On November 13, 2018 Vernalis Research, a Ligand Company, reported that it has earned multiple success milestones under its drug discovery collaboration with Daiichi Sankyo Company, Limited (Daiichi Sankyo) that began in December of 2017 (Press release, Vernalis, NOV 13, 2018, View Source [SID1234531261]).

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The research utilizes Vernalis’ fragment and structure-based drug discovery platform for two undisclosed oncology targets. Additionally, a final success payment has been earned for one target and the research collaboration continues for the second target. The financial terms of the collaboration are not disclosed.

Mike Wood, Ph.D. Research Director of Vernalis Research, commented, "We are delighted with the success we have achieved in our close collaboration with the scientists at Daiichi Sankyo. This is another excellent endorsement of our world-leading fragment and structure-based drug discovery platform and we look forward to the potential for continued success in our collaboration with Daiichi Sankyo."

On November 13, 2018 Novocure (NASDAQ: NVCR) reported more than 70 presentations on Tumor Treating Fields, including five oral presentations, reported that it will be featured at the 23rd Annual Meeting of the Society for Neuro-Oncology (SNO) on Nov. 15 through Nov. 19 in New Orleans. External authors prepared more than 50 of the presentations, pointing to a growing interest in Novocure’s proprietary Tumor Treating Fields platform. Presentations span 21 research areas with more than 5 percent of all conference abstracts at the 23rd Annual Meeting of the Society for Neuro-Oncology discussing Tumor Treating Fields.

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Novocure announces more than 70 presentations on Tumor Treating Fields at 23rd Annual Meeting of the Society for Neuro-Oncology

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"We are pleased to have a record number of presentations on Novocure’s proprietary platform featured this year at SNO’s Annual Meeting," said Dr. Eilon Kirson, Novocure’s Chief Science Officer and Head of Research and Development. "Presentations cover a broad range of topics from cell biology, radiation therapy and immunology to clinical trials and patient care, which we believe point to a growing and diversifying interest in Tumor Treating Fields from clinicians and researchers around the world. We are excited to engage the oncology community at SNO and to continue collaborating to realize the full potential of Tumor Treating Fields."

New clinical data from investigator sponsored pilot trials will be shared studying Tumor Treating Fields in progressive pediatric gliomas, Tumor Treating Fields prior to and with radiation for newly diagnosed glioblastoma (GBM),Tumor Treating Fields in combination with a personalized mutation-derived tumor vaccine for newly diagnosed GBM, and targeted skull remodeling surgery to maximize Tumor Treating Fields intensity for recurrent GBM.

Post-hoc analyses of Novocure’s EF-14 phase 3 pivotal trial in newly diagnosed GBM will highlight improved patient outcomes associated with higher delivered doses of Tumor Treating Fields, the potential combination of Tumor Treating Fields with lomustine and the absence of a negative impact on health-related quality of life in the EORTC QLQ-C30 and BN20 scales when Tumor Treating Fields was added to temozolomide.

Preclinical data will highlight the potential role of Tumor Treating Fields as an activator of the immune system, supporting further investigation into the combination of Tumor Treating Fields and immunotherapy. Other abstracts will include insights on the relative response to Tumor Treating Fields across certain cell lines, the potential for novel array layouts to improve efficacy of Tumor Treating Fields, the potential effect of Tumor Treating Fields on blood brain barrier permeability and the potential synergistic effect of Tumor Treating Fields in combination with PARP inhibitors.

Health economics and outcomes research data will discuss the cost effectiveness of Tumor Treating Fields across multiple populations and assessment frameworks.

Abstracts on Tumor Treating Fields can be viewed online and include the following:

Oral presentations

(HOUT-16) The cost effectiveness of Tumor Treating Fields treatment for patients with newly diagnosed glioblastoma based on the EF-14 trial. G. Guzauskas. 5:00 to 5:04 p.m. CST Saturday, Nov. 17. (E-talks group 3: Health outcomes / neurological complications of cancer and cancer therapy / quality of life / radiotherapy / surgical therapy / CNS metastases)

(ACTR-46) Higher doses of TTFields in the tumor are associated with improved patient outcome. M. Ballo. 5:32 to 5:36 p.m. CST Saturday, Nov. 17. (E-talks group 1: Adult therapeutics / immunology)

(ACTR-43) Open-label phase 1 clinical trial testing personalized and targeted skull remodeling surgery to maximize TTFields intensity for recurrent glioblastoma – Interim analysis and safety assessment. A. Korshoej. 9:40 to 9:45 a.m. CST Sunday, Nov. 18. (Concurrent session 7A: Adult clinical trials II)

