On October 27, 2016 Celgene Corporation (NASDAQ:CELG) reported net product sales of $2,969 million for the third quarter of 2016, a 28 percent increase from the same period in 2015. Net product sales growth includes a 1 percent negative impact from currency exchange effects (Press release, Celgene, OCT 27, 2016, View Source [SID1234516035]).

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Third quarter total revenue increased 28 percent to $2,983 million compared to $2,334 million in the third quarter of 2015.

Net income for the third quarter of 2016 based on U.S. GAAP (Generally Accepted Accounting Principles), was $171 million or $0.21 per diluted share compared to a net loss of $34 million or $0.04 per diluted share in the third quarter of 2015. The results for the third quarter of 2016 include increased research and development expenses as a result of the EngMab AG acquisition. The net loss in the third quarter of 2015 reflected costs related to strategic transactions including the collaboration with Juno Therapeutics and the acquisition of Receptos.

Adjusted net income for the third quarter of 2016 was $1,263 million or $1.58 per diluted share compared to $1,011 million or $1.23 per diluted share for the third quarter of 2015.

"Continued outstanding execution by our teams around the world led to another strong quarter of revenue growth and progress advancing many of our most important strategic programs," said Mark J. Alles, Chief Executive Officer of Celgene Corporation. "Our increasing enterprise-wide momentum has us on-track to exceed key 2016 objectives and positions us well for sustained long-term growth."

Third Quarter 2016 Financial Highlights

Unless otherwise stated, all comparisons are for the third quarter of 2016 compared to the third quarter of 2015. The adjusted operating expense categories presented below exclude share-based employee compensation expense, collaboration-related upfront expense, research and development asset acquisition expense and a litigation-related loss contingency accrual expense. Please see the attached Use of Non-GAAP Financial Measures and Reconciliation of GAAP to Adjusted Net Income for further information relevant to the interpretation of adjusted financial measures and reconciliations of these adjusted financial measures to the most comparable GAAP measures, respectively.

Net Product Sales Performance

REVLIMID sales for the third quarter increased 30 percent year-over-year to $1,891 million and were driven by new patient market share gains and increased duration. U.S. sales of $1,153 million and international sales of $738 million increased 29 percent and 32 percent year-over-year, respectively.
POMALYST/IMNOVID sales for the third quarter were $341 million, an increase of 33 percent year-over-year. U.S. sales were $203 million and international sales were $138 million, an increase of 35 percent and 30 percent year-over-year, respectively. POMALYST/IMNOVID sales grew due to increased volume from duration gains.
OTEZLA sales for the third quarter were $275 million, a 98 percent increase year-over-year. U.S. sales were $245 million and international sales were $30 million. Sales were driven by market share gains and increased prescriber adoption.
ABRAXANE sales for the third quarter were $233 million, a 1 percent increase year-over-year. U.S. sales of $144 million decreased 1 percent year-over-year. International sales were $89 million.
In the third quarter, all other product sales, which include THALOMID, ISTODAX, VIDAZA and an authorized generic version of VIDAZA drug product in the U.S., were $229 million compared to $234 million in the third quarter of 2015.
Research and Development (R&D)

On a GAAP basis, R&D expenses were $1,653 million for the third quarter of 2016 compared to $1,305 million for the same period in 2015. The increase was primarily driven by a $623.3 million asset acquisition expense associated with the purchase of EngMab AG and an increase in early research and clinical trial activity, partially offset by decreases in expenses related to collaboration-related upfront expenses. Adjusted R&D expenses were $644 million for the third quarter of 2016 compared to $488 million for the third quarter of 2015.

Selling, General, and Administrative (SG&A)

On a GAAP basis, SG&A expenses were $698 million for the third quarter of 2016 compared to $550 million for the same period in 2015. The increase was primarily due to a 2016 litigation-related loss contingency accrual expense as well as an increase in donations to independent patient assistance organizations. Adjusted SG&A expenses were $591 million for the third quarter of 2016 compared to $474 million for the third quarter of 2015.

Cash, Cash Equivalents, and Marketable Securities

Operating cash flow was $723 million in the third quarter of 2016. Celgene ended the quarter with approximately $6.9 billion in cash, cash equivalents and marketable securities.

In the third quarter of 2016, Celgene purchased approximately 2.5 million of its shares at a total cost of approximately $273 million. As of September 30, 2016, the Company had approximately $4.9 billion remaining under the stock repurchase program.

