On February 29, 2016 Exelixis, Inc. (Nasdaq: EXEL) reported financial results for the fourth quarter and full year of 2015 and provided an overview of key 2016 corporate objectives and clinical development milestones (Filing, Q4/Annual, Exelixis, 2015, FEB 29, 2016, View Source [SID:1234509290]).

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Corporate Updates and Key Priorities for 2016
In 2016, Exelixis will continue to focus its development efforts and financial resources on the opportunities for cabozantinib in advanced renal cell carcinoma (RCC) and advanced hepatocellular carcinoma (HCC). With regulatory applications under review for advanced RCC in the United States and European Union (EU), Exelixis is actively preparing for the potential commercialization of cabozantinib as a treatment for patients with advanced RCC and will soon be launch-ready for this indication should a positive regulatory decision come in the United States.
At the same time, Exelixis is working with its partner Genentech, a member of the Roche Group, to co-promote COTELLICTM (cobimetinib) in the United States. COTELLIC received U.S. approval in November 2015 as a treatment for patients with a BRAF V600E or V600K mutation-positive advanced melanoma, in combination with vemurafenib, also known as Zelboraf. Exelixis is entitled to an initial equal share of U.S. profits and losses, which will decrease as sales increase, and currently shares equally in U.S. marketing and commercialization costs. COTELLIC is also approved in the EU, Canada and Switzerland, and Exelixis will receive low double-digit royalties based upon sales outside the United States.

Cabozantinib Highlights
METEOR Trial of Cabozantinib in Advanced Renal Cell Carcinoma Delivers Positive Overall Survival Results. On February 1, 2016, Exelixis announced that a second interim analysis for overall survival (OS), a secondary endpoint of the METEOR pivotal trial, showed a highly statistically significant and clinically meaningful increase in OS for patients randomized to cabozantinib as compared to everolimus. As a result, among all the existing agents evaluated in large pivotal trials in patients with advanced RCC, including nivolumab, cabozantinib is the first and only therapy to unequivocally demonstrate robust and statistically-significant improvements in all three key efficacy parameters of OS, progression-free survival (PFS), and objective response rate (ORR). Exelixis has shared these data with U.S. and EU regulators and intends to present the results at a major medical meeting this year.

Additional Positive Data Presented from Subgroup Analyses from METEOR Trial. In January 2016, Exelixis announced positive results from subgroup analyses of the METEOR trial. This analysis contributed important details to the previously-released results conducted at the time of primary endpoint, demonstrating that the PFS and ORR benefits derived from cabozantinib treatment were consistent across various prespecified and post-hoc analysis subgroups. Importantly, observed benefits were independent of the location and number of organ metastases, tumor burden, the type, duration and number of prior VEGF receptor TKI therapies, and prior PD-1/PD-L1 therapy. These data were presented on January 9, 2016 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Genitourinary Cancers Symposium in San Francisco, CA.

U.S. Food and Drug Administration Accepts Filing for Advanced RCC, Grants Priority Review, and Assigns Action Date. In late January 2016, the U.S. Food and Drug Administration (FDA) deemed Exelixis’ New Drug Application (NDA) for cabozantinib as a treatment for patients with advanced RCC who have received one prior therapy to be sufficiently complete to permit a substantial review. The FDA also granted Priority Review designation to the filing and assigned a Prescription Drug User Fee Act action date of June 22, 2016. The NDA was considered filed on February 20, 2016, sixty days following submission.

European Medicines Agency Validates Advanced RCC Regulatory Filing, Grants Accelerated Assessment. On January 28, 2016, Exelixis announced that the European Medicines Agency (EMA) has accepted for review the company’s Marketing Authorization Application (MAA) for cabozantinib as a treatment for patients with advanced RCC who have received one prior therapy. With accelerated assessment, the MAA is eligible for a 150-day review, versus the standard 210 days (excluding clock stops when information is requested by the EMA).

Enrollment in CELESTIAL Continues; Data Anticipated in 2017. Exelixis continues to make progress in enrollment in CELESTIAL, a phase 3 pivotal trial comparing cabozantinib to placebo in patients with advanced HCC who have previously been treated with sorafenib. The study was initiated in September 2013. The trial is designed to enroll 760 patients at approximately 200 sites. Patients are being randomized 2:1 to receive 60 mg of cabozantinib daily or placebo. The primary endpoint for CELESTIAL is OS, and the secondary endpoints include PFS and ORR. Exelixis continues to anticipate top-line results from CELESTIAL in 2017. At this time, there is no approved treatment for HCC patients who progress following sorafenib treatment, the current standard of care.

