Oncolytic virotherapy represents an exciting new area of cancer treatment which exploits a virus’s ability to selectively replicate and kill tumor tissue while stimulating a patient-specific immune response against cancer. Interest in the field is at an all-time high following significant deals by Pfizer, Celgene, Amgen, BMS and Boehringer Ingelheim, however, questions still remain around delivery, product and clinical development, pre-clinical modelling, scale-up, manufacturing and suitable commercial models. CHI’s Second Annual Oncolytic Virus Immunotherapy conference brings together the leading industry and academic leaders to discuss the critical steps driving oncolytic virotherapy forward.
MONDAY, AUGUST 28
7:30 am Registration & Morning Coffee
8:25 Chairperson’s Opening Remarks
Brian R. Champion, Ph.D., CSO, Psioxus Therapeutics Ltd.
8:30 KEYNOTE PRESENTATION: Engineering and Bio-Selection to Optimize an Oncolytic Virus Platform
John Bell, Ph.D., Senior Scientist, Center for Innovative Cancer Research, Ottawa Hospital Research Institute
Oncolytic viruses are therapeutics that are designed or selected to specifically infect and destroy cancer cells. There are multiple strategies that can be employed to create viruses that replicate in and kill tumors; however, one common feature of malignant cells is that they lack a potent anti-viral response. I will discuss the molecular basis for these defects, how best to exploit them to create tumor killing therapeutics and strategies to improve manufacturing output of oncolytic viruses from manufacturing cell lines based upon these principles.
9:00 Tumor Selective HSV-Based Oncolytic Vectors for Treatment of GBM
Paola Grandi, Ph.D., Senior Research Director, Immunology/Virology, Oncorus, Inc.
Oncorus oHSV is controlled by certain microRNAs (miRNAs) that are present in healthy cells, but absent in cancer cells. Typically, miRNAs regulate the ability of classical messenger RNA (mRNAs) to be translated into protein or promote the degradation of mRNAs. By engineering miRNA binding sites into essential viral genes, oHSV replication and cellular destruction is prevented in healthy cells. Since cancer cells lack these specific miRNAs, Oncorus oHSV is free to replicate in and destroy them.
9:30 Coffee Break
10:00 WO-12, a Multi-Mechanistic Immuno-Oncolytic Therapy
Steve H. Thorne, CSO, Western Oncolytics Ltd.
The next generation of oncolytic viruses will likely combine multiple genetic modifications (transgenes and viral genetic alteration) that act to synergistically target tumors through multiple mechanisms. In particular, approaches that (i) enhance systemic delivery and viral spread within and between tumors, (ii) activate a potent anti-tumor T-cell response, and (iii) modify the tumor microenvironment to enhance the activity of both the viral therapy and other therapies would produce additional benefits. The Western Oncolytics platform and its lead product WO-12 aim to achieve these goals. WO-12 has demonstrated enhanced activity in preclinical models and will soon enter clinical testing.
10:30 Pepticrad, a Novel Oncolytic Virus-Based Therapeutic Cancer Vaccine
Sari Pesonen, Vice President, Clinical Development, Valo Therapeutics
PeptiCRAd (Peptide-coated Conditionally Replicating Adenovirus) is an innovative and unique way of combining two clinically proven cancer immunotherapy approaches: an oncolytic adenovirus and a cancer-specific peptide vaccine, to take advantage of the best features of both technologies. The idea is straightforward: to use immunogenic virus as active carrier of tumor-specific peptides to direct the immune system to specifically target and kill cancer cells.
11:00 Synthetic Virology: Modular Assembly of Designer Viruses for Cancer Therapy
Clodagh O’Shea, Ph.D., Howard Hughes Medical Institute Faculty Scholar; Associate Professor, William Scandling Developmental Chair, Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies
Design is the ultimate test of understanding. For oncolytic therapies to achieve their potential, we need a deep mechanistic understanding of virus and tumor biology together with the ability to confer new properties. To achieve this, we have developed combinatorial modular genome assembly (ADsembly) platforms, orthogonal capsid functionalization technologies (RapAd) and replication assays that have enabled the rational design, directed evolution, systematic assembly and screening of powerful new vectors and oncolytic viruses.
