On November 4, 2021 X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a leader in the discovery and development of novel CXCR4-targeted small molecule therapeutics to benefit people with diseases of the immune system, reported financial results for the third quarter and nine months ended September 30, 2021 (Press release, X4 Pharmaceuticals, NOV 4, 2021, View Source [SID1234594391]). The company also provided a summary of the data contained within the seven abstracts submitted and accepted for presentation and/or publication at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place in Atlanta, Georgia and virtually December 11-14, 2021.

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"This has been an amazing quarter of progress for all of us at X4, as we completed enrollment in the Phase 3 trial of mavorixafor in its first indication of WHIM syndrome and are now looking ahead to sharing a broad array of clinical and scientific data in the fourth quarter that further support the potential of mavorixafor across multiple additional therapeutic areas," said Paula Ragan, Ph.D., President and Chief Executive Officer of X4. "As we continue to expand our pre-commercial activities for WHIM in anticipation of top-line data late next year, we are also working to build out our pipeline – further advancing clinical trials of mavorixafor in neutropenia and rare oncology indications, while also advancing our pre-clinical programs towards the clinic."

Key Takeaways from ASH (Free ASH Whitepaper) Abstracts Published Today

WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome:

Mavorixafor continues to show durable increases in neutrophils and lymphocytes, sustained improvements in infections and warts, and good tolerability in the ongoing Phase 2 open-label extension trial in WHIM syndrome.
Patient interviews revealed that study participants experienced good tolerability and beneficial treatment effects when dosed with mavorixafor.
Broader understanding of the clinical spectrum of WHIM syndrome and genotype/phenotype correlations have enabled assessment of novel CXCR4 variants for disease-correlation, including a newly discovered missense mutation (p.D84H) that is relatively frequent in the general population.
The D84H mutation is the first mutation identified outside of the C-terminus of the CXCR4 receptor showing gain-of-function signaling and disease phenotype; the frequency of the D84H mutation derived from broad population genomic databases robustly supports current estimates of U.S. WHIM prevalence of 1,000 to 3,500 or more.
This and other related research will be shared at the Investor Day on December 16.
Analyses of insurance claim databases using artificial intelligence indicate that the U.S. population of WHIM patients may be much larger than currently reported in the literature.
Results showed that there may be as many as 3,700 WHIM patients based on WHIM-like phenotypes described.
Data are consistent with novel genetic variant discoveries and genotype-phenotype correlations, building further confidence in estimates of potentially treatable WHIM patients in the U.S.
The company’s global Phase 3 clinical trial in WHIM syndrome (now fully enrolled) is the first double-blind, placebo-controlled, randomized trial in this patient population and the only one exploring an oral therapy. All enrolled patients had severe neutropenia and more than half are pediatric patients, illustrative of the severity and early onset of the disease. Top-line data from the trial are expected in the fourth quarter of 2022.
Chronic neutropenia and other indications:

Mavorixafor alone or in combination with other therapies is the first oral treatment to acutely and chronically increase total peripheral white blood cells (WBCs) 1.5- to 3-fold across all disease populations examined (WHIM syndrome, Waldenström’s macroglobulinemia, clear cell renal cell carcinoma, and healthy volunteers).
Further, mavorixafor’s ability to increase circulating WBCs (neutrophils, lymphocytes, and monocytes) across various disease states and in healthy individuals supports its potential utility in the treatment of patients with immunodeficiency, regardless of the presence or absence of CXCR4 mutations.
A Phase 1b trial in chronic neutropenia populations is ongoing to assess the potential of mavorixafor to treat broader neutropenias by increasing neutrophil counts, as well as other white blood cell types; initial data from this trial are expected to be presented in an ASH (Free ASH Whitepaper) poster presentation and at the Investor Day on December 16.
Waldenström’s macroglobulinemia (WM):

