OMO-103 / Peptomyc - LARVOL DELTA

c-Myc-targeted therapy in breast cancer: A review of fundamentals and pharmacological Insights. (PubMed, Gene) - "Notably, the c-Myc inhibitor OMO-103 has shown promise in a Phase II clinical trial for advanced cancer patients. Further research is needed to develop new drugs targeting this gene, protein, or its pathways, and additional studies on cancer patients are encouraged."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • MYC • PGR

Osteomyc: A Phase 2 Pilot Study to Evaluate the Safety and the Anti-Tumour Activity of the Myc Inhibitor OMO-103 Administered Intravenously in Patients With Advanced High-Grade Osteosarcoma (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: Vall d'Hebron Institute of Oncology | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

OSTEOMYC: A PHASE 2 PILOT STUDY TO EVALIATE THE SAFETY AND THE ANTITUMOR ACTIVITY OF THE MYC INHIBITOR OMO-103 ADMINISTERED INTRAVENOUSLY IN PATIENTS WITH ADVANCED HIGH GRADE OSTEOSARCOMA (CTOS 2024) - "In addition,it will explore potential biomarkers. Patients ≥12 years with locally advanced/metastatic high-grade osteosarcoma who have received at least one line of standard chemotherapy containing cisplatin and anthracycline, and no more than 2 previous lines, will be included. N/A,N/A,N/A"

Clinical • Metastases • P2 data • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • MYC

OMO-103-02: Study to Evaluate the Safety, PK, and Efficacy of the Myc Inhibitor OMO-103 Administered Iv in Patients with PDAC (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Peptomyc S.L. | Phase classification: P1b ➔ P1 | N=18 ➔ 30

Enrollment change • Metastases • Phase classification • Endometrial Cancer • Hepatology • Oncology • Ovarian Cancer • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Discovery of a covalent inhibitor targeting the undruggable oncogene cMyc (EORTC-NCI-AACR 2024) - "Numerous efforts to target this notorious protein have been made, yet only OMO-103, a mini-protein drug, has demonstrated safety and anti-tumor activity in clinical trials...Our research underscores how covalent small molecules can open the door to transformative treatment options by targeting previously undruggable proteins such as cMyc. BridGene Biosciences aims to address the large patient population with cMyc amplification by developing a potent and selective covalent therapeutic, which could be crucial for reversing cancerous growth and restoring antitumor immune responses in cMyc-driven cancers."

Oncology • MYC

MYC Inhibition by OMO-103 Reprograms Tumor Immunity and Enhances Immunotherapy Efficacy in KRAS Mutant NSCLC (EORTC-NCI-AACR 2024) - P1/2 | "By upregulating activation molecules of the TNFR superfamily, MYC inhibition re-activates immune recognition, improving the therapeutic effect of immunotherapies. This presents a promising therapeutic approach for KRAS NSCLC, highlighting MYC inhibitors such as OMO-103 as potent candidates to overcome immunotherapy resistance and provide better cancer treatments."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • TNFA

Pharmacokinetic and pharmacodynamic analyses of OMO-103 in preclinical and patient tissues (EORTC-NCI-AACR 2024) - P1/2 | "Our results show evidence of the long-lasting half-life of functional OMO-103 in tumour tissues, suggestive of a different PK profile between serum and tissue. We also demonstrate target engagement by OMO-103 at the transcriptomic and proteomic levels, correlating clinical benefit with more efficient shutdown of MYC targets."

