On August 9, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP) reported financial results for the second quarter ended June 30, 2016, and provided an update on the Company’s recent activities (Press release, Ziopharm, AUG 9, 2016, View Source [SID:1234514473]).

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"ZIOPHARM had a very productive first half, with the achievement of pipeline and corporate milestones across the breath of our portfolio and the advancement of our goal to position the company at the forefront of those harnessing the immune system to target cancer," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM Oncology. "Central to this effort, we were pleased to have amended the terms of our collaboration with Intrexon to facilitate the commercialization of our immunotherapy assets. The benefit of this new structure is expected to be first realized with our gene therapy Ad-RTS-hIL-12 + veledimex program, which remains on track to move into a registrational trial in advanced glioblastoma in 2017."

Dr. Cooper added: "As we progress through the remainder of 2016, we will continue to work with our collaborators, including Intrexon Corporation and the MD Anderson Cancer Center, to advance new therapies into the clinic. We look forward in 2016 to seeing six clinical trials exploring immuno-oncology approaches and combinations, in addition to preclinical projects advancing towards the clinic. As these programs mature, we expect to see proof-of-concept clinical data that will drive value for all of our stakeholders."

Corporate and Program Updates

Corporate

Amended Exclusive Channel Collaborations with Intrexon to Improve Alignment as Programs Advance through Development. In June, ZIOPHARM and Intrexon Corporation (NYSE:XON) announced amendments to their Exclusive Channel Collaborations (ECCs) in the fields of oncology and graft-versus-host-disease (GvHD) to improve alignment between both companies as ZIOPHARM broadens its pipeline and advances multiple therapeutic programs in the clinic.

Under the terms of the amendments:

Operating profit rates payable to Intrexon from ZIOPHARM on products developed under its two existing collaborations will be reduced from 50% to 20%. This reduction will not apply to royalties or other payments made with respect to the companies’ existing collaboration with Merck Serono, the biopharmaceutical business of Merck KGaA;

Economics from any future sublicensing arrangements with potential third party collaborators will remain evenly split.
In consideration of the amendments, ZIOPHARM has issued shares of a new class of preferred stock that carries an initial stated value of $120 million and a monthly dividend of 1%, payable in additional preferred shares. Only upon the first approval of a product in the United States or upon certain fundamental transactions, such as a change of control of ZIOPHARM, the preferred shares issued to Intrexon will be converted into ZIOPHARM common stock equal to the aggregate stated value divided by the volume weighted average closing price of ZIOPHARM’s common stock over the 20 trading days ending on the date that the product approval or such transaction is announced.

Gene Therapies

Ad-RTS-hIL-12 + veledimex is a gene therapy candidate for the controlled expression of interleukin 12 (IL-12), a critical protein for stimulating an anti-cancer immune response, using the RheoSwitch Therapeutic System (RTS) gene switch. ZIOPHARM is currently enrolling patients in two studies of Ad-RTS-hIL-12 + veledimex: a multi-center Phase 1 study in patients with recurrent or progressive glioblastoma multiforme (GBM), an aggressive form of brain cancer, and a Phase 1b/2 study for the treatment of patients with locally advanced or metastatic breast cancer following standard chemotherapy.

Presented Clinical Data Highlighting Favorable Interim Survival Results in Phase 1 Study of Ad-RTS-hIL-12 + Veledimex in Brain Cancer. ZIOPHARM presented data from its Phase 1, multi-center dose-escalation study of patients with recurrent high-grade gliomas at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held June 3-7, 2016 in Chicago and updated at an American Society of Hematology (ASH) (Free ASH Whitepaper) Workshop on Genome Editing in Washington D.C. on July 14, 2016. These data demonstrate promising early activity in this medically fragile patient population, with a median overall survival that has not been reached with 11 of 14 patients alive and in follow up, and a median follow up of 8 months with 6 patients out of 7 patients alive in the study’s first dose cohort (20mg veledimex). The study also showed that IL-12 in the bloodstream was found to be proportional to the amount of veledimex administered, demonstrating that this orally-delivered activator crossed the blood brain barrier to activate the IL-12 gene programming deposited in the tumor and turned on the RheoSwitch technology in a dose-dependent manner. In June, ZIOPHARM announced the successful completion of enrollment in the first and second dosing cohorts (40mg veledimex) of the study, as well as the initiation of enrollment in a third cohort (30mg veledimex).

