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10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

Northwest Biotherapeutics has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, Northwest Biotherapeutics, MAR 17, 2015, View Source [SID1234502354]).

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10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

Celator Pharmaceuticals has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, Celator Pharmaceuticals, MAR 17, 2015, View Source [SID1234502306]).

Actavis Completes Allergan Acquisition

On March 17, 2015 Actavis plc (NYSE: ACT) reported that it has completed the acquisition of Allergan, Inc. (NYSE: AGN) in a cash and equity transaction valued at approximately $70.5 billion (Press release, Allergan, MAR 17, 2015, View Source [SID:1234512515]). The combination creates one of the world’s top 10 pharmaceutical companies by sales revenue, with combined annual pro forma revenues of more than $23 billion anticipated in 2015.

"The combination of Actavis and Allergan creates an exceptional global pharmaceutical company and a leader in a new industry model – Growth Pharma," said Brent Saunders, CEO and President of Actavis. "Anchored by world-renowned brand franchises, a leading global generics business, a premier pharmaceutical development pipeline and an experienced management team committed to maintaining highly efficient operations across the organization, we are creating an unrivaled foundation for long-term growth.

"Our combined company will be built around a customer-focused commitment to partnering with physicians, pharmacists and patients to deliver innovative treatments and enhance access to important therapies around the world. We have industry-leading global commercial strength, with sustainable blockbuster brand franchises in key therapeutic categories and broad commercial reach extending across approximately 100 countries. Our experienced field-based representatives will continue to deliver exceptional support on a broad range of products to physicians and specialists around the world. And our powerful global supply chain is broadly recognized as a world leader, with continued excellence in quality and customer service.

"Supporting the growth of this innovative industry model is our strategically focused R&D engine, built on novel compounds in specialty and primary care markets where there is significant unmet medical need, and fueled by approximately $1.7 billion in annual investment. With an innovative product development portfolio exceeding 20 near-term projects and a world-class generics pipeline, which continues to hold an industry-leading position in First-to-File opportunities in the U.S. and more than 1,000 marketing authorizations globally, we are uniquely positioned within our industry to ensure our development activities support sustainable long-term organic growth.

"With the acquisition now complete, we will immediately begin implementing our comprehensive integration plans to ensure that we leverage our strengthened global organization to generate sustainable organic earnings growth from our newly expanded base, and continue our ascent into the fastest-growing and most dynamic growth pharmaceutical company in global healthcare."

Financially Compelling Transaction

Actavis continues to expect the transaction to generate double-digit accretion to non-GAAP earnings within the first 12 months, including approximately $1.8 billion in operating and financial synergies to be realized within one year following the close. These synergies exclude any additional revenue or manufacturing synergies, and are in addition to the $475 million of annual savings previously announced by Allergan in connection with Project Endurance. Actavis further expects to generate strong operating cash flow in excess of $8 billion in 2016, which would enable the Company to rapidly de-lever the balance sheet.

Review of the Benefits of the Acquisition

The combination of Actavis and Allergan creates a pharmaceutical business with a growth profile unparalleled within the industry.

Significantly Expanded Brand Pharmaceutical Portfolio Supported by a World-Class Sales and Marketing Organization

The close of the transaction creates an exceptional global brand pharmaceutical business with leading positions in key therapeutic categories. The company has six blockbuster franchises with combined pro forma 2015 revenues of approximately $15 billion expected, including franchises with annual revenues in excess of $3 billion in Eye Care, Neurosciences/CNS and Medical Aesthetics/Dermatology/Plastic Surgery, as well as a portfolio of world-renowned brands including BOTOX, RESTASIS, JUVEDERM, NAMENDA XR, LINZESS and LO LOESTRIN Fe among others.

The combined company will continue to be recognized for its strong commitment as the partner of choice with physicians, specialists, pharmacists, regulators and patients. The combination is committed to creating the best customer experience, based on deeply-held relationships with customers and colleagues in approximately 100 countries around the world. The company’s experienced sales and marketing organization will continue to deliver exceptional support to more than a dozen medical specialists, including primary care physicians, ophthalmologists, optometrists, retinal specialists, neurologists, psychiatrists, dermatologists, aesthetic surgeons, medical aesthetic professionals, plastic surgeons, gastroenterologists, pulmonologists, OB-GYNs, urologists, cardiologists, infectious disease specialists, pain specialists and rehabilitation specialists.

