Clinical Investigation of a Humanized Anti-CD47 Antibody in Targeting Cancer Stem Cells in Acute Myelodi Leukaemia (and Solid Tumours).
Lead Research Organisation:
University of Oxford
Department Name: Weatherall Inst of Molecular Medicine
Abstract
Most normal tissues are maintained by a small number of stem cells that can both self-renew to maintain stem cell numbers, and also give rise to progenitors that make mature cells. We have shown that normal stem cells can accumulate mutations that cause progenitors to self-renew out of control, forming cancer stem cells (CSC). CSC make tumors composed of cancer cells, which are more sensitive to cancer drugs and radiation than the CSC. As a result, some CSC survive therapy, and grow and spread.
We sought to find therapies that include all CSC as targets. We found that all cancers and their CSC protect themselves by expressing a 'don't eat me' signal, called CD47, that prevents the innate immune system macrophages from eating and killing them. We have developed a novel therapy (anti-CD47 blocking antibody) that enables macrophages to eliminate both the CSC and the tumors they produce. This CIRM Grants System - Administration https://grants.cirm.ca.gov/applicant/grant_app/print/3385 anti-CD47 antibody eliminates human cancer stem cells when patient cancers are grown in mice. At the time of funding of this proposal, we will have fulfilled FDA/MHRA requirements to take this antibody into clinical trials, showing in animal models that the antibody is safe and well-tolerated, and that we can manufacture it to MHRA/FDA specifications for administration to humans.
Here, we propose the initial clinical investigation of the anti-CD47 antibody with parallel first-in-human Phase 1 clinical trials in patients with either Acute Myelogenous Leukemia (AML) or separately a diversity of solid tumors, who are no longer candidates for conventional therapies or for whom there are no further standard therapies. The primary objectives of our Phase I clinical trials are to assess the safety and tolerability of anti-CD47 antibody. The trials are designed to determine the maximum tolerated dose and optimal dosing regimen of anti-CD47 antibody given to up to 42 patients with AML and up to 70 patients with solid tumors. While patients will be clinically evaluated for halting of disease progression, such clinical responses are rare in Phase I trials due to the advanced illness and small numbers of patients, and because it is not known how to optimally administer the antibody. Subsequent progression to Phase II clinical trials will involve administration of an optimal dosing regimen to larger numbers of patients. These Phase II trials will be critical for evaluating the ability of anti-CD47 antibody to either delay disease progression or cause clinical responses, including complete remission. In addition to its use as a stand-alone therapy, anti-CD47 antibody has shown promise in preclinical cancer models in combination with approved anti-cancer therapeutics to dramatically eradicate disease.
Thus, our future clinical plans include testing anti-CD47 antibody in Phase IB/II studies with currently approved cancer therapeutics that produce partial responses. Ultimately, we hope anti-CD47 antibody therapy will provide durable clinical responses in the absence of significant toxicity.
We sought to find therapies that include all CSC as targets. We found that all cancers and their CSC protect themselves by expressing a 'don't eat me' signal, called CD47, that prevents the innate immune system macrophages from eating and killing them. We have developed a novel therapy (anti-CD47 blocking antibody) that enables macrophages to eliminate both the CSC and the tumors they produce. This CIRM Grants System - Administration https://grants.cirm.ca.gov/applicant/grant_app/print/3385 anti-CD47 antibody eliminates human cancer stem cells when patient cancers are grown in mice. At the time of funding of this proposal, we will have fulfilled FDA/MHRA requirements to take this antibody into clinical trials, showing in animal models that the antibody is safe and well-tolerated, and that we can manufacture it to MHRA/FDA specifications for administration to humans.
Here, we propose the initial clinical investigation of the anti-CD47 antibody with parallel first-in-human Phase 1 clinical trials in patients with either Acute Myelogenous Leukemia (AML) or separately a diversity of solid tumors, who are no longer candidates for conventional therapies or for whom there are no further standard therapies. The primary objectives of our Phase I clinical trials are to assess the safety and tolerability of anti-CD47 antibody. The trials are designed to determine the maximum tolerated dose and optimal dosing regimen of anti-CD47 antibody given to up to 42 patients with AML and up to 70 patients with solid tumors. While patients will be clinically evaluated for halting of disease progression, such clinical responses are rare in Phase I trials due to the advanced illness and small numbers of patients, and because it is not known how to optimally administer the antibody. Subsequent progression to Phase II clinical trials will involve administration of an optimal dosing regimen to larger numbers of patients. These Phase II trials will be critical for evaluating the ability of anti-CD47 antibody to either delay disease progression or cause clinical responses, including complete remission. In addition to its use as a stand-alone therapy, anti-CD47 antibody has shown promise in preclinical cancer models in combination with approved anti-cancer therapeutics to dramatically eradicate disease.
Thus, our future clinical plans include testing anti-CD47 antibody in Phase IB/II studies with currently approved cancer therapeutics that produce partial responses. Ultimately, we hope anti-CD47 antibody therapy will provide durable clinical responses in the absence of significant toxicity.
Technical Summary
Many cancers are organized as a cellular hierarchy initiated and maintained by cancer stem cells (CSC). CSC comprise a subset of tumor cells that are relatively resistant to current therapy, which often shrink tumors, but do not lead to long-term cures. Such cures require strategies to target all the CSC. CD47 is a immunomodulatory protein expressed on the surface of CSC and cancer cells from nearly all human tumors. CD47 binds SIRP-alpha on phagocytes, which delivers an inhibitory signal to block phagocytosis. CSC and cancer cells upregulate CD47 expression, presumably to suppress phagocytic attack. This proposal outlines a clinical development plan to evaluate the safety, tolerability, and efficacy of our therapeutic, the humanized anti-CD47 antibody Hu5F9-G4. Hu5F9-G4 is a blocking anti-human CD47 antibody that prevents the binding of CD47 to SIRP-alpha, disrupting its inhibitory signal, and enabling the phagocytic removal of CSC and cancer cells. In xenograft models, we have demonstrated that Hu5F9-G4 has potent efficacy against AML. In non-human primate toxicokinetic studies, Hu5F9-G4 was well-tolerated at doses able to achieve sustained serum levels in a potentially therapeutic range. Simultaneously, we generated a cGMP-qualified master cell bank, and have initiated GLP/GMP manufacturing of Hu5F9-G4. We have had positive initial regulatory interactions with the FDAand MHRA in the UK, and and are on track to file two separate IND/IMPDs, one for AML, and one for solid tumors by early 2014. Here, we propose parallel first-in-human Phase 1 clinical trials in the US and UK of Hu-5F9-G4 in patients with either AML or separately a diversity of solid tumors for whom there are no further standard therapies. The primary objective will be to assess the safety and tolerability of Hu5F9-G4, to identify the maximum tolerated dose (MTD) or optimal biologically effective dose (OBED), and to get a preliminary assessment of tumor reduction for further efficacy studies.
