Oncology FAQs

Production of Tigilanol Tiglate

How is tigilanol tiglate derived?
Tigilanol tiglate is derived from the seed of the Fontainea picrosperma (blushwood) tree.

Do you harvest commercial quantities of the blushwood from native forests?
No. QBiotics has established purpose-built commercial plantations for the long-term production of blushwood seed. While these plantations are coming on line, blushwood seed is sustainably harvested from native stands of blushwood trees in the Australian tropical rainforest.

Is there a risk that a natural disaster like fire or cyclone could affect supply of tigilanol tiglate?
QBiotics have well developed business continuity and contingency plans in place to manage a wide range of potential supply risks, including natural events. Therefore, QBiotics has a high degree of confidence in continuous long-term supply of tigilanol tiglate and our marketed veterinary anticancer pharmaceutical STELFONTA.

What is QBiotics doing to promote conservation of rainforests?
QBiotics believes that areas of high biodiversity are a significant source of novel molecules with pharmaceutical potential. Tropical rainforests are the most biodiverse regions on earth. Successful development of a drug that addresses major health problems that is sourced from these rainforests is a strong demonstration of the forests value, and thus a strong reason for conserving them. QBiotics has successfully developed, registered and marketed our anticancer veterinary pharaceutical STELFONTA and is in Clinical Phase II dvelopment of the drug candidate for the human market.  Note that the work QBiotics is doing in biodiscovery from the tropical rainforests is being noted in various media outlets on a global scale.  

Why can't others replicate or use tigilanol tiglate?
The purification process used to isolate tigilanol tiglate is proprietary to QBiotics. Tigilanol tiglate cannot be made synthetically. QBiotics' synthetic chemists have worked for many years to try to develop a synthetic pathway.  Consequently, tigilanol tiglate  must be isolated from the seed of blushwood trees. Tigilanol tiglates use as an anticancer agent is protected by patents in all major regions. Patent protection includes both composition of matter and use as an anticancer pharmaceutical.

Is there a generic form of tigilanol tiglate/STELFONTA available?
There is no generic form of tigilanol tiglate/STELFONTA. The internet has listings for generic human and veterinary products. However, these are counterfeit, unregulated, untested and potentially dangerous imitations not produced by QBiotics.

Can I buy the Fontainea picrosperma (blushwood) plant and produce tigilanol tiglate myself, or imitations of STELFONTA or EBC-46?
Unfortunately, this would not result in the same pharmaceutical and we would not recommend this as an alternative treatment option.

Tigilanol tiglate has been isolated using a complex extraction and purification process and is formulated with various excipients. It has undergone clinical trials and passed stringent manufacturing and analytical tests imposed by international regulatory authorities as a prescription pharmaceutical.

Obtaining blushwood seed and preparing extracts for use as an intratumoral injection is potentially highly dangerous as there are many compounds in the seed other than tigilanol tiglate which may have harmful impacts on the patient. As such, we highly discourage this as an alternative treatment option.

Why hasn't tigilanol tiglate been discovered before?
Discovery of the health benefits of tigilanol tiglate was through application of EcoLogic®, QBiotics' proprietary knowledge-based approach to drug discovery.

This approach combines predictions of cell signalling emergent properties resulting from plant ecological attributes with plant-animal interactions to produce search strategies for plant material that contains molecules with specific biological activity.

There is no reported indigenous use of blushwood and as such, discovery of tigilanol tiglate was not possible through the standard biodiscovery means.

In addition, the development process for tigilanol tiglate first as a veterinary prescription pharmaceutical, following closely by development for the human market, has taken many years of rigorous and lengthy safety, toxicology, clinical trials and manufacturing processes before approval can be obtained by pharmaceutical regulatory authorities.

About Tigilanol Tiglate Development For Humans

I saw EBC-46/tigilanol tiglate for sale online, can it be used in humans?
The products labelled as either EBC-46 or tigilanol tiglate you see for sale on the internet are counterfeit, unregulated, untested, and potentially dangerous imitations not developed by QBiotics.

EBC-46 (tigilanol tiglate) under the brand name STELFONTA® is only commercially available for use in dogs in Europe, and only available under prescription for a specific use in mast cell tumours. EBC-46 (tigilanol tiglate) is currently at Clinical Phase II development for humans.

Any product advertised on-line is not tigilanol tiglate and are likely non-registered imitations.

Use of non-registered products that imitate approved products or products in development may not be safe or efficacious (i.e. successfully treat the disease). These ‘imitation’ products may not have any active constituents (i.e. chemicals that act against the disease) and may be very harmful.

QBiotics recently received marketing authorisation approval from the regulatory authorities for a specific formulation of tigilanol tiglate in Europe and the UK. An application for marketing in the US is currently under review by the Food & Drug Administration – Center for Veterinary Medicines (FDA-CVM) and in Australia by the Australian Pesticides and Veterinary Medicines Authority (APVMA). This formulation is specifically for canine indications and not for use in humans. The human programme is concentrating on Phase I/II and II clinical trials. An extensive data set is required to support any regulatory submission for marketing approval. The data required for any product approved by a regulatory agency for use as a medicinal product needs to show that the product is made to stringent standards by approved facilities and the use of the product is both safe and performs in accordance with any label claim.

