On May 1, 2017 Lion Biotechnologies, Inc. (NASDAQ: LBIO), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported its first quarter 2017 financial results and provided a corporate update (Press release, Lion Biotechnologies, MAY 1, 2017, View Source [SID1234518772]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We started 2017 with a clear focus on execution toward expanding our manufacturing capacity, our clinical program and initiation of engagement with health authorities. During the first quarter of 2017, we increased our manufacturing capacity and are now focused on expansion of our clinical program as well as access to clinical data through collaborations. I am very excited about our recently announced collaboration with MD Anderson, which allows us access to rare patient populations as well as a new method of manufacturing TIL using the MD Anderson process. Lion now has strategic relationships with leading academic and governmental institutions in the U.S. researching TIL technology including the NCI, MD Anderson, and the H. Lee Moffitt Cancer Center as well as one of a leading institution in Europe, the Karolinska Institute, providing Lion the ability to pursue a much broader clinical program than would otherwise be possible as a standalone company," said Dr. Maria Fardis, PhD, MBA, Chief Executive Officer of Lion Biotechnologies. "With this new collaboration in place, by year-end we may have partner-sponsored trials in pancreatic, glioblastoma, ovarian cancer, various sarcomas and melanoma combination trials with three of the approved checkpoint inhibitors in addition to the three ongoing Lion-sponsored TIL clinical studies in metastatic melanoma, head and neck and cervical cancers. This gives us a robust pipeline based on our TIL technology."

First Quarter 2017 and Recent Highlights

Partnerships:

Multi-year strategic alliance with MD Anderson Cancer Center: Lion entered a multi-year strategic alliance agreement involving multi-arm clinical trials to evaluate the safety and efficacy of TIL therapy in ovarian cancer, various sarcomas and pancreatic cancer. In addition, Lion and MD Anderson will conduct preclinical research exploring the expansion of TIL in other rare tumor types.
Manufacturing services agreement with PharmaCell enables expansion of clinical studies in Europe: Lion has entered in to a new, three-year Manufacturing Services Agreement (MSA) with PharmaCell B.V. (PharmaCell), a contract manufacturing services company based in the Netherlands, to manufacture the Company’s autologous cell therapy products. PharmaCell will manufacture TIL products for Lion in its clinical and commercial facility in Geleen, the Netherlands.
Clinical Trial Progress:

Enrollment in LN-144 Phase 2 melanoma study continues: Lion has initiated enrolling patients into the second cohort of its LN-144 program. This cohort utilizes the generation 2 manufacturing process. This process reduces the time from excision to infusion from approximately six weeks to approximately three and half weeks.
Two new Phase 2 studies initiated: The Company has now initiated two Phase 2 trials for LN-145 for the treatment of head and neck and cervical cancers. Clinical trial sites are open for both studies and they are actively screening for patients.
Regulatory:

Global conduct of clinical trials: The Company is engaging health authorities outside the U.S. to gain clarity around conduct of clinical trials outside of US.
Publications:

Publication of new translational data in the journal Science: Lion highlighted a publication in the journal Science that provided new translational data from a clinical trial of TIL therapy for the treatment of advanced metastatic cervical cancer conducted at the Surgery Branch of the National Cancer Institute (NCI). This trial has been supported in part by Lion under a Cooperative Research and Development Agreement (CRADA) with Dr. Steven Rosenberg, Chief of the Surgery Branch, NCI, National Institutes of Health.
First Quarter 2017 Financial Results

As of March 31, 2017, the Company held $147.2 million in cash and cash equivalents and short-term investments, compared to $166.5 million as of December 31, 2016.

GAAP and Non-GAAP net loss

GAAP net loss for the quarter ended March 31, 2017 was $20.7 million, or ($0.33) per share, compared to GAAP net loss of $6.9 million or ($0.14) per share for the quarter ended March 31, 2016.

Non-GAAP net loss, which excludes amounts related to stock-based compensation, for the quarter ended March 31, 2017 was $17.4 million, or ($0.28) per share, compared to non-GAAP net loss of $5.1 million, or ($0.10) per share for the quarter ended March 31, 2016. The non-GAAP net loss for the quarter ended March 31, 2017 excludes $3.3 million of non-cash stock-based compensation.