Broad Cabozantinib Development Program Continues to Expand through NCI and Independent Investigators. While Exelixis pursues cabozantinib’s late-stage development in advanced RCC and advanced HCC, earlier-stage investigation continues through the company’s collaboration with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP), and its ongoing Investigator-Sponsored Trial (IST) program. Through these two programs, there are more than 45 ongoing or planned studies including trials in advanced RCC, bladder cancer, colorectal cancer, non-small cell lung cancer, and endometrial cancer. Results are expected from the following clinical studies this year:

• CABOSUN, the randomized phase 2 trial comparing cabozantinib to sunitinib in the treatment of first-line intermediate or poor risk RCC patients, which completed enrollment in early 2015. CABOSUN is being conducted by The Alliance for Clinical Trials in Oncology as part of Exelixis’ collaboration with the NCI-CTEP;

• A phase 1b trial of cabozantinib plus nivolumab alone, or in combination with ipilimumab, in patients with genitourinary tumors, including bladder cancer and RCC; and

• A phase 2 trial evaluating single agent cabozantinib in recurrent endometrial cancer.

Cobimetinib Highlights
Regulatory Approvals for COTELLIC Granted in the United States, European Union and Canada. In November 2015, Exelixis announced that the FDA approved COTELLIC as a treatment for patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib.

Also that month, Exelixis announced that the European Commission approved COTELLIC for use in combination with vemurafenib for the treatment of adult patients in the EU with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. Additionally, in February 2016, Health Canada approved COTELLIC in combination with vemurafenib for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

Positive Overall Survival Data for COTELLIC in Combination with Vemurafenib in Advanced Melanoma. In October 2015, Exelixis announced that the phase 3 coBRIM trial of COTELLIC in combination with vemurafenib met its secondary endpoint of demonstrating a statistically significant and clinically meaningful increase in OS for patients with unresectable locally advanced or metastatic melanoma carrying the BRAF V600E or V600K mutation. These data were the subject of a presentation at the Society for Melanoma Research 2015 Congress.

2016 Financial Guidance
The Company anticipates that operating expenses for the full year 2016 will be between $240 million and $270 million, including approximately $30 million of non-cash items related to stock-based compensation expense.

"Exelixis began 2016 with significant momentum as a result of the major milestones that occurred during and shortly after the fourth quarter," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "Most notably, we now have a more complete picture of cabozantinib’s clinical activity and potential in advanced renal cell carcinoma, a patient population greatly in need of new treatment options. With the announcement of positive overall survival data earlier this month, cabozantinib is now the only therapy to demonstrate in a phase 3 trial statistically significant improvements as compared to an active comparator, everolimus, in the three key efficacy parameters of overall survival, progression-free survival, and objective response rate in previously-treated patients with advanced renal cell carcinoma. As regulators continue to review our submitted applications, we are on track to be commercially ready in the United States by April 1, should we receive a regulatory decision in advance of the June 22 PDUFA date. And finally, with this afternoon’s announcement, in Ipsen we now have the ideal partner to maximize the potential for cabozantinib to have a positive impact on the treatment of cancer on a global basis."

"Our second Exelixis-discovered compound, cobimetinib, also saw numerous milestones in the fourth quarter, including regulatory approval in the United States and European Union, as well as the presentation of overall survival results in advanced melanoma. Approval in Canada was also obtained this month. The collective progress in advancing both of these compounds sets the company up for an impactful year, and we remain grateful for the support of our stakeholders as we continue to make progress in our mission to meaningfully improve the care and outcomes for people with cancer."

Fourth Quarter and Full Year 2015 Financial Results
Net revenues for the quarter ended December 31, 2015 were $9.9 million, and consisted almost entirely of net product revenue from the sale of COMETRIQ. This is compared to $7.4 million for the comparable period in 2014.

For the year ended December 31, 2015, net revenues were $37.2 million, compared to $25.1 million for the comparable period in 2014. Net revenues for the year ended December 31, 2015 included $3.0 million of contract revenues for a milestone payment received from Merck in the third quarter of 2015 related to their worldwide license of our PI3K-delta program as well as the net product revenue related to the sale of COMETRIQ.

Research and development expenses for the quarter ended December 31, 2015 were $23.5 million, compared to $39.7 million for the comparable period in 2014; and for the year ended December 31, 2015 were $96.4 million, compared to $189.1 million for the comparable period in 2014. The decreases for both the quarter and year ended December 31, 2015 were primarily related to a net decrease in clinical trial costs related to COMET, the Company’s phase 3 trial in metastatic castration-resistant prostate cancer and METEOR, the Company’s phase 3 trial in advanced RCC, and to a lesser degree, decreases in personnel related expenses resulting from an overall reduction in headcount. Those decreases were partially offset by an increase in stock-based compensation expense for performance-based stock-options tied to the positive top-line data received from the METEOR trial and the anticipated acceptance of our NDA filing with the FDA.

Selling, general and administrative expenses for the quarter ended December 31, 2015 were $17.1 million, compared to $9.8 million for the comparable period in 2014; and for the year ended December 31, 2015 were $57.3 million, compared to $50.8 million for the comparable period in 2014. The increases for both the quarter and year ended December 31, 2015 were primarily related to stock-based compensation expense due to the vesting of performance-based stock-options as a result of the positive top-line data received from the METEOR trial and the anticipated acceptance of our NDA filing with the FDA and higher marking expenses. Our 2015 selling, general and administrative expenses include a portion of COTELLIC commercialization expenses allocated to the collaboration which are under discussion between Exelixis and Genentech.