Why can't we use tigilanol tiglate (EBC-46) in humans now?
The development of a pharmaceutical must follow the stringent protocols and development procedures set down by the international regulatory authorities, such as the Therapeutic Goods Administration (TGA) in Australia, the Food and Drug Administration (FDA) in the USA and the European Medicines Agency (EMA) in Europe. Each step of the development process is examined by the authorities of the country where the drug is intended to be used and the drug must pass strict requirements prior to being approved for use. These pharmaceutical development steps are in place to ensure, as far as possible, the safety of the patient while providing the requisite benefits. QBiotics is currently developing tigilanol tiglate for use in humans according to this framework and will provide updates as milestones are reached.

About Tigilanol Tiglate For Dogs

What is tigilanol tiglate?
Tigilanol tiglate is a pharmaceutical approved as an intratumoural injection for treating mast cell tumours (MCT) in dogs, removing 75% of tumours with a single treatment (p=0.001).1

Where is tigilanol tiglate available?
Tigilanol tiglate (brand name STELFONTA®) is approved by the European Medicines Agency (EMA), the UK Veterinary Medicines Directorate (VMD) and Swissmedic as an oncology pharmaceutical for the treatment of all grades of non metastatic, non resectable mast cell tumours in dogs.2
Consequently, the drug is currently available in Europe and the UK.

Applications for marketing authorisation are currently under late-stage review by the US Food and Drug Administration – Center for Veterinary Medicines (FDA-CVM) and the Australian Pesticides and Veterinary Medicines Authority (APVMA). Our objective is for veterinarians across the globe to have access to tigilanol tiglate, as another treatment in their anticancer tool-kit.

What class of drug does tigilanol tiglate belong to?
Tigilanol tiglate is an epoxytigliane that has specific cell signalling capabilities. It functions as an anti-tumour drug via various processes part of which includes activation of specific isoforms of protein kinase C (PKC).

Epoxytiglianes (also know as diterpene esters) are a structurally diverse class of C20 natural molecules composed of two terpene units. The ester refers to a functional group, on rings of the diterpene molecule, that is derived from an acid where at least one hydroxyl (OH) has been replaced by an alkoxyl. There are 1000’s of diterpene molecules described from plants and animals and they have a wide range of biological and pharmacological activities including antimicrobial, anti-inflammatory and anticancer activity. In oncology, taxanes are an example of diterpenes in widespread clinical use.

What is the Mode of Action of tigilanol tiglate?
A single intratumoural injection of tigilanol tiglate has been shown to:

  • Elicit a rapid and localised inflammatory response, recruiting neutrophils and macrophage to the area as part of the tumour cell clean up and antimicrobial effect elicited by the drug.  This naturallu causes swelling and erythema extending to the tumour margins and immediate surrounds. This acute inflammatory response generally resolves within 48 to 96 hours;
  • Cause loss of integrity of the tumour vasculature; and
  • Induce tumour cell death.

These processes lead to tumour haemorrhagic necrosis and necrotic destruction of the tumour mass usually within 4 to 7 days of treatment.  Tigilanol tiglate also stimulates healing of the tumour deficit or 'wound' that remains after the tumour has been destroyed.

What is tigilanol tiglate’s success or efficacy rate? 
Success is measured by complete mast cell tumour (MCT) destruction (Complete Response). 75% of MCT achieved a complete response after a single tigilanol tiglate treatment (intratumoural injection) and 88% following a second  treatment. A complete response is determined as no tumour present at 4 weeks following tigilanol tiglate treatment according to RECIST (Response Evaluation Criteria in Solid Tumours) guidelines as determined by the Veterinary Cooperative Oncology Group (VCOG).1

What is the proof of efficacy for tigilanol tiglate?
Several clinical trials have shown significant efficacy in dogs. The European Medicines Agency’s (EMA) safety and efficacy approval is based on data provided in a pivotal clinical trial which was a randomised, owner and investigator masked, untreated controlled study that involved 11 study sites in the USA. Patient enrollment included 123 dogs with 80 dogs randomised to the tigilanol tiglate treatment group.  Note that the dogs randomised to the control group were also provided treatment with tigilanol tiglate following their 28 day initial 'control' assessment. 

Efficacy of tigilanol tiglate following a single treatment was 75% (60 of 80 dogs) complete response for cutaneous MCT and subcutaneous MCT located at or below the elbow and hock. This study was part of the subsequent approval by the EMA for tigilanol tiglate.

What is the disease-free interval after tigilanol tiglate treatment at the tumour site (non-recurrence rate)?
The disease-free interval at the tigilanol tiglate treatment site for patients treated in clinical trials is 90% at one year. The disease-free interval was assessed for those patients treated in the US clinical trial that achieved a complete response at four weeks following a single tigilanol tiglate treatment. There were 74 dogs available for assessment at 12 months following initial complete remission to tigilanol tiglate. Sixty-five dogs (88%) had no evidence of local MCT recurrence3

  1. De Ridder T, et al. Journal of Veterinary Internal Medicine 2020; doi 10.1111/jvim.15806
  2. www.ema.europa.eu/en/medicines/veterinary/EPAR/stelfonta
  3. Campbell J, et al. Veterinary Cancer Society Annual Conference 2019