On June 6, 2016 NewLink Genetics Corporation (NASDAQ:NLNK), a biopharmaceutical company focused on bringing novel immuno-oncology medicines to patients, reported the presentation of data from two studies on two posters highlighting the combination therapeutic potential of indoximod, an indoleamine-(2,3)-dioxygenase (IDO) pathway inhibitor, at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Press release, NewLink Genetics, JUN 6, 2016, View Source [SID:1234513051]).

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Both posters are available online here.

Updates on Phase 1b/2 trial of the IDO inhibitor indoximod plus checkpoint inhibitors for the treatment of unresectable stage 3 or 4 melanoma

The trial design allows for the combination of indoximod with either ipilimumab or one of the PD-1 checkpoint inhibitors pembrolizumab or nivolumab. The combination of indoximod with other checkpoint inhibitors has been well tolerated thus far with no increase in toxicity noted in this Phase 1b/2 study. Overall, 40 patients had been enrolled in the combined Phase 1b/2 study long enough to have response data available at the time of data cut off. The poster data presented at ASCO (Free ASCO Whitepaper) were based on data via site reported RECIST criteria available from 28 subjects, the objective response rate, comprised of complete response plus partial response, for these patients is 36 percent (10 of 28) with three complete responses. Interestingly, the subset of 15 patients who received indoximod in combination with pembrolizumab had an objective response rate of 53 percent (8 of 15) with two complete responses (13 percent). The trial continues to enroll, with 55 patients currently enrolled in Phase 2.

"Although early, the 53 percent response rate in patients with metastatic melanoma treated with indoximod and pembrolizumab appears promising," said Zakharia Yousef, M.D., Assistant Professor of Medicine, Division of Hematology, Oncology and Blood & Marrow Transplantation at the University of Iowa and Holden Comprehensive Cancer Center.

Phase 2 trial of the IDO pathway inhibitor indoximod plus gemcitabine/nab-paclitaxel for the treatment of metastatic pancreas cancer: interim analysis

The combination of indoximod and gemcitabine/nab-paclitaxel continues to be well tolerated by patients with metastatic pancreatic cancer. These data come from the Phase 1/2 trial in which treatment-naïve metastatic pancreatic cancer patients were treated with the combination therapy in continuous four week cycles. As of the data cut off for the analysis, a total of 45 patients (Phase 1 and 2) were enrolled in the trial long enough to potentially have cycle 4 imaging available by the ASCO (Free ASCO Whitepaper) presentation. Data via site reported RECIST criteria were available on 31 patients. At the time of this analysis, objective response rate was 45 percent (14 of 31) and multiple durable responses ≥6 months were observed. Two patients achieved a complete response (6 percent), both at Cycle 8, showing delayed kinetics that may indicate an immune based mechanism. The trial continues to enroll patients and a biopsy cohort expansion is underway.

"The objective response rate, observance of complete responses, and delayed and durable response patterns are promising for this combination regimen for patients with metastatic pancreas cancer," said Andrea Wang-Gillam, M.D., Ph.D., Assistant Professor of Medicine, Division of Oncology, Section of Medical Oncology, at Washington University School of Medicine.

Further Study of Indoximod Combinations Planned

"These are promising data as indoximod continues to demonstrate potential in combination therapies with other checkpoint inhibitors and with chemotherapies for different cancers, with encouraging rates for objective responses while being well-tolerated," said Charles Link, Jr., M.D., Chairman and Chief Executive Officer. "We believe these data further support that the IDO pathway is one of the key immune checkpoint targets. We anticipate continued clinical progress in these and additional indoximod combinations during 2016."

About Indoximod

Indoximod is an orally available small molecule that has shown the potential to interfere with multiple targets within the indoleamine 2,3-dioxygenase (IDO) pathway. It is designed to be used in combination with other therapeutic agents to maximize the body’s immune response against a range of tumor types. Indoximod is currently in multiple Phase 2 clinical trials for the treatment of patients with breast, prostate, pancreatic, melanoma and brain cancers and in Phase 1 clinical trials for the treatment of pediatric patients with primary malignant brain tumors.

On June 06, 2016 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that two analyses demonstrating the utility of the Myriad myRisk Hereditary Cancer test will be featured in oral presentations at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting (Press release, Myriad Genetics, JUN 6, 2016, View Source [SID:1234513049]). These presentations demonstrate the importance of using a 25-gene panel to evaluate risk for hereditary breast and ovarian cancers.

