- NDA Filing Accepted by U.S. FDA for Tivozanib
as a Treatment of Relapsed or Refractory Renal Cell Carcinoma;
Assigned PDUFA Target Action Date of March 31, 2021 -
- Preparations Underway to Support Potential
Commercial Launch of Tivozanib in the U.S.; New Debt and Equity
Financings, Partnership Milestones Potentially Provide for Working
Capital into 2022 -
- Company Evaluating Registrational
Opportunities for Ficlatuzumab and Tivozanib Immunotherapy
Combination Programs -
- Company on Track for AV-380 IND Submission by
Year-end; Phase 1 Clinical Study Planned for the First Quarter of
2021 -
AVEO Oncology (Nasdaq: AVEO) today reported financial results
for the second quarter ended June 30, 2020 and provided a business
update.
“The first half of 2020 was one of the most important periods in
AVEO’s history to date, with the successful completion of the
TIVO-3 study and the acceptance for filing and substantive review
of a New Drug Application (NDA) for tivozanib as a treatment for
relapsed or refractory renal cell carcinoma (RCC),” said Michael
Bailey, president and chief executive officer of AVEO. “Through
successful debt and equity financings, we now expect to have access
to the capital to ensure a robust launch of FOTIVDA® (tivozanib)
into 2022 to potentially address what we believe is a significant
unmet need for an effective, better tolerated drug. Currently, more
than half of patients are opting to forego third or later lines of
therapy, largely due to issues of tolerability and a lack of
evidence-based studies in this setting.1 Supported by positive
results from TIVO-3, we believe tivozanib could address these
challenges and allow patients to continue their fight against
cancer, and therefore has the potential to become a standard of
care in this large and growing segment of the market.”
Mr. Bailey added, “With TIVO-3 complete, we are now evaluating
several opportunities to initiate new pivotal studies for both
tivozanib and ficlatuzumab. Building on the TiNivo and DEDUCTIVE
trials in RCC and hepatocellular carcinoma (HCC) respectively, we
believe tivozanib’s activity, favorable safety profile, and ability
to significantly reduce regulatory T cells2 all have the potential
to make tivozanib a companion tyrosine kinase inhibitor of choice
in these settings. In addition, the early data we have seen in the
randomized head and neck cancer (HNSCC) study with ficlatuzumab
combined with cetuximab (ERBITUX®), which could serve as the basis
for pursuing a pivotal study in this tumor type, has led us to
initiate the process to evaluate securing additional clinical
manufacturing capacity. Finally, we expect AV-380 to enter into a
Phase 1 study in the first quarter of 2021, if an Investigational
New Drug (IND) application which we expect to file by year end
2020, is accepted by the U.S. Food and Drug Administration
(FDA).”
Tivozanib Updates
- Announced FDA Acceptance for Filing of an NDA for Tivozanib
as a Treatment of Relapsed or Refractory RCC. In June 2020,
AVEO announced that the FDA accepted for filing its NDA seeking
approval for tivozanib, the Company’s next-generation vascular
endothelial growth factor receptor tyrosine kinase inhibitor
(VEGFR-TKI), as a treatment for relapsed or refractory RCC. The FDA
has assigned the application standard review and a Prescription
Drug User Fee Act target action date of March 31, 2021. The FDA
also indicated that they do not currently plan on convening an
Oncologic Drug Advisory Committee (ODAC) to discuss the
application. The NDA submission is based on AVEO’s pivotal Phase 3
study, TIVO-3, comparing tivozanib to sorafenib in 3rd and 4th line
RCC. The application is also supported by three additional trials
in RCC and includes safety data from over 1,000 clinical trial
subjects.
- Preparations Underway to Support Potential Commercial Launch
of Tivozanib in the U.S. In preparation for the potential
commercial launch of tivozanib in the U.S., the Company is actively
engaged in the expansion of its sales, marketing, market access and
medical affairs teams, as well as working to enable distribution
capabilities by the end of the year. The Company also today
announced that the FDA has conditionally accepted “FOTIVDA®” as the
proprietary brand name for tivozanib in the U.S.
- Presented TIVO-3 Final Overall Survival Results at ASCO 2020
Virtual Scientific Program. In May 2020, the Company presented
data from the final overall survival (OS) analysis of the pivotal
Phase 3 TIVO-3 trial at the American Society of Clinical Oncology
(ASCO) 2020 Virtual Scientific Program. The final OS hazard ratio
(HR) of 0.97 was similar to those observed with prior approved
VEGFR TKI vs. VEGFR TKI pivotal studies in RCC.3-6 TIVO-3
represents the first positive Phase 3 superiority study designed to
help guide treatment decisions in third and fourth line RCC, a
growing patient population with a high unmet medical need for
effective and better tolerated therapies. A copy of the
presentation is available on the Publications & Presentations
section of AVEO’s website.
