• DEP^® irinotecan alone showed complete tumour regression and 100% survival in a human pancreatic cancer model. This is compared with only very limited inhibition (and no regression) with standard irinotecan (Camptosar^®) alone, and in combination with 5- fluorouracil (5-FU)
• The complete tumour regression induced by DEP^® irinotecan was despite the fact that the human pancreatic cancer model used virtually did not respond to conventional irinotecan (Camptosar^®) alone and in combination with 5-FU
• This efficacy study builds on previously announced excellent efficacy data for DEP^®irinotecan in human colon cancer models
• Starpharma is currently completing final development activities and undertaking finished product manufacture and other trial preparations for the DEP^® irinotecan phase 1 / 2 trial

Melbourne, Australia; 5 September 2018: Starpharma (ASX: SPL, OTCQX: SPHRY) today announced that its proprietary DEP^® irinotecan development candidate showed significant efficacy and safety benefits over standard irinotecan in combination with 5-FU in a mouse xenograft model of human pancreatic cancer (Figure 1 and 2). The human pancreatic tumour model used in this study virtually did not respond to the traditional irinotecan regimen (irinotecan + 5-FU), whereas complete tumour regression and 100% survival was achieved using Starpharma’s DEP^® irinotecan.

Pancreatic cancer is a leading cause of death among oncologic diseases, with a one-year relative survival rate of 20%, and a five-year survival rate of only 7%. Metastatic pancreatic cancer remains resistant to current chemotherapy and radiotherapy, where irinotecan containing combination therapies such as FOLFIRINOX (combination of 5-FU, leucovorin, irinotecan, and oxaliplatin) are used as a first line treatment. 

Irinotecan was originally commercialised under the brand name Camptosar^® and achieved peak annual sales of US$1.1 billion. Irinotecan has a US FDA “Black Box” warning for both severe diarrhoea and myelosuppression (including neutropenia), making it an ideal candidate for Starpharma’s DEP^® technology.

These efficacy results build on previously announced significant efficacy and safety benefit data for DEP^® irinotecan (announced on 6 June 2017) in a number of colon cancer models.   

Dr Jackie Fairley, Starpharma CEO, commented: “These results for DEP^® irinotecan of complete tumour regression and 100% survival are really impressive given the model used was virtually un-responsive to conventional irinotecan. Pancreatic cancer is known to have one of the lowest survival rates and remains an area of significant unmet medical need with substantial opportunity for better patient outcomes. These results provide additional validation of the DEP^® platform’s ability to significantly improve efficacy alone and in combination compared to relevant originator products.”

DEP^® irinotecan is expected to enter the clinic this financial year and will be Starpharma’s third internal DEP^® candidate to enter clinical development. In addition, Starpharma also has a number of partnerships, including a multiproduct licence with AstraZeneca for the application of the DEP^® technology to selected oncology drug candidates. The first DEP^® patent under this partnership was published on 31 August 2018 (link to announcement). 

In this human pancreatic cancer model, conventional irinotecan (Camptosar^®) alone or in combination with 5-FU displayed only limited tumour inhibition but no tumour regression whatsoever (Figure 1). In addition, conventional irinotecan alone or in combination with 5-FU showed no appreciable overall survival benefit compared to saline (Figure 2).

In contrast, Starpharma’s DEP^® irinotecan was significantly more efficacious than standard irinotecan alone and in combination with 5-FU, demonstrating significant anti-cancer efficacy with complete tumour regression (P<0.0001) (Figure 1). These impressive findings are despite the fact that this human pancreatic cancer model virtually did not respond to irinotecan alone or in combination with 5-FU.

Study Methods

This study was conducted for Starpharma by a leading international cancer research institution. The NOD-scid Interleukin 2 receptor gamma chain null mice were inoculated subcutaneously with CAPAN-1 (8 mice/group, respectively). Mice were dosed with saline vehicle, DEP^® irinotecan (Maximum Tolerated Dose[1]), irinotecan (40mg/kg) or irinotecan + 5FU (40 and 50 mg/kg) on days 1, 8 and 15 (all drug groups). Tumour growth data were analysed in GraphPad Prism for ANOVA followed by Dunnett’s post-hoc test. The tumour volume data represent the mean ± standard error of the mean (SEM). Kaplan-Meier survival curves were analysed using the Log-rank (Mantel-Cox) test.

Download ASX Announcement: DEP^® irinotecan outperforms in pancreatic cancer model (PDF, 155kb)

[1] Dose not disclosed pending intellectual property filings