On April 19, 2016 Kite Pharma, Inc. (Nasdaq:KITE) ("Kite") reported updated clinical results from the phase 1 portion of Kite’s ZUMA-1 trial of its lead product candidate, KTE-C19, in patients with chemorefractory, aggressive non-Hodgkin lymphoma (NHL) (Press release, Kite Pharma, APR 19, 2016, View Source [SID:1234511121]). KTE-C19 is an investigational therapy in which a patient’s T cells are genetically modified to express a chimeric antigen receptor (CAR) that is designed to target the antigen CD19, a protein expressed on the cell surface of B cell lymphomas and leukemias.

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David Chang, M.D., Ph.D., Kite’s Executive Vice President, Research and Development, and Chief Medical Officer, commented, "Today’s report affirms the early safety and efficacy profile of KTE-C19 in chemorefractory, aggressive NHL. We are encouraged by the ongoing complete remissions in patients with significant unmet need for new therapies. We remain on track to provide interim data from the pivotal phase 2 portion of the study later this year and to submit the KTE-C19 registration filing to the U.S. Food and Drug Administration (FDA) by the end of 2016."

"The data reported today are important because refractory DLBCL is incurable. Median survival for these patients is short and there is no standard therapy," noted Ronald Levy, M.D., Robert K. Summy and Helen K. Summy Professor of Medicine and Director of the Lymphoma Program at Stanford University School of Medicine and Associate Director of Translational Science for the Stanford Cancer Institute. "A rate of complete response and durability of response in the ranges of those reported today would be of profound clinical importance if replicated in the phase 2 portion of the ZUMA-1 study. Adoptive transfer of engineered T cells has the potential to become standard of care for patients with refractory NHL in the near future."

Updated Phase 1 Results from ZUMA-1: A Phase 1-2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-C19 (Anti-CD19 CAR T Cells) in Subjects with Refractory Aggressive Non-Hodgkin Lymphoma (NHL)

Session: Early Clinical Trials Evaluating Cell-based, Checkpoint Inhibitors, and Novel Immunotherapeutics; Abstract Number: CT135; Presenter: Armin Ghobadi, M.D., Washington University, St. Louis, MO

Phase 1 of ZUMA-1 treated a total of 7 patients with chemorefractory, diffuse large B cell lymphoma (DLBCL)
KTE-C19 related adverse events consisted predominantly of cytokine release syndrome (CRS) and neurotoxicity which were generally reversible
Grade 3 or higher CRS was observed in 14% and neurotoxicity in 57%; all were reversible except in one patient with dose-limiting toxicity
KTE-C19 achieved rapid and durable responses in patients with chemorefractory disease (objective response rate 71%, complete response rate 57%)
Ongoing complete response (CR) observed in 3 of 7 patients. One ongoing CR as of 9-month study follow-up and 2 ongoing CRs as of 6-month study follow-up.
In addition, two posters on KTE-C19 engineered cell manufacturing and characteristics were presented at AACR (Free AACR Whitepaper) on April 18, 2016.

Manufacturing and Characterization of KTE-C19 in a Multicenter Trial of Patients with Refractory Aggressive Non-Hodgkin Lymphoma (NHL) (ZUMA-1)

Session: Adoptive Cell Therapy; Abstract Number: 2308; Presenter: John Rossi, M.S., Kite Pharma

The optimized GMP-manufacturing process generated anti-CD19 CAR T cells rapidly and without the need for pre-selection of a defined composition of T cells
Biologically active anti-CD19 CAR T cells were manufactured for all patients enrolled in the multicenter phase 1 ZUMA-1 trial.
Comparative Evaluation of Peripheral Blood T Cells and Resultant Engineered Anti-CD19 CAR T Cell Products from Relapsed/Refractory Non-Hodgkin’s Lymphoma (NHL) Patients

Session: Adoptive Cell Therapy; Abstract Number: 2305; Presenter: Timothy J. Langer, Kite Pharma

CAR T cells were successfully manufactured for all patients enrolled in the study at the National Cancer Institute, Surgery Branch
CAR T cell products were composed of both CD4+ and CD8+ T cells with a less differentiated phenotype than the starting leukapheresis products
CAR T cells were polyfunctional and produced a wide range of immune homeostatic, modulating and effector cytokines/chemokines in response to antigen-positive target cells.

