AVEO Oncology said today it has agreed to license its drug candidate tivozanib in Russia, Ukraine, and the Commonwealth of Independent States (CIS) to Pharmstandard Group, for all human disease and condition indications except non-oncologic ocular conditions.
The deal could generate up to $9 million-plus for AVEO Oncology. Pharmstandard has agreed to pay AVEO $1.5 million upfront, as well as up to $7.5 million for the first marketing authorization of tivozanib approved in Russia—as well as $3 million for each additional approved indication.
However, the $7.5 million could be reduced to $3 million if Russian regulatory authorities require additional studies to be conducted by Pharmstandard prior to approval, AVEO acknowledged in a Form 8-K regulatory filing.
AVEO said it is also eligible for a “high” single-digit royalty from Pharmstandard on net sales in the countries covered by the agreement. An undisclosed percentage of all upfront, milestone, and royalty payments received by AVEO are due to Kyowa Hakko Kirin as a sublicensing fee required under a 2006 agreement between the companies.
Tvozanib is an oral, once-daily small molecule tyrosine kinase inhibitor of all three vascular endothelial growth factor (VEGF) receptors. Tivozanib has been the subject of Phase II and Phase III studies in renal cell carcinoma, a Phase II study in colorectal cancer that according to AVEO has yielded promising biomarker results, and additional studies in breast cancer.
In March, AVEO presented results from the 265-patient, Phase II BATON-CRC trial designed to explore the combination of mFOLFOX6 and tivozanib or bevacizumab as first-line treatment in patients with advanced metastatic CRC, at the 2015 American Association for Cancer Research (AACR) Tumor Angiogenesis and Vascular Normalization Conference. One biomarker explored in the study—neuropilin-1 (NRP-1), a signaling protein known to bind to VEGF-A in serum—was found to be a potential prognostic marker for angiogenesis inhibitor activity and may be predictive of tivozanib activity relative to bevacizumab, AVEO said.
However, in June, AVEO acknowledged that in the FDA’s view, “insufficient data exists to determine the appropriateness of this subgroup” for a Phase III study. As a result, AVEO said in a statement at the time, the company “plans to evaluate options to confirm the activity of tivozanib and FOLFOX in NRP-1 low CRC through a prospectively defined, randomized Phase II study, while continuing to work on the development of a commercially viable assay.”
AVEO regained all rights to tivozanib in August 2014 after Astellas Pharma terminated a three-year co-development collaboration. Three months later, AVEO entered into an option agreement with Ophthotech to investigate tivozanib as a potential treatment of non-oncologic diseases of the eye—a deal valued at up-to-$105.5 million-plus.
“Similar to our agreement with Ophthotech, this transaction represents an opportunity to monetize tivozanib in areas outside of our core strategic focus, and we believe that this agreement further validates the body of clinical data for, and unique product profile of, tivozanib,” AVEO president and CEO Michael Bailey said in a statement.
“We will continue to explore additional strategies to unlock the value of this asset, and remain committed to our goal of leveraging biomarker data and external partnerships to advance our pipeline,” Bailey added.