A Phase I/II Open-Label Study of ECT-001-Expanded Cord Blood Transplantation in Pediatric and Young Adult (<21year) Patients With High-Risk and Very High-Risk Myeloid Malignancies

Cord blood (CB) transplants are an option for patients lacking an HLA identical donor but are hampered by low cell dose, prolonged aplasia and high transplant related mortality. UM171, a novel and potent agonist of hematopoietic stem cell self renewal could solve this major limitation, allowing for CB's important qualities as lower risk of chronic GVHD and relapse to prevail. In previous trials (NCT02668315, NCT03913026, NCT04103879, and NCT03441958), the CB expansion protocol using the ECT-001-CB technology (UM171 molecule) has proven to be technically feasible and safe in adults.
UM171 expanded CB was associated with a prompt (D+17), robust (98%) and durable neutrophil recovery. Amongst patients who received a single UM171 CB transplant with a median follow-up of 18 months, risk of TRM (10%), grade 3-4 acute GVHD (13%) and moderate-severe chronic GVHD (2%) was low at 1 year post-transplant. Incidence of severe viral and bacterial infections was reduced and immunosuppression could be discontinued in 77% of patients at 1 year. Thus, PFS and GRFS were very promising, 72% and 59% at 12 months, 69% and 53% at 24 months, respectively, in particular accounting for a large proportion of very high-risk patients. By a 10-fold increase of CB accessibility, ECT-001-CB allowed access to smaller, better HLA matched CBs.
This new study seeks to test a similar strategy in a group of pediatric and young adult patients with high risk myeloid malignancies. 12 patients will be enrolled in the first stage of this 2-stage design protocol. If intervention is considered promising (<= 3 relapses in the first 12 patients), this study will open multicenter and be extended to a second stage (16 additional patients for a total accrual 28).

开始日期2021-12-01

申办/合作机构

ExCellThera, Inc.初创企业

[+1]

NCT04594031 / Withdrawn临床1期

A Phase I Multicenter Study of Hematopoietic Stem Cell Transplant of ECT-001-Expanded Cord Blood With a Reduced Toxicity Conditioning Regimen in Patients With Severe Sickle Cell Disease

The application of experimental hematopoietic cell transplantation (HCT) therapy in sickle-cell disease (SCD) must strike a balance between the underlying disease severity and the possibility of a direct benefit of the treatment, particularly in pediatric populations. Clinical studies in adults with SCD have focused on interventions that prolong survival and improve the quality of life. Unlike children, adults with SCD are much more likely to have a debilitating complication. As a result, the risk/benefit ratio of HCT is very favorable in adults, particularly if an approach to HCT that defines an acceptable level of toxicity can be established.
Whereas hematopoietic stem cell transplantation (HSCT) remains the only curative treatment currently available for patients with SCD, the morbidity, the frequent irreversible damage in target organs and the mortality reported in the natural course of patients with severe SCD are strong incentives to perform HSCTs in younger age groups. For those who lack a matched related donor, CB transplant is an appealing option, but despite been less problematic, CB accessibility related to cell dose of appropriately matched cord blood unit (CBU) remains a significant issue. Through a 7-day culture process of a CBU's hematopoietic stem cell HSCs with the UM171 compound, the total cell dose is increased mitigating this limitation.
UM171-CB expansion (ECT-001-CB) allows a greater CB accessibility, the selection of better matched cords that might translate into favourable clinical outcomes as reported in previous trials, including a lower risk of graft-versus-host disease. After CB selection and ex-vivo expansion, ECT-001-CB transplant will follow a myeloablative reduced-toxicity conditioning regimen consisting of rATG, busulfan and fludarabine with doses of all agents optimized to the individual using model-based dosing and will be followed by standard supportive care and GVHD prophylaxis consisting of tacrolimus and MMF.

