AVEO Oncology Announces Presentation of Long-Term Efficacy Follow Up, Additional Tolerability Data from the Phase 3 TIVO-3 Study of FOTIVDA® (tivozanib) in Relapsed or Refractory Renal Cell Carcinoma

AVEO Oncology (Nasdaq: AVEO), a commercial and clinical development stage biopharmaceutical company, today announced the presentation of additional data from the Phase 3 TIVO-3 study comparing FOTIVDA® (tivozanib) to sorafenib in relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. The data, which includes updated durability of response (DOR) and overall survival (OS) results, as well as an analysis of treatment-emergent adverse events (TEAEs) across study arms, will be featured in two poster presentations at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting being held June 4-8 in a virtual setting. FOTIVDA, AVEO’s oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI), is approved by the U.S. Food and Drug Administration for the treatment of adults with relapsed or refractory advanced RCC following two or more prior systemic therapies.

“With advances in RCC treatment, patients are living longer, increasing the need for proven, well tolerated options in the relapsed or refractory setting,” said Brian Rini, MD, Chief of Clinical Trials at Vanderbilt Ingram Cancer Center and principal investigator of the TIVO-3 trial. “The TIVO-3 study is the first positive Phase 3 study in RCC patients who received two or more prior systemic therapies, and these long-term follow up results continue to demonstrate the depth and durability of responses to FOTIVDA, as well as a tolerability profile that is particularly important in the later-stage treatment setting.”

“FOTIVDA has demonstrated a differentiated clinical profile, and we are very pleased with initial receptivity to this differentiation and to the importance of the unique dataset that the TIVO-3 study represents in the commercial setting,” said Michael Bailey, president and chief executive officer of AVEO. “We were also pleased to see efficacy advantages relative to sorafenib were maintained or improved with longer follow-up. We look forward to continuing to elucidate FOTIVDA’s potential in the clinic, particularly in the immunotherapy combination setting, with patient enrollment in the pivotal Phase 3 TiNivo-2 study of FOTIVDA in combination with OPDIVO® (nivolumab) anticipated to commence mid-year and execution of the Phase 2 hepatocellular carcinoma DEDUCTIVE trial in combination with IMFINZI® (durvalumab) ongoing.”

TIVO-3 ASCO Data

TIVO-3 is a Phase 3, open-label study that enrolled patients with metastatic RCC whose disease progressed on two or more prior systemic regimens, one of which included a VEGFR TKI. Patients were stratified by International Metastatic RCC Database Consortium (IMDC) risk category (favorable, intermediate, or poor) and type of prior therapy (two prior VEGFR TKIs, VEGFR TKI plus checkpoint inhibitor, VEGFR TKI plus any other systemic agent) then randomized 1:1 to receive tivozanib or sorafenib. Results from the study were published in Lancet Oncology (December 2019). Additional analyses and long-term follow up results from the TIVO-3 study to be presented at the 2021 ASCO Annual Meeting include:

• Durability of Response and Updated Overall Survival. Tivozanib demonstrated clinically meaningful and statistically significant improvements in overall response rate (ORR) and DOR compared to sorafenib in 350 patients randomized 1:1 with highly relapsed or refractory RCC. As of a January 15, 2021 data cutoff date, the median DOR for patients treated with tivozanib was 20.3 months (95% CI, 9.8-29.9 months) compared to 9.0 months (95% CI, 3.7-16.6 months) for patients treated with sorafenib. The ORR for patients treated with tivozanib was 23% compared to 11% for patients treated with sorafenib. Furthermore, long-term OS relative to sorafenib continues to improve (hazard ratio (HR): 0.91 [95% CI, 0.716-1.165; p=0.47]). The OS HR assesses the relative risk of death for the entirety of the data set.

• Temporal Characteristics of Treatment-Emergent Adverse Events and Dose Modifications. Patients in the TIVO-3 study had longer duration of treatment exposure with tivozanib than sorafenib (11.9 cycles vs. 6.7 cycles), but fewer all-grade and grade ≥3 TEAEs. TEAEs were generally similar with tivozanib and sorafenib. Time to dose modifications was longer with tivozanib than sorafenib. Among those with the same TEAEs, dose reductions, interruptions, or discontinuations were required more frequently with sorafenib than tivozanib.

A copy of each poster will be available at www.aveooncology.com after its presentation at the 2021 ASCO Annual Meeting.

ASCO Presentation Details

• Title: TIVO-3: Durability of response and updated overall survival of tivozanib versus sorafenib in metastatic renal cell carcinoma (mRCC).
• Abstract: 4546
• Track: Genitourinary Cancer—Kidney and Bladder
• Date and Time: June 4, 2021 at 9:00 a.m. Eastern Time

• Title: Temporal characteristics of treatment-emergent adverse events and dose modifications with tivozanib and sorafenib in the Phase 3 TIVO-3 study of relapsed or refractory mRCC.
• Abstract: 4567
• Track: Genitourinary Cancer—Kidney and Bladder
• Date and Time: June 4, 2021 at 9:00 a.m. Eastern Time

About FOTIVDA® (tivozanib)

FOTIVDA® (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021 for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models.1 FOTIVDA was discovered by Kyowa Kirin.

