On February 8, 2021 4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutic products (LBPs), a novel class of drug derived from the microbiome, reported a clinical trial collaboration and supply agreement with Merck KGaA, Darmstadt, Germany and Pfizer Inc. for BAVENCIO (avelumab), the first and only immunotherapy approved as a first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma (Press release, 4d Pharma, FEB 8, 2021, View Source [SID1234574743]). BAVENCIO is co-developed and co-commercialized by Merck KGaA, Darmstadt, Germany and Pfizer Inc.

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Under the collaboration, 4D pharma intends to commence a clinical trial in 2021 to evaluate BAVENCIO in combination with MRx0518 as a first-line maintenance therapy for patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.

"With this second clinical trial collaboration for MRx0518 with a leading immune checkpoint inhibitor, 4D is able to evaluate MRx0518 in a new combination and earlier treatment setting. Following the promising data already generated in combination with checkpoint inhibitor pembrolizumab in refractory patients, and MRx0518 monotherapy data demonstrating single agent immuno-modulation presented last year at SITC (Free SITC Whitepaper), this collaboration allows us to continue to build a broad understanding of the safety and efficacy of MRx0518 across a range of solid tumors and stages of disease," said Duncan Peyton, Chief Executive Officer, 4D pharma. "The combination of MRx0518 with BAVENCIO has the potential to further enhance the positive clinical outcomes achieved by BAVENCIO for the significant number of patients in this treatment setting."

About MRx0518

MRx0518 is single strain Live Biotherapeutic product in development for the treatment of cancer. It is delivered as an oral capsule and stimulates the body’s immune system, directing it to produce cytokines and immune cells that are known to attack tumours. It is currently being evaluated in three clinical trials in patients with cancer. MRx0518-I-001 is a neoadjuvant monotherapy study in a variety of solid tumours and is being conducted at Imperial College (London, UK). MRx0518-I-002 is in combination with KEYTRUDA (pembrolizumab) in patients whose disease has previously progressed on anti-PD-1 therapies. The Coordinating Investigator of the study is at The University of Texas MD Anderson Cancer Center, Houston, USA, with multiple additional sites in the US. The study is being conducted in collaboration with MSD, the tradename of Merck & Co., Inc., Kenilworth, NJ, USA. MRx0518-I-003 is in combination with preoperative radiotherapy in resectable pancreatic cancer. A fourth clinical trial of MRx0518 in combination with BAVENCIO (avelumab) in the first-line maintenance setting for urothelial carcinoma, conducted in collaboration with Merck KGaA, Darmstadt, Germany and Pfizer Inc., is expected to initiate in 2021.

Avelumab Approved Indications

Avelumab (BAVENCIO) is indicated in the US for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed with first-line platinum-containing chemotherapy. BAVENCIO is also indicated for the treatment of patients with locally advanced or metastatic UC who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Avelumab in combination with axitinib is approved in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

In the US, the FDA granted accelerated approval for BAVENCIO for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

Avelumab Important Safety Information from the US FDA-Approved Label

The warnings and precautions for avelumab (BAVENCIO) include immune-mediated adverse reactions (such as pneumonitis and hepatitis including fatal cases, colitis, endocrinopathies, nephritis, and other immune-mediated adverse reactions as a single agent or in combination with axitinib which can be severe and have included fatal cases), infusion-related reactions, hepatotoxicity in combination with axitinib, major adverse cardiovascular events (MACE) in combination with axitinib which can be severe and have included fatal cases, and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO monotherapy include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite, urinary tract infection and rash. Common adverse reactions (reported in at least 20% of patients) in patients receiving BAVENCIO in combination with axitinib include diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and headache. Grade 3-4 hematology laboratory value abnormalities reported in at least 10% of patients with Merkel cell carcinoma treated with BAVENCIO monotherapy include lymphopenia; in patients receiving BAVENCIO in combination with axitinib, grade 3-4 clinical chemistry abnormalities include blood triglyceride increased and lipase increased.

On February 8, 2021 The Sarah Cannon Transplant and Cellular Therapy Network, formerly the Sarah Cannon Blood Cancer Network, reported 19 abstracts and presentations have been accepted for presentation at the 2021 TCT | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held virtually from February 8-12, 2021 (Press release, Sarah Cannon Research Institute, FEB 8, 2021, View Source [SID1234574742]). The meetings bring together thousands of healthcare professionals for a full scientific program that address the most timely issues in hematopoietic cell transplantation (HCT) and cellular therapy.

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"We look forward to discussing the important developments in our rapidly evolving field at this year’s TCT meetings," says Fred LeMaistre, MD, Physician-in-Chief of Blood Cancers, Sarah Cannon. "Sarah Cannon experts will share presentations focused on immune effector cell therapy and the efficacy and treatment standards of HCT for both adult and pediatric patients. Together, the advances we are making across the network will ultimately better serve our patients."

The Sarah Cannon Blood Cancer Network has evolved, as have the therapies it offers, to become the Sarah Cannon Transplant and Cellular Therapy Network in 2021. This transition reflects the latest advancements in the field and the broader options now available to patients. In 2020, the Sarah Cannon Transplant and Cellular Therapy Network performed ~1,200 hematopoietic cell transplants and treated more than 100 patients with various cellular therapies, including both FDA-approved and research options, across eight Foundation For The Accreditation of Cellular Therapy (FACT)/Joint Accreditation Committee ISCT-Europe & EBMT (JACIE) accredited sites.

2021 TCT | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR oral and poster presentations with Sarah Cannon Transplant and Cellular Therapy Network experts as first authors will be presented by:

Haydar Frangoul, MD, MS, Medical Director, Pediatric Hematology/Oncology, Sarah Cannon Pediatric Transplant and Cellular Therapy Program at TriStar Centennial, who will present "Safety and Efficacy of CTX001 in Patients with Transfusion-Dependent β-Thalassemia (TDT) or Sickle Cell Disease (SCD): Early Results from the Climb THAL-111 and Climb SCD-121 Studies of Autologous CRISPR-Cas9-Modified CD34+ Hematopoietic Stem and Progenitor Cells (HSPCs)" in an oral presentation on February 10 from 3-5 p.m. CST.
Jesus G. Berdeja, MD, Director, Myeloma Research, Sarah Cannon Research Institute, who will present "Efficacy and Safety of Idecabtagene Vicleucel (ide-cel, bb2121) in Elderly Patients with Relapsed and Refractory Multiple Myeloma: KarMMa Subgroup Analysis" in a poster presentation on February 8 – February 12 from 8:30 a.m. – 5:30 p.m. CST.
Therese Dodd, BA, MBA, RN, CPHQ, Quality Improvement Director, Sarah Cannon Transplant and Cellular Therapy Network, who will present "Successful Virtual Mock FACT Inspection: How Sarah Cannon Blood Cancer Network and Texas Transplant Institute in San Antonio and Austin Made It Work" and "Resiliency During a COVID 19 Pandemic: The Quality Manager Perspective" in two poster presentations on February 8 – February 12 from 8:30 a.m. – 5:30 p.m. CST.
Alireza Eghtedar, MD, Associate Member Physician, Colorado Blood Cancer Institute at Presbyterian/St. Luke’s Medical Center- HealthONE, who will present "Non-Myeloablative Hematopoietic Stem Cell Transplantation (NMA HSCT) Utilizing Low-Dose Total Body Irradiation (TBI) Plus Fludarabine (Flu): A Comparison of Single-Center Based Flu 150 Mg/m2 Plus 400 Cgy TBI Versus Flu 90 Mg/m2 and 200 Cgy TBI Containing Regimens" in a poster presentation on February 8 – February 12 from 8:30 a.m. – 5:30 p.m. CST.
Racheal Peaytt, PharmD, PGY-2 Oncology Pharmacy Resident, Sarah Cannon Cancer Institute at TriStar Centennial Medical Center, who will present "The Impact of Early Versus Late Tocilizumab Use in Patients with Cytokine Release Syndrome Receiving Immune Effector Cell Therapy" in a poster presentation on February 8 – February 12 from 8:30 a.m. – 5:30 p.m. CST.

