1stOncology™: Cancer Intelligence Service – Page 15628 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Loxo Oncology to Present Updated LOXO-101 Phase 1 Data at the 2016 AACR Annual Meeting

On April 11, 2016 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported that the abstract titled "Clinical safety and activity from a phase 1 study of LOXO-101, a selective TRKA/B/C inhibitor, in solid-tumor patients with NTRK gene fusions" has been accepted for oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 16 – 20, 2016 in New Orleans (Press release, Loxo Oncology, APR 11, 2016, View Source [SID:1234510662]). Data from this trial were most recently presented at the AACR (Free AACR Whitepaper)-NCI-EORTC meeting in November 2015. The presentation will include an efficacy and durability update for enrolled patients with TRK fusions. The presentation was selected for inclusion in AACR (Free AACR Whitepaper)’s official press program, and study data will therefore remain embargoed until April 17, 2016 at 4:15 p.m. CT.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

The schedule for the oral presentation is as follows:

Oral Presentation Date & Time: April 17, 2016, 4:15 p.m. to 6:00 p.m. CT
Title: Clinical Safety and Activity from a Phase 1 Study of LOXO-101, a Selective TRKA/B/C Inhibitor, in Solid Tumor Patients with NTRK Gene Fusions
Abstract Number: CT008
Session Title: Precision Medicine Early Clinical Trials
Presenter: David Hong, M.D., deputy chair, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Location: La Nouvelle Orleans Ballroom, Morial Convention Center

Conference Call and Webcast Information

Loxo Oncology will host a conference call and live webcast on Monday, April 18, 2016 at 8:00 a.m. Eastern Time to discuss the LOXO-101 data. To participate in the conference call, please dial (877) 930-8065 (domestic) or (253) 336-8041 (international) and refer to conference ID 77038770. A live webcast of the presentation will be available at View Source A replay of the webcast will be available shortly after the conclusion of the call and archived on the company’s website for 30 days following the call.

About LOXO-101

LOXO-101 is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In an ongoing Phase 1 clinical trial, LOXO-101 has demonstrated encouraging preliminary efficacy. LOXO-101 is also being evaluated in a global Phase 2 multi-center basket trial in patients with solid tumors that harbor TRK gene fusions. For additional information about both the LOXO-101 clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123.

8-K – Current report

On April 8, 2016 Fennec Pharmaceuticals Inc. (TSX: FRX, OTCQB: FENCF) (the "Company" or "Fennec"), a specialty pharmaceutical company focused on the development of Sodium Thiosulfate (STS) for the prevention of platinum-induced chemotherapy ototoxicity in pediatric patients, reported that it intends to complete a non-brokered private placement (the "Offering") of 2,631,579 common shares for gross proceeds of US$5,000,000 (Filing, 8-K, Fennec Pharmaceuticals, APR 11, 2016, View Source [SID:1234510660]). The common shares of the Company (the "Shares") will be issued at a price of US$1.90 per Share. The current number of outstanding Shares, without giving effect to the Offering, is 11,006,988.

"We look forward to the future development of STS and the potential benefits it may provide to children treated with chemotherapeutic platinum agents. We eagerly await the results of SIOPEL 6, which may establish STS as an important therapy in reducing hearing loss. Sigma Tau Finanziaria remains committed to making new drugs available for rare diseases, where there is currently an unmet medical need." said Mario Artali, President of Sigma Tau Finanziaria SpA (together with its associates, "Sigma Tau Finanziaria").

"We are very pleased to welcome Sigma Tau Finanziaria as a major investor in Fennec," said Dr. Khalid Islam, Chairman of Fennec. "Sigma Tau Finanziaria has an impressive historical track record of partnering and investing in the development and commercialization of several compounds, including my experience with defibrotide at Gentium."

"We believe this investment not only strengthens our balance sheet, but validates the available clinical data and our development approach to STS" said Rosty Raykov, CEO of Fennec. "Sigma Tau Finanziaria brings extensive expertise and success in pediatric oncology and rare disease drug development, which will be of great benefit to Fennec."

