WHIPPANY, N.J. & SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Bayer and Atara Biotherapeutics, Inc. (Nasdaq: ATRA) today announced an exclusive worldwide license agreement and research, development and manufacturing collaboration for mesothelin-directed CAR T-cell therapies for the treatment of solid tumors. The agreement includes the development candidate ATA3271, an armored allogeneic T-cell immunotherapy, and an autologous version, ATA2271, for high mesothelin-expressing tumors such as malignant pleural mesothelioma and non-small-cell lung cancer.

Atara is a pioneer in allogeneic T-cell immunotherapy with industry-leading allogeneic cell manufacturing processes and CAR T technologies. The licensed technology leverages Atara's novel, proprietary Epstein-Barr Virus (EBV) T-cell platform combined with CAR T technologies targeting mesothelin to improve efficacy, persistence, safety, and durability of response.

This transaction is a fundamental element of Bayers new Cell & Gene Therapy strategy. It strengthens our development portfolio through allogeneic cell therapies and consolidates our emerging leadership in the field, said Wolfram Carius, Head of Bayers Cell & Gene Therapy Unit. We look forward to collaborating with Atara to develop off-the-shelf CAR T-cell therapies for patients with difficult-to-treat cancers.

This exciting collaboration between Atara and Bayer will accelerate the development of mesothelin-targeted CAR T-cell therapies for multiple solid tumors and helps us advance the power of our allogeneic cell therapy platform to patients as quickly as possible, said Pascal Touchon, President and CEO Atara. Bayers proven track record in oncology global development and commercialization, and growing presence in cell and gene therapy, enhances Ataras capabilities and complements our leading allogeneic T-cell platform.

Under the terms of the agreement, Atara will lead IND (Investigational New Drug)-enabling studies and process development for ATA3271 while Bayer will be responsible for submitting the IND and subsequent clinical development and commercialization. Atara will continue to be responsible for the ongoing ATA2271 phase 1 study, for which an IND filing has been accepted and the clinical trial has been initiated. Atara will receive an upfront payment of USD 60 million and is eligible to receive payments from Bayer upon achievement of certain development, regulatory and commercialization milestones totaling USD 610 million, as well as tiered royalties up to low double-digit percentage of net sales.

As part of the transaction, Atara will also provide translational and clinical manufacturing services to be reimbursed by Bayer. In addition, for a limited period of time, Bayer has a non-exclusive right to negotiate a license for additional Atara CAR T product candidates.

Atara Conference Call and Webcast Information

Atara will hold a conference call at 8:30 a.m. ET. Analysts and investors can participate in the conference call by dialing (888) 540-6216 for domestic callers and (734) 385-2715 for international callers, using the conference ID 3995182.

A live audio webcast can be accessed by visiting the Investors & Media News & Events section of atarabio.com. An archived replay will be available on the Company's website for 30 days following the live webcast.

About CAR-T cell therapy

T cells are a type of white blood cell that are critical in eliminating the body of abnormal and cancerous cells in healthy individuals. In cancer patients, these T cells frequently fail to either recognize or effectively engage cancer cells. CAR T-cell therapies involve engineering a human T cell to express a chimeric antigen receptor (CAR) that increases its ability to recognize cancer cells. These therapies use the immune system to fight cancer and have the potential to disrupt cancer care and potentially even provide a cure. Mesothelin is a tumor-specific antigen that is commonly expressed at high levels on the cell surface in many aggressive solid tumors and is an attractive target for immune-based therapies, including CAR T therapy.

About Bayers new Cell & Gene Therapy (C>) Unit

In order to build up its presence in C>, Bayer is strengthening its internal C> capabilities. At the same time, the company is pursuing external strategic collaborations, technology acquisitions and licensing. The goal is to build robust platforms with broad application across different therapeutic areas. Strategically, Bayer focuses on selected areas of C>, such as stem cell therapies (with focus on induced pluripotent cells or iPSCs), gene augmentation, gene editing and allogeneic cell therapies in different indications. Leveraging external innovation together with the expertise of the teams at Bayer represents a key value-driver, especially in the highly dynamic and competitive field of C>. Bayers operating model for C>, where partners operate autonomously and are fully accountable to develop and progress their portfolio and technology, is essential for preserving their entrepreneurial culture and positions Bayer as a partner of choice. The role of Bayers C> Platform is to steer strategically, ensuring the different parts of the organization complement each other and combining the best in Biotech and Pharma know-how. As part of the Pharmaceuticals Division, the C> Platform will combine multiple backbone functions providing support across the entire value chain for the research and development of cell and gene therapies. This includes expertise in Research and Preclinical Development, CMC (Chemistry, Manufacturing and Controls), Clinical Development, Commercial, Strategy Implementation and Project Management. With a high level of flexibility, it will orchestrate operations from science to launch in order to generate and maintain a sustainable pipeline, with the goal to bring new products to market as fast as possible.

About Ataras Mesothelin CAR-T Franchise

Two of Ataras investigational CAR T immunotherapy programs, developed in collaboration with Memorial Sloan Kettering Cancer Center (MSK), target mesothelinthe autologous ATA2271 program and allogeneic ATA3271 program. Mesothelin is a tumor-specific antigen that is commonly expressed at high levels on the cell surface in many aggressive solid tumors including mesothelioma, non-small cell lung cancer, ovarian cancer and pancreatic cancer.

Both ATA2271 and ATA3271 are engineered for use in solid tumors as they incorporate Ataras novel inclusion of both a PD-1 DNR construct to overcome checkpoint inhibition and a 1XX costimulatory domain on the CAR (chimeric antigen receptor) to enhance expansion and functional persistence of the CAR T cells. ATA3271, the allogeneic version of this CAR T, leverages Ataras EBV T-cell platform and is currently in IND-enabling studies. ATA2271, the autologous version has enrolled the first patient in an open-label, single-arm Phase 1 clinical study in November 2020.

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2019, the Group employed around 104,000 people and had sales of 43.5 billion euros. Capital expenditures amounted to 2.9 billion euros, R&D expenses to 5.3 billion euros. For more information, go to http://www.bayer.com

About Atara

Atara Biotherapeutics, Inc. is a pioneer in T-cell immunotherapy leveraging its novel allogeneic EBV T-cell platform to develop transformative therapies for patients with serious diseases including solid tumors, hematologic cancers and autoimmune disease. With our lead program in Phase 3 clinical development, Atara is the most advanced allogeneic T-cell immunotherapy company and intends to rapidly deliver off-the-shelf treatments to patients with high unmet medical need. Our platform leverages the unique biology of EBV T cells and has the capability to treat a wide range of EBV-associated diseases, or other serious diseases through incorporation of engineered CARs (chimeric antigen receptors) or TCRs (T-cell receptors). Atara is applying this one platform to create a robust pipeline including: tab-cel (tabelecleucel) in Phase 3 development for Epstein-Barr virus-driven post-transplant lymphoproliferative disease (EBV+ PTLD); ATA188, a T-cell immunotherapy targeting EBV antigens as a potential treatment for multiple sclerosis; and multiple chimeric antigen receptor T-cell (CAR T) immunotherapies for both solid tumors and hematologic malignancies. Improving patients lives is our mission and we will never stop working to bring transformative therapies to those in need. Atara is headquartered in South San Francisco and our leading-edge research, development and manufacturing facility is based in Thousand Oaks, California.

