On July 1, 2014 Seragon Pharmaceuticals whereby Seragon will be acquired for $725 million in cash up front along with $1.0 billion in contingent development milestone payments that could bring the total transaction value to $1.725 billion (Press release, Seragon Pharmaceuticals, JUL 1, 2014, View Source [SID:1234503263]). The acquisition includes Seragon’s entire SERD program, including its most advanced compound, ARN-810, a next generation SERD that is currently being evaluated in a Phase I trial in patients with estrogen receptor positive (ER+) metastatic breast cancer.

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Seragon, founded in August 2013, is an independent venture backed biotech company based in San Diego that was spun out of Aragon Pharmaceuticals, following its acquisition by Johnson & Johnson. Following the spin out, Seragon retained many members of the management and R&D team, including Richard A. Heyman, Ph.D., Chief Executive Officer and co-founder of Aragon and Seragon Pharmaceuticals. The Seragon team focused its attention to develop game changing therapies targeting ER+ breast cancer and other estrogen driven cancers including endometrial and ovarian cancers.

"This acquisition represents an ideal transition between biotech and pharma and may provide an optimal outcome for the SERD program and the breast cancer patient community. The Seragon team has been committed to bringing new therapies to cancer patients and we are excited to have Genentech carry forward these programs. Genentech has repeatedly demonstrated its leadership position the oncology field, and their development and commercial capabilities in the breast cancer area are unparalleled," said Rich Heyman.

In the US alone, there are approximately 229,000 new breast cancer diagnoses and 40,000 deaths/year related to breast cancer. The vast majority of these cancers are dependent on estrogen signaling and women with ER+ breast cancer are treated with 1st generation anti-hormonal therapies such as tamoxifen or the aromatase inhibitors. These therapies are initially effective, but many patients experience disease progression due to acquired resistance. Seragon’s SERDs are next generation therapies that have a dual mechanism of action in that they both bind to the estrogen receptor to antagonize hormone action, and they promote receptor degradation. These SERDs are initially being developed for the treatment of women with late-stage, progressive ER+ metastatic breast cancer, but they also have potential in treating patients with early-stage breast cancer. Furthermore they also may offer an opportunity to be the cornerstone for future combination therapies.

"I would like to sincerely acknowledge Rich and the entire Seragon team for their commitment and dedication in advancing the ground breaking science behind both Seragon and Aragon. In just five years since the founding of Aragon, in The Column Group’s offices, this team has advanced multiple compounds from an early idea to a clinical development program targeting hormone dependent cancers. I would also like to thank Dr. Charles Sawyers for his foundational work helping to elucidate the molecular determinants of resistance for hormone dependent prostate cancer. This is an ideal path, which will hopefully translate to improving the lives of patients," said Peter Svennilson, Founder and Managing Partner of The Column Group and Chairman of both Seragon and former Chairman of Aragon.

The closing of the transaction is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act. The transaction is expected to close in the third quarter of 2014.

Wilson Sonsini Goodrich & Rosati served as legal advisor to Seragon Pharmaceuticals in this transaction.

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.

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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.

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.

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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.

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]).

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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."

On June 27, 2014 Roche reported that the EU Committee for Medicinal Products for Human Use (CHMP) recommended that the European Commission approve the use of Avastin (bevacizumab) in combination with chemotherapy as a treatment for women with ovarian cancer that is resistant to platinum-containing chemotherapy (Press release Hoffmann-La Roche, JUN 26, 2014, View Source [SID:1234500690]). Ovarian cancer has the highest mortality rate of all gynaecological cancers.1 Of the 230,000 women diagnosed worldwide each year many will have advanced disease that will return after initial treatment.

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"Women with platinum-resistant ovarian cancer have limited medicines available for their difficult disease," said Sandra Horning M.D., Chief Medical Officer and Head, Global Product Development. "EU approval of Avastin for platinum-resistant ovarian cancer would be an important step in helping these women live longer without their disease progressing, and we look forward to receiving the final decision from the European Commission in the coming months."

