AVEO Reports Third Quarter 2018 Financial Results and Provides Business Update
“The recent announcement of positive topline results from the Phase 3
Tivozanib TIVO-3 Study North America Update
- Positive Topline Results from Phase 3
TIVO-3 Trial of Tivozanib in Renal Cell Carcinoma, with Goal to Submit NDA in Approximately Six Months. On Monday, November 5, 2018, AVEOannounced positive topline results from the primary analysis of the TIVO-3 trial, the Company’s Phase 3 randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in 351 subjects with 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). Patients receiving tivozanib demonstrated a 44% improvement in median PFS and a 26% reduction in risk of progression or death (hazard ratio (HR)=0.74; p=0.02). Preliminary overall survival (OS) at the time of the final PFS analysis was immature (only 46% of events reported) and showed no statistically significant difference (HR=1.06, p=0.69). 149 patients remain on treatment or in long term follow-up.
Tivozanib was generally well-tolerated, with adverse events consistent with those observed in previous tivozanib trials, including the Phase 3
TIVO-1 trial in front-line RCC. The most common adverse event in patients receiving tivozanib was hypertension, an on-target event known to reflect effective VEGF pathway inhibition and one managed by anti-hypertensive medication. Detailed results of the trial will be submitted for presentation at an upcoming major medical meeting.
Based on results from the
TIVO-3 trial, together with the previously completed TIVO-1 trial of tivozanib in the first-line treatment of RCC, the Company plans to submit a potential New Drug Application (NDA) with the U.S. Food and Drug Administration( FDA) in approximately six months.
Tivozanib TiNivo Study Update
- Updated Phase 2 Results from the TiNivo Trial of Tivozanib and
Nivolumab (OPDIVO®) in RCC Presented at the
2018 ESMO Annual Meeting. Updated Phase 2 data from the Phase 1b/2
TiNivo study of tivozanib in combination with nivolumab (OPDIVO®,
Bristol-Myers Squibb), an immune checkpoint, or PD-1, inhibitor, were presented at the 2018 European Society for Medical Oncology( ESMO) Annual Meeting in Munich. As of the date of the presentation, the Phase 1b/2 study had enrolled a total of 28 patients, and the Phase 2 portion of the study (n=22) was designed to assess the safety, tolerability, and anti-tumor activity of the full dose and schedule of oral tivozanib as established in the Phase 1b portion of the study.
The data demonstrated that the tivozanib-nivolumab combination continued to exhibit synergistic efficacy and favorable tolerability. Treatment-related Grade 3/4 adverse events occurred in 60% of patients, the most common of which was hypertension. Preliminary efficacy was assessed in all 25 patients, who were treated with the full dose and schedule of oral tivozanib in combination with intravenous nivolumab. Of these patients, 13 (52%) had received at least one prior systemic therapy, including 2 (8%) that had received prior PD-1 therapy, and 12 (48%) were treatment naïve. An overall response rate was observed in 14 patients (56%) (complete response plus partial response), including 1 patient (4%) achieving a complete response, and a disease control rate (complete response plus partial response plus stable disease) was observed in 24 patients (96%). The 2 patients (8%) who received prior PD-1 therapy both achieved a partial response. At the time of data collection, 13 patients (52%) remained on study and 18 patients (72%) had tumor shrinkage of at least 25%, with a majority of patients having disease control for at least 48 weeks.
Tivozanib (FOTIVDA®) European Union Updates
- Tivozanib (FOTIVDA®) Launched in
Sweden, the Netherlandsand Scotlandfor the Treatment of RCC. Since the beginning of the third quarter of 2018,FOTIVDA® was launched in Sweden, the Netherlandsand Scotlandfor the first-line treatment of adult patients with RCC, following price and reimbursement approvals within each country. FOTIVDA® is now available in Germany, the U.K., Austria, the Netherlandsand Sweden. FOTIVDA® was granted European Commissionapproval in August 2017for the treatment of adult patients with RCC in the European Unionplus Norwayand Iceland.
Under its agreement with EUSA Pharma, licensee for tivozanib in the territories of
Europe(excluding Russia, Ukraineand the Commonwealth of Independent States), Latin America(excluding Mexico), Africaand Australasiafor all diseases and conditions in humans, excluding non-oncologic diseases or conditions of the eye, AVEOis entitled to double-digit royalty payments on net sales of FOTIVDA® in Europe, up to $8.0 millionin milestone payments for potential reimbursement approvals for Germany, France, Italy, and Spainand a potential $20.0 millionR&D reimbursement payment for access to TIVO-3 trial data in addition to other regulatory and commercial milestone payments.
