Voyager-V1 / Vyriad - LARVOL DELTA

Phase I Trial of Systemic Administration of Vesicular Stomatitis Virus Genetically Engineered to Express NIS and Human Interferon, in Patients with Relapsed or Refractory Multiple Myeloma, Lymphomas, or Histiocytic/Dendritic Cell Neoplasms (ASH 2023) - P1 | "The virus was administered via IV infusion over 30 minutes, and patients received 650 mg acetaminophen and 50 mg diphenhydramine hydrochloride before infusion and every 6 hours for 24 hours to manage fever and hypotension...Ruxolitinib is added from days 2-5 or day -1 to day 9 depending on the arm to mitigate IFNβ toxicity...Spearman rank correlation tests are used evaluated correlations between laboratory-based measures, and Wilcoxon rank sum tests compared continuous measures between response groups. Response rates will be summarized by DL and disease group, with estimated response rates and corresponding 95% binomial confidence intervals calculated."

Clinical • P1 data • B Cell Lymphoma • Hematological Malignancies • Hypotension • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Plasmacytoma • T Cell Non-Hodgkin Lymphoma • IFNB1

Ph I/II Trial of Systemic VSV-IFNβ-NIS in Combination With Checkpoint Inhibitor Therapy in Patients With Select Solid Tumors (clinicaltrials.gov) - P1/2 | N=33 | Active, not recruiting | Sponsor: Vyriad, Inc. | Recruiting ➔ Active, not recruiting | N=86 ➔ 33 | Trial completion date: Dec 2025 ➔ Sep 2025 | Trial primary completion date: Dec 2025 ➔ Jul 2025

Checkpoint inhibition • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Endocrine Cancer • Genito-urinary Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • PD-L1

VSV-hIFNbeta-NIS With or Without Ruxolitinib Phosphate in Treating Stage IV or Recurrent Endometrial Cancer (clinicaltrials.gov) - P1 | N=34 | Active, not recruiting | Sponsor: Mayo Clinic | Trial completion date: Jul 2025 ➔ Jan 2028

Trial completion date • Carcinosarcoma • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Oncology • Sarcoma • Solid Tumor • Uterine Cancer

Viral Therapy in Treating Patient With Refractory Liver Cancer or Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: Mayo Clinic | Active, not recruiting ➔ Completed

Trial completion • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Ultrasound Guided Intratumoral Delivery of Immunotherapy in Breast Cancer (ASBrS 2025) - P1, P2 | " This is an IRB approved retrospective review of neoadjuvant patients who received intratumoral immunotherapy (IT) of talimogene laherparepvec (TVEC) for triple negative tumors, dendritic cell (DC1) vaccines for HER2+ tumors, or Voyager V1 oncolytic virus (VV1) for high-risk lesions on ISPY2 (ClinicalTrials.gov IDs: NCT05325632, NCT03387553, NCT05504707). Intratumoral injection is a safe and effective approach for local administration of immunotherapeutics. BC can be feasibly targeted with US guidance due to its superficial location and minimally invasive access. Although patients reported AEs, these tended to be mild and self-limited."

Breast Cancer • Fatigue • HER2 Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Musculoskeletal Pain • Oncology • Pain • Respiratory Syncytial Virus Infections • Solid Tumor • Triple Negative Breast Cancer • HER-2

Harnessing oncolytic virus VSV and combination therapy to advance treatments for relapsed refractory multiple myeloma using Vk*MYC models (AACR 2025) - "Addition of VV1 to either anti-PD-1 or bortezomib alone also increased survival time significantly. Studies are still ongoing to understand the mechanisms of VSV and its combination treatments in Vk*MYC models. This translational study will allow us to gain the knowledge needed to refine VSV treatments and provide novel therapy combinations to improve MM patient survival."

