BIND Therapeutics Presents Positive Data Highlighting Ability of Accurins

BIND Therapeutics, Inc. recently announced that clinical and preclinical data from its oncology pipeline, including proprietary and collaboration programs, were presented at the American Association of Cancer Research (AACR) Annual Meeting 2015. The presentations included data from the company’s lead proprietary Accurin drug candidate, BIND-014, and the Accurin drug candidate AZD2811, which is being developed in collaboration with AstraZeneca.

“Collectively, these data demonstrate the unique attributes of Accurins as a new therapeutic modality and their potential to produce therapeutics with a best-in-class profile,” said Andrew Hirsch, President and Chief Executive Officer of BIND. “The data describing optimized pharmacological properties across a range of key therapeutic parameters for our proprietary product candidate, BIND-014, and AZD2811, our Aurora B kinase inhibitor program with AstraZeneca, demonstrate the ability of Accurins to control biodistribution and accumulate in target tissue across a broad spectrum of therapeutic payloads.”

In a poster presentation entitled Pharmacokinetics of BIND-014 (docetaxel nanoparticles for injectable suspension) in preclinical species and patients with advanced solid tumors, BIND Therapeutics researchers presented clinical and preclinical data demonstrating that the Accurin BIND-014 provided prolonged circulation and controlled release of encapsulated docetaxel when compared to conventional docetaxel consistently across multiple species. The controlled biodistribution and potential for targeted and preferential tumor accumulation may result in increased efficacy and decreased toxicity with BIND-014.

• BIND-014 preclinical and clinical pharmacokinetics (PK) demonstrated monophasic plasma concentration-time profiles well differentiated from solvent-based docetaxel.
• The Accurin BIND-014 displayed higher peak plasma concentration [Cmax] and area under the curve [AUC] with reduced clearance [CL] and volume of distribution [V(d)] for total docetaxel compared to solvent-based docetaxel.
• In all species, the V(d) of BIND-014 was close to the blood volume. Cmax and AUC in human patients with solid tumors demonstrated dose linearity with an R2≥ 0.98; repeat dosing did not have a significant effect on Cmax.
• Evaluation of encapsulated docetaxel plasma concentrations in patients and cynomolgus monkeys demonstrated that most circulating docetaxel was encapsulated in nanoparticles.

In a poster presentation entitled AZD1152-hQPA Accurin™ nanoparticles inhibit growth of diffuse large B-cell lymphomas and small cell lung cancer in preclinical models, data were presented demonstrating that the Accurin nanoparticle AZD2811 exhibits promising in vivo and in vitro tumor growth inhibition as monotherapy in diffuse large B-cell lymphomas (DLBCL) and small cell lung cancer (SCLC). Time and duration of exposure is important and these data also indicate that the Accurin nanoparticle AZD2811 has the flexibility to be delivered with different doses/schedules, offering the potential to adapt the therapeutic regimen to different tumors while achieving an improved therapeutic index.

• Models of DLBCL and SCLC show sensitivity to monotherapy Aurora B kinase inhibitors and AZD2811, with increased time of exposure resulting in greater cell death.
• In vivo, Accurin nanoparticle AZD2811 inhibited tumor growth or resulted in tumor regression in multiple DLBCL and SCLC models.
• At 25mg/kg dosed on day 1 and 3, Accurin nanoparticle AZD2811 provided either equivalent or superior activity to AZD1152 delivered at 25mg/kg on days 1, 2, 3 and 4.
• Increased dose intensity resulted in increased anti-tumor effect, while modifying the timing and dose intensity of each dose cycle also influenced the anti-tumor activity.

In a poster entitled Imaging AZD1152-hQPA Accurin™ nanoparticle accumulation in preclinical tumors, data were presented that show the Accurin nanoparticle AZD2811 accumulates in tumors and achieves prolonged tumor drug exposure. This is the first time distribution of nanoparticles in tumors has been demonstrated.

• Imaging mass spectrometry analysis demonstrated that Accurin nanoparticle AZD2811 accumulates in preclinical tumor models and confirmed that the Accurin accesses the tumor and provides prolonged drug exposure and retention in the target tissue.
• Multiple imaging techniques demonstrated Accurin nanoparticle AZD2811 is still detected at nine days after nanoparticle administration, while no drug was detected 24 hours after the prodrug AZD1152 was administered.

Accurins are BIND’s targeted and programmable therapeutics, which are designed, utilizing BIND’s medicinal nanoengineering platform, with specified physical and chemical characteristics to target specific cells or tissues and concentrate a therapeutic payload at the site of disease to enhance efficacy while minimizing adverse effects on healthy tissues. 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. BIND has demonstrated in preclinical studies that Accurins can improve tumor growth suppression, achieve higher concentrations of the payload in tumors compared to the payload administered in conventional form, and have pharmacokinetics and tolerability differentiated from their therapeutic payloads.

BIND Therapeutics is a clinical-stage nanomedicine platform company developing a pipeline of Accurins, its novel targeted therapeutics designed to increase the concentration and duration of therapeutic payloads at disease sites while reducing exposure to healthy tissue. BIND is leveraging its Medicinal Nanoengineering platform to develop a pipeline of Accurins targeting hematological and solid tumors and has a number of strategic collaborations with biopharmaceutical companies to develop Accurins in areas of high unmet need. For more information, visit www.bindtherapeutics.com.