tigilanol tiglate (EBC-46) / Qbiotics - LARVOL DELTA

Harnessing tigilanol tiglate for local control of canine oral mucosal melanoma: a translational approach to rare human melanomas (ESMO 2026) - No abstract available

Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

Proof of concept for low dose and delayed release of tigilanol tiglate in the treatment of equine sarcoids. (PubMed, Front Vet Sci) - "Apart from mild leukotrichia that developed at some treatment sites, healing and cosmetic outcome was deemed excellent. Ongoing studies evaluating the clinical efficacy and safety of lowered tigilanol tiglate doses in a statistically relevant, representative equine population are required to further develop the reported treatment regimens."

Journal • Oncology • Skin Cancer

Exploiting Oncogenic Overactivation: PKC Activation as a Therapeutic Vulnerability in KRAS-Mutant PDAC (EACR 2026) - "The PKC activators Prostratin (PR) and Tigilanol Tiglate (TT) were used to pharmacologically activate PKC... Our findings indicate that PKC activation drives overactivation of the MAPK/ERK pathway in KRAS-mutant PDAC models, resulting in reduced viability and establishing oncogenic overactivation as a potent, therapeutically exploitable vulnerability in KRAS-mutant pancreatic cancer."

Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS • TNFA

Case Report: Severe wound formation following intratumoral tigilanol tiglate treatment resulting in limb amputation in a 10-year-old male dog. (PubMed, Front Vet Sci) - "Histopathology confirmed proximal cicatrix formation, necrosuppurative inflammation, and fibrosis without residual neoplasia. This case highlights that while TT can be effective for local tumor control, clinicians must recognize the potential for rare but severe localized complications that may require surgical intervention."

Journal • Fibrosis • Immunology • Infectious Disease • Oncology • Pancreatitis

Evaluation of ingenane diterpenoids for BL2 triple-negative breast cancer (AACR 2026) - "We found that BL2 TNBC cell lines are highly sensitive to protein kinase C (PKC)-activating diterpenes, including ingenol 3-angelate (I3A), tigilanol tiglate, and yuanhuacine, with potency in the nanomolar to picomolar range...By integrating tumor response with pharmacologic profiling, this work aims to define the relationships between PKC activation, compound potency, and subtype-selective efficacy to identify the most promising candidate for preclinical development. Ultimately, this research aims to leverage PKC activation as a targeted therapeutic strategy for BL2 TNBC, expanding treatment options for this lethal breast cancer subtype."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

QB46C-H07: A Clinical Study to Investigate the Efficacy of Intratumoral Tigilanol Tiglate in Soft Tissue Sarcoma (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: QBiotics Group Limited | Trial completion date: Feb 2027 ➔ Jun 2027 | Trial primary completion date: Oct 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Pharmacological Repurposing of Natural Products for Triple-Negative Breast Cancer (SABCS 2025) - "Further studies havedemonstrated that structurally and functionally related ingenane diterpenoids in clinicaldevelopment for the topical treatment of skin malignancies, including tigilanol tiglate andingenol-3-angelate, retain BL2 subtype-selective activity with over one-thousand-fold selectivity,providing a unique opportunity for drug repurposing.To support these efforts, we have taken a multipronged approach to identify the mechanism ofselectivity of these compounds against BL2 TNBC cells, perform structure-activity relationship(SAR) and pharmacokinetic studies to inform on repurposing this drug class for systemicadministration, and determine their efficacy in combination with standard of care chemotherapy.We have demonstrated that the selective activity of yuanhuacine and ingenane diterpenoids isdue to activation of PKCβ, which is elevated in cell lines representing the BL2 TNBC subtype.The evaluation of sixteen structurally related compounds with potency in BL2 cell..."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AR • HER-2 • PRKCB

CHARACTERIZING THE IMMUNE RESPONSE TO INTRATUMORAL TIGILANOL TIGLATE (TT) IN PATIENTS WITH ADVANCED AND/OR METASTATIC SOFT TISSUE SARCOMA (STS) IN A PHASE IIA TRIAL (NCT05755113) (CTOS 2025) - P2 | "Despite patients with STS having a markedly exhausted immune phenotype at baseline, intratumoral injection of TT was associated with systemic enrichment of TCR clones found in the injected tumors at baseline, suggesting a systemic immune response to intratumoral TT injection. This trial and translational research was funded by QBiotics Group Ltd."

