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DelMar Pharmaceuticals Invited to Present at The World NSCLC Summit on June 23-24, 2015

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).

Advaxis Submits Special Protocol Assessment Request to FDA for ADXS-HPV Phase 3 Clinical Trial in Cervical Cancer

On June 15, 2015 Advaxis reported the company has submitted a Special Protocol Assessment (SPA) request to the U.S. Food and Drug Administration (FDA) to initiate detailed design discussions for a Phase 3 clinical study of ADXS-HPV for the treatment of high-risk, locally advanced cervical cancer (HRLACC) (Press release, Advaxis, JUN 15, 2015, http://ir.advaxis.com/press-releases/detail/1166/advaxis-submits-special-protocol-assessment-request-to-fda-for-adxs-hpv-phase-3-clinical-trial-in-cervical-cancer [SID:1234505438]).

The Phase 3 trial is planned to be conducted in collaboration with the Gynecologic Oncology Group (GOG) Foundation, Inc. and to be led by principal investigator Thomas Herzog, M.D., Professor of Obstetrics & Gynecology and Clinical Director at the University of Cincinnati Cancer Institute, Cincinnati, Ohio.

The SPA request includes specific questions from Advaxis to facilitate a meaningful dialog with the FDA on the proposed study design. Following receipt, the FDA will determine the appropriateness of the SPA request and may take up to 45 calendar days to provide comments to Advaxis. The nature and extent of comments received will determine the need for additional rounds of review and/or a formal meeting. The FDA’s assessment of the SPA request, and all related valuable feedback, will aid to inform the development of ADXS-HPV in locally advanced cervical cancer.

The proposed Phase 3 clinical trial (AIM2CERV) is designed as an adequate and well-controlled double-blind, placebo-controlled multinational study of ADXS-HPV (ADXS11-001) administered in the adjuvant setting following concurrent chemoradiation given with curative intent in patients with HRLACC for whom recurrence has not yet occurred. Advaxis plans to initiate the Phase 3 trial by the end of 2015.

"Submitting our SPA request to the FDA is an important first step in the proposed Phase 3 program for ADXS-HPV in cervical cancer," said David J. Mauro, M.D., Ph.D., Executive Vice President and Chief Medical Officer of Advaxis. "The decision to evaluate ADXS-HPV in HRLACC is based on the encouraging survival data observed in metastatic cervical cancer (Lm-LLO-E7-15 and GOG-0265)’ and emerging clinical data on the adjuvant use of ADXS-HPV in the treatment of high-risk locally advanced anal cancer; and the adjuvant use of ADXS31-164 in canine osteosarcoma. We believe that ADXS-HPV may have an opportunity to demonstrate a more meaningful clinical impact on the lives of women with cervical cancer in an earlier disease setting and in a subpopulation of patients who are at high risk for recurrence."

About High-Risk, Locally Advanced Cervical Cancer (HRLACC)

Cervical cancer is the fourth most common cancer and the most common cause of mortality in women worldwide with 528,000 new cases reported annually and an estimated 266,000 deaths in 2012; the majority of which is diagnosed in less-developed countries. Within the United States, approximately 12,900 cases of invasive cervical cancer are diagnosed annually and up to 30 percent are diagnosed with locally advanced disease. Despite a well-established and adopted standard of care for the treatment of locally advanced cervical cancer, consisting of cisplatin and radiotherapy administered concurrently, a large percentage of these patients, particularly those with high risk features and/or poor prognostic factors, will experience cancer recurrence and ultimately die of their disease. These patients represent a subpopulation of locally advanced cervical cancer with the highest unmet medical need and where the need for new therapeutic options is greatest as there are no approved therapies for this specific patient population3.

