- Basic Science · OxPhos Biology · Metabolic Oncology
Targeting the Metabolic Vulnerability of Resistant Cancer
Cancer cells that develop resistance to standard therapies often shift to oxidative phosphorylation as their primary energy source. That dependency is their vulnerability — and lixumistat is designed to exploit it.
- The Problem
Acquired Resistance Leaves Patients Without Options
Across tumour types — pancreatic cancer, glioblastoma, melanoma, breast cancer — patients who initially respond to treatment will often relapse. When resistance develops, it frequently involves a metabolic shift: cancer cells rewire to depend on oxidative phosphorylation for energy production.
This metabolic rewiring is not a defence against lixumistat. It is the target.
Acquired Resistance in Malignant Melanoma
Pre-Treatment
Targeted Therapy Response (15 weeks post-treatment)
Post-Treatment Relapse (23 weeks post-treatment)
- The Mechanism
OxPhos Inhibition — Blocking Cancer's Backup Energy Source
Normal cells balance energy between glycolysis and oxidative phosphorylation. Treatment-resistant tumour cells often become heavily OxPhos-dependent. Lixumistat is a selective Complex I inhibitor that targets this pathway directly, with a well-established safety profile across completed Phase 1 studies.
- Tumour Types
Pan-Cancer Opportunity
OxPhos dependence has been documented across multiple cancer types where acquired resistance has developed. ImmunoMet’s current clinical focus is pancreatic cancer, with glioblastoma as the next planned indication.
Tumour Types
Phase 1b/2a active · MD Anderson
Next Indication
IND preparation underway
Pre-Clinical Data
BRAF/MEKi-resistant models
Pre-Clinical Data
ER+, endocrine/CDK4/6-resistant
Sources: Janku et al., Inv New Drugs, 2022. El-Botty et al., Nature Communications, 2023 (breast). Gopal et al., Clin Cancer Res, 2019 (melanoma). All cited in investor deck.
