1stOncology™: Cancer Intelligence Service – Page 18249 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Ambit Announces Initiation Of Quizartinib QUANTUM-R Phase 3 Trial

On April 8, 2014 Ambit Biosciences reported the initiation of the QUANTUM-R Phase 3 clinical trial (NCT02039726) comparing quizartinib as monotherapy to chemotherapy regimens in relapsed/refractory acute myeloid leukemia (AML) patients with the FMS-like tyrosine kinase-3 (FLT3)-ITD mutation (Press release Ambit Biosciences, APR 8, 2014, View Source [SID:1234500376]).
The trial will be conducted in FLT3-ITD positive AML patients over the age of 18 who have relapsed from, or are refractory to, frontline chemotherapy, including those patients relapsing following hematopoietic stem cell transplantation (HSCT). Patients will be dosed continually until disease progression or intolerable toxicity. Patients who proceed to HSCT after quizartinib treatment will be able to reinitiate treatment with quizartinib following the transplant.
The trial is expected to enroll approximately 326 patients in the United States, Western Europe, Canada and Australia. The primary endpoint for the Phase 3 clinical trial will be overall survival. An interim analysis will be conducted and will include an adaptive design component that will allow the Data Safety Monitoring Board (DSMB) to increase the number of patients, if warranted. Enrollment is expected to be completed in the second half of 2015, assuming there is no increase in the number of patients following the interim analysis.
The Phase 3 trial follows completion of the Phase 2 and Phase 2b clinical trials, which demonstrated the key clinical benefits of quizartinib as a monotherapy, including a high response rate in relapsed/refractory FLT3-ITD positive patients; a substantial number of patients who were bridged to a potentially curative HSCT; and median overall survival in FLT3-ITD positive patients which compared favorably to historical survival data reported for FLT3-ITD positive and negative AML patients. Results from these studies were presented at medical conferences in 2012 and 2013.

20-F/A [Amend] – Annual and transition report of foreign private issuers [Sections 13 or 15(d)]

Theratechnologies has filed a 20-F/A [Amend] – Annual and transition report of foreign private issuers [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Press release Theratechnologies, APR 7, 2014, View Source [SID1234500375]).

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!

(Press release Lion Biotechnologies, APR 7, 2014, View Source [SID:1234501577])

Roche and Oryzon announce collaboration to develop epigenetics-based medicines

On April 7, 2014 Roche and Oryzon Genomics reported they have entered into a worldwide collaboration to research, develop and commercialize inhibitors of Lysine Specific Demethylase-1 (LSD1; KDM1A), an epigenetic modulator that regulates gene expression (Press release Oryzon, APR 7, 2014, View Source [SID:1234500879]).
The lead molecule, ORY-1001, was granted orphan drug status by EMA in August 2013 and is currently in phase I/IIA for acute myeloid leukaemia (AML). Roche will have sole responsibility for developing and commercializing ORY-1001 and/or its backup compounds. The agreement includes the licensing of two patent families that Oryzon has created in its pioneering research in LSD1, and includes options for other Oryzon programs to be incorporated in future. The agreement also includes an initial two-year collaborative research program between Oryzon and Roche’s New York-based Translational Clinical Research Center (TCRC), Roche’s hub for research and early development activities in North America, to better understand the potential of LSD1 inhibitors in oncology and haematology.
John Reed, Roche’s Head of Pharma Research and Early Development, commented, "Oryzon is working at the leading edge of LSD1 inhibition, a technology with great potential to bring genuine patient benefit. Our TCRC in New York has been launched with a mandate to identify partnerships that drive innovation, providing an industryleading conduit between sources of breakthrough science and the broader Roche organization. This collaboration on LSD1 inhibition with Oryzon fulfils that mandate perfectly."
Carlos Buesa, CEO of Oryzon, added, "We are excited to work with Roche in developing ORY-1001 to make a significant difference for patients with AML and, hopefully, for patients in other disease areas as well. Roche is the global leader in oncology and haematology, with a tremendous expertise in clinical development; this was the primary reason to prioritize this alliance. The collaboration is recognition of our cutting-edge science and our experience in epigenetics, an approach that we believe holds great promise for many patient groups."
Under the terms of the agreement, Oryzon will receive an upfront payment and near-term milestones totalling $21 million, plus potential development, commercial and sales milestone payments across haematology, cancer and non-malignant indications that could exceed $500 million, together with tiered royalties on sales which range up to mid-double digits.

