On November 3, 2022 Magenta Therapeutics (Nasdaq: MGTA), a clinical-stage biotechnology company developing novel medicines designed to bring the curative power of stem cell transplant to more patients, reported that it will make three presentations relating to its ongoing clinical trials at the 2022 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, to be held in New Orleans from December 10-13, 2022 and virtually (Press release, Magenta Therapeutics, NOV 3, 2022, View Source [SID1234622919]). In addition, an academic collaborator will present data from a preclinical program from Magenta’s research platform.

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"We have made significant progress in the MGTA-117 Phase 1/2 clinical trial and look forward to presenting clinical evidence at ASH (Free ASH Whitepaper) that we believe supports proof-of-mechanism for MGTA-117. We are also very encouraged by the predictive value of our MGTA-117 preclinical modeling which has closely matched our pharmacokinetics and pharmacodynamics clinical experience in the early cohorts of the ongoing study. We expect these results will collectively inform the continued development of MGTA-117, our most advanced targeted antibody-drug conjugate, to enable more patients to benefit from stem cell transplant and gene therapies," said Jason Gardner, D.Phil., President and Chief Executive Officer, Magenta Therapeutics.

MGTA-117: Antibody Drug Conjugate (ADC) Targeted Conditioning
MGTA-117 is Magenta’s most advanced targeted conditioning product candidate designed to deplete target cells prior to a patient undergoing stem cell transplant or receiving an ex vivo gene therapy product. The program is currently enrolling patients with relapsed/refractory acute myeloid leukemia (AML), and myelodysplastic syndromes (MDS), in a Phase 1/2 dose escalation clinical trial. MGTA-117 is an anti-CD117 antibody conjugated to an amanitin payload. CD117, also known as c-Kit receptor, is highly expressed on hematopoietic stem cells, progenitor cells, and leukemic cells.

Oral presentation of updated clinical data from ongoing Phase 1/2 dose escalation clinical trial
Title: MGTA-117, an Anti-CD117 Antibody-Drug Conjugated with Amanitin, in Participants with Relapsed/Refractory Adult Acute Myeloid Leukemia (AML) and Myelodysplasia with Excess Blasts (MDS-EB): Safety, Pharmacokinetics and Pharmacodynamics Initial Findings from a Phase 1/2 Study
Date: Monday, December 12, 2022, 3:30 pm CT
Abstract Summary: Magenta is conducting a multicenter, open-label, dose-escalation clinical trial of MGTA-117 in relapsed/refractory AML patients. The abstract describes full clinical data from four patients in Cohort 1 and references the enrollment of the first two patients in Cohort 2 as of the August 2nd abstract submission date. The clinical data from the four patients in Cohort 1 showed evidence that MGTA-117 (i) binds to cells expressing CD117 target, (ii) depletes target cells and (iii) clears the body rapidly with no detectable free payload. In addition, and as previously referenced, one Cohort 1 patient achieved complete remission after receiving MGTA-117 and proceeded to a conditioning regimen followed by stem cell transplant. As described in the abstract, MGTA-117 was well-tolerated with no serious adverse events deemed related to MGTA-117 and no dose-limiting toxicities. As described separately, in addition to the results described in the published abstract, Magenta will present updated available clinical data.

Poster presentation characterizing MGTA-117 Pharmacokinetic (PK) and Pharmacodynamic (PD) in Non-Human Primates (NHPs)
Title: The Pharmacokinetic and Pharmacodynamic Characterization of MGTA-117, an Anti-CD117-Amanitin Antibody-Drug Conjugate for Targeted Conditioning Prior to Transplant, in Non-Human Primates
Date: Monday, December 12, 2022, 6:00-8:00 pm CT
Abstract Summary: MGTA-117 was designed to deplete target cells via a dual-mechanism: direct cell killing from the ADC payload plus blocking of stem cell factor binding by the antibody. Stem cell factor naturally binds to CD117 and is needed for cell survival and proliferation. MGTA-117 was administered across a range of doses in primates to assess the time course of PK, PD and depletion of stem cells. At multiple dose levels, MGTA-117 showed greater than 90% depletion of stem cells in the bone marrow. All dose levels showed rapid rates of MGTA-117 clearance that, together with evidence showing robust stem cell depletion, supports the potential use of MGTA-117 to deplete target cells prior to a patient’s hematopoietic stem cell transplant or infusion of any ex vivo gene therapy product. To date, the PK and PD data and modeled projections derived from this NHP study have been predictive of MGTA-117’s clinical experience.

