Cambridge Healthtech Institute’s Inaugural
Oncolytic Virus Immunotherapy
Clinical Successes and Commercialization Strategies
20-21 March 2019
Oncolytic
virotherapies have been emerging recently as potential in situ tumor vaccines with an attractive therapeutic combination of tumor-specific cell lysis together with patient-specific immune stimulation against cancer. The scientific community
has continued to be impressed by the effectiveness and safety profile of these approaches, which have generated significant interest in this field. Cambridge Healthtech Institute’s Inaugural Oncolytic Virus Immunotherapy conference recognizes
this active field and will bring together leading industry and academic leaders to discuss the critical steps needed to accelerate oncolytic virus immunotherapy into the clinic.
Final Agenda
WEDNESDAY 20 MARCH
7:45 Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
John Bell,
PhD, Senior Scientist, Center for Innovative Cancer Research, Ottawa Hospital Research Institute
8:35 Multiply Armed HSV-Based Oncolytic Immuno-Gene Therapy for the Treatment of Cancer, both Alone & in Combination with Immune Checkpoint Blockade
Colin Love,
PhD, COO, Replimune
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. A virus expressing a fusogenic glycoprotein and human GM-CSF (RP1) is currently in a large
Phase I/ II clinical trial as
single agent and in combination with
anti-PD1 blockade in multiple tumor types. Further viruses expressing proteins which act at the site of immune response initiation in tumors and draining lymph nodes are in development, including viruses additionally expressing anti-CTLA-4 and
immune co-stimulatory pathway ligands.
9:05 Vyriad’s Voyager-V1 Program: Pharmacological Enhancement of a Systemically Active, Single Cycle Oncolytic Virus
Stephen J. Russell, MD,
PhD, CEO, Vyriad, Inc.
Vyriad’s Voyager-V1 is a low seroprevalence virus capable of spreading systemically via the bloodstream. Voyager-V1 is armed with IFNβ and NIS transgenes to enhance its potency and to guide its successful clinical development. Early
Phase I clinical data provides a compelling endorsement of the MOA by intravenous and intratumoral routes, and as monotherapy or combination therapy. Phase II trials are planned in colorectal cancer and T cell lymphoma.
9:35 Plasmacytoid dendritic cells orchestrate Coxsackievirus A21 (CAVATAKÒ) immunotherapy
Fiona Errington-Mais, PhD, Lecturer, Immunology, University of LeedsCombination therapies offer the best chance of disease control; however, the design of successful combination strategies requires a deeper understanding of the mechanisms underpinning OV efficacy. Using disease models which were sensitive or resistant
to coxsackievirus A21 (CVA21)-direct oncolysis, we have demonstrated a role for both the innate and adaptive arms of the immune system for CVA21 efficacy. Upon further characterization of the immune response, we have identified type I
IFNs as the key mediators of NK cell activation, demonstrated that ICAM-1 expression on immune cell components was pivotal for CVA21-induced immunotherapy, and established that plasmacytoid dendritic cells orchestrate the immune response. Importantly,
a role for CVA21 immunotherapy, in disease models which were inherently resistant to CVA21-direct oncolysis, was also confirmed.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Building a Battleship to Treat Cancer: Next-Generation Viral Immunotherapy
Michael F. Burgess,
PhD, President, Research and Development, Turnstone Biologics Fiona Errington-Mais, PhD, Lecturer, Immunology, University of Leeds
Oncolytic viruses are well positioned to deliver multimodal therapy. We used a combination of functional genomics and bio-selection strategies to generate a novel oncolytic vaccinia backbone (termed SKV) containing a large genome deletion which exhibited
augmented oncolytic activity and improved tumor selectivity. Due to the exquisite tumor selectivity of
SKV we have been able to engineer and express three potent immune modulators that are safest and most effective when expressed within the TME: anti-CTLA4 antibody,
membrane tethered IL-12 and the antigen presenting cell activating ligand FLT-3L.
