Drug-Fc conjugates exhibit robust anti-tumour activity

Colorectal cancer

A novel, multi-specific CD73/PD-1 targeting drug-Fc conjugate (DFC) exhibited robust anti-tumour activity in humanised mouse models of colorectal cancer at low doses, according to data presented at the ESMO Immuno-Oncology (IO) Annual Congress.

“We are thrilled to be presenting promising preclinical data on our novel multi-specific DFC in colorectal cancer for the first time at ESMO-IO this year,” said Jeffrey Stein, President and Chief Executive Officer at Cidara. “Dual inhibition of both CD73 and PD-1 checkpoint pathways with a single DFC contributed to significant tumour growth reduction, highlighting the potential clinical benefits of this first-in-class multi-specific inhibitor derived from our Cloudbreak platform.”

In preclinical studies, CD73/PD-1 DFC, an inhibitor of hCD73 and hPD-1, reduced tumour growth by 56% at 1mg/kg and >70% at 3mg/kg doses. It demonstrated superior activity to a pembrolizumab biosimilar antibody and a matched CD73 DFC at one third the dose of the respective monotherapies.

The company also presented data for CBO421, an AMP-competitive inhibitor of CD73. It demonstrated a differentiated in vitro activity profile across several assays compared with small molecule and antibody inhibitors of CD73 in clinical development.

The in vitro potency, multiple mechanisms of action and favourable pharmacokinetics profile of CBO421 translated to antitumor efficacy in monotherapy and in combination with PD-1 therapy.

Cidara is currently advancing its dual CD73/PD-1 inhibitor DFC and CBO421 in preclinical studies.

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