On February 2, 2016 Starpharma (ASX: SPL, OTCQX: SPHRY) reported the final results of the preclinical study of its HER2-targeted DEP conjugate, which achieved complete tumour regression at the last study time point of 120 days post dosing (Press release, Starpharma, FEB 2, 2016, View Source [SID:1234508928]). These results are an extension of the previously announced findings that showed complete tumour regression at 60 days post dosing with the HER2-targeted DEP conjugate.

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Starpharma’s HER2-targeted DEP conjugate also significantly outperformed all other treatment groups, including Kadcyla (Trastuzumab-DM1), a Herceptin antibody-drug conjugate (ADC) currently marketed by Roche, with respect to both tumour regression and survival.

In the study, 100% of mice treated with Starpharma’s HER2-targeted DEP conjugate were tumour-free within three weeks of the commencement of treatment and remained that way for the total duration of the study. In contrast, only tumour stasis was observed during treatment in the Kadcyla group, with a maximum tumour volume inhibition of 32%1 with significant tumour regrowth occurring soon after the completion of dosing.

Starpharma Chief Executive, Dr Jackie Fairley, commented, "We are very excited by these latest results for our Targeted DEP conjugates and the feedback from commercial parties on the study data has been very positive indeed. Both the extent and the sustained nature of the anticancer effect seen with Starpharma’s DEP candidate have been considered most impressive. Discussions are now underway with a number of leading pharmaceutical companies in relation Targeted DEP conjugates and the application of Starpharma’s Targeted DEP platform to their proprietary drugs."

This study was conducted for Starpharma by an internationally recognised cancer organisation, as part of a wider program of studies to assess various Targeted DEP conjugates. The study was conducted using a well-established ovarian cancer model for assessing efficacy of therapies against HER2-positive cancer cell lines.

The results from this study clearly demonstrate significant and long term survival benefits for the Targeted DEP conjugate compared to other treatment groups, including Kadcyla.

The top 3 antibody based treatments in cancer (Rituxan, Avastin and Herceptin) had total sales in excess of $US20 billion in 2014. Targeted therapies for cancer, such as the ADCs Kadcyla and Adcetris, had combined sales in excess of US$1 billion in 2014, with Kadcyla sales growing at 144% versus the previous year. The market for ADCs is expected to grow to US$9 billion annually by 2023. 2

About the Study
These latest results are an extension of the previously announced 16th November 2015 xenograft study results at 60 days post dosing with the HER2-targeted DEP conjugate.

Groups of animals were dosed once per week for 3 weeks with the HER2-targeted DEP conujgate, Kadcyla, or a saline control. Another group of animals was treated with Herceptin twice a week for 3 weeks.

The animals treated with the HER2-targeted DEP conjugate showed vastly superior anticancer effectiveness compared with the saline, Kadcyla and Herceptin treated control groups, demonstrating significant ablation of the tumours even after the first dose. Subsequent dosing resulted in 100% of mice being completely tumour-free within three weeks after the commencement of treatment and remained such for the total duration of the study. All mice in the HER2-targeted DEP conjugate group remained within the acceptable body weight range during dosing and gained weight post dosing.

In contrast, only tumour stasis was observed during treatment in the Kadcyla group, with a maximum tumour volume reduction, as measured at study day 12, of 32% compared with the saline control group, with significant tumour regrowth occurring soon after the completion of dosing. In accordance with ethical requirements the Kadcyla and other control groups were discontinued at 42 days post dosing due to body weight loss and extensive tumour growth.

Targeted DEP Conjugates
Starpharma’s proprietary targeted DEP conjugate in this experiment consists of a dendrimer scaffold, a targeting group (in this case the monoclonal antibody, trastuzumab (Herceptin)) and a "payload" of anticancer drug.

Targeted DEP conjugates have a number of important advantages over standard ADCs including higher drug loading and manufacturing advantages.