Malignant Disease; Monday, February 8, 2021, 3:15PM CST / 4:15PM EST

Data from this preclinical study demonstrate the potential of MGTA-145 plus plerixafor to serve as an efficient, single-dose mobilization regimen for in vivo HSC gene therapy where stem cells could be gene corrected or edited without having to remove them from the body. This could potentially replace current mobilization regimens that rely on ex vivo gene therapy approaches to treat genetic diseases.

Title: MGTA-145, in Combination with Plerixafor in a Phase 1 Clinical Study, Mobilizes Large Numbers of Hematopoietic Stem Cells and a Graft with Potent Immunosuppressive Properties for Autologous and Allogeneic Transplant (Oral Abstract, #35)Presenting Author: Kevin Goncalves, Ph.D., Magenta TherapeuticsDate and Time of Presentation: Session E Consider the Source: Stem Cell Grafts and Donors; Tuesday, February 9, 2021, 4:00PM CST / 5:00PM EST

Data from this Phase 1 clinical trial with healthy volunteers further underscore the potential utility of MGTA-145 plus plerixafor as an effective, single-day mobilization and collection regimen for autologous and allogeneic HSC transplant. MGTA-145 plus plerixafor mobilized high numbers of HSCs and showed durable engraftment, successful gene-modification and immunosuppressive properties by reducing Graft-versus-Host disease (GvHD) in preclinical models.

Oral Presentation Showcasing Preclinical Study of MGTA-117 Targeted ADC Conditioning Program

Magenta is developing a suite of novel antibody-drug conjugates (ADCs) for conditioning, a step in the transplant process that currently relies on the use of systemic chemotherapy agents and radiation. Magentas targeted conditioning programs are designed to selectively eliminate stem cells and/or immune cells from a patient prior to transplant or gene therapy, and to reduce or potentially eliminate the need for high dose or high intensity chemotherapy-based treatments. These programs focus on developing targeted products that remove specific cell types, with an approach that is tailored to the patients disease and transplant requirements.

MGTA-117, Magentas most advanced conditioning program, is a CD117-targeted ADC designed to precisely deplete hematopoietic stem and progenitor cells to clear space in the bone marrow prior to transplant, and to support long-term engraftment and improved disease outcomes in patients. MGTA-117 has shown to be highly selective with potent activity, efficacy and tolerability in preclinical models.

Title: A Single Dose of a Novel Anti-Human CD117-Amanitin Antibody Drug Conjugate (ADC) Engineered for a Short Half-life Provides Dual Conditioning and Anti-Leukemia Activity and Extends Survival Compared to Standard of Care in Multiple Pre-clinical Models of Acute Myeloid Leukemia (AML) (Oral Abstract, #53)Presenting Author: Leanne Lanieri, M.S., Magenta TherapeuticsDate and Time of Presentation: Session H Novel Conditioning Regimens & Transplantation for Aged Populations, Wednesday, February 10, 2021, 4:00PM CST / 5:00PM EST

Hematopoietic stem cell transplant (HSCT) can often be a curative treatment for patients with acute myeloid leukemia (AML). There is currently a need for safer and more effective targeted conditioning agents, as current conditioning regimens are associated with severe toxicities and high post-transplant relapse or graft failure. MGTA-117 was studied in multiple human leukemic xenograft murine models to mimic untreated and refractory AML. In preclinical models, MGTA-117 significantly increased median survival versus a multi-day standard-of-care regimen using cytarabine. Data from this study demonstrate MGTA-117s potential as a potent, targeted HSCT conditioning agent with anti-leukemic activity, emphasizing its potential to improve HSCT outcomes in AML by reducing the risk of post-transplant relapse.

Poster Presentation Highlighting Preclinical Data of CD45-ADC Targeted Conditioning Program

Magentas other ADC-based conditioning program, CD45-ADC, targets both patient HSCs and disease-causing immune cells. The programs lead target is CD45, a cell surface molecule broadly expressed throughout the hematopoietic and immune systems. CD45-ADC has the potential to significantly increase the number of patients eligible to receive a stem cell transplant, particularly those patients with autoimmune diseases and acute leukemias.

Developing a broad targeting approach for safer patient conditioning prior to HSCT could bring the curative potential of allogeneic HSCT to more patients with both malignant and non-malignant disorders. Current conditioning regimens limit accessibility of this procedure due to toxicity.

