In the 4th edition of MarketsandMarkets Bioprocessing of Advanced Cellular Therapies & Regenerative Medicine, we would be focusing on the pre-clinical, manufacturing, clinical and regulatory aspects of cell therapies and regenerative medicine. This Congress event will be held on 10th and 11th March 2020 in London -UK

Since the past three editions of Bioprocessing of Advanced Cellular Therapies and Regenerative Medicine, MarketsandMarkets aims to provide a demonstrative approach to the latest developments in technologies of bioprocessing of cellular therapies.

What to expect:

The 4th edition of MarketsandMarkets Bioprocessing of Advanced Cellular Therapies & Regenerative Medicine would be concentrating on the pre-clinical, manufacturing, clinical and regulatory facets of cell therapies and regenerative medicine. The prime importance would be given on discussing topics such as tissue engineering, car-T cell-based immunotherapies, automated manufacturing, allogeneic therapies, from challenges in supply chain management and regulatory concern, point of view.

The conference will be useful for all the respective stakeholders of Advanced Cellular Therapies, majorly Pharma/Biotech delegates, Solution provider Delegates and Academic Delegates. The event will host VPs, directors, managers, leaders, engineers, scientists, academic heads, students which will boost the networking capacity of the attendees.

Download Agenda at https://www.reportsnreports.com/events/4th-annual-marketsandmarkets-bioprocessing-of-advanced-cellular-therapies-regenerative-medicine-congress/

Conference Agenda:

The two-day conference will have a list of agenda:

Key Pointers 4th Annual MarketsandMarkets Bioprocessing of Advanced Cellular Therapies & Regenerative Medicine Congress

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MarketsandMarkets 4th Annual Bioprocessing of Advanced Cellular Therapies & Regenerative Medicine Congress - Galus Australis

Cardiac Stem Cells Comments Off on MarketsandMarkets 4th Annual Bioprocessing of Advanced Cellular Therapies & Regenerative Medicine Congress – Galus Australis | December 9th, 2019

Led by researchers at Baylor College of Medicine, a study published in the journal Cell Stem Cell reveals a new mechanism that contributes to adult bone maintenance and repair and opens the possibility of developing therapeutic strategies for improving bone healing.

Adult bone repair relies on the activation of bone stem cells, which still remain poorly characterized. Bone stem cells have been found both in the bone marrow inside the bone and also in the periosteum - the outer layer of tissue - that envelopes the bone. Previous studies have shown that these two populations of stem cells, although they share many characteristics, also have unique functions and specific regulatory mechanisms."

Dr. Dongsu Park, corresponding author, assistant professor of molecular and human genetics and of pathology and immunology at Baylor

Of the two, periosteal stem cells are the least understood. It is known that they comprise a heterogeneous population of cells that can contribute to bone thickness, shaping and fracture repair, but scientists had not been able to distinguish between different subtypes of bone stem cells to study how their different functions are regulated.

In the current study, Park and his colleagues developed a method to identify different subpopulations of periosteal stem cells, define their contribution to bone fracture repair in live mouse models and identify specific factors that regulate their migration and proliferation under physiological conditions.

The researchers discovered specific markers for periosteal stem cells in mouse models. The markers identified a distinct subset of stem cells that contributes to life-long adult bone regeneration.

"We also found that periosteal stem cells respond to mechanical injury by engaging in bone healing," Park said. "They are important for healing bone fractures in the adult mice and, interestingly, their contribution to bone regeneration is higher than that of bone marrow stem cells."

In addition, the researchers found that periosteal stem cells also respond to inflammatory molecules called chemokines, which are usually produced during bone injury. In particular, they responded to chemokine CCL5.

Periosteal stem cells have receptors - molecules on their cell surface - that bind to CCL5, which sends a signal to the cells to migrate toward the injured bone and repair it. Deleting the CCL5 gene in mouse models resulted in marked defects in bone repair or delayed healing. When the researchers supplied CCL5 to CCL5-deficient mice, bone healing was accelerated.

The findings suggested potential therapeutic applications. For instance, in individuals with diabetes or osteoporosis in which bone healing is slow and may lead to other complications resulting from limited mobility, accelerating bone healing may reduce hospital stay and improve prognosis.

"Our findings contribute to a better understanding of how adult bones heal. We think this is one of the first studies to show that bone stem cells are heterogeneous and that different subtypes have unique properties regulated by specific mechanisms," Park said. "We have identified markers that enable us to tell bone stem cell subtypes apart and studied what each subtype contributes to bone health. Understanding how bone stem cell functions are regulated offers the possibility to develop novel therapeutic strategies to treat adult bone injuries."

Source:

Journal reference:

Ortinau, L.C., et al. (2019) Identification of Functionally Distinct Mx1+SMA+ Periosteal Skeletal Stem Cells. Cell Stem Cell. doi.org/10.1016/j.stem.2019.11.003.

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Study reveals new mechanism that contributes to bone maintenance and repair - News-Medical.net

Bone Marrow Stem Cells Comments Off on Study reveals new mechanism that contributes to bone maintenance and repair – News-Medical.net | December 9th, 2019

BOSTON--(BUSINESS WIRE)--Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to finding cures for blood cancers and serious blood diseases, today announced updated results from a Phase 1 clinical study of GDA-201, an investigational, natural killer (NK) cell-based cancer immunotherapy for the treatment of patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), at the 61st Annual Meeting of the American Society of Hematology (ASH), which is being held December 710 in Orlando, FL. Data from 22 patients in the ongoing study showed GDA-201 in combination with monoclonal antibodies was generally well tolerated and demonstrated early evidence of clinical activity in heavily pre-treated patients, including five complete responses observed among nine patients with NHL. Gamida Cell plans to initiate a Phase 1/2 multi-dose, multi-center study of GDA-201 in patients with NHL in 2020.

NK cells are increasingly recognized as a potential breakthrough approach in immunotherapy, and the data reported today provide early evidence that GDA-201 has the potential to be an important new treatment option, said Veronica Bachanova, M.D., Ph.D., Associate Professor of Medicine in the Division of Hematology, Oncology and Transplantation at the University of Minnesota and principal investigator of the study through the Masonic Cancer Center. Given the population of heavily pre-treated patients with advanced disease, its particularly encouraging to witness multiple complete responses. I look forward to the continued development of this investigational therapy.

New research was also presented today on the mechanism of action of Gamida Cells NAM-based cell expansion platform, which is designed to enhance the number and functionality of allogeneic donor cells. These data provide further scientific rationale for the favorable stem cell engraftment and patient outcomes observed in the Phase 1/2 clinical study of omidubicel, the companys advanced cell therapy currently in Phase 3 clinical development as a potential life-saving treatment option for patients in need of an allogeneic bone marrow transplant.

These mechanism of action data reinforce the transformative potential of our NAM therapeutic platform, which can be used to expand multiple cell types. Specifically for omidubicel, this research suggests that NAM modulates certain gene expression pathways that, collectively, mimic the hypoxic environment of the bone marrow to help preserve stem cell function and long-term engraftment ability, said Tracey Lodie, Ph.D., chief scientific officer of Gamida Cell. We expect to build on our findings by characterizing the metabolites produced when we expand stem cells to make omidubicel, and we are also beginning to conduct similar mechanism of action studies with GDA-201.

GDA-201 Phase 1 Clinical Data Presented at ASH

The oral presentation, Results of a Phase 1 Trial of GDA-201, Nicotinamide-Expanded Allogeneic Natural Killer Cells (NAM-NK) in Patients with Refractory Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma (MM) (Abstract #777), described data from the Phase 1 clinical study of GDA-201 in heavily pre-treated patients with advanced NHL and MM. Twenty-two patients were enrolled in the study, including nine patients with NHL and 13 patients with MM. Of these 22 patients, all were evaluable for safety and 21 were evaluable for response (NHL = 9; MM = 12).

In the study, cell therapy using GDA-201 with monoclonal antibodies was generally well tolerated and demonstrated early evidence of clinical activity. Of the nine patients with NHL, five achieved a complete response and one achieved a partial response. Among the patients with MM, one patient achieved a complete response, and five patients achieved stable disease.

GDA-201 was generally well tolerated, with no graft vs. host disease (GvHD), no tumor lysis syndrome, no neurotoxicity and no marrow aplasia observed. No dose limiting toxicities were observed. Hypertension and hematologic events were the most common Grade 3/4 adverse events observed. Most non-hematologic toxicities were attributed to cyclophosphamide/fludarabine, which was used as a pre-conditioning treatment.

NAM Therapeutic Platform Mechanism of Action Data Presented at ASH

The poster presentation, Nicotinamide (NAM) Modulates Transcriptional Signature of Ex Vivo Cultured UCB CD34+ Cells (Omidubicel) and Preserves Their Stemness and Engraftment Potential (Abstract #3718), included transcriptome, transcription factor, and pathway analysis to elucidate the pathways leading to the preservation of engraftment after ex vivo expansion of CD34+ hematopoietic stem cells derived from umbilical cord blood (the starting point for omidubicel) compared to CD34+ cells grown in the absence of NAM.

Analyses showed that the presence of NAM reduced the expression of genes involved in the production of reactive oxygen and nitrogen species, suggesting that cell stress was minimized during expansion. In addition, NAM also decreased growth factor pathways responsible for activation and differentiation of hematopoietic stem cells, suggesting NAM expanded cells while keeping them in an undifferentiated state. The presence of NAM also led to a decrease in the expression of genes responsible for matrix-metallo proteinase secretion, simulating the microenvironment of the bone marrow. Additionally, NAM led to an increased expression of telomerase genes, which is believed to enable cells to remain in a more quiescent, stem-like state. These data provide further scientific rationale for the favorable stem cell engraftment and patient outcomes that were observed in the Phase 1/2 clinical study of omidubicel.

About GDA-201GDA-201 (formerly known as NAM-NK) is being developed as an innate natural killer (NK) cell immunotherapy for the treatment of hematologic and solid tumors in combination with standard-of-care antibody therapies. NK cells have the ability to kill tumor cells, representing a novel immunotherapeutic approach to cancer treatment. GDA-201 is designed to address key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs of NK cells expanded in culture. GDA-201 is in Phase 1 development in patients with refractory non-Hodgkin lymphoma and multiple myeloma.1 For more information on the clinical study of GDA-201, please visit http://www.clinicaltrials.gov.

About OmidubicelOmidubicel (formerly known as NiCord), the companys lead clinical program, is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant solution for patients with hematologic malignancies (blood cancers). Omidubicel is the first bone marrow transplant product to receive Breakthrough Therapy Designation from the U.S. Food and Drug Administration and has also received Orphan Drug Designation in the U.S. and EU. In a Phase 1/2 clinical study, omidubicel demonstrated rapid and durable time to engraftment and was generally well tolerated.2 A Phase 3 study evaluating omidubicel in patients with leukemia and lymphoma is ongoing in the U.S., Latin America, Europe and Asia.3 Omidubicel is also being evaluated in a Phase 1/2 clinical study in patients with severe aplastic anemia.4 The aplastic anemia investigational new drug application is currently filed with the FDA under the brand name CordIn, which is the same investigational development candidate as omidubicel. For more information on clinical trials of omidubicel, please visit http://www.clinicaltrials.gov.

GDA-201 and omidubicel are investigational therapies, and their safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.

About the NAM Therapeutic PlatformGamida Cells proprietary NAM-based cell expansion platform is designed to enhance the number and functionality of donor cells in culture, enabling the creation of potentially transformative therapies that move beyond what is possible with existing approaches. The NAM therapeutic platform leverages the unique properties of nicotinamide to enable the expansion of multiple cell types including stem cells and natural killer (NK) cells with appropriate growth factors to maintain the cells original phenotype and potency. This can enable the administration of a therapeutic dose of cells with the potential to improve patient outcomes.

About Gamida CellGamida Cell is an advanced cell therapy company committed to finding cures for patients with blood cancers and serious blood diseases. We harness our cell expansion platform to create therapies with the potential to redefine standards of care in areas of serious medical need. For additional information, please visit http://www.gamida-cell.com.

Cautionary Note Regarding Forward Looking StatementsThis press release contains forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, including with respect to the initiation of new clinical trials and the continuation of the Companys clinical development program, which statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to the scope and progress of Gamida Cells clinical trials and other clinical, scientific, regulatory and technical developments. In light of these risks and uncertainties, and other risks and uncertainties that are described in the Risk Factors section of Gamida Cells public filing on Form 20-F, filed with the SEC on February 25, 2019, and other filings that Gamida Cell makes with the SEC from time to time (which are available at http://www.sec.gov), the events and circumstances discussed in such forward-looking statements may not occur, and Gamida Cells actual results could differ materially and adversely from those anticipated or implied thereby. Any forward-looking statements speak only as of the date of this press release and are based on information available to Gamida Cell as of the date of this release.

1ClinicalTrials.gov identifier NCT03019666.2 Horwitz M.E., Wease S., Blackwell B., Valcarcel D. et al. Phase I/II study of stem-cell transplantation using a single cord blood unit expanded ex vivo with nicotinamide. J Clin Oncol. 2019 Feb 10;37(5):367-374.3 ClinicalTrials.gov identifier NCT027302994 ClinicalTrials.gov identifier NCT03173937

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Gamida Cell Announces Results from Phase 1 Study of GDA-201 and New Mechanism of Action Data at ASH 2019 Annual Meeting - Business Wire

Bone Marrow Stem Cells Comments Off on Gamida Cell Announces Results from Phase 1 Study of GDA-201 and New Mechanism of Action Data at ASH 2019 Annual Meeting – Business Wire | December 9th, 2019

ORLANDO, Fla.--(BUSINESS WIRE)--Jasper Therapeutics, Inc., a new biotechnology company focused on enabling safer conditioning and therapeutic agents that expand the application of curative hematopoietic stem cell transplants and gene therapies, today announced that initial results from an ongoing Phase 1 dose-escalation study of its lead product candidate, JSP191 (formerly AMG191), will be presented today in an oral session at the American Society of Hematology (ASH) Annual Meeting & Exposition.