Planned Impact
1. Health care and economic benefits to UK and world wide: There are 2200 new AML cases/year in the UK. 80% of patients are >60 years of age; in an aging population, the disease is becoming more common. Current curative therapy is restricted to medically fit patients, usually <70 years old (~30% of patients). It consists of 2-4 cycles of toxic chemotherapy. A patient spends 3-4 weeks/cycle receiving expensive in-patient care (cost ~£20000/cycle/patient). In ~30% of patients this is followed by an allogeneic blood stem cell transplant (cost £45-60 000/patient). Even this programme only cures 40-50% patients <60 years old. Direct treatment cost to NHS hospitals ~£60-120 000/patient. Annual cost for 660 patients (30% of 2200 who receive curative approach) ~£40M-£80M. This does not include costs: (i) in primary care (ii) loss of earning (iii) tax revenue (iii) care at home (iv) care of problems secondary to initial treatment - e.g. chemotherapy-induced second malignancies (5-10% of patients). ~70% of AML do not receive curative therapy and 98% of these patients die within 4 months. They receive palliative supportive care. Some are entered into Phase I/II/III trials of newer therapies; data so far show none are curative and may benefit 10-40% of patients.
We plan to proceed to 2 Phase II trials (i) elderly untreated AML population (ii) younger patients with minimal residual disease. If Phase II trials show an efficacy signal we will move rapidly to a randomised UK AML Working Party driven Phase II/III looking for an impact on (i) overall survival (currently only 2% in elderly unfit AML patients and 30% in MRD+ve young patients), (ii) improved quality of life, and reduced use of health care resources. We will build in QoL assessment and health care utilisation into the randomised Phase II/III trials.
2. Establishing new class of therapy for AML (and cancers more broadly): If safe, and if the AML and solid trials shows an efficacy signal, it establishes CD47 as a novel therapeutic target and targeting programmed cell removal as a novel target pathway. This will impact the whole cancer community.
3. Ability to shape the Anti-CD47 Trial Programme: If Phase I/II programmes are successful it will allow UK investigators to lead, design and deliver pivotal licencing Phase III studies. This will impact on and build (i) knowledge, experience and training of UK teams (ii) a trial programme addressing UK health care needs (iv) world-wide reputation of UK AML clinical and translational programmes (iv) potentially allow to access anti-CD47 therapeutics at reduced cost.
4. Intellectual Property (IP) of clinical and laboratory dataset: The clinical and laboratory dataset from the Phase I/II trials will be important for design, submission and delivery of licencing Phase III studies. This IP will be jointly owned by Universities of Oxford and Stanford. With Stanford we will seek further funding for Phase III trials. The Stanford and Oxford groups want to lead a joint long-term programme for taking anti-CD47 to market.
5. Intellectual Property (IP) of LSC monitoring flow cytometry panel: University of Oxford have IP on aspects of the immunophenotyping panel and joint IP with Becton Dickinson and Stanford on other aspects of the flow cytometry panel. This panel has potential commercial value to identify patients who will respond to (i) anti-CD47 therapy (ii) new therapeutics directed against other stem cell antigens and (iii) identify antibody combination directed against different leukaemic stem cell antigens. Please see letter from Dr Richard Reschen from Issis Innovation.
6. Training of all staff directly involved in the programme and boosting the knowledge economy
7. Provide a paradigm (and thus incentive) for academics take therapeutic targets into clinical practice (particularly through the Phase I study setting) without commercial support thereby increasing value of the therapeutic product.
We plan to proceed to 2 Phase II trials (i) elderly untreated AML population (ii) younger patients with minimal residual disease. If Phase II trials show an efficacy signal we will move rapidly to a randomised UK AML Working Party driven Phase II/III looking for an impact on (i) overall survival (currently only 2% in elderly unfit AML patients and 30% in MRD+ve young patients), (ii) improved quality of life, and reduced use of health care resources. We will build in QoL assessment and health care utilisation into the randomised Phase II/III trials.
2. Establishing new class of therapy for AML (and cancers more broadly): If safe, and if the AML and solid trials shows an efficacy signal, it establishes CD47 as a novel therapeutic target and targeting programmed cell removal as a novel target pathway. This will impact the whole cancer community.
3. Ability to shape the Anti-CD47 Trial Programme: If Phase I/II programmes are successful it will allow UK investigators to lead, design and deliver pivotal licencing Phase III studies. This will impact on and build (i) knowledge, experience and training of UK teams (ii) a trial programme addressing UK health care needs (iv) world-wide reputation of UK AML clinical and translational programmes (iv) potentially allow to access anti-CD47 therapeutics at reduced cost.
4. Intellectual Property (IP) of clinical and laboratory dataset: The clinical and laboratory dataset from the Phase I/II trials will be important for design, submission and delivery of licencing Phase III studies. This IP will be jointly owned by Universities of Oxford and Stanford. With Stanford we will seek further funding for Phase III trials. The Stanford and Oxford groups want to lead a joint long-term programme for taking anti-CD47 to market.
5. Intellectual Property (IP) of LSC monitoring flow cytometry panel: University of Oxford have IP on aspects of the immunophenotyping panel and joint IP with Becton Dickinson and Stanford on other aspects of the flow cytometry panel. This panel has potential commercial value to identify patients who will respond to (i) anti-CD47 therapy (ii) new therapeutics directed against other stem cell antigens and (iii) identify antibody combination directed against different leukaemic stem cell antigens. Please see letter from Dr Richard Reschen from Issis Innovation.
6. Training of all staff directly involved in the programme and boosting the knowledge economy
7. Provide a paradigm (and thus incentive) for academics take therapeutic targets into clinical practice (particularly through the Phase I study setting) without commercial support thereby increasing value of the therapeutic product.