- Trials in Progress Poster for Phase 2 Study of Ficlatuzumab in
Combination with Cetuximab in HNSCC Presented at the 2018 ESMO Annual
Meeting. An investigator-sponsored Phase 2 trial of ficlatuzumab
and cetuximab (ERBITUX®), an EGFR-targeted antibody, in
patients with cetuximab-resistant, metastatic head and neck squamous
cell carcinoma (HNSCC) was presented as a trials in progress poster at
the 2018 ESMO Annual Meeting. This randomized multi-center study,
which is being conducted under the direction of
Julie E. Bauman, MD, MPH, Professor of Medicine, Chief, Division of Hematology/Oncology, Associate Director of Translational Research, University of Arizona Cancer Center, is expected to enroll approximately 60 patients randomized to receive either ficlatuzumab alone or ficlatuzumab and cetuximab.
CAN017 (AV-203) Update
- CANbridge IND for CAN017 (AV-203) Trial in Esophageal Squamous Cell
Cancer Accepted in
China. In August 2018, AVEOannounced that the China National Drug Administration(CNDA) accepted CANbridge Life Sciences’ Investigational New Drug (IND) Application for a Phase 1b/3 clinical trial of CAN017 (AV-203), AVEO’s clinical-stage ErbB3 (HER3) inhibitory antibody candidate, in esophageal squamous cell cancer (ESCC). Under the terms of a March 2016agreement, the acceptance of the IND triggered a $2.0 millionmilestone payment to AVEO from CANbridge Life Sciences. CANbridge licensed worldwide rights, excluding the United States, Canada, and Mexico, to AV-203 from AVEO, and AVEO is eligible to receive up to $40.0 millionin potential additional development and regulatory milestone payments and up to $90.0 millionin potential commercial milestone payments, assuming the successful achievement of specified development, regulatory and commercialization objectives.
- Secured Additional Funding through Offering of Common Stock. In
August 2018, AVEOannounced an underwritten public offering of 2,500,000 shares of common stock at a price of $2.26per share, resulting in aggregate gross proceeds of $5.7 million. In October and November 2018, the Company sold 3,781,389 shares of its common stock in at-the market transactions pursuant to its sales agreement with Leerink Partners LLC( Leerink) and received approximately $8.4 millionin net proceeds.
Third Quarter 2018 Financial Highlights
AVEOended Q3 2018 with $20.4 millionin cash, cash equivalents and marketable securities as compared with $33.5 millionat December 31, 2017.
Total revenue for Q3 2018 was approximately
$2.5 millioncompared with $4.6 millionfor Q3 2017.
Research and development expense for Q3 2018 was
$5.2 millioncompared with $4.7 millionfor Q3 2017.
General and administrative expense for Q3 2018 was
$2.7 millioncompared with $2.1 millionfor Q3 2017.
Net loss for Q3 2018 was
$22.2 million, or a loss of $0.18per basic and diluted share, compared with net loss of $26.4 millionfor Q3 2017, or a loss of $0.22per basic and diluted share. Approximately $16.2 millionof Q3 2018 net loss was a non-cash loss attributable to the increase in the fair value of the 2016 private placement warrant liability that principally resulted from the increase in the stock price that occurred within the quarter. In Q3 2017, the non-cash loss attributable to the increase in the fair value of such warrant liability was $23.5 million.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements of
AVEO PHARMACEUTICALS, INC.
Condensed Consolidated Statements of Operations
(In thousands, except per share amounts)
|Three Months Ended
|Nine Months Ended
|Collaboration and licensing revenue||$||2,335||$||4,614||$||3,651||$||7,497|
|Research and development||5,160||4,666||15,451||19,503|
|General and administrative||2,719||2,101||8,156||6,734|
|Loss from operations||(5,412||)||(2,153||)||(19,014||)||(18,740||)|
|Other expense, net:|
|Interest expense, net||(579||)||(655||)||(1,621||)||(1,736||)|
|Change in fair value of PIPE Warrant liability||(16,172||)||(23,538||)||(6,512||)||(47,947||)|
|Other expense, net||(16,751||)||(24,193||)||(8,133||)||(49,683||)|
|Loss before provision for income taxes||(22,163||)||(26,346||)||(27,147||)||(68,423||)|
|Provision for income taxes||—||(51||)||—||(101||)|
|Net loss per share - basic and diluted||$||(0.18||)||$||(0.22||)||$||(0.23||)||$||(0.67||)|
|Weighted average number of common shares outstanding||120,138||118,006||119,311||101,754|
Consolidated Balance Sheet Data
|Cash, cash equivalents and marketable securities||$||20,408||$||33,525|
|Prepaid expenses and other current assets||686||1,256|
|Liabilities and stockholders’ deficit|
|Accounts payable and accrued expenses||$||13,426||$||13,215|
|Loans payable, net of discount||18,877||18,477|
|Deferred revenue and research and development reimbursements||5,284||2,820|
|PIPE Warrant liability||43,157||37,746|
|Estimated settlement liability||-||17,073|
|Total liabilities and stockholders’ deficit||$||21,442||$||50,198|
Source: AVEO Oncology
David Pitts, 212-600-1902