Form 8-K AVEO PHARMACEUTICALS For: Nov 08

 

 

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): November 8, 2016

 

 

AVEO Pharmaceuticals, Inc.

(Exact Name of Registrant as Specified in 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

 

 

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))

 

 

 

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CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS:

This Form 8-K and the exhibit attached hereto contain forward-looking statements of AVEO Pharmaceuticals, Inc. (“AVEO” or the “Company”) that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this Form 8-K and the attached exhibit are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” “contemplate,” 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 leverage biomarkers and pursue strategic partnerships for certain of its assets; AVEO’s goals and business strategy; the timing, design and results of preclinical and clinical trials; the timing and outcome of meetings with and applications to regulatory authorities by AVEO and its partners; the competitive landscape for AVEO’s therapeutic 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 to successfully implement its strategic plans; AVEO’s ability to successfully develop, test and gain regulatory approval of its product candidates, including its companion diagnostics; the potential safety, efficacy, tolerability and other benefits of tivozanib as a single agent or in combination with other therapies; developments, expenses and outcomes related to AVEO’s ongoing shareholder litigation; AVEO’s ability to obtain necessary financing required to perform its clinical trials and achieve its other goals; AVEO’s ability to establish and maintain strategic partnerships; AVEO’s ability to obtain and maintain intellectual property rights; competition; AVEO’s dependence on its strategic partners and other third parties; adverse general economic and industry conditions; and those risk factors discussed in the “Risk Factors” and elsewhere in AVEO’s Annual Report on Form 10-K for the year ended December 31, 2015, and other periodic filings AVEO makes with the SEC. All forward-looking statements contained in this Form 8-K and the attached exhibit speak only as of the date of this presentation, and AVEO undertakes no obligation to update any of these statements, except as required by law. You should, therefore, not rely on these forward-looking statements as representing the Company’s views as of any date subsequent to the date of this Form 8-K.

 

Item 7.01.

Regulation FD.

From time to time, we conduct meetings with third parties in which we utilize a corporate slide presentation. A copy of our current corporate slide presentation is attached as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference. The presentation includes clinical, development and financial updates. We may amend or update this information at any time and from time to time through another Current Report on Form 8-K, a later company filing, or other means.

The information in this Item 7.01 and Exhibit 99.1 shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.

 

Item 9.01.

Financial Statements and Exhibits.

(d) The exhibit to this Current Report on Form 8-K is listed in the Exhibit Index attached hereto.

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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.

 

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EXHIBIT INDEX

 

Exhibit No.		Description
99.1		Corporate Presentation Slide Deck dated November 8, 2016

AVEO Overview November 2016 Exhibit 99.1

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Forward-Looking Statements This presentation contains forward-looking statements 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,” 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 leverage biomarkers and pursue strategic partnerships for certain of its assets; AVEO’s goals and business strategy; the timing, design and results of preclinical and clinical trials; the timing and outcome of meetings with and applications to regulatory authorities by AVEO and its partners; the competitive landscape for AVEO’s therapeutic 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 to successfully implement its strategic plans; AVEO’s ability to successfully develop, test and gain regulatory approval of its product candidates, including its companion diagnostics; the potential safety, efficacy, tolerability and other benefits of tivozanib as a single agent or in combination with other therapies; developments, expenses and outcomes related to AVEO’s ongoing shareholder litigation; AVEO’s ability to obtain necessary financing required to perform its clinical trials and achieve its other goals; AVEO’s ability to establish and maintain strategic partnerships; AVEO’s ability to obtain and maintain intellectual property rights; competition; AVEO’s dependence on its strategic partners and other third parties; adverse general economic and industry conditions; and those risk factors discussed in the “Risk Factors” and elsewhere in AVEO’s Annual Report on Form 10-K for the year ended December 31, 2015, and other periodic filings AVEO makes with the SEC.  All forward-looking statements contained in this presentation speak only as of the date of this presentation, and AVEO undertakes no obligation to update any of these statements, except as required by law.

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Retained North American Rights for Oncology Portfolio While Leveraging Partnerships to Advance Our Pipeline AV-380 GDF15 MAb Tivozanib VEGFR 123 TKI (Oncology Indications) AV-203 ERBB3 MAb Ficlatuzumab HGF MAb Value Creation Strategy Leverage partner resources to advance development, retain significant downstream value Retain NA Rights to Oncology Therapeutics Out-license Non-Oncology Pipeline Tivozanib VEGFR 123 TKI (Ocular Indications) Advance non-oncology pipeline with disease area experts and retain significant downstream value AV-353 Notch 3 Partnership discussions ongoing

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TIVO-1 (1st Line RCC) * Ocular SCCHN / AML (Investigator) Esophageal Cancer Cachexia TIVO-3 (U.S. Phase 3 Registration Study in RCC) TiNivo (+Opdivo® RCC) PAH Multiple Opportunities for Value Creation *Filed in EU by EUSA FEB 29, 2016, validated MAR 23, 2016 Seeking Partnership

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Tivozanib A potent, selective, long half-life inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2 and 3

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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.

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MAA Review TIVO-3 : Tivo v. Sorafenib US Approval Decision EU Approval Decision NDA Review 2016 2017 2018 2019 2020 Ph 2 expansion or Ph 3 Trial of Tivo + PD-1 Potential NDA Filing 2H 2018 PFS Data/OS Trend Estimated 1Q 2018 Ph 1 Data 1H 2017 Large and Growing RCC Opportunity Market opportunity currently ~$2.5 billion in Europe and North America* Future market needs: Improved tolerability Increased efficacy through combinations with immunotherapy * Total RCC market includes all stages of disease and treatment options. Source: Decision Resources : Tivo + Opdivo®

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Tivozanib RCC Front-line Setting

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Phase 3 TIVO-1: Proven Activity in 1st line RCC 517 patient, global, randomized Phase 3 in 1st line RCC First H2H RCC pivotal to meet primary PFS endpoint of superiority vs VEGF TKI OS confounded by crossover; NDA not approved; FDA requested additional study Demonstrated favorable tolerability profile Months Probability of PFS 0 Sorafenib 1.0 0.8 0.6 0.4 0.2 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Tivozanib Tivozanib N=260 Sorafenib N=257 Median (95% CI) 11.9 mo (9.3 – 14.7 mo) 9.1 mo (7.3 – 9.5 mo) Hazard ratio: 0.797 (95% CI: 0.639, 0.993) p-value = 0.042

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Comparable OS Despite Limited Subsequent Therapy

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Support for Tivozanib MAA Filing for RCC TIVO-1: Impact of Next-Line Therapy on OS * EU includes Bulgaria, Czech Republic, France, UK, Hungary, Italy, Poland, Romania (countries with patients enrolled in Study 301) ** EU5 includes UK, Italy, and France (EU5 countries with patients enrolled in Study 301) NR=not reached ^Statistically significant improvement in PFS (p<0.001) Region % of Patients Receiving Second Line Therapy OS Hazard Ratio (P Value) Median OS Tivozanib Sorafenib ITT N=517 36% 74% HR=1.245 (P=NS) T=28.8 mo S=29.3 mo NA and EU* N=186^ 50% 76% HR=0.89 (P=NS) T=35.9 mo S=31.0 mo NA and EU5** N=40 87% 82% HR=0.503 (P=NS) T=NR S=NR

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EUSA Pharma Oncology Licensing Agreement Specialty pharmaceutical company with commercial operations in the US and Europe, distribution network in 40 countries Spinout of Jazz Pharmaceuticals (Mar 2015) EU filing 2/29/16, validated 3/23/16, received 120 day questions July 2016 >$396M in Upfront and Potential Milestones $16M potential 2016/17 milestones* Tiered royalties from low double digits to mid twenties Milestone and royalty payments subject to the successful development or commercialization of the product All non-R&D payments received by AVEO subject to sublicense revenue obligation to Kyowa Hakko Kirin * Includes $4.0M in R&D reimbursement at approval and $2.0M per reimbursement approval in each EU5 country and $2.0M for approval in 3 of 5 defined countries beyond EU5 

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Tivozanib is Well Tolerated, and Has the Potential to Become the Preferred TKI for PD-1 Combination Therapy Single Agent Toxicity All grade (Gr 3/4) Sutent1 (n=548) Votrient1 (n=554) Inlyta5 (n=189) Nexavar3 (n=257) Lenvima4 (n=52) Cometriq2 (n=331) Tivozanib3 (n=259) Hypertension 30% (15%) 40% (4%) 49% (13%) 34% (17%) 48% (17%) 37% (15%) 50% (9%) Fatigue 63% (17%) 55% (10%) 33% (5%) 16% (4%) 50% (8%) 56% (9%) 18% (5%) Hand-Foot Syndrome 50% (11%) 29% (6%) 26% (7%) 54% (17%) 15% (0%) 42% (8%) 13% (2%) Diarrhea 57% (7%) 63% (9%) 50% (9%) 32% (6%) 72% (12%) 74% (11%) 22% (2%) 1 Motzer, et al. ESMO 2012 (COMPARZ): 1st line study, sutent vs. votrient 2 Choueri, et al. NEJM 2015: 2nd Line Study, cabozantinib vs. everolimus 3 Motzer, et al. ASCO: 1st Line TIVO-1 Study, tivozanib vs. sorafenib 4 Motzer et. Al Lancet Oncol 2015; 16: 1473–82 5 Hutson et.al. Lancet Oncol 2013 ; 14: 1245; 1L study vs sorafenib

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Favorable Tolerability vs. Approved TKIs in RCC Incidence (%) Incidence (%) Tivozanib1 Sorafenib Pazopanib3 Axitinib2 TIVO-11 AXIS2 Sunitinib4 Dose Reductions Dose Interruptions Tivozanib1 Sorafenib Pazopanib3 Axitinib2 TIVO-11 AXIS2 Sunitinib4 Cabozantinib5 Lenvatinib+Everolimus6 Motzer et.al JCO 10.2013, Vol 31 No 30; 2. INLYTA USPI v.01.2012; 3.Votrient USPI revised 01.2012; 4. Sutent USPI revised 05.2011; 5. Cabozantinib METEOR Trial NEJM 9/26/15; 6. Motzer et.al Lancet v16 Nov 2015.

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Top Three Toxicities Relevant to Patients with Advanced RCC* *Wong M, et al. J Med Econ. 2012;28:1-10. Additional months of PFS benefit patients require to accept adverse events >50% of pts on Nexavar <15% for Tivozanib >60% of pts on Sutent <20% for Tivozanib >50% of pts on Pazopanib, Axitinib and Sutent <25% for Tivozanib Additional Months of Progression-Free-Survival Benefit

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? 1 Motzer, et al. ESMO 2012 (COMPARZ): 1st line study, sutent vs. votrient 2 Hutson, et al. Lancet Oncol 2013 ; 14: 1245; 1L Phase 3 study vs sorafenib 3 Motzer, et al. JCO Oct 2013; 1st Line TIVO-1 Study, tivozanib vs. sorafenib 4 Choueri, et al. ESMO 2016. Poor and Intermediate risk patients only Increasing Patient Tolerability Tivozanib Uniquely Positioned in 1st Line RCC

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Tivozanib North American Registration Strategy

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TIVO-3: Phase 3 Study Design in Recurrent/Metastatic RCC to Confirm TIVO-1 N = ~322 F Recurrent/metastatic RCC Failed at least two prior regimens including VEGFR-TKI (not sorafenib) ECOG PS 0 or 1 RANDOMIZE 1:1 tivozanib sorafenib 1O: PFS 2O: OS, ORR, DoR, Safety and tolerability for ITT & Pre-Specified Biomarkers Phase 3, Randomized, Controlled, Multi-Center, Open-Label Study to Compare Tivozanib to Sorafenib in Subjects With Refractory Advanced Renal Cell Carcinoma Designed to support 1st and 3rd line indication Provides potential unique 3rd line dataset of patients with prior PD-1 exposure Enrollment initiated 2Q 2016 On track for topline data 1Q 2018

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Tivozanib Efficacy in VEGF TKI Refractory Setting * n= 389; investigator assessed PFS; independent PFS = 4.8 mo vs. 3.4 mo, HR = 0.741 (p=0.011) **investigator assessed PFS ^Cabozantanib USPI 1.Motzer et al Lancet Oncol 2013; 14: 552–62 2. Motzer et al Lancet Oncol 2014 3. Hutson et al ASCO 2015 4. Cabozantinib METEOR Trial NEJM 9/26/15 9 Study AXIS Phase 3, axitinib vs sorafenib (1:1)1 METEOR study Phase 3, cabozanitnib vs everlimous (1:1)4 TIVO-1 Phase 3, subset crossing over to tivozanib following sorafenib progression3 Dovitinib study Phase 3, dovitinib vs sorafenib (1:1)2 Setting 2nd line RCC 2rd line RCC 2nd line RCC 3rd line RCC Study Size n=361 (axitinib) n=362 (sorafenib) (54% sunitinib refract.) n=658 n=163 (tivozanib) n=280 (dovitinib) n=284 in sorafenib arm (TKI & mTOR refractory) PFS sunitinib refractory pts 6.5 mo (axitinib) 4.5 mo (sorafenib)* HR = 0.636, p<0.0002* 7.4 mo (cabozantinib) 3.8 mo (everlimous) sorafenib refract. pts 11.0 mo** (tivozanib) TKI & mTOR Refractory 3.9 mo (dovitinib)** vs. 3.9 mo (sorafenib)** HR 1.00, p=NS Prior Sutent (n=153) 9.1 mo (cabozantinib) 3.7 mo (everlimous) OS sunitinib refract. pts 15.2 mo (axitinib) 16.5 mo (sorafenib) 21.4 mo^ sorafenib refract. pts 21.6 mo (tivozanib) TKI & mTOR refractory 11.1 mo (dovitinib) vs. 11.0 mo (sorafenib)

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Tivozanib PD-1 Combination Setting

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Rationale for Combining VEGF + PD-(L)1 Inhibitors Gunturi, McDermott Current Treatment Options in Oncology 2014 Plimack International Kidney Cancer Symposium 2014

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Tivozanib has Immunomodulatory Properties: Regulatory T Cell Reduction May Enhance PD1 Activity Pawlowski N et al. AACR 2013. Poster 3971. Regulatory T cells suppress or downregulate induction and proliferation of effector T cells (e.g. CD4 and CD8) P=0.034

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Early Data for the Combination of PD1 +VEGF TKIs: Demonstrated Promising Responses with Challenging Toxicity 1 Atkins et al, ESMO 2016, 2 Larkin et al, ESMO 2016 Phase Ib dose-finding studies of axitinib plus pembrolizumab or avelumab in treatment-naïve patients with advanced renal cell carcinoma Safety Axitinib + Pembro1 - N (%) Axitinib + Avelumab2 - N (%) Adverse Events* All Grade N (%) Grade ≥3 N (%) All Grades N (%) Grade ≥3 N (%) Any AEs 52 (100) 34 (65.4) 6 (100) 4 (66.7) Efficacy Axitinib + Pembro1 - N (%) Total N=52 Axitinib + Avelumab2 - N (%) Total N=6 Complete Response 3 (5.8) 0 (0) Partial Response 34 (65.4) 5 (83.3) Stable disease 10 (19.2) 1 (16.7) ORR 37 (71.2) 5 (83.3)

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Sunitinib & Pazopanib, the most widely used VEGF TKIs, have potentially prohibitive overlapping toxicities with PD1s Courtesy of Dr. S. Pal, ASCO GU 2015

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Significant reductions of TKI dose to manage AEs have been recommended to safely combine some TKIs with PD1s in RCC CaboNivo1: Cabo recommended dose reduction from 60 to 40mg Lenvatinib + Pembro2: Lenv recommended dose reduction 24 to 20mg Reduced Dose May Adversely Impact Efficacy 1 Apolo et al, ESMO 2016, 2 Taylor et. Al, ESMO 2016 JCO Volume: 30, Issue: 13, Pages: 1484-1491, May 2012 ESMO 2014 Congress, September 26 -30 2014, Madrid, Spain CASE STUDY (Breast Cancer): Ph 2 SOLTI study3 Ph 3 RESILIENCE study4 Dose Sorafenib 800mg Sorafenib 600mg PFS 6.4 vs 4.1 mos 5.5 vs 5.4 mos Power HR 0.58 P=0.0006 NS G3/4 AEs 44% HFS (S+C)

