NECTIN1

ONCR-719 is uniquely engineered to use the Epidermal Growth Factor Receptor (EGFR/EGFRvIII) for viral entry, which is highly expressed in glioblastoma multiforme (GBM); data show that the canonical entry receptor for HSV-1, NECTIN-1, is only minimally expressed in human GBM tumors. ONCR-719 expresses four immunomodulatory payloads, including IL-12, an anti-PD-1 nanobody, 15-hydroxyprostaglandin dehydrogenase (HPGD), and a novel macrophage-modulating Fc-enhanced antibody to reverse GBM’s immunosuppressed tumor microenvironment.ONCR-719 is derived from a potent HSV-1 strain that is engineered with fusogenic mutations to enhance viral spread and oncolysis and with Oncorus’ clinically validated microRNA attenuation strategy for safety. ANDOVER, Mass., Nov. 18, 2022 (GLOBE NEWSWIRE) -- Oncorus, Inc. (Nasdaq: ONCR), a viral immunotherapy company focused on driving innovation to transform outcomes for cancer patients, today announced the presentation of preclinical data for ONCR-719 in a poster at the 2022 Society for Neuro-Oncology (SNO) Annual Meeting, taking place November 17-20, 2022 in Tampa, Florida. ONCR-719 is a novel, armed oncolytic HSV-1 vector engineered with targeted entry via EGFR/EGFRvIII and expresses four immunomodulatory payloads designed to reverse GBM’s immunosuppressive tumor microenvironment. In addition, ONCR-719 is derived from a potent HSV-1 isolate to drive oncolysis, is engineered with fusogenic mutations to enhance viral spread, and uses Oncorus’ clinically validated microRNA attenuation strategy to inhibit viral replication in healthy cells. Highlights from the preclinical poster describing ONCR-719, previously known as ONCR-GBM, include: Minimal expression of HSV-1 virus entry receptor, NECTIN-1, on human GBM samples suggests targeted oncolytic viruses are required to effectively treat human GBM tumors.ONCR-719 has been engineered to enter tumor cells using either EGFR/EGFRvIII or NECTIN-1 as an entry receptor, thereby increasing virus tropism for GBM tumors.EGFR-targeting and engineered fusogenic mutations in ONCR-719 enhance virus spread and tumor immunogenicity by driving syncytia formation in human GBM tumor cell lines.ONCR-719 is engineered to include IL-12, an anti-PD-1 nanobody, 15-hydroxyprostaglandin dehydrogenase (HPGD), and a novel macrophage modulating-Fc enhanced antibody. These payloads confer enhanced T cell recruitment and activation and target the immune suppressive macrophages and myeloid cells in the tumor microenvironment. Multiple payloads or transgenes were screened using in vivo orthotopic GBM models to identify immune-modulatory payloads to target the GBM microenvironment.Together, EGFR/EGFRvIII targeting, oncolytic potency, and incorporation of rationally designed payloads within ONCR-719 leads to enhanced anti-tumor efficacy and complete responses in preclinical orthotopic GBM models.ONCR-719 is engineered for safety in the central nervous system using multiple CNS-specific microRNA targets, Oncorus’ clinically proven strategy to limit viral replication in healthy cells. When injected intracranially in an HSV-1 sensitive mouse, ONCR-719 demonstrates a greater than 50,000-fold tolerability window compared to the unattenuated strain. “Oncolytic viruses are well-positioned to treat this aggressive form of brain cancer. We are excited to share ONCR-719 as a cutting-edge preclinical candidate that is engineered to improve outcomes and can stimulate a productive and durable anti-tumor immune response across multiple mouse models following a single intratumoral injection,” said Theodore (Ted) Ashburn, M.D., Ph.D., President and Chief Executive Officer of Oncorus. “Most notably, we’ve enabled the virus to use EGFR for entry, which is expressed at high levels in GBM. Underscoring the importance of this advance is our data showing that the canonical entry receptor for HSV, NECTIN-1, is only minimally expressed in GBM cells, which arguably makes using EGFR for entry an essential capability for such an agent. By utilizing our clinically proven microRNA attenuation strategy, ONCR-719 is engineered to protect healthy brain tissue while replicating at its full potential in tumor cells.” “GBM is the most common type of primary brain tumor in adults; it’s a devastating disease that has a great unmet need with a 5-year overall survival of approximately 7 percent,” said Tooba Cheema, Ph.D., Senior Director, Translational Medicine and ONCR-719 Program Leader at Oncorus. “We engineered ONCR-719 to overcome the common impediment that this treatment class faces, limited spread of virus in the highly immunosuppressive GBM tumor microenvironment. We are pleased with the results demonstrated in preclinical models and look forward to seeing how our innovations translate into improved outcomes for GBM patients.” ONCR-719 is the company’s second candidate from its HSV Platform and is developed from a clinical isolate of HSV-1 selected for oncolytic potency