AVEO Oncology Announces Oral Presentation of TIVO-3 Trial Topline Results at the 2019 ASCO Genitourinary Cancers Symposium

CAMBRIDGE, Mass.–(BUSINESS WIRE)–AVEO Oncology (NASDAQ:AVEO) today announced the presentation of data
from the Phase 3 TIVO-3 study of tivozanib (FOTIVDA®) versus
sorafenib in refractory advanced or metastatic renal cell carcinoma
(RCC). The data were presented by Brian Rini, MD, Professor of Medicine,
Cleveland Clinic Lerner College of Medicine of Case Western Reserve
University, and Director, Cleveland Clinic Genitourinary Cancer Program,
during an oral presentation titled, “TIVO-3: A Phase 3, Randomized,
Controlled, Multi-Center, Open-Label Study to Compare Tivozanib to
Sorafenib in Subjects with Refractory Advanced Renal Cell Carcinoma
(RCC)” at the 2019 American Society of Clinical Oncology (ASCO)
Genitourinary (GU) Cancers Symposium held February 14-16, 2019 in San
Francisco. A copy of the presentation will be available in the
Publications & Presentation section of the Company’s website.


“Tivozanib continues to demonstrate a unique activity and tolerability
profile among VEGF TKIs in the treatment of kidney cancer,” said Dr.
Rini. “This is underscored by a significant improvement in progression
free survival and overall response rate compared to sorafenib in
patients with treatment-refractory advanced RCC. I look forward to
understanding how this improvement impacts overall survival as the
TIVO-3 study continues to mature.”

“We remain committed to our goal of improving outcomes and patient
experience in RCC,” said Michael Bailey, president and chief executive
officer of AVEO. “The improvement in progression free survival in the
TIVO-3 study, particularly in patients who received prior immunotherapy,
is noteworthy. We are hopeful that these positive PFS outcomes translate
into an improved overall survival hazard ratio when we report a more
mature interim OS outcome in the fourth quarter of 2019. We expect to
make a new drug application filing decision following the availability
of more mature OS results.”

TIVO-3 Topline Study Results

The TIVO-3 trial is a Phase 3 randomized, controlled, multi-center,
open-label study designed to compare tivozanib (FOTIVDA®) to
sorafenib in 350 subjects with highly refractory advanced or metastatic
renal cell carcinoma (RCC). The trial met its primary endpoint of
demonstrating a statistically significant benefit in progression-free
survival (PFS). Tivozanib demonstrated a 44% improvement in median PFS
and 26% reduction in the risk of progression or death (Hazard Ratio
[HR]=0.74, p=0.02, see Figure 1). Median PFS was 5.6 months for
tivozanib compared to 3.9 months for sorafenib.

The TIVO-3 trial enrolled patients with RCC who have failed at least two
prior regimens. Among these, approximately 26% of patients received
checkpoint inhibitor (CPI) therapy in earlier lines of treatment. PFS
for tivozanib was longer than sorafenib both in patients who received
prior CPI therapy and those who received two prior VEGF TKI therapies.
Patients who received prior CPI therapy had a median PFS of 7.3 months
with tivozanib and 5.1 months with sorafenib (HR=0.55, p=0.03, see
Figure 2). One- and two-year PFS in patients who received tivozanib
following CPI therapy was 35% and 25%, respectively, and 4% and n/a for
patients receiving sorafenib following CPI therapy at those respective
time periods.

The secondary endpoint of overall response rate for patients receiving
tivozanib was 18% compared to 8% for patients receiving sorafenib
(p=0.02). Median duration of response (DOR) in patients receiving
tivozanib was not reached (95% CI:12.9,—) and was 5.7 months for
patients receiving sorafenib (95% CI:5.6,—). DOR probability at 1 year
was 71% and 46% for tivozanib and sorafenib, respectively, and 55% and
0% at two years.

The analysis of the secondary endpoint of overall survival (OS) was not
mature at the time of the final PFS analysis, and currently reflects
~50% of potential OS events. As previously disclosed, the updated
preliminary OS analysis conducted at an October 4, 2018 data cutoff
date, which included additional patients previously lost to follow-up,
showed a non-statistically significant difference in OS favoring
sorafenib (HR=1.12, p=0.44). The Company intends to conduct an
additional interim OS analysis in August 2019, the results of which are
expected to be reported in the fourth quarter of 2019.

Tivozanib was generally well-tolerated, with grade 3 or higher adverse
events consistent with those observed in previous tivozanib trials.
Infrequent but severe adverse events reported in greater number in the
tivozanib arm were thrombotic events similar to those observed in
previous tivozanib studies. The most common adverse event in patients
receiving tivozanib was hypertension, an adverse event known to reflect
effective VEGF pathway inhibition.

About Tivozanib (FOTIVDA®)

Tivozanib (FOTIVDA®) is an oral, once-daily, vascular
endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI)
discovered by Kyowa Hakko Kirin and approved for the treatment of adult
patients with advanced renal cell carcinoma (RCC) in the European Union
plus Norway and Iceland. It is a potent, selective and long half-life
inhibitor of all three VEGF receptors and is designed to optimize VEGF
blockade while minimizing off-target toxicities, potentially resulting
in improved efficacy and minimal dose modifications.1,2 Tivozanib
has been shown to significantly reduce regulatory T-cell production in
preclinical models3, and has demonstrated synergy in
combination with nivolumab (anti PD-1) in a Phase 2 study in RCC.
Tivozanib has been investigated in several tumor types, including renal
cell, hepatocellular, colorectal and breast cancers.