11:30 Adenovirus-based virotherapy for disseminated disease
David T. Curiel, MD, PhD., Distinguished Professor of Radiation Oncology, D=rector, Biologic Therapeutics Center, Washington University
Effective virotherapy for disseminated neoplastic disease required precise =umor targeting. The unique molecular plasticity of adenovirus offers the p=tential to achieve the tumor selectivity required for virotherapy for meta=tatic disease.
12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
12:30 Session Break
1:25 Chairperson’s Remarks
Fares Nigim, M.D., Massachusetts General Hospital and Harvard Medical School
1:30 Stroma Targeting Strategies for Oncolytic Virotherapy
Daniel Katzman, PhD., CEO, Unleash Immuno Oncolytics
2:00 Development of OV Immunotherapy Using a Novel Preclinical GBM Model
Hiroshi Nakashima, Ph.D., Instructor, Neuroscience, Brigham and Women’s Hospital
Mechanism of action of the Oncolytic virus includes direct tumor killing and vaccine adjuvant. Since OV immunotherapy is emerge to apply in incurable glioblastoma multiforme (GBM) for the durable therapeutic effects, our new glioma mouse model will provide new opportunity to evaluate the combined OV therapies that work under the patient-mimicked immunological condition.
2:30 Pexa-Vec: A Multi-Mechanistic Immunotherapeutic Modulator of the Tumor Microenvironment
Naomi De Silva, Associate Director, Preclinical Science, Sillajen Biotherapeutics, Inc.
Pexa-Vec (pexastimogene devacirepvec, JX-594) is an oncolytic and immunotherapeutic vaccinia virus, engineered to preferentially infect tumor cells, disrupt vasculature, and stimulate anti-tumor immune responses. A Phase III trial evaluating Pexa-Vec in the treatment of advanced primary liver cancer is underway.
3:00 Refreshment Break
3:30 Designing Clinical Trials to Elucidate Oncolytic Virus Mechanisms-of-Action
Caroline Breitbach, Ph.D., Vice President, Translational Development, Turnstone Biologics
Oncolytic viruses have been shown to target tumors by multiple complementary mechanisms-of-action, including direct oncolysis, tumor vascular targeting and induction of anti-tumor immunity. Phase I/II clinical trials can be designed to validate these mechanisms. Development experience of an oncolytic vaccinia virus and a novel rhabdovirus oncolytic vaccine will be summarized.
4:00 Development of an Attenuated Oncolytic Influenza a Virus Expressing Mycobacterial ESAT-6 Protein
Michael Bergmann, M.D., Ph.D., CMO, Vacthera
We have expressed ESAT-6 in a partial NS1-deletion influenza virus. ESAT-6 expressing viruses were associated with lower levels of NF-kB activating as compared to empty viral vectors. ESAT-6 expressing viruses led to higher titers in eggs up to 1010 TCID50. ESAT-6 expressing deletion viruses were still attenuated when applied to the upper respiratory tract of mice. Intra-tumoral application of virus into B16 melanoma significantly delayed tumor growth.
4:30 Testing and Characterization of Oncolytic Viruses
Jerrod Denham, Ph.D., Principal & Senior Consultant, Dark Horse Consulting
Testing and characterization of oncolytic viruses typically follow the current principles for the majority of gene therapy product critical quality attributes. There are specific challenges with respect to adventitious agent safety testing and viral clearance studies. This presentation will walk through examples of how these challenges were resolved.
5:00 End of Day
TUESDAY, AUGUST 29
7:00 am Registration
7:25 Breakout Discussion Groups with Continental Breakfast
8:25 Chairperson’s Opening Remarks
Matthew Mulvey, Ph.D., CEO, BeneVir Biopharm, Inc.
