Mar 16, 2021
DEP® HER2-lutetium outperforms in human breast cancer model
- Radiotheranostics represent an exciting and rapidly growing area of cancer therapy (radiopharmaceuticals) and diagnosis (radiodiagnostics)
- Starpharma’s DEP® radiopharmaceuticals/diagnostics program has already generated several candidates including DEP® lutetium, DEP® zirconium, and most recently, DEP®HER2-lutetium
- Starpharma’s newest radiopharmaceutical candidate, DEP® HER2-lutetium, showed complete tumour regression, outperforming Herceptin® labelled with lutetium, in a human breast cancer model
- Starpharma’s earlier candidate, DEP® lutetium - an untargeted dendrimer-lutetium conjugate without a HER2 targeting group - also achieved better efficacy than Herceptin® labelled with lutetium, including 100% survival, in this model
Melbourne, Australia; 16 March 2021: Starpharma (ASX: SPL, OTCQX: SPHRY) today announced that its second radiopharmaceutical candidate, DEP® HER2-lutetium, achieved potent and durable anticancer activity, with complete tumour regression, outperforming Herceptin® (trastuzumab) labelled with lutetium, in a human breast cancer model (BT474).
Radiotheranostics is a rapidly developing area of cancer treatment and diagnosis, which has recently generated several high-value deals and sales in this category are estimated to grow to $12–15 billion by 2030. Recent deals include the acquisition of Endocyte by Novartis for US$2.1 billion and the acquisition of Sirtex by CDH Genetech for ~A$1.9 billion.
Worldwide, breast cancer is the most common cancer in women and the second most common cancer in the US. HER2 (human epidermal growth factor receptor 2) is a growth-promoting protein on the outside of all breast cells. Breast cancer cells with higher-than-normal levels of HER2 are called HER2-positive. These cancers tend to grow and spread faster than other breast cancers but are much more likely to respond to treatments with drugs that target the HER2 protein (such as Herceptin®). The HER2 receptor also exists in some other cancers such as gastric, colon, bladder and biliary cancers.
HER2 cancer treatments include Roche’s Herceptin® and Perjeta® with sales of approximately US$7 billion and US$4 billion respectively.
DEP® HER2-lutetium (Figure 1) is a proprietary dendrimer developed by Starpharma which incorporates the radioisotope lutetium-177 (177Lu) and a novel HER2 targeting moiety (nanobody).
Figure 1: DEP® HER2- lutetium
This study evaluated the anticancer activity of different doses of DEP® HER2-lutetium and DEP® lutetium compared to Herceptin® labelled with lutetium in the BT474 human breast cancer model. The study was conducted at University of Queensland’s Centre for Advanced Imaging.
Dr Jackie Fairley, CEO of Starpharma commented: “We and our specialist radiotheranostics clinical advisers are very excited by these latest data. Starpharma now has multiple potential DEP® products in the radiopharmaceuticals and radiodiagnostic area. We are delighted to continue working with Professor Kristofer Thurecht at the University of Queensland’s Centre for Advanced Imaging, as well as building strong relationships with radionuclide specialists and clinicians.”
About DEP® radiotheranostics
DEP® radiotheranostics (i.e., radio diagnostics and therapeutics) incorporate radioisotopes on to the DEP® scaffold. DEP® radiopharmaceutical conjugates selectively penetrate and accumulate within tumours and more effectively delivers radiation to kill tumour cells, that may be unreachable by conventional therapies. The addition of targeting groups, such as HER2, onto the DEP radiopharmaceutical can further enhance efficacy. Patent applications for DEP® lutetium, DEP® zirconium and DEP® HER2- lutetium have been filed.
Starpharma’s DEP® platform
Starpharma’s proprietary drug delivery platform technology, DEP®, is being used to improve pharmaceuticals, to reduce key toxicities and enhance their performance. The DEP® platform is highly versatile and can be used with a wide range of targeting moieties (e.g., small molecules, peptides, antibodies, antibody fragments) and radioisotopes.
The Company has three clinical stage DEP® products, as well as numerous partnered programs. DEP® partnerships include oncology programs with AstraZeneca, with Merck in the area of Antibody Drug Conjugates (ADCs), with Chase Sun in the area of anti-infectives and other world leading pharmaceutical companies. Starpharma’s partnered DEP® programs have the potential to generate significant future milestones and royalties.
Treatment with either a 1x15 MBq or 2x9 MBq dose of DEP® HER2-lutetium showed a potent anti-tumour effect resulting in complete tumour regression in the BT474 human breast cancer model. These results outperformed the antitumour activity of Herceptin® labelled with lutetium (1x15 MBq) (both DEP® HER2-lutetium doses p<0.0001 vs. Herceptin® labelled with lutetium) (Figure 2, showing 15 MBq dose groups only). All dose regimens of DEP® HER2-lutetium were extremely well tolerated. There were no deaths due to treatment or as a result of tumour growth in any treatment group.
Figure 2: Comparative anticancer efficacy of DEP® HER2-lutetium (15 MBq) versus Herceptin® labelled with lutetium (15 MBq).
The study also compared DEP® lutetium (i.e., without HER2 targeting) (1x15 MBq) to Herceptin® labelled with lutetium (1x15MBq). The anticancer activity of DEP® lutetium was also better than the effect of Herceptin® labelled with lutetium (p<0.0001)5 (Figure 3).
These data demonstrate that Starpharma’s DEP® dendrimer (without HER2 targeting) has a potent anticancer effect which is greater than with Herceptin®, while the targeted DEP® HER2-lutetium provides even greater efficacy.
Figure 3: Comparative anticancer efficacy of DEP® lutetium (15 MBq) versus Herceptin® labelled with lutetium (15 MBq).
This study was conducted in the laboratory of Professor Kristofer Thurecht at the University of Queensland’s Centre for Advanced Imaging. This murine xenograft study implanted BT474 human mammary cancer cells in female Balb/c nude mice. Mice were injected subcutaneously in the breast mammary fat pad with BT474 cells and also received oestrogen. Tumours were measured 2-3 times weekly using electronic callipers. Tumour volume (mm3) was calculated at each timepoint. The tumour volume data represent the mean ± standard error of the mean (SEM).
Following tumour establishment, mice were dosed intravenously as follows:
- Vehicle - days 1 and 15 (group 1)
- 177Lu labelled Herceptin® (15 MBq 177Lu) - day 1 (group 2)
- DEP® HER2- lutetium (15 MBq 177Lu) - day 1 (group 3)
- DEP® lutetium (15 MBq 177Lu) - day 1 (group 4)
Download ASX Announcement: DEP® HER2-lutetium outperforms in human breast cancer model (pdf file, 252KB)
 Theranostics is the systematic integration of targeted diagnostics and therapeutics. The theranostic platform includes an imaging component that "sees" the lesions followed by administration of the companion therapy agent that "treats" the same lesions. This strategy leads to enhanced therapy efficacy, manageable adverse events, improved patient outcome, and lower overall costs. Radiotheranostics refers to the use of radionuclides for the paired imaging and therapy agents. https://pubmed.ncbi.nlm.nih.gov/29356634/
 Nuclear medicine world market report & directory, MEDraysintell, 2016
 Datamonitor HER2+ Breast Cancer publication December 2020, 2019 sales figures
 All p-values obtained from a Mixed-effects Model with Repeated Measures (MMRM) analysis of tumour volume over time as a percentage of initial tumour volume. Groups 2 and 4: n=4, Groups 1 and 3: n=3
 Note: If error bars do not display on the graphs, they are not visible because they are shorter than the height of the symbol at this scale.