Arsenal Biosciences Announces Presentation of Four Abstracts at AACR Annual Meeting Highlighting New CAR T-Focused Research

On April 5, 2024 Arsenal Biosciences, Inc. (ArsenalBio), a clinical-stage programmable cell therapy company focused on engineering advanced CAR T-cell therapies for solid tumors, reported the presentation of four abstracts at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in San Diego, CA., May 5-10, 2024 (Press release, ArsenalBio, APR 5, 2024, View Source [SID1234641829]). These data demonstrate the company’s continued progress in developing and understanding the ways logic gating and integrated circuit T cell technology can potentially address a range of solid tumor cancers.

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"We continue to build our knowledge of how integrated circuit T cells employing logic gating can be deployed as part of highly potent cell therapies and to study the range of ways these technologies can address areas of unmet medical need across a range of cancers"

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"We continue to build our knowledge of how integrated circuit T cells employing logic gating can be deployed as part of highly potent cell therapies and to study the range of ways these technologies can address areas of unmet medical need across a range of cancers," said Nick Haining, B.M., B.Ch., ArsenalBio’s Co-Founder and Chief Scientific Officer. "We look forward to sharing updates on our progress in advancing these therapeutic approaches and how we are applying them in the clinic as we study AB-1015 and prepare to enter the clinic with AB-2100, potential treatments for ovarian and kidney cancers, respectively."

The following abstracts will be presented as poster presentations during the AACR (Free AACR Whitepaper) annual meeting.

Abstract #38: AB-2100, a PSMA-inducible CA9-specific CAR T cell product for the treatment of ccRCC provides long-term tumor responses in preclinical mouse model
Date and Time: Sunday, April 7, 2024, 1:30 – 5:00 p.m. PDT
Presenter: Alba Gonzalez-Junca, Ph.D.

AB-2100 will be studied in a phase 1/2 clinical trial as a potential therapy for clear cell renal cell carcinoma (ccRCC) (NCT06245915). AB-2100 encodes a transcriptionally regulated sequential "AND" logic gate that comprises a priming receptor (PrimeR) specific for PSMA and an inducible CAR targeting CA9 antigen, which is widely expressed on local and metastatic lesions. By targeting both, the logic gate is intended to improve the safety profile of AB-2100, because PSMA and CA9 are not often co-expressed in normal tissues. Further, AB-2100 is designed with additional functionality including short-hairpin RNAs (snRNA) against Fas and TGFBR and a synthetic pathway activator (SPA) that drives enhanced antitumor activity. This approach was shown to be successful in the eradication of ccRCC targets in xenograft models.

Abstract #6319: Characterization of AB-1015 logic-gated CAR induction (ON kinetics), receptor turnover (OFF kinetics), and logic gate sensitivity to ALPG/P and MSLN
Date and Time: Tuesday, April 9, 2024, 1:30 – 5:00 p.m. PDT
Presenter: Xinyan Tang, Ph.D.

AB-1015 is being studied in a phase 1 clinical trial as a potential therapy for ovarian cancer (NCT05617755) contains an "AND" logic gate, consisting of a priming receptor (PrimeR) and an inducible chimeric antigen receptor (CAR) that is upregulated by PrimeR activation. This logic gate targets ALPG/P and MSLN, which are coexpressed in ovarian tumors but not in normal tissues. To better characterize CAR induction and receptor turnover, we conducted a series of assays, ultimately demonstrating preclinically that all PrimeR ICT cells have the potential to induce CAR. Leveraging a reductionist in vitro model system, we were also able to analyze CAR induction and receptor turnover.

Abstract #2854: Enhancing CAR and TCR T cell function in solid tumors through in vivo combinatorial screens and single-cell analysis
Date and Time: Wednesday, April 10, 2024, 9:00 a.m. – 12:30 p.m. PDT
Presenter: Dina Polyak, B. Pharm., Ph.D.

This preclinical study investigated ways to overcome the T cell exhaustion and factors of the tumor microenvironment that can limit the success of T cell therapies helping identify ways T cells can be reprogrammed to overcome these limitations. Researchers developed in vivo exhaustion models and conducted pooled CRISPR/Cas9 screens combined with single-cell RNA sequencing (scRNA-seq) to identify genetic changes capable of enhancing T cell function. The research leveraged CAR or T cell receptor (TCR) T cells and introduced genetic changes into the T cells before their transfer into the xenograft mouse models with established tumors. Researchers studied the relative success of many T cell phenotypes resulting from gain-of-function, loss-of-function, and combinations, and identified previously uncharacterized combinatorial perturbations that showed promise in addressing exhaustion and enabling greater success in addressing solid tumors.

