Category Archives: Cell Therapy

Former GSK Executive Will Build the CDMO's Cell Therapy Infrastructure

KING OF PRUSSIA, Pa., March 23, 2022 /PRNewswire/ --The Center for Breakthrough Medicines(CBM) announced today the appointment of John Lee, Ph.D. to Vice President, Head of Cell Therapy.Dr. Lee is an accomplished CAR-T immunobiologist with over 20 years of cancer cell biology expertise spanning small and large molecules, as well as cell-based therapeutics.

"We have an opportunity to become a global leader in cell therapy," John Lee, Ph.D.

Among his accomplishments, Dr. Lee possesses more than 15 years of clinical research and cell therapy experience including positions of increasing responsibility at The Wistar Institute, Janssen Pharmaceuticals, and GlaxoSmithKline.

"I am excited to lead cell therapy at CBM and for the opportunity to cure patients," said Dr. Lee. "My goal is to build a highly functional, diverse, and agile team that embraces the challenges associated with our shared mission. By creating an infrastructure that supports both the team and our clients, we have an opportunity to become a global leader in cell therapy."

Dr. Lee previously built the Cell Therapy Platform team at Janssen Pharmaceuticals. The group led and supported end-to-end therapy discovery and development across nearly a dozen CAR-T programs, including the recently approved cilta-cel (Carvykti). During his subsequent tenure as Vice President, Head of Oncology Cell Therapy at GlaxoSmithKline, Dr. Lee's team operated within a heavily matrixed organization to support an array of activities establishing multiple preclinical assets and several clinical-stage lete-cel programs targeting the NY-ESO cancer-testis antigen.

"My collective experience leading cell therapy programs in these large organizations will help me build a fit-for-purpose infrastructure here at CBM while also creating a culture where both the team and its individual contributors can thrive," he added.

A native Pennsylvanian (from Ambler, PA), Dr. Lee is passionate about the Philadelphia life science sector. He believes CBM has the solution to attract top talent and deliver services to the capacity-starved cell and gene contract development and manufacturing organization (CDMO) market. He also feels that King of Prussia (KoP) is an ideal location for employees seeking a high quality of life. Compared to other life science clusters like those found in Cambridge, San Francisco and New Jersey, KoP offers a better quality of life with lower taxes, more affordable housing, excellent schools, and world-class restaurants.

CBM is creating the world's largest end-to-end advanced therapy CDMO. CBM will provide preclinical through commercial manufacturing services including process development, plasmid DNA, viral vectors, cell banking, cell processing, and supporting testing capabilities.

A core element of CBM's growth strategy is the construction of 700,000 square feet of GMP facility in KoP. "This capacity is part of our mission to accelerate the development and manufacturing of life-saving advanced therapies," said Joerg Ahlgrimm, Chief Executive Officer, Center for Breakthrough Medicines. "We are assembling a world-renowned executive leadership team with unique combination of experience in cell and gene therapy. John's addition to the team is another vital step in our planning for success."

To support its rapid growth, CBM is hiring positions at all levels and is actively working to develop talent among emerging professionals coming out of colleges. The company is working closely with academic institutions, as well as initiatives to retrain displaced employees. CBM is also committed to building an organization that recognizes and values diversity.

CBM is Hiring

To learn more about all CBM's open positions please visit:

https://bullseyehiringsolutions.com/companies/breakthroughmedicines

About The Center for Breakthrough Medicines

CBM is a cell and gene therapy contract development and manufacturing organization (CDMO) based in the heart of Philadelphia's Cellicon Valley. CBM offers pre-clinical through commercial manufacturing capabilities including process development, plasmid DNA, viral vector manufacturing, cell banking, cell processing, and a full suite of complimentary testing and analytical capabilities. Through a single-source, end-to-end solution, CBM accelerates time to market without compromising quality.

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Center for Breakthrough Medicines Appoints John Lee, Ph.D. as Vice President, Head of Cell Therapy - 69News WFMZ-TV

ST. LOUIS & SAN DIEGO, March 24, 2022--(BUSINESS WIRE)--Wugen, Inc., a clinical-stage biotechnology company developing a pipeline of off-the-shelf cell therapies to treat a broad range of hematological and solid tumor malignancies, today announced that management will participate in a fireside chat and presentation at the Innate Killer Summit 2022 being held in San Diego, CA from Wednesday, March 30 Friday, April 1, 2022.

The details of Wugens fireside chat and presentation are as follows:

Format: Industry Leaders Fireside ChatPresenter: Dan Kemp, Ph.D., President and Chief Executive Officer, WugenDate & Time: Thursday, March 31, 2022 at 8:15 a.m. PT

Format: Presentation titled "Characterizing an Ideal NK Cell Phenotype Leveraging Assays to Indicate Therapeutic Benefit"Presenter: Ayman Kabakibi, Ph.D., Chief Operating Officer & Executive Vice President, Research & Development, WugenDate & Time: Thursday, March 31, 2022 at 11:30 a.m. PT

About WU-NK-101

WU-NK-101 is a novel immunotherapy harnessing the power of memory natural killer (NK) cells to treat liquid and solid tumors. Memory NK cells are hyper-functional, long-lasting immune cells that exhibit enhanced anti-tumor activity. This rare cell population has a superior phenotype, proliferation capacity, and metabolic fitness that makes it better suited for cancer therapy than other NK cell therapies. Wugen is applying its proprietary MonetaTM platform to advance WU-NK-101 as a commercially scalable, off-the-shelf cell therapy for cancer. WU-NK-101 is currently in development for acute myelogenous leukemia (AML) and solid tumors.

About Wugen

Wugen, Inc., is a clinical-stage biotechnology company developing the next generation of off-the-shelf memory natural killer (NK) and CAR-T cell therapies for cancer. Wugen is leveraging its proprietary MonetaTM platform and deep genomic engineering expertise to pioneer a new class of memory NK cell therapies to treat hematological and solid tumor malignancies. For more information, please visit http://www.wugen.com.

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Contacts

Investor Contact: Elsie Yau, Stern Investor Relations, Inc.212-698-8700elsie.yau@sternir.com

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Wugen to Present at the Innate Killer Summit 2022 - Yahoo Finance

CARLSBAD, Calif.--(BUSINESS WIRE)--Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, today announced that Brian M. Culley, the Companys Chief Executive Officer, will be presenting at the 2022 Virtual Growth Conference, presented by Maxim Group LLC and hosted by M-Vest. Mr. Culley will be participating in an Ophthalmology Panel hosted by Jason McCarthy, Ph.D., Senior Managing Director, Biotechnology, on March 28th, 2022 at 10am ET / 7am PT. Mr. Culley will also provide a corporate overview which will be available to investors on demand, starting on Monday March 28th, 2022.

The live panel and on-demand presentation will be available to registered users directly through the M-Vest platform: https://m-vest.com/events/2022-virtual-growth-conference. Registration is required for conference participation. An archived webcast of the corporate presentation will also be available on the Events and Presentations page of the Lineage website. Additional videos are available on the Media page of the Lineage website.

About Lineage Cell Therapeutics, Inc.

