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AGENDA for Oncolytic Virus Immunotherapy Unlocking Oncolytic Virotherapies: From Science to Commercialization CHI’S 4^TH ANNUAL IMMUNO-ONCOLOGY SUMMIT – AUGUST 29-30, 2016 | Marriott Long Wharf Hotel – Boston, MA

Reporter: Aviva Lev-Ari, PhD, RN

 

http://www.immuno-oncologysummit.com/uploadedFiles/Immuno_Oncology_Summit/Agenda/16/2016-The-Immuno-Oncology-Summit-Brochure.pdf

 

Oncolytic Virus Immunotherapy Unlocking Oncolytic Virotherapies: From Science to Commercialization

MONDAY, AUGUST 29 & 30

MONDAY, AUGUST 29

7:30 am Registration & Morning Coffee

REALIZING THE POTENTIAL OF ONCOLYTIC VIRUS IMMUNOTHERAPY

8:25 Chairperson’s Opening Remarks

Brian Champion, Ph.D., Senior Vice President, R&D, PsiOxus Therapeutics Ltd

8:30 T-Vec: From Market Approval to Future Plans

Jennifer Gansert, Ph.D., Executive Director, Global Development Lead, Amgen, Inc.

9:00 Oncolytic Virotherapies as a Single Shot Cure?

Stephen J. Russell, M.D, Ph.D., Professor, Mayo Clinic

Oncolytic virotherapy is increasingly used as a cancer immunotherapy. However, certain oncolytic viruses can also mediate wholesale tumor destruction independently of an antitumor immune response. This is the oncolytic paradigm, where a cytolytic virus with preferential tumor tropism spreads extensively at sites of tumor growth and directly kills the majority of the tumor cells in the body leaving only a few uninfected tumor cells to be controlled by the concomitant antitumor immune response.

9:30 Coffee Break

UNDERSTANDING MECHANISMS OF ACTION

9:55 Chairperson’s Remarks Fares Nigim, M.D., Massachusetts General Hospital and Harvard Medical School

10:00 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.

10:30 Seprehvir, an Icp34.5 Deleted OHSV with Both Direct and Covert Modes of Action

Joe Conner, Ph.D., CSO, Virttu Biologics

Seprehvir, an oncolytic HSV, is a complex biologic with multi-mechanistic modes of action. Lytic cytotoxicity, induction of Th1 cytokines/chemokine responses, recruitment of innate and adaptive immune cells and changes in the tumor microenvironment can enhance therapeutic efficacy in combination with other anti-cancer agents. How these modes of action intersect with PD-1 checkpoint inhibitors, CAR T cells and small molecule targeted therapies will be discussed.

11:00 The Mechanism of Action of Oncos-102, Oncolytic Adenovirus-Based Immune Activator

Antti Vuolanto, Ph.D., Executive Vice President, Targovax

ONCOS-102 is an engineered human serotype 5 adenovirus expressing GMCSF. A total of 12 cancer patients were treated with repeated intratumoral injections of ONCOS-102 in a Phase I study. Eleven

out of twelve patients showed a post-treatment increase in tumor-infiltrating immune cells including CD8+ T cells and two patients showed systemic induction of tumor specific CD8+ T cells.

11:30 Moving Toward MultiFunctionality in PoxvirusBased Oncolytic Virotherapy

Eric Quemeneur, Ph.D., Pharm.D., Executive VP and CSO, Transgene

Poxviruses are powerful immunotherapeutics and tumor-targeting platforms. We recently expanded Transgene’s portfolio of armed oncolytic Vaccinia Viruses (oVV) by engineering a vector that targets anti-PD1 IgG expression into the tumor. Local concentration of virus-encoded antibody was ~10-50 times higher than the reference mAb, leading to significant improvement of survival in a sarcoma preclinical model. Such results announce the next-generation oVVs, combining immunogenic oncolysis with the capacity to deliver complex therapeutic modalities in the tumor micro-environment.

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:30 Session Break

BIOMARKERS AND IMPROVING VIRUS ACTIVITY

1:25 Chairperson’s Remarks

David Kirn, M.D., CEO & Co-Founder, 4D Molecular Therapeutics & Adjunct Professor of Bioengineering, UC Berkeley

1:30 New Biomarkers that Predict Response to Oncolytic Virus Immunotherapy

Howard L. Kaufman, M.D., FACS, Associate Director, Clinical Sciences, Rutgers Cancer Institute of New Jersey; Professor and Chief, Division of Surgical Oncology, Rutgers Robert Wood Johnson Medical School

T-VEC is the first oncolytic virus approved for the treatment of melanoma, and will soon enter clinical trials for treatment of other cancers. Further studies using T-VEC in combination with T cell checkpoint inhibitors are underway and showing promising early results. The identification of predictive biomarkers of response would be helpful for improving patient selection and optimizing therapeutic outcomes. We have recently focused on HSV-1 entry receptors and oncogenic signaling pathways within cancer cells as potential biomarkers of T-VEC response.

2:00 Therapeutic Viral Vector Evolution: A Robust Platform for the Discovery of Optimized Vectors

David Kirn, M.D., CEO & Co-Founder, 4D Molecular Therapeutics; Adjunct Professor, Bioengineering, University of California, Berkeley

Therapeutic virus vectors hold great promise for cancer gene and immunotherapy. However, novel vectors with improved efficacy are needed. Therapeutic Vector Evolution is a discovery platform from which optimized and proprietary viral vectors can be identified with beneficial characteristics of interest.

