On April 5, 2017 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics, highlighted data presented during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting related to its clinical trial of tarextumab (anti-Notch2/3, OMP-59R5) and preclinical studies of rosmantuzumab (anti-RSPO3, OMP-131R10) and GITRL-Fc trimer (OMP-OMP-336B11) (Press release, OncoMed, APR 5, 2017, View Source [SID1234518493]).

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Data from OncoMed’s Phase 1b clinical study of tarextumab in extensive-stage small cell lung cancer show changes in circulating tumor cells (CTCs) appear to correlate with overall survival outcomes. The utility of using CTCs will be evaluated further in OncoMed’s Phase 2 PINNACLE trial of tarextumab.

In a series of preclinical studies, the combination of anti-RSPO3, now known as rosmantuzumab, with paclitaxel chemotherapy demonstrated synergistic anti-tumor activity in tumors with RSPO3 translocations as well as in tumors with Wnt pathway mutations. These data may be applied in future clinical trials to determine chemotherapy combinations and/or patient selection criteria.

Another set of preclinical studies identified and characterized biomarkers in tumors and in blood following administration of OncoMed’s GITRL-Fc trimer in syngeneic murine models that may be used in upcoming clinical trials to demonstrate activity. OncoMed is preparing to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) during the first half of 2017 for its novel GITRL-Fc trimer immuno-oncology agent.
"OncoMed is pursuing extensive efforts to identify pharmacodynamic markers that deepen our understanding of the mechanisms of action of our agents, as well as predictive biomarkers that may help us identify patients whose tumors are most likely to benefit from our therapeutic candidates," said Tim Hoey, Ph.D., OncoMed’s Senior Vice President of Cancer Biology and co-Chief Scientific Officer. "The data detailed in these AACR (Free AACR Whitepaper) presentations exemplify these translational research efforts and will have direct impact in informing future clinical trial design and analyses for our tarextumab, rosmantuzumab and GITRL-Fc trimer programs."

Abstract #1727 – Circulating Tumor Cells (CTCs) in patients with extensive-stage small cell lung cancer and their association with clinical outcome
OncoMed is currently conducting the Phase 2 portion of the PINNACLE Phase 1b/2 clinical study of tarextumab in combination with standard-of-care chemotherapy in patients with extensive-stage small cell lung cancer. Researchers looked at circulating tumor cell measurements taken from patients in the Phase 1b portion of the clinical trial to assess CTCs as a predictor of response and as pharmacodynamics biomarkers. Blood samples from 26 patients were collected at baseline and following treatment with tarextumab plus chemotherapy. CTCs were measured and correlated with clinical outcomes, including progression-free survival (PFS), overall survival (OS), best overall response and metastatic status. CTCs were present in 81 percent of patients (21/26). At baseline, higher CTC counts were associated with worse survival outcomes, liver metastasis and number of metastatic sites. Following treatment with tarextumab and platinum-based chemotherapy, CTC counts were significantly decreased, indicating potential treatment effects. This effect was most evident in patients treated with the designated Phase 2 dose of tarextumab (15 mg/kg) and less apparent at lower doses. Circulating tumor cell counts will be further evaluated in the Phase 2 portion of the PINNACLE trial.

Abstract #1911 — R-SPONDIN3 antagonism sensitizes colorectal cancer to taxane treatment
OncoMed’s clinical-stage candidate, rosmantuzumab, is currently being tested in a Phase 1b clinical trial as a single agent and in combination with chemotherapy. In the preclinical studies, tumors with RSPO3 translocations and overexpression were found to be sensitive to the combination of rosmantuzumab and a taxane, including a tumor resistant to treatment with anti-RSPO3, irinotecan or the combination of the two. In addition, ten patient-derived xenograft models of colorectal cancer containing Wnt pathway activating mutations in APC or beta catenin were treated with the combination of rosmantuzumab plus taxane-based chemotherapy. In these Wnt pathway mutated tumors typical of the majority of colorectal cancers, stromal cells in the tumor microenvironment are the source of RSPO3 expression. The combination of rosmantuzumab plus a taxane resulted in synergistic inhibition of tumor growth in eight of ten models. Anti-RSPO3 plus taxane treatment significantly reduced the number of tumor initiating cells. These data indicate that the synergistic activity of RSPO3 inhibition in combination with taxane chemotherapy may be an effective means to improve clinical outcomes in colorectal cancer patients whose tumors overexpress RSPO3 or have Wnt pathway activating mutations.