For additional information about the company, please visit atarabio.com and follow us on Twitter and LinkedIn.

Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayers public reports which are available on the Bayer website at http://www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

Forward-Looking Statements

This press release contains or may imply forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. For example, forward-looking statements include statements regarding: the development, timing and progress of ATA2271 or ATA3271, the potential characteristics and benefits of ATA2271 or ATA3271, and the progress and results of, and prospects for, any collaboration involving ATA2271 or ATA3271, including the potential financial benefits to Atara thereof. Because such statements deal with future events and are based on Ataras current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Atara could differ materially from those described in or implied by the statements in this press release. These forward-looking statements are subject to risks and uncertainties, including, without limitation, risks and uncertainties associated with the costly and time-consuming pharmaceutical product development process and the uncertainty of clinical success; the COVID-19 pandemic, which may significantly impact (i) our business, research, clinical development plans and operations, including our operations in South San Francisco and Southern California and at our clinical trial sites, as well as the business or operations of our third-party manufacturer, contract research organizations or other third parties with whom we conduct business, (ii) our ability to access capital, and (iii) the value of our common stock; the sufficiency of Ataras cash resources and need for additional capital; and other risks and uncertainties affecting Ataras and its development programs, including those discussed in Ataras filings with the Securities and Exchange Commission (SEC), including in the Risk Factors and Managements Discussion and Analysis of Financial Condition and Results of Operations sections of the Companys most recently filed periodic reports on Form 10-K and Form 10-Q and subsequent filings and in the documents incorporated by reference therein. Except as otherwise required by law, Atara disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date hereof, whether as a result of new information, future events or circumstances or otherwise.

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Bayer and Atara Biotherapeutics Enter Strategic Collaboration for Mesothelin-Targeted CAR T-cell Therapies for Solid Tumors - Business Wire

Newswise LOS ANGELES (Dec. 4, 2020) -- Cedars-Sinai has launched a center to manufacture the next generation of stem cell and gene therapies that will enable biomedical researchers, government medical programs, commercial entities and others to develop new biologic drugs and propel novel disease discoveries.

Biologic drugs are produced from living organisms or contain components of living organisms, such as cells, proteins or genes.

"TheCedars-Sinai Biomanufacturing Centerleverages our world-class stem-cell expertise, which already serves scores of clients, to provide a much-needed biomanufacturing facility in Southern California," saidClive Svendsen, PhD, executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute. "It is revolutionary by virtue of elevating regenerative medicine and its therapeutic possibilities to an entirely new level-repairing the human body."

Among the facility's initial clients is the Department of Defense, which has asked Cedars-Sinai scientists to manufacture banks of stem cells from multiple healthy volunteers for later use in repairing vascular injuries sustained by military personnel in combat.

The core technology of the Cedars-Sinai Biomanufacturing Center involves production of specialized cells known as induced pluripotent stem cells, or iPSCs. Scientists make iPSCs by genetically converting adult blood cells into cells that can self-renew indefinitely and differentiate into nearly any type of tissue. Each resulting cell carries the exact DNA of the person who donated the blood sample.

"IPSCs are powerful tools for understanding human disease and developing therapies," saidDhruv Sareen, PhD, executive director of the Biomanufacturing Center and director of the induced pluripotent stem cell facility at the Regenerative Medicine Institute. "These cells enable us to truly practiceprecision medicineby developing drug treatments tailored to the individual patient or groups of patients with similar genetic profiles."

The Biomanufacturing Center is designed to address a critical bottleneck in bringing cell- and gene-based therapies to the clinic. It will help relieve a nationwide shortage of facilities that can scale up production of cells for drug products that consistently meet current good manufacturing practice (cGMP) standards for strength, quality, and purity. These standards, set by the U.S. Food and Drug Administration, must be met when producing pharmaceuticals for use in humans.

To comply with the federal standards, the new Cedars-Sinai center features nine "clean rooms" that maintain rigorously aseptic conditions for handling of all biomaterials. These rooms are supported by staging areas, gowning rooms, quality control laboratories and storage rooms with ample freezers and liquid nitrogen tanks.

Other sections of the Biomanufacturing Center are devoted to research and production of iPSC cells, technology and development, training and collaboration laboratories, offices, and facilities maintenance equipment. Overall, the center occupies more than 28,000 square feet.

"Our expansive facilities provide complete, end-to-end support of biomedical research and development of cell therapies that are 'living medicines,'" said Sareen, assistant professor of Biomedical Sciences. "We enable our clients to explore and create new types of cells, use them to make discoveries about diseases and transform the resulting biomaterials into cGMP-compliant therapies for testing in clinical trials."

The recent grand opening of the Biomanufacturing Center, hosted on a virtual platform by Cedars-Sinai leadership, was attended by representatives of local and federal governments, biotechnology companies, funding organizations and other stakeholders. It was followed by another Cedars-Sinai virtual event, a "Symposium on Translational Medicine and Biomanufacturing," that drew world-renowned keynote speakers from academia and industry and hundreds of attendees to explore the latest developments in these fields.

"Our new Biomanufacturing Center reaffirms Cedars-Sinai's commitment to deliver the finest clinical care for our patients-and patients everywhere-by expanding the frontiers of medical science," said Svendsen, professor of Biomedical Sciences and Medicine.

Read more on the Cedars-Sinai Blog:What Are Induced Pluripotent Stem Cells?

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New Cedars-Sinai Biomanufacturing Center to Spur Cell Therapies - Newswise

Treatment with an off-the-shelf CAR T-cell therapy that targets B-cell maturation antigen (BCMA), ALLO-715, elicited responses in heavily pretreated patients with relapsed/refractory multiple myeloma in early findings from a first-in-human study presented at the 2020 ASH Meeting.1

The therapy generated responses in 6 of 10 patients (60%), including a very good partial-plus response (VGPR+) in 4 patients (40%), who were treated with ALLO-715 at a dose of 320 x 106 CAR cells plus a lymphodepleting regimen that included ALLO-647, an anti-CD52 monoclonal antibody, during the ongoing phase 1 UNIVERSAL study (NCT04093596).1

The findings mark the first results for an allogeneic CAR therapy directed at BCMA, said lead study author Sham Mailankody, MBBS, a medical oncologist and investigator in the Cellular Therapeutics Center at Memorial Sloan Kettering Cancer Center in New York, New York. BCMA, which is highly expressed on plasma and multiple myeloma cells, has sparked intensive research interest.2

These results demonstrate the feasibility and safety of an off-the-shelf CAR T cell therapy for multiple myeloma. In this first report of an allogeneic BCMA CAR T-cell therapy, we show that nearly 90% of patients were treated within 5 days of enrollment and without needing any bridging therapy, Mailankody said.