开始日期2021-07-13

申办/合作机构

ExCellThera, Inc.初创企业

[+1]

NCT04103879 / Active, not recruiting临床2期

A Phase II Open-Label Study of UM171-Expanded Cord Blood Transplantation in Patients With High and Very High Risk Acute Leukemia/Myelodysplasia

Cord blood (CB) transplants are an option for patients lacking an HLA identical donor but are hampered by low cell dose, prolonged aplasia and high transplant related mortality. UM171, a novel and potent agonist of hematopoietic stem cell self renewal could solve this major limitation, allowing for CB's important qualities as lower risk of chronic GVHD and relapse to prevail. In a previous trial (NCT02668315), the CB expansion protocol using the ECT-001-CB technology (UM171 molecule) has proven to be technically feasible and safe. UM171 expanded CB was associated with a median neutrophil recovery at day (D)+18 post transplant. Amongst 22 patients who received a single UM171 CB transplant with a median follow-up of 18 months, risk of TRM (5%) and grade 3-4 acute GVHD (10%) were low. There was no moderate-severe chronic GVHD. Thus, overall and progression free survival at 12 months were impressive at 90% and 74%, respectively. The UM171 expansion protocol allowed access to smaller, better HLA matched CBs as >80% of patients received a 6-7/8 HLA matched CB. Interestingly there were patients with high-risk hematologic malignancies and multiple comorbidities (5 patients who had already failed an allogeneic transplant and 5 patients with refractory/relapsed acute leukemia/aggressive lymphoma). Despite this high risk population, progression was 20% at 12 months.
This new study seeks to test a similar strategy in a group of patients with high risk acute leukemia/myelodysplasia.

开始日期2020-11-13

申办/合作机构

ExCellThera, Inc.初创企业

[+1]

100 项与 Stem cell therapeutics(ExCellThera, Inc.) 相关的临床结果

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100 项与 Stem cell therapeutics(ExCellThera, Inc.) 相关的转化医学

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100 项与 Stem cell therapeutics(ExCellThera, Inc.) 相关的专利（医药）

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项与 Stem cell therapeutics(ExCellThera, Inc.) 相关的文献（医药）

2024-01-11·Blood

KBTBD4-mediated Reduction of MYC Is Critical For Hematopoietic Stem Cell Expansion Upon UM171 Treatment.

Article

作者: Jalila Chagraoui ; Simon Girard ; Laure Mallinger ; Nadine Mayotte ; Maria Florencia Tellechea ; Guy Sauvageau

Ex vivo expansion of hematopoietic stem cells (HSCs) is gaining in importance for cell and gene therapy and requires a shift from dormancy state to activation and cycling. However, abnormal or excessive HSC activation results in reduced self-renewal ability and increased propensity for myeloid-biased differentiation. We now report that activation of the E3 ligase complex CRL3KBTBD4 by UM171 not only induces epigenetic changes through CoREST1 degradation but also controls chromatin bound MYC levels to prevent excessive activation and maintain lympho-myeloid potential of expanded populations. Furthermore, reconstitution activity and multipotency of UM171-treated HSC is specifically compromised when MYC levels are experimentally increased despite degradation of CoREST1.

2023-12-25·Experimental hematology

Purging myeloma cell contaminants and simultaneous expansion of peripheral blood mobilised stem cells.

Article

作者: Kantaro Ishitsuka ; Hidekazu Nishikii ; Takaharu Kimura ; Ayano Sugiyama-Finnis ; Satoshi Yamazaki

Human hematopoietic stem cells (HSCs) are widely used as a cellular source for hematopoietic stem cell transplantation (HSCT) in the clinical treatment of hematological malignancies. After transplantation therapy, delays in hematopoietic recovery due to insufficient donor-derived HSCs can lead to increased risks of life-threatening infections and bleeding. Our previous studies developed an efficient ex vivo expansion culture medium (3a medium) for umbilical cord blood-derived HSCs (CBSCs), offering a potential solution to this problem. Nevertheless, the broader applicability of our culture method to alternative cell sources, and, of greater significance, its efficacy in eliminating potentially disease-associated contaminated tumor cells, especially in autologous transplantation, raises critical clinical questions. In this study, we modified the 3a medium by incorporating UM729 to replace UM171, added Flt3 ligand, and adjusted the concentrations of butyzamide, 740Y-P, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PCL-PVAc-PEG, Soluplus^®ฎ) to create the modified 3a medium. This sophistication allowed efficient expansion of not only CBSCs but also peripheral blood mobilized HSCs (PBSCs). Additionally, we successfully removed contaminated myeloma cells by adding bortezomib and TNF-related apoptosis inducing ligand (TRAIL) at appropriate concentrations, while maintaining HSCs through the addition of lenalidomide. Our research findings present the potential for widespread clinical application of the modified 3a medium and suggest a safe ex vivo culture technique for expanding human HSCs within peripheral blood derived donor grafts used for autologous HSCT.

