Elevated concentrations of doxorubicin are found in eccrine sweat glands of the palms and soles. We therefore evaluated an antiperspirant as preventive treatment for palmar-plantar erythrodysesthesia (hand-foot syndrome) in patients with metastatic breast cancer treated with pegylated liposomal doxorubicin.
An antiperspirant containing aluminum chlorohydrate or placebo cream was applied to the left or right hand and foot in a double-blinded manner (intra-patient randomization). The primary endpoint was the rate of grade 2 or 3 palmar-plantar erythrodysesthesia. A secondary endpoint was the patient-reported symptom burden (tingling, numbness, pain, or skin problems). Using McNemar’s matched pairs design, 53 patients were needed to detect a 20% difference between the treatment and placebo sides with a significance level of 5% and power of 90%.
Grade 2 or 3 PPE occurred in 30 (58%) of 52 evaluable patients; in six patients adverse effects occurred on the placebo side but not on the treatment side, whereas one patient developed palmar-plantar erythrodysesthesia on the treatment side only (P = 0.07). Four patients developed grade 2 or 3 palmar-plantar erythrodysesthesia on their foot on the placebo side but not on the treatment side (P = 0.05). In the cohort with grade 2 or 3 palmar-plantar erythrodysesthesia there was a trend towards fewer dermatologic symptomatologies with the active treatment (P = 0.05), and no difference for other adverse events.
Using topical aluminum chlorohydrate as an antiperspirant appears to reduce the incidence of grade 2 or 3 palmar-plantar erythrodysesthesia following pegylated liposomal doxorubicin chemotherapy for metastatic breast cancer.
Copyright © 2014 Elsevier Ltd. All rights reserved.

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On February 24, 2016 Genoscience Pharma, a biopharmaceutical company dedicated to discovering and developing cancer treatment drugs, reported the arrival of four new members to its board of directors (Press release, GenoScience, FEB 24, 2016, View Source [SID:1234509200]). Dr Mahkam Zanganeh, Robert Duggan and Manmeet Soni, respectively the former chief operating officer, chief executive officer and chief financial officer of Pharmacyclics, are joining the board along with Chaim Hurvitz, who has worked in many management roles for Teva International Group. The new members will support the strategic and financial development of Genoscience, alongside existing board members – Antoine Béret, Jean-Marc Feryn, Vincent Fert and Chalom Sayada. Their arrival is accompanied by an increase in capital, the terms of which have not been disclosed.

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The four new members are all recognized biotechnology entrepreneurs. While at Pharmacyclics Pharmaceuticals, in less than seven years, Mahkam Zanganeh and Robert Duggan developed and brought to the market Imbruvica, a first-in-class compound treating patients with Mantle Cell Lymphoma (MCL), Chronic Lymphocytic Leukemia (CLL) and Waldenstrom’s macroglobulinemia (WM). In May 2015, Abbvie acquired Pharmacyclics for $21Bn (€18.9Bn), one of the biggest buyouts for a biotechnology company to date.

Genoscience Pharma’s most advanced compound, GNS561, is in preclinical development for the treatment of liver cancer. It is a small active molecule that works against a new target. It is unique as it targets not only hepatic cancerous cells, but also the progenitors of the cancerous hepatocyte stem cells. GNS561 begins its regulatory process with the aim of starting the first-in-man phase 1b/2a trials in 2017. Preclinical studies have demonstrated GN561’s potential to become a major therapeutic breakthrough in the treatment of hepatocellular carcinoma.

"I am delighted to welcome this high caliber team to our board of directors. Robert Duggan and Mahkam Zanganeh’s experience in the development of anti-tumor molecules will be a credit to our company," said Prof. Philippe Halfon, president and founder of Genoscience Pharma. "It is an honor and a true mark of recognition to be joined by such a team, who participate very selectively in high potential projects. Their scientific expertise in pharmaceutical development will undoubtedly help us achieve our objectives and get to phase 2 quickly."

"The next challenge in oncology is to cure cancer patients by targeting the seed of the disease; cancer stem cells which cause cancer to recur," said Dr. Mahkam Zanganeh. "The strategy proposed by Genoscience Pharma is unique and will allow us to make a decisive step forward in curing cancer."