Preclinical Studies Combining Ad-RTS-IL-12 + Veledimex and Immune Checkpoint Inhibitors in Brain Tumor Models Presented at ASGCT (Free ASGCT Whitepaper), Combination Study Expected to Initiate in 2016. In an oral presentation, ZIOPHARM presented data from preclinical studies of Ad-RTS-IL-12 + veledimex combined with immune checkpoint inhibitors (iCPI) in glioblastoma (GBM) mouse models at the 2016 Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper), which took place May 4-7, 2016 in Washington, D.C. Results demonstrated that survival of mice treated with Ad-RTS-IL-12 + veledimex and anti-PD-1 therapy was superior to either treatment alone, with a combination showing 100% survival. Because Ad-RTS-IL-12 and anti-PD-1 are clinically available, these data provide impetus for evaluating this combination immunotherapy in humans. ZIOPHARM plans to initiate a combination study in 2016.
Adoptive Cell Therapies

ZIOPHARM is developing various immuno-oncology programs, including chimeric antigen receptor T-cell (CAR-T), T-cell receptor (TCR), and natural killer (NK) adoptive cell-based therapies. These programs are being advanced in collaboration with Intrexon, MD Anderson Cancer Center, and Merck Serono (CAR-T only).

Announced Plans for Phase I Clinical Trial with CD33 CAR-T Cell Therapy. In July, ZIOPHARM announced plans for a Phase I adoptive cellular therapy clinical trial utilizing autologous T cells transduced with lentivirus to express a CD33-specific chimeric antigen receptor (CAR) in patients with relapsed or refractory acute myeloid leukemia (AML). The trial is based on preclinical studies, including in vitro data demonstrating that lentiviral-transduced CAR-T cells targeting CD33 exhibit specific killing activity for CD33+ AML cells and a proof-of-concept study utilizing an in vivo mouse model for AML, which showed that these CAR-T cells were able to eliminate disease and significantly enhance survival as compared to control groups. These positive preclinical results indicate biological activity and are suggestive of potential therapeutic effect for the treatment of AML.

Announced Publication of First-In-Human Trials using Non-Viral Sleeping Beauty System to Express CD19-Specific CAR in T cells in Journal of Clinical Investigation. In August, ZIOPHARM announced the publication of data highlighting the benefits of using the non-viral Sleeping Beauty (SB) system to genetically modify T cells to express a chimeric antigen receptor (CAR) for use against leukemias and lymphomas. The article, titled "Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells," was published in the Journal of Clinical Investigation (doi:10.1172/JCI86721), and is available online here.
The paper describes results for 26 patients with multiply relapsed B-lineage acute lymphoblastic leukemia (ALL, n=17) or B-cell non-Hodgkin lymphoma, (NHL, n=9) who were enrolled in two investigator-initiated clinical trials at the University of Texas MD Anderson Cancer Center infused with SB-modified T cells after autologous (n=7) or allogeneic (n=19) hematopoietic stem-cell transplantation (HSCT). Although the primary objective of these trials was not to establish efficacy, the recipients’ outcomes are encouraging, with apparent doubling of survivals compared to historical controls which is attributed to the persistence of the infused T cells. Additionally, by infusing a CD19-specific CAR T cells to target minimal residual disease after autologous and allogeneic HSCT, the approach may improve tolerability by avoiding cytokine storm.

Milestones

ZIOPHARM achieved and expects the following milestones to occur in 2016:

Intra-tumoral IL-12 RheoSwitch programs:
Clinical update presented from the Company’s Phase 1 study of GBM at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)
Update on Phase 1/2 study in Breast Cancer with standard of care presented at ASCO (Free ASCO Whitepaper)
Pre-clinical data presented at the American Society of Cell and Gene Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting for combining with checkpoint inhibitor therapy (anti PD-1)
Initiate combination study of Ad-RTS-hIL-12 with anti PD-1
CAR+ T programs:
Continuation of second generation CD19 CAR+ T clinical study
Initiate a CAR+ T clinical study for CD33
Preclinical data presented at ASGCT (Free ASGCT Whitepaper) for shortening the time of ex vivo manufacture of SB-modified T cells
Initiate CAR+ T-cell preclinical studies for other hematological malignancies and solid tumors
TCR-T programs
Initiate TCR-modified T-cell preclinical studies
NK cell programs
Initiate a Phase 1 study of off-the-shelf NK cells for AML
GvHD programs
Initiate preclinical studies
Pediatric programs
Pre-clinical data to be presented in the fall with intra-tumoral IL-12 under RheoSwitch control for brain tumor
The Company is also evaluating additional potential preclinical candidates and continuing discovery efforts aimed at identifying other potential product candidates under its Exclusive Channel Agreement with Intrexon. In addition, the Company may seek to enhance its pipeline in immuno-oncology through focused strategic transactions, which may include acquisitions, partnerships and in-licensing activities.

