Our Technology

The Need to do Better

The treatment of certain cancers has improved markedly over the past decade. Whereas many cancer treatments were historically limited to surgical removal, cytotoxic chemotherapy and/or radiation, recent advances target specific genetic changes in individual tumors or redirect the patient’s immune system, particularly T cells, to eliminate tumors to improve outcomes. Unfortunately, most patients do not respond to or relapse following treatment with these therapies.

While these therapies have advanced the treatment of cancer for some patients, many are still underserved, and therapies with improved clinical outcomes are still desperately needed.

The Promise of RNA Immunotherapies

The goal of immuno-oncology therapy is to harness an individual’s immune system and better enable it to identify, attack and kill tumor cells – and to form long lasting immunological memory against such tumors to prevent relapse.

We believe that the best way to significantly improve outcomes for cancer patients is to stimulate not only T cells, as has been the focus of approved immune checkpoint inhibitors and other recent advances in immuno-oncology, but also additional key immune cells within the innate and adaptive immune systems.

We believe RNA immunotherapies are the most promising modality available today to activate multiple arms of the immune system and improve outcomes for cancer patients.

A Unique Therapeutic Approach

Self-amplifying RNA immunotherapies have several properties that differentiate this class from other anti-tumor therapies and make them particularly attractive additions to today’s anti-cancer arsenal.

 

OUR SELECTIVELY SELF-AMPLIFYING RNA Platform

Combining viral immunotherapies with an RNA-based approach to fight cancer

There has been a notable rise in the development and approval of RNA-based vaccines, most prominently for COVID-19, and therapeutics for certain rare diseases. However, to date, there are no approved RNA-based cancer therapies.

The IV-administration of vRNA immunotherapies is an attractive approach for improving the standard of care for many oncology patients because it allows for all tumors in a patient, including micro-metastases that are sometimes difficult to detect and treat, to be treated directly.

To date, however, the therapeutic benefit of RNA modalities has been limited to rare and infectious diseases. Past investigational cancer programs that utilized IV-administered RNA medicines have failed to generate efficacy in the clinic. Additionally, several mRNA therapies in development for cancer require intratumoral delivery to generate anti-tumor responses.

Our proprietary IV-delivered, self-amplifying RNA platform involves a novel, highly innovative combination of RNA- and viral immunotherapy-based modalities, enabling the potential to deliver a new pillar in cancer therapy.

A Novel Selectively Self-Amplifying RNA Immunotherapy Strategy

Our pioneering IV-administered, self-amplifying RNA approach involves encapsulating the RNA genomes of viruses known to kill cancer cells (i.e., viral immunotherapies) in a lipid nanoparticle (or LNP), creating a vRNA/LNP immunotherapy.

This LNP delivery strategy evades the host immune response and allows for systemic distribution throughout the body to tumor sites. The LNP, which is intended to be less immunogenic than a natural viral capsid, is designed to overcome the challenges caused by neutralizing antibodies that have limited the efficacy of previous industry efforts to administer viruses intravenously to treat tumors.

Once inside the tumor cells, and as is the case with other viral immunotherapies, these genomes replicate and generate a burst of infectious virions that then spread locally and infect and kill adjacent tumor cells. In healthy cells, the innate immune system senses genomic replication, shuts down transcription, and no virions are produced.

Oncorus Selectively Self-Amplifying vRNA Mechanism of Action

 

 

Self-Amplifying vRNA Immunotherapy Programs

Our lead vRNA immunotherapy program, ONCR-021, is based on the RNA genome of coxsackievirus A21 (CVA21). This viral genome has demonstrated acceptable safety and tolerability when virions have been administered intravenously in early clinical trials conducted by others, but where efficacy was likely limited by the subsequent development of neutralizing antibodies.

ONCR-021 and any future immunotherapy product candidates to be developed from our selectively self-amplifying RNA platform will utilize shared formulation, regulatory and manufacturing strategies, allowing us to be more efficient in the development of subsequent product candidates.