Allogeneic CAR therapy offers the potential for scalable manufacturing for on-demand treatment with shorter waiting times, which would overcome some of the logistical challenges posed by autologous CAR therapy, Mailankody said. The T cells needed for ALLO-715 are harvested from healthy donors and genetically engineered to express CARs aimed at specific cancer targets, according to Allogene Therapeutics, the company developing the therapy.3

ALLO-715 includes a human-derived single-chain variable fragment anti-BCMA cell with a 4-1BB costimulatory domain. Mailankody said the 2 key attributes of the construct are a knockout of CD52, which allows for selective lymphodepletion with ALLO-647 to prevent graft rejection without affecting the CAR T cells, and a knockout of the TRAC gene, which also minimizes the risk of graft-versus-host disease (GVHD).1

The UNIVERSAL study, which is being conducted at 11 cancer centers in the United States, is recruiting patients with multiple myeloma who have received 3 or more prior therapies, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 agent, and are refractory to their last treatment. Participants must have an ECOG performance status score of 0 or 1.

The dose escalation portion of the study is testing ALLO-715 as a single infusion across 4 doses: 40, 160, 320, or 480 x 106 CARs. Lymphodepletion regimens consist of fludarabine (F; 30 mg/m2/day) plus cyclophosphamide (C; 300 mg/m2/day) given on 3 days with ALLO-647 (A; 13-30 mg x 3 days; FCA) or cyclophosphamide plus ALLO-647 (CA).

Among the 35 patients enrolled at the time of the presentation, 4 became ineligible because of organ failure due to rapidly progressing disease. Of 31 patients in the safety population, the median age was 65 years (range, 46-76). Nearly half of the patients (48%) have high-risk cytogenetics and 23% had extramedullary disease. The efficacy population at data cutoff on October 30, 2020, comprised 26 patients across the 4 dosing levels, with a median follow-up of 3.2 months.1

The overall response rate (ORR) varied across dosing cohorts and lymphodepleting regimens. No responses were observed among 3 patients each who received CARs at 40 x 106 with FCA or 160 x 106 with CA, both with low-dose ALLO-647. The ORRs were 50% in 4 patients who received CARs at 160 x 106 with lowALLO-647 FCA; 33% in 3 at 480 x 106 with lowALLO-647 FCA; and 67% in 3 at 320 x 106 with lowALLO-647 CA.

The most robust responses were seen among those who received ALLO-647 at 320 x106. For this cohort, the ORR was 60% among 10 patients, including 3 of 6 who received CARs with lowALLO-647 FCA and 3 of 4 who had the therapy with highALLO-647 FCA. Overall, 6 patients had a VGPR+, defined as stringent complete response, complete response, or VGPR. These included 1 at 160, 4 at 320, and 1 at 480 10 x 106 CARs. Of the VGPR+ patients, 5 were negative for measurable residual disease. Additionally, 6 of 9 patients treated at the 320 or 480 x 106 dose levels remain in response.

Mailankody highlighted the experience of 1 participant, a 71-year-old man whose myeloma had progressed after undergoing 9 prior lines of therapy including autologous stem cell transplant and an experimental BCMA-targeted therapy. The patient received a conditioning regimen of FCA with low-dose ALLO-647 and ALLO-715 at 320 x 106. He reached a VGPR on day 14 that deepened to a stringent complete response by day 28 that remains in effect at 6 months, while experiencing grade 1 cytokine release syndrome (CRS).

The patient is clinically doing very well and is back at work, Mailankody said.

Among 31 patients in the safety population, most adverse effects were of grade 1 or 2 severity. These included CRS in 14 patients (45%) and infusion-related reactions to ALLO-647 in 7 patients (23%). The use of drugs to manage CRS also was low, at 19% for tocilizumab and 10% for steroids.

All-grade infections were reported in 13 patients (42%), including grade 3 events in 4 (13%). One patient (3%) died from a presumed fungal pneumonia related to progressive disease and the CA conditioning regimen but unrelated to ALLO-715. There were no instances of neurotoxicity or GVHD.

Notably, the fact that we did not see any GVHD is encouraging for an off-the-shelf allogeneic product, Mailankody said.

In response to a question from a conference attendee, Mailankody said it is too soon to compare efficacy levels seen with this allogeneic CAR therapy with those observed with investigational autologous CARs, which have been under study for several years.

Moving forward, investigators are continuing to evaluate dosing levels for ALLO-715. UNIVERSAL is enrolling patients to the 480 x 106 cohort, Mailankody said, adding that the appropriate dose likely would land between 320 and 480 x 106.

References

1. Mailankody S, Matous JV, Liedtke M, et al. Universal: an allogeneic first-in-human study of the anti-Bcma ALLO-715 and the Anti-CD52 ALLO-647 in relapsed/refractory multiple myeloma. Presented at: 2020 American Society of Hematology Annual Meeting and Exposition. December 5-8, 2020; Virtual. Abstract 129. Accessed December 5, 2020. https://ash.confex.com/ash/2020/webprogram/Paper140641.html

2. Cho SF, Anderson KC, Tai YT. Targeting B cell maturation antigen (BCMA) in multiple myeloma: potential uses of BCMA-based immunotherapy. Front Immunol. 2019;9:1821. doi:10.3389/fimmu.2018.01821

3. AlloCAR T Therapy. Allogene Therapeutics. Accessed December 5, 2020. https://www.allogene.com/allocar-t-therapy

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ALLO-715, Off-the-Shelf CAR T-Cell Therapy, Produces Early Promise in Multiple Myeloma - Cancer Network

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Magenta Therapeutics (NASDAQ: MGTA) and bluebird bio, Inc. (NASDAQ: BLUE) today announced an exclusive clinical trial collaboration to evaluate the utility of MGTA-145, in combination with plerixafor, for mobilization and collection of stem cells in adults and adolescents with sickle cell disease (SCD). The data from this clinical trial could provide proof-of-concept for MGTA-145, in combination with plerixafor, as the preferred mobilization regimen for patients with SCD. bluebird bios experience with plerixafor as a mobilization agent in sickle cell disease aligns with Magentas combination therapy approach, utilizing MGTA-145 plus plerixafor with potential to achieve safe, rapid and reliable mobilization of sufficient quantities of high-quality stem cells to improve outcomes associated with stem cell transplantation. Under the collaboration, the stem cells will be fully characterized, and Magenta will undertake preclinical studies to evaluate the ability of these cells to be gene corrected and engrafted in mouse models. The companies will co-fund the clinical trial and Magenta will retain all rights to its product candidate.

We are excited to build upon our leading position in the field of ex-vivo gene therapy and the promising clinical data with LentiGlobin in SCD with a collaboration focused on achieving improved stem cell mobilization, said Dave Davidson, M.D., chief medical officer, bluebird bio. In this initial study, we hope to establish whether the combination of plerixafor with MGTA-145 can generate appropriate CD34+ stem cells with a single round of mobilization. If successful, we hope to evaluate this novel mobilization regimen with LentiGlobin to make another step forward in the treatment of patients with SCD.

Achieving reliable and rapid stem cell mobilization and a simplified collection process can ensure the entire patient experience is optimal with respect to therapeutic outcome. The incorporation of bluebird bios experience in this area of treatment will be immensely valuable in further developing MGTA-145 plus plerixafor to address the remaining unmet needs in gene therapy approaches for diseases like sickle cell disease, said John Davis Jr., M.D., M.P.H., M.S., Head of Research & Development and Chief Medical Officer, Magenta Therapeutics. We look forward to collaborating with bluebird bio to evaluate MGTA-145 as the preferred mobilization option for people with sickle cell disease.