2016 Guidance Updated

Previous 2016 Guidance Updated 2016 Guidance
Net Product Sales
Total Approximately $11.0B Approximately $11.2B
REVLIMID Approximately $6.8B Approximately $7.0B
GAAP diluted EPS $3.82 to $4.05 $3.12 to $3.29
Adjusted diluted EPS $5.70 to $5.75 $5.88 to $5.92
GAAP operating margin Approximately 37% Approximately 31%
Adjusted operating margin Approximately 54.0% Unchanged
Weighted average diluted shares 806M 804M
Net product sales guidance for POMALYST/IMNOVID, ABRAXANE and OTEZLA remain unchanged.

2017 Targets Updated

Total net product sales are expected to be at the high end of the range of $12.7 billion to $13.0 billion
REVLIMID net sales are expected to be more than $8.0 billion versus the previous target of approximately $8.0 billion
Adjusted diluted EPS is expected to be at the high end of the range of $6.75 to $7.00
The net product sales target for ABRAXANE and adjusted diluted share count remain unchanged.

Product and Pipeline Updates

Hematology/Oncology

A supplemental New Drug Application (sNDA) was filed with the U.S. Food and Drug Administration (FDA) for the expanded indication of REVLIMID as maintenance treatment in newly diagnosed multiple myeloma (NDMM) patients after receiving an autologous stem-cell transplant (ASCT). The sNDA was granted Priority Review and the Prescription Drug User Fee Act (PDUFA) date for the submission is February 24, 2017. In June, an application was submitted to the European Medicines Agency (EMA) for the review of REVLIMID as maintenance treatment in NDMM patients after receiving an ASCT. A decision on the European Union (EU) application is expected in the first half of 2017.
In August, the European Commission approved the inclusion of data from a pooled analysis of patients with relapsed and/or refractory multiple myeloma and impaired renal function in the IMNOVID label.
Celgene expects to submit a new drug application (NDA) to the FDA for enasidenib (AG-221) in relapsed and/or refractory acute myeloid leukemia (AML) with isocitrate dehydrogenase-2 (IDH2) mutation by year-end. The NDA will be based on data from an ongoing phase I/II trial in patients with relapsed and/or refractory AML and other advanced hematologic malignancies with an IDH2 mutation.
Data at hematology and oncology medical congresses presented in the third quarter and expected in the fourth quarter include:

Data from multiple sponsored and independent studies evaluating the use of ABRAXANE as a single agent or in combination with novel agents and novel regimens in patients with metastatic pancreatic cancer, metastatic breast cancer and non-small cell lung cancer (NSCLC) were presented during the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Annual Meeting in October.
Celgene’s collaboration partner Triphase Accelerator Corporation is expected to present results from a phase I trial evaluating marizomib in combination with bevacizumab in recurrent glioblastoma at the Society for Neuro-Oncology (SNO) meeting in November.
Data from the abound program of ABRAXANE in NSCLC are expected to be presented at the IASLC World Conference on Lung Cancer in December.
Data from the phase II tnAcity trial evaluating ABRAXANE in combination with gemcitabine or carboplatin in patients with triple negative breast cancer are expected at The San Antonio Breast Cancer Symposium (SABCS) in December.
At the 2016 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December, data presentations expected include:
Phase III Myeloma XI trial evaluating REVLIMID as induction and maintenance therapy in patients with NDMM following ASCT.
Final overall survival data from the phase III MM-020 trial evaluating REVLIMID in combination with low-dose dexamethasone in patients with NDMM who were not candidates for stem-cell transplant.
Phase III REMARC trial comparing REVLIMID maintenance to placebo in elderly patients with diffuse large B-cell lymphoma (DLBCL) previously treated with rituximab plus chemotherapy (R-CHOP).
Phase III CONTINUUM trial comparing REVLIMID maintenance to placebo in chronic lymphocytic leukemia following second-line therapy.
Interim data from the phase III MAGNIFYTM trial with REVLIMID in combination with R-CHOP in patients with relapsed and/or refractory indolent lymphoma.
Phase Ib trial evaluating CC-122 in combination with obinutuzumab in patients with relapsed and/or refractory DLBCL or indolent non-Hodgkin’s lymphoma.
Inflammation & Immunology (I&I)

Data at I&I medical congresses presented in the third quarter and expected in the fourth quarter include:

Long-term data from the phase II RADIANCE trial evaluating ozanimod in relapsing multiple sclerosis were presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in September.
Phase Ib trial evaluating the effects of oral GED-0301 (mongersen) on both endoscopic and clinical outcomes in patients with active Crohn’s disease were presented at the United European Gastroenterology Week (UEGW) in October. The phase III program continues to enroll with data expected in 2018.
Phase II trial of RPC4046 in patients with eosinophilic esophagitis were presented at UEGW and the American College of Gastroenterology (ACG) meetings in October.
Phase II TOUCHSTONE trial evaluating ozanimod as induction and maintenance in patients with ulcerative colitis presented at UEGW and ACG.
Pooled 3-year data analyses from ESTEEM 1 and 2 and PALACE 1-3 trials were presented at the European Academy of Dermatology and Venereology (EADV) meeting in October.
Phase IIb trial of OTEZLA in Japanese patients with moderate-to-severe psoriasis were presented at EADV. This trial will be used to support the regulatory approval in Japan.
At the 2016 American College of Rheumatology annual meeting in November, data presentations expected include:
Three-year safety and efficacy data from the PALACE program with OTEZLA in psoriatic arthritis.
Four-year safety and efficacy data from PALACE 3 trial with OTEZLA in DMARD- and/or biologic-experienced psoriatic arthritis patients.
Pooled three-year data from the PALACE program for the enthesitis and dactylitis and HAQ-DI endpoints.
52-week data from the PSA-006 trial of OTEZLA in biologic-naïve patients with active psoriatic arthritis.
Phase II safety and dose-ranging trial of CC-220 in systemic lupus erythematosus. The second part of the phase II trial evaluating improvement in skin manifestations and improvement in the Cutaneous Lupus Area and Severity Index (CLASI) score is enrolling.
An encore presentation of the phase Ib trial evaluating the effects of oral GED-0301 on both endoscopic and clinical outcomes in patients with active Crohn’s disease are expected at the Advances in Inflammatory Bowel Diseases (AIBD) meeting in December.
Business Update

In September, Celgene completed a transaction to acquire Switzerland-based, privately-held biotechnology company EngMab AG for $625.3 million plus contingent development, regulatory and commercial milestones. EngMab’s lead molecule is EM901, a T-cell bi-specific antibody targeting B-cell maturation antigen (BCMA). The acquisition includes an additional undisclosed program. The Company plans to file an Investigational New Drug (IND) application for EM901 in late 2017. The transaction was accounted as an asset acquisition, resulting in $623.3 million of research and development expense and $2.0 million of net working capital acquired.

On October 26, 2016 Dong-A ST Co., Ltd. (170900: Korea SE), the Korean pharmaceutical company, and Beactica AB, the Swedish fragment-based drug discovery company, reported a new multi-year research and drug discovery collaboration and licensing agreement (Press release, Dong-A ST, OCT 26, 2016, View Source [SID1234535725]). Beactica and Dong-A ST will jointly develop novel anti-cancer drugs against certain disease-related oncology targets.

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Under the terms of the agreement, Dong-A ST will gain exclusive global rights for the further development and commercialization of Beactica’s small molecule inhibitors against multiple members of a family of epigenetic enzymes. The partnership will pool existing compound series from both companies and combine Beactica’s unique early-stage lead generation capabilities with DONG-A ST’s strengths in downstream pre-clinical and clinical development of new therapeutic agents.

Beactica will receive an undisclosed upfront payment and is eligible to receive research funding as well as potential milestone payments for certain research, preclinical, clinical and regulatory milestones. In addition, Beactica is eligible to receive royalties on commercial sales of the products resulting from the partnership. Beactica is also entitled to a revenue share from any related future licensing activities by Dong-A. Full financial details remain undisclosed.

"This global research collaboration between Dong-A ST and Beactica which specializes in developing novel drug targets marks a big step forward in development of next generation anti-cancer therapeutics" said Dr Soo-Hyoung Kang, President and CEO of Dong-A ST. "This collaboration and licensing of Beactica’s small molecule inhibitors will greatly strengthen Dong-A ST’s current oncology pipeline and will further enhance Dong-A ST’s global competitiveness in the pharmaceutical industry."

"We’ve been impressed by Dong-A’s commitment to benefiting cancer patients through therapeutics that modulate epigenetic pathways and are excited to initiate this collaboration." said Dr Per Källblad, CEO of Beactica. "This is a ground-breaking partnership in terms of structure, scope and the potential clinical impact of therapeutics created through our complementary capabilities."

Epigenetics is the study of physiological changes caused by altered gene expressions originating from inherited changes other than the DNA sequence itself. Cancer epigenetics is a rapidly emerging research area with potential to provide new treatments for patients by modifying DNA and chromatin, both of which play important roles in tumour development.

