20-F – Annual and transition report of foreign private issuers [Sections 13 or 15(d)]

(Filing, Annual, Novartis, 2017, JAN 24, 2018, View Source [SID1234523540])

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Apexian Pharmaceuticals Opens Phase 1 Clinical Study of APX3330 in Patients with Solid Tumors

On January 24, 2018 Apexian Pharmaceuticals, a clinical-stage biopharmaceutical company, has reported the opening of a clinical trial for patients with advanced solid tumors (Press release, Apexian Pharmaceuticals, JAN 24, 2018, View Source [SID1234523543]). The study involves APX3330, an orally administered inhibitor of APE1/Ref-1, a dual-function protein that plays a critical role in promoting and maintaining a broad variety of cancers. Details of the study, including eligibility criteria, the location of participating clinical centers and referral contact information can be found at www.ClinicalTrials.gov, a website maintained by the National Institutes of Health.

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"The initiation of the APX3330 study is a significant step forward in Apexian’s mission to develop safe and effective treatments for cancer patients" said Steve Carchedi, President and CEO of Apexian Pharmaceuticals. "Despite recent advancements in cancer treatments, there continues to be a need for treatments that improve the survival of cancer patients. Apexian is committed to "moving mountains" to help these patients."

The APE1/Ref-1 protein regulates the activity of other cancer-associated proteins, including transcription factors HIF-1-alpha, AP-1, NF-kappa B, and STAT3, proteins that control the aggressiveness of many cancers. Data indicate that Apexian’s drug APX3330 inhibits the cancer-promoting activity of APE1/Ref-1 without causing the side effects normally associated with many types of chemotherapy. Additionally, in a variety of pre-clinical studies, APX3330 has been shown to not only have an anti-cancer effect, but to also prevent, and reverse the nerve damage caused by certain forms of chemotherapy.

The clinical study is the first to explore APX3330 use in patients with advanced cancer, and is the culmination of extensive research on APE1/Ref-1 and APX3330 conducted by Dr. Mark Kelley, Professor and Associate Director of Basic Science Research at Indiana University’s Simon Cancer Center as well as other scientists worldwide. Dr. Kelley’s work on APE1/Ref-1 and APX3330 has previously resulted in significant research grants provided through the National Cancer Institute in order to explore the potential benefit to cancer patients receiving APX3330.

According to Dr. Richard Messmann, Apexian’s Chief Medical Officer, "Apexian’s research, led by Dr. Kelley, has provided us with a clear path to understanding, and an ability to measure, the clinical benefit that may be obtained when cancer patients are treated with APX3330. It also lays the foundation for determining whether patients with chemotherapy-induced peripheral neuropathy (CIPN) may benefit when receiving APX3330. The clinicians involved in the study, including those at the Simon Cancer Center and at START SA (San Antonio, TX) and START Midwest (Grand Rapids, MI) have uniformly expressed excitement regarding their participation in the study."

Iovance Biotherapeutics Announces Preliminary Phase 2 Data for TIL Treatment in Head and Neck and Cervical Cancers

On January 24, 2018 Iovance Biotherapeutics, Inc. (Nasdaq:IOVA), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported preliminary clinical results from two ongoing open-label Phase 2 studies in head and neck and cervical cancers (Press release, Iovance Biotherapeutics, JAN 24, 2018, View Source;p=RssLanding&cat=news&id=2328242 [SID1234523547]).

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The company reported preliminary data from C-145-03, a multicenter Phase 2 study to evaluate the safety and efficacy of autologous Tumor Infiltrating Lymphocytes (LN-145) for the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Three of the eight patients treated with LN-145 had a reduction in tumor size of at least 30% and qualified as a Partial Response (PR) as per RECIST 1.1 criteria. The Objective Response Rate (ORR) in the study is 38% to date. These patients had a median of 4 prior treatments for their cancer and had all received prior anti-PD-1 therapy. Two of eight had also received prior anti-CTLA-4. The most common side effects were pyrexia, chills, and hypotension. Iovance will continue to enroll patients in this study to the full sample size of 47 per protocol.

The company also reported preliminary data from C-145-04, a multicenter Phase 2 study to evaluate the safety and efficacy of autologous Tumor Infiltrating Lymphocytes (LN-145) for the treatment of patients with recurrent, metastatic or persistent cervical carcinoma. Two patients are currently evaluable. One treated with LN-145 had a confirmed PR and one patient had stable disease.