Organisations
- University of Oxford (Lead Research Organisation)
- UNIVERSITY OF OXFORD (Collaboration)
- Royal Liverpool University Hospital (Collaboration)
- UNIVERSITY OF NOTTINGHAM (Collaboration)
- University Hospital of Wales (Collaboration)
- Cardiff University (Collaboration)
- Leeds Teaching Hospitals NHS Trust (Collaboration)
- Stanford University (Collaboration)
- UNIVERSITY OF BIRMINGHAM (Collaboration)
- THE CHRISTIE NHS FOUNDATION TRUST (Collaboration)
People |
ORCID iD |
| Paresh Vyas (Principal Investigator) | |
| Adam Mead (Co-Investigator) |
Publications
Amatangelo MD
(2017)
Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response.
in Blood
Bache I
(2020)
A shared somatic translocation involving CUX1 in monozygotic twins as an early driver of AMKL in Down syndrome.
in Blood cancer journal
Brierley CK
(2019)
The effects of monoclonal anti-CD47 on RBCs, compatibility testing, and transfusion requirements in refractory acute myeloid leukemia.
in Transfusion
Chagraoui H
(2018)
SCL/TAL1 cooperates with Polycomb RYBP-PRC1 to suppress alternative lineages in blood-fated cells.
in Nature communications
Craddock C
(2021)
Augmented Reduced-Intensity Regimen Does Not Improve Postallogeneic Transplant Outcomes in Acute Myeloid Leukemia.
in Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Craddock C
(2018)
Distinct factors determine the kinetics of disease relapse in adults transplanted for acute myeloid leukaemia.
in Journal of internal medicine
Craddock CF
(2017)
Outcome of Azacitidine Therapy in Acute Myeloid Leukemia Is not Improved by Concurrent Vorinostat Therapy but Is Predicted by a Diagnostic Molecular Signature.
in Clinical cancer research : an official journal of the American Association for Cancer Research
Crump NT
(2021)
Chromatin accessibility governs the differential response of cancer and T cells to arginine starvation.
in Cell reports
Cruz Hernandez D
(2020)
Sensitive, rapid diagnostic test for transient abnormal myelopoiesis and myeloid leukemia of Down syndrome.
in Blood
Cruz Hernandez D
(2019)
Oncogenic Drivers and Development.
in Cancer discovery
Daver N
(2020)
New directions for emerging therapies in acute myeloid leukemia: the next chapter.
in Blood cancer journal
Dennis M
(2021)
A randomised evaluation of low-dose cytosine arabinoside (ara-C) plus tosedostat versus low-dose ara-C in older patients with acute myeloid leukaemia: results of the LI-1 trial.
in British journal of haematology
Desborough M
(2016)
Alternative agents to prophylactic platelet transfusion for preventing bleeding in people with thrombocytopenia due to chronic bone marrow failure: a meta-analysis and systematic review.
in The Cochrane database of systematic reviews
DiNardo CD
(2021)
Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination With Azacitidine for Newly Diagnosed Acute Myeloid Leukemia.
in Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Fenaux P
(2020)
Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes.
in The New England journal of medicine
Garcia-Manero G
(2021)
Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes.
in Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Garnett C
(2020)
GATA1 and cooperating mutations in myeloid leukaemia of Down syndrome.
in IUBMB life
Gerstung M
(2015)
Combining gene mutation with gene expression data improves outcome prediction in myelodysplastic syndromes.
in Nature communications
Giustacchini A
(2017)
Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia.
in Nature medicine
Godfrey L
(2019)
DOT1L inhibition reveals a distinct subset of enhancers dependent on H3K79 methylation.
in Nature communications
Gooding S
(2022)
Loss of COP9 signalosome genes at 2q37 is associated with IMiD resistance in multiple myeloma.
in Blood
Gu Y
(2015)
Comparison of a restrictive versus liberal red cell transfusion policy for patients with myelodysplasia, aplastic anaemia, and other congenital bone marrow failure disorders.
in The Cochrane database of systematic reviews
Hanekamp D
(2020)
Applicability and reproducibility of acute myeloid leukaemia stem cell assessment in a multi-centre setting.
in British journal of haematology
Hashimoto M
(2021)
Combined inhibition of XIAP and BCL2 drives maximal therapeutic efficacy in genetically diverse aggressive acute myeloid leukemia.
in Nature cancer
ICGC/TCGA Pan-Cancer Analysis Of Whole Genomes Consortium
(2020)
Pan-cancer analysis of whole genomes.
in Nature
Ivey A
(2016)
Assessment of Minimal Residual Disease in Standard-Risk AML
in New England Journal of Medicine
Jakobsen NA
(2018)
From genomics to targeted treatment in haematological malignancies: a focus on acute myeloid leukaemia.
in Clinical medicine (London, England)
Josa-Culleré L
(2021)
Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[e][1,4]oxazepin-2(3H)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro.
in Molecules (Basel, Switzerland)
Josa-Culleré L
(2021)
A Phenotypic Screen Identifies a Compound Series That Induces Differentiation of Acute Myeloid Leukemia Cells In Vitro and Shows Antitumor Effects In Vivo.
in Journal of medicinal chemistry
Karamitros D
(2018)
Single-cell analysis reveals the continuum of human lympho-myeloid progenitor cells.
in Nature immunology
Khan N
(2015)
An immunophenotypic pre-treatment predictor for poor response to induction chemotherapy in older acute myeloid leukaemia patients: blood frequency of CD34+ CD38 low blasts.
in British journal of haematology
Li CH
(2020)
Sex differences in oncogenic mutational processes.
in Nature communications
Loke J
(2022)
Combination romidepsin and azacitidine therapy is well tolerated and clinically active in adults with high-risk acute myeloid leukaemia ineligible for intensive chemotherapy.
in British journal of haematology
Maloney KW
(2015)
Down syndrome preleukemia and leukemia.
in Pediatric clinics of North America
Marquis M
(2018)
High expression of HMGA2 independently predicts poor clinical outcomes in acute myeloid leukemia.
in Blood cancer journal
Mettananda S
(2017)
Editing an a-globin enhancer in primary human hematopoietic stem cells as a treatment for ß-thalassemia.
in Nature communications
Muskens IS
(2021)
The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis.
in Nature communications
Ossenkoppele G
(2020)
BCL-2 Inhibitor and Conventional Chemotherapy Combinations for Acute Myeloid Leukemia: Shifting From the Unfit to the Fit Patient With AML.