Combination therapy • IO biomarker • Oncolytic virus • Hematological Malignancies • Multiple Myeloma • Oncology • IFNB1

Phase 2 Trial of Voyager V1 in Combination with Cemiplimab in Cancer Patients (clinicaltrials.gov) - P2 | N=87 | Recruiting | Sponsor: Vyriad, Inc. | Trial completion date: Mar 2025 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Colorectal Cancer • Cutaneous Melanoma • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BRAF • MSI • PD-L1

Ph I/II Trial of Systemic VSV-IFNβ-NIS in Combination with Checkpoint Inhibitor Therapy in Patients with Select Solid Tumors (clinicaltrials.gov) - P1/2 | N=86 | Recruiting | Sponsor: Vyriad, Inc. | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Endocrine Cancer • Genito-urinary Cancer • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • IFNB1 • PD-L1

VSV-hIFNbeta-NIS With or Without Ruxolitinib Phosphate in Treating Stage IV or Recurrent Endometrial Cancer (clinicaltrials.gov) - P1 | N=34 | Active, not recruiting | Sponsor: Mayo Clinic | Trial completion date: Jul 2024 ➔ Jul 2025 | Trial primary completion date: Jun 2024 ➔ Aug 2023

Metastases • Trial completion date • Trial primary completion date • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Oncology • Sarcoma • Solid Tumor • Uterine Cancer

Intravenous Vesicular Stomatitis Virus in Patients With Peripheral T-cell Lymphoma (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Mayo Clinic

New P1 trial • Acute Myelogenous Leukemia • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Ph I/II Trial of Systemic VSV-IFNβ-NIS in Combination With Checkpoint Inhibitor Therapy in Patients With Select Solid Tumors (clinicaltrials.gov) - P1/2 | N=70 | Recruiting | Sponsor: Vyriad, Inc. | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Checkpoint inhibition • Combination therapy • Trial completion date • Trial primary completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IFNB1 • PD-L1

Phase 2 Trial of Voyager V1 in Combination With Cemiplimab in Cancer Patients (clinicaltrials.gov) - P2 | N=87 | Recruiting | Sponsor: Vyriad, Inc. | Trial primary completion date: Mar 2024 ➔ Dec 2024

Combination therapy • Trial primary completion date • Colorectal Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BRAF • MSI • PD-L1

VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia or Lymphoma (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Mayo Clinic | Trial completion date: Dec 2024 ➔ Apr 2032 | Trial primary completion date: Dec 2024 ➔ Dec 2028

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Mycosis Fungoides • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Phase 1/2 trial of vesicular stomatitis virus expressing human interferon-β and NIS (VSV-IFNβ-NIS), with ipilimumab and nivolumab, in patients with neuroendocrine carcinoma. (ASCO-GI 2024) - P1/2 | "The optimal systemic therapy beyond first line platinum and etoposide is not established...If at least one objective response is observed, and safety is confirmed, the regimen will be considered for future study. Clinical trial information: NCT03647163."

Clinical • P1/2 data • Gastrointestinal Cancer • Oncology • Solid Tumor • IFNB1

VSV-hIFNbeta-NIS With or Without Ruxolitinib Phosphate in Treating Stage IV or Recurrent Endometrial Cancer (clinicaltrials.gov) - P1 | N=34 | Active, not recruiting | Sponsor: Mayo Clinic | Recruiting ➔ Active, not recruiting | N=77 ➔ 34

Enrollment change • Enrollment closed • Metastases • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Oncology • Sarcoma • Solid Tumor • Uterine Cancer

Neoadjuvant systemic oncolytic vesicular stomatitis virus is safe and may enhance long-term survivorship in dogs with naturally occurring osteosarcoma. (PubMed, Mol Ther Oncolytics) - "An increase in tumor inflammation was observed in VSV-treated tumors and RNA-seq analysis showed that all the long-term responders had increased expression of a T cell anchored immune gene cluster. We conclude that neoadjuvant VSV-IFNβ-NIS is safe and may increase long-term survivorship in dogs with naturally occurring osteosarcoma, particularly those that exhibit pre-existing antitumor immunity."

IO biomarker • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • IFNB1

VSV-hIFNbeta-NIS With or Without Ruxolitinib Phosphate in Treating Patients With Stage IV or Recurrent Endometrial Cancer (clinicaltrials.gov) - P1 | N=77 | Recruiting | Sponsor: Mayo Clinic | Active, not recruiting ➔ Recruiting

Enrollment open • Metastases • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Oncology • Sarcoma • Solid Tumor • Uterine Cancer

VSV-hIFNbeta-NIS With or Without Cyclophosphamide or Ipilimumab and Nivolumab in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia or Lymphoma (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Mayo Clinic | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Mycosis Fungoides • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Vyriad Announces Expansion of T-Cell Lymphoma Trial at Mayo Clinic (PRNewswire) - "Vyriad, Inc., announces an expansion of a Phase 1 investigator-initiated trial at Mayo Clinic evaluating the safety and efficacy of Voyager-V1 (VSV-hIFNbeta-NIS) in patients with peripheral T-cell lymphoma (PTCL) following encouraging initial results. Voyager-V1 is an investigational therapy being co-developed with Regeneron Pharmaceuticals, Inc., to treat patients with recurrent or treatment resistant cancers....The trial is being conducted at Mayo Clinic Rochester and Mayo Clinic Arizona."

