Latest Announcement

FDA approves IND to initiate soft tissue sarcoma (STS) trial

US FDA approves QBiotics investigational new drug application to initiate tigilanol tiglate soft tissue sarcoma Phase II trial

25 July 2022

Investigational new drug (IND) approval received by QBiotics, to initiate a Phase II clinical trial investigating tigilanol tiglate in the treatment of patients with Soft Tissue Sarcoma (STS)
The open label trial will evaluate efficacy and dose ranging in patients with advanced or metastatic STS
Global Data estimates that there were 124,573 new cases of STS globally in 2021, with the incidence growing at 0.54% per year¹

BRISBANE, 25 July, 2022. QBiotics Group Limited (QBiotics), a life sciences company developing novel small molecule oncology and wound healing pharmaceuticals, has been granted approval of its Investigational New Drug (IND) application by the US Food and Drug Administration (FDA) for lead oncology molecule, tigilanol tiglate. The approval enables initiation of a Phase II clinical trial (QB46C-H07) in patients with STS.

The QB46C-H07 trial will be undertaken in the USA. This is an open label study that will enrol at least 10 patients with advanced or metastatic STS. Patients will receive up to five intratumoural treatments of tigilanol tiglate, administered four weeks apart, to evaluate the drug candidate’s efficacy and safety in the treatment of STS.

Tigilanol tiglate is a plant-derived small molecule, administered by injection directly into a solid tumour. Injected tumours are rapidly destroyed by tumour cell necrosis, tumour vascular disruption, and immune-mediated mechanisms².

Dr Victoria Gordon, Managing Director and CEO of QBiotics, said “IND approval for our Soft Tissue Sarcoma trial is an important milestone for QBiotics. It is QBiotics’ first FDA IND and the culmination of a very significant body of work by our team. IND approval is underpinned by a robust data package, including data from our first-in-human QBC46-H01 Phase I study, where tigilanol tiglate demonstrated clinically relevant monotherapy activity in 22 patients with a broad range of refractory solid tumours³.”

“This STS trial builds on our overall development approach for tigilanol tiglate, which is exploring this drug candidate’s potential as a pan-tumour treatment for a broad range of solid tumours. QBiotics is also undertaking clinical trials in melanoma and head and neck cancer as part of this broad programme. Implementing a clinical trial in a third cancer indication is a strong move for the company.”

“STS are a group of rare and heterogeneous solid tumours that occur in the soft tissues of the body, such as muscles and nerves,” continued Dr Gordon. “Due to the complexity of this disease, treatment is challenging⁴. We hope that through our research, we may be able to bring forward a new therapeutic option.”

Global Data estimates that there were 124,573 new cases of STS globally in 2021, with the incidence growing at 0.54% per year¹.

FURTHER INFORMATION
DR VICTORIA GORDON, CEO & MANAGING DIRECTOR, QBIOTICS GROUP
communications@qbiotics.com or

MEDIA ENQUIRIES
JANE LOWE, IR DEPARTMENT
jane.lowe@irdepartment.com.au or +61 411 117 774

ABOUT TRIAL QB46C-H07
QB46C-H07 is a Phase II, open label clinical trial to evaluate the efficacy and safety of intratumoural tigilanol tiglate in 10 patients with advanced and/or metastatic Soft Tissue Sarcomas of the extremities and body wall.

Primary objective:
Evaluate the degree of tumour ablation in tumours and or tumour segments treated with one or more injections of tigilanol tiglate.

Secondary and exploratory objectives:
Safety and tolerability assessments of tigilanol tiglate, and translational research to evaluate changes in the tumour micro environment, immune responses, and tumour recurrence rate after 6 months following treatment.

ABOUT QBIOTICS
QBiotics is a public unlisted Australian life sciences company that discovers and develops new pharmaceuticals derived from nature to address unmet medical need in humans and our companion animals. Our current clinical focus is on novel treatments for cancer and for debilitating chronic wounds. QBiotics’ lead oncology product, tigilanol tiglate, is a small molecule targeting a range of solid tumours across multiple species. QBiotics’ business model is to develop products that have application in both veterinary and human markets. Success in the veterinary programme validates QBiotics technology and de-risks human development, while having the potential to generate early revenue.
https://qbiotics.com

ABOUT TIGILANOL TIGLATE
Tigilanol tiglate is a small molecule being developed as an intratumoural treatment for solid tumours. Tigilanol tiglate has a multimodal action that involves injected tumour responses as well as systemic responses in non-injected tumours. Complete destruction of the injected tumour is mediated via tumour vascular disruption, death of tumour cells by oncosis and immune-mediated mechanisms². Following tumour destruction, rapid wound healing has been shown to ensue.
A veterinary formulation of tigilanol tiglate (STELFONTA^®) is approved to treat canine mast cell tumours. STELFONTA^® is marketed in Europe, the United Kingdom, the USA and Australia by QBiotics’ partner Virbac, a global animal health company. In a pivotal US veterinary study, a single injection of STELFONTA^® induced a complete response in 75% canine mast cell tumours, and an 88% complete response with two injections. There was no tumour recurrence in 89% of evaluable cases 12 months post-treatment⁵.