Clinical • Metastases • P2a data • Angiosarcoma • Fibrosarcoma • Leiomyosarcoma • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • B3GAT1 • CD4 • CD8 • HAVCR2 • TRB

A Clinical Study to Investigate the Efficacy of Tigilanol Tiglate Directly in Head and Neck Cancer (clinicaltrials.gov) - P2 | N=15 | Active, not recruiting | Sponsor: QBiotics Group Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

QBIOTICS REPORTS 80% OBJECTIVE RESPONSE RATE IN INJECTED TUMOURS IN STAGE 1 OF PHASE IIA CLINICAL TRIAL OF TIGILANOL TIGLATE FOR SOFT TISSUE SARCOMA (PRNewswire-Asia) - P2a | N=40 | NCT05755113 | Sponsor: QBiotics Group Limited | "Positive data from Stage 1 of the Phase IIa clinical trial (QB46C-H07) evaluating QBiotics' small molecule, tigilanol tiglate in 11 (10 evaluable) patients with advanced Soft Tissue Sarcoma (STS). An Objective Response Rate (ORR) of 80% was achieved, based on the Best Observed Response (BOR) at any time during the study, indicating 8 out of 10 evaluable patients saw either complete ablation (100% reduction in volume) or partial ablation (≥30% reduction in volume) of treated tumours. 22 of the 27 (81%) injected tumours across all patients showed complete or partial ablation (14 showing complete ablation and 8 showing partial ablation). None of the 14 completely ablated tumours recurred at 6 months, indicating tigilanol tiglate may provide durable responses."

P2a data • Soft Tissue Sarcoma

A Clinical Study to Investigate the Efficacy of Tigilanol Tiglate Directly in Head and Neck Cancer (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: QBiotics Group Limited | N=37 ➔ 20

Enrollment change • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Intratumoural tigilanol tiglate in the multicentre treatment of equine sarcoids and cutaneous melanomas. (PubMed, Equine Vet J) - "The observed therapeutic efficacy of TT supports clinical use as well as early interventions in horses. Successful use necessitates knowledge of the drug's mode of action and management of associated local site responses."

Journal • Cutaneous Melanoma • Melanoma • Oncology • Skin Cancer • Solid Tumor

QB46C-H07: A Clinical Study to Investigate the Efficacy of Intratumoral Tigilanol Tiglate in Soft Tissue Sarcoma (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: QBiotics Group Limited | N=10 ➔ 40 | Trial completion date: Mar 2025 ➔ Feb 2027 | Trial primary completion date: Sep 2024 ➔ Oct 2026

Enrollment change • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Synthesis and preclinical evaluation of tigilanol tiglate analogs as latency-reversing agents for the eradication of HIV. (PubMed, Sci Adv) - "Enabled by our previously reported scalable synthesis of EBC-46, we report herein the systematic design, synthesis, and evaluation of EBC-46 analogs, including those inaccessible from the natural source and their PKC affinities, ability to translocate PKC, nuclear factor κB activity, and efficacy in reversing HIV latency in Jurkat-Latency cells. Leading analogs show exceptional PKC affinities, isoform selectivities, and functional activities, serving as promising candidates for therapeutic applications."

Journal • Preclinical • Cardiovascular • Human Immunodeficiency Virus • Infectious Disease • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Intratumoural tigilanol tiglate induces immunogenic cell death and a localised immune response in HNSCC [WITHDRAWN] (ESMO-IO 2024) - No abstract available

Immunogenic cell death • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck

Epoxytiglianes induce keratinocyte wound healing responses via classical protein kinase C activation to promote skin re-epithelialization. (PubMed, Biochem Pharmacol) - "The prototype epoxytigliane, EBC-46 (tigilanol tiglate), is a potent anti-cancer agent in clinical development for local treatment of a range of human and animal tumors...PKC-βI/-βII isoform inhibition by enzastaurin (1 μM), significantly inhibited HaCaT proliferation and wound repopulation responses induced by both epoxytiglianes, especially at 1.51-151 nM. PKC-α inhibitor, Ro 31-8220 mesylate (10 nM), exerted lesser inhibitory effects on HaCaT responses...Phospho-PKC (p-PKC) studies confirmed that epoxytiglianes transiently activated classical PKC isoforms (p-PKCα, p-PKC-βI/-βII, p-PKCγ) in a dose- and time-dependent manner. By identifying how epoxytiglianes stimulate classical PKCs to facilitate keratinocyte healing responses and re-epithelialization, these findings support further epoxytigliane development as topical therapeutics for clinical situations involving impaired re-epithelialization, such as non-healing wounds in skin."