JSP191, a humanized antibody targeting CD117, is designed to replace or reduce the toxicity of chemotherapy and radiation therapy as a conditioning regimen to prepare patients for hematopoietic cell transplantation. The Phase 1 clinical trial is evaluating JSP191 as a conditioning agent to enable stem cell transplantation in patients with severe combined immunodeficiency (SCID) who received a prior stem cell transplant that had poor outcomes.

Life-threatening disorders such as SCID, and other conditions including autoimmune diseases and hematologic cancers, can be cured by hematopoietic cell transplantation, and those with certain genetic diseases can be cured with stem cell-directed gene therapies. However, the number of patients who can benefit from these approaches is limited because of the severe toxicity of the chemotherapy used for pre-transplant conditioning that is needed to allow room in the bone marrow for the stem cells to engraft, said Judith Shizuru, M.D., Ph.D., co-founder and member of the Board of Directors of Jasper Therapeutics. We are encouraged by the initial Phase 1 study results of JSP191 in these fragile patients with SCID and plan to expand clinical development of this antibody beyond patients with SCID. We expect to initiate clinical trials of JSP191 in 2020 to evaluate it as a conditioning agent in patients undergoing hematopoietic cell therapy for acute myeloid leukemia, myelodysplastic syndrome and Fanconi anemia, and IND-enabling studies for sickle cell disease and autoimmune indications.

Details of the oral presentation follow:

Abstract Title: Non-Genotoxic Anti-CD117 Antibody Conditioning Results in Successful Hematopoietic Stem Cell Engraftment in Patients with Severe Combined Immunodeficiency (abstract #800) Session Name: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Innovative Approaches in Allogeneic Transplantation for Pediatric or Nonmalignant DisordersPresenter: Rajni Agarwal, M.D., Associate Professor of Pediatrics and Stem Cell Transplantation, the Stanford University School of MedicineTime: 3:00 p.m. ETLocation: W311EFGH, Level 3, Orange County Convention Center

About Stem Cell Transplantation

Blood-forming, or hematopoietic, stem cells are cells that reside in the bone marrow and are responsible for the generation and maintenance of all blood and immune cells. These stem cells can harbor inherited or acquired abnormalities that lead to a variety of disease states, including immune deficiencies, blood disorders or hematologic cancers. Successful transplantation of hematopoietic stem cells is the only cure for most of these life-threatening conditions. Replacement of the defective or malignant hematopoietic stem cells in the patients bone marrow is currently achieved by subjecting patients to toxic treatment with radiation and/or chemotherapy that cause DNA damage and lead to short- and long-term toxicities, including immune suppression and prolonged hospitalization. As a result, many patients who could benefit from a stem cell transplant are not eligible. New approaches that are effective but have minimal to no toxicity are urgently needed so more patients who could benefit from a curative stem cell transplant could receive the procedure.

Safer and more effective hematopoietic cell transplantation regimens could overcome these limitations and enable the broader application of hematopoietic cell transplants in the cure of many disorders. These disorders include hematologic cancers (e.g., myelodysplastic syndrome [MDS] and acute myeloid leukemia [AML]), autoimmune diseases (e.g., lupus, rheumatoid arthritis, multiple sclerosis and Type 1 diabetes), and genetic diseases that could be cured with genetically-corrected autologous stem cells (e.g., severe combined immunodeficiency syndrome [SCID], sickle cell disease, beta thalassemia, Fanconi anemia and other monogenic diseases).

About JSP191

JSP191 (formerly AMG191) 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 cells to engraft.

Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in an animal model of MDS. This 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 80 healthy volunteers and patients. It is currently being evaluated as a sole conditioning agent in a Phase 1 dose-escalation trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplant for SCID, which is curable only by this type of treatment. For more information about the design of the clinical trial, visit http://www.clinicaltrials.gov (NCT02963064). Clinical development of JSP191 will be expanded to also study patients with AML or MDS who are receiving hematopoietic cell transplant.

About Jasper Therapeutics

Jasper Therapeutics is a biotechnology company focused on enabling safer conditioning and therapeutic agents that expand the application of curative hematopoietic stem cell transplants and gene therapies. Jasper Therapeutics lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a stem cell transplant. For more information, please visit us at http://www.jaspertherapeutics.com.

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Jasper Therapeutics Announces Upcoming Data Presentation on Lead Program, JSP191, at 61st American Society of Hematology (ASH) Annual Meeting &...

Bone Marrow Stem Cells Comments Off on Jasper Therapeutics Announces Upcoming Data Presentation on Lead Program, JSP191, at 61st American Society of Hematology (ASH) Annual Meeting &… | December 9th, 2019

NEW ORLEANS, Dec. 9, 2019 /PRNewswire/ --Autoimmune Technologies LLC, a biotechnology company developing diagnostics and therapies for non-infectious and infectious disease, has established a new subsidiary, Stadius Biopharma LLC, to focus on proprietary anti-infective antibody therapeutics for diseases that are inadequately addressed by current standard-of-care medicines.

"Within this standalone entity we'll concentrate on our unique fully human antibodies and our stem cell antibody delivery platform to treat opportunistic viral, bacterial, and fungal infections," said Michael Charbonnet, who will serve as CEO of the newly formed business unit in addition to his continuing responsibilities for the parent company. Current Stadius antibody targets include invasive candidiasis and cytomegalovirus (CMV) infection.

"Ourantibodies bind and disrupt the function of conserved sequences of novel virulence factors associated with pathology of various species of Candida," said CSO Russell Wilson. "Candida aurisis an emerging fungus that presents a serious global health threat, and we'reencouraged by our initial preclinical data that indicates activity against C. auris as well as C. albicans, which is prevalent in high risk patients," he said.

The CDC is monitoring the spread of C. auris colonization and infection in the United States.C. aurisis associated with a high rate of morbidity and mortality and is resistant to current standard of care antifungal treatments. Healthy individualsunknowingly colonized with C. aurisor other Candida species and can spread the fungal cells to surfaces in hospitals, long-term-care facilities, and other healthcare environments, where they pose a threat to people with weakened immune systems.

Also under development are antibody therapeutics to CMV infection. More than 50% of individuals in the U.S. over 40 years of age have been exposed to CMV and carry it without symptoms. It can re-activate in patients with subpar immune systems with the potential for multi-organ involvement, and it can be transmitted through body fluids such as breast milk and saliva. Over time, individuals can become re-infected with different strains of CMV, further complicating prophylaxis and treatment. CMV is the most frequent infectious complication following both solid organ transplantation and bone marrow transplantation.

The company is also developing its proprietary non-viral gene modified allogeneic stem cell platform for delivering antibodies in chronically immune compromised patients. The somatic adipose-derived mesenchymal stem cells, which have unique properties to allow prevention of rejection, are transfected with the genetic information needed to enable the implanted stem cells to produce inside the patient the antibodies needed to prevent or treat infection. Antibody delivery to patients via this platform is intended to provide continuous protection while reducing the requirement for more frequent dosing.

Follow Stadius Biopharma on http://www.stadiusbio.com.

View original content to download multimedia:http://www.prnewswire.com/news-releases/autoimmune-technologies-announces-new-subsidiary-to-develop-novel-antibody-and-allogeneic-somatic-stem-cell-therapeutics-for-the-treatment-of-invasive-candidiasis-and-other-infectious-disease-300971143.html

SOURCE Autoimmune Technologies LLC

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Autoimmune Technologies Announces New Subsidiary to Develop Novel Antibody and Allogeneic Somatic Stem Cell Therapeutics For the Treatment of Invasive...

Bone Marrow Stem Cells Comments Off on Autoimmune Technologies Announces New Subsidiary to Develop Novel Antibody and Allogeneic Somatic Stem Cell Therapeutics For the Treatment of Invasive… | December 9th, 2019

Forty Seven's data eat up the market, with positive results in MDS and AML  BioWorld Online

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Forty Seven's data eat up the market, with positive results in MDS and AML - BioWorld Online

Bone Marrow Stem Cells Comments Off on Forty Seven’s data eat up the market, with positive results in MDS and AML – BioWorld Online | December 9th, 2019

PALO ALTO, Calif.--(BUSINESS WIRE)--Jasper Therapeutics, Inc., a new biotechnology company focused on enabling safer conditioning and therapeutic agents that expand the application of curative hematopoietic stem cell transplants and gene therapies, today announced the launch of the company with a $35 million total Series A financing. Abingworth LLP and Qiming Venture Partners USA served as lead investors, with further investment from Surveyor Capital (a Citadel company) and participation from Alexandria Venture Investments, LLC. The proceeds will be used to advance the clinical development of the companys lead product candidate, JSP191, which is designed to replace or reduce the toxicity of chemotherapy and radiation therapy as a conditioning regimen to prepare patients for hematopoietic cell transplant.

Jaspers development of JSP191 is also supported by a collaboration with the California Institute for Regenerative Medicine (CIRM), which has been funding the program and is committed to providing a total of $23 million in grant support. As part of the Series A financing, Amgen, which discovered JSP191 (formerly AMG191), has licensed worldwide rights to Jasper that also include translational science and materials from Stanford University.

Jasper was co-founded by Judith Shizuru, M.D., Ph.D., a hematopoietic stem cell transplant expert at Stanford University, and Susan Prohaska, Ph.D., a Stanford University-trained immunologist, stem cell biologist and early-stage drug development professional. Dr Shizurus CIRM-funded lab advanced the understanding of the ability of anti-CD117 to impact hematopoietic stem cells and, together with the Lucile Packard Childrens Hospital Stanford and University of California, San Francisco (UCSF) pediatric transplant teams, was the first to study an anti-CD117 antibody in the clinic as a conditioning agent. That humanized antibody, now called JSP191, was first studied for conditioning for transplant in immune-deficient patients in collaboration with Amgen, UCSF and CIRM.

Stem cell transplantation is a potential curative therapy for people with hematologic cancers, autoimmune diseases, and debilitating genetic diseases. However, the pre-transplant conditioning required to prepare patients for transplant involves highly toxic chemotherapy, which can be life-threatening and limits the number of people who are able to benefit, said Dr. Shizuru, co-founder and member of the Board of Directors of Jasper Therapeutics. JSP191 is the only anti-CD117 antibody to demonstrate safety and efficacy in severely ill patients receiving stem cell transplant in the clinic. We plan to expand clinical development to patients receiving transplants for acute myeloid leukemia/ myelodysplastic syndrome or autoimmune diseases and to patients receiving stem cell-directed gene therapies.

Dr. Shizuru added, With an experienced executive team of biotech veterans and a strong syndicate of healthcare-focused investors, Jasper Therapeutics is well positioned to achieve our vision of building a leading biotech company starting with JSP191 and expanding to other novel therapies for immune modulation, graft engineering and cell and gene therapies.

JSP191 is currently being evaluated in an ongoing Phase 1 clinical trial as a conditioning agent to enable stem cell transplantation in patients with severe combined immunodeficiency (SCID) who received a prior stem cell transplant that failed. This severe genetic immune disorder leaves patients without a functioning immune system. Interim results of the study will be presented in an oral presentation (abstract #800) on Monday, December 9, at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Fla. Clinical studies to evaluate the safety and efficacy of JSP191 as a conditioning agent in patients undergoing hematopoietic cell therapy for hematologic cancers are planned for 2020.

Founding Management Team

Dr. Shizuru and Mr. Lis are joined on the Jasper Therapeutics Board of Directors by Kurt von Emster, Managing Partner of Abingworth LLP, and Anna French, Ph.D., Principal at Qiming Venture Partners USA. Dr. Prohaska is a Board observer.

With our investment in this program, were able to realize our mission of fast-tracking stem cell treatments by helping academic researchers rapidly advance the most promising discoveries in the lab into the clinics and to drug development with commercialization partners, said Maria T. Millan, M.D., President and CEO of CIRM. Jaspers two co-founders took a novel antibody with unique properties and moved it from the bench to the bedside relatively quickly, and were thrilled to partner with this talented team to potentially impact a broad group of people who could benefit from stem cell therapy.

About Stem Cell Transplantation

Blood-forming, or hematopoietic, stem cells are cells that reside in the bone marrow and are responsible for the generation and maintenance of all blood and immune cells. These stem cells can harbor inherited or acquired abnormalities that lead to a variety of disease states, including immune deficiencies, blood disorders or hematologic cancers. Successful transplantation of hematopoietic stem cells is the only cure for most of these life-threatening conditions. Replacement of the defective or malignant hematopoietic stem cells in the patients bone marrow is currently achieved by subjecting patients to toxic doses of radiation and/or chemotherapy that cause DNA damage and lead to short- and long-term toxicities, including immune suppression and prolonged hospitalization. As a result, many patients who could benefit from a stem cell transplant are not eligible. New approaches that are effective but have minimal to no toxicity are urgently needed so more patients who could benefit from a curative stem cell transplant could receive the procedure.

Safer and more effective hematopoietic cell transplantation regimens could overcome these limitations and enable the broader application of hematopoietic cell transplants in the cure of many disorders. These disorders include hematologic cancers (e.g., myelodysplastic syndrome [MDS] and acute myeloid leukemia [AML]), autoimmune diseases (e.g., lupus, rheumatoid arthritis, multiple sclerosis and Type 1 diabetes), and genetic diseases that could be cured with genetically-corrected autologous stem cells (e.g., severe combined immunodeficiency syndrome [SCID], sickle cell disease, beta thalassemia, Fanconi anemia and other monogenic diseases).

About JSP191

JSP191 (formerly AMG191) 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 cells to engraft.

Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in an animal model of MDS. This 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 80 healthy volunteers and patients. It is currently being evaluated as a sole conditioning agent in a Phase 1 dose-escalation trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplant for SCID, which is curable only by this type of treatment. For more information about the design of the clinical trial, visit http://www.clinicaltrials.gov (NCT02963064). Clinical development of JSP191 will be expanded to also study patients with AML or MDS who are receiving hematopoietic cell transplant.

About Jasper Therapeutics

Jasper Therapeutics is a biotechnology company focused on enabling safer conditioning and therapeutic agents that expand the application of curative hematopoietic stem cell transplants and gene therapies. Jasper Therapeutics lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a stem cell transplant. For more information, please visit us at http://www.jaspertherapeutics.com.

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Jasper Therapeutics Launches with $35 Million Series A Financing to Develop and Commercialize Innovative Conditioning Agents and Therapies to...