SCD is a serious, progressive and debilitating genetic disease caused by a mutation in the -globin gene that leads to the production of abnormal sickle hemoglobin (HbS), causing red blood cells (RBCs) to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and painful vaso-occlusive events (VOEs). For adults and children living with SCD, this means unpredictable episodes of excruciating pain due to vaso-occlusion as well as other acute complicationssuch as acute chest syndrome (ACS), stroke, and infections, which can contribute to early mortality in these patients.

Currently available mobilization drugs, including granulocyte-colony stimulating factor (G-CSF), a commonly used mobilization agent administered over the course of five to seven days in other transplant settings, is not used in sickle cell disease because it can trigger vaso-occlusive crises and even death in adults and adolescents. Plerixafor is used to mobilize a patients stem cells for collection prior to transplant and while an available treatment option, multiple cycles of apheresis and collection may sometimes be required to generate sufficient stem cells for gene therapy. Magenta is developing MGTA-145, in combination with plerixafor, to be the preferred mobilization regimen for rapid and reliable mobilization and collection of hematopoietic stem cells (HSCs) to improve stem cell transplantation outcomes in multiple disease areas, including genetic diseases such as sickle cell disease, as well as blood cancers and autoimmune diseases.

About Magenta Therapeutics MGTA-145

MGTA-145, in combination with plerixafor, has demonstrated, in a recently completed Phase 1 study in healthy volunteers, it can rapidly and reliably mobilize high numbers of functional stem cells in a single day, without the need for G-CSF. MGTA-145 works in combination with plerixafor to harness a physiological mechanism of stem cell mobilization to rapidly and reliably mobilize HSCs for collection and transplant across multiple indications.

Additionally, as shown in preclinical studies, stem cells mobilized with MGTA-145 can be efficiently gene-modified and are able to engraft, potentially allowing for safer and more efficient mobilization for gene therapy approaches to treat sickle cell disease and other genetic diseases.

Magenta completed its Phase 1 trial of MGTA-145 in healthy volunteers, demonstrating MGTA-145 was well tolerated and enables same-day dosing, mobilization and simplified collection of sufficient stem cells for transplant, meeting all primary and secondary endpoints.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, were developing gene and cell therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, were working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. Were putting our care and expertise to work across a spectrum of disorders: cerebral adrenoleukodystrophy, sickle cell disease, -thalassemia and multiple myeloma, using gene and cell therapy technologies including gene addition, and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

LentiGlobin and bluebird bio are trademarks of bluebird bio, Inc.

About Magenta Therapeutics

Magenta Therapeutics is a clinical-stage biotechnology company developing medicines to bring the curative power of immune system reset through stem cell transplant to more patients with autoimmune diseases, genetic diseases and blood cancers. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant world to revolutionize immune reset for more patients.

Magenta is based in Cambridge, Mass. For more information, please visit http://www.magentatx.com.

Follow Magenta on Twitter: @magentatx.

Forward-Looking Statement

This press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavour, potential, continue or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation risks set forth under the caption Risk Factors in Magentas Annual Report on Form 10-K filed on March 3, 2020, and in bluebird bios Annual Report on Form 10-K filed on February 18, 2020, as updated by each companys most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta and bluebird bio believe that the expectations reflected in the forward-looking statements are reasonable, neither Magenta nor bluebird bio can guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta or bluebird bio, nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. Neither Magenta nor bluebird undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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Magenta Therapeutics and bluebird bio Announce a Phase 2 Clinical Trial Collaboration to Evaluate Magenta's MGTA-145 for Mobilizing and Collecting...

This article was originally published here

Cytotherapy. 2020 Nov 9:S1465-3249(20)30932-4. doi: 10.1016/j.jcyt.2020.11.001. Online ahead of print.

ABSTRACT

The end of 2019 saw the beginning of the coronavirus disease 2019 (COVID-19) pandemic that soared in 2020, affecting 215 countries worldwide, with no signs of abating. In an effort to contain the spread of the disease and treat the infected, researchers are racing against several odds to find an effective solution. The unavailability of timely and affordable or definitive treatment has caused significant morbidity and mortality. Acute respiratory distress syndrome (ARDS) caused by an unregulated host inflammatory response toward the viral infection, followed by multi-organ dysfunction or failure, is one of the primary causes of death in severe cases of COVID-19 infection. Currently, empirical management of respiratory and hematological manifestations along with anti-viral agents is being used to treat the infection. The quest is on for both a vaccine and a more definitive management protocol to curtail the spread. Researchers and clinicians are also exploring the possibility of using cell therapy for severe cases of COVID-19 with ARDS. Mesenchymal stromal cells are known to have immunomodulatory properties and have previously been used to treat viral infections. This review explores the potential of mesenchymal stromal cells as cell therapy for ARDS.

PMID:33257213 | DOI:10.1016/j.jcyt.2020.11.001

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Stem cell therapy in coronavirus disease 2019: current evidence and future potential - DocWire News

Bayer has created a cell and gene therapy platform to support its growing pipeline of advanced therapy medicinal products. The platform is intended to enable Bayer to make its expertise and resources available to its partners while preserving their autonomy and culture.

Germanys Bayer has moved into cell and gene therapies on multiple fronts in recent years, buying up induced pluripotent stem cell specialist BlueRock Therapeutics and adeno-associated virus (AAV) gene therapy player Asklepios BioPharmaceutical while investing in a clutch of other biotechs. The deals have given Bayer a pipeline of five advanced assets and more than 15 preclinical prospects.

Rather than subsume BlueRock and AskBio, Bayer opted to allow the businesses to operate as independent companies in an attempt to preserve their cultures. Yet, Bayer also wants to enable the companies to realize the benefits that can come from being part of a larger organization.

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The cell and gene therapy platform is the result of that effort to get the best of both worlds. Bayer will use the platform to provide support to its cell and gene therapy businesses and orchestrate its operations in the area across the product life cycle. Specific areas of support offered by the platform span preclinical through to commercial, strategy implementation and project management.

Bayer is investing in its internal capabilities to strengthen the platform as well as looking to enter into strategic collaborations, acquire technologies and strike licensing deals. The deals entered into so far have given Bayer infrastructure as well as product candidates.

Notably, AskBio has a CDMO unit, Viralgen, specializing in AAV gene therapy production. As limited access to manufacturing capacity has been a barrier to speedy gene therapy development, buying the CDMO could help Bayer remove a constraint on the progress of its programs and become a more attractive partner for startups. Bayer thinks allowing acquired startups autonomy makes it attractive, too.

Wolfram Carius, who joined Bayer from Sanofi in 2016, is heading up the new cell and gene therapy platform. Carius said the platform is vital to accelerate innovation at its source, and to ensure its translation into tangible therapies for patients who have no time to wait in a statement.

Bayers platform is a twist on strategies being pursued by many of its peers, which have identified cell and gene therapies as growth areas and bought in assets but sought to avoid smothering the startups. Kite, for example, operates as its own business unit within Gilead Sciences, and Spark Therapeutics is an independent company within the Roche group.

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Bayer creates cell and gene therapy platform to support partners - FierceBiotech

An effective new treatment to restore vision is on the horizon that works by injecting genetically modified stem cells into the eye to mend the damaged retina.

Researchers found that the cells of damaged retinas send out a rescue signal to attract the stem cells that repair eye damage.

