1stOncology™: Cancer Intelligence Service – Page 18219 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

RedHill Biopharma Acquires Phase II Oncology Drug MESUPRON from WILEX AG

On June 30, 2014 RedHill Biopharma Ltd. (NASDAQ: RDHL; TASE: RDHL) ("RedHill"), an Israeli biopharmaceutical company focused on late clinical-stage drugs for inflammatory and gastrointestinal diseases, including cancer, and WILEX AG (ISIN DE0006614720 / WL6 / FSE) ("WILEX"), a biopharmaceutical company focused on oncology, based in Munich, Germany, reported that they have signed an exclusive license agreement for the oncology drug candidate MESUPRON (Press release, RedHill Biopharma, JUN 30, 2014, View Source;LNGID=1&TMID=178&FID=1342&PID=0&IID=1857 [SID1234517321]). The MESUPRON small molecule (INN: Upamostat) is a proprietary, first-in-class, urokinase-type plasminogen activator (uPA) inhibitor administered by oral capsule. Wilex has completed several clinical studies with MESUPRON in different indications, including two Phase II proof of concept studies for pancreatic cancer and metastatic breast cancer.

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!

Under the terms of the agreement, RedHill acquired the exclusive development and commercialization rights to MESUPRON, excluding China, Hong Kong, Taiwan and Macao, for all indications. RedHill will pay Wilex an upfront payment of USD 1 million and potential tiered royalties on net revenues, ranging from mid-teens up to 30%. RedHill will be responsible for all development, regulatory and commercialization of MESUPRON.

MESUPRON inhibits the uPA system, which has been shown to play a key role in tumor cell growth, invasion and the metastasis process. High uPA levels are associated with poor prognosis in various solid tumor cancers, such as pancreatic, gastric, breast and prostate cancers. MESUPRON presents a promising new non-cytotoxic approach to cancer therapy with several potential mechanisms of action to inhibit both tumor metastasis and growth. MESUPRON has completed several Phase I studies and two Phase II proof of concept studies. The first Phase II study in locally advanced non-metastatic pancreatic cancer and the second study in metastatic breast cancer, established the drug’s safety and tolerability profile. The Phase II studies with MESUPRON in both indications suggested activity as measured by both tumor response rate and overall survival of patients when administered in combination with first-line chemotherapeutic agents.

Dror Ben-Asher, RedHill’s CEO, said: "The acquisition of MESUPRON reflects our commitment to patients suffering from gastrointestinal and inflammatory diseases, including related cancers such as pancreatic cancer, gastric cancer and colorectal cancer. It adds to RedHill’s pipeline of six late clinical-stage drug candidates and fits well with our risk-mitigating business model. MESUPRON is a unique non-cytotoxic approach targeting oncology indications where there is a very strong demand for better therapeutic options. Thanks to the development work conducted by Wilex, MESUPRON is supported by extensive pre-clinical and clinical data, and we believe in its potential to become an important treatment option for cancer patients. Our experienced development team is enthusiastic to advance this important new drug. We look forward to collaborating with our new partner Wilex and would like to thank them for entrusting us with the development and commercialization of MESUPRON."

About MESUPRON :

MESUPRON is a proprietary, first-in-class urokinase-type plasminogen activator (uPA) inhibitor administered by oral capsule. The uPA system has been shown to play a key role in tumor cell growth, invasion and the metastasis process. High uPA levels are associated with poor prognosis in various solid tumor cancers, such as pancreatic, gastric, breast and prostate cancers. MESUPRON presents a promising new non-cytotoxic approach to cancer therapy with several potential mechanisms of action to inhibit both tumor metastasis and growth. MESUPRON has completed several Phase I studies and two Phase II proof of concept studies. The first Phase II study in locally advanced non-metastatic pancreatic cancer and the second study in metastatic breast cancer, established its safety and tolerability profile. The Phase II studies with MESUPRON in both indications suggested activity as measured by both tumor response rate and overall survival of patients when administered in combination with first-line chemotherapeutic agents.

Boston Strategics Corporation Announces Licensing Deal with Eisai Co., Ltd.

On June 30, 2014 Boston Strategics reported that it has entered into an exclusive licensing and development agreement with Japanese global pharmaceutical company Eisai Co., Ltd., for Eisai’s oncology drug, E6201 (Press release Boston Strategics, JUN 30, 2014, View Source [SID:1234501032]).

E6201 is a dual-targeted FLT3 and MEK inhibitor which has completed a Phase1 clinical trial showing preliminary antitumor activity and an acceptable safety profile. Building on a strong scientific rationale supported by recent preclinical data, BSC will undertake a clinical Proof of Concept (PoC) trial in the high unmet need FLT3 mutated AML patients.

Under this agreement with Eisai, BSC has worldwide rights to develop and commercialize E6201 for all Oncology indications.

This collaboration is a prime example of BSC applying its "True" Open Innovation platform to develop drug candidates with potential to significantly improve patients’ health care. As such it represents the next step toward BSC’s vision to create a novel and comprehensive approach to global pharmaceutical development.

"This is a critical milestone for BSC to validate our concept to move drug development programs forward by increasing the Probability of Success (PoS) and sharing risks with key strategic partners," says Eita Kitayama, President of Boston Strategics. "Eisai recognized the value of this approach and entrusted BSC with the development of E6201 for cancer indications to build on the foundation of this new platform. At BSC, we are deeply committed to proving that our innovative approaches can deliver breakthrough therapies with industry benchmark-beating timelines, quality, and financial investments, thus limiting the ever increasing costs of pharmaceutical innovation and development."

