Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma.

Multiple myeloma (MM) is characterized by an uninhibited, clonal growth of plasma cells. While first-degree relatives of patients with MM show an increased risk of MM, the genetic basis of inherited MM susceptibility is incompletely understood. Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR)=1.25; P=9.6 × 10(-10)). This gene encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells. We find that the MM risk allele harbours a Thr298Ala missense variant in an ELL2 domain required for transcription elongation. Consistent with a hypomorphic effect, we find that the MM risk allele also associates with reduced levels of immunoglobulin A (IgA) and G (IgG) in healthy subjects (P=8.6 × 10(-9) and P=6.4 × 10(-3), respectively) and, potentially, with an increased risk of bacterial meningitis (OR=1.30; P=0.0024).

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Biota Pharmaceuticals, Inc. Announces Name Change to Aviragen Therapeutics, Inc. (NASDAQ: AVIR)

On April 12, 2016 Biota Pharmaceuticals, Inc. (NASDAQ:BOTA) reported that the Company has changed its name to Aviragen Therapeutics, Inc., ("Aviragen Therapeutics"), a pharmaceutical company focused on the development of the next generation of direct-acting antivirals that address infections that have limited therapeutic options (Press release, Aviragen Therapeutics, APR 12, 2016, View Source [SID1234510705]).

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"A meaningful transformation has taken place over the last two years as we transitioned from a drug discovery and early-stage licensing organization to one focused on drug development and progressing key late-stage product candidates in important viral diseases. Our name change reflects this transition and better defines our strategic initiatives moving forward," said Joseph Patti, PhD, President and Chief Executive Officer of Aviragen Therapeutics. "Specifically, our recent initiation of a Phase 2a efficacy study of BTA585 for the treatment of RSV infections highlights our focus on bringing new medicines to treat and prevent viral infections with limited therapeutics options. As Aviragen Therapeutics, we will continue to advance and expand our promising pipeline of anti-viral drugs."

The name change become effective on April 11, 2016 and the Company’s common stock will begin trading on the NASDAQ Stock Exchange under the new ticker symbol "AVIR" on April 13, 2016. The Company will have a new website address: www.aviragentherapeutics.com.

A phase ib study of safety and pharmacokinetics of ramucirumab in combination with paclitaxel in patients with advanced gastric adenocarcinomas.

The pharmacokinetic results of this phase Ib study of ramucirumab combined with paclitaxel as second-line therapy in Japanese patients with metastatic gastric or gastro-esophageal junction adenocarcinoma are in line with previous ramucirumab studies.This combination at the doses and schedule given did not result in any dose-limiting toxicities and appeared to be safe and well tolerated.
This phase Ib study evaluated the tolerability and pharmacokinetics of ramucirumab, an anti-VEGFR-2 antibody, combined with paclitaxel as second-line therapy in Japanese patients with metastatic gastric or gastroesophageal junction adenocarcinoma after first-line therapy with fluoropyrimidines and/or platinum.
Patients received ramucirumab 8 mg/kg on days 1 and 15 and paclitaxel 80 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. Safety analyses included all patients (n = 6).
No dose-limiting toxicities occurred in the first cycle. All patients experienced ≥1 treatment-emergent adverse event (TEAE); 5 patients experienced grade ≥3 TEAEs. There were two deaths caused by disease progression. The best overall responses were stable disease (n = 5) and partial response (n = 1). Patients received ramucirumab and paclitaxel for a median of 12.5 weeks (range: 11.4-42.7 weeks) and 12.2 weeks (range: 11.0-41.0 weeks), respectively. Following a single dose of ramucirumab IV infusion 8 mg/kg, clearance was ∼0.017 L/hour, half-life (t1/2) was 138 to 225 hours, and steady-state volume of distribution (Vss) was ∼3 L.
The ramucirumab/paclitaxel combination appears to be well-tolerated in Japanese patients with advanced gastric adenocarcinomas. These results are in line with previous ramucirumab pharmacokinetic studies as anticipated.
©AlphaMed Press; the data published online to support this summary is the property of the authors.

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OncoSec Announces Poster Presentation with Heat Biologics, Inc. at the American Association for Cancer Research (AACR) Annual Meeting 2016

On April 12, 2016 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported that preclinical results from OncoSec’s collaboration with Heat Biologics, Inc. will be featured as a poster presentation at the upcoming American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting to be held on April 16-20, 2016 in New Orleans, LA (Press release, OncoSec Medical, APR 12, 2016, View Source [SID:1234510706]).

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Details of the poster presentation are as follows:

Abstract Title: In vivo intra-tumoral electroporation of Gp96-Ig/Fc-OX40L stimulates CD8+ T cell cross-priming to tumor specific neoantigens (Abstract ID #567)
Session Title: Immune Modulating Agents 1
Date and Time: April 17, 2016 at 1:00 p.m. – 5:00 p.m. CT
Location: Section 26

Discovery and characterization of a potent and selective EP4 receptor antagonist.

EP4 is a prostaglandin E2 receptor that is a target for potential anti-nociceptive therapy. Described herein is a class of amphoteric EP4 antagonists which reverses PGE2-induced suppression of TNFα production in human whole blood. From this class, a potent and highly bioavailable compound (6) has been selected for potential clinical studies. EP4 binding and functional data, selectivity, and pharmacokinetic properties of this compound are included.
Copyright © 2015 Elsevier Ltd. All rights reserved.

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