NUKED: Australia the nuclear power, with entX and Cyclowest

Can Australia create a mine to lab to bedside production line for radiopharmaceutical medicine? It has the reactor, biotechs and the hospitals to do that last two, and even has a growing pool of expertise to run these. 

What it doesn't have, yet, is many advanced manufacturers to do the first bits, the critical parts such as sifting through old mine tailings for precursor materials and making nuclear isotopes for industry use, such as clinical trials. 

In episode 4 of NUKED we speak with entX managing director Bryn Jones and Cyclowest head of production Dr Jacquie Cawthray about whether Australia has the 'it' factor to go it alone. 

Chapters

• 3:25 entX managing director Bryn Jones
• 18:07 Cyclowest head of production Dr Jacquie Cawthray

Transcript

Rachel Williamson: 0:00

If Australia wants to be a global leader in radiopharmaceuticals, that future is likely going to come down to advanced manufacturing. A section of industry, the country still hasn't come to grips with.

I'm Rachel Williamson, and this is Phase III.

Only South Australia so far has publicly come out and said 'we want Australia's radiopharmaceutical industry to be here'. It planted the flag earlier this year by backing a report called From Mines To Medicines. It has the infrastructure, the innovators, and the radioactive mine tailings from which to make the hot new isotopes.

But it's up against some heavy hitters. Victoria is the country's biotech hub. New South Wales hosts the country's only nuclear reactor in the Sydney suburb of Lucas Heights. The University of Queensland has the brand new federally funded ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals. That is a mouthful and more easily known as AMTAR. And Victoria and New south Wales are also where most of the patients are. Although, perhaps not for long given the way logistics companies are aiming to bring the medicine to the people rather than the other way around.

People are saying that Australia could have its own mine to bench to bed radiopharmaceutical industry. Australia has proved it can grow biotechs to global size. The A$7 billion dollar Telix Pharmaceuticals is an example of that in the radiopharmaceutical industry. You might remember in episode two of the series that I said it was a $6 billion company? Well, its market cap has gone up almost a billion dollars since we recorded that interview. Industry bodies have been training new people to work in this industry for some time now. And the country has a strong isotope supply chain thanks to a world-class reactor run by nuclear science agency ANSTO, and a growing number of cyclotrons and generators around the country. 

But what it's lacking are the precursor ingredients to make some of the more novel isotopes. And a level regulatory playing field for private manufacturers. 

entX is one of those companies that is making both isotopes and precursor ingredients. It is making lead 212 from thorium and radium, partly sourced from mining waste in Australia. And it has a top secret method for extracting the precursor materials needed to make in-demand isotopes lutetium 1 77 and terbium 161. 

And if you're keen on this sort of thing, managing director Bryn Jones says they're thinking about perhaps listing on the ASX. But I wanted to talk to him about something else: whether Australia has the 'it' factor needed to go it alone as a radiopharma global hub. And that means being able to make everything from ine as one report put it, to edicine. 

I know space is the first frontier for emtX. But the second frontier is nuclear medicine with your subsidiary IsoMedica. You personally have a background in uranium mining. But you saw radiopharmaceuticals as being a really promising area. Can you tell me why?

Bryn Jones: 3:45

I guess at entX our background is from the mining industry, from the resources industry. Back in 2016, I started talking to our chief technology officer, Julian Kelly, about, the sort of, growing radiopharmaceutical market and whether we could, access some of the sort of, what would traditionally be called waste materials from some of these mining operations and really look at where we could secure, isotopes of medical value and put them into the emerging supply chains for these, for these types of radioisotopes. So you know, in particular, I guess what we're focused on at the moment producing lead 212, and, uh, lutetium 177, which is you know, by far the biggest and, and fastest growing radio pharmaceutical.

Rachel Williamson: 4:30

Miners moving into medicine is not as weird a concept as it sounds. After all mining is just chemistry, and radioactive isotopes are a feature of that work. In fact, Bryn's old boss is the CEO of Energy Fuel, a US rare earths and uranium miner and processor. And they are also moving into medical isotopes. This industry is also turning other companies into miners of sorts. TerraPower in the US wants the waste from spent power station fuel to make thorium and then actinium 225. But Bryn, you are based in South Australia with your IsoMedica lab and that's in the South Australia Health and Medical Research Institute...

Bryn Jones: 5:12

Correct. Yeah. The SAMRI basements. That's right. Yeah. Uh, they lock us away three levels below ground level. And we, uh, do our work down there.

Rachel Williamson: 5:19

How feasible is the idea of an Australian made supply chain for all of the isotopes that are actually needed in radiopharmaceuticals?

