On June 06, 2016 Atara Biotherapeutics, Inc. (Nasdaq:ATRA), a biopharmaceutical company focused on developing meaningful therapies for patients with severe and life threatening diseases that have been underserved by scientific innovation, reported that its collaborating investigators at Memorial Sloan Kettering Cancer Center (MSK) reported clinical results for Atara’s allogeneic Epstein-Barr Virus Cytotoxic T-Lymphocyte (EBV-CTL) product candidate (Press release, Atara Biotherapeutics, JUN 6, 2016, View Source [SID:1234513088]). Data were presented from an on-going Phase 2 clinical trial, which enrolled a heterogeneous group of EBV associated malignancies including NPC and post-transplant lymphoproliferative disorders, at an oral presentation at the ASCO (Free ASCO Whitepaper) 2016 Annual Meeting. This data included safety and efficacy of EBV-CTL in the treatment of 14 patients with recurrent metastatic nasopharyngeal carcinoma (NPC). EBV-associated NPC accounts for approximately 6,000 cases annually in the US and EU combined and approximately 80,000 cases worldwide. Historical median survival rates range from five to eleven months for patients with metastatic disease.

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Dr. Susan Prockop, M.D., and colleagues reported the following data:

A 21% objective response rate in NPC patients, including one complete response, and two partial responses.
11 of the 14 NPC patients were alive with median 18-month follow-up.
EBV-CTLs expanded after administration to immunocompetent NPC patients without concomitant lymphodepleting chemotherapy.
Of the 126 patients enrolled across all indications, there were two grade 4 and seven grade 3 possibly related serious adverse events.
"We are pleased that this study has demonstrated the potential therapeutic benefit of an allogeneic therapy for patients with solid tumors," commented Chris Haqq M.D., Ph.D., Chief Medical Officer of Atara Bio. "We look forward to developing this product candidate as both a single agent and in combination with other therapies in NPC and other indications. In addition, we will be commencing our two upcoming pivotal trials in patients with rituximab refractory EBV Post-Transplant Lymphoproliferative Disorder (EBV-PTLD) after solid organ transplant (SOT) and hematopoietic stem cell transplant (HCT) later this year."

About EBV-CTL

T-cells are a critical component of the body’s immune system and can be harnessed to counteract viral infections and some cancers. By focusing the T-cells on specific proteins involved in cancers and infections, the power of the immune system can be employed to combat these diseases. Atara Bio’s EBV-CTL utilizes a technology in which T cells are collected from the blood of third-party donors and then exposed to EBV antigens. The resulting activated T cells are then expanded, characterized, and stored for future therapeutic use in an appropriate partially human leukocyte antigen, or HLA, matched patient, providing an "off-the-shelf", allogeneic, cellular therapeutic option for patients. EBV-CTLs are designed to find cancer cells expressing EBV and kill them. Phase 2 clinical results from trials conducted at MSK have been reported in multiple peer-reviewed forums. Atara Bio plans to commence two pivotal clinical trials of EBV-CTL for rituximab-refractory EBV Post-Transplant Lymphoproliferative Disorder (EBV-PTLD) following hematopoietic cell transplant (HCT), as well as solid organ transplant (SOT), towards the end of 2016.

On June 6, 2016 Heat Biologics, Inc. (Nasdaq:HTBX), an immuno-oncology company developing novel therapies that activate a patient’s immune system against cancer, reported that it presented a poster entitled "Broadening response rates to PD-1 therapy in advanced lung adenocarcinoma: Viagenpumatucel-L (HS-110) in combination with nivolumab in the ongoing DURGA trial" (Abstract #TPS9102) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Heat Biologics, JUN 6, 2016, View Source [SID:1234513020]). The poster was accepted within the Trials in Progress category and as such, reviewed the design and endpoints for the ongoing Phase 1b study of HS-110 in combination with anti-PD-1 checkpoint inhibitor, nivolumab, for the treatment of non-small cell lung cancer (NSCLC). Eight patients are currently enrolled.