- Announced Advancement to the Phase 2 Portion of Phase 1b/2
DEDUCTIVE Study of Tivozanib in Combination with IMFINZI®
(durvalumab) in Previously Untreated HCC After No Dose-Limiting
Toxicities Observed in Phase 1 Portion. In May 2020, AVEO
announced that the Phase 1b/2 DEDUCTIVE clinical trial evaluating
tivozanib in combination with IMFINZI® (durvalumab), AstraZeneca’s
human monoclonal antibody directed against programmed death-ligand
1 (PD-L1), in patients with first line metastatic HCC has
progressed to the Phase 2 portion of the trial. Advancement of the
study into the Phase 2 portion, for which enrollment is currently
underway, was based on findings from the recently completed Phase 1
portion of the combination in which no dose limiting toxicities
were observed. Taken together with positive results from the TiNivo
study, a Phase 1b/2 multicenter trial of tivozanib in combination
with PD-1 inhibitor nivolumab (OPDIVO®, Bristol-Myers Squibb) in
first or second line metastatic RCC, AVEO is currently evaluating
opportunities to initiate potential registrational immunotherapy
combination studies.
Tivozanib Non-Oncology Partnership Update
- $2.8 Million Development Milestone from Kyowa Kirin Co.,
Ltd. The Company recently announced that it earned a $2.8
million development milestone payment from partner Kyowa Kirin Co.,
Ltd. (Kyowa Kirin). The milestone relates to acceptance by the
Japanese Pharmaceuticals and Medical Devices Agency of an IND
application for tivozanib in a non-oncology indication being
developed by Kyowa Kirin. Under the terms of AVEO’s agreement with
Kyowa Kirin, in addition to the previously-paid upfront payment of
$25 million to AVEO, waiver of AVEO’s obligation to make an $18
million milestone payment upon AVEO gaining U.S. marketing approval
of tivozanib for RCC, and the $2.8 million IND development
milestone, Kyowa Kirin has also agreed to pay AVEO up to an
additional $388 million in potential milestone payments upon the
successful achievement of certain development, regulatory, and
commercial objectives in non-oncology indications of tivozanib.
Kyowa Kirin will also be obligated to make tiered royalty payments
on the net sales of a product for these indications, ranging from a
high single-digit to low double-digit percent.
Ficlatuzumab Update
- Based on Early Data from Randomized Phase 2 Study of
Ficlatuzumab in Combination with Erbitux in Head and Neck Cancer,
AVEO Currently Evaluating Phase 3 Study Opportunities. AVEO’s
potent hepatocyte growth factor (HGF) inhibitory antibody,
ficlatuzumab, which binds to the HGF ligand with high affinity and
specificity to inhibit HGF/c-Met biological activities, is being
studied in an ongoing randomized confirmatory Phase 2 study in
combination with cetuximab, an EGFR-targeted antibody, in
metastatic HNSCC. The study was designed to confirm findings from a
Phase 1 study of ficlatuzumab and cetuximab where the combination
was well tolerated and resulted in a disease control rate of 67%,
as well as prolonged progression free and OS compared to historical
controls. The Phase 2 multi-center study 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.
Enrollment is expected to conclude in the fourth quarter of 2020,
and results from the study are expected to be presented at a
scientific meeting in the first half of 2021. AVEO and its partner
Biodesix are evaluating the process to secure additional clinical
manufacturing of ficlatuzumab to potentially enable a Phase 3
clinical trial of ficlatuzumab for the treatment of HNSCC in
2022.
- Data from Phase 1 Study of Ficlatuzumab and Cetuximab in
HNSCC Published in Cancers. Data from the Phase 1 study of
ficlatuzumab and cetuximab in patients with HNSCC were recently
published in the journal Cancers. The combination of ficlatuzumab
and cetuximab demonstrated an acceptable safety profile and showed
promising antitumor activity in a refractory HNSCC patient
population. A link to the publication, titled, “Phase I Study of
Ficlatuzumab and Cetuximab in Cetuximab-Resistant,
Recurrent/Metastatic Head and Neck Cancer”, is available on the
Publications & Presentations section of AVEO’s website.
AV-380 Update
- Company on Track for IND Application Submission by Year-end,
with Phase 1 Clinical Study Planned for the First Quarter of
2021. AVEO plans to submit an IND application to the FDA for
AV-380, its first-in-class, potent, humanized inhibitory antibody
targeting growth differentiation factor 15 (GDF15), for the
treatment of cancer cachexia by year-end. Cachexia, a common
complication in patients with advanced cancer and other chronic
diseases, is a complex metabolic syndrome characterized by
malnutrition and severe involuntary weight loss due to the loss of
muscle and fat tissue, as well as the clinical manifestation of
anemia, inflammation and suppression of immune functions.
