Pipeline & Science

The phosphatidylinositol 3-kinase (PI3K) signalling pathway is one of the most commonly dysregulated pathways in cancer. PI3Kδ is one of four isoforms of the catalytic subunit of PI3K kinase. Whilst its expression is normally restricted to immunosuppressive cells such as regulatory T cells and myeloid-derived suppressive cells, some cancers intrinsically express high levels of PI3Kδ which acts to promote tumor cell survival.

We are developing a novel PI3Kδ inhibitor (IOA-244) with exquisite selectivity over other isoforms. 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 cancer cells and tumor-infiltrating immune cells.

Clinical data generated to-date has shown the drug to have an exceptional safety profile and promising clinical activity in solid tumors and hematological malignancies.

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) that has superior potency compared to clinical-stage ATX inhibitors. We are the first company to bring an ATX inhibitor to the clinic to treat cancer.

IOA-289 is an orally dosed molecule that has shown preclinically to inhibit the growth and proliferation of cancer cells, stimulate immune cell infiltration into tumors and inhibit the development of fibrosis.

IOA-289 is being developed as a first-in-class therapy for highly fibrotic cancer indications that overexpress ATX including pancreatic, liver, colorectal, ovarian and breast cancers.

A Phase 1b study of IOA-289 in combination with chemotherapy in metastatic pancreatic cancer started in Q4 2022.

Activation of the transforming growth factor beta (TGF-β) signaling pathway in tumors correlates with tumor aggressiveness, immune escape and resistance to therapy.

We are developing IOA-359, a novel small molecule TGF-β pathway inhibitor, in solid tumors. By characterising the resistance mechanisms that typically arise when targeting the TGF-β pathway alone, our data-driven precision oncology methods are being used to design novel combination treatments that promise to override tumor survival pathways.

CD73 is an enzyme that generates adenosine. Adenosine is a potent immunosuppressive factor that contributes to tumor growth and survival. We are developing a selective CD73 monoclonal antibody (IOA-237) that has superior potency on cell surface bound 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.

IOA-237 is in preclinical studies and is being developed as a monotherapy or in combination therapy with IOA-244 and IOA-289 in indications burdened by stroma and immune mediated resistance.

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 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 2021 with no negative safety or tolerability signals.

Additional study information can be found on clinicaltrials.gov

The IOA-289-102 Phase 1 study is investigating the safety, tolerability and activity of IOA-289 in combination with standard chemotherapy at escalating doses in approximately 24 patients with metastatic pancreatic cancer. It started in Q4 2022.