2023-11-22·Journal of cellular biochemistry

Synergistic effect and molecular mechanism of PVA and UM171 in ex vivo expansion of primitive hematopoietic stem cells.

Article

作者: Yan Ren ; Yanni Cui ; Jingyi Feng ; Yanhong Tan ; Fanggang Ren ; Yaofang Zhang ; Hongwei Wang

Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) used for transplantation; the number of cells in a single UCB is too small to quickly establish bone marrow (BM) implantation, and ex vivo expansion of HSCs has the potential to overcome this limitation. The purpose of this study is to explore the culture conditions conducive to the maintenance and expansion of hematopoietic stem and progenitor cells (HSPCs) and long-term hematopoietic stem cells (LT-HSCs) derived from human umbilical cord blood, compare the different effects of albumin (HSA) and polyvinyl alcohol (PVA), optimize the culture system using UM171 and investigate the molecular mechanism of PVA and UM171 promoting the expansion of primitive hematopoietic stem cells. CD34+ cells were purified from UCB using MacsCD34 beads, and then cultured in serum-free medium supplemented with cytokines for 12 days, with PVA or UM171 added according to experimental requirements; the relative percentage of different HSCs subsets after culture were detected by flow cytometry; CFU Assay Setup for detecting the multilineage differentiation potential of HSCs; RT-PCR detection of gene expression levels; reactive oxygen detection assessment of intracellular ROS levels. (1) The conditions of 20 ng/mlSCF, 100 ng/mlTPO, and 5% oxygen concentration are conducive to the maintenance of LT-HSCs. (2) Compared with HSA, PVA significantly increased the proportion of HSPCs and LT-HSCs, as well as dramatically promoted the expression of antioxidant enzymes and reduced the production of reactive oxygen species (ROS). (3) After adding UM171 to PVA-based medium, the proportion of HSPCs and LT-HSCs further increased, and downstream genes of Notch and Wnt pathways were selectively activated. (1) PVA may inhibit ROS production by upregulating the expression of antioxidant enzymes, which is beneficial for maintaining stemness and inhibiting differentiation of HSCs. (2) The antioxidant properties of PVA can delay differentiation, while UM171 can promote self-renewal by regulating the stem cell pathway, and the combination of them is beneficial for the maintenance and expansion of HSCs in vitro.

项与 Stem cell therapeutics(ExCellThera, Inc.) 相关的新闻（医药）

2024-01-02

·BioSpace

ExCellThera to Conduct Investor Meetings During the J.P. Morgan 42nd Annual Healthcare Conference and to Participate in Upcoming Investor Conferences

