Cambridge Healthtech Institute’s 3rd Annual

Oncolytic Virus Immunotherapy

Commercializing the Exciting Potential of Oncolytic Virotherapy

August 27-28, 2018

Oncolytic virotherapy (OV) represents an exciting new area of cancer treatment by exploiting 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 and developments by Pfizer, Celgene and Amgen, to name but a few, plus scientific developments in using OV in combination studies.

CHI’s Oncolytic Virus Immunotherapy conference brings together leading industry and academic leaders to discuss the critical steps needed to accelerate oncolytic virus immunotherapy, from delivery to combination therapy strategies, virus engineering to critical product updates.


Final Agenda

MONDAY, AUGUST 27

7:30 am Registration & Morning Coffee (Harbor Level)

FUTURE OF ONCOLYTIC VIROTHERAPY
Cityview 2

8:25 Chairperson’s Opening Remarks

Samuel D. Rabkin, PhD, Professor, Neurosurgery, Massachusetts General Hospital and Harvard Medical School


8:30 FEATURED PRESENTATION: Unlocking the Full Potential of Cancer Immunotherapy

Kirn_DavidDavid Kirn, MD, Co-Founder & Executive Chairman, IGNITE Immunotherapy

IGNITE Immunotherapy is working to unlock the full potential of cancer immunotherapy. Our optimized intravenous oncolytic cancer vaccines are designed to complement approved immune checkpoint inhibitors by igniting an immune response to patients’ cancers. This presentation will examine the current opportunities and future challenges.

9:00 Multiply Armed HSV-Based Immulytics for the Treatment of Cancer, Both Alone and in Combination with Immune Checkpoint Blockade

Coffin_RobertRobert Coffin, PhD, Co-Founder and CEO, Replimune

A number of oncolytic viruses have shown single agent clinical activity and evidence of clinical synergy with immune checkpoint blockade. However, not all patients respond, and as yet most of the promising clinical data has been in melanoma. With the objective of maximally vaccinating patients against their own cancer which will then provide maximal synergy with anti-PD1/L1 blockade, Replimune has developed a new oncolytic immunotherapy platform based on HSV. To augment the natural ability of HSV to kill tumors and activate the immune system, all of Replimune’s viruses are armed with two to four therapeutic genes.

9:30 Engineering Vaccinia Virus for Intratumoral Delivery to Generate “in situ Vaccination” against Cancer

Deng_LiangLiang Deng, MD, PhD, Lab Head, Dematologist, Memorial Sloan Kettering Cancer Center

Vaccinia virus is a large cytoplasmic DNA virus. Modified vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus, an important vaccine vector. I will discuss our published study on the intratumoral delivery of inactivated MVA to induces systemic antitumor immunity and to overcome resistance to immune checkpoint blockade. I will also discuss two platforms of vaccinia-based immunotherapeutics developed in our laboratory at Memorial Sloan Kettering Cancer Center.

10:00 Coffee Break (Harbor and Plaza Levels)

10:30 Novel Micro-RNA Attenuated Oncolytic HSV Virus with Combinatorial Immune Payloads for the Treatment of Metastatic Cancer

Queva_ChristopheChristophe Queva, PhD, CSO, Oncorus

Oncorus is developing the next generation HSV-based oncolytic virus with enhanced potency for tumor cell killing and recruitment of the immune system. Our innovative miR-attenuation strategy enables robust viral replication in tumor cells, while preventing replication in healthy tissue. Oncorus’ oHSV are armed with multiple immunomodulatory payloads to synergistically increase recruitment and effector function of immune cells, thus harnessing the full potential of OVs to evoke an abscopal immune response.

11:00 Targeted Oncolytic HSVs - Improving OV Potency, Targeting and Efficacy

Campadelli-Fiume_GabriellaGabriella Campadelli-Fiume, Dr, Professor, Microbiology and Molecular Virology, University of Bologna (UNIBO)

This class of o-HSVs are de-targeted from their natural receptors and re-targeted to cancer-specific surface antigens to selectively infect and kill cancer cells, yet preserve the full-blown virulence of wt-HSVs, and wt ability to elicit innate and adaptive immunity. They cause immunogenic cell death, recruit T cells at the tumor site and reactivate T cells in the tumor micro-environment. This next generation of oncolytic HSVs can be “armed” by encoding immunomodulatory molecules to potentiate the anti-tumor effect. They exert abscopal, long term protection, and prime for checkpoint blockade. They can be tailored to counteract multiple solid tumor indications.