Bone Marrow Stem Cells Comments Off on Jasper Therapeutics Launches with $35 Million Series A Financing to Develop and Commercialize Innovative Conditioning Agents and Therapies to… | December 9th, 2019

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of immune reset to more patients, today announced that new results from its CD117-ADC patient preparation program were presented at the 61st Annual Meeting of the American Society of Hematology (ASH). These results, which were highlighted in an oral presentation at ASH by John Tisdale, M.D., Director, Molecular and Clinical Hematology Section, National Institutes of Health, showed the first-ever successful transplant of gene-modified cells in non-human primates using a targeted, single-agent antibody-drug conjugate (ADC), without the use of chemotherapy or radiation.

Todays conditioning regimens involve high doses of chemotherapy, often paired with radiation, to remove the disease-causing cells. As a result, patients undergoing gene therapy or stem cell transplant are all faced with a difficult choice: whether to endure severe toxicity and risk infertility and cancer for the chance for a cure. Magentas portfolio of targeted ADCs represents an extremely promising new option to prepare patients for gene therapy or transplant with no need for toxic chemotherapy or radiation, said Dr. Tisdale. The results presented today show that a single dose of single agent CD117-ADC achieves the same level of depletion as four doses of busulfan chemotherapy to enable successful engraftment and persistence of stem cells modified with the -globin gene, the gene that causes sickle cell disease and -thalassemia when mutated. Importantly, the animals undergoing preparation with CD117-ADC showed none of the damaging toxicities associated with busulfan conditioning.

Magenta is the only company with the people, platforms and a product engine committed to comprehensively transforming immune and blood system reset, which includes revolutionizing the toxic methods that are used to prepare patients for gene therapy and transplant today. said Jason Gardner, D.Phil., Chief Executive Officer and President, Magenta Therapeutics. The gene therapy field has learned that higher levels of stem cell depletion, which meant higher doses of busulfan, were needed to ensure long-term engraftment of the gene-modified cells and persistence of gene therapy. Across all the modalities we have tested, we have seen that ADCs are most effective at achieving these high levels of stem cell depletion without chemotherapy to enable engraftment and long-term durability of the transplant. Todays impressive results provide important validation of the ADC approach as well as the CD117 target for patient preparation and underscore Magentas leadership in the field of conditioning.

Results from the CD117-ADC Patient Preparation Program

Title: A Single Dose of CD117 Antibody Drug Conjugate Enables Autologous Gene-Modified Hematopoietic Stem Cell Transplant (Gene Therapy) in Nonhuman Primates (Abstract #610)Presenter: John Tisdale, M.D., Director, Molecular and Clinical Hematology Section, National Institutes of Health, Bethesda, Md.

Magentas most advanced patient preparation program, CD117-ADC, targets CD117, a protein expressed on hematopoietic stem cells. CD117-ADC is designed to remove the genetically mutated cells in the bone marrow that cause certain genetic diseases, such as sickle cell disease, enabling curative stem cell transplant or gene therapy.

Results presented by Dr. Tisdale showed:

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 autoimmune diseases, genetic diseases and blood cancers. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant world to revolutionize immune reset for more patients.

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

Follow Magenta on Twitter: @magentatx.

Forward-Looking Statement

This press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavor, potential, continue or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation risks set forth under the caption Risk Factors in Magentas Registration Statement on Form S-1, 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 Demonstrates First-ever Successful Gene Therapy Transplant Without Chemotherapy in Primates Using a Single Dose of Antibody-drug...

Bone Marrow Stem Cells Comments Off on Magenta Therapeutics Demonstrates First-ever Successful Gene Therapy Transplant Without Chemotherapy in Primates Using a Single Dose of Antibody-drug… | December 9th, 2019

MB-107 preceded by low-dose busulfan conditioning continues to be well tolerated and results in development of functional immune system in newly diagnosed infants with XSCID

Enhanced transduction procedure is demonstrating improvements in older patients with XSCID who received prior hematopoietic stem cell transplantation

Data presented by St. Jude Childrens Research Hospital and National Institutes of Health at 61st American Society of Hematology Annual Meeting

NEW YORK, Dec. 09, 2019 (GLOBE NEWSWIRE) -- Mustang Bio, Inc. (Mustang) (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, announced today that updated Phase 1/2 clinical data for MB-107 lentiviral gene therapy for X-linked severe combined immunodeficiency (XSCID) were presented on Saturday by St. Jude Childrens Research Hospital (St. Jude) and today by the National Institutes of Health at the 61st American Society of Hematology (ASH) Annual Meeting.

MB-107 is currently being assessed in two Phase 1/2 clinical trials for XSCID: the first in newly diagnosed infants under the age of two at St. Jude, and the second in patients over the age of two who have received prior hematopoietic stem cell transplantation at the National Institutes of Health. Under a licensing partnership with St. Jude, Mustang intends to develop the lentiviral gene therapy for commercial use as MB-107. The U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to MB-107 for the treatment of XSCID in August 2019.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, The updated clinical data presented at the 2019 ASH Annual Meeting underscore the curative potential of MB-107 for newly diagnosed infants with XSCID, as well as its meaningful impact on older XSCID patients who received prior hematopoietic stem cell transplantation. St. Jude recently received the 2019 Smithsonian Magazine American Ingenuity Award for development of the lentiviral gene therapy, highlighting its potential to have an impact on this devastating disease. We are excited to be working with St. Jude and NIH to advance MB-107 and look forward to transferring the IND from St. Jude to Mustang in the first quarter of 2020.

Lentiviral Gene Therapy with Low Dose Busulfan for Infants with X-SCID Results in the Development of a Functional Normal Immune System: Interim Results of an Ongoing Phase I/II Clinical Study (Abstract Number: 2058)Poster presentation: Ewelina Mamcarz, M.D., Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Childrens Research Hospital, Memphis, TN, USA

Interim data from the multicenter Phase 1/2 clinical trial for infants under the age of two treated with the lentiviral gene therapy preceded by low exposure-targeted busulfan conditioning were published in the New England Journal of Medicine. Updated data presented at the 2019 ASH Annual Meeting include three more patients (n=11), 8 months additional median follow up (23.6 months; range: 1.5 to 33.9 months), more extensive analysis of T and B cell functional recovery, and detailed vector integration site studies.

Data Highlights:

The results from treatment with low-dose busulfan conditioning and the novel lentiviral gene therapy in newly diagnosed infants with XSCID continue to be very promising, said Dr. Mamcarz. We are pleased that the therapy has been well tolerated and all patients with a follow up of more than 3 months recovered from pre-existing infections, are off protective isolation and prophylactic antimicrobials, and have normal growth in respect to height and weight. This reinforces our belief that the lentiviral gene therapy has the potential to be an attractive alternative to current XSCID therapies.

Enhanced Transduction Lentivector Gene Therapy for Treatment of Older Patients with X-Linked Severe Combined Immunodeficiency (Abstract Number: 608)Oral presentation: Harry Malech, M.D., Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, USA

Early outcome data for five older children and young adults with XSCID who received the lentivector (also known as lentiviral) gene therapy as salvage therapy after having previously received haplo-identical hematopoietic stem cell transplantation (HSCT) as infants without chemotherapy-based conditioning were previously reported and published in Science Translational Medicine. By 2016, three additional patients were treated, and the cohort of eight patients (referred to as Cohort A) has now been followed for 3 to 7 years. Among Cohort A, gradual clinical benefit in the clearance of chronic norovirus and associated improved abdominal complaints, malabsorption, growth and IgG production were observed, and four patients were able to cease immunoglobulin replacement therapy.

While the results were positive, the relatively inefficient transduction of hematopoietic stem/progenitor cells (HSPCs) required large quantities of vector. This resulted in relatively low VCN in myeloid cells in some patients, with delayed immune cell recovery and persistent clinical disease, especially in the last patient treated (patient 8). To address this, NIH developed a refined enhanced transduction (ET) procedure consisting of a single overnight transduction after 48 hours pre-stimulation in cytokines (Stem cell factor, Thrombopoietin, Flt3-ligand; 100ng/mL) and incorporated transduction enhancers LentiBoost 1:100 and dimethyl prostaglandin 2 (dmPGE2; 1uM).

The presentation at the 2019 ASH Annual Meeting included data from six patients (referred to as Cohort B) treated by NIH, including re-treatment of patient 8. The patients, who were aged 12 to 36, had significant problems with donor T cell infiltration of liver, bone marrow and kidneys, and were nearly absent of B and NK cells. The enhanced transduction procedure achieved much greater transduction efficiencies than were observed in Cohort A, with greater than 10-fold less vector, and resulted in faster immune reconstitution and more significant clinical benefit by 3 months.

We are encouraged by the significantly improved measures of early clinical outcomes from lentivector gene therapy in older children and young adults with XSCID using an enhanced transduction procedure with the addition of LentiBoost and dmPGE2, said Dr. Malech. Notably, we have seen an early appearance of B and NK cells at much higher levels in Cohort B than we previously observed in Cohort A, even at years after treatment. We look forward to continuing to closely monitor patients and report outcomes.

About Mustang BioMustang Bio, Inc. (Mustang) is a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases. Mustang aims to acquire rights to these technologies by licensing or otherwise acquiring an ownership interest, to fund research and development, and to outlicense or bring the technologies to market. Mustang has partnered with top medical institutions to advance the development of CAR T and CRISPR/Cas9-enhanced CAR T therapies across multiple cancers, as well as a lentiviral gene therapy for XSCID. Mustang is registered under the Securities Exchange Act of 1934, as amended, and files periodic reports with the U.S. Securities and Exchange Commission. Mustang was founded by Fortress Biotech, Inc. (NASDAQ: FBIO). For more information, visit http://www.mustangbio.com.

ForwardLooking Statements This press release may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. Such statements include, but are not limited to, any statements relating to our growth strategy and product development programs and any other statements that are not historical facts. Forward-looking statements are based on managements current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; risks relating to the timing of starting and completing clinical trials; uncertainties relating to preclinical and clinical testing; our dependence on third-party suppliers; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law.

Company Contacts:Jaclyn Jaffe and William BegienMustang Bio, Inc.(781) 652-4500ir@mustangbio.com

Investor Relations Contact:Daniel FerryLifeSci Advisors, LLC(617) 430-7576daniel@lifesciadvisors.com

Media Relations Contact:Tony Plohoros6 Degrees(908) 591-2839tplohoros@6degreespr.com

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Mustang Bio Announces Updated Clinical Data on MB-107 Lentiviral Gene Therapy for Patients with X-Linked Severe Combined Immunodeficiency -...

Bone Marrow Stem Cells Comments Off on Mustang Bio Announces Updated Clinical Data on MB-107 Lentiviral Gene Therapy for Patients with X-Linked Severe Combined Immunodeficiency -… | December 9th, 2019

SUZHOU, Chinaand SHANGHAI, Dec. 9, 2019 /PRNewswire/ -- Gracell Biotechnologies Co., Ltd ("Gracell"), a clinical-stage immune cell therapy company, today announced the progressive clinical outcomes for leading product candidates FasTCAR-19, Dual CAR-19-22, and Dual CAR-BCMA-19 at the American Society of Hematology (ASH) Annual Meeting in Orlando, Florida, held from December 7-10. Multiple pilot studies intend to evaluate the safety and efficacy of Gracell's first-in-class FasTCAR-19 (GC007F), Dual CAR-19-22 (GC012F) and Dual CAR-BCMA-19 (GC022F) cell therapy.

FasTCAR-19FasTCAR-19 or GC007F uses Gracell's patented FasTCARTM solution, which genetically modifies a patient's T-cells to express CD19-specific chimeric antigen receptor (CAR) for the treatment of B-cell acute lymphoblastic leukemia (B-ALL).

Utilizing the unique bioprocessing, FasTCAR-19 cells can be produced overnight through viral transfection in use of Gracell's proprietary fully-closed manufacturing system (from apheresis to filling). These cells are considered far more potent and durable in comparison to current market alternatives. To date, all 37 patient samples have been successfully manufactured. The process has been proven efficient, stable and duplicable, with a median 36.8% (range 13.1%-70.3%) transfection success and a median copies of 0.95 (range 0.2-4.21).

As of November, this investigational study enrolled 37 adult and adolescent patients aged from 14 to 70 years, who suffered from r/r B-ALL and had failed to respond to multiple prior lines of therapy, from eight clinical centers. All patients received a single infusion of FasTCAR-19 at one of the three-dose level (low: 0.6*10^5/kg; mid: 1.0*10^5/kg, and high: 1.6*10^5/kg), followed by prior conditioning regimen of fludarabine-cyclophosphamide (FC).

The treatment efficacy was assessed in 35 patients over 28 days of follow-up, of which:

During the over six month-durable remission period, FasTCAR-19 demonstrated a good level of persistence in line with previous clinical trials. In terms of safety, all 37 patients tolerated the single infusion of FasTCAR-19 at different dose levels, with no dose-limiting toxicities observed. The most common safety concerns were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) where mild to moderate side effects were observed. Across 30 patients in the low to mid doses group, only 5 (16.7%) manageable Grade 3 CRS and 5 (16.7%) manageable Grade 3 ICANS were reported; while the remaining 23 (76.7%) had Grade 1-2 CRS. The low to mid doses group will likely be selected for extensive study in future clinical trials.

Beyond single-antigen CAR, Dual CAR-T cells can deliver promising clinical outcomesSingle-antigen CAR-T cells have demonstrated considerable efficacy; however, antigen loss and high relapse rate have been observed in a significant number of patients. To combat this, treatments containing two separate CARs and dual transduction (GC022 targeting CD19 and CD22, GC012 targeting BCMA and CD19) were developed. Following positive results from in vitro and in vivo studies, human clinical trials have commenced testing the safety and feasibility of Dual CAR-19-22 and Dual CAR-BCMA-19 to treat B-ALL and MM, respectively.

Dual CAR-19-22

Dual CAR-19-22 or GC022 has achieved a manufacturing success rate of 20/20, without any patient loss due to manufacturing failure. Enrolled patients aged from 4-45 years old who has B-ALL, received a single infusion of Dual CAR-19-22 at one of the three-dose levels (low: 0.5*10^6/kg; mid: 2.0*10^6/kg, and high: 3.0*10^6/kg), under conventional bioprocessing. The study demonstrated a very good safety profile and high efficacy at mid to high doses.