Title: Targeted CD45 Antibody Drug Conjugate Enables Full Mismatch Allogeneic Hematopoietic Stem Cell Transplantation in a Murine HSCT Model as a Single Agent (AML) (Poster #242)Lead Author: Sharon Hyzy, M.S., Magenta Therapeutics

Data from this study showed conditioning with single agent CD45-ADC enabled complete chimerism in a full mismatch allogeneic HSCT model.

Oral Presentation of MGTA-456 Stem Cell Therapy Expansion Program in Patients with Blood Cancer

Magenta is continuing long-term patient follow up to evaluate MGTA-456 in blood cancers through the investigator-initiated Phase 2 trial in blood cancers at the University of Minnesota and will assess best next steps for the program. Magenta previously announced in June 2020 it had discontinued enrollment in the Phase 2 trial of MGTA-456 in patients with inherited metabolic disorders.

Title: MGTA-456, A CD34 Expanded Cord Blood Product, Permits Selection of Better HLA Matched Units and Results in Rapid Hematopoietic Recovery, Uniform Engraftment and Reduced Graft-Versus-Host Disease in Adults with High-Risk Hematologic Malignancies (Oral Abstract, #31)Presenting Author: Heather Stefanski, M.D., Ph.D., Assistant Professor, Department of Pediatrics, University of MinnesotaDate and Time of Oral Presentation: Session E Consider the Source: Stem Cell Grafts and Donors; Tuesday, February 9, 2021, 3:00PM CST / 4:00PM EST

Twenty-two patients were enrolled in the study, with 18 transplanted with MGTA-456. Compared to transplant patients who had undergone the same conditioning, GvHD prophylaxis and supportive care, patients who received MGTA-456 showed faster neutrophil recovery (median of 17 days compared to 23 days) and better platelet recovery (median 36 days compared to 59 days). Additionally, incidence of grade 2-4 acute GvHD was lower (24% compared to 46%), likely because of the ability to find a better matched cord unit.

About Magenta Therapeutics

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

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

Follow Magenta on Twitter: @magentatx.

Forward-Looking Statement

This press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws, including express or implied statements regarding Magentas future expectations, plans and prospects, including, without limitation, statements regarding expectations and plans for presenting clinical data, projections regarding our long-term growth, cash, cash equivalents and marketable securities, the anticipated timing of our clinical trials and regulatory filings, the development of our product candidates and advancement of our clinical programs, the timing, progress and success of our collaborations, as well as other statements containing words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavor, potential, continue or the negative of such words or other similar expressions that can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation: uncertainties inherent in clinical studies and in the availability and timing of data from ongoing clinical studies; whether interim results from a clinical trial will be predictive of the final results of the trial; whether results from pre-clinical studies or earlier clinical studies will be predictive of the results of future trials; the expected timing of submissions for regulatory approval or review by governmental authorities; regulatory approvals to conduct trials or to market products; whether Magenta's cash resources will be sufficient to fund Magenta's foreseeable and unforeseeable operating expenses and capital expenditure requirements; risks, assumptions and uncertainties regarding the impact of the continuing COVID-19 pandemic on Magentas business, operations, strategy, goals and anticipated timelines, Magentas ongoing and planned pre-clinical activities, Magentas ability to initiate, enroll, conduct or complete ongoing and planned clinical trials, Magentas timelines for regulatory submissions and Magentas financial position; and other risks concerning Magenta's programs and operations set forth under the caption Risk Factors in Magentas Annual Report on Form 10-K filed on March 3, 2020, as updated by Magentas most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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Magenta Therapeutics to Present Additional Data from Phase 1 MGTA-145 Stem Cell Mobilization Program and Preclinical Updates on Targeting Conditioning...

During a Targeted Oncology Case-Based Peer Perspectives virtual event, Jason Westin, MD, MS, director, Lymphoma Clinical Research, section chief, Aggressive Lymphoma, and associate professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, evaluated the management of a 63-year-old patient with diffuse large B-cell lymphoma (DLBCL).

Targeted OncologyTM: What is your initial impression of the therapy used in this case? How would you treat the patient?

WESTIN: Theres not a right or wrong approach here. We dont have any randomized data yet saying that R-CHOP is clearly wrong. We have data from retrospective [analyses] from MD Anderson Cancer Center, as well as a cooperative group publication, saying that outcomes appear inferior with R-CHOP versus R-EPOCH [rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin]. But there are all types of biases when choosing to treat with R-CHOP for that patientis it because she was older and frail and couldnt tolerate EPOCH? [Its not a surprise that] elderly and frail patients dont live as long as patients who are more fit. Sometimes those kind of analyses have biases built into them that might favor the more aggressive treatment, just because of whom youre choosing to give it to. But I think most people feel that if the patient is able to tolerate a change in treatment, at least try it, at least see whether theyre able to tolerate R-EPOCH.

