On April 18, 2016 Celator Pharmaceuticals, Inc. (Nasdaq: CPXX) reported that an investigator-initiated clinical study at a university was reported as suspended on www.clinicaltrials.gov (Press release, Celator Pharmaceuticals, APR 18, 2016, View Source [SID:1234510991]). The study had previously been suspended due to institutional resource considerations at the university, unrelated to VYXEOS (CPX-351). The study is a phase 2 study of VYXEOS for the treatment of acute myeloid leukemia or higher risk myelodysplastic syndrome patients, who relapsed, or were refractory to, prior therapy with hypomethylating agents. Celator understands that the study has since been re-opened.

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!

"To eliminate any confusion, we want to inform investors, the medical community and study participants of these circumstances," said Scott Jackson, Chief Executive Officer of Celator Pharmaceuticals.

On April 18, 2016 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported preclinical data for each of its therapeutic candidates, CB-839 and CB-1158, at the 2016 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 16-20, 2016, in New Orleans, Louisiana (Press release, Calithera Biosciences, APR 18, 2016, View Source;p=RssLanding&cat=news&id=2157903 [SID:1234510990]). CB-839 is a potent, selective, orally bioavailable glutaminase inhibitor currently in phase I clinical trials. CB-1158 is a first-in-class immuno-oncology agent targeting arginase, a key immuno-suppressive enzyme that limits T-cell proliferation in a wide range of tumors.

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!

"Both CB-839 and CB-1158 have the distinction of targeting metabolic checkpoints which we believe through rational combinations, have the potential to be transformational in the treatment of cancer. For CB-839, we look forward to initiating a trial in combination with anti-PD-1 in the second quarter. We have made significant progress on our CB-1158 program, and remain on track to file an IND application in mid-2016," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera.

CB-839

Preclinical data will be presented in a poster titled, "Glutaminase inhibition with CB-839 enhances anti-tumor activity of PD-1 and PD-L1 antibodies by overcoming a metabolic checkpoint blocking T cell activation," by Matt Gross, Director of Pharmacology at Calithera Biosciences (Abstract #2329). Included in the presentation are the results of studies investigating the preclinical anti-tumor activity of CB-839 in combination with an anti-PD-L1 or an anti-PD-1 antibody. The combination of CB-839 and anti-PD-L1 or anti-PD-1 increased the number of tumor regressions seen in the CT-26 syngeneic colon carcinoma model. Synergistic effects with CB-839 and anti-PD-L1 were also observed in a B16 melanoma model. The mechanism of action of anti-PD-L1 combined with CB-839, two agents that affect metabolism in the tumor microenvironment, is being explored in further studies.

The following two abstracts were also presented at the meeting by Calithera’s collaborators:

Neurofibromatosis type 1 (NF1) status determines sensitivity of soft tissue sarcoma and melanoma cell lines to glutaminase inhibitors (Abstract #19). Presenter: Tahir Sheikh, PhD, Laboratory of Gary Schwartz, MD, Columbia University

GLS inhibitor CB-839 modulates cellular metabolism in AML and potently suppresses AML cell growth when combined with 5-azacitidine (Abstract #1004). Presenter: Tianyu Cai, PhD, Laboratory of Marina Konopleva, MD, University of Texas MD Anderson Cancer Center

CB-1158

Preclinical data was presented in a poster titled, "Immuno-oncology agent CB-1158 is a potent and selective arginase inhibitor and causes an immune mediated anti-tumor response," by Melissa Works, PhD, Scientist at Calithera Biosciences (Abstract #552). CB-1158, a highly selective, orally bioavailable, small molecule inhibitor of human arginase with nanomolar potency, demonstrated single agent efficacy in animal models. Inhibition of tumor growth was accompanied by an increase in the local concentration of arginine, and the induction of multiple pro-inflammatory changes in the tumor microenvironment. CB-1158 increased CD8+ T-cell infiltrates in a lung tumor model. The addition of CB-1158 to anti-CTLA-4 and anti-PD-1, significantly inhibited tumor growth and reduced metastases in a mouse model that was resistant to dual checkpoint inhibitor therapy. CB-1158 was well tolerated as a single agent and in combination with checkpoint inhibitors in animal studies.

