On May 9, 2015 Boehringer Ingelheim reported the enrolment of the first patient in the global Phase III trial evaluating the efficacy and safety of nintedanib in combination with pemetrexed/cisplatin, followed by continuing nintedanib monotherapy, as a first-line treatment for patients with unresectable malignant pleural mesothelioma (MPM) (Press release, Boehringer Ingelheim, MAY 9, 2016, View Source [SID:1234512157]). Patients will qualify for enrolment in the trial if they are not eligible to undergo surgical resection, have received no prior first-line therapies for MPM and hold an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

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Lead investigator, Professor Giorgio V. Scagliotti, Chair of the Department of Oncology, University of Torino, Italy, commented, "Malignant pleural mesothelioma is a rare cancer and despite years of research, patients continue to have a poor prognosis – less than 10% survive for five years following diagnosis. Due to the mode of action of nintedanib, it has the potential to be an effective treatment option for patients with pleural mesothelioma."

LUME-Meso [NCT01907100] will randomise 397 patients in a double-blind, multi-centre, global comparison of nintedanib in combination with pemetrexed/cisplatin or matching placebo in combination with pemetrexed/cisplatin as a first-line treatment. For patients whose disease has not progressed after a maximum of six cycles of chemotherapy, nintedanib or matching placebo will continue to be administered orally as a monotherapy on a daily basis, until disease progression or unmanageable side effects. The primary endpoint of the trial is progression-free survival and overall survival is the key secondary endpoint. Other secondary endpoints include objective tumour response and disease control.

Through its mode of action nintedanib targets the receptors of the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF) and proto-oncogene tyrosine-protein kinase (Src) pathways which play a role in tumour growth and the development of metastasis in MPM. No targeted therapies are currently approved for the treatment of this rare and difficult-to-treat cancer.

Dr Jörg Barth, Corporate Senior Vice President, Therapy Area Head Oncology, Boehringer Ingelheim said, "Over the last few years Boehringer Ingelheim has accumulated considerable expertise in the field of thoracic oncology. With the approval of Giotrif and Vargatef as well as a broad clinical pipeline we are building up a strong presence in this setting. The effort to develop a potential efficacious treatment for malignant pleural mesothelioma demonstrates our long-term commitment for patients with significant unmet medical need."

Nintedanib is also being evaluated in the LUME-Colon 1 trial [NCT02149108], a global Phase III trial in patients with advanced colorectal cancer. Recruitment is now complete and data are expected to be available later in 2016.

Nintedanib (Vargatef) in combination with docetaxel was approved in the EU in 2014 for use in adults with locally advanced, metastatic or locally recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma tumour histology after first-line chemotherapy.

* Nintedanib is approved in the EU under the brand name Vargatef for use in combination with docetaxel in adult patients with locally advanced, metastatic or locally recurrent NSCLC of adenocarcinoma tumour histology after first-line chemotherapy. Nintedanib is under regulatory review by health authorities in other countries outside the EU. Nintedanib is not approved in other oncology indications.

On May 9, 2016 X4 Pharmaceuticals, a clinical stage biotechnology company developing novel CXCR4 inhibitor drugs to improve immune cell trafficking and increase the ability for T-cells to track and destroy cancer, reported dosing of the first patient in a Phase 1/2 study of X4P-001, the Company’s lead CXCR4 inhibitor, in patients with advanced clear cell renal cell carcinoma (ccRCC) (Press release, X4 Pharmaceuticals, MAY 9, 2016, View Source [SID:1234512156]).

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The Phase 1 portion of the study will test the safety and tolerability of escalating doses of X4P-001 in combination with Inlyta (axitinib), a kinase inhibitor approved for the treatment of advanced RCC after failure of one prior systemic therapy. The study is designed to establish a maximum tolerated dose (MTD), or a recommended dose if the MTD is not achieved, for the drug combination. Preliminary results from the Phase 1 portion of the study are expected in early 2017, followed by the initiation of the Phase 2 portion of the study. Multiple U.S. cancer centers with leading renal cell carcinoma researchers will participate in the study. Pfizer is providing axitinib for use in the study.

"Many ccRCC patients do not achieve durable responses when treated with the currently approved targeted therapies or immunotherapies" said David McDermott, M.D, study investigator and lead of the Dana Farber/Harvard Cancer Center Kidney Cancer Program. "Based on the pre-clinical evidence in models of kidney cancer and a safety profile generated in prior clinical studies, X4P-001 has the potential to provide a meaningful new treatment option for ccRCC patients in combination with axitinib."