Tolero’s PIM Kinase Inhibitor Demonstrates Promising Activity in Preclinical Models of Urothelial Carcinoma

On June 30, 2014 Tolero Pharmaceuticals reported that recent studies in collaboration with the University of Utah examined the function of PIM kinases in cancer progression and the potential of these kinases to serve as therapeutic targets for treatment (Press release Tolero Pharmaceuticals, JUN 30, 2014, View Source [SID:1234500707]). PIM kinases are upregulated in multiple cancer indications, including lymphoma, leukemia, multiple myeloma, and prostate, gastric, and head and neck cancers. The overexpression of PIM family members often correlates with poor prognosis in tumors.

This work demonstrates that PIM kinases are overexpressed in urothelial carcinomas taken directly from patients and that targeting the PIM kinases with a novel small-molecule inhibitor (TP-3654) reduces the growth of solid tumor xenografts where the tumorigenicity is mediated by overexpression of PIM-1 or PIM-2, as well as human bladder carcinoma tumors. TP-3654 is poised to enter IND-enabling studies and Phase I clinical testing in solid tumors and hematological malignancies.

"These data support the long-standing effort to target cell survival kinases and may provide patients with new approaches to combat difficult to treat cancers, such as bladder carcinoma. Tolero is advancing TP-3654 to further validate the PIM kinases as therapeutic targets in the clinical setting," said Steven L. Warner, PhD, Vice President of Discovery and Development at Tolero Pharmaceuticals.

Tolero is also evaluating the utility of TP-3654 in skin inflammatory conditions, such as psoriasis.

Merck’s Investigational Anti-PD-1 Antibody, Pembrolizumab, Under Regulatory Review in Europe for the Treatment of Advanced Melanoma

On June 30, 2014 Merck & Co reported that the European Medicines Agency (EMA) has accepted for review a Marketing Authorization Application (MAA) for pembrolizumab (MK-3475), the company’s investigational anti-PD-1 antibody, for the treatment of advanced melanoma. If approved by the European Commission (EC), pembrolizumab has the potential to be the first anti-PD-1 therapy in Europe (Press release Merck & Co, JUN 30, 2014, View Source [SID:1234500606]). Additional regulatory filings in other countries outside of Europe are planned by the end of 2014.

“With the five-year survival rate for patients with advanced melanoma at less than 20 percent, there remains a need to offer patients additional options,” said Dr. Roy Baynes, senior vice president, clinical development, Merck Research Laboratories. “We are pleased to have regulatory applications under review in the United States and Europe as we work toward bringing pembrolizumab to patients around the world.”

Pembrolizumab (MK-3475) is an investigational, selective, humanized, monoclonal anti-PD-1 antibody designed to reactivate anti-tumor immunity. Pembrolizumab exerts dual ligand blockade of the PD-1 pathway by inhibiting the interaction of PD-1 on T cells with its ligands PD-L1 and PD-L2.

Today, pembrolizumab is being evaluated across more than 30 types of cancers, as monotherapy and in combination. It is anticipated that by the end of 2014, the pembrolizumab development program will grow to more than 24 clinical trials, enrolling an estimated 6,000 patients at nearly 300 clinical trial sites worldwide.

The Biologics License Application (BLA) for pembrolizumab is under priority review with the U.S. Food and Drug Administration (FDA) for the treatment of patients with advanced melanoma previously-treated with ipilimumab; the PDUFA date is October 28, 2014. Pembrolizumab has been granted FDA’s Breakthrough Therapy designation for advanced melanoma. If approved by the FDA, pembrolizumab has the potential to be the first anti-PD-1 therapy approved within the United States.

GSK and Genmab announce top-line results from a Phase III study of ofatumumab versus physicians’ choice for bulky fludarabine-refractory CLL

On June 27, 2014 GlaxoSmithKline and Genmab reported that the Phase III study of ofatumumab (Arzerra) versus physicians’ choice in patients with bulky fludarabine-refractory chronic lymphocytic leukaemia (CLL) did not meet its primary endpoint of progression free survival (PFS) (Press release Genmab, JUN 27, 2014, View Source [SID:1234500604]). The median PFS, as assessed by the Independent Review Committee, was 5.36 months for ofatumumab and 3.61 months for physicians’ choice (Hazard Ratio 0.79, p=0.267).

The result reported here is headline data; the full analysis of safety and efficacy data is underway and will be completed in the coming months. This study (OMB114242) was conducted to meet the requirements from the EU Commission for the conditional approval of ofatumumab for the treatment of CLL in patients who are refractory to fludarabine and alemtuzumab. The current indications in the EU or US do not include bulky fludarabine-refractory CLL patients.

“It was our priority to share this result with the scientific community as soon it became available. We will now work to further analyse the data and to better understand the totality of the efficacy and safety findings,” said Dr. Rafael Amado, Head of Oncology R&D at GSK. “We are very grateful to the CLL patients who participated in this trial.”

“Although ofatumumab performed broadly in-line with previous data, today’s result is disappointing. Based on this result, we do not anticipate applying for a label expansion for ofatumumab in this specific refractory CLL population,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the study
This Phase III open-label study randomised 122 patients with bulky fludarabine-refractory CLL to one of two treatment arms. Patients were randomised to either ofatumumab or physicians’ choice (2:1). Patients randomised to ofatumumab received an initial dose of 300 mg, followed 1 week later by 2,000 mg once weekly for 7 weeks, followed 4 weeks later by one infusion of 2,000 mg every 4 weeks for a total treatment duration of 6 to 12 months. Patients in the physicians’ choice arm received a treatment regimen chosen by a physician for up to six months.

The primary endpoint of the study was progression free survival as adjudicated by the Independent Review Committee. Secondary objectives are to evaluate response, overall survival, safety, tolerability and health-related quality of life of subjects treated with ofatumumab versus physicians’ choice of treatment.