On November 4, 2016 Atara Biotherapeutics, Inc. (Nasdaq:ATRA), a biopharmaceutical company developing meaningful therapies for patients with severe and life-threatening diseases that have been underserved by scientific innovation, reported financial results for the third quarter ended September 30, 2016 and recent operational highlights (Press release, Atara Biotherapeutics, NOV 4, 2016, View Source [SID1234516329]).

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"We are pleased to report that for our lead product candidate, EBV-CTL, we have received feedback from FDA on our approach to comparing material manufactured by our CMO with material previously produced at MSK and have commenced manufacturing to support our Phase 3 trials," said Isaac Ciechanover, Chief Executive Officer and President of Atara Bio. "We have also submitted our Phase 3 trial protocols to FDA, and we look forward to the initiation of these trials by year end."

Recent Highlights and Anticipated Upcoming Milestones

EBV-CTL

Submitted Phase 3 protocols to the U.S. Food and Drug Administration (FDA) incorporating its feedback on two trials of allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (EBV-CTL) in patients with rituximab refractory EBV-post transplant lymphoproliferative disorder (PTLD) following hematopoietic cell transplant (HCT) and solid organ transplant (SOT).
Phase 3 trials are expected to initiate by year end.

Completed manufacturing process transfer for EBV-CTL to our contract manufacturing organization (CMO).
Developed end-to-end supply chain and logistics to support manufacturing and distribution of EBV-CTL.

Received feedback from FDA regarding our comparability protocol designed to compare EBV-CTL material manufactured by our CMO with material previously produced at Memorial Sloan Kettering (MSK).
Commenced production of full scale EBV-CTL lots for the expanded access protocol (EAP) and the Phase 3 trials.

Granted access to priority medicines (PRIME) regulatory support by the European Medicines Agency (EMA) for allogeneic EBV-CTL for the treatment of EBV-PTLD after HCT.

Scientific Advice meeting with the EMA and health technology assessment groups (HTAs) scheduled in the 4th quarter of 2016 to discuss potential pathways for submission of a marketing authorization application (MAA) for EBV-CTL in the treatment of rituximab refractory EBV-PTLD after HCT.

First patient dosed in multi-center EAP trial of EBV-CTL in patients with rituximab refractory EBV-PTLD.
We plan to broaden our EAP trial to include enrollment of patients with other EBV-associated hematologic malignancies and solid tumors.
CMV-CTL

Conducted an end of Phase 2 meeting with the FDA to discuss late-stage development of allogeneic cytomegalovirus (CMV)-specific CTL (CMV-CTL) for the treatment of anti-viral refractory or resistant CMV infection following either HCT or SOT.
We expect to initiate a Phase 3 trial in 2017, once we have completed discussions with the FDA on trial design.

Received positive opinion from the EMA on orphan drug designation for the treatment of CMV infection in patients with impaired immune systems.
CTL Platform Expansion

Expanded our relationship with the Queensland Institute of Medical Research (QIMR Berghofer) including the development of allogeneic CTLs targeting human papilloma virus (HPV) and BK virus (BKV).
HPV is associated with a number of solid tumors including head and neck cancer, cervical cancer, and anal cancer.
BKV is a challenging clinical problem in kidney transplant patients and is a potential cause of organ loss.
Third Quarter 2016 Financial Results

Cash and investments as of September 30, 2016 totaled $278.1 million, which the Company believes will be sufficient to fund its planned operations through 2018.
The Company reported a net loss of $25.4 million, or $0.88 per share, for the third quarter of 2016, as compared to a net loss of $11.9 million, or $0.43 per share, for the third quarter of 2015.
Total research and development expenses were $18.8 million for the third quarter of 2016, compared to $8.1 million for the third quarter of 2015, including $2.6 million and $0.9 million of non-cash stock-based compensation expenses, respectively. The increase was primarily due to an increase in our clinical trial, research, regulatory and manufacturing expenses associated with our T-cell programs of $10.9 million and increased headcount related costs to support these activities of $4.4 million, offset by a decrease in costs associated with our other molecular programs of $4.6 million.
General and administrative expenses were $7.1 million for the third quarter of 2016, compared to $4.1 million for the third quarter of 2015, including $2.7 million and $1.3 million of non-cash stock-based compensation expenses, respectively. The increase was primarily due to a $1.4 million increase in non-cash stock-based compensation driven by new award grants, a $0.9 million increase in compensation-related expenses driven by increased headcount, and to a lesser extent, higher consulting and outside services costs.

On November 4, 2016 Lion Biotechnologies, Inc. (NASDAQ: LBIO), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte technology (TIL), reported its third quarter 2016 financial results and provided a corporate update (Press release, Lion Biotechnologies, NOV 4, 2016, View Source [SID1234516328]).

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"Lion continues building momentum in broadening the utility of our TIL technology in new indications through internal R&D as well as with our collaborators. We recently announced our collaboration with the Karolinska Institute which expands the utility of TIL into two new indications, glioblastoma and pancreatic cancer. We also extended our Cooperative Research and Development Agreement (CRADA) with Professor Rosenberg at the National Cancer Institute (NCI) for an additional 5 years. We continue our process development work in optimizing the process of manufacturing TIL. Some of our preliminary work on developing a more robust and lower cost processes for growth of TIL will be presented at the upcoming 2016 SITC (Free SITC Whitepaper) meeting. We are building our team to become a fully integrated immuno-oncology company with new members with extensive expertise in cell-based therapy as evident by our recent hire of our CFO, Greg Schiffman. We have now doubled the number of our employees since June 2016 and moved to our San Carlos headquarters," said Dr. Maria Fardis, Chief Executive Officer of Lion Biotechnologies.

Recent Business Highlights and Anticipated Milestones

Appointed New Chief Financial Officer: In October 2016, Greg Schiffman, was appointed Chief Financial Officer (CFO) of Lion. Mr. Schiffman has extensive experience in drug development and therapeutics using cellular technologies. Prior to joining Lion Biotechnologies, Mr. Schiffman was Executive Vice President and CFO of StemCells, Inc, a publicly traded company engaged in the research, development, and commercialization of stem cell therapeutics. Prior to that he served as Executive Vice President and CFO of Dendreon Corporation, a publicly traded biotechnology company engaged in the discovery, development and commercialization of novel therapeutics using a proprietary cellular immunotherapy technology.
Entered into License with PolyBioCept AB and Related Clinical Trials Agreement with Karolinska University Hospital: In September 2016, the Company entered into an Exclusive License Agreement with PolyBioCept AB, a Swedish corporation. PolyBioCept has filed two patent applications with claims related to a cytokine cocktail for use in expansion of lymphocytes. Under the License Agreement, the Company received the exclusive right and license to PolyBioCept’s intellectual property to develop, manufacture, market and genetically engineer TIL produced by expansion, selection and enrichment using a cytokine cocktail. The Company also received a co-exclusive license (with PolyBioCept) to develop, manufacture and market genetically engineered TIL under the same intellectual property. The licenses are for the use in all cancers and are worldwide in scope, with the exception that the uses in melanoma are not included for certain countries of the former Soviet Union. The agreement has an initial term of 30 years. Under the terms of the clinical trials agreement, Lion will fund two clinical studies in glioblastoma and pancreatic cancer to be conducted at the Karolinska University Hospital in which TIL is manufactured using the licensed combination of cytokines. Both Phase 1 trials are expected to begin in 2017.
Cooperative Research and Development Agreement with NCI Extended: In August 2016, the Company entered into the second amendment of the CRADA with the NCI, for research and development related to an adoptive cell therapy utilizing TIL in the treatment of metastatic melanoma. The amendment extended the term of the CRADA by five years to August 2021 and modified the focus on the development of TIL as a stand-alone therapy or in combination with FDA-licensed products and commercially available reagents routinely used for adoptive cell therapy.
Two Additional Programs to Enter Phase 2 in 2017: The Company plans to initiate Phase 2 trials for LN-145 for the potential treatment of head and neck and cervical cancers in 2017.
Enrollment in LN-144 Phase 2 Melanoma Study Continues: Lion continues enrollment of patients in the LN-144 Phase 2 melanoma study and intends to present initial data at an upcoming medical conference in 2017.
Headcount: During the three months ended September 30, 2016, the Company increased its headcount from 23 employees to 45 employees to support the expansion of the Company’s clinical product pipeline and development activities including next generation TIL technologies.
Opened New Corporate Headquarters: Lion’s corporate headquarters has now moved to the San Carlos, California location. Lion will, however, retain its existing New York City and Tampa offices.
Third Quarter and Year-to-Date 2016 Financial Results

As of September 30, 2016 the Company held $179.3 million in cash and cash equivalents and short-term investments, compared to $103.7 million as of December 31, 2015.

GAAP and Non-GAAP net loss attributable to common stockholders

GAAP net loss attributable to common stockholders, which included a one-time deemed dividend charge of $49.5 million incurred as a result of the conversion feature of the Series B convertible preferred stock, for the quarter ended September 30, 2016 was $68.2 million, or ($1.15) per share, compared to GAAP net loss attributable to common stockholders of $7.6 million or ($0.16) per share for the quarter ended September 30, 2015. The deemed dividend did not have any monetary impact for the Company.

Non-GAAP net loss attributable to common stockholders, which excludes amounts related to stock-based compensation and the non-cash deemed dividend, for the quarter ended September 30, 2016 was $10.1 million, or ($0.17) per share, compared to non-GAAP net loss attributable to common stockholders of $5.2 million, or ($0.11) per share for the quarter ended September 30, 2015. The non-GAAP net loss attributable to common stockholders for the three months ended September 30, 2016 excludes $8.6 million of non-cash stock-based compensation and a non-cash deemed dividend of $49.5 million. The stock compensation increase year-over-year of $6.3 million is primarily driven by the departure of the Company’s former CFO. The deemed dividend will only impact the current quarter’s financial statements.

GAAP net loss attributable to common stockholders for the nine months ended September 30, 2016, which includes a one-time deemed dividend related to a charge of $49.5 million incurred as a result of the conversion feature of the Series B convertible preferred stock was $86.7 million, or ($1.64) per share, compared to GAAP net loss attributable to common stockholders of $19.3 million or ($0.44) per share for the nine months ended September 30, 2015. Non-GAAP net loss, which excludes amounts related to stock-based compensation and the non-cash deemed dividend for the nine months ended September 30, 2016 was $21.4 million, or ($0.40) per share, compared to non-GAAP net loss of $13.5 million or ($0.31) per share for the nine months ended September 30, 2015.

The Company believes that it is important for investors to understand these non-cash charges as they are materially impacting the quarterly loss and EPS calculations. See "Use of Non-GAAP Financial Measures" below for a description of the Company’s Non-GAAP Financial Measures. Reconciliation between certain GAAP and Non-GAAP measures is provided at the end of this press release.

GAAP and Non-GAAP expenses

GAAP research and development (R&D) expenses of $8.5 million for the quarter ended September 30, 2016 increased by $3.5 million compared to the quarter ended September 30, 2015. The increase in R&D expense is due to increased spending on clinical activities for LN-144. In addition, R&D-associated stock option expenses were $0.6 million for the three months ended September 30, 2016 and $1.8 million for the nine months ended September 30, 2016. Non-GAAP R&D expenses of $7.8 million for the quarter ended September 30, 2016 increased by $3.7 million, compared to $4.1 million for the quarter ended September 30, 2015.

GAAP general and administrative (G&A) expenses of $10.5 million increased by $7.8 million compared to the quarter ended September 30, 2015. Non-GAAP G&A expenses of $2.5 million for the quarter ended September 30, 2016 increased by $1.3 million, compared to $1.2 million for the quarter ended September 30, 2015.

Reconciliation between certain GAAP and Non-GAAP measures is provided at the end of this press release.

Use of Non-GAAP Financial Measures

This press release contains non-GAAP financial measures, including expenses adjusted to exclude certain non-cash expenses. These measures are not in accordance with, or an alternative to, generally accepted accounting principles, or GAAP, and may be different from non-GAAP financial measures used by other companies. The items included in GAAP presentations but excluded for purposes of determining non-GAAP financial measures for the periods presented in this press release are: (i) the non-cash stock-based compensation expense which may fluctuate from period to period based on factors including the timing and accounting of grants for stock options and changes in the Company’s stock price which impacts the fair value of options granted, and (ii) the one-time non-cash deemed dividend related to the conversion feature of the Series B Preferred Stock. The Company believes the presentation of non-GAAP financial measures provides useful information to management and investors regarding various financial and business trends relating to our financial condition and results of operations. When GAAP financial measures are viewed in conjunction with non-GAAP financial measures, investors are provided with a more meaningful understanding of our ongoing operating performance. In addition, these non-GAAP financial measures are among those indicators the Company uses as a basis for evaluating operational performance, allocating resources and planning and forecasting future periods. Non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. To the extent this release contains historical or future non-GAAP financial measures, the Company has also provided corresponding GAAP financial measures for comparative purposes. Reconciliation between certain GAAP and non-GAAP measures is provided at the end of this press release.

2016 Cash Expectations

Lion anticipates the ending cash, cash equivalents and short-term investments as of December 31, 2016, to be in excess of $164.0 million.

Upcoming Events & Presentations

Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 31st Annual Meeting & Associated Programs in National Harbor, Maryland, November 9-13, 2016
Piper Jaffray 28th Annual Health Care Conference, at the Lotte New York Palace hotel in New York City, November 30 at 2:30 p.m. ET

On November 4, 2016 GenVec, Inc. (NASDAQ: GNVC) reported financial results for the third quarter ended September 30, 2016 (Press release, GenVec, NOV 4, 2016, View Source [SID1234516326]). For the three months ended September 30, 2016, the company reported a net loss of $1.2 million or $0.05 per share on revenues of $173,000. This compares to a net loss of $1.5 million or $0.09 per share on revenues of $193,000 for the same period in the prior year. For the nine months ended September 30, 2016, the company reported a net loss of $4.3 million or $0.21 per share on revenues of $489,000. This compares to a net loss of $4.9 million or $0.30 per share on revenues of $725,000 for the same period in the prior year. The company ended the third quarter of 2016 with $8.4 million in cash, cash equivalents, and investments.

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"During the third quarter, the FDA lifted the clinical hold on the CGF166 Phase 1/2 clinical trial, which allowed the drug to advance into the next patient cohort at a higher dose level," said Douglas J. Swirsky, president and CEO of GenVec. "Patient enrollment is currently underway in the fourth cohort and we look forward to updating our stockholders as further progress is made."

"Operationally, we remain focused on business development activities directed at forming new collaborations to maximize the value of our AdenoVerse platform," Mr. Swirsky continued. "Recently presented data demonstrate the potential of our proprietary vectors to deliver genes to immune cells and we believe our platform may offer unique advantages for applications in emerging areas such as cellular immunotherapy and gene editing."

Financial Results for the Three Months and Nine Months Ended September 30, 2016

Revenues for the three-month and nine-month periods ended September 30, 2016 were $173,000 and $489,000, respectively, which represent decreases of 10% and 33% as compared to $193,000 and $725,000 in the comparable prior year periods.

The decrease in revenue for the three-month period ended September 30, 2016 is primarily attributable to a reduced work scope under our hearing loss and balance disorders program, which resulted in a $42,000 reduction in revenue in the current period as compared to the same period in 2015. This was partially offset by an increase of $22,000 in revenue for work performed under our malaria program.

The decrease in revenue for the nine-month period ended September 30, 2016 is primarily attributable to the completion of our contract with the U.S. Department of Homeland Security related to our animal health program in February 2015. We recognized $0.2 million in revenue under this contract in the nine months of 2015 with no corresponding revenue associated with this contract in the same period in 2016. Revenue under our animal health program in 2016 is related to the second amendment to our license agreement with Merial Inc. Also contributing to the decrease was a reduced work scope under our hearing loss and balance disorders program, which resulted in a $0.1 million reduction in revenue in the current period as compared to the same period in 2015. Partially offsetting these decreases was an increase in revenue from our malaria program of $0.1 million, primarily attributable to our grant with the NIH. As noted previously, work under this grant was completed in March 2016.