Journal • Oncology • CCNB1 • CDKN1A • KRT17 • MMP1 • MMP10 • MMP7 • PRKCB

AN OPEN LABEL PHASE IIA STUDY EVALUATING THE PRELIMINARY EFFICACY OF INTRATUMORAL TIGILANOL TIGLATE TT) IN ADVANCED AND/OR METASTATIC SOFT TISSUE SARCOMA STS, NCT05755113) (CTOS 2024) - P2 | "Intratumoural TT appears safe for patients with STS. Efficacy in ablating injected tumours was observed across numerous histologic types, exceeding the primary endpoint for a promising response. The tolerability and promising response rate warrant further investigation of TT in patients with STS either alone or in combination with other agents."

Clinical • Metastases • P2a data • Angiosarcoma • Fibrosarcoma • Leiomyosarcoma • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Response to tigilanol tiglate in dogs with mast cell tumors. (PubMed, J Vet Intern Med) - "Tigilanol tiglate is an effective local treatment option for mast cell tumors in dogs with a predictable clinical course and response. Because of the unique mode of action and clinical course, client education and careful case selection is necessary before electing tigilanol tiglate for local treatment."

Journal • Oncology

An open label phase IIa study evaluating the preliminary efficacy of intratumoural tigilanol tiglate (TT) in advanced and/or metastatic soft tissue sarcoma (STS) (ESMO 2024) - P2 | "Intratumoural TT appears safe for patients with STS. Efficacy in ablating injected tumours was observed across different histologic types. The primary endpoint for a promising response was met within the first 5 evaluable patients."

Clinical • Metastases • P2a data • Angiosarcoma • Fibrosarcoma • Leiomyosarcoma • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

A Clinical Study to Investigate the Efficacy of Intratumoral Tigilanol Tiglate in Soft Tissue Sarcoma (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: QBiotics Group Limited | Phase classification: P2a ➔ P2

Metastases • Phase classification • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Tigilanol Tiglate-Induced Changes in Secretome Profiles Alter C-Met Phosphorylation and Cell Surface Protein Expression in H357 Head and Neck Cancer Cells. (PubMed, Cells) - "This was accompanied by rapid cleavage of the cellular junction adhesion protein Nectin-1 and the nerve growth factor receptor NGFRp75/TNFR16. These findings, that TT is a novel negative regulator of protumorigenic c-MET and NGFRp75/TNFR16 signalling, as well as regulating Nectin-1-mediated cell adhesion, further contribute to our understanding of the mode of action and efficacy of TT in the treatment of solid tumours."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • MET • NECTIN1 • NGFR • SDC1

Immunogenic oncolysis by tigilanol tiglate. (PubMed, Oncoimmunology) - "A recent study revealed the capacity of this pyroptosis inducer to elicit hallmarks of immunogenic cell death. In addition, intratumoral injection of tigilanol tiglate can sensitize subcutaneous cancers to subsequent immune checkpoint inhibitors targeting CTLA-4 alone or in combination with PD-1."

Journal • Oncology • PD-1

Tigilanol tiglate is an oncolytic small molecule that induces immunogenic cell death and enhances the response of both target and non-injected tumors to immune checkpoint blockade. (PubMed, J Immunother Cancer) - "These data demonstrate that TT is an oncolytic small molecule with multiple targets and confirms that cell death induced by this compound has the potential to augment antitumor responses to immunotherapy."

Checkpoint block • Checkpoint inhibition • Immunogenic cell death • Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CALR • CTLA4 • GSDME • HMGB1

Total Syntheses of Phorbol and 11 Tigliane Diterpenoids and Their Evaluation as HIV Latency-Reversing Agents. (PubMed, J Am Chem Soc) - "Fifth, further oxidation to the most densely oxygenated acerifolin A (23) and tigilanol tiglate (24) was realized through organizing a 3D shape of the B-ring. Assessment of the HIV latency-reversing activities of the 12 tiglianes revealed seven tiglianes (14-17 and 22-24) with 20- to 300-fold improved efficacy compared with prostratin (12), a representative latency-reversing agent. Therefore, the robust synthetic routes to a variety of tiglianes with promising activities devised in this study provide opportunities for advancing HIV eradication strategies."

Journal • Human Immunodeficiency Virus • Infectious Disease

QBiotics gains FDA orphan drug designation for cancer treatment (Investing.com) - "QBiotics Group Ltd has achieved a significant regulatory milestone as its pioneering intratumoural oncology asset, tigilanol tiglate, receives Orphan Drug Designation (ODD) from the United States Food and Drug Administration (FDA) for the treatment of soft tissue sarcoma."

Orphan drug • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor