VIO-01 / Valerio Therap - LARVOL DELTA

A Phase 1/2 Study of VIO-01 in Participants With Recurrent Solid Tumors (clinicaltrials.gov) - P1/2 | N=6 | Terminated | Sponsor: Valerio Therapeutics | N=165 ➔ 6 | Trial completion date: Dec 2028 ➔ Jan 2025 | Recruiting ➔ Terminated | Trial primary completion date: Jan 2026 ➔ Jan 2025; Business decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor

Valerio Therapeutics Reports its Half-Year 2024 Financial Results and Provides an Update on its Activities (Businesswire) - "Currently, the trial has enrolled 6 patients across two dose levels. The VIO-01 trial is currently in Phase 1 dose escalation, evaluating the safety, tolerability, dose-limiting toxicities, and recommended Phase 2 doses of VIO-01...VIO-01 has shown an acceptable safety profile and plans to proceed through dose escalation for the remainder of 2024. Once the recommended dose is determined, the trial is planned to proceed to the Phase 2 expansion, which will evaluate the activity of VIO-01 in HRD+ ovarian cancer and in HRRm/HRD+ solid tumors. The Phase 2 expansion is planned to assess the preliminary efficacy. Based on the evidence generated in the Phase1/2 trial further development may include additional combinations of chemotherapy or targeted therapies with VIO-01 or development in additional solid tumors."

Trial status • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • HRD

Valerio Therapeutics Provides Clinical Development Update on Its Phase 1/2 VIO-01 Clinical Trial (Businesswire) - "Valerio Therapeutics...announced the completion of dosing for the first cohort of subjects in its Phase 1/2 trial of lead candidate, VIO-01, a pan-DDR decoy for the treatment of solid tumors...The Clinical Review Committee (CRC) is composed of Valerio Therapeutics Medical and Safety teams as well as Principal Investigators convened to review all available and relevant safety information from the first cohort of 3 patients. No clinically significant adverse events or serious adverse events were reported and no MTD was declared, allowing the Clinical Review Committee to unanimously agree to escalate to the second dose cohort....The dose escalation to clinically relevant exposures and safety expansion is expected to continue through 2024."

DSMB • Trial status • Oncology • Solid Tumor

VIO-01, a pan-DDR DNA decoy mediating DNA repair abrogation and unleashing the anti-tumor immune response (AACR 2024) - "Our results provide a preclinical rationale for using VIO-01 to trigger DNA damage exhaustion and an antitumor immune response, paving the way for rapid clinical application in patients bearing HRD or HRP tumors."

Oncology • Ovarian Cancer • Solid Tumor • CD8 • MSH2 • MSH3

VIO-01, a pan-DDR DNA decoy triggering DNA repair abrogation and an enhanced antitumor immune response (ESMO-TAT 2024) - "Also, regulatory toxicology studies demonstrated a favorable safety profile of VIO-01 in non-human primate with the major findings being a transient increase in specific cytokines and complement factors, which was not confirmed in human serum at relevant VIO-01 concentrations. Conclusions Our results provide a preclinical rationale for using VIO-01 to trigger DNA damage exhaustion and an antitumor immune response, paving the way for rapid clinical application in patients bearing HRD or HRP tumors."

Oncology • Ovarian Cancer • Solid Tumor

A Phase 1/2 Study of VIO-01 in Participants With Recurrent Solid Tumors (clinicaltrials.gov) - P1/2 | N=165 | Recruiting | Sponsor: Valerio Therapeutics

New P1/2 trial • Breast Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor

ONXEO Provides Update on the Development Program For Its First-in-class Drug Candidate AsiDNA (Businesswire) - "'Additionally, this lays a strong foundation for our next first in class drug candidate OX425 which is sourced from the same proprietary PlatON™ platform and is a PARP/DDR specific decoy agonist thereby possibly not inducing tumor resistance to treatment. This profile represents a potential differentiation in safety and activity from other targeted therapies such as PARP inhibitors and we are on track to file an IND in mid- 2023'."

IND • Oncology

Onxeo Reports Full Year 2022 Financial Results and Provides Clinical Development Updates (Businesswire) - "In 2023, the Company will continue to pursue its value creation strategy based on the development of its therapeutic innovations until proof of concept in humans, with the following main milestones:...OX425: (i) Finalization of the IND-enabling preclinical studies; (ii) Preparation of an IND application with the FDA in S2 2023."

IND • Preclinical • Oncology

PARP1 hyperactivation by the decoy oligodeoxynucleotide OX425 mediates DNA repair abrogation and unleashes the anti-tumor immune response (AACR 2023) - "Our results provide preclinical rationale for using OX425 to trigger DNA damage exhaustion and STING activation in cancer cells and initiate inflammatory responses that can be actioned by immune checkpoint inhibitors in patients bearing HRD or HRP tumors"

IO biomarker • Breast Cancer • Endometrial Cancer • Oncology • Solid Tumor • BRCA1 • HRD

PARP1 trapping and hyperactivation by the decoy agonist OX425 induces DNA repair abrogation and a robust anti-tumor immune response (ESMO-TAT 2023) - "Importantly, OX425 treatment significantly delayed acquired resistance to olaparib in BRCA1 mutated MDA-MB-436 cell-derived xenografts. Conclusions Our results provide a safety profile and preclinical rationale for using OX425 in patients bearing HRD tumors, to trigger DNA damage exhaustion and initiate inflammatory responses in the tumor microenvironment."

Breast Cancer • Oncology • Solid Tumor • BRCA1 • HRD • PARP1

Immunotherapeutic activity of OX425 against PD-1 resistant HR+HER2- breast cancer (SITC 2022) - "Conclusions OX425 at doses < 500 µg/mice 2X per week is well tolerated in mice and mediates single-agent immunotherapeutic activity in models of PD-1-resistant HR + HER2 - breast cancer, with a potential for synergy with PD-1. Further investigation of the immunostimulatory and therapeutic properties of OX425 is warranted."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2 • PD-1