About cancer stem cells

Since 2012, Genoscience has been involved in an ambitious program to discover and develop compounds that target cancer stem cells. These stem cells, which are ultra-resistant to traditional chemotherapy and radiotherapy, form a minority subpopulation of the cells in a tumor and are responsible for tumor growth and metastases. They renew themselves indefinitely, differentiating themselves to form and maintain the tumor tissue. These cells do not respond to conventional chemotherapy that targets the majority of differentiated tumor cells. This explains the indefinite development of tumors as well as metastases and relapses. Consequently, eradicating cancer stem cells is essential in order to achieve lasting clinical remission and to improve the prognosis of cancer patients.

Genoscience is one of the pioneers in this emerging domain of cancer biology, which aims to revolutionize the traditional approach to treating cancer. Genoscience’s main candidate, GNS561, is also under evaluation for treating other cancers (kidney and colorectal), which could respond to its first-in-class action mechanism.

About liver cancer

Liver cancer (or HCC – hepatocellular carcinoma) is the third most common cause of death by cancer in the world[1]. The medical needs for treating it are considerable and not yet resolved. The only existing chemotherapy treatment for HCC is sorafenib, which slightly increases survival rates, but has many adverse effects[2].

On February 24, 2016 Nanomerics’ scientists reported they have demonstrated that encapsulating chemotherapy drugs within Nanomerics’ MET nanoparticles diverts the drug from the bone marrow, while enabling higher levels of drug to access the brain (Press release, Nanomerics, FEB 24, 2016, View Source [SID:1234509184]). Animals intravenously dosed with Nanomerics’ MET – lomustine formulations showed significantly improved survival rates when compared to the drug in solution and the effect of the drug on the bone marrow was comparable to the drug in solution. The work is described in a new paper published in Pharmaceutical Research View Source This data demonstrates the further utility of Nanomerics’ MET via the intravenous route. The MET formulation worked by enabling a higher dose of the hydrophobic drug lomustine to be administered and this higher dose did not result in higher levels of drug in the bone and liver, whereas levels of the drug in the brain were increased. The bone marrow is a major site of toxicity for alkylating agents such as lomustine and dose limiting myelosuppression compromises brain tumour therapy significantly.

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Nanomerics’ Chief Scientific Officer states, "this study provides evidence that Nanomerics’ MET nanoparticles are able to avoid the bone marrow and indeed the liver on intravenous administration and provide a method of administering a hydrophobic alkylating agent for the treatment of brain tumours."

On February 24, 2015 Fresenius Medical Care reported fourth quarter and full year 2015 results (Press release, Fresenius, FEB 24, 2016, View Source [SID:1234509182]).
 
Fourth quarter 2015 key figures:

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Net revenue: $4,348 million, +1% / +5%cc
Operating income (EBIT): $662 million, 0%
Operating income (EBIT) excluding special items2: $704 million, +5%
Net income1: $317 million, -6%
Net income excluding special items1,2: $347 million, +2%
Basic earnings per share: $1.04, -6%

Full year 2015 key figures:

Net revenue: $16,738 million, +6% / +11%cc
Operating income (EBIT): $2,327 million, +3%
Operating income (EBIT) excluding special items2: $2,388 million, +5%
Net income1: $1,029 million, -2%
Net income excluding special items1,2: $1,082 million, +2%
Basic earnings per share: $3.38, -2%

Dividend proposal:

Per share €0.80 +3%
cc = at constant currency rates
1 excluding special items: divestiture of dialysis business in Venezuela, sale of the European marketing rights to Vifor and settlement costs for an agreement in principle for the GranuFlo case in 2015 as well as closing of manufacturing plants in 2014
2 attributable to shareholders of Fresenius Medical Care AG & Co. KGaA

Rice Powell, Chief Executive Officer of Fresenius Medical Care stated: "Our commitment to our patients continues to produce substantial results. After investing heavily in new business activities, 2015 was a year that focused on operational excellence. Strong market dynamics in our core dialysis markets had been supported by new operating profitability levels. In 2016 we even want to accelerate the value creation for all our shareholders. We delivered on revenue, net income guidance for 2015 and confirm our targets for 2016: strong revenue growth combined with even higher net income growth."