When treating recurrent ovarian cancer, the time between receiving the last dose of platinum-based chemotherapy and disease recurrence is used to help determine the choice of chemotherapy used in the next line of treatment. Patients are said to have ‘platinum-resistant’ disease if their disease worsens between one and six months following completion of their platinum-based chemotherapy, and ‘platinum-sensitive’ disease if it worsens more than six months after. A quarter of those who relapse after initial treatment – nearly 60,000 women a year globally – will have platinum-resistant cancer, the most difficult to treat form of the disease. Median overall survival of patients with platinum-resistant ovarian cancer is approximately 12 months, and novel strategies are needed.

Ovarian cancer is associated with high concentrations of vascular endothelial growth factor (VEGF), a protein linked to tumour growth and spread. Studies have shown a correlation between a high concentration of VEGF and ascites development (excess fluid in the abdominal cavity), disease worsening, and a poorer prognosis in women with ovarian cancer. Avastin is designed to specifically target VEGF and is currently the only targeted therapy approved by the European Medicines Agency (EMA) for ovarian cancer. Avastin is EU approved as a front-line (first line following surgery) treatment of advanced ovarian cancer, and as a treatment for recurrent, platinum-sensitive ovarian cancer.

The new EU filing was based on results of the phase III AURELIA study which involved women with recurrent, platinum-resistant ovarian cancer who received either chemotherapy (weekly paclitaxel, topotecan or pegylated liposomal doxorubicin) or Avastin added to chemotherapy.4 Results showed that at a median follow-up of 13 months for women who had received chemotherapy alone and 13.9 months for those who had received the combination, the addition of Avastin to chemotherapy gave a clinically meaningful benefit, nearly doubling the median PFS from 3.4 months to 6.7 months (HR=0.38, p<0.0001).4,6 AURELIA is the fourth phase III study of Avastin in ovarian cancer (following GOG 0218, ICON7 and OCEANS) to show that adding Avastin to chemotherapy significantly increased the time women with ovarian cancer lived without their disease getting worse.
AURELIA additional study results

Women with recurrent, platinum-resistant ovarian cancer who received Avastin in combination with chemotherapy (weekly paclitaxel, topotecan or pegylated liposomal doxorubicin) had a median overall survival of 16.6 months compared to 13.3 months for women treated with chemotherapy alone (HR=0.87, p=0.27).
In addition, women who received Avastin in combination with chemotherapy had a significantly higher rate of tumour shrinkage (objective response rate, ORR) compared to women who received chemotherapy alone (28.2 percent versus 12.5 percent, p=0.0007).
The results of prespecified Quality of Life (QoL) analyses indicated that the benefits of Avastin in AURELIA extended beyond the prolongation of PFS to include greater improvements in ovarian cancer associated abdominal/gastrointestinal symptoms.
No new safety findings were observed in the AURELIA study and adverse events were consistent with those seen in previous trials of Avastin across tumour types for approved indications.4

About the AURELIA study

AURELIA is a multicentre, randomised, open-label, two-arm phase III study in 361 women with platinum-resistant recurrent epithelial ovarian, primary peritoneal or fallopian tube cancer. Women in AURELIA had received no more than two anticancer regimens prior to enrolment in the trial. The trial was designed to evaluate Avastin (10mg/kg every two weeks or 15mg/kg every three weeks) in combination with standard chemotherapy (either weekly paclitaxel or topotecan or pegylated liposomal doxorubicin) compared to standard chemotherapy alone.

The trial was set up in cooperation with the Group d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens (GINECO) and was conducted by the international network of the Gynecologic Cancer Intergroup (GCIG) and the pan-European Network of Gynaecological Oncological Trial Groups (ENGOT). The primary endpoint of the study was progression-free survival. The secondary endpoints of the study included overall survival, objective response rate, Quality of Life, safety and tolerability.