On April 5, 2024 Novocure reported 20 presentations on Tumor Treating Fields (TTFields) therapy will be delivered at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, to be held April 5 to 10 in San Diego (Press release, NovoCure, APR 5, 2024, View Source [SID1234641832]).

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The presentations, describing preclinical investigations, include new insights on how TTFields therapy can potentially enhance the immune system’s ability to combat cancer cells and on TTFields therapy’s effects and mechanisms in pancreatic cancer.

"The research we and our collaborators are presenting at the AACR (Free AACR Whitepaper) Annual Meeting underscores the potential of Tumor Treating Fields therapy in treating various solid tumor types," said Moshe Giladi, Ph.D., Novocure’s Chief Science Officer. "We continually explore the science of TTFields therapy to improve our product and make a difference in the lives of patients with cancer, and we are eager to discuss some of our latest insights with leading cancer investigators."

Highlights include:

A preclinical study in a murine model of pancreatic cancer showing that TTFields applied concurrently with standard chemotherapy led to significantly enhanced therapeutic effects. When used alongside gemcitabine and nab-paclitaxel (Gem/NabP), TTFields significantly reduced tumor growth compared to the control group, and a complete regression of tumors was observed in a number of animals. This is a treatment regimen similar to the PANOVA-3 clinical trial examining the efficacy of TTFields in patients with locally advanced pancreatic cancer.
A preclinical study demonstrating a novel immunomodulatory role for TTFields by promoting in vitro pro-inflammatory polarization of macrophages. Macrophages exposed to TTFields showed an increase in markers and chemicals that indicate a shift towards a pro-inflammatory, tumor-fighting mode. The study suggests TTFields can potentially modulate macrophages to better attack cancer cells by pushing them toward a state more hostile to tumors.
An in vitro study suggesting concomitant application of TTFields and PARP inhibitors in BRCA wild type pancreatic cancer cells leads to improvement over monotherapy. Applied individually, both PARP inhibitors and TTFields killed cancer cells, stopped them from multiplying, and triggered apoptosis. These effects were amplified when TTFields and PARP inhibitors were applied together. These findings contribute to existing data suggesting that TTFields induce a state of BRCAness in cancer cells.
Presentations from Novocure-sponsored and partner programs include:

Tumor Treating Fields (TTFields) targeted self assembling nanoparticles for pancreatic cancer treatment: In vitro and in vivo assessment. Presenter: P.P. Desai. 1:30 p.m. PDT on Sunday, April 7.

Tumor Treating Fields induce the integrated stress response, alter the transcriptional signatures of cellular metabolism, and modulate immune-related cytokines dependent and independent of p53. Presenter: P.R. Srinivasan. 1:30 p.m. PDT on Sunday, April 7.

Tumor Treating Fields (TTFields) disrupt cancer cell invasion by impacting cell-ECM traction forces. Presenter: S.M. Short. 9 a.m. PDT on Monday, April 8.

N-cadherin-mediated activation of PI3K/Akt pathway following application of Tumor Treating Fields (TTFields). Presenter: T. Voloshin. 9 a.m. PDT on Monday, April 8.

Genomic and proteomic analysis of glioblastoma recurrences during TTFields exposure. Presenter: M. Mazzanti. 9 a.m. PDT on Monday, April 8.

Co-treatment with KRAS G12D inhibitor MRTX1133 plus TTFields against human pancreatic and Colorectal cancer cell lines results in synergistic up-regulation of cleaved PARP in KRAS G12D & unexpectedly in KRAS G12V as well. Presenter: V. Tajiknia. 9 a.m. PDT on Monday, April 8.

Tumor Treating Fields (TTFields) for spinal metastasis: Clinical trial concept for use of conductive implants as waveguides to enhance TTFields strength. Presenter: C.E. Tatsui. 9 a.m. PDT on Monday, April 8.

Tumor Treating Fields (TTFields) increase cancer cell membrane permeability and improve sensitivity to doxorubicin in vitro and in vivo. Presenter: T. Voloshin. 9 a.m. PDT on Tuesday, April 9.

Development of paclitaxel-loaded nanoparticles with high charge density. Presenter: K.Y. Bang. 1:30 p.m. PDT on Tuesday, April 9.

Tumor Treating Fields alter PDGFR-β localization in immortalized human pericytes in an in vitro model of the blood-brain barrier. Presenter: C. Hagemann. 1:30 p.m. PDT on Tuesday, April 9.

Designing arrays for delivering Tumor Treating Fields (TTFields) to the mouse head. Presenter: I Tzchori. 1:30 p.m. PDT on Tuesday, April 9.

Tumor Treating Fields (TTFields) induce an anti-tumor immune response in a pancreatic cancer mouse model. Presenter: T. Voloshin. 9 a.m. PDT on Wednesday, April 10.

Macrophage pro-inflammatory phenotype skewing by the application of Tumor Treating Fields (TTFields). Presenter: T. Voloshin. 9 a.m. PDT on Wednesday, April 10.

Quantitative proteomics reveal the mechanism of TTFields therapy for glioblastoma. Presenter: Q. Mei. 9 a.m. PDT on Wednesday, April 10.

Treatment of pancreatic cancer cells with Tumor Treating Fields (TTFields) and PARP inhibitors. Presenter: E. Dor-On. 9 a.m. PDT on Wednesday, April 10.

