On December 6, 2024 Indapta Therapeutics, Inc., a privately held clinical stage biotechnology company developing next-generation differentiated cell therapies for the treatment of cancer and autoimmune diseases, reported a collaboration with Sanofi to explore the combination of its allogeneic g-NK cell therapy, IDP-023, with Sanofi’s CD38-targeting monoclonal antibody, Sarclisa (isatuximab) (Press release, Indapta Therapeutics, DEC 6, 2024, View Source [SID1234648859]).

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Indapta has amended its ongoing phase 1 study of IDP-023, to add a cohort of IDP-023 in combination with Sarclisa for patients with relapsed/refractory multiple myeloma. Up to three dose levels of IDP-023 will be explored in the combination.

Under the agreement, Indapta will sponsor the clinical trial, Sanofi will supply Sarclisa, and the Parties will co-fund the trial. As presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Meeting, IDP-023 administered with or without interleukin-2 achieved a mean maximum reduction in serum M-protein or light chain of 73% in eight relapsed/refractory myeloma patients. This appears to be superior to prior trials of natural killer cells in myeloma.

"With its deep experience in multiple myeloma and pipeline of products in hematologic malignancies and immunologic disorders, Sanofi is an excellent partner to help Indapta develop our differentiated natural killer cell product," said Robert Sikorski, Indapta’s Chief Medical Officer. "We look forward to a close collaborative relationship and leveraging Sanofi’s expertise in the design of potential subsequent studies."

Indapta’s Proprietary g-NK Cell Therapy

Indapta’s universal, allogeneic NK cell therapy platform consists of a potent subset of naturally occurring NK cells, known as "g minus" NK cells, or "g-NK" cells. g-NK cells arise from epigenetic changes resulting from exposure to cytomegalovirus (CMV). To generate IDP-023, Indapta preferentially expands g-NK cells from healthy donors, with low donor to donor variability. IDP-023 has several differentiated mechanisms of killing target cells without the need for genetic engineering, including highly robust antibody-dependent cell mediated cytotoxicity (ADCC), the targeting of HLA-E expressing cells via the NKG2C receptor, and the inherent anti-viral activity of g-NK cells.

Indapta’s g-NK can release dramatically more immune activating cytokines and cell-killing compounds than conventional NK cells. In preclinical studies, IDP-023 has demonstrated more potent and durable antitumor activity when combined with cancer targeting monoclonal antibodies as compared to conventional NK cells. (Bigley et al., Blood Advances 2021, View Source). g-NK cells in combination with a B cell targeting antibody can also deplete normal B cells from healthy donors or patients with autoimmune disease.

On December 6, 2024 BostonGene, a leading provider of AI-driven molecular and immune profiling solutions, reported the selection of 10 abstracts for poster presentations and two abstracts for online publication at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, which will be held December 7-10, 2024, in San Diego, California. BostonGene will exhibit in booth #1955 (Press release, BostonGene, DEC 6, 2024, View Source [SID1234648860]).

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"We are excited to present our research findings at ASH (Free ASH Whitepaper) that underscores the transformative potential of integrating molecular and immune profiling with advanced analytics. This approach is pivotal in advancing precision medicine and improving outcomes for individuals battling cancer," said Nathan Fowler, MD, Chief Medical Officer at BostonGene.

Details of the presentations are below:

Abstract: 1593
Title: Machine Learning-Based Approach to Improve Classification and Diagnostics of Peripheral T-Cell Lymphomas
Date & time: Saturday, December 7 | 5:30 PM -7:30 PM
Presenter: Anastasia Sobol, MS, BostonGene

BostonGene developed a machine learning-based classifier to aid in the diagnoses of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) cases. Using this transcriptomic classifier to examine over 400 cases, approximately 50% of PTCL-NOS cases were reclassified into specific subtypes based on the gene expression pattern of each sample. These findings may enhance the understanding of PTCL pathogenesis and lead to improved diagnostic methods.

