On April 8, 2022 Novocure (NASDAQ: NVCR) reported 19 presentations on Tumor Treating Fields (TTFields) will be delivered at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, to be held in New Orleans from April 8 to April 13, 2022 (Press release, NovoCure, APR 8, 2022, View Source [SID1234611737]). The research described in the presentations spans 10 tumor types and suggests the potential for broad usage of TTFields across multiple solid tumors.

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Presentation highlights include research on: transcriptomics (gene expression) analysis for identification of pathways that are activated in response to TTFields, concurrent treatment of ovarian cell lines with TTFields and PARP inhibitors, transient and reversible enhanced blood brain barrier permeability by TTFields in a human 3D in vitro model and efficacy of TTFields concomitant with radiation therapy in murine solid tumor models.

"We believe ongoing research on Tumor Treating Fields suggests the potential for TTFields applicability across a variety of tumor types," said Dr. Uri Weinberg, Novocure’s Chief Science Officer. "We are honored to participate in the exchange of scientific information and share new insights about the effects of TTFields on tumors, as revealed through a myriad of preclinical and clinical research, and treatment planning and modeling studies, by scientists around the world, at the AACR (Free AACR Whitepaper) Annual Meeting."

Presentations from Novocure-sponsored and partner programs include:

(Abstract #: CT234) PANOVA-3: A phase 3 study of Tumor Treating Fields (TTFields) with gemcitabine and nab-paclitaxel (GnP) for front-line treatment of locally advanced pancreatic adenocarcinoma. J. Finlay (Clinical Trials)

(Abstract #: 4138) Prediction of progression-free survival in patients with primary glioblastoma: MRI T2 relaxivity and deep learning. A. Rulseh (Clinical Research Excluding Trials)

(Abstract #: 3447) Tumor Treating Fields (TTFields) treatment planning for a patient with astrocytoma in the spinal cord. J. De Los Santos (Clinical Research Excluding Trials)

(Abstract #: 3450) Impact of model inaccuracy on dose estimation in TTFields therapy. T. Marciano (Clinical Research Excluding Trials)

(Abstract #: 1801) Application of Tumor Treating Fields (TTFields) to cancer cells enhances their membrane permeability. A. Haber (Experimental and Molecular Therapeutics)

(Abstract #: 2659) Inhibition of PI3K sensitized cancer cells to Tumor Treating Fields (TTFields). A. Klein-Goldberg (Experimental and Molecular Therapeutics)

(Abstract #: 3465) Efficacy of concomitant application of Tumor Treating Fields (TTFields), temozolomide and lomustine in glioblastoma cancer cells in vitro. E. Dor-On (Clinical Research Excluding Trials)

(Abstract #: 1866) Transcriptomics analysis for identification of pathways involved in the response to Tumor Treating Fields (TTFields). M. Giladi (Experimental and Molecular Therapeutics)

(Abstract #: 2601) Concomitant treatment of ovarian cell lines with Tumor Treating Fields (TTFields) and PARP inhibitors. E. Dor-On (Experimental and Molecular Therapeutics)

(Abstract #: 1305) Tumor Treating Fields (TTFields) promote a pro-inflammatory phenotype in macrophages. A. Klein-Goldberg (Immunology)

(Abstract #: 1833) Tumor Treating Fields induce DNA damage and apoptosis in medulloblastoma. R. Nitta (Experimental and Molecular Therapeutics)

(Abstract #: 3252) Tumor Treating Fields suppression of ciliogenesis enhances temozolomide toxicity. M. Sarkisian (Experimental and Molecular Therapeutics)

(Abstract #: 387) Blood brain barrier (BBB) disruption by Tumor Treating Fields (TTFields) in a human 3D in vitro model. C. Hagemann (Experimental and Molecular Therapeutics)

(Abstract #: 380) Tumor Treating Fields enhance cellular drug uptake in mesothelioma cell lines. M. Lupi (Experimental and Molecular Therapeutics)

(Abstract #: 2037) Spatial omic changes of malignant pleural mesothelioma following treatment using Tumor Treating Fields. E. Lou (Clinical Research Excluding Trials)

(Abstract #: 3156) Tumor Treating Fields reduce cellular survival of human mesenchymal stromal cells via apoptosis and senescence induction. A. Rühle (Tumor Biology)

(Abstract #: 299) Self-assembling nanoparticles: A novel approach for targeted cancer treatment using Tumor Treating Fields. P. Desai (Chemistry)