"Since our recent Series A financing, our team at X4 has rapidly executed on our clinical plan to initiate the study of X4P-001 as a potential treatment for patients with advanced ccRCC, a cancer with serious unmet needs." said Paula Ragan, PhD, President and CEO of X4. "Given the growing evidence that CXCR4 inhibition plays an important role modulating the tumor microenvironment, we see this as the beginning of multiple opportunities that we will pursue with our portfolio of CXCR4 inhibitors."

About X4P-001

X4P-001 is an oral, small molecule inhibitor of CXCR4, or C-X-C receptor type 4, the receptor for the chemokine CXCL12 (also known as stromal derived factor-1, or SDF-1). Recent studies demonstrate that CXCR4/CXCL12 is a primary receptor-ligand pair that cancer cells and surrounding stromal cells use to block normal immune function and promote angiogenesis through the trafficking of T-effector and T-regulatory cells, as well as myeloid derived suppressor cells (MDSCs), in the tumor microenvironment.1, 2 Pre-clinical studies have demonstrated X4P-001 activity alone and in combination with approved cancer therapies including tyrosine kinase inhibitors and checkpoint inhibitors resulted in an increased tumor-specific immune response and significant delays in tumor growth. X4P-001 was previously tested in over 70 subjects in four prior clinical trials in healthy volunteers and HIV-infected patients and was shown to be safe and well tolerated.

About Renal Cell Carcinoma

Kidney cancer is among the ten most common cancers in both men and women with more than 60,000 new diagnoses each year in the United States.3 Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, and advanced ccRCC accounts for approximately 20% of the patient population. Therapies for advanced ccRCC include immunotherapies, mammalian target of rapamycin (mTOR) kinase inhibitors, and angiogenesis inhibitors, such as vascular endothelial growth factor (VEGF) inhibitors.4 There continue to be unmet medical needs with advanced ccRCC because durable responses remain a serious clinical challenge for patients with advanced disease.

On May 09, 2016 NewLink Genetics Corporation (NASDAQ:NLNK) reported results of its Phase 3 clinical trial for algenpantucel-L for patients with resected pancreatic cancer (Press release, NewLink Genetics, MAY 9, 2016, View Source [SID:1234512136]).

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The IMPRESS Phase 3 study of algenpantucel-L for patients with resected pancreatic cancer did not achieve its primary endpoint. Overall survival from time of randomization was 29.3 months for both groups combined. There was no statistically significant difference between the two groups. The median survival was 30.4 months and 27.3 months for the control and study groups, respectively. There was also no statistical difference for long-term survival. Three year survival was 41.4% and 42.1% and four year survival was 32.6% and 32.7% for the control and study groups, respectively.

"We are deeply disappointed for patients that the IMPRESS Phase 3 study was not successful," said Nicholas N. Vahanian, M.D., President and Chief Medical Officer of NewLink Genetics. "We want to extend our sincere appreciation to all the patients, caregivers, investigators, research nurses, employees and others who contributed to the study. Given these results, we are evaluating the future of the HyperAcute platform. We remain committed to achieving our mission of developing immunotherapies to bring patients with cancer better treatment options."

The IMmunotherapy for Pancreatic RESectable cancer Study (IMPRESS) trial is a randomized, controlled, two-arm Phase 3 trial for patients with resected pancreatic cancer testing algenpantucel-L (300M cells every two weeks for six months followed by every month for another six months) in combination with the standard of care versus standard of care alone. A total of 722 patients with surgically removed cancers were enrolled at more than 70 sites in the United States from May 2010 to September 2013.

"Immunotherapy is rapidly establishing a role in the management of multiple malignancies," said George Fisher, M.D., Ph.D., Professor of Medicine at Stanford University, one of the investigators in the IMPRESS study. "The median overall survival of 29.3 months in this study represents a significant increase compared with prior trials and may be due to multiple factors, including the emergence of more effective treatment regimens for recurrent or metastatic disease. Although a negative study, these results represent an important and meaningful contribution to the understanding of the modern treatment of resected pancreatic cancer."

"In light of these negative results, our scientific and clinical teams will focus on other promising opportunities in our pipeline," said Charles Link, Jr., M.D., Chairman and Chief Executive Officer. "Our lead projects focus on our IDO checkpoint inhibitor technology employing indoximod and GDC-0919. We have substantial near-term catalysts in 2016 for these IDO inhibitor programs, including multiple trial updates from our proprietary and partnered IDO pathway inhibitors, and the financial resources to realize the potential of our product pipeline."

NewLink Genetics ended the first quarter on March 31, 2016, with cash, cash equivalents, and certificates of deposit totaling $178 million. The Company reiterates that its goal and expectation is to finish 2016 with two years of cash on hand.

