On January 25, 2016 Boston Biomedical, an industry leader in the development of novel compounds designed to target cancer stem cell (CSC) pathways, reported that three poster presentations were highlighted at the 2016 Gastrointestinal Cancers Symposium, held by the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), January 21 to 23, 2016, in San Francisco (Press release, Dainippon Sumitomo Pharma, JAN 25, 2016, View Source [SID:1234508858]).

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"We were pleased to share these data from napabucasin (BBI608) in advanced and difficult-to-treat tumor types at this year’s ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium," said Chiang J. Li, M.D. FACP, the President, CEO and Chief Medical Officer of Boston Biomedical, and the Head of Global Oncology for Sumitomo Dainippon Pharma Group. "These studies continue to show napabucasin’s safety and early efficacy across doses and in combination with a variety of established agents. We plan to apply these findings as we advance and expand our clinical development program for this first-in-category cancer stemness inhibitor."

Data presented at the symposium support the continued development of the investigational cancer stemness inhibitor napabucasin (also known as BBI608, BB608 or BBI-608) — an orallyadministered agent designed to inhibit cancer stem cell pathways by targeting the STAT3 pathway — for anti-cancer activity when used in combination with other agents across advanced, pretreated and untreated metastatic pancreatic cancers, as well as advanced, pretreated colorectal cancer.

"These clinical studies of napabucasin in advanced gastroenterological cancers, including the presentation of data in refractory colorectal cancer specifically, show encouraging clinical activity by targeting cancer stem cell pathways that contribute to cancer recurrence, metastases and resistance to therapies," commented Axel Grothey, M.D., professor of oncology, Mayo Clinic. "I look forward to the further investigation of this innovative approach to cancer treatment in additional clinical studies."

Overview of the Boston Biomedical poster presentations:

• Abstract #284 (NCT02231723), Poster Session B Board #E8: A Phase Ib study of Cancer Stem Cell (CSC) pathway inhibitor Napabucasin (BBI608) in combination with Gemcitabine and nab-Paclitaxel (nab-PTX) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) [Safi Shahda, M.D., IU Health University Hospital]

o Data from this phase Ib study demonstrate that napabucasin (BBI608) at 240 mg twice daily was combined with gemcitabine and nab-paclitaxel, resulting in early anti-tumor activity in patients with metastatic pancreatic ductal adenocarcinoma.

Of the 31 patients enrolled, 25 patients were treatment-naïve and 6 patients had received one prior line of systemic therapy in the adjuvant setting only. Safety data was available for 18 patients and efficacy data was available for 8 patients at clinical cut off for abstract submission for the 8-patient cohort of recommended phase II dose determination. Safety and efficacy data for the rest of the patients are being followed.

Of the 8 patients enrolled to determine the recommended phase II dose, 7 patients were evaluable for response and 100% had partial response (PR) or stable disease (SD). Tumor regression was observed in 6/7 patients (85.7%) with 3 PR (41.3%, 37.1% and 33.3% regression) and 3 SD (25.8%, 21.1%, and 20.5% regression). Six of 7 evaluable patients (85.7%) had prolonged PR or SD of 24 weeks or longer.

The most common adverse events included grade 1 diarrhea, nausea, fatigue, abdominal pain and anorexia.

• Abstract #196 (NCT01325441), Poster Session B Board #A6: Phase Ib/II Study of Napabucasin (BBI608) combined with Weekly Paclitaxel in Advanced Pancreatic Cancer [Tanios Bekaii-Saab, M.D., Ohio State University Wexner Medical Center]

o Results from this phase Ib/II extension study of napabucasin (BBI608) at 480 mg twice daily plus weekly paclitaxel showed early anti-cancer activity in patients with refractory, heavily pretreated pancreatic cancer, particularly in taxane-naïve patients. Durable disease control and prolonged overall survival in this study patient population were also observed.

The 41 patients enrolled had received a median of two prior lines of treatment including FOLFIRINOX (71%), gemcitabine/nab-paclitaxel (44%) or both (37%).

