On December 7, 2017 Seattle Genetics, Inc. (NASDAQ: SGEN) reported updated data from an ongoing phase 1 clinical trial evaluating ladiratuzumab vedotin in patients with metastatic triple negative breast cancer (TNBC) at the 2017 San Antonio Breast Cancer Symposium (SABCS), taking place December 5-9, 2017 (Press release, Seattle Genetics, DEC 7, 2017, View Source;p=RssLanding&cat=news&id=2321594 [SID1234522430]). Ladiratuzumab vedotin is an investigational antibody-drug conjugate (ADC) designed to deliver a potent and clinically validated cell-killing agent, monomethyl auristatin E (MMAE), to cancer cells which express the protein LIV-1. LIV-1 is expressed on multiple solid tumors including breast, prostate, melanoma, ovarian, uterine, and cervical cancers.

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"Overall, the phase 1 results we’ve presented at SABCS confirm previous findings that single-agent treatment with ladiratuzumab vedotin was generally well-tolerated and showed encouraging antitumor activity in patients with heavily-pretreated metastatic TNBC," said Robert Lechleider, M.D., Senior Vice President, Clinical Development at Seattle Genetics. "We continue to evaluate ladiratuzumab vedotin monotherapy in TNBC, with planned combination studies in earlier lines of treatment, demonstrating our overarching commitment to improve the health of women with this devastating disease."

Findings from this ongoing phase 1 study of ladiratuzumab vedotin in patients with metastatic breast cancer were last presented at the 2016 SABCS. The updated results presented today in a spotlight session describe the safety, tolerability, and antitumor activity of ladiratuzumab vedotin in 28 additional patients with TNBC.

Phase 1 Study of the Antibody-Drug Conjugate Ladiratuzumab Vedotin (SGN-LIV1A) in Patients with Heavily Pretreated Triple-Negative Metastatic Breast Cancer (Poster# PD3-14, Poster Session – Novel Drugs / Predicting Response for HER2+ Breast Cancer at 7:00 – 9:00 a.m. CT on Thursday, December 7, 2017)

A total of 81 patients with LIV-1-expressing metastatic breast cancer were treated with ladiratuzumab vedotin monotherapy given every three weeks. Patients enrolled in the study had received a median of four prior systemic metastatic therapies. Of these patients, 63 were diagnosed with TNBC and 18 had hormone receptor-positive / human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. At the completion of dose escalation at doses ranging from 0.5 to 2.8 milligrams per kilogram (mg/kg), TNBC expansion cohorts were opened at 2.0 and 2.5 mg/kg to further evaluate safety and antitumor activity of ladiratuzumab vedotin in metastatic TNBC patients. Based on efficacy and safety, the recommended dose is 2.5 mg/kg with a maximum dose of 200 mg per cycle.

Key findings in this heavily pre-treated patient population were presented by Dr. Jennifer Specht, Seattle Cancer Care Alliance and include:

Among the 60 efficacy-evaluable patients with metastatic TNBC, the objective response rate (ORR) was 25 percent, representing all partial responses (PR). The clinical benefit rate (CBR) was 28 percent. CBR is defined as patients achieving complete response (CR) or PR of any duration, plus patients achieving stable disease (SD) lasting at least 24 weeks. Of the 17 efficacy-evaluable patients treated at the recommended dose, 29 percent achieved an objective response (confirmed and unconfirmed), and the CBR was 29 percent.
The median progression-free survival (PFS) and median duration of response (DOR) for patients treated across all dose levels were 11 weeks and 13.3 weeks, respectively. In 19 patients treated at the recommended dose, the median PFS was 12.1 weeks, and the median DOR was 17.4 weeks.
At the recommended dose, ladiratuzumab vedotin was generally well-tolerated and most adverse events were Grade 1/2.
Of the 81 patients treated in the study, peripheral neuropathy events occurred in 16 patients (19.8 percent) and were generally low grade (Grades 1/2) and manageable. Seven patients discontinued treatment due to adverse events.
Grade 3/4 adverse events included neutropenia and anemia. The Grade 3/4 incidence of neutropenia at the 2.5 mg/kg dose was 38.7 percent. As previously reported, two patients experienced febrile neutropenia, and there was one treatment-related death due to presumed sepsis among patients who received doses greater than 200 mg. No other treatment-related deaths occurred in the study.
Enrollment continues for patients with metastatic TNBC at the recommended dose of 2.5 mg/kg, with a maximum dose of 200 mg per cycle.
Additional details about this spotlight poster presentation (Poster PD3-14) are available here. More information about the ladiratuzumab vedotin phase 1 clinical trial in TNBC, including enrollment centers, is available by visiting www.clinicaltrials.gov.

About Triple Negative Breast Cancer

Breast cancer is the most common cancer among women in the United States, excluding some forms of skin cancer. Of the more than 250,000 new cases expected in the United States this year, about 15 to 20 percent will be TNBC, which has a particularly poor prognosis. Breast cancers are commonly categorized by the expression (or lack thereof) of three proteins, which include the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC lacks expression of these three breast cancer-associated proteins that serve as key therapeutic targets. About one-third of breast cancer patients will eventually develop recurrent or metastatic disease, and current therapies for metastatic TNBC only delay progression. New treatment approaches are needed to improve outcomes for women with TNBC, where there are currently no available targeted therapies.

