AVEO Oncology Partners with HiberCell to Develop First-in-Human PERK Inhibitor for Renal Cell Carcinoma
Key Insights
AVEO Oncology and HiberCell (search) announced an exclusive development and option agreement for HC-5404, a first-in-human PERK (search) inhibitor, to be combined with AVEO's approved VEGFR (search) inhibitor FOTIVDA for renal cell carcinoma (search) treatment.
Pre-clinical studies demonstrate HC-5404's enhanced anti-tumor efficacy when combined with anti-angiogenic agents in multiple solid tumor models including gastric cancer (search) and RCC.
AVEO will conduct initial clinical development and has the option to obtain exclusive worldwide licensing rights during Phase 2 trials, with HiberCell (search) eligible for milestone payments and royalties.
AVEO Oncology, an LG Chem (search) company, and HiberCell (search) announced today that they have entered into an exclusive development and option agreement to advance HiberCell's first-in-human protein kinase RNA-like endoplasmic reticulum kinase (PERK (search)) inhibitor, HC-5404, both as a monotherapy and in combination with AVEO's FDA-approved VEGFR (search) tyrosine kinase inhibitor FOTIVDA® (tivozanib).
Novel PERK Inhibition Mechanism
HC-5404 represents a first-in-human selective and potent PERK (search) inhibitor targeting a novel mechanism of action. PERK is a kinase of the Unfolded Protein Response, an adaptive cellular program that cancer cells exploit to survive in harsh tumor microenvironments characterized by hypoxia, nutrient deprivation and oxidative stress. Pre-clinical studies of HC-5404 in multiple solid tumor models, including gastric cancer (search) and renal cell carcinoma (search), suggest the potential for enhanced anti-tumor efficacy when combined with an anti-angiogenic agent.
The compound has already been investigated in a Phase 1 clinical trial for solid tumors (NCT04834778), establishing its safety profile as it advances into Phase 1b development.
Strategic Partnership Structure
Under the agreement terms, AVEO will be responsible for conducting initial stage clinical development. During the Phase 2 clinical trial, AVEO will have the option to obtain an exclusive license for the development, manufacturing, and commercialization of HC-5404 in all therapeutic indications worldwide for an undisclosed option fee. If AVEO exercises its option, HiberCell (search) will be eligible to receive milestone payments and royalties for global net sales of HC-5404, contingent upon successful development and commercialization.
"AVEO and LG Chem (search) are excited to enter into this collaboration with HiberCell (search) to advance the development of this first-in-human PERK (search) inhibitor and to expand on our commitment to RCC patients," said Michael P. Bailey, President and CEO of AVEO. "HC-5404 has shown promising activity combined with VEGFR (search) TKIs which makes pairing it with tivozanib in RCC a logical first phase of development."
FOTIVDA's Established Profile in RCC
FOTIVDA® (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR (search)) tyrosine kinase inhibitor that serves as a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. The FDA approved FOTIVDA on March 10, 2021, for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (search) following two or more prior systemic therapies, based on data from the TIVO-3 trial comparing FOTIVDA to sorafenib.
The drug's safety profile includes hypertension in 45% of patients (22% ≥ Grade 3), with common adverse reactions including fatigue/asthenia, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis.
Expanding Therapeutic Horizons
Steven Gillis, Ph.D., Chairman and acting Chief Executive Officer at HiberCell (search), emphasized the strategic value of the partnership: "AVEO brings considerable scientific and clinical development capabilities across oncology, including significant expertise in renal cell carcinoma (search). This collaboration is an important step in assessing the combination of HC-5404 and tivozanib in RCC and may inform broader development across multiple tumor types."
HiberCell (search) is a clinical stage oncology company dedicated to advancing first-in-class agents with novel mechanisms targeting adaptive stress pathways and anti-tumor immunity. The company believes that therapeutic modulation of these mechanisms allows it to address tumor metastasis, treatment resistance, and cancer relapse—all significant drivers of cancer-related deaths. HiberCell's pipeline also includes GCN2 (search) activator HC-7366, currently under investigation in two Phase 1b trials in renal cell carcinoma (search) and acute myeloid leukemia (search).