Closing of the Offering is anticipated to occur in two tranches: (i) the first, representing gross proceeds of US$2,076,373.20 on April 8, 2016 and (ii) the second, representing gross proceeds of US$2,923,626.90 within two business days after the Toronto Stock Exchange (the "TSX") has confirmed that it has no objections to the personal information form submitted in connection with the Offering (as discussed in greater detail below), and the closing is subject to approval of the TSX. The issue price of the Shares represents approximately an 11% premium on the market price of the Shares on the date of a binding agreement, as defined by the TSX. Securities issued will be subject to a hold period, which will expire four months plus one day from the date of closing. To the knowledge of the Company, Sigma Tau Finanziaria does not own, directly or indirectly, any Shares.

It is anticipated that the net proceeds of the Offering will be used by the Company for the development of STS and general working capital purposes.

The Offering has been negotiated at arm’s length. In connection with the Offering, it is expected that:

● On the first closing, which is expected to occur on or about April 8, 2016, Sigma Tau Finanziaria will purchase 1,092,828 Shares.
● On the second closing, which is expected to occur within two business days after the TSX has confirmed that it has no objections to the personal information form submitted in connection with Sigma Tau Finanziaria’s investment in the Company, Sigma Tau Finanziaria will purchase 1,538,751 Shares.
● Following the first closing, Sigma Tau Finanziaria would hold 9.03% of the issued and outstanding Shares.
● Following the second closing, together with existing holdings, Sigma Tau Finanziaria would hold an aggregate of 19.30% of Shares.
● Sigma Tau Finanziaria will become a new insider of the Company, as that term is defined in applicable Canadian securities laws.

About Sigma Tau Finanziaria

Sigma Tau Finanziaria is an investment holding company with recognized experience in the rare diseases sector, employing approximately 200 people in its subsidiaries in the UK, the US, Switzerland and Germany and achieving around 60% of its turnover in the United States and 40% in the rest of the world.

Its product portfolio includes:

Treatments of Metabolic and Genetic Disorders
§ Adagen
§ Chenodeoxycholic acid
§ Cystaran
§ Carnitor in North America only

Cancer Treatments
§ Natulan/Matulane
§ Depocyt

In addition, the further development of the business can count on a pipeline of life cycle management of the above products and a number of R&D innovative technological platforms (ST-206 probiotic indicated for neonatal pathologies and heparanase inhibitors in multiple myeloma and other indications).

In addition to the commitment in the treatment and in the care of rare diseases, Sigma Tau Finanziaria holds qualified equity investments in listed and unlisted companies in the traditional pharmaceutical sector and in the rare diseases sector.

About Sodium Thiosulfate (STS)

Cisplatin and other platinum compounds are essential chemotherapeutic components for many pediatric malignancies. Unfortunately, platinum-based therapies cause hearing loss or ototoxicity in many patients, and are particularly harmful to the survivors of pediatric cancer.

In the U.S. and Europe there is estimated that 10,000 children are diagnosed with local cancers that may receive platinum based chemotherapy. Localized cancers have overall survival rates of greater than 80%, further emphasizing the importance of quality of life after treatment. The incidence of hearing loss in these children depends upon the dose and duration of chemotherapy, but it affects at least 60% of the patients. Many of these children require lifelong hearing aids and technically difficult and sub-optimal cochlear (inner ear) implants that have been shown to provide some marginal benefit. Post platinum exposure, infants and young children at critical stages of development lack speech language development and literacy, and older children and adolescents lack social-emotional development and educational achievement.

STS has been studied by cooperative groups in two Phase 3 clinical studies of reduction of ototoxicity, The Clinical Oncology Group Protocol ACCL0431 and SIOPEL 6. Both studies are closed to recruitment. The COG ACCL0431 protocol enrolled one of five childhood cancers typically treated with intensive cisplatin therapy for localized and disseminated disease, including newly diagnosed hepatoblastoma, germ cell tumor, osteosarcoma, neuroblastoma, and medulloblastoma. SIOPEL 6 enrolled only hepatoblastoma patients with localized tumors.

Endocyte Announces Presentations at American Association for Cancer Research (AACR) Annual Meeting 2016

On April 11, 2016 Endocyte, Inc. (NASDAQ:ECYT), a leader in developing targeted small molecule drug conjugates (SMDCs) and companion imaging agents for personalized therapy, reported that four posters will be presented by Endocyte scientists at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 to be held in New Orleans, April 16-20, 2016 (Press release, Endocyte, APR 11, 2016, View Source [SID:1234510659]).