The treatment efficacy was assessed in 20 patients with a 28-day follow-up, of which:

Dual CAR-19-22 proved effective on patients who had previously been treated with CD19 CAR-T cells and/or received allogeneic hematopoietic stem cell transplantation (allo-HSCT) for r/r B-ALL but failed to benefit from prior treatments. Among these five patients, four (80%) patients achieved MRD-CR with a 28-day follow-up. Surpassing the 3-month durable remission period, fifteenpatients still retain ongoing response.

Furthermore, Dual CAR-19-22 demonstrated an excellent safety profile, with 6/20 (30%) patients indicating no CRS, 14/20 (70%) reporting Grade 1 CRS. No ICANS events were reported.

Dual CAR-BCMA-19Dual CAR-BCMA-19 or GC012 has been demonstrated effective in eliminating multiple myeloma (MM) tumor cells both in vitro and in vivo. The first-in-human study showed a good safety profile and effectiveness. Beyond, FasTCARTM has successfully been applied to Dual CAR-BCMA-19, expected to enhance proliferation, potency, and migration in the human body.

"We are delighted to see that patients with relapsed/refractory B-ALL continue to gain substantial clinical benefit from FasTCAR-19. Furthermore, Dual CAR-19-22 with conventional bioprocess can generate promising clinical data. This marks our confidence to utilize FasTCAR technology to both Dual CAR programs for various indications," said Dr. William Cao, CEO of Gracell. "The results from our latest clinical trials reveal the immense potential of FasTCAR technology, and we are eager to see Gracell's highly efficacious, yet affordable therapies benefit more patients in China and worldwide."

About B-ALLAcute lymphoblastic leukemia (ALL), although rare, is one of the most common forms of cancer in children between the ages of two and five and adults over the age of 501. In 2015, ALL affected around 837,000 people globally and resulted in 110,000 deaths worldwide2. It is also the most common cause of cancer and death from cancer among children. ALL is typically treated initially with chemotherapy aimed at bringing about remission. This is then followed by further chemotherapy carried out over several years.

About MMMultiple myeloma (MM) is a cancer that forms in a type of white blood cell known as a plasma cell. MM cells are abnormal plasma cells (a type of white blood cell) that build up in the bone marrow and form tumors in many bones of the body. Healthy plasma cells make antibodies to help the body fight infection and disease. As the number of MM cells increases, more antibodies are produced. This can cause the blood to thicken and keep the bone marrow from making enough healthy blood cells. MM cells can also damage and weaken the bone. In 2018, MM affected around 160,000 people globally and resulted in 106,000 deaths worldwide3. Different types of treatments are available for patients with plasma cell neoplasms. Chemotherapy and targeted therapy are typical treatments; while stem cell transplant, biologic therapy, and radiation therapy, even surgery are also adopted.

About GracellGracell Biotechnologies Co., Ltd. ("Gracell") is a clinical-stage biopharma company, committed to developing highly reliable and affordable cell gene therapies for cancer. Gracell is dedicated to resolving the remaining challenges in CAR-T, such as high production costs, lengthy manufacturing process, lack of off-the-shelf products, and inefficacy against solid tumors. Led by a group of world-class scientists, Gracell is advancing FasTCARTM, TruUCARTM (off-the-shelf CAR), Dual CAR and Enhanced CAR-T cell therapies for leukemia, lymphoma, myeloma, and solid tumors.

CONTACT:

1https://www.cancer.org/cancer/acute-lymphocytic-leukemia/about/key-statistics.html2https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055577/3https://gco.iarc.fr/today/fact-sheets-cancers

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Gracell Announces Progressive Outcomes from Multiple Human Clinical Trials to Investigate FasTCAR and Dual CAR Cell Platform Technologies - PRNewswire

Bone Marrow Stem Cells Comments Off on Gracell Announces Progressive Outcomes from Multiple Human Clinical Trials to Investigate FasTCAR and Dual CAR Cell Platform Technologies – PRNewswire | December 9th, 2019

Using immunotherapy with genetically modified T cells that express chimeric antigen receptors or CARs designed to target tumor-associated molecules, have impressive efficacy in the treatment hematological malignancies.

A CAR is a synthetic construct that, when expressed in T cells, mimics T cell receptor activation and redirects specificity and effector function toward a specified antigen.[1]

In the treatment of cancer, this process is accomplished by linking an extracellular ligand-binding domain specific for a tumor cell surface antigen to an intracellular signaling module that activates T cells upon antigen binding.[1]

The presented studies include results from emerging second-generation cellular immunotherapy products that strive to overcome the limitations of existing products such as resistance and reduce toxicity and simplify treatment.

Cellular immunotherapy uses genetic engineering to enhance the ability of the immune system the bodys defense system against infection and disease to kill malignant cells in the blood, the bone marrow, and other sites, in order to keep cancer from coming back.

CAR T-cell TherapyChimeric antigen receptor T-cell therapies, better known as CAR T-cell therapies, are developed by harvesting a patients own T-cells, the immune systems primary cancer-killing cells, engineering them to target proteins specific to the surface of cancer cells, and reintroducing these modified T-cells back into the patients immune system to kill the cancer cells.

First generationFirst-generation CAR T-cell therapies primarily target CD-19, a protein found on the surface of most normal and malignant B cells in B cell cancers such as lymphoma. These therapies have been shown to produce long-term remissions in about one-third of patients with B-cell lymphomas that have not responded to prior therapies.

We are now seeing efforts to enhance the effectiveness of CAR T-cell therapy by designing products capable of attacking multiple targets, expand the availability of cellular immunotherapy to other blood cancers such as multiple myeloma and replace the complex manufacturing process required for CAR T-cell therapy with a uniform off-the-shelf product, noted Gary Schiller, MD, UCLA Health, an academic medical center which includes a number of hospitals and an extensive primary care network in the Los Angeles, California, region.

One of the phase I studies evaluates an off-the-shelf cellular immunotherapy product that targets two proteins found on the surface of lymphoma cells, including its potential to revive previously administered CAR T-cells that have stopped working.

Another study presents preclinical results for one of the first cellular immunotherapies to be based on off-the-shelf natural killer (NK) cells and the first, according to its manufacturer, to be genetically engineered to contain three active anti-tumor components.

The other two studies, also phase I studies, assess novel CAR T-cell therapies for multiple myeloma that test different dual-target strategies.

One investigational agent is genetically engineered to contain two proteins that attach to BCMA, a protein found almost exclusively on the surface of plasma cells, the immune-system cells that become cancerous in multiple myeloma.

The other is designed to target both BCMA and CD-38, another protein found on the surface of plasma cells. In both studies, many patients achieved minimal residual disease (MRD) negativity, which means that using highly sensitive testing fewer than one myeloma cell per 100,000 cells was identified in the bone marrow. Previous studies have shown that patients who achieve this milestone have a lower risk of relapse after more than three years of follow-up.

Dual-targeted CAR T-cell therapiesThe three phase I studies also hint at the possibility that dual-targeted CAR T-cell therapies might result in fewer patients experiencing moderate to severe cytokine release syndrome (CRS), a known adverse effect caused by an immune response in the body to the activated T cells that are attacking the cancer. CRS causes flu-like symptoms such as fever, body aches, and fatigue, and in severe cases can be life-threatening. Treatment with the drug tocilizumab can reduce CRS symptoms.

Dual-Targeted Antibody Elicits Durable ResponsesPatients with B-cell Non-Hodgkin Lymphoma (NHL) that had returned after or failed to respond to a median of three prior therapies showed complete responses (CR) and durable remissions after being treated with an investigational drug called mosunetuzumab (RG7828; Genentech/Roche). [2]

This investigational agent is a humanized, T-cell bispecific antibody designed to engage T cells and redirect their cytotoxic activity against malignant B cells. The drug works by activating the patients own T-cells, stimulating them to attack and kill cancerous B cells to which they have been introduced by the novel antibody.

Mosunetuzumab simultaneously binds to CD3 epsilon (CD3), a component of the T-cell receptor (TCR) complex, and to CD20, a B-cell surface protein expressed in a majority of B-cell malignancies. This results in crosslinking of the TCR, inducing downstream signaling events that leads to B-cell killing.

Among patients whose lymphoma progressed after treatment with CAR T-cell therapy, 22% had complete remissions when treated with mosunetuzumab. This new drug targets two proteins, one on the surface of tumor cells and the other on the surface of the recipients Tcells.

Unlike CAR T-cell therapy, mosunetuzumab is an off-the-shelf immunotherapy product that can be given to patients without having to genetically modify their T cells, noted lead author Stephen J. Schuster, MD, of Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor. Of particular interest, we are seeing durable complete remissions in patients whose lymphomas progressed after CAR T-cell therapy, he added.

The researchers observed many remissions continue after patients stop receiving the drug.

I have stopped therapy in some patients after six months and they have remained in remission. Some patients have remained in remission without additional therapy for more than a year, Schuster said.

New treatment options are needed not only for patients in whom CAR T-cell therapy has failed, but also for those patients whose lymphomas are getting worse so quickly that they cannot wait for CAR T-cell manufacturing, which takes several weeks, Schuster explained.

The data presented during the annual meeting of the American Society of Hematology included 270 patients (median age 62, 172 men) enrolled in the phase I trial in seven countries (the United States, Australia, Canada, Germany, South Korea, Spain, and the United Kingdom). All participating patients had B-cell lymphomas that had come back or not responded to a median of three prior therapies. Two-thirds of patients (67%) had fast-growing lymphomas; 85 (31%) patients had more slow-growing forms of the disease. In 30 patients (11%), the cancer was resistant to or returned after an initial response to CAR T-cell therapy; in 77 patients (29%), the disease had progressed after a stem cell transplant.

All patients were treated with mosunetuzumab by intravenous infusion. They had an imaging test at either six weeks or three months after starting therapy to assess the initial response to treatment, and responses continued to be followed every three months thereafter.

Forty-six of 124 patients with fast-growing lymphomas (37%) had measurable decreases in the extent of their cancer (objective response); 24 of 124 patients (19%) saw all detectable tumors disappear (complete response). A higher response rate was observed in patients with higher exposure to mosunetuzumab. Among patients with slow-growing lymphomas, 42 of 67 (63%) had objective responses and 29 of 67 (43%) had complete responses. Both objective response rate and complete response rate were maintained in subgroups of patients at high risk for relapse.

Complete remissions appear to be long lasting, Schuster said.

With a median follow-up of six months since first complete remission, 24 of 29 patients (83%) who achieved complete remissions of their slow-growing lymphomas and 17 of 24 patients (71%) who achieved complete remissions of their fast-growing lymphomas remain free of disease. In some patients whose cancers progressed after receiving CAR T-cell therapy, highly sensitive molecular testing showed that the previously administered CAR T cells increased in number.

This suggests that, in addition to its ability to kill cancerous B cells, mosunetuzumab may also help augment the effect of the prior CAR-T treatment, Schuster noted.

Cytokine-release syndromeIn this study, 29% of patients treated with mosunetuzumab experienced cytokine-release syndrome that was mostly mild.

Cytokine release syndrome or CRS is caused by a large, rapid release of cytokines into the blood from immune cells affected by the immunotherapy. While most patients have a mild reaction, sometimes patients may have a severe, life threatening, reaction.

In 3% of patients, CRS was treated with tocilizumab (Actemra; Genentech/Roche). Four percent of patients experienced moderately severe neurologic side effects. Patients who received higher doses of mosunetuzumab were no more likely to have CRS or neurologic side effects than patients treated at lower doses.

A study of a higher dose of mosunetuzumab is now enrolling patients and long-term follow-up of these patients will ultimately help to better evaluate the durability of response data.

Larger, randomized trials are needed to further confirm these promising data and determine whether the treatment benefit of mosunetuzumab is enhanced when it is used earlier in the course of lymphoma therapy or in combination with other agents, Schuster concluded.

Novel Off-the-Shelf CARPreclinical studies provide the first evidence that cellular immunotherapy for B cell cancers could ultimately become an off-the-shelf product, capable of being uniformly manufactured in large quantities as prescription drugs are.

We have taken the concept of traditional pharmaceutical drug development and applied it to cellular therapy, explained senior author Bob Valamehr, Ph.D, of Fate Therapeutics, a San Diego biopharmaceutical company.

The product called FT596, is among the first cellular immunotherapies to be based on off-the-shelf NK cells the first line of defense of the immune system and is the first cellular immunotherapy to be genetically engineered to contain three active anti-tumor components, Valamehr explained.

Comparable with standard CAR T-cell therapyFT596 demonstrated comparable ability to kill cancerous white blood cells as standard CAR T-cells and, when combined with the drug rituximab (Rituxan; Genentech/Roche), killed cancerous white blood cells that were no longer responding to standard CAR T-cell therapy due to loss of the CD19 antigen target.

The U.S. Food and Drug Administration (FDA) approved Fate Therapeutics Investigational New Drug Application for FT596 in September 2019 and the company hopes to begin a first-in-human phase I clinical trial for the treatment of B-cell lymphoma and chronic lymphocytic leukemia in the first quarter of 2020.

The primary purpose of this trial will be to assess the safety and activity of FT596 in patients.

ManufacturingThe development and manufacturing of FT596 begins with human induced pluripotent stem cells (iPSCs) that are uniquely capable of unlimited self-renewal and can differentiate into more than 200 types of human cells. These iPSCs are genetically engineered, after which a single genetically engineered cell or clone is selected and multiplied in the laboratory to create a master engineered cell line that can be repeatedly used to generate cancer-fighting immune-system cells such as NK and T cells.

Natural Kiler Cells or NK cells are a type of lymphocyte and a component of innate immune system, the bodys first line of defense against infection and disease. Unlike T-cells, which have to be trained to recognize their target and can kill only cells that display that target on their surface, NK cells do not need special preparation before going on the attack and can kill many different types of transformed or infected cells.

NK cells are multifaceted and can be viewed as a jack-of-all-trades when it comes to protecting the host, whereas T cells can act in only one way, Valamehr explained.

But NK cells are also different in other ways. They are inherently limited in their capacity to multiply and expand when infused into patients, and they have a shorter lifespan.

