Speculation of AstraZeneca/Starpharma indication - Could it be AZD0466
There has been talk of the indication under investigation with Starpharma's drug delivery platform is AstraZeneca's AZD0466
Some extracts from AstraZeneca's Innovative Medicines & Early Development Biotech Unit (IMED) 2016 - A Year in Review: regarding AZD0466
Paul Secrist
Paul Secrist is Director of Oncology Bioscience and had a significant impact on the pre-clinical portfolio this year - serving as the biology lead for two successful candidate drug investment decisions (CDIDs) for AZD5991 (MCL1) and AZD0466 (Bcl2/xL).
Paul was the major driver of the overall cell death strategy and has led multiple research collaborations with prominent academic laboratories in this exciting area of drug discovery. In addition, Paul co-leads the small molecule immuno-oncology strategy within AstraZeneca and has been instrumental in building both the pre-clinical portfolio and the rapidly expanding repertoire of immunological capabilities within IMED Oncology.
We progressed three molecules toward the clinic following promising pre-clinical data:
AZD5991 is a highly potent and selective MCL1 inhibitor which demonstrates tumour regression in multiple disease models in vivo, including acute myeloid leukaemia (AML), non-hodgkin lymphoma (NHL) and multiple myeloma (MM).
Working with the ‘Beat AML’ collaboration, AZD5991 has demonstrated a highly differentiated profile compared to BCL2 and BCLxL inhibitors and has broad potential in a range of myeloid and lymphoid malignancies.
AZD4573 is a selective CDK9 inhibitor with the appropriate PK to enable short-term target engagement. Recent pre-clinical studies have shown significant anti-cancer activity across different haematological malignancies, including AML, NHL, chronic lymphocytic leukaemia (CLL), and MM based on exciting clinical data, plus potential for combination use with acalabrutinib.
AZD0466 is a dual BCL2/xL inhibitor with broad pre-clinical activity in a range of haematological malignancies. Delivered as a nanomedicine formulation administered intravenously, it has been designed to improve the therapeutic window for thrombocytopenia, which has prevented agents of this profile delivering their full potential previously.
Targeting these pro-survival proteins of the BCL2 family in combination with other mechanisms, offers the potential to increase the fraction of tumour cells that are killed. All three agents were highlighted to investigators at the recent American Society of Haematology (ASH) meeting in San Diego and are being developed in combination between AstraZeneca and Acerta.
In December we nominated AZD0466 which is a dual Bcl2/xL inhibitor with broad pre-clinical activity in a range of haematologic malignancies. Bcl2 is a clinically validated target with venetoclax being approved by the FDA in 2016 for sub-types of chronic lymphocytic leukaemia (CLL). However our data suggests that venetoclax’s continuous oral dosing is not ideal in maximising cell kill whilst those cells that do survive are often able to exploit Bcl2/xL as a parallel survival mechanism. Consequently AZD0466 has the potential to be a best-in-class agent in this field with a highly-optimised i.v. nanomedicine formulation with a broader Bcl2/xL profile. Previous attempts to develop this dual profile were seriously compromised by on-target toxicities such as thrombocytopenia.
Melinda Merchant
Melinda Merchant is a Senior Medical Science Director who serves as lead for the Boston Oncology Therapeutic Medical Unit and represents ECD on the Site Leadership Team. A pediatric oncologist with a PhD in Immunology,
her prior expertise in immunotherapy has been valuable in the early clinical development of AZD4635 (A2aR) and implementation of the Phase I First-Time-in-Human trial this year. Her collaborative efforts with IMED and Acerta are reflected in the successful Candidate Drugs AZD5991 (MCL1), AZD0466 (Bcl2/xL), and AZD1390 (ATM-BBB).
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