The overall selling, general and administrative expenses increases were partially offset by a decrease in facilities costs and consulting and outside services. For the year ended December 31, 2015, there were also decreases in personnel related expenses resulting from an overall reduction in headcount and patent defense costs as compared to the comparable period in 2014.

Other income (expense), net for the quarter ended December 31, 2015 was a net expense of ($12.0) million compared to ($11.9) million for the comparable period in 2014. Other income (expense), net for the year ended December 31, 2015 was a net expense of ($48.3) million compared to $(44.3) million for the comparable period in 2014. The net expense is comprised primarily of interest expense which includes $7.1 million and $28.9 million, respectively of non-cash expense related to the accretion of the discounts on both the 4.25% Convertible Senior Subordinated Notes due 2019 and the Company’s indebtedness under the Deerfield Notes for the quarter and year ended December 31, 2015, as compared to $7.7 million and $29.5 million for the comparable periods in 2014.

Net loss for the quarter ended December 31, 2015 was ($43.6) million, or ($0.19) per share, basic, compared to ($58.0) million, or ($0.30) per share, basic, for the comparable period in 2014. Net loss for the year ended December 31, 2015 was ($169.7) million, or ($0.81) per share, basic, compared to ($268.5) million, or $(1.38) per share, basic, for the comparable period in 2014. The decreases in net loss for both the quarter and year were primarily due to decreases in research and development expenses and an increase in net revenues, partially offset by an increase in selling, general and administrative expenses.
Cash and cash equivalents, short- and long-term investments and short- and long-term restricted cash and investments totaled $253.3 million at December 31, 2015 compared to $242.8 million at December 31, 2014.

On February 29, 2016 Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, reported financial results for the fourth quarter and year ended December 31, 2015 (Filing, Q4/Annual, Puma Biotechnology, 2015, FEB 29, 2016, View Source [SID:1234509300]).

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Unless otherwise stated, all comparisons are for the fourth quarter and full year 2015 compared to the fourth quarter and full year 2014, respectively.

Based on accounting principles generally accepted in the United States (GAAP), Puma reported a net loss applicable to common stock of $61.7 million, or $1.90 per share, for the fourth quarter of 2015, compared to a net loss of $47.5 million, or $1.57 per share, for the fourth quarter of 2014. Net loss applicable to common stock for the full year 2015 was $239.3 million, or $7.45 per share, compared to $142.0 million, or $4.73 per share, for the full year 2014.

Non-GAAP adjusted net loss was $40.0 million, or $1.23 per share, for the fourth quarter of 2015, compared to non-GAAP adjusted net loss of $31.1 million, or $1.03 per share, for the fourth quarter of 2014. Non-GAAP adjusted net loss for the full year 2015 was $144.3 million, or $4.49 per share, compared to $102.8 million, or $3.43 per share, for the full year 2014. Non-GAAP adjusted net loss excludes stock-based compensation expense, which represents a significant portion of overall expense and has no impact on the Company’s cash position. 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.

Net cash used in operating activities for the fourth quarter of 2015 was $33.3 million. Net cash used in operating activities for the full year 2015 was $154.5 million. At December 31, 2015, Puma had cash and cash equivalents of $31.6 million and marketable securities of $184.3 million, compared to cash and cash equivalents of $38.5 million and marketable securities of $102.8 million at December 31, 2014. Puma’s current level of cash and cash equivalents and marketable securities includes net proceeds of approximately $205.1 million from a public offering of the Company’s common stock, which was completed in January 2015.

"During the fourth quarter of 2015, Puma accomplished several clinical and regulatory milestones that contributed significant value to the shareholders of the Company," said Alan H. Auerbach, Chairman, Chief Executive Officer and President of Puma. "From the clinical perspective, in December we reported additional data from our Phase III ExteNET trial at the San Antonio Breast Cancer Symposium (SABCS), which continued to demonstrate that after 3 years of follow up, treatment with neratinib resulted in a statistically significant benefit in disease-free survival in patients with early stage HER2 positive breast cancer who had completed one year of adjuvant trastuzumab therapy. In addition, at SABCS we presented interim data from the Phase II trial of neratinib in patients with HER2-negative breast cancer who have a HER2 mutation that showed compelling benefit with neratinib, both as a monotherapy and in combination with fulvestrant. We also announced the interim data from our Phase II trial of neratinib monotherapy in patients with early stage HER2- positive breast cancer who had completed treatment with adjuvant trastuzumab, which demonstrated that using the loperamide prophylaxis with neratinib monotherapy treatment resulted in a lower rate of overall diarrhea, specifically grade 3 diarrhea, and resulted in diarrhea that was short term in duration and self-limiting. From the regulatory perspective, in November we announced that based on our Marketing Authorization Application (MAA) pre-submission meeting with the European Medicines Agency (EMA), at which the EMA assessed that there were no critical concerns that would prevent us from submitting a complete MAA for European centralized review in support of neratinib for the extended adjuvant treatment of HER2-positive early stage breast cancer in patients who have previously been treated with a trastuzumab-containing regimen, that we anticipate submitting an MAA for neratinib in this indication in the first half of 2016.

