AVEO Announces Preliminary Results of Exploratory Phase 2 Study Evaluating HGF Inhibitor in First-Line Patients with Advanced

  AVEO Announces Preliminary Results of Exploratory Phase 2 Study Evaluating
  HGF Inhibitor in First-Line Patients with Advanced Lung Cancer

    Ficlatuzumab/Gefitinib Combination Was Well-Tolerated and Demonstrated
   Clinical Activity; Study Results Did Not Reach Statistical Significance

    Encouraging Signals of Anti-tumor Activity in Distinct Subpopulations

Business Wire

CAMBRIDGE, Mass. -- May 02, 2012

AVEO Pharmaceuticals Inc. (NASDAQ: AVEO) announced today preliminary data from
the exploratory, randomized Phase 2 study comparing the combination of
ficlatuzumab and gefitinib, an EGFR tyrosine kinase inhibitor (TKI), to
gefitinib monotherapy in previously untreated Asian subjects with non-small
cell lung cancer (NSCLC), a population with a high prevalence of EGFR
sensitizing mutations (SM+). In this study, encouraging signals of activity
were observed in unique subsets of patients based on EGFR mutation status and
c-Met expression level. EGFR TKI therapies are the standard of care for
patients with EGFR SM+.

“Some patients with EGFR sensitizing mutations do not respond well to EGFR TKI
therapy,” stated Tony Mok, M.D., professor, Department of Clinical Oncology,
The Chinese University of Hong Kong, and senior investigator of the Phase 2
trial. “This study has uncovered an important subset of patients with
non-small cell lung cancer that may be underserved by EGFR TKIs. Patients with
EGFR sensitizing mutations and low c-Met expression levels treated with the
combination of ficlatuzumab and gefitinib lived twice as long without their
disease progressing compared to those treated with gefitinib alone. These data
support a potential benefit from combining an EGFR targeted therapy with
ficlatuzumab and warrant further investigation in lung cancer.”

The primary endpoint of the study was overall response rate (ORR), and
progression free survival (PFS) was a secondary endpoint. Preliminary results
in the intent-to-treat (ITT) population (n=94 each arm) showed a trend
favoring the ficlatuzumab/gefitinib combination; however, as with data from
Phase 2 studies in NSCLC with other inhibitors of the Met pathway, study
results in the ITT population did not reach statistical significance. In the
ITT population, ORR was 43% for the ficlatuzumab/gefitinib combination
armversus 40% for the gefitinib monotherapy arm, and median PFS was 5.6 months
versus 4.7 months for the ficlatuzumab/gefitinib combination arm versus the
gefitinib monotherapy arm, respectively, favoring the combination arm.

Encouraging signals of activity were observed in biomarker subset populations.
Key findings are summarized in the following chart:

              Ficlatuzumab/Gefitinib           Gefitinib Alone
Biomarker      Combination
Subset         # of        Median                  # of       Median
              Subjects   PFS        ORR,%    Subjects  PFS       ORR,%
                           (months)                           (months)
EGFR
SM+/c-Met     10         11.0       70       9         5.5       44
Low
EGFR
SM+/c-Met     23         9.2        52       27        9.2       63
High
EGFR
SM-/c-Met     9          1.3        0        13        2.3       0
Low
EGFR
SM-/c-Met     11         1.8        27       16        1.8       13
High
                                                                 

No clinically meaningful differences in adverse event rates between the
combination and monotherapy arms were observed, and the combination was
well-tolerated. Complete data from this trial, which will include biomarker
analyses, are anticipated to be submitted for presentation at an upcoming
medical meeting in the second half of this year.

“These are important data for driving our ficlatuzumab program forward, as
well as for demonstrating the clinical value of AVEO’s proprietary Human
Response Platform,” stated William Slichenmyer, M.D., Sc.M., chief medical
officer of AVEO. “Through our platform, we were able to recognize the
interplay between the EGFR and HGF/c-Met pathways. These biomarker insights,
combined with the clinical data, support our continued development of
ficlatuzumab in combination with an EGFR inhibitor. We look forward to further
clinical investigation in lung cancer. In addition, we will be initiating a
clinical study in head and neck cancer later this year.”