MONTREAL, Jan. 02, 2024 (GLOBE NEWSWIRE) -- ExCellThera Inc. (ExCellThera), a world leader in blood stem cell therapies, announced today that its senior leaders will be holding investor meetings during the 42nd Annual J.P. Morgan Healthcare Conference, January 8-11, 2024, in San Francisco, CA, and will be participating in the following investor conferences in January: 2024 Biotech Showcase (Presentation) Presentation Date and Time: January 8, 2024 at 4:45 PM PT Speaker: David Millette, Chief Executive Officer Location: San Francisco, CA, Ballroom Franciscan D, Hilton Union Square ExCellThera will also hold one-on-one investor meetings during the 42nd Annual J.P. Morgan Healthcare Conference, January 8-11, 2024, in San Francisco, CA. To request a one-on-one meeting with ExCellThera, please contact sellinwood@kendallir.com. B Riley 4th Annual Oncology Conference (Fireside Chat) Presentation Date and Time: January 18, 2024 at 10:00 AM ET Speakers: Guy Sauvageau, Founder and Chief Scientific Officer and David Millette, Chief Executive Officer Location: Virtual About UM171 Cell Therapy UM171 Cell Therapy has been evaluated in over 100 patients to treat hematologic malignancies in clinical trials in the United States, Europe and Canada. UM171 Cell Therapy has received orphan drug designation and regenerative medicine advanced therapy (RMAT) designation from the FDA as well as orphan medicinal product designation, advanced therapy medicinal product (ATMP) classification and priority medicines (PRIME) designation from the EMA. High Unmet Medical Need UM171 Cell Therapy Patients with high and very high-risk acute leukemias and myelodysplasias, including patients with refractory or active disease, patients requiring a second transplant, and patients with TP53 mutations or other genetic abnormalities, have limited treatment options with low survival outcomes and high incidence of relapse under the current standard of care. UM171 Cell Therapy has successfully completed Phase 2 trials in high and very high-risk acute leukemias and myelodysplasias. A Phase 3 trial is planned in 2024 for UM171 Cell Therapy for the treatment of high and very high-risk acute leukemias and myelodysplasias. Patients with hematological malignancies requiring a stem cell transplant who lack a readily available suitable donor, including familial, unrelated or haploidentical donor, or cord blood of sufficient quantity. A Market Authorization Application (MAA) submission was completed and is under accelerated assessment with the European Medicines Agency (EMA) for the licensure of UM171 Cell Therapy for adult patients with hematological malignancies requiring a stem cell transplant who lack a readily available suitable donor. The use of UM171 Cell Therapy in other patient populations, including pediatric patients and patients with non-malignant hematological diseases, is also being explored. UM171 Cell Therapy is an investigational cell therapy, and its safety and efficacy have not been established by the FDA, EMA, Health Canada or any other health authority. About ExCellThera and UM171 Technology ExCellThera is a world leader in enhanced blood stem cell therapies. ExCellThera’s proprietary EnhanceTM platform for cell expansion and metabolic fitness is designed to deliver a greater dose of functional therapeutic stem cells by expanding HSCs from any source and counteracting the effects of culture or gene editing induced stress. ExCellThera partners with biopharmas to help them develop best-in-class cell and gene therapies by leveraging the technologies that form the EnhanceTM platform, including the proprietary molecule UM171 which has a first-in-class mechanism of action for ex vivo expansion and metabolic fitness of HSCs. For additional information, visit excellthera.com, and follow us on LinkedIn. Investor and Media Contact Sarah Ellinwood Kendall Investor Relations sellinwood@kendallir.com

细胞疗法孤儿药临床2期临床3期

2023-12-12

·GlobeNewswire-Health Care

ExCellThera Announces Positive Phase 2 Study Results from UM171 Cell Therapy in Patients with High-risk Leukemias and Myelodysplasias at American Society of Hematology (ASH) 2023 Annual Meeting

