On June 7, 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 cancer and autoimmune diseases, reported a combined long-term overall survival (OS) analysis from three clinical studies of tabelecleucel (tab-cel) in patients with Epstein-Barr virus-driven post-transplant lymphoproliferative disease (EBV+ PTLD) after solid organ transplantation (SOT) (Press release, Atara Biotherapeutics, JUN 7, 2021, View Source [SID1234583673]). The results are featured in an oral plenary presentation at the American Transplant Congress (ATC 2021 Virtual Connect), taking place June 4-9, 2021.

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Combined objective response rate (ORR) and OS data across two SOT subgroups – patients relapsed or refractory (R/R) to rituximab monotherapy and patients R/R to rituximab + chemotherapy (CT) – showed one- and two-year OS for patients achieving either complete response (CR) or those achieving partial response (PR). Data presented at ATC 2021 confirm benefit of tab-cel in SOT PTLD and show similar one- and two-year probability of OS irrespective of patients achieving CR or PR (according to Lugano criteria). Treatment response and OS data were assessed from two completed single-arm, Phase 2 studies (95-024, NCT00002663 and 11-130, NCT01498484) and the multi-center expanded access (EAP-201) study (NCT02822495).

"Patients who have received a solid organ transplant such as a new kidney, lung, heart or liver and go on to develop EBV+ PTLD that is relapsed or refractory to rituximab monotherapy or R-chemotherapy face a poor prognosis, with median survival of only about three months," said Jakob Dupont, M.D., Head of Global Research & Development at Atara. "There is a significant unmet need in these patients for whom there are no approved therapies, let alone therapies specifically designed to treat EBV+ PTLD. Combined data from across three clinical studies in SOT recipients with relapsed or refractory disease demonstrated similar long-term survival benefit in those who had either partial or complete response to treatment. These data indicate that tab-cel may help address an urgent unmet need in these patients with high rates of mortality."

Overall Survival (OS) by Best Overall Response (BOR)

All SOT recipients with EBV+ PTLD R/R to rituximab as monotherapy or combined with chemotherapy were treated with tabelecleucel, receiving a median (range) of 2.0 (1-9) cycles

Atara has previously shown benefit in patients with EBV+ PTLD after SOT who responded to tab-cel, including up to 100 percent two-year survival rates1,2. Data presented at EBMT 2021 demonstrated similar results in terms of overall survival in EBV+ PTLD patients who received tab-cel following hematopoietic cell transplantation (HCT).

Safety

Tab-cel was well-tolerated in this immunocompromised population with high disease burden and multiple comorbidities. Notably, there was no emerging safety concern and no instances of tumor flare reaction, infusion-related reactions, graft versus host disease (GvHD), cytokine release syndrome (CRS), neurotoxicity or organ rejection reported in these patients.

"We are excited to see the data presented at ATC 2021 reinforce the clinical benefit in patients who responded to tab-cel, including up to 100 percent two-year survival rates," said Pascal Touchon, President and Chief Executive Officer at Atara. "Atara understands the imperative to provide treatment options for these very sick, treatment-refractory and immunocompromised patients."

Atara Presentation at ATC 2021:

Title: Overall Survival by Best Overall Response with Tabelecleucel in Patients with Epstein-Barr Virus-Driven Post-Transplant Lymphoproliferative Disease after Solid Organ Transplant

Date & Time: Monday, June 7, 2021 at 10:30 a.m. ET

Oral Session & Number: Plenary Oral Abstract Session 3

On June 7, 2021 Repertoire Immune Medicines, a clinical-stage biotech company decoding the immune synapse to create novel immune therapies for cancer, immune disorders, infectious disease, and other serious diseases, reported the upcoming presentation of new data from DECODE, its epitope and T cell discovery platform (Press release, Repertoire, JUN 7, 2021, View Source [SID1234583672]). The company will present data from three accepted oral abstracts at the Federation of Clinical and Immunology Societies (FOCiS) 2021 Virtual Annual Meeting taking place from June 8-11, 2021.