Research conducted in collaboration with Weill Cornell Medicine

Abstract: 3610
Title: Novel Plasma Cell-Free RNA-Based Liquid Biopsy Approach for CLL
Date & time: Sunday, December 8 | 6:00 PM – 8:00 PM
Presenter: Andrey Shubin, PhD, BostonGene

To address gaps in disease monitoring for chronic lymphocytic leukemia (CLL) patients, BostonGene developed a novel liquid biopsy approach based on plasma cell-free RNA (cfRNA) sequencing. From a simple blood draw, the cfDNA assay revealed malignant B-cell fractions, B-cell receptor repertoires and clinically significant mutations from cfRNA transcriptomes, as well as associations between treatment and immune- or tissue-specific processes. This liquid biopsy platform may support longitudinal monitoring CLL dynamics and minimal residual disease with further validation.

Research conducted in collaboration with Massachusetts General Hospital and Harvard Medical School

Abstract: 2981
Title: Gene Expression-Based Classifier Reclassifies Burkitt Lymphoma, HGBL NOS, DLBCL NOS, and Double/Triple Hit Lymphomas into Subtypes with More Uniform Mutational and Microenvironment Landscapes and Treatment Response
Date & time: Sunday, December 8 | 6:00 PM – 8:00 PM
Presenter: Juan Pablo Alderuccio, MD, Sylvester Comprehensive Cancer Center at the University of Miami

A machine learning-driven, expression-based classifier was applied to high-grade B-cell lymphomas, identifying subgroups based on unique genomic and transcriptomic features. Validated using large datasets, this classifier could accurately and repeatedly divide aggressive lymphoma cases into diffuse large B-cell and Burkitt lymphoma-like groups based on gene expression. These findings illustrate the clinical applications of a gene expression-based classifier in identifying subsets of patients with aggressive lymphomas.

Research conducted in collaboration with the Sylvester Comprehensive Cancer Center at the University of Miami

Abstract: 3038
Title: Acalabrutinib with Rituximab is Highly Effective as a First Line Treatment for Older Patients with Mantle Cell Lymphoma
Date & time: Sunday, December 8 | 6:00 PM – 8:00 PM
Presenter: Preetesh Jain, MD, MBBS, PhD, DM, The University of Texas MD Anderson Cancer Center

A phase II clinical trial for mantle cell lymphoma patients receiving acalabrutinib and rituximab demonstrated a 94% overall response rate, with 90% of patients achieving complete remission. Correlative analyses with next-generation sequencing and immunoprofiling techniques revealed key features of the immune system’s dynamics and adaptive response following treatment with the combination.

Research conducted in collaboration with the MD Anderson Cancer Center

Abstract: 2982
Title: Use of Molecular Immune Signatures for Frontline Treatment Selection in Patients with Advanced Stage Follicular Lymphoma
Date & time: Sunday, December 8 | 6:00 PM – 8:00 PM
Presenter: Tony Zhuang, MD, MD Anderson Cancer Center

Transcriptomic analysis of pretreatment biopsies from advanced follicular lymphoma (FL) patients revealed that B-cell-associated gene signatures were linked with survival in FL patients receiving chemoimmunotherapy, while T-cell signatures correlated with improved outcomes in patients treated with lenalidomide and rituximab. These findings support the clinical application of transcriptomic profiling for FL patients.

Research conducted in collaboration with the MD Anderson Cancer Center

Abstract: 2958
Title: Circulating Tumor DNA Predicts Outcomes in Follicular Lymphoma: Analysis from a Prospective Study
Date & time: Sunday, December 8 | 6:00 PM – 8:00 PM
Presenter: Rahul Lakhotia, MBBS, National Institutes of Health

An ongoing prospective clinical trial examined the utility of serial circulating tumor DNA (ctDNA) for monitoring disease progression in follicular lymphoma patients. Detectable in over 90% of patients, baseline ctDNA levels correlated with FLIPI prognostic scores, total metabolic tumor volume and spontaneous regression. Serial ctDNA analysis accurately reflected tumor dynamics, demonstrating its value as a minimally invasive tool for tracking disease progression.

