Category Archives: Cell Medicine

TOKYO, MUNICH & BASKING RIDGE, N.J.--(BUSINESS WIRE)--New data from Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyos) patritumab deruxtecan (HER3-DXd), a HER3 directed antibody drug conjugate (ADC), demonstrated preliminary evidence of clinically meaningful and durable tumor response in patients with locally advanced or metastatic TKI-resistant, EGFR-mutated non-small cell lung cancer (NSCLC).

These extended follow-up data from the dose escalation portion and one expansion cohort of a phase 1 study of patritumab deruxtecan were presented today during an oral presentation (Abstract #9007) at the 2021 American Society of Clinical Oncology (#ASCO21) Virtual Scientific Program.

While the efficacy of targeted therapy with EGFR TKIs is well-established in the treatment of patients with advanced EGFR-mutated NSCLC, the development of a broad range of resistance mechanisms commonly leads to disease progression.1,2 Subsequent salvage therapies after EGFR TKI and platinum-based chemotherapy have limited efficacy with progression-free survival (PFS) of approximately 2.8 to 3.2 months.2 New treatment approaches are needed to overcome resistance and improve survival in these patients.

An objective response rate (ORR), as assessed by blinded central review, was 39% (CI 95%; 26-52%) in 57 evaluable patients treated with patritumab deruxtecan (5.6 mg/kg). One confirmed complete response and 21 partial responses were observed. The disease control rate was 72% (CI 95%; 59-83%). After a median follow-up of 10.2 months (range, 5.2-19.9 months), the estimated median duration of response was 6.9 months (CI 95%; range, 3.1-NE months) and the estimated median PFS was 8.2 months (CI 95%; range, 4.4-8.3 months). Confirmed responses were observed in patients across a spectrum of baseline tumor HER3 membrane expression levels, EGFR activating mutations and EGFR TKI resistance mechanisms, including EGFR activating mutations (Ex19del, L858R, G719Y), other EGFR mutations (T790M, C797S, Ex20ins), amplifications (EGFR, CCNE1, MET) and non-EGFR mutations and fusions (MET, KRAS). A subgroup of patients treated with osimertinib and platinum-based chemotherapy (n=44) prior to enrollment in the study demonstrated similar efficacy. An ORR of 39% (CI 95%; 24-55%) and PFS of 8.2 months (CI 95%; 4.0-NE) was observed in this subgroup. Additionally, the confirmed ORR and median PFS were similar in patients with or without a history of brain metastases.

EGFR TKIs are the standard of care for patients with advanced EGFR-mutated NSCLC. However, the activity of these agents is limited by the development of acquired resistance mechanisms, said Pasi A. Jnne, MD, PhD, Director, Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute. In this study, where patients were heavily pre-treated, efficacy was observed in patients with and without known EGFR TKI resistance mechanisms in a population that is often difficult to treat. Targeting HER3 with patritumab deruxtecan may be a novel and promising strategy, and we look forward to further evaluating clinical activity and safety in the pivotal HERTHENA-Lung01 trial.

The safety profile of patritumab deruxtecan in patients treated with the 5.6 mg/kg dose (n=57) is consistent with that seen across all patients (n=81) in both the dose escalation and dose expansion cohort 1 of the study (doses range from 3.2 to 6.4 mg/kg). Grade 3 or higher treatment emergent events (TEAEs) occurred in 64% of all patients (n=81). TEAEs grade 3 or higher severity occurring in 5% of all patients were platelet count decreased, neutrophil count decreased, fatigue, anemia, dyspnea, febrile neutropenia, hypoxia, white blood cell count decreased, hypokalemia and lymphocyte count decreased. There were four cases of treatment-related interstitial lung disease (ILD) reported, as determined by an independent adjudication committee, including two of grade 1 severity, one grade 2, and one grade 3. The median time to adjudicated onset of treatment-related ILD was 53 days (range, 13-130 days). There were five TEAEs associated with death including two cases of disease progression, two cases of respiratory failure and one case of shock. All TEAEs associated with death were considered not related to the study drug.

Treatment options that provide meaningful therapeutic benefit for patients with EGFR-mutated non-small cell lung cancer with disease progression following standard treatment with EGFR TKIs and platinum-based chemotherapy are limited, said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. HER3 represents a novel target for therapeutic development as it is broadly expressed in non-small cell lung cancer. These results are encouraging since the safety profile was consistent with previous findings and response to patritumab deruxtecan was seen irrespective of the level of HER3 expression or mechanism of resistance to prior therapies.