On October 26, 2016 X-Rx, Inc, a biotechnology company focused on the creation of small molecule drug candidates, and Mercachem BV, a leading chemistry CRO with expertise in medicinal and process chemistry, reported progress with two discovery-stage oncology programs from the portfolio of X-Rx (Press release, X-Rx, OCT 26, 2016, View Source [SID1234527704]). The programs target Mcl1, an anti-apoptotic target that is over-expressed in many liquid and solid tumor types, and TAK1, a member of the mitogen-activated protein kinase family.

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Under the service agreement with X-Rx, Mercachem is responsible for hit-to-lead and lead optimization campaigns targeting Mcl1 and TAK1. Mcl1-targeting agents could lead to inducing tumor cell death via apoptosis and via modulation of the tumor micro-environment, drive sensitivity to chemotherapy and other immunotherapy approaches. Blocking TAK1, a kinase that when over-expressed in many cell types can drive tumor onset and progression, fibrosis and autoimmune diseases, will have numerous clinical applications.

"In 2015, we successfully partnered two of our therapeutic programs with leading pharma organizations in major markets. We are committed to building on this initial success and bringing additional candidates towards a stage where significant value has been generated to partner them on favorable terms," said Dr. Lee Babiss, CEO of X-Rx. "With today’s news we are taking the next step in the discovery and development of our Mcl1 and TAK1 programs together with Mercachem."

"We are pleased that X-Rx has chosen Mercachem as their collaboration partner as they further explore the therapeutic potential of their two promising oncology targets using our competence and expertise with kinases and PPI targets," commented Dr. Gerhard Müller, SVP Medicinal Chemistry of Mercachem.

On October 26, 2016 Active Biotech AB (NASDAQ OMX NORDIC: ACTI) and NeoTX Therapeutics Ltd. reported that they have entered into a licensing agreementfor Active Biotech’s investigational compound Naptomumab estafenatox ("ANYARA") for cancer immunotherapy (Press release, Active Biotech, OCT 26, 2016, View Source [SID1234523671]). NeoTX will be responsible for the worldwide clinical development and commercialization of the drug.This partnership is a key milestone in NeoTX’s strategy to bring tumor recognition enhancing therapeutics to the market.

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"We are very enthusiastic about our collaboration with Active Biotech. At NeoTX, we are strongly committed to developing innovative immunotherapies for unmet medical needs. "Active Biotech brings to our collaboration outstanding scientific and intellectual capital, and a powerful commitment to positively impact the treatment of cancer," said Asher Nathan, Chief Executive Officer of NeoTX.

Dr. Marcel Rozencweig, Chief Medical Officer of NeoTX and former Head of Global Clinical Oncology Research at BMS said "We are looking forward to developing ANYARA for immuno-oncology applications. We believe that the ANYARA technology is well suited to increase tumor recognition by the immune system and has demonstrated synergistic activity in combination with checkpoint inhibitors in animal models. As such, ANYARA would be attractive in combination with checkpoint inhibitors whose efficacy can be limited by poor tumor recognition".

"We are excited about the partnership with NeoTX, who we consider as an ideal partner for ANYARA. This partnership constitutes the next step in the clinical development, as well as the commercialization strategy, for the project." said Tomas Leanderson, President & CEO of Active Biotech.

About the agreement
Under the terms of the agreement, Active Biotech grants NeoTX exclusive rights to develop and commercialize ANYARA worldwide in cancer indications. The total deal value amounts to $71 million and is contingent upon achievement of clinical, regulatory and commercial milestones whereof Active Biotech will receive $250 000 as an initial payment upon signing. In addition, NeoTX will pay Active Biotech progressive, double-digit royalties on its net sales.

About ANYARA
ANYARA is a TTS (Tumor Targeting Superantigen) compound that increases the ability of the immune system to recognize the tumor. Synergy has been reported in vivo with a combination of ANYARA and a checkpoint inhibitor in an experimental tumor model. Clinically, the development of ANYARA has primarily been focused on cancer indications with a high unmet medical need. Positive data was reported from clinical Phase I trials in lung cancer, renal cell cancer and pancreatic cancer, where ANYARA was studied both as a single agent (monotherapy) and in combination with an established tumor therapy – docetaxel (Taxotere) – in patients with advanced cancer. The results showed that ANYARA was well tolerated both as monotherapy and in combination with docetaxel, and increased tumor recognition by T cells.

A Phase 2/3 trial of ANYARA in combination with interferon alpha in renal cell cancer demonstrated acceptable safety but did not meet its primary efficacy endpoint in the ITT population. The upcoming clinical trial will be done in combination with drugs that inhibit checkpoint dampening of the immune system, a combination strategy in line with the mode of action of ANYARA and supported by preclinical data.