About GOG Foundation, Inc. (GOG Foundation)
The GOG Foundation, Inc. (GOG Foundation) is an independent international non-profit organization with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of gynecologic malignancies. The GOG Foundation is committed to maintaining the highest standards in clinical trials development, execution, analysis and distribution of results. Continuous evaluation of the organization’s processes is utilized in order to constantly improve the quality of patient care. The GOG Foundation conducts clinical trials for patients with a variety of gynecologic malignancies, including cancers that arise from the ovaries, uterus, cervix, vagina, and vulva. The GOG Foundation is a separate entity from the National Clinical Trials Network groups that are funded by the National Cancer Institute.

About ADXS-HPV
ADXS-HPV is Advaxis’s lead Lm-LLO immunotherapy product candidate for the treatment of HPV-associated cancers. It is currently under investigation in three HPV-associated cancers: invasive cervical cancer, head and neck cancer, and anal cancer. In a completed Phase 2 study in recurrent/refractory cervical cancer, ADXS-HPV has shown prolonged survival, objective tumor responses, and a manageable safety profile alone or in combination with chemotherapy, supporting further development of this Lm-LLO immunotherapy. The U.S. Food and Drug Administration (FDA) granted orphan drug designations for ADXS-HPV for the treatment of Stage II-IV invasive cervical cancer, HPV-associated head and neck cancer, and for HPV-associated anal cancer.

8-K – Current report

On June 15, 2015 Heat Biologics reported the development of its next-generation combination immunotherapy platform, which combines a pan-antigen T cell priming vaccine and T cell co-stimulator in a single product (Filing, 8-K, Heat Biologics, JUN 15, 2015, View Source [SID:1234505436]).

This platform, named ComPACT, has been engineered to incorporate various fusion proteins targeting co-stimulatory receptors (OX40, ICOS, 4-1BB), enabling the combination of two important immunotherapy pathways in a single therapy. Data generated using the ComPACT platform are being presented today at the Cell Symposia, ‘Cancer, Inflammation and Immunity’ in Sitges, Spain. The Company will also be hosting a Webcast today to present these data.

Taylor Schreiber, MD, PhD, Heat’s Vice President of Research, who led development of ComPACT, commented: "It is now widely recognized in the clinical community that combinations between checkpoint inhibitors, T cell co-stimulators, and vaccines can provide superior benefits to any single modality as monotherapy. The first challenge in developing these combinations is to systematically identify synergistic pathways from redundant or antagonistic ones. Another challenge is to deploy combination immunotherapies that may limit systemic toxicity and offer an advantageous overall cost structure compared to combining multiple biologic therapies. Heat’s ComPACT therapy is designed to achieve these goals."

The presentation by George Fromm, PhD, Heat’s Director of Research, reveals the first preclinical analysis of ComPACT, incorporating OX40L-Fc, demonstrates significant benefits as compared to traditional OX40 agonistic antibodies. Dr. Fromm commented: "The magnitude of T cell stimulation with ComPACT was somewhat unexpected, but clearly demonstrates substantial increases for both primary and memory immune response to those seen by co-administration of a vaccine and OX40 agonist antibody." The data illustrate that systemic OX40 stimulation through antibody therapy led to increased off-target T cell activation, and that the beneficial response with ComPACT may be due to increased specificity.

Although the data presented include combinations between gp96-Ig vaccination and stimulation of OX40, the platform has also been developed to target other T cell co-stimulatory receptors including ICOS, 4-1BB and other undisclosed co-stimulatory targets. Heat’s ComPACT therapy has the potential to provide a product that achieves the envisioned benefits of combination immunotherapy in a single therapy, without the need for multiple independent biologic products. Heat expects to file its first IND with the ComPACT platform in 2H, 2016.

ImmunoCellular Therapeutics Enters into Manufacturing Agreement with PCT LLC, a Caladrius Company, for US Production of ICT-107 for Phase 3 Registration Trial

On June 15, 2015 ImmunoCellular Therapeutics reported the selection of PCT, LLC, a subsidiary of Caladrius Biosciences, Inc. ("Caladrius") (NASDAQ:CLBS), as the US manufacturer for ImmunoCellular’s ICT-107 phase 3 registrational clinical program in newly diagnosed glioblastoma, anticipated to begin in the second half of 2015 (Press release, ImmunoCellular Therapeutics, JUN 15, 2015, View Source [SID:1234505433]).