"We look forward to continuing to contribute value to shareholders with neratinib during 2016. We anticipate (i) submitting a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) during the first quarter of 2016 and submitting the MAA to the EMA during the first half of 2016 for neratinib for the extended adjuvant treatment of HER2-positive early stage breast cancer based on the positive ExteNET Phase III trial; (ii) 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 during the first half of 2016; (iii) reporting additional Phase II data from the FB-7 neoadjuvant HER2-positive breast cancer trial in the subgroup of patients who are MammaPrint High, during the first half of 2016; (iv) reporting Phase II data from an investigator sponsored trial of neratinib in patients with HER2-negative breast cancer who have a HER2 mutation in mid-2016; (v) 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; (vi) reporting data from the Phase II trial of neratinib in metastatic breast cancer patients with brain metastases during the fourth quarter of 2016; and (vii) 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."

Operating Expenses
Operating expenses were $62.1 million for the fourth quarter of 2015, compared to $47.6 million for the fourth quarter of 2014. Operating expenses for the full year 2015 were $239.3 million compared to $142.3 million for the full year 2014.

General and Administrative Expenses:
General and administrative expenses were $9.6 million for the fourth quarter of 2015, compared to $8.1 million for the fourth quarter of 2014. General and administrative expenses for the full year 2015 were $31.8 million compared to $19.4 million for the full year 2014. Approximately $8.0 million of the year-over-year increase resulted from an increase in stock-based compensation expense, with the majority of the remaining increase made up of approximately $2.2 million in professional fees, $0.9 million in payroll and related expenses and $0.6 million in facility and equipment costs. These increases reflect our corporate growth.

Research and Development Expenses:
Research and development expenses were $52.5 million for the fourth quarter of 2015, compared to $39.5 million for the fourth quarter of 2014. Research and development expenses for the full year 2015 were $208.5 million, compared to $122.9 million for the full year 2014. Approximately $47.8 million of the year-over-year increase resulted from an increase in stock-based compensation expense, with the majority of the remaining increase made up of approximately $22.9 million in clinical trial expense, $9.0 million in internal costs such as payroll and related expenses, and $5.9 million in expenses related to consultants and contractors. These increases reflect our increased clinical trial activity.

On February 29, 2016 Kite Pharma, Inc. (Nasdaq:KITE), a clinical-stage biopharmaceutical company focused on developing engineered autologous cell therapy (eACT) products for the treatment of cancer, reported a corporate update and reported full-year and fourth quarter 2015 financial results for the period ended December 31, 2015 (Press release, Kite Pharma, FEB 29, 2016, View Source [SID:1234509308]).

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"2015 was a year of solid execution and transformation for Kite," noted Arie Belldegrun, M.D., FACS, Chairman, President, and Chief Executive Officer. "The development of KTE-C19, our breakthrough immunotherapy candidate for patients with refractory hematological malignancies who have limited or no treatment options, is currently advancing in four Kite-sponsored multi-center clinical studies. We expect interim pivotal data from ZUMA-1, our lead study of KTE-C19, in the second half of this year, positioning us to submit our registrational filing with the FDA by year end. Construction of our commercial manufacturing facility is complete, and commercial planning is currently progressing under the leadership of our Chief Commercial Officer, Shawn Tomasello, and her capable team."

Dr. Belldegrun continued, "We are advancing what we believe is the most robust clinical pipeline of chimeric antigen receptors and T cell receptors for both solid and hematological oncology. This effort is supported by our ongoing collaborations with distinguished academic and industry leaders in immuno-oncology. We expect that our pipeline progress in 2016 will include additional human proof of concept data supporting the potential of our TCRs for the treatment of solid tumors."

Full Year 2015 and Recent Highlights

KTE-C19 Program

Initiated Kite’s lead multi-center study (ZUMA-1) for KTE-C19 for the treatment of aggressive, refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B cell lymphoma (PMBCL), and transformed follicular lymphoma (TFL). DLBCL is the most common form of non-Hodgkin Lymphoma (NHL).

Announced positive data from the Phase 1 portion of ZUMA-1 and advanced the study to the pivotal phase. The overall safety, efficacy, and biomarker data were generally consistent with previously published data from the National Cancer Institute (NCI).

Initiated three additional pivotal multi-center studies of KTE-C19 for the treatment of relapsed/refractory mantle cell lymphoma (MCL), adult relapsed/refractory acute lymphoblastic leukemia (ALL), and pediatric relapsed/refractory ALL.

Received Breakthrough Therapy Designation for KTE-C19 for the treatment of patients with refractory DLBCL, PMBCL, and TFL.

Secured Orphan Drug Designations in the EU for KTE-C19 for all of Kite’s hematological indications.

Completed Kite’s clinical manufacturing facility that is manufacturing KTE-C19 and that will manufacture future product candidates.

Completed construction of Kite’s commercial manufacturing facility, which is on track for qualification and validation later this year.

Acquisition and Strategic Collaborations

Established European operations with the acquisition of T-Cell Factory, now known as Kite Pharma EU. Through this acquisition, Kite also gained the proprietary TCR-GENErator discovery platform developed by Ton Schumacher, Ph.D., Chief Scientific Officer of Kite Pharma EU.

Expanded clinical and research partnership with the NCI including:
An enhanced Cooperative Research and Development Agreement (CRADA) with the NCI’s Surgery Branch to advance multiple CAR and TCR programs led by Steven Rosenberg, M.D., Ph.D.
A separate CRADA with the NCI’s Experimental Transplantation and Immunology Branch to advance the development of a fully human anti-CD19 CAR product candidate. James Kochenderfer, M.D. is leading the Phase 1 study.

Expanded agreement with the Netherlands Cancer Institute for the exclusive option to license multiple TCR gene sequences for the development and commercialization of immunotherapy candidates targeting solid tumors.

Entered into a research and license agreement with Leiden University Medical Center in the Netherlands to identify and develop TCR product candidates targeting solid tumors that are associated with the human papillomavirus (HPV) type 16 infection.

Partnered with Amgen to develop and commercialize the next generation of novel CAR T cell immunotherapies.

Entered into a collaboration with bluebird bio to advance second-generation TCR cell therapy products to treat HPV-associated cancers.

Secured an exclusive license to Alpine Immune Sciences’ transmembrane immunomodulatory protein (TIPTM) technology for eACT-based products.

Corporate Milestones

Strengthened the organization with the addition of more than 100 new hires across all functions.

Formed Kite’s integrated commercial leadership team, led by Shawn Tomasello, Kite’s Chief Commercial Officer.

Appointed Dr. Franz B. Humer, former Chairman and Chief Executive of Roche Holding Ltd., to Kite’s Board of Directors.

Strengthened Kite’s Scientific Advisory Board with the addition of James Allison, Ph.D. and Padmanee Sharma, M.D., Ph.D., recognized immunotherapy leaders from MD Anderson Cancer Center.

Raised $272.6 million in net proceeds from a public offering in December 2015.

2016 Goals

Announce interim Phase 2 pivotal data from the ZUMA-1 study for the first 50 patients with 90-day follow-up in the second half of 2016.

Submit the KTE-C19 registration filing to the U.S. Food and Drug Administration (FDA) based on interim data from ZUMA-1 study by the end of 2016.

Expand KTE-C19 clinical program to Europe in preparation for a European registration filing in 2017.

Complete the qualification and validation testing of the commercial manufacturing facility in anticipation of pre-approval inspection by the FDA.

Initiate a second series of KTE-C19 studies for additional indications and earlier lines of therapy in DLBCL patients.

Present longer term follow-up KTE-C19 data in patients with refractory aggressive DLBCL from the Phase 1 portion of ZUMA-1.

File investigational new drug (IND) application with the FDA for a TCR product candidate that targets a MAGE antigen expressed on solid tumors.

Advance the Kite-Amgen collaboration resulting in the filing of an IND application with the FDA for a next generation CAR T cell immunotherapy candidate, the first of multiple INDs expected to originate from the collaboration.

Fourth Quarter and Full Year 2015 Financial Results

Revenue was $4.9 million for the fourth quarter of 2015 compared to $0 for the fourth quarter of 2014, and $17.3 million for the full year of 2015, compared to $0 for the full year of 2014. The increase was primarily due to revenue recognized under the Kite-Amgen collaboration.

Research and development expenses were $28.8 million for the fourth quarter of 2015, compared to $7.9 million for the fourth quarter of 2014, and $76.4 million for the full year of 2015 compared to $23.1 million in 2014. The full-year increase of $53.3 million was primarily attributable to a $31.5 million increase in research and development and manufacturing expenses supporting the advancement of KTE-C19 and other programs, $11.8 million in expenses related to increased personnel and consulting costs, and $10.0 million of non-cash stock-based compensation expense.

General and administrative expenses were $14.1 million for the fourth quarter of 2015, compared to $5.4 million for the fourth quarter of 2014, and $44.2 million for the full year of 2015, compared to $13.6 million in 2014. The full-year increase of $30.6 million was primarily attributable to an $8.2 million increase in personnel related expenses, $7.8 million for public company expenses and license obligations, and $14.6 million of non-cash stock-based compensation.

Net loss attributable to common stockholders was $38.2 million, or $0.85 per share, for the fourth quarter of 2015, compared to $13.0 million, or $0.33 per share, for the fourth quarter of 2014. For the full year of 2015, the net loss was $101.7 million, or $2.33 per share, compared to $43.7 million, or $1.91 per share, in 2014.

Non-GAAP net loss attributable to common stockholders for the fourth quarter of 2015 was $24.5 million, or $0.54 per share, which excludes non-cash stock-based compensation expense of $13.8 million for the fourth quarter of 2015. Non-GAAP net loss attributable to common stockholders for the full year of 2015 was $61.0 million, or $1.40 per share, which excludes non-cash stock-based compensation expense of $40.7 million for the full year of 2015.

As of December 31, 2015, Kite had $614.7 million in cash, cash equivalents, and marketable securities, compared to $367.0 million as of December 31, 2014.

