LOS ANGELES, March 15, 2018 /PRNewswire/ -- CytRx
Corporation (NASDAQ: CYTR), a biopharmaceutical research and
development company specializing in oncology, today announced that
it has selected four new, investigational LADR™ (Linker Activated
Drug Release) candidates for advancement toward clinical testing in
cancer patients. The candidates, preliminarily named LADR-7
(AE-Keto-Sulf07), LADR-8 (AE-Ester-Sulf07), LADR-9 (PP072) and
LADR-10 (FN296), were created using CytRx's novel LADR™ technology
which enables drug compounds to bind to albumin in the body's
bloodstream and controls the release of the drug at the tumor
site. All four candidates are eligible to advance into
Investigational New Drug (IND)-enabling studies with the goal of
filing IND applications on one or more candidates in 2018.
Supportive data demonstrating the impressive in vivo
antitumor efficacy of LADR-7, LADR-8, LADR-9 and LADR-10 will be
presented at the American Association for Cancer Research (AACR)
2018 Annual Meeting taking place April
14-18, 2018 in Chicago. All
studies submitted to AACR were selected for poster
presentations.
"The posters being presented at AACR this year highlight the
positive research supporting our decision to select LADR-7, LADR-8,
LADR-9 and LADR-10 as LADR™ drug candidates which are eligible to
advance toward IND-enabling studies," said Felix Kratz, PhD, CytRx's Vice President of Drug
Discovery. "For LADR-7 and LADR-8, the presented data will
describe the greatly improved antitumor efficacy of these compounds
compared to their parent compound auristatin E, along with their
potential to induce statistically significant, long-term partial or
complete remission in several tumor-bearing animal models.
For LADR-9 and LADR-10, the presented data document the synthesis
of a spectrum of novel maytansinoid derivatives that were
discovered to be as potent or more potent than the parent drug
maytansine in inhibiting the growth in a panel of human cancer
cells. Subsequently, two highly potent maytansinoid derivatives
were selected for developing the albumin-binding drug candidates
LADR-9 and LADR-10. Both LADR-9 and LADR-10 were well-tolerated and
induced long-term partial and complete tumor regressions in a
number of tumor-bearing animal models. These results are
statistically significant compared to maytansine which was
essentially devoid of in vivo antitumor activity. We are
excited about this new research and the selection of the LADR™
ultra high potency compounds, which we believe may have
breakthrough status against numerous solid tumors, and we look
forward to sharing our data with the medical and scientific
community at this year's AACR meeting."
Details for the poster presentations at AACR 2018:
Title: Superior efficacy of novel albumin-binding
auristatin E-based prodrugs compared to auristatin E in a panel of
human xenograft models in mice.
Abstract Number: 3703
Session Category and Title: Cancer Chemistry; Drug
Delivery
Session Date and Time: Tuesday, April 17,
2018 8:00 AM - 12:00 PM
Location: McCormick Place South, Exhibit Hall A, Poster
Section 30
Poster Board Number: 3
Summary: Auristatins are a highly cytotoxic family of
antimitotic tubulin-binding peptides. As a result, to date, only
one auristatin antibody drug conjugate (Adcetris®) has been
approved and marketed. Other auristatins have been investigated in
Phase 1 and 2 clinical trials, but due to systemic toxicity and low
antitumor activity they were discontinued. Due to the high
cytotoxicity, CytRx researchers hypothesized that delivery of
auristatins selectively to the tumor, avoiding premature release in
the blood circulation, would be beneficial. In this study, CytRx
researchers utilized the Company's novel LADR™ technology to
synthesize auristatin E-derived prodrugs (AE-Keto-Sulf07 and
AE-Ester-Sulf07) that are bound covalently to human albumin and is
designed to be liberated in the acidic environment of the tumor.
The researchers conducted a head-to-head comparison of
AE-Keto-Sulf07 and AE-Ester-Sulf07 to parent compound auristatin E
in human tumor xenograft models.
In this study, AE-Keto-Sulf07 showed excellent antitumor
response over a wide dose range, with optimal dosage at 4.5 mg/kg
twice per week over 4 weeks. AE-Ester-Sulf07 was also highly
efficacious. In contrast, auristatin E was only marginally active.
The results demonstrated that AE-Keto-Sulf07 and AE-Ester-Sulf07
successfully bound to circulating albumin, demonstrated promising
antitumor efficacy and induced statistically significant long-term
partial or complete remission.
Title: Structure-activity relationship studies and
biological evaluation of novel maytansinoids, a class of highly
selective tubulin inhibitors
Abstract Number: 1657
Session Category and Title: Cancer Chemistry; Target
Based Drug Discovery
Session Date and Time: Monday, April 16,
2018; 8:00 a.m. to 12:00 p.m.
