Pfizer to Acquire Anacor

On May 16, Pfizer Inc. (NYSE:PFE) and Anacor Pharmaceuticals, Inc. (NASDAQ:ANAC) reported that they have entered into a definitive merger agreement under which Pfizer will acquire Anacor for $99.25 per Anacor share, in cash, for a total transaction value, net of cash, of approximately $5.2 billion, which assumes the conversion of Anacor’s outstanding convertible notes (Press release, Pfizer, MAY 16, 2016, View Source [SID:1234512410]). The Boards of Directors of both companies have unanimously approved the transaction. Anacor’s flagship asset, crisaborole, a differentiated non-steroidal topical PDE4 inhibitor with anti-inflammatory properties, is currently under review by the U.S. FDA for the treatment of mild-to-moderate atopic dermatitis, commonly referred to as eczema.

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"We believe the acquisition of Anacor represents an attractive opportunity to address a significant unmet medical need for a large patient population with mild-to-moderate atopic dermatitis, which currently has few safe topical treatments available," said Albert Bourla, Group President of Pfizer’s Global Innovative Pharma and Global Vaccines, Oncology and Consumer Healthcare Businesses. "Crisaborole is a differentiated asset with compelling clinical data that, if approved, has the potential to be an important first-line treatment option for these patients and the physicians who treat them."

"Anacor will be a strong fit with Pfizer’s innovative business, further supporting our strategic focus on Inflammation and Immunology, and is expected to enhance near-term revenue growth for the innovative business. Our dedicated Inflammation and Immunology group has strong existing in-market franchises with Enbrel and Xeljanz, as well as a robust mid-stage pipeline, and this acquisition has the potential to add a near-term U.S. product launch. We believe we are well positioned to maximize crisaborole’s commercial potential through our strong relationships with pediatricians and primary care physicians," continued Bourla.

In both of its Phase 3 pivotal studies, crisaborole achieved statistically significant results on all primary and secondary endpoints and in March 2016, the FDA accepted for review Anacor’s New Drug Application seeking approval of crisaborole for the potential treatment of mild-to-moderate atopic dermatitis in children and adults. The Prescription Drug User Fee Act (PDUFA) goal date for the completion of the FDA’s review is January 7, 2017. If approved, Pfizer believes peak year sales for crisaborole have the potential to reach or exceed $2.0 billion.

"Today marks the beginning of an exciting new chapter for Anacor, which we believe will deliver significant value to our shareholders," said Paul L. Berns, Anacor’s Chairman and Chief Executive Officer. "We have a deep respect for Pfizer, and it is clear that they share our commitment to addressing the significant unmet medical needs in inflammatory disease. We are proud of the innovative company that our team has built and are confident that Pfizer will help accelerate Anacor’s important mission given the strength of its global platform and resources."

Atopic dermatitis is a common, relapsing, chronic, inflammatory skin disorder, with patients displaying a chronic rash characterized by inflammation and itching, often occurring in folds of the skin with symptoms lasting up to 14 days or more. Approximately 18 to 25 million people in the United States suffer from this condition, including between 8 and 18% of infants and children. Atopic dermatitis has been considerably underdiagnosed due to the lack of approved effective systemic agents, and limitations of current topical agents. There have been no new molecular entities for atopic dermatitis in the last 15 years.

Anacor also holds the rights to Kerydin, a topical treatment for onychomycosis (toenail fungus) that is distributed and commercialized by Sandoz Inc. in the U.S.

Pfizer anticipates financing the transaction through existing cash. Pfizer does not expect the transaction to impact its current 2016 financial guidance. Pfizer expects the transaction to be slightly dilutive to Adjusted Diluted Earnings Per Share (EPS)(1) in 2017 with accretion to Adjusted Diluted EPS(1) beginning in 2018 and increasing thereafter.

Under the terms of the merger agreement, a subsidiary of Pfizer will commence a cash tender offer to purchase all of the outstanding shares of Anacor common stock for $99.25 per share in cash. The closing of the tender offer is subject to customary closing conditions, including U.S. antitrust clearance and the tender of a majority of the outstanding shares of Anacor common stock. The merger agreement contemplates that Pfizer will acquire any shares of Anacor that are not tendered into the offer through a second-step merger, which will be completed promptly following the closing of the tender offer. Pfizer expects to complete the acquisition in the third-quarter 2016.

