IOA-359

Autotaxin inhibitor, IOA-289, recently received the proposed INN cambritaxestat Cambritaxestat is in the Phase I AION-02 trial in combination with chemotherapy in metastatic pancreatic cancer It is the first autotaxin inhibitor to be investigated in cancer patients AMSTERDAM and GENEVA, March 7, 2024 /PRNewswire/ -- iOnctura, a pioneering, clinical-stage biotechnology company developing transformative cancer therapies, today announces that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to its autotaxin inhibitor cambritaxestat for the treatment of pancreatic cancer. After assessing its novel chemical and biological properties including an attractive non-clinical safety and efficacy profile, the US FDA has granted Orphan Drug Status, conferring certain benefits during development and commercialization. Following a separate submission process the World Health Organization has proposed the International Nonproprietary Name (INN) of cambritaxestat. Cambritaxestat is being developed as a first-in-class therapy for highly fibrotic cancer indications. The drug's lead indication is metastatic pancreatic cancer where it is being combined with standard of care nab-paclitaxel and gemcitabine in the Phase I AION-02 study. Inhibition of autotaxin is a novel treatment strategy that offers a three-pronged attack on the tumor through direct cancer cell inhibition, immune effector stimulation and inhibition of fibrotic processes, giving drugs and immune cells better access to the tumor. Translational research showing the potential of cambritaxestat in multiple cancer models, including pancreatic cancer, has recently been published in the ESMO journal Immuno-Oncology and Technology (IOTECH), Cancer Research, the Journal of Experimental & Clinical Cancer Research, and Cancers. Across these publications, cambritaxestat showed strong reduction of metastasis and tumor outgrowth in preclinical models, as well as safe and tolerable dosing in healthy volunteers. Catherine Pickering, Chief Executive Officer, iOnctura, said: "There is an urgent need to develop new therapies for pancreatic cancer which is currently the third largest cause of death by cancer in the U.S., and the fourth in Europe. Although survival of patients with pancreatic cancer has improved in recent years, it still stands at just 13% after five years. This Orphan Drug Designation will support our goal to accelerate cambritaxestat through the clinic to provide a new treatment to patients with limited options." About iOnctura iOnctura is a clinical-stage biotech developing selective cancer therapies against targets that play critical roles in multiple tumor survival pathways. This pioneering approach to drug development is expected to offer significant clinical benefits over the traditional approach of targeting a single pathway alone. iOnctura has progressed two therapeutic candidates into mid-stage clinical development: Roginolisib, an allosteric modulator of PI3Kδ; and cambritaxestat, a highly selective, non-competitive autotaxin inhibitor. IOA-359, a TGF–β pathway inhibitor is also undergoing an extensive pre-clinical program in preparation for first-in-human studies. iOnctura is backed by specialist institutional investors including M Ventures, Inkef Capital, VI Partners, Schroders Capital, European Innovation Council and 3B Future Health Fund. iOnctura BV is headquartered in Amsterdam, The Netherlands with its wholly owned Swiss subsidiary, iOnctura SA, located in Geneva, Switzerland. About cambritaxestat (IOA-289) Cambritaxestat 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. Cambritaxestat is being developed as a first-in-class therapy for highly fibrotic cancer indications that overexpress autotaxin including pancreatic, liver, colorectal, ovarian and breast cancers. A Phase I study of cambritaxestat in combination with chemotherapy in metastatic pancreatic cancer started in Q4 2022 (NCT05586516). SOURCE iOnctura

