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.

On November 4, 2021 Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on creating and delivering engineered cells as medicines, reported that data will be presented during four poster presentations at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, to be held both in person in Atlanta, GA and virtually from Saturday, December 11 to Tuesday, December 14, 2021 (Press release, Sana Biotechnology, NOV 4, 2021, View Source [SID1234594374]).

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"We are excited to share data at ASH (Free ASH Whitepaper) that showcase scientific advancements from our in vivo CAR T and ex vivo allogeneic CAR T cell programs," said Steve Harr, Sana’s President and CEO. "These presentations and publications mark the growth of our science and our continued progress toward the clinic, as we intend to file our first IND as early as next year. We celebrate our scientists as they work toward our mission of creating and delivering engineered cells as medicines for patients."

Data on the progress of several of Sana’s programs were outlined in abstracts for poster presentations, which were made available to the public online today. Information about when the full posters will be available to ASH (Free ASH Whitepaper) conference participants is outlined below.

Engineered hypoimmune allogeneic CAR T cells exhibit innate and adaptive immune evasion even after sensitization in humanized mice and retain potent anti-tumor activity

Abstract 1690 (Poster Presentation)
Session Name: 703. Cellular Immunotherapies: Basic and Translational: Poster I
The session opens for viewing on Saturday, December 11, 2021, at 9:00 a.m. ET. Presentations are on Saturday, December 11, 2021, from 5:30 to 7:30 p.m. ET for in-person participants in the Georgia World Congress Center, Hall B5.
Presenter: Sonja Schrepfer
In addition, this abstract will be published online in the November supplemental issue of Blood, the journal of the American Society of Hematology (ASH) (Free ASH Whitepaper).
In vivo delivery of a CD20 CAR using a CD8-targeted fusosome in Southern pig-tail macaques (M. nemestrina) results in B cell depletion

Abstract 2769 (Poster Presentation)
Session Name: 703. Cellular Immunotherapies: Basic and Translational: Poster II
The session opens for viewing on Sunday, December 12, 2021, at 9:00 a.m. ET. Presentations are on Sunday, December 12, 2021, from 6:00 to 8:00 p.m. ET for in-person participants in the Georgia World Congress Center, Hall B5.
Presenter: Terry Fry
In addition, this abstract will be published online in the November supplemental issue of Blood, the journal of the American Society of Hematology (ASH) (Free ASH Whitepaper).
CD4-targeted fusosomes are capable of transducing resting T helper cells to generate highly potent CAR T cells

Abstract 2942 (Poster Presentation)
Session Name: 703. Cellular Immunotherapies: Basic and Translational: Poster II
The session opens for viewing on Sunday, December 12, 2021, at 9:00 a.m. ET. Presentations are on Sunday, December 12, 2021, from 6:00 to 8:00 p.m. ET for in-person participants in the Georgia World Congress Center, Hall B5.
Presenter: Christie Ciarlo
In addition, this abstract will be published online in the November supplemental issue of Blood, the journal of the American Society of Hematology (ASH) (Free ASH Whitepaper).
Specificity of CD8-targeted fusosomes in human PBMCs using single cell RNA and T cell receptor sequencing

Abstract 3983 (Poster Presentation)
Session Name: 801. Gene Therapies: Poster III.
The session opens for viewing on Monday, December 13, 2021, at 9:00 a.m. ET. Presentations are on Monday, December 13, 2021, from 6:00 to 8:00 p.m. ET for in-person participants in the Georgia World Congress Center, Hall B5.
Presenter: Hina Iftikhar
In addition, this abstract will be published online in the November supplemental issue of Blood, the journal of the American Society of Hematology (ASH) (Free ASH Whitepaper).
Abstracts are available online on the ASH (Free ASH Whitepaper) meeting website as of November 4, 2021, at 9:00 a.m. ET. Learn more at View Source

