Cambridge Healthtech Institute’s 5th Annual

Oncolytic Virus Immunotherapy

Engineering, Developing and Commercializing Oncolytic Virotherapy

October 6, 2020

The use of oncolytic viruses has expanded rapidly over the past five years with interest in the field at an all-time high following recent scientific breakthroughs and multi-million dollar investments from big pharma. Cambridge Healthtech Institute’s Fifth Annual Oncolytic Virus Immunotherapy conference brings together leading academics, clinicians and industry experts to discuss the latest developments in oncolytic virotherapy and the steps needed to accelerate product development – from virus engineering to new mechanisms of action; combinations to major clinical updates; delivery to commercialization.

Tuesday, October 6

LESSONS LEARNT FROM RECENT OV TRIALS

Noriyuki Kasahara, MD, PhD, Professor & Alvera L. Kan Endowed Chair, Neurological Surgery & Radiation Oncology, University of California, San Francisco (UCSF)

Toca 511, an optimized retroviral replicating vector for prodrugactivator gene therapy, showed evidence of therapeutic benefit in Phase I trials for recurrent high-grade glioma, leading to a Phase II-III trial completed recently (n=403, randomized 1:1 vs. standard chemotherapy), which appeared to show negative results overall. However, prodrug dosing was not optimal, and further subgroup analysis has shown promising possible efficacy. Further clinical investigation and translational development are ongoing.

9:20 am Session Break

ENGINEERING NEXT-GENERATION ONCOLYTIC VIROTHERAPIES

9:40 am

Rational Engineering of Recombinant Modified Vaccinia Virus Ankara to Enhance Both Innate and Adaptive Immunity for Cancer Immunotherapy

Liang Deng, MD, PhD, Associate Member/Laboratory Head, Department of Medicine, Memorial Sloan Kettering Cancer Center

Intratumoral (IT) delivery of immune-activating viruses can serve as an important strategy to turn “cold” tumors into “hot” tumors leading to overcoming resistance to immune checkpoint blockade (ICB). Modified vaccinia virus Ankara (MVA) is a highly attenuated, non-replicative vaccinia virus that has a long history of human use. In this presentation, I will discuss strategies to engineer recombinant MVA to enhance both innate and adaptive immunity in several preclinical murine tumor models, which synergies with ICB.

10:00 am Session Break - View Our Virtual Exhibit Hall

ONCOLYTICS IN COMBINATION

10:40 am Integrating Oncolytic Viruses into Combination Therapy for Cancer
Howard L. Kaufman, MD, Head, R&D, Immuneering Corp.; Clinical Associate, Division of Surgical Oncology, Massachusetts General Hospital

Oncolytic viruses (OVs) elicit immunogenic cell death and promote anti-tumor immunity. Given the induction of in situ vaccination against cancer cells and the safety profile of OVs, there has been increased interest in integrating OVs’ more rational combination strategies. We have recently shown potent synergy between MEK inhibition and T-VEC in preclinical tumor models. In this presentation, emerging data on how to optimize anti-tumor immunity with OVs will be reviewed.

11:00 am Combination with Oncolytic Adeno-Immunotherapy and CAR T Cells for Advanced Solid Tumors
Masataka Suzuki, PhD, Assistant Professor, Center for Cell & Gene Therapy, Department of Medicine, Baylor College of Medicine

In solid tumors, CAR T cells must overcome the challenges of the immunosuppressive tumor microenvironment. We hypothesized that pretreating tumors with our oncolytic adeno-immunotherapy that produces local oncolysis and expresses immunostimulatory molecules would enhance the antitumor activity of adoptively transferred CAR T cells. Our results indicate that local treatment of our “all-in-one” vector can systemically enhance both adoptive CAR T cell and endogenous adaptive T cell responses to cancer cells.

11:20 am Oncolytic HSV Combinations; Sometimes They Work
Samuel D. Rabkin, PhD, Professor, Neurosurgery, Massachusetts General Hospital and Harvard Medical School

Oncolytic herpes simplex virus (oHSV) is both directly cytotoxic and immunotherapeutic. To enhance efficacy, combination therapies are often used, especially those that alter the tumor microenvironment and immune milieu. Combinations include ‘arming’ oHSV with therapeutic transgenes or systemic administration of pharmacological agents, such as immune checkpoint antibodies and molecularly targeted drugs. We will discuss preclinical combination studies with oHSV and approved drugs that impacted immunological outcomes beneficially and adversely.

11:40 am ONCOS-102: Clinical Results from Melanoma and Mesothelioma Combination Trials
Erik Digman Wiklund, PhD, Chief Business Officer, Science & Business Development, Targovax ASA

Targovax is developing ONCOS-102, an armed oncolytic adenovirus, which is being tested in three Phase I/II combination trials in mesothelioma, melanoma, and peritoneal cancers. The mesothelioma and melanoma trials have reported encouraging efficacy data over the past months, and a summary of the findings to date will be presented.

