On February 18, 2107 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported encouraging results from the Phase II IMmotion150 study that compared TECENTRIQ (atezolizumab) plus Avastin (bevacizumab) and TECENTRIQ monotherapy to sunitinib alone in people with previously untreated, locally advanced or metastatic renal cell carcinoma (mRCC) (Press release, Hoffmann-La Roche, FEB 17, 2017, View Source [SID1234517752]). These results were presented at the 2017 Genitourinary Cancers Symposium taking place from February 16-18 in Florida, USA.

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IMmotion150 is the first randomised clinical trial to evaluate the combination of TECENTRIQ and Avastin in mRCC. The study was designed to inform further clinical development of this combination and these study results reinforce the potential of this combination in this setting.

The study showed that people whose disease expressed PD-L1 (programmed death-ligand 1) and were treated with TECENTRIQ plus Avastin had a 36 percent reduction in the risk of their disease worsening or death compared to people treated with sunitinib alone (median progression-free survival [mPFS]: 14.7 vs. 7.8 months; HR= 0.64; 95% CI 0.38, 1.08). No PFS advantage was observed compared to sunitinib in the intention-to-treat [ITT] population (mPFS: 11.7 vs. 8.4 months; HR = 1.00; 95% CI 0.69, 1.45). Median Duration of Response (DoR) has not yet been reached after 20.7 months of follow-up across treatment arms. Adverse events in the TECENTRIQ plus Avastin arm were consistent with those observed in previous studies of each medicine.

"These Phase II results support the scientific rationale for potentially combining TECENTRIQ and Avastin in people with this type of kidney cancer," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "There is a significant need for new treatment options for people living with advanced RCC, a disease where currently only about one in 10 people are alive beyond five years following diagnosis."

Roche is also evaluating TECENTRIQ plus Avastin vs sunitinib in a Phase III study (IMmotion151; NCT02420821) in people with previously untreated, locally advanced or metastatic RCC. A study of TECENTRIQ as adjuvant treatment for RCC began enrolling earlier this year.

About the IMmotion150 study
IMmotion150 is a global, multicentre, open-label, randomised Phase II study that was designed to evaluate the efficacy and safety of TECENTRIQ plus Avastin (Arm A), TECENTRIQ alone (Arm B) or sunitinib alone (Arm C) in 305 patients with previously untreated, locally advanced or metastatic RCC. People in Arm A received TECENTRIQ administered intravenously at 1200 mg every 3 weeks (6-week cycles) plus Avastin intravenously at 15 mg until disease progression or lack of clinical benefit. People in Arm B received TECENTRIQ alone (until disease progression or lack of clinical benefit), and people in Arm C received sunitinib 50 mg orally daily for 4 weeks followed by 2 weeks rest until disease progression.

The co-primary endpoints were PFS per RECIST v.1.1 via Independent Review Facility (IRF) assessment in all randomised patients (ITT population) and in the PD-L1 selected (IC1/2/3) subgroup. PD-L1 expression was assessed on tumour-infiltrating immune cells (IC) with an investigational immunohistochemistry (IHC) test based on the SP142 antibody being developed by Roche Tissue Diagnostics. Secondary endpoints included IRF-assessed overall response rate (ORR) and duration of response (DoR), investigator-assessed PFS, ORR, DoR and safety, and overall survival (OS). A summary of the efficacy data from Arms A, B and C of the IMmotion150 study is included below.

IMmotion150 was designed with planned crossover. Over three quarters (78 percent) of sunitinib patients (Arm C) who progressed subsequently received TECENTRIQ plus Avastin (Arm A) OS results were immature at time of analysis with only 35 percent of events having occurred.