About Ladiratuzumab Vedotin

Ladiratuzumab vedotin is a novel investigational ADC targeted to LIV-1 protein utilizing Seattle Genetics’ proprietary ADC technology. Most metastatic breast cancers express LIV-1, which also has been detected in a number of other cancers, including melanoma, prostate, ovarian, uterine, and cervical cancers. Ladiratuzumab vedotin consists of a LIV-1-targeted monoclonal antibody linked to a potent microtubule-disrupting agent, monomethyl auristatin E (MMAE) by a protease-cleavable linker, using the same technology as ADCETRIS (brentuximab vedotin). This novel ADC agent is designed to bind to LIV-1 on cancer cells and release the cell-killing agent into target cells upon internalization. Ladiratuzumab vedotin may also cause antitumor activity through other mechanisms, including activation of an immune response. Seattle Genetics currently has four clinical studies underway or planned for ladiratuzumab vedotin in breast cancer with a focus on TNBC.

Enzo Biochem has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Enzo Biochem, 2017, DEC 7, 2017, View Source [SID1234522436]).

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On December 7, 2017 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the company will be webcasting its corporate presentation at the BMO Capital Markets Healthcare Conference in New York, NY (Press release, Jazz Pharmaceuticals, DEC 7, 2017, View Source;p=RssLanding&cat=news&id=2321712 [SID1234522443]).

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Matt Young, executive vice president and chief financial officer, will provide an overview of the company and a business and financial update at the conference on Thursday, December 14, 2017 at 10:30 a.m. EST / 3:30 p.m. GMT.

A live audio webcast of the presentation may be accessed from the Investors section of the Jazz Pharmaceuticals website at www.jazzpharmaceuticals.com. Please connect to the website prior to the start of the presentation to ensure adequate time for any software downloads that may be necessary to listen to the webcast.

An archive of the webcast will be available for at least one week following the presentation on the Investors section of the company’s website at www.jazzpharmaceuticals.com.

On December 7, 2017 Syros Pharmaceuticals (NASDAQ: SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of disease-driving genes, reported that new preclinical data on SY-1365, its first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor currently in a Phase 1 clinical trial in advanced solid tumors, demonstrate anti-tumor activity across a broad panel of breast cancer cell lines and point to potential biomarkers predictive of response (Press release, Syros Pharmaceuticals, DEC 7, 2017, View Source [SID1234522431]). The Company also announced its identification of key genes driving relapse and metastasis in triple negative breast cancer (TNBC), pointing to potential new drug targets. These data were presented at the San Antonio Breast Cancer Symposium (SABCS).

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"These data speak to the power of our gene control platform to provide a new lens for understanding disease with important implications for developing much-needed therapies in defined subsets of patients," Eric R. Olson, Ph.D., Chief Scientific Officer of Syros. "Despite advances in the treatment of certain cancers, two of the biggest challenges in cancer treatment remain the ability to pair the right patients with the right drugs and to prevent the emergence of drug resistance in response to targeted therapies. By analyzing regulatory regions of the genome, we discovered potential biomarkers of response to SY-1365 within heterogeneous patient populations that we can further explore during clinical development. Separately, using our platform, we also identified new potential points of therapeutic intervention in TNBC with the potential to thwart the mechanisms cancer uses to become resistant to therapy and spread to other parts of the body."

New Preclinical Data on SY-1365
Syros scientists analyzed the anti-tumor activity of SY-1365 across a panel of more than 400 cancer cell lines, including 19 TNBC cell lines and 21 ER-positive, PR-positive and HER2-positive cells lines. They then grouped the cell lines according to sensitivity to SY-1365 and looked for markers of response using Syros’ gene control platform to analyze regulatory regions of the genome. The data showed:

SY-1365 induced cell death in 15 out of the 19 TNBC cell lines and 17 of the 21 ER-positive, PR-positive and HER2-positive cells lines.
Sensitivity to SY-1365 in these breast cancer cell lines was associated with a super-enhancer, a highly specialized regulatory region of the genome, that drives increased expression of the known oncogene MYC.
Sensitivity to SY-1365 was also associated with low expression of the mitochondrial apoptosis antagonist BCL2L1 in these cell lines.
Lowered expression of MCL1, a gene in the mitochondrial apoptosis pathway known to inhibit apoptosis, was associated with SY-1365 target engagement and anti-tumor activity in cell lines and a cell-derived xenograft model of TNBC.
The Phase 1 trial of SY-1365 is a multi-center, open-label trial enrolling patients with advanced solid tumors. The primary objective of the trial is to assess the safety and tolerability of escalating doses of SY-1365, with the goal of establishing a maximum tolerated dose and a recommended Phase 2 dose and regimen. The dose-escalation phase is open and expected to enroll approximately 35 solid tumor patients for whom standard curative or palliative measures do not exist or are no longer effective. Following the dose-escalation phase, expansion cohorts are planned to further evaluate the safety and anti-tumor activity of SY-1365 in patients with transcriptionally driven tumors and to enroll patients with tumors of any histology in a cohort focused on analyzing biopsied tumor tissue. Additional details about the trial can be found using the identifier NCT03134638 at www.clinicaltrials.gov. Syros expects to present initial clinical data from this study in 2018.

