BIND Therapeutics Presents Data Demonstrating Ability Of Accurins To Improve Efficacy And Tolerability Of Multiple Anti-Cancer Agents

CAMBRIDGE, Mass.--(BUSINESS WIRE)--BIND Therapeutics, Inc. (NASDAQ: BIND), a clinical-stage nanomedicine company developing targeted and programmable therapeutics called Accurins™, today reported data demonstrating the efficacy and tolerability of BIND’s Accurin platform with multiple anti-cancer agents. These data, which were presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics held in Boston, November 5-9, 2015, describe the ability of Accurins to control the biodistribution of therapeutic payloads across multiple active anti-cancer agents, pathways and targets, which results in either improved efficacy, tolerability or both.

“BIND-510 improves the pharmacokinetics, tolerability, tumor accumulation and tumor growth inhibition in preclinical models of cancer compared to vincristine sulfate”

The four posters presented include preclinical and clinical pharmacokinetic data from BIND’s clinical stage Accurin compound, BIND-014; data from BIND’s preclinical stage Accurin, BIND-510; and new data from a previously unannounced feasibility study with Merck, demonstrating the potential value of an Accurin formulation of Merck’s proprietary AKT inhibitor, MK-2206.

“We believe data from these posters reinforce the flexibility of the Accurin platform to incorporate multiple therapeutic payloads and target them to sites of disease while limiting exposure to healthy tissue,” said Andrew Hirsch, president and chief executive officer, BIND Therapeutics. “These data also demonstrate the ability of Accurins to create potentially best-in-class therapeutics, both with our proprietary product candidates as well as those of our collaborators, as demonstrated with the Merck AKT inhibitor MK-2206.”

“The ability of our Accurin platform to overcome the challenges often associated with narrow therapeutic windows of otherwise powerful drugs is reinforced by these data,” said Hagop Youssoufian, M.D., chief medical officer at BIND. “BIND-014 continues to demonstrate important and potentially differentiating points from docetaxel; BIND-510 exhibits promising pharmacokinetics, tumor accumulation, tolerability and anti-tumor activity across multiple tumor types in preclinical models; and the feasibility study with an Accurin formulation of Merck’s MK-2206 further validates the applicability of our Accurin platform to drugs with diverse mechanisms of action.”

Posters presented at AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics

BIND-014

1. “Evaluation of total and encapsulated drug pharmacokinetics for BIND-014 (docetaxel nanoparticles for injectable suspension) evaluated in a phase 1 study”
BIND researchers and collaborators evaluated the pharmacokinetic (PK) profile of BIND-014 in 28 patients with advanced or metastatic cancer and determined that PK properties of BIND-014 are primarily due to retention of encapsulated docetaxel within the vascular compartment and controlled release of docetaxel. These characteristics together with PSMA targeting, potentially lead to greater tumor uptake and improved activity of BIND-014 compared to conventional solvent-based docetaxel.

• BIND-014 was administered by a 60-minute intravenous infusion at doses ranging from 3.5–75 mg/m² on Day 1 of a 21-day cycle.
• Plasma concentrations of BIND-014 persisted for at least 48 hours at the higher dose levels.
• Clearance was independent of the administered dose, indicating a linear dose-concentration relationship following a single intravenous administration.
• The total concentration of BIND-014 found in circulation compared to the concentration of encapsulated docetaxel was similar, indicating that the majority of the circulating docetaxel was encapsulated in nanoparticles.
• Results are consistent with the favorable tolerability profile of BIND-014 despite the markedly higher plasma concentrations for total BIND-014 compared to published data for docetaxel at similar doses.
• BIND-014 displays a PK profile well differentiated from conventional docetaxel and consistent with retention of BIND-014 nanoparticles in the blood compartment and controlled release of docetaxel.

2. “Cardiovascular safety profile of BIND-014 (docetaxel nanoparticles for injectable suspension) evaluated in phase 1 and 2 studies”
BIND researchers determined that BIND-014, when administered on day 1 of a 21-day cycle with doses ranging from 3.5–75 mg/m², was well tolerated at all doses studied and has the potential to become a safe antitumor agent without the cardiovascular effects typically associated with docetaxel.