Additional preliminary clinical data are presented from the ongoing Phase 1b dose-escalation trial assessing the tolerability and efficacy, including clinical response rates, of mavorixafor in combination with ibrutinib in diagnosed WM patients with both MYD88 and CXCR4 mutations.
As of the abstract cutoff date of June 15, 2021, the overall response rate (minor response or better) for evaluable patients was 100% (N=8), with 4 of 8 patients achieving a major response (corresponding to >50% reduction in serum IgM) and 1 of 8 patients achieving very good partial response (corresponding to >90% reduction in serum IgM).
Additional clinical data are expected to be presented in an ASH (Free ASH Whitepaper) poster presentation and at the Investor Day on December 16.
Abstracts Accepted for Presentation and Publication at ASH (Free ASH Whitepaper)

Preliminary Clinical Response Data from a Phase 1b Study of Mavorixafor in Combination with Ibrutinib in Patients with Waldenström’s Macroglobulinemia with MYD88 and CXCR4 Mutations Poster Presentation on 12/11/2021 from 5:30 – 7:30 pm ET
Mavorixafor, an Oral CXCR4 Antagonist, for Treatment of Patients with WHIM Syndrome: Results from the Long-Term Extension of the Open-Label Phase 2 Study Poster Presentation on 12/11/2021 from 5:30 – 7:30 pm ET
Oral Administration of Mavorixafor, a CXCR4 Antagonist, Increases Peripheral White Blood Cell Counts across Different Disease States Poster Presentation on 12/12/2021 from 6:00 – 8:00 pm ET
Comprehensive in Vitro Characterization of CXCR4WHIM variants to Decipher Genotype–Phenotype Correlations in WHIM Syndrome Poster Presentation on 12/12/2021 from 6:00 – 8:00 pm ET
Characterization of a Novel Missense CXCR4 Mutation in a Patient With WHIM-like Syndrome Abstract Publication only
Application of an Artificial Intelligence/Machine Learning Model for Estimating Potential US Prevalence of WHIM Syndrome, a Rare Immunodeficiency, From Insurance Claims Data Abstract Publication only
Global Phase 3, Randomized, Placebo-Controlled Trial With Open-Label Extension Evaluating the Oral CXCR4 Antagonist Mavorixafor in Patients With WHIM Syndrome (4WHIM): Trial Design and Enrollment Abstract Publication only
Following the ASH (Free ASH Whitepaper) meeting, the company will be hosting an investor event on the morning of December 16. The call is expected to include commentary from prominent key opinion leaders (KOLs) as part of the program. Details will be forthcoming.

Third Quarter and Recent Highlights

X4 achieved a major milestone in early October, completing enrollment in the ongoing pivotal Phase 3 clinical trial (4WHIM) of mavorixafor in the treatment of patients with WHIM syndrome. Thirty-one adult and pediatric patients have been enrolled in the 4WHIM trial, which was originally designed to enroll 18-28 patients.
The company recently announced the appointment of Françoise de Craecker to the company’s Board of Directors and the recent hiring of Karolyn Park to the newly created role of Vice President, U.S. Commercial, significantly strengthening the company’s depth and breadth of commercial leadership experience in the strategic marketing of rare disease therapeutics.
The company announced the promotion of Mary DiBiase, Ph.D. to the newly created position of Chief Operating Officer, reflecting her long-standing contributions to the company and the advancement of mavorixafor into global late-stage clinical development.
Third Quarter 2021 Financial Results