On February 8, 2021 Seneca Therapeutics, Inc. ("STI"), a clinical-stage biopharmaceutical company dedicated to the development of targeted oncolytic immunotherapeutics based on Seneca Valley Virus (SVV-001), reported the expansion of its R&D pipeline with six new armed gene therapy/oncolytic constructs directed against important cancer targets and indications (Press release, Seneca Therapeutics, FEB 8, 2021, View Source [SID1234574741]). STI also announced an SVV-001 Armed Construct program developing precision medicine constructs expressing patient-specific Neo-antigens. Each of these new gene therapy technologies uses SVV to exclusively target cancer cells with TEM 8 expression. Normal cells lack significant expression of TEM 8 and are therefore not infected by SVV-001, and so the armed transgene will not express in normal cells. Studies in multiple human tumor types indicates TEM 8 expression is an adverse indicator of long-term survival and is associated with cancer metastasis. STI intends to develop each combination as an IV product, taking advantage of the multiple IV dosing program currently underway at the company:

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SVV-012- SVV+ Anti PD-L1 – "Addition of a checkpoint inhibitor is designed to enhance the CD8+ T-cell response against tumors"
SVV-024 – SVV+ Enhanced IL-2 Gene – "This construct is designed to bind IL-2 receptors to activate the immune response in tumors without activating CD25 and thereby avoid toxicities observed with the IL-2 protein"
SVV-037 – SVV+ CXCL-9 – "This construct is designed to express the chemokine CXCL-9 in the tumor microenvironment and promote recruitment of immune cells into treated tumors"
SVV-044 – SVV+ TGF-beta decoy – "This construct is designed to block TGF-beta signaling in tumors and avoid immunosuppression"
SVV- 058 SVV+ Nitroreductase – "This nitroreductase construct is designed to function as a prodrug and convert cytotoxic metabolites selectively in the tumor microenvironment"
SVV- 069 – SVV+ IL-2/IL-15 Fusion Protein – "Vectors delivering IL-2/IL-15 agonists are designed to improve immune cell trafficking and infiltration into tumors and provide both T-cell and NK-cell signals"
Each of these products either has been or is being produced in STI’s SVV platform. Animal studies for each product are anticipated to begin in 2Q21.

The SVV-001 Armed Construct for Neo-antigens program plans to use patient specific neo-antigens to take advantage of the rapid two-week development cycle for SVV-001 Armed Constructs.

"SVV itself has many distinct advantages over other forms of cancer therapy. Chief among these is the exquisite cancer cell specificity of both SVV replication and the expression of a transgene. Together, these make SVV a unique and powerful multi-modal platform," said Dr. Paul Hallenbeck, Ph.D. Founder and President of STI.

On February 8, 2021 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), 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 diseases, reported the presentation of data supporting the proposed mechanism of action of their lead product candidate, tabelecleucel (tab-cel), and five additional poster presentations at the Transplantation & Cellular Therapy (TCT) Meeting of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR), held virtually February 8-12, 2021 (Press release, Atara Biotherapeutics, FEB 8, 2021, View Source [SID1234574740]).

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"We are pleased to present key translational data advancing the clinical development of ATA188 and tab-cel, the most advanced allogeneic T-cell immunotherapy in development. Additional data being presented at TCT also support the further development of tab-cel in EBV-driven diseases, such as EBV+ acquired and primary immunodeficiency lymphoproliferative diseases (AID-LPD and PID-LPD) for which we’re currently enrolling patients for a clinical study," said Jakob Dupont, M.D., Head of Global Research & Development at Atara. "These are diseases with few treatment options and poor prognosis, and it is our goal to ultimately bring this potentially transformative therapy to patients in need. We look forward to advancing tab-cel, remaining on track to complete the Biologics License Application in the third quarter of this year based on very encouraging clinical data from an interim analysis of our pivotal trial."

