New research paper published: SMARCA2 PROTAC-dendrimer conjugates for the treatment of non-small cell lung cancer

Starpharma is pleased to share the publication of new preclinical research demonstrating how dendrimer-based drug delivery can significantly enhance the efficacy and tolerability of SMARCA2-targeting PROTACs in a non-small cell lung cancer model.

PROTACs (proteolysis-targeting chimeras) are an exciting area in drug discovery, as they enable targeted degradation of previously “undruggable” disease‑causing proteins rather than only inhibiting their activity. SMARCA2 is a protein that helps control gene expression, and in some cancers becomes a vulnerability that can be exploited using targeted protein degradation.

In this study, PROTACs were conjugated to Starpharma’s DEP® dendrimer platform to address key challenges commonly associated with this modality, including limited bioavailability and suboptimal pharmacokinetics that drive rapid systemic clearance, limited tumour exposure and dose‑limiting toxicity.

By tuning PROTAC release from the dendrimer, the study showed sustained tumour exposure and SMARCA2 degradation in a mouse xenograft model. A single dose of an optimised dendrimer-PROTAC conjugate achieved durable tumour stasis for up to 21 days at a significantly lower dose than the PROTAC alone, with no tolerability issues.

Importantly, this work highlights the ability of dendrimers to deliver PROTACs to solid tumours, to mitigate common PROTAC challenges – improving pharmacokinetics, pharmacodynamics, and tolerability – and to enable PROTACs from a broader medicinal chemistry design space.

We believe these findings further validate Starpharma’s dendrimer-enabled delivery for advancing targeted protein degradation in solid tumours and creating more patient‑first treatment regimens.

Huge congratulations to the Starpharma and Genentech authors on this publication. 👏

View the paper here: SMARCA2 PROTAC-dendrimer conjugates for the treatment of non-small cell lung cancer