Fourth quarter 2015

Revenue

Net revenue for the fourth quarter of 2015 increased slightly by 1% to $4,348 million (+5% at constant currency) as compared to the fourth quarter of 2014. Organic revenue growth was 5%. Net Health Care revenue grew by 4% to $3,462 million (+7% at constant currency). The organic growth rate was 6%. After a very strong first half in the product business, the dialysis product revenue was down by 11% to $886 million. The company generated more than 70% of the product business in the three International segments which implied a strong currency headwind. On a constant currency basis, dialysis product revenue decreased by 2%.

North America revenue for the fourth quarter of 2015 increased by 7% to $3,084 million. Organic revenue growth was 5%. Net Health Care revenue contributed $2,845 million (+8% on a year on year basis), the product business $239 million (+1% on a year on year basis). The Care Coordination business recorded revenue of $501 million – corresponding to a significant growth of 27% over the previous years fourth quarter. Organic revenue growth was 23%.

International revenue decreased by 12% to $1,257 million (an increase of 2% on a constant currency basis), clearly negatively impacted by currency translation. Organic revenue growth was 3%. Net Health Care revenue was $617 million (-10%, +5% at constant currency). Dialysis product revenue decreased by 13% to $640 million (-1% at constant currency).

International segments:
Europe, Middle East and Africa (EMEA) revenue decreased by 12% to $673 million. Constant currency and organic revenue growth was 1%. Net Health Care revenue decreased by 11% to $306 million (+4% at constant currency). Dialysis product revenue decreased by 13% to $367 million (-1% at constant currency and stable on an organic perspective).

Asia-Pacific revenue decreased by 6% to $394 million (+1% at constant currency). Net Health Care revenue amounted to $171 million (+3% at constant currency), dialysis product revenue decreased to $223 million (stable level at constant currency rates).

Latin America revenue decreased by 20% to $ 190 million. At constant currency revenue grew by 3%. Organic revenue growth was 15%. Net Health Care revenue decreased by 14% to $140 million (+9% at constant currency). With a plus of 27% organic growth was very strong. Dialysis product revenue decreased by 33% to $50 million (a decrease of 9% at constant currency).

Earnings
Operating income (EBIT) was $662 million, stable compared to last year. The sale of remaining European marketing rights to a Joint Venture was recognized in the fourth quarter resulting in an additional gain of $18 million. The company also reached an agreement in principle to resolve a product liability litigation in the United States involving GranuFlo/NaturaLyte. This caused a pre-tax charge of $60 million. Excluding both special items operating income increased 5% from $669 million to $704 million.

Operating income for North America for the fourth quarter of 2015 was $514 million, an increase of 4% as compared to the corresponding quarter in 2014. Excluding the $60 million settlement costs for the GranuFlo/NaturaLyte case the operating income was $574 million, a strong increase of 16%.

International segments:
Operating income for EMEA for the fourth quarter of 2015 increased by 20% to $172 million as compared to the same quarter 2014. Operating income, excluding the $ 18 million gain resulting from the sale of the European marketing rights, was $154 million, reflecting an increase of 8%. Operating income for Asia-Pacific was $79 million, a sequential improvement of $11 million and a decrease of 21% on a year on year basis. Operating income for Latin America for the fourth quarter of 2015 was $23 million (Q4 2014: $35 million).

The corporate costs were up at $ 126 million compared to $108 million in Q4 2014.

Net interest expense for the reported quarter was with $88 million clearly below Q4 of last year (-25%) due to higher interest income resulting from the early repayment of interest-bearing notes receivables and due to a decreased average debt level.

Income tax expense was $180 million for Q4 2015, which translates into an effective tax rate of 31.4%. This compares to income tax expense of $143 million and a tax rate of 26.2%, which was influenced favorably by the resolution of challenged deductions for the civil payments taken in prior years.

Net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA for the fourth quarter of 2015 was $317 million compared to $335 million in the fourth quarter of 2014. Excluding special items net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA was $347 million – this means an increase by 2%. Net income attributable to noncontrolling interest increased to $77 million ($68 million in Q4 2014).

Basic earnings per share (EPS) for the fourth quarter of 2015 was $1.04, compared to $1.11 for the corresponding period in 2014. The weighted average number of shares outstanding for Q4 2015 was approximately 305.1 million shares, compared to approximately 303.3 million shares.

Cash flow

In the fourth quarter of 2015, the company generated $548 million, representing approximately 13% of revenue, in net cash provided by operating activities, compared to the corresponding figure of last year of $588 million.

A total of $299 million was spent for capital expenditures, net of disposals. Free cash flow was $249 million compared to $306 million in the comparable quarter of 2014.

A total of $151 million in cash was spent for acquisitions and investments. Divestitures driven by the early repayment of interest bearing notes receivables were $209 million. Free cash flow after investing activities was $307 million as compared to -$419 million in Q4 2014

Full year 2015

Revenue and earnings

Net revenue for full year 2015 increased by 6% to $16,738 million (+11% at constant currency) as compared to fiscal 2014. Organic revenue growth worldwide was 6%.

Operating income (EBIT) for the full year 2015 decreased by 2% to $2,327 million. Excluding special items operating income grew by 5% and reached $2,388 million as compared to $2,271 million for fiscal 2014.

Net interest expense for fiscal 2015 was $391 million as compared to $411 million for the corresponding period in 2014.

Income tax expense for full year 2015 was $623 million, which translates into an effective tax rate of 32.1%. This compares to income tax expense of $584 million and a tax rate of 31.7% for 2014.

For full year 2015, net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA was $1,029 million compared to $ 1,045 million in 2014. Excluding special items net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA increased to $1,082 million, plus 2% compared with the comparable number of $1,058 million for fiscal 2014.

For fiscal year 2015, basic earnings per share (EPS) was down at $3.38 as compared to the corresponding number for full year 2014 ($3.46). The weighted average number of shares outstanding for 12 months of 2015 was approximately 304.4 million shares (full year 2014: 302.3 million).

Cash flow

In the reported period 2015, the company generated $1,960 million in net cash provided by operating activities, representing 11.7% of revenue, as compared to $1,861 million for the same period in 2014.

A total of $935 million was spent for capital expenditures, net of disposals. Free cash flow was $1,025 million as compared to $941 million in 2014, a strong increase of roughly 9% on a year on year basis.

A total of $66 million in cash was spent for acquisitions and investments, net of divestitures. Free cash flow after investing activities was $959 million as compared to ($829) million for the twelve months of 2014.

Employees
As of December 31, 2015, Fresenius Medical Care had 104,033 employees (full-time equivalents) worldwide, compared to 99,895 employees at the end of 2014. This increase of 4% was mainly attributable to our continued organic growth and acquisitions.

Balance sheet structure
The company´s total assets were slightly above last years level and amounted to $25,533 million (Dec. 31, 2014: $25,381 million). Current assets increased by 4% to $6,984 million (Dec. 31, 2014: $6,718 million). Goodwill and intangible assets as well as non-current assets remained stable with $13,863 million (Dec. 31, 2014: 13,951 million) and $4,686 million (Dec. 31, 2014: 4,712 million) respectively. Total equity increased by 5% to $10,496 million (Dec. 31, 2014: $10,028 million). The equity ratio was 41% as compared to 40% at the end of 2014. Total debt was $8,646 million (Dec. 31, 2014: $9,466 million).

Please refer to the attachments for a complete overview of the results for the fourth quarter and full year 2015.

Dividend
At the Annual General Meeting to be held on May 12, 2016, shareholders will be asked to approve a dividend of €0.80 per share, an increase of 3% compared to 2014 (€0.78). This would mean the 19th consecutive dividend increase, shareholders can expect.

Outlook 2016
Based on the projection Fresenius Medical Care provided for 2016, the company is guiding for revenue to grow 7-10% at constant currency excluding acquisitions in 2015 and 2016. Net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA is expected to increase by 15-20% in 2016 excluding acquisitions in 2015 and 2016, based on net income for 2015 of US$ 1,057 million (net income excluding settlement costs for an agreement in principle for the GranuFlo/NaturaLyte case of -$37 million and +$9 million acquisitions).