Safety in the TECENTRIQ plus Avastin arm appeared consistent with the known safety profile of the individual medicines. No new safety signals were identified. Frequency of all-grade treatment-related adverse events was similar between arms. The most common AE’s occurring in more than 20% of patients receiving Tecentriq plus Avastin and with a greater than 5% increase when compared to sunitinib included: arthralgia (38%), proteinuria (36%), epistaxis (28%), and pruritus (22%). Frequency of grade 3-4 AEs regardless of relationship to treatment were similar between patients treated with TECENTRIQ plus Avastin (63%) and sunitinib (69%). Treatment-related grade 3-4 events reported in 40% of TECENTRIQ plus Avastin treated patients and 57% of sunitinib treated patients. One person who was treated with TECENTRIQ plus Avastin experienced intracranial haemorrhage that led to death. Fifteen of 101 patients (15%) treated with TECENTRIQ plus Avastin discontinued treatment for adverse events.

About renal cell carcinoma
Renal cell carcinoma (RCC) is the most common type of kidney cancer and forms when abnormal cells develop in the small tubes (known as renal tubules) in the kidneys. Each year about 338,000 people are diagnosed with kidney cancer globally accounting for nearly 145,000 deaths worldwide.1 The disease is more prevalent in males and people aged 55–74 years.2 Currently there is a significant need for more effective treatments with only about one in ten people alive five years post diagnosis.2

About TECENTRIQ (atezolizumab)
TECENTRIQ is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death ligand-1), which is expressed on tumour cells and tumour-infiltrating immune cells. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this interaction, TECENTRIQ may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells.

About Avastin
With the initial approval for advanced colorectal cancer in 2004, Avastin became the first anti-angiogenic therapy made widely available for the treatment of patients with an advanced cancer. Today, Avastin is continuing to transform cancer care across the world through its proven survival benefit (overall survival and/or progression free survival) in several types of cancer, including colorectal cancer, non-small cell lung cancer, kidney cancer, breast cancer, ovarian cancer, cervical cancer, and glioblastoma. Avastin has made anti-angiogenic therapy a fundamental pillar of cancer treatment today with over 2.4 million patients treated with this medicine so far. With one of the largest clinical development programmes ever seen in oncology, Avastin will continue to transform how patients are treated as ongoing studies seek to understand the full potential of this medicine and its combinations with the most cutting edge therapies in development.

On February 17, 2017 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported new findings from the OlympiAD study that show its BRACAnalysis CDx test successfully identified patients with HER2-negative metastatic breast cancer who have BRCA mutations and who had improved response with Lynparza (olaparib), AstraZeneca’s PARP inhibitor (Press release, Myriad Genetics, FEB 17, 2017, View Source [SID1234517753]).

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The high level results — announced earlier today from AstraZeneca — are the first reported clinical data from the OlympiAD study (NCT02000622), which assessed the efficacy and safety of olaparib monotherapy versus physicians’ choice of chemotherapy (i.e., capecitabine, vinorelbine or eribulin) in the treatment of metastatic breast cancer. Of the 302 patients in the study, 98 percent (297/302) tested positive for germline BRCA1/2 mutations as determined by Myriad’s FDA-approved BRACAnalysis CDx test. The results demonstrated a statistically-significant improvement of progression-free survival (PFS) among BRCA-mutated patients treated with olaparib compared to those treated with physicians’ choice.

"We believe the results of the OlympiAD trial support use of the BRACAnalysis CDx test to help inform treatment decisions in the metastatic breast cancer setting and will expand the patient population who can benefit from BRCA testing," said Johnathan Lancaster, M.D., Ph.D., chief medical officer of Myriad Genetic Laboratories. "This study underscores Myriad’s commitment to our pharmaceutical partners and to advancing the field of personalized medicine so that new effective treatment options are available to patients."

It is estimated there are approximately 60,000 patients with metastatic breast cancer, two thirds of whom are not currently eligible for BRCA testing based upon family and personal history alone or current testing criteria. If approved as a new indication this would triple the number of patients with metastatic breast cancer who would benefit from BRCA testing.

