On December 12, 2018 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus, reported that the first patient was treated in a phase 1 dose escalation study combining pelareorep and carfilzomib with Bristol-Myers Squibb’s checkpoint inhibitor Opdivo (nivolumab) to treat relapsed multiple myeloma patients (Press release, Oncolytics Biotech, DEC 12, 2018, View Source [SID1234532025]). This study is based on findings from the NCI 9603 multiple myeloma study that combined pelareorep with carfilzomib that resulted in objective responses, elimination of multiple myeloma cells and most importantly, an inflamed phenotype with PD-L1 overexpression.

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"Having worked with pelareorep in multiple myeloma and understanding its ability to act as a potentiator of checkpoint blockade, I’m very excited to work with the Oncolytics team on this study," said Dr. Craig Hofmeister, Associate Professor, Department of Hematology and Medical Oncology Emory University School of Medicine. "Pelareorep has proven its ability to create an inflamed phenotype and its potential for upregulation of PD-1 on tumor-infiltrating lymphocytes. My hope is this study leads not only to an effective combination dosing schedule but provides quantitative data describing the expression of PD-1, along with correlative studies that reveal the roles of both immune-mediated and direct cytotoxic myeloma cell killing."

This open-label, phase 1 study, conducted by Dr. Hofmeister at Emory University, will enroll up to 62 patients to examine the side effects and best dosing schedule of pelareorep when given in combination with dexamethasone, carfilzomib, and nivolumab in treating participants with relapsed multiple myeloma. The primary objectives of the study are to determine the maximum tolerated dose of pelareorep in combination with carfilzomib and nivolumab. Secondary outcome measures include time to progression, progression-free survival and overall survival, as well as the characterization of an inflamed phenotype and confirmation of biomarker responses indicative of tumor inflammation.

"We now have our second checkpoint inhibitor combination study enrolling, and I’m excited for the potential of the immune and biomarker data to come from it," said Dr. Rita Laeufle, Chief Medical Officer of Oncolytics Biotech. "These studies, along with our soon to be initiated studies combining pelareorep with Merck’s Keytruda, also in multiple myeloma, and Roche’s Tecentriq in neoadjuvant breast cancer, will provide further evidence that pelareorep has the potential to expand the use of checkpoint inhibitors by priming tumors cells. The confirmation of our predictive biomarkers enhances the likelihood of success in registrational studies, thereby reducing both clinical and commercial risk making pelareorep more attractive to potential partners."

For more information about the study, including a comprehensive list of inclusion and exclusion criteria, please visit: www.clinicaltrials.gov (identifier: NCT03605719).

About Pelareorep
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 and has been demonstrated to be able to escape neutralizing antibodies found in patients.

On December 12, 2018 Aptose Biosciences Inc. (NASDAQ: APTO, TSX: APS) reported highlights from a Key Opinion Leader (KOL) breakfast featuring a presentation by Brian Druker, M.D., Professor of Medicine at the School of Medicine at Oregon Health & Science University (OHSU), Director of OHSU’s Knight Cancer Institute, and Aptose management team (Press release, Aptose Biosciences, DEC 12, 2018, View Source [SID1234532023]).

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The webcast of the presentation will be archived on Aptose’s website here.

William G. Rice, Ph.D., Chairman, President and Chief Executive Officer, first provided a recap on CG-806, Aptose’s highly potent pan-FLT3/pan-BTK inhibitor, and included the following key highlights:

CG-806 has a well-differentiated mechanism of action, selectively and potently inhibiting kinase clusters that include all forms of FLT3 and BTK, as well as rescue pathways that can allow resistance to other drugs, and avoiding other kinase clusters associated with toxicity
CG-806 demonstrated superior potency on acute myeloid leukemia (AML) patient cells relative to all other FLT3 inhibitors
CG-806 demonstrated superior potency on B-cell patient cells relative to ibrutinib
In preclinical mouse model studies, CG-806 induced rapid and sustained tumor eradication with no observed toxicity
CG-806’s safety profile remains clean: New results, recently presented at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting from 28-day GLP toxicity and toxicokinetic studies, continue to demonstrate a highly favorable safety profile with no adverse findings to date
Dr. Druker discussed the evolution of kinase inhibitors as anticancer drugs, reviewed the current treatment landscape in AML and B-cell cancers, emphasizing the medical needs for these patient populations, and highlighted his experience with CG-806 alone and in combination to potentially address these medical needs. Key highlights:

CG-806 potently killed primary malignant cells from patients with diverse hematologic malignancies
CG-806 demonstrated superior killing potency on cells from AML patients compared to five other FLT3 inhibitors
AML patient cells with the FLT3-ITD mutation, found in approximately 30% of AML patients, were highly sensitive to CG-806
Just presented at ASH (Free ASH Whitepaper), AML patient cells with the IDH-1 mutation were unexpectedly sensitive to CG-806, a new finding that further broadens CG-806’s potential use and potential paths for rapid development
CG-806 data demonstrated broad and superior killing potency compared to ibrutinib, which is the current standard of care for B-cell malignancies, on cells from patients with CLL and other B-cell cancers
Drug combination studies with CG-806 and venetoclax on patient bone marrow cells suggest the combination may become the preferred drug combination for patients with AML, CLL, ALL and other hematologic malignancies
"CG-806 is unlike any molecule we have investigated, and it is more than just a FLT3 and BTK inhibitor," said Dr. Druker. "806 has the unusual ability to suppress key driver and rescue pathways and overcome the resistance that develops with other kinase inhibitors, and it has demonstrated potent activity against actual primary cells from patients with hematologic malignancies. We are hopeful that clinical testing will prove it to be a new treatment for a patient population in need of new options."

Stephen B. Howell, M.D., Professor of Medicine at the University of California, San Diego, and Associate Director for Clinical Research at the Moores UCSD Cancer Center, who serves as Aptose’s Acting Chief Medical Officer, wrapped up the prepared remarks of the session with current development plans for CG-806:

IND-enabling GLP toxicology and safety studies with CG-806 are complete
As a result of its robust safety profile, Aptose plans to file an IND in the first quarter of 2019 to begin clinical testing of CG-806 both in healthy volunteers (HVS) and in patients with B-cell malignancies
After a therapeutic dose is identified from the HVS or B-cell malignancy clinical trials, Aptose intends to expand into acutely ill AML patients and other sensitive subpopulations
About CG-806
CG-806 is a preclinical stage oral, first-in-class pan-FLT3/pan-BTK multi-cluster kinase inhibitor. This small molecule demonstrates potent inhibition of wild type and all mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates acute myeloid leukemia (AML) tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML. Likewise, CG-806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG-806 may be developed for various B cell malignancy patients (including CLL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent BTK inhibitors. It is in development for acute myeloid leukemia (AML) and B cell lymphoma.

Brian J. Druker, M.D.
Brian Druker, M.D., is the director of the Knight Cancer Institute, Associate Dean for oncology of the OHSU School of Medicine, JELD-WEN Chair of Leukemia Research and a Howard Hughes Medical Institute investigator. He revolutionized the treatment of cancer through research that resulted in the development of imatinib, the first drug to target the molecular defect of a cancer while leaving healthy cells unharmed. Marketed under the name Gleevec, his discovery turned a once-fatal cancer, chronic myeloid leukemia, into a manageable condition. This work changed the life expectancy of patients with CML from an average of 3 to 5 years to a 95% five-year survival, and has resulted in a paradigm-shift in cancer treatment from non-specific chemotherapy to highly targeted therapeutic agents. He is a member of the National Academy of Medicine, the National Academy of Sciences and, among numerous awards, is the recipient of the 2009 Lasker-DeBakey Clinical Medical Research Award and most recently, the 2018 Tang Prize in Biopharmaceutical Science.

Dr. Druker currently serves as the Chair of the Scientific Advisory Board for Aptose. He receives compensation from Aptose for this role. He and his team at OHSU, through the BEAT AML collaboration, have directly conducted studies with CG-806 on fresh bone marrow samples from patients with various hematologic malignancies, and data from these studies serve as the cornerstone of presentations made by Aptose Biosciences.

