AVEO Announces Detailed Results of Exploratory Phase 2 Study Evaluating Ficlatuzumab in First-Line P

AVEO Announces Detailed Results of Exploratory Phase 2 Study Evaluating Ficlatuzumab in First-Line Patients with Advanced Non-small Cell Lung Cancer; New Data Presented at ESMO

Ficlatuzumab Phase 1 Pharmacodynamic Data Also Presented

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- AVEO Oncology (NAS: AVEO) today announced that detailed results from an exploratory, randomized Phase 2 study evaluating the combination of ficlatuzumab, the company's HGF inhibitory antibody, and gefitinib compared to gefitinib monotherapy in previously untreated Asian subjects with non-small cell lung cancer (NSCLC) were presented at the 2012 Congress of the European Society for Medical Oncology (ESMO). As previously reported, the study did not achieve its primary endpoint; however, the results presented at ESMO suggest that the addition of ficlatuzumab to gefitinib may be effective in select subsets of patients.

"The insights gleaned from the Phase 2 study, along with new pharmacodynamic data, show that inhibiting the HGF ligand may be important in the treatment of cancer," stated Tuan Ha-Ngoc, president and chief executive officer, AVEO. "We, along with our scientific advisors and clinical investigators, remain encouraged about ficlatuzumab and believe the program warrants further evaluation. Our top priority is the registration and commercialization of tivozanib, and with that in mind, we will be focusing our efforts on further ficlatuzumab development through external collaborations, including with academic institutions and cooperative groups."

"This study has identified potential predictive biomarkers for the use of ficlatuzumab in patients with advanced NSCLC," said Tony Mok, M.D., professor, Department of Clinical Oncology, The Chinese University of Hong Kong, and senior investigator of the study. "Based on these results, ficlatuzumab merits additional clinical investigation."

The primary endpoint of the study was overall response rate (ORR); secondary endpoints included progression-free survival (PFS), overall survival (OS) and correlation of biomarkers with clinical activity. In the intent to treat (ITT) population, the addition of ficlatuzumab to gefitinib did not result in statistically significant improved ORR or PFS in Asian treatment-naïve NSCLC patients. The preliminary OS hazard ratio in the ITT population for ficlatuzumab plus gefitinib versus gefitinib monotherapy was 0.84 (95% CI 0.52, 1.37). Final OS data will be presented once they are mature. The combination was well-tolerated, with no clinically meaningful differences in adverse event rates observed between the two arms.

The combination demonstrated a trend for improved ORR and PFS in patients with both EGFR-sensitizing mutations and low c-Met biomarker levels (n=19).

Preliminary OS results suggest that the addition of ficlatuzumab to gefitinib may have a favorable impact in the subset of patients with high stromal HGF (N=17 patients, HR=0, p=0.03). Trends for OS benefit in other biomarker subsets continue to be evaluated.

Results from a Phase 1 clinical study evaluating tumor pharmacodynamic changes post ficlatuzumab treatment were also presented at ESMO. In the majority of patients treated, 20 mg/kg of ficlatuzumab (the established Phase 2 dose of ficlatuzumab) resulted in pharmacodynamic modulation in liver metastasis by inhibiting the HGF/c-Met pathway and downstream signaling for cell proliferation, survival, and angiogenesis.

Exploratory Phase 2 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 each; 144 tumor tissue samples were collected for biomarker analysis. Subjects who demonstrated disease control (complete response, partial response, or stable disease for 12 weeks or longer) in the gefitinib arm were eligible to cross-over upon progression to the 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 the sole 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 its dysregulation is believed to play a role in cancer development, metastasis and drug resistance. HGF/c-Met has also 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. 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 resistance to EGFR-targeted therapies, and vice-versa. HGF has also been shown to be one of the most potent growth factors that can drive resistance to a panel of anti-cancer therapies.

Ficlatuzumab is a humanized IgG1κ antibody that binds to the HGF ligand with high affinity and specificity to inhibit the biological activities of the HGF/c-Met pathway. Studies have demonstrated that ficlatuzumab is well tolerated as a single agent as well as in combination with EGFR TKIs.

About AVEO

AVEO Oncology (NAS: 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.aveooncology.com.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements that involve substantial risks and uncertainties. Any statements in this press release about AVEO's future expectations, plans and prospects, including statements about: the potential efficacy and safety of ficlatuzumab; inhibition of the HGF ligand potentially being important in the treatment of cancer, advancement of the ficlatuzumab clinical development plans in lung cancer; and the registration process for tivozanib; ficlatuzumab's therapeutic potential in combination with EGFR targeted therapies, particularly in the subset of patients with high stromal HGF; the potential of AVEO's cancer biology platform 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 clinical trial 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 Quarterly Report on Form 10-Q 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.

Investors:
AVEO Oncology
Monique Allaire, 617-299-5810
or
Media:
AVEO Oncology
Rob Kloppenburg, 617-930-5595
or
Pure Communications
Dan Budwick, 973-271-6085

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