The 31 evaluable patients had a response rate (partial response, PR + complete response, CR) of 6% and disease control rate (stable disease, SD + PR + CR) of 48%. The 19 evaluable taxane-naïve patients had a response rate of 11% and disease control rate of 63%, and 16% were progression-free at 24 weeks. Overall for the 41 patients, median progression-free survival (mPFS) was 2.2 months and median overall survival (mOS) was 6.0 months, while the 23 taxane-naïve patients demonstrated mPFS of 3.9 months and mOS of 7.4 months.

The most common adverse events included grade 1 and 2 diarrhea, fatigue and abdominal pain, and grade 1 nausea, anorexia and vomiting.

• Abstract #569 (NCT02024607), Poster Session C Board #D18: A Phase Ib study of first-in-class cancer stemness inhibitor Napabucasin (BBI608) in combination with FOLFIRI with and without Bevacizumab in Patients with Advanced Colorectal Cancer [Joleen Hubbard, M.D., Mayo Clinic]

o This phase Ib study showed that napabucasin (BBI608) at 240 mg twice daily can be combined with FOLFIRI with and without bevacizumab, and demonstrated early anti-tumor activity in heavily pretreated colorectal cancer patients, even in those with prior progression on FOLFIRI-based therapy.
Of the 18 enrolled heavily pretreated patients (average of >3 prior lines of therapy), 10 patients previously progressed on FOLFIRI. Of the 17 evaluable patients, 8 patients received FOLFIRI and 9 received FOLFIRI with bevacizumab, both in combination with napabucasin.

Disease control (partial response, PR + stable disease, SD) was observed in 94% of evaluable patients (16 of 17). Ten evaluable patients (59%) achieved prolonged disease control (PR and SD) of 24 weeks or more.

The most common adverse events included grade 1 and 2 diarrhea, fatigue, nausea, vomiting, abdominal pain and anorexia; no dose limiting toxicity or new adverse events were seen and the safety profile was similar to that of each regimen as monotherapy.

The full posters of the above studies are available on the R&D publications page of the Boston Biomedical website.

On January 25, 2016 ArQule, Inc. (NASDAQ:ARQL) reported that an analysis of preliminary baseline tumor MET status of patients screened in the phase 3 METIV-HCC trial for tivantinib in second-line hepatocellular carcinoma (HCC) confirms previously presented data from the company’s phase 2 trial in the same patient population (Press release, ArQule, JAN 25, 2016, View Source [SID:1234508855]). In both trials MET status, as determined by immunohistochemistry, was more frequently high after first-line therapy and was a predictive and prognostic biomarker in the phase 2 trial. The data was presented in an oral presentation and poster at the 2016 Gastrointestinal Cancers Symposium (ASCO GI) on January 22, 2016.

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The METIV-HCC trial screened patient tumor biopsies for MET status as an inclusion criteria for Met-high patients. Approximately half of the more than 1,000 samples tested were MET-high. A higher MET-high rate (73%) was observed in those samples from patients analyzed following first-line treatment with sorafenib while a lower MET-high rate (39%) was observed in those samples analyzed prior to sorafenib treatment.

An additional analysis found that 70% (50 out of 71) of patients who tested MET-low before sorafenib treatment became MET-high after receiving sorafenib. The presentations can be accessed in the "Publications and Presentations" section of our website, www.arqule.com.

"The totality of the biomarker data presented further enforces our confidence in the design and target patient population that we have chosen for the METIV-HCC trial," said Dr. Brian Schwartz, Chief Medical Officer and Head of Research and Development at ArQule. "Having recently completed enrollment, we look forward to the planned interim analysis early in the second quarter."

The METIV-HCC trial, being conducted in western countries in partnership with Daiichi Sankyo, has completed enrollment and a planned interim analysis, which is triggered when 60% of events occur, is expected to take place early in the second quarter of 2016. The trial enrolled over 300 patients, is randomized 2:1 treatment to best supportive care, and has overall survival as its primary end-point.