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"Risk assessment for hereditary cancer is expanding with the use of the myRisk Hereditary Cancer 25-gene panel, approximately doubling the rate of mutation detection over BRCA1/2 testing alone. However, in these studies we sought to understand the magnitude of risk across 25 genes," said Johnathan Lancaster, M.D., Ph.D., chief medical officer, Myriad Genetic Laboratories. "We discovered that mutations in eight genes are associated with a two- to six-fold increase in breast cancer risk and mutations in 11 genes confer a two- to 40-fold increased risk for ovarian cancer. These important findings clarify the risk across diverse genes and support the use of myRisk as part of a clinical risk assessment for patients."

Results of the studies to be presented are described below and abstracts are available at: abstracts.asco.org. Follow Myriad on Twitter via @MyriadGenetics to stay informed about news and updates from the Company.

myRisk Hereditary Cancer Podium Presentations
Title: Magnitude of invasive breast cancer (BC) risk associated with mutations detected by multiple-gene germline sequencing in 95,561 women.
Presenter: Michael Hall, Stanford University Cancer Institute
Date: Monday, June 6, 2016, 8:00 — 11:30 a.m.; Discussion 1:15 — 2:30 p.m.
Location: S404, Abstract 1512, Poster Board 335

This study evaluated the magnitude of invasive breast cancer (BC) risk associated with mutations across a 25-gene panel test. A total of 95,561 patients underwent clinical testing with the myRisk Hereditary Cancer test. Seven percent of patients tested positive for a deleterious mutation. The majority of mutations occurred in BRCA1/2 genes (44 percent) or other genes associated with BC risk (40 percent). There was a significant association with personal BC history and mutations in BRCA1/2, PTEN, TP53, PALB2, CHEK2, BARD1 and ATM. Specifically, estimates ranged from two (ATM, CHEK2, BARD1) to six (BRCA1, PTEN) times increased risk for breast cancer. These findings demonstrate the BC risk across the diverse panel of 25 genes in the myRisk test.

Title: Ovarian cancer risk associated with mutations detected by multiple-gene germline sequencing in 95,561 women.
Presenter: Allison Kurian, Stanford University Cancer Institute
Date: Monday, June 6, 2016, 9:45 — 11:15 a.m.
Location: E450ab, Abstract: 5510

This study evaluated the magnitude of ovarian cancer (OC) risk with mutations across the 25 genes included in the myRisk Hereditary Cancer panel. Data from 95,561 patients were analyzed to examine the association between deleterious mutations and personal history of OC. The results showed that seven percent of patients tested positive for a deleterious mutation. Among 5,020 women affected by OC, 14 percent had a deleterious mutation (63 percent with BRCA1/2, 9.4 percent in Lynch Syndrome genes and 11.2 percent in other genes associated with OC). In this study, 11 genes were associated with a significant risk of OC, including the first report of OC risk associated with the ATM gene. Importantly, one-third of mutations in patients with OC were in non-BRCA and non-Lynch genes, demonstrating that panel testing with the myRisk test identified a broader spectrum of associated cancers.

About Myriad myRisk Hereditary Cancer Testing
The Myriad myRisk Hereditary Cancer test uses an extensive number of sophisticated technologies and proprietary algorithms in an 850 step laboratory process to evaluate 25 clinically significant genes associated with eight hereditary cancer sites including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma. For more information visit: View Source

On June 6, 2016 Kite Pharma, Inc. (Nasdaq:KITE) ("Kite") reported results from SCHOLAR-1 (Retrospective Non-Hodgkin Lymphoma Research), the first, large, systematic, multi-institutional, patient-level meta-analysis of outcomes from 635 patients with chemorefractory diffuse large B-cell lymphoma (DLBCL) (Press release, Kite Pharma, JUN 6, 2016, View Source [SID:1234513046]). The study showed that patients with chemorefractory disease – defined as disease that does not respond to treatment with a chemotherapy-based regimen or has relapsed less than 12 months after autologous stem cell transplant (ASCT) – have consistently poor outcomes regardless of refractory subgroup, line of therapy, and disease stage. The study will be presented today at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (abstract #7516).

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"These study results are important because they confirm the regrettable outcomes that have been observed in the clinical setting for people with this difficult-to-treat form of DLBCL," said Dr. John Kuruvilla, Associate Professor of Medicine at the University of Toronto, and a clinical investigator in the Department of Medical Oncology at Princess Margaret Cancer Centre in Toronto. "While DLBCL is considered curable with initial chemotherapy-based treatment, patients with chemorefractory DLBCL have limited-to-no treatment options and historically poor outcomes, underscoring the significant need for new therapies."

According to the American Cancer Society, non-Hodgkin lymphoma (NHL) accounts for about four percent of all cancers in the United States, making it one of the most common cancers diagnosed. DLBCL is the most common form of the disease, accounting for one out of every three cases of NHL.1 It is estimated that approximately 26,000 people will be diagnosed with DLBCL in the United States in 2016.

"Little is known about the outcomes of people with chemorefractory DLBCL, leaving a large gap in the treatment landscape. These data help to track the course of the disease and provide an important historical benchmark for studies in this patient population," said David Chang, M.D., Ph.D., Kite’s Executive Vice President, Research and Development, and Chief Medical Officer. "We are proud to partner with clinicians, scientists and researchers at MD Anderson Cancer Center, the Mayo Clinic, the University of Iowa, the Canadian Cancer Trials Group, and LYSARC (The Lymphoma Academic Research Organisation) to help establish a better understanding of the disease to determine how best to treat patients with chemorefractory DLBCL."

About the SCHOLAR-1 Study

The SCHOLAR-1 (Retrospective Non-Hodgkin Lymphoma Research) is a retrospective analysis of patients with chemorefractory DLBCL comprised of data from Phase 3 studies from the Canadian Cancer Trials Group (CCTG LY.12 Study) and LYSARC (CORAL Study) and large retrospective databases including from the MD Anderson Cancer Center, Mayo Clinic and University of Iowa Specialized Programs of Research Excellence (SPORE).

In the study, 635 patients with chemorefractory DLBCL were eligible for evaluation based on the following criteria: DLBCL defined as progressive disease as best response to chemotherapy; or stable disease as best response to chemotherapy (received at least 4 cycles of first-line or 2 cycles of later-line therapy); or relapse ≤ 12 months of ASCT. Patients must have received an anti-CD20 monoclonal antibody (unless CD20 negative) and an anthracycline as one of their prior regimens.

Results to be presented at ASCO (Free ASCO Whitepaper) showed:

The overall response rate (ORR; complete response plus partial response) across all 635 patients was 26% (165/635) with only 8% (51/635) achieving a complete response, showing no signs of the disease
The response rates were consistent ranging from 21% to 31% ORR and 2% to 15% complete response (CR) across centers and data sets
Median overall survival was 6.6 months and consistent across subgroups including refractory status, stage of disease and line of therapy

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 DelMar Pharmaceuticals, Inc. (OTCQX: DMPID) ("DelMar" and the "Company"), a company focused on developing and commercializing proven cancer therapies in new orphan drug indications, reported new data from its recently completed Phase I/II clinical trial of VAL-083 (dianhydrogalactitol) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s (ASCO) (Free ASCO Whitepaper) Annual Meeting on Saturday, June 4, 2016 (Press release, DelMar Pharmaceuticals, JUN 6, 2016, View Source [SID:1234513039]).

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"This year’s ASCO (Free ASCO Whitepaper) meeting was an opportunity to share the aggregate of our research to date with the global cancer research community," stated Jeffrey Bacha, chairman and CEO of DelMar Pharmaceuticals. "Based on our findings related to VAL-083’s unique mechanism of action and data from our Phase I/II clinical trial we believe that VAL-083 has the potential to offer a new treatment option for cancer patients whose tumors exhibit features correlated with resistance to currently available chemotherapy."

DelMar’s abstract entitled, "Phase I/II Study of Dianhydrogalactitol in Patients with Recurrent Glioblastoma", was presented during the Central Nervous System poster session on Saturday. The poster presentation can be viewed on DelMar’s website.