in Journal of clinical oncology : official journal of the American Society of Clinical Oncology
| Description | NHSBT Non-Executive Director |
| Geographic Reach | National |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | Ensuring quality and safe provision of blood and organs - Stem cells for England. |
| Description | NHSBT Non-Executive Director |
| Geographic Reach | National |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | Ensuring quality and safe provision of blood and organs. |
| Description | Amendment 4 Collaboration CyTOF Panels Mount Sinai |
| Amount | £43,800 (GBP) |
| Organisation | Bristol-Myers Squibb |
| Department | Celgene |
| Sector | Private |
| Country | United States |
| Start | 10/2019 |
| End | 09/2022 |
| Description | BD - Celgene Fellowship Agreement for Supat Thongjuea entitled "Single-Cell Computational Biology for Translational Medicine |
| Amount | £519,623 (GBP) |
| Organisation | Bristol-Myers Squibb |
| Department | Celgene |
| Sector | Private |
| Country | United States |
| Start | 11/2019 |
| End | 10/2022 |
| Description | BRC3 - Precision Medicine cluster funding |
| Amount | £112,500 (GBP) |
| Organisation | National Institute for Health Research |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2019 |
| End | 03/2020 |
| Description | Blood Cancer UK - Programme Continuity Grant |
| Amount | £300,000 (GBP) |
| Organisation | Blood Cancer UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 04/2020 |
| End | 04/2024 |
| Description | Celgene Translational Science Proposal |
| Amount | £1,065,908 (GBP) |
| Organisation | Bristol-Myers Squibb |
| Department | Celgene |
| Sector | Private |
| Country | United States |
| Start | 10/2019 |
| End | 01/2023 |
| Description | HIDI Award |
| Amount | £25,000 (GBP) |
| Organisation | National Institute for Health Research |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2018 |
| End | 07/2019 |
| Description | Haematology and Stem Cell Theme Oxford Biomedical Research Centre (NIHR) |
| Amount | £125,000,000 (GBP) |
| Organisation | National Institute for Health Research |
| Department | NIHR Biomedical Research Centre |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2017 |
| End | 03/2022 |
| Description | LLR - Leukaemia & Lymphoma Research. CTAP (Clinical Trial) |
| Amount | £308,470 (GBP) |
| Organisation | Leukaemia and Lymphoma Research |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2015 |
| End | 02/2018 |
| Description | Medical Research Council (MRC) - Molecular Haematology Unit Award |
| Amount | £1,387,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2017 |
| End | 04/2022 |
| Description | Oxford Comprehensive Biomedical Research Centre |
| Amount | £60,000 (GBP) |
| Organisation | National Institute for Health Research |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2018 |
| End | 04/2022 |
| Description | Clinical Trial of Anti-CD47 |
| Organisation | Leeds Teaching Hospitals NHS Trust |
| Department | Department of Clinical Haematology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I have written the Phase I clinical trial Protocol for use of Anti-CD47 in a first in class first in man clinical trial. I will coordinate CTA application and NRES application. My lab will perform exploratory PD biomarker analysis. I will be CI of the trial. Phase I trial to started 2015. Phase II trials to start 2017. |
| Collaborator Contribution | Stanford University have made the therapeutic. There are 5 UK hospitals site that will run the trial. A company, CD47 Inc, has spun out of Stanford University and is now the sponsor of this trial. Oxford University has a revenue sharing agreement with Stanford University. |
| Impact | 1. We successfully secured MRC (2015 and 2009 ) and Bloodwise (2015) funding for this trial. 2. The drug is safe we will aim to perform a Phase II trial in 2017 in AML. |
| Start Year | 2010 |
| Description | Clinical Trial of Anti-CD47 |
| Organisation | Royal Liverpool University Hospital |
| Department | Department of Haematology |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | I have written the Phase I clinical trial Protocol for use of Anti-CD47 in a first in class first in man clinical trial. I will coordinate CTA application and NRES application. My lab will perform exploratory PD biomarker analysis. I will be CI of the trial. Phase I trial to started 2015. Phase II trials to start 2017. |
| Collaborator Contribution | Stanford University have made the therapeutic. There are 5 UK hospitals site that will run the trial. A company, CD47 Inc, has spun out of Stanford University and is now the sponsor of this trial. Oxford University has a revenue sharing agreement with Stanford University. |
| Impact | 1. We successfully secured MRC (2015 and 2009 ) and Bloodwise (2015) funding for this trial. 2. The drug is safe we will aim to perform a Phase II trial in 2017 in AML. |
| Start Year | 2010 |
| Description | Clinical Trial of Anti-CD47 |
| Organisation | Stanford University |
| Department | Stem Cell Institute Stanford |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | I have written the Phase I clinical trial Protocol for use of Anti-CD47 in a first in class first in man clinical trial. I will coordinate CTA application and NRES application. My lab will perform exploratory PD biomarker analysis. I will be CI of the trial. Phase I trial to started 2015. Phase II trials to start 2017. |
| Collaborator Contribution | Stanford University have made the therapeutic. There are 5 UK hospitals site that will run the trial. A company, CD47 Inc, has spun out of Stanford University and is now the sponsor of this trial. Oxford University has a revenue sharing agreement with Stanford University. |
| Impact | 1. We successfully secured MRC (2015 and 2009 ) and Bloodwise (2015) funding for this trial. 2. The drug is safe we will aim to perform a Phase II trial in 2017 in AML. |
| Start Year | 2010 |
| Description | Clinical Trial of Anti-CD47 |
| Organisation | The Christie NHS Foundation Trust |
| Department | Haematology and Transplant Unit |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | I have written the Phase I clinical trial Protocol for use of Anti-CD47 in a first in class first in man clinical trial. I will coordinate CTA application and NRES application. My lab will perform exploratory PD biomarker analysis. I will be CI of the trial. Phase I trial to started 2015. Phase II trials to start 2017. |
| Collaborator Contribution | Stanford University have made the therapeutic. There are 5 UK hospitals site that will run the trial. A company, CD47 Inc, has spun out of Stanford University and is now the sponsor of this trial. Oxford University has a revenue sharing agreement with Stanford University. |