Enhanced Commercial Opportunities across Global Markets

The combination greatly enhances Actavis’ international commercial opportunities. The company has an expanded commercial presence now including approximately 100 countries, with an enhanced presence across Canada, Europe, Southeast Asia and Latin America and a strong footprint in China and India. The combined company will benefit from Allergan’s global brand equity, industry-leading consumer marketing capabilities and strong consumer awareness of key Allergan products in global markets, including BOTOX, RESTASIS, JUVEDERM, LATISSE, NATRELLE and others. On a pro forma basis, the company is expected to have approximately $5 billion in 2015 international revenue, and will have the unique opportunity to drive continued growth in international markets through its enhanced portfolio of brands, generics, branded-generic and over-the-counter products.

Strengthened and Expanded Pharmaceutical R&D Pipeline

The combined company will provide a strong commitment to R&D, with an exceptional level of investment of approximately $1.7 billion expected in 2015, focused on the strategic development of innovative and durable value-enhancing products within brands, generics, biologics and OTC portfolios. The company has more than 20 innovative products in near- or mid-term development, including Cariprazine, Eluxadoline, Esmya, Aczone X and Darpin AMD, among other promising candidates. The company’s pipeline is strategically focused within its core therapeutic areas, with key candidates in Dermatology and Aesthetics, Eye Care, CNS, GI, Anti-infectives, Women’s Health and Urology. The Company’s generics pipeline is also positioned to deliver sustainable growth, with approximately 230 Abbreviated New Drug Applications pending at FDA, including approximately 70 first-to-file applications, as well as nearly 1,000 marketing authorization applications filed outside of the U.S. in 2014.

Commitment to Being the Partner of Choice for Physicians, Patients and the Medical Community

The combined company will retain Allergan’s foundational commitment to being the partner of choice for physicians, patients and the medical community. The Company will continue to foster deep engagement with medical specialists, listening closely to their needs to help advance patient care and deliver treatments that address significant unmet medical needs. In addition, the Company will continue to go above and beyond to provide education and information – with the highest level of integrity – that helps patients fully understand the choices available to them and make well-informed treatment decisions with their doctors. Through these essential partnerships, the Company will continue to bring to bear scientific excellence and rigor to deliver leading products that improve patient outcomes.

Strong Combined Global Leadership Team with Deep Experience across the Business

The combined company’s expanded senior management team is comprised of leaders from both Actavis and Allergan. It is structured to leverage the strong talent from both organizations to ensure that the new company capitalizes on its expanded global commercial footprint and the proven track record of Allergan’s powerful and critically important product franchises, while maintaining Actavis’ continued dominance as a world leader in generics. With this structure in place beginning on Day 1, the company is immediately positioned to maximize growth across all of its global businesses.

Teva and Ignyta Announce Acquisition by Ignyta of Four Oncology R&D Assets from Teva

On March 17, 2015 Teva Pharmaceutical Industries and Ignyta reported the acquisition by Ignyta of the worldwide rights and assets relating to four targeted oncology development programs in exchange for 1.5 million shares (6%) of Ignyta’s common stock (Press release, Ignyta, MAR 17, 2015, View Source [SID:1234502343]).

"We intend to use the funds to further advance our precision oncology vision by developing targeted therapies that provide meaningful benefit to specific populations of cancer patients."

Concurrently, Ignyta has entered into stock purchase agreements with Teva, and selected additional healthcare investors, whereby Teva will purchase a further 1.5 million shares of common Ignyta stock at a price of $10 per share in a registered direct offering. The other investors will purchase an additional 2.7 million shares at $10 per share, valuing the total offering at approximately $41.6 million.

"Teva has committed to finding novel ways for the ongoing development of early clinical stage and pre-clinical oncology R&D programs, which hold significant promise for cancer patients," said Michael Hayden, Teva’s President of Global R&D and Chief Scientific Officer. "Ignyta’s capabilities and focus in oncology will give these assets the best chance of realizing their potential for patients, and of maximizing their value for Teva."

