On November 3, 2022 Genmab A/S (Nasdaq: GMAB) reported that 19 abstracts evaluating various investigational medicines in its pipeline have been accepted for presentation at the 64th Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper), being held at the Ernest N. Morial Convention Center in New Orleans, Louisiana, and virtually, December 10-13 (Press release, Genmab, NOV 3, 2022, View Source [SID1234622922]). The presentations will include four oral and six poster presentations highlighting data from several clinical trials evaluating the safety and efficacy of epcoritamab (DuoBody-CD3xCD20), an investigational subcutaneous IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology, alone or in combination for the treatment of patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL), R/R follicular lymphoma (FL), previously untreated FL and Richter’s syndrome.

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Additionally, abstracts evaluating two investigational medicines in Genmab’s early pipeline have been accepted for presentation, including the first-in-human data from the phase 1/2 trial evaluating GEN3014 (HexaBody-CD38), an investigational novel human CD38 monoclonal antibody, in patients with R/R multiple myeloma (MM). In addition, preclinical data from a novel drug candidate GEN3017 (DuoBody-CD3xCD30) will also be presented.

All abstracts accepted for presentation have been published on the ASH (Free ASH Whitepaper) website.

Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration. The companies are committed to evaluating epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of B-cell malignancies, including an ongoing phase 3, open-label, randomized clinical trial evaluating epcoritamab as a monotherapy in patients with relapsed/refractory LBCL, including DLBCL (NCT: 04628494) and a phase 3, open-label randomized clinical trial evaluating epcoritamab in combination in patients with relapsed/refractory follicular lymphoma (FL) (NCT: 05409066).

"As part of our commitment to the blood cancer community, we continue to advance our research and innovative technologies in an effort to develop differentiated therapies with the goal of transforming the future of treatment for patients," said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab. "The robust data being presented at this year’s American Society of Hematology (ASH) (Free ASH Whitepaper) meeting are encouraging and support the potential of epcoritamab to become a core therapy for B-cell malignancies."

2022 R&D Update and ASH (Free ASH Whitepaper) Data Review
On Monday, December 12, at 8:00 PM EST (7:00 PM CST / 1:00 AM GMT), Genmab will host its 2022 R&D Update and ASH (Free ASH Whitepaper) Data Review. The event will be conducted and webcast live. Details, including the webcast link and registration can be found here. This meeting is not an official program of the ASH (Free ASH Whitepaper) Annual Meeting.

Abstracts accepted at ASH (Free ASH Whitepaper):

Epcoritamab (DuoBody-CD3xCD20)

Abstract Number Abstract Title Type of Presentation Date/Time of Presentation
348 Subcutaneous Epcoritamab in Patients with Richter’s Syndrome: Early Results from Phase 1b/2 Trial (EPCORE CLL-1). Kater et. al. Oral Saturday, December 10, 4:00 PM – 5:30 PM
443 Subcutaneous Epcoritamab + R-DHAX/C in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma Eligible for Autologous Stem Cell Transplant: Updated Phase 1/2 Results. Abrisqueta et. al. Oral Sunday, December 11, 9:30 AM – 11:00 AM
609 Subcutaneous Epcoritamab with Rituximab + Lenalidomide in Patients with Relapsed or Refractory Follicular Lymphoma: Phase 1/2 Trial Update. Falchi et. al. Oral Sunday, December 11, 4:30 PM – 6:00 PM
611 Subcutaneous Epcoritamab in Combination with Rituximab + Lenalidomide (R2) for First-Line Treatment of Follicular Lymphoma: Initial Results from Phase 1/2 Trial. Falchi et. al. Oral Sunday, December 11, 4:30 PM – 6:00 PM
4251 Epcoritamab Monotherapy Provides Deep and Durable Responses Including Minimal Residual Disease (MRD) Negativity: Novel Subgroup Analyses in Patients with Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL). Phillips et. al. Poster Monday, December 12, 6:00 PM – 8:00 PM
3580 Improvements in Lymphoma Symptoms and Health-related Quality of Life in Patients with Relapsed or Refractory Large B-cell Lymphoma Treated with Epcoritamab. Phillips et. al. Poster Sunday, December 11, 6:00 PM – 8:00 PM
4912 Indirect Comparison of the Efficacy of Subcutaneous Epcoritamab Dose Expansion (EPCORE NHL-1 Trial) in Patients With Relapsed or Refractory Large B-cell Lymphoma. Salles et. al. Poster Monday, December 12, 6:00 PM – 8:00 PM
2874 Deep peripheral T cell subset immune-profiling in relapse/refractory non-Hodgkins lymphoma (NHL): Evaluation of baseline samples from the Epcoritamab 3013-01 trial. Blum et. al. Poster Sunday, December 11, 6:00 PM – 8:00 PM
2859 Transcriptomic Comparison of Non-Hodgkin Lymphomas in Relapsed/Refractory versus Newly Diagnosed Patients with Single Slides. Jabado et. al. Poster Sunday, December 11, 6:00 PM – 8:00 PM
1663 Phase 1b Trial of Subcutaneous Epcoritamab Among Pediatric Patients With Relapsed or Refractory Aggressive Mature B-Cell Neoplasms. Cairo et. al. Poster Saturday, December 10, 5:30 PM – 7:30 PM
4182 Evaluation of Epcoritamab and Rituximab Combination in Preclinical Models of B-cell non-Hodgkin’s Lymphoma (NHL). Epling-Burnette et. al. Poster Monday, December 12, 6:00 PM – 8:00 PM
4206 Phase 3 Trial of Subcutaneous Epcoritamab in Combination With Rituximab and Lenalidomide (R2) vs R2 Without Epcoritamab Among Patients With Relapsed or Refractory Follicular Lymphoma (EPCORE FL-1). Falchi et. al. Poster Monday, December 12, 6:00 PM – 8:00 PM
4271 Phase 2 Trial to Evaluate Safety of Subcutaneous Epcoritamab Monotherapy in the Outpatient Setting Among Patients With Relapsed or Refractory Diffuse Grade 1–3a Large B-Cell and Follicular Lymphoma. Sharman et. al. Poster Monday, December 12, 6:00 PM – 8:00 PM
5524 Assessing Safety, Tolerability, and Efficacy of Subcutaneous Epcoritamab in Novel Combinations with Anti-Neoplastic Agents in Patients with Non-Hodgkin Lymphoma in a Phase 1b/2, Open-Label Study. Sehn et. al. Publication NA
GEN3014 (HexaBody-CD38)