Pfizer’s financial advisors for the transaction were Centerview Partners and Guggenheim Securities, and Wachtell, Lipton, Rosen & Katz acted as its legal advisor. Citi served as Anacor’s financial advisor, and Davis Polk & Wardwell, LLP served as its legal advisor.

Aduro Biotech Announces Phase 2b ECLIPSE Trial Misses Primary Endpoint in Heavily Pretreated Metastatic Pancreatic Cancer

On May 16, 2016 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that the Phase 2b ECLIPSE trial did not meet the primary endpoint of an improvement in overall survival for patients with pancreatic cancer who had failed at least two prior therapies in the metastatic setting (Press release, Aduro BioTech, MAY 16, 2016, View Source [SID:1234512424]).

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Median overall survival (MOS) in this third-line and greater setting was 3.8 months for patients treated with the immunotherapy regimen of CRS-207 and GVAX Pancreas, 5.4 months for patients treated with CRS-207 alone and 4.6 months for patients administered chemotherapy. There were no unexpected safety findings with the combination of CRS-207 and GVAX Pancreas or CRS-207 alone, and the immunotherapies were generally well tolerated. Management will review these results in more detail on a conference call today at 6:00 am Pacific Time. Full study findings will be presented at a future scientific congress.

"This is an unexpected outcome, and we are disappointed particularly for the pancreatic cancer patients who are in need of additional treatment options," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "We would like to thank the patients and their families, investigators and staff involved in this Phase 2b trial for their support and participation in this study. While we are well aware of the very difficult-to-treat nature of late-stage metastatic pancreatic cancer, we are surprised by the divergence of these data from the results of our Phase 2a study. At the same time, we continue to look forward to the interim results later this year from our ongoing STELLAR trial, which is evaluating CRS-207 and GVAX Pancreas with and without the anti-PD1 checkpoint inhibitor nivolumab as a second-line therapy for patients with metastatic pancreatic cancer. We believe the scientific rationale for combining CRS-207 with a checkpoint inhibitor is compelling. Additionally, as a company, we are very well-positioned with a strong cash position and three differentiated, potentially synergistic immunotherapy platforms comprising our LADD, STING pathway activator and B-select monoclonal antibody programs."

"In the overall survival analysis, we were intrigued by activity seen with CRS-207 as a single-agent. While the median duration of 5.4 months appears greater for CRS-207, the overall survival curve of CRS-207 alone was comparable to overall survival seen with chemotherapy. Of note, due to a disproportionately high dropout rate in the single-agent chemotherapy arm, most of these patients instead received a variety of combination treatments, including chemotherapies, immunotherapies and targeted therapies," said Dirk Brockstedt, Ph.D., executive vice president, research and development for Aduro.

Andrew Ko, M.D., professor, Department of Medicine (hematology/oncology) at University of California San Francisco added, "As the scientific community continues to discover the optimal approach towards enlisting the power of the immune system in the fight against elusive diseases such as pancreatic cancer, I applaud Aduro for their pioneering contributions to the field. Immunotherapy is ushering in a new era in our fundamental understanding of human biology, and although the results are not what we had hoped for from this well-executed trial, they will provide important information for changing the treatment paradigm in the future."

About ECLIPSE
The ECLIPSE trial (Efficacy of Combination Listeria/GVAX Immunotherapy in the Pancreatic Cancer Setting) enrolled 303 adults with previously-treated metastatic pancreatic cancer in over 20 clinical trial sites in the U.S. and Canada. The open-label randomized, controlled 3-arm trial evaluated the safety, immune response and efficacy of the combination immunotherapy of CRS-207 with GVAX Pancreas (with low-dose cyclophosphamide (CY)) and CRS-207 alone, compared to chemotherapy. The primary endpoint of the trial was overall survival. Secondary endpoints included evaluation of clinical and immune response and safety.

CRS-207 has been engineered to induce an immune response to the tumor-associated antigen mesothelin. Mesothelin is over-expressed in many cancers, including mesothelioma and pancreatic, non-small cell lung, ovarian and gastric cancers.

