On April 18, 2018 Oncolytics Biotech Inc. (TSX: ONC) (OTCQX: ONCYF), currently developing REOLYSIN (pelareorep), an intravenously delivered immuno-oncolytic virus turning cold tumors hot, reported two posters highlighting data from pelareorep studies presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018. The conference takes place April 14-18, 2018, in Chicago (Press release, Oncolytics Biotech, 18 18, 2018, View Source [SID1234525555]).

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"These posters add additional confirmation of pelareorep’s promotion of an inflammatory signature in different cell lines," said Dr. Matt Coffey, President and CEO of Oncolytics Biotech. "The study by doctor Wilkinson demonstrates that pelareorep can establish an inflamed tumor phenotype and the presentation by doctor Goel highlights the synergistic combination of pelareorep and an anti-PD1 agent. Taken together, these findings highlight that pelareorep is priming the immune system and enhancing the activity of checkpoint blockade. As MSS CRC typically does not respond to checkpoint blockade, viral priming could expand the use of this drug class by making non-susceptible tissue susceptible by turning cold tumors hot. This work will of course lead to additional studies in combination with other immunotherapies."

Presenter: Sanjay Goel, MD, Associate Professor of Medicine, Montefiore Medical Center
Presentation Title: Potentiating effect of reovirus in anti-PD1 therapy in colorectal cancer
Session Title: Receptor Targeting and the Tumor Microenvironment
Location: Poster Section 38
Poster Board #: 17
Poster Number: 3917

Data presented in the poster demonstrated:

pelareorep administration increased PD-L1 expression on MSS CRC cells;

possible evidence of a vaccine effect: immunologically competent mice were re-challenged with the original tumor and the tumor was unable to propagate;

combination therapy made statistically significant improvements in survival compared to controls in both BALB/c (median 42 vs. 16 days, p=0.003) and C57BL/6 (median 24 vs. 17 days, p=0.02) mice; and

pelareorep treated xenografted tumor tissue showed a higher infiltration of T lymphocytes as confirmed by CD8-positive and intensified granzyme staining.

Presenter: Grey Wilkinson, PhD, Translational Scientist, Oncolytics Biotech
Presentation Title:
Pelareorep promotes the expression of a chemokine signature that predicts response to immunotherapy
Session Title: Immunomodulatory Agents and Interventions 2
Location: Poster Section 33
Poster Board #: 10
Poster Number: 4707

Data presented in the poster demonstrated:

the expression of a chemokine signature that predicts response to immunotherapy;

global changes in gene expression are unique and different for each cell line following pelareorep infection and changes in gene expression occur before significant cell lysis;

pelareorep differentially promotes the expression of innate and adaptive immunity related genes in HCC, CRC, NSCLC cell lines; and

pelareorep promotes the expression of gene signatures that predict response to immuno-therapies in HCC cells.

These posters are now available on the Posters & Publications page of the company’s website: www.oncolyticsbiotech.com/technology/posters-publications.

About REOLYSIN/Pelareorep
REOLYSIN, also known as pelareorep, is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers.

On April 18, 2018 OBI Pharma, Inc., a Taiwan biopharma company (TPEx: 4174), reported that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for a Phase I/II study of OBI-3424, a first-in-class DNA alkylating agent that targets cancers that overexpress the aldo-keto reductase 1C3 (AKR1C3) enzyme (Press release, OBI Pharma, APR 18, 2018, View Source [SID1234525525]).

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OBI plans to enroll patients with local solid tumors, including hepatocellular carcinoma (HCC) and castrate-resistant prostate cancer (CRPC). OBI Pharma’s Chief Medical Advisor, Tillman Pearce, M.D., noted, "This clinical trial intends to verify the safety and preliminary activity profile of OBI-3424, a novel first-in-class prodrug of a DNA alkylating cancer therapeutic that is selectively activated by AKR1C3, an enzyme that is overexpressed in a variety of solid and liquid tumors. We are delighted to conduct this first-in-man clinical trial at the University of Texas M.D. Anderson Cancer Center and The James Cancer Hospital and Solove Research Institute of Ohio State University, two of America’s leading academic oncology research institutions".

Amy Huang, General Manager of OBI Pharma, added, "OBI Pharma is proud to further develop our unique targeted cancer pipeline, including targets like the Globo series and AKR1C3. OBI-3424 enhances OBI’s pipeline in solid and liquid tumors for cancer patients who over-express AKR1C3. OBI is taking a first-step towards testing the safety and initial efficacy of a new class of AKR1C3 targeted therapy. We are excited to develop novel targeted therapeutics in the fight against cancers of unmet need."

About OBI-3424

OBI-3424 is a first-in-class novel small-molecule prodrug that selectively targets cancers overexpressing the enzyme aldo-keto reductase 1C3 (AKR1C3), and selectively releases a potent DNA alkylating agent in the presence of the AKR1C3 enzyme. This selective mode of activation distinguishes OBI-3424 from traditional alkylating agents, such as cyclophosphamide and ifosfamide, which are non-selective.

AKR1C3 overexpression has been documented in a number of treatment-resistant and difficult-to-treat cancers including: hepatocellular carcinomas (HCC), castrate-resistant prostate cancer (CRPC), and T-cell acute lymphoblastic leukemia (T-ALL). AKR1C3 is highly expressed in up to 15 solid and liquid tumors.

Furthermore, individualized patient selection by staining for AKR1C3 overexpression by immunohistochemistry can be performed based on tumor biopsies or circulating tumor cells to identify patients with other tumor types most likely to respond to treatment with OBI-3424, and thus offering the possibility for a streamlined clinical development strategy.

OBI Pharma holds worldwide rights for OBI-3424 with the exception of the following countries, whose rights are held by Ascenta Pharma: China, Hong Kong, Macao, Taiwan, Japan, South Korea, Singapore, Malaysia, Thailand, Turkey, and India.

On April 18, 2018 Bio-Path Holdings, Inc., (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported that data from pre-clinical studies supporting the potential of prexigebersen (BP1001, liposomal Grb2 antisense), in the treatment of solid tumors in gynecologic malignancies were presented in a poster at the annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), which took place in Chicago, IL (Press release, Bio-Path Holdings, APR 18, 2018, View Source [SID1234525522]).

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The poster titled, "Grabbing GRB2: The use of Liposome-incorporated Grb2 antisense oligonucleotides as a novel therapy in gynecologic malignancies," was presented by Olivia D. Lara, M.D., University of Texas MD Anderson Cancer Center, Department of Gynecologic Oncology during the Experimental and Molecular Therapeutics Poster Session. The data summarize results from studies investigating the expression of GRB2 in a series of in vitro experiments in high-grade serous (HGSC) and uterine (UC) carcinoma models. The study also examined the biological effects of prexigebersen in HGSC mice models (OVCAR 5), first in a dose-defining experiment then in combination with standard dose paclitaxel.

The data showed there was an eighty-six percent (86%) decrease in tumor burden (p<0.05), and multinodular burden (p<0.01) in the combination prexigebersen/paclitaxel group compared to control. In addition, there was no apparent toxicity with mice on combination therapy losing less weight than the paclitaxel-only group (P = 0.005).

"We are delighted to present these very encouraging findings at this year’s AACR (Free AACR Whitepaper) before an audience of the world’s leading cancer researchers and clinicians," stated Peter H. Nielsen, chief executive officer of Bio-Path Holdings. "Our research continues to suggest that prexigebersen-based combination therapy may offer an attractive method for targeting solid tumors and these findings establish the GRB2/GAB2 complex as an important target for prexigebersen. We look forward to advancing this promising therapy in gynecologic and other solid tumor cancers and plan to initiate first-in-human studies as early as the end of this year.

On April 18, 2018 AstraZeneca reported that the US Food and Drug AdministrationNSCLC (FDA) has approved Tagrisso (osimertinib) for the 1st-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) mutations, (exon 19 deletions or exon 21 L858R mutations), as detected by an FDA-approved test (Press release, AstraZeneca, APR 18, 2018, View Source [SID1234525521]).The approval is based on results from the Phase III FLAURA trial, which were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress and published in the New England Journal of Medicine.

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Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit at AstraZeneca, said: "Today’s FDA approval of Tagrisso in the 1st-line setting is an exciting milestone for patients and our company. Tagrisso delivered unprecedented median progression-free survival data across all pre-specified patient subgroups, including patients with or without CNS metastases, and could prolong the lives of more patients without their tumours growing or spreading."