- Data presented in an oral session at ASH 2023, building on strong data from prior Phase 1/2 trial and comparative registry studies - UM171 cell therapy achieved the primary endpoint of progression-free survival (63% at 2 years) in high and very high-risk cohort and demonstrated an excellent safety profile - Company plans to initiate a registrational Phase 3 trial in in high and very high-risk leukemias and myelodysplasias in 2024 MONTREAL, Dec. 12, 2023 (GLOBE NEWSWIRE) -- ExCellThera Inc. (ExCellThera), a world leader in blood stem cell expansion and metabolic fitness, announced today positive results from 50 patients in two multi-center Phase 2 trials for UM171 cell therapy conducted at transplant centers in the U.S., Canada and Europe, building on prior strong data from a Phase 1/2 trial and comparative registry studies (CIBMTR and EBMT). The data were presented for the first time in an oral session at the 65th American Society of Hematology Annual Meeting & Exposition (ASH) by Filippo Milano, M.D., Ph.D., Associate Professor, Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, and demonstrated excellent clinical outcomes at two years for this high and very high-risk cohort, including strong rates of overall survival (67%) and progression-free survival (63%), as well as low rates of non-relapse mortality (19%), relapse (18%) and moderate-to-severe chronic GVHD (7%). “There is an unmet need for new treatment options for patients with high and very high-risk leukemias and myelodysplasias who have low survival outcomes and high incidence of relapse,” said Filippo Milano, M.D., Ph.D., Director of Fred Hutch’s Cord Blood Transplant Program. “In these UM171 Phase 2 studies, about 70% of patients survived two years post-transplant without evidence of disease recurrence. These outcomes are encouraging considering that 30% of the enrolled patients did not benefit from previous stem cell transplantation. In addition, 20% of the study population had an identified TP53 genetic mutation, which has been associated with particularly dismal outcomes.” “Patients in high-risk categories, including those with refractory or active disease, with genetic abnormalities, or who have relapsed after a first transplant, have limited treatment options under the current standard of care,” said David Millette, Chief Executive Officer of ExCellThera. “We are very excited to share the positive Phase 2 results for UM171 cell therapy, building on strong data from our Phase 1/2 trial and comparative registry studies. We believe this establishes UM171 cell therapy as a potential treatment options for high-risk leukemias and myelodysplasias based on its combined efficacy and safety profile. Based on these highly compelling data, we are looking forward to advancing UM171 cell therapy forward to a registrational Phase 3 trial in high and very high-risk leukemias and myelodysplasias in 2024.” About UM171 Cell Therapy UM171 cell therapy has been evaluated in over 100 patients to treat hematologic malignancies in clinical trials in the United States, Europe and Canada. UM171 cell therapy has received orphan drug designation and regenerative medicine advanced therapy (RMAT) designation from the FDA as well as orphan medicinal product designation, advanced therapy medicinal product (ATMP) classification and priority medicines (PRIME) designation from the EMA. UM171 cell therapy has successfully completed Phase 2 trials in high and very high-risk acute leukemias and myelodysplasias, and a Phase 3 trial is expected as soon as possible. Patients with high and very high-risk acute leukemias and myelodysplasias, including patients with refractory or active disease, patients requiring a second transplant, and patients with TP53 mutations or other genetic abnormalities, have limited treatment options with low survival outcomes and high incidence of relapse under the current standard of care. The use of UM171 cell therapy in other patient populations, including patients unable to find a stem cell donor, pediatric patients and patients with non-malignant hematological diseases, is also being explored. UM171 cell therapy is an investigational cell therapy, and its safety and efficacy have not been established by the FDA, EMA, Health Canada or any other health authority. About ExCellThera ExCellThera is a world leader in blood stem cell expansion and metabolic fitness. ExCellThera’s proprietary Enhance™ platform for cell expansion and metabolic fitness is designed to deliver a greater dose of functional therapeutic stem cells by expanding HSCs from any source and counteracting the effects of culture or gene editing induced stress. ExCellThera partners with bio-pharmas to help them develop best-in-class cell and gene therapies by leveraging the technologies that form the EnhanceTM platform, including proprietary molecule UM171 which has a first-in-class mechanism of action for ex vivo expansion and metabolic fitness of HSCs. For additional information, visit excellthera.com, and follow us on LinkedIn.

