On June 15, 2015 Onconova reported the presentation of clinical data on rigosertib in HR-MDS at the 20th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Vienna, Austria, June 11 – 14, 2015 (Press release, Onconova, JUN 15, 2015, View Source [SID:1234505432]).

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Onconova collaborators from the United States and Europe presented multiple posters analyzing subgroup data, key clinical endpoints and eligibility criteria from the completed Phase 3 ONTIME trial of IV rigosertib in patients with HR-MDS previously treated with hypomethylating agents (HMAs). These data are being utilized in the design of a new global Phase 3 trial for IV rigosertib in HR-MDS, which Onconova expects to initiate in 2015, pending receipt of appropriate financing.

Electronic versions of the posters can be accessed by visiting "Posters" under the Investors and Media section of the Onconova website at www.onconova.com.

Abstract number: P616
Title: Overall Survival (OS) and Baseline Disease Characteristics in MDS Patients with Primary HMA Failure in a Randomized, Controlled, Phase III Study of Rigosertib
Primary Author: Guillermo Garcia-Manero, MD, MD Anderson Cancer Center, Houston, TX

Abstract number: P625
Title: Correlation of Overall Survival (OS) with Bone Marrow Blast (BMBL) Response in Patients (Pts) with Myelodysplastic Syndromes (MDS)
Primary Author : Lewis R. Silverman, MD, Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, NY

Abstract Number: E1227
Title: Prognostic and Predictive Value of IPSS-R in Assessing Overall Survival (OS) in a Phase III Study of Rigosertib in Second-line Higher-risk (HR) MDS Patients
Primary Author: Lewis R. Silverman, MD; Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, NY

Abstract Number: E1226
Title: Subgroup Analyses of a Phase 3 Study in Patients with Myelodysplastic Syndromes Failing HMA Treatment: Identification of a Homogeneous Population Who Benefit from Rigosertib Therapy
Primary Author: Gianluca Gaidano, MD; Amedeo Avogadro University of Eastern Piedmont, Novara, Italy

On Jun 15, 2015 BioLineRx reported the presentation of positive safety and efficacy results for its lead oncology candidate, BL-8040, as a novel approach for the collection of stem cells from the peripheral blood circulation (Press release, BioLineRx, JUN 15, 2015, View Source;p=RssLanding&cat=news&id=2059112 [SID:1234505431]). Treatment with BL-8040 as a single agent was found safe and well tolerated at all doses, and resulted in efficient stem-cell mobilization and collection in all study participants. Furthermore, the results support BL-8040 as a one-day, single-dose collection regimen, which is a significant improvement compared to the current standard of care. The full Phase 1 data set was presented yesterday in an oral presentation at the 20th Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Vienna, Austria.

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Robust stem-cell mobilization was evident in all treated participants across the different doses tested, leading to a median 9.5-fold increase of stem cells in the peripheral blood following a single BL-8040 treatment. Two to four hours after a single administration, BL-8040 enabled collection of a stem-cell yield exceeding the number of cells required to support a transplant in all treated participants, following only one collection procedure. These results support a novel approach to stem-cell collection for transplantation purposes in patients with hematological malignancies or other indications. Importantly, the collection of CD34+ cells was accompanied by mobilization and collection of colony-forming cells, as well as T, B and NK cells.

The collected human graft was further assessed for its viability and quality in vitro and in vivo. The cells collected from the subjects treated with BL-8040 showed excellent engraftment in irradiated mice, followed by a rapid reconstitution of normal hematopoiesis.

The Phase 1 clinical trial was performed on healthy volunteers and consisted of two parts. The first part of the study was a randomized, double-blind, placebo-controlled, dose-escalation study in three cohorts of eight participants each, with each participant receiving two consecutive injections of BL-8040. Results show that BL-8040 is safe and well tolerated up to a dose of 1 mg/kg, and that dramatic mobilization of hematopoietic stem and progenitor cells (HSPCs) was observed across all doses tested. The robust mobilization supports the further use of a single injection of BL-8040 for HSPC collection.

In the second part of the Phase 1 study, eight healthy participants received a single injection of BL-8040 at the highest dose of 1 mg/kg, and four hours later underwent a single, standard leukapheresis procedure. Robust and rapid stem-cell mobilization was evident in all treated participants, supporting a novel approach to stem-cell collection. The median level of collected stem cells was higher than 11 x 106 cells per kg, and the level of HPSCs in the peripheral blood circulation 24 hours after injection of BL-8040 enabled an additional apheresis on Day 2, if needed. These data support the use of BL-8040 as a single-agent, single-injection, one-day regimen for the collection of stem cells.

