On August 28, 2017 VBI Vaccines Inc. (Nasdaq: VBIV) (TSX: VBV) (VBI), reported that David Anderson, Ph.D., Chief Scientific Officer of VBI, will present new preclinical data demonstrating the mechanism by which VBI-1901 stimulates CMV-specific immunity in monkeys at The Immuno-Oncology Summit in Boston on Wednesday, Aug. 28, 2017 (Press release, VBI Vaccines, AUG 28, 2017, View Source [SID1234520322]). VBI-1901 is a novel immunotherapy developed using VBI’s eVLP technology to target CMV-positive (CMV+) tumors, including glioblastoma multiforme (GBM), the company’s lead immuno-oncology program.

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Dr. Anderson will present data in animal models which highlights VBI-1901’s ability to stimulate innate immunity, in turn enhancing the ability to restimulate CMV-specific T-cell immunity. In a preclinical study, CMV+ Rhesus Macaques were given VBI-1901 combined with granulocyte-macrophage colony-stimulating factor (GM-CSF), an adjuvant that recruits dendritic cells to the site of immunization and seeks to enhance immunity. After two doses, boosting of CMV-specific T-cell responses were seen in all animals, an observation consistent with other recent anti-CMV dendritic cell vaccine clinical studies against GBM where meaningful improvement in overall survival was observed.

"Broad evidence, both in preclinical research studies and in several human clinical trials, supports CMV as a cancer immunotherapeutic target and suggests that a CMV-based vaccine which can harness dendritic cells to re-stimulate CMV-specific T-cells has potential to confer positive clinical outcomes," said Dr. Anderson. "Additionally, a growing body of research has demonstrated that multiple tumors, including GBM, are susceptible to infection by CMV and can thus be targeted with CMV-specific immunity. We are very encouraged by these preclinical data, which support the Phase 1/2a clinical trial the company expects to initiate soon."

The FDA recently accepted VBI’s IND for VBI-1901. VBI expects to initiate enrollment in a multi-center Phase I/2a clinical study evaluating VBI-1901 in patients with recurrent GBM in the second half of 2017.

GBM Program Background

Glioblastoma is among the most common and aggressive malignant primary brain tumors in humans. In the U.S. alone, 12,000 new cases are diagnosed each year. The current standard of care for treating GBM is surgical resection, followed by radiation and chemotherapy. Even with aggressive treatment, GBM progresses rapidly and is exceptionally lethal, with median patient survival of less than 16 months.

Targeted immunotherapy may provide a promising adjunct or alternative to conventional GBM treatment. Immunotherapy is a fundamentally different way of treating cancer that stimulates the patient’s immune system to resume its attack on tumors. While conventional therapies are non-specific and may damage surrounding normal tissues, targeted immunotherapy may offer a highly specific and potentially long-lasting treatment approach that leverages the immune system to protect against cancer.

VBI Vaccines Inc. | 222 Third Street, Suite 2241 | Cambridge, MA 02142 | 617-830-3031 | [email protected]

Developing a broadly applicable GBM immunotherapy requires the identification of antigens that are consistently expressed on GBM tumor cells. Recent research has demonstrated that an anti-CMV dendritic cell vaccination regimen may extend overall survival in patients with GBM. Thus, effective targeting of CMV antigens may represent an attractive strategy for a GBM immunotherapy.

To learn more about VBI’s GBM immunotherapy program, visit: View Source

On August 28, 2017 Cascadian Therapeutics, Inc. (NASDAQ:CASC), a clinical-stage biopharmaceutical company, reported posters on tucatinib in multiple tumor types will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress being held September 8-12, 2017 in Madrid, Spain (Press release, Cascadian Therapeutics, AUG 28, 2017, View Source [SID1234520320]).

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Please visit the Cascadian Therapeutics booth #270 at ESMO (Free ESMO Whitepaper) for more information about tucatinib, the Company’s lead product candidate for the treatment of HER2-positive breast cancer being evaluated in a global, randomized pivotal trial known as HER2CLIMB. Abstracts will be available online at View Source Poster presentations will be available at www.cascadianrx.com as of the presentation date.