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Recent study findings, not presented at ASCO (Free ASCO Whitepaper), suggest that the addition of HS-110 to nivolumab does not significantly alter the nivolumab safety profile to-date. In addition, case studies of three trial patients (one non-responder and two responders) have been characterized. While all three patients showed a decrease in immune cell PD-1 expression, which is consistent with nivolumab’s mechanism of action, both responders also showed a decrease in immunosuppressor cells, as well as increases in activated effector T cells in the peripheral blood. Furthermore, the two responders showed an increase in CD8+ T cells in biopsy samples after treatment with the HS-110/nivolumab combination. ELISPOT analysis of patient blood samples demonstrated induction of antigen-specific immune responses to both total vaccine antigen and individual shared tumor antigens in both responding patients, but not the clinical non-responder. Finally, these responding patients also had low-grade injection site reactions in addition to rash, which the non-responder did not, suggesting their clinical and immune responses may be attributed to the HS-110 vaccine.

These data are included in the updated corporate presentation which is available on Heat’s corporate website at www.heatbio.com. As previously announced, full topline data on all eight patients is expected to be presented in the fourth quarter, including all primary and secondary endpoints.

"In these early data, we observed a correlation between patients’ clinical outcomes and their immunological responses, which we believe indicates that tumor response may be a result of increased immunological activity," said Melissa Price, Ph.D., Heat’s VP of Product Development. "Additionally, the two responders qualitatively converted from low to high tumor infiltrating lymphocytes (TILS), which is consistent with data previously reported from our bladder cancer study. This finding supports our hypothesis that patients with low levels of TILs, who typically do not respond well to single-agent checkpoint inhibitors, may respond to a combination with our ImPACT vaccine."

On June 6, 2016 Bio-Path Holdings, Inc., (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer and autoimmune drugs, reported that data from the Phase I study of BP1001 (Liposomal Grb2 Antisense) as a treatment for acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) and the safety segment of the Phase II combination therapy of BP1001 and low-dose cytarabine (LDAC) as a treatment for advanced AML were presented by Dr. Maro Ohanian, Assistant Professor at the University of Texas MD Anderson Cancer Center, during a poster presentation at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in a poster titled, "Phase I Study of BP1001 (Liposomal Grb2 Antisense) in Patients with Hematologic Malignancies (Filing, 8-K, Bio-Path Holdings, JUN 6, 2016, View Source [SID:1234513067])."

"While a small dataset, we are still very excited by these robust data showing that five of six evaluable patients demonstrated activity, especially for these refractory and resistant patients. We are also encouraged by the lack of toxicity as our Phase II efficacy segment will be in de novo fragile patients, for whom the drug side effect profile is particularly important," stated Peter H. Neilson, Chief Executive Officer of Bio-Path Holdings. "In addition, we were very pleased with BP1001’s pharmacokinetics, particularly its 30-hour half-life. The final analysis of these data, along with the demonstrated reductions in bone marrow blasts, suggests that 60 mg/m2 is the appropriate dose going forward."

The Phase I study of BP1001 comprised Cohorts 1 through 6 of the dose-finding monotherapy at doses up to 90 mg/m2 in refractory/relapsed leukemia patients. The safety segment of the Phase II study evaluated the toxicity of BP1001 in Cohorts 7 and 8 in doses of 60 mg/m2 and 90 mg/m2, combined with LDAC chemotherapy in refractory/relapsed patients with advanced AML.

Data from the safety segment of the Phase II combination therapy of BP1001 and LDAC showed no dose limiting toxicities. Of the six evaluable patients, four patients completed more than two cycles of treatment, three patients achieved complete remission and two patients achieved partial remission. BP1001 levels decreased bi-exponentially in plasma and the pharmacokinetics of BP1001 demonstrated a half-life at 60 mg/m2 of 30 hours.