• For all 110 patients tested, the vast majority of ECG data collected remained in normal or clinically insignificant abnormal limits.
• Vitals signs for heart rate, respiratory rate, and pulse were also within normal or clinically insignificant abnormal limits.
• The incidence and severity of cardiovascular adverse events was low, with only seven patients experiencing drug-related cardiovascular adverse events ranging from grade 1–3. Patients dosed below 60 mg/m2 did not experience any drug-related cardiovascular adverse events.

BIND-510

1. “BIND-510 improves the pharmacokinetics, tolerability, tumor accumulation and tumor growth inhibition in preclinical models of cancer compared to vincristine sulfate”
BIND researchers demonstrated that BIND-510 exhibited differentiated PK, tumor accumulation, tolerability and anti-tumor activity compared to conventional vincristine (VCR). In addition, PSMA expression was demonstrated in the neovasculature in hematological cancers, further supporting the feasibility of developing BIND-510 as a targeted clinical therapy with the potential for reduced toxicity and improved anti-tumor activity compared to currently available treatments.

• BIND-510 had a PK profile differentiated from VCR that results in increased accumulation of vincristine at the tumor, and increased tumor growth inhibition in multiple xenograft models.
• BIND-510 accumulated in nasopharyngeal carcinoma tumors at an 8-fold higher concentration than VCR, and was shown to be more tolerable than VCR.
• Single dose BIND-510 administered to mice with nasopharyngeal and breast carcinoma xenografts at the maximum tolerated dose (MTD) for VCR (1.5 mg/kg) resulted in a longer tumor growth delay compared to VCR.
• Due to improved tolerability, BIND-510 was able to be administered at higher doses, resulting in complete responses in some mice, and even longer tumor growth delay than VCR or BIND-510 dosed at 1.5 mg/kg.
• PSMA targeting of BIND-510 in PSMA-expressing prostate cancer tumor xenografts resulted in a tumor growth inhibition (TGI) of (79%) compared to non-targeted VCR nanoparticles which caused a 47 percent TGI at the same VCR dose level.
• Non-small cell lung cancer tumor xenografts that are insensitive to VCR at MTD are sensitive to BIND-510 when administered at higher dose levels.
• PSMA immunostaining was detected in the neovasculature of 27.5 percent lymphoma tumors and 35 percent of bone marrow malignancies analyzed.

MK-2206 (BIND-2206)

1. “Accurins improve the pharmacokinetics, pharmacodynamics, tolerability and anti-tumor activity of the AKT inhibitor MK-2206”
BIND researchers and collaborators at Merck demonstrated that Accurin formulations of MK-2206 (BIND-2206) developed with varying in vitro release rates had differentiated PK, increased tumor exposure, improved tolerability and a prolonged duration of target inhibition compared to the parent compound. Improving these biological attributes led to a significantly enhanced anti-tumor efficacy in an ovarian cancer model and tumor regressions in a prostate cancer model. In addition, the altered bio-distribution resulted in prolonged target engagement in tumor tissue and enhanced efficacy compared to the parent MK-2206, suggesting that Accurin formulations of the AKT inhibitor (BIND-2206) may provide improved tolerability and anti-tumor activity in a clinical setting.

• BIND-2206 Accurins significantly altered the pharmacokinetic parameters of MK-2206 in female nude mice following acute administration.
• Dosed at maximum feasible dose, BIND-2206 Accurins significantly enhanced tolerability measured by percent survival and prevented hyperglycemic blood glucose levels in mice following acute administration.
• BIND-2206 Accurins displayed significant tumor regressions in human prostate cancer models compared to MK-2206.
• BIND-2206 Accurins displayed significant anti-tumor activity in human ovarian cancer model compared to MK-2206.
• BIND-2206 Accurins as a single agent did not improve efficacy in a HER2 overexpressing breast cancer model but displayed significant and prolonged inhibition of the target in the tumor. This suggests that anti-tumor efficacy is model specific and that a combination strategy in breast cancer may be advantageous.

