Date: 2016-02-10
Type of information: Publication of results in a medical journal
phase: preclinical
Announcement: publication of results in Science Translational Medicine
Company: Bind Therapeutics (USA - MA)
Product: Accurins™
Action
mechanism: Accurins™ are polymeric nanoparticles that incorporate a therapeutic payload and are designed to have prolonged circulation within the bloodstream, enable targeting of the diseased tissue or cells, and provide for the controlled and timely release of the therapeutic payload. Tissue targeting is achieved by engineering the physical and chemical properties—size, shape and surface properties—of the Accurin to allow it to escape through gaps in the blood vessels surrounding tumors and other disease sites. Cellular targeting is achieved using proprietary targeting ligands on the surface of the Accurin that binds to specific cell surfaces or tissue markers. Accurins are designed with specific polymers that provide for the controlled and timely release of the therapeutic payload. Upon administration, the therapeutic payload begins to diffuse through the polymeric matrix. Subsequently, the polymer breaks down to lactic acid, a compound naturally found in the body. If the therapeutic payload releases before the Accurins accumulate at the disease site, the Accurins will be unable to effectively increase drug concentration in the diseased tissue and the anticipated therapeutic impact will be minimized or lost. Similarly, if the therapeutic payload is not released, or releases too slowly, the anticipated therapeutic impact will be lost or minimized and new toxicities may be created. By combining prolonged circulation, triple targeting and controlled and timely release of the therapeutic payload, Accurins have the potential to significantly increase the net clinical benefit associated with the therapeutic payload and result in efficacy and safety currently not achievable through other therapeutic modalities.
Disease:
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On February 10, 2016, Bind Therapeutics announced the publication of data highlighting the ability of Accurin polymeric nanoparticle technology to utilize hydrophobic ion pairing and improve the therapeutic index of a molecularly targeted anti-cancer drug. Previous efforts with nanotechnology have focused almost exclusively on encapsulating chemotherapy payloads; the publication describes one of the first efforts to apply nanotechnology to a molecular targeted agent. Results highlight the potential for Accurins® to control release kinetics and provide increased concentration of an aurora B kinase inhibitor, AZD2811, at tumor sites resulting in prolonged pharmacodynamic effects, superior tumor growth inhibition and a reduction in on-target but off-tissue toxicity. These data were published in the February 10, 2016 issue of Science Translational Medicine. In the paper entitled, "Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo," researchers demonstrated the accumulation and retention of a specific AZD2811 nanoparticle formulation in tumors, resulting in an extended reduction of tumor phosphorylated histone H3 levels in vivo for up to 96 hours following a single administration with minimal impact on bone marrow pathology. This formulation also demonstrated continuous drug release for more than one week in vitro, and displayed lower toxicity and increased efficacy in multiple tumor models at half the dose intensity of a water-soluble prodrug of AZD2811. These preclinical studies using ion pairing agents with AZD2811 and Accurin technology suggested improved tolerability as well as less frequent dosing. (Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo. Susan Ashton et al Bind is collaborating with AstraZeneca on the development of AZD2811. They have concluded an agreement to develop and commercialise an Accurin™in April 2013.
Science Translational Medicine 10 Feb 2016: Vol. 8, Issue 325, pp. 325ra17 DOI: 10.1126/scitranslmed.aad2355)