Aug. 9, 2016 /PRNewswire/ — Halozyme Therapeutics, Inc. (NASDAQ: HALO) today reported financial results and recent highlights for the second quarter ended June 30 (Press release, Halozyme, AUG 9, 2016, View Source [SID:1234514466]).

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"I am very pleased with the strong momentum in our ENHANZE platform leading to today’s increase in our 2016 revenue guidance, driven by continued royalty revenue growth and expansion of the addressable patient population through the approval of two new indications," said Dr. Helen Torley, president and chief executive officer. "With a range of new targets being tested in phase 1 trials, ENHANZE remains a growing value driver for the company.

"We also continue to see strong, ongoing interest and support from investigators for PEGPH20 as we initiated sites in our phase 3 study in pancreatic cancer, dosed the first metastatic breast cancer patient in our clinical trial with Eisai and resumed our trial in combination with KEYTRUDA (pembrolizumab) in lung and gastric cancer patients."

Second Quarter 2016 and Recent Highlights include:

Presenting key efficacy and safety data from stage 1 of its phase 2 clinical study in metastatic pancreatic cancer patients treated with PEGPH20 at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Conference. The results continued to show clinically meaningful efficacy for HA-high patients treated with PEGPH20 plus gemcitabine and ABRAXANE (nab-paclitaxel) versus gemcitabine and ABRAXANE alone, including median progression free survival of 9.2 months versus 6.0 months. Safety data presented from stage 2 of the study continued to show a reduction in the rate of thromboembolic events in both treatment arms as compared to stage 1.
The company expects to report mature response rate and progression free survival data from stage 2 of the study in the fourth quarter.
Progressing with site initiations in the HALO-301 | Pancreatic study towards the goal of approximately 90 percent of centers ready to screen patients by the end of 2016.
After assessing recruitment and the enrollment of increasingly later line patients, Halozyme has decided to discontinue the PRIMAL study of PEGPH20 with docetaxel in non-small cell lung cancer patients and focus on immuno-oncology therapy in its ongoing phase 1b study of PEGPH20 in combination with KEYTRUDA.
Resuming patient enrollment and dosing in its ongoing phase 1b clinical study evaluating PEGPH20 in combination with KEYTRUDA (pembrolizumab) in relapsed lung and gastric cancer patients under a revised clinical protocol. The revised protocol has been submitted to all institutional review boards (IRB) and is pending feedback from the FDA. The majority of IRBs have approved the amended protocol allowing the study to resume. The company continues to project that the study will move into the dose expansion phase by the end of 2016, pending feedback from the FDA.
Dosing of first patient in its phase 1b/2 clinical collaboration with Eisai evaluating eribulin in combination with PEGPH20 in women with advanced or metastatic, HER2-negative, HA-high breast cancer.
Shire launching the pediatric indication of HYQVIA in eight European countries to treat primary and certain secondary immunodeficiencies, following a marketing authorization granted by the European Commission in May. HYQVIA is co-administered with Halozyme’s ENHANZE technology.
Pfizer completing a phase 1 study of rivipansel with rHuPH20, demonstrating the feasibility of large volume subcutaneous administration in combination with Halozyme’s ENHANZE technology.
Roche receiving approval by the European Medicines Agency for an indication of Mabthera SC to treat patients with chronic lymphocytic leukemia.
Refinancing existing debt, increasing expected cash balances by $22 million in 2016 and 2017, with the option to borrow an additional $15 million in 2017.
Second Quarter 2016 Financial Highlights