As previously reported, data from the Phase I study demonstrated that BP1001 was well tolerated in refractory/relapsed leukemia patients at doses up to 90 mg/m2 with no drug related adverse events. It also decreased target Grb2 expression by an average of 50% in the 21 evaluable patients on BP1001 monotherapy. Of these patients in the Phase I study, seven patients completed more than two cycles of treatment, 10 patients had more than a 50% reduction in peripheral or bone marrow blasts and six patients had transient decline in blasts (n=3) and/or stable disease (n=3), with two patients experiencing transient improvement in leukemia cutis lesions.

About BP1001

BP1001 is a neutral-charge, liposome-incorporated antisense drug substance designed to inhibit Grb2 protein expression. The protein Grb2 is essential to cancer cell signaling because it is utilized by oncogenic tyrosine kinases to induce cancer progression. Suppressing the function or expression of Grb2 should interrupt its vital signaling function and have a therapeutic application in cancer.

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On June 6, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) reported new data informed by comprehensive genomic profiling (CGP) using FoundationOne Heme demonstrating the diverse and distinct genomic landscape of acute myeloid leukemia (AML) in children versus adults (Press release, Foundation Medicine, JUN 6, 2016, View Source [SID:1234513044]). Foundation Medicine conducted comprehensive genomic profiling of tumor samples from 558 patients with AML, including 104 pediatric and 454 adult patients, and identified age-associated genomic alterations in a subset of patients that could influence and personalize treatment and inform the selection of approved targeted therapies or access to novel therapies available in clinical trials.

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In collaboration with the Children’s Oncology Group AML Disease Committee, a clinical trials group supported by the National Cancer Institute (NCI), cases with known cytogenetic and molecular aberrations underwent CGP with FoundationOne Heme. The results demonstrated 100% concordance between FoundationOne Heme and conventional biomarker analysis across the various cytogenetic hallmarks of AML, including changes to inv(16) and t(8;21), as well as DNA mutations including FLT3/ITD, NPM1, and CEBPA. Importantly, FoundationOne Heme identified multiple additional mutations, such as structural alterations and copy number variations, including alterations that have therapeutic significance. These results suggest the potential clinical benefit of FoundationOne Heme in AML as compared to single gene or hotspot-based clinical testing, and underscore FoundationOne Heme’s unique capability to enhance risk stratification and identify molecular targets for therapeutic intervention.

The data showed a clear age-associated profile with distinct genomic make-up in pediatric versus adult patients. Novel transcripts such as NSD1-NUP98, KDM5A-NUP98 and CBFA2T3-GLIS2 were identified in 21 patients, 16 of whom were children. Fusions were markedly enriched in pediatric patients, while mutations in epigenetic modifiers occurred almost exclusively in adults, including DNMT3A (22 percent), IDH1/2 (21 percent) and TET2 (15 percent). Mutations in ASXL1 (21 percent), SRSF2 (14 percent) and BCOR (9 percent) were also prevalent in adults, but rare in children (0-6%).

"Like many blood cancers, AML is characterized by recurring genomic alterations that often provide information about disease progression and outcome, making comprehensive genomic profiling incredibly important to informing diagnosis and therapeutic decisions," said Vincent Miller, M.D., chief medical officer, Foundation Medicine. "Recognizing that there are fundamental differences between the genomic alterations in pediatric versus adult AML patients will ultimately arm clinicians with additional information to better understand each patient’s disease and guide therapeutic regimens best suited to a particular age group. We believe these data further support integration of FoundationOne Heme into oncology clinical practice."

The findings were presented in a poster titled, "Distinct Age-Associated Genomic Profiles Identified in Acute Myeloid Leukemia (AML) Using FoundationOne Heme," by Katherine Tarlock, M.D., pediatric hematology-oncology faculty at Seattle Children’s Hospital, and a member of the Children’s Oncology Group AML Committee. The data were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2016 taking place June 3-7 in Chicago.

