AVEO and Biodesix Announce Exploratory Analysis of VeriStrat-Selected Patients with Non-Small Cell Lung Cancer in Phase 2 Study of Ficlatuzumab

AVEO Oncology (NASDAQ: AVEO) and Biodesix, Inc. today announced the presentation of results from a retrospective exploratory analysis using VeriStrat®, a commercially available serum protein test, to identify patients most likely to benefit from the addition of ficlatuzumab, AVEO’s HGF inhibitory antibody, to epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) therapy in a randomized Phase 2 study of ficlatuzumab and gefitinib (IRESSA®) in previously untreated Asian subjects with non-small cell lung cancer (NSCLC).  The results, presented in a poster session (abstract #8195) at the 2014 Congress of the European Society for Medical Oncology (ESMO), suggest that VeriStrat may be selective of positive clinical response for ficlatuzumab plus gefitinib over gefitinib alone.

“EGFR TKIs are an important class of therapy for which VeriStrat has potential prognostic and predictive value,” said Tony Mok, M.D., Professor, Department of Clinical Oncology, The Chinese University of Hong Kong, and senior investigator of the study. “VeriStrat appears to measure a host response in which tumors may become stimulated by alternative pathways, such as HGF/c-MET, leading to resistance to EGFR TKI therapy. In this exploratory analysis, the addition of the HGF-targeted antibody ficlatuzumab to an EGFR TKI therapy has shown encouraging results in this subgroup, including significant improvements in overall survival and progression free survival.”

Exploratory Analysis Results in Detail

A total of 188 patients were enrolled in a randomized Phase 2 study (P6162) designed to compare the combination of ficlatuzumab and gefitinib with gefitinib alone in treatment-naïve Asian patients with non-small cell lung adenocarcinoma.  For this retrospective exploratory analysis, 180 serum samples were assigned a VeriStrat label of either “Good” (VSG) or “Poor” (VSP) (VSG=145, VSP=35).  While the study failed to demonstrate improved overall survival (OS) or progression-free survival (PFS) over gefitinib alone in the intent-to-treat population, the addition of ficlatuzumab to gefitinib provided significant clinical benefit to the VSP subgroup:

No benefit was observed in the VSG subgroup in either OS (Median 24.7 mo for ficlatuzumab + gefitinib [n=69] vs not reached for gefitinib alone [n=76]; HR 1.18, p=0.492) or PFS (Median 5.6 mo for ficlatuzumab + gefitinib vs 5.6 mo for gefitinib alone; HR 1.06, p=0.753). Despite the small sample sizes, similar patterns in OS and PFS based on VeriStrat stratification were also observed in patients with known EGFR mutations (n=71) and VSP classification (n=11):

Based on these data, in April 2014, AVEO and Biodesix® entered into a worldwide agreement to develop and commercialize ficlatuzumab with a Biodesix companion diagnostic test. As part of this agreement, AVEO and Biodesix plan to conduct a confirmatory Phase 2 study using a Biodesix VeriStrat “Poor” classification as a selective biomarker for the combination of ficlatuzumab and an EGFR-TKI, versus an EGFR TKI alone, in previously untreated, EGFR mutation-positive patients with advanced non-small-cell lung cancer.  The study is expected to initiate before year-end.

“This analysis suggests that VeriStrat Poor, EGFR TKI-sensitizing mutation-positive patients with NSCLC appear to have limited response to EGFR TKI alone, identifying a significant unmet medical need,” stated Tuan Ha-Ngoc, president and chief executive officer of AVEO.  “Given our scientific hypothesis, and the encouraging results in this well-defined patient subset, we believe further clinical evaluation of ficlatuzumab and an EGFR TKI therapy in this population is warranted.”

“These results suggest that a blood test may be used to more precisely classify the response of a subset of patients who, based on EGFR mutation status, should be candidates for an EGFR inhibitor yet appear not to respond to the mono-therapy without the addition of ficlatuzumab,” said David Brunel, chief executive officer of Biodesix. “By using biomarkers and Biodesix’ proprietary ‘predictive intelligence’ computational approach, we believe we can further identify patient sub-populations with differential predictive and prognostic outcomes to advance decisions for therapeutic guidance. Biomarkers are empowering oncologists and the healthcare community with an evidence-based medical approach that informs more precise decisions on diagnosis, prognosis, therapeutic guidance and quality of patient care.”

A copy of the poster presentation is available on AVEO’s website at www.aveooncology.com.

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 IgG1? 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 VeriStrat

VeriStrat, developed by Biodesix, is a multivariate, blood-based, protein test currently available to help physicians guide treatment decisions for patients with advanced non-small cell lung cancer. The test identifies patients who are likely to have “Good” or “Poor” outcomes after treatment with either epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy such as erlotinib or with chemotherapy. VeriStrat is based on Biodesix’ proprietary proteomics platform which enables the discovery of multivariate classifiers that characterize a patient’s condition or likely outcome in response to therapy. www.VeriStratSupport.com.

About AVEO

AVEO Oncology (NASDAQ: AVEO) is a biopharmaceutical company committed to discovering and developing targeted therapies designed to provide substantial impact in the lives of people with cancer by addressing unmet medical needs. AVEO’s proprietary Human Response Platform™ provides the company unique insights into cancer and related disease biology and is being leveraged in the discovery and clinical development of its therapeutic candidates. For more information, please visit the company’s website at www.aveooncology.com.

About Biodesix

Biodesix is a molecular diagnostics company advancing the development of innovative products for personalizing medicine. The company provides physicians with diagnostic tests for earlier disease detection, more accurate diagnosis, disease monitoring and better therapeutic guidance, which may lead to improved patient outcomes. Biodesix discovers, develops and commercializes multivariate protein diagnostics based on their proprietary mass spectrometry-based discovery platform. In addition to developing novel diagnostics independently, the company also partners with biotechnology and pharmaceutical companies to develop companion diagnostics to improve utility of therapeutic agents. For more information about Biodesix, please visit www.Biodesix.com.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements of AVEO within the meaning of The Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties.  All statements, other than statements of historical facts, contained in this press release are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “target,” “potential,” “could,” “should,” “seek,” 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 conduct a Phase 2 study of ficlatuzumab using Biodesix’s Veristrat test; the commencement of the Phase 2 study prior to year-end; and the ability for VeriStrat to be predictive of positive clinical response for ficlatuzumab plus gefitinib over gefitinib alone.  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 to execute on its business strategy and enter into and maintain new strategic partnerships and collaboration agreements; AVEO’s ability to successfully enroll and complete clinical trials and preclinical studies of its product candidates; AVEO’s ability to demonstrate to the satisfaction of the FDA, or equivalent foreign regulatory agencies, the safety, efficacy and clinically meaningful benefit of its product candidates; AVEO’s ability to achieve and maintain compliance with all 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 and technologies; developments and expenses related to AVEO’s ongoing shareholder litigation and SEC inquiry; AVEO’s ability to raise the substantial additional funds required to achieve its goals; adverse general economic and industry conditions; competitive factors; and those risks discussed in the section titled “Risk Factors” included in AVEO’s most recent Quarterly Report on Form 10-Q and in its other filings with the SEC. The forward-looking statements 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, 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 subsequent to the date of this press release.

AVEO Contact:

David Pitts, Argot Partners

(212) 600-1902

aveo@argotpartners.com

Biodesix Contacts:
Kena Hudson or Kelly Quigley, 510-908-0966
Biodesix@Chempetitive.com

For Customer Support, call: (866) 432-5930