MGTA-145 Stem Cell Mobilization and Collection
Magenta is developing MGTA-145, in combination with plerixafor, to improve the process by which stem cells are stimulated out of the bone marrow and into the bloodstream, known as stem cell mobilization. The mobilized cells are then collected and available for transplant. This is the first step for patients and is required for the majority of transplants and stem cell gene therapies.

Poster presentation of the ongoing Phase 2 clinical study in sickle cell disease
Title: A Phase 2, Open-Label Study to Evaluate the Efficacy and Safety of MGTA-145 in Combination with Plerixafor for the Mobilization of Hematopoietic Stem Cells in Patients with Sickle Cell Anemia
Date: Monday, December 12, 2022, 6:00-8:00 pm CT
Abstract Summary: This is a Phase 2 open-label clinical trial designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of one or two doses of MGTA-145 combined with plerixafor for the mobilization of hematopoietic stem cells in patients with sickle cell disease. The primary endpoint is the total number of collected stem cells. Key exploratory endpoints include characterization of the phenotype and function of cells collected by apheresis and assessment of the potential for collected cells to undergo gene modification. The results of this clinical trial will provide direction regarding the potential of MGTA-145, in combination with plerixafor, to rapidly and safely mobilize sufficient numbers of high-quality stem cells for hematopoietic stem cell transplant in patients with sickle cell disease.

Magenta Research Platform
Magenta’s research platform is focused on discovering, engineering and advancing novel molecules, including ADCs, that target specific cells for depletion in patients receiving stem cell transplants and cell and gene therapies. Targeted depletion is intended to improve the efficacy and safety of stem cell transplant and cellular therapies by replacing or reducing the use of chemotherapy.

Oral presentation of Magenta Research ADC in a NHP transplant model (Academic Collaborator)
Title: Targeted Deletion of Activated T Cells with a Single Dose of Anti-CD137-Antibody Drug Conjugate Protects Against Acute GVHD (AGVHD) and Promotes Tolerogenic T Cell Reconstitution after Haplo-Identical Hematopoietic Stem Cell Transplantation (HSCT)
Date: Sunday, December 11, 2022, 4:30 pm CT
Abstract Summary: This collaborative preclinical study compared the outcomes of an allogeneic transplant in NHPs treated with either no graft-versus-host-disease (GVHD) prophylaxis (NoRx) or a single dose of an ADC targeting CD137 post-transplant (CD137-ADC). CD137 (4-1BB) is a cell surface target that is rapidly upregulated on activated T-cells following transplant, making this a promising drug target to prevent GVHD before it is initiated. All NHP transplant recipients receiving the ADC engrafted with donor cells demonstrating > 90% chimerism. NHPs treated with a single dose of CD137-ADC had a median survival of 97 days, which was significantly longer than the 8 days median survival in the control NoRx group. There were no treatment-related toxicities. This preclinical proof-of-concept for a CD137-based, single-dose, targeted therapy to prevent acute GVHD shows the potential of ADC-based targeted cell depletion to improve the efficacy and safety of allogeneic stem cell transplant and cell therapies.

