MTI-301 / Modulation Therap - LARVOL DELTA

When fat fuels cancer: targeting SCD in melanoma brain metastases (EANO 2026) - "Our novel SCD inhibitor, MTI-301, demonstrates promising results in its ability to produce anti-tumor effects and prolong survival in murine models. These findings reveal metabolic vulnerabilities in MBM that can be exploited therapeutically. In targeting the lipidated profiles of the tumor and associated immune cells, immune dysregulation can be overcome, creating opportunities for immune cells to fight tumor progression and improve patient prognosis."

IO biomarker • Melanoma • Oncology • Solid Tumor • SCD

Targeting the lipid desaturation network in cancer: from metabolic plasticity to precision therapeutics. (PubMed, J Exp Clin Cancer Res) - "This metabolic rewiring provides a strong biological rationale for precision therapeutics.We trace the clinical development of desaturase inhibitors, highlighting the recent entry of SCD1 inhibitor, MTI-301, in a Phase 1 clinical trial for solid tumors and the potential repurposing of Aramchol, while detailing how FADS2 plasticity (the "sapienic shunt") drives therapeutic resistance. By integrating these insights into desaturation lipidomics, metabolic modulation via diet-drug interactions, synergistic combination regimens, and stimuli-responsive nanomedicine, we highlight the translational potential of targeting lipid desaturation to overcome metabolic plasticity and treatment resistance in aggressive malignancies."

Journal • Review • Metabolic Disorders • Oncology • Solid Tumor • FADS2 • SCD

The SCD inhibitor MTI-301 reduces steatohepatitis and ratio of C18:1/C18:0 levels in diet-induced murine models of MASH. (PubMed, Sci Rep) - "MTI-301 treatment decreased lipid droplets in both models, a finding that correlated with reduced desaturation indices (16:1/16:00 and 18:1/18:0) measured in the liver. Collectively our data suggests that the MTI-301 is an attractive drug for further development for the treatment of patients with fatty liver disease."

Journal • Preclinical • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor • SCD

Inhibition of stearoyl-CoA desaturase 1 (SCD1) by SSI-4 as a therapeutic strategy in non-small cell lung cancer (AACR 2026) - "SSI-4 (a.k.a MTI-301) is a selective SCD1 inhibitor currently in Phase I clinical evaluation for metastatic, unresectable, or refractory solid cancers, but its activity in non-small cell lung cancer (NSCLC) has not yet been characterized...Collectively, these findings demonstrate that SSI-4 selectively inhibits proliferation in a subset of NSCLC cells through an SCD1-dependent mechanism by reducing MUFA availability and activating stress and apoptotic signaling. This work establishes a framework for subsequent in vivo studies and lays the foundation for exploring SCD1 inhibition as a potential therapeutic strategy for patients with limited treatment options in NSCLC, while also advancing understanding of the mechanisms by which SCD1 supports tumor survival."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • SCD

Metabolic and immune reprogramming via SCD1 inhibition enhances chemo-immunotherapy response in TNBC (SABCS 2025) - P1 | "We have developed an SCD1 inhibitor, MTI-301 and shown anti-tumor activity in murine TNBC cell lines with MTI-301 alone and in combination with paclitaxel. SCD1 high TNBC tumors are associated with immune suppressive TME, FA metabolism, and dysregulated PI3K pathway, positioning SCD1 as a metabolic driver of therapy resistance and immune evasion and support its targeting to enhance chemo-ICI efficacy. SCD1 inhibitor, MTI-301 significantly reduced tumor growth and enhanced effector immune cell infiltration in TNBC murine models with combinatorial activity with chemo-ICI, indicating that pharmacologic modulation of SCD1 is a promising strategy for cancer therapy. We will be conducting Phase I clinical trial with MTI-301 in pts with advanced tumors including TNBC (NCT NCT06911008)."

IO biomarker • Breast Cancer • Triple Negative Breast Cancer • AKT1 • ALDH1A1 • ALDH1A2 • ALDH1A3 • BTLA • CD69 • CD8 • CXCL13 • DUSP6 • ENTPD1 • GZMB • HAVCR2 • HIF1A • IFNG • IL10 • ITGAE • KLF4 • KLRG1 • LAG3 • NANOG • NF1 • PIK3CA • PIK3R1 • PRF1 • PTEN • SCD • SOCS3 • TGFB1 • TIGIT

Inhibition of stearoyl-CoA desaturase prevents immunosuppressive phenotypic switch of macrophages and reprograms lipid metabolism in melanoma brain metastases (SNO 2025) - "The potential for SCDi to synergize with ICB in MBM may improve patient outcomes. MTI-301 is approved for first-in-human clinical trial starting end of 2025."

Melanoma • Metabolic Disorders • Solid Tumor • SCD

Inhibition of stearoyl-CoA desaturase prevents immunosuppressive phenotypic switch of macrophages and reprograms lipid metabolism in melanoma brain metastases (WFNOS 2025) - "The potential for SCDi to synergize with ICB in MBM may improve patient outcomes. MTI-301 is approved for first-in-human clinical trial starting end of 2025."

Melanoma • Metabolic Disorders • Oncology • Solid Tumor • SCD

MTI-301 for the Treatment of Metastatic or Unresectable and Refractory Solid Cancers (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Mayo Clinic | Not yet recruiting ➔ Recruiting

Enrollment open • First-in-human • Oncology • Solid Tumor

MTI-301 for the Treatment of Metastatic or Unresectable and Refractory Solid Cancers (clinicaltrials.gov) - P1 | N=42 | Not yet recruiting | Sponsor: Mayo Clinic | Initiation date: Sep 2025 ➔ Dec 2025

First-in-human • Trial initiation date • Oncology • Solid Tumor

MTI-301 for the Treatment of Metastatic or Unresectable and Refractory Solid Cancers (clinicaltrials.gov) - P1 | N=42 | Not yet recruiting | Sponsor: Mayo Clinic | Initiation date: Jun 2025 ➔ Sep 2025

Trial initiation date • Oncology • Solid Tumor