On November 4, 2021 Genmab A/S (Nasdaq: GMAB) reported that multiple abstracts evaluating several investigational medicines in the company’s pipeline, or created using Genmab’s innovative drug development platforms, will be presented at the 63rd Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper), being held at the Georgia World Congress Center, in Atlanta, GA, and virtually, December 11-14. The presentations will include data from the phase 1b/2 EPCORE NHL-2 clinical trial evaluating the safety and preliminary efficacy of epcoritamab (DuoBody-CD3xCD20) in various combinations for the treatment of patients with B-cell non-Hodgkin lymphoma (NHL). In addition, preliminary data from the phase 1b/2 EPCORE CLL-1 clinical trial, evaluating epcoritamab in patients with relapsed, refractory chronic lymphocytic leukemia (CLL), will be presented. Results from more than 20 clinical trials evaluating Janssen Biotech, Inc. (Janssen)’s daratumumab, the subcutaneous formulation of daratumumab, and Janssen’s bispecific programs leveraging Genmab’s DuoBody technology platform, will be presented.

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

Epcoritamab is being co-developed by Genmab and AbbVie (NYSE: ABBV). Daratumumab is being developed by Janssen under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab, and the companies have a research and license agreement to create and develop bispecific antibodies using Genmab’s DuoBody technology platform.

"The data being presented at this year’s ASH (Free ASH Whitepaper) represent our focus on harnessing the power of antibodies to develop differentiated cancer treatments and our commitment to delivering new therapeutic options to patients through our own research and development and through industry partnerships," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "We are especially encouraged by the data from the early-stage epcoritamab clinical trials and look forward to seeing results from additional studies."

On Tuesday, December 14, at 2:00 PM EST (8:00 PM CET / 7:00 PM GMT), Genmab will host its 2021 Virtual R&D Update and ASH (Free ASH Whitepaper) Data Review. The event will be webcast live. Details, including the webcast link, will be available on Genmab’s website, www.genmab.com. This meeting is not an official program of the ASH (Free ASH Whitepaper) Annual Meeting.

Abstracts accepted for presentation at ASH (Free ASH Whitepaper) include:

Epcoritamab (DuoBody-CD3xCD20):

Subcutaneous Epcoritamab in Combination with R-CHOP in Patients with Previously Untreated High-Risk Diffuse Large B-cell Lymphoma: Preliminary Results from a Phase 1/2 Trial

Subcutaneous Epcoritamab in Combination with R2 (Rituximab and Lenalidomide) in Patients with Relapsed or Refractory Follicular Lymphoma: Preliminary Results from a Phase 1/2 Trial

Subcutaneous Epcoritamab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Preliminary Results from the EPCORE CLL-1 Trial
Phase 3 Trial (EPCORE DLBCL-1) of Epcoritamab versus Standard of Care in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Daratumumab:

Daratumumab (DARA) with Bortezomib, Thalidomide, and Dexamethasone (VTd) in Transplant-Eligible Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM): Analysis of Minimal Residual Disease (MRD) Negativity in CASSIOPEIA Part 1 and Part 2
Efficacy of Daratumumab, Lenalidomide, and Dexamethasone Based on Lenalidomide Starting Dose in Transplant-ineligible Patients With Newly Diagnosed Multiple Myeloma and Impaired Renal Function From the Phase 3 MAIA Study
Subcutaneous Daratumumab With Bortezomib, Cyclophosphamide, and Dexamethasone (VCd) in Patients With Newly Diagnosed Light Chain (AL) Amyloidosis: 18-month Landmark Analysis of the Phase 3 ANDROMEDA Study
Pomalidomide and Dexamethasone With or Without Subcutaneous Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma: Updated Analysis of the Phase 3 APOLLO Study
Subcutaneous Daratumumab with Rapid Corticosteroid Tapering in Relapsed or Refractory Multiple Myeloma Patients: Part 3 Update of the Open-label, Multicenter, Phase 1b PAVO Study
Progression-free Survival Outcomes by Response Status for Bortezomib, Melphalan, and Prednisone With or Without Daratumumab in Newly Diagnosed Multiple Myeloma: Pooled Subgroup Analysis of OCTANS and ALCYONE
Daratumumab, Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma: Pooled Analysis of OCTANS and ALCYONE

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 tumors to elicit an immune response towards malignant cells. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T cell mediated killing of lymphoma B cells.i CD20 is a clinically validated therapeutic target, and is expressed on many B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.ii,iii Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ broad oncology collaboration.