Preparations for a Phase 1 trial are currently underway.
Corporate Updates
- Raised Gross Proceeds of $51.1M in Oversubscribed Public
Offering. In June 2020, AVEO announced the closing of an
oversubscribed underwritten public offering yielding aggregate
gross proceeds of approximately $51.1 million, before deducting
underwriting discounts and commissions and offering expenses
payable by AVEO. The financing was led by investors Deerfield
Management, New Enterprise Associates and Cormorant Capital.
- Announced Restructuring of Existing Term Loan with Closing
of New Tranched, $35 Million Debt Facility, Potentially Providing
for Working Capital into 2022. The Company announced today the
closing of a tranched, $35 million debt facility with Hercules
Capital, Inc. and its affiliates. The new facility has a maturity
of 36 months, extendable up to 48-months, and an interest-only
period of 12 months, extendable up to 30 months upon the
achievement of performance milestones related to the approval and
commercialization of tivozanib. Under the terms of the agreement,
the initial tranche of $15 million fully refinanced AVEO’s existing
Hercules term loan facility, which had an outstanding principal
amount of approximately $9.7 million, providing net new proceeds of
$5.3 million. A second $10 million tranche is contingent upon the
approval of the tivozanib NDA by the FDA as a treatment for RCC,
and certain other terms and conditions. An additional two $5
million tranches will become available after that time – one if net
product revenues of tivozanib reach $20.0 million within a
specified time frame, and the other at the lender’s consent. As
previously announced, the FDA has assigned AVEO’s NDA a
Prescription Drug User Fee Act target action date of March 31,
2021.
Second Quarter 2020 Financial Results
- AVEO ended Q2 2020 with $71.4 million in cash, cash equivalents
and marketable securities as compared with $47.7 million at
December 31, 2019.
- Total revenue was approximately $0.7 million in each of Q2 2020
and Q2 2019.
- Research and development expense for Q2 2020 was $4.4 million
compared with $2.6 million for Q2 2019.
- General and administrative expense for Q2 2020 was $3.7 million
compared with $3.0 million for Q2 2019.
- Net loss for Q2 2020 was $7.3 million, or net loss of $0.42 per
basic and diluted share, compared with net loss of $3.1 million for
Q2 2019, or net loss of $0.20 per basic and diluted share,
respectively. The net loss in Q2 2019 reflects a $2.2 million
non-cash gain that was attributable to the decrease in fair value
of the 2016 private placement warrant liability that principally
resulted from a decrease in the stock price that occurred within
the period.
Financial Guidance
AVEO believes that its as-adjusted $79.5 million in cash, cash
equivalents and marketable securities as of June 30, 2020,
consisting of $71.4 million in cash, cash equivalents and
marketable securities at June 30, 2020 together with the $2.8
million KKC milestone and the $5.3 million in new loan funding from
Hercules, along with partnership cost sharing reimbursements,
royalties from EUSA’s FOTIVDA sales and, if the pending marketing
application for FOTIVDA is approved by the FDA, resulting product
revenues upon commercial launch and the potential additional $20
million in credit under the Hercules loan, would allow the Company
to fund planned operations into 2022.
In accordance with Accounting Standards Update No. 2014-15,
Disclosure of Uncertainties about an Entity’s Ability to Continue
as a Going Concern (Accounting Standards Codification Subtopic
205-40), cash flows that are contingent on FDA approval, such as
product revenues, cannot be reflected in the going concern
assessment. As a result, Hercules loan funding contingent on such
approval and revenue is also excluded from our going concern
assessment. Accordingly, the Company continues to have a going
concern opinion.
About Tivozanib (FOTIVDA®)
Tivozanib (FOTIVDA®) is an oral, once-daily, next-generation
vascular endothelial growth factor receptor (VEGFR) 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 and other countries in the EUSA
territory. 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.8,9
Tivozanib is being studied in the TIVO-3 trial, which is supporting
a regulatory submission of tivozanib in the U.S. seeking marketing
approval as a treatment for relapsed or refractory RCC. Tivozanib
has been shown to significantly reduce regulatory T-cell production
in preclinical models2 and has demonstrated synergy in combination
with nivolumab (anti PD-1) in a Phase 2 study in RCC.10 Tivozanib
has been investigated in several tumor types, including renal cell,
hepatocellular, colorectal, ovarian and breast cancers. Tivozanib
is also being studied by partner Kyowa Kirin in non-oncology
indications.
About AVEO Pharmaceuticals, Inc.
AVEO is developing an oncology pipeline designed to provide a
better life for patients with cancer. AVEO’s strategy is to focus
its resources toward 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, tivozanib (FOTIVDA®) is approved in the
European Union and other countries by AVEO’s partner EUSA for the
treatment of adult patients with advanced renal cell carcinoma.