View our Pipeline to learn more

Oncorus Publications & Presentations

ONCR-719, a Novel, Armed Oncolytic HSV-1 Vector Engineered for Efficacy and Safety in Glioblastoma

Society for Neuro-Oncology (SNO), November 16-20, 2022

Craig A. Strathdee, Federico Giovannoni, Martina Malgora, Linxing Kong, Michael Floyd, Jian Teng, Yulia Gyulakian, Peter Grezsik, Terry Farkaly, Agnieska Denslow, Sonia Feau, Judith Jacques, Edward M. Kennedy, Lorena Lerner, Christophe Quéva, Tooba Cheema, Marco Colonna, and Francisco J. Quintana

Development of intravenously administered synthetic RNA virus immunotherapy for the treatment of cancer

Nature Communications, October 7, 2022

Edward M. Kennedy, Agnieszka Denslow, Jacqueline Hewett, Lingxin Kong, Ana De Almeida, Jeffrey D. Bryant, Jennifer S. Lee, Judy Jacques, Sonia Feau, Melissa Hayes, Elizabeth L. McMichael, Daniel Wambua, Terry Farkaly, Amal A Rahmeh, Lauren Herschelman, Danielle Douglas, Jacob Spinale, Sanmit Adhikari, Jessica Deterling, Matt Scott, Brian B. Haines, Mitchell H. Finer, Ted T Ashburn, Christophe Quéva & Lorena Lerner. Nature Communications. October 7, 2022; DOI: 10.1038/s41467-022-33599-w.

Development of ONCR-788, a synthetic oncolytic virus based on Seneca Valley Virus for the treatment of neuroendocrine tumors

American Association for Cancer Research (AACR), April 8-13, 2022

Edward M. Kennedy, Agnieszka Denslow, Jacqueline Hewett, Lingxin Kong, Ana De Almeida, Jeffrey Bryant, Jennifer S. Lee, Judy Jacques, Sonia Feau, Melissa Hayes, Elizabeth L. McMichael, Daniel Wambua, Jacob Spinale, Matthew Scott, Jessica Deterling, Sean Essex, Jason Auer, Brian B. Haines, Mitchel H. Finer, Ted Ashburn, Christophe Quéva, and Lorena Lerner

ONCR-021 as a systemic intravenous synthetic RNA virus immunotherapy for the repeat treatment of cancer

American Association for Cancer Research (AACR), April 8-13, 2022

Jeffrey Bryant, Agnieszka Denslow, Jacqueline Hewett, Chris Dupont, Lingxin Kong, Ana De Almeida, Irene Rodriguez Sanchez, Jennifer S. Lee, Judy Jacques, Sonia Feau, Daniel Wambua, Adrienne Yanez, Pamela Wang, Jessica Deterling, Matthew Scott, Jason Auer, Brian B. Haines, Christophe Quéva, Lorena Lerner, and Edward M. Kennedy

Initial results of a Phase 1 study of intratumoral ONCR-177, an oncolytic herpes-simplex virus-1 expressing five immunomodulatory transgenes, in subjects with advanced injectable tumors

Society for Immunotherapy of Cancer (SITC), November 12-14, 2021

Jong Chul Park, Hatem Soliman, Gerald Falchook, Taofeek K. Owonikoko, Anna Spreafico, Erminia Massarelli, Meredith McKean,  Laura QM Chow, Patrick A. Ott, Robert Wesolowski, Christos Fountzilas, Corey Whalen, Adrienne G. Yanez, Christopher D. Dupont, Julia Auer, Tooba Cheema, John Goldberg, Ted T.  Ashburn and Igor Puzanov

Synthetic Oncolytic Virus Therapy for Repeat Systemic Treatment of Cancer

International Oncolytic Virus Conference (IOVC), November 5 - 7, 2021

ONCR-GBM: A Novel, Armed Oncolytic HSV-1 Vector Engineered for Efficacy and Safety in Glioblastoma

International Oncolytic Virus Conference (IOVC), November 5 - 7, 2021

Craig A. Strathdee, Federico Giovannoni, Peter Grzesik, Terry Farkaly, Michael Floyd, Lingxin Kong, Sanmit Adhikari, Judith Jacques, Agnieszka Denslow, Edward M. Kennedy, Brian B. Haines, Lorena Lerner, Christophe Quéva, and Francisco J. Quintana

ONCR-177, an oncolytic HSV-1 designed to potently activate systemic antitumor immunity