"Acquiring these four development stage programs from Teva is truly transformational for Ignyta and well aligned with our strategic focus on developing first-in-class and best-in-class precision medicines to help cancer patients with unmet needs," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "These oncology programs add critical mass to our pipeline and further enable us to leverage our precision oncology platform, including our proprietary multiplex diagnostic assays and our CLIA certified, QSR compliant diagnostic laboratory. Furthermore, these new assets complement our entrectinib development program and extend our ability to target the majority of known oncogenic drivers across multiple solid tumor indications. For example, in non-small cell lung cancer alone, we believe that our product candidates have potential activity against many of the most frequent oncogenic drivers in this disease, and we plan to explore these opportunities through innovative clinical trial designs such as master protocols."

"We are also grateful to Teva and the financial investors who share Ignyta’s precision oncology vision and invested in this latest financing," continued Dr. Lim. "We intend to use the funds to further advance our precision oncology vision by developing targeted therapies that provide meaningful benefit to specific populations of cancer patients."

Overview of Asset Acquisition Transaction

Under the terms of the asset purchase agreement with Teva, Ignyta is acquiring all of Teva’s assets and worldwide rights relating to four oncology development programs in exchange for 1.5 million shares of Ignyta’s common stock. Teva has agreed not to sell or otherwise transfer any of these shares until March 17, 2016, and Ignyta is required to register the resale of these shares with the Securities and Exchange Commission (SEC) prior to such date.

The development programs Ignyta purchased from Teva include:

CEP-32496, which Ignyta has renamed RXDX-105, a potent small molecule inhibitor of BRAF, EGFR and RET that is currently in a Phase I/II dose escalation clinical trial;
CEP-40783, which Ignyta has renamed RXDX-106, a potent, highly selective, pseudo-irreversible inhibitor of AXL and cMET that is in late preclinical development;
CEP-40125, which Ignyta has renamed RXDX-107, a nanoformulation of a modified bendamustine with potential activity in solid tumors that is in late preclinical development; and
TEV-44229, which Ignyta has renamed RXDX-108, a potent, selective inhibitor of the atypical kinase PKCiota that is in preclinical studies. Ignyta has also acquired next generation PKCiota inhibitors in addition to the lead compound.

Ignyta also assumed all of Teva’s ongoing obligations under certain contracts relating to the purchased programs, including the agreements under which Teva in-licensed rights to the assets.

Concurrent Equity Financing

Teva has agreed to purchase 1.5 million shares of Ignyta common stock for a purchase price of $10 per share, resulting in gross proceeds to Ignyta of $15 million. Ignyta has also entered into stock purchase agreements with several additional investors that will purchase an aggregate of 2.7 million additional shares of Ignyta common stock. The offering is expected to result in aggregate gross proceeds to Ignyta of approximately $41.6 million. The offering closed concurrently with the asset purchase. Ignyta did not use a placement agent in connection with this transaction.

A shelf registration statement relating to the shares of common stock issued in the offering was filed with, and declared effective by, the SEC. A prospectus supplement relating to the offering will be filed with the SEC. This press release shall not constitute an offer to sell or a solicitation of an offer to buy any shares of common stock. No offer, solicitation or sale will be made in any jurisdiction in which such offer, solicitation or sale is unlawful.

Ignyta Slide Deck and Conference Call

Ignyta has posted a slide presentation relating to the Teva transaction, its new development programs and the concurrent equity financing on the Investors page of the company’s website at View Source On Tuesday, March 17, 2015, Ignyta will host a conference call with interested parties beginning at 5:00 p.m. ET (2:00 p.m. PT) to discuss the transactions and related matters. A live webcast of the conference call will be available online on the Investors page of the company’s website at View Source The call will also be archived and accessible at that site for one year. Alternatively, callers may participate in the conference call by dialing (888) 734-0328 (domestic) or (678) 894-3054 (international), and entering passcode 5138138.

Discussion during the conference call may include forward-looking statements regarding such topics as, but not limited to, Ignyta’s development plans for its new product candidates, its other product candidates and discovery programs, the company’s financial status, and any comments the company may make about its future plans or prospects in response to questions from participants on the conference call.