Om May 9, 2016 Epizyme, Inc. (NASDAQ:EPZM), a clinical stage biopharmaceutical company creating novel epigenetic therapies for people with cancer, reported that it has entered into a collaboration agreement with the Lymphoma Study Association (LYSA) to investigate the combination of tazemetostat with R-CHOP as a front-line treatment in patients with diffuse large B-cell lymphoma (DLBCL) (Press release, Epizyme, MAY 9, 2016, View Source [SID:1234512113]).

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LYSA is a premier cooperative group in France dedicated to clinical and translational research for lymphoma, and is certified by the French National Cancer Institute. Under the agreement, the phase 1b/2 trial will be jointly conducted with the Lymphoma Academic Research Organisation (LYSARC), the operational arm of LYSA.

"We are pleased to have established a collaboration with LYSA and to conduct the first investigation of tazemetostat in the front-line treatment setting," said Robert Bazemore, President and Chief Executive Officer, Epizyme. "This study agreement aligns with Epizyme’s strategy of partnering with world-class research organizations to accelerate our development programs. The planned combination trial builds on preclinical evidence of synergy between tazemetostat and R-CHOP, and will add to what we know about the utility of tazemetostat in patients with non-Hodgkin lymphoma."

The open-label, clinical study will be sponsored by LYSARC and conducted at multiple sites in France. The study will enroll elderly, high-risk patients with newly diagnosed DLBCL, the most common form of non-Hodgkin lymphoma. Patients will receive tazemetostat in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), a standard treatment in newly diagnosed DLBCL. Epizyme and LYSARC jointly designed the study, which is expected to begin enrolling patients mid-year.

About the Tazemetostat Clinical Trial Program
Tazemetostat, a first-in-class EZH2 inhibitor, is currently being studied in ongoing phase 2 programs in both non-Hodgkin lymphoma and certain genetically defined solid tumors, including INI1-negative and SMARCA4-negative tumors and synovial sarcoma.

The company has announced plans to initiate additional clinical evaluations of tazemetostat in 2016, including a combination study with an immune checkpoint inhibitor in patients with NHL and a monotherapy study in adults with mesothelioma.

On May 9, 2016 Incyte Corporation (Nasdaq:INCY) and ARIAD Pharmaceuticals, Inc. (Nasdaq:ARIA) reported the entry into a definitive agreement for Incyte to acquire ARIAD’s European operations (Press release, Ariad, MAY 9, 2016, View Source [SID:1234512107]). At the close of the transaction, the companies will also enter into a license agreement whereby Incyte will obtain an exclusive license to develop and commercialize Iclusig (ponatinib) in Europe and other select countries.

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The planned acquisition of a fully-integrated and established pan-European team of 125 employees, including medical, sales and marketing personnel, will further Incyte’s strategic plan and accelerate the establishment of its operations in Europe, helping to optimize clinical development and maximize the potential of future European launches for Incyte’s portfolio of products in development.

The agreement to divest its European operations and out-license Iclusig in Europe will enable ARIAD to focus its promotion of Iclusig on the highly valuable U.S. market, while strengthening its financial position and maintaining important optionality through a potential buy-back provision for the Iclusig license rights in the event of a change-in-control of ARIAD, as described further below.

Under the terms of the license agreement, Incyte will receive an exclusive license to develop and commercialize Iclusig, the only approved BCR-ABL inhibitor with activity against the T315I mutation, throughout Europe and in other select countries. Iclusig is approved in Europe for the treatment of patients with chronic myeloid leukemia (CML) and Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) who are resistant to or intolerant of certain second generation BCR-ABL inhibitors and all patients who have the T315I mutation.

"The acquisition of ARIAD’s European operations is a unique and strategic opportunity for Incyte, which will further establish our medical and commercial footprint in Europe," said Hervé Hoppenot, chief executive officer of Incyte. "Adding the ARIAD team’s experience, talent, resources and relationships to our existing European organization accelerates our planned global expansion and leaves us well-positioned to maximize the potential future European launches from our rich development portfolio."

"The decision to divest our European operations and out-license the commercial rights to Iclusig in Europe is one of the key outcomes of our ongoing strategic review," stated Paris Panayiotopoulos, president and chief executive officer of ARIAD. "We are delighted to have Incyte as a committed partner to continue Iclusig’s strong revenue growth in Europe, while significantly strengthening our financial position and maintaining future strategic optionality with a potential buy-back of Iclusig."