Valamehr and his colleagues used genetic engineering to address these shortcomings. In addition to engineering FT596 to carry a CAR targeting the CD19 protein, which is produced by nearly all B-cell lymphomas and leukemias, they inserted two other novel proteins: CD16, which boosts and broadens the NK cells ability to kill cancer cells, and IL15, which stimulates FT596 to proliferate and persist.

Valamehr explained that FT596 has been designed to address two more limitations of CAR T-cell therapy .

The investigational agent is an off-the-shelf product. As a result, it significantly improves the current patient-by-patient CAR T-cell treatment paradigm by eliminating the time-consuming and costly process that is currently required to treat a patient with CAR T-cells.

The addition of the CD16 protein gives FT596 broader therapeutic activity and versatility. In combination with rituximab, FT596 has the potential to lead to deeper and more durable responses and overcome resistance that hampers the long-term efficacy of CAR T-cell therapy.

Eliminating the high production cost, weeks of manufacturing time, and complex manufacturing process required for CAR T-cell therapy and replacing it with a mass-produced, off-the-shelf product, promises to expand access to effective cell-based cancer immunotherapy to many more patients who may benefit from it, Valamehr concluded.

Results from CARTITUDE-1 in R/R Multiple MyelomaPatients with multiple myeloma who had received a median of five prior therapies, and for whom standard-of-care treatments were no longer working, had a high response rate when treated with the investigational CAR T-cell therapy JNJ-68284528 (JNJ-4528), which targets BCMA, a protein commonly found on the surface of multiple myeloma cancer cells.

These patients participated in a clinical trials (NCT03548207), supported by Janssen Research & Development, designed to characterize safety of and establish the recommended Phase II dose (RP2D) (Phase Ib) and to evaluate the efficacy of JNJ-68284528 (Phase II).

We are seeing a high response rate, with most patients achieving MRD negativity, noted lead study author Deepu Madduri, MD, of The Tisch Cancer Institute at Mount Sinai in New York.

Considering these patients have all received multiple prior therapies, these results are extremely encouraging, Madduri added.

All evaluable patients receiving this CAR T-cell therapy have achieved MRD-negative disease state and 27 of 29 patients are progression free at a median follow-up of six months, Madduri said.

Multiple myeloma is a cancer of plasma cells, which are found in the bone marrow and are part of the immune system, the bodys defense system against infection. Typical signs and symptoms of multiple myeloma may be bone pain or fractures, high levels of calcium in the blood, kidney damage, and anemia. Multiple myeloma affects an estimated 160,000 people each year, occurs most often in people over 60. The disease is slightly more common in men than in women.

Although new therapies for multiple myeloma have recently become available that can extend patients life expectancy, a cure for the disease remains elusive.

We can get the disease into remission, but most patients unfortunately relapse, and outcomes are very poor for patients who have relapsed multiple times, she said.

Researchers explained that JNJ-4528 is a novel CAR T-cell therapy featuring two molecules that bind to BCMA, a protein found on the surface of multiple myeloma cells.

We are learning that every CAR T-cell therapy is different, Madduri said.

JNJ-4528 has a unique CAR T-cell composition in patients, preferentially enriched in CD8 T cells, which are believed to be one of the most important T cells in killing cancer cells, she noted.

This phase Ib/II trial is continuing to enroll patients.

During the 2019 annual meeting of the American Society of Hematology, Madduri reported results for the first 29 patients enrolled.

Patients T-cells were collected and sent to a laboratory where they were genetically engineered to express JNJ-4528. Prior to re-infusing these CAR T-cells, the patients received three days of chemotherapy to make room in their immune systems for the engineered T-cells.

Following chemotherapy, each patient received a single infusion of the JNJ-4528 CAR T-cells.

After a minimum of 28 days, these patients had blood and bone marrow exams, which was followed by exams at six months, and one year after treatment to assess their response. The primary aims of the trial are to assess the therapys safety and to confirm the dose to be tested in a larger, phase II trial.

The median follow-up time in the current analysis is six months. Overall, 100% of patients had a clinical response to JNJ-4528. Moreover, 66% had a stringent complete response, meaning that sensitive laboratory and microscopic tests found no evidence for myeloma proteins or cells in blood, urine, or bone marrow.

Most patients (93%) experienced some form of CRS. One patient had severe (grade 3) CRS, and one patient died from its complications 99 days after the CAR T-cell infusion. In 76% of patients, CRS was treated with tocilizumab.

To see some patients in this heavily pretreated population surviving for a year or more with a one-time treatment and a manageable safety profile is remarkable, Madduri explained.

These patients feel that they have their quality of life back. They no longer have to come into the clinic for weekly treatments and some are well enough to travel, Madduri concluded.

The phase II portion of this study is ongoing to evaluate the overall response rate of patients treated with JNJ-68284528 (JNJ-4528). Additional clinical studies are evaluating the safety and efficacy of JNJ-4528 in different multiple myeloma treatment settings.

BreakthroughEarlier this week the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for JNJ-68284528 (JNJ-4528).

The granting of Breakthrough Therapy Designation for JNJ-68284528 (JNJ-4528) is a significant milestone as we continue to accelerate the global development of this innovative CAR-T therapy in collaboration with Legend Biotech, noted Sen Zhuang, MD, Ph.D., Vice President, Oncology Clinical Development, Janssen Research & Development.

We look forward to continuing to work closely with the U.S. Food and Drug Administration to advance the clinical development program for JNJ-68284528 (JNJ-4528) and ultimately bring this BCMA-targeted immunotherapy to patients living with multiple myeloma who are in need of a new therapeutic option, Zhuang concluded.

Encouraging Results for Dual-Targeted CAR T-Cell TherapyMore than three out of four patients with multiple myeloma that returned or did not respond to at least two therapies remained in remission seven months after treatment with a novel CAR T-cell therapy targeting two proteins that are frequently found on myeloma cells.

Nine patients experiencing sustained remissions in this study, which ws supported by the National Natural Science Foundation of China, the Major Technological Innovation Special Project fund of Hubei Province of China, and Cellyan Therapeutics, were diagnosed with a difficult-to-treat form of multiple myeloma in which the disease has spread beyond the bone marrow.

Roughly one in 10 patients with multiple myeloma develop tumors in the organs or soft tissues such as the blood vessels, muscles, and nerves. These so-called extramedullary tumors respond poorly to treatment, and patients who develop them have a poor outlook and poor health related quality of life (hrQoL)

Our results show that this CAR T-cell product can effectively achieve elimination of extramedullary tumors, said study author Yu Hu, MD, Ph.D, of Union Hospital, Huazhong University of Science and Technology in Wuhan, China.

Although these are preliminary data, they are encouraging for patients with multiple myeloma who have not responded to other therapies, Hu added.

Hu and his colleagues are developing the first CAR T-cell therapy to be genetically engineered to target BCMA and CD38, two proteins found on the surface of plasma cells. Multiple myeloma is a cancer of plasma cells, which are found in the bone marrow and are part of the immune system, the bodys defense system against infection and disease.

Our thinking was that targeting both of these proteins would improve treatment efficacy without increasing toxicity, and induce deeper, more durable remissions, Hu noted.

The first-in-humans phase I trial enrolled 22 patients whose average age was 59, of whom 11 were men. All had multiple myeloma that had returned or not responded to at least three therapies. Nine of the 22 patients had extramedullary tumors. The study aims were to determine the safest and most effective dose of the CAR T-cell therapy as well as to initially evaluate its effectiveness.

Just like in other trials with CAR T-cell therapies, the participating patients received three days of chemotherapy to make room in their immune systems for the engineered T-cells. Then each patient was infused with the dual-targeted CAR T cells. Patients were divided into five groups, with each group receiving a higher dose than the previous one. Depending on the cell dose, patients received either one or two infusions.

At a median of 36 weeks of follow-up, 18 patients (90.9%) had MRD-negative disease. Twelve patients (54.5%) had a stringent complete response, meaning that no plasma cells were detected in the bone marrow. Seven patients (31.8%) had a good or very good partial response, meaning that the level of M-protein (an abnormal protein produced by cancerous plasma cells) in the blood or urine was reduced but still detectable. In eight of the nine patients with extramedullary lesions, these tumors were undetectable on their computed tomography scans. For the 17 patients who remained in remission at seven months after treatment, the median duration of response was 28.8 weeks.

The adverse events observed included 20 patients who experienced CRS, of whom six needed treatment. No serious adverse neurologic effects such as seizures, movement impairment, difficulty speaking or understanding speech, or fatal swelling in the brain were reported.

With this dual-targeted CAR T-cell therapy, we have demonstrated a high response rate, especially a higher rate and longer duration of stringent complete response, compared with other therapies, as well as effective elimination of extramedullary lesions, with no serious neurologic adverse effects and manageable levels of other adverse effects, Hu concluded.

The investigators continue to follow the patients for the next two years. They are also planning to conduct a phase II trial in both China and the United States to test the treatments effectiveness in a larger number of patients.

Clinical trialsA Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1) NCT03548207

References[1] Srivastava S, Riddell SR. Chimeric Antigen Receptor T Cell Therapy: Challenges to Bench-to-Bedside Efficacy. J Immunol. 2018;200(2):459468. doi:10.4049/jimmunol.1701155 [Abstract][2] Schuster SJ, Bartlett NL, Assouline S, Yoon SS, Bosch F, Sehn LH, Cheah CY, Shadman M, et al. Mosunetuzumab Induces Complete Remissions in Poor Prognosis Non-Hodgkin Lymphoma Patients, Including Those Who Are Resistant to or Relapsing After Chimeric Antigen Receptor T-Cell (CAR-T) Therapies, and Is Active in Treatment through Multiple Lines. 61st annual meeting of the American Society of Hematology. Program: General Sessions. Session: Plenary Scientific Session. Hematology Disease Topics & Pathways: antibodies, Follicular Lymphoma, CRS, Diseases, Biological, Therapies, neurotoxicity, Adverse Events, CAR-Ts, Non-Hodgkin Lymphoma, DLBCL, immunotherapy, Lymphoid Malignancies. [Abstract][3] Goodridge JP, Mahmood S, Zhu H, Gaidarova S, Blum R, Bjordahl R, Cichocki F, et al. FT596: Translation of First-of-Kind Multi-Antigen Targeted Off-the-Shelf CAR-NK Cell with Engineered Persistence for the Treatment of B Cell Malignancies. 61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral. Session: 625. Lymphoma: Pre-ClinicalChemotherapy and Biologic Agents: Targeting Apoptosis Pathways in Lymphoma.[Abstract][4] Madduri D, Usmani SZ, Jagannath S, Singh I, Zudaire E, Yeh TM, Allred AJ, Banerjee A, et al. Results from CARTITUDE-1: A Phase 1b/2 Study of JNJ-4528, a CAR-T Cell Therapy Directed Against B-Cell Maturation Antigen (BCMA), in Patients with Relapsed and/or Refractory Multiple Myeloma (R/R MM). 61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral Session: 653. Myeloma: Therapy, excluding Transplantation: Novelty in CAR T in Relapsed/Refractory Multiple Myeloma. [Abstract][5] Li C, Mei H, Hu Y, Guo T, Liu L, Jiang H, Tang L, Wu Y, et al. A Bispecific CAR-T Cell Therapy Targeting Bcma and CD38 for Relapsed/Refractory Multiple Myeloma: Updated Results from a Phase 1 Dose-Climbing Trial61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral. Session: 653. Myeloma: Therapy, excluding Transplantation: Novel Therapy for Relapsed Myeloma. Hematology Disease Topics & Pathways: Biological, Diseases, Adult, Therapies, Lymphoma (any), Adverse Events, CAR-Ts, Elderly, Biological Processes, Technology and Procedures, Cell Lineage, Study Population, Clinically relevant, Lymphoid Malignancies.

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ASH 2019: Second-gen CAR T-Cell Therapy Overcome Resistance, Reduce Toxicity and Simplify Treatment - OncoZine

Bone Marrow Stem Cells Comments Off on ASH 2019: Second-gen CAR T-Cell Therapy Overcome Resistance, Reduce Toxicity and Simplify Treatment – OncoZine | December 9th, 2019

Investor call to be held December 9 at 8:30 am ET / 1:30 pm GMT to review data

LONDON, Dec. 07, 2019 (GLOBE NEWSWIRE) -- Autolus Therapeutics plc (Nasdaq: AUTL) announced today new data highlighting progress on its next-generation programmed T cell therapies to treat patients with acute lymphoblastic leukemia (ALL) and adults with relapsed/refractory diffuse large B cell lymphoma (DLBCL). The data were presented in oral presentations at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, FL. Additional data on pediatric patients with ALL will be presented on December 8.

The data on AUTO1 presented at this years ASH meeting demonstrate the favorable safety profile and high level of clinical activity of AUTO1 in both adults and pediatric patients with ALL, and we look forward to initiation of the pivotal program in adult ALL in the first half of 2020, said Dr. Christian Itin, chairman and chief executive officer of Autolus.

Acute Lymphoblastic Leukemia Data Presented

Title: AUTO1 A novel fast off CD19CAR delivers durable remissions and prolonged CAR T cell persistence with low CRS or neurotoxicity in adult ALL (Abstract # 226)

Updated results for ALLCAR19, the Phase 1 trial evaluating AUTO1 in adults with recurrent/refractory ALL, were presented by Dr. Claire Roddie MB, PhD, FRCPath, honorary senior lecturer, Cancer Institute, University College London (UCL), in an oral presentation. The trial is designed to assess the primary endpoints of safety ( Grade 3 toxicity) and feasibility of product generation, as well as other secondary endpoints, including efficacy. The trial enrolled patients with a high tumor burden (44% had 50% BM blasts), who were considered high-risk for experiencing cytokine release syndrome (CRS). Product was manufactured for 19 patients; product for 13 of those patients was manufactured using a semi-automated closed process, which will be used for commercial supply.

As of the data cut-off date of November 25, 16 patients had received at least one dose of AUTO1. AUTO1 was well tolerated, with no patients experiencing Grade 3 CRS, and 3 of 16 patients (19%), who had high leukemia burden, experiencing Grade 3 neurotoxicity that resolved swiftly with steroids.