The ongoing collaboration between Myriad and AstraZeneca to develop a novel companion diagnostic test to identify candidates for treatment with olaparib began in 2007. In Dec. 2014, Myriad received FDA approval for BRACAnalysis CDx to help identify patients with advanced ovarian cancer who are eligible for fourth-line treatment with olaparib. BRACAnalysis CDx is Myriad’s first FDA-approved companion diagnostic and was the first-ever laboratory developed test reviewed and approved by the FDA.

About BRACAnalysis CDx
BRACAnalysis CDx is an in vitro diagnostic device intended for the qualitative detection and classification of variants in the protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA. Single nucleotide variants and small insertions and deletions (indels) are identified by polymerase chain reaction (PCR) and Sanger sequencing. Large deletions and duplications in BRCA1 and BRCA2 are detected using multiplex PCR. Results of the test are used as an aid in identifying ovarian cancer patients with deleterious or suspected deleterious germline BRCA variants eligible for treatment with Lynparza (olaparib). This assay is for professional use only and is to be performed only at Myriad Genetic Laboratories, a single laboratory site located at 320 Wakara Way, Salt Lake City, UT 84108.

About Lynparza
Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumour DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DNA damage response (DDR) mechanisms in cancer cells. Lynparza is currently approved by regulatory health authorities in the EU for use as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. It is also approved in the US as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-
test) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Lynparza is currently being investigated in another separate non-metastatic breast cancer Phase III study called OLYMPIA. This study is still open and recruiting patients internationally.

On February 16, 2017 Cytokinetics, Inc. (Nasdaq:CYTK) reported total revenues for the fourth quarter of 2016 were $33.1 million, compared to $9.8 million, during the same period in 2015. Net income for the fourth quarter was $7.2 million, or $0.18 and $0.16 per basic and diluted share, respectively (Press release, Cytokinetics, FEB 16, 2017, View Source;p=RssLanding&cat=news&id=2246868 [SID1234517762]). This is compared to a net loss for the same period in 2015 of $9.2 million, or $0.24 per basic and diluted share. As of December 31, 2016, cash, cash equivalents and investments totaled $163.9 million. The 2016 year-end cash and cash equivalents does not include $100 million received from a royalty monetization deal with Royalty Pharma that closed in February 2017.

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"2016 culminated with another productive quarter marked by progress and momentum across our pipeline of late-stage muscle biology-directed drug candidates," said Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. "With two drug candidates in Phase 3 clinical trials and a third advancing in multiple Phase 2 clinical trials, we are executing well against our Vision 2020 strategic initiative, alone and in collaboration with our partners. We expect 2017 to be a pivotal year highlighted by the expected results from VITALITY-ALS, our Phase 3 trial of tirasemtiv, as well as key data from our Phase 2 trial of CK-2127107 in patients with spinal muscular atrophy."

Recent Highlights

Cardiac Muscle Program

omecamtiv mecarbil

Announced the start of GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), the Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil which is being conducted by Amgen, in collaboration with Cytokinetics.

Announced additional results from COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure), a Phase 2 trial evaluating omecamtiv mecarbil in patients with chronic heart failure, showing that omecamtiv mecarbil improved left atrial (LA) structure and function in patients with chronic heart failure with reduced systolic function. The results were presented in a Clinical Poster Session at the American Heart Association’s Scientific Sessions 2016 in New Orleans.

Completed enrollment of a Phase 2 clinical trial of omecamtiv mecarbil in Japanese patients with chronic heart failure.
Skeletal Muscle Program

tirasemtiv

Announced the first patient has been enrolled in VIGOR-ALS (Ventilatory Investigations in Global Open-Label Research in ALS), an open-label extension clinical trial designed to assess the long-term safety and tolerability of tirasemtiv, in patients with ALS who have completed their participation in VITALITY-ALS.

Announced new data at the 27th International Symposium on ALS/MND in Dublin, Ireland including:

– Baseline characteristics from VITALITY-ALS showed patients enrolled in VITALITY-ALS are similar to those from BENEFIT-ALS and other recently conducted clinical trials in patients with ALS.