11:15 T-SIGn Gene Therapy Vectors for Solid Tumor Therapy: Designing Candidate Products to Match Tumor Phenotypes
NEW: Brian Champion,
PhD, Chief Scientific Officer, PsiOxus Therapeutics
Enadenotucirev is an Ad11p/Ad3 chimeric adenovirus with potent and selective anti-tumor activity, with a blood stability profile that enables systemic dosing. It has been administered intravenously to over 100 cancer patients. Tumor-Specific Immuno-Gene
Therapy (T-SIGn) gene therapy vectors are modified viruses that retain all the functional properties of
enadenotucirev, while also mediating the expression of therapeutic transgenes. Each T-SIGn virus is designed to target a different immunological phenotype of
tumor.
11:45 Second-Generation Non-Attenuated Oncolytic HSVs: An Opportunity for Checkpoint Blockade
Gabriella Campadelli-Fiume, Sc. Dr., Professor, University of Bologna
OVs in clinical trials did not meet
to the expectations raised by preclinical studies. Less attenuated OVs are needed. The second-generation non-attenuated tropism retargeted o-HSVs selectively infect cancer cells, preserve the full-blown virulence of wt-HSV. In essence, they
are fully virulent in their target cells and highly safe. The retargeted o-HSVs deeply modify the suppressive tumor microenvironment, exert strong abscopal effect and greatly increase the efficacy of checkpoint inhibitors. They can be tailored
to specifically counteract a variety of solid tumor indications and, given the ample genome space, can be armed simultaneously with multiple immunomodulatory molecules to potentiate the antitumor effects.
12:15 Enjoy Lunch on Your Own
12:45 Dessert Break in the Exhibit Hall with Poster Viewing
13:15 Session Break
14:00 Chairperson’s Remarks
Stephen J. Russell, MD,
PhD, CEO, Vyriad, Inc.
14:05 FEATURED PRESENTATION: Advancing Treatment for Brain Tumors with Oncolytic Adenoviruses
Frank Tufaro,
PhD, CEO, DNAtrix, Inc.
DNX-2401 (
tasadenoturev), which encodes an RGD motif in its fiber to target tumor cells, is the basis for DNAtrix’s adenovirus OV platform. DNAtrix is conducting several clinical trials with armed and unarmed viruses with or without CPIs, in the
US, Canada and EU: two ongoing studies for recurrent GBM (rGBM) in adults and one for DIPG in children. The CAPTIVE study, now fully enrolled, in collaboration with Merck, is investigating the use of DNX-2401 adenovirus followed by pembrolizumab
for rGBM. Early analysis indicates an excellent safety profile and encouraging efficacy. Clinical data will be discussed.
14:35 Adenovirus-Mediated CD40L and 4-1BBL Gene Therapy – From Bench to Bedside
Angelica Loskog, CEO, Lokon Pharma AB
Immunostimulatory gene therapy utilizing viruses to deliver immune stimulation in the tumor microenvironment is an appealing method to stimulate anti-tumor immunity. We have developed an oncolytic adenovirus that encodes a designed trimerized CD40L
and a
full length 4-1BBL. These transgenes are expressed by both tumor and stroma post intratumoral injection and drive DC and T cell activation. Two Phase I/ II trials are ongoing.
15:05 Problem Solving Roundtable Discussions
Virotherapy for Peritoneal Carcinomatosis
Moderator: Ulrich M. Lauer, MD, Professor & Vice Chairman, Internal Medicine VIII, Medicine, University Hospital Tübingen
The Power of Reporter Gene Imaging: The Pharmacologists Dream
Moderator: Stephen J. Russell, MD,
PhD, CEO, Vyriad, Inc.
16:05 Refreshment Break in the Exhibit Hall with Poster Viewing
16:35 Oncolytic Virus Vaccines and Immune Checkpoint Inhibitors
John Bell,
PhD, Senior Scientist, Center for Innovative Cancer Research, Ottawa Hospital Research Institute
Oncolytic viruses are designed to infect and kill cancer cells,
however an important and critical component of their therapeutic activity is the stimulation of
anti-tumour immunity. We have engineered oncolytic viruses to be potent stimulators of
anti-tumour immunity and therapeutics that are optimally active when combined with immune checkpoint inhibitor antibodies.
17:05 ParvOryx02: A Phase II Trial of Intravenous and Intratumoral Administration of Parvovirus H-1 in Patients with Metastatic Pancreatic Cancer
Guy Ungerechts, MD,
PhD, Deputy Director, Medical Oncology Department, National Center for Tumor Diseases (NCT), University Hospital Heidelberg
ParvOryx02 trial with parvovirus H-1 for patients with metastatic pancreatic cancer treated with repeated intravenous and subsequent intralesional (liver metastases) administration has been completed.
