• AstraZeneca (AZ) will present two scientific posters on AZD0466, their first DEP^® oncology product, at the 63^rd American Society of Hematology (ASH) Annual Meeting 2021
• One poster provides an overview of the study design and rationale for the ongoing NIMBLE phase I/II clinical study of AZD0466 in patients with advanced relapsed/refractory hematological malignancies (blood cancers), which is currently recruiting
• The second poster highlights combination therapy of AZD0466 with acalabrutinib to overcome therapeutic resistance in an aggressive venetoclax-resistant mantle cell lymphoma model

AstraZeneca will present two scientific posters each accompanied by a presentation at the 2021 American Society of Hematology (ASH) Annual Meeting, showcasing AstraZeneca’s first DEP^® oncology product, AZD0466.

ASH is the world’s premier event in malignant and non-malignant hematology, and will take place in Atlanta, Georgia from 11-14 December 2021. 

AZD0466 is a novel drug-dendrimer conjugate of AZ’s highly potent Bcl-2/xL dual inhibitor AZD4320, developed under Starpharma’s multi-product DEP^® licence with AstraZeneca, and is currently in a global multi-centre phase 1/2 clinical trial. AZD0466 is a dendrimer formulation of AZD4320, which allows for efficient delivery of the highly potent but poorly soluble active drug and a release profile that was designed to mitigate potential maximum concentration (Cmax)-dependent BCL-xL mediated effects (Patterson et al, Nature Communications Biology 2021).

The first AZD0466 poster is titled ‘NIMBLE: A Phase I/II Study of AZD0466 Monotherapy or in Combination in Patients with Advanced Haematological Malignancies’. It provides an overview of the phase I/II clinical study of AZD0466 as a monotherapy or in combination in patients with advanced hematological malignancies (blood cancers), which is actively enrolling patients at sites in the USA, South Korea and Australia, with plans to open recruitment in Europe as part of the program’s global expansion announced in February 2021.

Dual Bcl-2/xL inhibition with AZD4320/AZD0466 has potential for broader activity than the marketed Bcl-2-specific inhibitor, venetoclax (Venclexta). In 2020, Venclexta had sales of ~US$1.34 billion, growing 69 per cent from 2019.

AZD0466 is a drug-dendrimer conjugate consisting of a pegylated poly-L-lysine dendrimer covalently conjugated to multiple AZD4320 molecules which are gradually released. Preclinical efficacy studies provide rationale for testing AZD0466 in patients with refractory acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in the ‘NIMBLE’ trial.

The second poster highlights a study, conducted at the MD Anderson Cancer Center, of AZD0466 in combination with acalabrutinib to overcome therapeutic resistance in aggressive venetoclax-resistant mantle cell lymphoma (MCL) models. MCL is an aggressive subtype of non-Hodgkin’s lymphoma, largely due to frequent relapses after therapies such as ibrutinib and acalabrutinib (Calquence), and BCL-2 inhibitor venetoclax. Compared to single agents AZD4320/AZD0466 and acalabrutinib, combination therapy demonstrated significant anti-MCL synergy both in vitro and in vivo.

Dr Jackie Fairley, CEO of Starpharma, commented: “We are delighted to see AZD0466, AstraZeneca’s first DEP^® oncology product, showcased at the prestigious ASH Meeting this year in December. These poster presentations highlight the clinical program and impressive preclinical performance for this innovative oncology agent and the benefits Starpharma’s DEP^® technology can deliver.”

Poster Abstracts:

Poster 1: 2353 NIMBLE: A Phase I/II Study of AZD0466 Monotherapy or in Combination in Patients with Advanced Hematological Malignancies

https://ash.confex.com/ash/2021/webprogram/Paper147482.html

Poster 2: 1867 Combination Therapy of Bcl-2/XL dual Inhibitor AZD0466 with Acalabrutinib to Overcome Therapeutic Resistance in Aggressive R/R Mantle Cell Lymphoma

https://ash.confex.com/ash/2021/webprogram/Paper151609.html