Avacta Group has presented pre-clinical data describing the novel pre|CISION proteasome inhibitor, AVA3996, at the 2023 American Association for Cancer Research (AACR) Annual Meeting in Florida, US.
Proteasome inhibitors are effective anti-cancer drugs that could benefit from application of our preICISION technology to expand their use. While the global proteasome inhibitors market is expected to reach nearly $2.3 billion by 2026, these drugs are primarily indicated for the treatment of multiple myeloma. Severe, dose limiting toxicities have prevented application to a broader range of cancers, in particular to solid tumours.
AVA3996 combines a proprietary proteasome inhibitor (called AVA2727D) with Avacta’s tumour targeting chemistry, creating the potential to reduce the systemic toxicities and thereby make it possible to treat solid tumours with a proteasome inhibitor for the first time.
AVA3996 is in pre-clinical development with the aim of submitting an Investigational New Drug (IND) application to allow clinical development to begin during 2024.
Comparison to Velcade
In a head-to-head study, AVA2727D killed cancers cells (ex-vivo) as effectively as bortezomib (Takeda’s Velcade) which is one of the approved proteasome inhibitors on the market.
In three different in vivo (mouse) cancer models (melanoma, sarcoma and colorectal cancer), AVA3996 was as effective as bortezomib in restricting tumour growth, and in the case of the melanoma model, as effective as trametinib, the standard of care for unresectable melanoma.
The significant toxicities associated with bortezomib observed in these in-vivo models were not observed in the case of AVA3996, suggesting that the systemic exposure to the drug had been reduced.
AVA3996 pre-clinical data poster: https://avacta.com/about/resources/
Dr Alastair Smith, Chief Executive Officer, Avacta Group plc, commented: “We are delighted with the progress being made in the pre-clinical development of AVA3996, the second drug candidate based on our preICISION platform. The potential to apply a proteasome inhibitor to the treatment of solid tumours is very exciting and, as can be seen from our poster presented at the prestigious AACR meeting, the pre-clinical data we are generating is very encouraging in that regard.
“We are focused on accelerating AVA3996 through to IND filing as soon as possible so that it can follow AVA6000 into the clinic next year.”