[Podcast: Access is Everything, with GlyTherix and Telix...

[Podcast: Access is Everything, with GlyTherix and Telix Pharmaceuticals | Phase III]

Rachel Williamson:

Who knew those Cold War nuclear waste stockpiles would come in so handy? They've gone from worthless to almost priceless in a few years. I'm Rachel Williamson, and this is Phase III.

In early 2023, one of the first two really big radiopharmaceutical drugs hit a problem. The brand new prostate cancer treatment Pluvicto was suddenly in short supply, snarling up just-in-time treatment schedules. The cause? Radiopharmaceutical company Novartis, its owner, had just one manufacturing site, and that was in Italy for a drug that needed to be delivered within five days. This was causing some big logistical challenges, and yet, Pluvicto still made Novartis almost $1 billion that year.

Fast forward to 2024. This year's supply chain scandal is around isotopes and specifically actinium-225, which has a 10-day half-life before it decays. This time, supply is under pressure because so many companies want it for clinical trials. In June, biotech company RayzeBio famously hit pause on part of its Phase III cancer clinical trial; it simply couldn't get enough actinium from its Russian supplier.

Rachel:

Russia, you say? Yes, medical exemptions allow Russia to export nuclear material despite the Ukraine war sanctions, much to the relief of the biotech industry, which is deeply in need of its nuclear resources. RayzeBio is owned by Bristol Myers Squibb, so it is part of a huge pharmaceutical company. If they can't get hold of the stuff they need, what does that mean for a tiny biotech at the start of its career?

Australian company GlyTherix is just such a tiny biotech, using zirconium-89 for an upcoming Phase 1B clinical trial. I asked the CEO, Dr. Brad Walsh, how they're negotiating supplies.

Dr. Brad Walsh:

Our key focus is in developing the drug. To that end, strategic alliances and supply agreements are the current pathway. We can focus on developing the drug, which is unique to us, and make sure that the drug is manufactured all the way through. The isotope suppliers are key, but in the future, once you get to kind of a Phase II, you might want to start thinking about a strategic alliance or even an acquisition of someone that can actually supply that downstream material you need.

Rachel:

I'd love for you to give me a breakdown of where GlyTherix gets its isotopes.

Dr. Walsh:

At the moment, GlyTherix gets its isotopes in Australia because of the stage we're at. We're still in those Phase I studies, and Australia is a great place for that. We have a supply agreement with ANSTO, which is for lutetium. This is the beta emitter used for therapy, so it's of key importance. We've had that locked in for about three years now.

Rachel:

Building your own cyclotron is an option. Would you go down that route?

Dr. Walsh:

Building your own is doable to an extent. Many companies have built cyclotrons, but there is a substantial capital commitment to do that. At the moment, our phase is better served by working with good partners who can provide those things for us. Building such a facility where you can make isotopes and put them onto drugs costs anywhere between $20 and $100 million.

Rachel:

That sounds like a high-wire act!

Dr. Walsh:

Indeed, it is. We've partnered with Cyclowest in Australia, which has built a cyclotron in Western Australia. They're rolling out cyclotrons in other places, which is quite exciting. We formed an alliance with Cyclowest, and they have invested in us, so we’re working closely together to bring that opportunity forward.

Rachel:

Globally, even the workhorse of cancer diagnostics, technetium, is in short supply. Actinium-225 is the latest example of what happens when too much demand meets physics. It's made from radioactive thorium-229, mostly found in dwindling nuclear waste stockpiles. Russia's state-owned nuclear agency, Rosatom, has invested heavily in being a key supplier. Nuclear medicine consultant Richard Zimmermann wrote that Germany and the US are the only other high-quality producers. Plans are in place worldwide to beef up manufacturing using new methods, but these need to deliver five to six times more of the material by 2032.

Rachel:

What geopolitical pressure points do you and your peers have to deal with in this industry?

Dr. Walsh:

The US is looking at Chinese suppliers, particularly for biologics and conjugations. Some fantastic companies, like GenScript and WuXi, are in China, but the US is pushing back due to perceived sovereign risks. There may be legislation to stop manufacturers from utilizing Chinese capabilities. On top of that, you have the issue of relying on Russia for supplies like actinium. Companies are now considering alternatives, including new isotopes like terbium and lead. ANSTO is working on supplying terbium-161 in Australia.

Rachel:

Our next guest, Dr. Chris Behrenbruch, CEO of Telix Pharmaceuticals, is on the other end of the spectrum, building a global, in-house manufacturing supply chain. Telix has invested heavily in this area, including acquiring isotope makers in Canada and radiochemistry companies in California.

Dr. Chris Behrenbruch:

Outsourcing isotope supply early in a biotech’s life is a necessary evil but one that hands over control to another company. Taking the keys back as early as possible was critical for Telix. When we acquired the Seneffe site in Belgium, part of the business case was building technological autonomy to scale up in-house production if needed.

Rachel:

Where are the next sourcing locations if not Russia?

Dr. Behrenbruch:

The field is maturing. Some countries, like India and some in Latin America, are investing heavily in nuclear medicine production. China, in particular, has an oncology problem due to its rapid industrialization. They’re investing heavily in radiation oncology and nuclear medicine as cost-effective ways to address the crisis.

Rachel:

Radiopharmaceuticals is a land grab right now for isotope supply. Even Telix is doing it through acquisitions. Are you a buyer like Eli Lilly or Novartis, or a takeover target?

Dr. Behrenbruch:

We’re focused on building the infrastructure to ensure these medicines get to patients. If a large company buys us out one day, it will be because we executed spectacularly. For now, we’re focused on controlling our supply chain and scaling up our production to meet future needs.

Rachel:

Thank you, Dr. Behrenbruch. That was Telix Pharmaceuticals CEO, Dr. Chris Behrenbruch.

Rachel:

Health systems are no strangers to complexity, but radiopharmaceuticals take that to another level. Supply chains will likely limit the number of companies that can truly succeed. The raw materials for isotopes, the limited locations where they can be made, and the logistical capabilities needed to move them around the world make this field a complex yet fascinating landscape.

Rachel:

Our next episode will delve into the complexities biotechs are more familiar with: making drugs and wrangling investors.

[End of Podcast]