临床结果临床2期细胞疗法ASH会议孤儿药

2023-11-03

·GlobeNewswire-Health Care

ExCellThera announces new UM171 data to be presented at ASH 2023

MONTREAL, Nov. 03, 2023 (GLOBE NEWSWIRE) -- ExCellThera Inc. (ExCellThera), a world leader in blood stem cell expansion and fitness, announced today several UM171 presentations, including an oral session on new data from Phase 2 studies of investigational UM171 cell therapy in high-risk blood cancer patients, at the 65th American Society of Hematology Annual Meeting & Exposition (ASH), taking place December 9-12, 2023, in San Diego, California. The abstracts are now available on the ASH website at www.hematology.org/meetings/annual-meeting/abstracts. ASH 2023 presentation details: Title:Infusion of UM171 Expanded Cord Blood Led to Excellent Survival in Patients with High-Risk Leukemias: Results from Two Independent Phase II Studies (Publication no. 1040)Date & Time:Monday, December 11, 2023, at 4:45 PM PT (7:45 PM ET)Location:Ballroom 20AB, San Diego Convention CentreSession:Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Expanding the Donor Pool (Oral Session no. 721)Presenter:Filippo Milano, MD, PhD, Fred Hutchison Cancer Center, Seattle Title:UM171 Expanded Cord Blood Transplantation Outcomes Compare Favorably to All Different Stem Cell Sources: An EBMT Registry Case-Control Analysis (Publication no. 4977)Date & Time:Monday, December 11, 2023, 6-8 PM PT (9-11 PM ET)Location:Halls G-H, San Diego Convention CentreSession:Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster III (Poster Session no. 732)Presenter:Sandra Cohen, MD, FRCP, Maisonneuve Rosemont Hospital, Montreal Title:UM171 Enhances Fitness and Engraftment of Gene Modified Hematopoietic Stem Cells from Sickle Cells Disease Patients (Publication no. 18)Date & Time:Saturday, December 9, 2023 at 10:45 AM PT (1:45 PM ET)Location:Room 29, San Diego Convention CentreSession:Sickle Cell Disease, Sickle Cell Trait and Other Hemoglobinopathies, Excluding Thalassemias: Basic and Translational: Emerging Therapies for Sickle Cell Disease Presentation (Oral Session no. 113)Presenter:Boya Liu, PhD, Boston Children’s Hospital Title:Deciphering the Boundaries of KBTBD4-CoREST1 Axis Modulation to Maximally Expand Human HSCs (Publication no. 2681)Date & Time:Sunday, December 10, 2023, 6-8 PM PT (9-11 PM ET)Location:Halls G-H, San Diego Convention CentreSession:Hematopoietic Stem and Progenitor Cells and Hematopoiesis: Basic and Translational: Poster II (Poster Session no. 501)Presenter:Maria F. Tellechea, PhD, University of Montreal About UM171 Cell Therapy UM171 Cell Therapy has been evaluated in over 100 patients to treat hematologic malignancies in clinical trials in the United States, Europe and Canada. UM171 Cell Therapy has received orphan drug designation and regenerative medicine advanced therapy (RMAT) designation from the FDA as well as orphan medicinal product designation, advanced therapy medicinal product (ATMP) classification and priority medicines (PRIME) designation from the EMA. UM171 Cell Therapy is an investigational cell therapy, and its safety and efficacy have not been established by the FDA, EMA, Health Canada or any other health authority. About ExCellThera ExCellThera is a world leader in blood stem cell expansion and fitness. ExCellThera’s proprietary EnhanceTM platform for cell expansion and fitness is designed to deliver a greater dose of functional therapeutic stem cells by expanding HSCs from any source and counteracting the effects of culture or gene editing induced stress. ExCellThera partners with bio-pharmas to help them develop best-in-class cell and gene therapies by leveraging the technologies that form the EnhanceTM platform, including proprietary molecule UM171 which has a first-in-class mechanism of action for ex vivo expansion and fitness of HSCs. For additional information, visit excellthera.com, and follow us on LinkedIn.

细胞疗法ASH会议临床2期孤儿药临床结果

100 项与 Stem cell therapeutics(ExCellThera, Inc.) 相关的药物交易

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研发状态

适应症	最高研发状态	国家/地区	公司
急性淋巴细胞白血病	临床2期	美国更多	ExCellThera, Inc.初创企业更多
血液肿瘤	临床2期	美国更多	ExCellThera, Inc.初创企业更多
费城染色体阳性慢性粒细胞白血病	临床2期	美国更多	ExCellThera, Inc.初创企业更多
骨髓增生异常综合征	临床2期	荷兰更多	ExCellThera, Inc.初创企业更多
急性髓性白血病	临床2期	荷兰更多	ExCellThera, Inc.初创企业更多

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分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04103879 \| NCT03913026 (GlobeNewswire) 人工标引	临床2期	白血病 \| 骨髓增生异常综合征	50	UM171	(壓窪遞鏇積築夢遞淵餘) = 鹹餘獵鏇醖窪鬱築憲襯觸繭膚淵鏇製築壓憲遞 (選築鏇醖鏇觸醖夢蓋範 ) 更多	积极	2023-12-12