Under the terms of the multi-year agreement, PCT will provide current good manufacturing practice (cGMP) services for the manufacture of clinical supplies of ICT-107, a dendritic cell-based immunotherapy targeting six tumor-associated antigens. PCT, which was previously engaged by ImmunoCellular to manufacture clinical supplies of ICT-107 and the Company’s other cancer immunotherapy clinical programs, is also working with ImmunoCellular’s European contract manufacturer, PharmaCell B.V., to perform a technology transfer process to harmonize the EU and US methods of production of ICT-107 for the planned phase 3 registration trial. PCT’s facilities are registered with the FDA as human cells, tissues, and cellular and tissue-based products (HCT/Ps) facilities, and maintain GMP-compliant quality systems.

ImmunoCellular Therapeutics Logo.
"Selecting our US manufacturer for the ICT-107 phase 3 trial is an important step toward initiation of our registration program," said Andrew Gengos, ImmunoCellular Chief Executive Officer. "We have been pleased with PCT’s ability to provide high quality, cost-effective and consistent manufacturing, and have confidence in their ability to support our phase 3 trial. Over the coming weeks, we look forward to announcing additional key milestones toward initiating the phase 3 trial, which have the potential to be major value-creating events for our Company. We expect to be in position to begin patient enrollment in the late third quarter or early fourth quarter of this year."

"We are extremely pleased that the leadership team at ImmunoCellular has chosen to develop a long-term relationship partnership with PCT in order to maintain the cell therapy manufacturing reliability, quality, and cost efficiencies they have come to expect," said Dr. Robert A. Preti, President of PCT, and Chief Technology Officer of Caladrius. "We feel our clients significantly reduce their clinical development risk by manufacturing with PCT and leveraging our Innovation and Quality infrastructure."

Tosedostat In Combination With Low Dose Cytarabine Achieves Primary Endpoint In Phase 2 Study In Elderly Patients With AML

On June 15, 2015 CTI BioPharma reported findings from an investigator-sponsored Phase 2 trial in patients with either primary (de novo) acute myeloid leukemia (AML) or AML that has evolved from myelodysplastic syndrome (MDS) (Press release, CTI BioPharma, JUN 14, 2015, View Source;p=RssLanding&cat=news&id=2059047 [SID:1234505424]). Results showed the combination of tosedostat with low dose cytarabine/Ara-C (LDAC) resulted in an overall response rate (ORR) of 54 percent in elderly patients with AML – with 45 percent of patients achieving durable complete responses (CR). These final results were presented by Dr. Giuseppe Visani, Director of Hematology and Stem Cell Transplant Center at AORMN, Pesaro, Italy in a poster session (abstract #P564) during the 20th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), June 11-14, 2015 in Vienna, Austria.

AML is the most common acute leukemia affecting adults, and its incidence increases with age. AML may develop from the progression of other diseases, such as MDS, which is a blood cancer that also affects the bone marrow and leads to a decrease in circulating red blood cells. Tosedostat is a potential first-in-class selective inhibitor of aminopeptidases, which are required by tumor cells to provide amino acids necessary for growth and tumor cell survival.

"Both the types and length of responses in this trial with tosedostat are very encouraging – particularly given the limited options and poor outcomes historically observed in elderly patients with acute myeloid leukemia, either de novo or secondary after myelodysplastic syndrome," said Dr. Visani. "Importantly, through this study we have also identified potential biomarkers that may help identify high-risk patients in which we are more likely to see these clinically meaningful results – the findings of which are quite compelling and warrant further study."