across cancer cell lines. Further development of ONCR-719 is dependent on a strategic partnership or additional financing. About Oncorus At Oncorus, we are focused on driving innovation to deliver next-generation viral immunotherapies to stimulate the immune system and transform outcomes for cancer patients. We are advancing a portfolio of intratumorally (iTu) and intravenously (IV) administered viral immunotherapies for multiple indications with significant unmet need based on our Herpes Simplex Virus (HSV) and self-amplifying viral RNA/LNP Platforms. Designed as a next-generation viral immunotherapy, our HSV Platform improves upon key characteristics of this therapeutic class to enhance systemic activity with immune stimulating payloads. Our lead HSV program, ONCR-177, currently in the clinic, is designed to be directly administered into a tumor, resulting in high local concentrations of therapeutic agent and its five encoded transgenes, as well as low systemic exposure to the therapy, which could limit systemic toxicities. Our pioneering self-amplifying vRNA/LNP Platform, highlighted by our product candidates ONCR-021 and ONCR-788, involves a highly innovative, novel combination of RNA and LNP-based modalities designed to realize the potential of RNA medicines for cancer. Please visit www.oncorus.com to learn more. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding the utility and potential of Oncorus’ HSV Platform and the engineering of ONCR-719, including its ability to reverse GBM’s immunosuppressed tumor microenvironment, enhance viral spread and oncolysis, inhibit viral replication in certain healthy cells and increase virus tropism for GBM tumors; the ability of oncolytic viruses to treat aggressive brain cancer; ONCR-719’s ability to improve patient safety and efficacy outcomes; and Oncorus’ ability to progress ONCR-719 into the clinic. The words “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “expect,” “estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “target” and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: Oncorus’ ability to successfully demonstrate the safety, tolerability and efficacy of its product candidates and obtain regulatory approval thereof; the adequacy of Oncorus’ existing capital resources and availability of financing on commercially reasonable terms; Oncorus’ ability to obtain the requisite components for its product candidates manufactured in accordance with regulatory requirements; the expansion of Oncorus’ in-house manufacturing capabilities; the impact of COVID-19 on Oncorus’ operations and the timing and anticipated results of its ongoing and planned clinical trials; the accuracy of the Oncorus’ estimates regarding expenses, future revenue, capital requirements and needs for additional financing; and Oncorus’ ability to obtain, maintain and protect its intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Oncorus’ Annual Report on Form 10-K for the year ended December 31, 2021, filed with the Securities and Exchange Commission (“SEC”) on March 9, 2022, and Oncorus’ Quarterly Reports on Form 10-Q for the quarters ended March 31, 2022, June 30, 2022 and September 30, 2022, filed with the SEC on May 4, 2022, August 4, 2022 and November 2, 2022, respectively, as well as discussions of potential risks, uncertainties, and other important factors in the other filings that Oncorus makes with the SEC from time to time. These documents are available under the “SEC filings” page of the Investors section of Oncorus’ website at http://investors.oncorus.com. Any forward-looking statements represent Oncorus’ views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Oncorus explicitly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Oncorus Investor Contact:Stern Investor Relations Julie SeidelJulie.seidel@sternir.com

ANDOVER, MA, USA I November 18, 2022 I Oncorus, Inc. (Nasdaq: ONCR), a viral immunotherapy company focused on driving innovation to transform outcomes for cancer patients, today announced the presentation of preclinical data for ONCR-719 in a poster at the 2022 Society for Neuro-Oncology (SNO) Annual Meeting, taking place November 17-20, 2022 in Tampa, Florida. ONCR-719 is a novel, armed oncolytic HSV-1 vector engineered with targeted entry via EGFR/EGFRvIII and expresses four immunomodulatory payloads designed to reverse GBM’s immunosuppressive tumor microenvironment. In addition, ONCR-719 is derived from a potent HSV-1 isolate to drive oncolysis, is engineered with fusogenic mutations to enhance viral spread, and uses Oncorus’ clinically validated microRNA attenuation strategy to inhibit viral replication in healthy cells. Highlights from the preclinical poster describing ONCR-719, previously known as ONCR-GBM, include: “Oncolytic viruses are well-positioned to treat this aggressive form of brain cancer. We are excited to share ONCR-719 as a cutting-edge preclinical candidate that is engineered to improve outcomes