PROSPECTUS SUPPLEMENT SUMMARY
This summary does not contain all of the information that you should consider before investing in our securities. You should read this
entire prospectus supplement and the accompanying prospectus carefully, including the financial statements and other information incorporated by reference in this prospectus supplement and the accompanying prospectus, before making an investment
decision. In addition, please read the Risk Factors section of this prospectus supplement beginning on page
S-17
and the risk factors contained in our Annual Report on Form
10-K
for the year ended December 31, 2018.
Overview
We are a biopharmaceutical company seeking to advance targeted medicines for oncology and other unmet medical needs. We are working to develop
and commercialize our lead candidate tivozanib in North America as a treatment for advanced or metastatic renal cell carcinoma, or RCC. In November 2018, we announced that our phase 3 randomized, controlled, multi-center, open-label trial comparing
tivozanib to an approved therapy, sorafenib (Nexavar
®
), in 350 subjects as a third- and fourth-line treatment for RCC, including subjects with prior checkpoint inhibitor therapy, which we
refer to as the
TIVO-3
trial, met its primary endpoint of improving progression-free survival, or PFS. Data for the secondary endpoint of the
TIVO-3
trial, overall
survival, or OS, was not mature as of the time of the final PFS analysis. In January 2019, the U.S. Food and Drug Administration, or FDA, recommended that we not submit a new drug application, or NDA, for tivozanib at this time as the preliminary OS
results from the
TIVO-3
trial did not allay its concerns about a potential detriment in OS from our previously completed phase 3 trial for tivozanib in the first-line treatment of RCC, which we refer to as the
TIVO-1
trial. Following discussion with the FDA, we have extended the timeline for the
TIVO-3
trial OS analysis and plan to conduct another interim OS analysis in
August 2019. We anticipate reporting the results of this analysis in the fourth quarter of 2019, and plan to provide an update regarding the potential submission of an NDA for tivozanib to the FDA.
We are leveraging several collaborations in the development of tivozanib. We have sublicensed tivozanib, marketed under the brand name
FOTIVDA
®
, for oncological indications in Europe and other territories outside of North America. Through our partner, tivozanib is approved in the European Union, or EU, as well as Norway and
Iceland, for the first-line treatment of adult patients with RCC and for adult patients who are vascular endothelial growth factor receptor, or VEGFR, and mTOR pathway
inhibitor-naïve
following disease
progression after one prior treatment with cytokine therapy for RCC. We also have clinical collaborations to study tivozanib in combination with immune checkpoint inhibitors in RCC and in hepatocellular carcinoma, or HCC. We are conducting
a phase 2 clinical trial of tivozanib in combination with Opdivo
®
(nivolumab), a
PD-1
inhibitor, in the first-line and the second-line treatment of RCC,
which we refer to as the TiNivo trial. Leveraging early monotherapy results in HCC, we have a clinical collaboration to study tivozanib in combination with IMFINZI
®
(durvalumab), a
PD-L1
inhibitor, for the treatment of advanced, unresectable HCC. In addition, a new formulation of tivozanib is in preclinical development for the treatment of
age-related
macular degeneration.
As part of our strategy, we have also entered into partnerships
to help fund the development and commercialization of our other product candidates. Ficlatuzumab, a hepatocyte growth factor, or HGF, inhibitory antibody, is currently being tested in several investigator sponsored studies jointly funded by us
and one of our development partners for the potential treatment of squamous cell carcinoma of the head and neck, or HNSCC, acute myeloid leukemia, or AML, and pancreatic cancer. Our partner for
AV-203,
an
anti-ErbB3 monoclonal antibody, is planning to initiate clinical studies in China in 2019 in esophageal squamous cell carcinoma, or ESCC, and has committed to funding the development of
AV-203
through
proof-of-concept. We
have recently regained the rights to
AV-380,
a humanized IgG1 inhibitory monoclonal antibody targeting growth
differentiation factor 15, or GDF15, a divergent member of the
TGF-ß
family, for the potential treatment of cancer cachexia, and are working to initiate preclinical toxicology studies in 2019 to support
the potential