8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): September 10, 2019

 

 

AVEO Pharmaceuticals, Inc.

(Exact Name of Registrant as Specified in its Charter)

 

 

 

Delaware   001-34655   04-3581650

(State or Other Jurisdiction

of Incorporation)

 

(Commission

File Number)

 

(IRS Employer

Identification No.)

One Broadway, 14th Floor

Cambridge, Massachusetts

  02142
(Address of Principal Executive Offices)   (Zip Code)

Registrant’s telephone number, including area code: (617) 588-1960

(Former Name or Former Address, if Changed Since Last Report)

 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class

  

Trading

Symbol(s)

  

Name of each exchange

on which registered

Common Stock, $0.001 par value    AVEO    Nasdaq Capital Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company  ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  ☐

 

 

 


Item 8.01 Other Events.

On September 10, 2019, AVEO Pharmaceuticals, Inc. (the “Company”) issued a press release announcing updated overall survival results in its TIVO-3 trial, the Company’s Phase 3 trial of tivozanib in advanced renal cell carcinoma. The full text of the press release issued in connection with the announcement is attached as Exhibit 99.1 to this Current Report on Form 8-K.

A copy of the Company’s current corporate slide presentation is attached as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference. The presentation includes the updated results of the TIVO-3 trial and clinical, collaboration and financial updates. The Company may amend or update the information in this slide presentation at any time and from time to time through another Current Report on Form 8-K, a later company filing, or other means.

Item 9.01. Financial Statements and Exhibits.

(d)    Exhibits

 

99.1    Press release issued by the Company on September 10, 2019
99.2    Corporate slide presentation, dated September 10, 2019


SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

 

AVEO Pharmaceuticals, Inc.

By:   /s/ Michael Bailey
 

Michael Bailey

 

President and Chief Executive Officer

Date: September 10, 2019

EX-99.1

Exhibit 99.1

 

LOGO

AVEO Oncology Announces Updated Overall Survival Hazard Ratio of 0.99 in Phase 3

TIVO-3 Trial of Tivozanib in Renal Cell Carcinoma

- 20 Patients Remain Progression Free on Tivozanib Arm vs. 2 on Sorafenib Arm -

- Company Plans to Discuss Updated Results with FDA -

- AVEO to Host Conference Call Today at 8:00 am Eastern Time -

CAMBRIDGE, Mass. – September 10, 2019 – AVEO Oncology (NASDAQ: AVEO) today announced results from the second prespecified analysis of overall survival (OS) in the TIVO-3 trial. TIVO-3 is the Company’s Phase 3 randomized, controlled, multi-center, open-label study to compare tivozanib (FOTIVDA®) to sorafenib in 350 subjects with highly refractory metastatic renal cell carcinoma (RCC). These results include an OS hazard ratio (HR) below 1.00, favoring tivozanib (HR=0.99; 95% CI: 0.76-1.29; p=0.95). An OS hazard ratio assesses the relative risk of death for the entirety of the data set. TIVO-3 is the first and only positive Phase 3 study in 3rd and 4th line RCC, and the first Phase 3 study in RCC to investigate a predefined subpopulation of patients who received prior immunotherapy, an emerging standard of care for earlier lines of therapy.

The data cutoff date for the second prespecified analysis was August 15, 2019, two years from the last patient enrolled and approximately ten months from the data cut-off date for the first prespecified analysis. Between the two data cut-off dates, 16 additional OS events were reported on the tivozanib arm and 28 on the sorafenib arm, resulting in a total of 114 OS events on the tivozanib arm and 113 on the sorafenib arm. Median OS, a point in time value separating the earlier half of events from the latter half within each arm, was 16.4 months for tivozanib (95% CI: 13.4-22.2) and 19.7 months for sorafenib (95% CI: 15.0-24.2). Twenty patients remain progression free on the tivozanib arm and two on the sorafenib arm, with a median duration on study of 32.5 months.