Abstract #7034: Pooled CRISPR screening coupled with single-cell sequencing identifies modifiers of CAR T cell state in the context of chronic antigen stimulation
Date and Time: Wednesday, April 10, 2024, 9:00 a.m. – 12:30 p.m. PDT
Presenter: Sahil Joshi

T cell exhaustion from chronic antigen stimulation and an immunosuppressive tumor microenvironment limits the efficacy of T cell therapies used to treat solid tumors. This research used CRISPR/Cas9-based screening paired with deep sequencing to characterize perturbation-dependent T cell states following chronic antigen stimulation to understand how genetic perturbations shift T cells away from exhaustion associated states and whether such changes could increase the potency of immunotherapies. The preclinical results demonstrated the potential for pool CRISPR screening with single cell readouts to identify novel target genes which could enhance the success of CAR T cell therapies.

For more information about ArsenalBio, visit www.arsenalbio.com.

Incendia Therapeutics Announces Upcoming Presentations at the American Association for Cancer Research 2024

On April 5, 2024 Incendia Therapeutics, a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), reported that it will have three poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, taking place April 5-10, 2024 in San Diego, California (Press release, Incendia Therapeutics, APR 5, 2024, View Source [SID1234641828]).

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"We look forward to presenting these posters at AACR (Free AACR Whitepaper), which highlight our work to characterize immune exclusion in the TME," said Laura Dillon, PhD, Vice President of Translational Medicine & Bioinformatics at Incendia Therapeutics. "The data continue to validate that Discoidin Domain Receptor 1 (DDR1), the target of Incendia’s PRTH-101 program that is currently in the clinic, is highly correlated with immune exclusion in the tumor microenvironment across epithelial tumors. Additionally, they demonstrate the power of applying H&E-based biomarkers, driven by machine learning, to better interrogate the TME. We look forward to further exploring the potential of this technology, combined with our novel class of anti-cancer therapies, to better treat cancer patients by targeting the tumor microenvironment."

Presentation details for AACR (Free AACR Whitepaper) 2024 are as follows:

Title: Discoidin Domain Receptor 1 (DDR1) expression is associated with degree of immune exclusion across epithelial tumors
Abstract Number: 2916 / 24
Presenting Author: Laura Dillon, Ph.D., Vice President of Translational Medicine & Bioinformatics at Incendia Therapeutics
Session: The Tumor Microenvironment as a Drug Target
Date and Time: Monday, April 8 from 1:30 – 5:00 PM PDT (4:30 – 8:00 PM EDT)

Key Highlights:
DDR1 mRNA and protein expression levels are correlated with immune exclusion of lymphocytes, CD8+ T cells, and CD45+ immune cells across epithelial tumor types (R: 0.31-0.56, adjusted p values: 0.04-0.07). While the degree of the correlation varied by indication and immune cell type considered, pancreatic cancer exhibited the strongest correlation between the lymphocyte-based Immune Exclusion Scores (IES) and DDR1 mRNA and protein expression (R: 0.48-0.54, adjusted p values: 0.04-0.07). This work provides additional insight into the role of DDR1 in human cancers and has utility for selecting indications and stratifying patients for DDR1-targeted therapies.

Title: Machine learning-based identification of H&E-derived morphologic features associated with CD8+ T cell immune exclusion
Abstract Number: 7392 / 20
Presenting Author: Yanchao Wang, Ph.D., Data Scientist at Incendia Therapeutics
Session: Artificial Intelligence and Machine/Deep Learning 4
Date and Time: Wednesday, April 10 from 9:00 AM – 12:30 PM PDT (12:00 PM – 3:30 PM EDT)

Key Highlights:
Morphologic features derived from H&E images can be effective predictors of CD8-defined immune exclusion, providing an option for patient stratification by immune phenotype using widely available H&E images. We developed an Ens-L1-SVM model that identified 6 H&E features predictive of CD8-defined immune phenotypes. CD8-based immune phenotypes were classified by the Ens-L1-SVM model with an estimated accuracy of 97% using only the H&E-based features as input.

