Agreements

Date: 2017-08-28

Type of information: Licensing agreement

Compound: tivozanib (N-{2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N´-(5-methyl-3-isoxazolyl) urea hydrochloride monohydrate)

Company: Aveo Oncology (USA - MA) Eusa Pharma (UK)

Therapeutic area: Cancer - Oncology

Type agreement: licensing

Action mechanism:

kinase inhibitor/tyrosine kinase inhibitor. Tivozanib is an oral, potent, selective inhibitor of vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI) with a long half-life and activity against all three VEGF receptors. It is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications. Tivozanib has been evaluated in several tumors types, including renal cell, colorectal and breast cancers.

Disease: advanced renal cell carcinoma

Details:

• On December 21, 2015, Aveo Oncology and EUSA Pharma announced an exclusive license agreement in which Aveo has granted EUSA Pharma European rights to tivozanib for the treatment of advanced renal cell carcinoma. The agreement also includes a number of additional territories outside North America, including South America and South Africa, and additional potential indications. EUSA Pharma plans to submit a Marketing Authorization Application for tivozanib as a first line treatment for advanced RCC to the European Medicines Agency in the first quarter of 2016. Under the terms of the agreement, EUSA Pharma will undertake and fund future regulatory and commercial activities to bring tivozanib to market and commercialize the product within the agreement’s territories.

Financial terms:

Under the terms of the agreement, EUSA Pharma will pay Aveo an upfront research and development funding payment of $2.5 million, and up to $394 million in potential payments and milestones, assuming successful achievement of specified development, regulatory and commercialization objectives, as well as a tiered royalty ranging from a low double-digit up to mid-twenty percent on net sales of tivozanib in the agreement’s territories. A percentage of milestone and royalty payments received by Aveo are due to Kyowa Hakko Kirin as a sublicensing fee.

Latest news:

• On August 28, 2017, the European Commission has approved Fotivda® (tivozanib) for the first line treatment of adult patients with advanced renal cell carcinoma and adult patients who are vascular endothelial growth factor receptor (VEGFR) and mTOR pathway inhibitor-naïve following disease progression after one prior treatment with cytokine therapy for advanced renal cell carcinoma.
Under the terms of their December 2015 agreement, EUSA Pharma has agreed to pay Aveo up to $394 million in future milestone payments and research and development funding, assuming successful achievement of specified development, regulatory and commercialization objectives. In addition, a tiered royalty will be due to Aveo ranging from a low double-digit up to mid-twenty percent on net sales of tivozanib in the agreement’s territories. European marketing approval for tivozanib triggers a $4 million research and development payment from EUSA, and Aveo will also be eligible for up to $12 million in additional milestones from EUSA based on reimbursement and regulatory approvals. In the territories licensed to EUSA, thirty percent of milestone and royalty payments received by Aveo, excluding research and development funding, are due to Kyowa Hakko Kirin (KHK) as a sublicensing fee. In the territories retained by Aveo, the royalty obligation to KHK ranges from the low- to mid-teens on net sales.