In November 2018, the Company announced positive final results for the primary endpoint of progression-free survival (PFS) and the secondary endpoint of overall response rate (ORR). Statistically significant improvements favoring tivozanib were reported for PFS (HR=0.73; p=0.0165) and ORR (18% vs. 8%; p=0.02). The Company also announced that tivozanib was found to be generally well-tolerated, with grade 3 or higher adverse events consistent with those observed in previous tivozanib trials. Infrequent but severe adverse events reported in greater number in the tivozanib arm were thrombotic events similar to those observed in previous tivozanib studies. The most common adverse event in patients receiving tivozanib was hypertension, an adverse event known to reflect effective VEGF pathway inhibition.

The Company plans to discuss the updated OS results with the U.S. Food and Drug Administration to identify the appropriate path forward for tivozanib in RCC in the fourth quarter, and to provide an update regarding the potential submission of a New Drug Application for tivozanib in RCC following these discussions.

“These are the first data to demonstrate durable improvements in this highly refractory advanced kidney cancer population, including the post-immunotherapy setting, a predefined subset of the


TIVO-3 trial,” said Brian Rini, MD, Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Director, Cleveland Clinic Genitourinary Cancer Program, and principal investigator of the TIVO-3 trial. “The TIVO-3 study suggests the potential for tivozanib to serve as an important new treatment option for patients with advanced RCC. I look forward to seeing tivozanib studied further in the immunotherapy combination setting, and to continuing to explore its full potential in the evolving RCC treatment landscape.”

“We are pleased to see that the positive PFS and ORR outcomes from TIVO-3 have translated into an improved OS hazard ratio,” said Michael Bailey, president and chief executive officer of AVEO. “On behalf of the entire AVEO team, we once again offer our sincerest thanks to the patients, caregivers and investigators for participating in this study. AVEO remains committed to improving outcomes for patients with RCC, and we look forward to discussing these results with the FDA.”

Conference Call and Webcast

In connection with this announcement, AVEO will host a conference call and audio webcast today, September 10, 2019, at 8:00 am Eastern Time. The call can be accessed by dialing (844) 882-7841 (U.S. and Canada) or (574) 990-9828 (international). The passcode for the conference call is 3275406. To access the live audio webcast, or the subsequent archived recording, please visit the Investors section of the AVEO website at www.aveooncology.com. The webcast will be recorded and available for replay on AVEO’s website for two weeks.

About TIVO-3

The TIVO-3 trial was designed to enroll patients with RCC who have failed at least two prior regimens, including VEGFR-TKI therapy. Eligible patients may also have received checkpoint inhibitor therapy in earlier lines of treatment. Patients were randomized 1:1 to receive either tivozanib or sorafenib, with no crossover between arms. The primary endpoint of the study is progression free survival (PFS). Secondary endpoints include overall survival (OS), overall response rate (ORR), and safety and tolerability. TIVO-3, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of RCC, is designed to support a regulatory submission of tivozanib in the U.S. as a treatment for RCC in multiple lines of therapy. TIVO-3 patients were exclusively enrolled in North America, Western Europe, and Central Europe.

About Tivozanib (FOTIVDA®)

Tivozanib (FOTIVDA®) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway, New Zealand and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.1,2 Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models3 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC4. Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal, ovarian and breast cancers.


About AVEO

AVEO Pharmaceuticals is a biopharmaceutical company seeking to advance targeted medicines for oncology and other unmet medical needs. The Company’s lead candidate is tivozanib, a potent, selective, long half-life inhibitor of vascular endothelial growth factor 1, 2 and 3 receptors, which AVEO is working to develop and commercialize in North America as a treatment for renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) and other cancers. Tivozanib (FOTIVDA®) is approved by the European Commission for the treatment of adult patients with advanced RCC in the European Union plus Norway, New Zealand and Iceland. AVEO is leveraging or seeks to leverage partnerships to develop and commercialize its pipeline of products and product candidates, including tivozanib in oncology and other indications in various geographies, and ficlatuzumab (HGF MAb) in head and neck cancer, pancreatic cancer and acute myeloid leukemia. AVEO’s earlier-stage pipeline includes AV-203 (anti-ErbB3 MAb), AV-380 (GDF15 MAb) and AV-353 (Notch 3 MAb), drug candidates being developed for various oncology indications.