Revenue for the second quarter was $33.3 million compared to $43.4 million for the second quarter of 2015. Revenue in the prior year period included $23 million for the initiation of the company’s partnership with AbbVie. Excluding the $23 million payment, revenue grew 64 percent year-on-year. Revenue for the second quarter included $12.3 million in royalties, $9.5 million in sales of bulk rHuPH20 primarily for use in manufacturing collaboration products and $4.2 million in HYLENEX recombinant (hyaluronidase human injection) product sales.
Research and development expenses for the second quarter were $35.5 million, compared to $21.2 million for the second quarter of 2015. The planned increases were primarily due to a ramp in spending associated with PEGPH20 study HALO-301, the investment in studies to explore the pan-tumor potential of PEGPH20 and manufacturing and clinical supply expenses that are reimbursed by ENHANZE partners.
Selling, general and administrative expenses for the second quarter were $11.2 million, compared to $9.8 million for the second quarter of 2015. The increase was primarily due to personnel expenses, including stock compensation, for the period.
Net loss for the second quarter was $26.9 million, or $0.21 per share, compared to net income in the second quarter of 2015 of $3 million, or $0.02 per share.
Cash, cash equivalents and marketable securities were $230 million at June 30 compared to $238.6 million at March 31, 2016.
Financial Outlook for 2016

For the full year 2016, the company updated its prior guidance and now expects:

Net revenues to be in the range of $140 million to $150 million, an increase from the prior range of $130 million to $145 million;
Operating expenses to continue to be in the range of $245 million to $260 million;
Cash flow to be in the range of $65 million to $85 million, an increase from the prior range of $45 million to $65 million; and
Year-end cash balance to be in the range of $170 million to $190 million from the prior range of $150 million to $170 million, which was increased on June 8 when the company announced a debt refinancing agreement
– See more at: View Source#sthash.dbGsP3hr.dpuf.

On August 9, 2016The Endoscopy Division of FUJIFILM Medical Systems U.S.A., Inc. reported that it will sponsor a complimentary online educational webinar for thoracic surgeons, interventional pulmonologists, pulmonologists, nurse practitioners and physician assistants entitled "Lung Cancer: The State of the Disease" on Thursday, August 25th from 2PM-3PM EST (Press release, Fujifilm, AUG 9, 2016, View Source [SID:1234514465]). David Feller-Kopman, MD, Director of Bronchoscopy & Interventional Pulmonology at Johns Hopkins Hospital and Associate Professor of Medicine & Otolaryngology–Head and Neck Surgery, Johns Hopkins University will deliver the presentation and also participate in a Q&A session.

More people die every year from lung cancer than from colon, breast and prostate cancer combined. Dr. Feller-Kopman’s presentation will focus on the epidemiology of lung cancer, as well as the very latest on screening trends, diagnosis, staging, and treatment.

"Lung cancer is an epidemic, and physicians and healthcare professionals must take the lead in improving outcomes for patients," said Dr. Feller-Kopman. "During this webinar, I will cover research, trends and ways to improve the quality of life for patients with lung cancer, including the use of EBUS, a highly valuable tool in the staging of lung cancer."

Dr. Feller-Kopman’s research over the years has focused on pleural pathophysiology and the evaluation and management of patients with lung cancer. He regularly uses Fujifilm’s Endobronchial Ultrasound System (EBUS) in his lab work as well as with patients. He has published more than 150 original investigations and review articles and has trained 13 fellows in interventional pulmonology. He is the immediate past president of the American Association for Bronchology and Interventional Pulmonology (AABIP), the past chair of the Interventional Chest / Diagnostic Procedure Network of the American College of Clinical Pharmacy (ACCP) and an active member of the American Thoracic Society (ATS) Thoracic Oncology Assembly.

Medical professionals in the field of pulmonology have recognized Fujifilm’s innovative Endobronchial Ultrasound System (EBUS)—specifically designed for supporting advanced diagnosis and staging within the lungs—for its performance and high-quality imaging.

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On August 9, 2016 Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company"), a specialty biopharmaceutical company engaged in developing and commercializing novel treatments in oncology, endocrinology and women’s health, reported financial and operating results for the second quarter ended June 30, 2016.

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Commenting on recent key developments, David A. Dodd, President and Chief Executive Officer of the Company, stated, "After the end of Q2, we concluded two important out-license agreements for Zoptrex, confirming the market’s interest in our lead oncology compound, Zoptrex (zoptarelin doxorubicin). Zoptrex is a novel synthetic peptide carrier linked to doxorubicin as a New Chemical Entity (NCE). Based on recent information regarding the survival of patients in the Phase 3 clinical trial of Zoptrex, we expect to complete the trial by year-end. If the results of the trial warrant doing so, we intend to file a new drug application for Zoptrex in the first half of 2017."

