On August 9, 2016 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical-stage pharmaceutical company focused on discovering and developing novel small molecule drugs directed against tumor and tumor immune cell metabolism targets for the treatment of cancer, reported its financial results for the second quarter ended June 30, 2016. As of June 30, 2016, cash, cash equivalents and investments totaled $60.4 million (Press release, Calithera Biosciences, AUG 9, 2016, View Source;p=RssLanding&cat=news&id=2194344 [SID:1234514418]).

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"During the second quarter, we significantly advanced our pipeline of novel cancer therapeutics," said Susan Molineaux, Ph.D., President and Chief Executive Officer of Calithera. "Data presented on the tumor metabolism drug CB-839 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) helped us to define a path forward for clinical development in renal cell carcinoma and triple negative breast cancer. With the FDA’s acceptance of our IND for our metabolic immune checkpoint drug candidate CB-1158, we now have two novel metabolic agents targeting tumor and immune cell metabolism in clinical development."

Second Quarter 2016 and Recent Highlights

FDA acceptance of Investigational New Drug Application for CB-1158. In July 2016, the U.S. Food and Drug Administration (FDA) accepted the company’s Investigational New Drug (IND) application for CB-1158 for the treatment of solid tumors. CB-1158 is a first-in-class immuno-oncology metabolic checkpoint inhibitor targeting arginase, an immunosuppressive enzyme in myeloid-derived suppressor cells responsible for T-cell suppression. Arginase exerts its immunosuppressive effect by depleting the amino acid arginine in the tumor microenvironment and preventing activation and proliferation of the immune system’s cytotoxic T-cells and natural killer (NK) cells. Inhibition of arginase activity reverses this immunosuppressive block and restores T-cell function. The Phase I clinical trial will enroll patients with advanced solid tumors treated with CB-1158 as a monotherapy, as well as in combination with an anti-PD1 antibody.
CB-839 solid tumor combination data presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper). In June 2016, Calithera presented clinical data for CB-839 in combination with everolimus in renal cell carcinoma, and CB-839 in combination with paclitaxel in triple negative breast cancer. Among ten renal cell carcinoma patients treated in the everolimus combination group, the overall disease control rate was 80%, including one partial response. Among eight clear cell and papillary patients, the disease control rate was 100%. The median time on study exceeded the expected progression free survival for everolimus alone in this population. Fifteen triple negative breast cancer patients were treated with CB-839 in combination with paclitaxel. The majority of patients had received at least three prior lines of therapy. Most patients had received prior taxanes in either the neo-adjuvant, adjuvant or metastatic setting. Among patients treated with CB-839 doses of at least 600 mg bid (n=8), there were 3 partial responses (38%) and disease control (response or stable disease) in 7 patients (88%). Two of the partial responses were observed in patients refractory to paclitaxel in a prior course of therapy. CB-839 in combination with either everolimus or paclitaxel has been well tolerated to date, with adverse events that have been manageable and reversible.
Selected Second Quarter 2016 Financial Results

Research and development expenses were $7.8 million for the three months ended June 30, 2016, compared with $5.5 million for the same period in the prior year. The increase of $2.2 million was primarily attributed to increased development activities in Calithera’s arginase inhibitors program.

General and administrative expenses were $2.7 million for the three months ended June 30, 2016, compared with $2.3 million for the same period in the prior year. The increase of $0.3 million was primarily due to higher employment related expenses, including stock-based compensation expense.

Net loss for the three months ended June 30, 2016 was $10.4 million, or $0.55 per share.

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

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

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

Second Quarter 2016 and Recent Highlights include:

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

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

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

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

On August 9, 2016 Portola Pharmaceuticals Inc. (NASDAQ:PTLA) reported a corporate update and reported its financial results for the quarter ended June 30, 2016 (Press release, Portola Pharmaceuticals, AUG 9, 2016, View Source;p=RssLanding&cat=news&id=2194332 [SID:1234514564]).

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"We made significant progress in the second quarter to advance our goal of commercializing multiple medicines that could change current medical practices for treating patients with thrombotic disorders and hematological cancers," said Bill Lis, chief executive officer of Portola. "We expect more milestone momentum in the remainder of this year as we prepare for the anticipated U.S. commercial launch of AndexXaTM, which is currently on track to be our first marketed product. As a potential universal antidote for Factor Xa inhibitor anticoagulants, AndexXa may fulfill an unmet need for a specific reversal agent for Factor Xa inhibitor-treated patients who suffer life-threatening bleeding. During the quarter, we also presented and published full results of the Phase 3 APEX study of betrixaban. We believe these results support its potential approval and use as the first anticoagulant for extended-duration blood clot prevention in acute medically ill patients. We expect to submit the betrixaban NDA to the FDA later this year. Finally, we enrolled the first patients in our Phase 2a study of cerdulatinib, and anticipate presenting data on this promising compound at a medical meeting later this year."