and can stimulate a productive and durable anti-tumor immune response across multiple mouse models following a single intratumoral injection,” said Theodore (Ted) Ashburn, M.D., Ph.D., President and Chief Executive Officer of Oncorus. “Most notably, we’ve enabled the virus to use EGFR for entry, which is expressed at high levels in GBM. Underscoring the importance of this advance is our data showing that the canonical entry receptor for HSV, NECTIN-1, is only minimally expressed in GBM cells, which arguably makes using EGFR for entry an essential capability for such an agent. By utilizing our clinically proven microRNA attenuation strategy, ONCR-719 is engineered to protect healthy brain tissue while replicating at its full potential in tumor cells.” “GBM is the most common type of primary brain tumor in adults; it’s a devastating disease that has a great unmet need with a 5-year overall survival of approximately 7 percent,” said Tooba Cheema, Ph.D., Senior Director, Translational Medicine and ONCR-719 Program Leader at Oncorus. “We engineered ONCR-719 to overcome the common impediment that this treatment class faces, limited spread of virus in the highly immunosuppressive GBM tumor microenvironment. We are pleased with the results demonstrated in preclinical models and look forward to seeing how our innovations translate into improved outcomes for GBM patients.” ONCR-719 is the company’s second candidate from its HSV Platform and is developed from a clinical isolate of HSV-1 selected for oncolytic potency across cancer cell lines. Further development of ONCR-719 is dependent on a strategic partnership or additional financing. About Oncorus At Oncorus, we are focused on driving innovation to deliver next-generation viral immunotherapies to stimulate the immune system and transform outcomes for cancer patients. We are advancing a portfolio of intratumorally (iTu) and intravenously (IV) administered viral immunotherapies for multiple indications with significant unmet need based on our Herpes Simplex Virus (HSV) and self-amplifying viral RNA/LNP Platforms. Designed as a next-generation viral immunotherapy, our HSV Platform improves upon key characteristics of this therapeutic class to enhance systemic activity with immune stimulating payloads. Our lead HSV program, ONCR-177, currently in the clinic, is designed to be directly administered into a tumor, resulting in high local concentrations of therapeutic agent and its five encoded transgenes, as well as low systemic exposure to the therapy, which could limit systemic toxicities. Our pioneering self-amplifying vRNA/LNP Platform, highlighted by our product candidates ONCR-021 and ONCR-788, involves a highly innovative, novel combination of RNA and LNP-based modalities designed to realize the potential of RNA medicines for cancer. Please visit www.oncorus.com to learn more. SOURCE:

CAMBRIDGE, Mass. , Jan. 20, 2021 (GLOBE NEWSWIRE) -- Oncorus, Inc. (Nasdaq: ONCR), a clinical stage biopharmaceutical company developing next-generation, systemically active viral immunotherapies to transform outcomes for cancer patients, announced today the recent publication of preclinical data supporting the clinical development of its lead oncolytic Herpes Simplex Virus (oHSV) clinical candidate, ONCR-177. In the paper, entitled, “ONCR-177, an Oncolytic HSV-1 Designed to Potently Activate Systemic Antitumor Immunity” (Haines, et al., 2020), published online in the journal Cancer Immunology Research, ONCR-177 demonstrated potent and durable antitumor activity in multiple immune-competent tumor models. The preclinical findings demonstrate that the activity of ONCR-177, an intratumorally administered viral immunotherapy engineered for systemic activity currently in a Phase 1 study, is driven by Oncorus’ unique combination of five complementary immunomodulatory transgene payloads in addition to its retention of γ34.5. A herpes simplex virus 1 (HSV-1) gene, γ34.5 allows the virus to replicate in the presence of host antiviral immune responses. ONCR-177’s safety strategies and their ability to enhance oHSV tolerability without impeding potency were previously characterized in a paper published by Oncorus in September 2020 in Molecular Therapy on ONCR-159, the unarmed version of ONCR-177, (Kennedy et al., 2020) titled, “Design of an Interferon-Resistant Oncolytic HSV-1 Incorporating Redundant Safety Modalities for Improved Tolerability.” “We are pleased to share these encouraging preclinical findings, which supported our advancement of ONCR-177 into clinical development last year. These data give important insight into how our proprietary engineering of ONCR-177 may enable systemic activity without compromising safety, and position us to advance our mission to realize the full potential of this therapeutic class for cancer patients,” said Theodore (Ted) Ashburn, M.D., Ph.D., President and Chief Executive Officer at Oncorus. “We believe viral immunotherapies as a