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Phase 1 TiNivo Study Tivozanib (1.0 mg/day) QD/21 days + nivolumab 240 mg Q 2 weeks N = 6 - 12 ECOG PS ≤ 1 and life expectancy ≥ 3 months Tivozanib (1.5 mg/day) QD/21 days + nivolumab 240 mg Q 2 weeks Further evaluate the antineoplastic activity and safety Phase 1 Phase 2 Maximum tolerated dose N = ~20 A Phase 1/2, Open-Label, Multi-Center Study of Tivozanib in Combination with Nivolumab (Opdivo®) in Subjects with Metastatic Renal Cell Carcinoma (TINIVO) 1o safety, tolerability, and maximum tolerated dose 2o antineoplastic activity

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High Potential Value Non-Oncology Programs

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Tivozanib in Ocular Diseases* >$105M total in upfront and potential option & milestone payments Potential for up to $10M in 2016/17 Tiered, double digit royalties, up to the mid-teens, on net sales** Option, milestone and royalty payments subject to the successful development and/or commercialization of the product All payments received by AVEO subject to sublicense revenue obligation to Kyowa Hakko Kirin * Non-oncologic ** Assumes execution of option by Ophthotech

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AV-380 in Cachexia Milestone and royalty payments subject to the successful development and/or commercialization of the product *A percentage of proceeds will be shared with SVH, including $1.5 million of upfront GDF-15 inhibitor Mab Indication: cachexia $327M in upfront & potential milestones Tiered royalties from high single digits to a low double-digit, for worldwide rights Congestive Heart Failure Cancer Chronic Kidney Disease Chronic Obstructive Pulmonary Disease Cachexia (Wasting Syndrome) Cancer ~400,000 pts In US ~960,000 pts In US ~150,000 pts In US ~3,200,000 pts In US Morley et al; Am J Clin Nutr 2006;83:735– 43

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AV-353: 1st-in-class opportunity to address major unmet need in pulmonary arterial hypertension (PAH) as potential to be first drug with disease modifying properties Binding specificity to Notch 3 reduces risks of pan-Notch toxicities that have hampered competitors Large Market Opportunity 2014 sales of $3.45B à 2024 sales of $4.75B Significant development opportunity with big market in additional oncology indications AV-353 in Pulmonary Arterial Hypertension Pathophysiology of PAH AVEO owns worldwide rights to AV-353 and is actively seeking partners to help realize the full potential of the asset

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Financials & Summary

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Financial Highlights Cash and anticipated operational milestones to fully fund North American tivozanib development strategy to topline data $30.8M in cash and investments as of 3Q 2016 Amended debt agreement provides potential access to another $5M tranche and deferred repayment of principal for existing debt >$35M in potential payments through 2017 including: ~$10M in operational, non-clinical milestones (IND filings, tech transfer) Streamlined operations with a headcount of ~20 Shares outstanding as of 10/28/16: ~75.9M

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Potential Corporate Milestones 2016 2017 Regulatory decision in EU (1H17) Proof of concept in AMD and option exercise (2016/17) TIVO-3 PFS data/OS trend (1Q18) Other Potential Milestones Partnership for AV-353 Other tivozanib geographic partnerships Development milestones for AV-380 Manufacturing transfer and re-initiation of AV-203 clinical dev. Phase 1 data (1H17) 2018

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AVEO Oncology Highlights Retained significant North American rights for all oncology therapeutic assets Executing on development strategies for Tivozanib Enrolling Ph 3 refractory RCC study (TIVO-3) to support 1st & 3rd line indications Initiating Ph 1/2 tivozanib + Opdivo® combination study (TiNivo) in RCC Advancing portfolio through development and commercialization partnerships Tivozanib: Partner-led regulatory review in EU for 1st line RCC; Partner-funded development for non-oncology ocular indications Ficlatuzumab: Ongoing investigator sponsored trials in SCCHN & AML AV-203: Partner-funded development through POC AV-380: Partner-funded development for cachexia AV-353: Seeking partner for PAH development Cash and anticipated operational milestones to fully fund tivozanib development strategy to topline data Lean organization, experienced management team and Board

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AVEO Overview November 2016

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