(Abstract #: 2315) Synergic antitumoral activity of TTFields stimulation and Chloride Intracellular Channel 1 (CLIC1) inhibition in human glioblastoma primary culture. M. Mazzanti (Molecular/Cellular Biology and Genetics)

(Abstract #: 3316) Tumor Treating Fields in combination with radiation cause significant delay in tumor growth in in-vivo mice model. D. Saha (Experimental and Molecular Therapeutics)

About Tumor Treating Fields

Tumor Treating Fields, or TTFields, are electric fields that disrupt cancer cell division. Fundamental scientific research extends across more than two decades and, in all preclinical research to date, TTFields have demonstrated a consistent anti-mitotic effect. TTFields therapy is intended principally for use together with other standard-of-care cancer treatments. There is a growing body of evidence that supports TTFields’ broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies. In clinical research and commercial experience to date, TTFields therapy has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect. The TTFields global development program includes a network of preclinical collaborators and a broad range of clinical trials across all phases, including four phase 3 pivotal trials in a variety of tumor types. To date, more than 22,000 patients have been treated with TTFields therapy.

On April 8, 2022 Agilent Technologies Inc. (NYSE: A) reported cancer research innovations in cell analysis and genomics that will be on show at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held April 8 – 13, 2022 in New Orleans, Louisiana (Press release, Agilent, APR 8, 2022, View Source [SID1234611736]).

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"Cancer research is an important focus area for Agilent. The AACR (Free AACR Whitepaper) conference presents an exciting opportunity to engage with customers, partners, and thought leaders in this field," said Jodi Barrientos, vice president of Commercial Marketing for Agilent’s Diagnostics and Genomics Group. "We look forward to highlighting products that enable the analysis of different sample types by leveraging multimodal approaches to cancer research spanning cell analysis, LCMS, and genomics."

Agilent is committed to helping cancer researchers achieve their scientific objectives by providing a broad toolkit of innovative products and solutions. Furthermore, Agilent’s portfolio of cancer-relevant solutions serves customers globally in their work on cancer research, diagnosis, and therapeutic development.

One of the solutions on show at ACCR is the Agilent Magnis NGS Prep System. This automated benchtop solution has an onboard wizard that allows assays to be set up in under five minutes, enabling molecular pathologists to profile samples for various generic aberrations using a single, cost-effective, and efficient platform.

Also featured will be the Agilent XF Pro Analyzer demonstrating its advanced functionality, particularly its capability to enhance critical aspects of monitoring live cells in real-time. The XF Pro incorporates enhancements that improve measurement performance and data interpretation, making it easier to identify novel drug targets, validate target effect on cellular function, optimize disease models, and determine drug safety and antitumor potential of T cell therapies.

On April 8, 2022 SimBioSys, the technology company that predicts tumor responses to therapy, reported it will present nine posters at the AACR (Free AACR Whitepaper) Annual Meeting 2022, taking place in New Orleans from April 8-13 (Press release, SimBioSys, APR 8, 2022, View Source [SID1234611734]). The posters will show the breadth of applications for the platform, from clinical uses in evaluating existing treatment options for patients with breast cancer, to metabolic profiling of solid tumors such as breast, prostate, and pancreatic cancers, as well as melanoma.

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SimBioSys will showcase TumorScope at the AACR (Free AACR Whitepaper) for the first time in a poster session on April 11. The biophysical simulation platform allows physicians and patients to better visualize and understand cancer and predict treatment response using only standard of care data to select the best possible therapy based on the patient’s own unique biology.

"As the number of oncology therapeutics continues to increase, it is of critical importance to have tools like TumorScope that can accurately predict patient outcomes prior to therapy to facilitate effective personalized care," said Tushar Pandey, CEO of SimBioSys.

At AACR (Free AACR Whitepaper), the company will present data on an independent validation study of TumorScope in collaboration with the University of Cincinnati. The study demonstrates how TumorScope predicts the pathological complete response (pCR) in breast cancer patients using only standard of care diagnostic data with an accuracy above 90 percent. This robust performance was observed across all breast cancer subtypes.

The utility of TumorScope transcends the clinic, where another poster highlights the use of the technology in a systems medicine-based approach to perform comprehensive metabolic profiling of various tumor types. The combination of RNA-sequencing data and metabolic network modeling made possible the identification of specific metabolic profiles, potentially key drivers of the tumor response to therapy thereby contributors of patient outcome. The results include data on breast cancer, lung adenocarcinoma, pancreatic adenocarcinoma, metastatic melanoma, clear renal cell carcinoma and salivary cystic adenoid carcinoma. This approach can be utilized as a systematic way to identify metabolic targets for treatment.