GlobalData^®
Cullen et al., 2021. Activation of PKC supports the anticancer activity of tigilanol tiglate and related epoxytiglianes. Scientific Reports 11:207. DOI: 10.1038/s41598-020-80397-9.
Panizza et al., 2019. Phase I dose-escalation study to determine the safety, tolerability, preliminary efficacy and pharmacokinetics of an intratumoral injection of tigilanol tiglate (EBC-46). EBioMedicine DOI: 10.1016/j.ebiom.2019.11.037.
Damerell et al., 2021. Molecular mechanisms underpinning sarcomas and implications for current and future therapy. Signal Transduction and Targeted Therapy 6:246. DOI: 10.1038/s41392-021-00647-8.
De Ridder et al., 2020. Randomized controlled clinical study evaluating the efficacy and safety of intratumoral treatment of canine mast cell tumors with tigilanol tiglate. Journal of Veterinary Internal Medicine 1-15. DOI: 10.1111/jvim.15806.

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Tigilanol tiglate: Human oncology

Our lead molecule, tigilanol tiglate, is a novel small molecule administered directly into a solid tumour mass. A single intratumoural injection of tigilanol tiglate rapidly destroys injected tumours, with minimal tumour recurrence.

Tigilanol tiglate acts directly via disrupting the tumour blood vessels that supply the tumour, and by tumour direct cell killing through a process called oncosis. Tigilanol tiglate also induces rapid healing of the tumour site. Non-injected tumours may also be targeted by indirect systemic anti-tumour responses (Fig 1).

Source: Biopharma Dealmakers (Biopharm Deal) ISSN 2730-6283 (online)

Fig. 1 | Intratumoural treatment with tigilanol tiglate induces injected and systemic non-injected tumour responses.
(a) Injected tumours are rapidly destroyed by tumour cell necrosis and tumour vascular disruption. (b) The disrupted tumours release tumour-derived antigens which generate systemic anti-tumour responses against non-injected neighbouring or distant tumours. DAMPs, damage-associated molecular patterns.

We have clinical and pre-clinical evidence that tigilanol tiglate has “agnostic activity” with the potential to treat a broad range of solid tumours. While effective as a single agent therapy, it also induces synergistic anti-tumour responses when combined with other cancer therapies, including immune checkpoint inhibitors, chemotherapy and radiotherapy.

QBiotics is now pursuing both monotherapy and combination therapy avenues in clinical trials.

Oncology Human Trials
*QB46C-H06 trial is a clinical collaboration with MSD (trade name of Merck & Co. Inc., Kenilworth, USA) in patients with immune checkpoint-inhibitor-refractory unresectable melanoma.

Tigilanol tiglate has the potential for improved efficacy over other intratumoral treatments. It can completely destroy the injected tumour with a single treatment, and without damaging normal tissue. Therefore, it may significantly improve outcomes for patients with unresectable tumours, tumours in locations that are difficult to access, or where surgery could affect patients’ ability to hear, see, smell, swallow or taste such as in head and neck cancer.

Strong efficacy signals from a first-in-human, dose-escalation safety trial

A dose-escalation safety Phase 1 trial in 22 patients with a broad range of cutaneous and subcutaneous solid tumours¹ showed:

tigilanol tiglate was generally well tolerated with a maximum tolerated dose (MTD) not declared;
Injected tumour control rate (CR/PR/SD)* of 60% from a single injection
Best Target Tumour Response (RECIST 1.1; Day 1-22)
- Four patients (18%) achieved a Complete Response (CR, full tumour destruction)
- Five patients (22%) achieved a partial response (PR or >30% tumour reduction)
- Fourteen patients (64%) had stable disease (SD)

* CR= Complete Response; PR = Partial Response or >30% tumour reduction; SD = Stable Disease

Two patients with metastatic melanoma also had distal tumour responses, so-called abscopal or anenestic responses, where their non-injected tumours also responded to tigilanol tiglate treatment.

Strong tumour responses observed in the first-in-human Phase I trial with tigilanol tiglate

chart Fig. 2 | Waterfall plot showing percentage change in volume (mm³) of injected tumours following treatment with tigilanol tiglate in Phase I study (QB46C-H01)

Although phase 1 trials are not powered for efficacy, the strong tumour responses observed in the first human study is supported by impressive efficacy data seen in dogs. In dogs, tigilanol tiglate is approved as a first-line alternative to surgery in non-metastatic mast-cell tumours, meeting an unmet need in the veterinary market.

In a pivotal multicentre study in 123 canine patients with mast-cell tumours, a single injection induced a 75% Complete Response at 28 days post-treatment, with an Objective Tumour Response of 80%. Two injections led to an 88% Complete Response. One year later, 89% of the dogs had no tumour recurrence.

These spontaneous tumours in animals provide a clinically relevant and highly validated model for cancer in humans.

Panizza et al. (2019). EBioMedicine, 9(41), 1-9.