AVEO is working to develop and commercialize tivozanib in North
America as a treatment for renal cell carcinoma and hepatocellular
carcinoma. AVEO has previously reported promising early clinical
data on ficlatuzumab (anti-HGF mAb) in head and neck cancer, acute
myeloid leukemia and pancreatic cancer and is conducting a
randomized Phase 2 confirmatory clinical trial of ficlatuzumab in
head and neck cancer. AVEO’s earlier-stage pipeline includes
several monoclonal antibodies in oncology development, including
AV-203 (anti-ErbB3 mAb), AV-380 (anti-GDF15 mAb) and AV-353
(anti-Notch 3 mAb). AVEO is committed to creating an environment of
diversity and inclusion as a foundation for innovation.
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,” “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 tivozanib as a
treatment option for patients with advanced HCC or
relapsed/refractory or advanced RCC, following earlier TKI and
immunotherapy treatment; 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
tivozanib in the United States; the period in which AVEO expects to
have cash to fund its operations and the contingencies upon which
such guidance is dependent ;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: whether the results
of TIVO-3 are sufficient to obtain marketing approval for tivozanib
in the U.S., which turns on the ability of AVEO to demonstrate to
the satisfaction of the FDA the safety and efficacy of tivozanib
based upon the findings of tivozanib’s clinical trials, including
its data with respect to PFS, the rate of adverse events, OS and
other information that the FDA may determine for approval; 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 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, including its ability to
successfully launch and commercialize tivozanib if it may be
approved for commercialization by the FDA; 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;
AVEO’s ability to access up to $20.0 million of the Hercules loan
facility, which turns on the achievement of milestones related to
the approval and commercialization of tivozanib in the U.S., which
milestones may not be achieved; adverse general economic 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
- Decision Resources, 2019
- Pawlowski N et al. AACR 2013. Poster 3971
- Hutson et al. Clinical Genitourinary Cancer; Vol. 15, No. 1,
72-6.
- Choueiri et al. European Journal of Cancer 2018; 94:
115e125
- Motzer et. al. Lancet Oncol 2013; 14: 552–62.
- Motzer, et al. N Engl J Med. 2014;370(18):1769-1770.
- ZS Assoc. 2017 Sales Revenue
- Fotivda (Tivozanib) SmPC August 2017
- Motzer RJ, Nosov D, Eisen T, et al. J Clin Oncol 2013; 31(30):
3791-9
- Barthelemy et al. ESMO 2018. Poster 878P
AVEO PHARMACEUTICALS,
INC.
Condensed Consolidated
Statements of Operations
(In thousands, except per
share amounts)
(Unaudited)
Three Months Ended
June 30,
Six Months Ended
June 30,
2020
2019
2020
2019
Revenues:
Collaboration and licensing revenue
$
494
$
493
$
987
$
1,947
Partnership royalties
255
210
546
367
749
703
1,533
2,314
Operating expenses:
Research and development
4,419
2,611
12,245
9,463
General and administrative
3,737
2,986
7,409
5,441
8,156
5,597
19,654
14,904
Loss from operations
(7,407
)
(4,894
)
(18,121
)
(12,590
)
Other income (expense), net:
Interest expense, net
(349
)
(451
)
(664
)
(1,015
)
Change in fair value of PIPE Warrant
liability
450
2,210
3,098
11,025
Other income (expense), net
101
1,759
2,434
10,010
Net loss
$
(7,306
)
$
(3,135
)
$
(15,687
)
$
(2,580
)
Net loss per share - basic and diluted
$
(0.42
)
$
(0.20
)
$
(0.94
)
$
(0.18
)
Weighted average number of common shares
outstanding
17,364
15,902
16,722
14,574
Consolidated Balance Sheet
Data
(In thousands)
(Unaudited)
June 30,
2020
December 31,
2019
Assets
Cash, cash equivalents and marketable
securities
$
71,449
$
47,745
Accounts receivable
1,208
1,631
Prepaid expenses and other current
assets
1,571
1,224
Property and equipment, net
96
—
Operating lease right-of-use asset
1,120
—
Other assets
158
—
Total assets
$
75,602
$
50,600
Liabilities and stockholders’
equity
Accounts payable and accrued expenses
$
8,906
$
9,482
Loans payable, net of discount
11,133
15,766
Deferred revenue and research and
development reimbursements
3,798
4,619
PIPE Warrant liability
1,999
5,097
Operating lease liability
924
—
Other liabilities
790
790
Stockholder’s equity
48,052
14,846
Total liabilities and stockholders’
equity
$
75,602
$
50,600
View source
version on businesswire.com: https://www.businesswire.com/news/home/20200810005711/en/
AVEO Contact: David Pitts, Argot Partners (212) 600-1902
aveo@argotpartners.com
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