(HOUT-18) Cost effectiveness of treating glioblastoma patients age 65 years or older with Tumor Treating Fields plus temozolomide versus temozolomide alone. G. Guzauskas. 10:30 to 10:40 a.m. CST Sunday, Nov. 18. (Concurrent session 8B: Practical & applied neuro-oncology II)

(IMMU-71) Evaluating the compatibility of tumor treating electric fields with key anti-tumoral T cell functions. G. Diamant. 11:50 to 11:55 a.m. CST Sunday, Nov. 18. (Concurrent session 8C: Immunology – Preclinical and clinical II)

Poster presentations: Adult clinical trials – Non-immunologic

(ACTR-01) Safety Analyses of Tumor Treating Fields in Combination with Lomustine in the EF14 Phase 3 Clinical Study. A. Kinzel. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(ACTR-49) Pricottf: A Phase I/II Trial of Tumor Treating Fields Prior and Concomitant to Radiotherapy in Newly Diagnosed Glioblastoma. M. Glas. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

Poster presentation: Angiogenesis

(ANGI-11) Tumor Treating Fields (TTFields) Inhibit Cancer Cell Migration and Invasion by Inducing Reorganization of the Actin Cytoskeleton and Formation of Cell Adhesions. M. Giladi. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

Poster presentations: Adult clinical trials – Immunologic

(ATIM-02) Tumor Treating Fields in Combination with Bevacizumab in Recurrent or Progressive Meningioma in a Phase 2 Study. P. Kumthekar. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(ATIM-03) TTFields and Pulsed Bevacizumab in Patients with Bevacizumab-refractory Recurrent Glioblastoma: A Phase 2 Study. D. Tran. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(ATIM-31) Phase I Study of Tumor Treatment Fields and a Personalized Mutation-derived Tumor Vaccine in Patients with Newly Diagnosed Glioblastoma. A. Hormigo. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

Poster presentations: Cell biology and metabolism

(CBMT-03) A Novel Metabolic PET Tracer Strategy to Determine Early Effects of Tumor Treating Fields (TTFields). C. Patel. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(CBMT-29) Induction of Autophagy Following TTFields Application Serves as a Survival Mechanism Mediated by AMPK Activation. M. Giladi. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

Poster presentations: Computational omics

(COMP-15) Meta-analysis of Cancer Cell Lines Based on Their Response to Tumor Treating Fields (TTFields). M. Giladi. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(COMP-19) Water-content Based Electric Property Tomography (wEPT) for Modelling Delivery of Tumor Treating Fields to the Brain. Z. Bomzon. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

Poster presentation: Drug resistance

(DRES-11) A Systems Approach for Determining the Mechanism of Resistance to Tumor Treating Fields in Glioblastoma. D. Chen. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

Poster presentations: Experimental therapies

(EXTH-01) Modeling the Safety of Topical Agents for Skin Toxicity Associated with Tumor Treating Fields Therapy in Glioblastoma. M. Lacouture. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(EXTH-24) Exposure to Tumor Treating Fields Inhibits DNA Repair, Induces Replication Stress and Renders Tumor Cells Sensitive to Agents That Impinge upon These Pathways. M. Story. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(EXTH-38) A New Computational Method for Comprehensive Estimation of Anti Tumor Efficacy of Tumor Treating Fields (TTFields). A. Korshoej. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(EXTH-40) Optimizing Array Layouts for Glioblastoma Therapy with Tumor Treating Fields (TTFields). A. Korshoej. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(EXTH-41) Effects of Tumor Treating Fields (TTFields) on Blood Brain Barrier (BBB) Permeability. A. Kessler. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(EXTH-62) The Dielectric Properties of Malignant Glioma Tissue. M. Proescholdt. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(EXTH-74) Molecular Mechanisms of Anti-tumor Action of TTFields Determined by Measurements and Modeling of Electro-conductive Properties of Microtubules. J. Tuszynki. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

