International Conference on Molecular Targets and Cancer Therapeutics, overview

By Fiona McLaughlin

At Avacta we are developing innovative oncology drugs leveraging our two proprietary platforms, pre|CISIONTM and Affimer®, with the aim to transform treatment outcomes and improve the lives of cancer patients.

We presented encouraging preclinical findings for two assets currently in development at the recent International Conference on Molecular Targets and Cancer Therapeutics hosted by American Association for Cancer Research – National Cancer Institute (NCI) – EORTC – European Organisation for Research and Treatment of Cancer in Boston.

pre|CISIONTM is a tumour microenvironment targeting platform aimed at delivering potent warheads directly to the tumour, reducing systemic exposure and toxicity and thereby dramatically improving tolerability to enhance efficacy of the treatment. This targeted approach to delivering cancer treatments is now clinically validated by our lead molecule AVA6000.  In an ongoing Phase 1a trial, AVA6000 shows not only a  strong safety profile, but  concentrates  the doxorubicin warhead in the tumour.

While our lead pre|CISIONTM candidate AVA6000, is progressing through clinical development at pace, we continue to develop other potentially high value assets.

AVA3996, is a FAP-α-activated proteasome inhibitor based on our pre|CISIONTM technology which facilitates the precise release of a potent proteasome inhibitor at the tumour site. AVA3996 has the potential to become a targeted cancer treatment for multiple solid tumour indications, overcoming cytotoxicity issues, such as peripheral  neuropathy, displayed when the  non-targeted form of proteasome inhibitor is  administered to patients.

Alongside our pre|CISIONTM platform, we are progressing our  Affimer® molecules towards the clinic.  Affimer® is a novel biologic platform based on a naturally occuring human protein called Stefin A. Affimer® molecules have significant advantages compared to antibodies, including their ability to bind difficult drug targets. They are are small in size (~15kDa), can be formatted to generate multi-specific binders and are exquisitely specificic for the target of interest.

Our lead Affimer AVA032 is an anti-PD-L1 Affimer® fused to the pro-inflammatory cytokine interleukin 15 (IL-15). This  bispecific molecule has dual activity that works to reverse the immunosuppressive tumour micro-environment, inducing a lasting immune response aimed at stimulating a patient’s immune system to destroy cancer cells. While many single agent PD-L1 inhibiting agents are available to patients, the number of patients who respond to these agents is limited. Combination treatment with immune response-boosting treatments produces a sustained immune response and maximising response to IO therapy .

Overall, we are greatly encouraged by these findings as our team continues to expand the potential of our therapeutics, developing a deep pipeline with potential first-in-class medicines for cancer patients.