On November 9, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new immunotherapies, reported financial results for the third quarter ended September 30, 2016, and provided an update on the Company’s recent activities (Press release, Ziopharm, NOV 9, 2016, View Source [SID1234516793]).

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"ZIOPHARM continues to advance a broad portfolio of immuno-oncology programs, including our gene therapy platform, and our chimeric antigen receptor, T-cell receptor, and natural killer adoptive cell-based therapies," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM Oncology. "These programs ensure that ZIOPHARM participates across the spectrum of cell-based therapies, with technologies spanning non-viral and viral T-cell gene transfer, cytokines, and controlled expression of biologics after infusion. What is particularly exciting about our progress is that most of these technologies will be in clinical testing in 2017, moving us toward realization of these transformative ideas including individualized therapies targeting neoantigens and continued shortening of cell manufacturing to infuse T cells after gene transfer. These ideas will allow us to leapfrog current technologies and address some of the most important challenges in cancer treatment today."

Francois Lebel, M.D., Chief Medical Officer of ZIOPHARM Oncology added: "In the near-term, we look forward to presenting updated results at the Society for Neuro-Oncology Annual Meeting next week from our Phase 1, multi-center study of Ad-RTS-hIL-12 + veledimex in patients with brain cancer. To date, intracranial administration of Ad-RTS-hIL-12 + veledimex has demonstrated a favorable safety profile, with a survival benefit compared to historical control that provides a strong rational for moving to a phase 2/3 trial."

Corporate and Program Updates

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.

Updated Clinical Data from Phase 1 Study of Ad-RTS-hIL-12 + Veledimex in High-Grade Gliomas to be presented at Society of Neuro-Oncology (SNO) Annual Meeting. ZIOPHARM will present updated data from its Phase 1, multi-center study of Ad-RTS-hIL-12 + veledimex in patients with recurrent high-grade gliomas at the upcoming 21st Annual SNO Scientific Meeting being held November 17-20, 2016 in Scottsdale, Arizona. Subjects with relapsed high-grade gliomas undergoing re-resection were intra-tumorally injected once with Ad-RTS-hIL-12 followed by oral doses of veledimex to activate production (transcription) of IL-12. The Company previously showed that the measurement of veledimex in serum and in the brain tumor correlates with production of IL-12 and activation of IFN-gamma, demonstrating not only that this oral drug can be used to start and stop cytokine production, but the generation of IL-12 is proportional to the dosing of veledimex. These data will be updated for recipients taking veledimex at 20 mg/day, 30 mg/day and 40 mg/day. The Company previously reported 6-month overall survival in the study at 100%. Twelve month survival data will be reported at SNO.

The presentation, entitled "Phase 1 study of intra-tumoral viral delivery of Ad-RTS-hIL-12 + oral veledimex is well tolerated and suggests survival benefit in recurrent high grade glioma" will be presented on Friday, November 18, 2016. The Company will host a conference call to discuss these data on Thursday, November 17, 2016 at 8:00 am ET.

Upcoming Pre-Clinical Data of Ad-RTS-mIL-12 + Veledimex as Therapy for Pediatric Glioma to be presented at Society of Neuro-Oncology Annual Meeting. ZIOPHARM will present data on the ability of the RTS gene switch to control mouse IL-12 production to treat glioma in the pontine region. These data are based on a single injection of Ad-RTS-mIL-12 and oral administration of veledimex and serve as a basis to advance our viral therapy in 2017 for the investigational treatment of pediatric brain tumors, including diffuse intrinsic pontine glioma.

Presented Data Demonstrating Activation of Anti-Tumor Immune Response Using Ad-RTS-hIL-12 in Patients with Advanced Breast Cancer. In October, 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 show 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 intra-tumoral influx of CD8+ T cells and IFN-gamma were present six 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 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 (CAR-T only).

Results from Four Studies of Adoptive Cell-based Therapeutic Programs to be Presented at the 2016 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. In November, ZIOPHARM announced that four abstracts highlighting data from the Company’s adoptive cell-based therapeutic programs have been accepted for presentation at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. The meeting will be 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 quickly produced with the Sleeping Beauty system and that this non-viral approach to gene therapy can be harnessed to generate CAR and TCR expressing effector cells.

Announced Plans for Phase I Clinical Trial with CD33 CAR-T Cell Therapy; Supporting Preclinical Results to be Presented at ASH (Free ASH Whitepaper) 58th Annual Meeting & Exposition. In July, following a review by the Recombinant DNA Advisory Committee, ZIOPHARM announced plans for a Phase I adoptive cellular therapy clinical trial utilizing autologous T cells transduced with lentivirus to express a CD33-specific CAR in patients with relapsed or refractory acute myeloid leukemia (AML). Preclinical studies, including in vitro data, demonstrated that lentiviral-transduced CAR-T cells targeting CD33 exhibited specific killing activity for CD33+ AML cells and a proof-of-concept study utilizing an in vivo mouse model for AML, 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. The Company recently announced that associated data will be presented at the 58th ASH (Free ASH Whitepaper) Annual Meeting.

Announced Publication of Data from 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 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.

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 Sleeping Beauty-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 to target minimal residual disease after autologous and allogeneic HSCT, the approach may improve tolerability by avoiding cytokine release syndrome.
Milestones

Intra-tumoral IL-12 RheoSwitch programs:
Clinical data from Phase 1 of Ad-RTS-hIL-12 + veledimex for GBM to be presented at SNO 2016
Initiate Phase 2/3 clinical trial for GBM in 2017
Clinical update presented at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting for Phase 1 study of GBM
Pre-clinical data presented at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 2016 for combining with immune checkpoint inhibitor
Initiate combination study of Ad-RTS-hIL-12 + veledimex with checkpoint inhibitor therapy (PD-1) during the first half of 2017
Pre-clinical data for Ad-RTS-mIL-12 + veledimex to support pediatric brain tumors to be presented at SNO 2016
Initiate Phase 1 study in the treatment of brain tumors in children during the first half of 2017
Update on Phase 1/2 study in Breast Cancer with standard of care presented at the 2016 ASCO (Free ASCO Whitepaper) meeting
Clinical update presented at the 2016 ESMO (Free ESMO Whitepaper) meeting for Phase 1/2 Breast Cancer study
CAR-T programs:
Continuation of CD19 CAR+ T clinical study in 2016
Initiate a CD33 specific CAR+ T clinical study for relapsed or refractory AML in the first half of 2017
Preclinical data on CD33 to be presented at ASH (Free ASH Whitepaper) 2016
Preclinical data presented at ASGCT (Free ASGCT Whitepaper) 2016 and ASH (Free ASH Whitepaper) 2016 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 in 2016
TCR-T programs
Initiate TCR-modified T-cell preclinical studies in 2016
Preclinical data to be presented at ASH (Free ASH Whitepaper) 2016
NK cell programs
Initiate a Phase 1 study of off-the-shelf NK cells for AML in 2017
GvHD programs
Initiate preclinical studies in 2016
SNO 21st Annual Scientific Meeting Conference Call and Slide Webcast

ZIOPHARM will host a conference call and webcast slide presentation Thursday, November 17, 2016, at 8:00 am ET to discuss updated data from the Company’s Phase 1 study of Ad-RTS-hIL-12 + veledimex in high-grade glioma. The call can be accessed by dialing (844) 309-0618 (U.S. and Canada) or (661) 378-9465 (international). The passcode for the conference call is 11110235. To access the slides and live audio webcast, or the subsequent archived recording, visit the "Investors & Media" section of the ZIOPHARM website at www.ziopharm.com. The webcast will be recorded and available for replay on the Company’s website for two (2) weeks.

Third-Quarter 2016 Financial Results

Net loss applicable to common shareholders for the third quarter of 2016 was $14.5 million, or $(0.11) per share, compared to a net loss of $18.2 million, or $(0.14) per share, for the third quarter of 2015. The decrease in net loss for the three months ended September 30, 2016 is primarily due to a one-time charge of $10.0 million for in process research and development with Intrexon for GvHD programs incurred in September 2015. This decrease was offset by a $2.0 million increase in expenses related to the gene therapy and cell therapy programs, decreased revenue of $0.3 million, increased general and administrative costs of $0.4 million and income attributable to preferred stockholders of $3.6 million.

Research and development expenses were $9.0 million for the third quarter of 2016 compared to $17.0 million for the third quarter of 2015. The decrease in research and development expenses for the three months ended September 30, 2016 is primarily due to a one-time charge of $10.0 million for in process research and development with Intrexon for GvHD programs incurred in September 2015. This decrease was offset by a $2.0 million increase in expenses related to the gene therapy and cell therapy programs.