Lineage Cell Therapeutics is a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs. Lineages programs are based on its robust proprietary cell-based therapy platform and associated in-house development and manufacturing capabilities. With this platform Lineage develops and manufactures specialized, terminally differentiated human cells from its pluripotent and progenitor cell starting materials. These differentiated cells are developed to either replace or support cells that are dysfunctional or absent due to degenerative disease or traumatic injury or administered as a means of helping the body mount an effective immune response to cancer. Lineages clinical programs are in markets with billion dollar opportunities and include four allogeneic (off-the-shelf) product candidates: (i) OpRegen, a retinal pigment epithelium transplant therapy in Phase 1/2a development for the treatment of dry age-related macular degeneration, which is now being developed under a worldwide collaboration with Roche and Genentech, a member of the Roche Group; (ii) OPC1, an oligodendrocyte progenitor cell therapy in Phase 1/2a development for the treatment of acute spinal cord injuries; (iii) VAC2, a dendritic cell therapy produced from Lineages VAC technology platform for immuno-oncology and infectious disease, currently in Phase 1 clinical development for the treatment of non-small cell lung cancer and (iv) ANP1, an auditory neuronal progenitor cell therapy for the potential treatment of auditory neuropathy. For more information, please visit http://www.lineagecell.com or follow the Company on Twitter @LineageCell.

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Lineage to Present at the 2022 Virtual Growth Conference Presented by Maxim Group LLC on March 28, 2022 - Business Wire

MONROVIA, Calif. & TOA BAJA, Puerto Rico--(BUSINESS WIRE)--CytoImmune Therapeutics, a clinical-stage immunotherapy company that is developing a novel class of engineered natural killer (NK) cell-based cancer therapies, today announced the opening of the Companys clinical cell manufacturing facility in Toa Baja, which was celebrated with a visit from the Governor of Puerto Rico, Pedro R. Pierluisi. The Secretary of Economic Development and Commerce, Manuel Cidre, and the Mayor of the municipality, Bernardo Betito'' Mrquez, were also in attendance during the opening of the facility.

In Puerto Rico we have the talent, the resources and the potential for this type of biotechnology company to successfully establish operations here. The opening of this new facility shows our commitment to this investment which has a direct effect on job creation and economic development. This investment impacts all of Puerto Rico and the patients in the trials, said Governor Pedro R. Pierluisi.

We chose Puerto Rico to develop and manufacture these innovative cancer treatments based on the significant scientific capabilities of our local talent and the decades of experience on the island in biopharmaceutical manufacturing. Our goal is to create cellular immunotherapies for patients to recognize and kill cancer cells. The work by the Company here holds the potential to positively impact patients around the world," said Jos Eduardo Vidal, Ph.D., Chief Operating Officer of the company.

CytoImmune is leveraging proprietary, robust and well characterized natural killer (NK) cell expansion and engineering technologies to advance its tumor-reactive NK (TRACK-NK) cell therapies for patients with cancer. The cells are engineered to directly attack cancer cells and broadly stimulate both the innate and adaptive arms of the human immune system through the potent release of interleukin 15, enabling robust and specific tumor killing. The CytoImmune clinical cell manufacturing facility in Toa Baja is custom designed to support all manufacturing needs for the Companys cell therapies, allowing the Company to accelerate the research and development efforts.

The early investment in our manufacturing capabilities will accelerate our clinical trials with collaboration between our clinical teams and the supply chain management. Further, developing this internal expertise in manufacturing also shortens the time needed to advance our newest innovations from the laboratory bench to patients, explained Christina Coughlin M.D., Ph.D., CEO of CytoImmune Therapeutics, Inc.

Just over a year ago we announced the establishment of Cytolmmune Therapeutics Puerto Rico and today we are glad to be witnesses of its opening in Toa Baja. This operation will be the first on the Island whose purpose is to conduct research, development and manufacturing in the 37,000 square-foot facility. A main part of our economic development strategy relies on innovation in the biopharmaceutical sector, where research and development are in the front line. Thank you for being part of Puerto Ricos transformation and for trusting our capable workforce, expressed Manuel Cidre, secretary of the Department of Economic Development and Commerce.

About CytoImmune Therapeutics:

CytoImmune Therapeutics is a clinical-stage biopharmaceutical company focused on the development and commercialization of novel cancer immunotherapy products designed to utilize the power of the engineered cells to activate the patients immune system to eliminate cancer cells. The company is advancing a differentiated pipeline of off-the-shelf NK cell therapies, using proprietary, robust and well characterized NK cell expansion and engineering technologies that are designed to provide effector cell therapy with broad immune stimulation, to enable effective tumor killing in both solid tumors and hematologic malignancies. For more information, please visit Cytoimmune.com

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CytoImmune Therapeutics, Inc. Opens the Company's Clinical Cell Manufacturing Facility in Toa Baja - Business Wire

SOMERSET, N.J.--(BUSINESS WIRE)--Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global biotechnology company developing, manufacturing and commercializing novel therapies to treat life-threatening diseases, was named Newcomer of the Year at the tenth annual Foreign Investment Trophy ceremony hosted by Flanders Investment & Trade (FIT).

Flanders Investment and Trade is a Flemish government organization that facilitates investment projects in Flanders, a northern region of Belgium, and supports Flemish companies. The Foreign Investment Trophy recognizes international firms with investment projects in Flanders, and FITs Newcomer of the Year award is conferred upon organizations who have recently embarked on substantial investment projects in the region.

Legend Biotech earned the honor for its joint investment in a state-of-the-art manufacturing facility in Flanders with Janssen Pharmaceutica N.V. (Janssen). The cell therapy facility is the first-ever cell therapy manufacturing site located in Flanders, and it will serve as a regional hub for the companies cell therapy production for patients in Europe, the Middle East and Africa.

The 26,000-square-meter manufacturing hub is part of Legends collaboration with Janssen to advance the manufacturing of ciltacabtagene autoleucel (cilta-cel), a B cell maturation antigen-directed CAR-T treatment being evaluated for the treatment of relapsed or refractory multiple myeloma by the European Medicines Agency. In April 2019, cilta-cel was granted PRIME (Priority Medicines) designation. PRIME offers enhanced interaction and early dialogue with the developers of promising medicines to optimize drug development plans and speed up the evaluation of cutting-edge, scientific advances that target a high unmet medical need.

The European manufacturing hub is anticipated to come on-line in 2023 and will be managed by Legend Biotech.

As he accepted the award in Belgium, Ying Huang, PhD, CEO and CFO of Legend Biotech, said: This award is special recognition of our investment in Flanders, one of Europes most exciting biotechnology hubs. The Newcomer of the Year award marks how far weve come in since Legend was established to apply cell therapy to rare and uncommon diseases. We look forward to advancing that goal and to playing a meaningful role in the Ghent ecosystem for years to come.

About Legend Biotech

Legend Biotech is a global biotechnology company dedicated to treating, and one day curing, life-threatening diseases. Headquartered in Somerset, New Jersey, we are developing advanced cell therapies across a diverse array of technology platforms, including autologous and allogenic chimeric antigen receptor T-cell, T-cell receptor (TCR-T), and natural killer (NK) cell-based immunotherapy. From our three R&D sites around the world, we apply these innovative technologies to pursue the discovery of safe, efficacious and cutting-edge therapeutics for patients worldwide.

Learn more at http://www.legendbiotech.com and follow us on Twitter and LinkedIn.

About Flanders Investment & Trade

Flanders Investment & Trade (FIT) actively promotes sustainable international business in Flanders as a key element of the regions socio-economic development. FIT accomplishes this by supporting Flanders-based companies in their international business ventures and by attracting foreign investors. FIT assists businesses across Flanders in their international endeavors and provides custom advice and support. Companies can call on the agencys local and international networks of contacts, while FIT also offers financial support and information about the financial incentives available.