Poster Presentations

Title: Progression-free survival and site of first progression in HER2-positive metastatic breast cancer patients with or without brain metastases: A pooled analysis of tucatinib phase I studies
Date: Monday, September 11, 2017, 1:15-2:15 p.m. CEST
Poster: 264, Location: Hall 8

Title: Tucatinib, a HER2 selective kinase inhibitor, is active in patient derived xenograft (PDX) models of HER2-amplified colorectal, esophageal and gastric cancers
Date: Monday, September 11, 2017, 1:15-2:15 p.m. CEST
Poster: 1639, Location: Hall 8

Title: Evaluation of drug-drug interactions (DDI) between tucatinib and capecitabine in patients with advanced HER2-positive metastatic breast cancer from a phase 1b study
Date: Monday, September 11, 2017, 1:15-2:15 p.m. CEST
Poster: 297, Location: Hall 8

About Tucatinib

Tucatinib is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER2 without inhibition of the EGFR. Inhibition of EGFR has been associated with clinically relevant toxicities, including skin rash and diarrhea. Tucatinib has shown activity as a single agent and in combination with both chemotherapy and other HER2 directed agents such as trastuzumab and T-DM1.1,2 Studies of tucatinib in these combinations have shown activity both systemically and in brain metastases. HER2 is a growth factor receptor that is overexpressed in multiple cancers, including breast, ovarian and gastric cancers. HER2 mediates cell growth, differentiation and survival. Tumors that overexpress HER2 (HER2-positive) are more aggressive and historically have been associated with poor overall survival, compared with HER2-negative cancers.

On August 28, 2017 AVEO Oncology (NASDAQ: AVEO) reported that the European Commission (EC) has approved FOTIVDA (tivozanib) for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway and Iceland (Press release, AVEO, AUG 28, 2017, View Source [SID1234520319]). Tivozanib is indicated for the first line treatment of adult patients with advanced RCC and for adult patients who are vascular endothelial growth factor receptor (VEGFR) and mTOR pathway inhibitor-naïve following disease progression after one prior treatment with cytokine therapy for advanced RCC.i EUSA Pharma, a specialty pharmaceutical company with a focus on oncology and oncology supportive care, is the European licensee for tivozanib. Tivozanib is an oral, once-daily, potent and highly-selective vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI).

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Dr. Bernard Escudier, Medical Oncologist and member of the Genitourinary Tumour Board of Gustave Roussy, France, commented "This is excellent news for patients with metastatic RCC. Outcomes in this disease have greatly improved with the introduction of targeted therapies, meaning that patients are living for longer. However, we are still in need of effective and well tolerated new treatments in metastatic RCC and thus, tivozanib is a welcomed addition."

The approval from the EC follows the recommendation from the Committee for Medical Products for Human Use (CHMP).i1 The decision was primarily based on data from a global, open-label, randomized, multi-center Phase 3 trial (TIVO-1)i,iii which evaluated the efficacy and tolerability of tivozanib compared to a currently available comparator VEGFR-TKI treatment (sorafenib) in 517 patients with advanced RCC. Patients treated with tivozanib experienced superior PFS (11.9 vs. 9.1 months in the overall population [HR, 0.797; 95% CI, 0.639 to 0.993; P =.042] and 12.7 vs. 9.1 months in treatment naïve patients [HR, 0.756; 95% CI, 0.580 to 0.985; P =.037]) versus sorafenib.iii There was also an improved side effect profile with tivozanib, with only 14% (versus 43% with sorafenib) requiring a dose reduction due to adverse events (AEs). In addition, fewer people on tivozanib experienced burdensome side effects, such as diarrhea (23% vs 33%) and hand-foot syndrome (14% vs 54%).iii

EUSA Pharma has indicated that it intends to now work with the necessary health authorities to make tivozanib available to advanced RCC patients across Europe as quickly as possible.

"The European Commission’s decision is the first regulatory approval of tivozanib globally, and a tremendous accomplishment for AVEO and its partner, EUSA Pharma. We are very pleased that tivozanib is now available to patients in Europe," said Michael Bailey, president and chief executive officer of AVEO. "We also continue to make progress on the next two pillars in our tivozanib strategy: U.S. registration, driven by the pivotal Phase 3 TIVO-3 trial, which is expected to read out in the first quarter of 2018; and immunotherapy combination trials, starting with the TiNivo trial, our Opdivo combination trial. European approval further strengthens our balance sheet by triggering an R&D payment to AVEO and provides AVEO the opportunity to achieve multiple potential commercial milestone payments, as well as royalty payments on sales, that would support our execution of the tivozanib strategy."

