iOnctura is a clinical-stage biotechnology company developing precision small molecule therapies that target tumour-intrinsic and immune-mediated resistance mechanisms in hard-to-treat cancers.
Why did you decide to focus on small molecules at iOnctura?
Actually, when we founded iOnctura our focus was more on the mechanism rather than the modality. At the time, immunotherapies and especially checkpoint inhibitors were the big trend, but the tumour was already developing resistance mechanisms to evade those therapies. Many thought it would be easy to just block those resistance mechanisms, but that has not been the case. So while immunotherapies remained fashionable, we saw an opportunity to address these complex resistance mechanisms, and that led us to investigate a mix of large molecules and small molecules. However, it was really the highly selective, differentiated small molecules that got us most excited. Also, as a small company, it is easier to develop small molecules because they require less upfront investment to get into the clinic. For first-in-class drugs, I think small molecules are easier when it comes to raising money.
Could you explain the tumor-stroma-immune interface and how you target it?
The targets we have selected are ones the tumor upregulates in order to survive. That means the targets are active within the tumor itself, but also help the tumor manipulate its environment to evade the immune system. For example, in our lead program, the tumor upregulates the PI3Kδ target to survive and also orchestrates an immune response to suppress active immune cells that would otherwise attack it. By inhibiting the PI3Kδ target with our highly selective allosteric modulator roginolisib, we have a dual mechanism to directly stop tumor proliferation as well as to unveil the tumor to the immune system.
Similarly, our second program targets autotaxin, which is an attractive proposition in pancreatic cancers as well as in GI tumors like gastric, colorectal, and liver cancers. These tumors upregulate autotaxin to survive, while also forming a fibrotic shell and manipulating surrounding cells to avoid immune attack. So, the autotaxin target functions with a dual mechanism here too: one intrinsic to the tumor and one influencing its microenvironment. The tumor microenvironment is like an orchestra—the tumor is the conductor, directing the cells and stroma around it to protect itself from the immune system. Our job is to silence that orchestra.
Your lead candidate is targeting uveal melanoma and is now entering Phase 2. Could you share a few words on its promise and progress so far?
We brought this program in at the preclinical stage when we founded the company. Interestingly, the molecule was initially developed for lupus and never went into patients, but it came from a place of high precision and safety—important for chronic diseases. We repurposed it for cancer, did extensive preclinical work, and found it suitable for oncology indications that upregulate PI3Kδ and have immunosuppressive environments.
We have taken it into uveal melanoma and have just dosed the first patient in a randomized Phase 2 study. We are also exploring lung cancer, myelofibrosis and blood cancers, in parallel Phase 2 studies. So, we will soon have four Phase 2 studies recruiting. The mechanism spans multiple metastatic cancers, and we have selected indications that align with our dual mechanism approach.
What can patients hope for should these studies progress well?
We are very focused on prolonging health span and overall survival for patients with later-stage cancers. In our phase 1b study with 29 uveal melanoma patients, we doubled overall survival compared to historic controls. Importantly, the drug showed a very safe profile. It is a once-daily pill patients take at home without the toxicities typically seen in this class.
To give you concrete figures: in second or third-line metastatic uveal melanoma, patients typically have a survival of five to eight months. We achieved a median overall survival of 16 months. That is significant and something we are very proud of. Our data is available through our ASCO and ESMO-IO posters on our website.
Your Series B funding was partly supported by the European Innovation Council Fund. What is your perspective on doing biotech business in Europe compared to the US?
I cannot speak for my US counterparts, but for us, the challenge has been about having the right data. Once we had a differentiated product and a clear route to market, we were successful in fundraising. I think both in Europe and the US, biotech companies are struggling to attract the right financing—it is not just a European issue.
As a European company, we do have access to certain advantages. For example, we can run four phase 2 studies at a much lower cost than in the US, and we can engage directly with European clinical centers. That allows us to complement our data with US data later, while keeping budgets reasonable. There are certainly pros to being in Europe, and we are balancing that with expansion to the US.
Why should our readers remember the name iOnctura?
iOnctura means “to combine” in latin, and our pipeline consists of precision small molecules and tools to advance combinations targeting highly resistant tumors. We have a leading pipeline of highly selective drugs that strike the tumor where it hurts, and we are committed to succeeding in treating very difficult, hard-to-treat cancers.
