DEP-Trastuzumab =
HER2-targeted DEP™ Conjugate
I believe this is the ADC (antibody drug conjugate) that is currently under investigation with one or two of the undisclosed new partners
Remember the pre clinical trials resulted in complete tumor regression and survival rate compared to Kadcyla (Roche) and Adcetris (Takeda) - which had combined sales of over a billion dollars in 2014
Just a refresher link for those that are new it forum
Targeted DEP™ shows sustained superior performance
2 February 2016
Melbourne, Australia; Starpharma (ASX: SPL, OTCQX: SPHRY) today announced 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. 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.
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
Anticancer efficacy and survival curves are illustrated in the graphs below.
Figure 1. Efficacy of HER2-targeted DEP™ Conjugate vs Kadcyla® and Herceptin® in an Ovarian* Cancer Model
|
Column 1 |
| 1 |
*SKOV-3 Ovarian cancer xenograft in NOD-SCID mice (5-6/group)Saline, Kadcyla® (10mg/kg) and Targeted DEP™ conjugate were dosed once/wk for 3 wks; Herceptin® (20mg/kg) dosed twice/wk for 3 wks. Statistical analysis at day 40. Kadcyla® vs Targeted DEP™; P <0.0001. (ANOVA followed by Tukey’s post hoc test). |
Figure 2. Kaplan Meier Survival Curve3 : Targeted DEP™ Conjugate vs Kadcyla® and Herceptin®
Figure 3. Percent Tumour Inhibition Compared to Saline control
*The HER-2 targeted DEP
TM conjugate continued to display complete tumour inhibition for the duration of the experiment.
About the Study
These latest results are an extension of the previously announced 16
th 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.