Arginase is a critical immunosuppressive enzyme that inhibits T-cell proliferation and function. Arginase depletes arginine, a nutrient that is critical for the activation, growth and survival of two of the body’s cancer-fighting immune cells, known as cytotoxic T -cells and natural killer (NK) cells. Arginase inhibitors can restore arginine levels and reverse the immuno-suppressive effect of arginase-secreting myeloid-derived suppressor cells (MDSCs). MDSCs are present in many human tumors and are correlated with poor prognosis. CB-1158 has the potential for anti-tumor activity in a variety of malignancies, including non-small cell lung cancer, colorectal cancer, gastric cancer and bladder cancer, among other tumor types that are highly infiltrated with MDSCs.

On April 18, 2016 bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic and rare diseases and T cell-based immunotherapies for cancer, reported that data from clinical, preclinical, and research and manufacturing programs will be highlighted in ten presentations at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 19th Annual Meeting, taking place May 4-7, 2016 in Washington, D.C (Press release, bluebird bio, APR 18, 2016, View Source;p=RssLanding&cat=news&id=2158031 [SID:1234510988]).

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!

Two oral presentations given by bluebird’s academic collaborators will highlight previously presented data from bluebird bio’s ongoing gene therapy clinical trials. David Williams, M.D., chief of hematology/oncology at Boston Children’s Hospital will present interim data from the Starbeam Study of Lenti-D in cerebral adrenoleukodystrophy, and Marina Cavazzana, M.D., Ph.D., of Hospital Necker, University Paris Descartes, will present interim data from the HGB-205 study of LentiGlobin in severe sickle cell disease and transfusion-dependent β-thalassemia.

Eight additional presentations will be featured at the meeting, highlighting progress across the company’s preclinical, research and process development activities.

"As bluebird continues to build a differentiated T cell oncology franchise, we are excited to present three oncology abstracts that highlight our work on the next generation of technology for T cell-based immunotherapy – including methods of generating T cells with sustained anti-tumor activity, small-molecule regulated chimeric antigen receptors (CARs) and genome editing to generate improved CAR T cells," said Philip Gregory, D.Phil., chief scientific officer, bluebird bio. "From our hematopoietic stem cell programs, we will also share updates in five presentations covering improvements in scalable manufacturing, transduction efficiency and assay development – critical areas for making gene therapy available to more patients."

The abstracts are now available online on the ASGCT (Free ASGCT Whitepaper) Annual Meeting website.

Details of bluebird bio’s oral presentations are as follows:

Title: A Phase 2/3 Study of the Efficacy and Safety of Ex Vivo Gene Therapy With Lenti-D Lentiviral Vector for the Treatment of Cerebral Adrenoleukodystrophy
Abstract Number: 250
Session: Clinical Trials Spotlight Symposium
Date: Thursday, May 5, 2016
Time: 9:00 – 9:20 a.m.
Location: Thurgood Marshall North/East
Note: Data previously presented at the 2016 American Academy of Neurology Annual Meeting

Title: Small Molecule-regulated Antigen Recognition System for Inducible T Cell Targeting of Cancer Cells
Abstract Number: 277
Session: Cancer-Immunotherapy, Cancer Vaccines I
Date: Thursday, May 5, 2016
Time: 5:15 – 5:30 p.m.
Location: Washington 4

Title: Clinical Outcomes of Gene Therapy with BB305 Lentiviral Vector for Sickle Cell Disease and β-Thalassemia
Abstract Number: 279
Session: Hematologic & Immunologic Diseases I
Date: Thursday, May 5, 2016
Time: 4:00 – 4:15 p.m.
Location: Washington 5-6
Note: Data previously presented at the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting

Title: Towards the Clinical Application of BCMA CAR T cells: The Importance of Reduced Tonic Signaling and Methods to Enhance Memory T Cells
Abstract Number: 747
Session: Cancer-Immunotherapy, Cancer Vaccines III
Date: Saturday, May 7, 2016
Time: 10:45 – 11:00 a.m.
Location: Thurgood Marshall North

Details of bluebird bio’s poster presentations are as follows:

Title: PGE2 Increases Lentiviral Vector Transduction Efficiency of Human HSC
Abstract Number: 229
Session: Hematologic & Immunologic Diseases I
Date: Wednesday, May 4, 2016
Time: 5:30 p.m. – 7:30 p.m.
Location: Exhibit Hall C & B South