– Results from the first part of a research collaboration to refine and prospectively validate a computer model developed by Origent Data Sciences to predict the course of ALS disease progression analyzing data from the placebo groups of earlier clinical trials in patients with ALS (including BENEFIT-ALS, Cytokinetics’ Phase 2b clinical trial of tirasemtiv) and the open-access Pro-Act database. The analyses showed that the Gradient Boosting Machine (GBM) algorithm was the optimal model to predict slow vital capacity (SVC) at times subsequent to baseline and that forced vital capacity (FVC) records could be used to predict slow vital capacity (SVC) scores of ALS patients using this machine learning technique.

– Results of an international physician survey on the use of non-invasive ventilation (NIV) in the treatment of ALS presented by Terry Heiman-Patterson, M.D., Director of the Center for Neurodegenerative Disorders, and Professor of the Department of Neurology at the Lewis Katz School of Medicine at Temple University, revealed similarities in best practices for initiating NIV in North America and Europe, and differences in the time to initiation.
CK-2127107

Continued enrollment of Cohort 1 in the Phase 2 clinical trial of CK-2127107 in patients with spinal muscular atrophy (SMA), conducted by Cytokinetics in collaboration with Astellas.

Continued enrollment in a Phase 2 clinical trial of CK-2127107 in patients with COPD, conducted by Astellas in collaboration with Cytokinetics.
Pre-Clinical Research

Continued research activities under our joint research program with Amgen directed to the discovery of next-generation cardiac muscle activators and under our joint research program with Astellas directed to the discovery of next-generation skeletal muscle activators. In addition, company scientists continued independent research activities directed to our other muscle biology programs.

Announced the publication of preclinical data characterizing a smooth muscle myosin inhibitor that induces smooth muscle relaxation. The manuscript titled, "Highly Selective Inhibition of Myosin Motors Provides the Basis of Potential Therapeutic Application," published in PNAS, Proceedings of the National Academy of Sciences, illustrates a mechanism of action with potential relevance for diseases of smooth muscle hypercontractility such as asthma and chronic obstructive pulmonary disease.
Corporate

Received a $26.7 million milestone payment from Amgen coincident to the start of GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), the Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil which is being conducted by Amgen in collaboration with Cytokinetics.

Announced Cytokinetics has been selected for addition to the Nasdaq Biotechnology Index (NBI) as part of the annual re-ranking of the NBI.

Announced that Cytokinetics has agreed to sell to Royalty Pharma a 4.5% royalty on potential worldwide sales of omecamtiv mecarbil for $90 million and $10 million of Cytokinetics common stock.

Announced that Cytokinetics agreed to exercise its option under its collaboration agreement with Amgen to co-invest $40 million in the Phase 3 development program of omecamtiv mecarbil. As a result, Cytokinetics is eligible to receive an incremental royalty of up to 4% on increasing worldwide sales of omecamtiv mecarbil outside of Japan. Exercising its option and co-funding will afford Cytokinetics the right to co-promote omecamtiv mecarbil in institutional care settings in North America, with reimbursement by Amgen for certain sales force activities.
Financials

Revenues for the fourth quarter of 2016 were $33.1 million, compared to $9.8 million during the same period in 2015. Revenues for the fourth quarter of 2016 included $26.0 million from our collaboration with Amgen, and $3.6 million of research and development revenues and $3.2 million of license revenues from our collaboration with Astellas, and $0.3 million in research and development revenues from our collaboration with The ALS Association (ALSA). Revenues from our collaboration with Amgen included $26.7 million in a milestone payment, and $0.6 million in research and development revenue, partially offset by a payment of $1.3 million related to the option to co-fund a Phase 3 clinical trial for an increased royalty percentage. Revenues for the same period in 2015 were comprised of $5.1 million of license revenues and $4.0 million of research and development revenues from our collaboration with Astellas, and $0.6 million of research and development revenues from our collaboration with Amgen.