CT
Location: McCormick Place South, Exhibit Hall A, Poster
Section 30
Poster Board Number: 12
Summary: Maytansine is a potent microtubule-targeting
compound that inhibits proliferation of cancer cells, but its
narrow therapeutic window prevents most clinical application and to
date only one maytansinoid antibody (Kadcyla®) has been approved
for use in resistant breast cancer. Prior research has shown that
the potent cytotoxic activity of maytansinoids is related to the
nature of the substituent at the C3 acyloxy chain. In this study,
CytRx researchers synthesized a library of novel maytansine analogs
that can be attached to serum albumin in vivo via an
acid-sensitive linker which releases the maytansinoid at the tumor
site, thereby diminishing dose-limiting side effects. Each of the
novel maytansine analogs were analyzed in vitro for potency
and cytotoxicity against 11 cancer cell lines, compared to
maytansine. Of the 32 newly synthesized maytansinoid analogs, seven
were found to be more potent than the parent drug maytansine in
inhibiting the growth of human cancer cells. Clear
structure-activity relationships were identified. Based on these
results, lead compounds have been selected for creating
albumin-binding derivatives and their further in vivo
evaluation.
Title: Novel albumin-binding maytansinoids inducing
long-term partial and complete tumor regressions in several human
cancer xenograft models in nude mice.
Abstract Number: 2661
Session Category and Title: Cancer Chemistry;
Antitumor Agents
Session Date and Time: Monday, April 16,
2018 1:00 PM - 5:00 PM
Location: McCormick Place South, Exhibit Hall A, Poster
Section 30
Poster Board Number: 1
Summary: The goal of this study was to determine if novel
maytansinoids could be created using CytRx's LADR technology that
would carry the same potent cell killing properties as maytansine,
while reducing cytotoxic side effects. In this study, CytRx
researchers synthesized a library of potent maytansinoids that were
attached to a water-solubilizing hydrazone linker utilizing the
Company's novel LADR™ technology. Maytansinoid-linker derivatives
selectively bind to human albumin and are designed to be liberated
in the acidic environment of the tumor. The researchers conducted a
head-to-head comparison of the novel albumin-binding maytansinoids
with parent drug maytansine in human tumor xenograft models.
Treatment with CytRx's novel albumin-binding maytansinoids was
better tolerated than with maytansine and maximum tolerated doses
were 4 to 7 times higher showing no significant body weight loss
(<5%). The novel albumin-binding maytansinoids demonstrated a
significantly higher antitumor activity compared to both the
control-group and the group treated with maytansine and induced
long-term partial and complete tumor regressions in all
experiments.
Following the conclusion of the poster presentations, PDF copies
of the posters will be available at
http://cytrx.com/investors/presentations.
About the LADR™ Technology Platform
CytRx's innovative LADR™ (Linker Activated Drug Release)
technology employs a broad portfolio of novel linker molecules that
selectively bind to circulating albumin and can be linked to a wide
variety of anti-cancer payloads. The Company's research efforts
currently center on creating new molecules from the combination of
ultra-high potency cytotoxic payloads with tunable linkers. The
molecules that CytRx is currently evaluating concentrate at the
tumor site providing targeted delivery of the cell killing
payloads.
About CytRx Corporation
CytRx Corporation (NASDAQ: CYTR) is a
biopharmaceutical company specializing in research and clinical
development of novel anti-cancer drug candidates that employ linker
technologies to enhance the accumulation and release of drug at the
tumor. CytRx is rapidly expanding its pipeline of
ultra-high potency oncology candidates at its laboratory facilities
in Freiburg, Germany, through its LADR™ (Linker Activated Drug
Release) technology platform, a discovery engine designed to
leverage CytRx's expertise in albumin biology and linker
technology for the development of a new class of potential
breakthrough anti-cancer
therapies. Aldoxorubicin, CytRx's most advanced drug
conjugate, is an improved version of the widely used anti-cancer
drug doxorubicin and has been out-licensed to NantCell,
Inc.
About AACR
AACR is the oldest and largest scientific organization in the
world focused on every aspect of high-quality, innovative cancer
research. Its reputation for scientific breadth and excellence
attract the premier researchers in the field. The organization's
programs and services foster the exchange of knowledge and new
ideas among scientists dedicated to cancer research, provide
training opportunities for the next generation of cancer
researchers, and increase public understanding of cancer.
Presentations at the AACR Annual Meeting will cover the latest
basic, translational, clinical, and prevention-focused research in
the field, including important areas such as early detection,
cancer interception, and survivorship in all populations.
Forward-Looking Statements
This press release contains forward-looking statements. Such
statements involve risks and uncertainties that could cause actual
events or results to differ materially from the events or results
described in the forward-looking statements, including risks and
uncertainties relating to the ability of NantCell, Inc., to
obtain regulatory approval for its products that use aldoxorubicin;
the ability of NantCell, Inc., to manufacture and
commercialize products or therapies that use aldoxorubicin; the
amount, if any, of future milestone and royalty payments that we
may receive from NantCell, Inc.; our ability to develop new
ultra-high potency drug candidates based on our
LADRTM technology platform; and other risks and
uncertainties described in the most recent annual and quarterly
reports filed by CytRx with the Securities and
Exchange Commission and current reports filed since the date
of CytRx's most recent annual report. All forward-looking
statements are based upon information available
to CytRx on the date the statements are first
published. CytRx undertakes no obligation to publicly
update or revise any forward-looking statements, whether as a
result of new information, future events or otherwise.
Investor Relations Contact:
Argot Partners
Michelle Carroll/Sean Augustine-Obi
(212) 600-1902
michelle@argotpartners.com
sean@argotpartners.com
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