11:30 Downstream Processing of Shear-Sensitive Oncolytic Viruses

Ales Strancar, Managing Director, BIA Separations

Filtration and chromatography are powerful tools for virus purification but they can impose shear forces that potentially damage the product. Lipid enveloped viruses frequently experience inactivation, sometimes accompanied by removal of the outer envelope. Outer envelope removal is not a concern for non-lipid-enveloped species but some are brittle and also suffer serious loss of function. This presentation will re-cap sources of shear in filtration and chromatography devices and discuss the effects of common process variables.

Oncolys Biopharma12:00 pm Luncheon Presentation: Multidisciplinary Telomerase-Specific Oncolytic Virotherapy for Esophageal Cancer

Fujiwara_ToshiyoshiToshiyoshi Fujiwara, MD, PhD, Professor & Chairman, Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences

Telomelysin (OBP-301) is an attenuated oncolytic adenovirus, in which the telomerase promoter drives expression of E1 genes. To determine the feasibility, efficacy, and pharmacokinetics of Telomelysin in combination with radiotherapy, an investigator-driven clinical study was designed. Multiple courses of endoscopic Telomelysin injection with radiotherapy were feasible and well tolerated in patients with esophageal cancer, and appeared to provide clinical benefit.


12:30 Session Break

IMPROVING OV POTENCY, TARGETING AND EFFICACY
Cityview 2

1:25 Chairperson’s Remarks

Fares Nigim, MD, Massachusetts General Hospital and Harvard Medical School

1:30 A Novel Oncolytic Vaccinia Virus

Larissa Pikor, PhD, Post Doctoral Fellow, John Bell Lab, Ottawa Hospital, General Campus

Vaccinia virus has a still incompletely understood genome although several strains of this virus are already in clinical development as oncolytics. We designed studies to obtain a more in depth understanding of the genetic elements of vaccinia which could be modulated to improve the oncolytic/therapeutic characteristics of the virus. A novel oncolytic candidate has been bioselected and engineered and the key enhanced therapeutic properties of this virus will be presented.

2:00 A novel oncolytic virus expressing multiple immune regulatory factors to change tumor immune microenvironment

William Jia, PhD., Associate Professor, Surgery, University of British Columbia

VG161 oncolytic virus expressing 3 immune regulatory factors caused strong anti-tumor specific immune response and and lasting complete tumor eradication in animal models

2:30 VSV-GP Oncolytic Virus Therapy Works through Direct Tumor Lysis and Stimulation of an Anti-Tumor Immune Response

Monika Petersson, PhD, Scientist, ViraTherapeutics GmbH

VSV-GP combines the tumour cell killing efficacy of Vesicular Stomatitis Virus (VSV) with an enhanced safety profile and remarkable immune stimulatory properties, making it an excellent candidate for clinical development as treatment option for advanced cancers. We have demonstrated that VSV-GP infects and cures a range of xenograft and syngeneic mouse tumor models. In addition to direct tumor cell killing VSV-GP treatment leads to a strong as well as durable anti-tumor immune response and immunological memory formation.

3:00 Breakout Discussion Groups and Refreshment Break (Harborview)

This session features discussion groups that are led by a moderator who ensures focused conversations around the key issues listed. Attendees choose to join a specific group, and the small, informal setting facilitates sharing of ideas and active networking. Details on the topics and moderators are available on the conference website.

4:10 Chairperson's Remarks

Matthew Mulvey, PhD, CEO, BeneVir Biopharm, Inc.

4:15 Profiling Anti-Tumor Activities of Seprehvir and Seprehvec

Robert Allen, Head of Oncolytic Immunotherapy, Oncolytic Virotherapy, Sorrento Therapeutics

Seprehvir and Seprehvec, as monotherapies or in combination with Sorrento antibodies and cell-based therapeutics, provide a flexible means of directing and enhancing anti-tumor immunity. The Seprehvec platform has been designed to express mediators of anti-tumor immunity following systemic, intratumoral, and local-regional delivery of virus.

4:45 Enadenotucirev: An Adenovirus with Immunotherapeutic Potential in Its Native Form, or as a Vector for Therapeutic Transgenes

Morris_CharlesCharles Morris, PhD, CDO, Psioxus

Enadenotucirev is a potent, chimeric Ad11p/Ad3 adenovirus with selective oncolytic activity against a range of epithelial cancer cells. An ongoing clinical study is investigating whether this inflammatory infiltrate can lead to clinical efficacy in combination with an immune checkpoint inhibitor in tumors not otherwise likely to respond to such treatment. A number of potential clinical candidate armed viruses have been produced and will be described.