Abstract #5621 – Prevalence of GITR expression and pharmacodynamic (PD) biomarkers in syngeneic tumor models treated by a GITR agonist (GITRL-Fc)
A series of experiments was conducted to characterize the prevalence of GITR expression in human cancer tissues and to identify pharmacodynamic biomarkers that reflect the mechanism of action of GITRL-Fc. GITR is expressed at varying levels in multiple solid tumors on both tumor cells and immune cells. In multiple syngeneic mouse models, GITRL-Fc trimer showed potent single-agent, dose dependent anti-tumor efficacy in large established breast, colon and melanoma tumors. Using these models, a multi-platform approach was taken to investigate GITRL-Fc pharmacodynamic biomarkers in tumors and in blood. It was found that GITRL-Fc increased the gene expression associated with cytotoxic T cells and NK cells. GITRL-Fc also activated CD4+ effector cells, decreased Treg frequency and increased the ratio of CD8+ T cell/Treg in the tumor. The pharmacodynamic biomarker changes in immune-related gene expression and immune cell populations observed in these preclinical models define the GITRL-Fc trimer mechanism of action and will be explored in the Phase 1 clinical trial planned for later this year.

On April 5, 2017 Oncolytics Biotech Inc. (Oncolytics or the Company) (TSX:ONC) (OTCQX:ONCYF) reported data demonstrating a statistically significant (p=0.03) overall survival (OS) benefit for patients with mutated p53 metastatic breast cancer, when treated with REOLYSIN, an immuno-oncology viral agent, in combination with paclitaxel (Press release, Oncolytics Biotech, APR 5, 2017, View Source [SID1234518492]). Results from IND 213, an open-label, randomized, phase 2 study were presented at the Annual Meeting of the American Association of Cancer Research (AACR) (Free AACR Whitepaper), April 1-5, 2017 in Washington, D.C.

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"Mutations of the p53 tumor suppressor gene play an increasingly challenging role throughout the life cycle of cancer," said Dr. Matt Coffey, President & Chief Executive Officer of Oncolytics. "As breast cancer progresses clinically, p53 mutations become more prominent and negatively impact therapeutic efficacy and overall survival. These data provide evidence that combining REOLYSIN with paclitaxel may improve survival for this difficult-to-treat, well characterized, patient population."

The open-label, randomized, phase 2 study enrolled 74 patients with metastatic breast cancer, 82 percent (61 patients) of whom presented with p53 mutated tumors. The results show patients with mutated p53 metastatic breast cancer that were treated with REOLYSIN in combination with paclitaxel (n=30) had a median OS of 20.9 months versus 10.4 months (n=31) in patients treated only with paclitaxel. The study was designed and conducted by the Canadian Cancer Trials Group (CCTG, formerly known as the National Cancer Institute of Canada – NCIC).

"The observed survival benefit is very exciting and reinforces the effectiveness and tolerability of REOLYSIN in patients with mutated p53 metastatic breast cancer, while demonstrating its potential utility in earlier lines of treatment for this difficult-to-treat, high-risk group of patients," said Dr. Andres Gutierrez, Chief Medical Officer of Oncolytics. "These data indicate overall survival is more than doubled for patients when treatment with REOLYSIN is added to the standard of care and highlight key considerations for the design and execution of a registration study in breast cancer. Our immediate next steps include seeking advice from key opinion leaders and regulators on refining our go-forward regulatory strategy and registration pathway."

In the abstract for the poster, the CCTG had previously reported that in the intention-to-treat patient population there was an improvement in median OS (secondary endpoint) from 10.4 months on the control arm to 17.4 months on the test arm (Hazard ratio 0.65, 80% CI 0.46-0.91, p=0.1) meeting the pre-specified significance threshold with powering of 90 percent. Consistent with REOLYSIN acting as an immune therapy agent, there was no meaningful improvement in either progression free survival (the primary endpoint), or response rate (secondary endpoint). With this overall survival data and the additional data from the p53 patient group, the company has commenced the planning of a registration study in metastatic breast cancer with overall survival as the primary endpoint.

The poster, authored by Bernstein et al, "A Randomized (RCT) Phase II Study of Oncolytic Reovirus (Pelareorep) plus Standard Weekly Paclitaxel (P) as Therapy for Metastatic Breast Cancer (mBC)" will be available on the Oncolytics website at: View Source

About Breast Cancer
The National Cancer institute reported 246,660 new cases of breast cancer diagnosed in the United States and 40,450 deaths from the disease in 2016.

On April 5, 2017 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that it has published the third clinical validation study and second clinical utility study for its myPath Melanoma test, which completes the reimbursement dossier for the product (Press release, Myriad Genetics, APR 5, 2017, View Source [SID1234518491]). The Company also announced it will submit the reimbursement dossier to Medicare and private insurers three months earlier than expected. myPath Melanoma is an objective genetic test that measures 23 genes to help differentiate malignant melanoma from benign lesions.