Recent Achievements, Upcoming Events and Milestones

AndexXa (andexanet alfa) – a Factor Xa inhibitor antidote in development for patients treated with a Factor Xa inhibitor when reversal of anticoagulation is needed due to life-threatening bleeding or when urgent surgery is required; designated a Breakthrough Therapy and an Orphan Drug by the U.S. Food and Drug Administration (FDA)

Preparing for a U.S. commercial launch; PDUFA date of August 17, 2016, under an FDA Accelerated Approval pathway
Manufacturing of Generation 1 supply at CMC Biologics on track for commercial launch; plan to initiate validation campaign for Generation 2 long-term supply at Lonza
Enrollment remains on track for the Phase 3b/4 ANNEXA-4 study
ANNEXA-4 interim data to be presented in a late-breaking science session at ESC Congress on August 30
Plan to submit a Marketing Authorization Application (MAA) with the European Medicines Agency in the third quarter of 2016
Betrixaban – an oral Factor Xa inhibitor anticoagulant in development for the prevention of venous thromboembolism (VTE) in acute medically ill patients; designated Fast Track status by the FDA

Presented full results of the pivotal Phase 3 APEX study in a late-breaking clinical trial session at the ISTH SSC Meeting; simultaneously published online in The New England Journal of Medicine
Plan to submit a New Drug Application and an MAA later this year
Expect to present additional APEX data at upcoming medical conferences later this year
Cerdulatinib – an oral, dual Syk/JAK inhibitor in development to treat resistant or relapsed hematologic cancer patients

Presented new pharmacokinetic and pharmacodynamic outcomes data from the completed Phase 1 study at the ASCO (Free ASCO Whitepaper) Annual Meeting
Presented final results of the Phase 1 study at the EHA (Free EHA Whitepaper) Congress
Initiated enrollment in a Phase 2a study evaluating the safety and efficacy of cerdulatinib in patients with relapsed/refractory B-cell malignancies who have failed multiple therapies
Expect to present initial Phase 2a data at a medical meeting later this year
Second Quarter 2016 Financial Results
Collaboration revenue earned under Portola’s collaborations with Bristol-Myers Squibb Company and Pfizer, Bayer Pharma and Janssen Pharmaceuticals, Daiichi Sankyo and Lee’s Pharmaceutical was $4.2 million for the second quarter of 2016 compared with $2.4 million for the second quarter of 2015. The increase in revenue was primarily due to a collaboration and license agreement that Portola entered into with BMS/Pfizer to develop and commercialize andexanet alfa in Japan and a clinical collaboration agreement that Portola entered into with Bayer to include its Factor Xa inhibitor in the andexanet alfa development program in Japan.

Total operating expenses for the second quarter of 2016 were $61.9 million compared with $61.2 million for the same period in 2015. Total operating expenses for the second quarter of 2016 included $7.6 million in stock-based compensation expense compared with $4.8 million for the same period in 2015.

Research and development expenses were $44.8 million for the second quarter of 2016 compared with $52.3 million for the second quarter of 2015. The decrease in research and development expenses was primarily due to lower development costs following the completion of enrollment in the APEX study of betrixaban and lower development costs related to cerdulatinib due to the timing of activities. These decreased costs were partially offset by an increase in costs to advance AndexXa and support early research programs.

Selling, general and administrative expenses for the second quarter of 2016 were $17.0 million compared with $8.9 million for the same period in 2015 as the Company increased headcount to support its growth and increased commercial launch preparation activities for AndexXa.

For the second quarter of 2016, Portola reported a net loss of $57.3 million, or $1.02 net loss per share, compared with a net loss of $58.3 million, or $1.12 net loss per share, for the same period in 2015. Shares used to compute net loss per share attributable to common stockholders were approximately 56.4 million for the second quarter of 2016 compared with approximately 52.1 million for the same period in 2015.

As of June 30, 2016, cash, cash equivalents and investments totaled $353.6 million compared with cash, cash equivalents and investments of $460.2 million as of December 31, 2015.

On August 9, 2016 Genmab reported its Interim Report for First Half 2016 (Press release, Genmab, AUG 9, 2016, View Source [SID:1234514420]).