Cancer Immunology Research, December 22, 2020

Brian B Haines, Agnieszka Denslow, Peter Grzesik, Jennifer S Lee, Terry Farkaly, Jacqueline Hewett, Daniel Wambua, Lingxin Kong, Prajna Behera, Judith Jacques, Caitlin Goshert, Michael Ball, Allison Colthart, Mitchel H. Finer, Melissa W Hayes, Sonia Feau, Edward M. Kennedy, Lorena Lerner and Christophe Quéva. ONCR-177, an Oncolytic HSV-1 Designed to Potently Activate Systemic Antitumor Immunity. Cancer Immunology Research. December 22, 2020; DOI: 10.1158/2326-6066.CIR-20-0609

Design of an interferon-resistant oncolytic HSV-1 incorporating redundant safety modalities for improved tolerability

Molecular Therapy: Oncolytics, August 8, 2020

Edward M. Kennedy, Terry Farkaly, Peter Grzesik, Jennifer Lee, Agnieszka Denslow, Jacqueline Hewett, Jeffrey Bryant, Prajna Behara, Caitlin Goshert, Daniel Wambua, Ana De Almeida, Judith Jacques, Damian Deavall, James B. Rottman, Joseph C. Glorioso, Mitchell H. Finer, Brian B. Haines, Christophe Quéva, and Lorena Lerner.  Molecular Therapy: Oncolytics, Vol 18, pages 476-490.; https://doi.org/10.1016/j.omto.2020.08.004

mONCR-177 oncolytic virotherapy stimulates anti-tumor response

ACCR Annual Meeting Virtual Meeting II, June 22 - 24, 2020

Development of ONCR-177, an armed oncolytic HSV-1 designed for potent and systemic stimulation of antitumor immunity

6th Annual Immuno-Oncology 360°, New York, New York, February 26 – 28, 2020

Design of ONCR-177 base vector, a next generation oncolytic herpes simplex virus type-1, optimized for robust oncolysis, transgene expression and tumor-selective replication

AACR Annual Meeting, Atlanta, Georgia, March 29 – April 3, 2019

Development of ONCR-148, a miR-attenuated oncolytic HSV-1 designed to potently activate antitumor T cell response

AACR Annual Meeting, Atlanta, Georgie, March 29 – April 3, 2019

Development of ONCR-NEP, a lipid nanoparticle delivered oncolytic virus capable of robust in situ amplification resulting in tumor lysis and regression

AACR Annual Meeting, Atlanta, Georgia, March 29 – April 3, 2019

Arming oHSV with ULBP3 drives abscopal immunity in lymphocyte-depleted glioblastoma

JCI Insight, July 11, 2019

Hans-Georg Wirsching, Huajia Zhang, Frank Szulzewsky, Sonali Arora, Paola Grandi, Patrick J. Cimino, Nduka Amankulor, Jean S. Campbell, Lisa McFerrin, Siobhan S. Pattwell, Chibawanye Ene, Alexandra Hicks, Michael Ball, James Yan, Jenny Zhang, Debrah Kumasaka, Robert H. Pierce, Michael Weller, Mitchell Finer, Christophe Quéva, Joseph C. Glorioso, A. McGarry Houghton, and Eric C. Holland.  Arming oHSV with ULBP3 drives abscopal immunity in lymphocyte-depleted glioblastoma. JCI Insight. 2019;4(13):e128217.  https://doi.org/10.1172/jci.insight.128217

 

Cooperation of oncolytic virotherapy with with VEGF-neutralizing antibody treatment in IDH wildtype glioblastoma depends on MMP9

Neuro-Oncology, December 2019

Hans-Georg Wirsching, Sonali Arora, Huajia Zhang, Frank Szulzewsky, Patrick J Cimino, Christophe Quéva, A McGarry Houghton, Joseph C Glorioso, Michael Weller, Eric C Holland, Cooperation of oncolytic virotherapy with VEGF-neutralizing antibody treatment in IDH wildtype glioblastoma depends on MMP9, Neuro-Oncology, Volume 21, Issue 12, December 2019, Pages 1607–1609, https://doi.org/10.1093/neuonc/noz145

Additional Resources

Optimizing oncolytic virotherapy in cancer treatment

Harrington, K., Freeman, D.J., Kelly, B. et al. Optimizing oncolytic virotherapy in cancer treatment. Nat Rev Drug Discov 18, 689–706 (2019). https://doi.org/10.1038/s41573-019-0029-0

Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy

Ribas, A., Dummer, R., et al. Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Cell 170, 1109-1119 (2017). https://www.cell.com/fulltext/S0092-8674(17)30952-2