Poster presentations: Health outcome measures

(HOUT-06) Pattern of low field intensity recurrence in high-grade gliomas following Tumor Treatment Field therapy. R. Briggs. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(HOUT-09) Using the ASCO (Free ASCO Whitepaper) and ESMO (Free ESMO Whitepaper) Frameworks to Assess the Clinical Value of Tumor Treating Fields for Newly Diagnosed Glioblastoma Multiforme. C. Proescholdt. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(HOUT-17) Elderly Patients >65 years of Age with Newly Diagnosed Glioblastoma Multiforme Gain Life Time from Treatment with Tumor Treating Fields and Temozolomide. G. Guzauskas. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(HOUT-25) Adherence to Tumor Treating Fields in Patients with High-grade Glioma – A Single Center Experience. A. Kessler. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(HOUT-26) Survival Outcomes in Glioblastoma Patients Using TTFields: The Baylor Scott & White Medical Center in Central Texas Experience. A. Padhye. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(HOUT-27) The Challenge of Health Utility Values for Glioblastoma Patients with Long-term Survival. C. Proescholdt. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(HOUT-28) Clinical Experience with Tumor Treating Fields (TTFields, Optune) in Israel – Patient Acceptance and Safety. T. Siegal. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(HOUT-30) Tumor Treating Fields (TTFields) in Combination with Lomustine (CCNU) and Temozolomide (TMZ) in Patients with Newly Diagnosed Glioblastoma (GBM). M. Glas. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(HOUT-31) Care patterns and treatment efficacy: A clinical series of primary glioblastoma with an emphasis on older adults. M. Hultman. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(HOUT-36) Institutional Compliance with Tumor Treating Fields for Glioblastoma. R. Bonomi. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

Poster presentations: Immunology

(IMMU-42) TTFields Induces Immunogenic Cell Death and STING Pathway Activation Through Cytoplasmic Double-stranded DNA in GBM. D. Chen. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(IMMU-52) Tumor Treating Fields (TTFields) Induce Immunogenic Cell Death Resulting in Enhanced Antitumor Efficacy When Combined with anti-pd-1 Therapy. T. Voloshin. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(IMMU-53) Impact of Tumor-treating Fields (TTFields) on the Immunogenicity of Glioma Cells. M. Silginer. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

Poster presentations: Innovations in patient care

(INNV-01) PROTECT Study: PRO Phylactic Skin Toxicity Therapy with Clindamycin and Clobetasol or Skin Barrier in Glioblastoma Patients Treated with Tumor Treating Fields. M. Lacouture. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(INNV-03) Safety and Adverse Event Profile of Tumor Treating Fields Use in the EMEA Region – a Real-world Data Analysis. M. Glas. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(INNV-04) Safety and Adverse Event Profile of Tumor Treating Fields in Glioblastoma – a Global Post-market Surveillance Analysis. U. Weinberg. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(INNV-17) Tumour Treating Fields: Acceptable to a UK Population? M. Jenkinson. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(INNV-23) Safety and Adverse Event Profile of Tumor Treating Fields in Elderly Patients – a Post-market Surveillance Analysis. W. Shi. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(INNV-24) Safety of Tumor Treating Fields in Glioblastoma Patients with Implanted Non-programmable and Programmable Shunts, and Pacemakers/defibrillators. Y. Kew. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(INNV-29) Experience with TTFields (Optune) in Pediatric High Grade Glioma Patients in Israel. M. Yalon. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(INNV-30) Tumor Treating Fields and Radiotherapy for Newly Diagnosed glioblastoma: Safety and Efficacy Results from a Pilot Study. R. Grossman. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(INNV-31) User Experience with New, Aesthetically Improved Transducer Arrays for Delivery of Tumor Treating Fields for Glioblastoma. A. Kinzel. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(INNV-48) Tumor Treating Fields Utilization in a Glioblastoma Patient with a Preexisting Cardiac Pacemaker: The First Reported Case. S. McClelland. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

Poster presentation: Neurological complications of cancer and cancer therapy

(NCMP-21) Real-world Surveillance Data for Tumor Treating Fields Affirm the Tolerability of Tumor Treating Fields for the Treatment of Glioblastoma in the United States. D. Tran. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

Poster presentation: Neuro-cognitive outcomes

(NCOG-06) Predicting Tumor Treating Field Compliance Using Neurocognitive Testing. K. Qualls. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

Poster presentations: Neuro-imaging

(NIMG-04) Diffusion Restriction on MR Imaging in the T2 Hyperintense, but Otherwise Normal-appearing White Matter of Glioblastoma Patients Treated with TTFields Correlates with Survival. J. Vymazal. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(NIMG-34) The Impact of Tumor Treating Fields (TTFields) on Brain Anatomy Using Computational Anatomy Analysis. A. Hottinger. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(NIMG-48) Volumetric Response to TTFields in Newly Diagnosed GBM. C. Freyschlag. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(NIMG-49) Electric Field Intensities Delivered by Tumor-treating Fields (TTFields) to Glioblastoma Regions: Effect on Treatment Response Assessed by Amino Acid PET. C. Juhasz. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(NIMG-72) A Novel Array Layout for Delivering TTFields to the Whole Brain. Z. Bomzon. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