"These early data from the head and neck study show the potential safety and efficacy of TIL therapy in tumor types other than melanoma, and demonstrate the broad utility of TIL therapy in various solid tumors. Recently approved anti-PD-1 therapies have resulted in overall response rates of 13-16% in head and neck cancer patients with a median of 2 prior therapies or similar disposition. We are therefore excited by this early data and believe that LN-145 may offer patients who have failed prior therapies, including anti-PD-1 checkpoints, an important treatment alternative," said Dr. Maria Fardis, PhD, MBA, president and chief executive officer of Iovance Biotherapeutics. "We are also encouraged by the preliminary data reported today in cervical cancer. Previously published data from the National Cancer Institute (NCI) had shown a response in three of nine cervical cancer patients treated with TIL therapy. Patients with metastatic cervical cancer have limited effective treatment options, with no transformative new systemic therapies having been approved over the last several decades."

Pfizer Announces Positive Top-Line Results For Potential Biosimilar To Rituxan®/MabThera®

On January 24, 2018 Pfizer Inc. reported that REFLECTIONS B3281006, a comparative safety and efficacy study of PF-05280586 versus MabThera (rituximab-EU), met its primary endpoint. PF-05280586 is being developed by Pfizer as a potential biosimilar to Rituxan (rituximab-US)/MabThera1 (Press release, Pfizer, JAN 24, 2018, View Source [SID1234523567]).

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The trial demonstrated equivalence in overall response rate (ORR) for the first-line treatment of patients with CD20-positive, low tumor burden, follicular lymphoma.

"We are pleased to report on our fifth proposed biosimilar monoclonal antibody (mAb) with positive study results. These results reinforce the potential of our proposed rituximab biosimilar in providing a safe and effective treatment option for patients," said Amrit Ray, MD, global president, Pfizer Essential Health Research and Development. "As a global leader in novel biologics, and with one of the broadest global portfolios in oncology, we are delivering on our commitment to advancing high-quality medicines for the millions of patients with cancer around the world today and in the future."

Pfizer’s biosimilars pipeline consists of seven distinct biosimilar molecules in mid to late stage development, with three of these in oncology, as well as several others in early stage development.

About the REFLECTIONS B3281006 Study

REFLECTIONS B3281006 is a randomized, double-blind clinical trial evaluating the efficacy, safety, pharmacokinetics and immunogenicity of PF-05280586 versus MabThera (rituximab-EU)for the first-line treatment of patients with cd20-positive, low tumor burden, follicular lymphoma. The primary endpoint measure, ORR, is defined according to the revised response criteria for malignant lymphoma [Time Frame: Week 26]. Results of the study will be presented in full at a future medical meeting or summarized in publication.

More information about the PF-05280586 REFLECTIONS B3281006 study can be found at www.clinicaltrials.gov.

About PF-05280586

PF-05280586 is a monoclonal antibody (mAb) that is in development as a potential biosimilar to Rituxan/MabThera. Rituxan/MabThera is indicated for the treatment of patients with certain types of CD20-positive non-Hodgkin’s lymphoma; CD20-positive chronic lymphocytic leukemia; rheumatoid arthritis; granulomatosis with Polyangiitis and Microscopic Polyangiitis; and other region-specific indications.

PF-05280586 is an investigational compound and has not received regulatory approval in any country. Biosimilarity has not yet been established by regulatory authorities.

Abbott Reports Fourth-Quarter 2017 Results

On January 24, 2018 Abbott (NYSE: ABT) reported financial results for the fourth quarter ended Dec. 31, 2017 (Press release, Abbott, JAN 24, 2018, View Source [SID1234523542]).

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Fourth-quarter worldwide sales of $7.6 billion increased 42.3 percent on a reported basis and 7.7 percent on a comparable operational* basis.

Reported diluted EPS from continuing operations under GAAP was a $(0.50) loss in the fourth quarter, primarily due to the net expense of $1.46 billion for the estimated1 impact of the Tax Cuts and Jobs Act (U.S. tax reform). Excluding the impact of U.S. tax reform and other specified items, adjusted diluted EPS from continuing operations was $0.74 in the fourth quarter, at the high end of the previous guidance range of $0.72 to $0.74.
Abbott issues full-year 2018 guidance for diluted EPS from continuing operations on a GAAP basis of $1.22 to $1.32. Projected full-year adjusted diluted EPS from continuing operations is $2.80 to $2.90, reflecting 14.0 percent growth2 at the midpoint.

In October, Abbott received U.S. FDA clearance for its Confirm Rx Insertable Cardiac Monitor (ICM), the world’s first and only smartphone-compatible ICM designed to help physicians remotely identify cardiac arrhythmias, and obtained CE Mark for XIENCE Sierra, the newest generation of the company’s gold-standard XIENCE everolimus-eluting coronary stent system.

In November, Abbott initiated the U.S. launch of FreeStyle Libre, the only continuous glucose monitoring (CGM) system available that comes factory-calibrated and removes the need for routine fingersticks3 for people with diabetes. In January, Abbott announced that FreeStyle Libre is now available and approved for coverage by the U.S. Center for Medicare & Medicaid Services (CMS).