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 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,” “expect,” “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 tivozanib as a treatment option for patients with advanced RCC; AVEO’s plans to discuss the updated OS results from TIVO-3 with the FDA to identify the path forward for tivozanib in RCC and to provide an update regarding a potential NDA submission; the potential efficacy, safety, and tolerability of tivozanib, as a single agent and in combination with other therapies in several indications, such as RCC and HCC; and AVEO’s strategy, prospects, plans and objectives for its product candidates and for the Company 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, 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, including, in particular, tivozanib; AVEO’s ability to successfully file an NDA for tivozanib; and 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 faces other risks relating to its business as well, including risks relating to the timing and costs of seeking and obtaining regulatory approval; AVEO’s and its collaborators’ ability to successfully enroll and complete clinical trials; AVEO’s ability to maintain compliance with 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; AVEO’s ability to successfully implement its strategic plans; AVEO’s


ability to raise the substantial additional funds required to achieve its goals, including those goals pertaining to the development and commercialization of tivozanib; unplanned capital requirements; adverse general economic and industry conditions; 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.

Fotivda (Tivozanib) SmPC August 2017.

2.

Motzer RJ, Nosov D, Eisen T, et al. J Clin Oncol 2013; 31(30): 3791-9.

3.

Pawlowski N et al. AACR 2013. Poster 3971.

4.

Barthelemy et al. ESMO 2018. Poster 878P.

AVEO Contact:

David Pitts, Argot Partners

(212) 600-1902

aveo@argotpartners.com

EX-99.2

Slide 1

AVEO Overview September 2019 Exhibit 99.2


Slide 2

Cautionary Note Regarding Forward-Looking Statements This presentation contains forward-looking statements 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 presentation are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” “contemplate,” “seek,” “look forward,” “advance,” “goal,” “strategy,” “promising,” “opportunity” 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 goals and business strategy, prospects, plans and objectives; AVEO’s plans regarding communications with, and potentially submitting a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for tivozanib; the timing, design and results of preclinical and clinical trials, including AVEO’s plans, and expectations regarding the results of overall survival analyses for the Phase 3 TIVO-3 study of tivozanib in RCC; the timing and outcome of meetings with and applications to regulatory authorities by AVEO and its partners; the competitive landscape for, and the potential utility of, AVEO’s product candidates, AVEO’s statements regarding the potential efficacy, safety and tolerability profile of tivozanib, including with respect to overall survival; the potential commercial opportunity of tivozanib and AVEO’s other product candidates and AVEO’s estimates for its cash runway. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements AVEO makes due to a number of important factors, including substantial risks and uncertainties relating to: AVEO’s ability, and the ability of its licensees, to demonstrate to the satisfaction of applicable regulatory agencies such as the FDA and the EMA the safety, efficacy and clinically meaningful benefit of AVEO’s product candidates, including, in particular, tivozanib; AVEO’s ability to successfully file an NDA for tivozanib; AVEO’s and its collaborators’ ability to successfully enroll and complete clinical trials; 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; the timing and costs of seeking and obtaining regulatory approval; AVEO’s ability to maintain compliance with 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; AVEO’s ability to successfully implement its strategic plans; AVEO’s ability to raise the substantial additional funds required to achieve its goals, including those goals pertaining to the development and commercialization of tivozanib; unplanned capital requirements; adverse general economic and industry conditions; 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 SEC and in other filings that AVEO may make with the SEC in the future. All forward-looking statements contained in this presentation speak only as of the date of this presentation, and AVEO undertakes no obligation, and specifically disclaims any obligation, to update any of these statements, except as required by law.


Slide 3

AVEO Oncology: Strategy for Value Creation Value Enhancing Partnerships Deep Pipeline Addressing Significant Unmet Needs Multiple oncology and non-oncology pipeline opportunities FOTIVDA™ (tivozanib) – IO Combinations (RCC, HCC, other) Highly specific VEGFR TKI has potential to enable unique tolerability in combination FOTIVDA™ (tivozanib) – Monotherapy (RCC) Differentiated VEGFR TKI has potential to deliver unsurpassed efficacy AND favorable tolerability Partnerships advance programs and provide capital