Patients receiving 5.6 mg/kg (n=57) of patritumab deruxtecan were pre-treated with a median of four prior lines of therapy (range, 1-9), including EGFR TKIs (100%), platinum-based chemotherapy (91%) and immunotherapy (40%). A majority (86%) were previously treated with osimertinib. Of the 57 patients, 27 patients had brain metastases at baseline. As of data cut-off on September 24, 2020, 32% of patients remain on treatment with patritumab deruxtecan.

Summary of Results

Efficacy Measure

HER3-DXd Dose Escalation 5.6 mg/kgPlus Dose Expansion 5.6 mg/kg (n=57) iv

Prior TKIPBC(n=57)

Prior OSI and PBC(n=44)

ORR (%) (95% CI) i, ii

39% (26-52)

39% (24-55)

CR (%)

2%

2%

PR (%)

37%

36%

SD (%)

33%

30%

PD (%)

16%

18%

NE (%)

12%

14%

DCR (%) (95% CI)iii

72% (59-83)

68% (52-81)

Time to response (months)

2.6 months (1.2-5.4)

2.7 months (1.2-5.4)

Median DOR (months) (95% CI)

6.9 months (3.1-NE)

7.0 months (3.1-NE)

Median PFS (months) (95% CI)

8.2 months (4.4-8.3)

8.2 months (4.0-NE)

CI, confidence interval; CR, complete response; DCR, disease control rate; DOR, duration of response; OSI, osimertinib; NE, not estimable; PBC, platinum-based chemotherapy; PD, progressive disease; PR, partial response; PFS, progression-free survival; SD, stable disease; TKI; tyrosine kinase inhibitori As assessed by independent central reviewii ORR is (CR + PR)iii DCR is (CR + PR + SD)iv Median follow up: 10.2 (range, 5.2-19.9) months

About the Phase 1 Non-Small Cell Lung Cancer Study

The global, multicenter, open label, two-part phase 1 study is evaluating patritumab deruxtecan in previously treated patients with metastatic or unresectable NSCLC.

The dose escalation part of the study evaluated patients with EGFR-mutated disease either with progression on osimertinib or T790M-negative after progression on erlotinib, gefitinib or afatinib. The primary objective of this part of the study was to assess the safety and tolerability of patritumab deruxtecan and determine the recommended dose for expansion (RDE).

The dose expansion part of the study is evaluating patritumab deruxtecan at the RDE (5.6 mg/kg every three weeks) in three cohorts. Cohort 1 includes patients with locally advanced or metastatic EGFR-mutated NSCLC who experienced disease progression after taking one or more EGFR TKIs and one or more platinum based chemotherapy regimens. Cohort 2 includes patients with squamous or non-squamous NSCLC without EGFR-activating mutations following platinum-based chemotherapy and following an anti-PD-1 or anti-PD-L1 antibody regimen. Cohort 3 includes patients with NSCLC with EGFR-activating mutations including any histology other than combined small cell and non-small cell lung cancer; patients in Cohort 3 are randomized 1:1 to receive the 5.6 mg/kg RDE regimen (Cohort 3a) or an escalating up-titration regimen of patritumab deruxtecan (Cohort 3b).

Preliminary data from the dose escalation part of the study were presented previously at the 2019 World Conference on Lung Cancer, and early data from the dose escalation part (5.6 mg/kg dose) and Cohort 1 of the dose expansion were presented at the 2020 European Society of Medical Oncology (ESMO) Virtual Congress. Exploratory biomarker analyses assessing genomic alterations of patient tumors were presented at the 2020 World Conference on Lung Cancer.

The primary objective of the dose expansion part of the study is to assess efficacy of patritumab deruxtecan as measured by confirmed objective response rate assessed by blinded independent central review. Secondary study endpoints include investigator-assessed objective response rate; safety, tolerability and preliminary efficacy; and characterization of the pharmacokinetics of patritumab deruxtecan. The study enrolled patients at multiple sites in the U.S., Europe, Japan and other countries in Asia. For more information, visit ClinicalTrials.gov.