2:30 Enhancing Oncolytic Virus Activity by Engineering of Artificial MicroRNAs

John Bell, Ph.D., Senior Scientist, Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Professor, Departments of Medicine and Biochemistry, Microbiology & Immunology, University of Ottawa

We have devised a novel strategy to enhance the ability of oncolytic viruses to infect malignant cells by expressing artificial microRNAs (amiRNAs) from the oncolytic virus genome. We have screened a variety of amiRNAs and identified a number that enhance virus replication within tumour but not normal cells. The characterization of these miRNAs and their targets will be discussed.

3:00 Refreshment Break

3:30 KEYNOTE PRESENTATION: ONCOLYTIC IMMUNOTHERAPY IN THE ERA OF CHECKPOINT BLOCKADE

Robert Coffin, Ph.D., CEO, Replimmune

Oncolytic immunotherapy treats cancer by virus-mediated tumor cell lysis and generation of a patient specific cancer vaccine, including to neo-antigens, in situ directly in the patient. Both are likely important for the clinical efficacy seen with single agent use, and also for the clinical synergy observed with immune checkpoint blockade. Background and data supporting single agent and combination use will be discussed, and future directions described.

4:00 Arming the Oncolytic Virus Enadenotucirev to Develop Tumor-Localized Combination Immunotherapeutics

Brian Champion, Ph.D., Senior Vice President, R&D, PsiOxus Therapeutics Ltd.

We have developed a systemically deliverable, oncolytic adenoviral platform for directing efficient and selective local production of a combination of biotherapeutic agents selectively within the tumor. This has

the potential for enhanced efficacy while reducing side effects by limiting systemic exposure. Up to three separate biomolecules can be encoded in the same virus without affecting oncolytic properties of the virus.

4:30 Immuno-Oncolytic Viruses as Cancer Therapies

Stephen Thorne, Ph.D., Professor and Scientific Advisor, Inventor, Western Oncolytics

Oncolytic viruses primarily act as immunotherapies, yet most vectors still rely on the virus’ inherent immune activation, often coupled to single cytokine transgene expression. However, for optimal activity they will need to overcome the tumor¹s immunosuppressive microenvironment, to raise anti-tumor CTL and allow repeated systemic delivery. Approaches to achieve all of these activities in a single vector are being developed.

5:00 End of Day

 

TUESDAY, AUGUST 30

8:00 am Morning Coffee

TRANSLATIONAL AND CLINICAL UPDATES

8:25 Chairperson’s Opening Remarks

8:30 Phase I of Intravenous Vcn-01 in Patients with Advanced Cancer: Update on Clinical & Biologic Data

Manel Cascallo, Ph.D., Co-Founder, President and CEO, VCN Biosciences

A first-in-human Phase I dose escalation study of intravenous administration of VCN-01 (an oncolytic adenovirus with RB tumour-targeting properties and expressing hyaluronidase) with or without gemcitabine and Abraxane is ongoing for patients with advanced solid tumours including pancreatic cancer. Dose dependent tolerability data and VCN-01 levels in different biological samples (including blood and tumour biopsies) are available.

 

8:50 T-Stealth Technology Mitigates Antagonism between Oncolytic Viruses and the Immune System through Viral Evasion of Anti-Viral T-Cells

Matthew Mulvey, Ph.D., CEO, BeneVir

Simultaneous combination of OV and immune checkpoint inhibitors (ICI) are antagonistic because ICI enhance anti-viral T-cell effector activity and speed OV clearance. BeneVir’s T-StealthTM armed OV mitigate antagonism between OV and ICI because they evade anti-viral T-cells. This allows OV and ICI to be administered simultaneously over several treatment cycles to maximize the likelihood of a synergistic clinical response

9:10 Reolsyin: A Clinical Update of a Directed Cytotoxic Agent and Immune Modulator

Brad Thompson, Ph.D., CEO, Oncolytics Biotech

REOLYSIN was initially investigated for its potential as a selective cytotoxin. However, recent research shows that it also functions as an immune modulator. This dual mechanism of action for a single viral agent suggests that the potential of viral therapies may be broader than previously anticipated.

9:30 Retroviral Replicating Vectors for Cancer-Selective Immuno/Gene Therapy: Translational and Clinical Update

Noriyuki Kasahara, M.D., Ph.D., Professor, Departments of Cell Biology and Pathology, CoLeader, Viral Oncology Program, University of Miami

Pro-drug activator gene therapy with retroviral replicating vectors is tumor-selective, and can lead to development of anti-tumor immunity. Ascending dose Phase I trials by Tocagen Inc. in recurrent high-grade glioma demonstrated favorable safety and tolerability, intratumoral virus spread, radiographic responses, and survival surpassing historical benchmarks. Based on these results, a randomized controlled Phase II/III trial is now underway.

10:00 Sponsored Presentations (Opportunities Available)

10:30 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

11:15 Virus Manufacturing Comes of Age: Turning Bugs into Features Anthony Davies, Ph.D., COO, 4D Molecular Therapeutics

Viruses destroy the host in which you’re trying to produce them and then must be separated from all components of those cells. Many solutions to these challenges have been invented since the earliest production of viral vaccines in primary cells obtained directly form animals. But few have proven amenable to cost-effective, compliant and scaleable operation.

11:45 Manufacturing Large Enveloped Oncolytic Viruses for Human Clinical Trials

Mark J. Federspiel, Ph.D., Professor and Director, Viral Vector Production Laboratory, Mayo Clinic

The large-scale production and purification of larger enveloped oncolytic viruses are particularly challenging. We have developed enveloped virus GMP production processes using suspension cells in combination with gentle but effective purification using hollow fiber tangential flow filtration that result in greater than 99.5% removal of contaminants and greater than 100-fold increases in final infectious virus titers.

12:15 pm Close of Oncolytic Virus Immunotherapy