The phase 2 study, completed in the third quarter of 2011 and published in The Lancet Oncology medical journal in November 2012, enrolled 107 HCC patients who progressed or were intolerant to one prior systemic therapy. Multiple biomarkers were evaluated as part of the study, and tumor MET status as determined by immunohistochemistry emerged as the strongest predictor of tivantinib response.

About Hepatocellular Carcinoma (HCC)

Liver cancer is the sixth most common cancer globally with about 782,000 new cases in 2012 and is the second most common cause of cancer-related death with 746,000 deaths in 2012.i HCC accounts for about 90 percent of primary liver cancers.ii Cirrhosis, chronic hepatitis B and C and smoking are recognized worldwide as factors increasing the risk of HCC.ii

About MET and Tivantinib (ARQ 197)

Tivantinib is an orally administered, selective inhibitor of MET, a receptor tyrosine kinase, which is currently in two phase 3 clinical trials. In healthy adult cells, MET can be present in normal levels to support natural cellular function, but in cancer cells, MET can be inappropriately and continuously activated. When abnormally activated, MET plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis. The activation of certain cell signaling pathways, including MET, has also been associated with the development of resistance to anti-EGFR (epidermal growth factor receptor) antibodies such as cetuximab and panitumumab.

Pre-clinical data have demonstrated that tivantinib inhibits MET activation in a range of human tumor cell lines and shows anti-tumor activity against several human tumor xenografts. In clinical trials to date, treatment with tivantinib has been generally well tolerated and has shown clinical activity in a number of tumors studied. Tivantinib has not yet been approved for any indication in any country.

In December 2008, ArQule and Daiichi Sankyo signed a license, co-development and co-commercialization agreement for tivantinib in the U.S., Europe, South America and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan.

In November 2015, ArQule exercised its co-commercialization option for tivantinib in the U.S. A co-commercialization agreement is expected to be finalized in the first quarter of 2016.

On January 25, 2016 The MediGene AG (MDG 1, Frankfurt, Prime Standard), an immune oncology company with clinical development projects focused on developing T-cell-targeted therapy platforms to fight cancer, reported that it is in a collaboration agreement with the University of Lausanne known in Switzerland, which has the goal to establish a better and faster method for selection of tumor-specific T cells (Press release, MediGene, JAN 25, 2016, View Source [SID:1234508854]). These actions deal with T-cell receptors (TCRs) expressing to be transferred to MediGene’s growing TCR library. Through the agreement, MediGene receives access to ultramodern NTAmer technology which is marketed by TCMetrix, a spin-off of the Ludwig Institute for Cancer Research in Lausanne and continuously developed together with leading scientists of the University of Lausanne. Financial details of the agreement were not disclosed.

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Prof. Dolores J. Schendel, Chief Scientific Officer and designated CEO of MediGene AG, comments: "Through this collaboration, we can explore the latest technologies for the completion of our highly innovative TCR platform The NTAmer technology helps us, through the study of living. T cells additional information on the structural avidity [1] to win our T-cell receptors. This helps us to select the optimal TCR antigen sensitivity for our TCR library that we use for the treatment of patients with different MHC build patterns and various cancers. "

Prof. Dr. George Coukos, Professor at the University of Lausanne and director of the Ludwig Institute for Cancer Research in Lausanne adds: "The development of personalized, cell-based immune therapies is a main objective of the Ludwig Institute in Lausanne, since such approaches hold great promise for the treating cancers are. We are pleased about the cooperation with MediGene to its innovative TCR technology and are confident that they will once again be of significant benefit for cancer patients, especially those with advanced and refractory disease. "

As part of the collaboration, scientists of the Department of Oncology at the University of Lausanne will perform kinetic Dissoziationsanalysen on human T cells (T-cells with MediGene’s own TCR candidates) by means of innovative NTAmer technology. This technology determines the so-called structural TCR avidity by measuring dissociation monomeric TCR-peptide-MHC complexes on cell surfaces of TCR-candidates to enable Medi genes for the selection of tumor-specific T cells with an optimal functional avidity for various cancers. The tailored NTAmer reagents are patented and are of TCMetrix Ltd. produced.

