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Starpharma -DEP® Radiotheranostics

FromStarpharma Holdings Limited

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DEP® radiotheranostic conjugates have the potential to minimise off-target toxicity, optimise pharmacokinetics and enhance efficacy when used alone or in combination with other therapeutic approaches. The versatility of Starpharma’s DEP® platform means it can be used with a wide range of therapies and types of molecules (e.g., small molecule drugs, peptides, antibodies, radioisotopes). This flexibility has allowed Starpharma to develop a range of DEP® radiotheranostics as well as its other DEP® programs. Radiotheranostics is a rapidly developing area of cancer treatment and diagnosis, and sales in this category are estimated to grow to $12–15 billion by 2030 (source: Nuclear medicine world market report & directory, MEDraysintell, 2016). The area has also seen several significant commercial acquisitions in recent years.

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DEP® radiotheranostics have the potential to target cancer tissue, minimise off-target toxicity and enhance efficacy.

DEP® radiotheranostics preclinical results

Starpharma has developed multiple novel DEP® radiotheranostic candidates. DEP® radiotherapeutics incorporate radioisotopes on to the DEP® scaffold and patent applications have been filed for DEP® radiotherapeutic candidates.

Radiotherapeutics

DEP® lutetium

Preclinical studies demonstrated that DEP® lutetium showed highly statistically significant anti-cancer activity, with tumour regression and 100% survival in a human prostate cancer model (DU-145). DEP® lutetium is a Starpharma patented nanoparticle that incorporates the radioisotope, Lutetium-177, on a DEP® dendrimer scaffold.

DEP® HER2-lutetium

In March 2021, Starpharma announced that its second radiotherapeutic candidate, DEP® HER2-lutetium, achieved complete tumour regression, outperforming Herceptin® (trastuzumab) labelled with lutetium (p<0.0001), in a human breast cancer model (BT474). DEP® HER2-lutetium was extremely well tolerated. DEP® HER2-lutetium is a proprietary targeted dendrimer developed by Starpharma, which incorporates the radioisotope lutetium-177 (177Lu) and a novel HER2 targeting moiety (nanobody).

Radiodiagnostic

DEP® HER2-zirconium

In preclinical studies, Starpharma’s DEP® radiodiagnostic candidate, DEP® HER2-zirconium achieved significant tumour accumulation (>100x in tumour vs blood) in a human HER2-positive ovarian cancer model. The DEP® HER2-zirconium accumulation in tumour was significantly greater than nanobody alone products due to dendrimer delivery advantages (EPR effect).

Targeted DEP® theranostics offer multiple benefits

Flexibility in size and structure of nanoparticle (allowing different targeting groups and pharmacokinetics)

Enhanced tumour accumulation due to the EPR effect (10x nanobody alone)

Enhanced tissue targeting and retention due to specific receptor binding (and internalization)

Enhanced entry and specific accumulation allows for enhanced PET visualization (diagnostic)

Enhanced accumulation and cellular internalization in tumours delivers enhanced efficacy and less off-target toxicity