Poster presentation: Molecular pathology and classification – Adult and pediatric

(PATH-27) Identifying the Genetic Signature of Response in a Phase II Study of Tumor Treating Fields in Recurrent Glioblastoma. D. Tran. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

Poster presentations: Pediatric clinical trials

(PDCT-07) Feasibility Trial of Optune for Children with Recurrent or Progressive Supratentorial High-grade Glioma and Ependymoma: A Pediatric Brain Tumor Consortium Study. E. Hwang. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(PDCT-11) Surveillance Data Demonstrates the Tolerability of Tumor Treating Fields in Pediatric Glioma Patients. D. Hanson. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(PDCT-12) A Phase I Trial of Tumor Treating Fields with and Without Concomitant Temozolomide and Bevacizumab in Pediatric Patients with High-grade Glioma and Ependymoma. D. Hanzon. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

Poster presentation: Pediatric tumors

(PDTM-19) Tumour Treating Fields (TTFields) Exhibit Efficacy on High-grade Paediatric Brain Tumour Cell Lines. J. Branter. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

Poster presentations: Quality of life and palliative care

(QOLP-01) Effects of Tumor Treating Fields on Health-related Quality of Life (HRQoL) in Newly Diagnosed Glioblastoma: An Exploratory Analysis of the EF-14 Randomized Phase III Trial. T. Walbert. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(QOLP-15) Safety and Adverse Event Profile of Tumor Treating Fields in Anaplastic Glioma – a Post-marketing Surveillance Analysis. D. Bota. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

Poster presentation: Randomized brain tumor trials in development

(RBTT-05) Tumor Treating Fields and Radiosurgery for Supra- and/or Infratentorial Brain Metastases (1-10) from NSCLC in the Phase 3 METIS Study. M. Mehta. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

Poster presentations: Radiation biology and DNA repair

(RDNA-02) Tumor Treating Fields Differentially Alter Homologous Recombination in Patient Derived Glioma Cells versus Established Lines. L. Bronk. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(RDNA-07) idh1-mutant Glioblastoma (GBM) Cells from a Patient Post-tumor Treating Fields (TTFields) Therapy Are Sensitive to TTFields in vitro. S. Mittal. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(RDNA-10) Histopathological and Genomic Characterization of Glioblastoma (GBM) Resected After Tumor Treating Fields (TTFields) Therapy. S. Michelhaugh. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(RDNA-17) Power Density Loss Can Be Used to Defined Tumor Treating Fields Dose. Z. Bomzon. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

Poster presentations: Radiation therapy

(RTHP-12) Comparative Analysis of Tumor Treating Fields Using Conventional versus Alternative Array Placement for Posterior Fossa Glioblastoma. E. Wong. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(RTHP-13) Tumor-treating Fields Therapy Is Compatible with Standard Chemoradiotherapy for Glioblastoma. L. Kleinberg. 7:30 to 9:30 p.m. CST Friday, Nov. 16.

(RTHP-14) Tumor-treating Fields for Glioblastoma: Numerical Simulation Explores Sub-cellular Mechanisms. K. Carlson. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

Poster presentations: Tumor microenvironment

(TMIC-10) Autopsy Study on the Effects of Tumor Treatment Fields in Recurrent Glioblastoma: Preliminary Results. A. Barrington. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

(TMIC-38) Enhanced Efficacy of Tumor Treating Fields and Aurora B Kinase Inhibitor Combination in Glioma Cell Lines. M. Giladi. 5:00 to 7:00 p.m. CST Saturday, Nov. 17.

On November 13, 2018 Tempest Therapeutics Inc. reported a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting in Washington, D.C., describing lead compound TPST-1120’s two-pronged mechanism of directly targeting tumor cells dependent on fatty acid metabolism and driving a metabolic shift in the tumor microenvironment to glycolysis from fatty acid oxidation (Press release, Tempest Therapeutics, NOV 13, 2018, View Source [SID1234531259]). The resulting significant reductions in tumor growth and stimulation of durable anti-tumor immunity support Tempest’s rationale to advance the first-in-class oral small molecule inhibitor of PPAR alpha into clinical studies in patients with advanced solid tumors in early 2019.