About MediGene TCR technology: MediGene’s technology for T cell receptor (TCR) modified T cells is one of the highly innovative and complementary immunotherapy platforms of the company. These adoptive T-cell therapy is designed for the treatment of patients with advanced tumor stages. MediGene is preparing first TCR product candidates for clinical development.

The TCR technology aims to equip the body’s own T cells of patients with tumor-specific T cell receptors. The receptor-modified T-cells are then able to detect tumor cells and efficiently destroy. This immunotherapeutic approach seeks the existing tolerance towards cancer cells and the tumor-induced immunosuppression in patients to overcome by the T cells of the patient are activated and modified outside the body (ex vivo). A large number of specific T-cells, which can fight the tumor, is made available so for patients within a short time.

MediGene is building under this platform to an extensive library of recombinant T cell receptors. In addition, a method for combining these receptors with the patient’s own T cells in accordance with the regulatory GMP standards (Good Manufacturing Practice, GMP) is currently being established.

MediGene is preparing the clinical development of initial product candidates. In addition, new TCRs are specifically isolated and characterized for promising tumor-associated antigens. MediGene is planning in the coming years the development of up to ten lead molecules for TCR technology and strives for this therapeutic approach the launch of up to three clinical trials, one of which is to start first in the first half 2016 (IIT Phase I trial with MediGene participation, subject to public funding). MediGene was responsible and funded studies are expected to begin in the second half of 2017 and the second half of 2018th

On January 25, 2016 OncoMed Pharmaceuticals Inc. (NASDAQ: OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported an update on the Phase 2 ALPINE clinical trial following a pre-planned January 23 interim efficacy assessment of the clinical trial by an independent data safety monitoring board (DSMB) (Filing, 8-K, OncoMed, JAN 25, 2016, View Source [SID:1234508853]). The DSMB assessed data from 172 patients treated as of a January 6, 2016 data cutoff date.

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From a safety standpoint, the DSMB recommended that the study proceed to completion without modification. No unexpected safety findings emerged from its review.

However, the DSMB informed OncoMed of several findings regarding futility of the trial, notably:

• A statistically significant worsening of response rate and progression-free survival (PFS) in the treatment arm in the overall intent-to-treat population, as well as a negative trend in each Notch biomarker subgroup

• A strong trend to lack of benefit in the treatment arm for overall survival (OS), regardless of Notch biomarker levels, suggesting a low probability of achieving a statistically significant OS benefit based on analyses reviewed by the DSMB

Based on this information, OncoMed is in the process of unblinding the trial to carefully assess the current results and determine appropriate next steps for this fully enrolled trial. Eighteen patients remain on study drug treatment (tarextumab or placebo) between 172 and 527 days.

"The findings communicated by the DSMB suggest a low likelihood of a statistically significant benefit in overall survival in the tarextumab ALPINE pancreatic cancer trial," said Paul J. Hastings, Chairman and CEO. "Our aim is to quickly unblind the trial and work with our clinical sites and investigators to verify, analyze, interpret, and fully understand the data, including Notch biomarker subgroup trends, and determine next steps."

The Phase 2 ALPINE trial is a randomized, double-blinded, multicenter clinical trial designed to evaluate the efficacy of tarextumab in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in patients with previously untreated Stage IV pancreatic cancer. The ALPINE study completed enrollment of 177 patients in August 2015. The trial was designed to compare the overall survival of patients receiving tarextumab 15 mg/kg every two weeks versus placebo in combination with Abraxane plus gemcitabine. Secondary and exploratory endpoints, including progression-free survival and overall response rate, pharmacokinetics, safety and other biomarkers, are to be evaluated. Overall survival, progression-free survival and overall response rates will be assessed using a predictive biomarker for high tumor Notch3 expression. Increased Notch3 expression is estimated to occur in approximately 70 percent of pancreatic tumors and is associated with poor patient outcomes.

