On November 4, 2025 AVEO Oncology, an LG Chem company (AVEO), and HiberCell, Inc. (HiberCell) reported that the companies have entered into an exclusive development and option agreement to develop HiberCell’s first-in-human human protein kinase RNA-like endoplasmic reticulum kinase (PERK) inhibitor, HC-5404, alone and in combination with AVEO’s potent and selective vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), FOTIVDA (tivozanib). FOTIVDA is an anti-angiogenic agent approved by the U.S. Food and Drug Administration in March of 2021 for the treatment of adult patients with relapsed or refractory renal cell carcinoma (RCC) following two or more prior systemic therapies. Pre-clinical studies of HC-5404 in multiple solid tumor models, including gastric cancer and RCC, suggest the potential for enhanced anti-tumor efficacy when combined with an anti-angiogenic agent.

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Under the terms of the agreement, AVEO is 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. In addition, if AVEO exercises its option, HiberCell 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 are excited to enter into this collaboration with HiberCell to advance the development of this first-in-human PERK 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 TKIs which makes pairing it with tivozanib in RCC a logical first phase of development. The combinability with our current portfolio in RCC, coupled with the opportunity to expand to other oncology indications, make this collaboration an important step in our vision to become a global leader in oncology."

"We are excited to be partnering with AVEO to help us explore the combination activity of HC-5404 and tivozanib in metastatic renal cell carcinoma," said Steven Gillis, Ph.D., Chairman and acting Chief Executive Officer at HiberCell. "AVEO brings considerable scientific and clinical development capabilities across oncology, including significant expertise in renal cell carcinoma. 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."

About FOTIVDA (tivozanib)
FOTIVDA (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021, for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies, based on data from the TIVO-3 trial comparing FOTIVDA to sorafenib. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner Recordati UK Ltd. for the treatment of adult patients with advanced RCC. FOTIVDA was discovered by Kyowa Kirin.

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTION

Hypertension was reported in 45% of patients (22% ≥ Grade 3). Hypertensive crises were reported in 0.8% of patients. Do not initiate FOTIVDA in patients with uncontrolled hypertension. Monitor for hypertension and treat as needed. Reduce the FOTIVDA dose for persistent hypertension not controlled by anti-hypertensive medications. Discontinue FOTIVDA for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Cardiac failures were reported in 1.6% of patients (1% ≥ Grade 3); 0.6% of events were fatal. Monitor for signs or symptoms of cardiac failure during treatment with FOTIVDA. Manage with dose interruption, dose reduction, or discontinuation.

Cardiac ischemia were reported in 3.2% of patients; 0.4% of events were fatal. Arterial thromboembolic events were reported in 2.0% of patients, including death due to ischemic stroke (0.1%). Closely monitor patients at risk for, or who have a history of these events. Discontinue FOTIVDA in patients who develop severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thrombotic Events (VTE) were reported in 2.4% of patients, including 0.3% fatal events. Closely monitor patients who are at increased risk for these events. Discontinue in patients who develop serious VTEs.

Hemorrhagic Events were reported in 11% of patients; 0.2% of events were fatal. Use FOTIVDA with caution in patients who are at risk for or who have a history of bleeding.

Proteinuria was reported in 8% of patients (2% = Grade 3). Monitor during treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or interrupt treatment. Discontinue in patients who develop nephrotic syndrome.

Gastrointestinal (GI) Perforation including fatal cases, has been reported in patients receiving FOTIVDA. Monitor for symptoms of GI perforation or fistula formation periodically throughout treatment with FOTIVDA. Permanently discontinue FOTIVDA in patients who develop severe or life-threatening GI perforation.

Thyroid Dysfunction events were reported in 11% of patients (0.3% ≥ Grade 3). Monitor thyroid function before and during treatment with FOTIVDA.

Wound Healing Complications: Withhold FOTIVDA for at least 24 days prior to elective surgery and do not administer for at least 2 weeks after major surgery and until adequate wound healing is observed.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) can occur with FOTIVDA. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue if signs or symptoms of RPLS occur.

Embryo-fetal Toxicity: FOTIVDA can cause fetal harm. Advise patients of the potential risk to a fetus, to avoid becoming pregnant and to use contraception during treatment and for one month after the last dose of FOTIVDA. Advise males with female partners of reproductive potential to use effective contraception during treatment and for one month after the last dose of FOTIVDA.

Allergic Reaction to Tartrazine: FOTIVDA 0.89 mg capsule contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS

Common adverse reactions include fatigue/asthenia, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis.

Serious adverse reactions include bleeding (3.5%), venous thromboembolism (3.5%), arterial thromboembolism (2.9%), acute kidney injury (2.3%), and hepatobiliary disorders (2.3%).

DRUG INTERACTIONS

Avoid coadministration with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Advise women not to breastfeed during treatment and for at least 1 month after the last dose.

The recommended dosage for patients with end-stage renal disease has not been established.

Reduce the FOTIVDA dose for patients with moderate hepatic impairment. The recommended dosage in patients with severe hepatic impairment has not been established.

To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information for FOTIVDA (tivozanib).

(Press release, AVEO, NOV 4, 2025, View Source [SID1234659391])