• Starpharma advances a new internal DEP^® candidate, DEP^® gemcitabine, into development
• DEP^® gemcitabine demonstrated significantly enhanced anti-tumour activity compared with Gemzar^® (gemcitabine), both alone and in combination with Nab‑paclitaxel (Abraxane^®), in a human pancreatic cancer model
• Gemzar^® (gemcitabine), used alone or in combination with Abraxane^®, is the current standard of care therapy for pancreatic cancer
• A patent has been filed for Starpharma’s proprietary DEP^® gemcitabine, providing coverage to 2040

Melbourne, Australia: Starpharma (ASX: SPL, OTCQX: SPHRY) today announced results for its next internal development candidate, DEP^® gemcitabine.

Starpharma’s proprietary DEP^® gemcitabine demonstrated significantly enhanced anti‑tumour activity compared with Gemzar^® (gemcitabine), both alone and in combination with Nab-paclitaxel (Abraxane^®) in a preclinical human pancreatic cancer model. This data has formed the basis of a new patent application, which will provide coverage over DEP^® gemcitabine to 2040. DEP^® gemcitabine is one of several internal DEP^® candidates under preclinical development by Starpharma.

DEP^® gemcitabine is a DEP^® version of Lilly’s Gemzar^® (gemcitabine) - a well-established anti-cancer drug, which had peak sales of US$1.7 billion. Gemzar^® (gemcitabine) is one of the leading chemotherapeutic drugs used to treat pancreatic cancer. It can be administered as a monotherapy or in combination with other therapies such as Abraxane^®.

DEP^® gemcitabine demonstrated significantly improved anti-tumour activity, compared to Gemzar^®, the standard form of gemcitabine, in the human pancreatic cancer xenograft model (p<0.0001). When used in combination with Abraxane^®, DEP^® gemcitabine significantly outperformed a combination of Gemzar^® (gemcitabine) and Abraxane (p<0.005).

Pancreatic cancer is a leading cause of cancer death, with a 1-yr survival rate of 20%, and a 5-yr survival rate of only 7%, with current therapeutic approaches (gemcitabine and Abraxane^®) having significant bone marrow toxicities. An important attribute of DEP^® products is a lack of bone marrow toxicities in both preclinical and clinical studies.

Dr Jackie Fairley, Starpharma CEO, commented: “We are delighted to be progressing yet another internal candidate through development and to have achieved such impressive results in this important cancer type with otherwise limited options for patients.”

Study Results

DEP^® gemcitabine vs Gemzar^® alone

DEP^® gemcitabine showed significantly enhanced tumour inhibition as compared to standard gemcitabine (Gemzar^®) in this human pancreatic cancer (CAPAN-1) xenograft model (p<0.0001; figure 1).

Figure 1:  Enhanced efficacy of DEP^® gemcitabine, compared to standard gemcitabine, in a human pancreatic cancer model (CAPAN-1)

DEP^® gemcitabine + Abraxane^® vs Gemzar^® + Abraxane^® combination

The anti-tumour effect of the DEP^® gemcitabine + Abraxane^® combination was significantly better than for the Gemzar^® (gemcitabine) + Abraxane^® combination (P<0.005).

Figure 2:  Enhanced efficacy of DEP^® gemcitabine + Abraxane^®, compared to standard gemcitabine + Abraxane^®, in a human pancreatic cancer model (CAPAN-1)

Study Methods

The mouse xenograft study used CAPAN-1 human pancreatic cancer cells and was conducted for Starpharma by an internationally recognised translational cancer group. A xenograft study uses human cancer cells, which are then implanted in a mouse, and is a well‑established means of assessing efficacy of anti-cancer therapies before clinical trials.

Balb/c mice were inoculated subcutaneously with the human pancreatic cancer (CAPAN-1) cells (10 mice/group). Mice were dosed with saline (vehicle), DEP^® gemcitabine[1], standard gemcitabine (Gemzar^®) (120 mg/kg) and Abraxane^® (40mg/kg) IV on days 1, 10 and 18.

Tumours were measured twice weekly using electronic callipers. Tumour volume (mm³) was calculated as length (mm)/2 x width (mm)². Tumour growth inhibition data was analysed in GraphPad Prism and statistical analysis of treatment groups v vehicle control was one-way ANOVA with Dunnets multiple comparison test. Statistical analysis between different groups was conducted via a one-way ANOVA with Sidaks multiple comparison test. The tumour volume data represent the mean ± standard error of the mean (SEM). Note: If error bars do not display on the graphs, they are not visible because they are shorter than the height of the symbol.

 About Gemzar^® (Gemcitabine)

Gemzar^® (gemcitabine) is a chemotherapy drug used to treat cancer of the pancreas, bladder, ovary and breast, and non-small cell lung cancer. Gemcitabine is used as a first-line treatment alone for pancreatic cancer, and in combination with Abraxane^® for the treatment of metastatic Adenocarcinoma of the pancreas. Gemcitabine also has a role in the treatment of metastatic bladder cancer, advanced or metastatic non-small cell lung cancer, ovarian cancer and breast cancer. Myelosuppression is the principal dose-limiting toxicity with gemcitabine.

About Starpharma’s DEP^® platform

Starpharma’s internal pipeline includes a number of pre-clinical DEP^® candidates, including DEP^® gemcitabine, as well as three clinical stage assets - DEP^® docetaxel, DEP^® cabazitaxel and DEP^® irinotecan. A fourth DEP^® drug, DEP^® AZD0466 (AstraZeneca’s Bcl2/xL DEP^® program), is expected to enter the clinic later this year.

Download ASX Announcement: DEP® gemcitabine outperforms Gemzar® in human pancreatic cancer model (PDF, 105kb)

[1] For intellectual property reasons, doses of DEP^® gemcitabine are not disclosed