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"The pivotal results from these two studies join a number of additional publications, which is the culmination of five years of extensive scientific research and innovation," said Vicki Fish, vice president, Dermatology Business Unit, Myriad Genetic Laboratories. "We believe that our reimbursement dossier is exceptionally strong, and we will work with health plans to ensure this test is widely accessible to the physicians and patients who need it."

The third clinical validation titled "Diagnostic Distinction of Malignant Melanoma and Benign Nevi by a Gene Expression Signature and Correlation to Clinical Outcomes" was published in the journal Cancer Epidemiology, Biomarkers & Prevention. The study assessed the performance of the myPath Melanoma test in an independent cohort of 182 patients with melanocytic lesions against clinically proven outcomes (99 primary melanomas with distant metastases and 83 benign moles). The median time to melanoma metastasis was 18 months and the median follow-up time for benign moles was 75 months. The results showed that the myPath Melanoma test had an overall diagnostic accuracy of 95 percent to effectively differentiate melanoma from benign lesions. These strong findings demonstrate that the myPath Melanoma test closely correlates with long-term clinical outcomes and adds valuable information to assist in the accurate diagnosis of melanoma.

The second clinical utility study titled "The Influence of a Gene Expression Signature on the Treatment of Diagnostically Challenging Melanocytic Lesions" was published in the journal Personalized Medicine. This study was designed to evaluate changes in real world patient management based upon the myPath Melanoma test result. Samples from 77 patients with suspicious skin lesions (i.e., melanocytic neoplasms) were tested using the myPath Melanoma test accompanied by pre-test documentation of the intended treatment recommendations. The actual treatment provided by dermatologists was then documented after testing. The results showed there was a 71 percent change in patient management from pre-test recommendations and an 81 percent reduction in biopsy site re-excisions for patients with a benign test result. Based on these findings, the myPath Melanoma test significantly influenced the physicians’ treatment of patients.

A list of the key analytic validation, clinical validation and clinical utilities studies that comprise the myPath Melanoma reimbursement dossier follows below.

Key Elements of myPath Melanoma Reimbursement Dossier

Study Key Result Peer-Reviewed Publication
Clinical Validation 1 (n=437) • >90 percent diagnostic accuracy Journal of Cutaneous Pathology (2015)
Clinical Validation 2 (n=736) • >91 percent diagnostic accuracy Cancer (2016)
Clinical Validation 3 (n=182) • >95 percent diagnostic accuracy Cancer Epidemiology, Biomarkers & Prevention (2017)
Analytic Validation (n=544) • Only 2.5 percent standard deviation of the score High dynamic range, precision, RNA yield Biomarkers in Medicine (2015)
Clinical Utility 1 ( n=218) • >50 percent increase in definitive diagnoses for cases that were originally diagnosed as indeterminate.
• ~50 percent change in treatment recommendations for diagnostically challenging cases. Medicine (2016)
Clinical Utility 2 (n=77) • 71 percent change in patient management from pre-test recommendations
• 81 percent reduction in excisions for patients with a benign test. Personalized Medicine (2017)
Health Economic • 8.3 percent reduction in 10-year costs per patient.
• Savings of $.067 per member per month. Journal of Medical Economics (2014).

"Melanoma is one of the fastest growing cancers in the United States, and there is demand among physicians for an objective, high quality, clinically validated molecular diagnostic test to be used as an adjunct to conventional tools like the microscope," said Loren Clarke, M.D., board-certified dermatopathologist and medical director, Dermatology, Myriad Genetic Laboratories. "We believe myPath Melanoma is one of the most studied and accurate molecular diagnostic tests ever developed. It has enormous potential to help save the lives of people with melanoma, spare people with benign moles from unneeded treatment and lower costs for our healthcare system."

Follow Myriad on Twitter via @MyriadGenetics to stay informed about news and updates about myPath Melanoma from the Company.

About Melanoma
Melanoma is one of the fastest growing cancers in the United States and can strike people of all ages, races and skin types. With a one-in-50 lifetime risk of developing melanoma, nearly 87,000 Americans are expected to be diagnosed with Stage I-IV melanoma and another 75,000 will be diagnosed with melanoma in situ — totaling approximately 162,000 total diagnoses. Early and accurate diagnosis of melanoma is critical for long-term survival. For more information visit: www.mypathmelanoma.com/.

About Myriad myPath Melanoma
Myriad myPath Melanoma is a clinically validated test to be used as an adjunct to histopathology when the distinction between a benign nevus and a malignant melanoma cannot be made confidently by histopathology alone. The test measures the expression of 23 genes and accurately distinguishes melanoma from benign nevi.