Terms of the Agreements

Pursuant to the terms of a share purchase agreement (the "SPA"), Incyte will acquire all shares of ARIAD Pharmaceuticals (Luxembourg) S.a.r.l., the parent company of ARIAD’s European subsidiaries responsible for the commercialization of Iclusig in the licensed territory, for a payment to ARIAD of $140 million that will be funded by Incyte through available cash on hand.

In addition to the SPA, the parties have agreed to enter into a license agreement (the "License Agreement"), upon the closing of the SPA, pursuant to which Incyte will be granted an exclusive license to develop and commercialize Iclusig in the European Union and 22 other countries, including Switzerland, Norway, Turkey, Israel and Russia. ARIAD will be entitled to receive tiered royalties of between 32 and 50 percent on net sales of Iclusig in the territory and up to $135 million in potential development and regulatory milestones for Iclusig in new oncology indications in the territory. ARIAD may also become eligible to receive additional milestones for non-oncology indications, if approved, in the territory. Incyte has also agreed to fund a portion of the ongoing clinical development of Iclusig in ARIAD’s OPTIC and OPTIC-2L clinical trials through cost-sharing payments of up to $7 million in each of 2016 and 2017.

The terms of the License Agreement also include an option for an acquirer of ARIAD to buy back the rights to Iclusig by repaying the upfront and milestone payments, plus paying an additional amount based on Iclusig sales during the previous 12 months and royalties of 20 to 25 percent on sales for the remaining royalty term. The buy-back provision cannot be exercised before two years or after six years from the closing of this transaction, and includes a transition period of up to one year.

The transaction is expected to close on or about June 1, 2016, subject to customary closing conditions, and is expected to reduce ARIAD’s 2017 annual operating expenses by approximately $65 million. The transaction is expected to be earnings accretive for Incyte in 2018.

Both Incyte and ARIAD expect to file additional disclosure documents with the Securities and Exchange Commission related to this transaction.

About CML and Ph+ ALL

CML is a cancer of the white blood cells that is diagnosed in approximately 7,000 patients each year in Europe1. CML is characterized by an excessive and unregulated production of white blood cells by the bone marrow due to a genetic abnormality that produces the BCR-ABL protein. After a chronic phase of production of too many white blood cells, CML typically evolves to the more aggressive phases referred to as accelerated phase and blast crisis. Ph+ ALL is a subtype of acute lymphoblastic leukemia that carries the Ph+ chromosome that produces BCR-ABL. It has a more aggressive course than CML and is often treated with a combination of chemotherapy and tyrosine kinase inhibitors. The BCR-ABL protein is expressed in both of these diseases.

About Iclusig (ponatinib) tablets

Iclusig is a kinase inhibitor. The primary target for Iclusig is BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Iclusig was designed using ARIAD’s computational and structure-based drug-design platform specifically to inhibit the activity of BCR-ABL. Iclusig targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs.

Iclusig is approved in the U.S., EU, Australia, Switzerland, Israel and Canada.

In the U.S., Iclusig is a kinase inhibitor indicated for the:

Treatment of adult patients with T315I-positive chronic myeloid leukemia (chronic phase, accelerated phase, or blast phase) or T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).

Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated.

These indications are based upon response rate. There are no trials verifying an improvement in disease-related symptoms or increased survival with Iclusig.

IMPORTANT SAFETY INFORMATION, INCLUDING THE BOXED WARNING

WARNING: VASCULAR OCCLUSION, HEART FAILURE, and HEPATOTOXICITY

See full prescribing information for complete boxed warning

Vascular Occlusion: Arterial and venous thrombosis and occlusions have occurred in at least 27% of Iclusig treated patients, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Patients with and without cardiovascular risk factors, including patients less than 50 years old, experienced these events. Monitor for evidence of thromboembolism and vascular occlusion. Interrupt or stop Iclusig immediately for vascular occlusion. A benefit risk consideration should guide a decision to restart Iclusig therapy.

Heart Failure, including fatalities, occurred in 8% of Iclusig-treated patients. Monitor cardiac function. Interrupt or stop Iclusig for new or worsening heart failure.

Hepatotoxicity, liver failure and death have occurred in Iclusig-treated patients. Monitor hepatic function. Interrupt Iclusig if hepatotoxicity is suspected.

Please see the full U.S. Prescribing Information for Iclusig, including the Boxed Warning, for additional important safety information.

In the EU, Iclusig is approved for the treatment of adult patients with chronic phase, accelerated phase or blast phase chronic myeloid leukemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation, or the treatment of adult patients with Philadelphia-chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation.

Click here to view the Iclusig EU Summary of Medicinal Product Characteristics. Click here to view the EU Dear Healthcare Provider Letter (PDF).