About Non-Small Cell Lung Cancer

Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide. There were an estimated 2.2 million new cases of lung cancer and 1.8 million deaths in 2020.3 Most lung cancers are diagnosed at an advanced or metastatic stage.4 Non-small cell lung cancer (NSCLC) accounts for 80 to 85% of all lung cancers.5

The introduction of targeted therapies and checkpoint inhibitors in the past decade has improved the treatment landscape for patients with advanced or metastatic NSCLC; however, the prognosis is particularly poor among patients who have progressed after treatment with standard therapies. For patients who are not eligible for current treatments, or whose cancer continues to progress, new therapeutic approaches are needed.6

The mutationally-activated EGFR tyrosine kinase is a well-established oncogenic driver and molecular target for management of advanced stage NSCLC.7 For patients with advanced EGFR-mutated NSCLC, targeted therapy with EGFR TKIs offer higher response rates and progression-free survival compared to chemotherapy.7 However, most patients eventually develop resistance to these therapies, and standard treatment options are limited.8 Treatment options used in this setting historically have demonstrated limited efficacy with progression free survival of up to 6.4 months for platinum-based chemotherapy and 3.2 months for other salvage therapies.3,9 New treatment approaches are needed to overcome resistance and improve survival in these patients.

About HER3

HER3 is a member of the EGFR family of receptor tyrosine kinases, which are associated with aberrant cell proliferation and survival.10 Approximately 25 to 30% of lung cancers worldwide have an EGFR-activating mutation, and it is estimated that about 83% of all NSCLC tumors express the HER3 protein, which can be associated with an increased incidence of metastases, reduced survival and resistance to standard of care treatment.11,12,13 Currently, no HER3 directed medicines are approved for the treatment of cancer.

About Patritumab Deruxtecan

Patritumab deruxtecan (HER3-DXd) is one of three lead DXd ADCs in the oncology pipeline of Daiichi Sankyo. Designed using Daiichi Sankyos proprietary DXd ADC technology, patritumab deruxtecan is comprised of a human anti-HER3 antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Patritumab deruxtecan is currently being evaluated in a comprehensive development program across multiple cancers as both a monotherapy and in combination with other anticancer treatments. The development program includes HERTHENA-Lung01, a pivotal phase 2 study in patients with locally advanced or metastatic EGFR-mutated NSCLC previously treated with a TKI and platinum-based chemotherapy; a phase 2 study in patients with advanced/metastatic colorectal cancer with disease progression following at least two prior lines of systemic therapy; a phase 1/2 study in HER3 expressing metastatic breast cancer; a phase 1 study in combination with osimertinib in locally advanced/metastatic EGFR-mutated NSCLC; and, a phase 1 study in previously treated patients with metastatic or unresectable NSCLC.

Patritumab deruxtecan is an investigational medicine that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo

Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose to contribute to the enrichment of quality of life around the world. In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an Innovative Global Healthcare Company Contributing to the Sustainable Development of Society. For more information, please visit http://www.daiichisankyo.com.

References:

1 Engelman JA, et al. Science. 2007;316:1039-1043.2 Schoenfield AJ, et al. J Thorac Oncol 2020;15:18-21.3 Yang CJ, et al. BMC Pharmcol Toxicol. 2017,18(1).4 World Health Organization. GLOBOCAN 2020. Lung Cancer Fact Sheet. January 2021.5 American Cancer Society. Lung Cancer Early Detection, Diagnosis. May 2021.6 American Cancer Society. Types of Non-Small Cell Lung Cancer. 2019.7 Economopoulou P, et al. Ann Transl Med. 2018;6(8):138.8 Planchard D, et al. Ann Oncol. 2018;29(4):iv192237.9 Morgillo F, et al. ESMO Open. 2016;1:e000060.10 Han B, et al. Onco Targets Ther 2018;11; 2121-2129.11 Mishra R, et al. Oncol Rev. 2018;12:355.12 Zhang YL, et al. Oncotarget. Vol. 7 No 49. 78985-78993.13 Muller-Tidow C, et al. Cancer Res. 2005;65:1778-1772.14 Scharpenseel, et al. Scientific Reports. 2019;9:7406.

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Patritumab Deruxtecan Data at ASCO Demonstrates Tumor Response Across Multiple Resistance Mechanisms in Patients with Advanced EGFR-Mutated NSCLC -...

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

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...

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

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