Primary endpoint was safety and feasibility. To identify immunological and molecular signatures of responses/non-responses, three serial liver biopsies (before, during, and after treatment) allowed for in-depth analyses of pathological tumor
characteristics, tumor-infiltrating immune cells, quantification of cytokines and chemokines, and investigation of viral replication and tropism.
17:35 Virotherapy for Peritoneal Carcinomatosis - Update on Preclinical & Clinical Studies
Ulrich M. Lauer, MD, Professor & Vice Chairman, Internal Medicine VIII, Medicine, University Hospital Tübingen
Malignancies often disseminate throughout the lining of the abdominal cavity which is referred to as peritoneal carcinomatosis. Oncolytic viruses, employed as a locoregional treatment in these patients, hold a great promise for improving treatment
results obtained with conventional (non-immunological) therapeutic interventions, such as systemic or regional chemotherapies with/without cytoreductive peritonectomy. In this context, an update on preclinical & clinical studies for virotherapy
in peritoneal carcinomatosis is provided.
18:05 Networking Reception in the Exhibit Hall with Poster Viewing
19:05 Close of Day
THURSDAY 21 MARCH
8:00 Morning Coffee
8:30 Chairperson’s Opening Remarks
Frank Tufaro,
PhD, CEO, DNAtrix, Inc.
8:35 Oncolytic Viruses and Adoptive Natural Killer Cell Therapy: A Match Made in Heaven?
Evren Alici, MD,
PhD, Head, Gene and Cell Therapy Group, Division of Hematology, Medicine, Karolinska University Hospital
9:05 Using Oncolytic Adenovirus Armed with TNFa and IL-2 to Modulate the Tumor Microenvironment for Effective T-Cell Therapy and Checkpoint Inhibition
Akseli Hemminki, MD,
PhD, Founder, CEO & Chairman of the Board, TILT Biotherapeutics
I will talk about the observations and patient data from
Advanced Therapy Access Program treated with different oncolytic viruses and share our latest results for TILT Biotherapeutics lead product TILT-123: TNFa and IL-2 armed oncolytic adenovirus.
9:35 Attend Concurrent Track
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Novel Poxviruses for Oncolytic Virotherapy
Eric Quemeneur, PharmD,
PhD, CSO, Transgene
Vaccinia has proven to be an efficient platform for the engineering of armed oncolytic viruses, and many Vaccinia-based products are currently in clinical development. Other poxviruses are also considered to generate new platforms with improved therapeutic
index or biodistribution profiles. In this perspective, we recently studied cowpox, pseudocowpox, and deVV5, a novel virus obtained after shuffling 4 Vaccinia strains. They display interesting complementary features to existing OV platforms.
11:15 NEW: Preclinical Development of Next-Generation Oncolytic Vaccinia Viruses for Use as Immunotherapies
Daniel
Byrd,
PhD, Scientist, Western Oncolytics
Vaccinia virus represents a potent backbone for use in oncolytic viral vectors due to its immune activating properties and systemic delivery potential. Although several oncolytic vaccinia vectors have demonstrated this potential in a clinical
setting,
a next generation of viruses in preclinical development may more effectively combine with existing IO therapies. Several approaches to developing enhanced and more effective vaccinia-based OV therapies will be discussed.
11:45 Replicating Retroviral Vectors as Targeted Immuno-Oncology Agents with Significant Clinical Therapeutic Potential and Safety Record
Douglas J. Jolly,
PhD, Executive Vice President, Research & Pharmaceutical Development, Tocagen, Inc.
Toca 511 is a gammaretroviral replicating vector encoding cytosine deaminase that selectively infects tumor cells and converts the antifungal drug 5-fluorocytosine into the antineoplastic drug 5-fluorouracil, which directly kills tumor cells and
stimulates antitumor immune responses. As part of clinical monitoring of Phase I clinical trials in recurrent high-grade glioma, we have performed extensive molecular analyses of patient specimens to track vector fate.
12:15 Enjoy Lunch on Your Own
12:45 Dessert Break in the Exhibit Hall with Poster Viewing
13:30 Close of Oncolytic Virus Immunotherapy