Title: Staurosporine Increases Lentiviral Transduction of Human CD34+ Cells
Abstract Number: 221
Session: Hematologic & Immunologic Diseases I
Date: Wednesday, May 4, 2016
Time: 5:30 p.m. – 7:30 p.m.
Location: Exhibit Hall C & B South

Title: Qualification of a p24 ELISA Assay for Quantitation of Total Lentiviral Vector Concentration
Abstract Number: 473
Session: Pharmacology/Toxicology Studies or Assay Development
Date: Thursday, May 5, 2016
Time: 6:00 p.m. – 8:00 p.m.
Location: Exhibit Hall C & B South

Title: Efficient Generation of CART Cells by Homology Directed Transgene Integration into the TCR-Alpha Locus
Abstract Number: 323
Session: Targeted Genome Editing II
Date: Thursday, May 5, 2016
Time: 6:00 p.m. – 8:00 p.m.
Location: Exhibit Hall C & B South

Title: Development of a Stable Producer Cell Line for Scalable Lentiviral Vector Production for Gene Therapy of Hemoglobinopathies
Abstract Number: 458
Session: Vector and Cell Engineering/Manufacturing I
Date: Thursday, May 5, 2016
Time: 6:00 p.m. – 8:00 p.m.
Location: Exhibit Hall C & B South

Title: Characterization of Nanoparticles in Lentiviral Vector Preparations
Abstract Number: 709
Session: Vector and Cell Engineering/Manufacturing II
Date: Friday, May 6, 2016
Time: 6:00 p.m. – 8:00 p.m.
Location: Exhibit Hall C & B South

On April 18, 2016 Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) reported that they have presented a poster on ARC-HIF2, its preclinical development program targeting HIF2-α for the treatment of renal cell carcinoma (RCC), at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 (AACR16), in New Orleans (Press release, Arrowhead Pharmaceuticals, APR 18, 2016, View Source [SID:1234510987]). ARC-HIF2 is Arrowhead’s first RNAi therapeutic program to target tissues outside the liver.

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!

The poster titled, "Novel HIF-2α targeted RNAi therapeutic for renal cell carcinoma" (abstract 2064), describes data from various stages of development of ARC-HIF2, including RNAi trigger selection, HIF2-α target validation, delivery and targeting ligand validation, and multiple RCC tumor models. These data show that important advancements are being made in this program and for Arrowhead’s Dynamic PolyconjugateTM (DPCTM) delivery platform generally, including the following key findings:

Proof-of-concept ligand dependent, functional delivery was demonstrated using the DPC targeted delivery platform
Silencing HIF2-α expression by RNA interference resulted in reduction of HIF-2α regulated genes
In two different RCC tumor bearing mouse models, ARC-HIF2 inhibited tumor growth and promoted tumor cell death and structural degeneration

Lenalidomide and bevacizumab have antitumor activity in various tumor types. We conducted a phase I study of this combination in patients with advanced cancer.
A "3 + 3" study design was used. Lenalidomide 10 or 20 mg (orally, days 1-21) and bevacizumab 5, 7.5, or 10 mg/kg, (intravenously, every 2 weeks) were given at four escalating dose levels, followed by an expansion phase at the highest maximum tolerated dose (MTD) (1 cycle = 4 weeks). Dose-limiting toxicity (DLT), MTD, adverse events, and clinical outcomes were assessed.
Thirty-one patients were enrolled (median age, 60 years; men, 52 %). The most common tumor types were colorectal carcinoma (n = 11) and melanoma (n = 5). Overall, 105 cycles (median, 2) were administered. No DLTs were observed. The maximum tested dose (level 4) was used in the expansion phase. The most common toxicities were fatigue (n = 7, 23 %) and skin rash (n = 4, 13 %). One patient developed a transient ischemic attack (3.2 %); prophylactic anticoagulation became mandatory in the subsequent 17 treated patients. Of 31 patients, 27 were evaluable for response. Stable disease (SD) was noted in 10 (37 %) patients, including five patients with SD for ≥6 months (tumor types: clear cell sarcoma, germ cell tumor, colorectal carcinoma, and melanoma). The median progression-free survival and overall survival were 2.8 and 5.5 months, respectively.
The combination of lenalidomide with bevacizumab in patients with advanced solid tumors was safe. Prolonged stable disease was noted in selected tumor types, warranting further clinical evaluation.

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!