On October 26, 2017 GeneCentric Therapeutics reported that it will present data on the potential of non-small cell lung cancer (NSCLC) biologic subtypes based on its Cancer Subtyping Platform (CSP) to provide novel biomarkers for response to PARP inhibitors (Press release, GeneCentric Therapeutics, OCT 26, 2017, View Source [SID1234521242]). The data will be presented at a poster session during the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) – National Cancer Institute – European Organization for Research and Treatment of Cancer (AACR-NCI-EORTC) (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Therapeutics being held October 27-30, 2017 at the Philadelphia Convention Center, Philadelphia, PA.

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GeneCentric’s core CSP technology is based on generating high resolution, genomic-defined cancer subtypes that characterize disease-related molecular pathways and immune cell expression, and employing the subtypes as biomarkers for response to specific drugs. To date the company has generated subtype-based profilers for NSCLC, head and neck, and bladder cancers.

In the research to be presented at the AACR (Free AACR Whitepaper)-NCI-EORTC meeting company scientists evaluated the potential susceptibility of GeneCentric lung adenocarcinoma and lung squamous cell carcinoma gene expression subtypes to PARP inhibitors. By examining differential expression of homologous recombination genes and several previously published BRCAness signatures, the study identifies subtype-associated differences that might inform likely response to PARP inhibitors, an emerging class of drugs targeting DNA damage response. The researchers show that variable expression of DNA damage response genes in lung squamous cell carcinoma is maintained following adjustment for proliferation and BRCAness signatures, suggesting underlying biologic differences in lung squamous cell carcinoma subtype susceptibility to DNA damage response inhibitors. Confirmation of these findings via prospective cohorts could substantiate their utility as novel biomarkers for PARP inhibitor response.

Details of the presentation are as follows:

Title: “Differences in BRCAness/PARP inhibitor response signatures and homologous recombination
gene expression across lung adenocarcinoma and squamous cell carcinoma gene expression subtypes.”
Poster Number: 37
Abstract Number: A037
Date: Saturday, October 28, 2017
Time: 12:30 PM – 4:00 PM ET
Location: Hall E, Pennsylvania Convention Center
Presenter: Hawazin Faruki, DrPH, Chief Scientific Officer, GeneCentric

To read the abstract, please visit: View Source!/4557/presentation/144

La Jolla Pharmaceutical has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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On October 26, 2017 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported that it will report third quarter 2017 financial results on Thursday, November 2, 2017. Karyopharm’s management team will host a conference call and audio webcast at 8:30 a.m. ET on Thursday, November 2, 2017 to discuss the financial results and recent business developments (Press release, Karyopharm, OCT 26, 2017, View Source [SID1234521226]).

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To access the conference call, please dial (855) 437-4406 (local) or (484) 756-4292 (international) at least 10 minutes prior to the start time and refer to conference ID 98527624. A live audio webcast of the call will be available under “Events & Presentations” in the Investor section of the Company’s website, investors.karyopharm.com/events.cfm. An archived webcast will be available on the Company’s website approximately two hours after the event.

On October 26, 2017 Syros Pharmaceuticals (NASDAQ: SYRS), a biopharmaceutical company pioneering the development of medicines to control the expression of disease-driving genes, reported that it has identified alterations in regulatory regions of the genome in immune, tumor and stromal cells isolated from pancreatic cancer patient tumors, leading to the identification of new drug targets (Press release, Syros Pharmaceuticals, OCT 26, 2017, View Source [SID1234521261]). These findings, which were made as part of a research collaboration with the Lowy laboratory at the University of California San Diego (UCSD) Moores Cancer Center, were highlighted in an oral presentation at the American College of Surgeons (ACS) 2017 Clinical Congress.

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“One of the biggest challenges in treating cancer is its ability to manipulate and evade the body’s immune response to fuel its growth,” said Andrew Lowy, M.D., Professor of Surgery and Chief of the Division of Surgical Oncology at the Moores Cancer Center. “Syros’ gene control platform provides a unique lens for understanding the regulatory mechanisms cancers use to govern cells within the tumor microenvironment. Through investigation of immune, tumor and stromal cells from patient tumors, our hope is to develop medicines that can unleash the body’s natural defenses to fight cancer.”

