A new class of highly selective targeted and programmable therapeutics called AccurinsTM has been developed by BIND Biosciences, a clinical-stage biopharmaceutical company that are capable of up to a ten-fold increase in drug concentration at tumor sites, has published preclinical and clinical data in Science Translational Medicine revealing promising effects in solid tumors and successful clinical translation of BIND-014, the first targeted and programmed nanomedicine to penetrate human clinical studies.
In the paper titled "Preclinical Development and Clinical Translation of a PSMA-Targeted Docetaxel Nanoparticle with a Differentiated Pharmacological Profile," BIND scientists describe BIND-014's ability to concentrate in tumors and provide preclinical and clinical data demonstrating efficacy, safety and pharmacological properties that are superior to and highly differentiated from the parent chemotherapeutic drug, docetaxel. BIND-014 is the first clinical-stage targeted therapeutic nanoparticle with programmable pharmacological properties, including particle circulation time, pharmacokinetic profile, biodistribution and release profile. BIND-014 has been shown to effectively target a receptor expressed in tumors to achieve high drug concentrations at the site of disease."These seminal data on BIND's first clinical stage Accurin, BIND-014, demonstrates for the first time that it is possible to generate medicines with both targeted and programmable properties that can concentrate the therapeutic effect directly at the site of disease, potentially revolutionizing how complex diseases such as cancer are treated," commented Omid Farokhzad, M.D, BIND Founder and Associate Professor, Harvard Medical School.
Advertisement"BIND's data are a giant leap forward in achieving the true promise of nanomedicine by enabling the design of therapeutics with highly-differentiated efficacy and safety that go above and beyond the capabilities of traditional drug design through medicinal chemistry." "Previous attempts to develop targeted nanoparticles have not translated into clinical success because of the inherent difficulty of designing and scaling up a particle capable of targeting, long-circulation via immune-response evasion, and controlled drug release," commented Robert Langer, Sc.D., BIND Founder and David H. Koch Institute Professor at MIT. "BIND-014 is the first therapeutic of its kind to reach clinical evaluation and has demonstrated an increases of up to ten fold in drug concentration in tumors, which lead to substantially better efficacy and safety. This represents a major advance in cancer therapy and a significant milestone for science, technology and medicine.
"Key findings include:
- Preclinical data including pharmacokinetic characteristics consistent with prolonged circulation and controlled drug release with plasma concentrations remaining up to at least 100-fold higher than conventional docetaxel for over 24 hours, as well as up to a ten-fold increase in intratumoral drug concentrations with prolonged and enhanced tumor growth suppression in multiple tumor models compared with conventional docetaxel.
- Initial clinical data in a heavily pretreated patient population with 17 patients with advanced or metastatic solid tumor cancers indicate that BIND-014 displays pharmacological characteristics consistent with preclinical findings of differentiated pharmacokinetics and accumulation at tumor sites with clinical effects seen at doses as low as 20% of the normally prescribed docetaxel dose and in cancers in which docetaxel has minimal activity.
- BIND-014 has been administered at doses of up to 75 mg/m2 and dose escalation is ongoing. BIND-014 is generally well tolerated with no new toxicities observed to date.
About BIND-014BIND-014 is a programmable nanomedicine that combines a targeting ligand and a therapeutic nanoparticle. BIND-014 contains docetaxel, a proven cancer drug which is approved in major cancer indications including breast, prostate and lung, encapsulated in FDA-approved biocompatible and biodegradable polymers. BIND-014 is targeted to prostate specific membrane antigen (PSMA), a cell surface antigen abundantly expressed on the surface of cancer cells and on new blood vessels that feed a wide array of solid tumors. In preclinical cancer models, BIND-014 was shown to deliver up to ten-fold more docetaxel to tumors than an equivalent dose of conventional docetaxel. The increased accumulation of docetaxel at the site of disease translated to marked improvements in antitumor activity and tolerability. BIND-014 is currently in Phase 1 human clinical testing in patients with advanced or metastatic solid tumor cancers (NCT01300533). The early development of BIND-014 was funded in part by the National Cancer Institute and the U.S. National Institutes of Standards and Technology (NIST) under its Advanced Technology Program (ATP).
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