5:15 Progress with Oncolytic Vesicular Stomatitis Viruses

Russell_StephenStephen J. Russell, MD, PhD, CEO, Vyriad, Inc.

Vesicular Stomatitis Virus (VSV) has low seroprevalence, is readily engineered to encode additional transgenes and can easily be manufactured to high titers for systemic administration to human subjects. Vyriad is developing and testing different different VSV designs for the treatment of human cancer. Voyager-V1, a recombinant VSV carrying transgenes coding for interferon-β and the sodium iodide symporter, is currently being evaluated in three Phase 1 clinical trials. Fully retargeted VSVs encoding fusogenic measles virus glycoproteins are also under development. Preclinical and clinical progress with Vyriad’s lead clinical and preclinical stage virotherapies will be discussed.

5:45 End of Day

TUESDAY, AUGUST 28

7:30 am Morning Coffee (Harbor Level)

IMPROVING OV POTENCY, TARGETING AND EFFICACY
Cityview 2

8:25 Chairperson’s Remarks

Douglas Jolly, PhD, Executive Vice President, R&D, Tocagen, Inc.

8:30 Treatment with Conditionally Lytic Retroviral Replicating Vector Toca 511 Leads to Long Term Survival in Recurrent High Grade Glioma Patients

William Accomando, PhD | Research Scientist 1, R&D Discovery Medicine, Tocagen, Inc.

Toca 511 is a non-lytic retroviral replicating vector encoding an optimized humanized yeast cyosine deaminase, that productively infects tumors with significant specificity. Upon subsequent administration of Toca FC (an extended release formulation of 5---fluorocytosine) about 6 weeks later in recurrent high grade glioma patients undergoing re-resection, tumor regression, durable reponses and extended survival compared to historical controls were observed. These Phase I data provided justification for the ongoing Phase III trial in the same types of patients.

9:00 Gene-Mediated Cytotoxic Immunotherapy and Immune Checkpoint Blockade for Primary Glioblastoma Treatment; A Translational Journey

Lawler_SeanSean Lawler, PhD, Assistant Professor, Managing Director, Harvey Cushing Neurooncology Laboratories, Department of Neurosurgery, Brigham and Women’s Hospital

Recent clinical trial data showed encouraging results when GMCI was used in primary glioblastoma patients in combination with standard of care (median survival 25 months after total gross resection). We have performed preclinical studies in murine glioblastomas which shows very high cure rates with a combination of GMCI and anti-PD1. This concept has now been moved forward and a multi-institutional clinical trial of the combination of GMCI and anti-PD1 is now underway. The data, challenges and outlook for this approach will be discussed.

9:30 An Integrated Approach to Managing Immunogenicity Risk and Drug Immune Modulation

Knowlton_EmileeEmilee Knowlton, Immunology Sales Specialist, Sales, ProImmune, Inc.

ProImmune provides key tools and technologies for studying the mechanisms of cancer immunology at a molecular and cellular level applicable to all areas of cancer immunotherapy. Assays essential in the drug development stage includes Mass Spectrometry assay for characterization of antigen presentation, DC-T/T cell proliferation assays for biologic lead selection and an undiluted whole blood cytokine storm assay, while multimers and IFN gamma ELISpots can be used to measure immune responses during clinical trials.

10:00 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)

LATE STAGE DEVELOPMENTS AND MANUFACTURING
Cityview 2

10:55 Chairperson’s Remarks

Douglas Jolly, PhD, Executive Vice President, R&D, Tocagen, Inc.

11:00 Designing Clinical Trials to Elucidate Oncolytic Virus Mechanisms-of-Action

Breitbach_CarolineCaroline Breitbach, PhD, 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.

11:30 Development and Characterization of Novel Micro-RNA Attenuated Oncolytic Herpes Simplex Viruses

Paglia_MichaelMichael Paglia, MSc, Vice President, CMC Operations, Oncorus

Oncorus is developing next generation HSV-based oncolytic virus with enhanced potency for tumor cell killing and recruitment of the immune system. Our innovative miR-attenuation strategy enables robust viral replication in tumor cells, while preventing replication in healthy tissue. The development and characterization of therapeutic oHSV requires thorough product understanding gained through process characterization. Strategies for development and characterization of manufacturing processes centered around a strong organizational infrastructure will be presented.

12:00 pm Close of Oncolytic Virus Immunotherapy

#IOSummit