On December 12, 2018 NETRIS Pharma, a clinical-stage company developing novel anticancer therapies targeting dependence receptors, reported successful completion of the first-in-human study on the effects of netrin-1 inhibition in patients with advanced solid tumors (Press release, Netris Pharma, DEC 12, 2018, View Source [SID1234532018]). The Phase 1 dose-escalation study showed that NP137, a first-in-class monoclonal anti-netrin-1 blocking antibody, was safe and well tolerated up to 20mg/kg, with no dose limiting toxicity (DLT), meeting the primary objective. In addition, patients with advanced uterine cancers exhibited encouraging signs of anti-tumor activity, including prolonged stable disease and objective response.

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"We are very pleased with the safety and tolerability profile of NP137 in this study, which enabled evaluation of netrin-1 inhibition in advanced solid tumors," said Philippe Cassier, MD, PhD, Head of Phase 1 unit at Centre Léon Bérard and Principal Investigator of the NP137 study.

"I am really impressed by the preliminary anti-tumor activity observed in this study with patients showing objective response and prolonged one-year disease control," added Professor Jean Yves Blay, MD, Ph.D. General Director of the Centre Léon Bérard and past president of EORTC.

The Phase 1 study was designed to evaluate the maximum tolerated dose, pharmacokinetics and pharmacodynamics, and establish the recommended dose for the Phase 1b/2 expansion study. NP137 was dosed every other week starting from 1 mg/kg up to 20mg/kg in heavily pre-treated patients with advanced solid tumors. Additional study objectives were to evaluate the adverse events (AE), pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of NP137. The study enrolled a total of 19 patients in three French centers, the Centre Léon Bérard in Lyon, the Institut Claudius Régaud in Toulouse and the Institut de Cancérologie de l’Ouest in Nantes. A Phase 1 extension study with an additional 24 patients is ongoing to confirm the safety and tolerability of NP137, collect biopsies before and after treatment to allow measurement of potential biomarkers and confirm the preliminary clinical activity seen during dose escalation. The final phase 1a data will be submitted for presentation at an upcoming international medical conference.

"Meeting the primary objective of the dose-escalation part of this study and generating preliminary positive efficacy data, particularly in such chemotherapy-resistant patients, provide an important confirmation of our dependence receptor science and lay the groundwork for larger clinical studies with NP137 as a targeted approach to treat solid tumors in combination with chemotherapy, immune checkpoint inhibitors and tyrosine kinase inhibitors, » said Prof. Patrick Mehlen, Chief Executive Officer of NETRIS Pharma. « Additionally, we would like to thank the investigators, patients and caregivers for their participation in this study, and for contributing to our understanding of NP137 as we work to address a significant medical need. »

About NP137

Most types of tumors produce an abnormal amount of dependence receptors’ ligands, which prevents cells from dying. Netrin-1 is overexpressed in a large percentage of human cancers, including over two thirds of gynecologic cancers. Expression of netrin-1 often correlates with disease severity and no therapy has ever been tested against this new pathway.

NP137, a humanized monoclonal antibody of isotype IgG1 directed against netrin-1, is the first drug candidate developed by NETRIS Pharma. NP137 prevents the binding of netrin-1 on its dependence receptors, thereby re-inducing cancer cell death and impacting tumor cell plasticity. Pre-clinical studies show NP137 to have an anti-cancer effect as a monotherapy as well as synergistic effects in combination with chemotherapy, immune checkpoint inhibitors or tyrosine kinase inhibitors.

On December 12, 2018 BerGenBio ASA (OSE:BGBIO), a clinical-stage biopharmaceutical company focused on developing a pipeline of first-in-class AXL kinase inhibitors to treat multiple cancer indications, reported that the Company will be presenting key results from its Phase II clinical programme with selective AXL inhibitor bemcentinib at the DNB’s 9th Annual Nordic Healthcare Conference in Oslo, Norway, today at 10:15-10:40 CET (Press release, BerGenBio, DEC 12, 2018, View Source [SID1234532017]).