Cautionary Note Regarding Forward-Looking Statements

Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to Legend Biotechs strategies and objectives; statements relating to CARVYKTI, including Legend Biotechs expectations for CARVYKTI, such as Legend Biotechs manufacturing and commercialization expectations for CARVYKTI and the potential effect of treatment with CARVYKTI; statements about submissions for cilta-cel to, and the progress of such submissions with, the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), the Chinese Center for Drug Evaluation of National Medical Products Administration (CDE) and other regulatory authorities; the anticipated timing of, and ability to progress, clinical trials, including patient enrollment; the submission of Investigational New Drug (IND) applications to, and maintenance of such applications with, regulatory authorities; the ability to generate, analyze and present data from clinical trials; and the potential benefits of Legend Biotechs product candidates. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, should, target, will, would and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors. Legend Biotechs expectations could be affected by, among other things, uncertainties involved in the development of new pharmaceutical products; unexpected clinical trial results, including as a result of additional analysis of existing clinical data or unexpected new clinical data; unexpected regulatory actions or delays, including requests for additional safety and/or efficacy data or analysis of data, or government regulation generally; unexpected delays as a result of actions undertaken, or failures to act, by our third party partners; uncertainties arising from challenges to Legend Biotechs patent or other proprietary intellectual property protection, including the uncertainties involved in the U.S. litigation process; competition in general; government, industry, and general public pricing and other political pressures; the duration and severity of the COVID-19 pandemic and governmental and regulatory measures implemented in response to the evolving situation; as well as the other factors discussed in the Risk Factors section of the Legend Biotechs Annual Report filed with the Securities and Exchange Commission on April 2, 2021. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described in this press release as anticipated, believed, estimated or expected. Any forward-looking statements contained in this press release speak only as of the date of this press release. Legend Biotech specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.

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Flanders Investment and Trade Names Legend Biotech Newcomer of the Year - Business Wire

Natural killer (NK) cells are a viable cancer immunotherapy alternative to T cells. Clinical studies were being conducted to test adoptive therapeutics using allogeneic, cytokine-activated NK cells. The appropriate cytokine support following adoptive transfer to increase NK cell growth and persistence, on the other hand, was unknown. Correlative studies from two independent clinical trial cohorts treated with major histocompatibility complex-haploidentical NK cell therapy for relapsed/refractory acute myeloid leukemia revealed systemic interleukin-15 (IL-15; N-803) cytokine support resulted in lower clinical activity compared to IL-2.

Researchers postulated that the mechanism was IL-15/N-803 activating recipient CD8 T-cells, which increased donor NK cell rejection. The hypothesis was validated by higher proliferating CD8+ T-cell counts in patients treated with IL-15/N-803 versus IL-2. Furthermore, in mixed lymphocyte responses, IL-15/N-803 increased responder CD8 T-cell activation and proliferation when compared to IL-2 alone. Furthermore, IL-15/N-803 increased the capacity of responder T cells to eliminate stimulator-derived memory-like NK cells, suggesting that more IL-15 could speed up donor NK cell removal.

As a result, using systemic IL-15 to assist allogeneic cell treatment might paradoxically reduce their therapeutic window of opportunity and clinical efficacy. The study suggested that inducing patient CD8 T-cell allo-rejection responses might severely restrict allogeneic cellular treatment with IL-15.

Reference:ashpublications.org/blood/article-abstract/139/8/1177/482704/Systemic-IL-15-promotes-allogeneic-cell-rejection?redirectedFrom=fulltext

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Systemic IL-15 Induces Allogeneic Cell Rejection in Patients - Physician's Weekly

DUBLIN, March 21, 2022 /PRNewswire/ -- The "Cell and Gene Therapy Bioassay Services Market by Type of Therapy, Therapeutic Area, Scale of Operation and Geography: Industry Trends and Global Forecasts, 2021-2030" report has been added to ResearchAndMarkets.com's offering.

This report features an extensive study of the current landscape and the likely future potential of cell and gene therapy bioassay service providers, over the next decade. The study also features an in-depth analysis, highlighting the capabilities of various industry stakeholders engaged in this field.

Given the various advantages of cell and gene therapies and their ability to address the underlying causes of serious clinical conditions, the preference for such therapeutic modalities has increased over the years. As a result, several cell and gene therapies have been developed and approved for the treatment of a wide range of disease indications. In fact, at the time of this report's publication, more than 30 such therapies had been approved and over 1,200 therapeutic leads are under evaluation in different stages.

Owing to their rising popularity, these upcoming advanced therapeutic products are on the verge of becoming one of the highest valued therapeutic segments within the biopharmaceutical industry. Having said that, as is the case for all biological products, the development of cell and gene therapies is a complex, challenging and cost intensive process. Outsourcing is, therefore, a preferred operational model, with cell and gene therapy innovators relying heavily on specialty contract service providers to handle various aspects of their product development and manufacturing operations. In fact, over three quarters of the biopharmaceutical companies prefer to outsource their operations to the contract service providers and a large part of their expenditure goes to outsourcing services.

Amongst the various operations, the outsourcing of analytical testing services, including environment testing, bioanalytical testing, analytical testing, chemistry and stability testing, method development and validation, and product characterization, has witnessed significant rise in recent years.

The rising demand for outsourcing bioanalytical services has prompted the emergence of several contract research organizations that claim to offer bioassay services for cell and gene therapies. These companies usually have relatively more experience and are well equipped with the instruments and technological platforms to offer both pre-developed and customized bioassays.

In fact, these companies assist in bringing out the maximum efficiency of study design by offering several cost benefits and reducing the associated timelines. Given the benefits of outsourcing the bioassay services and the ongoing efforts of service providers to further improve / expand their respective offerings, we believe that the cell and gene therapy bioassay services market is likely to evolve at a steady pace, till 2030.

In addition to other elements, the study includes:

Key Questions Answered

Key Topics Covered:

1. PREFACE

2. EXECUTIVE SUMMARY

3. INTRODUCTION

4. MARKET LANDSCAPE

5. COMPANY COMPETITIVENESS ANALYSIS5.1. Chapter Overview5.2. Methodology5.3. Key Parameters5.4. Competitiveness Analysis: Companies Offering Cell and Gene Therapy Bioassay Services in North America5.5. Competitiveness Analysis: Companies Offering Cell and Gene Therapy Bioassay Services in Europe and Asia-Pacific

6. CELL AND GENE THERAPY BIOASSAY SERVICE PROVIDERS IN NORTH AMERICA: COMPANY PROFILES6.1. Chapter Overview6.2. CCRM6.2.1. Company Overview6.2.2. Cell and Gene Therapy Bioassay Service Portfolio6.2.3. Recent Developments and Future Outlook6.3. Nexelis6.3.1. Company Overview6.3.2. Cell and Gene Therapy Bioassay Service Portfolio6.3.3. Recent Developments and Future Outlook6.4. Pacific BioLabs6.4.1. Company Overview6.4.2. Cell and Gene Therapy Bioassay Service Portfolio6.4.3. Recent Developments and Future Outlook6.5. PPD Laboratories6.5.1. Company Overview6.5.2. Cell and Gene Therapy Bioassay Service Portfolio6.5.3. Recent Developments and Future Outlook6.6. WuXi Advanced Therapies6.6.1. Company Overview6.6.2. Cell and Gene Therapy Bioassay Service Portfolio6.6.3. Recent Developments and Future Outlook

7. CELL AND GENE THERAPY BIOASSAY SERVICE PROVIDERS IN EUROPE AND ASIA-PACIFIC: COMPANY PROFILES7.1. Chapter Overview7.2. AnaBioTec7.2.1. Company Overview7.2.2. Cell and Gene Therapy Bioassay Service Portfolio7.2.3. Recent Developments and Future Outlook7.3. Intertek Pharmaceutical Services7.3.1. Company Overview7.3.2. Cell and Gene Therapy Bioassay Service Portfolio7.3.3. Recent Developments and Future Outlook7.4. Lonza7.4.1. Company Overview7.4.2. Cell and Gene Therapy Bioassay Service Portfolio7.4.3. Recent Developments and Future Outlook7.5. Porton Bio7.5.1. Company Overview7.5.2. Cell and Gene Therapy Bioassay Service Portfolio7.5.3. Recent Developments and Future Outlook