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

GAAP and Non-GAAP expenses

GAAP research and development (R&D) expenses were $16.6 million for the quarter ended March 31, 2017, an increase of $12.4 million compared to the quarter ended March 31, 2016. The increase in R&D expense is due to increased spending on clinical activities and expansion of manufacturing capabilities. This level of spending is consistent with cell therapy companies at Lion’s stage of clinical development. In addition, R&D-associated stock option expenses were $1.4 million for the three months ended March 31, 2017. Non-GAAP R&D expenses were $15.2 million for the quarter ended March 31, 2017, an increase of $11.6 million, compared to $3.6 million for the quarter ended March 31, 2016.

GAAP general and administrative (G&A) expenses were $4.3 million, an increase of $1.4 million compared to the quarter ended March 31, 2016. The increase in G&A expense is primarily due to the increase in headcount and legal and outside services. Non-GAAP G&A expenses were $2.4 million, which excludes amounts related to stock-based compensation of $1.9 million, for the quarter ended March 31, 2017 an increase of $0.8 million, compared to $1.6 million for the quarter ended March 31, 2016.

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

Use of Non-GAAP Financial Measures

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

On May 1, 2017 AstraZeneca and its global biologics research and development arm, MedImmune, reported that the US Food and Drug Administration (FDA) has granted accelerated approval to Imfinzi (durvalumab) (Press release, AstraZeneca, MAY 1, 2017, View Source [SID1234518771]). Imfinzi is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery. Imfinzi is approved under the FDA’s accelerated approval pathway, based on tumour response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Pascal Soriot, Chief Executive Officer of AstraZeneca, said: "We are excited to offer Imfinzi as a breakthrough therapy for patients with locally-advanced or metastatic bladder cancer. Imfinzi is the cornerstone of our extensive Immuno-Oncology programme, in development across many tumour types, as monotherapy and in combination. This first approval for Imfinzi is an important milestone in our return to growth and brings us another step closer to our goal of redefining the way cancer is treated."

Imfinzi is also under investigation in the Phase III DANUBE trial as 1st- line treatment in urothelial carcinoma as monotherapy and in combination with tremelimumab.

Nicholas J. Vogelzang, MD, FACP, FASCO, Clinical Professor at the University of Nevada School of Medicine; SWOG GU Vice Chair; US Oncology Research GU Chair; Comprehensive Cancer Centers of Nevada, said: "The usual course of treatment for patients with advanced bladder cancer begins with a standard platinum-containing chemotherapy. Patients who have disease progression during or following chemotherapy are left with few other treatment options. The approval of Imfinzi to treat this population of select patients signifies hope for those who are currently suffering, or may find themselves with limited options in the future."

The recommended dose of Imfinzi is 10 mg/kg body weight administered as an intravenous infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity.

The accelerated FDA approval of Imfinzi, a human monoclonal antibody that blocks PD-L1, is based on data from Study 1108. This Phase I/II trial evaluated the safety and efficacy of Imfinzi in patients with locally-advanced or metastatic urothelial carcinoma of the bladder. Patients had progressed while on or after a platinum-containing chemotherapy, including those who progressed within 12 months of receiving therapy in a neoadjuvant or adjuvant setting.

In the trial, Imfinzi demonstrated rapid and durable responses, with an objective response rate (ORR) of 17.0% (95% confidence interval [CI]: 11.9; 23.3) in all evaluable patients, regardless of PD-L1 status, and 26.3% (95% CI: 17.8; 36.4) in patients with PD-L1 high-expressing tumours (as determined by the VENTANA PD-L1 (SP263) Assay, Ventana Medical Systems Inc., a member of the Roche Group). PD-L1 high was defined as ≥25% of tumour cells (TC) or tumour-infiltrating immune cells (IC) expressing membrane PD-L1 if ICs involved >1% of the tumour area, or TC≥25% or IC=100% if ICs involved ≤1% of the tumour area. Additionally, approximately 14.3% of all evaluable patients achieved partial response and 2.7% achieved complete response. Of patients who had received only neoadjuvant or adjuvant therapy prior to trial entry, 24% (n=9) responded. Based on a secondary endpoint in this single-arm trial, median time to response was six weeks. Among the total 31 responding patients, 14 patients (45%) had ongoing responses of six months or longer and five patients (16%) had ongoing responses of 12 months or longer.