PK/PD data • Preclinical • Oncology • Solid Tumor • MYC

Osteomyc: A Phase 2 Pilot Study to Evaluate the Safety and the Anti-Tumour Activity of the Myc Inhibitor OMO-103 Administered Intravenously in Patients with Advanced High-Grade Osteosarcoma (clinicaltrials.gov) - P2 | N=10 | Not yet recruiting | Sponsor: Vall d'Hebron Institute of Oncology

Metastases • New P2 trial • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Pharmacokinetic analysis of OMO-103 in patient tissues with advanced solid tumors. (ASCO 2024) - P1/2 | "We demonstrate the utility of targeted MS assay for precise quantification of therapeutic (mini)proteins in clinical tissue samples. Thanks to its multiplexing capability, up to 60 peptides (epitopes) can be monitored simultaneously which enables high sequence coverage and profiling of additional PD or other supporting biomarkers. Clinical trial information: NCT04808362."

Clinical • Metastases • PK/PD data • Oncology • Solid Tumor

MYCure: Phase 1/2 Study to Evaluate Safety, PK and Efficacy of the MYC-Inhibitor OMO-103 in Solid Tumours (clinicaltrials.gov) - P1/2 | N=22 | Terminated | Sponsor: Peptomyc S.L. | Active, not recruiting ➔ Terminated; Phase 1completed; sponsor decided to change strategy to a combination study

Metastases • Trial termination • Breast Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • KRAS

Targeting MYC as a novel therapeutic strategy for an epigenetic-driven cancer: NUT Carcinoma (AACR 2024) - "It induces cell apoptosis, differentiation, and cell cycle arrest in vitro, and when tested in xenografts in vivo, OMO-103 reduces tumor growth and enhances mouse survival, particularly when combined with a chemotherapy regimen. This study presents a promising therapeutic strategy for an incurable and aggressive cancer type."

NUT Midline Carcinoma • Oncology • BRD4 • SOX2 • TP63

A big step for MYC-targeted therapies. (PubMed, Trends Cancer) - "We highlight a recent report by Garralda et al. of a Phase 1 clinical trial of OMO-103 in patients with solid malignancies."

Journal • CNS Disorders • Oncology • Psychiatry • Solid Tumor

MYC targeting by OMO-103 in solid tumors: a phase 1 trial. (PubMed, Nat Med) - P1/2 | "In addition, we identified soluble factors that are potential pharmacodynamic and predictive response markers. Based on all these data, the recommended phase 2 dose was determined as DL5 (6.48 mg kg-1).ClinicalTrials.gov identifier: NCT04808362 ."

Journal • P1 data • Oncology • Solid Tumor

OMO-103-02: Study to Evaluate the Safety, PK, and Efficacy of the Myc Inhibitor OMO-103 Administered iv in Patients With PDAC (clinicaltrials.gov) - P1b | N=18 | Recruiting | Sponsor: Peptomyc S.L.

Metastases • New P1 trial • Endometrial Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Ovarian Cancer • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Peptomyc Announces the Approval of Its Phase 1b Trial Testing OMO-103 in Combination With Standard of Care in PDAC Patients (Issuer Direct) - "Peptomyc S.L....announces that it has received full study approval for its new Phase 1b clinical trial, which will evaluate the combination of the first-in-class MYC inhibitor, OMO103, together with the standard of care (SoC) regimen Gemcitabine and Nab-Paclitaxel in metastatic Pancreatic Ductal Adenocarcinoma (PDAC) patients in first line....This Phase 1b combination study will be conducted in four sites in Spain....The study is planned to start in Q3/2023."

New P1 trial • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Progress in the development of a clinically viable MYC inhibitor (EACR 2023) - "An Omomyc-based mini-protein therapeutic developed by Peptomyc S.L. – OMO-103 – has recently successfully completed a Phase 1 clinical study, demonstrating safety and clear signs of target engagement...ConclusionMYC inhibition is finally progressing through clinical trials and it is revealing new aspects of MYC biology, including in the context of immune modulation. The pleiotropic role of MYC in drug resistance and survival suggests that MYC inhibition could be useful to increase the efficacy of – and prevent resistance to – standard-of-care therapies."