8. MARKET TREND ANALYSIS

9. GLOBAL EVENT AND STRATEGIC INITIATIVE ANALYSIS

10. CASE STUDY: MARKET LANDSCAPE OF CELL AND GENE THERAPIES10.1. Chapter Overview10.2. Cell Therapy Market10.2.1. T-Cell Immunotherapies: Development Pipeline10.2.1.1. Analysis by Type of Product10.2.2. CAR-T Cell Therapies: Development Pipeline10.2.2.1. Analysis by Phase of Development10.2.2.2. Analysis by Therapeutic Area10.2.2.3. Analysis by Type of Developer10.2.2.4. Key Industry Players: Analysis by Number of CAR-T Cell Therapies in Development10.2.3. TCR-based Therapies: Development Pipeline10.2.3.1. Analysis by Phase of Development10.2.3.2. Analysis by Therapeutic Area10.2.3.3. Analysis by Type of Developer10.2.3.4. Key Industry Players: Analysis by Number of TCR-based Therapies in Development10.2.4. TIL-based Therapies: Development Pipeline10.2.4.1. Analysis by Phase of Development10.2.4.2. Analysis by Therapeutic Area10.2.4.3. Analysis by Type of Developer10.2.4.4. Key Industry Players: Analysis by Number of TIL-based Therapies in Development10.3. Gene Therapy Market10.3.1. Gene Therapy Market: Clinical and Commercial Pipeline10.3.1.1. Analysis by Phase of Development10.3.1.2. Analysis by Therapeutic Area10.3.2. Gene Therapy Market: Development Pipeline10.3.2.1. Analysis by Phase of Development10.3.2.2. Analysis by Therapeutic Area

11. LIKELY PARTNERS FOR CELL THERAPY BIOASSAY SERVICE PROVIDERS11.1. Chapter Overview11.2. Scope and Methodology11.3. Potential Strategic Partners for Cell Therapy Bioassay Service Providers11.3.1. Likely Partner Opportunities for Stem Cell Therapy Bioassay Service Providers11.3.2. Likely Partner Opportunities for CAR-T Therapy Bioassay Service Providers11.3.3. Likely Partner Opportunities for Dendritic Cell Therapy Bioassay Service Providers11.3.4. Likely Partner Opportunities for Tumor Cell Therapy Bioassay Service Providers11.3.5. Likely Partner Opportunities for NK Cell Therapy Bioassay Service Providers

12. LIKELY PARTNERS FOR GENE THERAPY BIOASSAY SERVICE PROVIDERS12.1. Chapter Overview12.2. Scope and Methodology12.3. Potential Strategic Partners for Gene Therapy Bioassay Service Providers12.3.1. Likely Partner Opportunities in North America12.3.2. Likely Partner Opportunities in Europe12.3.3. Likely Partner Opportunities in Asia-Pacific

13. MARKET FORECAST AND OPPORTUNITY ANALYSIS

14. CONCLUSION

15. EXECUTIVE INSIGHTS

16. APPENDIX 1: TABULATED DATA

17. APPENDIX 2: LIST OF COMPANIES AND ORGANIZATIONS

For more information about this report visit https://www.researchandmarkets.com/r/5d7pa0

Media Contact:

Research and Markets Laura Wood, Senior Manager [emailprotected]

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716

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Global Cell and Gene Therapy Bioassay Services Market to 2030 - by Type of Therapy, Therapeutic Area, Scale of Operation and Geography - PR Newswire

CAMBRIDGE, Mass. and ROTTERDAM, Netherlands and SUZHOU, China, March 24, 2022 /PRNewswire/ -- Harbour BioMed ("HBM" or the "Company"; HKEX: 02142), a global biopharmaceutical company committed to the discovery, development and commercialization of novel antibody therapeutics focusing on oncology and immunology, today reported full year 2021 annual results. During the reporting period, the Company's product development continued to make outstanding breakthroughs, unleashing the power of innovative technology platforms and globalization advantages.

Logo (PRNewsfoto/Harbour BioMed)

"2021 was a year of strong momentum for Harbour BioMed. The company has been making significant progress with respect to our highly differentiated pipeline products and business operations," said Jingsong Wang, Founder, Chairman and Chief Executive Officer. "Our 10 clinical trials are ongoing while two of them, Batoclimab and Tanfanercept, are in pivotal phase III trials and are progressing towards BLA (Biologics License Application) submission. We've seen encouraging data of the global clinical trials of HBM4003 and solid progress of multiple assets through pre-clinical development. The value of our platforms has been further validated with more than 50 leading partners around world.

Moving forward in 2022, we will continue to explore more differentiated novel therapeutics on a global basis, leveraging in-house technology platforms and strong research and development capabilities. I believe that each of our innovative products empowered by our unique platforms has the potential to benefit the patients globally, accelerating our mission to lead a healthy life with breakthrough medicines globally."

Recent Highlights:

Continued advancement across broad pipeline of core assets

10 clinical trials are ongoing.

2 products, Batoclimab (HBM9161 for patients with myasthenia gravis) and Tanfanercept (HBM9036 for patients with dry eye disease), are in pivotal phase III trials and are progressing towards BLA submission.

Global clinical trials of HBM4003 in both monotherapy and combination therapy are also rapidly advancing at full pace, with encouraging data and promising results to date.

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Multiple assets are progressing through pre-clinical development

6 innovative and differentiated products are nearing clinical stages of development.

Another 7 INDs are approved. This portfolio of innovative and differentiated products entering the clinical stage demonstrates the value of the Company's technology platforms.

The Company is actively exploring new scientific discoveries in novel therapeutic areas to address unmet medical needs

Leveraging in-house technology platforms, the Company is incubating NK cell therapy, bispecific NK cell engager and developing innovative antibody drug conjugate (ADC) products.

The Company's scientific research team strives to scale new heights in science with its strong research and development capabilities

In the period, 65 patents were filed.

The Company also participated in multiple academic conferences, presenting scientific achievements while highlighting its strong innovation capabilities.

Further advanced its global strategy through multiple collaborations

Entered into a research collaboration agreement with the Dana-Farber Cancer Institute of the Affiliated Hospital of Harvard Medical School.

Reached a strategic collaboration on artificial intelligence with BioMap, integrating the Company's AI technology advantages into the Harbour Mice platform.

Further expanded an academic collaboration with the Icahn School of Medicine at Mount Sinai.

Advanced the strategic collaboration with Hualan Bio, and several assets are expected to enter the clinical stage this year.

The value of the Company's platforms is further validated with more than 50 leading partners around the world.

Driving antibody drug development through innovation

The Company remains committed to the discovery and development of differentiated antibody therapeutics focusing on oncology and immunology. Powered by Harbour BioMed's unique technology platforms, it has developed a differentiated portfolio and innovation engine for sustained long-term expansion and growth of its self-developed pipeline.

Harbour BioMed is at the forefront of developing next generation immuno-oncology therapeutics, including innovative immune cell engager bispecific antibodies, unique Treg depletion mechanism, and novel immune escape pathway. Cancer treatment market unfolds vast opportunities, and the Company seeks to develop oncology therapeutics that address situations where 70%-80% of patients do not respond to or are resistant to PD1/PD-L1, in its pursuit of next-generation immuno-oncology therapeutics which tap the potential value of this $100 billion market.