Efficacy results for Study 1 (bladder cancer cohort of Study 1108


All Patients
(N=182)
PD-L1
High
(N=95)
PD-L1 Low/Negative (N=73)
PD-L1 Not Evaluable (N=14)
Objective Response Rate (ORR) by BICR*, n (%)
(95% confidence interval [CI])
31 (17.0%)
(11.9; 23.3)
25 (26.3%)
(17.8; 36.4)
3 (4.1%)
(0.9; 11.5)
3 (21.4%)
(4.7; 50.8)
Complete Response (CR)
5
3
1
1
Partial Response (PR)
26
22
2
2
Median Duration of Response (DoR), months (range)
Not reached
(0.9+; 19.9+)
Not reached
(0.9+; 19.9+)
12.3
(1.9+; 12.3)
Not reached
(2.3+; 2.6+)
*BICR=Blinded Independent Central Review
+ Denotes a censored value

Patients should be monitored for immune-mediated adverse reactions including pneumonitis, hepatitis, colitis, endocrinopathies (including adrenal insufficiency, hypophysitis, or Type 1 diabetes mellitus), nephritis, rash, thrombocytopenic purpura, infection, infusion-related reactions, or embryo-fetal toxicity. Serious adverse reactions occurred in 46% of patients. The most frequent serious adverse reactions (>2%) were acute kidney injury (4.9%), urinary tract infection (4.4%), musculoskeletal pain (4.4%), liver injury (3.3%), general physical health deterioration (3.3%), sepsis, abdominal pain, and pyrexia/tumour associated fever (2.7% each). Eight patients (4.4%) who were treated with Imfinzi experienced Grade 5 adverse events of cardiorespiratory arrest, general physical health deterioration, sepsis, ileus, pneumonitis, or immune-mediated hepatitis. Three additional patients were experiencing infection and disease progression at the time of death. Imfinzi was discontinued for adverse reactions in 3.3% of patients.

Clinical trials have demonstrated that patients with PD-L1 high-expressing tumours have a higher likelihood of response through blockade of the PD-1/PD-L1 pathway. PD-L1 expression testing may be a useful tool to help guide physicians in their treatment decisions, but it is not required for use of Imfinzi.

About Imfinzi (durvalumab)

Imfinzi (durvalumab, previously known as MEDI4736) is a human monoclonal antibody directed against PD-L1, which blocks the interaction of PD-L1 with PD-1 and CD80.

Durvalumab is also being tested in the 1st-line treatment of patients with unresectable and metastatic bladder cancer as a monotherapy and in combination with tremelimumab, a checkpoint inhibitor that targets CTLA-4, as part of the DANUBE Phase III trial, which had the last patient commenced dosing during the first quarter of 2017 (global trial, excluding China). Additional clinical trials are ongoing to investigate durvalumab as monotherapy or in combination in multiple solid tumours and blood cancers.

About bladder cancer

Urothelial bladder cancers arise from the epithelium of the bladder and are the ninth most common form of cancer worldwide. It is estimated that in 2016, about 430,000 people were diagnosed with bladder cancer around the world and 165,000 did not survive. Metastatic bladder cancer remains an area of unmet medical need in particular; among patients treated with standard-of-care chemotherapy, the five-year survival rate is below 15%.

The tumour microenvironment of urothelial carcinoma (UC) significantly impairs lymphocyte function, helping the cancer to evade immune detection by exploiting inhibitory checkpoint pathways, such as PD-L1/PD-1. PD-L1 is widely expressed in tumour and immune cells in UC patients and helps tumours to evade detection from the immune system through binding to the PD-1 receptor on cytotoxic T lymphocytes.

On May 1, 2017 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported company highlights and financial results for the first quarter ended March 31, 2017 (Press release, Ignyta, MAY 1, 2017, View Source [SID1234518768]). The company is issuing this press release in lieu of conducting a conference call.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited by the continued advancement of our pipeline of precision medicine therapies for the benefit of patients with cancer, including the progress of STARTRK-2, the registration-enabling Phase 2 clinical trial of our lead product candidate, entrectinib, our novel, investigational, orally available, CNS-active tyrosine kinase inhibitor targeting tumors that harbor TRK, ROS1, or ALK fusions," said Jonathan Lim, M.D., Chairman and CEO of Ignyta.