Details on Incendia’s poster which is a collaboration with Alpenglow Biosciences:

Title: 3D spatial quantification of lymphocyte infiltration and collagen features in the tumor microenvironment using a novel assay: 3D I/O Pro
Abstract Number: 2309 / 20
Presenting Author: Bonnie Phillips, Ph.D., Director, Commercial Development at Alpenglow Biosciences
Session: Liquid Biopsy and Precision Oncology
Date and Time: Monday, April 8 from 9:00 AM – 12:30 PM PDT (12:00 PM – 3:30 PM EDT)

Key Highlights:
An end-to-end 3D spatial biology workflow, Alpenglow’s 3D I/O Pro, was applied to colorectal cancer (CRC) tissues stained with nuclear and general protein fluorescent dyes to quantify lymphocyte density in tumor parenchyma and stroma and analyze collagen features, including orientation, within 3D regions of interest in the TME. The ratio of stromal to parenchymal lymphocytes (lymphocyte infiltration ratio) varied from 1.4 up to 9.1 in 3D volumes and 1 to 25 in 2D virtual sections taken throughout all 5 CRC samples. Qualitatively, areas with perpendicular collagen had more lymphocyte infiltration into the tumor parenchyma than areas with parallel collagen orientation. This work highlights how the 3D I/O Pro workflow can characterize tumors based on complex spatial relationships within the tumor microenvironment, and could have broad applicability in research and development of novel cancer therapies that target tumor fibrosis or other features of the TME.

RenovoRx to Present at the Canaccord Genuity Horizons in Oncology Virtual Conference on April 15, 2024

On April 5, 2024 RenovoRx, Inc. ("RenovoRx" or the "Company") (Nasdaq: RNXT), a clinical-stage biopharmaceutical company developing novel precision oncology therapies based on a local drug-delivery platform, reported that Shaun Bagai, RenovoRx’s Chief Executive Officer, will present at the Canaccord Genuity 2024 Horizons in Oncology Virtual Conference to be held on April 15, 2024 (Press release, Renovorx, APR 5, 2024, View Source [SID1234641827]).

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Mr. Bagai will meet with investors and participate in a panel discussion hosted by Bill Maughan, Senior Analyst at Canaccord Genuity. The panel is titled "Delivering High Local Concentrations of Chemotherapy for Solid Tumors," and takes place on Monday, April 15, 2024, at 8:00 am ET. He will discuss the initial positive interim analysis in the Company’s pivotal Phase III TIGeR-PaC clinical trial. The study is evaluating the Company’s lead product candidate, RenovoGem, and proprietary Trans-Arterial Micro-Perfusion (TAMP) therapy platform for the treatment of locally advanced pancreatic cancer.

Mr. Bagai will also discuss the Company’s plans for 2024 and beyond as well as recent milestones, including the completion of a private placement in January 2024. The private placement extended cash runway, allowing the Company to advance towards its near-term key milestone of a second interim analysis for TIGeR-PaC that will be triggered by the 52nd event (death), which is estimated to occur in late 2024.

CG 2024 Horizons in Oncology Virtual Conference
Date: April 15, 2024
Time: 8:00am ET – 8:50am ET
Speaker: Shaun Bagai, CEO
Location: Virtual

To schedule a one-on-one investor meeting with Mr. Bagai, please contact your Canaccord representative or KCSA Strategic Communications at [email protected].

Inocras to Present Enhancing Genomic Analysis in Cancer Diagnostics at the 2024 AACR Annual Meeting

On April 5, 2024 Inocras, a leading provider of precision healthcare solutions company advancing whole-genome technology, reported that it is making an impact at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2024 annual meeting from April 5 to 10, held in San Diego (Press release, Inocras, APR 5, 2024, View Source [SID1234641826]). This event premieres Inocras’s substantial research and pioneering innovation in cancer diagnostics, driven by cutting-edge machine learning technology.

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In their poster presentation, Inocras showcases the refined approach of machine learning in examining whole-genome sequencing (WGS) data from tissues preserved in formalin-fixed paraffin-embedded (FFPE) samples, a common preservation technique in clinical environments. The research focuses on addressing the challenges posed by the distorted genomic profiles in FFPE-derived tissues, which complicate precise cancer diagnosis. The study delves into the genomic changes induced by FFPE processing and devises computational strategies to eliminate these artifacts. This is achieved by analyzing 55 matched FFPE and fresh-frozen (FF) sample pairs across a variety of cancer types and different FFPE storage duration.

The study unveils a cutting-edge machine learning strategy to accurately identify genetic changes caused by FFPE processing. Concentrating on detecting single-nucleotide variants (SNVs), small insertions and deletions (indels), and copy-number variations (CNVs), the researchers crafted sophisticated algorithms to sift through these genomic distortions. These algorithms not only improve the precision and reliability of the genomic analysis but also tackle the inherent variability of clinical FFPE specimens. The developed classifiers show exceptional ability in differentiating actual genetic variants from FFPE-related errors. Moreover, this research sheds light on specific FFPE-induced genetic alteration patterns, such as cytosine deamination and unique mutational signatures, while proving its efficacy in assessing vital cancer and genomic metrics, including homologous recombination deficiency (HRD) and tumor mutational burden (TMB).