INDICATIONS

FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose.

Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA.

Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events.

Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding.

Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA.

Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA.

Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased.

DRUG INTERACTIONS

Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise not to breastfeed.

Females and Males of Reproductive Potential: Can impair fertility.

Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see FOTIVDA Full Prescribing Information which is available at www.FOTIVDA.com.

About Advanced Renal Cell Carcinoma

According to the American Cancer Society’s 2021 statistics, renal cell carcinoma (RCC) is the most common type of kidney cancer, which is among the ten most common cancers in both men and women. Approximately 73,750 new cases of kidney cancer will be diagnosed annually and about 14,830 people will die from this disease. In patients with late-stage disease, the five-year survival rate is 13%. Agents that target the vascular endothelial growth factor (VEGF) pathway have shown significant antitumor activity in RCC.2 According to a 2019 publication, 50% of the approximately 10,000 patients who progress following two or more lines of therapy choose not to receive further treatment,3 which may be attributable to tolerability concerns and a lack of data to support evidence-based treatment decisions in this highly relapsed or refractory patient population.

About AVEO Pharmaceuticals, Inc.

AVEO is an oncology-focused biopharmaceutical company committed to delivering medicines that provide a better life for cancer patients. AVEO’s strategy is to focus its resources toward the development and commercialization of its product candidates in North America, while leveraging partnerships to support development and commercialization in other geographies. AVEO’s lead candidate, FOTIVDA® (tivozanib), received U.S. Food and Drug Administration (FDA) approval on March 10, 2021 for the treatment of adult patients with relapsed or refractory renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA® was approved in August 2017 in the European Union and other countries in the EUSA territory for the treatment of adult patients with advanced RCC. AVEO has previously reported promising clinical data on ficlatuzumab (anti-HGF IgG1 mAb) in head and neck cancer squamous cell carcinoma (HNSCC), pancreatic cancer and acute myeloid leukemia, and expects to make a go/no-go decision on the initiation of a pivotal Phase 3 study of ficlatuzumab in HPV negative HNSCC following feedback from the FDA. AVEO’s pipeline of product candidates also includes AV-380 (anti-GDF15 IgG1 mAb). AVEO has previously reported the acceptance of its investigational new drug application in the U.S. for AV-380 and its initiation of a Phase 1 clinical trial for the potential treatment of cancer cachexia. AVEO’s earlier-stage pipeline includes monoclonal antibodies in oncology development, including AV-203 (anti-ErbB3 mAb) and AV-353 (anti-Notch 3 mAb). AVEO is committed to creating an environment of diversity and inclusion.

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 fact, contained in this press release are forward-looking statements. The words “anticipate,” “believe,” “design,” “expect,” “hope,” “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: the potential for FOTIVDA as a treatment option for patients with relapsed or refractory advanced RCC; the potential efficacy, safety, and tolerability of tivozanib, both as a stand-alone drug candidate and in combination with other therapies in several indications; AVEO’s execution of its clinical and regulatory strategy for tivozanib; AVEO’s plans and strategies for current and future clinical trials of tivozanib, ficlatuzumab and AV-380 and for commercialization of FOTIVDA in the United States; the advancement of AVEO’s pipeline, including the advancement of ficlatuzumab and AV-380 in multiple clinical studies; the potential outcomes from studies of ficlatuzumab to provide AVEO with opportunities to pursue regulatory strategies; the potential clinical utility of ficlatuzumab and AV-380 in areas of unmet need; and AVEO’s strategy, prospects, plans and objectives for FOTIVDA and its product candidates and for AVEO 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 to successfully implement its strategic plans, including its ability to successfully commercialize FOTIVDA and to obtain and maintain market and third party payor acceptance of FOTIVDA; AVEO’s ability to raise the substantial additional funds required to achieve its goals, including those goals pertaining to the commercialization of FOTIVDA; 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, and risks relating to the timing and costs of seeking and obtaining regulatory approvals; AVEO’s dependence on third-party vendors for the development, manufacture, supply, storage and distribution of FOTIVDA and its product candidates; 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’s and its collaborators’ ability to successfully enroll and complete clinical trials; AVEO’s ability to maintain compliance with regulatory requirements applicable to FOTIVDA and its product candidates; AVEO’s ability to obtain and maintain adequate protection for intellectual property rights relating to FOTIVDA and its product candidates;; adverse general economic, political and industry conditions; the potential adverse effects of the COVID-19 pandemic on AVEO’s business continuity, financial condition, results of operations, liquidity and ability to successfully and timely enroll, complete and read-out data from its clinical trials; 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. Pawlowski N et al. AACR 2013. Poster 3971
2. J Angulo and O Shapiro, Cancers (Basel) 2019 Sep; 11(9): 1227. [10.3390/cancers11091227]
3. Decision Resources. RCC landscape and forecast. December 12, 2019.

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