"We are very happy to report these outstanding results supporting BL-8040 as an effective one-day monotherapy for collection of sufficient stem cells for hematopoietic cell transplantation. This is a major improvement over currently available procedures, which are lengthier and sometimes require the combination of several agents and multiple time-consuming apheresis sessions. Moreover, we see an improvement in composition of the collected cells, suggesting the potential of a better quality graft that may improve stem cell transplantation outcomes," said Dr. Kinneret Savitsky, CEO of BioLineRx. "We intend to meet with the U.S. Food and Drug Administration (FDA) in order to discuss our next steps in the clinical development program for this indication, including the design of the planned follow-up Phase 2 study. In addition, we are looking forward to reporting top-line results from the on-going Phase 2 study of BL-8040 for treating relapsed and refractory acute myeloid leukemia patients, which we expect in the fourth quarter of 2015. We also look forward to initiating clinical studies for BL-8040 in three additional indications over the next few months, thus expanding and enhancing the potential of our oncology platform."

At the same conference, the Company also presented positive preclinical results for the treatment of acute myeloid leukemia (AML) at a poster session. The results show that BL-8040 rapidly and efficiently induces cell death of AML cells, and demonstrates for the first time that CXCR4 inhibition is associated with induction of terminal differentiation of AML cells.

About Stem-Cell Mobilization

High-dose chemotherapy followed by stem-cell transplantation has become an established treatment modality for a variety of hematologic malignancies, including multiple myeloma, as well as various forms of lymphoma and leukemia. Modern peripheral stem-cell harvesting often replaces the use of traditional surgical bone marrow stem-cell harvesting. In the modern method, stem cells are mobilized from the bone marrow using granulocyte colony-stimulating factor (G-CSF), often with the addition of a mobilizing agent such as Plerixafor (Mozobil), harvested from the donor’s peripheral blood by apheresis, and infused to the patient after chemotherapy ablation treatment. This treatment is highly effective, the peripheral stem cells are easier to collect, and the treatment allows for a quicker recovery time and fewer complications.

About BL-8040

BL-8040 is a clinical-stage drug candidate for the treatment of acute myeloid leukemia, as well as other hematological indications. It is a short peptide that functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis (growth of new blood vessels in the tumor), metastasis (spread of the disease to other organs or organ parts) and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a Phase 1/2, open-label, dose escalation, safety and efficacy clinical trial in 18 multiple myeloma patients, BL-8040, when combined with G-CSF, demonstrated an excellent safety profile at all doses tested and was highly effective in the mobilization of hematopoietic stem cells and white blood cells from the bone marrow to the peripheral blood. Additionally, in a Phase 1 stem-cell mobilization study in healthy volunteers, BL-8040 as a single agent was safe and well tolerated at all doses tested and resulted in efficient stem-cell mobilization and collection in all study participants. Importantly, the results of this study support the use of BL-8040 as one-day, single-dose collection regimen, which is a significant improvement upon the current standard of care.

BL-8040 also mobilizes cancer cells from the bone marrow and may therefore sensitize these cells to chemo- and bio-based anti-cancer therapy. Importantly, BL-8040 has also demonstrated a direct anti-cancer effect by inducing apoptosis. Pre-clinical studies show that BL-8040 inhibits the growth of various tumor types including multiple myeloma, non-Hodgkin’s lymphoma, leukemia, non-small cell lung carcinoma, neuroblastoma and melanoma. BL-8040 significantly and preferentially stimulated apoptotic cell death of malignant cells (multiple myeloma, non-Hodgkin’s lymphoma and leukemia). Significant synergistic and/or additive tumor cell killing activity has been observed in-vitro and in-vivo when tumor cells were treated with BL-8040 together with Rituximab, Bortezomib, Imatinib, Cytarabine and the FLT-3 inhibitor AC-220 (in NHL, MM, CML, AML, and AML-FLT3-ITD models, respectively). In addition, the current Phase 2 clinical trial in AML patients has demonstrated robust mobilization and apoptosis of cancer cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

On June 15, 2015 DelMar Pharmaceuticals reported that it has been invited to present at The World NSCLC Summit being held June 23-24, 2015 in Boston, MA (Press release, DelMar Pharmaceuticals, JUN 15, 2015, View Source [SID:1234505427]).

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Jeffrey A. Bacha, president & CEO of DelMar Pharmaceuticals, will present a scientific talk regarding the anti-cancer mechanism of VAL-083 (dianhydrogalactitol) as a potential treatment of non-small cell lung cancer ("NSCLC") and the Company’s plans for expanding its clinical research with VAL-083 into human clinical trials for NSCLC.

VAL-083 is a "first-in-class" bi-functional alkylating agent mediating inter-strand DNA crosslinks at N7 of guanine. VAL-083 has previously demonstrated activity against lung cancer in preclinical and clinical trials and is approved for the treatment of lung cancer in China. DelMar is currently conducting a Phase I/II clinical trial with VAL-083 as a potential treatment for glioblastoma multiforme, the most common and deadly form of brain cancer.