Etirinotecan Pegol (NKTR-102) Prolonged Median Overall Survival by 2.1 Months versus Active Control in Patients with Advanced Breast Cancer in Phase 3 Study; Trial Did Not Achieve Statistical Significance (p=0.08)

On March 17, 2015 Nektar Therapeutics reported topline results from its Phase 3 BEACON study evaluating single-agent NKTR-102 in patients with advanced breast cancer (Press release, Nektar Therapeutics, MAR 17, 2015, View Source [SID:1234502307]). BEACON compared NKTR-102 to an active control arm comprised of a single chemotherapy agent of physician’s choice (TPC) in patients who were heavily pre-treated with a median of three prior therapies for metastatic disease. In a topline analysis of 852 patients from the trial, NKTR-102 provided a 2.1 month improvement in median overall survival (OS) over TPC (12.4 months for patients receiving NKTR-102 compared to 10.3 months for patients receiving TPC). Based on a stratified log-rank analysis, the primary endpoint measuring the Hazard Ratio (HR) for survival in the NKTR-102 group compared to the active control arm was 0.87 with a p-value of 0.08, which did not achieve statistical significance.

In a pre-specified subgroup of patients with a history of brain metastases, NKTR-102 showed an improvement of 5.2 months in median OS (10.0 months compared to 4.8 months, n=67, HR 0.51, p-value < 0.01). The proportion of patients with brain metastases with 12-month survival was 44.4% in the NKTR-102 arm as compared to 19.4% in the control arm.

In a pre-specified subgroup of patients with baseline liver metastases at study entry, NKTR-102 showed an improvement of 2.6 months in median OS (10.9 months versus 8.3 months, n=456, HR 0.73, p-value < 0.002). In these patients with baseline liver metastases, the proportion of patients with 12-month survival was 46.9% in the NKTR-102 arm as compared to 33.3% in the control arm.

Breast cancer is the second leading cause of cancer related death among women, according to the National Cancer Institute. This year, an estimated 207,000 women will be diagnosed with breast cancer, and over 39,000 women will die from the disease in the U.S. Brain metastases are diagnosed in 30% of patients with advanced breast cancer.1 Liver metastases develop in approximately half of all women with metastatic breast cancer and are typically associated with advanced disease and poor outcome.2

"In BEACON, NKTR-102 provided a clinically meaningful benefit with a greater than two month survival advantage in these late-stage breast cancer patients, many who were refractory to existing therapies," said Dr. Cortes. "NKTR-102 exhibited a lower rate of high grade adverse events including a reduced rate of neutropenia as compared to active control, which dramatically decreased the need for growth factor support in the NKTR-102 arm of the study. Of particular significance, median survival in patients with brain metastases was more than double on NKTR-102 and the 12-month survival rate for this sub-group was impressive at 44% compared to 19% with other active agents."

Dr. Edith Perez, Deputy Director of the Mayo Clinic Cancer Center and Dr. Javier Cortes, Director of the Breast Cancer Program at Vall d’Hebron University Hospital in Spain, served as co-principal investigators of the global, multi-center study. BEACON enrolled 852 patients with advanced breast cancer whose disease had progressed following treatment with anthracycline, taxane and capecitabine (ATC).

"Given the frequency of cross-resistance and overlapping toxicities observed with many available agents, NKTR-102 would offer a new mechanism of action for physicians and patients in the fight against advanced breast cancer," said Dr. Joyce O’Shaughnessy, a lead BEACON investigator and steering committee member in the United States and Chair, Breast Cancer Research, The US Oncology Network and the Baylor Sammons Cancer Center, Texas Oncology, Dallas, Texas. "The results in the subgroups of patients with both liver and brain metastases are noteworthy because NKTR-102 is designed to enhance concentration of its active metabolite in highly vascular tumor environments. From a clinician’s perspective, the combination of NKTR-102’s clinical benefit and improved tolerability supports its value as a potential new treatment option in late stage breast cancer."

Secondary endpoints in the BEACON study included objective response rate (ORR) and progression-free survival (PFS), which did not achieve statistical significance in the study.