Bryn Jones: 5:29

I look, I think entirely possible. And obviously we're blessed with the natural resources that host some of these materials. We're obviously trying to be ahead of the curve there in terms of responding not only to the market as it could be in 30 years, but responding to the market now and then growing as the market grows, which I think's critical in these sort of radiation handling. Cause as I said, we're permitting a facility to commercially produce these types of isotopes in South Australia here, but it's certainly not a walk up start.

Is it feasible in South Australia? Absolutely. We have the natural resources up, up front. Um, we have groups like entX that are more than willing to...

Rachel Williamson: 6:04

Natural resources like the Olympic Dam uranium mine? Up in the middle-ish of South Australia? That's BHP's isn't it?

Bryn Jones: 6:13

Yeah, yeah, Olympic Dam amongst others. We have actually some, some tailings at Port Pirie, which is from historical uranium mining operations. That has a lot of this material and so it's really just about finding that material, finding pathways to extract the value components from those materials, and then getting it into quality environments that can meet the pre-medical sort of, qualifications you would need to supply that material into the medical industry.

Rachel Williamson: 6:41

But you've got that deal with Tellus Holdings as well, the company that runs the Sandy Ridge low level radioactive waste facility in Western Australia. And it takes a whole range of waste, including mining tailings. And so do you just say to them, 'sell us all your nuclear waste and we'll turn it into medicine'?

Bryn Jones: 6:58

Well, so we have a joint developer agreement with Tellus so that they sort of keep an eye on what's coming through their facility. And if there's something that comes across their desk that has a medically valuable sort of component to it, they'll give us a call and say, 'Hey, this is the material. What do you think?' And we might collect a sample of that material and put it through our process and say, You know, either yes, that's great material for us, or or, um, the economics don't quite work. And so we've got this, this fantastic sort of mutually beneficial arrangement for effectively looking at some of those waste materials that are coming through their process.

Rachel Williamson: 7:37

What kinds of rock don't work? What can't you easily get thorium say or ytterbium out of.

Bryn Jones: 7:43

There's some wastes that are a little bit, you know, a tough nut to crack in terms of the chemistry. Uh say if you, if you've got a stream that has a high gypsum component, for example, with gypsum is one of those materials that's notoriously hard to, to leach and to dissolve, so if you had to dissolve a lot of material that had gypsum as its host that might cost a lot of money. And so you've got to then make an economic determination on whether, you know, the money you're throwing at the waste material is going to pay you back in terms of the medical value that you can extract from that material.

Rachel Williamson: 8:16

I think now is an obvious time to talk about entX's secret technology. You're wanting to make lead 212 and ytterbium 1 76, the precursor to lutetium 1 77. How, with what and, and why these ones?

Bryn Jones: 8:33

Yeah, so two, sort of two different supply chains there. We might keep on the lead 212 track for now. Um, where where it comes from is effectively the, the, the thorium, so naturally occurring thorium, uh, which you quite often find in the rare earth industry. So monazite, uh, bastinite are a couple of rare earth minerals that are commercially processed to make rare earths

Rachel Williamson: 8:54

And you're sourcing all of the thorium from Australia?

Bryn Jones: 8:58

Australia and Europe at the moment is our two, our two focuses. So we, um, uh, we certainly have been working with a number of sources. Um, so when you, when you have that sort of natural thorium the way radiation decay works, it, it, it goes from one through several steps before it ends up as lead 212 and, and radium is one of those sort of intermediary steps and that's the, really the basis of our technology is to, is to capture and concentrate that radium, so that we can then, uh, milk a product off of that radium that goes into the lead 212 supply chain.

Rachel Williamson: 9:34

And what about lutetium? Is that a similar process?

Bryn Jones: 9:37

Lutetium, effectively is, is produced by concentrating a particular isotope of ytterbium. Ytterbium has five natural isotopes. And what you want to make lutetium is basically you want concentrate up the ytterbium 176 uh, isotope within that natural ytterbium. And then that ytterbium 176 goes into a nuclear reactor where a small portion of that ytterbium gets made into lutetium by neutron bombardment within the nuclear reactor. Obviously ytterbium in its natural form is non-radioactive, so in this case we're not really working with radioactivity, what we are doing is manipulating the isotope ratios of that natural ytterbium to concentrate up the ytterbium 176 component.

Rachel Williamson: 10:29

Here, I'm going to call a timeout. 

There is a reason why entX is keen on ytterbium and one other company in Australia, Silex Systems, is too. All lutetium in Australia has to be made in the Sydney reactor by the nuclear tech agency ANSTO. But Bryn says Russia supplies 80% of the world's ytterbium 176 feedstock. Russia, also supplies most gadolinium the precursor to the newest, sexy isotope, terbium 161. entX is also looking at making gadolinium. 