With the R&D advantages of HBM's unique and highly efficient antibody discovery platforms under one organizational umbrella, the Company developed a number of first-in-class clinical and preclinical products. Among them, the bispecific antibody HBM7008 (B7H4/4-1BB) and the monoclonal antibody HBM1020 (B7H7) which represents the next generation of immune checkpoint inhibitors with significant differentiated advantages. In addition, the monoclonal antibody HBM1022 targets the Treg cell protein CCR8. CCR8 is recognized globally as a challenging target but one which is garnering increased attention in immuno-oncology. The Company's use of mRNA immunization technology combined with its proprietary antibody platforms allow for a suite of solutions of G protein-coupled receptor (GPCR) antibody discovery. These noted products were all developed by the Company and indicative of the encouraging progress HBM has made in overcoming the challenges faced across the competitive landscape. The Company looks forward to continuing this success with promising clinical results as these and other programs move forward in their development lifecycles.

The rapid advancement of HBM's clinical pipeline has continued into 2022, with multiple milestones reported in the first quarter. In February, the fully human monoclonal antibody HBM9378 (or SKB378) generated from the Company's H2L2 platform was approved for an investigational new drug ("IND") clinical trial application for the treatment of moderate to severe asthma; in the same month, HBM7008 (B7H4/4-1BB), the world's first-in-class product from the HBICE bispecific antibody platform, was officially approved by the Independent Review Board (IRB) in Australia and could potentially provide improved efficacy with better safety as compared to traditional monoclonal antibody therapies. The Company expects 4-6 products to enter the clinical stage this year and to rapidly push forward innovative products with blockbuster potential, laying a solid foundation for building a global competitive advantage.

HBM's cutting-edge fully human antibody platforms enable unique innovation and differentiation

HBM's antibody discovery platforms are the engine of its portfolio innovation: HBICE - a fully human bispecific antibody platform for immune cell engagers, a fully human heavy-chain-only antibody HCAb platform for monoclonal antibodies, and a fully human heavy and light chain antibody H2L2 platform with global patent protection. These robust technology platforms drive the Company to continuously advance antibody drug development while move towards more novel and challenging targets to address unmet medical needs, providing the momentum for sustained therapeutics innovation worldwide.

It is worth noting that, in the field of bispecific antibodies development, the Company's fully human HBICE bispecific platform for immune cell engagers, the highly differentiated bispecific antibody technology platform globally, is built upon the fully human HCAb based formats for immune cell engagers, which is also a patented achievement independently developed by the Company. The HBICE platform focuses on immune cell engagers, which can flexibly generate multiple molecular structures adapting to different biological mechanisms of action and effectively solving the problem of heavy and light chain mismatch in antibody engineering. The technology platform connects tumor cells with immune cells, activates immune cells, and kills tumor cells specifically, which can improve the effectiveness of treatment and reduce the risk of cytokine storm, avoiding the toxicity risk of systemic activation. Thus, safety is significantly improved, which is conducive to creating more innovative, differentiated, and safe products.

HBM is actively strengthening globalization presence to empowering its long-term development goals

As innovation and development across the biopharmaceutical industry continues to become more global, the Company is thriving on its three global innovation research centers and four major clinical sites, which reflects the Company's global ambition and continued investment into its R&D capabilities. By integrating R&D centers established in the US, the Netherlands and China, the Company is capable to consolidate leading global scientific and technological innovation resources. By maximizing regional innovation success, resource utilization is improved and translational clinical research results are advanced, accelerating bringing about differentiated innovative therapeutics, facilitating cooperation within the industry for the benefit of patients. At the same time, following the strategy of international research and development, HBM set up with four clinical sites in China, the US, Australia, and Europe to speed up the global development of its self-developed products.

Importantly, innovative solutions shape the global biopharmaceutical industry. The Company is jointly developing the next generation of innovative therapeutics through its proprietary technology platforms and global innovation network; an approach that has been validated by over 50 industry and academia partners with more than 10 products having entered the clinical stage. External collaborations include those with Eli Lilly, AbbVie, Pfizer, BeiGene, Innovent, Dana-Farber Hospital of Harvard Medical School, and Icahn School of Medicine of Mount Sinai Medical System in New York. Our global footprint enables the value proposition the Company's antibody technology platforms, which can be continuously tapped into and increasing the commercial income generating potential of its R&D capabilities.

In addition, the Company previously announced that it will initiate exploration of NK cell and ADC therapeutics. The Company hopes to leverage its novel technology across these frontier therapeutic areas, expand the application of its technology platforms, and lead next drug development programs to address areas of significant unmet clinical needs.

Accelerating clinical development to unlock potential value

As of now, the Company has independently developed more than ten highly differentiated products, two of which are in pivotal clinical phase III trials and are moving towards Biologics License Application (BLA) submission namely Batoclimab (HBM9161), which has obtained the national Breakthrough Therapeutics Designation for myasthenia gravis, and Tanfanercept (HBM9036), the first globally innovative biological drug for dry eye disease in China.

Specifically, Batoclimab is a next generation fully human monoclonal antibody that selectively binds to and inhibits the neonatal crystal fragment receptor (FcRn) and has the potential for breakthrough treatment of various autoimmune diseases. Tanfanercept is the most advanced product candidate currently being developed by the Company for the treatment of moderate-to-severe dry eye disease, which has a bright market potential in the emerging dry eye drug market in China. These two products are highly differentiated and have large potential market opportunities.

As people begin to emerge from the global pandemic, good health is even more in focus now. In the increasingly competitive biopharmaceutical market, innovation is no doubt the core commodity. Harbour BioMed has built a broad moat with its innovation engine and differentiated pipeline, leveraging its unique and robust antibody technology platforms, regional global innovation ecosystem, and accelerated clinical operations of its core products.

About Harbour BioMed

Harbour BioMed (HKEX: 02142) is a global biopharmaceutical company committed to the discovery, development and commercialization of novel antibody therapeutics focusing on immunology and oncology. The Company is building its robust portfolio and differentiated pipeline through internal R&D capability, collaborations with co-discovery and co-development partners and select acquisitions.

The Company's proprietary antibody technology platforms Harbour Mice generate fully human monoclonal antibodies in two heavy and two light chain (H2L2) format, as well as heavy chain only (HCAb) format. Building upon the HCAb antibodies, the HCAb-based immune cell engagers (HBICE) are capable of delivering tumor killing effects unachievable by traditional combination therapies. Integrating Harbour Mice with single B cell cloning platform, our antibody discovery engine is highly unique and efficient for development of next generation therapeutic antibodies.

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Harbour BioMed Reports Full Year 2021 Financial Results: Empower Value Creation with Global Innovation Capabilities - Yahoo Finance

Phase 1 trials increased by 32% in 2021, representing a considerable transition of advanced therapies into first-in-human trials, said the CGT Catapult as it released its 2021 Advanced Therapy Medicinal Product (ATMP) clinical trials database and report.

Moreover, commercially sponsored trials now represent nearly 80% of all UK ATMP clinical trials, demonstrating the attractiveness of the UKs ecosystem, said the organization.

Matthew Durdy, CEO of CGT Catapult, said that the rising and sustained commercial investment in these trials showcases the incredible strength and dynamism of the UK ATMP industry and "isa testament to the ongoing support of the UK government and the industry.

Fewer ATMP trials were reported as completed in 2021 compared to 2020, however, and this is likely due to the ongoing COVID-19 pandemic, which has resulted in trial delays, said the organization.