The incidence of Grade 3 and higher adverse events (AEs) was lower in the NKTR-102 arm (48%) compared to the TPC arm (63%). The most common Grade 3 and above AEs observed with NKTR-102 were diarrhea (9.6%), neutropenia (9.6%), anemia (4.7%) and fatigue (4.5%). There was no Grade 4 diarrhea reported with NKTR-102 in the trial. The most common Grade 3 and above AEs observed with TPC were neutropenia (30.8%), anemia (4.7%), and dyspnea (4.4%). Severe neuropathy (G3 or higher) was seen in 3.7% of patients on TPC versus 0.5% of patients in the NKTR-102 arm. Rates of G1/G2 alopecia in the NKTR-102 arm were also lower (10%) than in the TPC arm (23%).

"It is clear from our BEACON study that NKTR-102 has potential as an important anti-cancer agent when compared to the best available treatment options today for women with advanced breast cancer," said Howard W. Robin, president and chief executive officer of Nektar Therapeutics. "Given the significant need for new drugs to treat patients with this devastating disease, we will be exploring potential paths forward for NKTR-102 in metastatic breast cancer with regulatory agencies."

NKTR-102 was designed to be the first topoisomerase I inhibitor with a novel molecular structure that concentrates the drug in vascularized tumors and extends its circulation time in the plasma. In 2012, the FDA designated NKTR-102 as a Fast Track development program for the treatment of patients with locally recurrent or metastatic breast cancer progressing after treatment with ATC.

Nektar will continue to review and analyze the data from the BEACON study. Data from the BEACON study will be submitted for presentation at an upcoming medical meeting.

Conference Call, Slide Presentation and Webcast Information
Nektar will host a conference call and webcast slide presentation today, March 17, 2015, at 4:45 PM Eastern Time. The call can be accessed by dialing (877) 881-2183 (U.S.) or (970) 315-0453 (international), and entering passcode 9310762. To access the live webcast, or the subsequent archived recording, visit the Investor Relations section of the Nektar website at www.nektar.com. The webcast will be available for replay on Nektar’s website through March 31, 2015.

About the BEACON Study Design
The open-label, randomized, multicenter study enrolled 852 women with locally recurrent or metastatic breast cancer who previously had been treated with ATC and had progressed following treatment. The study was conducted at 139 sites worldwide including in North America, Europe and the Republic of Korea. Nearly half of the patients enrolled in BEACON were located in North America. Patients were randomized on a 1:1 basis to receive 145 mg/m2 of single-agent NKTR-102 once every three weeks or a single agent of the physician’s choice, including ixabepilone, vinorelbine, gemcitabine, eribulin or a taxane. Randomization was stratified by geographic region, prior use of eribulin and receptor status.

The primary endpoint of the BEACON study was overall survival; key secondary endpoints included objective tumor response rates and progression-free survival. The study also evaluated specific biomarker data to assess correlation with efficacy and safety outcomes.

About NKTR-102
NKTR-102 is the first long-acting topoisomerase I inhibitor with an extended half-life and a unique structure that is designed to concentrate the drug in tumors. In patients, NKTR-102 leads to greatly prolonged plasma SN38 exposure compared with irinotecan (elimination half-life of 50 days compared with 2 days) yet peak SN38 concentrations are at least 5- to 10-times less, which may also result in a favorable tolerability profile.

About Metastatic Breast Cancer
Breast cancer is the most frequently diagnosed cancer and is the leading cause of cancer death among women worldwide.i More than 1.6 million new cases of breast cancer were diagnosed among women around the world in 2010.ii Approximately 425,000 women around the world died from the disease in 2010.iii There are approximately 200,000 new cases of breast cancer in the United States and 430,000 in Europe each year.iv Metastatic breast cancer refers to cancer that has spread from the breast to distant sites in the body.

Anthracyclines and taxanes (AT) are the most active and widely used chemotherapeutic agents for breast cancer. However, the increased use of these agents at an early stage of disease often renders tumors resistant to these drugs by the time the disease recurs, thereby reducing the number of treatment options for metastatic disease. Drugs used to treat patients who progress following AT treatment can have response rates as high as 20 to 30 percent. However, resistance develops rapidly and new agents with different mechanisms of action, such as topoisomerase I inhibitors, are needed to allow novel ways to overcome the problem of drug resistance.v There are currently no FDA-approved topoisomerase I inhibitors to treat breast cancer.