Kite expects the full year 2016 net cash burn to be $235 to $250 million dollars, which includes approximately $20 million in capital expenditures, but excludes any inflows or outflows from business development activities. The estimated full year 2016 net cash burn is primarily driven by an estimated net loss of $295 to $310 million, which includes an estimated $80 million of non-cash stock-based compensation expense.

On February 29, 2016 ArQule, Inc. (NASDAQ:ARQL) reported its financial results for the fourth quarter and full year of 2015 (Press release, ArQule, FEB 29, 2016, View Source [SID:1234509263]).

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For the quarter ended December 31, 2015, the Company reported a net loss of $2,852,000 or $0.05 per share, compared with net loss of $3,512,000 or $0.06 per share, for the quarter ended December 31, 2014. The Company reported a net loss of $13,774,000 or $0.22 per share, for the year ended December 31, 2015, compared with a net loss of $23,391,000 or $0.37 per share, for the year ended December 31, 2014.

At December 31, 2015, the Company had a total of approximately $38,772,000 in cash and marketable securities.

Key Highlights

Tivantinib pivotal phase 3 trial, METIV-HCC, completed enrollment and preliminary biomarker data analysis reported at ASCO (Free ASCO Whitepaper) GI: The biomarker-driven phase 3 trial for tivantinib, METIV-HCC, in second line hepatocellular carcinoma (HCC) completed patient enrollment of over 300 patients. The planned interim assessment is expected to occur by early in the second quarter of 2016. Additionally, preliminary biomarker data from the METIV-HCC trial presented at the Gastrointestinal Symposium Conference (ASCO GI) confirmed Phase 2 data demonstrating that MET status, as determined by immunohistochemistry, was more frequently high after first-line therapy.

ARQ 087 trial continues to enroll: Enrollment in the phase 2 portion of the company’s trial with its FGFR inhibitor, ARQ 087, in intrahepatic cholangiocarcinoma (iCCA) continues to enroll patients at centers in Italy and the U.S. where they are screening patients for FGFR2 fusions. As this is an open label study the company remains encouraged by the ongoing clinical benefit observed in recently enrolled patients.

ARQ 092 Phase 1 trial for Proteus syndrome completed enrollment of the first cohort: Our collaborator, the National Institutes of Health (NIH), has completed enrollment of the first cohort of the Phase 1 trial with ARQ 092 in Proteus syndrome. To date, the drug has been well tolerated. As a next step, the NIH expects to begin enrolling the second cohort including patients 12 years and older.

ARQ 092 Phase 1b trial in oncology has five partial responses (PRs), four of which are now confirmed to have AKT1/PI3K mutations: A phase 1b trial of ARQ 092 as a single agent completed enrollment in the lymphoma and endometrial cohorts. The final cohort in patients with cancers harboring the AKT1 or P13K mutations is still enrolling. We continue to monitor duration of response and safety and will provide an update on the study later in the year.

ARQ 751, next generation AKT inhibitor, received investigational new drug approval from the Food and Drug Administration (FDA): ARQ 751 expands the company’s AKT portfolio. ARQ 751 has demonstrated signal abrogation and efficacy in pre-clinical in vitro and in vivo models harboring AKT1 and PI3K mutations. A phase 1 trial in oncology is expected to begin during the first half of 2016 targeting AKT1 and PI3K mutations.

Company announced it has entered into definitive agreements with institutional and accredited investors to raise $15.3 million through a registered direct offering of common stock: Net proceeds from the offering will be used to advance ArQule’s proprietary pipeline and for general business purposes, including working capital. The proceeds are expected to fund company operations into 2018.

2016 Goals

ARQ 092 – AKT Inhibitor

Analyze phase 1 data in Proteus syndrome and make decisions on next steps
Analyze phase 1b data in oncology and make decisions on next steps
Explore opportunities in other rare over-growth diseases

ARQ 087 – FGFR Inhibitor

Complete phase 2 portion of trial in iCCA and make decisions on next steps
Complete phase 1b portion of trial in oncology and make decisions on next steps

ARQ 751 – next-generation AKT inhibitor

Initiate phase 1 trial in oncology in patients with AKT1 and PI3K mutations

Tivantinib

Complete METIV-HCC planned interim analysis by early Q2’16 and make decisions on next steps

"We are extremely pleased with the progress we made in 2015," said Paolo Pucci, Chief Executive Officer of ArQule. "From reducing our cash utilization, to progressing two proprietary compounds in three indications in the clinic, and ultimately completing enrollment of the METIV-HCC trial, it has been a productive year at ArQule. Our accomplishments in 2015 are moving us closer to being able to provide therapeutic options to patients with unmet needs through the use of precision medicine."

"2015 was a successful year for us in pipeline development," said Dr. Brian Schwartz, M.D., Head of Research and Development and Chief Medical Officer at ArQule. "We initiated two new trials within our proprietary pipeline, presented data at six scientific meetings and had two manuscripts published on ARQ 092 in peer reviewed medical journals. We are also beginning to see the value of our precision medicine approach through the clinical results we have accumulated in the ARQ 092 oncology trial and the ARQ 087 iCCA trial."

