AstraZeneca starts clinical trial with Accurin AZD2811 in solid tumors

AZD2811, a novel, selective inhibitor of Aurora B kinase that has been shown to be active in both solid and hematological tumors in preclinical models, is the second Accurin candidate to enter clinical development.

The phase 1 trial is enrolling patients with advanced solid tumors, including patients with small cell lung cancer, and is being conducted by AstraZeneca under the companies’ 2013 collaboration agreement with BIND managing all chemistry, manufacturing and control activities. BIND earned a $4.0 million clinical milestone for dosing of the first patient.

BIND Therapeutics president and CEO Andrew Hirsch said: "The preclinical data seen to date suggest Accurin AZD2811 can overcome the limitations that have hindered development of this class of potent kinase inhibitors.

"There has been a great deal of promise in the biology of inhibiting the Aurora B pathway but success to date has been limited due to on-target but off-tissue toxicities. Based on preclinical data we’ve seen to date, we believe our Accurin technology has the potential to overcome these limitations and make AZD2811 a best-in-class therapeutic with a profile unachievable through other therapeutic modalities.

"This milestone further demonstrates the value of our leading nanomedicine platform and we look forward to exploring the potential benefits this product may bring to patients with cancer."

AstraZeneca oncology innovative medicines unit head Susan Galbraith said: "We had already achieved clinical proof of principle with the Aurora Kinase B inhibitor in a phase 2 trial in elderly patients with acute myeloid leukemia.

"Through our collaboration we can now deliver this drug in a BIND Accurin nanoparticle. BIND’s Accurin technology has the potential to significantly improve the therapeutic activity of our Aurora B Kinase inhibitor and we look forward to sharing data from this trial as we advance AZD2811 through clinical development."

The phase 1 clinical trial is designed to evaluate the safety and tolerability of AZD2811 at increasing doses. The first part of the two-part study will evaluate the maximum tolerated dose (MTD) and the recommended phase 2 dose will be identified.

The study will also characterize the pharmacokinetic (PK) profile of AZD2811 and will explore the potential biological activity by assessing anti-tumor activity. The second part of the study will begin upon determination of the MTD and will further explore PK parameters, safety, tolerability and preliminary anti-tumor activity of AZD2811. Additional information on this study can be found at: https://www.clinicaltrials.gov.

Preclinical data on the Accurin AZD2811 were presented at the 2015 American Association of Cancer Research (AACR) annual meeting in April 2015, including data that demonstrated promising in vivo and in vitro tumor growth inhibition as monotherapy in diffuse large B-cell lymphomas (DLBCL) and small cell lung cancer (SCLC) models.

Additional data showed that Accurin AZD2811 delivers prolonged exposure of active drug with 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.

Previously, preclinical tumor model data were presented showing that Accurin AZD2811 minimizes the bone marrow toxicity seen with the parent compound, which has limited the clinical utility of Aurora B kinase inhibitors as a class.

Under terms of the collaboration, AstraZeneca is responsible for clinical development and commercialization and BIND is responsible for conducting clinical manufacturing. In addition to earning a $4m milestone payment for the first patient dosed in a phase 1 clinical trial, BIND received an upfront payment of $4m in 2013 and achieved a $1m development milestone in March 2015.

BIND has the potential to receive additional milestone payments totaling up to $60m upon achievement by AstraZeneca of specified clinical events and up to $128m in the aggregate upon achievement by AstraZeneca of all specified regulatory and commercial events, as well as tiered royalties in the low-single digit to the low-double digit percentages of aggregate worldwide net sales of licensed product, if any.

Based on the $4m AstraZeneca clinical milestone payment, the previously announced $2.5m Pfizer option exercise fee and anticipated R&D reimbursement for the next stage of the Pfizer collaboration, BIND reiterates that it expects that its cash, cash equivalents and short-term investments will fund operating expense and capital expenditure requirements into the fourth quarter of 2016.

This expectation is based on BIND’s current operating plans and research and development funding that it expects to receive under its existing collaborations, but excludes any potential milestone payments under its collaboration agreements.