Of 15 patients evaluable for efficacy, 13 (87%) achieved MRD negative CR at 1 month and all patients had ongoing CAR T cell persistence at last follow up. CD19-negative relapse occurred in 22% (2 of 15) patients. In the patients dosed with AUTO1 manufactured in the closed process, 9 of 9 (100%) achieved MRD negative CR at 1 month and 6 months event free survival, and overall survival in this cohort was 100%.

Adult ALL patients, who face a median survival of less than one year after their ALL recurs or relapses, have a significant need for a CAR T cell therapy that is highly active, safe and is a standalone therapy not requiring a stem cell transplant, said Dr. Hagop M. Kantarjian, Chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center.

The novel CD 19 CAR-T therapy, AUTO1, is potentially transformative as a standalone curative option for patients with r/r ALL, especially in adults, given its favorable safety profile, said Dr. Max Topp associate professor of Internal Medicine, Hematology and Oncology at the University of Wuerzburg.

Title: Therapy of pediatric B-ALL with a lower affinity CD19 CAR leads to enhanced expansion and prolonged CAR T cell persistence in patients with low bone marrow tumor burden, and is associated with a favorable toxicity profile (Abstract # 225)

Dr. Sara Ghorashian, honorary senior lecturer, Great Ormond Street Institute of Child Health, University College London, presented updated data from the phase 1 CARPALL study of AUTO1 in pediatric ALL patients with low bone marrow tumor burden. The trial is intended to assess the primary endpoints of safety and proportion of patients in molecular complete remission at 1 month. The study recruited a total of 25 patients and stratified them into 2 cohorts. Fourteen patients were treated in cohort 1, which utilized a manual manufacturing process; product was unable to be generated in 3 patients. Median follow-up was 27 months in cohort 1. Seven patients were treated in cohort 2, which utilized the semi-automated closed manufacturing process, which will be used for commercial supply. The aim of cohort 2 was to demonstrate feasibility of manufacture at scale. Product was generated for 100% of patients. Median follow-up was 7 months in cohort 2.

AUTO1 was well-tolerated overall, with no patients experiencing Grade 3 CRS and 1 of 21 (5%) experiencing Grade 4 neurotoxicity, which was considered unrelated to CAR T therapy.

Nineteen of 21 treated patients (90%) achieved molecular complete remission at 1 month post infusion. Consistent with pre-clinical data, CAR T cell expansion was excellent and detectable by flow in a number of patients up to 36 months. Persistence was noted in 15 of 21 patients at last follow-up, up to 36 months. In cohort 2, 100% of patients achieved molecular complete remission at 1 month post infusion.

In the 14 patients in cohort 1, the overall survival at 6 months was 86% and at 12 months was 71%; event free survival (EFS) at 6 months was 71% and at 12 months was 54%. The patients in cohort 2 are not yet evaluable for these parameters. Overall, nine patients relapsed; 5 of 8 evaluable relapses were due to loss of CD19 antigen on the tumor cells.

Title: Clonal dynamics of early responder and long-term surviving CAR-T cells in humans (Abstract # 52)

Dr. Luca Biasco, senior research associate at University College London, presented a detailed analysis of CAR T products, and insertion site analysis from the CARPALL phase 1 patients. This analysis revealed highly polyclonal engraftment, even at very late time-points. Dr. Biasco hypothesized that the propensity for high level polyclonal long-term engraftment was due to favorable phenotype of the CAR T product and the binding kinetic of the receptor.

Diffuse Large B-cell Lymphoma Data Presented

Title: Phase 1/2 study of AUTO3, the first bicistronic chimeric antigen receptor (CAR) targeting CD19 and CD22 followed by an anti-PD1 in patients with relapsed/refractory (r/r) Diffuse Large B Cell Lymphoma (DLBCL): Results of cohort 1 and 2 of the ALEXANDER study (Abstract # 246)

Dr. Kirit Ardeshna, consultant hematologist, Department of Hematology, University College London Hospital NHS Foundation Trust, presented updated data from the ALEXANDER Phase 1/2 study of AUTO3, the first bicistronic CAR T targeting CD19 and CD22 followed by an anti-PD1, in diffuse large B cell lymphoma (DLBCL). 16 patients were treated, and fourteen patients were evaluable at one month. AUTO3 was well-tolerated, with no patients experiencing Grade 3 CRS with primary treatment, and 1 of 14 experiencing Grade 3 neurotoxicity that resolved swiftly with steroids. Five of 14 had a complete response, with 4 of 5 complete responses ongoing, the longest at 18 months.

DLBCL is an aggressive and rapidly progressing cancer, and early response is critical to ensuring positive outcomes for these patients. These early data show the promise of AUTO3 in DLBCL, and we expect to advance AUTO3 to a decision point in relapsed/refractory DLBCL by the middle of next year, said Dr. Christian Itin, chairman and chief executive officer of Autolus. In addition, we look forward to presenting the data from the AMELIA trial of AUTO3 in pediatric ALL during poster sessions on Sunday, December 8, 6:00 8:00 PM ET.

Investor call to review data on Monday, December 9

Autolus management will host an investor conference call on Monday, December 9, at 8:30 a.m. EDT/ 1:30pm GMT, to review the data presented at ASH.

To listen to the webcast and view the accompanying slide presentation, please go to: https://www.autolus.com/investor-relations/news-and-events/events.

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID 9796038. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID 9796038.

About AUTO1

AUTO1 is a CD19 CAR T cell investigational therapy designed to overcome the limitations in safety - while maintaining similar levels of efficacy - compared to current CD19 CAR T cell therapies. Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, AUTO1 may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the T cells' abilities to engage in serial killing of target cancer cells. In 2018, Autolus signed a license agreement under which Autolus acquired global rights from UCL Business plc (UCLB), the technology-transfer company of UCL, to develop and commercialize AUTO1 for the treatment of B cell malignancies. AUTO1 is currently being evaluated in two Phase 1 studies, one in pediatric ALL and one in adult ALL.

About AUTO3

AUTO3 is a programmed T cell therapy containing two independent chimeric antigen receptors targeting CD19 and CD22 that have each been independently optimized for single target activity. By simultaneously targeting two B cell antigens, AUTO3 is designed to minimize relapse due to single antigen loss in patients with B cell malignancies. AUTO3 is currently being tested in pediatric ALL in the AMELIA clinical trial and in diffuse large B cell lymphoma in the ALEXANDER clinical trial.

About Autolus Therapeutics plc

Autolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T cell programming technologies, the company is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of hematological malignancies and solid tumors. For more information please visit http://www.autolus.com.

Forward-Looking Statement

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to, statements regarding Autolus financial condition and results of operations, as well as statements regarding the anticipated development of Autolus product candidates, including its intentions regarding the timing for providing further updates on the development of its product candidates, and the sufficiency of its cash resources. Any forward-looking statements are based on management's current views and assumptions and involve risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied in such statements. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section titled "Risk Factors" in Autolus' Annual Report on Form 20-F filed on November 23, 2018 as well as discussions of potential risks, uncertainties, and other important factors in Autolus' future filings with the Securities and Exchange Commission from time to time. All information in this press release is as of the date of the release, and the company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required by law.

Investor and media contact: Silvia TaylorVice President, Corporate Affairs and CommunicationsAutolus+1-240-801-3850s.taylor@autolus.com

UK:Julia Wilson+44 (0) 7818 430877j.wilson@autolus.com

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Autolus Therapeutics Announces New Data Showcasing Clinical Progress of Programmed T Cell Therapy Pipeline in Blood Cancers - BioSpace

Bone Marrow Stem Cells Comments Off on Autolus Therapeutics Announces New Data Showcasing Clinical Progress of Programmed T Cell Therapy Pipeline in Blood Cancers – BioSpace | December 9th, 2019

In 2019, the market size of Hematopoietic Stem Cell Transplantation (HSCT) is million US$ and it will reach million US$ in 2025, growing at a CAGR of from 2019; while in China, the market size is valued at xx million US$ and will increase to xx million US$ in 2025, with a CAGR of xx% during forecast period.

In this report, 2018 has been considered as the base year and 2019 to 2025 as the forecast period to estimate the market size for Hematopoietic Stem Cell Transplantation (HSCT).

Get a Sample PDF at:https://www.researchmoz.us/enquiry.php?type=S&repid=2276986

This report studies the global market size of Hematopoietic Stem Cell Transplantation (HSCT), especially focuses on the key regions like United States, European Union, China, and other regions (Japan, Korea, India and Southeast Asia).This study presents the Hematopoietic Stem Cell Transplantation (HSCT) sales volume, revenue, market share and growth rate for each key company, and also covers the breakdown data (sales, revenue and market share) by regions, type and applications. history breakdown data from 2014 to 2019, and forecast to 2025.For top companies in United States, European Union and China, this report investigates and analyzes the production, value, price, market share and growth rate for the top manufacturers, key data from 2014 to 2019.

In global market, the following companies are covered:Regen Biopharma IncChina Cord Blood CorpCBR Systems IncEscape Therapeutics IncCryo-Save AGLonza Group LtdPluristem Therapeutics IncViaCord Inc

Market Segment by Product TypeAllogeneicAutologous

Market Segment by ApplicationPeripheral Blood Stem Cells Transplant (PBSCT)Bone Marrow Transplant (BMT)Cord Blood Transplant (CBT)

Key Regions split in this report: breakdown data for each region.United StatesChinaEuropean UnionRest of World (Japan, Korea, India and Southeast Asia)

The study objectives are:To analyze and research the Hematopoietic Stem Cell Transplantation (HSCT) status and future forecast in United States, European Union and China, involving sales, value (revenue), growth rate (CAGR), market share, historical and forecast.To present the key Hematopoietic Stem Cell Transplantation (HSCT) manufacturers, presenting the sales, revenue, market share, and recent development for key players.To split the breakdown data by regions, type, companies and applicationsTo analyze the global and key regions market potential and advantage, opportunity and challenge, restraints and risks.To identify significant trends, drivers, influence factors in global and regionsTo analyze competitive developments such as expansions, agreements, new product launches, and acquisitions in the market

Inquire More About This Report @https://www.researchmoz.us/enquiry.php?type=E&repid=2276986

In this study, the years considered to estimate the market size of Hematopoietic Stem Cell Transplantation (HSCT) are as follows:History Year: 2014-2018Base Year: 2018Estimated Year: 2019Forecast Year 2019 to 2025

For More Information Kindly Contact:ResearchMozMr. Nachiket Ghumare,90 State Street,Albany NY,United States 12207Tel: +1-518-621-2074USA-Canada Toll Free: 866-997-4948Email:sales@researchmoz.usFollow us on LinkedIn @http://bit.ly/1TBmnVGMedia Release:https://www.researchmoz.us/pressreleaseFollow me on :http://marketresearchlatestreports.blogspot.com/

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Hematopoietic Stem Cell Transplantation (HSCT) Market Global Industry Study, Trends, Overview, Insights And Outlook 2019-2025 - Markets Gazette 24

Bone Marrow Stem Cells Comments Off on Hematopoietic Stem Cell Transplantation (HSCT) Market Global Industry Study, Trends, Overview, Insights And Outlook 2019-2025 – Markets Gazette 24 | December 9th, 2019

BOSTON, Dec. 09, 2019 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing and commercializing novel cancer therapeutics that reactivate mutant tumor suppressor protein p53, presented results at the 2019 ASH Annual Meeting from its U.S. Phase Ib/II clinical trial in MDS and AML. The trial is evaluating the safety and efficacy of APR-246 in combination with azacitidine for the treatment of TP53 mutated MDS and AML. The clinical trial is sponsored by the Moffitt Cancer Center with financial support from the MDS Foundation and the Aplastic Anemia and MDS International Foundation as administrator for the Evans MDS Clinical Research Consortium.

As of the data cutoff, the overall response rate (ORR) in 33 evaluable MDS patients was 88%, with a 61% complete remission (CR) rate, by International Working Group (IWG) criteria. With a median duration of follow-up of 10.8 months, the median duration of response was 8.4 months and the median duration of CR was 7.3 months. Seventeen (52%) evaluable MDS patients discontinued therapy to pursue stem cell transplant. Median overall survival (OS) for all enrolled patients (n=55) was 10.8 months. Median OS in responding patients versus non-responders was 13.7 vs. 3.9 months. Adverse events, regardless of causality, were mostly grade 1/2. Grade 3+ adverse events occurring in 20% of patients were limited to cytopenias and infection, consistent with underlying hematopoietic malignancies, and no exacerbation of the expected AZA-related safety profile has been observed.

About the Clinical Trial

Eligible patients in the Phase Ib/II clinical trial include HMA-nave, TP53 mutated MDS, oligoblastic acute myeloid leukemia (AML, 30% blasts), MDS-myeloproliferative neoplasm (MDS-MPN) overlap and chronic myelomonocytic leukemia (CMML). In the Phase Ib part of the clinical trial, patients received APR-246 in a 3+3 dose escalation design (50, 75, 100 mg/kg lean body weight) IV daily over 4 days in a lead-in phase (days -14 to -10), followed by the same dose of APR-246 (days 1-4) and AZA 75 mg/m2 SC/IV daily for 7 days (days 4-10 or 4-5 and 8-12) in 28-day cycles. In the Phase II part of the clinical trial, patients receive APR-246 as a 4,500 mg fixed dose IV daily (days 1-4) and AZA daily for 7 days (days 4-10 or 4-5 and 8-12) in 28-day cycles. Primary objective in Phase Ib part of the clinical trial was safety, with AEs graded by CTCAE v4.03 and DLT assessment over 6 weeks. Secondary endpoints included response rate by IWG 2006 criteria, PFS, OS, as well as serial next generation sequencing and p53 immunohistochemistry for evaluation of clonal suppression and depth of remission. In the Phase II part of the clinical trial the primary endpoint is CR rate.

About Myelodysplastic Syndrome

Myelodysplastic syndromes (MDS) represents a spectrum of hematopoietic stem cell malignancies in which bone marrow fails to produce sufficient numbers of healthy blood cells. Approximately 30-40% of MDS patients progress to acute myeloid leukemia (AML) and mutation of the p53 tumor suppressor protein is thought to contribute to disease progression. Mutations in p53 are found in up to 20% of MDS and AML patients and are associated with poor overall prognosis.

