Aravive Announces Publication of AVB-500 Nonclinical Study in Treatment-Resistant ccRCC Animal Models in Cancer Research
October 18 2019 - 8:00AM
Aravive, Inc. (Nasdaq: ARAV), a clinical-stage biopharmaceutical
company developing treatments designed to halt the progression of
life-threatening diseases, including cancer and fibrosis, today
announced publication of data from a nonclinical study of AVB-500,
the company’s lead product candidate, which demonstrated reduction
in tumor size and blood vessel density in animal models of clear
cell renal cell carcinoma (ccRCC). The research elucidates the role
of GAS6/AXL signaling in promoting tumor angiogenesis through
control of plasminogen receptor S100A10. The study, entitled
“S100A10 is a critical mediator of GAS6/AXL-induced angiogenesis in
renal cell carcinoma” was published in the October edition of the
peer-reviewed journal Cancer Research.
“This study has important therapeutic implications, suggesting
that an anti-GAS6 therapy may be a potentially effective approach
to prevent and treat tyrosine kinase inhibitor (TKI)-resistant
disease, supporting the rationale for combining AVB-500 with
antiangiogenic agents in the treatment of advanced kidney cancer,”
said Gail McIntyre, Ph.D., chief scientific officer of Aravive.
“The research supports our plans to develop AVB-500 in ccRCC, and
we remain on track to initiate clinical development in
4Q2019/1Q2020.”
Key conclusions of the study include:
- Genetic inhibition of AXL in ccRCC cells reduces tumor vessel
density and growth.
- GAS6/AXL signaling promotes S100A10 expression in ccRCC cells
through SRC family kinase activity.
- GAS6 inhibition by AVB-500 synergizes with pazopanib and
axitinib to reduce ccRCC patient-derived xenograft growth and
vessel density.
- GAS6 inhibition by AVB-500 reduces the growth of a TKI
resistant ccRCC patient-derived xenograft.
About Clear Cell Renal Cell Carcinoma
Clear cell renal cell carcinoma (ccRCC) is the most common type
of kidney cancer and has been increasing in prevalence in the U.S.
and Europe over the last several decades. As many as 25 percent of
patients already have metastatic disease at the time of diagnosis.
ccRCC tumors are highly vascularized and initially respond to
antiangiogenic therapies, including tyrosine kinase inhibitors.
While antiangiogenic therapy has significantly increased
progression-free survival in people with advanced renal cancer, the
majority of individuals treated with these agents eventually become
resistant and progress.
About AVB-500
AVB-500 (previously called AVB-S6-500) is a therapeutic
recombinant fusion protein that has been shown to neutralize GAS6
activity by binding to GAS6 with very high affinity. In doing so,
AVB-500 selectively inhibits the GAS6-AXL signaling pathway. In
preclinical studies, GAS6-AXL inhibition has shown anti-tumor
activity, both as a single agent or in combination with a variety
of anticancer therapies including radiation therapy,
immuno-oncology agents, and chemotherapeutic drugs that affect DNA
replication and repair. Increased expression of AXL and GAS6 in
tumors is correlated to poor prognosis and survival and has been
implicated in therapeutic resistance to conventional
chemotherapeutics and targeted therapies.
Aravive is currently enrolling the expansion cohort in the phase
1b portion of a phase 1b/2 clinical trial of AVB-500 in
platinum-resistant recurrent ovarian cancer. An
investigator-studied Phase 1 study of AVB-500 in combination with
durvalumab in patients with platinum-resistant, recurrent
epithelial ovarian cancer is also ongoing. A Phase 1 clinical trial
in healthy volunteers (NCT03401528) investigating the safety,
pharmacokinetics, and pharmacodynamics of AVB-500 met the safety
and tolerability endpoints and demonstrated clinical
proof-of-mechanism for AVB-500 in neutralizing GAS6. Based on
AVB-500’s favorable safety profile, coupled with its specifically
targeted mechanism of action, the protein has the potential to be
used both in combination with existing therapies, as well as a
maintenance drug. U.S. FDA granted Fast Track Designation to
Aravive Biologics’ AVB-500 in platinum-resistant recurrent ovarian
cancer in 2018.