Together with the Lowy laboratory, Syros used its proprietary gene control platform to analyze and compare highly specialized regulatory regions of the genome, known as super-enhancers, in cells from pancreatic cancer patient tumors to those in cells from normal pancreatic tissues. Because super-enhancers control the expression of genes that determine cell function, their analysis can point to disease-driving changes in the expression of genes most critical to a given cell, as well as potential drug targets. The data presented at ACS showed that:

Leukemia inhibitory factor (LIF) gene demonstrated one of the most significant changes in enhancer size from pancreatic tumors in comparison to normal pancreatic tissue. In preclinical mouse models, LIF enhanced the anti-tumor activity of chemotherapy and produced a survival benefit when inhibited using a monoclonal antibody.
Many of the super-enhancers associated with cells in pancreatic tumor tissue are associated with genes involved in immune signaling pathways, including antigen presentation, IL10 signaling and macrophage activation, suggesting the importance of the immune system in the development and growth of pancreatic cancer and the identification of potential therapeutic targets.
Immunosuppressive tumor-associated macrophages had a distinct super-enhancer profile, pointing to genes critical for driving the immunosuppressive state and potential drug targets to reactivate immune cells. Tumor-associated macrophages are of significant interest in immuno-oncology because they play a key role in the immune response to cancer, with M1 macrophages promoting immune-mediated tumor regression and M2 macrophages promoting tumor immune evasion.
“These findings underscore the promise of Syros’ gene control platform to glean important biological insights that can lead to the identification of new drug targets and pave the way for medicines to increase killing of tumor cells by the immune system,” said Eric Olson, Ph.D., Chief Scientific Officer of Syros. “We believe our focus on analyzing the regulatory genomes of immune, tumor and stromal cells isolated from patients’ tumors represents a distinct approach to immuno-oncology with the potential to lead to novel therapies that provide a profound and durable benefit for subsets of cancer patients.”

Syros has a broader immuno-oncology drug discovery effort outside of the Lowy collaboration, which is focused on identifying and drugging novel targets to control the function of immune cells within the tumor microenvironment. Syros has identified a drug target that, when inhibited, may reduce the immunosuppressive capacity of tumor-associated macrophages and has a program based on this discovery in preclinical development. Syros’ immuno-oncology research is focused on cancers in which the tumor microenvironment is known to play a key role in disease progression, including glioblastoma and pancreatic, triple negative breast and ovarian cancers. By analyzing immune and tumor cells directly in patient tumors, Syros aims to better understand the heterogeneity of immune responses among patients and identify subsets of patients most likely to respond to specific immunotherapy strategies.

On October 26, 2017 Rgenix, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and antibody cancer therapeutics, reported that Dr. Monica Mita of Cedars-Sinai Medical Center and Principal Investigator of the RGX-104-001 study, will present at the 2017 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Press release, Rgenix, OCT 26, 2017, View Source [SID1234523090]). The conference is scheduled to take place from Thursday, October 26 to Monday, October 30 in Philadelphia.

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The details of Rgenix’s presentation are as follows:

Event: AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper): Discovery, Biology, and Clinical Applications

Date: October 29, 2017

Time: 12:30 P.M. – 4:00 P.M. EST

Description: Poster B001, "A phase 1 trial of RGX-104, a first-in-class immunotherapy targeting the liver-X nuclear hormone receptor (LXR), in patients with refractory malignancies"

Location: Hall E, Pennsylvania Convention Center, 1101 Arch St, Philadelphia, PA 19107

Dr. Mita will present data from the Phase 1 trial of RGX-104, a first-in-class investigational immunotherapy.

About RGX-104

RGX-104 is a potent small molecule agonist of the Liver X Receptor (LXR). Activation of the LXR-ApoE pathway by RGX-104 stimulates the innate immune response in cancer via depletion of myeloid-derived suppressor cells and activation of dendritic cells, leading to stimulation of T cells and anti-tumor immunity in tumor models. LXR activation also blocks the ability of tumors to recruit blood vessels. These combined effects result in suppression of tumor growth and metastasis in a broad array of pre-clinical models. The LXR-ApoE pathway was originally identified as a cancer target using a novel microRNA-based discovery platform developed by Rgenix’s scientific co-founders at The Rockefeller University.

Rgenix is conducting a Phase 1a/b clinical trial of RGX-104 in patients with advanced solid malignancies and lymphoma—for more information about the clinical trial, please visit: View Source