class are a proven modality and represent the most promising approach in development today to activate multiple arms of the immune system and improve outcomes for cancer patients.” Oncorus is conducting a Phase 1 study to evaluate the safety and tolerability of ONCR-177 as well as to evaluate preliminary antitumor activity in patients with solid tumors (NCT04348916) as a monotherapy and in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) via a clinical trial collaboration and supply agreement signed with Merck in July 2020. Oncorus expects to report initial interim data from the monotherapy dose escalation part of this trial in the second half of 2021 with addition data readouts through the second half of 2022. Christophe Quéva, Ph.D., Oncorus’ Chief Scientific Officer and Senior Vice President, Research, commented, “We have designed our proprietary oHSV Platform to safely maximize the impact of viral immunotherapies to foster the development of a potent systemic antitumor activity. With our Phase 1 study of ONCR-177 now well underway, we look forward to the potential of these preclinical findings translating into improving patient outcomes.” In addition to ONCR-177, Oncorus plans to nominate a second intratumorally administered oHSV clinical candidate to specifically target cancers of the central nervous system, including glioblastoma multiforme, in the second half of 2021 (ONCR-GBM). In the first half of 2021, Oncorus plans to nominate intravenously administered Synthetic Coxsackievirus A21 and Synthetic Seneca Valley Virus clinical candidates from its Synthetic Virus Platform for difficult-to-inject tumors such as those of the lung. Preclinical Data Highlights Highlights from Oncorus’ preclinical data described in these papers include: The murine version of ONCR-177 (mONCR-171) demonstrated durable complete tumor regressions and abscopal activity in four syngeneic tumor models: A20, MC38, CT26 and B16F10N1. Durable survival was achieved in both A20 and CT26 models versus the unarmed version of ONCR-177 (i.e., ONCR-159), specifically demonstrating the impact that ONCR-177’s arming strategy has in driving systemic activity in these in vivo models of cancer. Re-challenge experiments in long term responders to mONCR-171 demonstrated that tumor antigen-specific protective memory responses were achieved. The retention of a gene coding for γ34.5 demonstrated more robust replication in the presence of interferon-γ versus viruses that do not contain this gene. Of note, ONCR-159, which also retains γ34.5 expression, demonstrated statistically significant improvement in an in vivo bi-lateral CT26 model of survival. The addition of systemic anti-PD-1 augmented the activity of mONCR-171, particularly for un-injected tumors, suggesting that utilizing systemic anti-PD-1 immunotherapy may augment the systemic antitumor effect of ONCR-177. Directional viral promoters, CAG and MND, were shown to elicit strong transgene expression in injected tumors. Furthermore, the addition of the five complementary immunomodulatory transgenes and other modifications in ONCR-177 remain potently oncolytic in vitro in cancer cell lines. The oncolytic activity of ONCR-177 is on par with what has been reported for talimogene laherparepvec (IMLYGIC®), which is commonly referred to as “T-VEC”.1 In vivo biodistribution analyses suggest that viral DNA and transgene expression were relegated primarily to the injected tumor. As previously disclosed, no dose limiting toxicities were observed in the first four patients dosed with ONCR-177 suggesting that the safety strategies incorporated into ONCR-177 are working as intended. About ONCR-177 ONCR-177, Oncorus’ lead viral immunotherapy candidate, is designed to mount a multidimensional attack on cancer. It induces immunogenic cancer cell death and ignites innate and adaptive immunity to drive a lasting and systemic anti-tumor response. Five Complementary Immunomodulatory Transgene Payloads to Recruit Multiple Arms of Immune System ONCR-177 is armed with five complementary transgenes with strong clinical and preclinical validation, IL-12, FLT3LG, CCL4, anti-PD-1 and anti-CLTA-4, which were selected by Oncorus to comprehensively drive the Cancer-Immunity Cycle2 at multiple nodes: IL-12 is known to activate and expand CD8, CD4 TH1 and natural killer (NK) cells. FLT3LG is well understood to expand antigen cross-presenting classical dendritic cells, and CCL4 is known facilitate dendritic and CD8 T cell recruitment. ONCR-177’s local expression of agonists to PD-1 (via a proprietary PD-1 nanobody) and CTLA-4 (using the ipilimumab sequence) is intended to counteract compensatory upregulation of key immune checkpoints. γ34.5 Retention to Enable Resistance to Host Antiviral Immune Responses and Additional Innovations ONCR-177 also retains a copy of γ34.5 to enable resistance to host antiviral interferon responses. γ34.5 is known to play a more central role in inhibition of antiviral