Radiotherapies: Q&A with Thijs Spoor

Thijs Spoor
CEO
Perspective Therapeutics

Treating cancers can often result in damage to organs and other parts of the body. Thijs Spoor, CEO of Perspective Therapeutics, spoke with Pharmaceutical Executive about how radiopharmaceuticals are helping researchers target tumors more directly and avoid collateral damage.

Pharmaceutical Executive: Can you describe your primary focus at Perspective Therapeutics?
Thijs Spoor: We are developing next-gen radio-therapy agents. We invest a lot of time in our business in chemistry to develop best-in-class category killers. A nice thing about this field is that if you pick the right isotopes, you can almost prove in advance what you’re trying to show. You can de-risk things massively by showing proof-of-concept in animals, and then imaging and treating animals before moving on to humans. Before we’re treating humans, we believe we’ve taken the root development risk way down.

PE: Can you discuss the science behind radiopharmaceuticals?
Spoor: There are a few ways to think about it. We need to bind to a cell and then kill that cell. The mechanism of action for the radiopharm is to bind to it, and then you’re going to smash it apart with an alpha particle. It’s not subtle, but it works.

Antibody drug conjugates (ADCs) target the cells, but there are a few more steps. You must internalize the drug, have the payload get cleaved off, and then have the payload perform an action in the cell. At the end of the day, radiopharms and ADCs are both targeted therapies, but we believe we’re saving some steps.

The luxury we have with the isotopes that we’ve chosen is that we’re using the same elemental twins or chemical to show what’s happening to the human or animal in real time. We can inject the drug and then see what happens within one hour of injection versus the following day, without causing any damage to the patient. There’s an imaging version of radiopharms, which is injected before the therapy version. It’s the same chemical, you just swap the isotope from the version that gives off the gamma image to one that fires off an alpha particle that kills cancer cells.

You design the drug to deliver the therapy to the cancer cell and attach it, like a mine against a ship. If you think of another a weapons analogy, it’s like using tracer bullets and then regular bullets. The imaging molecule shows where it’s going ahead of time, so we can be very precise with where the damaging stuff hits. We have the ability to localize the impact.

PE: What are the benefits of this method?
Spoor: If we think about how we’re going to deposit the alpha particle on the tumor, we can use the imaging molecule in real-time. In a series of mouse images, we used three different compounds that can bind directly to tumors. In one image, we identified a sarcoma in the mouse’s shoulder, along with some energy in the kidneys. In a different image of the same mouse, we were able to get an image of the activity in the kidneys, while the sarcoma didn’t show up as well. In a third image of the mouse, we were able to target the sarcoma more directly with very little activity being shown from the kidneys.

Picture a 300-degree piece of metal coming out of the oven. If someone throws it to you and you throw it away very quickly, you probably won’t get badly burned. But if you catch it and grip it, then you’ll be very badly burned. What really matters with the payload is knowing not just where it’s going to go, but where it’s lingering. If it lingers on the tumor for a day, you’ll burn that tumor, which is good. However, if it lingers on the kidneys for a while, that’s a bad outcome. You want it to go just to the tumor and nowhere else.

PE: What are the practical uses for this?
Spoor: You’re using these to identify patients that you can treat. For the most part, we’re not interested in trying to diagnose the disease. PET scans looking for cancer are picking up every glucose-hungry cell in the body, which is why they work. They identify hyper-metabolically active cells, which are likely tumors. However, these will also pick up a lot of activity in the brain, which is why PET scans aren’t used to image for tumors in the brain.

Radiotherapeutics, however, target certain biomarkers which we find are present in certain cancers. Not all cancer patients, however, will express these targets or express them in a useable way. What we can do is target biomarkers and show where a therapy has a good chance at working.

We can identify which sites will be hit by a systemic therapy and how to do so in a way that minimizes damage to other organs.