Cash, Cash Equivalents & Restricted Cash: X4 had $77.7 million in cash, cash equivalents, and restricted cash as of September 30, 2021. The company continues to expect that its cash and cash equivalents will fund company operations into the fourth quarter of 2022.
Research and Development Expenses were $13.2 million for the third quarter ended September 30, 2021, as compared to $11.4 million for the comparable period in 2020. R&D expenses include $0.6 million and $1.0 million of certain non-cash expenses for the quarters ended September 30, 2021 and 2020, respectively.
General and Administrative Expenses were $5.9 million for the third quarter ended September 30, 2021, as compared to $5.6 million for the comparable period in 2020. G&A expenses include $0.9 million and $1.2 million of certain non-cash expenses for the quarters ended September 30, 2021 and 2020, respectively.
Net Loss: X4 reported a net loss of $20.2 million for the quarter ended September 30, 2021, as compared to a net loss of $17.4 million for the comparable period in 2020. Net losses include $1.5 million and $2.2 million of certain non-cash expenses for the quarters ended September 30, 2021 and 2020, respectively.
Conference Call and Webcast
X4 will host a conference call and webcast today at 9:05 a.m. ET to discuss the financial results and business highlights, as well as the abstracts accepted to this year’s ASH (Free ASH Whitepaper) Annual Meeting. The conference call can be accessed by dialing (866) 721-7655 from the United States or (409) 216-0009 internationally, followed by the conference ID: 7582968. The live webcast can be accessed on the investor relations section of X4 Pharmaceuticals’ website at www.x4pharma.com. Following the completion of the call, a webcast replay of the conference call will be available on the company website.

On November 4, 2021 Athenex, Inc., (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer and related conditions, announced today data from the ANCHOR Phase 1 study of KUR-502 to be highlighted in a poster presentation at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, being held from December 11th to December 14th, 2021 (Press release, Athenex, NOV 4, 2021, View Source [SID1234594378]). The data demonstrates that allogeneic CD19 CAR-NKT cells are well-tolerated and can mediate objective responses in B-cell relapsed/refractory non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL) patients even at the low doses tested.

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"The early safety and clinical activity data are very encouraging," said Carlos Ramos, M.D., Professor at the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children’s Hospital and Houston Methodist Hospital and Principal Investigator. "The availability of a safe and effective off-the-shelf product would be a major advance in the care of these patients, and we are looking forward to treating additional patients at higher dose levels to further evaluate KUR-502."

Dan Lang, M.D., President, Athenex Cell Therapy, Vice President, Corporate Development and Communication commented, "We are excited about these early promising results from our first-in-human allogeneic study of CD19 CAR NKT cells in heavily pre-treated patients, including two patients who had previously failed autologous CAR-T therapies. We are encouraged that we have been able to demonstrate homing of allogeneic CAR-NKT cells to tumor, which is a differentiating feature of this platform. We look forward to accelerating clinical enrollment by bringing on additional clinical sites to the current study to generate more data, and further characterize the unique features and benefits of NKT cells over other cell therapy products based on T cells and NK cells."

Allogeneic NKT Cells Expressing a CD19-specific CAR in Patients with Relapsed or Refractory B-cell Malignancies: An Interim Analysis

The primary and secondary objectives of the phase I dose-escalation trial are to assess safety and anti-tumor activity of allogeneic NKT cells engineered to co-express a CD19-specific CAR, IL-15, and shRNAs targeting HLA class I and II molecules. Patients received a single infusion of 107 (DL 1) or 3×107 (DL 2) allogeneic CAR-NKT cells per square meter of body surface area following lymphodepleting conditioning with cyclophosphamide/fludarabine.

Four patients with relapsed/refractory B-cell non-Hodgkin’s lymphoma (NHL, cohort A) were enrolled on DL 1 (NHL-1, -2, -3) and DL 2 (NHL-4), and 1 patient with relapsed acute B-lymphoblastic leukemia (ALL, cohort B) was enrolled on DL 1 (ALL-1). Allogeneic CAR-NKT cells were manufactured from the leukapheresis product of one HLA-unmatched healthy individual and cryopreserved.

The most common adverse effects observed were nausea and grade 3-4 hematologic toxicities related to the lymphodepletion chemotherapy. There were no early adverse events attributable to the cellular product except grade 1 cytokine release syndrome in one patient.

Of the 4 NHL patients, 2 had a partial response (NHL-1, -and -4) and 1 had a CR (NHL-2). The ALL patient achieved a CRi and showed no evidence of leukemia by morphology, flow cytometry, or next-generation sequencing at 4 weeks.