For many patients, R-EPOCH is not that much more toxic than R-CHOP. Its the same drugs; etoposide is added and stretched over 5 days, basically continuous infusion for the first 4 days and then the cyclophosphamide on day 5. It is the same dose for CHOP. So its more complicated for oncologists to give than the [regimen of] 1 day every 3 weeks in the infusion area. But in terms of patients, the adverse effects [AEs] generally line up to be similar. I also...give CNS [central nervous system] prophylaxis. Patients with double-hit lymphoma have a higher risk of CNS disease. Its not through the roof, but the incidence is usually somewhere in the 10% to 20% range of patients who could have a relapse in the brain.

How do you prefer to give patients CNS prophylaxis?

Theres no wrong answer, so whatever you like to use is OK. Many people use intrathecal [IT] chemotherapy because its easier than having to stop CHOP and give methotrexatewhat if theres renal dysfunction, or what if the liver function tests [get worse], and then you have to delay the next cycle?

For EPOCH, cytopenias are sometimes a challenge in that second week when youre trying to give somebody IT or intravenous [IV] methotrexate. Many people would give it as concurrent IT with EPOCH. There were data from the 2020 American Society of Hematology annual meeting that IT and IV might not [make a difference in AE recurrence].1 There was a large meta-analysis from multiple sites across the United States and internationally showing that for patients who are at high risk of CNS relapse, whether they receive treatment via IT or IV, both [delivery methods] still have a high risk of relapse in the brain. This is totally controversial, and the [definitive] answer is that we dont know.

Most people will continue to use IT or IV methotrexate. You just want to make sure if youre giving IV that youre maintaining the schedule and dosing intensity for the systemic chemotherapy, that youre not compromising and [there are] 5 weeks between doses of EPOCH so you can give them methotrexate in the middle.

What other regimens besides EPOCH are being used in this setting?

There are places around the world that dont use EPOCH. They use hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone] or CODOX-M [cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate]. In the United States, EPOCH [in] publications from the National Cancer Institute from Wyndham Wilson, MD, PhD, and Kieron Dunleavy, MD, showed good results in the mediastinal subtype and some patients with Burkitt lymphoma; Ive shifted over to using it.

EPOCH is a fairly widely used regimen, but its not [wrong to use] hyper-CVAD, CODOX-M, or the intensified regimen from Europe. Its basically [moving up] from R-CHOP to something more intense.

Which trials are relevant right now for the population with DLBCL?

Axicabtagene ciloleucel [axi-cel (Yescarta)] was the first CAR [chimeric antigen receptor] T cell approved for adults with DLBCL in the United States, based on the pivotal trial [ZUMA-1 (NCT02348216)].2 [Eligible patients had] no response to last chemotherapy or relapse less than 12 months after autologous stem cell transplant, so basically patients with refractory disease or who were relapsing post transplant. They had to have [received] a prior [anti-CD20 therapy] and a prior anthracycline, which most patients with DLBCL have had.

The trial enrolled 108 patients in 2 cohorts. The [cohort] well focus on is the DLBCL cohort. Generally, the schema for CAR T cells [is] a lymphodepleting chemotherapy thats given ahead of timecyclophosphamide and fludarabine. This is to help the T cells grow, not to control disease; this is to get a favorable cytokine and microenvironment for cell growth when those T cells are infused. These are autologous cells. Its a 1-time treatment of 2 106 CAR T cells, and in this trial, 99% of patients who were enrolled were able to [have their cells] manufactured and 91% were dosed with the cells.

This [study is] changing our management of disease for patients because the overall response rate [ORR] was 83% and 58% had a complete response [CR].3 In this population post transplant or in those who are refractory to heavy-duty chemotherapy, there is a progression-free survival [PFS] of 5.9 months. There was a [significant] proportion of patients who otherwise probably would have died of their disease.

What other CAR T-cell therapies are available?

The second CAR T-cell therapy that was approved for adults with DLBCL, tisagenlecleucel [tisa-cel; Kymriah], was based on findings of the pivotal JULIET study [NCT02445248].4 This schema was basically the same for all the CAR T-cell therapies where patients undergo apheresis, which is similar to but not the same for transplant apheresis. This is [for patients] not getting CD34-positive cells...giving T cells that are cryopreserved for tisa-cel. Theyre then shipped to manufacturing. Patients could get bridging therapy on this clinical trial, which was not the case for the ZUMA-1 trial. They had undergone lymphodepletion with chemotherapy for 5 days, 4 days, and 3 days before receiving the infusion of the CAR T cells on day 0, and then theyre followed.