These clinical and research application studies, along with data on the biology behind racial disparities in breast cancer and pathology data, will also be presented at the conference.

"We are excited to present our technology and our research for the first time at the AACR (Free AACR Whitepaper)," said Pandey. "It is the ideal platform to showcase Tumor Scope’s utility not only in the clinic, but as a powerful cancer research tool with applicability in drug development."

The full nine abstracts and posters can be found here. For more information on these studies, please visit www.simbiosys.com.

On April 8, 2022 Boundless Bio, a next-generation precision oncology company developing innovative therapeutics directed against extrachromosomal DNA (ecDNA) in oncogene amplified cancers, reported that it will present a new finding at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, held in New Orleans and virtually from April 8-13, 2022 (Press release, Boundless Bio, APR 8, 2022, View Source [SID1234611733]). The poster, Replication stress and the inability to repair damaged DNA, the potential "Achilles’ heel" of ecDNA+ tumor cells, is available to registered attendees online starting today and for in-person presentation on April 11, 2022 at 1:30 PM – 5:00 PM CT.

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"Replication stress has long been known to be a driver of genomic instability in cancer," said Christian Hassig, Ph.D., Chief Scientific Officer of Boundless Bio. "This study demonstrates ecDNA-enabled gene amplified cancers have inherently high replication stress, thereby providing a unique point of intervention for our novel ecDNA-directed therapeutics (ecDTx). This work is an important scientific advancement both in our understanding of gene amplifications on ecDNA and in translating the science into novel therapeutics for patients with gene amplified cancers who currently have few treatment options."

Boundless Bio previously demonstrated that cancers with oncogenes amplified on ecDNA are associated with poor clinical prognosis1 and generally do not respond to targeted therapies, underscoring the urgent need to identify clinical strategies to treat ecDNA amplified cancers. For the first time, we present data showing a relationship between ecDNA and DNA replication stress, a known form of genomic instability that contributes to oncogenesis and tumor evolution. While the drivers of replication stress remain unclear, excessive replication stress leads to extensive DNA damage and cancer cell death. The results demonstrate ecDNA-enabled colorectal cancer cells have intrinsically elevated levels of replication stress and are hypersensitive to replication stress inducing agents. These novel findings highlight replication stress as a potential synthetic lethal approach in ecDNA amplified cancers.

Poster available at Boundless Bio website.

Reference
1Kim, Nguyen, Turner et al. Nature Genetics 2020

About ecDNA

Extrachromosomal DNA ("ecDNA") are circular units of nuclear DNA found within cancer cells, and which contain highly transcriptionally active genes, including oncogenes, but are physically distinct from chromosomes and lack centromeres. ecDNA replicate within cancer cells and, due to their lack of centromeres, can be asymmetrically passed to daughter cells during cell division, leading to focal gene amplification and copy number heterogeneity in cancer. By leveraging the plasticity afforded by ecDNA, cancer cells have the ability to increase or decrease copy number of select oncogenes located on ecDNA to enable survival under selective pressures, including targeted therapy, immunotherapy, chemotherapy, or radiation, thereby making ecDNA one of cancer cells’ primary mechanisms of growth, recurrence, and treatment resistance. ecDNA are not found in healthy cells but are present in many solid tumor cancers. They are a key driver of the most aggressive and difficult-to-treat cancers, specifically those characterized by high copy number amplification of oncogenes.

On April 8, 2022 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 presentation of preclinical data investigating NKT2152’s mechanism of action, in vivo pharmacokinetic and pharmacodynamic profile, and anti-tumor effect in multiple xenograft models including ccRCC and hepatocellular carcinoma at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, NiKang Therapeutics, APR 8, 2022, View Source [SID1234611732]).

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"The NKT2152 preclinical data presented today highlight its best-in-class potential with excellent potency and PK profile and support the advancement of this molecule into clinical studies," said Zhenhai Gao, Ph.D., Co-founder, President and Chief Executive Officer of NiKang. "The anti-tumor effect observed in several xenograft models suggests NKT2152 may have broader activity in other solid tumors beyond ccRCC that lack a VHL gene deficiency. We will explore such opportunities with the goal of helping more patients in need."

About NKT2152

NKT2152 is a small molecule that inhibits HIF2α. It is currently in a phase 1/2 dose escalation and expansion trial (NCT05119335). This trial is designed to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity in patients with advanced ccRCC. Once an appropriate dose is identified, combination studies including NKT2152 will commence.