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Net Sales of DARZALEX (daratumumab) by Janssen for the first half of 2016 were USD 209 million, resulting in royalty income of USD 25 million (DKK 168 million)
2016 financial guidance improved
Announced European conditional marketing authorization of DARZALEX for heavily pre-treated or double-refractory multiple myeloma
Achieved USD 30 million milestone for first commercial sale of DARZALEX in Europe
Announced positive topline result in Phase III POLLUX study of daratumumab in relapsed or refractory multiple myeloma
Announced that U.S. Food and Drug Administration (FDA) granted priority review to sBLA for ofatumumab (Arzerra) in combination with fludarabine and cyclophosphamide (FC) in relapsed chronic lymphocytic leukemia (CLL)
Announced that the Committee for Medicinal Products for Human Use (CHMP) issued a negative opinion for Arzerra as maintenance therapy in relapsed CLL
Announced Phase III studies of ofatumumab in relapsing multiple sclerosis
"The two major highlights during the second quarter were the rapid European approval of DARZALEX and positive Phase III data from the POLLUX study. DARZALEX was successfully launched by our collaboration partner Janssen shortly after the approval, triggering a milestone payment of USD 30 million to Genmab. We were also very excited about the Phase III POLLUX study data which showed that daratumumab in combination with lenalidomide and dexamethasone led to a significant improvement in progression free survival in treatment of relapsed or refractory multiple myeloma," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.
Financial Performance First Half
Revenue was DKK 524 million in the first half of 2016 compared to DKK 281 million in the first half of 2015. The increase of DKK 243 million, or 86%, was mainly driven by higher royalty and milestone revenue under our daratumumab collaboration with Janssen.
Operating expenses were DKK 366 million in the first half of 2016 compared to DKK 244 million in the first half of 2015. The increase of DKK 122 million, or 50%, was due to the additional investment in our pipeline of products, including the advancement of tisotumab vedotin, HuMax-AXL-ADC, HexaBody-DR5/DR5, DuoBody-CD3xCD20, and our other pre-clinical programs.
Operating income was DKK 158 million in the first half of 2016 compared to DKK 212 million in the first half of 2015. The decrease of DKK 54 million, or 25%, was driven by the one-time reversal of the ofatumumab funding liability of DKK 176 million in 2015 combined with increased operating expenses in 2016, which were partly offset by higher revenue in 2016.
On June 30, 2016, Genmab had a cash position of DKK 3,762 million compared to DKK 3,493 million at December 31, 2015. This represented a net increase of DKK 269 million, which was driven primarily by income from operations and the proceeds from the exercise of warrants for DKK 82 million.
Business Progress Second Quarter

Daratumumab
May: Achieved a USD 30 million milestone triggered by the first commercial sale of DARZALEX in Europe.
May: Announced that the European Commission (EC) granted a conditional marketing authorization for DARZALEX for heavily pre-treated or double-refractory multiple myeloma. The approval followed a positive recommendation for DARZALEX from the CHMP of the European Medicines Agency (EMA) in April.

May: Announced that the Phase III POLLUX study (MMY3003) of daratumumab in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma met the primary endpoint at a pre-planned interim analysis (Hazard Ratio (HR) = 0.37 (95% CI 0.27-0.52), p<0.0001). Patients who received treatment with daratumumab in combination with lenalidomide and dexamethasone had a 63% reduction in risk of their disease progressing, compared to those who did not receive daratumumab. The median progression free survival (PFS) for patients treated with daratumumab in combination with lenalidomide and dexamethasone has not been reached, compared to an estimated median PFS of 18.4 months for patients who received lenalidomide and dexamethasone alone. Janssen will engage in a dialogue with health authorities about the potential for a regulatory submission for this indication.

April: Reported more detailed data from the Phase III CASTOR (MMY3004) study of daratumumab in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. The study met the primary endpoint of improving PFS; HR = 0.39, p<0.0001. The median PFS for patients treated with daratumumab has not been reached, compared to median PFS of 7.2 months for patients who did not receive daratumumab.

April: Announced that MorphoSys filed a complaint at the U.S. District Court of Delaware against Genmab and Janssen Biotech, Inc. (Janssen), for patent infringement under U.S. patent no. 8,263,746 based on activities relating to the manufacture, use and sale of DARZALEX in the United States. Genmab and Janssen disagree with the allegations made by MorphoSys in its complaint for patent infringement and intend to vigorously contest those allegations.

Ofatumumab
June: Announced that the CHMP of the EMA issued a negative opinion on the use of Arzerra as maintenance therapy for patients with relapsed CLL.

June: Announced that Novartis will start Phase III studies of the subcutaneous formulation of ofatumumab in relapsing multiple sclerosis (MS) with enrollment of patients to start in September 2016.

May: Announced that the U.S. FDA granted Priority Review to the supplemental Biologics License Application (sBLA) for the use of ofatumumab in combination with FC for the treatment of patients with relapsed CLL.

Subsequent Event
July: The U.S. FDA granted Breakthrough Therapy Designation for DARZALEX injection in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Breakthrough Therapy Designation is a program intended to expedite the development and review of drugs to treat serious or life-threatening diseases in cases where preliminary clinical evidence shows that the drug may provide substantial improvements over available therapy.

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

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

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

Corporate and Program Updates

Corporate

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

Under the terms of the amendments:

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

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

Gene Therapies

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

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

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

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

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

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

Milestones

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

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