QBiotics current focus for human health is oncology and wound healing.
Cancer is a leading cause of death worldwide. It is estimated that globally more than 17.5 million people are diagnosed with cancer and 8.7 million people die of the disease each year.1 The majority of these cancers are of the solid tumour type.2 There are currently a large range of anticancer treatments available for solid tumours. However, there is considerable interest in the development of new treatments mainly driven by the ongoing need to treat late stages of disease.3
QBiotics' leading anticancer pharmaceutical, tigilanol tiglate (EBC-46), is a novel small molecule diterpene ester in development as a local treatment for solid tumours. Tigilanol tiglate was discovered by applying the EcoLogic™ approach to drug discovery from the tropical rainforests of Queensland Australia. The drug is not synthetically tractable and is isolated from the Australian native plant Blushwood. Tigilanol tiglate is a protein kinase C (PKC) activator and when injected into solid tumours causes PKC-dependent haemorrhagic necrosis, rapid tumour cell death and ultimate destruction of solid tumours.3
QBiotics recently completed a first-in-human dose escallation safety study of tigilanol tiglate in patients across four Australian hospitals. This Phase I/IIA clinical trial was conducted in 22 patients with refractory skin and subcutis solid tumours (specifically melanoma, basal cell carcinoma, squamous cell carcinoma, breast and colorectal adenocarcinoma, angiosarcoma, fibrosarcoma, adenoid cystic sarcoma and fibroxanthoma). Results reported were good tolerability following intratumoral injection of tigilanol tiglate. Adverse events were generally limited to transient tumour site swelling and associated pain, responses that were expected given the mode of action of the drug*. In addition, encouraging signs of efficacy were demonstrated in all tumour types, with full tumour destruction (Complete Response) observed in patients where the dosing met the 50% volume/volume of tumour (note this is an intratumoural treatment where dosing is calculated on tumour volume rather than patient size)*. As well, good healing of the injection site was observed and a maximum tolerated dose (MTD) was not reached. The results of this study underpin further development of the drug.
QBiotics is currently conducting a Phase I/II clinical trial evaluating the optimal dosing and safety of tigilanol tiglate in patients with head and neck squamous cell carcinoma (HNSCC). The Phase I/II open label “QBC46-H03” study, is a dose escalation study in patients with HNSCC aimed at determining the maximum tolerated dose (MTD) and recommended dose level for further studies. The study will also investigate safety, tolerability and tumour response following a single or multiple (two to three) doses of tigilanol tiglate.
Local treatment with tigilanol tiglate to date has concentrated on cutaneous and subcutaneous tumours and our ongoing strategy is to continue later stage development and bring this promising natural product to market as soon as possible. However, we also seek to determine if tigilanol tiglate has the potential to treat a range of internally situated solid tumours where injection can be guided by imaging.
The intellectual property and commercial production of tigilanol tiglate has been secured. Composition of matter and use patents have been granted in all major regions and extension patening is currently underway. The source plant of tigilanol tiglate, Blushwood, is produced in commercial plantations and a mature good manufacturing process (GMP) for active pharmaceutical ingredient and drug product is established. As a result of these processes, the future commercial supply of tigilanol tiglate is assured.
Chronic wounds, such as slow to heal leg ulcers, present a significant health problem due to an aging population and a sharp rise in the incidence of diabetes and obesity. In the USA alone, chronic wounds affect 6.5 million patients annually and an excess of US$25 billion a year is spent on supportive treatments for sufferers.5 Current treatments fail to address the complex problems of wound healing in both humans and animals.
EBC-1013 is a semi-synthetic novel diterpene ester being developed as a wound healing pharmaceutical for treatment of a spectrum of wound types. The human development program for EBC-1013 is initially focusing on the treatment of chronic wounds, including the high demand and unmet medical need areas of venous leg ulcers and diabetic foot ulcers. Future wound healing indications under evaluation include the treatment of acute wounds, burns, photo-damaged skin and as an anti-scarring treatment.
EBC-1013 has a novel mechanism of action that addresses all stages of wound healing and has the potential to:
- Accelerate wound closure
- Minimise scarring
- Reduce the incidence of infectious complications through antimicrobial activity.
EBC-1013 is formulated as a topical gel that is easy to use. It is applied over the wound at a dose that is dependent on the size of the wound being treated.
To date, EBC-1013 has been used to treat a range of difficult to manage wounds in veterinary clinical cases*, including:
- Chronic infected wounds
- Non-healing surgical wounds
- Acute wounds with extensive local tissue damage and high infection risk
- Acute hyper-granulating wounds in horses, which have a high scarring risk.
*Data on file QBiotics
EBC-1013 is currently in the preclinical stage of development for the human market and early clinical for the veterinary market. Intellectual property and commercial production of EBC-1013 is under progress. Composition of matter and use patents are currently under examination in all major regions. The GMP production process for the active pharmaceutical ingredient has commenced and the formulation of drug products has been finalised.
1 Global Burden of Disease Cancer Collaboration; JAMA Oncol. 2017;3(4):524-548.
2 National Cancer Institute USA Website www.cancer.gov
3 GBI Research 2011; GBI Research Report "Oncology Therapeutics Market to 2017 - High Unmet Need in the Management and Treatment of Metastatic Cancers to Drive Drug Development" GBIHC125MR; December 2011.
4 Boyle GM, et al. (2014) Intra-Lesional Injection of the Novel PKC Activator EBC-46 Rapidly Ablates Tumors in Mouse Models. PLoS ONE 9(10): e108887. doi:10.1371/journal.pone.0108887
5 Sen, C K, et al. (2009) Human Skin Wounds: A Major and Snowballing Threat to Public Health and the Economy. Wound Repair Regen. 17(6): 763-771.