So let's talk about why Russia is such a big dog. Russia's nuclear agency, Rosatom, has been building the kind of infrastructure needed for medical isotopes since it launched a nuclear industry, The basis of this technology is the calutron. A calutron exploits the tiny mass differences between the different isotopes of ytterbium to physically separate them. Contrast this to the US which wanted to kill its last calutron in 2002. Russia hawks blocked that move because it would have made the us completely reliant on their former, and again, current arch rival for critical isotopes. 

Proving just how shaky that supply is right now. The US has just banned imports of enriched uranium from Russia. US president Joe Biden signed the bi-partisan law in May, to put more pressure on Russian leader, Vladimir Putin, over his war in Ukraine. It's supposed to be just for nuclear power sources. But it's still a reminder that all things nuclear can still be at politically radioactive. It also came with $US2.7 billion in funding to get companies like entX up and running. Back to Bryn. 

How are you concentrating ytterbium 176 without being in Russia or owning a calutron?

Bryn Jones: 12:34

So we we're taking a slightly different tack. It's a bit of a proprietary sort of technology, but we've actually developed an ion exchange resin that will, um, selectively concentrate the ytterbium 176 component and it works on the different sizes and shapes of the of the atoms. 

The platform technology that we've developed for lutetium 177 will be applicable for gadolinium as well. So there'll be a few tweaks we'll have to make to the technology, but effectively the development work that we've done for lutetium will be equally applicable to the, to the gadolinium. Again, what we're seeking to do is, displace Russian supply effectively for that, precursor, which in this case is gadolinium 160, is to supply that gadolinium 160 into say, ANSTO as a customer long term.

Rachel Williamson: 13:20

Ion exchange resins are common in water softening. A negatively charged resin bead attracts positively charged minerals in the water. In the case of nuclear isotopes, the resin beads attract ytterbium 17,6. entX will have a fully operational commercial factory for making isotopes in South Australia by the end of 2025. lead 212 is the lead product. It conveniently has a 10 hour half-life, so delivery from South Australia to major patient centres in Victoria and New South Wales isn't such a problem. 

But there is one issue on the horizon that could throw a massive spanner in the works for a growing radiopharmaceutical industry in Australia, let alone South Australia. AUKUS. 

Bryn are you concerned at all about the Australia, UK, US military submarine pact leeching talent away from you, with high salaries and so forth?

Bryn Jones: 14:19

Yeah. It's, it's it's certainly something that we, we think about. A lot of the, the skill sets that we have in house are skill sets that the AUKUS community in, in more broadly would, would want, right? So we've got high radiation competence, we've got great project management skills, we've, we've got all the components that would lend themselves well to that type of environment. 

The reason we've been so successful in, keeping staff is the fascinating work we do. A lot of these people, uh, sort of high performing, intellectually capable people that we, that we employ have really curious minds and want to be, want to be active. If you sort of said to those people, well, you can, you can earn 15% more potentially, but you're going to be sitting at a desk doing paperwork. They might think about it, but, um, we like to think that we provide a pretty stimulating work environment, um, and then some leverage to success of the company as well.

Rachel Williamson: 15:10

That was entX managing director, Bryn Jones. He's building a company that builds on mining know-how to move into medical chemistry. And entX is not the only one doing this in Australia. Silex Systems began testing it's ytterbium-concentrating tech with ANSTO in 2023. 

These kinds of technologies lay the groundwork for a raw material supply chain that can feed the isotope makers like ANSTO. Which can feed the radiochemists, who can deliver drugs and diagnostics to patients. 

Our following guest is from the next step up in the chain. She is one of the isotope makers.

Charis Palmer: 15:54

Hi there, I'm Charis Palmer, producer of Phase III. When Rachel and I set about building a new podcast for life science leaders, scientists, and long suffering biotech investors, we looked at what was missing in this space. We believe Phase III serves an unmet need for in-depth conversations in a world where nuance matters and AI-written investment articles simply won't cut it. If you agree, please follow us and sign up to our newsletter via LinkedIn, pledge financial support at phasethree.Buzzsprout.com and rate and review the podcast on the podcast platform you use, to help bring it to the attention of others. Now, back to the show.

Rachel Williamson: 16:33

There are some hurdles in the way of Australia building a standalone supply chain of radiopharmaceuticals. 

We've mentioned that the AUKUS nuclear submarine packed. Many fear, it will suck talent away from the emerging medical sector. 

And if Australia were to attempt to build one nuclear power plant, let alone seven, the drag on talent and resources would be even worse. 