Dr. Suresh S. Ramalingam, Principal Investigator of the FLAURA trial, from Winship Cancer Institute of Emory University, Atlanta, said: "The approval of osimertinib in the 1st-line setting represents a major advance in the treatment of patients with EGFR mutations and a significant change in the treatment paradigm. Osimertinib provides robust improvements in progression-free survival with no unexpected safety signals compared to the previous generation of EGFR inhibitors."

The FLAURA trial compared Tagrisso to current 1st-line EGFR tyrosine kinase inhibitors (TKIs), erlotinib or gefitinib, in previously-untreated patients with locally-advanced or metastatic EGFR-mutated (EGFRm) NSCLC. Tagrisso met the primary endpoint of progression-free survival (PFS) (see table below). PFS results with Tagrisso were consistent across all pre-specified patient subgroups, including in patients with or without central nervous system (CNS) metastases. Overall survival data were not mature at the time of the final PFS analysis.

Safety data for Tagrisso in the FLAURA trial were in line with those observed in prior clinical trials. Tagrisso was generally well tolerated, with Grade 3 or higher adverse events (AEs) occurring in 34% of patients taking TAGRISSO and 45% in the comparator arm. The most common adverse reactions (≥20%) in patients treated with Tagrisso were diarrhoea (58%), rash (58%), dry skin (36%), nail toxicity (35%), stomatitis (29%), fatigue (21%) and decreased appetite (20%).

In the US, Tagrisso is already approved for the 2nd-line treatment of patients with metastatic EGFRm NSCLC, whose disease has progressed on or after a 1st-line EGFR-TKI therapy and who have developed the secondary T790M mutation, as detected by an FDA-approved test. In 2017, Tagrisso was granted Breakthrough Therapy and Priority Review designations by the US FDA in the 1st-line treatment setting. Tagrisso is under regulatory review in the European Union and Japan for use in the 1st-line treatment setting with regulatory decisions anticipated in the second half of 2018.

Tagrisso received its first approval for 1st-line use based on the FLAURA data in Brazil in patients with metastatic EGFRm NSCLC on April 16, 2018

NOTES TO EDITORS
About NSCLC

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths, more than breast, prostate and colorectal cancers combined. Approximately 10-15% of patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC. These patients are particularly sensitive to treatment with EGFR-TKIs, which block the cell-signalling pathways that drive the growth of tumour cells. Tumours almost always develop resistance to EGFR-TKI treatment, however, leading to disease progression. Approximately half of patients develop resistance to approved EGFR-TKIs such as gefitinib, erlotinib and afatinib due to the EGFR T790M resistance mutation. There is also a need for medicines with improved CNS efficacy, since approximately 25% of patients with EGFRm NSCLC have brain metastases at diagnosis, increasing to approximately 40% within two years of diagnosis.

About Tagrisso

Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI designed to inhibit both EGFR-sensitising and EGFR T790M-resistance mutations, with clinical activity against CNS metastases. Tagrisso 40mg and 80mg once-daily oral tablets have been approved in the US and Brazil for 1st-line EGFRm advanced NSCLC, and in more than 75 countries including the US, EU, Japan and China for patients with EGFR T790M mutation-positive advanced NSCLC. Tagrisso is also being investigated in the adjuvant setting and in combination with other treatments.

About the FLAURA trial

The FLAURA trial assessed the efficacy and safety of Tagrisso 80mg once daily vs. standard-of-care EGFR-TKIs (either erlotinib [150mg orally, once daily] or gefitinib [250mg orally, once daily]) in previously-untreated patients with locally-advanced or metastatic EGFRm NSCLC. The trial was double-blinded and randomised, with 556 patients across 29 countries.