Abstract Number Abstract Title Type of Presentation Date/Time of Presentation
3254 Preliminary Dose-Escalation Results From a First-in-Human Phase 1/2 Study of GEN3014 (HexaBody-CD38) in Patients (pts) With Relapsed or Refractory (R/R) Multiple Myeloma (MM). Spencer et. al. Poster Sunday, December 11, 6:00-8:00 PM
GEN3017 (DuoBody-CD3xCD30)

Abstract Number Abstract Title Type of Presentation Date/Time of Presentation
1366 DuoBody-CD3xCD30 shows potent preclinical anti-tumor activity in vitro in CD30+ hematologic malignancies. Oostindie et. al. Poster Sunday, December 11, 6:00 PM – 8:00 PM
Real-World Evidence

Abstract Number Abstract Title Type of Presentation Date/Time of Presentation

2978 Real-World Outcomes in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma Treated with Standard of Care: a COTA Database Analysis. Ip et. al. Poster Sunday, December 11, 6:00 PM – 8:00 PM
2296 Treatment Patterns and Outcomes in Patients With Follicular Lymphoma Receiving at Least 3 Lines of Therapy: a Real-World Evaluation in the United States. Phillips et. al. Poster Saturday, December 10, 5:30 PM – 7:30 PM
2215 Health Care Resource Utilization and Costs of CAR T Therapy in Patients With Large B-Cell Lymphoma: A Retrospective US Claims Database Analysis. Davies et. al. Poster Saturday, December 10, 5:30 PM – 7:30 PM
About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response towards target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B-cells and induces T cell mediated killing of CD20+ cells.i CD20 is expressed on B-cells and a clinically validated therapeutic target in many B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.ii,iii

On November 3, 2022 Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported that clinical data from expansion cohorts in its Phase 1 study of plamotamab, a CD20 x CD3 bispecific antibody, in patients with relapsed or refractory non-Hodgkin’s lymphoma will be presented in a poster session during the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in New Orleans, Louisiana on Monday, December 12, 2022 (Press release, Xencor, NOV 3, 2022, View Source [SID1234622921]).

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"Plamotamab continues to be generally well tolerated and demonstrates encouraging clinical activity in our recommended intravenous dosing regimen," said Allen Yang, M.D., Ph.D., senior vice president and chief medical officer at Xencor. "Along with Janssen scientists, we plan to advance plamotamab as part of highly active chemotherapy-free regimens across B-cell cancers, importantly with tumor-selective, co-stimulatory CD28 bispecific antibodies. Xencor’s first combination study, evaluating plamotamab in combination with tafasitamab plus lenalidomide, is enrolling patients with advanced, aggressive lymphoma."