Then there is the fact that Australians haven't traditionally been super keen on nukes in their back yard. Several people warned us not to report anything too scary because of jitters about how Australians might react to the idea of nuclear medicine factories in their local hospitals. 

But in a country where nuclear power is banned, nuclear medicine is flourishing, corralled by rules from a swathe of different regulators. 

Dr. Jacquie Cawthray is the head of production at Cyclowest and an affiliate investigator with AMTAR. Cyclowest is a brand new cyclotron operator. The second private operator in Australia after Cyclotek. And the only one in Western Australia. It has ambitions northwards into Asia. 

Jacquie brings deep experience of making isotopes overseas and in Australia. So I asked her: what is the difference between no nukes Australia, and Canada where she cut her teeth in this industry and, with its 19 reactors,s much more comfortable with the concept.

Jacquie Cawthray: 18:09

I spent about 12 years in Canada, um, initially as a postdoc doing, um, radio chemistry over there with Triumph and UBC, and then moved to out in the prairies in the frozen tundra in Saskatchewan, and was at the cyclotron facility there. The Sylvia Fedorik Cyclotron facility that was a GMP licensed facility with Health Canada, but also had a research wing. 

So the end user, which is really the doctors, that end user was much more involved here in Australia than in Canada. I think the even though there was radio pharmaceuticals in Canada and nuclear industry in general is very sort of well accepted industry in Canada, that drive to to introduce new radiopharmaceuticals was not as great as what it is here in Australia. 

Australia really punches above its weight in terms of radiopharmaceuticals globally and, and the use of novel radiopharmaceuticals and the, the ability to, to try new things in the clinic. So that can only happen if there is a good supply chain. It's an opportunity Australia really has a chance to be a leader but if we don't kind of address the whole supply chain and therefore the regulatory environment, then it's going to be quite tricky.

Rachel Williamson: 19:36

To your point about supply, Australia leans on ANSTO, which runs the research reactor in Sydney. And the International Atomic Agency counts 17 cyclotrons here, most of which are in hospitals. Relying on a reactor, and hospital-based cyclotrons, what impact does that have on building up an isotope supply chain in this country?

Jacquie Cawthray: 20:02

I think the opportunity is there but as an industry we need to sort of work together to highlight the, um, the supply chain issues and also highlight the need for a more level playing field. So although hospitals may not have the regulatory burden in regards to manufacturing licensing and that, they, also not set up to, to support industry, like in terms of supporting companies that have, clinical trial radiopharmaceuticals. They're there to just produce standard radiopharmaceuticals, such as FDG, to produce that for the hospitals for direct use.

Whereas companies like Cyclowest are really set up to help support other companies such as GlyTherix that are coming through with novel, uh, radiopharmaceuticals and help them ensure that they have the correct supply chain that they need to get their radiopharmaceutical into the market, which in the long run benefits the patient.

Rachel Williamson: 21:06

Cycloest is an Australian-born cyclotron company. And as of today, when we're talking, you're about two weeks out from starting to make your first product, which will be FDG, a glucose sugar combined with fluorine 18, how long has it taken to get to this point?

Jacquie Cawthray: 21:27

It's taken Cyclowest from, um back before it was a empty block of land to a fully functional facility with a TGA license, it has been... I want to say four years in the making. 

We have designed the building -- it's not a normal building construction. There's a lot of things you have to take into account -- extra shielding, uh, floor restrictions -- and then there's a clean space you have to create as well. Then after that, once the building's done, there's still the equipment install. The validation of all the equipment is quite an extensive task in itself. And then once all that's done, there is also building a quality management system that is required to show that you are in control of your processes. The final step is achieving that manufacturing license from the regulators here in Australia the. TGA. So yeah, four years altogether, which is a long time, but in terms of what has been done, it's probably actually one of the fastest facilities I've worked on to go from nothing to complete it.

Rachel Williamson: 22:36

How many have you worked on?

Jacquie Cawthray: 22:38

I've worked on four. So three constructions and one already built establishment.

Rachel Williamson: 22:46

What are the regulatory hoops that Cyclowest had to go through in order to get to this point? Because it's a little bit different for you guys as a standalone isotope maker using a cyclotron than it is for say a hospital, isn't it?

Jacquie Cawthray: 23:00

Yeah, the regulatory sort of environment and framework here in Australia is is a little bit, it's a little bit different. We fall under the pharmaceutical manufacturing regulations, but at the same time, radio pharmaceuticals are slightly different. We make it, we test it, it's injected and used all within a matter of hours. So the ongoing stability issues that you have with normal pharmaceuticals don't necessarily apply here. 