response than US11.3 Furthermore, ONCR-177 contains a gB:N/T mutation in a surface fusion protein shown to broaden tropism beyond Herpesvirus entry mediator (HVEM) and nectin-1 to include nectins-2, 3 and 4 and enhance infectivity.4 Lastly, ONCR-177 contains inactivating null mutations in ICP47 intended to improve antigen presentation.5 Orthogonal Safety Strategies to Enable Selective Attenuation and Retention of γ34.5 Oncorus’ oHSV platform incorporates two complementary and proprietary approaches to limit viral replication in normal tissues. First, Oncorus’ microRNA attenuation strategy leverages the known differential expression of certain microRNA in tumors versus normal tissues to allow unencumbered viral replication in tumor cells, while preventing replication in healthy tissues. This microRNA attenuation strategy allows ONCR-177 to retain the ability to express the gene encoding for γ34.5, a feature unique among oHSV-based therapies such as T-VEC and others in development today. In addition, ONCR-177 also has engineered proprietary mutations into UL37 to eliminate the virus’ ability to transport, replicate and establish latency inside neurons.6 About Oncorus At Oncorus, we are focused on driving innovation to deliver next-generation, systemically active viral immunotherapies to transform outcomes for cancer patients. We are advancing a portfolio of intratumorally and intravenously administered viral immunotherapies for multiple indications with significant unmet needs based on our oncolytic Herpes Simplex Virus (oHSV) Platform and Synthetic Virus Platform. Designed to deliver next-generation viral immunotherapy impact, our oHSV Platform improves upon key characteristics of this therapeutic class to enhance potency without sacrificing safety, including greater capacity to encode transgenes to drive systemic immunostimulatory activity, retention of full replication competency to enable high tumor-killing potency, and orthogonal safety strategies to restrict viral activity in tumor cells. Oncorus’ lead oHSV program, ONCR-177, is designed to be directly administered into a tumor, resulting in high local concentrations of the therapeutic agent, as well as low systemic exposure to the therapy, which we believe could potentially limit systemic toxicities. Please visit us at to learn more. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding: expectations with respect to Oncorus’ ability to advance its clinical and preclinical pipelines, including statements regarding the clinical development of ONCR-177 and timing and anticipated data read-outs for the ongoing Phase 1 clinical trial; Oncorus’ expectations regarding upcoming milestones for its other potential product candidates, including the timing for nomination of clinical candidates from its two Synthetic Virus Platform development programs and its second oHSV Platform clinical candidate; and the therapeutic potential and clinical benefits of Oncorus’ existing and potential product candidates. The words "may," “might,” "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," “expect,” "estimate," “seek,” "predict," “future,” "project," "potential," "continue," "target" and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: the impact of COVID-19 on Oncorus’ operations and the timing and anticipated results of its ongoing and planned preclinical studies and clinical trials; the risk that the preliminary results of preclinical studies or clinical trials may not be predictive of future results in connection with future clinical trials; Oncorus’ ability to successfully demonstrate the safety and efficacy of ONCR-177 and obtain regulatory approval and that Oncorus’ other preclinical or clinical programs do not advance or result in approved products on a timely or cost effective basis or at all; and Oncorus’ ability to obtain, maintain and protect its intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Oncorus’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, which was filed with the Securities and Exchange Commission on November 12, 2020, as well as discussions of potential risks, uncertainties, and other important factors in the other filings that Oncorus makes with the Securities and Exchange Commission from time to time. These documents are available under the “SEC filings” page of the Investors section of Oncorus’ website at . Any forward-looking statements represent Oncorus’ views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Oncorus explicitly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Investor Contact: Alan Lada Solebury Trout 617-221-8006 alada@soleburytrout.com Media Contact: Liz Melone liz.melone@oncorus.com ___________________________________________________ 1 Moesta, et al, Cancer Research 2017 2 Chen and Mellman, Immunity 2013 3 Mulvey et al., J. Virol. 2004 and Peters et al., J. Virol. 2018 4 Uchida, J. Virol. 2010 5 Twumasi-Boateng, Nat. Rev. Cancer 2018 6 Richards et al., PLoSPathog. 2017