The Company recently presented an abstract at the annual meeting of the American Association of Cancer Research ("AACR") entitled, "In vitro activity of dianhydrogalactitol alone or with platinum drugs in the treatment of NSCLC."

The activity of VAL-083 against solid tumors, including lung cancer, has been established in both pre-clinical and human clinical trials conducted by the NCI. VAL-083 has been approved by the Chinese Food and Drug Administration ("CFDA") for the treatment of lung cancer. However, sales of VAL-083 in China have been limited by a lack of modern data, poor distribution, and preference for targeted therapies such as tyrosine kinase inhibitors ("TKIs") in the modern era.

DelMar’s data demonstrate that VAL-083’s mechanism is distinct from platinum-based chemotherapy, the current standard of care for NSCLC and that VAL-083 retains its high level of anti-cancer activity in p53 mutated NSCLC cell lines, which are highly resistant to platinum based therapy. DelMar’s data also suggest that the combination of VAL-083 with either cisplatin or oxaliplatin provides a super-additive (synergistic) effect against NSCLC cell lines, including those resistant to TKI therapy in vitro.

DelMar believes these new data suggest the potential of VAL-083 to be used in combination with platinum-based chemotherapy and to address modern unmet medical needs in the treatment of TKI-resistant NSCLC, especially where platinum-based therapy has already failed or is predicted to give sub-optimal outcomes. In addition, VAL-083 readily crosses the blood brain barrier suggesting that it may be possible for VAL-083 to treat patients whose lung cancer has spread to the brain.

As a next step, DelMar plans to initiate a clinical trial in NSCLC in collaboration with Guangxi Wuzhou Pharmaceutical Group Co. Ltd. (Guangxi Wuzhou Pharma). Under the terms of the Company’s collaboration agreement with Guangxi Wuzhou Pharma, DelMar is responsible for establishing protocols and conducting clinical trials, and Guangxi Wuzhou Pharma is responsible for the costs associated with clinical trials conducted in China. DelMar’s goal is to work with Guangxi Wuzhou Pharma to develop new clinical data to help support product growth of VAL-083 in China and to establish clinical proof of concept to expand globally its independent drug development efforts with VAL-083 as a potential treatment for NSCLC.

About The World NSCLC Summit
The World NSCLC Summit will bring together over 100 senior level attendees from the pharmaceutical industry to discuss the challenges in the development of new therapies for the treatment of NSCLC. Over the two days the World NSCLC Summit feature presentations on the latest updates from the NSCLC pipelines of small and large drug developers, and feature discussions around all the latest trends in personalized medicine, as pertaining to this disease area, through case studies from early discovery to commercial development.
For more information, visit View Source

About NSCLC
Lung cancer is a leading cause of cancer-related mortality around the world and effective treatment for lung cancer remains a significant global unmet need despite advances in therapy. In general, prognosis for lung cancer patients remains poor, with 5-year relative survival less than 14% among males and less than 18% among females in most countries. Globally, the market for lung cancer treatment may exceed $7 billion by 2019 according to a report published by Transparency Market research.

Non-small cell lung cancer ("NSCLC") is the most common type of lung cancer. There are three common forms of NSCLC: adenocarcinomas are often found in an outer area of the lung; squamous cell carcinomas are usually found in the center of the lung next to an air tube (bronchus); and large cell carcinomas, which can occur in any part of the lung and tend to grow and spread faster than adenocarcinoma. NSCLC accounts for 85% of all lung cancer cases in the United States and approximately 90% of lung cancer cases diagnosed in China.

The current standard of care for newly diagnosed NSCLC is platinum-based combination therapy or TKI therapy for patients whose cancer exhibits epidermal growth factor receptor ("EGFR") mutations. Patients exhibiting EGFR mutations have shown an initial response rate to TKIs which exceeds the response rate for conventional chemotherapy. However, TKI resistance has emerged as an important unmet medical need.

About VAL-083
VAL-083 is a "first-in-class", small-molecule chemotherapeutic. In more than 40 Phase 1 and 2 clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated safety and efficacy in treating a number of cancers including lung, brain, cervical, ovarian tumors and leukemia. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia and lung cancer and has received orphan drug designation in Europe and the U.S. for the treatment of gliomas.

DelMar is currently studying VAL-083 in a multi-center Phase I/II clinical trial for patients with refractory glioblastoma multiforme (GBM) in accordance with the protocol that has been filed with the U.S. Food and Drug Administration ("FDA"). (ClinicalTrials.gov Identifier NCT01478178). As a potential treatment for glioblastoma, VAL-083’s mechanism of action appears to be unaffected by the expression of MGMT, a DNA repair enzyme that causes chemotherapy resistance to front-line treatment with Temodar (temozolomide).