Young Seok Ju, Chief Genome Officer of Inocras, expresses excitement about the studies to be presented at AACR (Free AACR Whitepaper) 2024 and emphasizes the company’s commitment to transforming cancer care through machine learning technology. "We are thrilled to showcase the pioneering work we are doing at Inocras in leveraging machine learning to pull out the full potential of WGS analysis in cancer diagnostics and therapeutics. Our research findings presented at AACR (Free AACR Whitepaper) 2024 will underscore the potential of machine learning in revolutionizing personalized cancer treatment strategies."

Inocras’s participation in AACR (Free AACR Whitepaper) 2024 showcases the company’s relentless dedication to leveraging technological innovation to revolutionize cancer research and clinical practice. The presentations underscore Inocras’s commitment to providing personalized and exhaustive insights for better patient outcomes, solidifying the company’s position as a leader in AI-powered solutions for cancer diagnostics and therapeutics.

For more information about Inocras and its groundbreaking research presented at AACR (Free AACR Whitepaper) 2024, please visit Inocras.

Presentations at AACR (Free AACR Whitepaper) 2024 featuring Inocras:
Enhancing genomic analysis in cancer diagnostics: A machine learning approach for removing artifacts in FFPE specimens (Section 37, April 7, 2024, 1:30 pm – 5:00 pm)

Tempus Announces 18 Abstracts Accepted For Presentation at the American Association for Cancer Research Annual Meeting 2024

On April 5, 2024 Tempus, a leader in artificial intelligence and precision medicine, reported 18 abstracts were accepted for presentation at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which convenes from April 5-10, in San Diego, California (Press release, Tempus, APR 5, 2024, View Source [SID1234641825]). Tempus researchers will demonstrate how the company’s AI-enabled precision medicine platform collects and analyzes high-quality, multimodal datasets to advance cancer research.

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"We look forward to presenting 18 abstracts at AACR (Free AACR Whitepaper) this year, demonstrating the breadth and depth of our research both at Tempus and with our biopharma collaborators," said Ezra Cohen, MD, Chief Medical Officer, Oncology at Tempus. "Our research showcases the power of combining our molecular profiling offerings with our multimodal database to better understand cancer biology, treatment response, and patient outcomes."

Research highlights include:

Poster Presentation: A circulating tumor fraction DNA biomarker response stratified by ESR1 mutation status correlates with overall survival in patients with HR+ HER2- metastatic breast cancer
Session Date & Time: Monday, April 8, 2024; 1:30 p.m. – 5:00 p.m. PT
Location: Poster Section 41
Overview: Tempus xM used for treatment response monitoring (TRM) is an algorithm that quantifies changes in circulating DNA tumor fraction (TF) and can be simultaneously used to detect the emergence of ESR1 mutation (ESR1m) variants. In a heterogeneous real-world cohort of ER+ HER2- metastatic breast cancer patients, we showed that the combined effect of molecular response and ESR1 mutation status, a mutation associated with resistance to aromatase inhibitors (AIs), was associated with real-world overall survival outcomes. These preliminary findings suggest that xM used for TRM can identify patients with ESR1m and poor response on AI who may benefit from switching therapy.
Abstract: Leveraging a comprehensive genomic data library for detecting clonal hematopoiesis in liquid biopsy
Session Date & Time: Monday, April 8, 2024; 9:00 a.m. – 12:30 p.m. PT
Location: Poster Section 37
Overview: To more efficiently filter out clonal hematopoiesis (CH) variants from tumor-derived variants, the team trained a random forest classifier on advanced, pan-solid tumor cancer samples sequenced using liquid biopsy and solid-tumor NGS with matched buffy coat assays (n=660). On a held-out validation set of samples (n=661), the classifier could reliably distinguish between CH and other tumor-derived variants with high accuracy, sensitivity, and specificity using only liquid biopsy data for predictions, providing an operationally simpler alternative to combined liquid and solid-based methodologies.
Poster Presentation: Association of a ctDNA biomarker of treatment response with clinical outcomes in a real-world pan-cancer cohort treated with tyrosine kinase inhibitors
Session Date & Time: Tuesday, April 9, 2024; 9:00 a.m. – 12:30 p.m. PT
Location: Poster Section 44
Overview: By analyzing changes in circulating DNA tumor fraction (ctDNA TF) in a real-world pan-cancer cohort of patients treated with Tyrosine kinase inhibitors (TKIs), the research team found that patients classified as molecular responders (defined as ≥ 50% in ctDNA tumor fraction) had significantly improved real-world overall survival and progression-free survival compared to molecular non-responders. Based on these findings, xM used for TRM may be used to optimize treatment decision making for patients treated with TKIs, sparing patients who do not respond to TKIs from ineffective therapy.
To learn more, visit www.tempus.com/events/aacr-annual-meeting-2024.