About DARZALEX(daratumumab)
DARZALEX (daratumumab) is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration approval to treat certain multiple myeloma indications. Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. The subcutaneous formulation of daratumumab (daratumumab and hyaluronidase-fihj) is the first subcutaneous CD38 antibody approved for the treatment of certain multiple myeloma indications and the first and only approved treatment for certain patients with light-chain (AL) amyloidosis.iv,v,vi

Please see local country prescribing information for all labeled indication and safety information.

(Press release, Genmab, NOV 4, 2021, View Source [SID1234594373])

On November 4, 2021 Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, reported third quarter financial results and provided business and clinical highlights (Press release, Sangamo Therapeutics, NOV 4, 2021, View Source [SID1234594372]).

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"We are delighted to share clinical data and business updates across several programs demonstrating that Sangamo has three important assets progressing toward late-stage development. Our gene therapy portfolio is advancing with accumulating safety and efficacy data in our Fabry and hemophilia A programs, and preliminary proof-of-concept data demonstrate the clinical potential of our zinc finger genome engineering technology in sickle cell disease. These data readouts show the progression of our first-generation genomic medicine pipeline and potentially pave the way for new treatments. Our next generation programs focus on genome regulation and allogeneic CAR-Treg cell therapy, where we have a robust preclinical pipeline in neurological and autoimmune diseases. We are energized by this momentum and look forward to continued execution of our corporate strategy," said Sandy Macrae, Chief Executive Officer of Sangamo.

Recent Clinical and Business Highlights

Fabry Disease – First four patients dosed exhibited above normal α-Gal A activity; Phase 3 planning initiated

Earlier today, we announced preliminary clinical data from the first four patients treated in our Phase 1/2 STAAR study evaluating isaralgagene civaparvovec, or ST-920, our wholly owned Fabry disease gene therapy product candidate. Data as of the September 17, 2021 cutoff date from the four patients in the first two dose cohorts showed that isaralgagene civaparvovec was generally well tolerated. All four patients exhibited above normal alpha-galactosidase A (α-Gal A) activity, which was maintained for up to one year for the first patient treated and through 14 weeks for the most recently treated patient. Activity of 2-fold to 15-fold above mean normal was observed at last measurement as of the cutoff date. Withdrawal from enzyme replacement therapy (ERT) has taken place for one patient and is planned for the other patient on ERT, based on the stability of their α-Gal A activity following treatment.
The fifth patient in the STAAR study, who is the first patient in the third cohort (3e13vg/kg), was dosed after the cutoff date. The sixth patient is currently in screening also for the third dose cohort. We expect to provide updated data throughout 2022 and present these results at a medical meeting.
Based on the STAAR study results to date, we have initiated planning for a Phase 3 Fabry disease clinical trial.
Sickle Cell Disease – Preliminary-proof-of-concept data will be presented at ASH (Free ASH Whitepaper) as clinical program advances

Preliminary proof-of-concept results from the Phase 1/2 PRECIZN-1 study investigating SAR445136, formerly BIVV003, an investigational zinc finger nuclease gene edited cell therapy, in patients with severe sickle cell disease (SCD) will be presented at the 63rd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) on December 12, 2021. Results as of the June 25, 2021 cutoff date show that all four treated patients did not require blood transfusions post engraftment and had no adverse or serious adverse events related to SAR445136 through 65 weeks of follow-up for the longest treated patient. The four treated patients all experienced increases in total hemoglobin, fetal hemoglobin and percent F cells.
We and Sanofi continue to advance the sickle cell disease program. We recently obtained manufacturing requirements guidance from FDA in preparation for further potential clinical studies. Separately, we and Sanofi made the business decision to cease development of the beta thalassemia indication in order to focus resources on the sickle cell disease program. ST-400 for beta thalassemia was developed with the support of a grant from the California Institute for Regenerative Medicine (CIRM).
Hemophilia A – Four patients at highest dose experienced mean FVIII activity of 30.9% at week 104