Slide 4

Clinical Preclinical Phase 1 Phase 2 Phase 3 Regulatory Filing Marketed Partner Tivozanib (RCC) VEGFR 123 TKI Tivozanib (HCC) VEGFR 123 TKI Ficlatuzumab HGF MAb AV-203 (CAN017) ERBB3 MAb Multiple Potential Opportunities for Value Creation TIVO-1 (Phase 3 Registration Study in 1st Line RCC) TIVO-3 (Phase 3 Registration Study in 3rd Line RCC) TiNivo (+OPDIVO® RCC) SCCHN (Ficla +/- ERBITUX®) Esophageal Pre-Clinical Tivozanib VEGFR 123 TKI AV-380 GDF15 MAb AV-353 Notch 3 MAb Cachexia Oncology DEDUCTIVE (1st line HCC+ IMFINZI®) Ongoing or complete In Planning (Europe) CyFi2 (HiDac +/- Ficla AML) Pancreatic (Ficla + Nab-paclitaxel + Gemcitabine) Non-Oncology


Slide 5

Financial Highlights Cash on hand to fund planned operations into 3Q 2021* $40.2M in cash, cash equivalents, and marketable securities as of 2Q 2019 $25.0M upfront payment from Kyowa Kirin due in 3Q 2019 Kyowa Kirin buy back of tivozanib non-oncology rights: $25M upfront payment Waiver of the $18M potential payment due to Kyowa Kirin upon an AVEO U.S. approval for tivozanib $391M in potential development and commercial milestones Tiered high single-digit to low double-digit royalties on tivozanib net sales in non-oncologic indications EUSA royalties and potential milestones: Tiered low double-digit to mid-twenties royalties on FOTIVDA® (tivozanib) net sales in Europe, Latin America, Africa, and Australia $6M in potential reimbursement and regulatory approval milestones $20M in R&D reimbursement for access to TIVO-3 data, if optioned $335M in potential tiered commercial milestones Approximately $32 million ATM availability through SVB Leerink sales agreement Streamlined, experienced team with a headcount of ~20 *This estimate excludes, subject to our decision whether to submit a New Drug Application (NDA) for tivozanib to the U.S. Food and Drug Administration (FDA), remaining costs to prepare and filing fees in connection with a possible NDA submission, and pre-commercialization activities that we may undertake. This estimate also assumes no receipt of additional milestone payments from our partners, no funding from new partnership agreements, no additional equity financings, no debt financings, no additional sales of equity under our sales agreement with SVB Leerink and no additional sales of equity through the exercise of our outstanding warrants. Accordingly, the timing and nature of activities contemplated for the remainder of 2019 and thereafter will be conducted subject to the availability of sufficient financial resources.


Slide 6

FOTIVDA® (tivozanib) TIVO-3 Pivotal Phase 3 Study


Slide 7

Tivozanib: VEGFR 1, 2 and 3 Tyrosine Kinase Inhibitor Potent, selective inhibitor of VEGFRs 1, 2 and 3 with a long half-life that is designed to optimize blockade while minimizing off-target toxicities1,2 1 Nakamura K et al. Cancer Res 2006;66:9134–9142. 2 Eskens FA et al. Clin Cancer Res 2011;17:7156–7163.


Slide 8

TIVO-3: Study Design N = 350 F Recurrent/metastatic RCC Failed at least two prior regimens including VEGFR-TKI Stratified by prior regimen (TKI-TKI; TKI-PD1; TKI-Other) ECOG PS 0 or 1 RANDOMIZE 1:1 tivozanib sorafenib 1O: PFS 2O: OS, ORR, DoR, Safety and Tolerability for ITT 60% 3rd line patients, 40% 4th line+ Phase 3, Randomized, Controlled, Multi-Center, Open-Label Study to Compare Tivozanib to Sorafenib in Subjects With Refractory Advanced Renal Cell Carcinoma First stratified 3rd line dataset of patients with prior PD-1 exposure


Slide 9

Primary Endpoint: Progression-Free Survival per IRC (ITT)* Median PFS, mo (95% CI) Tivozanib 5.6 (5.3, 7.3) Sorafenib 3.9 (3.7, 5.6) HR, 0.73 (95% CI: 0.56, 0.94) P=0.0165 2yr PFS 18% 5% 28% 1yr PFS 11% 44% improvement in median PFS 27% risk reduction for progression or death *Final analysis, as of Oct 4, 2018


