On June 30, 2015 CytRx reported unveiled its proprietary LADR (Linker Activated Drug Release) technology platform, a discovery engine designed to leverage the Company’s expertise in albumin biology and linker technology for the development of a new class of anti-cancer therapies (Press release, CytRx, JUN 30, 2015, View Source [SID:1234506012]). Schedule your 30 min Free 1stOncology Demo! CytRx expects the LADR platform to rapidly expand its pipeline of oncology drug candidates, providing an avenue for the development of propriety drug candidates that complement its global Phase 3 aldoxorubicin program. Among the cancers being pursued are liver, pancreatic, and non-small cell lung cancer.
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"LADR is a creative, novel approach to the development of next-generation therapeutic drug conjugates, which we have rationally designed to control release in tumors of high-potency chemotherapeutics that are attached to either albumin or anti-cancer antibodies," stated Dr. Felix Kratz, Vice President of Drug Discovery at CytRx. "These therapies have release properties that minimize their toxic effects on non-cancerous cells, may substantially reduce drug resistance and maximize their anti-cancer potency. With the first drug candidates from this platform expected to enter the clinic in 2016, we look forward to further validating the great potential of this platform in the near future. Our LADR Technology can also be easily combined with immunotherapies to potentially improve outcomes."
"CytRx is committed to improving and extending the lives of patients with cancer through the development of new and innovative therapies," said Steven A. Kriegsman, Chairman and CEO of CytRx. "LADR is an important platform, one that combines our deep knowledge of albumin biology with cutting-edge chemistry and linker technology to deliver a highly potent next-generation albumin and antibody drug conjugate (ADC) drug candidates for cancer treatment. We believe this platform provides us with a number of avenues for near- and long-term value creation."
LADR Platform Mechanism
LADR technology was invented and developed by CytRx at its laboratories in Freiberg, Germany. The platform employs a portfolio of novel linker molecules that bind to albumin in the blood and could also be tied to a variety of antibodies, including antibodies directed at cancer targets. Because of the linker’s ability to modulate release of the highly potent chemotherapy drugs attached to them at the site of cancer cells, it may be possible to reduce toxicity and increase efficacy using these conjugates.
As Dr. Kratz has previously demonstrated, these drug conjugates can form a covalent bond to albumin, the most abundant protein in the blood stream, almost instantaneously. The cytotoxic drug is then held inactive while it circulates throughout the body. Due to highly dysfunctional vasculature surrounding tumors, macromolecules like albumin are able to leak out of the blood vessel and into the tumor itself. This allows for the albumin-bound drug conjugate to accumulate at the tumor but avoid concentration in less permeable normal tissues. The linkers then allow the controlled release of selected payload agents under a variety of conditions that are present in tumors, such as low pH levels. Cleaving of the linker occurs within specific compartments in the cancer cells or can occur in the acidic conditions in and around the tumor. Since most normal tissues are not acidic, the linker does not release the drug, thereby minimizing toxicity to healthy tissues.
Once released in the tumor, the payload induces cell death based on the selected molecule. In current candidates under preclinical development, CytRx has bound very high potency drugs (10-1,000x more potent than standard chemotherapeutics), as well as modified standard chemotherapeutics that are able to avoid drug resistance mechanisms. The first group of these drugs are expected to enter the clinic in 2016.
Broad Intellectual Property Portfolio Covering LADR Technology
CytRx has filed a patent application including comprehensive claims directed to the LADR (Linker Activated Drug Release) technology platform, and compositions of matter and methods related to the technology.