The company expects to spend capital expenditures of $1.0 – $1.1 billion and around $750 million on acquisitions. The debt/EBITDA ratio is expected to be below 3.0 by the end of 2016.

On February 24, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP) reported financial results for the fourth quarter ended December 31, 2015, and provided an update on the Company’s recent activities (Press release, Ziopharm, FEB 24, 2016, View Source [SID:1234509180]).

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"We look forward to a number of important milestones throughout 2016 across our gene and cell therapy platforms," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. "For our lead gene therapy, Ad-RTS-IL-12 + veledimex, this includes data presentations in the first half of the year from our Phase 1 brain cancer trial, our Phase 1/2 breast cancer trial and from a translational, preclinical study demonstrating powerful antitumor effects when combining with checkpoint inhibitors. Through the balance of 2016, we expect to initiate or continue prosecuting up to six proof-of-concept generating studies across multiple platforms, including viral and non-viral delivery of DNA, CAR-T and NK-cell therapies based upon autologous and allogeneic, or off-the-shelf, strategies. These studies will help inform potential registration pathways and validate technologies that will enable us to achieve our game-changing goals, including delivering therapies for urgent unmet needs, such as progressive brain cancer, and developing personalized TCR-based cell therapies for solid tumors."

"To accelerate the success of our exciting clinical programs, we are building out our clinical and regulatory infrastructure by hiring additional personnel in these important areas of our company," said Caesar J. Belbel, Executive Vice President, Chief Operating Officer and Chief Legal Officer of ZIOPHARM. "Through the highly efficient management of our cash, the addition of these resources in support of our aggressive clinical strategy has had a minimal impact on the projection of our financial resources, which we anticipate will be sufficient to fund our currently planned operations into the fourth quarter of 2017."

Program Updates

Ad-RTS-IL-12 + veledimex

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 T-cell 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 Phase 1b/2 study for the treatment of patients with locally advanced or metastatic breast cancer following standard chemotherapy and a multi-center Phase 1 study in patients with recurrent or progressive glioblastoma multiforme (GBM), an aggressive form of brain cancer.

Encouraging data from Phase 1 brain tumor study reported at SNO; first patient treated in second dose cohort. In November 2015, the Company reported biologic data from the multicenter, Phase 1 gene therapy study of GBM at the Society for Neuro-Oncology (SNO) 20th Annual Scientific Meeting. Following reporting of encouraging data from the first cohort of the study at the initial dosing of Ad-RTS-IL-12 + veledimex, the Company announced this week that the first patient has been enrolled in the study’s second dose cohort. The Company plans to report updated results from the study at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2016.

Encouraging data from Phase 1b/2 breast cancer study reported. In December 2015, the Company reported encouraging data, including achievement of the 12 week progression free survival endpoint by the first patient, from a Phase 1b/2 study of Ad-RTS-hIL-12 + veledimex following standard chemotherapy for the treatment of patients with locally advanced or metastatic breast cancer. The study is being conducted at the Memorial Sloan Kettering Cancer Center in New York. A trial in progress poster describing the study was presented at the San Antonio Breast Cancer Symposium in December 2015. The Company expects to present updated data from the study in 2016.

Preclinical studies combining Ad-RTS-IL-12 + veledimex and checkpoint inhibitors in brain tumor models. ZIOPHARM anticipates presenting data from preclinical studies of Ad-RTS-IL-12 + veledimex combined with checkpoint inhibitors in glioblastoma mouse models at the 2016 Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) in Washington D.C., May 4-7, 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 and the MD Anderson Cancer Center and the biopharmaceutical business of Merck KGaA, Darmstadt, Germany (CAR-T only).

Favorable overall survival (OS) and progression free survival (PFS) data from non-viral CAR-modified T cells targeting CD19 presented at ASH (Free ASH Whitepaper). In December 2015, ZIOPHARM announced results from its non-viral CD19-specific CAR T-cell therapy programs were presented at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Two investigational therapies infused T cells genetically modified to express a CD19-specific CAR into patients with advanced CD19+ malignancies after hematopoietic stem-cell transplantation (HSCT). This was based on non-viral gene transfer using the Sleeping Beauty platform to express the CAR. Long-term follow up data were used to distinguish the benefit of the CAR-T therapies over HSCT. The results demonstrated favorable PFS and OS trends compared to historical controls, with a near doubling of 3-year PFS rates for patients with Diffuse Large B-cell Lymphoma enrolled in the autologous cohort, and a doubling to tripling of 1-year OS rates results for patients with Acute Lymphoblastic Leukemia enrolled in the allogeneic cohort. The non-viral Sleeping Beauty-modified T cells also demonstrated in vivo survival that compared favorably to published results of virally-modified cells.