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They identified two of these cell signals known as Ccr5 and Cxcr6 and then genetically engineered the stem cells to make them more sensitive to those signals.

When these modified stem cells were transplanted back into mice and human tissue samples in the lab they flocked to the retina cells in much greater numbers, keeping the tissue of the damaged retina alive and functioning.

The technique holds promise for improving sight in people with poor vision and potentially even to cure blindness altogether but the researchers cautioned that any such development was some years away and required much bigger studies to confirm their findings.

One of the main hurdles in using stem cells to treat damaged eyesight is low cell migration and integration in the retina, says Pia Cosma, at the Centre for Genomic Regulation in Barcelona.

After the cells are transplanted they need to reach the retina and integrate through its layers. Here we have found a way to enhance this process using stem cells commonly found in the bone marrow, but in principle can be used with any transplanted cells, Dr Cosma said.

There is still considerable work to be done, but our findings could make stem cell transplants a feasible and realistic option for treating visual impairment and restoring eyesight, she said.

Retinal damage, which is currently incurable, inevitably leads to visual disabilities and in most cases blindness. With a growing and ageing population, the number of people affected by retinal damage is estimated to increase dramatically over the next few decades.

Stem cell therapies have been touted as one way of treating degenerative retinal conditions. Stem cells can be transplanted into the eye, releasing therapeutic molecules with neuroprotective and anti-inflammatory properties that promote the survival, proliferation and self-repair of retinal cells. The stem cells can also generate new retinal cells, replacing lost or damaged ones.

The researchers used mesenchymal stem cells, which are found in bone marrow and can differentiate into lots of types of cells, including retinal cells that respond to light.

Mesenchymal stem cells can also be easily grown outside an organism, providing abundant starting material for transplantation compared to other cell sources such as hematopoietic stem cells.

The study is published in the journal Molecular Therapy.

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Treatment to restore vision by injecting stem cells into the eye could help people with damaged eyesight - iNews

Trusted Business Insights answers what are the scenarios for growth and recovery and whether there will be any lasting structural impact from the unfolding crisis for the Stem Cell Therapy market.

Trusted Business Insights presents an updated and Latest Study on Stem Cell Therapy Market 2020-2029. The report contains market predictions related to market size, revenue, production, CAGR, Consumption, gross margin, price, and other substantial factors. While emphasizing the key driving and restraining forces for this market, the report also offers a complete study of the future trends and developments of the market.The report further elaborates on the micro and macroeconomic aspects including the socio-political landscape that is anticipated to shape the demand of the Stem Cell Therapy market during the forecast period (2020-2029).It also examines the role of the leading market players involved in the industry including their corporate overview, financial summary, and SWOT analysis.

Get Sample Copy of this Report @ Stem Cell Therapy Market Research Report Forecast to 2029 (Includes Business Impact of COVID-19)

Abstract, Snapshot, Market Analysis & Market Definition: Stem Cell Therapy MarketIndustry / Sector Trends

Stem Cell Therapy Market size was valued at USD 7.8 billion in 2018 and is expected to witness 10.2% CAGR from 2019 to 2025.

U.S. Stem Cell Therapy Market Size, By Type, 2018 & 2025 (USD Million)

Rising prevalence of chronic diseases will positively impact the stem cell therapy market growth. Cardiovascular diseases, neurological disorders and other chronic conditions have resulted in high mortality over past few years. Conventional therapeutic methods and treatments are currently replaced due to lack of efficiency and efficacy. Recently developed stem cell therapies are capable of replacing defective cells to treat diseases that has reduced morbidity drastically. Therefore, people have now started relying on stem cell therapy that has long term positive effects.

Advancements in stem cell therapy in developed regions such as North America and Europe have boosted the industry growth. Since past few years, there have been several researches carried out for stem cell therapy. Currently developed stem cell therapies have shown positive outcomes in treatment of leukemia. Similarly, due to advancements in regenerative medicine, several other chronic conditions such as muscular dystrophy and cardiovascular diseases also have been cured. Aforementioned factors have surged the industry growth. However, high cost of allogenic stem cell therapy may hamper the industry growth to some extent.

Market Segmentation, Outlook & Regional Insights: Stem Cell Therapy Market

Stem Cell Therapy Market, By Type

Allogenic stem cell therapy segment held around 39% revenue share in 2018 and it is anticipated to grow substantially during the analysis timeframe. Allogenic stem cell is available as off the shelf therapy and it is easily scalable that helps in providing treatment without delay. Moreover, the procedure includes culturing donor-derived immunocompetent cells that are highly effective in treatment of several diseases. Stem cells obtained in allogenic therapy are free of contaminating tumor cells. This reduces risk for disease recurrence that will surge its demand thereby, stimulating segment growth.

Autologous stem cell therapy segment is estimated to witness 10.1% growth over the forthcoming years. People usually prefer autologous stem cell therapy as it has minimum risk of immunological rejection. However, on introduction of allogenic stem cell therapy, demand for autologous stem cell therapy has declined as it is difficult to scale up. However, there are concerns regarding risk of cross contamination during large scale manufacturing of autologous stem cell lines that will impede segmental growth to some extent.

Stem Cell Therapy Market, By Application

The neurology segment was valued at around USD 1.6 billion in 2018 and it is estimated that it will witness significant growth over the forthcoming years. Stem cells are used to replenish the disrupted neurological cells that help in quick patient recovery. Pluripotent stem cells provide a replacement for cells and tissues to treat Alzheimers, Parkinsons disease, cerebral palsy, amyotrophic lateral sclerosis, and other neurodegenerative diseases. Thus, the pivotal role of stem cells in treating the life-threatening neurological condition will escalate segment growth.

The cardiovascular segment will witness 10% growth over the analysis timeframe. Considerable segmental growth can be attributed to development in stem cell therapies that have enhanced recovery pace in patients suffering from cardiovascular diseases. Recently developed allogeneic stem cell therapies are efficient and easily available that have reduced the mortality rates in cardiovascular patients. Above mentioned factors will propel cardiovascular segment growth in near future.

Stem Cell Therapy Market, By End-users

The hospital segment held over 56% revenue share in 2018 and it is anticipated to grow significantly in near future. The rising preference for stem cell therapies offered by hospitals proves beneficial for business growth. Hospitals have affiliations with research laboratories and academic institutes that carry out research activities for developing stem cell therapies. On the introduction and approval of any novel stem therapy, hospitals implement it immediately. Associations with research and academic institutes further help hospitals to upgrade its stem cell treatment offerings that positively impact the segmental growth.

The clinics segment is expected to grow at around 10% during the forecast timeframe. Clinics specializing in providing stem cell therapies are well-equipped with advanced medical devices and superior quality reagents required for imparting stem cell therapies. However, as clinics offer specialized stem cell therapies, their treatment cost is much higher as compared to hospitals that may reduce its preference.

Stem Cell Therapy Market, By Region

North America stem cell therapy market held around 41.5% revenue share in 2018 and it is estimated to grow substantially in near future. Increasing the adoption of novel stem cell therapies will prove beneficial for regional market growth. Moreover, favorable government initiatives have a positive impact on regional market growth. For instance, the government of Canada has initiated Strategic Innovation Fund Program that invests in research activities carried out for stem cell therapies enabling development in stem cell therapy. Above mentioned factors are expected to drive the North America market growth.