Updated follow-up results from the Phase 1/2 Alta study of giroctocogene fitelparvovec gene therapy in patients with severe hemophilia A will be presented at ASH (Free ASH Whitepaper) on December 12, 2021. For the four patients in the highest dose 3e13vg/kg cohort who have reached 104 weeks of follow-up as of the May 19, 2021 cutoff date, mean Factor VIII (FVIII) activity was 30.9% at week 104 as measured by chromogenic assay. In this cohort, the annualized bleeding rate was zero for the first year after treatment and 0.9 throughout total duration of follow-up. Giroctocogene fitelparvovec was generally well tolerated.
We and Pfizer also announced that some of the patients treated in the Phase 3 AFFINE trial of giroctocogene fitelparvovec experienced FVIII activity greater than 150% following treatment. None of these patients have experienced thrombotic events and some have been treated with direct oral anticoagulants to reduce thrombotic risk. Pfizer voluntarily paused screening and dosing of additional patients in the trial to implement a protocol amendment intending to provide guidance regarding the management of patients with FVIII levels that exceed 150%. On November 3, 2021, Pfizer was informed that the FDA has put this trial on clinical hold. The next step is to share the proposed protocol amendment with health authorities and respond to the clinical hold, after which the Companies will be able to provide updated timing for the trial.
Renal Transplant – First patient enrolled, expect two patients to be dosed by mid-2022

The first patient has been enrolled in our Phase 1/2 STEADFAST study evaluating TX200, our wholly owned autologous HLA-A2 CAR Treg cell therapy product candidate treating patients receiving an HLA-A2 mismatched kidney from a living donor. We expect the first two patients in this study to be dosed by the middle of 2022 following kidney transplantation. We continue to open study sites and screen patients.
Research, Manufacturing, and Corporate Updates

Biogen announced type 1 myotonic dystrophy (DM1) as the previously undisclosed neuromuscular preclinical target in our collaboration.
We recently completed and brought online our in-house cell therapy manufacturing facility in our Brisbane, California headquarters and remain on track to complete our in-house cell therapy manufacturing facility in Valbonne, France by year-end.
We appointed D. Mark McClung as Chief Operating Officer, an important organizational step to support the multiple advancing wholly owned and partnered programs.
Third Quarter 2021 Financial Results

Consolidated net loss attributable to Sangamo for the third quarter ended September 30, 2021 was $47.7 million, or $0.33 per share, compared to a net loss attributable to Sangamo of $1.6 million, or $0.01 per share, for the same period in 2020.

Revenues

Revenues for the third quarter ended September 30, 2021, were $28.6 million, compared to $57.8 million for the same period in 2020, a decrease of $29.2 million.

The reduction in revenue was primarily due to a $39.3 million decrease related to our giroctocogene fitelparvovec and C9ORF72 collaboration agreements with Pfizer, resulting from the completion of our activities in 2020, and a $2.3 million decrease related to our collaboration agreement with Sanofi. These decreases were partially offset by higher revenues of $11.5 million and $1.3 million related to our collaboration agreements with Novartis and Biogen, respectively.

GAAP and Non-GAAP operating expenses

Total operating expenses on a GAAP basis for the third quarter ended September 30, 2021 were $77.0 million compared to $61.5 million for the same period in 2020. Non-GAAP operating expenses, which exclude stock-based compensation expense, for the third quarter ended September 30, 2021 were $69.1 million compared to $54.8 million for the same period in 2020.

The increase in total operating expenses on a GAAP basis was primarily driven by our higher clinical and manufacturing supply expenses along with our increased headcount to support the advancement of our clinical trials and our ongoing collaborations.

Cash, cash equivalents and marketable securities

Cash, cash equivalents and marketable securities as of September 30, 2021 were $519.0 million compared to $692.0 million as of December 31, 2020.

Revised Financial Guidance for 2021

We are revising our full-year operating expense guidance initially provided on February 24, 2021 and reiterated most recently on August 5, 2021 as follows:

Conference Call

Sangamo will host a conference call today, November 4, 2021, at 9:15 a.m. Eastern Time, which will be open to the public. The call and live Q&A will be webcast.

The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 5178059. Participants may access the live webcast via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. Call replay will be available for one week following the conference call. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 5178059.