Operating expenses were $1.7 million and $5.6 million for the three-month and nine-month periods ended September 30, 2016, respectively, which are in-line with the comparable prior year periods.

General and administrative expenses for the three-month and nine-month periods ended September 30, 2016 increased 18% and 4%, respectively, with expenses of approximately $1.2 million and $3.8 million in 2016 as compared to $1.0 million and $3.6 million, respectively, in 2015. The increase is primarily attributable to higher expenses for professional services in the three-month period ended September 30, 2016 as compared to the same period in 2015. For the nine-month period ended September 30, 2016, the increase is primarily attributable to higher personnel costs due to the expansion of our workforce by three full-time employees as compared to the same period in 2015.

Research and development expenses for the three-month and nine-month periods ended September 30, 2016 decreased 26% and 10%, respectively, with expenses of approximately $0.5 million and $1.8 million in 2016 as compared to $0.7 million and $2.0 million, respectively, in 2015. The decreases are primarily attributable to lower expenses for personnel and professional services in both the three- and nine-month periods ended September 30, 2016 as compared to the same periods in 2015.

Other income, net for the three-month and nine-month periods ended September 30, 2016 was $323,000 and $841,000, respectively, as compared to $6,000 and $19,000, respectively, for the same periods in 2015. The increases in the 2016 periods were due to a $0.3 million and $1.1 million change in the fair value of the warrant liabilities in connection with our May 10, 2016 registered offering, respectively, for the three- and nine-month periods ended September 30, 2016, partially offset by financing expenses of $250,000 related to the offering, in the nine-month period ended September 30, 2016.

2016 Guidance

For 2016, GenVec continues to anticipate a cash burn between $6.0 million and $6.5 million, exclusive of our May 2016 financing. We believe our existing resources are sufficient to fund operations into 2018.

On November 4, 2016 Shire plc (LSE: SHP, NASDAQ: SHPG), the leading global biotechnology company focused on serving individuals with rare diseases, reported the depth and breadth of the data it will be presenting at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place December 3-6 in San Diego, California (Press release, Shire, NOV 4, 2016, View Source [SID1234516323]). The company’s robust research in hematology, oncology and genetic disease will be showcased in 4 oral presentations and 12 poster presentations.

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"Shire’s extensive presence at ASH (Free ASH Whitepaper) 2016 reinforces our commitment to discovering and delivering transformative treatments for patients with rare conditions," said Philip J. Vickers, Ph.D., Head of Research and Development, Shire. "We aim to continually lead the scientific dialogue for rare hematologic research and address some of the most urgent unmet needs for patients facing these challenging diseases."

HEMATOLOGY
Data in hematology, the largest portfolio for the company, will focus on research that continues to build on the proven approach of direct factor replacement as the global standard of care for hemophilia. Data presentations will showcase the continued growth of the portfolio and new strategies to improve outcomes for people with hemophilia and other bleeding conditions. The company will also present research on several of its promising early- and late-stage pipeline programs:

Target Joint Status in Patients with Hemophilia A During 18 Consecutive Months of Prophylaxis with a Pegylated Full-Length Recombinant Factor VIII with Extended Half-Life Pub #2592. Session #322. Session Title: Disorders of Coagulation or Fibrinolysis. Poster # II. Sunday, Dec. 4, 2016 6 p.m. – 8 p.m. in Hall GH (San Diego Convention Center)
Modelling FVIII Levels for Prediction of Zero Spontaneous-Joint Bleeding in a Cohort of Severe Hemophilia A Subjects with Target Joints Initiated on Tertiary Prophylaxis Pub #2576. Session #322. Session Title: Disorders of Coagulation or Fibrinolysis. Poster # II. Sunday, Dec. 4, 2016 6 p.m. – 8 p.m. in Hall GH (San Diego Convention Center)
Pharmacodynamic Profile of a Recombinant ADAMTS13 (BAX930) in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome (USS)) Pub #135. Session #311. Session Title: Disorders of Platelet Number of Function: TTP and HUS. Saturday, Dec. 3, 2016 12 p.m. – 1:30 p.m. in Room 29 (San Diego Convention Center)
Appearance of High-Affinity Antibodies Precedes Clinical Diagnosis of FVIII Inhibitors – Preliminary Analysis from the Hemophilia Inhibitor PUP Study (HIPS) Pub #328. Session #322. Session Title: Disorders in Coagulation or Fibrinolysis: Hemophilia Inhibitors. Sunday, Dec. 4, 2016 9:30 a.m. – 11 a.m. in Room 33 (San Diego Convention Center)
ONCOLOGY
As part of Shire’s focus on serving individuals with rare diseases, the company is committed to addressing unmet needs in areas of oncology where patients and providers have limited treatment options. Shire has pipeline assets and research targets for rare cancers including metastatic pancreatic cancer, colorectal cancer and targets in checkpoint inhibitors and allogeneic CAR-T, as well as a biologic treatment approved as part of a multi-agent chemotherapeutic regimen for the treatment of acute lymphocytic leukemia (ALL), ONCASPARTM (pegaspargase), that is approved by the U.S. Food & Drug Administration (FDA) and all 27 EU member states. Data presented at ASH (Free ASH Whitepaper) will include a focus on pegaspargase as a therapeutic option for ALL.