Study Overview

The open-label, two-arm, randomized exploratory Phase 2 study was designed to
compare the combination of ficlatuzumab and gefitinib versus gefitinib
monotherapy, in clinically selected Asian subjects with previously untreated
advanced NSCLC who have a high likelihood of harboring activating EGFR
mutations. Ninety-four(94) patients were randomized to gefitinib and
ficlatuzumab/gefitinib arms, respectively; 144 tumor tissue samples were
available for biomarker analysis. Subjects who demonstrated disease control
(complete response, partial response, or stable disease for 12 weeks or
longer) in the gefitinib alone arm were eligible to cross-over upon
progression to a combination of gefitinib and ficlatuzumab to assess whether
acquired resistance to gefitinib can be overcome with the addition of
ficlatuzumab.

About Ficlatuzumab and the HGF/c-MET Pathway

HGF is a ligand that binds to and activates a receptor called c-Met.
Activation of the HGF/c-Met pathway is believed to be important in normal
processes in embryonic development and wound healing, but is also believed to
trigger many activities involved in cancer development and metastasis.
HGF/c-Met has been shown to be one of the most potent drivers of tumor growth
in AVEO’s Human Response Platform.

HGF/c-Met over-expression is observed in many solid tumors including breast,
colorectal, gastric, head and neck, lung and prostate, as well as hematologic
malignancies^1. Additionally, c-Met and EGFR are frequently co-amplified and
co-expressed in a variety of tumor types; HGF/c-Met pathway upregulation can
render EGFR-targeted therapy resistance, and vice-versa^2-4.

Ficlatuzumab is a humanized IgG1 antibody that binds to the HGF ligand with
high affinity and specificity to inhibit the biological activities of the
HGF/c-Met pathway.

About AVEO

AVEO Pharmaceuticals (NASDAQ: AVEO) is a cancer therapeutics company committed
to discovering, developing and commercializing targeted therapies to impact
patients’ lives. AVEO’s proprietary Human Response Platform™ provides the
company unique insights into cancer biology and is being leveraged in the
discovery and clinical development of its cancer therapeutics. For more
information, please visit the company’s website at www.aveopharma.com.

Cautionary Note Regarding Forward-Looking Statements

Any statements in this press release about AVEO’s future expectations, plans
and prospects, including statements about: the potential efficacy and safety
of ficlatuzumab; advancement of the ficlatuzumab clinical development plans in
lung cancer and head and neck cancer; ficlatuzumab’s therapeutic potential in
combination with EGFR targeted therapies; the potential of AVEO’s cancer
biology platform and biomarker capabilities to offer a unique advantage in
oncology drug development; and other statements containing the words
"believes," "anticipates," "plans," "expects," "potential," "will" and similar
expressions, constitute forward-looking statements within the meaning of The
Private Securities Litigation Reform Act of 1995. Actual results may differ
materially from those indicated by such forward-looking statements as a result
of various important factors, including risks relating to: AVEO’s ability to
successfully research, develop and obtain and maintain regulatory approvals
for ficlatuzumab and its other product candidates, including risks relating to
its ability to successfully advance clinical development of ficlatuzumab for
the treatment of lung cancer; the possibility that favorable historical
preclinical and clinicaltrial results may not be predictive of the results in
future preclinical and clinical trials; AVEO’s ability to obtain and maintain
adequate protection for intellectual property rights relating to its product
candidates and technologies; unplanned operating expenses; AVEO’s ability to
raise substantial additional funds to achieve its goals, including with
respect to the further development of ficlatuzumab; competition; general
economic and industry conditions; and other factors discussed in the "Risk
Factors" section of AVEO’s Annual Report on Form 10-K filed with the
Securities and Exchange Commission, and in other filings that AVEO
periodically makes with the SEC. In addition, the forward-looking statements
included in this press release represent AVEO’s views as of the date of this
press release. AVEO anticipates that subsequent events and developments will
cause its views to change. However, while AVEO may elect to update these
forward-looking statements at some point in the future, AVEO specifically
disclaims any obligation to do so. These forward-looking statements should not
be relied upon as representing AVEO’s views as of any date subsequent to the
date of this press release.

1. Christensen JG, et al. Cancer Letters: 225:1-26.
2. Engelman JA, et al. Science. 316:1039-43.
3. Turke AB, et al. Cancer Cell. 17:77-88.
4. Yano S, et al. Cancer Res. 68:9479-87.

Contact:

Investor Contact:
AVEO Pharmaceuticals
Monique Allaire, 617-299-5810
or
Media Contacts:
AVEO Pharmaceuticals
Rob Kloppenburg, 617-930-5595
or
Pure Communications
Dan Budwick, 973-271-6085
 
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