The MHRA does not need to be notified of interruptions to trials due to COVID-19, therefore the true impact of the pandemic on all stages of clinical trials is not yet completely understood.

The division of therapeutic indications among the ongoing ATMP trials remains largely unchanged from previous years. Oncology, which includes hematological malignancies and solid tumors, remains the dominant therapeutic area accounting for 37% of ATMP clinical trials, followed by ophthalmology (12%) and hematological (11%).

Again, little difference in the cell types investigated in ATMP clinical trials last year: T cells continue to be the dominant cell type, accounting for 47% of UK ATMP clinical trials. This is as expected since research into oncology, the largest therapeutic area, is largely T cell focused and is consistent with previous years.

The majority of the 168 ATMP clinical trials ongoing in the UK in 2021 were gene therapies (72%) followed by somatic-cell therapies (19%). Tissue engineered therapies accounted for approximately 9% of the ongoing clinical trials, noted the publication.

Of the ongoing gene therapy clinical trials, similar numbers of ex vivo (46%), which includes CAR-T, and in vivo (54%) genetic modifications were investigated.

For in vivo gene therapy clinical trials, AAV based vectors remain the main vector of choice (72%), followed by oncolytic viruses (17%).

Overall, the majority of the UK ATMP clinical trials ongoing in 2021 are currently recruiting (45%) or in follow- up (29%), indicated the report.

There has been an increase in the overall number of ATMP clinical trials for both autologous and allogeneic therapies since 2016, but the proportion of autologous to allogeneic products has remained fairly consistent, with approximately 70% being autologous and 30% allogeneic, it also noted.

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'Rising and sustained' commercial investment in advanced therapy trials in UK - BioPharma-Reporter.com

This section will focus on past, present and future clinical trials that use stem cells as a treatment modality for HF and their degree of success in improving various parameters of cardiac function such as left ventricular ejection fraction (LVEF), left ventricular end systolic volume (LVESV), left ventricular end diastolic volume (LVEDV) end-systolic volume (ESV) and end diastolic volume (EDV). Though there are varying degrees of success depending on the cell type, successful application relies heavily on the engraftment and survivability of stem cells into the host myocardium, their revascularization potential and electromechanical coupling to beat in synchrony with resident cardiomyocytes[26].

Both ESCs and iPSCs are considered pluripotent stem cells (PSCs). By definition, these cells are those that can form all three germ layers of the embryo[27]. Although there are some subtle differences in potency between the two cell types, the major distinction between the two comes from their difference in origin. Embryonic stem cells are derived from human embryos, while iPSCs are derived from mature somatic cells that have been engineered in laboratories to regain pluripotent capacity. Nonetheless, PSCs have the unique advantage of being able to be differentiated in a tightly controlled, stepwise fashion. This allows researchers to create lineage-specific progenitors such as cardiac progenitor cells (CPCs)[28].

To date, there have been few preclinical or clinical trials investigating the safety and efficacy of ESCs in animals and humans. In non-human primates, human ESC-derived cardiomyocytes were administered via the intramyocardial (IM) route in two preclinical trials[29,30]. In these studies, human ESC-derived cardiomyocytes were administered 2- and 4-wk post-MI into immunocompromised Macaque monkeys. These studies produced some positive results: as hearts exhibited significant remuscularization within the infarcted area, ESC-grafts successfully reperfused the host vasculature and electromechanically coupled with host cardiomyocytes. There were also no signs of immune rejection or teratoma formation. However, there was no significant improvement in LVEF and non-fatal ventricular arrhythmias were seen in all monkeys[29,30]. Interestingly, these findings were reproduced in a similar preclinical experiment administering human ESC-derived cardiomyocytes into a post-MI porcine model[31]. Together, these three studies demonstrated the feasibility of producing and using human ESC-derived cardiomyocytes on a clinical scale and opened the door for phase 1 clinical trials in humans. The first human trial using human ESC-derived CPCs to treat HF was completed and illustrated some encouraging preliminary results[32]. The ESCORT trial investigated the feasibility and safety of implanting a fibrin patch embedded with human ESC-derived CPCs on the epicardium during coronary artery bypass grafting (CABG). In total, 6 patients with left ventricular (LV) dysfunction (EF < 35%) and a history of MI received treatment. The study produced positive safety outcomes, as no patients presented with arrhythmias and there were no tumours detected during follow-up[32]. Notably, three of the six patients presented with clinically silent alloimmunization. At the 1-year follow-up, all patients reported a symptomatic improvement via the NYHA functional class, a median increase in the 6 min walk test, a significant increase in heart wall motion of cell treated areas and a modest increase in LVEF, though statistically insignificant. Results of this study should be interpreted with caution as the sample size was extremely small and there are various confounding variables involved. Nonetheless, the principal discovery of this trial was successful in showing that human ESC-derived CPCs can be produced on a clinical scale and show no major signs of adverse effects after implantation. This trial displays the potential for human ESCs to be used in the treatment of HF, and further clinical trials that incorporate larger sample sizes are certainly warranted to investigate the full extent of their clinical usefulness.

There has been great interest in the therapeutic potential of iPSCs as they serve as an unlimited source of cells with an extensive proliferation potential[11]. They have been investigated for various diseases, including Parkinsons disease, immunotherapy for cancer and now heart disease[33]. Several preclinical studies have validated that iPSCs could play an important role in cardiac repair. It was demonstrated that the IM administration of a fibrin patch embedded with human iPSC-derived cardiomyocytes, among other cells and growth factors, produced a significant improvement in LV function and decreased infarct size in a post-MI porcine model[34]. In a recent study, extracellular vesicles secreted by murine iPSCs were shown to cause a significant improvement in LV function and a decrease in infarct size in a post-MI mouse model[35].

There are currently two clinical trials that have been approved for utilizing iPSCs in the treatment of chronic cardiomyopathy in humans. The world's first clinical trial was approved in Japan in 2018 and aims to administer a patch of human reprogrammed iPSC cardiomyocytes into the damaged myocardium[36]. Details about the trial are scarce, but three patients with chronic ischemic cardiomyopathy have been treated and the clinical trial aims to involve 10 patients over three years. Follow-up will occur at 1-year post-implantation and the primary endpoints investigated will be safety and efficacy. The second clinical trial is an open-label trial taking place in China. Five patients with HF will be treated with direct epicardial injection of allogeneic human iPSC-derived cardiomyocytes and assessed for safety and efficacy. There are currently no published results from either trial, although these should be expected within the next year.

One of the major barriers that arose during preclinical trials is that cardiomyocytes derived from PSCs (ESCs or iPSCs) have an immature phenotype compared to human adult cardiomyocytes[26]. Moreover, human PSC-derived cardiomyocytes are functionally immature in terms of sarcomere organization, calcium handling properties, and metabolism compared to adult cardiomyocytes[37]. This hinders their ability to efficiently integrate with host cardiomyocytes and is believed to be the reason that ventricular arrhythmias can arise[38]. The problem may not be with the potency of the cells themselves, but rather, the differentiation techniques that are currently used to create cardiomyocytes. Strategies that enhance the differentiation of PSC-derived cardiomyocytes include the use of bioengineered scaffolds, chemical factors, mechanical loading, and electrical stimulation[38]. Although clinical trial data is still quite limited, initial results regarding safety are quite promising, suggesting that the challenges of cell integration surrounding the immature cardiomyocyte phenotype may not be as severe in humans. Future studies should shift towards confirming safety in larger cohorts and optimizing the efficacy of PSCs.

