Turning Shelved Drugs into a New Promise for Immuno-Oncology

After working for 12 years at Merck, Catherine Pickering decided to take a risk and create iOnctura, a spin-out company exploring a new application in immuno-oncology for a drug candidate that had been shelved. 

In the last decade, there has been a massive boom in the development of cancer therapies that use and enhance the body’s natural ability to fight cancer. However, the initial promises of immuno-oncology therapies such as checkpoint inhibitors don’t seem to have been fulfilled yet.

“I’m not sure that checkpoint inhibitors have become the dream that everyone thought they would,” Catherine Pickering told me. “It is expected that the market size of these checkpoint inhibitors will reach over $30Bn by 2025. I find this eye-watering when one considers that they work in only a small percentage of patients.”

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Pickering has been close to the immuno-oncology field throughout her career. She started her professional journey with a PhD at the Institute of Cancer Research in London, where she then worked as a manager at the tech transfer unit when it was just starting out. After an MBA and working in business development at the biotech company Antisoma, she was recruited by Merck.

Pickering was heading Merck’s business development oncology team during the immuno-oncology boom. At the time, Merck was developing Bavencio, a checkpoint inhibitor drug that is now approved to treat metastatic forms of skin and bladder cancer.

“I was responsible for the Pfizer deal on Bavencio,” said Pickering. “Actually, that stimulated me to think about branching out on my own.”

For a while, Pickering had wanted to start a project of her own. Her plans panned out when she found a drug candidate around which she could build a business. Pickering got over €2M in seed funding from Merck for her idea, and two years ago she founded iOnctura in Geneva, Switzerland.  

“Our lead asset, which we’re about to bring into the clinic, was actually developed by Merck for lupus,” Pickering explained. After a first study in humans, Merck decided to stop its development. “They shelved the molecule for strategic reasons and did nothing with it.” 

The drug candidate targets PI3K-delta, a molecule that has historically been linked to diseases affecting the blood — including lupus, whose many symptoms include several blood conditions such as anemia. But a few years after the drug candidate was shelved, academic researchers started to figure out that PI3K-delta was present in several types of immune cells. Pickering realized that this meant the drug had potential in a completely different field. 

“We’ll be the first company to actually look at PI3K-delta as a single agent or as a monotherapy in solid tumors,” said Pickering. 

In particular, the company will be targeting those tumors that have high levels of PI3K-delta. It is known that lowering the levels of this molecule can deplete regulatory T cells, which are a type of immune cells that can be recruited by tumors to protect them against immune attacks. 

In addition, iOnctura has found that even in animal models without immune cells, the drug can make tumors with high levels of PI3K-delta shrink. The company is now going to explore this additional mechanism of action in its first clinical trial in humans, which is expected to start later this year. 

First of all, iOnctura will seek to demonstrate the potential of this drug as a single therapy. But going forward, Pickering is confident that this new take into immuno-oncology could offer a solution to the limitations of checkpoint inhibitors. 

“One of the issues with a lot of cancer indications is that they’re heavily burdened by this immunosuppressive tumor microenvironment. If PI3K-delta can redress the balance of active versus immunosuppressive immune cells, it will enhance the activity of the checkpoint inhibitors. We have quite a lot of data in several models that show this synergistic effect.”

Interestingly, other drugs in iOnctura’s pipeline have also been historically used for indications other than cancer. Two of its programs, coming from Cancer Research UK, center around autotaxin inhibitors. These molecules are being developed as treatments for fibrotic diseases — for example, the Belgian company Galapagos is running phase III trials with an autotaxin inhibitor to treat pulmonary fibrosis. 

The company has given these molecules a new spin. They can be used to target fibrosis produced by cancer. In solid tumors, a fibrotic shell can grow around the tumor. “It’s actually a physical barrier to the immune system,” explained Pickering. “We believe that if you take down levels of autotaxin in the tumor’s microenvironment, you allow the immune system to enter by breaking down the fibrotic barrier.”

With fresh ideas to test out, iOnctura is now getting ready for a major next step: its first clinical trial. The company is now in the process of closing a Series A round that will allow the company to start a phase I trial later this year. Looking ahead, Pickering is considering working with pharma to study the combination of the drugs in the pipeline with checkpoint inhibitors. Meanwhile, Merck will be following what this new company is able to do with a molecule that had been shelved and forgotten for years. 

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