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Independent Researchers Find Genprex’s TUSC2 Prevents Tumor Growth in Triple-Negative Breast Cancer

On September 11, 2019 Genprex, Inc. (NASDAQ: GNPX), a clinical-stage gene therapy company, reported that independent researchers reported in a recent study that TUSC2, a tumor suppressor gene and the active agent in Genprex’s Oncoprex immunogene therapy, prevented tumor growth in triple-negative breast cancer (TNBC), which is currently considered an incurable cancer with limited therapeutic options (Press release, Genprex, SEP 11, 2019, View Source [SID1234539442]). Genprex has no affiliation with these researchers.

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The study, published in Nature, first found MicroRNA-138 as a diagnostic biomarker for TNBC, which currently lacks targeted therapies due to its inability to express the estrogen and progesterone hormone receptors and the human epidermal growth factor receptor 2 (HER2), thus the name for triple-negative breast cancer. Depletion of miR-138 was found to lead to apoptotic cell death in vitro and prevented tumorigenesis in vivo. TUSC2 was found to be a direct target of miR-138, and TUSC2 mimics the effects of miR-138 knockdown, preventing tumor growth. The researchers deduced that TUSC2 is a downstream tumor suppressor that is directly repressed by miR-138.

The study reports that triple-negative breast cancer is an extremely aggressive subtype of breast cancer which is associated with poor prognosis and high mortality rates. The lack of targeted treatment for triple-negative breast cancer makes it an increasingly feared diagnosis.

Genprex is conducting clinical and pre-clinical research to evaluate the effectiveness of TUSC2 when combined with targeted therapies and immunotherapies for non-small cell lung cancer. Existing pre-clinical data also suggest that TUSC2 may be effective against glioblastoma, head and neck cancer, kidney cancer, and soft tissue sarcomas. Now, this new independent study raises the possibility that TUSC2 expression, through miR-138 targeting, may also be used to treat the most aggressive subset of breast cancer.

"The results of the study evaluating TUSC2 for the treatment of triple-negative breast cancer are encouraging," said Rodney Varner, Genprex’s Chairman and Chief Executive Officer. "We believe that the data reported in this Nature article by independent researchers supports our belief that TUSC2 may be effective to treat a variety of cancers, including some of the most deadly types of cancer."

OncoCell MDx, Inc. Raises $22.2 Million in Series B Financing

On September 11, 2019 OncoCell MDx, Inc., a pan-disease immunogenomics platform company developing novel noninvasive blood-based tests to optimize patient care, reported it has raised $22.2 million in a Preferred Series B financing (Press release, OncoCell MDx, SEP 11, 2019, View Source [SID1234539441]). The financing was led by Savitr Capital, LLC (Savitr) with participation from existing investors.

OncoCell MDx has raised more than $30 million to date in support of its vision to simultaneously detect and stage cancer and other diseases using a single blood sample. This funding bolsters the company’s balance sheet and supports ongoing development and commercialization of its pan-disease diagnostic testing platform. The company plans to launch a blood test for detection and grading of aggressive prostate cancer next year.

"OncoCell is harnessing the power of the immune system and leveraging their proprietary immunogenomics technology to diagnose and stage disease early when there is the greatest opportunity for cure," said Andrew Midler, Managing Member at Savitr.

"We are developing and commercializing novel noninvasive tests that provide accurate diagnostic information quickly to physicians and their patients to help optimize patient treatment and improve patient outcomes," said Mark McDonough, President and CEO of OncoCell MDx.

"In a relatively short time, we have built a database of over 2,000 patient subjects analyzed with RNA-Seq and identified unique immunogenomic signatures that can discriminate healthy patients from those with indolent versus aggressive disease, he said. In prostate cancer, we’ve developed a blood test to enable improved staging and determine if a patient can safely forego invasive surgery or radiation therapy. Then, by virtue of our noninvasive approach, the patient can be serially tested to rule out disease progression, reducing the cost of care and improving quality of life."

DelMar Pharmaceuticals to Present at the Fall Investor Summit on September 16, 2019

On September 11, 2019 DelMar Pharmaceuticals, Inc. (Nasdaq: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development of novel cancer therapies, reported that CEO Saiid Zarrabian will deliver a presentation on the Company and meet with investors at the Fall Investor Summit on September 16, 2019 at 1:30 PM ET in Track 1 at Essex House, 160 Central Park South in New York City (Press release, DelMar Pharmaceuticals, SEP 11, 2019, View Source [SID1234539440]). The conference is being held September 16-17, 2019.

Interested investors may register for the conference at https://fall-investor-summit.events.issuerdirect.com/signup, or may request a meeting time by contacting John Marco at Core IR, either by calling 516-222-2560 or via [email protected].

Merck KGaA, Darmstadt, Germany, Announces FDA Breakthrough Therapy Designation for Investigational Therapy Tepotinib in Patients with Metastatic NSCLC with METex14 Skipping Alterations

On September 11, 2019 Merck KGaA, Darmstadt, Germany, a leading science and technology company, which operates its biopharmaceutical business as EMD Serono in the US and Canada, reported that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for the investigational targeted therapy tepotinib* in patients with metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations who progressed following platinum-based cancer therapy (Press release, Merck KGaA, SEP 11, 2019, View Source [SID1234539439]).

"Tepotinib was associated with robust objective responses with durability that has not previously been seen in patients with metastatic NSCLC harboring MET exon 14 skipping alterations, selected by either tissue or liquid biopsy approaches," said Luciano Rossetti, Global Head of Research & Development for the Biopharma business of Merck KGaA, Darmstadt, Germany. "This breakthrough therapy designation further underscores the potential of tepotinib, and we aim to advance this program and deliver this medicine as quickly as possible to NSCLC patients who may benefit."

Lung cancer is the most common type of cancer worldwide, with 2 million cases diagnosed annually.1 Alterations of the MET signaling pathway are found in various cancer types, including 3-5% of NSCLC cases, and correlate with aggressive tumor behavior and poor clinical prognosis.2-4

Discovered in-house at Merck KGaA, Darmstadt, Germany, tepotinib is an investigational oral MET kinase inhibitor that is designed to be highly potent and selective5 and to inhibit the oncogenic signaling caused by MET (gene) alterations, including both MET exon 14 skipping alterations and MET amplifications, or MET protein overexpression.

In March 2018, tepotinib’s potential was recognized by the Japanese Ministry of Health, Labour and Welfare (MHLW), which granted SAKIGAKE ‘fast-track’ designation for tepotinib in advanced NSCLC harboring MET exon 14 skipping alterations. SAKIGAKE designation promotes research and development in Japan, aiming at early practical application for innovative pharmaceutical products, medical devices and regenerative medicines.

Tepotinib is also being investigated in the INSIGHT 2 study (NCT03940703) in combination with the tyrosine kinase inhibitor (TKI) osimertinib in epidermal growth factor receptor (EGFR) mutated, MET amplified, locally advanced or metastatic NSCLC having acquired resistance to prior EGFR TKI.

The Breakthrough Therapy Designation is based on data from the ongoing VISION study (NCT02864992), showing preliminary clinical evidence that tepotinib may offer an improvement over available therapy in patients with metastatic NSCLC harboring MET exon 14 skipping alterations detected by liquid biopsy (LBx) or tissue biopsy (TBx) across different lines of treatment.

Results from an interim analysis of the ongoing VISION study in 73 efficacy-evaluable patients with NSCLC with MET exon 14 skipping alterations identified by LBx or TBx testing demonstrate overall objective response rate (ORR) of 50.0% for LBx-identified patients as assessed by Independent Review Committee (IRC), and 55.3% as assessed by investigators. The ORR for TBx-identified patients was 45.1% and 54.9%, respectively. The overall median duration of response (DOR) was 12.4 months and 17.1 months among LBx-identified patients, as assessed by IRC and investigators, respectively, while among TBx-identified patients, 15.7 and 14.3 months were observed, respectively.

Most treatment-related adverse events (TRAEs) were Grade 1 and 2. No Grade 4 or 5 TRAEs were observed. Any grade TRAEs reported by ≥10% of 87 patients evaluable for safety were peripheral edema (48.3%), nausea (23.0%) diarrhea (20.7%) and increased blood creatinine (12.6%). Other relevant TRAEs of any grade include increased lipase (4.6%), fatigue (3.4%) and vomiting (3.4%). TRAEs led to permanent discontinuation in four patients (two patients due to peripheral edema, one due to interstitial lung disease, one due to diarrhea and nausea).

Results from this study were presented in an oral presentation at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.6 The use of both LBx and TBx to identify patients for the VISION study is intended to support improved patient selection and is consistent with the company’s focus on patient-centric drug development.

*Tepotinib is the recommended International Nonproprietary Name (INN) for the MET kinase inhibitor (MSC2156119J). Tepotinib is currently under clinical investigation and not approved for any use anywhere in the world.

