DO-2 / DeuterOncology, Octimet, J&J - LARVOL DELTA

Safety and activity of the MET-TKI DO-2 in patients with advanced solid tumors: Phase I study (ESMO 2025) - P1 | "Conclusions DO-2 is well tolerated, with no drug-induced edema. Early signs of antitumor activity supports further evaluation of DO-2 in patients with METex14 advanced NSCLC in the expansion phase."

Clinical • Metastases • P1 data • Esophageal Cancer • Gastric Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Food for thought: Effect of a high-fat meal on DO-2, a novel MET-kinase inhibitor (ESMO 2025) - P1 | "DO-2 is a redeveloped deuterated version of JNJ-38877605 to reduce toxic metabolite formation via AOX-1. Since an 8–10 hour ToT is ideal for efficacy and toxicity, food optimises the pharmacokinetic profile of DO-2, which is further evaluated in the extension phase of the phase 1 study in patients. Potentially, EGCG could reduce M3 formation."

Oncology • Solid Tumor

Preliminary Safety and PK of the MET-TKI Do-2 in Advanced Solid Tumors With MET Aberrations: Phase I Study (IASLC-WCLC 2025) - "The primary endpoint was safety and tolerability; secondary objectives included PK of DO-2, the primary metabolites DO-5 and M3 and anti-tumor activity according to RECIST 1.1. The dose limiting toxicity (DLT) observation period was 4 weeks. Response assessment was performed every 8 weeks."

Clinical • Metastases • P1 data • Oncology • Solid Tumor

A High-Fat Meal Optimizes the Pharmacokinetic Profile of DO-2, a Novel MET-Kinase Inhibitor for NSCLC (IASLC-WCLC 2025) - P1 | "DO-2 is a deuterated version of JNJ-38877605, redesigned to reduce toxic metabolite (M5) formation via AOX-1...Total exposures (AUC 0-24h ) to DO-2, DO-5 and M3 are similar with and without food. Since an 8-10 hour ToT is ideal for efficacy and toxicity, food optimizes the pharmacokinetic profile of DO-2, which is further evaluated in the extension phase of the phase 1 study in patients (NCT05752552). Possibly, EGCG could reduce M3 formation and should be studied further."

PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • MET

DeuterOncology to Present Promising Phase I DO-2 MET Kinase Inhibitor Data at WCLC 2025 (PRNewswire) - "The study's primary findings demonstrate that DO-2 treated patients showed a remarkable 100% Disease Control Rate (DCR) and saw tumor shrinkage in 100% of MET exon 14 skip mutation-positive NSCLC patients without alternative oncogenic drivers and reached efficacious drug exposures (10/10 patients). RECIST 1.1 Partial responses (>30% reduction) were observed in 2 out of these 10 patients."

P1 data • Non Small Cell Lung Cancer

Study to Determine the Safety and Pharmacokinetics of DO-2 in Patients With Advanced or Refractory Solid Tumours (clinicaltrials.gov) - P1 | N=25 | Active, not recruiting | Sponsor: DeuterOncology | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Thyroid Gland Papillary Carcinoma

Study to Determine the Safety and Pharmacokinetics of DO-2 in Patients with Advanced or Refractory Solid Tumours (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: DeuterOncology | Trial completion date: Apr 2025 ➔ Dec 2026 | Trial primary completion date: Oct 2024 ➔ Dec 2025

Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Thyroid Gland Papillary Carcinoma

Preliminary Safety and Pharmacokinetics of the MET-TKI DO-2 in Patients with Advanced Solid Tumors Harboring MET Aberrations: A Phase I Study (EORTC-NCI-AACR 2024) - "Plasma levels of the parent compound DO-2, an active metabolite DO-5 and an inactive metabolite M3 show linear dose-exposure relationships (Cmax and AUC0-24). Encouraging signs of clinical benefit and prolonged disease control observed with no evidence of peripheral edema or liver enzyme elevations. BID dosing is currently being explored further."

Clinical • Metastases • P1 data • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Residence time of DO-2, a novel deuterated MET kinase inhibitor on the endogenous target: Differentiates DO-2 from competitor agents. (EORTC-NCI-AACR 2024) - P1 | "The high affinity, fast on and fast off rates of DO-2 that we have observed, indicates that the PK profile of DO-2 is a direct corolally of target inhibition. Modulating the PK profile of DO-2 allows optimizing efficacy whilst reducing on target toxicities.The use of FCCS to quantify the target occupancy on endogenous MET offers a potentially new strategy that will enable personalized dosing for patients."

Oncology

Study to Determine the Safety and Pharmacokinetics of DO-2 in Patients With Advanced or Refractory Solid Tumours (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: DeuterOncology | N=15 ➔ 25 | Trial completion date: Nov 2024 ➔ Apr 2025 | Trial primary completion date: Apr 2024 ➔ Oct 2024

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Thyroid Gland Papillary Carcinoma

Quantification and clinical validation of the selective MET kinase inhibitor DO-2 and its metabolites DO-5 and M3 in human plasma. (PubMed, J Pharm Biomed Anal) - "All values for accuracy, within-run and between-run precisions met the criteria set by the Food and Drug Administration. The method was effectively employed in the analysis of samples obtained from a clinical trial."

Journal

Preclinical and emerging Phase 1 study data indicates that novel deuterated MET kinase inhibitor DO-2 mitigates the side effects seen with current approved MET kinase inhibitors: Preventing deleterious 'de-hinging' to improve tolerability. (AACR-NCI-EORTC 2023) - No abstract available

Adverse events • P1 data • Preclinical • Oncology

Study to Determine the Safety and Pharmacokinetics of DO-2 in Patients With Advanced or Refractory Solid Tumours (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: DeuterOncology | Active, not recruiting ➔ Recruiting | Trial completion date: Jun 2024 ➔ Nov 2024

Enrollment open • Metastases • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Thyroid Gland Papillary Carcinoma

Study to Determine the Safety and Pharmacokinetics of DO-2 in Patients With Advanced or Refractory Solid Tumours (clinicaltrials.gov) - P1 | N=1 | Active, not recruiting | Sponsor: DeuterOncology | Recruiting ➔ Active, not recruiting | N=25 ➔ 1

Enrollment change • Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Thyroid Gland Papillary Carcinoma

Study to Determine the Safety and Pharmacokinetics of DO-2 in Patients With Advanced or Refractory Solid Tumours (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: DeuterOncology

Metastases • New P1 trial • Oncology • Solid Tumor • Thyroid Gland Papillary Carcinoma

DeuterOncology closes €5.65M Series A financing round (PharmiWeb) - "DeuterOncology...announces the closing of its €5.65 million ($6.1M) Series A financing, with participation from historical investor Newton Biocapital and new investors Noshaq and Investsud Tech. This funding will enable the company to start the phase I clinical study for its lead product DO-2, an improved MET kinase inhibitor currently being developed as a potential best-in-class targeted therapy for lung cancer....'We expect to obtain phase I results by Q2, 2024'."

Financing • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology