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Pivotal Study Results for Myriad’s myPathÂ® Melanoma Test Highlighted In Two Additional Scientific Publications

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.

Loxo Oncology Announces Acceptance of Larotrectinib Oral Presentations at the American Society of Clinical Oncology (ASCO) Annual Meeting

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."

"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.

Kura Oncology Presents Preclinical Data Demonstrating Significant Anti-Tumor Activity of KO-947 and KO-539

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]).

"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.

Idera Pharmaceuticals Presents Clinical Translational and Pre-Clinical Data from IMO-2125 Development Program at the American Association for Cancer Research (AACR) 2017 Annual Meeting

On April 5, 2017 Idera Pharmaceuticals, Inc. (NASDAQ:IDRA), a clinical-stage biopharmaceutical company developing toll-like receptor and RNA therapeutics for patients with cancer and rare diseases, reported additional clinical translational and pre-clinical data from its ongoing intratumoral IMO-2125 development program at the AACR (Free AACR Whitepaper) 2017 Annual Meeting being held in Washington, DC (Press release, Idera Pharmaceuticals, APR 5, 2017, View Source [SID1234518486]).

In the poster presentation entitled, "Translational evidence of reactivated innate and adaptive immunity with intratumoral IMO-2125 in combination with systemic checkpoint inhibitors from a Phase 1/2 study in patients with anti-PD-1 refractory metastatic melanoma," Cara Haymaker, Ph.D. from the University of Texas, MD Anderson Cancer Center, presented an update on the translational findings from the ongoing Phase 1/2 trial of intratumoral IMO-2125 in combination with ipilimumab in patients with anti-PD-1 refractory metastatic melanoma.

The key findings in Dr. Haymaker’s presentation were that intratumoral IMO-2125 monotherapy in the injected lesions results in activation and maturation of dendritic cells, and the induction of type-1 interferon gene signature by 24 hours after first dose. After 8 weeks of therapy with intratumoral IMO-2125 and ipilimumab, increased immune infiltration has been observed in distant lesions of responding patients, suggesting an abscopal effect. Dr. Haymaker concludes that activation of intratumoral dendritic cells and induction of the associated downstream immune cascade enhances T-cell priming. In combination with checkpoint blockade, this mechanism may be an important key in treating patients who have been refractory to prior immune oncology approaches.

"We are excited to be examining the significant amounts of data emerging from this trial, which goes far beyond merely conducting clinical outcome analysis and to our knowledge has not been done to this depth before," stated Sri Chunduru, Ph.D., Idera’s Vice President, Translational Research. "The data emerging from the serial biopsies in these patients is highly informative to the guidance of our ongoing development program with IMO-2125 and leads us to a significantly greater understanding of tumor microenvironment before, during, and after immune therapy. We look forward to continuing to build upon this body of data as our study continues to enroll further patients. Importantly, we are very pleased that the data that has been generated validates our understanding of IMO-2125’s mechanism of action correlated with clinical results also generated to date."

A second poster presentation entitled, "Local treatment with novel TLR9 agonist IMO-2125 demonstrates anti-tumor activity in preclinical models of pancreatic cancer," presented by Daqing Wang, Ph.D., Principal Scientist & Group Leader, Idera Pharmaceuticals, demonstrated that intratumoral IMO-2125 showed dose-dependent antitumor responses associated with the increased tumor-infiltrating lymphocytes (TILs) in treated tumors of the Panc02 pancreatic cancer model. These antitumor responses and TILs were also observed in the distant, untreated tumors. In this study, treated mice, which remained tumor-free, showed lack of tumor growth upon rechallenge with the same tumor cells, suggesting an antitumor memory response.

Furthermore, a local treatment of IMO-2125 was evaluated by administering intraperitoneally in a peritoneal metastasis Panc02 model. Mice treated with intraperitoneal IMO-2125 showed increased survival compared to mice treated with placebo, control oligo compound or subcutaneous IMO-2125. Histological analysis showed significant reduction of tumor growth in the peritoneal cavity. This illustrates that while local treatment is necessary, routes of administration other than i.t. may also be effective to generate an antitumor response in pancreatic cancer. Overall, we believe these data demonstrate that treatment with IMO-2125 modulates the tumor microenvironment and increases infiltration by TILs and that these changes are associated with antitumor activity in pancreatic cancer models, and indicate that IMO-2125 may potentiate checkpoint inhibitor therapy for the treatment of pancreatic cancer.