The use of cardiac stem cells (CSCs) in clinical research showed great promise in the literature until it was discovered that the field was heavily compromised due to Dr. Piero Anversa, who was accused of scientific misconduct. He falsely claimed that CSCs did, in fact, produce viable and functional myocardium, which sparked a huge interest in the medical community and public media[39]. Many researchers attempted to replicate Anversas findings but failed to do so. Following these events, Harvard Medical School and the Brigham and Womens Hospital launched investigations on Anversa, which in 2014 led to the retraction of the SCIPIO trial that used c-kit+ CSCs in patients with HF[40]. By October 2018, the investigation revealed that 31 publications included falsified or fabricated data. Following these events, the National Institute of Health suspended the CONCERT-HF trial in November 2018 due to its scientific foundations. This trial was the first to evaluate a combination of c-kit+ CSCs and mesenchymal stem cells (MSCs) in patients with HF[41]. These alarming findings had a major impact on cardiac cell therapeutics and discredited the current advancements being made in this field.

To date, c-kit+ CSCs and cardiosphere-derived cell (CDC) phenotypes have been utilized in clinical trials. In the CADUCEUS trial, the intracoronary (IC) injection of CDCs has shown to reduce scar tissue size, improve regional contractility and viable heart mass on MRI. However, changes in ESV, EDV and LVEF did not differ between groups[42]. This clinical trial did not note any significant adverse events, alluding to a positive safety profile for CDCs. Likewise, the TAC-HFT-II trial will soon compare therapy with autologous MSCs alone vs MSCs combined with c-kit+ CSCs[41]. Indeed, the field of adult stem cells is highly compromised and has yet to demonstrate any clinical benefit for patients. Clinical trials with rigorous scientific standards are warranted in order to confirm the true efficacy of CSCs in the future. However, it is likely that the implications of Piero Anversas 31 retracted papers will remain far-reaching within the field.

Bone marrow-derived stem cells (BMDSCs) have been one of the most heavily tested cell types in the treatment of cardiovascular disease to date. Previous studies have shown that autologous bone marrow mononuclear cells (BMMNCs) have the potential to improve heart function through angiogenesis and direct myocardial regeneration[43]. Additionally, BMMNCs are an attractive source for therapy, as they have been found to be safe for clinical use and are easily harvested. When isolated, their biological characteristics are largely unaffected. The first-ever clinical trial using autologous BMMNCs was published in 2003. It included 21 patients with chronic HF who received transendocardial injection of autologous BMMNCs. After 4 mo, there was a significant increase in LVEF and a reduction in ESV, improvements in perfusion and myocardial contractility[44]. No significant safety concerns were noted. Similar results were found in the TOPCARE-CHD trial, which showed a significant improvement in global cardiac function, regional contractility, a decrease in brain natriuretic peptide and decreased mortality in response to IC administration of BMMNCs[45]. The STAR-heart study demonstrated that up to 5 years after IC administration, autologous bone marrow cells improved long-term mortality, LVEF and NYHA functional class[46]. In addition, a decreased LV preload, ESV, systolic wall stress, occurrence of arrhythmias, and area of infarction was noted. To this point, all clinical trials had also demonstrated a positive safety profile for BMDSCs. This initial success set the stage for the larger phase 2, randomized, double-blind FOCUS-CCTRN trial. This trial enrolled 92 patients with chronic HF and aimed at administering autologous BMMNCs via transendocardial injection. The positive results from smaller clinical trials could not be replicated, as there were no significant improvements in LVEF, maximal oxygen consumption, or infarct size[47]. Results were similar in the CELLWAVE trial, where IC or transendocardial injection of BMMNCs produced only modest improvements in LV function, maximal oxygen consumption and reversibility of ischemia[48].

In the TAC-HFT trial, patients received either transendocardial injections of autologous BMMNCs, autologous MSCs, or placebo. Results showed that only MSC therapy decreased infarct size, improved the 6 min walk test distance and regional function of the heart[49]. No improvements were noted in LVEF. The Cardio133 clinical trial noted a high frequency of adverse events in patients receiving CD133 (+) bone marrow cells delivered via CABG. It was concluded that although some improvements in scar size and perfusion may have occurred, injection of CD133 (+) cells has no effect on clinical symptoms of HF nor on global LV function[50]. Another clinical trial with 60 participants showed that the administration of BMMNCs via CABG improved LVEF, LVESV, wall motion index score and improved distance on the 6 min walk test and increased exercise tolerance. Moreover, brain natriuretic peptide levels decreased significantly, indicating that BMMNCs can improve heart function in patients with previous MI who suffer from chronic HF[43]. These cells may have a positive impact on the long-term prognosis of HF. After more than a decade of research, a systematic review and meta-analysis was published, providing clarity on the overall effectiveness of BMDSCs in the treatment of HF. In total, 38 randomized controlled trials including 1907 participants were included in the updated review. It was found that there is low-quality evidence that treatment with BMDSCs reduces mortality and improves LVEF on short and long-term follow-up[51]. There was also low-quality evidence that BMDSCs improve NYHA functional class in people with HF. Notably, 23 trials of the 38 were at high or unclear risk of selection bias. Given these findings, there is no current consensus on whether or not BMDSCs are truly efficacious in improving outcomes for HF patients. However, there are generally few safety concerns surrounding BMDSCs aside from the Cardio133 trial.

Mesenchymal stem cells are located in various tissues of the body including the bone marrow, adipose tissue and umbilical cord tissue. Evidence in preclinical and clinical studies suggests that MSCs may provide some benefits in the treatment of MI and HF due to a greater likelihood of vascular proliferation and direct myocardial regeneration[2,52]. Other BMDSCs have different mechanisms as they seem to trigger favorable forms of inflammation[2] rather than direct regeneration. Moreover, MSCs exhibit important reparative properties such as immunomodulation and promote antifibrotic, pro-angiogenic and anti-oxidative effects, making them great contenders for treating cardiomyopathies such as HF[53]. Among the different BMDSCs, MSCs seem to show the greatest promise for regeneration of myocardium, likely due to their strong paracrine effect[28]. The MSC-HF trial was the first placebo-controlled study conducted in chronic HF patients, which indicated that IM injection of autologous MSC is safe, improves myocardial function and reduces hospital admissions[54]. The POSEIDON randomized control trial compared the transendocardial delivery of autologous and allogeneic MSCs in HF patients. Results indicate that in a post-MI state, both autologous and allogeneic MSCs reduced adverse cardiac remodeling, infarct size and improved LV function. These structural and functional improvements were witnessed without significant safety concerns[55]. Similarly, the POSEIDON-DCM clinical trial demonstrated greater improvements in functional capacity and quality of life with allogeneic MSCs vs autologous MSCs in patients with non-ischemic dilated cardiomyopathy. Interestingly, allogeneic MSCs produced a constellation of clinically significant effects, such as improvements in EF, the 6 min walk test and higher scores in the Minnesota Living With HF Questionnaire vs autologous MSCs[56]. Evidence supports the superiority of allogeneic MSCs in regards to efficacy and endothelial function. Like the POSEIDON trial, transendocardial injection of autologous and allogeneic MSCs provided a highly acceptable safety profile in the POSEIDON-DCM trial.

Cardiopoietic stem cells are more specialized cells derived from a pure MSC population in the bone marrow. The C-CURE trial is one of the first using cardiopoietic cells in the treatment of HF. Findings demonstrated an increased LVEF, improved quality of life and a lower LVESV after 2 years while demonstrating feasibility and safety in chronic HF patients[57]. The findings of the C-CURE trial catalyzed larger studies to take place such as the CHART-1 trial which had a greater sample size, sharing similar results as the latter[58]. Both the C-CURE and CHART-1 trials indicate that stem cell therapy is safe and has the potential to provide long-lasting benefits on cardiac function in those affected by HF[57-59]. Larger randomized controlled trials, along with a comprehensive assessment of the impact of MSCs on cardiac function, would further establish a conclusive risk-benefit ratio for MSCs.