12:00 pm Session Break – View Our Virtual Exhibit Hall

ADVANCES IN HSV-BASED ONCOLYTIC VIROTHERAPY

12:30 pm

Engineering Oncolytic Picornaviruses as RNA-Based Therapeutics to Enhance Oncolytic Immunotherapy

Autumn J Schulze, PhD, Assistant Professor, Molecular Medicine, Mayo Clinic and Foundation

 

Several picornaviruses, including CVA21, have proven safe and demonstrated preliminary efficacy based on oncolytic and immunotherapeutic mechanisms. Formulating oncolytic picornaviruses as synthetic infectious RNA provides a mechanism for enhancing cytolytic activity during repeat dosing that can in turn augment the antitumor immune response. Both full-length picornaviral genomes and self-amplifying replicons encoding immune-modulating cargo can be formulated as infectious RNA. Preclinical development of both platforms will be discussed in this presentation.


 

12:50 pm Next-Generation Oncolytic Immuno-Gene Therapy Based on HSV
Robert Coffin, PhD, CEO & Founder, Replimune Ltd

Replimune has developed enhanced potency versions of oncolytic HSV designed to maximize direct tumor destruction and immunogenic cell death, and also maximize the systemic anti-tumor immune response then generated through arming with genes encoding multiple immune-stimulating proteins. Progress with
the development of this plaform, the lead product from which is now in registration-directed clinical development, will be discussed.

1:10 pm Impact of Oncolytic HSV on NOTCH Signaling
Balveen Kaur, PhD, Professor, Vice Chair, Research, John P. and Kathrine G. McGovern Endowed Chair, Department of Neurosurgery, University of Texas

Oncolytic HSV therapy is a biotherapy that can change both tumor and tumor microenvironment. NOTCH signaling is a signaling pathway that communicates between cells and plays an important role in tumor biology. The impact of oncolytic HSV therapy on NOTCH signaling has not been described to our knowledge. Impact of HSV virotherapy on NOTCH signaling will be discussed in this presentation.

1:30 pm Session Break - View Our Virtual Exhibit Hall

ADVANCES IN HSV-BASED ONCOLYTIC VIROTHERAPY

2:05 pm

Update from CG Oncology

Paola Grandi, PhD, CSO, CG Oncology, Inc.

CG Oncology is currently investigating the company’s first product, CG0070, for the treatment of non-muscle invasive bladder cancer in the BCG-unresponsive patient population. In addition, CG Oncology is exploring the use of CG0070 in combination with immune checkpoint inhibitors in various solid tumors.

2:25 pm ONCR-177, an Oncolytic HSV-1 Designed to Potently Activate Systemic Antitumor Immunity
Lorena Lerner, PhD, Vice President, Molecular Biology and Virology, Oncorus, Inc.

ONCR-177 is a highly engineered recombinant oncolytic Herpes Simplex Virus (oHSV) designed to be a well-tolerated and efficacious therapy for the treatment of solid tumors. ONCR-177 is armed with five transgenes selected for activation of antitumor immunity. Significant efficacy, survival benefit, and the elicitation of protective immunity were demonstrated in multiple syngeneic tumor models and warrant the clinical investigation of ONCR-177 in patients with metastatic cancer.

2:45 pm PANEL DISCUSSION:

Current Challenges in Oncolytic Virotherapy

Panel Moderator:
Samuel D. Rabkin, PhD, Professor, Neurosurgery, Massachusetts General Hospital and Harvard Medical School
Panelists:
Robert Coffin, PhD, CEO & Founder, Replimune Ltd
Stephen J. Russell, MD, PhD, CEO, Vyriad, Inc.
Paola Grandi, PhD, CSO, CG Oncology, Inc.
Noriyuki Kasahara, MD, PhD, Professor & Alvera L. Kan Endowed Chair, Neurological Surgery & Radiation Oncology, University of California, San Francisco (UCSF)
3:15 pm Session Break - View Our Virtual Exhibit Hall
3:35 pm Interactive Breakout Discussions - View Our Virtual Exhibit Hall

Join your colleagues and fellow delegates for a focused, informal discussion moderated by a member of our speaking faculty.  A small group format allows participants to meet potential collaborators, share examples from their own work and discuss ideas with peers.

The Future of Oncolytic Viruses in Immuno Oncology

Fares Nigim, M.D, PhD, Research Fellow, Neurosurgery, Massachusetts General Hospital
4:05 pm Close of Oncolytic Virus Immunotherapy Conference





Final Agenda Available

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