A copy of the poster presentations are currently available on Idera’s corporate website at View Source

About IMO-2125
Toll-like receptors (TLRs) play a central role in the innate immune system, the body’s first line of defense against invading pathogens, as well as damaged or dysfunctional cells including cancer cells. The innate immune system is also involved in activating the adaptive immune system, which marshals highly specific immune responses to target pathogens or tissue. Cancer cells may exploit regulatory checkpoint pathways to avoid being recognized by the immune system, thereby shielding the tumor from immune attack. Checkpoint inhibitors such as agents targeting CTLA4 or programmed cell death protein 1 (PD-1) are designed to enable the immune system to recognize tumor cells. In this setting, intratumoral TLR9 agonist administration may increase the tumor-infiltrating lymphocytes (TILs), and thereby potentiate anti-cancer activity of checkpoint inhibitors in the injected tumor as well as systemically.

Idera’s TLR9 agonist, IMO-2125 has been created using the company’s proprietary chemistry-based discovery platform. IMO-2125 has been shown in various scientific presentations and publications to activate dendritic cells and induce interferon. Idera selected IMO-2125 to advance into clinical development in combination with checkpoint inhibitors based on this immunological profile. In previously completed clinical trials, subcutaneous administration of IMO-2125 was generally well tolerated in about 80 patients with hepatitis C. Idera has conducted further preclinical and clinical research evaluating the potential of IMO-2125 to enhance the anti-tumor activity of other checkpoint inhibitors in cancer immunotherapy with data being presented at several medical conferences during the past two years. The posters from these presentations can be found at View Source

About Metastatic Melanoma
Melanoma is a type of skin cancer that begins in a type of skin cell called melanocytes. As is the case in many forms of cancer, melanoma becomes more difficult to treat once the disease has spread beyond the skin to other parts of the body such as by through the lymphatic system (metastatic disease). Melanoma accounts for only one percent of skin cancer cases, but causes a large majority of skin cancer deaths. The American Cancer Society estimates that in 2017, there will be 87,110 new cases of melanoma in the U.S., and about 9,730 will die of this disease.

Bio-Path Holdings Presents Results Showing Potential of BP1002 as Treatment for Aggressive Non-Hodgkin’s Lymphoma

On April 5, 2017 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 drugs, reported results of preclinical in vitro and in vivo studies supporting the potential of BP1002 in the treatment of aggressive non-Hodgkin’s lymphoma (NHL) (Press release, Bio-Path Holdings, APR 5, 2017, View Source [SID1234518485]). These results are being presented at the annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) taking place in Washington, DC.

The poster titled, "Activity of Bcl-2 antisense therapeutic in aggressive non-Hodgkin’s lymphoma," summarizes results from two studies: an in vitro study in which 15 cells lines of aggressive NHL subtypes were incubated with BP1002; and two in vivo studies in which mice with follicular lymphoma xenografts were treated with BP1002. BP1002 was shown to have strong anti-NHL activity in each of these studies.

"Survival for patients with aggressive NHL has improved with the use of certain chemotherapy regimens, but the prognosis remains poor for the 30% of patients who relapse after treatment," said Peter Nielsen, chief executive officer of Bio-Path Holdings. "Aggressive NHL is associated with high levels of Bcl-2 expression, making it an ideal candidate for treatment with BP1002, a potent and targeted inhibitor of Bcl-2. While these results are early, we believe they indicate a potential for BP1002 to provide a survival benefit to patients with aggressive NHL. We look forward to initiating a clinical study later this year to assess this candidate in patients with NHL."

In the in vitro study, cell lines of germinal center B-cell lymphoma diffuse large B-cell lymphoma (DLBCL), activated B-cell DLBCL, mantle cell lymphoma and Burkitt’s lymphoma were incubated with BP1002. After four days, it was determined that BP1002 induced greater than 50% inhibition in 11 of the 15 cell lines tested. In the two animal studies, none of the untreated or control (empty liposome) mice survived beyond 39 days. In the BP1002 arms, a combined 87% of treated mice survived until the end of the 5-week studies.

About BP1002
BP1002 (Liposomal Bcl-2 antisense), Bio-Path’s second product candidate, is a neutral-charge, liposome-incorporated antisense drug designed to inhibit protein synthesis of Bcl-2, a protein that promotes cellular survival and inhibits apoptosis. Bcl-2 is overexpressed in a majority of non-Hodgkin’s lymphoma subtypes, including follicular lymphoma and diffuse large B cell lymphoma, as well as in a wide variety of solid tumors. Bio-Path is preparing to submit an investigational new drug (IND) application for BP1002, and is planning to initiate a Phase 1 clinical trial for lymphoma in 2017.