In December, Abbott received U.S. FDA approval for magnetic resonance (MR)-conditional labeling for its Quadra Assura and Quadra Assura MP cardiac resynchronization therapy defibrillator (CRT-D) devices and its Fortify Assura implantable cardioverter defibrillator (ICD). With these approvals, Abbott has MR-conditional labeling for its full suite of pacemaker, ICD and CRT-D devices.

"2017 was a great year for us – we performed well, our new product pipeline was highly productive and we took some very important strategic steps forward," said Miles D. White, chairman and chief executive officer, Abbott. "We’re entering 2018 with very good momentum."

FOURTH-QUARTER BUSINESS OVERVIEW

Note: Management believes that measuring sales growth rates on a comparable operational basis is an appropriate way for investors to best understand the underlying performance of the business.

Comparable operational sales growth:

Includes prior year results for St. Jude Medical, which was acquired on Jan. 4, 2017, and reflects a reduction to St. Jude Medical’s historic sales related to administrative fees paid to conform to Abbott’s presentation;
Excludes prior year and current year results for the Abbott Medical Optics (AMO) and St. Jude Medical vascular closure businesses, which were divested during the first quarter 2017;
Excludes the current year results for Rapid Diagnostics, which reflect results for Alere, Inc., which was acquired on Oct. 3, 2017; and Excludes the impact of exchange.

* Total Abbott sales from continuing operations include Other Sales of $17 million. In 2016, the AMO business, which was divested during the first quarter 2017, was reported as part of the Medical Devices group. Comparable operational growth rates above exclude results from the AMO business.

* In 2017, total Abbott sales from continuing operations include Other Sales of $237 million, including sales of $175 million from the AMO business, which was divested during the first quarter 2017. In 2016, the AMO business was reported as part of the Medical Devices group. Comparable operational growth rates above exclude results from the AMO business.

n/a = Not Applicable.

Note: In order to compute results excluding the impact of exchange rates, current year U.S. dollar sales are multiplied or divided, as appropriate, by the current year average foreign exchange rates and then those amounts are multiplied or divided, as appropriate, by the prior year average foreign exchange rates.

Fourth-quarter 2017 worldwide sales of $7.6 billion increased 42.3 percent on a reported basis. On a comparable operational basis, worldwide sales increased 7.7 percent. Refer to tables titled "Non-GAAP Reconciliation of Comparable Historical Revenue" for a reconciliation of comparable historical revenue.

Worldwide Nutrition sales increased 3.0 percent on a reported basis in the fourth quarter, including a favorable 1.0 percent effect of foreign exchange, and increased 2.0 percent on an operational basis.

Worldwide Pediatric Nutrition sales increased 2.4 percent on a reported basis in the fourth quarter, including a favorable 0.9 percent effect of foreign exchange, and increased 1.5 percent on an operational basis. In the U.S., continued above-market growth was led by Abbott’s market-leading toddler brands, PediaSure and Pedialyte. International sales decreased 0.2 percent on an operational basis, as growth in China and India was offset by continued challenging market conditions in certain other international countries.

Worldwide Adult Nutrition sales increased 3.6 percent on a reported basis in the fourth quarter, including a favorable 0.8 percent effect of foreign exchange, and increased 2.8 percent on an operational basis. Worldwide sales growth was led by Ensure, Abbott’s market-leading complete and balanced nutrition brand, and Glucerna, Abbott’s market-leading diabetes-specific nutrition brand.

* Rapid Diagnostics reflects sales from Alere, Inc., which was acquired on Oct. 3, 2017. Comparable operational growth rates above exclude results from the Rapid Diagnostics business.

Worldwide Diagnostics sales increased 51.7 percent on a reported basis in the fourth quarter. On a comparable operational basis, sales increased 6.7 percent. Refer to tables titled "Non-GAAP Reconciliation of Comparable Historical Revenue" for a reconciliation of comparable historical revenue.

Core Laboratory Diagnostics sales increased 9.4 percent on a reported basis in the fourth quarter, including a favorable 2.2 percent effect of foreign exchange, and increased 7.2 percent on an operational basis, reflecting continued above-market growth driven by share gains globally.

Molecular Diagnostics sales increased 4.2 percent on a reported basis in the fourth quarter, including a favorable 1.8 percent effect of foreign exchange, and increased 2.4 percent on an operational basis. As expected, growth in infectious disease testing, Abbott’s core area of focus in the molecular diagnostics market, was partially offset by a planned scale down in other testing areas, primarily in the U.S.

Point of Care Diagnostics sales increased 7.2 percent on a reported basis in the fourth quarter, including a favorable 0.4 percent effect of foreign exchange, and increased 6.8 percent on an operational basis, led by continued adoption of Abbott’s i-STAT handheld system.

Rapid Diagnostics sales of $540 million were led by infectious disease testing, including flu and strep testing.