Umbilical cord MSCs have also been utilized in various clinical trials. The RIMECARD trial investigated the intravenous infusion of such cells in a sample of 30 patients. Results demonstrate that umbilical MSCs were not associated with significant acute adverse events or other safety concerns[60]. Moreover, there were improvements in LVEF, but no noteworthy reductions in LVESV or LVEDV. Another study delivered umbilical cord MSCs via the IC method, in combination with various medications, such as beta-blockers, angiotensin converting enzyme-inhibitors or ARBs, diuretics and digoxin[61]. HF symptoms such as cough, chest tightness, dyspnea and shortness of breath were alleviated 24 h after transplantation. In contrast, symptoms of fatigue, chest tightness and dyspnea were high in the treatment group after 1 mo of transplantation. There were some improvements in the 6 min walking distance test, but no improvements in LVEF. In addition, the mortality rate and NT-pro brain natriuretic peptide levels were statistically lower than those in the control group[61]. Results must be interpreted with caution, as the improvements seen may have been linked to the medications that were prescribed in addition to the MSCs.

Another study looked into the transendocardial injection of mesenchymal precursor cells (MPCs) to a cohort of 60 patients. Adverse events and all-cause mortality were similar across groups, suggesting the safety and feasibility of MPCs. This study suggests that high-dose allogeneic MPC treatment may reduce HF-major adverse cardiac events, reduce adverse LV remodeling and provide a readily available, off-the-shelf cell product that may be available in the future[62]. A recent study did not note any significant safety concerns in the intramyocardial injection of MSCs in HF patients. Results demonstrated improvements in LVEF, stroke volume and myocardial mass in HF patients[63]. More studies are required to confirm this hypothesis. Other trial results are pending, such as the DREAM-HF-1 trial that is evaluating the efficacy of transendocardial delivery of allogeneic MPCs in patients with advanced chronic HF[64].

A systematic review and meta-analysis investigated the efficacy of MSC therapy on ischemic and non-ischemic cardiomyopathy. Of the 29 randomized controlled trials, the majority demonstrated clinical benefits including improvements in LVEF, LVESV, NYHA functional class, quality of life and exercise capacity[65]. More specifically, patients who received stem cells in combination with CABG had the greatest improvements in LVEF vs other techniques. Reductions in LVESV were observed in more than half of the trials, suggesting that MSC therapy may decrease adverse cardiac remodeling in HF patients. Another recent systematic review and meta-analysis which included 23 studies in total, investigated the safety and efficacy of adult stem cell therapy for the treatment of acute MI and HF. In total, 12 of the 23 studies evaluated the efficacy of adult MSCs in ischemic HF. Post-treatment, there was a significant improvement in LVEF, but no differences in mortality between groups[52]. However, upon further subgroup analysis, improvements in LVEF were no longer found to be significant. Positive results were observed in other clinical outcomes of HF, as there were significant improvements in quality of life and the 6 min walk test. Overall, evidence suggests that MSC therapy seems to be safe, as no association between treatment and acute adverse outcomes for patients were noted[52]. Larger randomized, double-blind trials with longer follow-up periods are warranted to determine which combination of cell type and route of administration will yield the greatest improvements and reduce safety concerns in HF patients. The surge of incoming clinical trials should help clarify the true therapeutic potential of MSC therapy.

Early preclinical trials showed promise as skeletal myoblasts (SMs) appeared to have the capabilities to differentiate into cardiomyocytes and improve cardiac function in animal models[66,67]. The fact that these cells are abundant in the body and are already differentiated into muscle cells made them an attractive option. As a result, SMs were quickly rushed into clinical trials, and the results were disappointing. In the myoblast autologous grafting in ischemic cardiomyopathy (MAGIC) trial, the intramyocardial injection of SMs did not improve LVEF and failed to improve regional and global heart function. In addition, patients receiving SMs had a significantly greater risk of arrhythmias vs placebo[68]. On long-term follow-up, the findings of the MAGIC trial were confirmed, as SMs did not improve LV function[69]. Notably, the follow-up cohort only consisted of 7 patients while the original group consisted of 120 patients. For this reason, it is very difficult to establish the true long-term clinical impact of this study. Another small-sample study with 7 patients investigated the safety and efficacy of SM sheets for the treatment of severe HF. In 5 out of the 7 subjects, LVEF was maintained and showed improvement over time on echocardiography at 26 wk post-transplantation[70]. Among the 6 subjects, improvements in NYHA functional class and some improvements in the 6 min walk were noted, though this study had a very small sample size and there was no control group. No arrhythmias were noted and no other serious adverse effects were observed. Similar to the MAGIC trial, the MARVEL study did not demonstrate improvements in LV function or changes in the Minnesota Living with HF score, although some moderate improvements in the 6 min walk test distance were noted[71]. The MARVEL trial also revealed that the IM injection of SMs posed an increased risk of developing ventricular tachycardia, although such a complication appears to be transient and treatable[71]. Interestingly, a small clinical trial discovered that the transfection of muscle-derived progenitor cells with the connexin-43 gene administered transendocardially attenuated the proarrhythmic potential of SMs in the myocardium[72]. Nonetheless, since these landmark trials have come out, researchers have transitioned away from using skeletal myoblasts in hopes of finding a safer, more effective alternative cell type (Tables and ).

Summary of landmark human clinical trials

Safety parameters of various stem cell types

In the last decade, there has been a considerable amount of interest in the role of exosomes and microvesicles and their role in cardiovascular homeostasis. Exosomes are extracellular microvesicles that deliver active ribonucleic acid, lipids, proteins and various signaling molecules to a cell target[73,74]. Various cell types including cardiomyocytes, cardiac fibroblasts and endothelial cells release exosomes to help the survival, proliferation and normal apoptotic processes of cells, promoting a stable biological environment in the heart[75]. An MI damages the resident cardiac cells, subsequently reducing these endogenous, protective processes[73]. Exosomes can be derived from a range of stem cells including MSCs, CPCs, and iPSCs, all of which can be harnessed to provide a cell-free strategy with the goal of improving cardiac function and endogenous regeneration, reducing the risk of eliciting an immune response[73,76].

It is established that MSCs possess important paracrine signaling properties, which have shown to reduce inflammation and induce cell growth[77,78]. Thus, the premise of using exosomes as a therapeutic tool is that the majority of the benefit from stem cell therapy comes from paracrine effects. Preclinical studies indicate that extracellular vesicles from MSCs provided anti-apoptotic effects, reduced infarct size post-MI and reduced cardiomyocyte necrosis post-injury[79-82]. In addition to MSCs, iPSCs and ESCs have shown also to possess cardioprotective exosomes that may improve outcomes in HF patients[73]. Although many preclinical studies show promise in exosome-based therapeutics, there has yet to be a major breakthrough in human clinical trials. Recently, a small phase 1 clinical trial was initiated using allogeneic MSC-derived exosomes in the treatment of acute ischemic stroke (trial ID: {"type":"clinical-trial","attrs":{"text":"NCT03384433","term_id":"NCT03384433"}}NCT03384433). Exosomes are incredibly complex and we are still unsure on various parameters of therapy such as the loading, targeting and optimal method of delivery. Successful human clinical trials in the treatment of HF are still required before reaching any conclusions on whether or not exosomes are a feasible, safe, and effective solution in cardiac regeneration.

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Stem cell therapy for heart failure: Medical breakthrough ...