Research conducted in collaboration with the National Cancer Institute, University of South Florida, National Institutes of Health, Medical College of Georgia, University of Virginia, Adaptive Biotechnologies

Abstract: 4341
Title: Comprehensive Analysis of Malignant B-Cell Receptors Provides Insights into B-Cell Lymphoma Pathogenesis
Date & time: Monday, December 9 | 6:00 PM – 8:00 PM
Presenter: Evgeniia Alekseeva, PhD, BostonGene

Aimed at characterizing B-cell receptor (BCR) repertoires, BostonGene leveraged a blood-based approach to discover biomarkers capable of distinguishing B-cell lymphoma subtypes. Several features, including BCR isotype, IGVH somatic hypermutation rate and chain structure, were associated with specific subtypes, highlighting the potential for diagnostic biomarkers within BCR repertoires.

Abstract: 4377
Title: Radiation Therapy and Monocyte Activation in Large B-cell Lymphoma Patients Treated with CAR T-Cell Therapy
Date & time: Monday, December 9 | 6:00 PM – 8:00 PM
Presenter: Penny Fang, MD Anderson Cancer Center

A study evaluating CART-treated large B-cell lymphoma (LBCL) patients revealed radiation therapy reshapes the immune landscape, particularly by increasing monocyte levels, proliferation and cytotoxicity. This shift suggested radiation therapy is a viable bridging therapy for CART LBCL patients, promoting a suppressive immunotype linked with decreased toxicity and increased treatment response.

Research conducted in collaboration with the MD Anderson Cancer Center

Abstract: 4348
Title: Genomic and Spatial Proteomic Characterization of the Microenvironment of Diffuse Large B-Cell Lymphoma in African American Patients
Date & time: Monday, December 9 | 6:00 PM – 8:00 PM
Presenter: Michelle Lee, MD, PhD, Winship Cancer Institute of Emory University

A flagship multiomics study characterizing diffuse large B-cell lymphoma (DLBCL) in African American patients revealed the prevalence of immune-inflamed microenvironments, molecular alterations and distinct spatial cellular communities. These findings suggest tumor-specific factors may drive the disparity in survival outcomes and underscore the need for larger, more diverse clinical cohorts.

Research conducted in collaboration with the Winship Cancer Institute of Emory University, MD Anderson Cancer Center and Georgia Institute of Technology

Abstract: 4364
Title: Evaluating the clinical utility of comprehensive whole exome sequencing (WES) and RNA-seq for patients with lymphoma
Date & time: Monday, December 9 | 6:00 PM – 8:00 PM
Presenter: Dai Chihara, MD, PhD, MD Anderson Cancer Center

The BostonGene Tumor PortraitTM test, featuring integrated genomic and transcriptomic profiling, was used to generate clinically relevant findings, treatment recommendations and matched clinical trials for lymphoma patients. With a median turnaround time of just 8 days, the Tumor PortraitTM test’s robust findings and rapid turnaround time demonstrated the utility of integrated whole exome and transcriptome sequencing for lymphoma patients.

Research conducted in collaboration with the MD Anderson Cancer Center

Online only
Title: Tumor Genomics and Microenvironment Characterization of Diffuse Large B-Cell Lymphoma in Asian and Pacific Islander Patients

Integrated whole exome and transcriptome sequencing was performed on diffuse large B-cell lymphoma (DLBCL) tumors from the Hawaii Surveillance, Epidemiology, and End Results residual tissue repository, constituting an initial characterization of the DLBCL microenvironment in Asian and Pacific Islander patients, an under-represented population in prior studies. The findings suggest existing classification systems may not represent DLBCL heterogeneity in non-European populations, illustrating the need for studies with more diverse patient populations to reveal how ancestry, socioeconomic elements and environmental factors contribute to DLBCL pathobiology and outcomes.