| Impact | 1. We successfully secured MRC (2015 and 2009 ) and Bloodwise (2015) funding for this trial. 2. The drug is safe we will aim to perform a Phase II trial in 2017 in AML. |
| Start Year | 2010 |
| Description | Clinical Trial of Anti-CD47 |
| Organisation | University Hospital of Wales |
| Department | Department of Haematology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I have written the Phase I clinical trial Protocol for use of Anti-CD47 in a first in class first in man clinical trial. I will coordinate CTA application and NRES application. My lab will perform exploratory PD biomarker analysis. I will be CI of the trial. Phase I trial to started 2015. Phase II trials to start 2017. |
| Collaborator Contribution | Stanford University have made the therapeutic. There are 5 UK hospitals site that will run the trial. A company, CD47 Inc, has spun out of Stanford University and is now the sponsor of this trial. Oxford University has a revenue sharing agreement with Stanford University. |
| Impact | 1. We successfully secured MRC (2015 and 2009 ) and Bloodwise (2015) funding for this trial. 2. The drug is safe we will aim to perform a Phase II trial in 2017 in AML. |
| Start Year | 2010 |
| Description | Clinical Trial of Anti-CD47 |
| Organisation | University of Nottingham |
| Department | Haematology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I have written the Phase I clinical trial Protocol for use of Anti-CD47 in a first in class first in man clinical trial. I will coordinate CTA application and NRES application. My lab will perform exploratory PD biomarker analysis. I will be CI of the trial. Phase I trial to started 2015. Phase II trials to start 2017. |
| Collaborator Contribution | Stanford University have made the therapeutic. There are 5 UK hospitals site that will run the trial. A company, CD47 Inc, has spun out of Stanford University and is now the sponsor of this trial. Oxford University has a revenue sharing agreement with Stanford University. |
| Impact | 1. We successfully secured MRC (2015 and 2009 ) and Bloodwise (2015) funding for this trial. 2. The drug is safe we will aim to perform a Phase II trial in 2017 in AML. |
| Start Year | 2010 |
| Description | Clinical Trial of Anti-CD47 |
| Organisation | University of Oxford |
| Department | Department of Oncology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I have written the Phase I clinical trial Protocol for use of Anti-CD47 in a first in class first in man clinical trial. I will coordinate CTA application and NRES application. My lab will perform exploratory PD biomarker analysis. I will be CI of the trial. Phase I trial to started 2015. Phase II trials to start 2017. |
| Collaborator Contribution | Stanford University have made the therapeutic. There are 5 UK hospitals site that will run the trial. A company, CD47 Inc, has spun out of Stanford University and is now the sponsor of this trial. Oxford University has a revenue sharing agreement with Stanford University. |
| Impact | 1. We successfully secured MRC (2015 and 2009 ) and Bloodwise (2015) funding for this trial. 2. The drug is safe we will aim to perform a Phase II trial in 2017 in AML. |
| Start Year | 2010 |
| Description | Collaboration on therapy of high risk MDS and AML. |
| Organisation | University of Birmingham |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Understanding AML Leukaemic stem cell biology. Assessment of Leukaemic stem cells (LSC) as a marker of minimal residual disease. This is evaluated using samples from clinical trials. |
| Collaborator Contribution | Clinical Trial Lead |
| Impact | Quek L*, Ferguson P*, Metzner M, Ahmed I, Kennedy A, Garnett C, Jeffries S, Walter C, Piechocki K, Timbs A, Danby R, Raghavan M, Peniket A, Griffiths M, Bacon A, Ward J, Wheatley K, Vyas P*, Craddock C*. Mutational Analysis of Disease Relapse in Patients Allografted for Acute Myeloid Leukemia Khan N, Hills RK, Knapper S, Steadman L, Qureshi U, Rector JL, Bradbury C, Russell NH, Vyas P, Burnett AK, Grimwade D, Hole PS, Freeman SD. Normal Hematopoietic Progenitor Subsets Have Distinct Reactive Oxygen Species, BCL2 and Cell-Cycle Profiles That Are Decoupled from Maturation in Acute Myeloid Leukemia PLoS One. 2016 Sep 26;11(9):e0163291. PMID: 27669008 Craddock C, Jilani NY, Siddique S, Yap C, Khan JN, Nagra S, Ward J, Ferguson P, Hazlewood P, Buka R, Vyas P, Goodyear OC, Tholouli E, Crawley C, Russell N, Byrne J, Malladi R, Snowden JA, Dennis M. Tolerability and clinical activity of post-transplant Azacitidine in patients allografted for Acute Myeloid Leukaemia treated on the RICAZA trial. Biol Blood Marrow Transplant. Sep 9. pii: S1083-8791(15)00609-6. doi: 10.1016/j.bbmt.2015.09.004. (2015). Bradbury C, Houlton AE, Akiki S, Gregg R, Rindl M, Khan J, Ward J, Khan N, Griffiths M, Nagra S, Hills R, Burnett A, Russell N, Vyas P, Grimwade D, Craddock C, Freeman SD. Prognostic value of monitoring a candidate immunophenotypic leukemic stem/progenitor cell population in patients allografted for acute myeloid leukemia. Leukemia. 29 p988-91. (2014) PMID:25425198. Craddock C, Goardon N, Quek L, Freeman S, Siddique S, Raghavan M, Schuh A, Grimwade D, Virgo P, Hills R, McSkeane T, Arrazi J, Gilkes A, Knapper, Adam Ivey, Brookes C, Miles O, Davies B, Chaudhury S, Pollard T, Price A, Atzberger A, Wall K, Kaur H, Griffiths M, Cavenagh, Majeti R, Weissman I, Burnett A, Vyas P. Azacitidine fails to eradicate leukemic stem/progenitor cell populations in patients with acute myeloid leukemia and myelodysplasia. Leukaemia 27:p1028-36 (2013). Goodyear O, Dennis M, Loke J, Jilani N, Siddique S, Ryan G, J Nunnick, Khanum R, Raghavan M, Cook M, Snowden J, Griffiths M, Russell N, Yin J, Crawley C, Cook G, Vyas P, Moss P, Malladi R, Craddock C. Azacitidine Induces Expansion of Regulatory T Cells and Induces a Tumor Antigen Specific Response after Allogeneic Stem Cell Transplantation in patients with AML. Blood. 119: p3361-9. (2012). Co-administration of Vorinostat Does Not Improve Outcome of Patients with of Acute Myeloid Leukemia Treated with Azacitidine Charles Craddock, MD, PhD1, Aimee E Houlton, BSc, MSc2*, Lynn Swun Quek, DPhil, FRCPath, Paul Ferguson, MBChB MRCP PhD3; Emma Gbandi, Corran Roberts (affiliation and degree needed), *, Marlen Metzner, Alison Kennedy, Manoj Raghavan4*, Sandeep Nagra1*, Louise Dudley, BSc, MRes5*, DPhil, MBBS6*, Sharon Love, Jamie D. Cavenagh7, Michael Dennis, FRCPath8*, Mary Frances McMullin, MD9, Srinivas P Pillai10*, Richard Kelly, BSc, MD11*, Shamyla Siddique12*, Keith Wheatley, DPhil13 and Paresh Vyas, BM, DPhil, FRCP, FRCPath14 Submitted Grants: 2015-2018 Therapy Acceleration Programme £92 778. Leukaemia Lymphoma Research Funded Trial Infrastructure Programme |