Company Highlights

Updated Progress Towards Entrectinib Dual TRK and ROS1 NDA Submissions

In April 2016, we announced a comprehensive program update on entrectinib and the STARTRK-2 trial. As of that update:

Entrectinib program is more than 85% enrolled to goal for the primary efficacy analysis to potentially support a TRK tissue agnostic NDA submission
More than 50 patients with ROS1 fusion-positive NSCLC were enrolled; interim data from 32 of these patients as assessed by investigator demonstrated 75% (24 of 32) confirmed RECIST ORR and 17.2 months DOR
Entrectinib demonstrated a confirmed RECIST ORR of 64% (7 of 11) in ROS1 NSCLC patients with CNS metastases
The program is tracking towards dual NDA submissions in TRK and ROS1 in 2018 if supported by clinical data, with anticipated US commercial launch in both indications in 2019.

Multiple Entrectinib Peer-Reviewed Publications

In March 2017, a case report on the successful treatment with entrectinib of a clinical trial patient with a primary brain tumor harboring an NTRK1 fusion was published in the peer-reviewed journal, Precision Oncology. The genomic analysis study, led by researchers at Massachusetts General Hospital, reported three NTRK fusions out of 26 tumors evaluated, and reported that in a patient with a BCAN-NTRK1 fusion, clinical trial treatment with entrectinib resulted in a 60 percent regression in tumor size and a resolution of clinical symptoms that was maintained for 11 months on treatment.

In February 2017, updated results from two Phase 1 trials of entrectinib were published in the peer-reviewed journal, Cancer Discovery. We believe this is the largest published safety experience of any TRK inhibitor in clinical development. Highlights of that publication included:

Findings that entrectinib continues to be well tolerated
As of September 2016 data cutoff, RECIST responses were noted in 3 of 3 patients with TRK-positive extracranial solid tumors, with the longest ongoing TRK responder on therapy for 17 months; and RECIST responses in 12 of 14 patients with ROS1-positive solid tumors, with the longest ongoing ROS1 responder on therapy for 32 months
RECIST responses were noted in 63% of patients (5 out of 8) with TRK, ROS1, or ALK fusions, and primary or metastatic disease involving the brain
Amendment of Lilly Agreement

In March 2017, the company announced that it was exploring strategic options for taladegib – an orally bioavailable small molecule hedgehog/smoothened inhibitor – and had entered into an amended and restated license, development and commercialization agreement with Eli Lilly and Company for the taladegib oncology program.

First Quarter 2017 Financial Results

For the first quarter of 2017, net loss was $40.2 million, or $0.96 per share, compared with $25.5 million, or $0.79 per share, for the first quarter of 2016. The vast majority of the increase was due to $12.8 million ($9.8 million of which was non-cash) recorded in 2017 in connection with the amendment of the Lilly license. This amount represents the remaining $12.0 million of timing-based milestones owed over the subsequent three calendar years, discounted back to today’s cash value, and booked as a largely non-cash expense.

Ignyta did not record any revenue for the first quarter of 2017, or for the first quarter of 2016.

Research and development expenses for the first quarter of 2017 were $34.0 million, compared with $19.8 million for the first quarter of 2016. This increase was due to the $12.8 million charge recorded in 2017 in connection with the Lilly license amendment and increased facilities costs of $1.2 million due to the expansion of our leased facilities space. We also incurred additional stock compensation costs of $0.2 million due to the increase in the number of outstanding stock options.

General and administrative expenses were $5.6 million for first quarter of 2017, compared with $5.2 million for first quarter of 2016. The increase in general and administrative expenses was primarily attributable to an increase in our facilities costs.

At March 31, 2017, the company had cash, cash equivalents and available-for-sale securities totaling $108.0 million and current and long-term debt of $32.0 million. At December 31, 2016, the company had cash, cash equivalents and available-for-sale securities totaling $133.0 million and current and long-term debt of $32.0 million. Excluding a $3.0 million milestone payment related to the Lilly license, cash burn in the quarter was $22.0 million.

On May 1, 2017 ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP), a biopharmaceutical company focused on new immunotherapies, reported its financial results for the first quarter ended March 31, 2017, and provided an update on the company’s recent activities (Filing, Q1, Ziopharm, 2017, MAY 1, 2017, View Source [SID1234518767]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"ZIOPHARM is making significant advances, including progress towards finalizing a registration path for Ad-RTS-hIL-12 + veledimex for recurrent glioblastoma and furthering development in our point-of-care approach with T-cell CAR-based therapies," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM Oncology. "ZIOPHARM is assessing several paths for the pivotal trial, including a single-arm study of Ad-RTS-hIL-12 + veledimex compared to historical controls. With a commercialization path in view, we are evaluating partnership opportunities for Ad-RTS-hIL-12 + veledimex to understand the breadth of options available to ZIOPHARM for bringing this important therapeutic candidate to patients."

"The IL-12 data from the brain cancer trial firmly establishes that the RheoSwitch Therapeutic System works as a switch in humans," added Dr. Cooper. "By combining the most clinically advanced non-viral gene integration platform, Sleeping Beauty, and transcriptional switch system, RheoSwitch, we will use our point-of-care approach to significantly shorten the time to manufacture T cells and to tailor the expression of introduced genes after infusion using veledimex. This will address two major issues with CAR-based therapies, namely the cost of therapy and control of T cells to reduce toxicity."

Recent Updates
Ad-RTS-hIL-12 + veledimex
Ad-RTS-hIL-12 + veledimex is ZIOPHARM’s gene therapy candidate for the controlled expression of interleukin-12 (IL-12), a critical protein for stimulating an anti-cancer immune response, using a RheoSwitch Therapeutic System (RTS) inducible gene-delivery system, or switch, that enables controlled in vivo expression of therapeutic proteins. 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.
ZIOPHARM will be presenting updated results from its Phase 1, multicenter, dose-escalation study of Ad-RTS-hIL-12 + veledimex in patients with recurrent or progressive glioblastoma at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 5, 2017.

"Our initial discussions with regulators have been encouraging, and we look forward to moving Ad-RTS-hIL-12 + veledimex into a pivotal study as quickly as possible this year. Details of the pivotal Phase 3 trial will be made available following completion of discussions with regulators and clinical advisors," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "We continue to see encouraging outcomes in our Phase 1, multi-center study of Ad-RTS-hIL-12 + veledimex in patients with recurrent high-grade gliomas and plan to share updated results from this study at ASCO (Free ASCO Whitepaper)."

The Company also expects to initiate Phase 1 studies of Ad-RTS-hIL-12 + veledimex in pediatric brain cancer, as well as in combination with an anti-PD-1 checkpoint inhibitor in adult glioblastoma, as planned, in the first half of 2017.

Adoptive Cell Therapies
ZIOPHARM is developing 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, MD Anderson Cancer Center, the National Cancer Institute and Merck Serono, the biopharmaceutical business of Merck KGaA (CAR+ T only).
Announced Advancement of Next-Generation Non-Viral CAR+ T Platform Empowered by Membrane-Bound IL-15 Under RTS Gene Switch Control. In April 2017, ZIOPHARM and its partners, Intrexon and Merck KGaA, Darmstadt, Germany, announced the advancement of a unique approach to develop therapeutic candidates for two CAR+ T targets expressed on a wide range of tumor types, including hematologic malignancies and solid tumors. The distinctive methodology centers on the proprietary RTS platform to regulate production of membrane-bound interleukin-15 (mbIL15) co-expressed with CARs and Sleeping Beauty, a non-viral genetic modification system to genetically modify clinical-grade T cells. The companies expect to advance this innovative approach towards the clinic in 2018.