About BIND Therapeutics

BIND Therapeutics is a clinical-stage nanomedicine 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. BIND’s lead drug candidate, BIND-014, is a prostate-specific membrane antigen (PSMA) -targeted Accurin that contains docetaxel, a clinically-validated and widely-used cancer chemotherapy drug. BIND is currently enrolling patients in a trial with BIND-014 for non-small cell lung cancer, or NSCLC, with KRAS mutations or squamous histology. In addition, BIND is enrolling patients in a clinical trial with BIND-014 for advanced cervical, bladder, head and neck and cholangio cancers. BIND is advancing BIND-510, its second PSMA-targeted Accurin drug candidate containing vincristine, a potent microtubule inhibitor with dose limiting peripheral neuropathy in its conventional form, through important preclinical studies to position it for an Investigational New Drug (IND) application filing with the U.S. Food and Drug Administration. BIND is also developing Accurins designed to inhibit PLK1 and KSP, both of which BIND believes are promising anti-mitotic targets that have been limited in the clinic due to systemic toxicity at or below therapeutic doses.

BIND has announced ongoing collaborations with Pfizer Inc., AstraZeneca AB, F. Hoffmann-La Roche Ltd., Merck & Co., or Merck (known as Merck Sharp & Dohme outside the United States and Canada) and Macrophage Therapeutics (a subsidiary of Navidea Biopharmaceuticals) to develop Accurins based on their proprietary therapeutic payloads and/or targeting ligands. BIND’s collaboration with AstraZeneca has resulted in FDA clearance to begin clinical trials with the Aurora B Kinase inhibitor Accurin AZD2811, which the Company expects to be the second Accurin candidate to enter clinical development. BIND’s collaboration with Pfizer has resulted in the selection of an Accurin candidate that is entering IND-enabling studies.

For more information, please visit the Company’s web site at www.bindtherapeutics.com.

Forward-Looking Statements Disclaimer

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including expectations regarding Accurins, including without limitation their ability to improve efficacy and tolerability of therapeutic payloads and create best-in-class therapeutics; our interpretation of the data from studies of BIND-014, BIND-510 and MK-2206 presented at AACR; statements regarding our collaborations with Pfizer, AstraZeneca, F. Hoffmann-La Roche Ltd., Merck and Macrophage; and statements regarding upcoming events and presentations.

These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the fact that the Company has incurred significant losses since its inception and expects to incur losses for the foreseeable future; the Company’s need for additional funding, which may not be available; raising additional capital may cause dilution to its stockholders, restrict its operations or require it to relinquish rights to its technologies or drug candidates; the Company’s limited operating history; the terms of the Company’s credit facility place restrictions on its operating and financial flexibility; failure to use and expand its medicinal nanoengineering platform to build a pipeline of drug candidates and develop marketable drugs; the early stage of the Company’s development efforts with only BIND-014 in clinical development; failure of the Company or its collaborators to successfully develop and commercialize drug candidates; clinical drug development involves a lengthy and expensive process, with an uncertain outcome; delays or difficulties in the enrollment of patients in clinical trials; serious adverse or unacceptable side effects or limited efficacy observed during the development of the Company’s drug candidates; inability to maintain any of the Company’s collaborations, or the failure of these collaborations; the Company’s reliance on third parties to conduct its clinical trials and manufacture its drug candidates; the Company’s inability to obtain required regulatory approvals; any conclusion by the FDA that BIND-014 does not satisfy the requirements for approval under the Section 505(b)(2) regulatory approval pathway; the fact that a fast track or breakthrough therapy designation by the FDA for the Company’s drug candidates may not actually lead to a faster development or regulatory review or approval process; the inability to obtain orphan drug exclusivity for drug candidates; failure to obtain marketing approval in international jurisdictions; any post-marketing restrictions or withdrawals from the market; effects of recently enacted and future legislation; failure to comply with environmental, health and safety laws and regulations; failure to achieve market acceptance by physicians, patients, or third-party payors; failure to establish effective sales, marketing and distribution capabilities or enter into agreements with third parties with such capabilities; effects of substantial competition; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; product liability lawsuits; failure to retain key executives and attract, retain and motivate qualified personnel; difficulties in managing the Company’s growth; risks associated with operating internationally, including the possibility of sanctions with respect to our operations in Russia; the possibility of system failures or security breaches; failure to obtain and maintain patent protection for or otherwise protect our technology and products; effects of patent or other intellectual property lawsuits; the price of our common stock may be volatile and fluctuate substantially; significant costs and required management time as a result of operating as a public company; and any securities class action litigation. These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission, or SEC, on November 2, 2015, and our other reports filed with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.