Updated safety and clinical efficacy data presented at leading immuno-oncology conference Exploratory studies suggest roginolisib boosts antitumoral immunity, whilst simultaneously disrupting tumor survival mechanisms Data suggest the potential of radiomics to assess changes in lesions over time, adding value above RECIST (Response Evaluation Criteria in Solid Tumors) GENEVA and AMSTERDAM, Dec. 8, 2023 /PRNewswire/ -- iOnctura, a clinical-stage biotech developing selective cancer therapies against targets that play critical roles in multiple tumor survival pathways, today announces clinical results for roginolisib, a first-in-class oral allosteric modulator of PI3Kδ, presented at the ESMO Immuno-Oncology Congress 2023 in Geneva. Roginolisib is in development for solid and hematologic malignancies including uveal melanoma, a rare cancer of the eye. The poster presentation titled 'Safety and clinical efficacy of Roginolisib (IOA-244), the first oral allosteric modulator of phosphoinositide 3-kinase inhibitor delta (PI3Kδ)' demonstrated that roginolisib continues to be well tolerated over long periods of treatment and continues to show a favourable trend in overall survival exceeding the overall survival previously reported with immune checkpoint inhibitors. Mass cytometry data showed treatment with roginolisib led to an increase in activated anti-cancer CD8+ T-cells and natural killer (NK) cells, increased interferon signalling and a decrease in cancer-promoting Regulatory T-cells. This shifts the balance of the immune system enabling a more-effective attack on cancer. Boosting of antitumoral immunity was observed in patients with long-term disease control after roginolisib treatment but not patients with progressive disease. An exploratory analysis from a patient with uveal melanoma outlined the potential of radiomics, an advanced AI driven analysis of imaging data, as a way of tracking changes in cancer lesions over time in addition to standard RECIST measurements. Overall, these findings are consistent with prior studies in pre-clinical models and support the development of roginolisib in uveal melanoma and other malignancies with immune suppressed conditions. Catherine Pickering, Chief Executive Officer of iOnctura, said: "These safety and clinical efficacy data demonstrate iOnctura's progression of roginolisib. Our first-in-class allosteric modulator of PI3Kδ continues to show a favourable trend in overall survival and is well tolerated over very long periods of treatment, now up to 38 months in patients with uveal melanoma. An exploratory readout also shows that patients who respond well to roginolisib, with prolonged stabilisation of their disease, exhibit signs of an activated immune system better able to fight the tumor. We eagerly anticipate a final clinical readout in 2024." About iOnctura iOnctura is a clinical-stage biotech developing selective cancer therapies against targets that play critical roles in multiple tumor survival pathways such as cellular proliferation; escape from immune detection; and drug resistance. iOnctura's pioneering approach to drug development is expected to offer significant clinical benefits over the traditional approach of targeting a single pathway alone. iOnctura has progressed two therapeutic candidates into mid-stage clinical development: Roginolisib (IOA-244), an allosteric modulator of PI3Kδ; and IOA-289, a highly selective, non-competitive autotaxin (ATX) inhibitor. IOA-359, a TGF–β pathway inhibitor is also undergoing an extensive pre-clinical program in preparation for first-in-human studies. iOnctura is backed by specialist institutional investors including M Ventures, Inkef Capital, VI Partners, Schroders Capital, and 3B Future Health Fund. iOnctura BV is headquartered in Amsterdam, The Netherlands with its wholly owned Swiss subsidiary, iOnctura SA, located in Geneva, Switzerland. About roginolisib Roginolisib (IOA-244) is a first-in-class small molecule allosteric modulator of PI3Kδ. Its unique structural and selectivity features drive a unique way of inhibiting PI3Kδ which translates into a highly beneficial tolerability and clinical benefit profile. PI3Kδ over-expression stimulates multiple cancer mechanisms and has an oncogenic role in many tumor types. Roginolisib has a multi-modal effect on cancer; directly preventing cancer cell proliferation, harnessing an anti-tumor immune response via an effect on regulatory T-cells and cytotoxic T cells and potentiating the effect of immunotherapy. Roginolisib is currently in the extension phase of the DIONE-01 trial, a two-part, first-in-human dose study evaluating the drug in advanced cancers and as a combination partner for conventional and immune-therapies (NCT04328844). SOURCE iOnctura