GENETIC DISEASE
Shire is also dedicated to helping patients with inherited illnesses. Type I Gaucher disease is a rare, inherited metabolic condition, and the most common of a family of rare diseases known as lysosomal storage disorders (LSDs). It affects approximately 1 in 50,000 to 1 in 100,000 people in the general population, and 1 in 855 people in the Ashkenazi Jewish community. Every type I Gaucher patient is unique and will experience varying symptoms and degrees of disease severity, making type I Gaucher disease difficult to diagnose. To this end, Shire will be hosting an engaging, case-based presentation to raise disease awareness:

Product Theater: Julie M: A Diagnostic Journey. Monday, Dec. 5, 12:15 p.m. to 1:15 p.m.
Important Information for ADYNOVATE [Antihemophilic Factor (Recombinant), PEGylated]

Indications
ADYNOVATE, [Antihemophilic Factor (Recombinant), PEGylated], is a human antihemophilic factor indicated in adolescent and adult patients (12 years and older) with hemophilia A (congenital factor VIII deficiency) for:

On-demand treatment and control of bleeding episodes
Routine prophylaxis to reduce the frequency of bleeding episodes
ADYNOVATE is not indicated for the treatment of von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION

CONTRAINDICATIONS
ADYNOVATE is contraindicated in patients who have had prior anaphylactic reaction to ADYNOVATE, to the parent molecule (ADVATE), mouse or hamster protein, or excipients of ADYNOVATE (e.g. Tris, mannitol, trehalose, glutathione, and/or polysorbate 80).

WARNINGS & PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions are possible with ADYNOVATE. Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with other recombinant antihemophilic factor VIII products, including the parent molecule, ADVATE. Early signs of hypersensitivity reactions that can progress to anaphylaxis may include angioedema, chest tightness, dyspnea, wheezing, urticaria, and pruritus. Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur.

Neutralizing Antibodies
Formation of neutralizing antibodies (inhibitors) to factor VIII can occur following administration of ADYNOVATE. Monitor patients regularly for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled with expected dose.

ADVERSE REACTIONS
Common adverse reactions (≥1% of subjects) reported in the clinical studies were headache and nausea.

For Full Prescribing Information, visit http://www.shirecontent.com/PI/PDFs/ADYNOVATE_USA_ENG.pdf

Important Information for ADVATE [Antihemophilic Factor (Recombinant)]

Indications
ADVATE [Antihemophilic Factor (Recombinant)] is a recombinant antihemophilic factor indicated for use in children and adults with hemophilia A (congenital factor VIII deficiency) for:

Control and prevention of bleeding episodes
Perioperative management
Routine prophylaxis to prevent or reduce the frequency of bleeding episodes
ADVATE is not indicated for the treatment of von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION

CONTRAINDICATIONS
ADVATE is contraindicated in patients who have life-threatening hypersensitivity reactions, including anaphylaxis, to mouse or hamster protein or other constituents of the product.

WARNINGS & PRECAUTIONS
Hypersensitivity Reactions
Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with ADVATE. Symptoms include dizziness, paresthesia, rash, flushing, facial swelling, urticaria, dyspnea, pruritus, and vomiting. Discontinue ADVATE if hypersensitivity symptoms occur and administer appropriate emergency treatment.

Neutralizing Antibodies
Neutralizing antibodies (inhibitors) have been reported following administration of ADVATE predominantly in previously untreated patients (PUPs) and previously minimally treated patients (MTPs). Monitor all patients for the development of factor VIII inhibitors by appropriate clinical observation and laboratory testing. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures factor VIII inhibitor concentration.

ADVERSE REACTIONS
Serious adverse reactions seen with ADVATE are hypersensitivity reactions, including anaphylaxis, and the development of high-titer inhibitors necessitating alternative treatments to factor VIII. The most common adverse reactions observed in clinical trials (frequency ≥5% of subjects) were pyrexia, headache, cough, nasopharyngitis, arthralgia, vomiting, upper respiratory tract infection, limb injury, nasal congestion, and diarrhea.

For Full Prescribing Information, visit http://www.shirecontent.com/PI/PDFs/ADVATE_USA_ENG.pdf

Important Information for ONCASPARTM (pegaspargase)

Indications
ONCASPAR is an asparagine specific enzyme indicated as a component of a multi-agent chemotherapeutic regimen for treatment of patients with:

First line acute lymphoblastic leukemia
Acute lymphoblastic leukemia and hypersensitivity to asparaginase
DETAILED IMPORTANT RISK INFORMATION

CONTRAINDICATIONS
ONCASPAR is contraindicated in patients who have:

History of serious allergic reactions to ONCASPAR
History of serious thrombosis with prior L-asparaginase therapy
History of pancreatitis with prior L-asparaginase therapy
History of serious hemorrhagic events with prior L-asparaginase therapy
WARNINGS & PRECAUTIONS
Anaphylaxis and Serious Reactions
Anaphylaxis and serious allergic reactions can occur therefore, patients should be observed for one hour after administration. Discontinue ONCASPAR in patients with serious allergic reactions.

Thrombosis
Serious thrombotic events, including sagittal sinus thrombosis can occur Discontinue ONCASPAR in patients with serious thrombotic events.

Pancreatitis
Pancreatitis can occur. Evaluate patients with abdominal pain for evidence of pancreatitis. Discontinue ONCASPAR in patients with pancreatitis.

