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Pipeline
iOnctura is developing a pipeline of next generation, differentiated molecules that are at the forefront of pioneering new therapies for the treatment of cancer.
Target Product Candidate Indication Development Phase ABCDEFPreclinicalIND Enabling StudiesCTA/IND SubmissionPhase IPhase Ib/IIPivotal Phase II/IIIPI3Kδ IOA-244 Uveal Melanoma Phase Ib/IIOther Treg-driven tumors Phase IAutotaxin IOA-289 Pancreatic Cancer Phase Ib/IIOther CAF-driven tumors Phase ICD73 IOA-237 Selected Solid Tumors PreclinicalIOA-244
Target Indication Development Phase PreclinicalIND Enabling StudiesCTA/IND SubmissionPhase IPhase Ib/IIPivotal Phase II/IIIPI3Kδ Uveal Melanoma Phase Ib/IIOther Treg-driven tumors Phase IIOA-289
Target Indication Development Phase PreclinicalIND Enabling StudiesCTA/IND SubmissionPhase IPhase Ib/IIPivotal Phase II/IIIAutotaxin Pancreatic Cancer Phase Ib/IIOther CAF-driven tumors Phase IIOA-237
Target Indication Development Phase PreclinicalIND Enabling StudiesCTA/IND SubmissionPhase IPhase Ib/IIPivotal Phase II/IIICD73 Selected Solid Tumors PreclinalIOA-244 (PI3Kδ Inhibitor)
Indication Combination Agent Development Phase PreclinicalIND Enabling StudiesCTA/IND SubmissionPhase IPhase Ib/IIPivotal Phase II/IIICombination Partners Cutaneous Melanoma N Preclinical— Y Phase Ib/II— Uveal Melanoma N IND Enabling Studies - Fast Track— Mesothelioma Y Phase Ib/II— Y CTA/IND Submission— Myelofibrosis N Phase II/III— NSCLC Y Phase Ib/II— Y Phase Ib/II— Non-Hodgkin's Lymphoma N Phase Ib/II - Fast Track— Y Phase Ib/II— Y Phase Ib/II— IOA-289 (Autotaxin Inhibitor)
Indication Combination Agent Development Phase 6 ABCDEFPreclinicalIND Enabling StudiesCTA/IND SubmissionPhase IPhase Ib/IIPhase II/IIICombination Partners Pancreatic Cancer N Phase Ib/II— Y Phase Ib/II— Myelofibrosis Y Phase Ib/II— IOA-237 (CD73 Inhibitor)
Indication Combination Agent Development Phase 7 PreclinicalIND Enabling StudiesCTA/IND SubmissionPhase IPhase Ib/IIPhase II/IIICombination Partners Solid Tumors N Phase Ib/II— IOA-359 (Undisclosed Target)
Indication Combination Agent Development Phase 8 PreclinicalIND Enabling StudiesCTA/IND SubmissionPhase IPhase Ib/IIPhase II/IIICombination Partners Solid Tumors N Phase Ib/II— Each of iOnctura’s programs target core mechanisms of resistance and relapse at the tumor-stroma-immune interface.
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IOA-244
The only semi-allosteric PI3Kδ inhibitor, with a unique chemical structure and binding mode
IOA-244 is currently in Phase I/II clinical development in indications burdened by immune mediated resistance and a high intrinsic expression of PI3Kδ in both the cancer cells and in the tumor immune landscape.
The phosphatidylinositol 3-kinase (PI3K) signalling pathway is one of the most dysregulated pathways in cancer. We are developing a novel PI3Kδ inhibitor (IOA-244) with exquisite selectivity over PI3Kγ, translating into a new first in class mechanism in solid tumors and a class-leading safety and PK profile.
IOA-244 is an orally dosed molecule that modifies the balance of immune cells to harness a natural and sustained anti-tumor response.
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IOA-289
The only Autotaxin inhibitor being developed in oncology
IOA-289 has completed a Phase 1a healthy volunteer study and a Phase 1b study in pancreatic cancer is in planning - it is being developed as a first-in-class therapy for indications that over express ATX and are burdened with by stroma mediated resistance.
Autotaxin (ATX) is an extracellular enzyme that generates lysophosphatidic acid (LPA). LPA is a bioactive phospholipid that stimulates the proliferation, migration and survival of many cell types and has been implicated in a wide range of diseases, including cancer. We are developing a novel ATX inhibitor (IOA-289) with superior potency compared to clinical-stage ATX inhibitors.
IOA-289 is an orally dosed molecule that inhibits the growth and proliferation of cancer cells, stimulates immune cell infiltration into tumors and inhibits the development of fibrosis.
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IOA-237
The immune modifying mAb with combination potential
IOA-237 is in preclinical studies and is being developed as a combination therapy with IOA-244 and IOA-289 in indications burdened by stroma and immune mediated resistance.
CD73 is an enzyme that generates adenosine. Adenosine is a potent immunosuppressive factor contributing to tumor growth and survival. We are developing a selective CD73 monoclonal antibody (IOA-237) that has superior potency on cell surface and soluble CD73 compared to clinical stage competitors.
IOA-237 is a fully human mAb that disrupts CD73-mediated adenosine production. It is cross-reactive to mouse and human CD73, enabling a rapid development pathway.
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Clinical trials
IOA-244-101 STUDY NCT04328844 (DIONE-01)
IOA-244-101 is a Phase 1a/1b, open label, dose escalation and expansion multicentre study of IOA-244, an orally bioavailable, selective PI3Kδ inhibitor in patients with metastatic malignancies. This is a two-part first-in-human study in approximately 60 participants, where Part A is a dose-escalation study with IOA-244 and Part B is a dose-expansion in parallel cohorts, including malignancies of Uveal Melanoma, Cutaneous Melanoma, Mesothelioma, Myelofibrosis, Non-Hodgkin Lymphoma and NSCLC.