About Breakthrough Therapy Designation

Breakthrough Therapy Designation is designed to expedite the development and review of drugs which are intended to treat a serious condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s). The FDA’s granting of the Breakthrough Therapy Designation for advanced NSCLC does not alter the standard regulatory requirement to establish the safety and effectiveness of a drug through adequate and well-controlled studies to support approval.

About Non-Small Cell Lung Cancer

With 2 million cases diagnosed annually, lung cancer (including trachea, bronchus and lung) is the most common type of cancer worldwide, and the leading cause of cancer-related death, with 1.7 million mortality cases worldwide.1 Alterations of the MET signaling pathway, including MET exon 14 skipping alterations and MET amplifications, occur in 3-5% of NSCLC cases.2-4

About Tepotinib

Tepotinib, discovered in-house at Merck KGaA, Darmstadt, Germany, is an investigational oral MET inhibitor that is designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations, including both MET exon 14 skipping alterations and MET amplifications, or MET protein overexpression. It has been designed to have a highly selective mechanism of action, with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations.

Tepotinib is currently being investigated in NSCLC and Merck KGaA, Darmstadt, Germany is actively assessing the potential of investigating tepotinib in combination with novel therapies and in other tumor indications.ray F, et al. CA Cancer J Clin. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 2018;68(6):394–424. View Source View Source.
Reungwetwattana T, et al. Lung Cancer 2017;103:27-37.
Mo HN, et al. Chronic Dis Transl Med 2017; 3(3):148-153.
Lutterbach B, et al. Cancer Res 2007;67:2081–8.
Bladt, F, et al. Clin Cancer Res 2013;19:2941-2951.
Paik P, et al. J Clin Oncol 2019;37: (suppl; abstr 9005).
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Veracyte Announces Publication of Clinical and Analytical Validation Data for Afirma Xpression Atlas

On September 11, 2019 Veracyte, Inc. (Nasdaq: VCYT) reported the publication of new data demonstrating the clinical and analytical validity of its Afirma Xpression Atlas (XA) genomic test, which is used to help guide surgery and treatment decisions for patients with likely or confirmed thyroid cancer (Press release, Veracyte, SEP 11, 2019, View Source [SID1234539437]). The new findings appear online in the journal Frontiers in Endocrinology.

The Afirma XA uses RNA whole-transcriptome sequencing to detect expressed DNA variants and RNA fusion partners in over 500 genes that are associated with thyroid cancer. The test is performed on fine needle aspiration (FNA) samples of thyroid nodules deemed suspicious for cancer by Veracyte’s Afirma Genomic Sequencing Classifier (GSC), as well as those that are suspicious for or have been diagnosed as cancer based on cytopathology. Importantly, the Afirma XA is performed on the same FNA sample as the Afirma GSC, obviating the need for patients to undergo an additional FNA procedure to obtain this genomic information about their thyroid.

To evaluate the Afirma XA’s clinical validity, researchers compared the test’s ability to identify genomic variants in an FNA sample’s transcriptome to currently accepted methods of targeted DNA and RNA sequencing. Using 943 blinded FNA samples, they found the Afirma XA had high positive predictive agreement (PPA) with targeted DNA sequencing (88 percent) and targeted RNA sequencing (89 percent). Similarly, using 695 blinded FNA samples to look for RNA fusions, the Afirma XA had an 82 percent PPA with targeted RNA sequencing. Conversely, 95 percent or more of variants and fusions identified by Veracyte’s RNA whole-transcriptome sequencing test were also identified by the reference method.

"Our findings suggest that the Afirma XA is sensitive and accurate in identifying gene alterations that are associated with thyroid cancer and confirm that the test can do this using one patient sample for all molecular testing," said Trevor E. Angell, assistant professor of clinical medicine at the Keck School of Medicine of USC and lead author of the new paper. "The extensive genomic-alteration information provided by the Afirma test can help physicians tailor initial treatment for patients with likely or confirmed cancer and also provides information about the potential benefits of targeted therapies for those cancers that don’t respond to standard treatment."

The researchers also investigated the reproducibility of the Afirma XA across laboratories and reagent lots. Using 69 variant-positive FNA samples, they found that the Afirma XA showed high accuracy between two different labs with different personnel for detecting variants (90 percent) and fusions (94 percent).

"The use of pre-operative molecular testing with minimally invasive FNA samples is expanding beyond cytologically indeterminate thyroid nodules to include those nodules with clear malignancy. Our findings demonstrate that physicians can be confident in the Afirma XA’s results at the time of diagnosis, which help guide surgery and treatment decisions," said Richard T. Kloos, M.D., medical director of endocrinology for Veracyte and an author of the new study.