The presentation materials will be available on Endocyte’s website following presentation at the conference.

Presentations are as follows:

Abstract #: 262
Title: Combination therapy of folate-targeted chemotherapeutics with anti-PD-1 antibody against folate receptor-positive tumors in immunocompetent murine models
When: Sunday, April 17, 1 p.m. – 5 p.m. EDT
Session Title: Combination Chemotherapy
Location: Halls G-J, Poster Section 15

Abstract #: 3035
Title: Development and characterization of CCK2R-targeted SMDCs and identification of GIST as a potential therapeutic indication
When: Tuesday, April 19, 8 a.m. – 12 p.m. EDT
Session Title: Novel Targets and Pathways
Location: Halls G-J, Poster Section 17

Abstract #: 3754
Title: Pre-clinical studies of a highly potent Folate receptor targeted DNA crosslinking agent
When: Tuesday, April 19, 1 p.m. – 5p.m. EDT
Session Title: Novel Antitumor DNA-Reactive Agents
Location: Halls G-J, Poster Section 16

Abstract #: 4735
Title: Designing Novel Warheads for Targeted Therapies: SAR and Efficient Strategies for Synthesis of Analogs of Tubulysin
When: Wednesday, April 20, 8 a.m. – 12 p.m. EDT
Session Title: HDAC, Methyltransferase Inhibitors, and Novel Anticancer Agents

Computer-aided identification of new histone deacetylase 6 selective inhibitor with anti-sepsis activity.

Histone deacetylase (HDAC) inhibitors have been recognized as promising approaches to the treatment of various human diseases including cancer, inflammation, neurodegenerative diseases, and metabolic disorders. Several pan-HDAC inhibitors are currently approved only as anticancer drugs. Interestingly, SAHA (vorinostat), one of clinically available pan-HDAC inhibitors, shows an anti-inflammatory effect at concentrations lower than those required for inhibition of tumor cell growth. It was also reported that HDAC6 selective inhibitor tubastatin A has anti-inflammatory and anti-rheumatic effect. In our efforts to develop novel HDAC inhibitors, we rationally designed various HDAC inhibitors based on the structures of two hit compounds identified by virtual screening of chemical database. Among them, 9a ((E)-N-hydroxy-4-(2-styrylthiazol-4-yl)butanamide) was identified as a HDAC6 selective inhibitor (IC50 values of 0.199 μM for HDAC6 versus 13.8 μM for HDAC1), and it did not show significant cytotoxicity against HeLa cells. In vivo biological evaluation of 9a was conducted on a lipopolysaccharide (LPS)-induced mouse model of sepsis. The compound 9a significantly improved 40% survival rate (P = 0.0483), and suppressed the LPS-induced increase of TNF-α and IL-6 mRNA expression in the liver of mice. Our study identified novel HDAC6 selective inhibitor 9a, which may serve as a potential lead for the development of anti-inflammatory or anti-sepsis agents.
Copyright © 2016 Elsevier Masson SAS. All rights reserved.

VarDict: a novel and versatile variant caller for next-generation sequencing in cancer research.

Accurate variant calling in next generation sequencing (NGS) is critical to understand cancer genomes better. Here we present VarDict, a novel and versatile variant caller for both DNA- and RNA-sequencing data. VarDict simultaneously calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors. It performs local realignments on the fly for more accurate allele frequency estimation. VarDict performance scales linearly to sequencing depth, enabling ultra-deep sequencing used to explore tumor evolution or detect tumor DNA circulating in blood. In addition, VarDict performs amplicon aware variant calling for polymerase chain reaction (PCR)-based targeted sequencing often used in diagnostic settings, and is able to detect PCR artifacts. Finally, VarDict also detects differences in somatic and loss of heterozygosity variants between paired samples. VarDict reprocessing of The Cancer Genome Atlas (TCGA) Lung Adenocarcinoma dataset called known driver mutations in KRAS, EGFR, BRAF, PIK3CA and MET in 16% more patients than previously published variant calls. We believe VarDict will greatly facilitate application of NGS in clinical cancer research.
© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.