About p53 and APR-246

The p53 tumor suppressor gene is the most frequently mutated gene in human cancer, occurring in approximately 50% of all human tumors. These mutations are often associated with resistance to anti-cancer drugs and poor overall survival, representing a major unmet medical need in the treatment of cancer.

APR-246 is a small molecule that has demonstrated reactivation of mutant and inactivated p53 protein by restoring wild-type p53 conformation and function and thereby induce programmed cell death in human cancer cells. Pre-clinical anti-tumor activity has been observed with APR-246 in a wide variety of solid and hematological cancers, including MDS, AML, and ovarian cancer, among others. Additionally, strong synergy has been seen with both traditional anti-cancer agents, such as chemotherapy, as well as newer mechanism-based anti-cancer drugs and immuno-oncology checkpoint inhibitors. In addition to pre-clinical testing, a Phase I/II clinical program with APR-246 has been completed, demonstrating a favorable safety profile and both biological and confirmed clinical responses in hematological malignancies and solid tumors with mutations in the TP53 gene.

A pivotal Phase 3 clinical trial of APR-246 and azacitidine for frontline treatment of TP53 mutant MDS is ongoing. APR-246 has received Orphan Drug and Fast Track designations from the FDA for MDS, and Orphan Drug designation from the EMA for MDS, AML and ovarian cancer.

About Aprea Therapeutics

Aprea Therapeutics Inc., (NASDAQ: APRE) is a biopharmaceutical company headquartered in Boston, Massachusetts with research facilities in Stockholm, Sweden, focused on developing and commercializing novel cancer therapeutics that reactivate mutant tumor suppressor protein, p53. The Companys lead product candidate is APR-246, a small molecule in clinical development for hematologic malignancies, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). For more information, please visit the company website at http://www.aprea.com.

The Company may use, and intends to use, its investor relations website at http://www.ir.aprea.com as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD.

The Company will host a 2019 ASH Clinical Update meeting and webcast as follows:

Time and Date: Monday, December 9 at 12:00 pm ETLocation: Hyatt Regency Orlando, Rainbow Spring 2 Room, 9801 International Drive, Orlando, FloridaWebcast: The Clinical Update meeting will be webcast live and can be accessed from "Events Calendar" in the News and Events section of the company's website at LinkPresentation: The presentation will be available as a PDF on the Companys website at Link

Forward-Looking Statements

Certain information contained in this press release includes forward-looking statements, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, related to our clinical trials and regulatory submissions. We may, in some cases use terms such as predicts, believes, potential, continue, anticipates, estimates, expects, plans, intends, may, could, might, likely, will, should or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team that involve risks, potential changes in circumstances, assumptions, and uncertainties. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward-looking statements are subject to risks and uncertainties including risks related to the success and timing of our clinical trials or other studies and the other risks set forth in our filings with the U.S. Securities and Exchange Commission, including our Quarterly Report on Form 10-Q. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this press release. We undertake no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstances.

Corporate Contacts:

Christian S. Schade

President and Chief Executive Officer

chris.schade@aprea.com

Gregory A. Korbel

Vice President of Business Development

greg.korbel@aprea.com

Source: Aprea Therapeutics, Inc.

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Aprea Therapeutics Presents Results From U.S. Phase Ib/II Clinical Trial of APR-246 and Azacitidine (AZA) in Patients with TP53 Mutant Myelodysplastic...

Bone Marrow Stem Cells Comments Off on Aprea Therapeutics Presents Results From U.S. Phase Ib/II Clinical Trial of APR-246 and Azacitidine (AZA) in Patients with TP53 Mutant Myelodysplastic… | December 9th, 2019

Rockville, MD, Dec. 09, 2019 (GLOBE NEWSWIRE) --

MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, today announced updated results from a Phase 1/2 dose expansion study of flotetuzumab, an investigational, bispecific CD123 x CD3 DART molecule in patients with primary induction failure and early relapsed acute myeloid leukemia (AML). The data were presented in an oral session at the 61st Annual Meeting of the American Society of Hematology (ASH) in Orlando, FL, taking place December 7-10, 2019.

Patients with AML who have failed primary induction therapy or relapsed early after an initial response represent a significant unmet medical need. A remission rate of 32% observed in the ongoing study of flotetuzumab in this extremely challenging patient population is noteworthy, said Geoffrey Uy, M.D., Associate Professor, Department of Medicine, Division of Oncology at the Washington University School of Medicine in St. Louis. Importantly, by implementing a lead-in dosing schedule for flotetuzumab, as well as early intervention with tocilizumab in this study, we were able to mitigate cytokine release syndrome, known to be associated with T-cell engagers.

In the Phase 1/2 (NCT02152956) open-label, dose expansion study, 30 patients classified as primary induction failure or early relapsed AML who had received a median of four prior therapies were treated with flotetuzumab at the recommended phase 2 dose (RP2D) of 500 ng/kg/day by continuous infusion. Data were reported as of the cut-off date of November 1, 2019. The study is currently ongoing, with additional patients being enrolled.

Responses, including complete remission (CR), CRh (CR with partial hematological recovery) and CRi (CR with incomplete hematological improvement) per a modified International Working Group (IWG) Response Criteria for AML, are summarized in the table below. Four responders received allogeneic hematopoietic stem cell transplantation as consolidation therapy and remain in remission after 6 to 21 months.

The most common treatment-related adverse event (TRAE) was infusion-related reaction/cytokine release syndrome (IRR/CRS) that occurred in all (30/30) patients. However, most CRS events observed were of short duration and mild to moderate (grade 1 or 2) in severity, with only one grade 3 event reported in one patient.

Based on the encouraging data from this study, and pending anticipated discussions with the FDA in the first half of 2020, we are planning for a potential registration-enabling study of flotetuzumab in this high unmet need population of patients with refractory AML, who have limited treatment options, said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics.

A separate oral presentation described translational research that showed an inflammatory (IFN--related) gene expression signature in a subset of patients with AML that correlated with a lack of response to induction chemotherapy. Furthermore, the same gene signature was associated with patients more likely to respond to flotetuzumab, supporting the mechanism being exploited by this molecule. In addition, AML patients with an immune-infiltrated tumor micro-environment show high expression of immune checkpoint molecules, including PD-L1, which provides a scientific rationale for combining flotetuzumab with checkpoint blockade as a potential mechanism for enhanced anti-leukemic activity. MacroGenics has initiated a study combining flotetuzumab with MGA012, an anti-PD-1 antibody, given the strong preclinical and translational data that indicate the combination may enhance CD123-directed T cell killing.

Flotetuzumab Presentations at ASH

Oral Presentations

Poster Presentations

These slide and poster presentations are available on the Events & Presentations page on MacroGenics' website at http://ir.macrogenics.com/events.cfm.

Conference Call & Webcast

MacroGenics management and external guest speakers will host a conference call and audio webcast today at 8:00 p.m. ET to review the flotetuzumab data presented at the ASH Annual Meeting and discuss ongoing clinical development plans.

To participate in the MacroGenics ASH 2019 Conference Call, please dial (877) 303-6253 (domestic) or (973) 409-9610 (international) five minutes prior to the start of the call and provide the Conference ID: 3625435. A listen-only slide and audio webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company's website at http://ir.macrogenics.com/events.cfm. A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company's website for 30 days.

About Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a hematopoietic stem cell malignancy characterized by differentiation arrest and uncontrolled clonal proliferation of neoplastic precursors that prevent normal bone marrow hematopoiesis. Nearly 20,000 new cases of AML are diagnosed in the U.S. each year, with a median age of 69 years at diagnosis. Approximately 40-50% of newly diagnosed patients fail to achieve a complete remission with intensive induction therapy (primary induction failure) or experience disease recurrence after a short remission duration (<6 months; early relapsed). A very small number of these patients are expected to respond to salvage therapy. In addition, although new targeted agents have been approved for the treatment of frontline or relapsed/refractory AML in recent years, approximately 50% of patients have no known targetable mutations.

About Flotetuzumab

Flotetuzumab (also known as MGD006) is a clinical-stage molecule that recognizes both CD123 and CD3. CD123, the interleukin-3 receptor alpha chain, has been reported to be over-expressed on cancer cells in AML and other hematologic malignancies. The primary mechanism of action of flotetuzumab is believed to be its ability to redirect T lymphocytes to kill CD123-expressing cells. To achieve this, the DART molecule combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123 on the target cancer cells.

Flotetuzumab is currently being evaluated in the U.S. and Europe in a Phase 1/2 dose expansion study designed to assess the safety, tolerability, and initial anti-leukemic activity of the molecule in patients with relapsed/refractory AML. The U.S. Food and Drug Administration has granted orphan drug designation to flotetuzumab for the treatment of AML. A Phase 1/2 study in combination with MGA012, a proprietary anti-PD-1 monoclonal antibody, in patients with relapsed/refractory AML is being conducted ex-U.S. MGA012 (also known as INCMGA00012) was exclusively licensed to Incyte Corporation in 2017 under a global collaboration and license agreement; MacroGenics retains the right to develop its pipeline molecules with MGA012. MacroGenics retains global development and commercialization rights to flotetuzumab.

About MacroGenics, Inc.

MacroGenics is a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer. The Company generates its pipeline of product candidates primarily from its proprietary suite of next-generation antibody-based technology platforms, which have applicability across broad therapeutic domains. The combination of MacroGenics' technology platforms and protein engineering expertise has allowed the Company to generate promising product candidates and enter into several strategic collaborations with global pharmaceutical and biotechnology companies. For more information, please see the Company's website at http://www.macrogenics.com. MacroGenics, the MacroGenics logo and DART are trademarks or registered trademarks of MacroGenics, Inc.

Cautionary Note on Forward-Looking Statements

Any statements in this press release about future expectations, plans and prospects for the Company, including statements about the Company's strategy, future operations, clinical development of the Company's therapeutic candidates, milestone or opt-in payments from the Company's collaborators, the Company's anticipated milestones and future expectations and plans and prospects for the Company and other statements containing the words "subject to", "believe", "anticipate", "plan", "expect", "intend", "estimate", "project", "may", "will", "should", "would", "could", "can", the negatives thereof, variations thereon and similar expressions, or by discussions of strategy constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation and enrollment of future clinical trials, expectations of expanding ongoing clinical trials, availability and timing of data from ongoing clinical trials, expectations for regulatory approvals, other matters that could affect the availability or commercial potential of the Company's product candidates and other risks described in the Company's filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company's views only as of the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so, except as may be required by law. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date hereof.

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MacroGenics Presents Flotetuzumab Data in Patients with Primary Induction Failure and Early Relapsed Acute Myeloid Leukemia at the 2019 ASH Annual...

Bone Marrow Stem Cells Comments Off on MacroGenics Presents Flotetuzumab Data in Patients with Primary Induction Failure and Early Relapsed Acute Myeloid Leukemia at the 2019 ASH Annual… | December 9th, 2019

Pigs engineered to have a small amount of monkey cells have been brought to full term and were even born alive, surviving for a few days after birth. Although the piglets died, it is claimed the experiment - performed in China - marks a major milestone for the future of lab-grown organs.

"This is the first report of full-term pig-monkey chimeras," Tang Hai of the State Key Laboratory of Stem Cell and Reproductive Biology in Beijing told New Scientist.

The research is part of an ongoing effort to develop animals - whether they are sheep or pigs - that can grow human organs we could then harvest for transplants, a process called xenogeneic organogenesis.

Research has been done on both pig and sheep embryos with transplanted human stem cells; in both cases, the embryos continued to develop until the experiment was deliberately terminated.

That's because, due to ethical concerns, these chimeras - organisms that incorporate the genetic material of another species - cannot be cultivated or studied in the later stages of embryonic development. Some scientists worry that some of the human stem cellscould end upin other parts of the animal or even in its brain, with unintended consequences.

For that reason, in this experiment the team used stem cells from crab-eating macaques (Macaca fascicularis). These were imbued with fluorescent proteins so that they would glow under fluorescent light, and derived to produce fluorescing embryonic cells.

These cells were then injected into over 4,000 five-day-old pig embryos fertilised using IVF; the modified pig embryos were subsequently implanted into sows.

This fiddly and painstaking work produced just 10 piglets that made it to full term and were born alive. And only two of these were chimeric, with between one in 1,000 and one in 10,000 functional monkey cells to pig cells.

The monkey cells had migrated to the heart, liver, lungs, spleen and skin of the piglet hosts, but were not found in other organs, such as testes and ovaries, due to the low rate of chimerism, the researchers said.

Sadly, before a week was out, the piglets died - not just the two chimeras, but the other eight normal piglets, too. Because all the pigs died, Hai told New Scientist, the cause of death likely had less to do with chimerism, and more to do with IVF - a procedure that is notoriously tricky in pigs.

The low chimerism rate is also somewhat discouraging. However, the researchers remain optimistic. Although the birth rate was low, and the pigs didn't survive, the team now has a wealth of data they can apply to future experiments.

The scientists are planning to try again, increasing the chimeric cell ratio. And they believe their data may help other scientists working in the field.

"Here, we have used monkey cells to explore the potential of reconstructing chimeric human organs in a large animal model," they wrote in their paper.

"We believe this work will facilitate the development of xenogeneic organogenesis by providing a better understanding of the processes of xenogeneic recognition, fate determination, and the proliferation and differentiation of primate stem cells during porcine development.

"The findings could pave the way toward overcoming the obstacles in the re-engineering of heterogeneous organs and achieve the ultimate goal of human organ reconstruction in a large animal."

The research has been published in Protein & Cell.

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Pig-Monkey Chimeras Have Been Brought to Term For The First Time - ScienceAlert

Skin Stem Cells Comments Off on Pig-Monkey Chimeras Have Been Brought to Term For The First Time – ScienceAlert | December 9th, 2019

ORLANDO, Fla.--(BUSINESS WIRE)--Amnion of Florida, a leading provider of alternative medicine utilizing cryopreserved placental cell allograft and advanced bioactive facial rejuvenation, is pleased to announce their vendor choice to round out regenerative anti-aging therapies.

Amnion announces a partnership with Merakris Therapeutics, LLC to advance the development of Merakris topical bioactive anti-aging hydrogel technology. Christopher Broderick, President, and Founder of Merakris Therapeutics stated, dedication to science-based outcomes is our primary focus, thus were delighted to be selected based upon our scientific approach to youth maintenance and rejuvenation technologies.