Under the terms of their December 2015 agreement, EUSA Pharma has agreed to pay AVEO up to $394 million in future milestone payments and research and development funding, assuming successful achievement of specified development, regulatory and commercialization objectives. In addition, a tiered royalty will be due to AVEO ranging from a low double-digit up to mid-twenty percent on net sales of tivozanib in the agreement’s territories. European marketing approval for tivozanib triggers a $4 million research and development payment from EUSA, and AVEO will also be eligible for up to $12 million in additional milestones from EUSA based on reimbursement and regulatory approvals. In the territories licensed to EUSA, thirty percent of milestone and royalty payments received by AVEO, excluding research and development funding, are due to Kyowa Hakko Kirin (KHK) as a sublicensing fee. In the territories retained by AVEO, the royalty obligation to KHK ranges from the low- to mid-teens on net sales.

About RCC in Europe

RCC is the most common form of kidney cancer,iv which accounts for an estimated 49,000 deaths in Europe each year.v It is expected to be one of the fastest increasing cancers over the next ten years.vi Tyrosine Kinase Inhibitor (TKI) vascular endothelial growth factor (VEGF) inhibitors are the standard of care treatment for advanced RCC in Europe, however, patients on current treatments can often experience significant side effects.iii,vii

About Tivozanib (FOTIVDA)

Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Hakko Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma in the European Union plus Norway and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications. Tivozanib has been investigated in several tumors types, including renal cell, colorectal and breast cancers.

On August 28, 2017 Gilead Sciences, Inc. (Nasdaq: GILD) and Kite Pharma, Inc. (Nasdaq: KITE) reported that the companies have entered into a definitive agreement pursuant to which Gilead will acquire Kite for $180.00 per share in cash (Press release, Kite Pharma, AUG 28, 2017, View Source [SID1234520318]). The transaction, which values Kite at approximately $11.9 billion, was unanimously approved by both the Gilead and Kite Boards of Directors and is anticipated to close in the fourth quarter of 2017. The transaction will provide opportunities for diversification of revenues, and is expected to be neutral to earnings by year three and accretive thereafter.

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Kite is an industry leader in the emerging field of cell therapy, which uses a patient’s own immune cells to fight cancer. The company has developed engineered cell therapies that express either a chimeric antigen receptor (CAR) or an engineered T cell receptor (TCR), depending on the type of cancer. Kite’s most advanced therapy candidate, axicabtagene ciloleucel (axi-cel), is a CAR T therapy currently under priority review by the U.S. Food and Drug Administration (FDA). It is expected to be the first to market as a treatment for refractory aggressive non-Hodgkin lymphoma, which includes diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL) and primary mediastinal B-cell lymphoma (PMBCL). The FDA has set a target action date of November 29, 2017 under the Prescription Drug User Fee Act (PDUFA). A marketing authorization application (MAA) has also been filed for axi-cel for the treatment of relapsed/refractory DLBCL, TFL and PMBCL with the European Medicines Agency (EMA), representing the first submission in Europe for a CAR T therapy. Approval in Europe is expected in 2018. Kite has additional candidates in clinical trials in both hematologic cancers and solid tumors, including KITE-585, a CAR T therapy candidate that targets BCMA expressed in multiple myeloma.

"The acquisition of Kite establishes Gilead as a leader in cellular therapy and provides a foundation from which to drive continued innovation for people with advanced cancers," said John F. Milligan, PhD, Gilead’s President and Chief Executive Officer. "The field of cell therapy has advanced very quickly, to the point where the science and technology have opened a clear path toward a potential cure for patients. We are greatly impressed with the Kite team and what they have accomplished, and share their belief that cell therapy will be the cornerstone of treating cancer. Our similar cultures and histories of driving rapid innovation in order to bring more effective and safer products to as many patients as possible make this an excellent strategic fit."

Research and development as well as the commercialization operations for Kite will remain based in Santa Monica, California, with product manufacturing remaining in El Segundo, California.