Research conducted in collaboration with the Winship Cancer Institute of Emory University and MD Anderson Cancer Center

Title: Comprehensive Molecular Characterization of Monomorphic Post-Transplant Lymphoproliferative Disorder (PTLD)

Comparative analysis of Epstein-Barr virus (EBV)-positive and -negative post-transplant lymphoproliferative disorder (PTLD) patients with diffuse large B-cell lymphoma (DLBCL) uncovered distinct immune signatures and a higher prevalence of protumor elements among EBV-positive PTLD patients. When compared with immunocompetent-DLBCL, PTLD samples contained a higher fraction of plasma B-cells. While EBV-negative PTLDs largely resembled de novo DLBCLs, EBV-positive PTLDs were enriched with unique molecular features. These findings emphasize the role of EBV status in PTLD biology and associated clinical outcomes.

Research conducted in collaboration with the MD Anderson Cancer Center

In addition to the poster presentations, the abstracts have been published online in the November supplemental issue of "Blood."

On December 6, 2024 EpimAb Biotherapeutics, a global clinical stage biotechnology company specializing in the development of bispecific antibodies, reported the acceptance of a late-breaking abstract featuring our novel BCMA targeted T cell engager (TCE) EMB-06 (CND106) as an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California to be held between December 7-10, 2024 (Press release, EpimAb Biotherapeutics, DEC 6, 2024, View Source [SID1234654055]).

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This presentation will highlight the full Phase I clinical results for EMB-06 (CND106), a novel BCMA targeting TCE designed with an optimized efficacy and safety profile, in relapsed or refractory multiple myeloma patients. EpimAb recently granted the exclusive rights to develop and commercialize EMB-06 (CND106) outside of Greater China to Candid Therapeutics. The oral presentation details are as follows:

Title: A Phase I Study of a Novel BCMA×CD3 Bispecific Antibody EMB-06 in Relapsed or Refractory Multiple Myeloma
Session Date: December 8
Session Time: 10:45 – 11:00AM local time
Location: Pacific Ballroom Salons 18-19 (Marriott Marquis San Diego Marina)
Presentation number: 498

"We are very pleased to share the full results of the EMB-06 FIH study as an oral presentation at the ASH (Free ASH Whitepaper) Annual Conference, and we believe the data highlights EMB-06’s differentiated efficacy and safety profile in multiple myeloma patients," said Dr. Chengbin Wu, Founder and CEO of EpimAb. "The results of this study also provide validation of our TCE technology platform and we will further leverage this expertise to advance novel therapies for diseases with significant unmet need."

About EMB-06

EMB-06 is a novel 2+2 BCMA×CD3 T-cell engaging bispecific antibody discovered using EpimAb’s proprietary CD3 panel and bispecific platforms. Importantly, this molecule has demonstrated lower levels of cytokine release in preclinical and clinical studies.

On December 6, 2024 Alpha Tau Medical Ltd. ("Alpha Tau", or the "Company") (NASDAQ: DRTS, DRTSW), the developer of the innovative alpha-radiation cancer therapy Alpha DaRT, reported that CFO Raphi Levy will present at the Ladenburg Oncology Innovators & Investors Symposium (Press release, Alpha Tau Medical, DEC 6, 2024, View Source [SID1234648851]).

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Event: Ladenburg Oncology Innovators & Investors Symposium
Format: Presentation and 1-on-1 Meetings
Date: December 12, 2024
Time: 11:00AM – 11:25AM EST
Location: Virtual

Please reach out to your Ladenburg representative to schedule 1-on-1 meetings with Mr. Levy.