On April 5, 2017 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported that larotrectinib (LOXO-101) interim clinical data across the RECIST-evaluable TRK fusion clinical trial database from all three ongoing clinical trials will be presented in a late-breaking oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held June 2 – 6, 2017 in Chicago, Illinois (Press release, Loxo Oncology, APR 5, 2017, View Source [SID1234518489]). The presentation is entitled, "The efficacy of larotrectinib (LOXO-101), a selective tropomyosin receptor kinase (TRK) inhibitor, in adult and pediatric TRK fusion cancers." Additionally, interim pediatric Phase 1 clinical trial data, included in the aforementioned data set, will also be presented in a separate oral presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting, entitled, "A pediatric phase 1 study of larotrectinib, a highly selective inhibitor of the tropomyosin receptor kinase (TRK) family."

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"Completing enrollment more quickly than anticipated created an opportunity to present data from our registrational program at ASCO (Free ASCO Whitepaper) this year," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "We hope that the oral presentations help build awareness in the oncology community around TRK fusions as therapeutic targets across solid tumor diagnoses and the importance of comprehensive testing in patients with advanced cancer. Due to the late-breaking nature of the data, the presentations will be based on interim follow-up and local radiology assessments of patients in the registrational program, while the NDA/MAA submissions will rely on independent central radiology review and longer follow-up of these patients. In the second half of 2017, consistent with previous guidance, we plan to announce top-line registrational data for the program, including longer follow-up and results of the central radiology review."

The Company will be hosting a conference call and webcast to discuss the data after they are presented at ASCO (Free ASCO Whitepaper). Details regarding date and time will be announced closer to the ASCO (Free ASCO Whitepaper) conference.

About Larotrectinib (LOXO-101)
Larotrectinib (LOXO-101) is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In an ongoing Phase 1 clinical trial, larotrectinib has demonstrated encouraging preliminary efficacy. Larotrectinib is also being evaluated in the NAVIGATE global Phase 2 multi-center basket trial in patients with solid tumors that harbor TRK gene fusions, and the SCOUT Phase 1/2 trial in pediatric patients, including patients with advanced cancer, TRK gene fusions and infantile fibrosarcoma. Larotrectinib has been granted Breakthrough Therapy Designation and Rare Pediatric Disease Designation by the U.S. FDA. For additional information about the larotrectinib clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or visit www.loxooncologytrials.com.

On April 5, 2017 Kura Oncology, Inc. (NASDAQ:KURA), a clinical stage biopharmaceutical company focused on the development of precision medicines for oncology, reported the presentation of preclinical data for KO-947, its development candidate targeting the ERK1/2 kinases, and KO-539, its development candidate targeting the menin-MLL interaction, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017 (Press release, Kura Oncology, APR 5, 2017, View Source [SID1234518488]).

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"We are progressing multiple programs aimed at addressing the urgent needs of cancer patients facing a poor prognosis and limited treatment options," said Troy Wilson, Ph.D., J.D., President and CEO of Kura Oncology. "The data presented today illustrate that KO-947 and KO-539 demonstrate significant anti-tumor activity in preclinical models, supporting their continued advancement as potential therapeutics."

About KO-947

KO-947 is a potent and selective inhibitor of ERK1/2 kinases, which are critical components of the MAPK pathway. Aberrant signaling caused by mutations or dysregulation of the MAPK pathway are frequent contributors to the development of cancer and are associated with numerous tumor types, including lung, colorectal and pancreatic adenocarcinomas and squamous cell carcinomas. Although small molecule inhibitors of BRAF and MEK have demonstrated clinical activity in selected patients, duration of response has been limited, and resistance is often associated with reactivation of the MAPK signaling pathway. In preclinical studies presented at AACR (Free AACR Whitepaper), KO-947 demonstrated prolonged inhibition of the MAPK pathway. Durable tumor regression was observed in preclinical cell line and patient derived xenograft models, including KRAS- and BRAF-mutant adenocarcinomas and squamous cell carcinomas lacking BRAF/RAS mutations, when KO-947 was administered on schedules ranging from daily to once weekly. Kura anticipates initiating a Phase 1 clinical trial for KO-947 in 1H 2017.

About KO-539

KO-539 is a potent and selective inhibitor of the interaction between the menin protein and the MLL fusion proteins, which characterize MLL leukemias. MLL-rearranged leukemia patients typically have a poor prognosis with a 5-year survival rate estimated to be 40%. As the leukemogenic activity of MLL fusion proteins has been shown to be dependent on their direct interaction with menin, the development of small molecules that block the menin-MLL interaction is a promising therapeutic strategy for the treatment of this disease. In preclinical studies presented at AACR (Free AACR Whitepaper), KO-539 demonstrated robust, sustained tumor regressions in multiple aggressive models of MLL-rearranged leukemias that correlated with modulation of target gene expression. KO-539 has been nominated as a development candidate, and further efforts are currently underway to assess potential utility of menin-MLL inhibitors in additional hematological malignancies and solid tumor indications.