Glucose Intolerance
Glucose intolerance can occur. In some cases, glucose intolerance is irreversible. Monitor serum glucose.

Coagulopathy
Increased prothrombin time, increased partial thromboplastin time, and hypofibrinogenemia can occur. Monitor coagulation parameters at baseline and periodically during and after treatment.

Hepatotoxicity and Abnormal Liver Function
Hepatotoxicity and abnormal liver function can occur. Perform appropriate monitoring.

ADVERSE REACTIONS
Most common adverse reactions (≥2%) are allergic reactions (including anaphylaxis), hyperglycemia, pancreatitis, central nervous system (CNS) thrombosis, coagulopathy, hyperbilirubinemia, and elevated transaminases.

Hyperlipidemia (hypercholesterolemia and hypertriglyceridemia) has been reported in patients exposed to ONCASPAR.

For Full Prescribing Information, visit http://www.shirecontent.com/PI/PDFs/ONCASPAR_USA_ENG.pdf

Important Information for VPRIV (velaglucerase alfa for injection)

Indications
VPRIV is a hydrolytic lysosomal glucocerebroside-specifi enzyme indicated for long-term enzyme replacement therapy (ERT) for patients with type 1 Gaucher disease.

DETAILED IMPORTANT RISK INFORMATION

CONTRAINDICATIONS
None

WARNINGS & PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis, have occurred with VPRIV. The most commonly observed symptoms of hypersensitivity reactions were headache, dizziness, hypotension, hypertension, nausea, fatigue/asthenia, and pyrexia/body temperature increased. Additional hypersensitivity reactions of chest discomfort, dyspnea, and pruritus have been reported with VPRIV. As with any intravenous protein product, hypersensitivity reactions are possible, therefore appropriate medical support including personnel adequately trained in cardiopulmonary resuscitative measures and access to emergency measures should be readily available when VPRIV is administered. If anaphylactic or other acute reactions occur, immediately discontinue the infusion of VPRIV and initiate appropriate medical treatment. Discontinue VPRIV if hypersensitivity symptoms occur.

ADVERSE REACTIONS
Most common adverse reactions during clinical studies in ≥10% of patients were hypersensitivity reactions, headache, dizziness, abdominal pain, nausea, back pain, joint pain, prolonged activated PTT, fatigue/asthenia, and pyrexia.

For Full Prescribing Information, visit http://pi.shirecontent.com/PI/PDFs/Vpriv_USA_ENG.pdf

On November 4, 2016 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported financial results for the third quarter of 2016 and provided a business update (Press release, Regeneron, NOV 4, 2016, View Source [SID1234516295]).

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Financial Highlights

($ in millions, except per share data)

Three Months Ended
September 30,

2016

2015*

% Change
EYLEA U.S. net product sales

$
854

$
734

16
%
Total revenues

$
1,220

$
1,137

7
%
GAAP net income

$
265

$
210

26
%
GAAP net income per share – diluted

$
2.27

$
1.82

25
%
Non-GAAP net income(2)

$
365

$
276

32
%
Non-GAAP net income per share – diluted(2)

$
3.13

$
2.38

32
%

* See Table 3 of this press release for an explanation of revisions made to 2015 non-GAAP amounts previously reported.

"In the third quarter, we saw continued U.S. sales growth with EYLEA in retinal diseases and with Praluent in hypercholesterolemia," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "We are preparing for a potential approval and launch for Dupixent in atopic dermatitis and continuing to advance our pipeline at all stages."

Business Highlights

Marketed Product Update

EYLEA (aflibercept) Injection for Intravitreal Injection

In the third quarter of 2016, net sales of EYLEA in the United States increased 16% to $854 million from $734 million in the third quarter of 2015. Overall distributor inventory levels remained within the Company’s one- to two-week targeted range.
Bayer commercializes EYLEA outside the United States. In the third quarter of 2016, net sales of EYLEA outside of the United States(1) were $471 million, compared to $371 million in the third quarter of 2015. In the third quarter of 2016, Regeneron recognized $171 million from its share of net profit from EYLEA sales outside the United States, compared to $131 million in the third quarter of 2015.
Praluent (alirocumab) Injection for the Treatment of Elevated Low-Density Lipoprotein (LDL) Cholesterol

In the third quarter of 2016, global net sales of Praluent were $38 million, compared to $4 million in the third quarter of 2015. Product sales for Praluent are recorded by Sanofi, and the Company shares in any profits or losses from the commercialization of Praluent. Praluent was launched in the United States in the third quarter of 2015 and in certain countries in the European Union commencing in the fourth quarter of 2015.
In the second quarter of 2016, the U.S. Food and Drug Administration (FDA) accepted for review a supplemental Biologics License Application (sBLA) for a monthly dosing regimen of Praluent, with a target action date of January 24, 2017. In addition, a regulatory application for a monthly dosing regimen of Praluent was filed in the European Union.
In July 2016, the Japanese Ministry of Health, Labour and Welfare granted marketing and manufacturing authorization for Praluent for the treatment of uncontrolled LDL cholesterol, in certain adult patients with hypercholesterolemia at high cardiovascular risk.
In August 2016, the Company and Sanofi presented data from the Phase 3 ODYSSEY ESCAPE study in patients with heterozygous familial hypercholesterolemia (HeFH) who were undergoing LDL apheresis therapy. The trial demonstrated that adding Praluent to existing therapy reduced LDL cholesterol by approximately 50% from baseline (compared to a 2% increase for placebo). The trial also achieved its primary endpoint, demonstrating that patients who added Praluent to their existing treatment regimen significantly reduced the frequency of their apheresis therapy by 75%, compared to placebo.
The ODYSSEY OUTCOMES trial remains ongoing, and is assessing the potential of Praluent to demonstrate cardiovascular benefit. An independent Data Monitoring Committee will conduct a second interim analysis for futility and overwhelming efficacy (hazard ratio < 0.802 corresponding to p < 0.0001) for the primary endpoint with consistency across subgroups and regions, positive trends for secondary end points including all-cause mortality, and no excess non-cardiovascular mortality. This second interim analysis is expected by the end of this month.
Pipeline Progress