Total research and development (R&D) expenses for the fourth quarter of 2016 were $18.8 million, compared to $13.2 million for the same period in 2015. The $5.6 million increase in R&D expenses for the fourth quarter of 2016, compared with the same period in 2015, was primarily due to an increase of $4.0 million in outsourced clinical costs mainly associated with VITALITY-ALS, our ongoing Phase 3 trial of tirasemtiv, an increase of $1.2 million in personnel related expenses due to increased headcount costs and increased non-cash stock compensation expense, and an increase of $0.3 million in laboratory expenses, partially offset by a decrease of $0.3 million in outsourced pre-clinical costs.

Total general and administrative (G&A) expenses for the fourth quarter of 2016 were $6.7 million compared to $5.5 million for the same period in 2015. The $1.2 million increase in G&A expenses for the fourth quarter of 2016, compared to the same period in 2015, was primarily due to an increase of $0.8 million in personnel related expenses due to increased headcount and non-cash stock compensation expense and an increase of $0.2 million in outsourced costs related to commercial development, recruitment, consulting, and patent legal fees.

Revenues for the twelve months ended December 31, 2016 were $106.4 million, compared to $28.7 million for the same period in 2015. Revenues for the twelve months of 2016 included $62.2 million of license revenues, $13.1 million of research and development revenue, and $2.0 million of milestone payments from our collaboration with Astellas, and $27.9 million from our collaboration Amgen, and $1.1 million in research and development revenues from our collaboration with ALSA. Revenues from our collaboration with Amgen included $26.7 million in a milestone payment, and $2.5 million in research and development revenue, partially offset by a payment of $1.3 million related to the option to co-fund a Phase 3 clinical trial for an increased royalty percentage. Revenues for the same period in 2015 included $13.9 million of license revenues and $12.2 million of research and development revenues from our collaboration with Astellas, and $2.5 million of research and development revenues from our collaboration with Amgen.

Total R&D expenses for the twelve months ended December 31, 2016 were $59.9 million, compared to $46.4 million for the same period in 2015. The $13.5 million increase in R&D expenses for the twelve months of 2016, over the same period in 2015, was primarily due to an increase of $12.1 million in outsourced clinical costs, $4.5 million in personnel related expenses and non-cash stock compensation expense, and $0.8 million in outsourced research costs, partially offset by a decrease of $4.2 million in outsourced preclinical costs mainly associated with clinical manufacturing activities. The increase in outsourced clinical costs was comprised of an increase of $16.6 million in outsourced clinical costs mainly associated with VITALITY-ALS offset by a $4.5 million litigation settlement in June 2016 from a contract research organization for BENEFIT-ALS, our Phase 2 clinical trial of tirasemtiv which was concluded in 2014.

Total G&A expenses for the twelve months ended December 31, 2016 were $27.8 million, compared to $19.7 million for the same period in 2015. The $8.1 million increase in G&A spending in the twelve months of 2016 compared to the same period in 2015, was primarily due to $4.2 million in personnel related expenses due to increased headcount and non-cash stock compensation expense, an increase of $1.7 million in corporate and patent legal fees, and an increase of $1.7 million in outsourced costs related to commercial development, grants and sponsorships, and accounting and finance and recruitment related costs.

Net income for the twelve months ended December 31, 2016, was $16.5 million, or $0.41 and $0.39 per basic and diluted share, respectively, compared to a net loss of $37.5 million, or $0.97 per basic and diluted share, for the same period in 2015.

2017 Financial Guidance

Cytokinetics also announced financial guidance for 2017. The company anticipates cash revenue will be in the range of $21 to $23 million, cash R&D expenses will be in the range of $108 to $112 million, and cash G&A expenses will be in the range of $30 to $32 million. This guidance excludes approximately $7.0 million in unearned revenue from the 2014 amendment of our collaboration with Astellas, which will be recognized in 2017 under generally accepted accounting principles, as well as any potential future milestones that may be achieved in accordance with our collaboration agreements with our partner Astellas. This guidance also excludes an estimated $8.9 million in non-cash related operating expenses primarily related to stock compensation expense.