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The DECODE platform deciphers antigens and their precise epitopes presented by cells and recognized by the immune system. These interactions form the basis for cellular immunity and provide an opportunity for the creation of novel immune medicines.

"Repertoire is focused on advancing science to harness the power of the immune synapse using the company’s proprietary DECODE platform, which allows us to discover novel epitopes and the phenotypes of T cells that they activate and apply these to develop novel immune medicines," said Anthony Coyle, Ph.D., President, Research and Development, Repertoire. "Our presentations at FOCiS 2021 encompass our work across cancer, autoimmune disorders and infectious disease, and further reinforces the breadth of the platform."

Session details:

Comprehensive decoding of the immune synapse to SARS-CoV-2: Epitope discovery, HLA restriction, and the relationship to endemic coronaviruses and new emerging variants. Oral Presentation. Daniel Pregibon, Ph.D., et al.

The ability to comprehensively characterize the cellular response to SARS-CoV-2 has implications for new vaccine design, patient risk stratification and assessment, and potential prevention of the threat from emerging viral variants. Repertoire’s technologies provide new insights into the immune response to SARS-CoV-2 and can more broadly facilitate deeper quantification of cellular responses to pathogens where T cell immunity is poorly understood.
Identification of Novel Epitopes and their Associated MHC- Restricted T-cell Clonotypes in the Periphery of Patients with Type 1 Diabetes. Oral Presentation. Daniel S. Rivera et al.

Decoding the immune synapse will allow an in-depth understanding of the T-cell repertoire in type 1 diabetes, which is essential in identifying the key drivers of diabetogenesis. These insights will provide disease stratifying biomarkers and will open up new possibilities to develop novel targets for therapeutic intervention. Repertoire has discovered and validated TCR-antigen pairs across patient cohorts. The epitopes seen by multiple type 1 diabetes patients and recognized by T cells with memory or effector phenotypes enable the development of novel therapeutics to induce tolerance of autoreactive cells in patients with type 1 diabetes.
Understanding the Immune Synapse with DECODE Provides Unique Insights into the T Cell Repertoire in Cancer Patients, Defines Immunological Memory in Infectious Disease and Identifies Auto-reactive T Cells in Autoimmune Diseases. Oral Presentation. Joanna Swain, Ph.D., et al.

The development of transformative immune medicines that can harness and manipulate T cell responses has been severely limited by the inability to understand the codes that determine T cell behavior and function. To unlock these codes, it is essential to know how the entire peptidome is presented, its associated HLA allelic context, and the diversity of the reactive T cell repertoire. Repertoire has developed an extensive suite of state-of-the-art tools that enable decoding of all the components of the immune synapse with both depth and precision. Decoding all aspects of the immune synapse will shed more light on the immunological diversity, allowing development of the next generation of potential therapies in cancer, infectious disease and autoimmune disorders.

On June 7, 2021 IASO Biotherapeutics, a clinical-stage biopharmaceutical company engaged in the discovery and development of novel cell therapies for oncology and autoimmune diseases, reported that its clinical trial application for the in-house developed CD19xCD22 fully human dual-targeted CAR T-cell therapy (CT120) for treatment of its second indication for relapsed/refractory B-cell non-Hodgkin’s lymphoma (B-NHL), has been accepted by the National Medical Products Administration (NMPA) (Acceptance No.: CXSL2101088, CXSL2101089) (Press release, IASO BioMed, JUN 7, 2021, View Source [SID1234583671]). This acceptance came just one day after the acceptance of the drug’s first indication for treatment of CD19xCD22 positive relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). These successful clinical trial applications highlight the company’s speed and strength in developing innovative novel CAR-T therapies.

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CT120 is developed on IASO Bio’s fully human antibody platform IMARS and high throughput CAR-T drug selection platform. IMARS is one of the industry’s top antibody discovery platforms in terms of database capacity. With over 240 billion candidate antibodies, the platform has powerful capacity and provides speedy antibody screening. The company’s high-throughput CAR-T drug selection platform, which uses cutting-edge single-cell analysis and next-generation sequencing (NGS) technology, can implement cost effective, high efficiency functional CAR-T candidate screening. CT120 is prepared at IASO Bio’s integrated good manufacturing practice (GMP) compliant manufacturing facility in Nanjing, which is fully equipped to produce high quality plasmids, viral vectors and gene edited cellular products cost-efficiently.

B-cell non-Hodgkin’s lymphoma (B-NHL) is a group of hematologic malignancies of B-lymphocytes origin. Current standard of care (SOC) include chemotherapy, radiotherapy, hematopoietic stem cell transplant, molecular targeted drug, and more. While most patients can achieve short-term remission following standard care, relapsed or refractory disease is common. For such patients, conventional therapies are limited, and CAR-T therapy is considered to be a promising alternative. And while CD19-targeted single-targeted CAR-T therapy has shown good efficacy in clinical studies, some patients still experience progression or recurrence a short time after such therapy (Nature). It is thought that CD19 antigen escape on the surface of tumor cells is one of the possible reasons.

Studies have shown that both CD22 and CD19 are generally expressed on the surface of multiple B-cell tumors, including B-NHL. Similar to CD19, CD22 is also expressed on tumors with certain specificity, which makes it another ideal therapeutic target. In light of this, CD19xCD22 dual-targeted CAR-T therapy theoretically can reduce the risk of treatment evasion due to missing a single target. As a result, it shows good potential for further reducing disease recurrence and thus, yielding long-term survival benefits for patients.

"Investigator initiated trials (IITs) underway at Tongji Hospital – which is affiliated with Tongji Medical College of Huazhong University of Science & Technology and the First Affiliated Hospital, College of Medicine, Zhejiang University – show that fully human dual-targeted CT120 not only benefits CAR-T naïve relapsed/refractory B-ALL patients but also those whose disease progressed during or after murine single-targeted CD19 CAR-T. Therefore, the therapy shows promise in terms of both market landscape and patient benefits," said Dr. Wang Wen, CEO, IASO Biotherapeutics. "Importantly, our IND submission for this product marks the maturation of the company’s phage antibody library-based antibody discovery platform. We expect that fully human antibody products based on this antibody library will continuously contribute to the company’s cell therapy and antibody therapy pipelines. At IASO Biotherapeutics, we will continue to expand and exploit new product pipelines to benefit more patients in the future."

About CT120：

CT120 is an autologous dual-target CAR-T therapy. Its extra cellular domain contains two fully-human scFv sequences that can specifically recognize CD19 and CD22. Dual-antigen specific CAR-T cells, which have the potential to persistent in vivo longer than mono-specific CAR-T cells, enhance therapeutic effects by reducing relapse resulting from antigen escape.

CT120 proves to be significantly effective in an ongoing IIT trial in China. Results show that CT120 not only has a durable response on CAR-T treatment-naive relapsed/refractory B-ALL patients, but also has a curative effect on relapsed patients who have previously received mono-specific CAR-T treatment. CT120 can reduce the risk of antigen escape and tumor relapse as a result of lower/loss of CD19 or CD22 expression following mono-specific CAR-T treatment, resulting in better therapeutic outcomes and longer survival benefits for patients.

About Non-Hodgkin Lymphoma (NHL):

Lymphomas of immune system cells origin may cause damage to any organ in the body and give rise to a variety of accompanying complicated pathologic processes. Lymphomas are divided into two categories: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Approximately 85% of non-Hodgkin’s lymphomas are of B-cell origin. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL. DLBCL accounts for 31% of NHLs in European and American countries and more than 40% of NHLs in Asian countries. The incidence of the disease increases with age. According to statistics from 2006 to 2016, the standardized morbidity and mortality rates of NHLs in China were 4.29/100,000 and 2.45/100,000, respectively (Biomed Central).

On June 7, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a dermatologic diagnostics company providing personalized genomic information to inform treatment decisions, reported that Derek Maetzold, president and chief executive officer, is scheduled to present a company overview at the Baird 2021 Healthcare ESG Symposium on June 17, 2021, at 11:20 a.m. Eastern time (Press release, Castle Biosciences, JUN 7, 2021, View Source [SID1234583669]).