| Start Year | 2012 |
| Description | WGS and additional biologic studies of haem tumours. |
| Organisation | Cardiff University |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Design of the program of WGS and integrated multi-"omic" reseatch program on AML UK NCRI AML clinical trial samples to define clonal structures in human AML and how they change in response to therapy. To determine molecular and cellular mechanisms of therapy resistance. |
| Collaborator Contribution | University of Oxford - Lead of AML GECIP (Vyas) and overall haem GECIP (Schuh) University of Cardiff - Sponsor of Trial |
| Impact | Zabkiewicz J, Gilmour M, Hills R, Vyas P, Bone E, Davidson A, Burnett A, Knapper S. The targeted histone deacetylas inhibitor tefinostst (CHR-2845) shows selective in vitro efficacy in monocytoid-lineage leukaemias. Oncotarget. 2016 Feb 25. doi: 10.18632/oncotarget.7692. PMID: 26934551 Ivey A, Hills RK, Simpson MA, Jovanovic JV, Gilkes A, Grech A, Patel Y, Bhudia N, Farah H, Mason J, Wall K, Akiki S, Griffiths, M, Solomon E, McCaughan F, Linch D, Gale R, Vyas P, Freeman S, Russell N, Burnett, A and Grimwade D, for the UK National Cancer Research Institute AML Working Group. Assessment of Minimal Residual Disease in Standard Risk AML. NEJM 374 p422-33. (2016). PMID: 26789727 |
| Start Year | 2015 |
| Description | WGS and additional biologic studies of haem tumours. |
| Organisation | University of Oxford |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Design of the program of WGS and integrated multi-"omic" reseatch program on AML UK NCRI AML clinical trial samples to define clonal structures in human AML and how they change in response to therapy. To determine molecular and cellular mechanisms of therapy resistance. |
| Collaborator Contribution | University of Oxford - Lead of AML GECIP (Vyas) and overall haem GECIP (Schuh) University of Cardiff - Sponsor of Trial |
| Impact | Zabkiewicz J, Gilmour M, Hills R, Vyas P, Bone E, Davidson A, Burnett A, Knapper S. The targeted histone deacetylas inhibitor tefinostst (CHR-2845) shows selective in vitro efficacy in monocytoid-lineage leukaemias. Oncotarget. 2016 Feb 25. doi: 10.18632/oncotarget.7692. PMID: 26934551 Ivey A, Hills RK, Simpson MA, Jovanovic JV, Gilkes A, Grech A, Patel Y, Bhudia N, Farah H, Mason J, Wall K, Akiki S, Griffiths, M, Solomon E, McCaughan F, Linch D, Gale R, Vyas P, Freeman S, Russell N, Burnett, A and Grimwade D, for the UK National Cancer Research Institute AML Working Group. Assessment of Minimal Residual Disease in Standard Risk AML. NEJM 374 p422-33. (2016). PMID: 26789727 |
| Start Year | 2015 |
| Title | AG221 AML-005: |
| Description | A Safety and Efficacy Study of Oral AG-120 Plus Subcutaneous Azacitidine and Oral A-221 Plus Subcutaneous Azacitidine in Subjects With Newly Diagnosed Acute Myeloid Leukemia (AML) Vyas is UK CI. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Late clinical evaluation |
| Year Development Stage Completed | 2016 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| Impact | Impact awaited. |
| URL | https://clinicaltrials.gov/show/NCT02677922 |
| Title | Camellia trial |
| Description | First-in-class Phase I trial of Humanized Monoclonal Antibody anti-CD47 in Acute Myeloid Leukemia. This is an academically funded, 7-year collaboration between my laboratory and Weissman Laboratory Stanford University. Sponsored by Stanford University. Oxford University is Sponsor in the EU. Oxford Oncology Clinical Trials Unit is running this multi-centre UK trial. Trial will complete in 6/2017. Phase II trials planned. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2009 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| Impact | This first-in-class trial of a new monoclonal therapeutic antibody provides a rare example of academically funded work going from a laboratory observation through to development, manufacture and pre-clinical testing of a clinical therapuetic all the way to first clinical trial within the envelope of an entirely academically funded program. This work is a collaboration between my laboratory, my clinical work in Oxford, the Oxford Clinical Oncology Early phase Trial Unit, the UK AML NCRI Clinical Trial Group and Stanford Unviersity. I am CI of the AML trial. The Stanford PI Dr Weissman has established a spin out company CD47 Inc to take this program further in clinical development. |
| URL | http://www.isrctn.com/ISRCTN28039294 |
| Title | Celgene Aza-AML-001: |
| Description | Phase 3, Multicenter, Randomized, Open-label, Study Of Azacitidine Versus Conventional Care Regimens For The Treatment Of Older Subjects With Newly Diagnosed Acute Myeloid Leukaemia. Vyas was local PI. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Late clinical evaluation |
| Year Development Stage Completed | 2011 |
| Development Status | Closed |
| Clinical Trial? | Yes |
| Impact | Has led to EMA licence for Aza for AML. NICE refused to fund under TA. Celgene will put forward a patient access scheme for UK patients. |
| URL | https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012346-23 |
| Title | Celgene Aza-MDS-001: |
| Description | A Multicenter, Randomized, Open-Label, Parallel-Group, Phase 3 Trial Of Subcutaneous Azacitidine Plus Best Supportive Care Versus Conventional Care Regimens Plus Best Supportive Care For The Treatment of Myelodysplastic Syndromes (MDS). Vyas is local PI. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Late clinical evaluation |
| Year Development Stage Completed | 2008 |
| Development Status | Under active development/distribution |
| Impact | Led to licencing of Aza for MDS. NICE approved drug. Now standard of care for this patient group. |
| Title | Celgene MDS003 |
| Description | A Phase 3, Multicenter, Randomized, Double-blind Study To Compare The Efficacy And Safety Of Oral Azacitidine Plus Best Supportive Care Versus Placebo Plus Best Supportive Care In Subjects With Red Blood Cell Transfusion-dependent Anemia and Thrombocytopenia Due To IPSS Lower-risk Myelodysplastic Syndromes. Vyas is UK national CI. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Late clinical evaluation |
| Year Development Stage Completed | 2013 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| Impact | This Phase III licencing study will provide clincial dataset that could potential licence oral Azacitidine. |
