LOS ANGELES, April 18, 2018 /PRNewswire/ -- CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development
"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.
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.
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.
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 PartnersMichelle Carroll(212) 600-1902 firstname.lastname@example.org
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