Slide 10

IO Subgroup Progression-Free Survival per IRC (26% of ITT)* Median PFS, mo (95% CI) Tivozanib 7.3 (5.3, 11.1) Sorafenib 5.1 (3.6, 7.4) HR, 0.55 (95% CI: 0.32, 0.94) P=0.028 35% 1yr PFS 4% 2yr PFS 25% 43% improvement in median PFS 45% risk reduction for progression or death *Final analysis, as of Oct 4, 2018


Slide 11

Secondary Endpoint – ORR* Final Analysis - Superior Overall Response Rate and Durability Statistically significant benefit in ORR, p=0.02 Durable responses with tivozanib: 55% remaining in response past 2 years Median DoR: tivozanib not reached vs sorafenib 5.7 months *Final analysis, as of Oct 4, 2018


Slide 12

Treatment-Related Adverse Events* (≥20% frequency in either arm) Tivozanib (N=173)^ Sorafenib (N=170)^ Preferred Term All Grades % Grade 3/4 % All Grades % Grade 3/4 % Treatment Related AEs 84 44 94 55 Hypertension 36 20 25 14 Diarrhea 33 2 50 9 Fatigue 29 4 19 5 Decreased Appetite 26 4 21 2 Dysphonia 24 1 8 0 Asthenia 21 5 17 4 PPE* 16 1 38 10 Rash 4 0 24 8 >5% difference between arms *Palmar-plantar erythrodysesthesia syndrome, also know as hand-foot syndrome ^Safety population *Analysis as of Oct 4, 2018


Slide 13

Tivozanib (N=173)^ Sorafenib (N=170)^ Mean Number of Cycles Initiated 10.3 6.3 AEs Leading to Dose Reductions (%) 24 38 AEs Leading to Dose Interruption (%) 48 63 Treatment Related SAEs (%) 11 10 Treatment Related Deaths (%) 0 0 Deaths within 30 days of Tx (N) 15 12 Exposure Adj Deaths per Month of Tx** 0.93% 1.21% Tolerability Results* ^Safety population *Analysis as of Oct 4, 2018 **Exposure Adj Deaths Based on 48,656 tivozanib Tx days and 29,883 sorafenib Tx days through 10/4/2018 data cut P=0.005 P=0.007


Slide 14

Secondary Endpoint – Overall Survival Initial OS Analysis (Oct 4, 2018): HR* >1.00 Analysis based on 183 OS events Prespecified OS Analysis update (Aug 15, 2019): HR*=0.99 Analysis based on 227 OS events 95% CI: 0.76-1.29; p=0.95 44 additional events since Oct 4, 2018 data cut 16 tivozanib events and 28 sorafenib events Median OS: tivozanib=16.4 mo (95% CI: 13.4-22.2), sorafenib=19.7 mo (15.0-24.2)** 20 tivozanib patients remain progression free and on study and 2 sorafenib patients *Hazard Ratio (HR): assesses the relative risk of death for the entirety of the dataset **Median OS: point in time value separating the earlier half of events from the latter half within each arm


Slide 15

TIVO-3 Conclusions Tivozanib significantly improves PFS and ORR compared to sorafenib in patients with treatment-refractory advanced RCC Tivozanib was superior in patients previously treated with checkpoint inhibitors as well as two VEGFR-TKIs Responses with tivozanib were more durable than sorafenib Tivozanib was well tolerated, with hypertension as the most common AE Lower rates of hand-foot syndrome, diarrhea, and rash were observed for tivozanib compared to sorafenib OS hazard ratio less than 1 in updated analysis (Aug 15, 2019) 20 tivozanib patients remain progression free and on study vs 2 sorafenib patients Company plans to discuss updated OS results with the FDA


Slide 16

PD-1 Combination Opportunities


Slide 17

Tivozanib Properties May Provide Advantages in Combination with IO Therapy Nakamura K et al. Cancer Res 2006;66:9134–9142. Pawlowski N et al. AACR 2013. Poster 3971. Hammers, Emerging VEGF-I/O Combinations, ASCO 2017