Mechanisms of Relapse and Metastasis in TNBC
Using its gene control platform, Syros scientists, in collaboration with the lab of Robert Weinberg, Ph.D. at the Whitehead Institute, analyzed regulatory regions of the genome in cancer-stem cell enriched TNBC cell lines. Cancer stem cells (CSCs) are known to be involved in resistance to chemotherapies, relapse of disease and development of metastasis. The analysis revealed key genes that may be involved in driving disease relapse and metastasis, with implications for the discovery and development of novel therapies for TNBC. Notably, TP73 was found to be a core driver of transcriptional circuitry in CSCs, controlling super-enhancer associated genes involved in cell migration, signal transduction and developmental processes. TP73 is a gene that encodes a DNA-binding transcription factor called p73. The set of TP73-controlled genes provide new leads for drug discovery and development with potential to yield much-needed new therapies for TNBC patients.

On December 7, 2017 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, reported the commercial availability of new Vantage 3D Hematology assays as well as the highlights of more than 45 nCounter-based research abstracts that will be presented at the 59th Annual Meeting of the America Society of Hematology being held December 9-12, in Atlanta (Press release, NanoString Technologies, DEC 7, 2017, View Source [SID1234522444]).

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The company announced the launch of new Vantage 3D hematology assays. Three of the studies presented at ASH (Free ASH Whitepaper) (Abstracts 1758, 2481 and 3945) include data from early access versions of NanoString’s Vantage 3D DNA:RNA:Protein Heme Assays, which are launching commercially at ASH (Free ASH Whitepaper). These assays enable simultaneous, multi-analyte analysis of single nucleotide variants (SNVs), RNA, protein, and phospho-protein. The assay includes curated content that covers clinically actionable SNVs and Indels, and provide comprehensive expression profiling of RNA, protein, and phospho-protein in key pathways including PI3K, JAK-STAT, BCR, and TCR signaling.

One of the presentations will be made by Dr. Sergio Rutella, M.D. Ph.D. FRCPath., Professor of Cancer Immunotherapy at the John van Geest Cancer Research Centre at Nottingham Trent University. Dr. Rutella stated, "AML is a rare disease and we need to maximize the amount of information we collect. We are using NanoString’s Vantage 3D DNA:RNA:Protein Heme Assay to capture information about single nucleotide variants, mutations, and new antigens that could be compiled into a ‘super signature’ to better characterize the disease and stratify the treatment of patients."

"Our customers and collaborators are presenting a record body of nCounter-based research at the 59th annual ASH (Free ASH Whitepaper) conference," said Brad Gray, president and chief executive officer of NanoString Technologies. "This research demonstrates the advances that are being enabled with the nCounter platform in subtyping lymphomas and optimizing regimens to achieve better clinical outcomes."

The ASH (Free ASH Whitepaper) Annual Meeting will include at least four oral presentations and forty-one posters in various leukemia, lymphoma, and myeloma malignancies that demonstrate the utility of the nCounter platform across the heme-oncology spectrum. In particular, NanoString’s collaborators in Diffuse Large B-Cell Lymphoma (DLBCL) are presenting 11 abstracts highlighting the potential clinical relevance of NanoString’s Lymphoma Subtyping Test (LST) and its potential for directing treatment decisions, including:

Results from the frontline prospective Phase III BIO-DLBCL04 study conducted by the Fondazione Italiana Linfomi (FIL). The results show that ABC subtype determined by the NanoString LST assay is associated with a worse outcome in untreated, poor-risk, young DLBCL (Abstract #4010).

Researchers from the European Institute of Oncology found that the NanoString LST robustly identifies DLBCL subgroups according to the Cell-of-Origin (COO). The molecular definition of the COO can be used to identify patients at high risk of poor outcome when treated with R-CHOP and who may benefit by intensified high dose chemotherapy or experimental new treatments (Abstract #3998).

Results from an exploratory biomarker analysis of the Phase 3 GOYA Trial comparing the efficacy and safety of obinutuzumab plus CHOP (G-CHOP) with R-CHOP in patients with previously untreated DLBCL. Using the NanoString LST assay and a new cutoff on the Linear Predictor Score (LPS), a new distinct molecular subgroup of GCB DLBCL, referred to as "strong-GCB", was identified. Results from the exploratory analysis show that treatment with G-CHOP confers substantial clinical benefit over R-CHOP in this new subgroup of DLBCL (Abstract #1543).
The table below includes a selection of 2017 ASH (Free ASH Whitepaper) abstracts that best illustrate the potential clinical utility of nCounter across multiple tumor types. You can learn more about the capabilities of the nCounter platform by visiting NanoString at booth #2465 at ASH (Free ASH Whitepaper).