Established Pharmaceuticals sales increased 17.0 percent on a reported basis in the fourth quarter, including a favorable 3.0 percent effect of foreign exchange, and increased 14.0 percent on an operational basis.

Key Emerging Markets comprise several countries that represent the most attractive long-term growth opportunities for Abbott’s branded generics product portfolio. Sales in these geographies increased 15.0 percent on a reported basis in the fourth quarter, including a favorable 2.5 percent effect of foreign exchange, and increased 12.5 percent on an operational basis. Operational sales growth was led by double-digit growth across several geographies, including India, China and Latin America.

Other sales increased 19.6 percent on an operational basis primarily due to the favorable timing of sales in certain countries during the fourth quarter.

Worldwide Medical Devices sales increased 102.2 percent on a reported basis in the fourth quarter. On a comparable operational basis, sales increased 9.6 percent. Refer to tables titled "Non-GAAP Reconciliation of Comparable Historical Revenue" for a reconciliation of comparable historical revenue.

In Cardiovascular and Neuromodulation, worldwide sales in the fourth quarter were led by double-digit growth in Electrophysiology, Heart Failure, Structural Heart and Neuromodulation. In Electrophysiology, during the fourth quarter, Abbott initiated the U.S. launch of its Confirm Rx Insertable Cardiac Monitor (ICM), the world’s first and only smartphone-compatible ICM designed to help physicians remotely identify cardiac arrhythmias. Growth in Structural Heart was driven by MitraClip, Abbott’s market-leading device for the minimally-invasive treatment of mitral regurgitation. In Heart Failure, sales growth was led by market uptake of Abbott’s HeartMate 3 system, which received U.S. FDA approval in the third quarter of 2017. In Neuromodulation, strong double-digit growth was led by several recently launched products for the treatment of chronic pain and movement disorders.

In the fourth quarter, in Rhythm Management, Abbott received U.S. FDA approval for MR-conditional labeling for its Quadra Assura and Quadra Assura MP cardiac resynchronization therapy defibrillator (CRT-D) devices and its Fortify Assura implantable cardioverter defibrillator (ICD). In Vascular, Abbott obtained CE Mark for its XIENCE Sierra drug-eluting coronary stent system, which enhances its competitive position in this category of the market.

In Diabetes Care, worldwide sales increased 33.2 percent on a reported basis in the fourth quarter, including a favorable 5.6 percent effect of foreign exchange, and increased 27.6 percent on an operational basis. Strong double-digit international sales growth was led by FreeStyle Libre, Abbott’s revolutionary CGM system. FreeStyle Libre is the only CGM system available that comes factory-calibrated and removes the need for routine fingersticks3 for people with diabetes. During the fourth quarter, Abbott initiated the U.S. launch of FreeStyle Libre, and in January 2018, Abbott announced that FreeStyle Libre is now available and approved for coverage by CMS.

ABBOTT ISSUES FINANCIAL OUTLOOK FOR 2018

Abbott is issuing full-year 2018 guidance for diluted earnings per share from continuing operations under Generally Accepted Accounting Principles (GAAP) of $1.22 to $1.32.

Abbott forecasts net specified items for the full year 2018 of approximately $1.58 per share. Specified items include intangible amortization expense, acquisition-related expenses, charges associated with cost reduction initiatives and other expenses.

Excluding specified items, projected adjusted diluted earnings per share from continuing operations would be $2.80 to $2.90 for the full year 2018.

Abbott is issuing first-quarter 2018 guidance for diluted earnings per share from continuing operations under GAAP of $0.16 to $0.18. Abbott forecasts specified items for the first quarter of $0.41 per share primarily related to intangible amortization expense, acquisition-related expenses, cost reduction initiatives and other expenses. Excluding specified items, projected adjusted diluted earnings per share from continuing operations would be $0.57 to $0.59.

Abbott has stated its commitment to reduce its debt levels following the recent acquisitions of St. Jude Medical and Alere, Inc. For the full year 2017, Abbott generated operating cash flow in excess of $5.0 billion and free cash flow4 in excess of $4.0 billion. In January 2018, Abbott repaid $4.0 billion of debt and anticipates additional debt repayments throughout 2018.

ABBOTT ANNOUNCES INCREASE IN QUARTERLY DIVIDEND

On Dec. 15, 2017, the board of directors of Abbott increased the company’s quarterly dividend to $0.280 per share from $0.265 per share. Abbott’s cash dividend is payable Feb. 15, 2018, to shareholders of record at the close of business on Jan. 12, 2018. This marks the 376th consecutive quarterly dividend to be paid by Abbott.

Abbott has increased its dividend payout for 46 consecutive years and is a member of the S&P 500 Dividend Aristocrats Index, which tracks companies that have annually increased their dividend for at least 25 consecutive years.