On December 5, 2024 Theriva Biologics (NYSE American: TOVX), a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, reported the outcomes of a recent Type D meeting with the U.S. Food and Drug Administration (FDA) to obtain guidance on the design of a Phase 3 clinical study of lead clinical candidate VCN-01 in combination with standard-of-care chemotherapy for the treatment of metastatic pancreatic adenocarcinoma (PDAC) (Press release, Theriva Biologics, DEC 5, 2024, View Source [SID1234648836]). The Company recently announced the completion of target enrollment into the multinational VIRAGE Phase 2b clinical study evaluating intravenous VCN-01 in combination with gemcitabine/nab-paclitaxel as a first line therapy for PDAC patients.

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Type D meetings are focused on a narrow set of issues that are used to discuss issues at key decision points to provide timely feedback critical to moving a drug development program forward. The FDA advised that the on-going VIRAGE Phase 2b study should not be expanded into a Phase 3 study; rather, the optimal path forward for the VCN-01 PDAC program is to conduct a stand-alone Phase 3 study of VCN-01 with gemcitabine/nab-paclitaxel. The FDA provided general agreement with Theriva’s proposed design for a Phase 3 clinical study and indicated that inclusion of additional standard-of-care chemotherapy for PDAC was not necessary as it would complicate the study design and analysis. The FDA meeting also highlighted the FDA’s preferences regarding certain statistical elements of confirmatory clinical studies, including methods for sample size estimation and the study population(s) used for data analysis.

"The FDA’s advice on key elements of a potential confirmatory Phase 3 study evaluating VCN-01 plus gemcitabine/nab-paclitaxel as a first-line treatment for metastatic PDAC patients is critical as the VIRAGE study has entered final patient follow-up and we are actively planning the next steps in VCN-01 development," said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. "The feedback from the FDA and European regulatory agencies will facilitate the design of a Phase 3 study protocol that is expected to maximize our ability to provide a new therapeutic option to patients suffering this terrible disease."

An additional meeting with the FDA will be requested after the completion of the VIRAGE study to discuss the details of the proposed confirmatory Phase 3 study protocol.

About Pancreatic Ductal Adenocarcinoma

Cancer of the pancreas consists of two main histological types: cancer that arises from the ductal (exocrine) cells of the pancreas or, much less often, cancers may arise from the endocrine compartment of the pancreas. Pancreatic ductal adenocarcinoma ("PDAC") accounts for more than 90% of all pancreatic tumors. It can be located either in the head of the pancreas or in the body/tail. Pancreatic cancer usually metastasizes to the liver and peritoneum. Other less common metastatic sites are the lungs, brain, kidney, and bone. In its early stages, pancreatic cancer does not typically result in any characteristic symptoms. In many instances, progressive abdominal pain is the first symptom. Therefore, in most cases, pancreatic cancer is diagnosed in its late stages (locally advanced non-metastatic or metastatic stage of the disease) when surgical resection and possibly curative treatment is not possible. It is generally assumed that only 10% of cases are resectable at presentation, whereas 30-40% of patients are diagnosed at local advanced/unresectable stage and 50-60% present with distant metastases.

About VCN-01

VCN-01 is a systemically administered oncolytic adenovirus designed to selectively and aggressively replicate within tumor cells and degrade the tumor stroma that serves as a significant physical and immunosuppressive barrier to cancer treatment. This unique mode-of-action enables VCN-01 to exert multiple antitumor effects by (i) selectively infecting and lysing tumor cells; (ii) enhancing the access and perfusion of co-administered chemotherapy products; and (iii) increasing tumor immunogenicity and exposing the tumor to the patient’s immune system and co-administered immunotherapy products. Systemic administration enables VCN-01 to exert its actions on both the primary tumor and metastases. VCN-01 has been administered to 142 patients to date in Company- and investigator-sponsored clinical trials of different cancers, including PDAC (in combination with chemotherapy), head and neck squamous cell carcinoma (with an immune checkpoint inhibitor), ovarian cancer (with CAR-T cell therapy), colorectal cancer, and retinoblastoma (by intravitreal injection). More information on these clinical trials is available at Clinicaltrials.gov.