Slide 18

Demonstrated Favorable Safety Results 60% of patients experienced treatment related grade 3/4 adverse event Excluding uncomplicated hypertension, only 44% of patients experienced grade 3/4 adverse event Minimal off-target AEs observed, likely due to high specificity of tivozanib Barthelemy et al. ESMO 2018


Slide 19

Encouraging Preliminary Efficacy Results 56% ORR and 96% DCR 72% had tumor shrinkage ≥25% as of August 2018 4% (1/25) of patients had a complete response 52% (13/25) of pts remain on therapy Results suggest additive or synergistic efficacy for tivozanib + PD1 Barthelemy et al. ESMO 2018 Updated Results Expected at ESMO 2019


Slide 20

Immuno-Oncology Clinical Collaboration with AstraZeneca Clinical Rationale:  Single agent activity demonstrated for tivozanib and durvalumab in HCC2,3.  Combination of two agents has potential to show enhanced efficacy and best in class tolerability profile among TKI/IO regimens. Planned phase 1/2 study: costs shared equally and clinical drug supplied by each company HCC Market – Key Opportunity 1 Decision Resources HCC Disease Landscape and Forecast – Dec 2018 2 Lee S et al, ASCO GI 2018 3 Wainberg et al, ASCO 2017


Slide 21

Tivozanib Commercial Opportunity


Slide 22

If Approved, Significant Potential Commercial Opportunity for Tivozanib in the United States 1st Line Market (est. 2020) ~$1.6B1 2nd Line Market (est. 2020) ~$700M1 3rd Line+ Market (est. 2020) ~$300M1 Expect opportunity to expand Potential to be first agent indicated for 3rd & 4th line Only pivotal dataset in RCC stratified by prior PD-1 NA royalties to KHK are low- to mid-teens on net sales 1 Decision Resources Pharmacor 2020 Market Projections July 2019 Extended OS from IO may expand population eligible for 3rd line treatment 2 1 >PFS with tivozanib may extend treatment duration 65%1 50%1 Efficacy + tolerability may increase patients opting for 3rd and 4th line treatment 1st Line 2nd Line 3rd Line 3 Composition of matter patent into 2022 with potential for extension into 2027 for both Europe and North America 4th Line 25%1


Slide 23

Potential Relevance of Tivozanib in Refractory RCC Source: AVEO blinded Third-Party US Oncologist Market Research using approximate TIVO-3 PFS and AE profile - Dec 2018 n=100 Treatments with proven efficacy are needed for patients who have failed 2 or more lines of treatment for RCC I prefer using drugs that do not often require me to adjust or interrupt dose due to patient tolerability issues Blinded Tivo Profile Ratings compared to current treatment options in refractory patients Likelihood to Prescribe 67% 80% Not at all likely Neutral Extremely Likely


Slide 24

First-line treatment for patients with good or intermediate risk Second-line patients following TKIs Launched in Germany, Spain and UK Approved in New Zealand https://www.esmo.org/Guidelines/Genitourinary-Cancers/Renal-Cell-Carcinoma FOTIVDA Commercialization in EU and ROW This Photo by Unknown Author is licensed under CC BY-SA ESMO Guidelines updated to include FOTIVDA® (tivozanib)1 – Feb 2019 Launched in 3 of the EU5 Countries (Each Launch Triggers $2M milestone) $20M in R&D reimbursement for access to TIVO-3 data, if optioned $335M in potential tiered commercial milestones Tiered low double-digit to mid-twenties royalties on FOTIVDA® (tivozanib) net sales in Europe, Latin America, Africa, and Australia Approved in 1 of 5 non-EU countries (3 of 5 triggers $2M milestone) KKC entitled to 30% of all royalties and milestones, a portion of R&D reimbursement is excluded


