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

OPENING KEYNOTE SESSION

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

Robert Coffin, PhD, Co-Founder and CEO, 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 Sponsored Presentation (Opportunity Available)

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

MULTIPLEX PLATFORM

10:45 Building a Battleship to Treat Cancer: Next-Generation Viral Immunotherapy

Michael F. Burgess, PhD, President, Research and Development, Turnstone Biologics

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

John Beadle, MD, MBA, CEO, 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 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Dessert Break in the Exhibit Hall with Poster Viewing

13:15 Session Break

ADVANCES IN CLINICAL TRIALS

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

ADVANCES IN CLINICAL TRIALS (CONT.)

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

MODULATING THE IMMUNE SYSTEM

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 Sponsored Presentation (Opportunity Available)

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

DISCOVERING NEW OV PLATFORMS

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 Preclinical Development of Next-Generation Oncolytic Vaccinia Viruses for Use as Immunotherapies

Steve H. Thorne, CSO, 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 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Dessert Break in the Exhibit Hall with Poster Viewing

13:30 Close of Oncolytic Virus Immunotherapy