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The slides are available for download at the Company’s website: www.bergenbio.com/investors/presentations/

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "We have made significant progress during 2018 establishing clinical proof of concept for the remarkable utility of bemcentinib in cancers with high unmet clinical need and large market potential. We have shown that our once-a-day, oral selective AXL inhibitor is well tolerated as a monotherapy and in combination with immune-, targeted and chemotherapies. What is more, consistently we have seen that efficacy scales with AXL biomarker expression leading to superior response rates in AXL biomarker positive relapsed/refractory AML and MDS as a monotherapy as well as non-small cell lung cancer where we are combining with the immunotherapy blockbuster Keytruda. We have met all our operational milestones this year and are looking forward to starting a randomised phase II programme towards the end of H1 2019 based on key results obtained this year".

On December 12, 2018 Aduro Biotech, Inc. (NASDAQ: ADRO) reported the publication of a peer-reviewed paper in Cell Reports authored by Aduro scientists and Novartis collaborators as part of their ongoing research to study intratumoral stimulator of interferon genes (STING) pathway activation as a potential therapeutic approach for the treatment of cancer (Press release, Aduro Biotech, DEC 12, 2018, View Source;p=RssLanding&cat=news&id=2380389 [SID1234532015]). In this study, researchers determined an intratumoral dosing regimen of STING pathway activator, ADU-S100, optimized for adaptive immunity in mouse models. While high doses of ADU-S100 were effective at clearing injected tumors, researchers found that higher tumor ablative dosing regimens could compromise durable anti-tumor immunity. Lower immunogenic doses of ADU-S100 were shown to optimally elicit CD8+ T cell responses required for systemic and durable anti-tumor immunity, and were also found to be efficacious in combination with checkpoint inhibitor therapy.

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"We previously established that intratumoral STING pathway activation by ADU-S100 results in tumor regression in preclinical models. Our publication in Cell Reports now highlights the importance of optimizing the therapeutic dose regimen for STING agonists with the aim to balance innate and adaptive immune responses triggered by STING activation in the tumor microenvironment," stated Andrea van Elsas, Ph.D. chief scientific officer of Aduro. "Our findings support the use of immunogenic doses of ADU-S100 with checkpoint inhibitors to drive efficacious anti-tumor CD8+ T cell responses. We are encouraged by the potential of ADU-S100 as a novel treatment for cancer as we continue clinical evaluation of our lead compound in combination with checkpoint inhibitors."

The paper titled "Magnitude of Therapeutic STING Activation Determines CD8+ T-Cell Mediated Anti-Tumor Immunity," can be accessed online ahead of the print version in the peer-reviewed Journal Cell Reports.

ADU-S100 is the first STING pathway activator compound to enter the clinic and is currently being evaluated in a Phase 1 clinical trial as a single agent and in combination with ipilimumab (see www.clinicaltrials.gov, identifier NCT02675439) and in a Phase 1b combination trial with spartalizumab (PDR001), Novartis’ investigational anti-PD-1 monoclonal antibody (see www.clinicaltrials.gov, identifier NCT03172936).

About STING Pathway Activator Technology
The Aduro-proprietary STING pathway activator product candidates, including ADU-S100 (MIW815), are synthetic small molecule immune modulators that are designed to target and activate human STING. STING is generally expressed at high levels in immune cells, including dendritic cells. Natural activation of STING is not always sufficient to prevent the growth and spread of cancer cells. In preclinical models, ADU-S100 directly activates STING to further amplify the natural anti-tumor response. Once activated, the STING receptor initiates a profound innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of a systemic tumor antigen-specific T cell adaptive immune response.

Aduro’s lead molecule, ADU-S100, is the first therapeutic in development specifically targeting STING. In collaboration with Novartis, it is being tested in a Phase 1 clinical trial as a single agent and in combination with ipilimumab, and in a Phase 1b combination trial with spartalizumab (PDR001), an investigational anti-PD-1 monoclonal antibody. These studies are enrolling patients with cutaneously accessible, advanced/metastatic solid tumors or lymphomas. The trials are evaluating the ability of ADU-S100 to activate the immune system and recruit specialized immune cells to attack the injected tumor, leading to a broad immune response that seeks out and kills distant metastases.