About AVEO

AVEO Pharmaceuticals, Inc. (the “Company” or “AVEO”) is a
biopharmaceutical company dedicated to advancing a broad portfolio of
targeted medicines for oncology and other areas of unmet medical need.
The Company’s strategy is to retain North American rights to its
oncology portfolio while securing partners in development and
commercialization outside of North America. The Company is seeking to
develop and commercialize its lead candidate tivozanib in North America
as a treatment for advanced or metastatic renal cell carcinoma (“RCC”).
The Company has outlicensed tivozanib (FOTIVDA®) for
oncological indications in Europe and other territories outside of North
America. Tivozanib is approved in the European Union, 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
and mTOR pathway inhibitor-naïve following disease progression after one
prior treatment with cytokine therapy for RCC. In addition, a new
formulation of tivozanib is being explored in ocular conditions. The
Company has entered into partnerships for the development and
commercialization of AV-203 (CAN017) and ficlatuzumab, both clinical
stage assets in oncology. The Company is currently seeking a partner to
develop the AV-353 platform, a preclinical asset, worldwide for the
potential treatment of pulmonary arterial hypertension and oncology. The
Company has recently regained the rights to its AV-380 program for the
potential treatment of cachexia and is initiating toxicology studies to
support the filing of an initial new drug application and advance the
program’s development.

For more information, please visit the Company’s website at www.aveooncology.com.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements of AVEO that
involve substantial risks and uncertainties. All statements, other than
statements of historical fact, contained in this press release are
forward-looking statements. The words “anticipate,” “believe,” “expect,”
“intend,” “may,” “plan,” “potential,” “could,” “should,” “would,”
“seek,” “look forward,” “advance,” “goal,” “strategy,” or the negative
of these terms or other similar expressions, are intended to identify
forward-looking statements, although not all forward-looking statements
contain these identifying words. These forward-looking statements
include, among others, statements about: AVEO’s plans to make a NDA
filing decision following the availability of more mature OS results;
AVEO’s plans to complete an interim OS analysis for the TIVO-3 trial in
August 2019 and to report the results of this analysis in the fourth
quarter; AVEO’s plans to present TIVO-3 data at ASCO GU; AVEO’s
expectation that the OS outcome will be more mature by August 2019;
AVEO’s hope that the positive PFS outcome will translate into an
improved hazard ratio; AVEO’s intent to continue to work with the FDA to
determine tivozanib’s risk-benefit profile as a single agent in RCC; the
efficacy, safety, and tolerability of tivozanib, as a single agent and
in combination with other therapies in several indications, such as RCC
and HCC; AVEO’s plans and strategies for commercialization of tivozanib
in the United States and Europe; AVEO’s plans to develop the AV-353
platform; AVEO’s plans regarding AV-380 and AVEO’s other strategy,
prospects, plans and objectives for its product candidates and for the
Company generally. AVEO has based its expectations and estimates on
assumptions that may prove to be incorrect. As a result, readers are
cautioned not to place undue reliance on these expectations and
estimates. Actual results or events could differ materially from the
plans, intentions and expectations disclosed in the forward-looking
statements that AVEO makes due to a number of important factors,
including risks relating to: AVEO’s ability, and the ability of its
licensees, to demonstrate to the satisfaction of applicable regulatory
agencies such as the FDA the safety, efficacy and clinically meaningful
benefit of AVEO’s product candidates, including, in particular,
tivozanib; AVEO’s ability to successfully file an NDA for tivozanib; and
AVEO’s ability to enter into and maintain its third party collaboration
and license agreements, and its ability, and the ability of its
strategic partners, to achieve development and commercialization
objectives under these arrangements. AVEO faces other risks relating to
its business as well, including risks relating to the timing and costs
of seeking and obtaining regulatory approval; AVEO’s and its
collaborators’ ability to successfully enroll and complete clinical
trials; AVEO’s ability to maintain compliance with regulatory
requirements applicable to its product candidates; AVEO’s ability to
obtain and maintain adequate protection for intellectual property rights
relating to its product candidates; AVEO’s ability to successfully
implement its strategic plans; AVEO’s ability to raise the substantial
additional funds required to achieve its goals, including those goals
pertaining to the development and commercialization of tivozanib;
unplanned capital requirements; adverse general economic and industry
conditions; competitive factors; and those risks discussed in the
sections titled “Risk Factors” and “Management’s Discussion and Analysis
of Financial Condition and Results of Operations—Liquidity and Capital
Resources” included in AVEO’s quarterly and annual reports on file with
the Securities and Exchange Commission (SEC) and in other filings that
AVEO makes with the SEC. The forward-looking statements in this press
release represent AVEO’s views as of the date of this press release, and
subsequent events and developments may cause its views to change. While
AVEO may elect to update these forward-looking statements at some point
in the future, it specifically disclaims any obligation to do so. You
should, therefore, not rely on these forward-looking statements as
representing AVEO’s views as of any date other than the date of this
press release. Any reference to AVEO’s website address in this press
release is intended to be an inactive textual reference only and not an
active hyperlink.

References

1. Fotivda (Tivozanib) SmPC August 2017

2. Motzer RJ, Nosov D, Eisen T, et al. J Clin Oncol 2013;
31(30): 3791-9.

3. Pawlowski N et al. AACR 2013. Poster 3971.

Contacts

AVEO:
David Pitts, Argot Partners
(212) 600-1902
aveo@argotpartners.com