General and administrative expenses were $3.5 million for the third quarter of 2016 compared to $3.1 million for the third quarter of 2015. The increase for the three months ended September 30, 2016 was primarily due to increased employee related costs.
The Company ended the quarter with cash and cash equivalents of approximately $94.7 million, which the Company believes will be sufficient to fund its currently planned activities into the fourth quarter of 2017.

On November 9, 2016 Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a clinical stage biopharmaceutical company focused on discovering and developing novel cellular immunotherapies for cancers and orphan inherited blood disorders, reported financial results for the third quarter ended September 30, 2016 (Press release, Bellicum Pharmaceuticals, NOV 9, 2016, View Source;p=RssLanding&cat=news&id=2221084 [SID1234516507]).

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"We are pleased with recent progress, as the pediatric trial of our lead product candidate BPX-501 continues to enroll at a strong pace. We are preparing for a comprehensive data update of this program at ASH (Free ASH Whitepaper) 2016, and are working with regulators in the European Union and the U.S. to finalize registration pathways for BPX-501 and rimiducid," said Tom Farrell, President and Chief Executive Officer of Bellicum. "In the coming weeks, we expect to initiate the Phase 1 clinical trials of our BPX-601 GoCAR-T and BPX-701 TCR product candidates. We continue to build upon our differentiated technology platform and believe its potential to address the safety and efficacy issues of adoptive cell therapies will provide competitive advantage."

Third Quarter and Recent Highlights

Bellicum continued to advance its BPX-501 lead program and will provide a clinical update at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December. The BP-004 pediatric clinical trials in the U.S. and Europe have enrolled over 100 patients with orphan inherited blood disorders and blood cancers. Three abstracts, including an oral presentation focused on pediatric patients with immune deficiencies, were accepted for presentation at ASH (Free ASH Whitepaper) 2016. Bellicum will also host an investor and analyst luncheon on Monday, December 5, 2016. A full schedule can be found in the News & Events section of the Company’s website.
The Company is completing preparations for the start of Phase 1 clinical trials for BPX-601 and BPX-701. BPX-601 GoCAR-T contains Bellicum’s proprietary iMC activation switch and is designed to treat solid tumors expressing prostate stem cell antigen, with the initial clinical trial in non-resectable pancreatic cancer to be conducted at Baylor Sammons Cancer Center. BPX-701 incorporates the CaspaCIDe safety switch and is designed to target malignant cells expressing the preferentially-expressed antigen in melanoma (PRAME), with the initial clinical trial in Refractory or Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes, to be conducted at Oregon Health and Science University and Leiden University Medical Center.
Bellicum expanded its collaboration with Ospedale Pediatrico Bambino Gesù (OPBG) to develop novel CAR T and TCR cell therapies engineered with the CaspaCIDe safety switch. Under the agreement, the organizations agreed to jointly develop CARs and other cell therapies discovered by OPBG, with a clinical trial for a CaspaCIDe-enabled CD19 CAR T cell therapeutic anticipated to begin in 2017.
Bellicum continued to innovate and build upon its differentiated cellular control technologies; will present data highlighting preclinical results from the application of its GoCAR-T and GoTCR technologies in two poster presentations at ASH (Free ASH Whitepaper) 2016.
Third Quarter and Nine Months Ended September 30, 2016 Financial Results

Bellicum reported a net loss of $17.7 million for the third quarter of 2016 and $49.3 million for the nine months ended September 30, 2016, compared to a net loss of $13.4 million and $31.7 million for the comparable periods in 2015. The results included non-cash, stock-based compensation charges of $3.1 million and $9.2 million for the third quarter and nine months ended September 30, 2016 and $2.3 million and $5.9 million for the comparable periods in 2015.

As of September 30, 2016, cash and investments totaled $129.1 million, which included $5.0 million borrowed in September under the agreement with Hercules Capital. Bellicum now expects that it will end 2016 with at least $100 million in cash, cash equivalents and investments, and continues to expect that current cash resources will be sufficient to meet operating requirements through 2017.

Research and development expenses were $13.3 million and $36.5 million for the three and nine months ended September 30, 2016, respectively, compared to $9.8 million and $23.5 million during the comparable periods in 2015. The higher expenses in the 2016 periods were primarily due to an increase in manufacturing and clinical expenses as a result of increased patient enrollment in the BPX-501 clinical trials, increased expenses for the IND-enabling activities for product candidates BPX-601 and BPX-701, and increased personnel and infrastructure costs.

General and administrative expenses were $4.3 million and $12.7 million for the three and nine months ended September 30, 2016, respectively, compared to $3.9 million and $8.9 million during the comparable periods in 2015. The higher expenses in the 2016 periods were primarily due to the growth of the organization, including an increase in costs related to personnel, higher facility costs and increased legal, accounting and travel related expenses.

On November 9, 2016 Kite Pharma, Inc. (Nasdaq: KITE), a clinical-stage biopharmaceutical company focused on developing engineered autologous cell therapy (eACT) products for the treatment of cancer, reported financial results for the third quarter 2016 and recent business highlights (Press release, Kite Pharma, NOV 9, 2016, View Source [SID1234516569]).

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Kite also announced that it has met with the U.S. Food and Drug Administration (FDA) to discuss the company’s plans to submit the Biologics License Application (BLA) for KTE-C19. Kite currently intends to file for the broader label of aggressive non-Hodgkin lymphoma, which includes chemorefractory diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL). The BLA submission will be based on the primary analysis of the ZUMA-1 pivotal trial. Kite plans to initiate the rolling submission of the BLA for accelerated approval of KTE-C19 by the end of December 2016 with a targeted completion by the end of the first quarter 2017 and a potential approval and commercial launch of KTE-C19 in 2017.

"We are making history with each step we take toward bringing engineered T-cell therapy to patients. We are very pleased with the outcome from our productive discussions with the FDA and their willingness to partner with us to advance this innovative therapy," said Arie Belldegrun, M.D., FACS, Chairman, President, and Chief Executive Officer. "We will focus on initiating and finalizing the submission based on the FDA feedback and look ahead to the potential approval of KTE-C19 in 2017."

Third Quarter 2016 and Recent Highlights

Reported positive topline results from the pre-planned interim analysis in the KTE-C19 ZUMA-1 pivotal trial in patients with aggressive non-Hodgkin lymphoma, which includes chemorefractory DLBCL (n=51), and TFL and PMBCL (n=11). The study met the pre-specified response endpoint with an objective response rate of 76 percent in DLBCL (Cohort 1). Thirty nine percent of patients maintained complete response at three-month follow up. Grade 3 or higher cytokine release syndrome (CRS) and neurological toxicity was observed in 18 percent and 34 percent of patients, respectively. Treatment emergent Grade 5 events were observed in 3 percent of patients.
Reported ongoing complete responses in three of seven patients at the 12-month follow-up in the Phase 1 portion of the ZUMA-1 study of KTE-C19 in chemorefractory DLBCL at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper).
Announced planned oral and poster presentations of KTE-C19 clinical and manufacturing data at the 2016 annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper). The presentations will include additional clinical data from the interim analysis of the ZUMA-1 pivotal trial as well as clinical and manufacturing data from the ZUMA-3 and ZUMA-4 clinical studies in adult acute lymphoblastic leukemia (ALL) and pediatric ALL, respectively. Preliminary results from a clinical study of a fully human anti-CD19 chimeric antigen receptor (CAR) conducted at the National Cancer Institute will also be shared in an oral presentation.
Initiated patient enrollment in a Phase 1b/2 combination study of KTE-C19 and atezolizumab, Genentech’s anti-PD-L1 monoclonal antibody. This is the first combination study of an anti-CD19 engineered CAR T-cell and a checkpoint inhibitor.
At the Kite investor day on October 18, 2016:
Detailed manufacturing and commercial preparations for potential KTE-C19 commercial launch;
Outlined KTE-C19 expansion studies with the potential to deliver six additional indications in B-cell malignancies;
Announced the expansion of Kite’s T-cell receptor (TCR) and CAR T development pipeline with four new INDs planned in the 2016-2018 timeframe; and
Presented "T cells 2.0" next-generation cell programming technologies to realize the full potential of engineered T-cell therapy.
Licensed multiple neoantigen directed TCR product candidates to treat solid tumors expressing mutated KRAS antigens from the National Institutes of Health.
Third Quarter 2016 Financial Results

Revenue was $7.3 million for the third quarter of 2016.
Research and development expenses were $57.3 million for the third quarter of 2016, and includes $8.9 million of non-cash stock-based compensation expense.
General and administrative expenses were $25.0 million for the third quarter of 2016, and includes $10.3 million of non-cash stock-based compensation expense.
Net loss attributable to common stockholders was $73.9 million, or $1.49 per share, for the third quarter of 2016.
Non-GAAP net loss attributable to common stockholders for the third quarter of 2016 was $54.7 million, or $1.10 per share, which excludes non-cash stock-based compensation expense of $19.3 million.
Cash burn for the third quarter was $54.0 million. It is expected that the company’s cash, cash equivalents, and marketable securities of $477.1 million as of September 30, 2016 will be sufficient to fund its current operations, including planned clinical development programs, through the first half of 2018.
About Kite Pharma

Kite Pharma, Inc., is a clinical-stage biopharmaceutical company engaged in the development of novel cancer immunotherapy products, with a primary focus on engineered autologous cell therapy (eACT) designed to restore the immune system’s ability to recognize and eradicate tumors. Kite is based in Santa Monica, CA. For more information on Kite Pharma, please visit www.kitepharma.com. Sign up to follow @KitePharma on Twitter at View Source

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as "predicts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "expected," "plans," "intends," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the ability and timing of obtaining KTE-C19 data, initiating and completing a submission of the BLA for KTE-C19 with the FDA, obtaining regulatory approval based on the studies of KTE-C19, commercially launching KTE-C19, researching and developing additional product candidates, expectations regarding the clinical effectiveness and safety of KTE-C19 and the sufficiency of Kite’s cash, cash equivalents and marketable securities. Various factors may cause differences between Kite’s expectations and actual results as discussed in greater detail in Kite’s filings with the Securities and Exchange Commission, including without limitation in its Form 10-Q for the quarter ended September 30, 2016. Any forward-looking statements that are made in this press release speak only as of the date of this press release. Kite assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

On November 9, 2016 BioSpecifics Technologies Corp. (NASDAQ: BSTC), a biopharmaceutical company that originated and continues to develop collagenase based-therapies with a first in class collagenase-based product collagenase clostridium histolyticum, or CCH, marketed as XIAFLEX in the U.S. and Xiapex in Europe reported its financial results for the third quarter ended September 30, 2016 and provided a corporate update (Press release, BioSpecifics Technologies, NOV 9, 2016, View Source [SID1234516537]).

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"BioSpecifics concentrates on developing XIAFLEX for medically necessary indications, and we look forward to the initiation of our Phase 1 clinical trial for the treatment of uterine fibroids by the end of this year," said Thomas L. Wegman, President of BioSpecifics. "Our partner Endo continues to see XIAFLEX as a core U.S. branded product and growth driver going forward. Cellulite is their main focus for non-marketed indications and they plan to announce Phase 2b data upon the completion of that trial. Endo is conducting a full commercial assessment and analysis of the R&D pipeline which will determine the clinical trial timelines moving forward."

Third Quarter 2016 Financial Results
BioSpecifics reported net income of $3.1 million for the third quarter ended September 30, 2016, or $0.43 per basic share and $0.42 per share on a fully diluted basis, compared to net income of $2.9 million, or $0.42 per basic share and $0.39 per share on a fully diluted basis, for the same period in 2015.

Total revenue for the third quarter ended September 30, 2016 was $6.9 million, compared to $6.3 million for the same period in 2015. The increase in total revenue was due to increased royalties received and licensing fees related to the exercise of an opt-in right by Endo International plc (Endo) for the human lipoma indication.

Royalty and mark-up on cost of goods sold (COGS) revenues recognized under BioSpecifics’ agreement with Endo for the third quarter ended September 30, 2016 were $6.1 million, compared to $5.3 million for the same period in 2015, an increase of $0.8 million, or 15 percent. This increase in royalties and the mark-up on cost of goods sold was primarily due to the increase in sales of XIAFLEX for the treatment of Dupuytren’s contracture and Peyronie’s disease.

Licensing revenue consists of licensing fees, sublicensing fees and milestones. BioSpecifics recognized licensing fees related to the exercise of an opt-in right by Endo for the human lipoma indication of $750,000 for the three months ended September 30, 2016 as compared to zero in the corresponding 2015 period. In addition, the Company recognized certain licensing fees related to the cash payments received under the agreement with Endo in prior years and amortized them over the expected development period. For each of the three month periods ended September 30, 2016 and 2015, the Company recognized licensing revenue related to the development of injectable collagenase of approximately $12,000.

Milestone revenue recognized for the three months ended September 30, 2016 was zero as compared to $1.0 million for the corresponding 2015 period. The $1.0 million milestone revenue recognized in the corresponding 2015 period related to the first commercial sale of XIAFLEX by Asahi Kasei Pharma Corporation for the treatment of Dupuytren’s contracture in Japan.
Research and development (R&D) expenses for each of the third quarters ended September 30, 2016 and 2015 were $0.3 million.
General and administrative expenses for the third quarter ended September 30, 2016 were $1.8 million, compared to $1.7 million for the same period in 2015.

Provision for income taxes for the third quarter ended September 30, 2016 were $1.8 million, compared to $1.5 million for the same period in 2015.

As of September 30, 2016, BioSpecifics had cash and cash equivalents and investments of $51.3 million, compared to $37.1 million as of December 31, 2015.

XIAFLEX U.S. Commercial Highlights
On November 8, 2016, Endo reported U.S. commercial highlights for XIAFLEX for the third quarter of 2016 (Endo’s third quarter 2016 financials are reported in BioSpecifics’ fourth quarter 2016 financials). For the third quarter of 2016, U.S. net sales were $47.7 million, an increase of 19 percent compared to the third quarter of 2015.

CCH Pipeline Updates and Anticipated Upcoming Milestones
BioSpecifics manages the development of collagenase clostridium histolyticum (CCH) for uterine fibroids, and initiates the development of CCH in new potential indications, not licensed by Endo. In addition to Dupuytren’s contracture and Peyronie’s disease, Endo’s licensed rights include human and canine lipoma, adhesive capsulitis, cellulite, lateral hip fat and plantar fibromatosis.

BioSpecifics expects to initiate a Phase 1 clinical trial of CCH in uterine fibroids in the fourth quarter of 2016.
Top-line data for the Phase 2b clinical trial of CCH for cellulite will be reported upon the completion of that trial.
Endo has announced that they are conducting a full commercial assessment and analysis for the R&D pipeline to determine the clinical trial timelines moving forward.

BioSpecifics will present a company update at the upcoming Stifel 2016 Healthcare Conference on Tuesday, November 15, 2016 at 8:00 AM E.T. in New York, NY.

On November 9, 2016 Nektar Therapeutics (Nasdaq: NKTR) reported that new Phase 1 clinical data for Nektar’s lead immuno-oncology agent, NKTR-214, were presented at the SITC (Free SITC Whitepaper) 2016 Annual Meeting (Press release, Nektar Therapeutics, NOV 9, 2016, View Source [SID1234516469]). NKTR-214 is an investigational immuno-stimulatory therapy designed to expand specific cancer-fighting T cells and Natural Killer (NK) cell abundance directly in the tumor micro-environment and increase expression of PD-1 on these immune cells. The results were presented by Adi Diab, MD, Assistant Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in an oral presentation during today’s session entitled "New Cancer Immunotherapy Agents in Development."

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Interim results presented were from the ongoing Phase 1 dose-escalation, first-in-human, trial of single-agent NKTR-214 in patients with locally advanced or metastatic solid tumors, including melanoma, renal cell carcinoma (RCC), bladder, colorectal and other solid tumor cancers. A total of 20 patients were treated in four separate every three-week (q3w) dose cohorts (ranging from 0.003 mg/kg q3w to 0.012 mg/kg q3w) with 18 of these patients evaluable for anti-tumor activity. Based upon encouraging anti-tumor activity and tolerability of NKTR-214 observed at the 0.006 mg/kg q3w dose, an every two week (q2w) cohort of the 0.006 mg/kg dose began enrolling in September 2016 with an additional 5 patients enrolled to this cohort, all of which are continuing on therapy.

"NKTR-214 resulted in robust activation of the immune system and encouraging anti-tumor activity, including a partial response observed in a patient who continues to be treated with NKTR-214," said Dr. Ivan Gergel, Senior Vice President, Drug Development & Chief Medical Officer of Nektar. "NKTR-214 was also well tolerated in patients when administered as an every two-week or every three-week outpatient therapy. We are very encouraged by the clinical profile emerging for NKTR-214 and the totality of the data from this ongoing single-agent trial of NKTR-214."