"2016 will be a year of clinical data at ArQule," said Mr. Pucci. "With the METIV-HCC interim assessment and final results on the horizon, we will have our first potential opportunity to move towards commercialization. Results from our earlier stage clinical trials, including ARQ 092 in oncology and Proteus syndrome, and ARQ 087 in iCCA, could provide us with our first opportunity to bring proprietary assets into the final stages of clinical development. We look forward to providing updates on our pipeline as the year progresses."

Revenues and Expenses

Revenues for the quarter ended December 31, 2015, were $2,797,000, compared with revenues of $3,015,000 for the quarter ended December 31, 2014. Revenues for the year ended December 31, 2015 were $11,239,000 compared with revenues of $11,254,000 for the year ended December 31, 2014. Research and development revenue in 2015 and 2014 includes revenue from the Daiichi Sankyo tivantinib development agreement and the Kyowa Hakko Kirin exclusive license agreement.

Research and development expenses in the fourth quarter of 2015 were $3,641,000, compared with $4,290,000 for the fourth quarter 2014. Fiscal 2015 research and development expenses were $15,561,000, compared with $22,271,000 for fiscal 2014.

The $0.6 million decrease in research and development expense in the fourth quarter of 2015 was primarily due to lower labor related costs of $0.2 million from reduced headcount and facility costs of $0.4 million. The $6.7 million decrease in research and development expense in fiscal 2015 was primarily due to lower labor related costs of $2.4 million from reduced headcount, outsourced clinical and product development costs of $1.7 million, facility costs of $1.9 million and lab expenses of?$0.7 million.

General and administrative expenses in the fourth quarter of 2015 were $2,028,000, compared with $2,836,000 for the fourth quarter of 2014. General and administrative expenses for fiscal 2015 were $9,830,000, compared to $12,154,000 for fiscal 2014.

General and administrative expense in the fourth quarter of 2015 decreased primarily due to lower facility costs of $0.8 million. General and administrative expense in 2015 decreased $2.3 million primarily due to lower labor related costs from reduced headcount of $0.7 million and facility costs of $1.5 million.

2016 Financial Guidance

For 2016, ArQule expects net use of cash to range between $23 and $25 million. Revenues are expected to range between $4 and $5 million. Net loss is expected to range between $24 and $27 million, and net loss per share to range between $(0.38) and $(0.43) for the year. ArQule expects to end 2016 with between $29 and $31 million in cash and marketable securities, inclusive of the $15.2 million of funds expected to be received upon the closing of the recent stock offering.

On February 27,2016 Celgene Corporation (NASDAQ:CELG) reported that two interim analyses of exploratory quality of life (QoL) endpoints in the ongoing phase III ABOUND.sqm clinical study investigating ABRAXANE (paclitaxel protein-bound particles for injectable suspension)(albumin-bound) in patients with advanced, squamous non-small cell lung cancer (NSCLC) were presented at the 2016 ASCO (Free ASCO Whitepaper) Quality Care Symposium (Press release, Celgene, FEB 27, 2016, View Source [SID:1234509247]).

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In the ABOUND.sqm study, patients received four 21-day cycles of ABRAXANE (100 mg/m2 on days 1, 8 and 15) plus carboplatin (AUC6 on day 1) and those with a response or stable disease could be randomized to receive either ABRAXANE (100 mg/m2 on days 1, 8) plus best supportive care or best supportive care alone in 21-day cycles until disease progression.

The analyses included 159 patients from the study who were evaluable for radiological response and QoL. In the two analyses 99% of patients had an ECOG performance status of 0-1 and pre-defined QoL measures including the LCSS (Global Score, Average Total Score, 3-Item Index, Average Symptom Burden Index and Lung Cancer Symptoms) and EuroQol EQ-5D-5L assessment were taken on day one of each cycle during the initial treatment phase.

The first analysis evaluated the therapeutic impact of chemotherapy on patient symptoms and activities. For all patients in the analysis, quality of life as measured by the LCSS and EuroQoL (EQ-5D-5L) was generally either maintained or improved throughout the entire treatment course.

The second analysis assessed the impact of radiological response on Quality of Life. In this analysis, 93/159 patients had an unconfirmed radiological response and 66/159 did not. Responders had a greater improvement in lung cancer symptom score, as measured by the LCSS and EQ-5D-5L scores.

Importantly, among patients who reported problems with mobility, self care, usual activities of living, pain/discomfort, or anxiety/depression prior to treatment, 38 – 47% reported complete resolution of these problems at least once during treatment. This was more pronounced in patients who achieved a radiological response, with complete resolution at least once reported in 42 – 59% of patients.

"Inclusion of quality of life measures is particularly important when so few prospective trials in advanced non-small cell lung cancer currently include such analyses," said Dr. Corey Langer of the University of Pennsylvania and lead investigator of one of the analyses. "These data demonstrate a correlation between radiologic response and patient reported quality of life."

Indication

ABRAXANE is indicated for the first-line treatment of locally advanced or metastatic non-small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.