About Aravive
Aravive, Inc. (Nasdaq: ARAV) is a clinical-stage
biopharmaceutical company developing treatments designed to halt
the progression of life-threatening diseases, including cancer and
fibrosis. Aravive’s lead product candidate, AVB-500, is an
ultra-high affinity decoy protein that targets the GAS6-AXL
signaling pathway. By capturing serum GAS6, AVB-500 starves the AXL
pathway of its signal, potentially halting the biological
programming that promotes disease progression. AXL receptor
signaling plays an important role in multiple types of malignancies
by promoting metastasis, cancer cell survival, resistance to
treatments, and immune suppression. The GAS6-AXL signaling pathway
also plays a significant role in fibrogenesis. Aravive is
evaluating AVB-500 in platinum-resistant ovarian cancer, and
intends to expand development into additional oncology and fibrotic
indications. Aravive is based in Houston, Texas and received a
Product Development Award from the Cancer Prevention & Research
Institute of Texas (CPRIT) in 2016. Aravive was one of
FierceBiotech's Fierce 15 in 2017. For more information, please
visit www.aravive.com.
Forward Looking Statements This
communication contains forward-looking statements (including within
the meaning of Section 21E of the United States Securities Exchange
Act of 1934, as amended, and Section 27A of the United States
Securities Act of 1933, as amended), express or implied, concerning
the Company’s goals, intentions and expectations as to future plans
or events, including statements regarding the suggestion that GAS6
therapy may be a potentially effective approach to prevent and
treat tyrosine kinase inhibitor (TKI)-resistant disease, supporting
the rationale for combining AVB-500 with antiangiogenic agents in
the treatment of advanced kidney cancer, plans to develop AVB-500
in ccRCC, remaining on track to initiate clinical development in
4Q2019/1Q2020, the potential of AVB-500 to be used both in
combination with existing therapies, as well as a maintenance drug
and the expansion of the development of AVB-500 into additional
oncology and fibrotic indications. Forward-looking statements are
based on current beliefs and assumptions, are not guarantees of
future performance and are subject to risks and uncertainties that
could cause actual results to differ materially from those
contained in any forward-looking statement as a result of various
factors, including, but not limited to, risks and uncertainties
related to: the Company’s ability to expand development into
additional oncology and fibrotic indications, the Company’s
dependence upon AVB-500, AVB-500’s ability to have favorable
results in clinical trials or receive regulatory approval,
potential delays in the Company's clinical trials due to regulatory
requirements or difficulty identifying qualified investigators or
enrolling patients; the risk that AVB-500 may cause serious side
effects or have properties that delay or prevent regulatory
approval or limit its commercial potential; the risk that the
Company may encounter difficulties in manufacturing AVB-500; if
AVB-500 is approved, risks associated with its market acceptance,
including pricing and reimbursement; potential difficulties
enforcing the Company's intellectual property rights; the Company's
reliance on its licensor of intellectual property and financing
needs. The foregoing review of important factors that could cause
actual events to differ from expectations should not be construed
as exhaustive and should be read in conjunction with statements
that are included herein and elsewhere, including the risk factors
included in the Company's Annual Report on Form 10-K and Form
10-K/A for the fiscal year ended December 31, 2018, recent
Current Reports on Form 8-K and subsequent filings with
the SEC. Except as required by applicable law, the Company
undertakes no obligation to revise or update any forward-looking
statement, or to make any other forward-looking statements, whether
as a result of new information, future events or otherwise.
Contacts:
Investors:
Christina Tartaglia
Stern Investor Relations
christina@sternir.com
Media:
Heidi Chokeir, Ph.D.
Canale Communications
heidi@canalecomm.com
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