CCMO approval for Phase I hVEGF26-104 vaccine

On April 7, 2014 ImmuNovo and VUmc reproted that they have received CCMO approval for Phase I with hVEGF26-104 vaccine in combination with the RFASE based adjuvant in the Department of Medical Oncology of VUmc Amsterdam headed by Professor Dr Henk Verheul (Press release Immunovo, APR 7, 2014, View Source [SID:1234500781]).
ImmuNovo’s CEO Joost van Bree PhD: ‘We are delighted to make this important step forward.’

More than a dozen different proteins have been identified as angiogenic activators, including vascular endothelial growth factor (VEGF). The VEGF family and their receptors (VEGFR) are receiving increasingly more attention in the field of neoplastic vascularization. VEGF is a powerful angiogenic agent in neoplastic tissues, as well as in normal tissues. Under the influence of certain cytokines and other growth factors, the VEGF family appears in cancerous tissue and the adjacent stroma, and plays an important role in neovascularization.

ImmuNovo and VUmc’s Medical Oncology are working on the development of hVEGF-trunc vaccine in combination with the RFASE based adjuvant for the treatment of cancer. A pro-angiogenic phenotype can be triggered by hypoxia resulting from the increasing distance between the growing tumor cells and the capillaries or from the inefficiency of new vessels. Hypoxia induces the expression of VEGF and its receptor via hypoxia-inducible factor-1α (HIF-1α). Tumor cells feed on the new blood vessels by producing VEGF and then secreting it into the surrounding tissue. Secreted VEGF binds its receptors (VEGFR1 and VEGFR2) on the outer surface of the endothelial cell. Once VEGF binds its receptor, a sequence of events follows that lead to angiogenesis. First, activated vascular endothelial cells produce matrix metalloproteinases (MMPs). MMPs cause degradation of the extracellular matrix (ECM). Next, the endothelial cells migrate into the surrounding tissues and begin to divide. Finally, the endothelial cells differentiate in order to form a functional blood vessel. ImmuNovo is working on the development of hVEGF26-104 vaccine in combination with the RFASE based adjuvant for the treatment of cancer.

The vaccine hVEGF26-104/RFASE consists of a truncated synthetic mimic of the human VEGF protein (hVEGF26-104) emulsified in the adjuvant RFASE. hVEGF26-104 is a new chemical entity based on Pepscan’s and ImmuNovo’s joint proprietary peptide technology. hVEGF26-104 consists of a continuous sequence out of the VEGF protein (residue 26-104) that covers the β1 to β6 and α2 region of the full protein sequence. Correct formation of the cys-knot fold gives both the β1/2/α2/β3 loop (first loop) and the β5/β6 loop (second loop) the correct 3D conformation that is required for a correct mimicry of the VEGF protein surface. In its oxidized form it is used as an antigen for VEGF directing the body’s subsequent polyclonal antibody response towards the active site of the VEGF molecule. The important issue is that antibodies raised against the synthetic molecule hVEGF26-104 strongly cross-react with endogenous VEGF and after binding of the antibodies to endogenous VEGF this hormone will no longer be able to bind to its receptors (VEGFR1 and VEGFR2) and consequently will no longer exert its angiogenic effect.

To enhance the immune response, RFASE will be used as an adjuvant. RFASE belongs to the adjuvant group of sulpholipopolysaccharides.

Preclinical data has already demonstrated the feasibility of this approach.