LOS ANGELES, April 18, 2018 /PRNewswire/ -- CytRx
Corporation (NASDAQ: CYTR), a biopharmaceutical research and
development company specializing in oncology, today announced the
presentation of all three of its accepted posters at the American
Association for Cancer Research (AACR) 2018 Annual Meeting taking
place April 14-18, 2018 in
Chicago. The posters feature
comprehensive and statistically significant efficacy data for the
Company's albumin binding ultra high potency LADR™ (Linker
Activated Drug Release) drug candidates, LADR-7, LADR-8, LADR-9 and
LADR-10. Each of the candidates are rationally designed using
CytRx's novel LADR™ technology, which enables drug compounds to be
molecularly bound to albumin in the body's bloodstream and controls
its release at the tumor site. LADR™ maximizes tumor cell kill
potential while minimizing systemic toxicity. As previously
announced, 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.
"The goal of our ongoing research is to utilize CytRx's unique
LADR™ technology to harness the power and potential of known,
efficacious anti-cancer compounds where development has been
impeded due to systemic toxicity," said Felix Kratz, PhD, CytRx's Vice President of Drug
Discovery. "A critical element of the LADR™ platform is its
ability to bind anti-cancer molecules to albumin, the most
ubiquitous protein in human blood plasma, and then to release the
highly potent cytotoxic payload at the tumor site. This technology
allows for the delivery of higher doses of drug directly to the
tumor, while avoiding much of the off-target toxicity observed with
the parent molecules. The posters presented at AACR this year
highlight the positive scientific findings that led to our decision
to select auristatin E (AE) derivatives LADR-7 and LADR-8, and
maytansine derivatives LADR-9 and LADR-10, as the next LADR™
candidates eligible to advance toward IND-enabling studies. The
compounds demonstrated excellent, long-term antitumor activity
across a wide range of human solid tumor cancer types, including
lung, breast, ovarian, head and neck, renal cell, and
melanoma."
Superior Efficacy with LADR-7 and LADR-8
The data highlights the superior antitumor efficacy of
albumin-binding auristatin E (AE) derivatives LADR-7 and LADR-8 in
human solid tumor models of melanoma, ovarian, non-small cell lung
cancer (NSCLC), and head and neck cancers.
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. The goal of these studies was to
investigate the antitumor activity of novel, albumin-binding ultra
high potency drug candidates LADR-7 and LADR-8. In this study,
CytRx researchers conducted a head-to-head comparison of LADR-7 and
LADR-8 with a control group or the parent compound AE in human
tumor xenograft models. Both LADR-7 and LADR-8 demonstrated
statistically significant antitumor activity, inducing long-term
complete and partial responses in median relative tumor volume in
all models studied, including melanoma, ovarian, NSCLC, and head
and neck cancers.
For LADR-7, of the 14 pre-clinical models in the melanoma group,
11 (79%) achieved a complete response (CR) and 2 (14%) achieved a
partial response (PR) for total efficacy of 93%. Of the 14 in the
ovarian cancer group, 5 (36%) achieved a CR and 7 (50%) achieved a
PR for total efficacy of 86%. All (100%) of the 15
pre-clinical models in the NSCLC group achieved a CR. For
LADR-8, of the 15 in the ovarian cancer group, 8 (53%) achieved a
CR and 2 (13%) achieved a PR for total efficacy of 66%. Of the 15
in the NSCLC group, 4 (30%) achieved a CR and zero achieved a PR.
Significantly, durable responses averaged 60 – 90 days.
In addition, both LADR-7 and LADR-8 consistently demonstrated
statistically significant superiority over both the control group
and the parent compound AE at its maximum tolerated dose
(p<0.05) in nine of the nine models tested. Importantly,
treatment with LADR-7 and LADR-8 was highly effective, even in
large tumors with starting volumes of 270-380 mm3.
Toxicity findings included average body weight increase of >6%
for LADR-7 and body weight loss of >15% for LADR-8, only in the
NSCLC models. Skin lesions due to scratching and biting were
observed with LADR-8.