Slide 25

Pipeline and Near-Term Milestones


Slide 26

Tivozanib * Does not include potential PTE up to 5 yr max VEGFR 1, 2 and 3 Tyrosine Kinase Inhibitor Launched in Europe by EUSA as FOTIVDA in first line RCC in November 2017 TIVO-3 study on-going for potential U.S. registration for RCC IO combination study with OPDIVO® in collaboration with BMS underway in RCC IO combination study with IMFINZI® in collaboration with AZ launching soon in HCC AVEO retains milestones and royalties for non-oncology indications in key markets Composition of Matter (COM) and other IP to at least 2022* Potential Tivozanib (VEGFR 1, 2 and 3 TKI) Milestones 2H19 1H20 2H20 OS Update / Regulatory Discussion HCC Ph 1/2 (Durvalumab + Tivo) Enrollment Start RCC (Nivolumab + Tivo) Final PFS Presentation


Slide 27

Ficlatuzumab * Does not include potential PTE up to 5 yr max HGF Inhibitory Antibody with Optimal Blockade of c-Met AML: Phase 1/2 Trial of ficlatuzumab and cytarabine in refractory AML patients Demonstrated 50% complete response in patients refractory to initial therapy Randomized phase 2 in planning SCCHN: Randomized Phase 2 Trial ongoing (Ficlatuzumab +/- ERBITUX®) Pancreatic Cancer: Phase 1/2 Trial ongoing (Ficlatuzumab + Nab-paclitaxel + Gemcitabine) Composition of Matter (COM) and other IP to at least 2027* Potential Ficlatuzumab (HGF Inhibitory Antibody) Milestones 2H19 1H20 2H20 AML Randomized Ph2 POC (HiDAC +/- Ficlatuzumab) Initiation Pancreatic Ph 1/2 (Ficlatuzumab + Nab-paclitaxel + Gemcitabine) Presentation SCCHN Randomized (Ficlatuzumab +/-ERBITUX®) Ph2 POC Data


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Anti-ERBB3 Mab with Broad Therapeutic Potential CANbridge to fund clinical development through Phase 2 POC study Potential additional $40M development and regulatory/$90M commercial milestone Tiered low double-digit royalties for ex-NA rights Planned indication: squamous cell esophageal cancer (IND accepted in China August 2018) Composition of Matter (COM) and other IP ranging from 2031 to 2032* CAN017 (AV-203) * Does not include potential PTE up to 5 yr max Potential CAN017 (AV-203) (Anti-ERBB3 MAb) Milestones 2H19 1H20 2H20 Squamous Cell Esophageal Cancer Ph 1/2 Study Initiation


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First-in-Class, Anti-GDF15 MAb for Cachexia Affects approximately 5 million patients in the US alone; affects up to 80% of advanced cancer patients and is responsible for approximately 30% of all cancer deaths1,2 Pre-clinical development underway to enable planned IND submission in 2020 Composition of Matter (COM) through at least 2033* and in licensed methods of use patent AV-380 Morley et al; Am J Clin Nutr 2006;83:735– 43 Lerner, et al. MAP3K11/GDF15 axis is a critical driver of cancer cachexia, J Cachexia Sarcopenia Muscle. 2016 Sep; 7(4): 467–482. * Does not include potential PTE up to 5 yr max Potential AV-380 (Inhibitory Antibody targeting GDF15) Milestones 2H19 1H20 2H20 AV-380 IND Submission


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AVEO Key Near Term Potential Milestones Tivozanib (VEGFR 1, 2 and 3 TKI) 2H19 1H20 2H20 TIVO-3 OS Update / Regulatory Discussion DEDUCTIVE HCC Ph 1/2 (Durvalumab + Tivo) Enrollment Start TiNivo RCC (Nivolumab + Tivo) Final PFS Presentation Ficlatuzumab (HGF Inhibitory Antibody) 2H19 1H20 2H20 AML Randomized Ph2 POC (HiDAC +/- Ficlatuzumab) Initiation Pancreatic Ph 1/2 (Ficlatuzumab + Nab-paclitaxel + Gemcitabine) Presentation SCCHN Randomized (Ficlatuzumab +/-Erbitux) Ph2 POC Data CAN017 (AV-203) (Anti-ERBB3 MAb) 2H19 1H20 2H20 Squamous Cell Esophageal Cancer Ph 1/2 Study Initiation AV-380 (Inhibitory Antibody targeting GDF15) 2H19 1H20 2H20 AV-380 IND Submission


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AVEO Overview September 2019