2017 Corporate Milestones

Skeletal Muscle Program
Tirasemtiv

Expect results from VITALITY-ALS in Q4 2017.

Expect to continue to enroll patients who complete VITALITY-ALS into VIGOR-ALS, an open-label extension trial throughout 2017.
CK-2127107

Expect data from a Phase 2 clinical trial of CK-2127107 in patients with SMA in 2H 2017.

Expect Astellas to continue enrollment in a Phase 2 clinical trial of CK-2127107 in patients with COPD in 2017.

Expect Astellas to begin a Phase 1b clinical trial of CK-2127107 in elderly patients with limited mobility in 1H 2017.

Expect to begin a Phase 2 clinical trial of CK-2127107 in patients with ALS in mid-2017.
Cardiac Muscle Program

omecamtiv mecarbil

Expect to continue to enroll patients with chronic heart failure in GALACTIC-HF, our Phase 3 clinical trial of omecamtiv mecarbil, throughout 2017.

Expect data from a Phase 2 clinical trial of omecamtiv mecarbil in Japanese patients with chronic heart failure in Q3 2017.
Pre-Clinical Research

Expect to continue research activities under our joint research program with Amgen directed to the discovery of next-generation cardiac muscle activators and under our joint research program with Astellas directed to the discovery of next-generation skeletal muscle activators.

(Filing, 20-F, Compugen, FEB 16, 2017, View Source [SID1234517734])

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On February 16, 2017 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new immunotherapies, reported financial results for the fourth quarter ended December 31, 2016, and provided an update on the Company’s recent activities (Press release, Ziopharm, FEB 16, 2017, View Source [SID1234517763]).

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"ZIOPHARM made significant progress over the course of 2016, putting us on track to enter a pivotal study and prosecute multiple high-value studies across our oncology programs in 2017, focusing on gene therapy, CAR and TCR T-cell therapies, as well as off-the-shelf NK cells," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. "This strategy moves us not just into a registration pathway with Ad-RTS-hIL-12 + veledimex, but clinically validates the broad potential of our technologies, including our switch systems and the Sleeping Beauty non-viral platform. These advances will be applied across our program areas, enabling us to increase control, reduce complexity, and manage costs, addressing some of the most significant needs in gene and cell therapy. Ultimately, the ability to deliver controlled, point-of-care therapy makes individualized treatment targeting each patient’s tumor neoantigens possible, a goal with profound clinical implications."

Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM, added: "In a recently updated presentation of results from our Phase 1, multi-center study of Ad-RTS-hIL-12 + veledimex in patients with recurrent high-grade gliomas, we observed a median overall survival of 12.7 months in the 20mg veledimex dose group. This remains a very encouraging outcome compared to historic controls. We look forward to providing an update on our registration pathway in this indication in the first quarter, and to initiating a pivotal study by the end 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 immune response, using the RheoSwitch Therapeutic System (RTS) gene switch. ZIOPHARM is currently conducting a multi-center Phase 1 study of Ad-RTS-hIL-12 + orally-administered veledimex in patients with recurrent or progressive glioblastoma multiforme (GBM), an aggressive form of brain cancer.

Announced End-of-Phase 2 Meeting with the FDA. In its presentation at the 35th Annual J.P. Morgan Healthcare Conference, the Company announced that it was granted an end-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) to determine a pivotal trial design for Ad-RTS-hIL-12 + veledimex for recurrent GBM. The Company expects to announce the outcome of this meeting in the first quarter of 2017, with the goal of initiating a pivotal clinical trial of Ad-RTS-hIL-12 + veledimex in recurrent GBM in 2017.