In summary, DelMar’s presentation noted:

VAL-083 attacks cancer cells via a unique mechanism of action which is distinct from other chemotherapies used in the treatment of glioblastoma multiforme (GBM). Specifically, VAL-083 is active independent of MGMT, a DNA repair enzyme which is highly expressed in approximately 2/3 of GBM patients and correlated with resistance to temozolomide, the current front-line chemotherapy in the treatment of GBM. Of patients tested in the DelMar trial, 84% exhibited high MGMT.
Median survival of 22 patients receiving an assumed therapeutic dose of VAL-083 (≥20mg/m2) was 8.35 months, suggesting that VAL-083 may offer improved survival for GBM patients following bevacizumab (Avastin) failure in comparison to currently available salvage therapy. Median survival for VAL-083 treated patients following bevacizumab failure compared with published literature demonstrating survival of approximately three to five months with common salvage therapy regimens.
VAL-083 compared to published literature

Reference
Post Avastin
Salvage Therapy
Median Survival from
Bevacizumab Failure

Rahman (2014)
nitrosourea
4.3 months

Mikkelson (2011)
TMZ + irinotecan
4.5 months

Lu (2011)
dasatinib
2.6 months

Reardon (2011)
etoposide
4.7 months

Reardon (2011)
TMZ
2.9 months

Iwomoto (2009)
various
5.1 months

DelMar Trial
VAL-083
8.35 months

A dose of 40 mg/m2/day VAL-083 administered on the first three days of every three week cycle is well tolerated in refractory GBM patients and has been selected for study in subsequent clinical trials.
DelMar recently announced the completion of a successful end of Phase II meeting with the US FDA and its plans to advance VAL-083 into a pivotal clinical trial for GBM patients whose tumors have recurred following front-line therapy and second line treatment with bevacizumab.

DelMar’s advanced development program will feature a single randomized Phase 3 study measuring survival outcomes compared to a "physicians’ choice" control, which, if successful, would serve as the basis for a New Drug Application (NDA) submission for VAL-083. The control arm will consist of a limited number of salvage chemotherapies currently utilized in the treatment of Avastin-failed GBM. The final pivotal trial design will be confirmed with the FDA following further discussions with the Company’s clinical advisors.

In addition to the pivotal trial, DelMar also plans to initiate two separate Phase II clinical trials in earlier-stage GBM patients.

A randomized, non-comparative, biomarker-driven, Phase 2 study to determine if treatment of MGMT-unmethylated recurrent GBM with VAL-083 or CCNU improves overall survival at 9 months, compared to historical control in bevacizumab naïve patients. (clinicaltrials.gov identifier: NCT02717962)
A single arm Phase 2 clinical trial to confirm the tolerability of DelMar’s dosing regimen in combination with radiotherapy (XRT) and to explore the activity of VAL-083 in newly diagnosed MGMT-unmethylated GBM patients whose tumors are known to express high levels of MGMT.
"We wish to thank the patients, their families, and the physicians who participated in our Phase I/II clinical trial," said Mr. Bacha. "We are pleased to be advancing VAL-083 into these new trials that we believe, if successful, will serve as the basis for a new treatment paradigm in the treatment of GBM."

About VAL-083
VAL-083 is a "first-in-class," small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated clinical activity against a range of cancers including lung, brain, cervical, ovarian tumors and leukemia both as a single-agent and in combination with other treatments. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia (CML) and lung cancer, and has received orphan drug designation in Europe and the U.S. for the treatment of malignant gliomas. DelMar recently announced that the USFDA’s Office of Orphan Products had also granted an orphan designation to VAL-083 for the treatment of medulloblastoma.

DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by the expression of MGMT, a DNA repair enzyme that is implicated in chemotherapy resistance and poor outcomes in GBM patients following standard front-line treatment with Temodar (temozolomide).

DelMar conducted a Phase I/II clinical trial in GBM patients whose tumors have progressed following standard treatment with temozolomide, radiotherapy, bevacizumab and a range of salvage therapies. Patients were enrolled at five clinical centers in the United States: Mayo Clinic (Rochester, MN); UCSF (San Francisco, CA) and three centers associated with the Sarah Cannon Cancer Research Institute (Nashville, TN, Sarasota, FL and Denver, CO) (clinicaltrials.gov identifier: NCT01478178). DelMar announced the completion of enrollment in a Phase II expansion cohort in September, 2015.

About Glioblastoma Multiforme (GBM)
Glioblastoma multiforme (GBM) is the most common and most malignant form of brain cancer. Approximately 15,000 people are diagnosed with GBM each year in the U.S., with similar incidence in Europe. Standard of care is surgery, followed by either radiation therapy, or radiation therapy combined with temozolomide. Approximately 60 percent of GBM patients treated with temozolomide experience tumor progression within one year. More than half of glioblastoma patients will fail the currently approved therapies and face a very poor prognosis.