About AstraZeneca in Lung Cancer

AstraZeneca is committed to developing medicines to help every patient with lung cancer. We have three approved medicines and a growing pipeline that targets genetic changes in tumour cells and boosts the power of the immune response against cancer. Our unrelenting pursuit of science aims to deliver more breakthrough therapies with the goal of extending and improving the lives of patients across all stages of disease and lines of therapy.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as a key growth platform for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On April 18, 2018 Tarveda Therapeutics, Inc., a clinical stage biopharmaceutical company discovering and developing Pentarins as a new class of potent and selective cancer medicines, reported that presented data on the efficacy of PEN-866, a novel miniature drug conjugate comprised of a Heat Shock Protein 90 (HSP90) targeting ligand attached through a cleavable linker to SN-38 when combined with Poly ADP ribose polymerase (PARP) inhibitors in preclinical models of human cancer (Press release, Tarveda Therapeutics, 18 18, 2018, View Source [SID1234525520]). SN-38 is a potent topoisomerase 1 inhibitor, and is the active metabolite of irinotecan. The poster titled, "Combination of the miniature drug conjugate PEN-866 with PARP inhibitors as a rational approach to overcoming limitations of PARP inhibitor monotherapy" was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 14-18, 2018 in Chicago.

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The data presented evaluates the use of PEN-866 in combination with PARP inhibitors as an approach to overcoming limitations of PARP inhibitor monotherapy, such as dose limiting toxicities, in preclinical models of human cancer. In efficacy studies carried out in both BRCA mutant and BRCA wildtype tumor xenografts, combinations of PEN-866 and PARP inhibitors resulted in greater efficacy than that of the monotherapy in both tumor types.

"Results presented today show that when combined with PARP inhibitors, PEN-866 could avert the dose limiting toxicities often seen when PARP inhibitors are combined with other anti-cancer therapies," said Richard Wooster, Ph.D., President of Research and Development and Chief Scientific Officer of Tarveda Therapeutics. "The high levels of accumulation and retention of the combination of PEN-866 and a PARP inhibitor in xenograft tumors demonstrate the potential for greater efficacy compared to single agent therapy."

PEN-866’s linker cleavage provides sustained release of SN-38 at a high local tumor concentration leading to DNA damage and apoptosis of tumor cells, which results in broad antitumor activity in a range of preclinical xenograft models. When PEN-866 is administered in combination with PARP inhibitors, the inhibitors reduce DNA repair activity in tumor cells, enabling PEN-866 to maximize its efficacy in damaging cancer cell DNA. A pharmacodynamic assessment of DNA damage performed in tumors responsive to the combination treatment further demonstrated the efficacy of the therapy.

"The mechanistic synergy of PEN-866, carrying the payload SN-38 which is a potent topoisomerase I inhibitor, and PARP inhibitors suggests that this combination therapy could be an attractive approach in the clinical evaluation of PEN-866," said Drew Fromkin, President and Chief Executive Officer of Tarveda Therapeutics. "We look forward to continued studies of PEN-866, including our first-in-human Phase 1 clinical trial of PEN-866 to evaluate safety and efficacy."

About PEN-866
PEN-866 exploits the activation of Heat Shock Protein 90 (HSP90) in tumors to accumulate and release its potent anti-cancer payload, SN-38. PEN-866 is a miniature conjugate that comprises a small molecule, HSP90-targeting ligand linked to SN-38, the active metabolite of irinotecan. The conjugate accumulates and is retained in tumors and, by way of a sustained release of SN-38, causes prolonged DNA damage and tumor regressions in multiple patient-derived and other xenograft tumor models. PEN-866 is currently being studied in first-in-human clinical trials to evaluate safety and efficacy in patients with advanced solid tumors.

About Pentarins
Tarveda is developing Pentarins, potent and selective miniature drug conjugates with high affinity for specific cell surface and intracellular targets. Pentarins are engineered to bind to their tumor cell targets and provide sustained release of their potent therapeutic payloads deep into solid tumor tissue. Comprised of a targeting ligand conjugated to a potent cancer cell killing agent through a tuned chemical linker, Pentarins are designed to overcome the deficits of both larger antibody drug conjugates and small molecules that limit their therapeutic effectiveness against solid tumors. Together, the components of Tarveda’s Pentarins have distinct, yet synergistic, anticancer attributes: the small size of Pentarins allows for rapid and deep penetration into the tumor tissue, the ligand’s targeting ability allows for specific binding and retention in tumor cells, and the chemical linker is tuned to optimize the release of the potent, cell killing payload inside the cancer cells for efficacy.