Regeneron has sixteen product candidates in clinical development. These consist of EYLEA and fifteen fully human monoclonal antibodies generated using the Company’s VelocImmune technology, including five in collaboration with Sanofi. In addition to EYLEA and Praluent, highlights from the antibody pipeline include:

Sarilumab, the Company’s antibody targeting IL-6R for rheumatoid arthritis, is currently being studied in the global Phase 3 SARIL-RA program.

On October 28, 2016, the Company and Sanofi announced that the FDA issued a Complete Response Letter (CRL) regarding the Biologics License Application (BLA) for sarilumab. The CRL refers to certain deficiencies identified during a routine good manufacturing practice inspection of the Sanofi fill and finish facility in Le Trait, France. Satisfactory resolution of these deficiencies is required before the BLA can be approved. Sanofi submitted a comprehensive corrective action plan to the FDA, is implementing the corrective actions, and is working closely with the FDA towards a timely resolution. The CRL does not identify any concerns relating to the safety or efficacy of sarilumab.
In July 2016, the European Medicines Agency (EMA) accepted for review the Marketing Authorization Application (MAA) for sarilumab. In addition, in October 2016, an application for marketing approval for sarilumab was submitted in Japan.
Dupixent (dupilumab), the Company’s antibody that blocks signaling of IL-4 and IL-13, is currently being studied in atopic dermatitis, asthma, nasal polyps, and eosinophilic esophagitis.

The FDA previously designated Dupixent as a Breakthrough Therapy for the treatment of adult patients with inadequately controlled moderate-to-severe atopic dermatitis, and in September 2016, accepted the BLA for priority review with a target action date of March 29, 2017.
In October 2016, the FDA granted Breakthrough Therapy designation for Dupixent for the treatment of moderate to severe (12 to less than 18 years of age) and severe (6 months to less than 12 years of age) atopic dermatitis in pediatric patients who are not adequately controlled with, or who are intolerant to, topical medication.
In October 2016, additional data from LIBERTY AD SOLO 1 and SOLO 2 atopic dermatitis studies of Dupixent were presented at the European Academy of Dermatology and Venereology conference and simultaneously published in the New England Journal of Medicine.
The pivotal Phase 3 LIBERTY ASTHMA QUEST study of dupilumab for the treatment of asthma completed enrollment during the third quarter of 2016.
Fasinumab, the Company’s antibody targeting Nerve Growth Factor (NGF), is being studied in patients with pain due to osteoarthritis and chronic low back pain.

In October 2016, the FDA placed the Phase 2b study of fasinumab in chronic low back pain on clinical hold and requested an amendment of the study protocol after observing a case of adjudicated arthropathy in a patient receiving high dose fasinumab who had advanced osteoarthritis at study entry. The Company completed an unplanned analysis which showed clear evidence of efficacy with improvement in pain scores in all fasinumab groups compared to placebo at the 8- and 12-week time points, and preliminary safety results are generally consistent with what has been previously reported with the class. The Company and Teva plan to design a pivotal Phase 3 study in chronic low back pain that excludes patients with advanced osteoarthritis.
In October 2016, the Company announced that at the 36-week analysis of the Phase 2/3 clinical study of fasinumab in patients with moderate-to-severe osteoarthritis pain of the hip or knee, the incidence of adjudicated arthropathies was found to be potentially dose-dependent, with a higher rate of patients experiencing arthropathies in the higher dose groups. In the ongoing fasinumab osteoarthritis pivotal Phase 3 program, the Company and Teva are planning to advance only the lower doses from the Phase 2/3 study, subject to discussion with the FDA and other health authorities.
Nesvacumab, the Company’s antibody to Ang2 co-formulated with aflibercept for intravitreal injection, is currently being studied in patients with wet AMD and diabetic macular edema (DME). The Phase 2 RUBY study of nesvacumab/aflibercept for the treatment of DME completed enrollment during the fourth quarter of 2016.

Rinucumab, the Company’s antibody to PDGFR-beta co-formulated with aflibercept for intravitreal injection, is currently being studied in patients with neovascular age-related macular degeneration (wet AMD). In September 2016, the Company announced top-line results from the Phase 2 CAPELLA study. These data showed that at 12 weeks, rinucumab in combination with aflibercept did not add to the improvement in best corrected visual acuity (BCVA) that was demonstrated with intravitreal aflibercept injection monotherapy, the primary endpoint of the study. Results in the EYLEA monotherapy arm of the CAPELLA study were consistent with the efficacy and safety seen in Phase 3 pivotal studies of EYLEA in wet AMD.

