ONCOLOGY THERAPY
had collaborated while at Merck. Pickering says the next phase of cancer drug development will look at stromal targets and, to this effect, targeting the tumour stroma and the immune space is the backbone of the company’s platform, she says. One of its lead drugs, PI3Kdelta inhibitor
IOA-244, is being studied in a Phase Ib trial for patients with uveal melanoma, after being trialled in a Phase Ia study. PI3Kdelta and PI3Kgamma are expressed exclusively on immune cells, unlike alpha and beta isoforms. As per data from the Cancer Genome Atlas,
high levels of PI3Kdelta in the tumour are associated with an immunosuppressive microenvironment. Pickering says the drug’s clinical development is banking on that, with the Phase Ia study having enrolled cancers with a high expression of the PI3Kdelta and a high burden of regulatory T or Treg cells. Uveal melanoma is a cancer type with a high
PI3Kdelta expression. Late last year, iOnctura presented Phase Ia dose escalation IOA-244 data in mesothelioma and cutaneous and uveal melanoma at the ESMO (European Society for Medical Oncology) Immuno-Oncology Congress. No dose-limiting toxicities were detected. While the uveal melanoma trial is recruiting in
Italy and the UK, iOnctura plans to file an IND (investigational new drug) application with the Food and Drug Administration for it to expand in the US. Even though uveal melanoma is rare, there have been no enrolment challenges in recruiting patients so far, Pickering says, noting this could be due to high unmet need. Uveal melanoma is an aggressive disease and 50% of patients who undergo surgery targeting the primary tumour are still likely to develop metastatic disease. The company also plans to explore the
resistance mechanism of checkpoint inhibition in melanoma, which is driven by Tregs, where IOA-244 will be combined with a checkpoint inhibitor once the patient has progressed on the latter, Pickering notes. Preclinical data has shown that the drug
doesn’t compete with ATP, unlike others that target PI3Kdelta, which makes it a very selective PI3Kdelta inhibitor, Pickering says. Drugs that target this mechanism have had a burdensome safety profile in the past, but the selective nature of this therapy avoids this issue, she adds.
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“One of the company’s lead drugs, PI3Kdelta inhibitor IOA-244, is being studied in a Phase Ib trial for patients with uveal melanoma. Preclinical data has shown that the drug doesn’t compete with ATP, unlike others that target PI3Kdelta, which makes it a very selective PI3Kdelta inhibitor”
Funding strategies As for fundraising plans, iOnctura is talking to several VCs to fund the next phase of the company. It is important that the next fundraise should involve a syndicate that will support the company going public at the right time, Pickering says. Hence the company is talking to US crossover investors and larger European investors, she adds. iOnctura is also having discussions to consider nondilutive financing and expanding beyond its core geographies, so there is a lot of optionality for its funding strategies. iOnctura has also recently completed a Phase
Ia study of the company’s autotaxin inhibitor, IOA-289, in healthy volunteers. Once the right dose is identified, the drug will be investigated in a pancreatic cancer trial.
Image: iOnctura
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