Presented Data Demonstrating Survival Benefits in Patients with Recurrent Brain Cancer Treated with Ad-RTS-hIL-12 + Veledimex. In November 2016, ZIOPHARM presented clinical data for Ad-RTS-hIL-12 + veledimex for recurrent brain cancer at the 21st Annual Scientific Meeting of the Society for Neuro-Oncology (SNO) in Scottsdale, Arizona. In the study, recombinant IL‑12, leading to the body’s production of interferon-gamma (IFN-gamma), were measured in the bloodstream and found to be proportional to the three doses of veledimex (20mg, n=7; 30mg, n=4; and 40mg, n=6), demonstrating that this orally-delivered activator crossed the blood-brain barrier to engage the RTS gene switch and express IL-12 and IFN-gamma in a dose-dependent manner. Toxicities were consistent with those previously reported and all related side effects were reversed upon cessation of veledimex. Based on tolerability and survival benefit (median OS=12.7 months, n=15, as of January 6, 2017), 20 mg was selected for an expansion cohort, with patients being followed for overall survival. Updated results from the study have been submitted for presentation at an upcoming scientific meeting.

Presented Results of Pre-Clinical Study Supporting Initiation of New Clinical Trial of Ad-RTS-hIL-12 + Veledimex in Pediatric Brain Tumors. In November 2016, ZIOPHARM presented results from a preclinical study of Ad-RTS-mIL-12 + veledimex as an investigational therapy for pediatric glioma in a poster titled "Local regulated IL-12 expression as an immunotherapy for the treatment of pontine glioma" at the 21st Annual Scientific Meeting of the SNO in Scottsdale, Arizona. In an orthotopic pons model, veledimex was shown to cross the blood-brain barrier to control mouse IL-12 production from the tumor, which stimulated the immune system and resulted in increased overall survival. Based on these results, the Company plans to initiate a Phase 1 clinical trial in pediatric brain tumors, including diffuse intrinsic pontine glioma (DIPG) in 2017.

Presented Data Demonstrating Activation of Anti-Tumor Immune Response Using Ad-RTS-hIL-12 + Veledimex in Patients with Advanced Breast Cancer. In October 2016, ZIOPHARM announced the presentation of preliminary data from the Company’s 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 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress in Copenhagen, Denmark. Results showed that Ad-RTS-hIL-12 + seven days of veledimex consistently elicited production of IL-12 which in turn produced IFN-gamma. It was notable that the influx of CD8+ T cells making IFN-gamma within the tumor were present five weeks after completion of veledimex, consistent with the ability of Ad-RTS-hIL-12 to favorably impact the tumor environment over the long term. In two patients, Ad-RTS-hIL-12 + veledimex provided a meaningful chemotherapy holiday, with durable responses for 18 and 35 weeks.
Adoptive Cell Therapies

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

Announced Advances in Point-of-Care Approach for Rapidly Producing CAR-Expressing T Cells Utilizing the Sleeping Beauty System. In January 2017, ZIOPHARM announced improved production times utilizing its non-viral platform to engineer T cells in an ongoing Phase 1 study of second-generation Sleeping Beauty (SB) CD19-specific CAR+ T cells. Plans to progress the Company’s point-of-care (POC) approach with administration of CAR-T cell therapy in less than 2 days are also underway, helping expand access to innovative T-cell therapies.

Cooperative Research and Development Agreement with the National Cancer Institute Utilizing Sleeping Beauty System to Generate T cells Targeting Neoantigens. In January 2017, ZIOPHARM and partner Intrexon announced the signing of a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) for the development of adoptive cell transfer-based immunotherapies genetically modified using the SB system to express TCRs for the treatment of solid tumors. Research conducted under the CRADA will be at the direction of Steven A. Rosenberg, M.D., Ph.D., Chief of the Surgery Branch at the NCI’s Center for Cancer Research.

Results from Four Studies of Adoptive Cell-based Therapeutic Programs Presented at the 2016 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. In December 2016, ZIOPHARM presented data from the Company’s adoptive cell-based therapeutic programs at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition held December 3-6, 2016 in San Diego. The research, conducted at the MD Anderson Cancer Center and Intrexon, demonstrates, among other results, that T cells can be very rapidly produced with the SB system and that a non-viral approach to gene therapy can be harnessed to generate CAR- and TCR-expressing effector cells.