REGN3500 entered Phase 1 clinical development for the treatment of inflammatory diseases in the third quarter of 2016. Sanofi exercised its right to opt-in to co-develop REGN3500.

Business Development Update

In July 2016, the Company and Adicet Bio, Inc. entered into a license and collaboration agreement to develop next-generation engineered immune-cell therapeutics with fully human chimeric antigen receptors and T-cell receptors directed to disease-specific cell surface antigens in order to enable the precise engagement and killing of tumor cells.
In September 2016, the Company and Teva Pharmaceuticals International GmbH (Teva), a wholly owned subsidiary of Teva Pharmaceutical Industries Ltd., entered into a collaboration agreement to develop and commercialize fasinumab. Under the terms of the agreement, the Company will lead global development and commercialization in the United States, and Teva will lead development and commercialization in territories outside the United States (excluding certain Asian countries that are subject to a separate collaboration agreement previously entered into between the Company and Mitsubishi Tanabe Pharma Corporation).
Third Quarter 2016 Financial Results

Product Revenues: Net product sales were $857 million in the third quarter of 2016, compared to $738 million in the third quarter of 2015. EYLEA net product sales in the United States were $854 million in the third quarter of 2016, compared to $734 million in the third quarter of 2015.

Total Revenues: Total revenues, which include product revenues described above, increased by 7% to $1,220 million in the third quarter of 2016, compared to $1,137 million in the third quarter of 2015. Total revenues also include Sanofi and Bayer collaboration revenues of $336 million in the third quarter of 2016, compared to $382 million in the third quarter of 2015. Collaboration revenues in the third quarter of 2016 decreased primarily due to lower reimbursable research and development expenses and an increase in the Company’s share of losses primarily from the commercialization of Praluent and pre-commercialization activities for sarilumab and Dupixent under the Company’s antibody collaboration with Sanofi, partly offset by an increase in the Company’s net profit from commercialization of EYLEA outside the United States.

Refer to Table 4 for a summary of collaboration revenue.

Research and Development (R&D) Expenses: GAAP R&D expenses were $543 million in the third quarter of 2016, compared to $426 million in the third quarter of 2015. The higher R&D expenses in the third quarter of 2016 were principally due to the $25 million up-front payment made in connection with the July 2016 license and collaboration agreement with Adicet, higher development costs, including manufacturing drug supplies, primarily related to fasinumab, Dupixent, and REGN2810, and higher headcount to support the Company’s increased R&D activities, partly offset by lower development costs primarily related to Praluent and sarilumab. In addition, in the third quarter of 2016, R&D-related non-cash share-based compensation expense was $81 million, compared to $64 million in the third quarter of 2015.

Selling, General, and Administrative (SG&A) Expenses: GAAP SG&A expenses were $270 million in the third quarter of 2016, compared to $210 million in the third quarter of 2015. The increase was primarily due to higher commercialization-related expenses in connection with EYLEA and Praluent, and higher headcount. In addition, in the third quarter of 2016, SG&A-related non-cash share-based compensation expense was $49 million, compared to $36 million in the third quarter of 2015.

Cost of Goods Sold (COGS): GAAP COGS was $30 million in the third quarter of 2016, compared to $67 million in the third quarter of 2015. COGS primarily consists of costs in connection with producing U.S. EYLEA commercial supplies, various start-up costs in connection with the Company’s Limerick, Ireland commercial manufacturing facility, and royalties. COGS decreased principally due to a decrease in royalties since the Company’s obligation to pay Genentech based on U.S. sales of EYLEA ended in May 2016.

Cost of Collaboration and Contract Manufacturing (COCM): GAAP COCM was $14 million in the third quarter of 2016, compared to $42 million in the third quarter of 2015. COCM decreased primarily due to lower royalties since the Company’s obligation to pay Genentech based on sales of EYLEA outside the United States also ended in May 2016.

Income Tax Expense: In the third quarter of 2016, GAAP income tax expense was $101 million and the effective tax rate was 27.6%, compared to $183 million and 46.5% in the third quarter of 2015. The effective tax rate for the third quarter of 2016 was positively impacted, compared to the U.S. federal statutory rate, by the tax benefit associated with stock-based compensation, the domestic manufacturing deduction, the federal tax credit for increased research activities, and changes to tax reserves, partly offset by the negative impact of losses incurred in foreign jurisdictions with rates lower than the federal statutory rate and the non-tax deductible Branded Prescription Drug Fee. As described in Table 3 of this press release, the Company adopted Accounting Standards Update 2016-09 (ASU 2016-09), Compensation – Stock Compensation, Improvements to Employee Share-Based Payment Accounting, during the second quarter of 2016. ASU 2016-09 requires companies to recognize all excess tax benefits and tax deficiencies in connection with stock-based compensation as income tax expense or benefit in the income statement (previously, excess tax benefits were recognized in additional paid-in capital on the balance sheet).

GAAP and Non-GAAP Net Income: The Company reported GAAP net income of $265 million, or $2.53 per basic share and $2.27 per diluted share, in the third quarter of 2016, compared to GAAP net income of $210 million, or $2.04 per basic share and $1.82 per diluted share, in the third quarter of 2015.

The Company reported non-GAAP net income of $365 million, or $3.48 per basic share and $3.13 per diluted share, in the third quarter of 2016, compared to non-GAAP net income of $276 million, or $2.67 per basic share and $2.38 per diluted share, in the third quarter of 2015.

A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.