Preliminary encouraging evidence of anti-tumor activity has been observed to date in the ongoing study:

12/18 (67%) evaluable patients had stable disease at the initial 8 week scan
7/18 (39%) evaluable patients had radiographic reductions in tumor size per RECIST 1.1 on NKTR-214
One patient with metastatic melanoma (prior treatment with ipilimumab and a BRAF inhibitor) has received 13 cycles of treatment (0.003 mg/kg q3w) with stable disease and continues on therapy with NKTR-214
In the 18 evaluable patients, a total of 5 patients with metastatic RCC who had progressed on 1 prior tyrosine kinase inhibitor (TKI) were treated with NKTR-214 at the 0.006 mg/kg q3w dose level:
1/5 (20%) of these RCC patients had a uPR per RECIST 1.1 (at 16 week scan) and treatment with NKTR-214 is ongoing
2/5 of these RCC patients had additional tumor reductions of 6% and 10% per RECIST 1.1 while on NKTR-214
NKTR-214 also demonstrated a favorable safety and tolerability profile with convenient, outpatient q2w or q3w administration in 25 patients evaluable for safety to-date:

No immune-related AEs were observed (e.g. colitis, dermatitis, hepatitis pneumonitis, adrenal insufficiency)
No deaths or grade 4 AEs related to NKTR-214
No capillary leak syndrome was observed at any dose
One patient experienced a dose-limiting toxicity (DLT) of hypotension/syncope at 0.012 mg/kg q3w and continued on treatment at 0.006 mg/kg q3w
3/25 patients experienced grade 3 hypotension, which was rapidly reversed with fluid administration and all patients continued on treatment with NKTR-214
Most common grade 1-2 adverse events were fatigue, pruritis, cough, decreased appetite, pyrexia, and hypotension
Immune pheno-typing was conducted and biomarkers of immune activation were measured in patients with evaluable tumor biopsies and blood samples. Treatment with NKTR-214 produced a robust elevation in immune cell frequency and activation, including:

Increase in total and newly proliferating (Ki67+) CD4+ T cells, CD8+ T cells, and Natural Killer (NK) cells in 9/9 patients with blood samples evaluated in the trial to-date, with increases of up to 30-fold observed
Increase in frequency of PD-1+ T cell subsets of up to 9-fold in the blood
Increase in CD8+ T cells and Natural Killer (NK) cells of up to 10-fold in the tumor micro-environment in patients with evaluable tumor biopsies (pre-dose and post-dose at week 3), with minimal intratumoral changes to T regulatory cells
Increase in expression of cell-surface PD-1 on T cell subsets of up to 2-fold in the tumor micro-environment
Induction of an activation gene signature in the tumor micro-environment, including increases of 5-fold or greater in expression of interferon γ, perforin and granzyme B genes
Changes in T cell repertoire (TCR), which is a measure of T cell clonality, in the tumor micro-environment
"We are extremely pleased with the single-agent activity of NKTR-214 and the potential of NKTR-214 to transform the immuno-oncology landscape," said Howard W. Robin, President & CEO of Nektar Therapeutics. "As the first I-O agent to demonstrate that it can increase tumor-infiltrating lymphocytes (TILs) and increase PD-1 expression on immune cells in humans, NKTR-214 complements not only existing checkpoint inhibitors, such as nivolumab, but also other I-O mechanisms in development."

In September 2016, Nektar entered into a clinical collaboration with Bristol-Myers Squibb to evaluate NKTR-214 as a potential combination treatment regimen with Bristol-Myers Squibb’s Opdivo (nivolumab) in five tumor types and seven potential indications. The Phase 1/2 clinical trials will enroll up to 260 patients and will evaluate the potential for the combination of Opdivo (nivolumab) and NKTR-214 to show improved and sustained efficacy and tolerability above the current standard of care in melanoma, kidney, triple-negative breast cancer, bladder and non-small cell lung cancer patients. The initial dose-escalation trial is underway with Opdivo (nivolumab) and NKTR-214.

NKTR-214 is an experimental therapy designed to stimulate cancer-killing immune cells in the body by targeting CD122 specific receptors found on the surface of these immune cells, known as CD8+ effector T cells and Natural Killer (NK) cells. In preclinical studies, treatment with NKTR-214 resulted in a rapid expansion of these cells and mobilization into the tumor micro-environment.1 NKTR-214 has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines. A Phase 1/2 clinical study is ongoing to evaluate single-agent NKTR-214 in cancer patients.