| URL | https://clinicaltrials.gov/show/NCT01099267 |
| Title | Evaulation of anti-PD-L1 in high risk MDS and AML. |
| Description | A Randomized, Multicenter, Open-label, Phase 2 Study Evaluating The Efficacy And Safety of Azacitidine Subcutaneous In Combination with Durvalumab (MEDIA4736) In Previously Untreated subjects With Higher-risk Myelodysplastic Syndromes (MDS) Or In Elderly (= 65 years) Acute Myeloid Leukemia (AML) Subjects Not Eligible For Hematopoietic Stem Cell Transplantation (HSCT). Vyas is local PI. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Late clinical evaluation |
| Year Development Stage Completed | 2016 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| Impact | Impact awaited |
| URL | https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003596-30 |
| Title | IDH2 inhibitor trial |
| Description | A PHASE 3, MULTICENTER, OPEN-LABEL, RANDOMIZED STUDY COMPARING THE EFFICACY AND SAFETY OF AG-221 (CC-90007) VERSUS CONVENTIONAL CARE REGIMENS IN OLDER SUBJECTS WITH LATE STAGE ACUTE MYELOID LEUKEMIA HARBORING AN ISOCITRATE DEHYDROGENASE 2 MUTATIO International Phase III trial of a first-in-class oral IDH2 inhibitor in Acute Myeloid Leukaemia. Sponsored by Celgene. Vyas is UK CI. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Late clinical evaluation |
| Year Development Stage Completed | 2016 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| Impact | Impact still awaited. |
| URL | https://clinicaltrials.gov/show/NCT01915498 |
| Title | Novartis Telesto Trial |
| Description | A multi-center, randomized, double-blind, placebo- controlled clinical trial of deferasirox in patients with myelodysplastic syndromes (low/int-1 risk) and transfusional iron overload (TELESTO) International Phase III trial of an oral iron chelator in Myelodsplastic Syndrome. Sponsored by Novartis. Vyas is UK CI. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Late clinical evaluation |
| Year Development Stage Completed | 2012 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| Impact | Impact awaited. Trial data closed and data being analysed. |
| URL | https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012418-38 |
| Title | RavVa trial: |
| Description | Phase II Randomised Trial of 5-Azacitidine versus 5- Azacitidine in combination with Vorinostat in patients with Acute Myeloid Leukaemia or High Risk Myelodysplastic Syndromes Ineligible for Intensive Chemotherapy). 250 patients. Fully recruited. Vyas is co-Investigator and Scientific Lead. Trial completed. Manuscript submitted. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Late clinical evaluation |
| Year Development Stage Completed | 2013 |
| Development Status | Closed |
| Clinical Trial? | Yes |
| Impact | This trial is helping to define azacitidine based combination therapies. |
| URL | http://www.isrctn.com/ISRCTN68224706 |
| Title | Roche RO504337 in Acute Leukaemia |
| Description | A Multi-center, Open-label, Phase I Study of Single Agent RO5045337 Administered Orally In patients with Acute Myelogenous Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myelogenous Leukemia (CML) In Blast Phase, Or Refractory Chronic Lymphocytic leukemia/Small Cell Lymphocytic Lymphoma (CLL/SCLL). Vyas was local PI. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2014 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| UKCRN/ISCTN Identifier | 623870 |
| Impact | Phase II trials started. |
| URL | https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-010591-20 |
| Title | UK AML NCRI Working Group AML 17, AML 18, AML 19 and LI1. |
| Description | Phase III UK AML trials: AML 19, LI1. Vyas is Lead for Genome England Program and flow cytometric leukaemic stem cell MRD studies. |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Late clinical evaluation |
| Year Development Stage Completed | 2012 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| UKCRN/ISCTN Identifier | AML 17 - 55675535 , AML18 - 31682779 , AMl 19 78449203 , LI1 18218 |
| Impact | PV to write |
| Description | American Association of Cancer Research Myeloid Meeting |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Title: "Molecular Features Associated with Response to Combination Therapy with Enasidenib (ENA) Plus Azacitidine (AZA) in Newly Diagnosed IDH2-Mutated Acute Myeloid Leukemia (AML)" Co-authors: Alberto Risueño, PhD, Wendy L. See, PhD, Courtney D. DiNardo, MD, MSCE, Hartmut Döhner, MD, Eytan Stein, MD5, Amir T. Fathi, MD6, Paresh Vyas, DPhil, FRCP, FRCPath, MRCP, MRCPath, Lynn Quek, MD PhD, Thomas Prebet, MD, PhD, Anita K. Gandhi, PhD9 and Maroof Hasan, MD |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://ash.confex.com/ash/2022/webprogram/Session22525.html |
| Description | Belgian Academy of Sciences |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Paresh VYAS (Professor of Haematology at the University of Oxford, Oxford, UK) : Paresh Vyas : Clonal Cell Heterogeneity in Tissues With Aging Alters Function: Using Whole Genome Sequencing and Single Cell Sequencing To Study These Processes In Blood Cells As An Exemplar Ruud Delwel (Professor "Molecular Leukemogenesis", Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands): How good genes can become Evil in leukemia Steven O. Smith (Professor - Director of Structural Biology, Department of Biochemistry and Cell Biology Stony Brook, NY USA) : Lessons from brain-derived amyloid fibril structures from Alzheimer's Disease patients https://www.youtube.com/watch?v=GjyrzYunfPU See also: https://www.facebook.com/probramedecine/ |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.youtube.com/watch?v=GjyrzYunfPU |
| Description | Conference / Exposition: American Association of Cancer Research Myeloid Meeting |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Title: "Molecular Features Associated with Response to Combination Therapy with Enasidenib (ENA) Plus Azacitidine (AZA) in Newly Diagnosed IDH2-Mutated Acute Myeloid Leukemia (AML)" Co-authors: Alberto Risueño, PhD, Wendy L. See, PhD, Courtney D. DiNardo, MD, MSCE, Hartmut Döhner, MD, Eytan Stein, MD5, Amir T. Fathi, MD6, Paresh Vyas, DPhil, FRCP, FRCPath, MRCP, MRCPath, Lynn Quek, MD PhD, Thomas Prebet, MD, PhD, Anita K. Gandhi, PhD9 and Maroof Hasan, MD |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://ash.confex.com/ash/2022/webprogram/Session22525.html |