Mr. Dodd continued his commentary with an update on the development of Macrilen (macimorelin), "We are pleased to announce that we should complete enrollment in our confirmatory Phase 3 study of Macrilen for the evaluation of adult growth hormone deficiency by the end of August. As a result, we are very confident that the study of Macrilen will be concluded in 2016. If our expectations for completion of the confirmatory Phase 3 study are realized and if the top-line results indicate that the product attained the primary endpoint of the Phase 3 study, we expect to file an NDA for Macrilen during the first half of 2017. Since the regulatory review period for the Macrilen confirmatory study is six months, we could begin commercializing the product late in 2017."

Second Quarter 2016 Financial Highlights

R&D costs were $3.7 million for the three-month period ended June 30, 2016 and $7.4 million for the six-month period then ended, compared to $4.5 million and $8.9 million, respectively, for the three-month and six-month periods ended June 30, 2015. The decrease for the three-month and six-month periods ended June 30, 2016, as compared to the same period in 2015, is mainly attributable to lower comparative third-party costs. Third-party costs attributable to Zoptrex decreased considerably during the three-month and six-month periods ended June 30, 2016, as compared to the same periods in 2015, mainly due to the fact that dosing of patients in the ZoptEC trial was completed in February 2016. This is consistent with our expectations as we are approaching the end of the clinical trials. In addition, during 2015, we started the confirmatory Phase 3 clinical trial of Macrilen, which explains the increase in costs for this product candidate. The overall decrease in R&D costs is also explained by lower employee compensation and benefits costs, lower facilities rent and maintenance as well as lower other costs. A substantial portion of this decrease is due to the realization of cost savings in connection with our effort to streamline our R&D activities and to increase our commercial operations and flexibility by reducing our R&D staff, which was started in 2014, and for which a provision was recorded in the third quarter of 2014.

G&A expenses were $1.9 million for the three-month period ended June 30, 2016, and $3.8 million for the six-month period then ended, compared to $2.0 million and $5.4 million, respectively, for the three-month and six-month periods ended June 30, 2015. The comparative decrease for the six-month period is mainly attributable to the recording, in the prior year quarter, of certain transaction costs allocated to warrants in connection with the completion of the March 2015 Offering.

Selling expenses were $1.7 million for the three-month period ended June 30, 2016 and $3.4 million for the six-month period then ended, essentially unchanged as compared to the three-month and six-month periods ended June 30, 2015. The selling expenses for the three- and six-month periods ended June 30, 2016 and 2015 represent the costs of our contracted sales force related to the co-promotion activities as well as our internal sales management team. Those activities were launched during the fourth quarter of 2014.

Net loss for the three-month and six-month periods ended June 30, 2016 were $7.0 million and $10.7 million, respectively, or $0.71 and $1.08, respectively, both per basic and diluted share. During the same three-month and six-month periods in 2015, our net loss was $15.1 million and $24.8 million, respectively, or $13.65 and $27.22, respectively, per basic and diluted share for the same period in 2015. The decrease in net loss for the three-month and six- month periods ended June 30, 2016, as compared to the same periods in 2015, is due largely to lower operating expenses and higher comparative net finance income.

Cash and cash equivalents were approximately $26.2 million as at June 30, 2016, compared to approximately $33.0 million as at March 31, 2016.

On August 9, 2016 Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, reported financial results for the second quarter ended June 30, 2016 (Press release, Puma Biotechnology, AUG 9, 2016, View Source [SID:1234514457]).

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Unless otherwise stated, all comparisons are for the second quarter and six months ended June 30, 2016, compared to the second quarter and six months ended June 30, 2015.

Based on accounting principles generally accepted in the United States (GAAP), Puma reported a net loss applicable to common stock of $66.6 million, or $2.05 per share, for the second quarter of 2016, compared to a net loss applicable to common stock of $64.7 million, or $2.01 per share, for the second quarter of 2015. Net loss applicable to common stock for the first half of 2016 was $137.6 million, or $4.23 per share, compared to $117.1 million, or $3.68 per share, for the first half of 2015.