In vivo expansion of donor-derived NKT and CAR-NKT cells was detected in the peripheral blood of NHL-4 and ALL-1 that peaked at 1 week post-infusion in both cases as determined by flow cytometry and qPCR. While CAR-NKT cells were not detected in the peripheral blood of the first three NHL patients beyond three hours post-infusion, they were found in tumor tissues collected from the two biopsied NHL patients at up to 5 weeks post infusion. In patient NHL-2, a 2000-fold expansion of recipient NKTs with a skewed T cell receptor repertoire was also observed; this population peaked at 6 weeks post-treatment and remain elevated through 12 weeks.

About the Phase I Study of KUR-502 (Allogeneic CD19 CAR-NKT Cells) in Patients with Relapsed or Refractory B-Cell Malignancies (ANCHOR)

The phase I study is an open-label, dose-escalation study. NKT cells were isolated from the leukapheresis product of one HLA-unmatched healthy individual, transduced with the CAR, expanded ex vivo for 14 days (99.8% NKT purity), and cryopreserved. Patients received 107 (DL 1) or 3×107 (DL 2) CAR-NKT cells per square meter of body surface area following lymphodepleting conditioning with cyclophosphamide/fludarabine. Adverse events were evaluated per NCI criteria. When accessible, patients underwent core biopsies of an involved site at 2-5 weeks post-infusion. Response to therapy was assessed at 4 weeks per Lugano Criteria (for NHL) or NCCN guidelines (for ALL).

For further information about the study, visit ClinicalTrials.gov, identifier: NCT03774654.

On November 4, 2021 Geron Corporation (Nasdaq: GERN), a late-stage biopharmaceutical company focused on the development and commercialization of treatments for hematologic malignancies, reported that three abstracts related to imetelstat, the Company’s first-in-class telomerase inhibitor, have been accepted as poster presentations at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting to be held from December 11-14, 2021 (Press release, Geron, NOV 4, 2021, View Source [SID1234594377]). The abstracts are available on the ASH (Free ASH Whitepaper) website at www.hematology.org.

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"The abstracts for this year’s ASH (Free ASH Whitepaper) Meeting reflect the breadth of ongoing activity with imetelstat from pre-clinical studies in a new indication, as well as use of imetelstat as a single agent and in combination with other therapies, to analyses of clinical data supporting our Phase 3 development," said Aleksandra Rizo, M.D., Ph.D., Geron’s Chief Medical Officer. "We look forward to continued work in these areas as we expand the potential applications for imetelstat in hematologic malignancies."

Clinical Data – Lower Risk Myelodysplastic Syndromes (MDS)

Abstract Title: On-Target Activity of Imetelstat Correlates with Clinical Benefits, Including Overall Survival (OS), in Heavily Transfused Non-Del(5q) Lower Risk MDS (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESAs)

The abstract describes new analyses of data from the IMerge Phase 2 clinical trial. In the analyses, a significant correlation was observed between achieving an optimal pharmacodynamic (PD) effect in imetelstat-treated patients with durable red blood cell transfusion independence (RBC-TI). In addition, a trend of improved overall survival rate was seen in patients who achieved optimal PD effect. The authors believe these results demonstrate a potential link between imetelstat activity and clinical efficacy. Additionally, patients in IMerge Phase 2 who achieved an optimal PD effect with imetelstat treatment did not have higher rates of cytopenias or liver enzyme elevations compared to patients without an optimal PD effect.

Poster Presentation Details
Abstract: #2598
Date: Sunday, December 12, 2021
Time: 6:00 p.m. – 8:00 p.m. ET

Pre-Clinical Data – Pediatric Acute Myeloid Leukemia

Abstract Title: Imetelstat Significantly Reduces Leukemia Stem Cells in Patient-Derived Xenograft Models of Pediatric AML

The abstract reports results from pre-clinical studies of imetelstat in pediatric acute myeloid leukemia (AML) cell lines (in vitro studies) and patient derived (PDX) mouse models (in vivo studies). The efficacy of imetelstat either as a single agent or in combination with chemotherapy or azacitidine was evaluated. In cell line experiments, imetelstat treatment resulted in cell apoptosis/death of leukemia stem cells (LSCs) in a dose-dependent manner. In the in vivo studies, imetelstat treatment reduced LSC numbers and increased median survival in mice. In addition, combining imetelstat with chemotherapy or azacitidine further enhanced activity against LSCs. The authors conclude that the results of these pre-clinical studies suggest imetelstat could represent an effective therapeutic strategy for pediatric AML.