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The poster titled "Antagonism of Peroxisome Proliferator Activated Receptor Alpha (PPARα) by TPST-1120 Suppresses Tumor Growth and Stimulates Anti-Tumor Immunity" describes studies that demonstrate significant anti-tumor efficacy of TPST-1120. As monotherapy, TPST-1120 prevented fatty acid oxidation and directly inhibited primary human tumor cells in culture and in human tumor xenografts in immune-deficient mice. In tumor-bearing immune-competent animals, TPST-1120 inhibited tumor growth as a single agent and in combination with chemotherapy or with anti-PD-1 antibodies.

For example, TPST-1120 plus gemcitabine significantly increased the long-term survival of mice with pancreatic tumors. TPST-1120 in combination with anti-PD-1 antibodies in mouse models of ovarian and colon cancer showed suppression of tumor growth and complete remissions in some animals. Importantly, cured mice were completely protected against autologous tumor re-challenge in the ovarian model, strongly suggesting immunological T cell memory against the primary tumor.

TPST-1120 elicits its potent anti-tumor effects through direct binding of the PPAR alpha transcription factor, inhibiting the expression of its regulated genes that are critical for fatty acid oxidation. Several malignancies such as hepatocellular carcinoma and renal cell cancer are reliant on fatty acid oxidation. In addition, suppressive immune cells in the tumor microenvironment such as a particular subset of macrophages, regulatory T cells and myeloid-derived suppressor cells all favor fatty acid oxidation. The utilization of fatty oxidation by tumor cells and suppressive immune cells underlines the tumor-intrinsic and tumor-extrinsic anti-tumor properties of TPST-1120.

"Immuno-metabolism is a rapidly evolving field, and it is increasingly recognized that regulating particular metabolic checkpoints that are essential to promote bio-energetic pathways necessary for sustaining tumor growth are important new targets in oncology. Our poster provides the rationale for advancing TPST-1120 into patients with advanced cancers and also provides insights into the clinical development of this first-in-human molecule," said Tom Dubensky, Ph.D., president and CEO of Tempest.

On November 13, 2018 Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, reported preclinical data on SY-1365, its first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor, showing synergistic anti-tumor activity in combination with carboplatin, a standard-of-care therapy, in models of ovarian cancer and providing a mechanistic rationale for the ongoing investigation of the combination in the Phase 1 clinical trial of SY-1365 (Press release, Syros Pharmaceuticals, NOV 13, 2018, View Source [SID1234531258]). The Company also announced the first preclinical data on its class of highly selective oral CDK7 inhibitors, which showed significant anti-proliferative activity in preclinical models of breast and ovarian cancers. These data were presented at the 30th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium in Dublin.

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"Selective CDK7 inhibition represents a potentially transformative approach for treating a range of cancers that have eluded effective treatment," said Eric R. Olson, Ph.D., Syros’ Chief Scientific Officer. "Our presentations at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) meeting highlight our leadership in the field and support the ongoing clinical development of SY-1365 as well as the selection of SY-5609, a highly selective oral CDK7 inhibitor, as our next development candidate. Given the broad potential of CDK7 inhibitors as a new class of medicines, we believe physicians and patients will seek options across multiple modalities and believe an oral molecule could serve as an important complement to SY-1365. We are committed to maximizing the potential of CDK7 inhibition for patients, as we work to achieve our vision of developing new medicines that provide profound benefit for patients."

SY-1365 Preclinical Combination Data
The preclinical data presented at EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) provide a strong mechanistic rationale for the ongoing clinical investigation of SY-1365 in combination with carboplatin in ovarian cancer patients. Homologous recombination deficiency (HRD), a cellular defect caused by the disruption of normal DNA damage repair processes, sensitizes cells to treatment with DNA repair inhibitors, including PARP inhibitors and DNA-damaging agents such as carboplatin. In preclinical models of ovarian cancer, SY-1365 was shown to inhibit DNA repair and decrease the expression of homologous recombination repair (HRR) genes, which are important for repairing harmful breaks in DNA. These data suggest that SY-1365 induces an HRD-like state, which may result in enhanced sensitivity to DNA-damaging agents and DNA repair inhibitors.

Consistent with the proposed mechanism-of-action, SY-1365 demonstrated synergy with carboplatin in ovarian cancer cell lines and demonstrated greater anti-tumor activity in combination with carboplatin in xenograft models of ovarian cancer than either agent alone.

Syros is currently conducting a Phase 1 clinical trial assessing the safety and efficacy of SY-1365 as a single agent and in combination with standard-of-care therapies in multiple ovarian and breast cancer patient populations. The ongoing trial includes a study cohort evaluating SY-1365 in combination with carboplatin in ovarian cancer patients who have relapsed after one or more prior therapies. Additional details about the trial can be found using the identifier NCT03134638 at www.clinicaltrials.gov.

Preclinical Data from Oral CDK7 Inhibitor Program
Syros created a suite of highly selective and potent orally available CDK7 inhibitors. The preclinical data at EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) detail for the first time the selectivity, potency and anti-tumor activity of these inhibitors. Using a representative member of Syros’ suite of oral CDK7 inhibitors, these data show:

200- to 1,200-fold greater selectivity for CDK7 over other members of the CDK family, including CDK2, CDK9 and CDK12.
Robust anti-proliferative activity in triple negative breast cancer and ovarian cancer cell lines, which was associated with the induction of apoptosis and cell cycle arrest.
Strong correlation between biochemical potency, CDK7 target engagement and tumor growth inhibition.
Substantial anti-tumor effects in multiple cell-line and patient-derived xenograft models of triple negative breast and ovarian cancers.
These data helped support the selection of SY-5609 as the Company’s next development candidate. Syros is currently advancing SY-5609 into Investigational New Drug (IND) application-enabling preclinical studies.

The poster presentations on the SY-1365 preclinical combination data and on the oral CDK7 inhibitor program are now available on the Publications and Abstracts section of the Syros website at www.syros.com.

On November 13, 2018 Castle Biosciences, Inc., the skin cancer diagnostics company providing molecular diagnostics to improve cancer management decisions, reported study results showing that the DecisionDx-Melanoma test accurately predicts risk for patients with cutaneous melanoma when using either biopsy or wide local excision (WLE) as the tissue source (Press release, Castle Biosciences, NOV 13, 2018, View Source [SID1234531257]). Highlights of the study were presented during an oral presentation at the American Society of Dermatopathology 55th Annual Meeting held November 8-11, 2018 in Chicago.

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"This study demonstrates that the DecisionDx-Melanoma test provides an accurate, independent prediction of risk regardless of tissue source," said Sarah Estrada, M.D., FACP, Affiliated Dermatology, Scottsdale AZ, a study investigator. "Using biopsy or wide local excision tissue does not impact the ability of the DecisionDx-Melanoma test to accurately predict risk and inform patient management decisions."

Study Background

The DecisionDx-Melanoma test has been shown to provide an accurate, independent prediction of risk for patients with cutaneous melanoma.
The test has shown robust analytic reliability with 99% inter-assay concordance and 100% intra-assay concordance. Technical success exceeded 98% on samples with sufficient tumor content.
This study assessed whether test results or patient outcomes were associated with tissue source (biopsy or WLE) in an archival cohort of 537 patients with Stage I-III cutaneous melanoma for whom the tissue source was known.
Key Study Results

Among those who had biopsy tissue tested, a higher percentage had Stage I disease (68%) compared to those who had WLE tissue tested (19% Stage I; p<0.001).
Patients who had WLE tissue tested were significantly more likely to have Stage III melanoma (50%) compared to those who had biopsy tissue tested (17% Stage III; p<0.001).
Patients who had WLE tissue tested also were more likely to have higher risk pathologic features such as ulceration and increased Breslow thickness.
For both tissue sources, patients who had the lowest risk DecisionDx-Melanoma test result (Class 1A) had significantly improved distant metastasis-free survival and melanoma-specific survival rates compared to those who had the highest risk test result (Class 2B).
After adjusting for pathologic features among patients in the two tissue source groups, use of WLE tissue was not significantly associated with DecisionDx-Melanoma test class result.
In multivariate analysis, DecisionDx-Melanoma Class 2B (highest risk) was a significant independent predictor of recurrence, distant metastasis and melanoma-specific survival, while WLE tissue source was not found to be predictive of outcomes.
These results demonstrate that the DecisionDx-Melanoma test provides an accurate, independent prediction of risk regardless of tissue source.
About DecisionDx-Melanoma

The DecisionDx-Melanoma test uses tumor biology to predict individual risk of melanoma recurrence and sentinel lymph node positivity independent of traditional factors. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in three multi-center studies that have included 690 patients and have demonstrated consistent results. Performance has also been confirmed in four prospective studies including 702 patients. The consistent high performance and accuracy demonstrated in these studies, which combined have included over 1,300 patients, provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results.

Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter studies that included over 1,400 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in multi-center and single-center studies. More information about the test and disease can be found at www.SkinMelanoma.com.