Asia Pacific stem cell therapy market is anticipated to witness 10.8% growth in the near future owing to increasing awareness amongst people pertaining to the benefits of advanced stem cell therapies. Additionally, favorable initiatives undertaken by several organizations will promote industry players to come up with innovative solutions. For instance, according to Pharma Focus Asia, members of the Asia-Pacific Economic Cooperation collaborated with Life Sciences Innovation Forum to involve professionals having expertise in stem cell therapies from academia and research centers to promote developments in stem cell research. Thus, growing initiatives by organizations ensuring the availability of new stem cell therapies will foster regional market growth.

Latin America Stem Cell Therapy Market Size, By Country, 2025 (USD Million)

Key Players, Recent Developments & Sector Viewpoints: Stem Cell Therapy Market

Key industry players in the stem cell therapy market include Astellas Pharma Inc, Cellectis, Celyad, Novadip Biosciences, Gamida Cell, Capricor Therapeutics, Cellular Dynamics, CESCA Therapeutics, DiscGenics, OxStem, Mesoblast Ltd, ReNeuron Group, and Takeda Pharmaceuticals. Chief industry players implement several initiatives such as mergers and acquisitions to sustain market competition. Also, receiving approvals for stem cell therapy products from regulatory authorities fosters the companys growth. For instance, in March 2018, the European Commission approved Takedas Alofisel that is off-the-shelf stem cell therapy. Product approval will help the company to gain a competitive advantage and capture market share.

Stem Cell Therapy Industry Viewpoint

The stem cells industry can be traced back to the 1950s. In 1959 first animals were made by in-vitro fertilization by preserving the stem cells. Till 2000, research was being carried out on stem cells to study its therapeutic effect. In 2000, fund allocations were made to research on cells derived from aborted human fetuses. In the same year, scientists derived human embryonic stem cells from the inner cell mass of blastocytes. Later, in 2010, clinical trials for human embryonic stem cell-based therapy were initiated. As technology progressed, stem cell therapy for treating cancer was developed. However, due to ethical issues, the use of stem cells for curing diseases witnessed slow growth for a few years. But as the regulatory scenario changed, people started preferring stem cell therapies due to its better efficacy. Stem cell therapy is in the developing stage and has numerous growth opportunities in developing economies with a high prevalence of chronic diseases.

Key Industry Development

In September 2020, Takeda Pharmaceutical Company Limited announced the expansion of its cell therapy manufacturing capabilities with the opening of a new 24,000 square-foot R&D cell therapy manufacturing facility at its R&D headquarters in Boston, Massachusetts. The facility provides end-to-end research and development capabilities and will accelerate Takedas efforts to develop next-generation cell therapies, initially focused on oncology with the potential to expand into other therapeutic areas.

The R&D cell therapy manufacturing facility will produce cell therapies for clinical evaluation from discovery through pivotal Phase 2b trials. The current Good Manufacturing Practices (cGMP) facility is designed to meet all U.S., E.U., and Japanese regulatory requirements for cell therapy manufacturing to support Takeda clinical trials around the world.

The proximity and structure of Takedas cell therapy teams allow them to quickly apply what they learn across a diverse portfolio of next-generation cell therapies including CAR NKs, armored CAR-Ts, and gamma delta T cells. Insights gained in manufacturing and clinical development can be quickly shared across global research, manufacturing, and quality teams, a critical ability in their effort to deliver potentially transformative treatments to patients as fast as possible.

Takeda and MD Anderson are developing a potential best-in-class allogeneic cell therapy product (TAK-007), a Phase 1/2 CD19-targeted chimeric antigen receptor-directed natural killer (CAR-NK) cell therapy with the potential for off-the-shelf use being studied in patients with relapsed or refractory non-Hodgkins lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Two additional Phase 1 studies of Takeda cell therapy programs were also recently initiated: 19(T2)28z1xx CAR T cells (TAK-940), a next-generation CAR-T signaling domain developed in partnership with Memorial Sloan Kettering Cancer Center (MSK) to treat relapsed/refractory B-cell cancers, and a cytokine and chemokine armored CAR-T (TAK-102) developed in partnership with Noile-Immune Biotech to treat GPC3-expressing previously treated solid tumors.

Takedas Cell Therapy Translational Engine (CTTE) connects clinical translational science, product design, development, and manufacturing through each phase of research, development, and commercialization. It provides bioengineering, chemistry, manufacturing, and control (CMC), data management, analytical, and clinical and translational capabilities in a single footprint to overcome many of the manufacturing challenges experienced in cell therapy development.

Key Insights Covered: Exhaustive Stem Cell Therapy Market

1. Market size (sales, revenue and growth rate) of Stem Cell Therapy industry.

2. Global major manufacturers operating situation (sales, revenue, growth rate and gross margin) of Stem Cell Therapy industry.

3. SWOT analysis, New Project Investment Feasibility Analysis, Upstream raw materials and manufacturing equipment & Industry chain analysis of Stem Cell Therapy industry.

4. Market size (sales, revenue) forecast by regions and countries from 2019 to 2025 of Stem Cell Therapy industry.

Research Methodology: Stem Cell Therapy Market

Looking for more? Check out our repository for all available reports on Stem Cell Therapy in related sectors.

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Stem Cell Therapy Market Research Report Forecast to 2029 (Includes Business Impact of COVID-19) - Cheshire Media

Updated data for a second anti-BCMA therapy, idecabtagene vicleucel (ide-cel) from Bristol Myers Squibb/bluebird bio, will be presented, including health-related quality of life results from the KarMMA study in patients with heavily pretreated R/R multiple myeloma. FDA has assigned a March 27, 2021, target date for action on this therapy.

Also anticipated are results from the APOLLO study in relapsed multiple myeloma, which will show that adding daratumumab and hyaluronidase-finj, called Darzalex Faspro by Janssen, to pomalidomide and dexamethasone reduces the risk of disease progression or death by 37% compared with pomalidomide and dexamethasone alone.

Notably, this phase 3 study involves subcutaneous administration of daratumumab, which offers significantly reduced treatment time and burden for patients. Janssen has submitted results from APOLLO to FDA and the European regulators.

The subcutaneous formulation of daratumumab offers patients and physicians a 3- to 5-minute administration experience and the potential to reduce systemic administration-related reactions compared to intravenous administration of daratumumab, said Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Athens, Greece, who is the studys principal investigator.

The REACH3 study, a phase 3 randomized study of ruxolitinib (Jakavi) vs best-available-therapy, will have important implications in chronic graft-vs-host-disease (GvHD). This condition occurs when new T cells from a stem cell transplant identify the patients cells as foreign and attack them, creating reactions from rashes to gastrointestinal issues to harm to the liver.

Results involving transplant in myelodysplatic syndromes (MDS) could have important implications for reimbursement. Corey Cutler, MD, MPH, FRCPC, of Dana-Farber Cancer Institute will present results that show transplantation of hematopoietic stem cells from compatible donors nearly doubled the survival rate of patients aged 50 to 75 years.

Even though transplant is frequently used in younger patients, it has not been widely used among older patients. Lack of Medicare coverage is a major barrier, Cutler explained. This study adds to a growing body of evidence that suggests its time to revisit the reimbursement question.