A PDF copy of the presented poster can be accessed here.
Positive Results for LADR-9 and LADR-10
The data highlights the statistically significant anti-tumor
activity of LADR-9 and LADR-10 in preclinical models of lung,
breast, ovarian, renal cell, and head and neck cancers.
The goal of this study was to investigate the antitumor activity
of novel maytansinoids LADR-9 and LADR-10. In this study, CytRx
researchers conducted a head-to-head comparison of LADR-9 and
LADR-10 to vehicle or the parent drug maytansine in human tumor
xenograft models. Both LADR-9 and LADR-10 showed excellent
antitumor activity, inducing long-term partial and complete
reductions in relative tumor volume in all cancer models studied,
including lung, breast, ovarian, renal cell, and head and neck
cancers. In addition, both LADR-9 and LADR-10 consistently
demonstrated statistically significant superiority over the parent
drug maytansine (p<0.05). In addition, durable responses
averaged 60 – 90 days. Importantly, treatment with LADR-9 and
LADR-10 was highly effective even in large tumors with starting
volumes up to 350 mm3. Treatment with LADR-9 and LADR-10
was generally well tolerated. Toxic effects were strongly dependent
on the tumor model, and body weight loss was observed in three of
the six xenograft models.
A PDF copy of the presented poster can be accessed here.
The Creation of Novel Maytansinoids
Maytansine is a potent microtubule-targeting compound that
inhibits proliferation of cancer cells, but its narrow therapeutic
window prevents most clinical applications and to date only one
maytansinoid antibody (Kadcyla®) has been approved for use in
Herceptin®-resistant breast cancer. The goal of this preclinical
research was to identify novel, potent derivatives of maytansine
for the development of LADR™ maytansine-based anti-cancer agents
with the potential for reduced cytotoxic effects. CytRx researchers
synthesized a total of 35 maytansine analogs and evaluated each for
cytotoxicity and stability in vitro. In cell-based
cytotoxicity assays, eight compounds were identified that are
equally or even more active than maytansine (geomean
IC50 values <222 pm) at inhibiting the growth of
cancer cells. Based on their cytotoxicity and stability profile,
several of these derivatives were evaluated as albumin-binding
drugs in vivo, and two promising maytansinoid
derivatives were selected for further development.
A PDF copy of the presented poster can be accessed here.
LADR™ Superiority over Antibody-Drug Conjugates
(ADC's)
Company Strategic Advisor, Eric L.
Curtis, MBA, long-time executive at large global
pharmaceutical companies including Bayer, GlaxoSmithKline, and
Johnson & Johnson, commented on the outlook for the LADR™
platform versus the multi-billion-dollar antibody drug conjugate
drugs.
"I believe the LADR™ platform will eventually dominate this
field. The competitive advantages of LADR™ against ADC's are
overwhelming, including broad therapeutic utility and patient
populations, low risk of immune responses, low cost of goods,
simplicity in manufacturing and no requirement of antibody
receptors," said Mr. Curtis.
Strategic Alliances
In discussing the future for the platform, Mr. Curtis also said
"we are currently in due diligence with over ten large global
pharmaceutical companies and already have two companies under
CDA."
"Our goal for our Freiburg Lab operations is to close a major
strategic alliance during the fourth quarter of 2018," Mr. Curtis
concluded.
Conference Call and Webcast
CytRx management will be hosting a conference call and webcast
today beginning at 11:00 a.m. Eastern
Time / 10:00 a.m. Central
Time. To access the live conference call, dial +1
844-358-6753 and enter the passcode: 2798507. A link to the live
and archived webcast will be available in the News & Events
section of the Company's website, www.cytrx.com, under the Events
Calendar tab, or by clicking here:
https://edge.media-server.com/m6/p/3qznwaat. A replay of the call
and webcast will begin approximately two hours after the live call
has ended. To access the replay for the call, dial +1 855-859-2056
and enter the passcode: 2798507.
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 LADR™ 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
(212) 600-1902
michelle@argotpartners.com
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