Findings Presented at EHA (Free EHA Whitepaper)
Final results presented at EHA (Free EHA Whitepaper) show that responding patients had a significant improvement in overall survival based on response rates compared to non-responding patients (p=0.018). In the intent-to-treat population (ITT), the ORR was 54 percent – with CR observed in 45 percent of patients (n=15/33). In the responding patients, the median time for achieving best response was 74 days (range: 22-145 days) and 55 percent (n=10/18) were still in remission after a median follow-up of 319 days. Safety analysis show that tosedostat in combination with LDAC was generally well tolerated. The primary adverse events observed were pneumonitis (12 percent), cardiac (6 percent), brain hemorrhage (3 percent), and asthenia (3 percent).

One of the secondary endpoints was to identify possible biomarkers associated with sensitivity and/or drug resistance. A gene expression profile (GEP) was performed on purified AML cells obtained from 29 patients. Analysis of these patient cells identified a molecular signature associated with clinical response (CR vs. no CR). Based on the differentially expressed genes (n=212), samples were divided according to either CR or no CR. Results showed that these differentially expressed genes were associated with relevant biological functions and pathways – including B-catenin (beta-catenin), TNFA-NFkB, ERB2, inflammatory response, and epithelial-mesenchimal transition – and showed that the achievement of a CR could be efficiently predicted by GEP.

"The results observed with tosedostat in acute myeloid leukemia add to a growing body of data showing the anti-tumor activity of this aminopeptidase inhibitor and the potential of using this approach to treat blood-related cancers," Alan K. Burnett, M.D., Global Lead for Myeloid Diseases at CTI BioPharma. "Based on the clinical data observed to date, we are advancing the development for tosedostat including the potential for a Phase 3 registrational study for primary acute myeloid leukemia or acute myeloid leukemia that evolves from myelodysplastic syndrome."

About the Study Design
The Phase 2 multicenter clinical trial was designed to assess tosedostat (orally once-daily) in combination with intermittent LDAC (twice daily) in 33 elderly patients (median age = 75 years) with either primary AML or secondary AML after MDS. Courses of LDAC were repeated every four weeks for up to eight cycles in the absence of disease progression or unacceptable toxicity. The primary objective was to exceed the upper limit of institutional expected CR rates (P0=10%, P1= 25%, α=0.05, 1-β=80%); secondary objectives include safety and toxicity, stable disease, overall survival, and progression-free survival as well as the identification of a possible biomarker associated with sensitivity and/or disease resistance through global gene expression profiling (GEP, Affymetrix Transciptome Array 2.0).

The poster for Abstract #P564 – "Tosedostat plus low dose cytarabine induces a high rate of responses that can be predicted by genetic profiling in AML: Final results of a Phase II multicenter study" – is available at www.ctibiopharma.com.

About Tosedostat
Tosedostat is an oral aminopeptidase inhibitor that has demonstrated anti-tumor responses in blood-related cancers and solid tumors in Phase 1-2 clinical trials. Tosedostat is currently being evaluated in multiple Phase 2 clinical trials for the treatment of patients with AML or high-risk MDS and are intended to inform the design of a Phase 3 registration study to support potential regulatory approval. Tosedostat is not approved or commercially available.

About Acute Myeloid Leukemia and Myelodysplastic Syndrome
AML is a cancer characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute leukemia affecting adults, and its incidence increases with age.1 The symptoms of AML are caused by the replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells, platelets, and normal white blood cells, leading to infections and bleeding. AML progresses rapidly and is typically fatal within weeks or months if left untreated. In 2015, approximately 20,830 new cases of AML are expected to be diagnosed in the United States and an estimated 10,460 are expected to die from the disease.2 While AML may occur at any age, adults at least 60 years of age are more likely than younger people to develop the disease.2 Although a substantial proportion of younger individuals who develop AML can be cured, AML in the elderly typically responds poorly to standard therapy with few complete remissions.

AML may develop from the progression of other diseases, such as MDS. MDS are a group of diverse bone marrow disorders in which the bone marrow does not produce enough healthy blood cells. MDS is often referred to as a "bone marrow failure disorder."