Asked his thoughts on whether CMS might change its policy, Cutler said, I cant speak for the agency, but I will tell you there are several studies that do suggest it should be covered.We are, of course, reaching out to CMS.

Fridays press briefing ahead of the opening of ASH highlighted the results for MDS and daratumumab and others that are expected to be practice changing. To know that older patients do well with transplant is a really important message, said Lisa Hicks, MD, MSc, a hematologist from St. Michaels Hospital in Canada, who moderated the briefing.

Ian Flinn, MD, of Tennessee Oncology, who is an author on several studies being presented at ASH involving venetoclax (Venclexta) and Brutons tyrosine kinase (BTK) inhibitors in chronic lymphocytic leukemia, said he was interested to see the results of the CAPTIVATE trial.

He said that right now, venetoclax is a fixed-duration therapy. Now, we need to figure out whether thats a good idea or not, Flinn said. CAPTIVATE will help clinicians understand whether they should keep patients on venetoclax plus ibrutinib after they have reached the point of minimal residual disease.

The ASH meeting will also highlight research examining disparities in care, as well as the effects of COVID-19 on outcomes. On Saturday, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), will discuss the latest information on COVID-19 and its impact on hematologic conditions in a fireside chat with ASH President Stephanie J. Lee, MD, MPH.

This week, President-elect Joe Biden announced that Fauci will be a chief medical adviser, in addition to retaining his longtime role at NIAID during the new administration.

Maggie L. Shaw contributed to this report.

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ASH Goes Remote as CAR T-Cell Therapy Competition Heats Up - AJMC.com Managed Markets Network

Ankit Kansagra, MD, an assistant professor in theDepartment of Internal Medicineat UT Southwestern Medical Center and assistant director of theOutpatient Stem Cell Transplant Program, discusses chimeric antigen receptor T-cell agents in the pipeline for multiple myeloma (MM) and how these therapies may impact the treatment landscape pending future approvals.

In part two of this interview with Dr. Kansagra, available December 8, he discusses potential new combination therapy options for MM.

DocWire News: Dr. Kansagra, can you discuss some of the CAR T-cell therapies in development for multiple myeloma, including their targets, clinical trial data that weve seen, and your expectations for any future FDA approvals?

Dr. Kansagra: In multiple myeloma, a few of the CAR T-cell therapy targets, which in the most developments, have been the BCMA-targeted CAR T-cell therapies. Those have been most exciting because they have made it to the phase I to phase II trials, especially the registrational studies from Celgene or Bluebird, BMS, the bb2121 compound or the Janssen compound 4538, being farthest out in the clinical development for CAR T-cell therapy. There are certainly a few other CAR T-cell therapies for multiple myeloma, which have grown, and theyre probably in the earlier development of therapy. An example being the CD38 CAR T-cell therapy, the SLAMF CAR T-cell therapy, and GPR5CD CAR T-cell therapy. Those are the three different targets which are being evaluated as T-cell targets.

DocWire News: How do you see the approval of these CAR T-cell therapy impacting the treatment landscape for multiple myeloma?

Dr. Kansagra: I think its going to be a huge improvement in our momentum of our treatment options. We have already seen cell therapy in myeloma have impressive results in terms of the response rates. I think the first important step is you have these patients who have got six or seven different lines of treatment, and now they are getting a novel product or a novel mechanism of action and also novel target and seeing an impressive response rate. That was amazing. Thats step number one.

Step number two is, as we have got further into the clinical development of CAR T-cell therapy, we have seen the safety of these products because that is extremely important that our products are safer.

Then the third thing which we have seen is that long-term follow-ups are not there, but what we have started seeing is that our responses, which could last up to a year or a year and a half for the population, where we would have usually seen maybe barely a response in a matter of months.

I think those are exciting times for our patients with multiple myeloma, where they have failed a lot of therapies. I think the more exciting times are going to come when we will start seeing these CAR T-cell therapies, potentially even in earlier lines of treatment options, where they could use maybe as a second-line treatment or as a first-line treatment after stem cell transplant or in lieu of stem cell transplant, maybe we can have deeper and longer remission rates.

DocWire News: With some of these agents potentially coming to market, do you foresee any challenges, either associated with adverse events or the ability to make these treatments widely available to patients?

Dr. Kansagra: Access to care is certainly near and dear to me, and thinking about those challenges is extremely, extremely important. I think were going to probably face challenges in a lot of different ways.

The first thing is, obviously, how can we get our patients to the centers who are giving CAR T-cell therapy? How are we going to bring them? We know from our autologous stem cell transplant over the last three to four decades, that still not every eligible transplant patient is referred to a transplant center, for whatever reasons. There are multiple reasons; there are socioeconomic reasons; there are distance reasons. But a lot of them are fixable reasons. There are some which are unfixable, but there are some fixable. I think the first and the foremost important thing is going to be to get our patients to a place who is delivering CAR T-cell therapy. Thats the challenge number one.

Challenge number two is, once they are in there, making sure that they are able to get that thing. So it means theyre not coming too late in their game, so trying to make sure theyre referred in earlier points, so that processes in place, that insurance approval has got started, if we need to work on the sociodemographic issues, how are they going to stay in a particular area? What is the social help, what is the family help theyre going to need? If they had referred earlier on, thats another, I call it, bottleneck that we need to think of that. Thats where we need to act on it.

The hard thing is obviously the cost. We dont know what is going to be the cost of the myeloma CAR T-cell therapy, or what is the price of those things. We can certainly estimate that its not going to be as cheap given the three CAR-Ts, which are not FDA-approved. I think its going to be expensive. You will have to think of the cost of care model of how we are going to work with this.

Last but not least of the challenges are the CAR-T itself. These are in the logistical challenge bucket. Then there are the challenges in the CAR-T landscape or the product itself. We still know that these are second-generation CAR T-cell therapies. They dont work for everybody. They have a high response rates, but they dont last that long. We hope to see longer remissions. An example I give, in comparison to large-cell lymphoma, we had 50% of the people who plateaued out, now coming up to about three years. In myeloma, we havent obviously made it to three years since the CAR T-cell therapy have started, but we do worry that there is a tail end of the curve that people are already relapsing to it. Obviously, that goes to the product itself or the construct itself, which needs to be developed in multiple different ways. I think of them as two major challenges ahead of us.

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Hematologist Discusses the Impact a Myeloma CAR T-Cell Approval Would Have on the Treatment Landscape - DocWire News

Ciltacabtagene autoleucel (cilta-cel; JNJ-68284528) demonstrated a significant response rate and showed a manageable safety profile at the recommended phase 2 dose in patients with relapsed or refractory multiple myeloma, according to combined results from the CARTITUDE-1 trial (NCT03548207).1

The objective response rate (ORR) was 96.9%, consisting of stringent complete responses (sCRs) in 67.0% of patients, very good partial responses in 25.8%, and partial responses in 4.1%.

We saw how heavily pretreated these patients were, and to see a one-time treatment give these kinds of response rates is quite exceptional, said Deepu Madduri, MD, in a presentation during the 2020 American Society of Hematology (ASH) Annual Meeting. Whats even more impressive is that 72% of these patients are still maintaining their response at the time of data cut off.