On November 3, 2022 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported that it will present initial data from the safety lead-in portion of its ongoing SELECT-AML-1 Phase 2 clinical trial at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place December 10-13, 2022 in New Orleans, LA (Press release, Syros Pharmaceuticals, NOV 3, 2022, View Source [SID1234622918]). The SELECT-AML-1 trial is evaluating tamibarotene, Syros’ first-in-class selective retinoic acid receptor alpha (RARα) agonist, in combination with venetoclax and azacitidine in patients with newly diagnosed, unfit acute myeloid leukemia (AML) with RARA gene overexpression.

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Details of the poster presentation are as follows:

Presentation Title: Initial Results from SELECT-AML-1, a Phase 2 study of Tamibarotene in Combination with Venetoclax and Azacitidine in RARA-positive Newly Diagnosed AML Patients Ineligible for Standard Induction Chemotherapy
Session Title: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster I
Session Date & Time: Saturday, December 10, 2022, 5:30 – 7:30 pm CT (6:30 – 8:30 pm ET)
Location: Ernest N. Morial Convention Center, Hall D
Publication Number: 1444

The abstract is now available online on the ASH (Free ASH Whitepaper) Conference website at:
View Source

On November 3, 2022 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported that four abstracts related to imetelstat, a first-in-class telomerase inhibitor, have been accepted for presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place from December 10-13 in New Orleans, Louisiana (Press release, Geron, NOV 3, 2022, View Source [SID1234622917]). A fifth abstract has been published on the ASH (Free ASH Whitepaper) website and will be available in Blood. These abstracts assess the potential of imetelstat in various blood cancers, or hematologic malignancies, including lower risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), myelofibrosis (MF) and lymphoid malignancies.

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"The upcoming presentation at ASH (Free ASH Whitepaper) of the longer-term follow-up data from our Phase 2 IMerge trial showing unprecedented greater than one-year continuous transfusion independence in approximately one-third of the 38 lower risk MDS patients in the study highlights the differentiating qualities of imetelstat that could address significant unmet needs in this indication," said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron. "We look forward to reporting top-line results from the Phase 3 IMerge trial shortly after ASH (Free ASH Whitepaper), in early January 2023."

Dr. Feller continued: "Further, I am pleased to see other abstracts representing our imetelstat pipeline at ASH (Free ASH Whitepaper), demonstrating broad potential for the drug in hematologic malignancies."

Clinical Data – Lower Risk Myelodysplastic Syndromes (MDS)

Abstract #459: "Imetelstat Achieved Prolonged, Continuous Transfusion Independence in Patients With Heavily Transfused Non-Del(5q) Lower Risk MDS (LR-MDS) Relapsed/Refractory to Erythropoiesis Stimulating Agents Within the IMerge Phase 2 Study"

Oral Presentation on December 11, 2022, at 5pm CT

The abstract describes the 29% (11/38) of patients in Phase 2 IMerge who achieved a greater than one-year sustained transfusion independence (TI). These transfusion dependent patients were treated with imetelstat for a median of 126.1 weeks (range: 70.1-168.1), and their median duration of TI was 92.4 weeks (95% CI: 69.6, 92.4). After a median follow-up of 51.5 months, median progression-free survival (PFS) was 34.2 months (95% CI: 25.1, 39.2), median overall survival (OS) was 57.0 months (95% CI: 29.4, NE), and none of these patients progressed to AML.

Mutation data was available for the majority of the patients who achieved greater than 1-year sustained TI, and 89% had any reduction in SF3B1 variant allele frequency (VAF) while 56% achieved greater than or equal to 50% VAF reduction. Reduction in VAF correlated with longer TI duration and shorter time to onset of TI.

Safety findings for these patients were consistent with the overall population, and the most frequent adverse events were reversible thrombocytopenia and neutropenia.

The abstract concludes that the greater than one-year periods of transfusion independence observed in these patients represents relief from iron overload and other transfusion associated complications, and decreased demand on healthcare resources. Furthermore, durable TI, meaningful reduction in mutational burden, and good survival post-ESA suggest imetelstat may have disease-modifying activity.

Non-Clinical Data – Acute Myeloid Leukemia

Abstract #201: "Imetelstat-Mediated Alterations in Lipid Metabolism to Induce Ferroptosis As Therapeutic Strategy for Acute Myeloid Leukemia"

Oral Presentation on December 10, 2022, at 2:30pm CT

This abstract describes results from non-clinical in vitro and animal in vivo experiments of imetelstat using AML cell lines and AML patient samples. Conducted by Geron collaborators in Australia, Germany and the U.S., the experiments found that imetelstat promotes the formation of polyunsaturated fatty acids-containing phospholipids which cause excessive levels of lipid peroxidation and oxidative stress in AML cells, potentially leading to programmed cell death. The abstract concludes that this mechanistic insight could be leveraged to develop an optimized therapeutic strategy using oxidative stress-inducing chemotherapy to sensitize patient samples to imetelstat causing significant delay of relapse in AML.

Trials in Progress Poster Presentations – Myelofibrosis

Abstract #3037: "MYF3001: A Randomized Open Label, Phase 3 Study to Evaluate Imetelstat Versus Best Available Therapy in Patients with Intermediate-2 or High-Risk Myelofibrosis Relapsed/Refractory to Janus Kinase Inhibitor"

Poster Presentation on December 11, 2022, 6-8pm CT

MYF3001, or IMpactMF (NCT04576156), is a Phase 3, randomized (2:1), open label multicenter study of imetelstat compared with best available therapy (BAT) in approximately 320 adult patients with Intermediate-2 or High-Risk MF whose disease has relapsed after or is refractory to janus associated kinase inhibitor, or JAKi, treatment. The primary endpoint is overall survival and secondary endpoints include symptom and spleen response rates at Week 24, progression-free survival, clinical response assessments, time to and duration of response, reduction in degree of bone marrow fibrosis, safety, pharmacokinetics and patient-reported outcomes. Biomarkers and mutation analyses will be performed to evaluate the impact of imetelstat on reduction/depletion of malignant clones. Approximately 180 sites are planned in North and South America, Europe, Middle East, Australia and Asia. The study is actively enrolling.

Abstract #1713: "An Open Label, Dose Escalation and Expansion, Phase 1/1b Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of Imetelstat in Combination with Ruxolitinib in Patients with Intermediate-1, Intermediate-2 or High-Risk Myelofibrosis"

Poster Presentation on December 10, 5:30-7:30pm CT

MYF1001, or IMproveMF (NCT05371964), is a single arm, open label, two-part Phase 1 study to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of imetelstat in combination with ruxolitinib as a frontline treatment in patients with Intermediate-1 or -2 or High-risk MF (frontline MF). In both parts, patients will receive ruxolitinib followed by imetelstat. Part 1 will enroll up to 20 frontline MF patients who, at the time of enrollment, have received an optimized dose of ruxolitinib, to which imetelstat treatment will be added at increasing dose levels based on safety and tolerability. The primary purpose of Part 1 is to identify a safe dose for treating frontline MF patients with a combination of imetelstat and ruxolitinib. If a safe dose is identified in Part 1, participants in Part 2 will be JAK inhibitor naïve and will receive treatment with ruxolitinib after screening and enrollment at a starting dose based on standard-of-care or local prescribing information. Treatment with single-agent ruxolitinib will continue for at least 12 weeks, including four consecutive weeks at a stable dose prior to the addition of imetelstat. Part 2 is designed to confirm the safety profile of imetelstat in combination with ruxolitinib and to evaluate for preliminary clinical activity of the combination. Part 1 is open for enrollment, with approximately three sites planned in North America.

Non-Clinical Data – Lymphoid Malignancies

Published online in Blood: "Pharmacological Inhibitory Effect of Imetelstat, A Novel Human Telomerase Inhibitor in Diffuse Large B-cell Lymphoma and Peripheral T-Cell Lymphoma"

This abstract describes the characterization of telomerase activity and telomere length, as well as results from in vitro experiments of imetelstat, on a panel of diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphomas (PTCL) cell lines. This work was conducted by Geron collaborators at MD Anderson Cancer Center. These in vitro experiments found that imetelstat reduced cell viability and increased apoptosis in DLBCL cell lines. In contrast, imetelstat single-agent activity on cell viability was limited in PTCL cell lines, even though a time and dose-dependent reduction of telomerase activity were noted. The greater inhibitory effect of imetelstat in DLBCL, compared to PTCL cell lines, may be attributed to higher telomerase activity observed in DLBCL compared to PTCL cells. Furthermore, the PTCL cell lines had a ~7.3 fold longer telomere length than DLBCL cell lines, which potentially also influenced the lower response to imetelstat.

The abstracts are available on the ASH (Free ASH Whitepaper) website at www.hematology.org.

In accordance with ASH (Free ASH Whitepaper) policies, abstracts submitted to the ASH (Free ASH Whitepaper) Annual Meeting are embargoed from the time of submission. To be eligible for presentation at the ASH (Free ASH Whitepaper) Annual Meeting, any additional data or information to be presented at the Annual Meeting may not be made public before the presentation. The presentations and posters will be available at www.geron.com/r-d/publications following the ASH (Free ASH Whitepaper) Annual Meeting presentations.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from Phase 2 clinical trials provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment.

On November 3, 2022 ALX Oncology Holdings Inc., ("ALX Oncology") (Nasdaq: ALXO), a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint pathway, reported the Company will be presenting clinical data from the dose escalation portion of ASPEN-05, a Phase 1 study evaluating evorpacept in combination with azacitidine and venetoclax for the treatment of acute myeloid leukemia ("AML") at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) ("ASH") Annual Meeting held December 10-13, 2022 in New Orleans, Louisiana (Press release, ALX Oncology, NOV 3, 2022, View Source [SID1234622916]).

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The accepted abstract is listed below and is now available online on the ASH (Free ASH Whitepaper) website: View Source

Poster Presentation Details

Title: Evorpacept (ALX148), a CD47-Blocking Myeloid Checkpoint Inhibitor, in Combination with Azacitidine and Venetoclax in Patients with Acute Myeloid Leukemia (ASPEN-05): Results from Phase 1a Dose Escalation Part

Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III

Presentation Date and Location: Monday, December 12, 2022, 6:00pm – 8:00pm CT, Ernest N. Morial Convention Center, Hall D

Publication Number: 4076

On November 3, 2022 Imago BioSciences, Inc. ("Imago") (Nasdaq: IMGO), a clinical stage biopharmaceutical company discovering and developing new medicines for the treatment of myeloproliferative neoplasms (MPNs) and other bone marrow diseases, reported two abstracts have been accepted for oral presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, to be held December 10-13, 2022 (Press release, Imago BioSciences, NOV 3, 2022, View Source [SID1234622915]).

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ASH 2022 Presentation Details:

Oral Presentation Title: "A Phase 2 Study of the LSD1 Inhibitor Bomedemstat (IMG-7289) for the Treatment of Essential Thrombocythemia (ET)"
Session Name: Myeloproliferative Syndromes: Clinical and Epidemiological: Novel Therapies and Surrogate Endpoints in ET and PV
Presentation Date/Time: Monday, December 12, 2022, at 11:45 AM ET
Location: Ernest N. Morial Convention Center, 217-219
Presenting Author: Harinder Gill, Queen Mary Hospital University of Hong Kong

Poster Presentation Title: "A Phase 2 Study of the LSD1 Inhibitor Bomedemstat (IMG-7289) for the Treatment of Advanced Myelofibrosis (MF): Updated Results and Genomic Analyses"
Session Name: Myeloproliferative Syndromes: Clinical and Epidemiological: Poster III
Presentation Date/Time: Monday, December 12, 2022, at 7:00 PM ET
Location: Ernest N. Morial Convention Center, Hall D
Presenting Author: Kristen Pettit, University of Michigan