About STELLAR
The randomized, controlled STELLAR trial (Safety and Therapeutic Efficacy of Live-attenuated Listeria/GVAX with Anti-PD1 Regimen) is expected to enroll approximately 102 adults with metastatic pancreatic cancer who have received one prior chemotherapy to treat metastatic disease. The trial includes two arms: Arm A with CRS-207 and GVAX Pancreas as well as the checkpoint inhibitor, nivolumab, and Arm B with CRS-207 and GVAX Pancreas. The primary objective of this study is to compare the overall survival (OS) of patients in Arm A and Arm B. Secondary endpoints include evaluation of clinical and immune response and safety. For more information, please visit ClinicalTrials.gov (Identifier: NCT02243371).

About Metastatic Pancreatic Cancer
Each year, it is estimated that more than 337,000 people worldwide are diagnosed with pancreatic cancer and more than 330,000 people die from the disease. Despite steady advances in diagnosis and treatment that have dramatically improved outcomes and extended survival in many tumor types, pancreatic cancer remains one of the world’s deadliest cancers, with a five-year survival rate of eight percent. While pancreatic cancer is the eleventh most common cancer in the United States, it is now the third leading cause of cancer-related death.I

Most often diagnosed when it has already metastasized (or spread) to other parts of the body, unresectable (not able to be surgically removed) pancreatic cancer is highly resistant to conventional treatments, including chemotherapy and radiation. It is rapidly fatal, often within months of diagnosis. The need for new, more effective treatments for this patient population has ignited interest in the potential of immunotherapies to engage the patient’s own immune system to extend survival.

U.S. FDA APPROVES ADDITIONAL INDICATION FOR EISAI’S ANTICANCER AGENT LENVIMA(R) IN COMBINATION WITH EVEROLIMUS AS TREATMENT FOR ADVANCED RENAL CELL CARCINOMA

On May 16, 2016 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that its U.S. subsidiary Eisai Inc. has received approval from the U.S. Food and Drug Administration (FDA) for an additional indication for Eisai’s in-house developed novel anticancer agent Lenvima (lenvatinib mesylate) in combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy (Press release, Eisai, MAY 16, 2016, View Source [SID:1234512409]).

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This is the only combination regimen to significantly prolong progression-free survival (PFS) when compared with a standard of care in patients with advanced renal cell carcinoma following prior anti-angiogenic therapy. Lenvima was designated as a Breakthrough Therapy by the FDA and also received a Priority Review, with approval obtained approximately six months after application submission.

The approval was based on a Phase II clinical study (Study 205)1 that compared the safety and efficacy of Lenvima alone, and in combination with everolimus, in patients with unresectable advanced or metastatic renal cell carcinoma following one prior vascular endothelial growth factor-targeted therapy. From the results of the study, the group who received the combination of Lenvima plus everolimus demonstrated a significant extension in PFS, the study’s primary endpoint, as well as a higher objective response rate compared to the everolimus alone group. The most common treatment-emergent adverse events (TEAEs) reported in the lenvatinib plus everolimus group were diarrhea, decreased appetite and fatigue.

The most common TEAEs of Grade 3 or higher were diarrhea, hypertension and fatigue. The number of patients with kidney cancer in the United States is estimated to be approximately 58,000, 2 and renal cell carcinoma comprises more than 90% of all malignancies of the kidney.3 For advanced or metastatic renal cell carcinoma that is difficult to treat with surgery, the standard treatment is molecular targeted drug therapy, however with low 5-year survival rates, this is a disease with significant unmet medical need.

Lenvima was first approved for the treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer in the United States in February 2015, and has since been approved for thyroid cancer in over 40 countries including Japan, in Europe, South Korea and Canada. A new drug application seeking approval for an indication covering advanced or metastatic renal cell carcinoma submitted in Europe in January 2016 is under review, and Eisai intends to discuss further steps regarding submission strategies for this potential indication with the regulatory authorities in Japan as well. Furthermore, Eisai is conducting clinical studies of Lenvima in several other tumor types including a Phase III study of the agent in hepatocellular carcinoma.

Through this additional approval, Eisai is committed to maximizing the clinical value as well as exploring the potential clinical benefits of Lenvima in order to address the diverse needs of, and further contribute to, patients with cancer and their families.

About Lenvima (lenvatinib mesylate)
Lenvima is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other proangiogenic and oncogenic pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumor proliferation.