Poster Presentation Details
Abstract: #3352
Date: Monday, December 13, 2021
Time: 6:00 p.m. – 8:00 p.m. ET

Trials in Progress Poster Presentation – IMpactMF Phase 3 trial in Refractory MF

Abstracts for this category describe innovative clinical trials that have not reached their primary endpoint to provide opportunities for early engagement and collaboration amongst investigators, translational research, clinical and industry investigators, statisticians and regulators.

Abstract Title:A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat Versus Best Available Therapy (BAT) in Patients with Intermediate-2 (Int-2) or High-risk Myelofibrosis (MF) Refractory to Janus Kinase Inhibitor (JAKi)

Poster Presentation Details
Abstract: #1503
Date: Saturday, December 11, 2021
Time: 6:00 p.m. – 8:00 p.m. ET

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 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 myeloid 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 4, 2021 Magenta Therapeutics, Inc. (Nasdaq: MGTA), a clinical-stage biotechnology company developing novel medicines designed to bring the curative power of stem cell transplants to more patients, reported financial results for the third quarter ended September 30, 2021, and recent program highlights (Press release, Magenta Therapeutics, NOV 4, 2021, View Source [SID1234594376]).

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"We are pleased with our recent execution across the portfolio as we look to continue to allocate our capital efficiently to our value-creating opportunities," said Jason Gardner, D.Phil., President and Chief Executive Officer, Magenta Therapeutics. "In mid-September, we cleared the IND process for the MGTA-117 targeted conditioning program and are now conducting the clinical trial start-up activities with the continued expectation of opening the trial this year. The MGTA-145 stem cell mobilization program also continues to advance with a fully enrolled investigator-initiated trial in multiple myeloma patients, a Phase 2 clinical trial in allogeneic transplant and the expected start of a Phase 2 clinical trial evaluating mobilization and collection of stem cells from patients with sickle cell disease."

Business Highlights:

In October 2021, Magenta welcomed Jeffrey Humphrey, M.D. to its Executive Team as Chief Medical Officer.

Program Highlights:

MGTA-145 Stem Cell Mobilization and Collection

Recent and Planned Activity:

Autologous Stem Cell Transplant: Multiple Myeloma

Investigator-Initiated Phase 2 Clinical Trial Design, Topline Data and Next Steps.
Trial Design: Surbhi Sidana, M.D., Assistant Professor of Medicine in the Division of Blood and Marrow Transplantation and Cellular Therapy at Stanford University School of Medicine led this investigator-initiated, Phase 2 open-label clinical trial. The trial evaluated the ability of MGTA-145, in combination with plerixafor, to mobilize stem cells for autologous stem cell transplantation in patients with multiple myeloma.
Top-Line Clinical Data in Poster Presentation at 2021 ASH (Free ASH Whitepaper) Annual Meeting: Top line clinical data from the fully enrolled investigator-initiated clinical trial will be included in a poster presentation at the ASH (Free ASH Whitepaper) Annual Meeting, held December 11-14, 2021. As disclosed separately, the clinical data showed that eighty-eight percent (88%) of patients (22/25) treated with MGTA-145 plus plerixafor met the primary endpoint of sufficient stem cell mobilization and collection for transplant. Also, as of the time of the data submission for the ASH (Free ASH Whitepaper) meeting, all patients (18/18) transplanted with stem cells mobilized by MGTA-145 plus plerixafor successfully engrafted. MGTA-145 plus plerixafor was well tolerated.
Next Steps in Multiple Myeloma: The results from this investigator-initiated trial represent a positive step forward in the development of MGTA-145, in combination with plerixafor, as a potential first line stem cell mobilization regimen. Based on the encouraging collection and engraftment data, the company intends to explore further development of MGTA-145 in a Phase 2b clinical setting. This approach would enable a comprehensive evaluation of the multiple myeloma patient population and allow for adjustments of dosing and administration which the company, in both cases, has identified as opportunities for optimization as a result of this investigator-initiated study and the company’s other MGTA-145 development efforts.
Allogeneic Stem Cell Transplant: Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL) and Myelodysplastic Syndromes (MDS)
Phase 2 Clinical Trial and Next Steps.
Trial Design. This Phase 2 clinical trial is designed to evaluate MGTA-145 in combination with plerixafor, in the mobilization and collection of stem cells from allogeneic donors for transplant in patients with AML, ALL and MDS.
Next Steps. Based on what Magenta has learned to date from the totality of the MGTA-145 program-related clinical trial data and other relevant information, Magenta believes it has identified an opportunity to optimize certain elements of the dosing and administration of the MGTA-145 mobilization regimen. Accordingly, Magenta intends to amend the Phase 2 allogeneic clinical trial to include a higher dose of MGTA-145 that matches the dose level used in the Phase 2 multiple myeloma clinical trial.
Stem Cell Mobilization of Patients with Sickle Cell Disease in Collaboration with bluebird bio. Magenta expects to open the Phase 2 clinical trial in December 2021. The trial is designed 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 where mobilization and collection is difficult and there is a clear unmet medical need.
MGTA-117 Targeted Conditioning

Recent and Planned Activity:

Phase 1/2 Clinical Trial Start-Up Activities Ongoing. The IND for the company’s MGTA-117 antibody-drug conjugate (ADC) targeted conditioning program is active with the U.S. Food and Drug Administration (FDA). The company expects to open the multi-center Phase 1/2 clinical trial in December 2021. The Phase 1/2 trial is designed to utilize dose escalating cohorts to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of MGTA-117 as a single dose with possible anti-tumor therapeutic benefit in patients with relapsed/refractory AML and MDS. As previously disclosed, Magenta expects to work with the FDA on an ongoing basis to transition the clinical trial to the primary target population of hematopoietic stem cell (HSC) transplant-eligible patients with AML and MDS after adequate data related to the safety, pharmacokinetics and pharmacodynamics of MGTA-117 have been collected in this initial patient population. As the program progresses, Magenta also plans to explore MGTA-117 as a targeted conditioning agent prior to the delivery of gene-corrected cells associated with stem cell gene therapy.
Oral Presentation at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. As disclosed by Magenta in a separate press release, preclinical data showing that a single dose of a tool CD117 antibody drug conjugate (CD117-ADC) supports efficient engraftment of gene-modified CD34+ stem cells in a rhesus gene therapy model. The CD117-ADC utilized in this study had minimal toxicities unlike busulfan conditioning. The data will be the subject of an oral presentation at the ASH (Free ASH Whitepaper) Annual Meeting on December 13, 2021.
Financial Results:

Cash Position: Cash, cash equivalents and marketable securities as of September 30, 2021, were $192.6 million, compared to $148.8 million as of December 31, 2020. Magenta anticipates that its cash, cash equivalents and marketable securities will be sufficient to fund operations and capital expenditures into the third quarter of 2023.

Research and Development Expenses: Research and development expenses were $10.8 million in the third quarter of 2021, compared to $11.8 million in the third quarter of 2020. The decrease was driven primarily by the completion of the GMP manufacturing activities to support the IND application for MGTA-117 and future clinical trials offset by an increase in personnel related costs.

General and Administrative Expenses: General and administrative expenses were $7.5 million for the third quarter of 2021, compared to $6.6 million for the third quarter of 2020. The increase was primarily due to an increase in personnel related costs.