Results presented at TCT detail new findings from a comprehensive multiomic analysis of modes of activation for tab-cel. Each component of the assessment contributes to building the overall understanding of therapeutic activity, mechanisms of action and extended characteristics.

In this analysis, a subset of tab-cel lots were used to confirm and establish the consistency of the product’s profile, regardless of donor.

These results demonstrated, that upon stimulation, tab-cel exhibits a consistent activation signature at the level of gene expression, T-cell receptor engagement (TCR), and secretion of factors associated with effective T cell responses. Results further illustrated that the tab-cel manufacturing process results in complementary clonal expansion and consistent enrichment of TCRs associated with productive engagement of EBV-driven diseases.

Atara will also report additional data sets related to tab-cel, as well as preclinical findings demonstrating the potent anti-tumor activity of the Company’s next-generation CD19-based CAR T, ATA3219.

Additionally, the Company is presenting data on an innovative testing solution to detect and quantify non-engineered allogeneic T-cell therapies such as ATA188. As demonstrated in partnership with CareDx, AlloCell is a precise and reproducible method that resolves the analytical barrier for non-engineered allogeneic cell therapies, which do not have transgenes available to support standard quantitative pharmacokinetic (PK) assay development. The novel testing solution offers potential applications in clinical development for determining PK profiles and correlating with response and other clinical endpoints, including the understanding of fundamental aspects of pharmacology such as presence and expansion in the patient’s body.

"Together these analyses represent a leading edge for allogeneic cell therapy research, leveraging state-of-the-art profiling technologies and innovating new methodologies in collaboration with CareDx to support development of Atara’s programs," said Blake Aftab, Head of Preclinical Science and Translational Medicine at Atara. "These methods not only support our novel allogeneic EBV T-cell development programs, but also have potential for wide-ranging applications for patients."

Atara Poster Presentations at TCT 2021:
All posters will be available for viewing at the start of the meeting on Monday, February 8, 2021.

Title: Comprehensive activation profiling of tabelecleucel, an off-the-shelf, allogeneic EBV-specific T cell therapy
Poster #: 206

Title: A sensitive and precise universal surveillance solution for pharmacokinetic monitoring of off-the-shelf cell therapies (in collaboration with CareDx)
Poster #: 204

Title: Clinical experience of tabelecleucel in patients with EBV+ primary (PID) or acquired immunodeficiency (AID) associated lymphoproliferative disease (encore from ASH (Free ASH Whitepaper) 2020)
Poster #: 219

Title: Clinical experience of tabelecleucel in patients with life-threatening complications of Epstein–Barr virus viremia (encore from ASH (Free ASH Whitepaper) 2020)
Poster #: 223

Title: A multicenter, multicohort, open-label, single arm per cohort, Phase II study to assess the efficacy and safety of tabelecleucel in patients with EBV-associated diseases using an adaptive two-stage study design (encore from ASH (Free ASH Whitepaper) 2020)
Poster #: 532

Title: ATA3219: A potent next-generation allogeneic off-the-shelf CD19 CAR-T therapy without the need for gene editing (encore from ASH (Free ASH Whitepaper) 2020)
Poster #: 203

On February 8, 2021 Akebia Therapeutics, Inc. (Nasdaq: AKBA), a biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease, reported plans to release its financial results for the fourth quarter and full-year 2020 ended December 31, 2020, on Thursday, February 25, 2021, before the opening of the financial markets (Press release, Akebia, FEB 8, 2021, View Source [SID1234574739]).

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Akebia will host a conference call at 9:00 a.m. Eastern Time on Thursday, February 25, 2021 to discuss its fourth quarter and full-year 2020 financial results and recent business highlights. To listen to the conference call, please dial (877) 458-0977 (domestic) or (484) 653-6724 (international) using conference ID number 5455117. The call will also be webcast live and can be accessed via the Investors section of the Company’s website at View Source

A replay of the conference call will be available two hours after the completion of the call through March 3, 2021. To access the replay, dial (855) 859-2056 (domestic) or (404) 537-3406 (international) and reference conference ID number 5455117. An online archive of the conference call can be accessed via the Investors section of the Company’s website at View Source