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A live audio webcast of the company’s presentation will be available by visiting Castle Biosciences’ website at View Source A replay of the webcast will be available for two weeks following the conclusion of the live broadcast.

On June 7, 2021 Agendia, Inc., a world leader in precision oncology for breast cancer, reported positive results from an analysis using its 70-gene MammaPrint assay on samples from the NSABP B-42 trial (Press release, Agendia, JUN 7, 2021, View Source [SID1234583668]). These results were reported as an oral presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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The abstract, titled "Utility of the 70-gene MammaPrint assay for prediction of benefit from extended letrozole therapy (ELT) in the NRG Oncology/NSABP B-42 trial" and presented by Dr. Priya Rastogi of the NSABP, detailed a retrospective evaluation of 1,866 samples, almost half of the original trial’s tissue samples, which were representative of the entire cohort. The data showed that genomic testing with MammaPrint could identify a subset of patients in the NSABP B-42 cohort who were most likely to benefit from ELT. Patients with a MammaPrint Low Risk profile had significantly better rates of distant recurrence (DR), disease-free survival (DFS) and breast cancer free interval (BCFI) when treated with extended endocrine therapy. Conversely, genomically High Risk patients did not see this same benefit and likely could have been spared extended endocrine therapy.

Patients with a genomic Low Risk result were stratified into Ultra Low Risk and Low Risk groups. The benefit of extended endocrine therapy was primarily observed in the Low Risk (non-Ultra Low) group. The benefit of extended endocrine therapy in these MammaPrint Low Risk patients ranged from a 4.0% improvement in DR rate to a 9.5% increase in DFS. MammaPrint was the only test that predicted a 52% relative benefit reduction in BCFI events (7.9% absolute benefit) and a 36% relative benefit reduction in DFS events (9.5% absolute benefit) with ELT. Another genomic test, the BCI-H/I ratio, evaluated samples from the NSABP B-42 trial and did not confirm the predictive value of BCI for the efficacy of extended endocrine therapy; further study is needed to evaluate the test’s predictive ability.

"By stratifying patients beyond High or Low Risk, we are able to see a larger breadth of difference in genomic signatures," said Adam Brufsky, MD, PhD, Co-Director of the Women’s Cancer Center at Magee Women’s Hospital of UPMC Hillman Cancer Center. "More granular information such as this allows us to better understand the biology of a tumor, and gets us closer to ensuring that each patient receives the data she needs to have informed discussions with her physician to decide on the best treatment path, even years after her initial treatment."

The original NSABP B-42 trial, designed to determine whether ELT improves DFS after a standard 5 years of aromatase inhibitor-based therapy, enrolled nearly 4,000 postmenopausal women with stage I-IIIA hormone receptor-positive breast cancer, who were disease-free after about 5 years of treatment with an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor. The trial arms were randomly assigned to either receive 5 years of letrozole – an endocrine therapy used commonly in adjuvant settings – or a placebo. The trial showed a numerical DFS benefit of 3.3% at 10 years from ELT for the entire study cohort; however, no clinical features that indicated which women would achieve this benefit were identified in the trial. This led to the search for genomic biomarkers which could predict the benefit of ELT, and was the basis for this translational study.

"We are pleased to have contributed to the NSABP B-42 trial findings, with the important observation that genomic profiling with MammaPrint identifies the cohort most likely to benefit from ELT, and those who are unlikely to benefit," said William Audeh, MD, Chief Medical Officer at Agendia. "These data will be of value to clinicians, and women with breast cancer, as they make the challenging decision as to whether to undertake an additional five years of endocrine therapy, a decision for which clinical features offered little guidance."

At ASCO (Free ASCO Whitepaper) 2021, Agendia also presented additional data about the Ultra Low Risk threshold from the MINDACT study as well as a larger suite of data from the company’s groundbreaking FLEX registry, a large-scale, prospective, observational breast cancer study using whole transcriptome sequencing. FLEX enables true precision oncology by recruiting patients from various ethnicities, ages and genders representative of the total breast cancer population as part of an ongoing effort to increase representation of diverse populations and data in clinical trials.