Preclinical effects of Tumor Treating Fields (TTFields) with PARP inhibitors in ovarian cancer. Presenter: E. Dor-On. 9 a.m. PDT on Wednesday, April 10.

Preclinical investigations of concomitant Tumor Treating Fields (TTFields) with cisplatin for treatment of cervical cancer. Presenter: I. Tzschori. 9 a.m. PDT on Wednesday, April 10.

Tumor Treating Fields (TTFields) can induce immunogenic cell death in GBM resulting in enhanced immune modulation. Presenter: R.T. Nitta. 9 a.m. PDT on Wednesday, April 10.

Tumor Treating Fields (TTFields) show efficacy in Triple-Negative breast cancer (TNBC) cells alone and in combination with PARP inhibitor Talazoparib. Presenter: M. Ghandali. 9 a.m. PDT on Wednesday, April 10.

TTFields and imipridone ONC206 co-treatment inhibits p-AKT and spheroid growth and upregulates caspase-10 in human GBM cell lines. Presenter: V. Tajiknia. 9 a.m. PDT on Wednesday, April 10.

ABOUT TUMOR TREATING FIELDS THERAPY

Tumor Treating Fields (TTFields) are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. TTFields do not significantly affect healthy cells because they have different properties (including division rate, morphology, and electrical properties) than cancer cells. The multiple, distinct mechanisms of TTFields therapy work together to selectively target and kill cancer cells. Due to its multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and demonstrates enhanced effects across solid tumor types when used with chemotherapy, radiotherapy, immune checkpoint inhibition, or PARP inhibition in preclinical models. TTFields therapy provides clinical versatility that has the potential to help address treatment challenges across a range of solid tumors. To learn more about Tumor Treating Fields therapy and its multifaceted effect on cancer cells, visit tumortreatingfields.com.

On April 5, 2024 Immunome, Inc. (Nasdaq: IMNM), a biotechnology company focused on developing first-in-class and best-in-class targeted cancer therapies, reported that it will present preclinical data for IM-3050, the company’s lead lutetium-177 radioligand therapy (RLT) targeting fibroblast activation protein (FAP) (Press release, Immunome, APR 5, 2024, View Source [SID1234641831]). Jack Higgins, PhD, Chief Scientific Officer at Immunome, will present the data in a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, which is taking place April 5-10 in San Diego, California.

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"FAP is an attractive target for cancer therapy, but trials with first-generation FAP-RLTs have produced modest clinical responses, indicating the need for novel agents with improved therapeutic properties," commented Dr. Higgins. "We believe IM-3050 has best-in-class potential and look forward to sharing preclinical data for the program at AACR (Free AACR Whitepaper)."

Immunome expects to submit an Investigational New Drug application to the U.S. Food & Drug Administration for IM-3050 in the first quarter of 2025.

Poster Presentation Details:

Title: A novel lutetium-177 radioligand therapy targeting FAP has potent antitumor activity in xenograft cancer model (Abstract #6026)

Presenter: Jack Higgins, PhD, Chief Scientific Officer

Date: April 9, 2024 1:30 p.m. – 5:00 p.m. PDT

A copy of the poster will be available on the Events & Presentations section of Immunome’s website following the conference.

On April 5, 2024 NiKang Therapeutics Inc. ("NiKang"), a clinical stage biotech company focused on developing innovative small molecule oncology medicines to help patients with unmet medical needs, reported the unveiling of NKT3447 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 (Press release, NiKang Therapeutics, APR 5, 2024, View Source [SID1234641830]). NKT3447 is an orally bioavailable small molecule CDK2 inhibitor that exhibits high selectivity against CDK1 and other CDKs, prolonged pharmacodynamic effects, and a distinct mechanism of action. It downregulates cyclin E and suppresses activating phosphorylation of CDK2 on Thr160.

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"We are pleased to share the discovery of NKT3447, a highly selective CDK2 inhibitor with unique properties, at the AACR (Free AACR Whitepaper) Annual Meeting", said Zhenhai Gao, Ph.D., co-founder, president, and CEO of NiKang. "This is the first of three programs targeting the cell cycle that we are expecting to bring to clinic. We have strong conviction in CDK2 as an oncology target and have built an industry-leading potential best in class and/or first in class portfolio that also includes a CDK2-selective degrader and a CDK2/4 dual degrader. Despite clinical success with drugs targeting the cell cycle, it has been challenging to identify inhibitors of CDK2 which have sufficient selectivity against CDK1, and which do not cause a compensatory increase of cyclin E. We have developed a platform to bring unique and selective drugs targeting CDK2 which address these challenges to clinic. We appreciate the opportunity to share the unique properties of NKT3447 and are enthusiastic about exploring the potential of NKT3447 in treating various cancers driven by CDK2 and cyclin E."

NiKang has initiated a phase 1/1b, open-label, dose escalation and expansion study of NKT3447 as a single agent. This first-in-human study (NCT06264921) is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity of NKT3447, administered orally, in adult patients with advanced or metastatic solid tumors.

Poster Presentation Details:

Title:

Discovery of a selective slow-off CDK2 inhibitor NKT3447 with distinct features of suppressing CDK2, downregulating cyclin E, and achieving prolonged pathway inhibition

Presenter:

Ke Liu, Ph.D.

Abstract Number:

5705/5 (link to abstract)

Session:

Pharmacologic Targeting of Cell Cycle Proteins

Date/Time:

1:30 – 5:00pm PT on April 9, 2024

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.

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.