Aug 29, 2019

Positive results with Targeted DEP® using antibody fragment in human ovarian cancer model

Positive results with Targeted DEP® using antibody fragment in human ovarian cancer model

Melbourne, Australia: Starpharma today announced that treatment with a novel HER-2 Targeted DEP® conjugate from its internal Targeted DEP® program resulted in tumour regression and 100% survival in a preclinical human ovarian cancer model. 

This finding builds on Starpharma’s previously announced Targeted DEP® data with a full-length antibody and its work in this area with Targeted DEP® (antibody-drug conjugate) partner programs. This experiment used a novel antibody fragment, which, like a whole antibody, binds actively and selectively to a specific antigen. Using antibody fragments instead of full-sized antibodies has a number of commercial and technical benefits which stem from their small size, high potency, stability and ease of manufacture.

Starpharma’s HER-2 Targeted DEP® conjugate in this experiment consisted of a dendrimer scaffold, a targeting group (in this case a novel HER-2 targeted antibody fragment) and a “payload” of anti‑cancer drug.

Targeted DEP® conjugates, whether using whole antibodies or their fragments, have a number of important advantages over standard antibody-drug conjugates (ADCs) that include the potential for higher drug loading, new intellectual property, easier characterisation and manufacturing advantages.

The use of ADCs in cancer therapy continues to grow, with 2018 sales of Roche’s Kadcyla® now exceeding US$1 billion and Adcetris US$870 million[1]. Interest in the area also continues to grow with new ADC product launches planned. Corporate activity in the area is also strong as illustrated by the recent licensing deal between AstraZeneca and Daiichi Sankyo, with an announced value of up to US$6.9 billion for rights to a HER-2 targeted ADC[2].

Starpharma’s novel HER-2 Targeted DEP® drug conjugate binds to the same target (HER-2) as the leading monoclonal antibody cancer therapy Herceptin® which had 2018 sales in excess of US$7 billion. In the study, Starpharma’s novel HER-2 Targeted DEP® drug conjugate significantly outperformed both Kadcyla® (T-DM1), a HER-2 targeted antibody-drug conjugate (ADC), and Herceptin® (Trastuzumab) itself, in a human ovarian cancer model.

Anti-cancer efficacy and survival curves for Starpharma’s novel HER-2 Targeted DEP® drug conjugate, Kadcyla® and Herceptin® in this human ovarian cancer model are illustrated in the graphs below.

Efficacy of the novel HER-2 Targeted DEP® drug conjugate vs Kadcyla® and Herceptin® in human ovarian cancer model

The novel HER-2 Targeted DEP®-treated group[3] showed significantly improved anti-cancer effectiveness compared to both Kadcyla® (P<0.0001) and Herceptin® (P<0.0001), even after the first dose, with tumour regression seen in 100% of the novel HER-2 Targeted DEP® -treated group. In the Kadcyla® group, only tumour growth inhibition was seen and there was minimal response to Herceptin® in this xenograft model.

 

Kaplan Meier Survival Curve: Targeted DEP® Conjugate vs Kadcyla® and Herceptin®

Survival in the novel HER-2 Targeted DEP®-treated group was statistically significantly improved (P<0.0001), with 100% survival seen at day 50 (study still ongoing), whereas by day 50, only one third of the Kadcyla®-treated group had survived, and all of the Herceptin®-treated group had died. Survival results are presented below.

Dr Jackie Fairley, Starpharma CEO, commented: “We’re very pleased to present these impressive results for Starpharma’s novel HER-2 Targeted DEP® conjugate which significantly outperforms the leading HER-2 ADC, Kadcyla®, and once again demonstrates the significant advantages conveyed by the DEP® platform. We’re excited to be developing a DEP® product in such an innovative and cutting-edge area and will be exploring this and other Targeted DEP® candidates in a number of potential applications.”

Starpharma is filing a patent application for this novel HER-2 Targeted DEP® conjugate.

Study Methods:

This experiment was conducted in a human ovarian cancer (SKOV-3) xenograft model in NOD SCID mice by an internationally recognised translational Cancer group. Groups of animals (6/group) were dosed once per week for 3 weeks with the novel HER-2 Targeted DEP® conjugate, Kadcyla®, or a saline control. Another group of animals was treated with Herceptin® twice a week for 3 weeks. The tumour volume data represent the mean ± standard error of the mean (SEM) and significance values determined using a Two-Way ANOVA (Tukey’s post hoc). Survival analysis was carried out using Kaplan-Meier survival curves and the Log-rank test. (Note: If error bars do not display on the graphs, they are shorter than the height of the symbol and not visible.)

Download ASX Announcement: Positive results with Targeted DEP® using antibody fragment in human ovarian cancer model (PDF, 100kb)

[1] Medtrack

[2] https://www.astrazeneca.com/media-centre/press-releases/2019/astrazeneca-and-daiichi-sankyo-enter-collaboration-for-novel-her-2-targeting-antibody-drug-conjugate.html

[3] For intellectual property reasons, doses of the HER-2 Targeted DEP® conjugate are not disclosed

 This contains certain forward-looking statements.