Trial status • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Preliminary pharmacokinetic and safety data after a single intravenous infusion of Voyager-V1 (VV1, VSV-IFNβ-NIS) oncolytic virus in patients with relapsed refractory hematologic malignancies. (ASCO 2023) - P1 | "The 30 minute infusion rate was considered the best as its PK provides the highest Cmax and AUC with no significant CRS differences among other groups. IL-6 and IFNα markers at hour 4 indicate a likely CRS and hour 24 provides a possible prediction of the grade. Cmax and AUC were also highest at 1.7e11 TCID50."

Clinical • IO biomarker • Oncolytic virus • PK/PD data • Hematological Disorders • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma • IFNA1 • IFNB1 • IL6

Systemic VSV-IFNβ-NIS oncolytic virotherapy in patients with relapsed refractory T-cell lymphoma. (ASCO 2023) - P1 | "In the TCL cohort: at DL4 Group A (no Ruxolitinib), 12 pts were registered, but only 11 pts were treated (mycosis fungoides (MF) N=3; ALK- ALCL N=1; PTCL-NOS N=2; AITL N=4; Nodal PTCL, TFH N=2; ages 33-79)... These updated results of single agent VSV-IFNβ-NIS which include pts with PTCL treated at the highest dose level and a dose expansion cohort demonstrates not only the safety of VSV-IFNβ-NIS but also a strong efficacy signal in pts with PTCL with impressive durable responses. Two expansion cohorts at DL4 have been added (20 additional PTCL, 10 B-cell lymphoma pts) to obtain additional data on tolerability and efficacy and biomarkers of response in these pts. Clinical trial information: NCT03017820."

Clinical • Oncolytic virus • Acute Myelogenous Leukemia • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Immune Modulation • Lymphoma • Multiple Myeloma • Mycosis Fungoides • Neutropenia • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • ALK • IFNB1

VSV-hIFNbeta-NIS With or Without Ruxolitinib Phosphate in Treating Patients With Stage IV or Recurrent Endometrial Cancer (clinicaltrials.gov) - P1 | N=77 | Active, not recruiting | Sponsor: Mayo Clinic | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Oncology • Sarcoma • Solid Tumor • Uterine Cancer

VSV-hIFNbeta-NIS With or Without Ruxolitinib Phosphate in Treating Patients With Stage IV or Recurrent Endometrial Cancer (clinicaltrials.gov) - P1 | N=77 | Recruiting | Sponsor: Mayo Clinic | Trial completion date: Jul 2023 ➔ Jul 2024 | Trial primary completion date: Jun 2023 ➔ Jun 2024

Metastases • Trial completion date • Trial primary completion date • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Oncology • Sarcoma • Solid Tumor • Uterine Cancer

Clinical Activity of Oncolytic Virus Voyager-V1 in Patients with Relapsed Refractory Lymphoma (ASGCT 2023) - "A number of clinical trials investigating safety and activity of VV1 are ongoing, utilizing VV1 as a monotherapy, or in combination with cemiplimab, an anti-PD1 antibody. Adverse events were manageable, with transient decreases in lymphocyte counts and grade 1-2 cytokine release syndrome that is transient and resolving by 24h. Two cohort are added to the study to enroll 20 additional T cell lymphoma and 10 additional B cell lymphoma patients to obtain additional safety and efficacy signal and deeper analysis of biomarkers of responses."

Clinical • IO biomarker • Oncolytic virus • Hematological Malignancies • Immune Modulation • Infectious Disease • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • IFNB1

Phase 2 Trial of Voyager V1 in Combination With Cemiplimab in Cancer Patients (clinicaltrials.gov) - P2 | N=87 | Recruiting | Sponsor: Vyriad, Inc. | N=152 ➔ 87

Combination therapy • Enrollment change • Colorectal Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BRAF • EGFR • MSI • PD-L1