The results of this clinical trial [showed] ORR was a little lower at 52% and CR rate at 40% [compared with ZUMA-1]. But for those with a CR, there was an impressive Kaplan-Meier curve that showed patients being a year or more out, and 80% or more of them are holding their response. Median overall survival was 12 months for patients who were infused on this study.

How do the available CAR T-cell therapies compare?

Comparing the 2 products I just mentioned that are already FDA approved, as well as the one with impending approval, lisocabtagene maraleucel [liso-cel]...there was fairly robust follow-up now, 27 months, 14 months, 18 months [with axi-cel, tisa-cel, and liso-cel, respectively]; were seeing median PFS level out around 6 months.3-5 We see the same plateau occur in all these CAR T-cell studies, where theres a proportion somewhere in the 30% to high 40% range of patients who are long-term responders. With tisa-cel and liso-cel, the median overall survival was 12 months and 21 months, respectively; for axi-cel, its not reached, which is awfully impressive for this otherwise refractory population.

The trade-off is that it works but can be toxic. The cytokine release syndrome that people talk about, which is the dreaded complication, was seen in the studies at relatively low frequency and was characterized as grade 3 or 4. The tisacel grade 3/4 AEs were higher [23%], but it used a different grading system than the other 2. If [the AEs were] graded with the same system, it was pretty similar, around 10% or so. All 3 of them have an incidence of grade 3 or 4 cytokine release syndrome, but its relatively infrequent. The neurotoxicity is different, however, and for axi-cel, about 1 in 3 patients will have grade 3 or 4 neurotoxicity, which is sometimes prohibitive for this being utilized outside specialized centers that do this frequently. These are some of the reasons that it can be a challenge to administer these drugs.

What other kinds of drugs are available in this setting, and what data support them?

Another option approved recently is polatuzumab vedotin [Polivy], an antibody-drug conjugate, plus bendamustine and rituximab [BR].6 Approval was based on a randomized phase 2 trial for patients with relapsed disease, and it was randomized to either BR or polatuzumab/BR. Patients could not receive [this regimen] after transplant, either allogeneic or autologous, if they had significant neuropathy or if they were eligible for autologous transplant.

The patients ages were typical for this population. The International Prognostic Index score was fairly well balanced, although it was a bit higher risk in the BR arm. The median number of prior lines of treatment was 2 in both arms and about the same for the proportion of patients who had more than 3 prior lines. Seventy-five percent of patients [in the polatuzumab arm] and 85% [in the BR-only arm] had been refractory to the most recent therapy, [so this was a] highly refractory group. The germinal center B-cell subtype was fairly even between these groups.

Polatuzumab had an objective response rate of around 45% and a CR rate of 40%. Bendamustine is not the best drug combination for patients, [and BR had a] 17.5% objective response rate.

The PFS was statistically significant, 9.5 versus 3.7 months for the investigator review as well as the central review [HR, 0.36; 95% CI, 0.21-0.63; P < .001]. Every subgroup favored the polatuzumab/BR regimen.

Bendamustine has toxicities, but polatuzumab/BR has a bit more in terms of the cytopenias. Neutropenia was more common. Febrile neutropenia was fairly even. A bit more neutropenia but not more febrile neutropenia. Then the peripheral neuropathy, which we know from this drug class...is an issue. Not so much with bendamustine, but about 40% of patients had some degree of mild neuropathy on the polatuzumab side.

Have there been other approvals in this setting?

Selinexor [Xpovio] was approved [in 2020 based on results of the SADAL] trial [NCT02227251].7 This evaluated patients with relapsed DLBCL who were transplant ineligible. They had to be at least 60 days post treatment or 14 weeks if they had less than a partial response. So this was not a refractory population.

The response rates [were] 28% ORR, 12% CR, and its fairly similar across the different cell of origin subtypes. There was a good group of patients who got some benefit even if they didnt get a CR, and theres no patient variable that came out as a predictor for response.

Treatment AEs [included] thrombocytopenia as the big one. It was basically 60% or so of patients have some degree of thrombocytopenia; 15%, grade 4. About half the patients had some nausea, some anorexia, and some weight loss. Seventeen percent of patients discontinued because of treatment AEs, and 5 patients died because of treatment AEs.

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Westin Evaluates Management of DLBCL With CAR T-Cell Therapy - Targeted Oncology