On April 20, 2016 CTI BioPharma Corp. (CTI) (NASDAQ and MTA:CTIC) reported findings from an investigator-sponsored preclinical study indicating that pacritinib, an inhibitor of JAK2, FLT3, IRAK1 and CSF1R, may be effective in reducing survival of myelofibrosis and acute myeloid leukemia (AML) repopulating cells (Press release, CTI BioPharma, APR 19, 2016, View Source;p=RssLanding&cat=news&id=2158522 [SID:1234511114]). Further, this study also demonstrated that the combination of pacritinib at low nanomolar concentrations with dasatinib may eliminate self-renewing leukemia stem cells in blast crisis of chronic myeloid leukemia (CML) with minimal toxicity toward normal progenitors. In myeloid leukemias, these leukemic stem cells can evade initial treatment and hide within the bone marrow microenvironment, develop resistance to current therapies, self-renew and eventually cause relapse.

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These findings were presented by Larissa Balaian, Ph.D. from the Moores Cancer Center, University of California San Diego in a poster presentation (abstract #3338) titled: "Pacritinib reduces human myeloid leukemia stem cell maintenance in a defined niche," during the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting held April 16-20 in New Orleans, LA.

"The potential ability for pacritinib to eradicate therapy resistant leukemia stem cells in relapse AML as a single-agent, as well as eliminate self-renewing stem cells in CML, when used in combination with standard of care therapy, demonstrates that targeting niche-dependent signaling with pacritinib could represent a new approach to treating patients with refractory acute myeloid leukemia and blast crisis of CML," said Dr. Balaian.

Additional data being presented at the meeting include:

A poster (abstract #2602) titled: "The nonclinical toxicology profile of pacritinib, a JAK2/FLT3 inhibitor with no dose-limiting clinical myelosuppression." In this poster, CTI BioPharma researchers presented data from studies of pacrinitib in nonclinical models that were evaluated in comparison to publicly available information for the currently approved JAK inhibitors. The nonclinical toxicology profile findings showed that pacritinib is unique for its mild myelosuppressive effects in the nonclinical studies. Of interest, only pacritinib was not associated with increased opportunistic infections in the long-term toxicology studies.

A poster (abstract #1609) titled: "Investigation of absorption, metabolism, excretion, and mass balance of [14C]-pacritinib in healthy subjects: a phase 1 study." In this poster, CTI BioPharma researchers investigated clearance pathways, excretion, pharmacokinetics and recovery of pacritinib’s major metabolites in healthy volunteers. Intact pacritinib was minimally excreted in urine and feces while most radioactivity was recovered as metabolites in feces, suggesting extensive biliary clearance and hepatic metabolism of pacritinib. No dose adjustments are anticipated to be required for patients with renal impairment.

The foregoing summaries of such reported findings and posters are not complete and are qualified in their entirety by reference to the referenced posters. These and other poster presentations are available in the publication section of the CTI BioPharma website at ctibiopharma.com.

About Pacritinib

Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. In August 2014, pacritinib was granted Fast Track designation by the FDA for the treatment of intermediate and high risk myelofibrosis including, but not limited to, patients with disease-related thrombocytopenia (low platelet counts); patients experiencing treatment-emergent thrombocytopenia on other JAK2 inhibitor therapy; or patients who are intolerant of, or whose symptoms are not well controlled (sub-optimally managed) on other JAK2 therapy. Clinical studies for pacritinib are currently subject to a full clinical hold issued by the U.S. Food and Drug Administration in February 2016. The Company is in the process of responding to the full clinical hold by working through the FDA’s recommendations prior to requesting a meeting with them. In March 2016, the FDA expressed interest in allowing patients who were receiving benefit from pacritinib treatment at the time the clinical hold was imposed to submit requests to the FDA to resume pacritinib treatment under a Single Patient IND (SPI) program on a case-by-case basis. The Company is working with investigators in submitting SPI requests to the FDA. Separately, the FDA has informed clinical investigators that emergency requests may be submitted to the FDA for individual patient Expanded Access to pacritinib. Expanded Access, sometimes called "compassionate use," is the use outside of a clinical trial of an investigational medical product. Pacritinib does not have regulatory approval and is not commercially available.

CTI BioPharma and Baxalta Incorporated are parties to a worldwide license agreement to develop and commercialize pacritinib. CTI BioPharma and Baxalta will jointly commercialize pacritinib in the U.S., while Baxalta has exclusive commercialization rights for all indications outside the U.S.