8:30 Rationale for Oncolytic Viruses as the Backbone of Combination Immunotherapy Regimens
Robert Coffin, PhD., Co-founder and CEO, Replimune
Oncolytic viruses (OVs) mediate anti-tumor activity through direct cell lysis and induction of host anti-tumor immunity. The ability to attract and activate T cells within the tumor microenvironment and induce interferon release suggests that OVs could be used as the backbone in combination immunotherapy strategies designed to promote anti-tumor immunity. Emerging clinical data is demonstrating significant improvement in studies of melanoma, and further clinical development for other cancers is anticipated.
9:00 FEATURED PRESENTATION: Developing Tumor-Specific Immunogene (T-Sign) Combination Immunotherapies by Arming the Oncolytic Group B Adenovirus Enadenotucirev
Brian R. Champion, Ph.D., CSO, Psioxus Therapeutics Ltd.
We have developed a broadly applicable platform system, based on the potent chimeric oncolytic adenovirus enadenotucirev (EnAd), for directing the selective localized production of a combination of immunotherapeutic agents within tumors following systemic dosing, while minimizing the potential for systemic off-target effects of such combination approaches. The presentation will highlight recent data supporting both the platform and specific T-SIGn virus candidates.
9:30 T-Stealth Technology Promotes Synergy between Oncolytic Viruses and Immuno-Stimulatory Agents
Matthew Mulvey, Ph.D., CEO, BeneVir Biopharm, Inc.
BeneVir is developing an OV platform based on T-Stealth Technology, which hides infected cells from anti-viral T-cells. This allows an OV to complete its replication program, produce progeny viruses, and spread in the tumor microenvironment despite a robust anti-viral T-cell response. In immune-competent murine tumor models, regimens that simultaneously combine immuno-stimulatory agents with T-Stealth armed OV show efficacy. However, there is no effect on tumor burden in these models when simultaneous combination regimens utilize a “Visible” OV that does not encode T-Stealth Technology. BeneVir’s lead OV will enter a Phase I trial in solid tumors in Q2 2018.
10:00 Poster Presentation: Neural Stem Cell Mediated Oncolytic Virotherapy for Ovarian Cancer
Jennifer Batalla, Graduate Student, Karen Aboody Laboratory Irell & Manella Graduate Program
10:30 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing
11:15 What Does It Take to Cure Glioblastoma; Combinations Plus?
Samuel D. Rabkin, Ph.D., Professor, Neurosurgery, Massachusetts General Hospital and Harvard Medical School
We will discuss combination therapies for glioblastoma in representative preclinical models, involving oncolytic herpes simplex viruses (oHSV), cytokine expression, and immune checkpoint inhibitors. OHSV induce anti-tumor immunity and can be armed with therapeutic transgenes. The complex multicomponent strategy illustrates both the difficulty in treating non-immunogenic tumors and the opportunities in coupling immunovirotherapy with other immunotherapeutic approaches.
11:45 Oncolytic Virus-Induced Rad51 Degradation: Synergy with Poly(Adp-Ribose) Polymerase Inhibitors in Treating Glioblastoma
Jianfang Ning, Ph.D., Instructor, Neurosurgery, Massachusetts General Hospital, Harvard Medical School
Oncolytic herpes simplex virus (oHSV) sensitized glioblastoma stem cells (GSCs) to poly(ADP-ribose) polymerase inhibitors (PARPis), irrespective of their PARPi sensitivity through selective proteasomal degradation of key DNA damage response protein, Rad51, mediating the combination effects. This synthetic lethal-like interaction increased DNA damage, apoptosis, and cell death in vitro and in vivo. Combined treatment of mice bearing PARPi-sensitive or -resistant GSC-derived brain tumors greatly extended survival compared to either agent alone.
12:15 pm Close of Oncolytic Virus Immunotherapy