Important Safety Information

WARNING – NEUTROPENIA

Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE

Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS
CONTRAINDICATIONS

Neutrophil Counts

ABRAXANE should not be used in patients who have baseline neutrophil counts of < 1500cells/mm3
Hypersensitivity

Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS

Hematologic Effects

Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In a clinical study, Grade 3-4 neutropenia occurred in 47% of patients with non-small cell lung cancer (NSCLC)

Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15

Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1500 cells/mm3

In the case of severe neutropenia ( < 500 cells/mm3 for 7 days or more) during a course of ABRAXANE therapy, reduce the dose of ABRAXANE in subsequent courses in patients with NSCLC

Resume treatment if recommended at permanently reduced doses for both weekly ABRAXANE and every-3-week carboplatin after ANC recovers to at least 1500 cells/mm3 and platelet count of at least 100,000 cells/mm3 on Day 1 or to an ANC of at least 500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Days 8 or 15 of the cycle

Nervous System

Sensory neuropathy is dose- and schedule-dependent

The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification

If ≥ Grade 3 sensory neuropathy develops, withhold ABRAXANE treatment until resolution to ≤ Grade 1 followed by a dose reduction for all subsequent courses of ABRAXANE

Hypersensitivity

Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported

Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug

Hepatic Impairment

Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with caution

Patients with hepatic impairment may be at an increased risk of toxicity, particularly from myelosuppression, and should be monitored for development of profound myelosuppression

For NSCLC, the starting dose should be reduced for patients with moderate or severe hepatic impairment

Albumin (Human)

ABRAXANE contains albumin (human), a derivative of human blood

Use in Pregnancy: Pregnancy Category D

ABRAXANE can cause fetal harm when administered to a pregnant woman

If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus

Women of childbearing potential should be advised to avoid becoming pregnant while receiving ABRAXANE

Use in Men

Men should be advised not to father a child while receiving ABRAXANE

ADVERSE REACTIONS

Non-Small Cell Lung Cancer (NSCLC) Study

The most common adverse reactions (≥20%) of ABRAXANE in combination with carboplatin are anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, nausea, and fatigue

The most common serious adverse reactions of ABRAXANE in combination with carboplatin for NSCLC are anemia (4%) and pneumonia (3%)

The most common adverse reactions resulting in permanent discontinuation of ABRAXANE are neutropenia (3%), thrombocytopenia (3%), and peripheral neuropathy (1%)

The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (24%), thrombocytopenia (13%), and anemia (6%)

The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (41%), thrombocytopenia (30%), and anemia (16%)

The following common (≥10% incidence) adverse reactions were observed at a similar incidence in ABRAXANE plus carboplatin-treated and paclitaxel injection plus carboplatin-treated patients: alopecia (56%), nausea (27%), fatigue (25%), decreased appetite (17%), asthenia (16%), constipation (16%), diarrhea (15%), vomiting (12%), dyspnea (12%), and rash (10%); incidence rates are for the ABRAXANE plus carboplatin treatment group

Adverse reactions with a difference of ≥2%, Grade 3 or higher, with combination use of ABRAXANE and carboplatin vs combination use of paclitaxel injection and carboplatin in NSCLC are anemia (28%, 7%), neutropenia (47%, 58%), thrombocytopenia (18%, 9%), and peripheral neuropathy (3%, 12%), respectively

Adverse reactions with a difference of ≥5%, Grades 1-4, with combination use of ABRAXANE and carboplatin vs combination use of paclitaxel injection and carboplatin in NSCLC are anemia (98%, 91%), thrombocytopenia (68%, 55%), peripheral neuropathy (48%, 64%), edema peripheral (10%, 4%), epistaxis (7%, 2%), arthralgia (13%, 25%), and myalgia (10%, 19%), respectively

Neutropenia (all grades) was reported in 85% of patients who received ABRAXANE and carboplatin vs 83% of patients who received paclitaxel injection and carboplatin

Postmarketing Experience With ABRAXANE and Other Paclitaxel Formulations

Severe and sometimes fatal hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied

There have been reports of congestive heart failure, left ventricular dysfunction, and atrioventricular block with ABRAXANE, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs

There have been reports of extravasation of ABRAXANE. Given the possibility of extravasation, it is advisable to monitor closely the ABRAXANE infusion site for possible infiltration during drug administration

DRUG INTERACTIONS

Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4

USE IN SPECIFIC POPULATIONS

Nursing Mothers

It is not known whether paclitaxel is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother

Pediatric

The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated

Geriatric

Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients ≥65 years of age treated with ABRAXANE and carboplatin in NSCLC

Renal Impairment

There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance < 30 mL/min)

DOSAGE AND ADMINISTRATION

Do not administer ABRAXANE to any patient with total bilirubin greater than 5 x ULN or AST greater than 10 x ULN

Reduce starting dose in NSCLC patients with moderate to severe hepatic impairment

Dose reductions or discontinuation may be needed based on severe hematologic or neurologic toxicity

Monitor patients closely

Please see full Prescribing Information, including Boxed WARNING.