On April 19, 2016 Peloton Therapeutics, Inc., a drug discovery and development company focused on advancing first-in-class, small molecule cancer therapies targeting unexploited molecular vulnerabilities, reported preclinical data on its lead investigational candidate, PT2385, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans, LA (Press release, Peloton Therapeutics, APR 19, 2016, View Source [SID:1234511099]). PT2385 is the first clinical stage antagonist of hypoxia inducible factor-2α (HIF-2α), a transcription factor implicated in the development and progression of renal and other cancers.

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"PT2385, a Novel HIF-2α Antagonist, Combines with Checkpoint Inhibitor Antibodies to Inhibit Tumor Growth in Preclinical Models by Modulating Myeloid Cells and Enhancing T Cell Infiltration"
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In addition to its direct role in transcription regulation of growth-promoting genes in renal tumors, HIF-2α has been proposed to affect the tumor microenvironment. In a poster titled "PT2385, a Novel HIF-2α Antagonist, Combines with Checkpoint Inhibitor Antibodies to Inhibit Tumor Growth in Preclinical Models by Modulating Myeloid Cells and Enhancing T Cell Infiltration," the combination of PT2385 with antibodies to immune checkpoint control molecules (PD-1, PD-L1, and CTLA4) yielded additive or synergistic efficacy in preclinical tumor models. HIF-2α is not detected in the mouse tumor cells, but is expressed in the stroma. Tumor growth inhibition by these combination regimens was accompanied by modulation of a variety of immune markers such as infiltrating T-cells, macrophage and myeloid-derived suppressor cell populations in the tumors. The combination of PT2385 and immune checkpoint inhibitors is planned for evaluation in clinical trials.

"PT2385 has now been shown to affect the tumor microenvironment, even for tumors that do not express HIF-2α. This potentially broadens the applicability of PT2385 to a larger variety of tumor types, including melanoma and lung cancers, which have been shown to have a strong immunological component," said John Josey, Ph.D., Peloton’s Chief Executive Officer.

About PT2385

PT2385 is a first-in-class small molecule inhibitor of hypoxia-inducible factor-2α (HIF-2α), a transcription factor implicated in the development and progression of kidney cancer. It is currently being investigated in a Phase 1 clinical trial for the treatment of advanced or metastatic clear cell renal cell carcinoma (ccRCC). Loss of the von Hippel-Lindau tumor suppressor (VHL) is the key oncogenic event in up to 95% of patients with ccRCC. With the loss of the VHL protein (pVHL), the transcription factor HIF-2α accumulates and drives the unbalanced expression of numerous gene products. Preclinical data indicate that orally bioavailable PT2385 disrupts HIF-2α activity in ccRCC and thereby blocks the expression of multiple tumorigenic factors responsible for unrestrained cancer cell growth and proliferation, tumor angiogenesis, and suppression of anti-tumor immune responses characteristic of ccRCC.

About Renal Cell Cancer

The American Cancer Society estimates that more than 62,000 new cases of kidney cancer will be diagnosed and more than 14,000 people will die from this disease this year. The National Cancer Institute reports that the prognosis for any treated renal cell cancer patient with progressing, recurring, or relapsing disease is poor, regardless of cell type or stage.

On April 19, 2016 X4 Pharmaceuticals, a clinical stage biotechnology company developing novel CXCR4 inhibitor drugs to improve immune cell trafficking and increase the ability for T-cells to track and destroy cancer, reported the presentation of preclinical data for X4P-001, its lead drug candidate in development for the treatment of clear cell renal cell carcinoma (ccRCC) at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, held April 16-20 in New Orleans . The data demonstrated synergistic anti-tumor effects of CXCR4 inhibition in combination with axitinib, a tyrosine kinase inhibitor(Press release, X4 Pharmaceuticals, APR 19, 2016, View Source [SID:1234511098]) approved for use as a targeted therapy for renal cell carcinoma (RCC), in animal models of RCC. The data also showed that X4P-001 suppressed the increased MDSC tumor infiltration caused by axitinib treatment.

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"We are excited to share these early findings with clinicians who know the challenges of treating patients with RCC," said James W. Mier, M.D., Associate Professor of Medicine at the Beth Israel Deaconess Medical Center and senior author of the poster presentation. "We believe there are opportunities to improve outcomes beyond the available targeted therapies, such as kinase inhibitors, which can be hindered by resistance. By inhibiting CXCR4, X4P-001 offers an approach to target a key mechanism of resistance and address unmet needs for cancer patients."