The IL-15 cytokine is increasingly recognized as a key driver of therapeutic effect in CAR+ T therapy, including in a recent Journal of Clinical Oncology publication which correlated lymphoma remissions in patients whose IL-15 levels were elevated after lymphodepleting chemotherapy. Through the RTS gene switch, the expression of mbIL15 can be regulated to help CARs target cancers in a controlled manner, thus providing a new paradigm in T-cell therapy.
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-modified CD19-specific CAR+ T cells. ZIOPHARM continues to refine its Sleeping Beauty system to further reduce time to manufacture genetically modified T cells. Preclinical studies of third-generation Sleeping Beauty-modified CAR+ T cells co-expressing mbIL15 demonstrated reduced time to administration (less than two days) through elimination of the need for in vitro T-cell activation and propagation. Plans to progress this point-of-care approach with infusion of CAR+ T cells in less than two days are underway. The combination of Sleeping Beauty and RTS-mbIL15, has the potential to solve the dual problems of cost and toxicities as genetically modified T cells can be rapidly produced for preclinical testing, and the RTS is a clinically validated switch, which may be used with veledimex to control T-cell persistence via conditional expression of mbIL15. The Company expects to advance towards a Phase 1 study evaluating the point-of-care in 2017.

Announced Cooperative Research and Development Agreement (CRADA) With the National Cancer Institute Utilizing Sleeping Beauty System to Generate T Cells Targeting Neoantigens. In January 2017, ZIOPHARM and its partner, Intrexon, announced the signing of a CRADA with the National Cancer Institute (NCI) for the development of adoptive cell transfer-based immunotherapies genetically modified using the Sleeping Beauty system to express TCRs targeting neoantigens 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. The Company anticipates that this program will advance to Phase 1 during the second half of 2017.
Anticipated and Achieved 2017 Milestones

• Intra-tumoral IL-12 RheoSwitch programs:

• Updated clinical data from Phase 1 of Ad-RTS-hIL-12 + veledimex for recurrent GBM to be presented at ASCO (Free ASCO Whitepaper)

• Initiate pivotal clinical trial for recurrent GBM

• Initiate combination study of Ad-RTS-hIL-12 + veledimex with iCPI (anti-PD-1) for recurrent GBM during the first half

• Initiate Phase 1 study in the treatment of brain tumors in children during the first half

• CAR+ T programs:

• Continue CD19-specific CAR+ T second-generation clinical study, enrolling patients under shortened manufacturing

• Advance CD19 third-generation mbIL15 towards a Phase 1 clinical study evaluating point-of-care

• Initiate a CD33-specific CAR+ T clinical study in adults and children for relapsed or refractory acute myeloid leukemia

• Advance CAR+ T-cell preclinical studies for at least one hematological malignancy under a shortened manufacturing process towards point-of-care

• TCR programs

• Execute CRADA with NCI utilizing Sleeping Beauty to generate T cells targeting neoantigens for treatment of patients with solid tumor malignancies

• Advance development of process for delivering personalized gene-modified T-cell products against neoantigens

• NK cell programs

• Initiate a Phase 1 study of off-the-shelf (OTS) NK cells for elderly patients with acute myeloid leukemia not eligible for standard intensive chemotherapy

• GvHD (graft-versus-host disease) programs

• Advance preclinical studies

First-Quarter 2017 Financial Results

• Net loss applicable to the common shareholders for the first quarter of 2017 was $19.7 million, or $(0.15) per share, compared to a net loss of $12.0 million, or $(0.09) per share, for the first quarter of 2016. The increase in net loss for the three months ended March 31, 2017 is primarily due to decreased collaboration revenue of $0.4 million, an increase in operating expenses of $1.5 million, an increase in the charge for the change in derivative liabilities of $1.6 million and income attributable to preferred shareholders of $4.2 million.

• Research and development expenses were $12.0 million for the first quarter of 2017, compared to $10.2 million for the first quarter of 2016. The increase in research and development expenses for the three months ended March 31, 2017 is primarily due to our gene therapy and cell therapy programs, along with increased headcount.

• General and administrative expenses were $3.6 million for the first quarter of 2017, compared to $3.8 million for the first quarter of 2016. The decrease in general and administrative expenses is primarily due to decreased employee-related expenses.

• The Company ended the quarter with cash and cash equivalents of approximately $66.4 million, which the Company believes will be sufficient to fund its currently planned activities through the fourth quarter of 2017, including initiating a pivotal trial for Ad-RTS-hIL-12 + veledimex.