Clinical • Breast Cancer • Immune Modulation • Immunology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • KRAS

"Biomarkers of response to OMO-103, a novel MYC inhibitor #AACR23 @VJOncology @LauraSoucek @peptomyc https://t.co/8jwg2o4NcM" (@peptomyc)

Biomarker • Oncology

Dose escalation study of OMO-103, a first in class Pan-MYC-Inhibitor in patients (pts) with advanced solid tumors (AACR-NCI-EORTC 2022) - "RP2D has been determined to be DL5 with 6.48mg/kg. Dose expansion cohorts (Phase 2a) are already planned."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Salivary Gland Cancer • Sarcoma • Solid Tumor

Identification of potential biomarkers of response to OMO-103, a first-in-modality pan-MYC inhibitor, in patients with advanced solid tumors (AACR 2023) - "OMO-103 demonstrates a favorable safety profile, with encouraging signs of activity supported by predictive and pharmacodynamic biomarkers worthy of further investigation."

Biomarker • Clinical • Metastases • Oncology • Solid Tumor

MYC inhibition by OMO-103 induces immune cell recruitment in preclinical models of NSCLC and modulates the cytokine and chemokine profiles of Phase I patients showing stable disease (AACR-NCI-EORTC 2022) - "Our findings support the therapeutic opportunity to induce a potent antitumor immune response in NSCLC by pharmacological MYC inhibition with Omomyc. In addition, they suggest that OMO-103 can also induce immune activation in patients displaying stable disease."

IO biomarker • P1 data • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • EGFR • HAVCR2 • KRAS • PD-1 • TP53

Omomyc mini-protein can be directly and continuously delivered to the brain to prevent glioblastoma in patient-derived xenograft mouse models (AACR-NCI-EORTC 2022) - P1/2 | "Material and methods We use the Omomyc mini-protein (OMO-103), currently in early-phase clinical trials for all-comer solid tumours (NCT04808362, sponsored by Peptomyc). Omomyc reduced proliferation and increased cell death in a panel of patient-derived GBM neurospheres in culture, showing efficacy regardless of their Myc levels, and had additive effects in combination with the standard of care, temozolomide. Conclusions These results extend the clinical applicability of the Omomyc mini-protein to GBM patients and provides an administration route to deliver the mini-protein drug to this hard-to-reach organ."

Preclinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Phase I Trial Shows Experimental Mini-Protein May Be Able to Inhibit the Cancer-Driving MYC Gene (THE ASCO POST) - "'These results showing that patients typically experienced mild adverse side effects to OMO-103 are important when considering next steps and how it might be combined with chemotherapy. We look forward to the results from the phase II trial with interest,' said James L. Gulley, MD, PhD...who was not involved in the study."

Media quote

Direct MYC Inhibitor Passes First Clinical Test. (PubMed, Cancer Discov) - "The first direct inhibitor of MYC to enter human clinical testing appears to be safe, with signs of antitumor activity in patients with advanced solid cancers. Treatment with OMO-103 led to stable disease in about half of trial participants, but the drug's mechanism of action and the extent of on-target engagement remain matters of debate."

Journal • Oncology • Solid Tumor

MYCure: Phase 1/2 Study to Evaluate Safety, PK and Efficacy of the MYC-Inhibitor OMO-103 in Solid Tumours (clinicaltrials.gov) - P1/2 | N=22 | Active, not recruiting | Sponsor: Peptomyc S.L. | Recruiting ➔ Active, not recruiting | N=74 ➔ 22

Enrollment change • Enrollment closed • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • KRAS

PEPTOMYC SL Announces Treatment of First Patient with its Lead Compound OMO-103 in a Phase I/II Clinical Trial (GlobeNewswire) - "Peptomyc...reported that on Tuesday 4th May the first patient has been dosed with OMO-103, its anti-MYC lead compound, in a Phase I/II study...The entire Phase I/II study will enroll up to 74 patients...The objective of this first in human Phase I/II study is to evaluate the safety of OMO-103, as well as its preliminary anti-tumor efficacy."

Trial status • Oncology • Solid Tumor