Non-GAAP adjusted net loss was $37.9 million, or $1.17 per share, for the second quarter of 2016, compared to non-GAAP adjusted net loss of $36.5 million, or $1.13 per share, for the second quarter of 2015. Non-GAAP adjusted net loss for the first half of 2016 was $79.3 million, or $2.44 per share, compared to $68.8 million, or $2.16 per share, for the first half of 2015. Non-GAAP adjusted net loss excludes stock-based compensation expense, which represents a significant portion of overall expense and has no impact on the cash position of the Company. For a reconciliation of GAAP net loss to non-GAAP adjusted net loss and GAAP net loss per share to non-GAAP adjusted net loss per share, please see the financial tables at the end of this news release. The Company anticipates that non-GAAP net loss will continue to decrease in subsequent quarters due to a continued reduction in clinical trial expenses and due to a reduction in expenses associated with the completion of the regulatory filings for neratinib for the extended adjuvant treatment of HER2-positive early stage breast cancer in Europe and the United States, which were submitted in June and July, respectively.

Net cash used in operating activities for the second quarter of 2016 was $30.8 million. Net cash used in operating activities for the first half of 2016 was $65.8 million. At June 30, 2016, Puma had cash and cash equivalents of $57.8 million and marketable securities of $85.9 million, compared to cash and cash equivalents of $31.6 million and marketable securities of $184.3 million at December 31, 2015. The Company anticipates that net cash used in operating activities will continue to decrease in subsequent quarters due to a reduction in the expenses described above.

"We are very pleased with the accomplishments of the Company," said Alan H. Auerbach, Chairman, Chief Executive Officer and President of Puma. "These milestones include the submission of the Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in June and the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in July for neratinib for the extended adjuvant treatment of HER2-positive early stage breast cancer based on the positive ExteNET Phase III trial. We also reported positive Phase II data from an investigator sponsored trial of neratinib in patients with HER2 mutated, non-amplified breast cancer in June. In addition, our Phase II trial of neratinib in the front-line treatment of HER2-positive metastatic breast cancer (NEfERT-T trial) was published in JAMA Oncology in April, and positive results from the I-SPY 2 Phase II clinical trial of neratinib for the neoadjuvant treatment of breast cancer was published in the July 7 issue of The New England Journal of Medicine.

"In the second half of 2016, we look forward to several regulatory and clinical milestones with neratinib. From the regulatory perspective, we look forward to working with the EMA and FDA as they review our MAA and NDA submission, respectively. We also look forward to continuing our development of neratinib in the second half of 2016 and beyond. We anticipate (i) reporting additional data from the Phase II trial of neratinib as an extended adjuvant treatment in HER2-positive early stage breast cancer using loperamide prophylaxis in the fourth quarter of 2016; (ii) reporting additional Phase II data from the FB-7 neoadjuvant HER2-positive breast cancer trial in the subgroup of patients who are MammaPrint High in the fourth quarter of 2016; (iii) reporting data from the Phase II trial of neratinib plus fulvestrant in patients with HER2 non-amplified breast cancer that has a HER2 mutation during the fourth quarter of 2016; (iv) reporting data from the Phase III trial of neratinib in third-line HER2-positive metastatic breast cancer patients in either the fourth quarter of 2016 or the first quarter of 2017; and (v) reporting data from the Phase II trial of neratinib in metastatic breast cancer patients with brain metastases during the fourth quarter of 2016."

Operating Expenses

Operating expenses were $66.5 million for the second quarter of 2016, compared to $64.9 million for the second quarter of 2015. Operating expenses for the first half of 2016 were $137.7 million compared to $117.5 million for the first half of 2015.

General and Administrative Expenses:

General and administrative expenses were $12.3 million for the second quarter of 2016, compared to $5.5 million for the second quarter of 2015. General and administrative expenses for the first half of 2016 were $23.3 million compared to $13.4 million for the first half of 2015. The increase of approximately $9.9 million resulted primarily from increases of approximately $4.6 million in stock-based compensation, $2.9 million in professional fees and expenses, $1.3 million in payroll and related costs, and $1.0 million in facility and equipment costs. These increases reflect higher legal and compliance expenses, as well as overall corporate growth.

Research and Development Expenses:

Research and development expenses were $54.2 million for the second quarter of 2016, compared to $59.4 million for the second quarter of 2015. Research and development expenses for the first half of 2016 were $114.4 million, compared to $104.1 million for the first half of 2015. The increase of approximately $10.3 million resulted primarily from increases of approximately $5.3 million in stock-based compensation and $4.3 million for internal clinical development, regulatory and quality assurance expenses. We expect research and development expenses to decrease in subsequent quarters as we complete clinical trials and as our regulatory filings for neratinib for the extended adjuvant treatment of HER2-positive early stage breast cancer have been submitted in the United States and European Union.