"From the release of our pivotal data for axi-cel, to our potential approval by the FDA, this is a year of milestones. Each and every accomplishment is a reflection of the talent that is unique to Kite. We are excited that Gilead, one of the most innovative companies in the industry, recognized this value and shares our passion for developing cutting-edge and potentially curative therapies for patients," said Arie Belldegrun, MD, FACS, Chairman, President and Chief Executive Officer of Kite. "CAR T has the potential to become one of the most powerful anti-cancer agents for hematologic cancers. With Gilead’s expertise and support, we hope to fulfill that potential by rapidly accelerating our robust pipeline and next-generation research and manufacturing technologies for the benefit of patients around the world."

Benefits of the Transaction

Near-term Product Opportunity

Axi-cel approval for refractory aggressive non-Hodgkin lymphoma is expected in Q4 2017 in the United States and in 2018 in Europe
U.S. commercial launch and manufacturing preparations complete
Building infrastructure in Europe
Robust Pipeline and Technology Platform to Drive Future Growth

Multiple development programs ongoing to broaden axi-cel utilization in earlier lines of therapy in aggressive NHL and other B-cell malignancies
Advancing additional CAR Ts to treat multiple myeloma and acute myeloid leukemia
Progressing TCRs for potential use in solid tumors
Positions Gilead to be a Global Leader in Oncology and Cell Therapy

Cell therapy has generated compelling clinical data in patients for whom all other treatments have failed
Axi-cel, coupled with Kite’s leading manufacturing capabilities and its portfolio of next-generation technologies and therapy candidates, will serve as a foundation for Gilead’s efforts to build an industry-leading cell therapy franchise
Leverages Gilead’s Core Capabilities to Maximize the Value of Kite’s Portfolio

Ability to drive continuous scientific and medical innovation that improves or replaces existing products
Demonstrated ability to scale complicated manufacturing processes to meet patient demand
Rapid design and execution of clinical development programs that shorten development timelines
Successful track record of launching innovative, specialty medicines
Transaction Terms

Under the terms of the merger agreement, a wholly-owned subsidiary of Gilead will promptly commence a tender offer to acquire all of the outstanding shares of Kite’s common stock at a price of $180.00 per share in cash. Following successful completion of the tender offer, Gilead will acquire all remaining shares not tendered in the offer through a second step merger at the same price as in the tender offer.

The consummation of the tender offer is subject to various conditions, including a minimum tender of at least a majority of outstanding Kite shares on a fully diluted basis, the expiration or termination of the waiting period under the Hart Scott Rodino Antitrust Improvements Act, and other customary conditions.

Gilead plans to finance the transaction with a combination of cash on hand, bank debt and senior unsecured notes. The tender offer is not subject to a financing condition.

The $180.00 per share acquisition price represents a 29 percent premium to Kite’s closing on Friday, August 25, and a 50 percent premium to the company’s 30-day volume weighted average stock price.

BofA Merrill Lynch and Lazard are acting as financial advisors to Gilead. Centerview Partners is acting as exclusive financial advisor to Kite. Jefferies LLC and Cowen and Company, LLC also provided advice to Kite. Skadden, Arps, Slate, Meagher & Flom is serving as legal counsel to Gilead and Sullivan & Cromwell LLP and Cooley LLP are serving as legal counsel to Kite.

On august 28, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for Gazyva (obinutuzumab) in combination with chemotherapy followed by Gazyva alone for people with previously untreated follicular lymphoma, one of the most common blood cancers among adults (Press release, Hoffmann-La Roche, AUG 28, 2017, View Source [SID1234520315]). Follicular lymphoma, a slow-growing (indolent) form of non-Hodgkin lymphoma, is incurable and characterized by cycles of remission and relapse.
"Follicular lymphoma becomes harder to treat each time it returns, and the goal of initial treatment is to prevent the cancer from progressing for as long as possible," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Based on the GALLIUM study, Gazyva-based treatment significantly improved progression-free survival over the current standard of care, and we are committed to bringing this potential new option to patients as soon as possible."

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The sBLA is based on results of the GALLIUM study, which is the first Phase III study in previously untreated follicular lymphoma to show superior progression-free survival (PFS) over Rituxan (rituximab)-based treatment, the current standard of care. Adverse events (AEs) with either Gazyva or Rituxan were consistent with those seen in previous studies.