Acquired resistance of tumors to certain anti-cancer therapies has been associated with increased trafficking of key immune cells, such as T-regulatory cells and myeloid derived suppressor cells (MDSCs), in and around the tumor. Trafficking of these cells is controlled by chemokines such as CXCL-12 and its receptor, CXCR4. CXCR4 inhibition blocks the infiltration of these cells and neutralizes the immunosuppressive microenvironment, enabling the cancer-fighting T-cells to reach the tumor.

"These data confirm our belief that CXCR4 inhibition can play an important therapeutic role in immune cell trafficking with the potential to improve treatment outcomes for patients," said Robert Arbeit, M.D., Sr. Vice President of Clinical Development and Translational Research for X4 Pharmaceuticals and an author of the poster presentation. "The data also provide a strong rationale for our upcoming clinical study evaluating the combination of X4P-001 and axitinib in patients with advanced ccRCC."

The poster entitled "Regulation of MDSC trafficking and function in RCC by CXCR4 in the presence of a VEGF-R antagonist" will be presented on Tuesday, April 19th (Abstract number: 4155; 1-5pm). The reported findings include:

X4P-001 in combination with axitinib demonstrated synergistic anti-tumor activity in two renal xenograft models; tumor regression was observed
X4P-001 suppressed the increased MDSC tumor infiltration caused by axitinib treatment
About X4P-001

X4P-001 is an oral, small molecule inhibitor of CXCR4, or C-X-C receptor type 4, the receptor for the chemokine CXCL12 (also known as stromal derived factor-1, or SDF-1). Recent studies demonstrate that CXCR4/CXCL12 is a primary receptor-ligand pair that cancer cells and surrounding stromal cells use to block normal immune function and promote angiogenesis through the trafficking of T-effector and T-regulatory cells, as well as myeloid derived suppressor cells (MDSCs), in the tumor microenvironment.1, 2 Pre-clinical studies have demonstrated X4P-001 activity alone and in combination with approved cancer therapies including tyrosine kinase inhibitors and checkpoint inhibitors resulting in an increased tumor-specific immune response and significant delays in tumor growth. X4P-001 was previously tested in over 70 subjects in four prior clinical trials in healthy volunteers and HIV-infected patients and was shown to be safe and well tolerated.

About Renal Cell Carcinoma

Kidney cancer is among the ten most common cancers in both men and women with more than 60,000 new diagnoses each year in the United States.3 Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, and advanced ccRCC accounts for approximately 20% of the patient population. Therapies for advanced ccRCC include immunotherapies, mammalian target of rapaymcin (mTOR) kinase inhibitors, and angiogenesis inhibitors, such as vascular endothelial growth factor (VEGF) inhibitors.4 There continue to be unmet medical needs with advanced ccRCC because durable responses remain a serious clinical challenge for patients with advanced disease.

On April 19, 2016 Euclises Pharmaceuticals, Inc., a biopharmaceutical company focused on the discovery and development of novel COX-2 inhibitors for the treatment of cancer, reported that its Late-Breaking Abstract has been accepted for presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans on April 19, 2016 (Press release, Euclises, APR 19, 2016, View Source [SID:1234511093]).

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Entitled, "Anti-tumor effects of ECP-1014 in combination with erlotinib in HT-29 xenograft murine colon carcinoma model," the presentation will report the results of key preclinical experiments using Euclises’ COX-2 inhibitor candidate, ECP-1014. The study, conducted in collaboration with Guangzhou Institute of BioMedicine and Health, builds upon recent research demonstrating a role for overactive COX-2 in maintaining an immunosuppressive microenvironment for a variety of tumors, including colorectal and non-small cell lung cancers.

"The epidermal growth factor (EGFR) inhibitor erlotinib is the current standard of care for advanced colorectal cancer," said Dr. Bobby W. Sandage, Jr., Ph.D., CEO of Euclises. "In this preclinical study, we demonstrate a substantial additional benefit in tumor suppression from combining erlotinib with our third-generation COX-2 inhibitor."

"The research to be presented at AACR (Free AACR Whitepaper) strongly validates Euclises’ approach," added Rick Ryan, Ph.D., chairman of Euclises’ board. "These results comprise an important step towards the clinical translation and commercialization of effective COX-2 inhibitors for colorectal cancer patients."

Dr. Sandage will present the research on Tuesday morning, April 19, in Section 11 of the Late-Breaking Research: Experimental and Molecular Therapeutics 3 poster session.