Expansion cohorts in the Phase 1 study are actively recruiting patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) and are dosing using the proposed intravenous recommended Phase 2 regimen to evaluate the safety and efficacy of plamotamab monotherapy. The recommended dose (RD) was previously identified as an intravenous, 50 mg flat dose every two weeks after step-up dosing during the first two cycles of treatment. Subcutaneous administration of plamotamab is currently being incorporated into the study.

Key Highlights from the Abstract

The accepted abstract with data from the study is accessible through the ASH (Free ASH Whitepaper) website. Updated results will be shared at the ASH (Free ASH Whitepaper) Annual Meeting.

At data cut off on July 25, 2022, 36 patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL) had been enrolled on or before April 1, 2022 and received the RD. Patients had a median age of 67 years and had received a median of 4 prior therapies. At baseline, 11.1% of patients had stage III disease, and 69.4% had stage IV disease. Additionally, 50% of patients received CAR-T as a prior therapy.

The safety analysis included all 36 patients. The most common adverse event (AE) was cytokine release syndrome (CRS), which occurred in 72.2% of patients, with no patients experiencing Grade 3 or 4 CRS. Grade 3 AEs affecting greater than 10% of patients included anemia (19.4%), neutropenia (16.7%), neutrophil count decrease (16.7%) and thrombocytopenia (11.1%). AEs leading to plamotamab discontinuation occurred in five patients (13.9%).

The efficacy analysis included 25 evaluable patients at the RD. In patients with diffuse large B-cell lymphoma (DLBCL), the overall response rate (ORR) was 47.4% (9/19), and the complete metabolic response/complete response (CMR/CR) rate was 26.3% (5/19). In patients with follicular lymphoma, the ORR was 100% (6/6), and the CMR/CR rate was 50% (3/6).

Prior CAR-T therapy was received by 18 patients, and 13 patients, all with DLBCL, were evaluable for efficacy. The ORR for patients with prior CAR-T therapy was 46.2% (6/13), and the CMR/CR rate was 30.8% (4/13).

An analysis of the plamotamab exposure-response (ER) relationship from the dose-escalation portion of the Phase 1 study examined IL6 levels, CRS incidence, high-grade AEs and ORR. The ER analysis showed that during step-up dosing, the ratio of post-dose maximum plamotamab concentration (Cmax) to minimum pre-dose concentration (Ctrough) predicted CRS events, but in contrast, once the target dose was reached, there was no relationship of exposure to CRS. This analysis provides guidance for improving dosing regimens in future clinical studies of plamotamab.

Presentation Details

Abstract 4262, "A Phase 1 Study of Plamotamab, an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Non-Hodgkin’s Lymphoma: Recommended Dose Safety-Efficacy Update and Escalation Exposure-Response Analysis"
Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster III
Date & Time: Monday, December 12, 2022. 6:00 – 8:00 p.m. CST
Location: Ernest N. Morial Convention Center, Hall D
About Plamotamab

Plamotamab is an investigational tumor-targeted XmAb bispecific antibody that contains both a CD20 binding domain and a cytotoxic T-cell binding domain (CD3). CD20 is highly expressed across a range of B-cell tumors, including non-Hodgkin lymphoma (NHL). Engagement of CD3 by plamotamab activates T cells for highly potent and targeted killing of CD20-expressing tumor cells.

Safety and anti-tumor activity from the ongoing Phase 1 clinical study has indicated that plamotamab was generally well tolerated and demonstrated encouraging clinical activity as a monotherapy. Plamotamab is also being evaluated in a Phase 2 study, in combination with tafasitamab plus lenalidomide, in patients with relapsed or refractory diffuse large B-cell lymphoma. The study consists of two parts, a safety run-in intended to establish the safety of the triple combination and a two-arm, open-label cohort where patients will be randomized to receive either the triple combination or tafasitamab plus lenalidomide.

Xencor has entered an exclusive collaboration and worldwide license agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize plamotamab and novel XmAb B-cell targeting bispecific antibodies that are designed to conditionally activate T cells through the CD28 co-stimulatory receptor.

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 financial results for the third quarter ending September 30, 2022, and recent program highlights (Press release, Magenta Therapeutics, NOV 3, 2022, View Source [SID1234622920]).

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"We are building momentum in the MGTA-117 clinical trial with new clinical results and are making progress across our pipeline, including our second targeted conditioning program CD45-ADC," said Jason Gardner, President and Chief Executive Officer of Magenta Therapeutics, Inc. "In the MGTA-117 Phase 1/2 clinical trial, we continue to enroll and generate clinical data in higher-dose cohorts. Our preclinical work has been particularly helpful in predicting our clinical experience in these early dose cohorts regarding MGTA-117 activity at different exposure levels and the overall tolerability profile. We look forward to presenting available clinical data at ASH (Free ASH Whitepaper) and using our data to support interactions with regulators as we plan to advance MGTA-117 to stem cell transplant-eligible patients and into gene therapy."

Program Highlights:
MGTA-117 Phase 1/2 Clinical Trial Progression and Data Disclosure Expectations
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.

Enrollment Progress. Magenta has completed enrollment in Cohort 1 and Cohort 2. In addition, Magenta has enrolled a sufficient number of patients to complete Cohort 3, provided that the patients complete their respective dose-limiting toxicity (DLT) observation periods. No serious adverse events have been deemed to be related to MGTA-117, and no dose-limiting toxicities have been observed to date. Our clinical experience has confirmed that patients with relapsed/refractory AML are at high risk for multiple disease complications, including susceptibility to infection, all of which can rapidly progress at any time leading to severe morbidity or mortality. All enrolled patients have contributed data to the clinical trial independent of the completion of the DLT period.
Proof-of-Mechanism. Available clinical data, including new data since the ASH (Free ASH Whitepaper) abstract submission in August 2022, support proof-of-mechanism for MGTA-117 due to evidence of its ability to bind CD117-expressing cells, deplete CD117-expressing cells, clear the body rapidly and be well-tolerated.
Regulatory Plans. Magenta has initiated requests for formal engagement with multiple regulatory authorities for the purpose of transitioning the clinical program into transplant-eligible AML and MDS patients. The pending regulatory interactions are expected to focus on MGTA-117’s clinical data relating to target binding, drug clearance and stability and tolerability across multiple dose levels. All available clinical data will be used to support these regulatory interactions, as well as the predictive preclinical modeling in non-human primates that has closely matched our clinical experience to date.
Gene Therapy. Magenta expects data from the Phase 1/2 trial to also inform clinical development planning and enable regulatory engagements for MGTA-117 as a potential monotherapy prior to patients undergoing autologous ex vivo gene therapy. Magenta has existing clinical collaborations with gene therapy companies and anticipates entering into additional collaborations as data progresses.
ASH Presentations. As disclosed separately, Magenta will present clinical and preclinical data at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2022. The MGTA-117 clinical presentation will include data on pharmacokinetics, pharmacodynamic activity and the tolerability of MGTA-117. In light of the need to collect and finalize complete Cohort 3 data, Magenta currently anticipates presenting Cohort 1 and Cohort 2 clinical data at ASH (Free ASH Whitepaper). Any data not included in the ASH (Free ASH Whitepaper) presentation is anticipated to be available at a scientific conference in Q1 2023.
CD45-Antibody Drug Conjugate (ADC): Second Targeted Conditioning Program
Magenta’s CD45-ADC is designed to selectively target and deplete both stem cells and immune cells and is intended to replace the use of chemotherapy and radiation-based conditioning prior to stem cell transplant in patients with blood cancers and autoimmune diseases.

Magenta has completed a dose-ranging toxicology preclinical study successfully with no unexpected findings. The data inform dosing for a Good Laboratory Practices toxicology study intended to support a planned Investigational New Drug (IND) application.
Manufacturing and other IND-enabling activities are ongoing, and Magenta is preparing for regulatory interactions and clinical development activities.
Magenta expects to provide a further update on the CD45-ADC program in December 2022.
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 released 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.

Magenta, in partnership with bluebird bio, has initiated a Phase 2 clinical trial in sickle cell disease to evaluate the utility of MGTA-145, in combination with plerixafor, for the mobilization and collection of stem cells in patients with sickle cell disease. Mobilization and collection are difficult in sickle cell disease patients where granulocyte colony-stimulating factor (GCSF) cannot be used, and there is a clear unmet medical need.
Magenta anticipates generating initial data from this clinical trial in December 2022 followed by a more comprehensive data set in H1 2023.
Financial Results:
Cash Position: Cash, cash equivalents and marketable securities as of September 30, 2022, were $128.3 million, compared to $176.9 million as of December 31, 2021. The September cash balance includes gross proceeds of $3.0 million from our "at-the-market" facility. Magenta anticipates that its cash, cash equivalents and marketable securities will be sufficient to fund its current operational plan into Q2 2024.

Research and Development Expenses: Research and development expenses were $11.2 million in the third quarter of 2022, compared to $10.8 million in the third quarter of 2021. The increase was driven primarily by higher preclinical and manufacturing costs to support our IND-enabling studies for CD45-ADC, offset by a decrease in clinical trial costs related to our mobilization program.

General and Administrative Expenses: General and administrative expenses were $6.1 million for the third quarter of 2022, compared with $7.5 million in the third quarter of 2021. The decrease was primarily due to a decrease in stock-based compensation.

Net Loss: Net loss was $16.1 million for the third quarter of 2022, compared to net loss of $17.4 million for the third quarter of 2021.

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