Currently, Eisai has obtained approval for Lenvima as a treatment for refractory thyroid cancer in over 40 countries including in the United States, Japan, Europe, Korea and Canada, and is undergoing regulatory review throughout the world including in Asia, Russia, Australia, Brazil and Mexico. Specifically, Eisai has obtained approval for the agent indicated in the United States for treatment for locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer, in Japan for the treatment of unresectable thyroid cancer, and in Europe for the treatment of adult patients with progressive, locally advanced or metastatic differentiated (papillary, follicular, Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine, respectively.

Lenvima is now also approved for an additional indication in the United States in combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy. A new drug application seeking approval for an indication covering advanced or metastatic renal cell carcinoma submitted in Europe in January 2016 is under review, and Eisai intends to discuss further steps regarding submission strategies for this potential indication with the regulatory authorities in Japan.
Meanwhile, Eisai is conducting clinical studies of Lenvima in several other tumor types such as hepatocellular carcinoma (Phase III), endometrial carcinoma (Phase II), biliary tract cancer (Phase II), and in combination with an immune checkpoint inhibitor (Phase Ib/II).

About the Phase II Clinical Study (Study 205)1
Study 205 was a multicenter, randomized, open-label study of the combination of Lenvima (18 mg) plus everolimus (5 mg), Lenvima alone (24 mg), and everolimus alone (10 mg) in patients with unresectable advanced or metastatic renal cell carcinoma following one prior VEGF-targeted therapy, and was conducted in Europe and the United States. 153 patients were randomized in a 1:1:1 ratio to one of three treatment arms to compare the efficacy and safety of these three regimens.

From the results of the study, the combination of Lenvima plus everolimus group demonstrated a significant extension in the study’s primary endpoint of progression free survival (PFS) compared to the everolimus alone group (median PFS for the Lenvima plus everolimus group: 14.6 months vs median PFS for the everolimus alone group: 5.5 months; Hazard Ratio (HR) 0.40 [95% CI: 0.24-0.68], p=0.0005). Additionally, median PFS for the Lenvima alone group was 7.4 months, demonstrating an extension in PFS compared to the everolimus alone group (HR: 0.61 [95% CI: 0.38-0.98]).

The study also assessed objective response rate (ORR) and overall survival (OS) as secondary endpoints. Regarding ORR, both the Lenvima plus everolimus group and the Lenvima alone group showed an improvement in ORR compared to the everolimus alone group (Lenvima plus everolimus: 43%, Lenvima alone: 27%, everolimus alone: 6%). Furthermore, regarding OS, an updated analysis carried out in December 2014 suggested that Lenvima plus everolimus extends OS compared to everolimus alone (HR 0.51 [95% CI=0.30-0.88]).

The most common treatment-emergent adverse events (TEAEs) reported in the lenvatinib plus everolimus group were diarrhea, decreased appetite and fatigue. The most common TEAEs of Grade 3 or higher were diarrhea, hypertension and fatigue.
For further information on Lenvima in the United States, including Important Safety Information (ISI), please visit the Lenvima product website (View Source).

About Renal Cell Carcinoma
The number of patients with renal cancer was estimated to be approximately 338,000 worldwide, including approximately 58,000 in the United States, 115,000 in Europe and 17,000 in Japan.2 Renal cell carcinoma comprises more than 90% of all malignancies of the kidney, 3 and occurs when malignant cells are found in the lining of the tubules of the kidney. The incidence of renal cell carcinoma in people aged in their late 50s is rising, and is more likely to affect men than women. For advanced or metastatic renal cell carcinoma that is difficult to treat with surgery, the standard treatment method is molecular targeted drug therapy, however with low 5-year survival rates, this is a disease with significant unmet medical need.

At CIMT 2016 Lytix presented LTX-315’s ability to make tumors more T-cell inflamed

On May 11, 2016 Lytix Biopharma reported LTX-315’s ability to enhance infiltration of CD8 positive T-cells in murine and human tumors, and T-cell clonality in B16 melanomas (Press release, Lytix Biopharma, MAY 14, 2016, View Source [SID:1234514842]). These abilities make LTX-315 an ideal partner for beeing combined with other types of immunotherapy. The strong synergy between LTX-315 and anti-CTLA-4 in preclinical cancer model was also presented.

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10-Q – Quarterly report [Sections 13 or 15(d)]

XBiotech has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, XBiotech, 2017, MAY 13, 2016, View Source [SID1234521614]).

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