The completed dose-escalation phase (Part A) evaluated the safety and tolerability of IOA-244 as monotherapy and documented preliminary signs of clinical efficacy benefit of IOA-244 as single agent in solid tumors.
The ongoing dose-expansion phase (Part B) evaluates the safety and tolerability of IOA-244 as monotherapy at the biological effective dose and in combination with standard of care therapies, such as pemetrexed/cisplatin and immune checkpoint inhibitors. Preliminary signs of clinical efficacy including overall response rate [ORR], progression-free survival [PFS], duration of response [DOR] and overall survival [OS] will be evaluated.
Additional study information can be found on clinicaltrials.gov
IOA-289-101 STUDY NCT05027568 (AOIN-01)IOA-289-101 was a randomized, double-blind, placebo-controlled, dose escalation study for the assessment of safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses (SAD) of IOA-289, an orally bioavailable, selective ATX inhibitor in healthy volunteers. The trial successfully completed in December 2022 with no negative safety or tolerability signals.
Additional study information can be found on clinicaltrials.gov
IOA-289-102 STUDY (AOIN-02)The IOA-289-102 Phase 1 study will investigate the safety, tolerability and activity of IOA-289 at the biologically effective dose in approximately 24 patients with pancreatic cancer. It is currently in preparation.
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Publications
- Poster presentation at ASCO 2022 (3-7 June 2022) entitled "First-in-human (FIH) phase I study of the highly selective phosphoinositide 3-kinase inhibitor delta (PI3Kδ) inhibitor IOA-244 in patients with advanced cancer: Safety, activity, pharmacokinetic (PK), pharmacodynamic (PD) resultsFirst-in-human (FIH) phase I study of the highly selective phosphoinositide 3-kinase inhibitor delta (PI3Kδ) inhibitor IOA-244 in patients with advanced cancer: Safety, activity, pharmacokinetic (PK), pharmacodynamic (PD) results". View
- Press coverage: BioWorld 26 May 2022; "iOnctura's IOA-244 to revive PI3K delta inhibitors?". View
- Poster presentation at the Cambridge Pancreatic Cancer Symposium (9-10 May 2022) entitled "The Role of CAF in Promoting Cancer Cell Proliferation". View
- Poster presentation at AACR 2022 (8-13 April 2022) entitled "iOnctura data at AACR demonstrates unique mechanism of action for clinical stage autotaxin inhibitor IOA-289". View
- Poster presentation at ESMO-IO 2021 (8-11 December 2021) entitled “Translating a novel autotaxin inhibitor from preclinical proof of concept in pancreatic cancer to a biomarker response in human subjects”. View
- Poster presentation at ESMO-IO 2021 (8-11 December 2021) entitled “First-in-human (FIH), pharmacokinetic (PK) and pharmacodynamic (PD) study of IOA-244, a phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, in patients with advanced metastatic mesothelioma, uveal and cutaneous melanoma”. View
- "Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8+ T cells". Cell Reports 37, 110013, November 16, 2021. View
- Poster presentation at SITC 2021 (10-14 November 2021) entitled “A novel autotaxin inhibitor, IOA-289, modulates tumor, immune and stromal cell function and has monotherapy activity in fibrotic cancer models”. View
- Poster presentation at ATS 2021 (14-19 May 2021) entitled “IOA-289 - a Novel, Clinical Stage Autotaxin Inhibitor for the Treatment of Fibrotic Lung Disease”. View
- Poster presentation at AACR 2021 (10-15 April 2021) entitled “IOA-237 - A potent anti-CD73 mAb demonstrates monotherapeutic and combination efficacy in solid tumour models”. View
- Poster presentation at ICCS 2020 (27-31 July 2020) entitled “The modulatory effects of a PI3Kδ specific small molecule inhibitor (IOA-244) on basophil degranulation measured by flow cytometry”. View
- Poster presentation at AACR 2020 Virtual Meeting II (22-24 June 2020) entitled “Characterisation of novel CD73 antibodies as a therapeutic method of adenosine regulation”. View
- Poster presentation at AACR 2020 Virtual Meeting II (22-24 June 2020) entitled “A novel, highly selective PI3Kδ inhibitor for the treatment of solid malignancies that express high levels of target protein as assessed by immunohistochemistry”. View
- Poster Presentation at MAP 2019 (7-9 November 2019, London, UK) entitled “Preclinical development of a novel, highly selective PI3Kδ inhibitor, IOA-244 for the treatment of solid malignancies”. View
- Oral Presentation at the PI3K/PTEN pathway: from basic science to clinical translation (18-20 July 2019, Bruxton UK) entitled “Preclinical development of a novel, highly selective PI3Kδ inhibitor, IOA-244, for the treatment of solid malignancies”. View
- Poster Presentation at FASEB 2019 (July 7-12, 2019, Lisbon, Portugal) entitled “Autotaxin as an emerging target in immunotherapy”. View
- Oral Presentation at 3rd Annual Next-Gen Immuno-Oncology Congress (14-15 March 2019, London, UK) entitled “PI3Kδ: A New Era in Immuno-Oncology”. View
- Oral Presentation at AACR 2019 (29 March - 3 April 2019, Atlanta, USA) entitled “Preclinical development of a novel, highly selective PI3Kδ inhibitor, IOA-244, for the treatment of solid malignancies”. View
- Oral Presentation at 4th Annual ICI Europe (27-29 November 2018, Berlin, DE) entitled “PI3Kδ: A New Era in Immuno-Oncology”. View
- Poster presentation at ECI 2018 (2-5 September 2018, Amsterdam NL) entitled “Characterisation of novel CD73 antibodies as a therapeutic method of adenosine regulation”. View