Net Loss: Net loss was $17.4 million for the third quarter of 2021, compared to net loss of $17.7 million for the third quarter of 2020.

On November 4, 2021 Magenta Therapeutics (Nasdaq: MGTA), a clinical-stage biotechnology company developing novel medicines designed to bring the curative power of stem cell transplants to more patients, reported positive top-line results from an investigator-initiated Phase 2 clinical trial of MGTA-145 stem cell mobilization in multiple myeloma (Press release, Magenta Therapeutics, NOV 4, 2021, View Source [SID1234594375]). The data were accepted for a poster presentation at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, to be held in Atlanta and virtually from December 11-14, 2021. Oral and poster presentations of preclinical data related to the company’s CD117 targeted conditioning program will also be made at the ASH (Free ASH Whitepaper) Annual Meeting.

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"We have made significant progress with our mobilization and targeted conditioning programs and we look forward to the presentation of the data that have been generated to support both programs," said Jason Gardner, D.Phil., President and Chief Executive Officer, Magenta Therapeutics.

Stem Cell Mobilization and Collection Program (MGTA-145)

Poster Presentation Highlighting Investigator-Initiated Phase 2 Clinical Data of MGTA-145 Stem Cell Mobilization in Multiple Myeloma:

Title: MGTA-145 + Plerixafor Provides G-CSF-Free Rapid and Reliable Hematopoietic Stem Cell Mobilization for Autologous Stem Cell Transplant in Patients with Multiple Myeloma: A Phase 2 Study (Poster #3888)

Date and Time to View Poster Presentation: Monday, December 13, 2021, 6:00pm – 8:00pm ET

Trial Design

Surbhi Sidana, M.D., Assistant Professor of Medicine in the Division of Blood and Marrow Transplantation and Cellular Therapy at Stanford University School of Medicine led this investigator-initiated, Phase 2 open-label clinical trial. The trial evaluated the ability of MGTA-145, in combination with plerixafor, to mobilize stem cells for autologous stem cell transplantation in patients with multiple myeloma. This trial had broad inclusion criteria and included the transplant-eligible population of patients with multiple myeloma who may have a variety of risk factors for mobilization.

Topline Clinical Data

Primary and Secondary Endpoints. The trial has fully enrolled 25 patients with multiple myeloma. 88% of patients (22/25) treated with MGTA-145 plus plerixafor met the primary endpoint of mobilization and collection of 2 million CD34+ stem cells per kg in up to two days of same-day mobilization and apheresis. 68% of patients (17/25) achieved the primary endpoint in a single day of dosing and collection. Three patients who did not meet the primary endpoint successfully collected hematopoietic stem cells (HSCs) with subsequent G-CSF plus plerixafor dosing and 2-3 apheresis sessions. Secondary endpoints of 4 million and 6 million CD34+ stem cells per kg in up to two days were met in 68% (17/25) and 40% (10/25) patients, respectively.
Days of Stem Cell Collection. The median number of 5.0 million CD34+ stem cells per kg were collected cumulatively over one or two days of dosing and stem cell collection. In contrast, current standard of care with G-CSF-based regimens require a minimum of five days of dosing prior to initiating stem cell collection over one to four days.
Safety Profile. The regimen of MGTA-145 and plerixafor was well tolerated. Treatment emergent pain was seen in 44% of patients (11/25). Acute, transient, MGTA-145-related grade 1 bone or musculoskeletal pain was observed in 38% of patients (9/25) shortly after MGTA-145 infusion, resolving within seven minutes for all patients.
Engraftment. All transplanted patients (18/18), evaluable as of the cutoff date, successfully engrafted. Neutrophils recovered after a median of 12 days and platelets after a median of 17.5 days, which are comparable to historical data. Red blood cell transfusion was needed in 17% of patients (3/25).
100 Day Follow-Up. All 14 transplanted patients as of the data cut-off date had completed day-100 follow up with durable engraftment.
CD34+CD90+ Cells. The collected CD34+ stem cells contain a high percentage of CD34+CD90+ cells, a stem cell population associated with multi-lineage, long-term engraftment. 74% of grafts (17/23) were negative for minimal residual disease using next generation flow cytometry.
Next Steps in Multiple Myeloma

As described in the company’s third quarter earnings release, the results from this investigator-initiated trial represent a positive step forward in the development of MGTA-145, in combination with plerixafor, as a potential first line stem cell mobilization regimen. Based on the encouraging collection and engraftment data, the company intends to explore further development of MGTA-145 in a Phase 2b clinical setting. This approach would enable a comprehensive evaluation of the multiple myeloma patient population and allow for adjustments of dosing and administration which the company, in both cases, has identified as opportunities for optimization as a result of this investigator-initiated study and the company’s other MGTA-145 development efforts.

"While Dr. Sidana and her team are collecting and analyzing additional patient-level data, these topline results are encouraging and support further development of MGTA-145." commented Dr. Jeffrey Humphrey, M.D., the company’s Chief Medical Officer. "We believe this novel mobilization regimen has the potential to replace G-CSF regimens and to enable reliable, predictable, rapid and well-tolerated mobilization of stem cells for both transplant and gene therapies."

MGTA-145 is also being evaluated for its ability to mobilize stem cells for collection from donors for allogenic transplantation in patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) in a Phase 2 clinical trial. The company is planning to open an additional Phase 2 clinical trial for mobilization and collection of stem cells for patients with sickle cell disease in December 2021.

Antibody-Drug Conjugate (ADC) Targeted Conditioning Program

Oral Presentation Showcasing Non-human Primate Data of Targeted ADC Conditioning for Gene Therapy

Title: CD117 Antibody Drug Conjugate-Based Conditioning Allows for Efficient Engraftment of Gene-Modified CD34+ Cells in a Rhesus Gene Therapy Model (Oral Abstract #560)

Presenting Author: Naoya Uchida, M.D., National Institutes of Health

Date: Sunday, December 12, 2021, 4:45pm ET

This preclinical study evaluated escalating doses of a tool CD117-ADC. As monotherapy conditioning, a single dose of the CD117-ADC allowed for efficient engraftment of gene-modified autologous stem cells in a rhesus model of gene therapy, without chemotherapy or radiation conditioning. Engraftment of gene-modified stem cells achieved with monotherapy CD117-ADC was robust and durable, equivalent to that achieved with four doses of myeloablative busulfan conditioning. Sustained gene expression of hemoglobin F was confirmed at the protein level in this CD117-ADC-conditioned rhesus transplant model of gene therapy for sickle cell disease. Compared to chemotherapy or radiation-based conditioning regimens, conditioning with monotherapy CD117-ADC could be both sufficiently potent and well tolerated to improve the safety and risk benefit profile for gene therapies that require stem cell transplantation.

Poster Presentation Highlighting Preclinical Data of Targeted ADC Conditioning Program:

Title: CD117-Targeted ADC, in Combination with Lymphodepleting Antibodies, Enables Allogeneic Hematopoietic Stem Cell Transplantation in Mice without Chemotherapy or Radiation (Poster #1682)

Presenting Author: Leanne Lanieri, M.S., Magenta Therapeutics, Inc.

Date to View Poster Presentation: Saturday, December 11, 2021, 5:30pm – 7:30pm ET

This study evaluated the combination of a tool CD117-ADC with lymphodepleting antibodies as the conditioning regimen in a murine model of allogeneic HSC transplantation. The targeted conditioning regimen enabled complete donor chimerism in a fully mismatched allogeneic HSC transplant murine model, without use of chemotherapy or radiation. Antibody-based targeted conditioning regimens could offer a more favorable risk-benefit profile over chemotherapy and radiation-based conditioning regimens. An improved risk benefit profile, in turn, could extend the curative potential of allogeneic HSC transplantation to more patients with malignant and non-malignant diseases who otherwise would not be eligible for HSC transplantation.