Cilta-cel is a second-generation chimeric antigen receptor (CAR) T-cell therapy consisting of a CD3 signaling domain, a 4-1BB costimulatory domain, and 2 B-cell maturation antigen (BCMA) binding domains.

CARTITUDE-1 is a phase 1b/2 study exploring the safety and efficacy of cilta-cel in patients with progressive multiple myeloma per IMWG criteria who have received at least 3 prior therapiesincluding a proteasome inhibitor, immunomodulatory drug, and anti-CD38 therapyor who are double refractory, and have an ECOG performance status of 0 or 1.

Once patients were screened and enrolled in the study, they underwent apheresis and bridging therapy, if necessary, followed by lymphodepleting chemotherapy of cyclophosphamide at 300 mg/m2 and fludarabine at 30 mg/m2 on days 5 to 3 prior to CAR T-cell infusion. The target dose was 0.75 x 106 viable CAR-positive T cells/kg, but the median dose administered was 0.71 x 106 (range, 0.51-0.95 x 106).

Primary objectives for the phase 1b portion of the study were to characterize the safety of the agent and set the recommended phase 2 dose; and in phase 2, the primary end point was to evaluate efficacy by ORR.

Previously, results of the phase 1b portion of the study were presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program showing responses in all 29 patients, including a very good partial response or higher rate of 97%.2

The presentation at ASH covered findings for all patients treated with cilta-cel in the phase 1b and 2 portions of the study (N = 97). Of these patients, 86% are still on the trial.

Median turnaround time for cilta-cel manufacturing was 29 days, and no patients discontinued from the study due to manufacturing failure.

At baseline, the median age of all patients was 61 (range, 43-78), 58.8% were male, and 13.4% had extramedullary disease. Almost one-fourth of patients (23.7%) had a high-risk cytogenetic profile, most often including del(17p), and 91.9% had tumor BCMA expression of at least 50%. The median number of prior therapies was 6 (range, 3-18), indicating a heavily pretreated population, with 87.6% being triple-class refractory and 42.3% being penta-refractory. Ninety-nine percent of patients were refractory to their last line of therapy, which was not required for inclusion in this study, noted Madduri. Additionally, 89.7% previously underwent autologous stem cell transplant and 8.2% received allogenic transplant.

Responses were ongoing at cutoff in 72.2% of patients and the median time to first response was 1 month (range, 0.9-8.5). Of 57 patients evaluable for minimal residual disease (MRD), the negativity rate at 10-5 was 93.0%, accounting for 54.6% of the overall population. A total of 33 patients (34.0%) achieved both sCR and MRD negativity. The median time to MRD negativity was also 1 month (range, 0.8-7.7).

Early, deep, and durable responses are observed in this heavily pretreated population, said Madduri, who is an assistant professor of medicine, hematology, and medical oncology at Mount Sinai Medical Center in New York.

The median progression-free survival (PFS) was not reached in responders but at 12 months, the PFS rate was 76.6% (95% CI, 66.0%-84.3%). In those who achieved an sCR, the 12-month PFS rate was 84.5% (95% CI, 72.0%-91.8%) and was 68.0% (95% CI, 46.1%-82.5%) in patients who had a very good partial response.

Patients with relapsed/refractory myeloma have a median overall survival of only 9.2 months in triple-refractory [disease] and only 5.6 months in penta-refractory. In this study, we know that the median PFS is at least a full year and we still haven't even reached a median PFS after a median duration of follow-up of 12.4 months, Madduri commented.

At 1 year, the overall survival rate was 88.5% (95% CI, 80.2%-93.5%). The median overall survival was also not yet reached.

The most common grade 3/4 adverse events (AEs) were hematologic and observed in 99.0% of all patients, consisting of neutropenia in 94.8%, anemia in 68.0%, leukopenia in 60.8%, and thrombocytopenia in 59.8%. The median time to recovery of these grade 3/4 cytopenias was 2 weeks for neutropenia and 4 weeks for thrombocytopenia. The rate of any-grade infections was 57.7%, and the most common grade 3/4 infections were pneumonia (8.2%) and sepsis (4.1%).

Grade 3/4 non-hematologic toxicities were not common in the study, including hypophosphatemia at 7.2%, fatigue at 5.2%, aspartate aminotransferase increase at 5.2%, and hyponatremia at 4.1%.

Additionally, cytokine release syndrome (CRS), a common CAR T-cell therapyrelated AE, was reported in 94.8% of patients at any grade, but only 4.1% were grade 3/4 in severity.

One distinguishing aspect of this study is the median time to onset of CRS, which is 7 days, with 89% of these patients having CRS at day 4 or later and 74% of these patients having CRS at day 6 or later, opening the possibility of outpatient administration. This may be explained by the fact that the maximum peripheral expansion of cilta-cel occurred generally around a median of 13 days, Madduri said.

Tocilizumab and corticosteroid support were required in 69.1% and 21.6% of patients, respectively. CRS resolved in 98.9% of all patients within 14 days of onset.

Neurotoxicity, another known complication of CAR T-cell therapies, was reported in 20.6% of patients at any grade and of grade 3 or higher in 10.3%. Specifically, immune effector cellassociated neurotoxicity syndrome (ICANS) cases were reported in 16.5% at any grade and of grade 3 or higher in 2.1%. All ICANS occurred within a median of 8 days (range, 3-12) and resolved within a median of 4 days (range, 1-12).

Other neurotoxicities, which were reported in 12 patients (12.4%), occurred after resolution of CRS or ICANS and included 5 patients with movement and/or neurocognitive changes and 7 with nerve palsy or peripheral motor neuropathy; 6 of these resolved. In the other 6 patients, 1 patient died from complications of the AE, 4 died of other causes, and 1 has ongoing neurotoxicity. The median time to onset for these toxicities was 27 days (range, 11-108) with recovery in a median of 75 days (range, 2-160).

We saw no clear etiology in the other neurotoxicities, but we saw that maybe there could be some mild associations with high tumor burden, prior CRS, ICANS, or even the higher expansion and persistence of these CAR T cells. So we did implement some mitigation strategies in our subsequent CARTITUDE development program allowing patients to have more chemotherapy, having more aggressive steroids for ICANS, like early intervention and extensive monitoring, Madduri said in the question-and-answer portion of the session following her presentation.

A total of 14 patients died during the study within 45 to 694 days of infusion. Five patient deaths were due to progressive disease, 3 were due to AEs that were not related to treatment, and 6 were due to AEs considered to be related to treatment with cilta-cel. These AEs included sepsis and/or septic shock in 2 patients, and CRS or hemophagocytic lymphohistiocytosis, lung abscess, respiratory failure, and neurotoxicity in 1 patient each.

Cilta-cel is continuing to be studied in patients with multiple myeloma in other clinical trials, including in earlier-line settings. Additionally, both the CARTITUDE-2 (NCT04133636) and CARTITUDE-4 (NCT04181827) studies are considering whether cilta-cel can safely be given in an outpatient setting.

In December 2019, cilta-cel was granted an FDA breakthrough therapy designation for the treatment of patients with previously treated multiple myeloma based on earlier results of the CARTITUDE-1 trial.3

References

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Cilta-Cel CAR T-cell Therapy Impresses With High ORR in R/R Multiple Myeloma - Targeted Oncology