Conference Call Today

OncoMed management will host a conference call today beginning at 8:30 a.m. ET/5:30 a.m. PT to answer investor and analysts questions regarding the ALPINE Phase 2 program.

Analysts and investors can participate in the conference call by dialing 1-855-420-0692 (domestic) and 1-484-756-4194 (international) using the conference ID# 37742080. The web broadcast of the conference call will be available for replay through February 15, 2016 via a link in the Investor Relations section of the OncoMed website.

About Tarextumab (anti-Notch2/3, OMP-59R5)

Tarextumab (anti-Notch2/3, OMP-59R5) is a fully human monoclonal antibody that targets the Notch2 and Notch3 receptors. Preclinical studies have suggested that tarextumab exhibits two mechanisms of action: (1) by downregulating Notch pathway signaling, tarextumab appears to have anti-cancer stem cell effects, and (2) tarextumab affects pericytes, impacting stromal and tumor microenvironment. Tarextumab is currently being studied in two randomized Phase 2 clinical trials. The "ALPINE" study (Antibody therapy in first-Line Pancreatic cancer Investigating anti-Notch Efficacy and safety) is assessing tarextumab with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in first-line advanced pancreatic cancer patients. The "PINNACLE" study (A Phase 1b/2 Study of OMP-59R5 in Combination with Etoposide and Platinum Therapy in Subjects with Untreated Extensive Stage Small Cell Lung Cancer) is testing tarextumab in combination with etoposide and cisplatin and etoposide and carboplatin in first-line extensive-stage small cell lung cancer patients. Tarextumab is part of OncoMed’s collaboration with GlaxoSmithKline (GSK). GSK has an option to obtain an exclusive license to tarextumab during certain time periods through completion of the proof-of-concept Phase 2 trials.

On January 25, 2016 AstraZeneca together with GlaxoSmithKline and Johnson & Johnson reported that they have partnered with three world-class universities, Imperial College London, the University of Cambridge and University College London (UCL), to create the Apollo Therapeutics Fund (Press release, AstraZeneca, JAN 25, 2016, View Source [SID:1234508852]). This pioneering new consortium aims to convert outstanding academic science from the three universities into innovative medicines for a broad range of diseases.

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The fund will bring academic preclinical research through to the stage of development stage at which it can either be taken forward by one of the industry members following an internal bidding process or be out-licensed. Each industry member will contribute £10 million over 6 years to the venture and may provide in-house expertise and additional resources to assist with the commercial evaluation and development of projects. The Tech Transfer Office (TTO) for each university (Imperial Innovations plc, Cambridge Enterprise and UCL Business) is each contributing a further £3.3 million.

An independent Drug Discovery Team of ex-industry scientists will be employed by the Fund to work with the universities and their TTOs in identifying and shaping projects at an early stage, optimising the chances of their onward development. The Apollo Investment Committee, comprising representatives from each member organisation, will make all investment decisions. All therapy areas and all modalities (including small molecules, peptides, proteins, antibodies, cell and gene therapies) are in scope. For projects that become successful therapies, the originating university and TTO will receive 50% of future commercial revenues or out-licensing fees and the remaining 50% will be divided amongst all Apollo members.

Mene Pangalos, Executive Vice President of Innovative Medicines and Early Development Biotech Unit at AstraZeneca, said: "We’re delighted to be part of The Apollo Therapeutics Fund, which brings together the complementary skills of academia and business. This partnership is another example of our commitment to being an integral part of the research community in the UK and takes a highly innovative approach to sharing both the risks and the rewards of applied research. I am confident that by working with scientists from world leading universities in the UK, we will help convert ground breaking science into important new treatments for patients."