The FDA is expected to make a decision on approval under Priority Review by 23 December, 2017. Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention or diagnosis of a serious disease. Additional submissions of the GALLIUM data to health authorities around the world are ongoing.

About the GALLIUM study
GALLIUM (NCT01332968) is a global Phase III open-label, multicenter, randomized two-arm study examining the efficacy and safety of Gazyva plus chemotherapy followed by Gazyva alone for up to two years, as compared head-to-head against Rituxan plus chemotherapy followed by Rituxan alone for up to two years. Chemotherapies used were CHOP, CVP or bendamustine and were selected by each participating study site prior to beginning enrollment.

GALLIUM included 1401 patients with previously untreated indolent non-Hodgkin lymphoma (iNHL), of which 1202 patients had follicular lymphoma. The primary endpoint of the study was investigator-assessed progression-free survival (PFS) in patients with follicular lymphoma, with secondary endpoints including PFS assessed by independent review committee (IRC) in patients with follicular lymphoma, PFS in the overall study population (iNHL), response rate (overall response, ORR; and complete response, CR), overall survival (OS) and safety. The study is being conducted in cooperation with the GLSG (Germany), the East German Study Group Hematology and Oncology (OSHO; Germany) and the NCRI (United Kingdom). Results after a follow-up period of 41.1 months showed:
Gazyva-based treatment reduced the risk of disease worsening or death (PFS, as assessed by investigator) by 32 percent compared to Rituxan-based treatment (HR=0.68; 95 percent CI 0.54-0.87; p=0.0016).

IRC-assessed PFS was consistent with investigator-assessed PFS. As assessed by IRC, Gazyva-based treatment reduced the risk of disease worsening or death by 28 percent compared to Rituxan-based treatment (HR=0.72; 95 percent CI 0.56-0.93; p=0.0018). Median PFS has not yet been reached in either treatment arm.

The most common Grade 3-5 AEs that occurred more often in the Gazyva arm compared to the Rituxan arm were low white blood cell count (neutropenia, 46.7 percent vs. 39.5 percent), infections (20.3 percent vs. 16.4 percent), infusion-related reactions (IRRs, 12.4 percent vs. 6.7 percent), low platelet count (thrombocytopenia, 6.1 percent vs. 2.7 percent), new tumors (second malignancies, 4.7 percent vs. 2.7 percent) and cardiac events (3.9 percent vs. 2.8 percent).

GALLIUM is the third positive Phase III study for Gazyva, following the CLL11 study in patients with previously untreated chronic lymphocytic leukaemia (CLL) and the GADOLIN study in patients with indolent (slow-growing) non-Hodgkin lymphoma whose disease progressed during or within six months of prior Rituxan-based therapy.

About Gazyva (obinutuzumab)
Gazyva is an engineered monoclonal antibody designed to attach to CD20, a protein expressed on certain B cells, but not on stem cells or plasma cells. Gazyva is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system.

Gazyva is marketed as Gazyvaro in the EU and Switzerland. Gazyva/Gazyvaro is currently approved in more than 80 countries in combination with chlorambucil, for people with previously untreated chronic lymphocytic leukaemia (CLL), and in combination with bendamustine for people with certain types of previously treated follicular lymphoma. The approvals in CLL were based on the CLL11 study, showing significant improvements with Gazyva/Gazyvaro plus chlorambucil across multiple clinical endpoints, including PFS, overall response rate (ORR), complete response rate (CR), and minimal residual disease (MRD) when compared head-to-head with MabThera/Rituxan plus chlorambucil.

The approvals in certain types of previously treated follicular lymphoma were based on the phase III GADOLIN study, in people with follicular lymphoma who did not respond to or who progressed during or within six months of prior MabThera/Rituxan-based therapy, showing a significant improvement in PFS and overall survival (OS) with Gazyva/Gazyvaro-based therapy compared to bendamustine alone.

Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

About Follicular Lymphoma
Follicular lymphoma is the most common indolent (slow-growing) form of non-Hodgkin lymphoma (NHL), accounting for about one in five cases of NHL1. It is considered incurable and relapse is common. Every day, more than 50 people in Europe are diagnosed with this type of NHL2. It is estimated that more than 75,000 people are diagnosed with follicular lymphoma each year worldwide2.
About Roche in haematology