| Description | Conference / Exposition: University of Texas South Western |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | PLENARY SESSION 8: CELL AND IMMUNE TARGETING IN MYELOID MALIGNANCIES SESSION CHAIR: PARESH VYAS, UNIVERSITY OF OXFORD, OXFORD, UNITED KINGDOM 12:00 P.M.-1:45 P.M. Talk title: "Graft versus Leukemia (GvL): Identification and characterization of alloreactive antigens and cognate T cell responses in acute myeloid leukemia" |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://www.aacr.org/meeting/acute-myeloid-leukemia-and-myelodysplastic-syndrome/program/ |
| Description | EHA (European Haematology Association) Annual Meeting. |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | TOLERABILITY AND EFFICACY OF THE FIRST-IN-CLASS ANTI-CD47 ANTIBODY MAGROLIMAB COMBINED WITH AZACITIDINE IN FRONTLINE PATIENTS WITH TP53-MUTATED ACUTE MYELOID LEUKEMIA: PHASE 1B RESULTS Dr. Naval G Daver Author(s): Naval G Daver, Paresh Vyas, Suman Kambhampati, Monzr M Al Malki, Richard Larson, Adam Asch, Gabriel Mannis, Wanxing Chai-Ho, Tiffany Tanaka, Terrence Bradley, Deepa Jeyakumar, Eunice Wang, Guan Xing, Mark Chao, Giri Ramsingh, Camille Renard, Indu Lal, Joshua Zeidner, David Sallman (Abstract release date: 05/26/22) EHA Library. G Daver N. 06/10/2022; 356996; S132 |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://library.ehaweb.org/eha/2022/eha2022-congress/356996/naval.g.daver.tolerability.and.efficacy.... |
| Description | ESH (European Society of Haematology) Treatment of Leukaemias (Virtual) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | (Latest session from 2022 not recorded. Earlier talk from 2019 recorded at URL provided below): The AML Global Portal were delighted to speak to Paresh Vyas, University of Oxford, Oxford, UK, during the European School of Hematology (ESH) Translational Research Conference on AML. We asked Paresh Vyas: When do you use single-cell MRD assessment in AML? Paresh Vyas discusses the role of measurable residual disease (MRD) monitoring in informing clinical practice and reviews different approaches such as next-generation sequencing (NGS), flow cytometry and single-cell measurement of disease. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://aml-hub.com/medical-information/esh-2019-or-when-do-you-use-single-cell-mrd-assessment-in-am... |
| Description | Hosted Work Experience Programme |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Other audiences |
| Results and Impact | Run a session on haematology for students in the MRC WIMM work experience programme. Included go fish game, activities on gene expression using legos and microscopy and leukaemia diagnosis |
| Year(s) Of Engagement Activity | 2019 |
| Description | MDS Support group |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Multiple talks to a patient support group Improved patient understanding. Increased patient advocacy |
| Year(s) Of Engagement Activity | 2013 |
| Description | MRC Festival 2019 on Cancer immunotherapy - Grigore |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Part of working group that developed activities for MRC Festival 2019 on Cancer immunotherapy |
| Year(s) Of Engagement Activity | 2019 |
| Description | Myeloid Workshop (Cincinnati, USA) |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Since 1995, the Workshop on Molecular Aspects of Myeloid Stem Cell Development and Leukemia has offered a highly successful presentation series from approximately 40-50 renowned national and international researchers and clinicians. The goal of these biennial workshops is to bring together investigators with expertise in complementary aspects of stem cell biology and myelopoiesis - from normal myelopoiesis to myeloid leukemias and myelodysplastic/myeloproliferative syndromes. Basic researchers and clinician investigators from both sides of the Atlantic, Australia and Japan come together biennially to discuss their latest findings in a close and informal setting. The workshop brings together scientists with expertise in normal and abnormal hematopoiesis and clinicians who treat leukemia/MDS/MPD patients and also have active research programs in these diseases. Participants achieve a better understanding of critical steps/factors that regulate hematopoiesis, their impact in leukemogenesis, and potential relevance in clinical settings. Although there are other workshops and meetings dedicated to understanding the regulation of hematopoiesis or clinical advances in leukemia, this workshop uniquely brings together both clinicians and scientists in a relaxed forum. Speakers: (See URL) |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://myeloidmeeting.org |
| Description | Patient Support Group |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | Giving support and advice to patients, families and carers. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Science in the supermarket, MRC Festival 2019 - Douzi & Grigore |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Science in the supermarket, MRC Festival 2019 |
| Year(s) Of Engagement Activity | 2019 |
| Description | University of Texas South Western |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | PLENARY SESSION 8: CELL AND IMMUNE TARGETING IN MYELOID MALIGNANCIES SESSION CHAIR: PARESH VYAS, UNIVERSITY OF OXFORD, OXFORD, UNITED KINGDOM 12:00 P.M.-1:45 P.M. TITLE: "Graft versus Leukemia (GvL): Identification and characterization of alloreactive antigens and cognate T cell responses in acute myeloid leukemia" |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://www.aacr.org/meeting/acute-myeloid-leukemia-and-myelodysplastic-syndrome/program/ |
| Description | iWAL (International Workshop on Acute Leukemia) Workshop (Nice, France): iWAL 2022 Session V: Mechanisms of resistance to targeted therapies in AML |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | iwAL 2022 Session V: Mechanisms of resistance to targeted therapies in AML Tuesday Dec 06, 2022 The 4th International Workshop on Acute Leukemias (iwAL) 2022 took place in Nice, France, and brought together leading experts in the field as they discussed several topics. In this podcast series, you will hear the latest updates in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and gain an insight into the sessions that took place at this year's meeting. In this podcast, Naval Daver, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, Paresh Vyas, MRCP, FRCP, FRCPath, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK, Alexander Perl, MD, University of Pennsylvania, Philadelphia, PA, and Carsten Müller-Tidow, MD, University Hospital Heidelberg, Heidelberg, Germany, discuss mechanisms of resistance to targeted therapies in AML, and the role of epigenetics. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://vjhemonc.podbean.com/e/iwal-2022-session-v-mechanisms-of-resistance-to-targeted-therapies-in... |