FoundationOne Heme, an integrated DNA/RNA platform using targeted hybrid-capture next-generation sequencing, is a comprehensive genomic profile developed to detect all types of genomic alterations with therapeutic relevance, including single-nucleotide substitutions, insertions and deletions, copy number alterations and rearrangements, which are not fully evaluated using conventional diagnostic assays. FoundationOne Heme simultaneously detects all classes of genomic alterations in the DNA of 405 cancer-related genes and employs RNA sequencing across 265 genes to capture a broad range of gene fusions, a type of alteration that is a common driver of hematologic cancers. It is designed to provide physicians with clinically actionable information to guide treatment options for patients based on the genomic profile of their cancer.

About Foundation Medicine

Foundation Medicine (NASDAQ:FMI) is a molecular information company dedicated to a transformation in cancer care in which treatment is informed by a deep understanding of the genomic changes that contribute to each patient’s unique cancer. The company offers a full suite of comprehensive genomic profiling assays to identify the molecular alterations in a patient’s cancer and match them with relevant targeted therapies, immunotherapies and clinical trials. Foundation Medicine’s molecular information platform aims to improve day-to-day care for patients by serving the needs of clinicians, academic researchers and drug developers to help advance the science of molecular medicine in cancer. For more information, please visit View Source or follow Foundation Medicine on Twitter (@FoundationATCG).

On June 6, 2016 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that updated data from the ongoing Phase 1 trial of FPA144 was featured today in an oral presentation during the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Press release, Five Prime Therapeutics, JUN 6, 2016, View Source [SID:1234513068]). Dr. Jeeyun Lee from the Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, gave the presentation, titled Antitumor Activity and Safety of FPA144, an ADCC-enhanced, FGFR2b Isoform-Selective Monoclonal Antibody, in Patients with FGFR2b+ Gastric Cancer and Advanced Solid Tumors (Abstract 2502). The presentation is available on the Five Prime website: View Source

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Part 1 of the trial evaluated escalating doses of FPA144 as a single agent in 27 patients, 19 with advanced solid tumors in Part 1a and 8 with advanced gastric cancer in Part 1b, including 6 with FGFR2b-overexpressing tumors. Enrollment is underway in Part 2 of the trial, evaluating the safety, pharmacokinetics (PK) and efficacy (objective response rate and duration of response) of biweekly 15 mg/kg infusions of FPA144 across multiple cohorts: gastric cancer patients whose tumors have high, moderate and low levels of FGFR2b protein overexpression and gastric cancer patients whose tumors do not have FGFR2b protein overexpression. Five Prime plans to expand the scope of this trial further by the end of 2016 to include a cohort of patients with a tumor type (other than gastric) that overexpresses FGFR2b.

Safety findings presented in this update are consistent with initial data presented during the ASCO (Free ASCO Whitepaper) Gastrointestinal Symposium in January 2016. Data across 40 patients in the full safety population of this trial (all gastric and solid tumor patients receiving any portion of at least one dose of FPA144) suggest that FPA144 has an acceptable safety profile in doses up to 15 mg/kg:

No dose-limiting toxicities (DLTs); maximum-tolerated dose (MTD) was not reached
No treatment-related serious adverse events (SAEs); 17 reported SAEs across 9 patients
No treatment-related adverse events (AEs) resulting in treatment discontinuation
No treatment-related hyperphosphatemia or retinal toxicity (differentiated from small molecule kinase inhibitors targeting FGF receptor tyrosine kinases)
The most common treatment-related AEs ( > 5%) were all grades 1 or 2: fatigue (22.5%), nausea (20%) and vomiting (12.5%)
One transient treatment-related Grade 3 AE of decreased neutrophil count
Comparable safety between gastric cancer patients and full safety population

FPA144 monotherapy demonstrated early evidence of anti-tumor efficacy in the 9 gastric cancer patients with FGFR2b protein overexpression (6 from Part 1b of the trial; 3 from Part 2) that were available for analysis as of the April 1, 2016 data cutoff. These patients were heavily pre-treated, having received between 1 and 6 prior therapies with a median of 2 prior therapies. The activity observed includes:

3 confirmed partial responses (PRs) out of 9 gastric cancer patients treated (33%) (one of these three PRs confirmed after the April 1, 2016 data cutoff)
7 of 9 gastric cancer patients with disease control (3 PRs + 4 stable disease), disease control rate (DCR) = 77%
12-week progression-free survival (PFS) in 6 of 9 gastric cancer patients (67%)
Median duration of treatment of 112 days (range 42-182 days), with 2 of 9 gastric cancer patients still on study
1 complete response (CR) in a patient with metastatic bladder cancer
In addition to the 3 PRs noted above, there was an additional unconfirmed PR in the 10th gastric cancer patient with FGFR2b protein overexpression (the 4th patient in the 15 mg/kg cohort). This 10th patient’s scan became available after the data cutoff of April 1, 2016, and the patient remains on treatment.

"The data suggest that FPA144 is an active drug that warrants further clinical development. The initial single-agent efficacy and safety data seen during the dose escalation portion of the study is encouraging," said Dr. Charles Fuchs, Director of the Center for Gastrointestinal Cancer, Dana Farber Cancer Institute. "Patients with advanced gastric cancer have a significant unmet medical need, and the literature suggests that those with tumors that overexpress FGFR2b have an even worse prognosis. New treatments options are needed for these patients."

"We are pleased with the data from this ongoing trial," said Lewis T. "Rusty" Williams, M.D., Ph.D., president and chief executive officer of Five Prime. "The data we have observed in this trial suggest that FPA144 has an acceptable safety profile and can be dosed biweekly. FPA144 monotherapy also showed evidence of clinical activity in the first nine FGFR2b+ gastric cancer patients that were available for analysis, with a disease control rate of 77% and a 12-week progression free survival of 67%. We were also pleased to see an unexpected complete response in a patient with bladder cancer in part 1a of the trial. We look forward to continuing the study and to further exploring FPA144 in gastric cancer with varying levels of FGFR2b protein overexpression as well as additional FGFR2b+ tumors."

About the FPA144 Phase 1 Trial
Parts 1a and 1b of the Phase 1 study evaluated the safety and pharmacokinetics (PK) of escalating doses of FPA144 in 27 patients with solid tumors, including gastric cancer patients. Enrollment is underway in Part 2 of the trial, evaluating the safety, PK and efficacy (response rate and duration of response) of biweekly 15 mg/kg infusions of FPA144 across multiple cohorts: gastric cancer patients with high, moderate and low levels of FGFR2b protein overexpression, FGFR2b- gastric cancer patients, and FGFR2b+ patients with other tumor types. Up to 30 patients may be enrolled in each tumor setting. Tumors will be biopsied pre- and post-treatment in order to determine levels of FGFR2b protein overexpression and FGFR2 gene amplification, and to detect PD-L1 and immune infiltrate changes within the tumor. Testing for FGFR2b protein overexpression is being conducted centrally, using a proprietary immunohistochemistry assay.

About FPA144
FPA144 is an anti-FGF receptor 2b (FGFR2b) humanized monoclonal antibody in clinical development as a targeted immune therapy for tumors that over-express FGFR2b, as determined by a proprietary immunohistochemistry (IHC) diagnostic assay. FGFR2 gene amplification (as identified by FISH) is found in a number of tumors, including in approximately 5% of gastric cancer patients, and is associated with poor prognosis.

FPA144 is designed to block tumor growth through two distinct mechanisms. First, it has been engineered to drive immune-based killing of tumor cells by antibody-dependent cell-mediated cytotoxicity (ADCC) and the recruitment of natural killer (NK) cells and T cells. Second, it binds specifically to FGFR2b and prevents the binding of certain fibroblast growth factors that promote tumor growth. When combined with PD-1 blockade, FPA144 has shown an additive effect in tumor growth inhibition in preclinical models. Five Prime retains global development and commercialization rights to FPA144.