So there is some, um, recognition of that with the regulators. And so they've created these exemptions. However, the exemptions aren't across the board. The exemptions apply to manufacturing cyclotrons attached to hospitals. So therefore a hospital is able to produce and supply to that hospital without having a manufacturing license. Whereas Cyclowest as a standalone manufacturing company has to apply and receive and comply with the TGA regulations to ensure that we produce a safe product. So even though there is that recognition there that radiopharmaceuticals are not necessarily the same as, you know, pharmaceuticals, that recognition does not apply across the board. So therefore the hurdle for us to become a licensed manufacturing company is much greater than cyclotrons attached to a hospital.

Rachel Williamson: 24:31

What effect do you think that is going to have on the accessibility of radio isotopes in Australia?

Jacquie Cawthray: 24:39

The barrier to us to be a manufacturing facility and commercially supply is much higher than a hospital pharmacy there that has a cyclotron. So therefore the barrier to us to create and, and work with companies to produce new radiopharmaceuticals, is significantly greater than what it is for a hospital or for anyone falling under the exemption. So therefore it makes it much harder for us to do that and therefore access to those new radiopharmaceuticals, any breakthrough radio pharmaceuticals where their benefits have already been shown to get them through into clinical trials, makes it harder as well.

Rachel Williamson: 25:25

I'm really keen to understand where the real upside is for a company like Cyclowest. You are still producing an item and then sending it out. So you're not going to see that explosive growth that comes with, say, a drug approval. You're, you're the manufacturer. But pharmaceutical companies in the US in particular are becoming very interested in your sort of company, um, buying big stakes and then buying them out entirely. I know you've done that deal with GlyTherix -- you guys benefit if their drugs work and come through clinical trials. So where is the growth for a company like Cyclowest, where's the upside for you guys?

Jacquie Cawthray: 26:09

We support companies that have new radiopharmaceuticals and and we support them so that they have a supply chain, then they're able to grow. And it's, it's almost like a symbiotic relationship. If they grow, we grow. 

But then there's also, that's for small companies, but also for much larger companies, companies like Telix or Novartis, the supply issues are the same for them. So they really need that supply of isotopes. They need that infrastructure such as a cyclotron facility. They need that trained team. That's something I haven't mentioned, but to have a team that runs a cyclotron facility, it's a very niche skill set and it's very difficult to find and so that's not something a company can, a big company can just pick up and run with. So with Cyclowest establishing sites just beyond what we have here in Perth, that becomes sort of an interesting growth path just for Cycloest but also for other companies because it supports them and their supply chain of radiopharmaceuticals.

Rachel Williamson: 27:15

Yeah, and if you can do those, those equity deals where you can actually share in some of the upside from these biotechs and pharmaceuticals companies, then that starts to become very, very interesting. Now, I understand Cyclowst has ambitions northwards to Asia. Can you tell me a little bit about that, and why Asia?

Jacquie Cawthray: 27:36

So predominantly at the moment, we're making FDG. It has a very short half life to two hours. Every two hours we lose 50% of it. But one of the growing areas for radiopharmaceuticals is radiometals. So, uh, their half lives are a lot longer. So we have the ability to supply further. Radiopharmaceuticals isn't just an industry here in Australia. It's a global industry. So Asia as well is an expanding market. So it makes sense for us to be looking at where we can fit into there and also support the supply chain of radio pharmaceuticals there. You need to make that isotope, especially if it is F 18, FDG, you need to have a localised infrastructure. So you need to have that cyclotron locally. We wouldn't be able to ship FDG to Asia from here. We might be able to ship longer half lives, but they still need that F18 supply chain there locally.

Rachel Williamson: 28:34

So is Cyclowest looking at sites to set up somewhere in the Asia region?

Jacquie Cawthray: 28:40

I think at the moment, Cyclowest is exploring opportunities and there are opportunities there. And, Asia obviously is a very big market. And it's a market that like if we compare it to the US market, the US market is quite full already. So Asia makes sense. It's it's, you know, developing and there's room there for more players and room there for the supply chain to, to be completed.

Rachel Williamson: 29:06

That was Cyclowest head of production, Dr. Jackie Cawthray. 

Australia has some work to do on the regulatory and policy front to create a radiopharmaceutical system that is also geared towards innovation, rather than simply fixing patients. 

Australia is good at supporting miners and biotechs. And it has some very good hospitals and research organisations. But it's still coming to grips with the return of advanced manufacturing. This is an issue that many industries are grappling with right now. From energy to medtech, to defence. 

In our next episode, we'll switch gears to something that Australia is really excelling it: radiopharmaceutical IP.