Amnion is focused on attracting women and men seeking affordable non-surgical options for youth maintenance via cell activated procedures, hair restoration, joint repair, dermal rejuvenation, and anti-aging treatments.

Our team of experienced medical professionals and aestheticians at Amnion are excited to utilize the Merakris Therapeutics product suite, including medical-grade, sterile filtered amniotic fluid serums and hydrogels at our newest Spa in Sanford, FL, said Eusebio Coterillo, President of Amnion.

In a constantly changing field, Amnion of Florida, under the guidance of the on-site medical staff, provides the highest level of quality products and procedures in cosmetic medicine. They offer cutting edge treatments that are proven by research, the use FDA cleared or registered products, and are widely published and peer endorsed.

More about Amnion of Florida

Amnion of Florida, based in Central Florida, is a leading provider of alternative medicine using cryopreserved placental cell transplants or allografts, processed from donated cellular birth tissue, which are natural alternatives to autologous regenerative medicine products. The primary function of our allogeneic regenerative treatments is to promote soft tissue joint/skin repair and regeneration mediated by growth factors and cells naturally found in placental tissue. These treatments have shown safety and efficacy in treating a variety of ailments including osteoarthritis, chronic ulcerative wounds, joint pain, skin rejuvenation, hair restoration, urinary incontinence, and ED. Learn more http://www.amnion.us.

More about Merakris Therapeutics, LLC

Merakris Therapeutics, based in Research Triangle Park, North Carolina, is focused on researching, developing, and marketing regenerative healthcare products. Merakris is pioneering commercially scalable biotherapeutic technologies derived from stem cells that have various clinical applications. Our vision is to improve global patient care and outcomes through the pioneering and innovation of acellular regenerative biotechnologies. Learn more at http://www.merakris.com.

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Top Florida Medical Spa, Amnion of Florida, Partners With Merakris Therapeutics to Advance Their Non-Surgical Treatment Options - Business Wire

Skin Stem Cells Comments Off on Top Florida Medical Spa, Amnion of Florida, Partners With Merakris Therapeutics to Advance Their Non-Surgical Treatment Options – Business Wire | December 9th, 2019

Beijing: In a world first, researchers have been able to produce pig-monkey hybrids in a Chinese laboratory, a media report said. Two piglets - having monkey tissues in their hearts, liver and skin - were born in the State Key Laboratory of Stem Cell and Reproductive Biology in Beijing but died within a week, the Mirror reported.

The announcement to this effect was made by Tang Hai. The experiment comes in the wake of Spanish scientist Juan Carlos Izpisua Belmonte's attempt to create pig-human hybrids two years ago. Tang and his team injected genetically modified monkey cells into more than 4,000 pig embryos before these were implanted into sows, the New Scientist magazine reported.

Only two of the 10 piglets thus born were hybrids - with tissues in the heart, liver, spleen, lung and skin, partly consisting of monkey cells. Experts suspected that the failure has to do with the IVF process.

Critics have now warned that the scientific development will create "disturbing" dilemmas over the ethics of human-animal hybrids. Doctor Angel Raya, director of the Barcelona Regenerative Medicine Centre, told the Spanish daily El Pais: "What happens if the stem cells escape and form human neurons in the brain of the animal? Would it have consciousness? And what happens if these stem cells turn into sperm cells?''

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Meet the world's first pig-monkey hybrid - Free Press Journal

Skin Stem Cells Comments Off on Meet the world’s first pig-monkey hybrid – Free Press Journal | December 9th, 2019

SEATTLE--(BUSINESS WIRE)--Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune/inflammatory diseases, presented Phase 1 data yesterday from the healthy volunteer study of ALPN-101, a first-in-class dual CD28/ICOS antagonist, and details on its upcoming Phase 1/2 BALANCE study of ALPN-101 in steroid-resistant or steroid-refractory acute graft-versus-host disease (GVHD) at the 61st American Society of Hematology Annual Meeting (ASH) in Orlando, FL.

Jan Hillson, MD, Senior Vice President of Clinical Development at Alpine, presented An Open Label Study of ALPN-101, a First-in-Class Dual CD28/ICOS Antagonist, in Subjects with Steroid-Resistant or Steroid-Refractory Acute Graft Versus Host Disease (BALANCE) as part of the oral session, Chemical Biology and Experimental Therapeutics: Novel Compounds and Mechanisms of Action.

Highlights included:

Despite decades of intense research, GVHD remains a major cause of morbidity and mortality after hematopoietic stem cell transplantation, commented Sophie Paczesny, MD, PhD, Professor of Immunology and Pediatrics at Indiana University School of Medicine and lead of the Biomarkers Stem Cell Transplantation Program and one of Alpine's research collaborators. Current therapies are associated with significant toxicities or are simply insufficient to control the disease. CD28 and ICOS appear to be key pathways in the pathogenesis of GVHD, and the presented data with ALPN-101 appear uniquely strong. I look forward to the BALANCE study, which may demonstrate the therapeutic potential of ALPN-101.

About Graft Versus Host Disease (GVHD)

Graft versus host disease (GVHD) is the most common life-threatening complication of a hematopoietic cell transplant. It occurs when donor cells see recipient cells as foreign and attack them. Acute GVHD typically occurs within the early weeks and months after transplant, usually involving the skin, liver, and gastrointestinal tract. GVHD patients remain at risk of organ system damage and increased mortality due to the disease and to high dose glucocorticoids.

About ALPN-101

ALPN-101 is a novel Fc fusion protein of a human inducible T cell costimulator ligand (ICOSL) variant immunoglobulin domain (vIgD), and a first-in-class therapeutic designed to inhibit simultaneously the CD28 and ICOS inflammation pathways. CD28 and ICOS are closely-related costimulatory molecules with partially overlapping roles in T cell activation likely playing a role in multiple autoimmune and inflammatory diseases. In preclinical models of graft versus host disease, inflammatory arthritis, connective tissue disease, and multiple sclerosis, ALPN-101 demonstrates efficacy superior to agents blocking the CD28 CD80/86 or ICOS - ICOSL pathways alone.

About Alpine Immune Sciences, Inc.

Alpine Immune Sciences, Inc. is committed to leading a new wave of immune therapeutics, creating potentially powerful multifunctional immunotherapies to improve patients lives via unique protein engineering technologies. Alpine has two lead programs. The first, ALPN-101 for autoimmune/inflammatory diseases, is a selective dual T cell costimulation blocker engineered to reduce pathogenic T and B cell immune responses by blocking ICOS and CD28. ALPN-101 has recently completed enrollment in a Phase 1 healthy volunteer trial. The second, ALPN-202 for cancer, is a conditional CD28 costimulator and dual checkpoint inhibitor. Alpine is backed by world-class research and development capabilities, a highly-productive scientific platform, and a proven management team. For more information, visit http://www.alpineimmunesciences.com.

Forward-Looking Statements

This release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not based on historical fact and include statements regarding our platform technology and potential therapies, the timing of and results from clinical trials and pre-clinical development activities, clinical and regulatory objectives and the timing thereof, expectations regarding the sufficiency of cash to fund operations, the potential efficacy, safety profile, future development plans, addressable market, regulatory success, and commercial potential of our product candidates, the timing of our public presentations and potential publication of future clinical data, the efficacy of our clinical trial designs, expectations regarding our ongoing collaborations, and our ability to successfully develop and achieve milestones in our development programs. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions and include words such as may, will, should, would, expect, plan, intend, and other similar expressions, among others. These forward-looking statements are based on current assumptions that involve risks, uncertainties, and other factors that may cause actual results, events, or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties, many of which are beyond our control, include, but are not limited to: clinical trials may not demonstrate safety and efficacy of any of our product candidates; our ongoing discovery and pre-clinical efforts may not yield additional product candidates; our discovery-stage and pre-clinical programs may not advance into the clinic or result in approved products; any of our product candidates may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; we may not achieve additional milestones in our proprietary or partnered programs; the impact of competition; adverse conditions in the general domestic and global economic markets; as well as the other risks identified in our filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof and we undertake no obligation to update forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements.

Secreted Immunomodulatory Proteins, SIP, Transmembrane Immunomodulatory Protein, TIP, Variant Ig Domain, vIgD and the Alpine logo are registered trademarks or trademarks of Alpine Immune Sciences, Inc. in various jurisdictions.

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Alpine Immune Sciences Presents ALPN-101 Phase 1 Healthy Volunteer Study Data and Details of Upcoming Phase I/II BALANCE GVHD Study at the 61st...

Skin Stem Cells Comments Off on Alpine Immune Sciences Presents ALPN-101 Phase 1 Healthy Volunteer Study Data and Details of Upcoming Phase I/II BALANCE GVHD Study at the 61st… | December 9th, 2019

The letter follows.

Dear AgeX Stockholders,

In this, our first year as a public company, we have built a foundation for a revolutionary company in the fields of cell therapy and tissue regeneration. To date, conventional pharmaceutical approaches to the chronic degenerative conditions associated with aging have provided little benefit, often only offering relief from the symptoms of disease, rather than targeting underlying disease processes. Our belief is that this is about to change through harnessing the power of new cellular and molecular technologies. We aim to lead this coming revolution with our pioneering technologies which could generate and deliver new cells to patients through our cell therapy focus, and which may reverse the age of cells already in the body through our iTR platform. We believe that our new technologies will lead to true cell regeneration and replacement to potentially cure degenerative diseases by targeting aged or damaged cells, tissues and organs.

Over the last year, we have worked hard to achieve certain goals to set the fundamental basis to create shareholder value going forward:

To optimize shareholder value, we have undertaken a strategic review of our business opportunities, and we have four key take-away messages for the coming year and beyond:

UniverCyte would potentially be game-changing for the whole cell therapy industry by allowing the transplantation of non-self, donor cells into all patients without the need for powerful immunosuppressant drugs, which are associated with serious side effects, including infections and cancers, as well as kidney and liver toxicity. The UniverCyte platform aims to utilize a proprietary, novel, modified form of the powerful immunomodulatory molecule HLA-G, which in nature seems to be a dominant player in protecting a baby from destruction by the mother's immune system during pregnancy, the only known physiological state of immune tolerance toward foreign tissue in humans.

On the other hand, our pluripotent stem cell-based PureStem platform could potentially overcome numerous industry barriers. PureStem cells would have eight potential advantages compared to other adult stem cell- or pluripotent stem cell-based therapies, including lower manufacturing costs, industrial scalability, off-the-shelf usage, high purity, non-tumorgenicity, young age (so they are not prone to the disadvantages associated with older cells), aptitude for permanent cell engraftment, and potential to manufacture any human cell type.

We have two in-house product candidates, both targeting highly prevalent diseases of old age, with a high unmet medical need, and which are for multi-billion-dollar markets. Our lead internal program going forward will be AgeX-BAT1, which is brown fat cells for the treatment of type II diabetes. The last year has seen significant investment in cell therapy product candidates for diabetes by investors and large biotech. Earlier this year, we published a paper, Clonal Derivation of White and Brown Adipocyte Progenitor Cell Lines from Human Pluripotent Stem Cells, in the peer-reviewed scientific journal Stem Cell Research & Therapy, which showed that our PureStem platform generated highly pure, identifiable and scalable brown adipose cells, expressing active adipokines. Our second internal program will be AgeX-VASC1, composed of vascular endothelial progenitor cells for tissue ischemia, such as peripheral vascular disease and potentially cardiac and CNS ischaemia. Once we have a UniverCyte-modified pluripotent stem cell cGMP master cell bank, we will re-derive universal versions of AgeX-BAT1 and AgeX-VASC1 and then work to establish proof-of-concept in animal models.

We care deeply about our mission and the needs of our stockholders. We appreciate your support and the dedication of our scientists and employees as we forge a new future for medicine. We invite you to join us for the Annual Meeting of Stockholders on Monday, December 30, 2019. For those of you who cannot attend in person, our corporate update from that meeting will be webcast for your convenience.

Sincerely,

Michael D. West, Ph.D.

Gregory Bailey, M.D.

Chief Executive Officer

Chairman of the Board

About AgeX Therapeutics

AgeX Therapeutics, Inc. (NYSE American: AGE) is focused on developing and commercializing innovative therapeutics for human aging. Its PureStem and UniverCyte manufacturing and immunotolerance technologies are designed to work together to generate highly-defined, universal, allogeneic, off-the-shelf pluripotent stem cell-derived young cells of any type for application in a variety of diseases with a high unmet medical need. AgeX has two preclinical cell therapy programs: AGEX-VASC1 (vascular progenitor cells) for tissue ischemia and AGEX-BAT1 (brown fat cells) for Type II diabetes. AgeXs revolutionary longevity platform induced Tissue Regeneration (iTR) aims to unlock cellular immortality and regenerative capacity to reverse age-related changes within tissues. AGEX-iTR1547 is an iTR-based formulation in preclinical development. HyStem is AgeXs delivery technology to stably engraft PureStem cell therapies in the body. AgeX is developing its core product pipeline for use in the clinic to extend human healthspan and is seeking opportunities to establish licensing and collaboration agreements around its broad IP estate and proprietary technology platforms.

For more information, please visit http://www.agexinc.com or connect with the company on Twitter, LinkedIn, Facebook, and YouTube.

Forward-Looking Statements

Certain statements contained in this release are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Any statements that are not historical fact including, but not limited to statements that contain words such as will, believes, plans, anticipates, expects, estimates should also be considered forward-looking statements. Forward-looking statements involve risks and uncertainties. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the business of AgeX Therapeutics, Inc. and its subsidiaries, particularly those mentioned in the cautionary statements found in more detail in the Risk Factors section of AgeXs Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commissions (copies of which may be obtained at http://www.sec.gov). Subsequent events and developments may cause these forward-looking statements to change. AgeX specifically disclaims any obligation or intention to update or revise these forward-looking statements as a result of changed events or circumstances that occur after the date of this release, except as required by applicable law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20191209005356/en/

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AgeX Therapeutics Issues Year-End Letter to Shareholders - BioSpace

Cardiac Stem Cells Comments Off on AgeX Therapeutics Issues Year-End Letter to Shareholders – BioSpace | December 9th, 2019