Announced Publication Demonstrating Membrane-bound IL-15 (mbIL15) Enhanced Persistence of CD19-Specific T Cells. In November 2016, ZIOPHARM announced the publication of data demonstrating enhanced persistence of genetically modified T cells targeting leukemia through utilization of its non-viral SB system to co-express mbIL15 and a CD19-specific CAR. The article, titled "Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells," was published in the Proceedings of the National Academy of Sciences and is available online here.

Using the SB system, researchers generated genetically modified T cells that preserved stem-cell memory (TSCM) cells by co-expressing the CAR with mbIL15. Engineered T cells were effective in treating established CD19+ leukemia in mice by facilitating the long-term persistence of TSCM cells sustained by signaling through recombinant IL-15. These findings provide for a translational pipeline of immunotherapies with improved potential by combining mbIL15 and T cells with diverse specificities.

The Company previously announced the publication of data highlighting the benefits of using the non-viral SB system to genetically modify T cells to express a CAR for use against CD19-expressing 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.
Anticipated 2017 Milestones

Intra-tumoral IL-12 RheoSwitch programs:
– Clinical data from Phase 1 of Ad-RTS-hIL-12 + veledimex for GBM to be presented at a scientific meeting in 2017
– Initiate pivotal clinical trial for GBM in 2017
– Initiate combination study of Ad-RTS-hIL-12 + veledimex with immune checkpoint inhibitor (PD-1) during the first half of 2017
– Initiate Phase 1 study in the treatment of brain tumors in children during the first half of 2017
CAR-T programs:
– Continue CD19-specific CAR+ T clinical study in 2017 enrolling patients under shortened manufacturing process towards point of care
– Initiate a CD33-specific CAR+ T clinical study for relapsed or refractory AML in 2017
– Advance CAR+ T-cell preclinical studies for at least one hematological malignancy under a shortened manufacturing process towards point of care
TCR-T programs:
– Execute CRADA with NCI utilizing SB to generate T cells targeting neoantigens
NK cell programs:
– Initiate a Phase 1 study of off the shelf NK cells for AML in 2017
GvHD programs:
– Advance preclinical studies in 2017
2017 RBC Global Healthcare Conference

The Company also announced that Dr. Cooper will present at the 2017 RBC Global Healthcare Conference on Thursday, February 23rd, 2017 at 1:35 p.m. ET. The conference will be held at the Lotte New York Palace in New York City.

To access a live audio webcast of the presentation, please visit the Investor Relations section at www.ziopharm.com.

Fourth-Quarter 2016 Financial Results

Net loss applicable to common shareholders for the fourth quarter of 2016 was $14.8 million, or $(0.11) per share, compared to a net loss of $9.5 million, or $(0.07) per share, for the fourth quarter of 2015. The increase in net loss for the three months ended December 31, 2016 is primarily due to a $1.2 million increase in expenses related to the gene therapy and cell therapy programs, decreased collaboration revenue of $0.3 million, an increase in the charge for the change in derivative liabilities of $0.1 million and income attributable to preferred stockholders of $3.5 million.

Research and development expenses were $9.4 million for the fourth quarter of 2016 compared to $8.1 million for the fourth quarter of 2015. The increase in research and development expenses for the three months ended December 31, 2016 is primarily due to a $1.2 million increase in expenses related to the gene therapy and cell therapy programs.

General and administrative expenses were $3.3 million for the fourth quarter of 2016 and 2015.
The Company ended the quarter with cash and cash equivalents of approximately $81.1 million, which the Company believes will be sufficient to fund its currently planned activities into the fourth quarter of 2017. The cash burn is expected to increase substantially during 2017 due to the anticipated initiation of a pivotal trial in GBM.