First patient enrolled in Phase 1 study of second generation non-viral CD19-specific CAR T-cell therapy for advanced lymphoid malignancies. In February 2016, ZIOPHARM announced that the first patient was enrolled in a new Phase 1 clinical study of its second generation non-viral CD19-specific CAR modified T-cell therapy in patients with advance lymphoid malignancies. The CD19-specific T cells were modified using the Sleeping Beauty system to stably express the CAR in T cells. This second-generation study employs a revised CAR construct designed to improve persistence and anti-tumor response over the first generation therapy. Additionally, this investigational treatment is independent of HSCT. The trial, which is being conducted at MD Anderson, will provide further proof-of-concept for the Sleeping Beauty system in a disease setting well studied using virally modified CD19-specific T cells, allowing the system to be applied to areas where viral therapy is more challenging to implement, such as the targeting of neoantigens in solid tumors.

Sleeping Beauty non-viral gene transfer technology featured in Nature Medicine. In January 2016, the Sleeping Beauty non-viral gene transfer technology was featured in a perspectives article in the journal Nature Medicine (Volume 22, Number 1, 26-36), titled "Prospects for gene-engineered T cell immunotherapy for solid cancers." The article describes how adoptive transfer of TCR-engineered T cells for solid tumors may come from the "arduous task of targeting the unique set of mutations that cause each patient’s cancer." Because of the challenges of achieving this goal, the authors note that non-viral integration systems will likely be considerably cheaper to manufacture and easier to implement for single-use applications compared with viral vectors and that, among non-viral platforms, Sleeping Beauty has advanced furthest in clinical development.

The Sleeping Beauty transposon-transposase is a unique non-viral system for introducing genes encoding CARs and TCRs into lymphocytes and is exclusively licensed by Intrexon through MD Anderson and accessed as part of ZIOPHARM’s collaboration with Intrexon. This non-viral approach has several potential advantages over viral delivery systems, including a lower cost of generating genetically modified T cells as well as the ability to generate T cells with minimal ex vivo processing and can serve as a conduit to targeting solid tumor neoantigens using TCRs.

Upcoming Studies

As previously announced, ZIOPHARM anticipates launching clinical studies in three new programs in 2016:

A Phase 1 clinical trial in patients with glioblastoma using the combination of Ad-RTS-IL-12 + veledimex and a selected checkpoint inhibitor.

A Phase 1 study of a viral-based CAR T-cell therapy for myeloid malignancies. Details of the study and antigen target will be provided as the Company initiates the study.

A Phase 1 clinical trial using off-the-shelf primary NK cells for investigational therapy of acute myeloid leukemia, building on promising proof-of-principle trials such as ongoing at MDACC infusing autologous and allogeneic NK cells.

Fourth-Quarter 2015 Financial Results

Net loss for the fourth quarter of 2015 was $9.5 million, or $(0.07) per share, compared to a net loss of $10.4 million, or $(0.09) per share, for the fourth quarter of 2014.

Research and development expenses were $8.1 million for the fourth quarter of 2015 which is consistent with $8.1 million for the fourth quarter of 2014. In 2015, research and development costs include $4.5 million related to CAR-T programs, $1.6 million related to gene therapy programs, $1.3 million in employee related expenses and $0.7 million in other R&D activities.

General and administrative expenses were $3.3 million for the fourth quarter of 2015 compared to $2.9 million for the fourth quarter of 2014. The increase of $0.4 million in general and administrative expenses is primarily attributable to non-cash equity compensation and other employee related expenses.

The Company ended the quarter with cash and cash equivalents of approximately $140.7 million. Given current development plans, the Company anticipates that current cash resources will be sufficient to fund our planned operations into the fourth quarter of 2017.