VAXXED: Deadly infection, with Imugene and ImmVirX

Cancer vaccines are a very niche section of cancer treatments. But two companies in Australia – the only two so far to go public with their work in this arena –are working on an even niche area within this. And one says their work is not a vaccine. The other does. 

So what gives? Well it depends on what you want to focus on: the deadly infectious nature of an oncolytic virus that bursts tumour cells from the inside, or the resulting immune memory that can fight that cancer as well as others that look similar. 

We speak with Imugene CEO and managing director Leslie Chong and ImmVirX founder Dr Malcolm McColl about why they think that finally the time has come for this underloved field and what they plan to do with their science if they can prove it up. 

Chapters

• 2:46 Imugene CEO and managing director Leslie Chong
• 13:53 ImmVirX CEO Dr Malcolm McColl

Transcript

Rachel Williamson: 0:00

When is a vaccine, not a vaccine? When it's... a virus? This is about to get complicated. I'm Rachel Williamson, and this is Phase III. 

There's a bit happening around cancer vaccines in Australia, from research through to biotechs testing ideas. But aside from BioNTech and Pfizer and Moderna and Merck, which are working on mRNA cancer vaccines here, there are really only two local companies focused on the space and public about it yet. 

Imugene and ImmVirX. 

Both are working with oncolytic viruses. But Imugene CEO Leslie Chong says their DNA based virus is not a vaccine. ImmVirX CEO Dr Malcolm McCall says their RNA version absolutely is. 

This opens the door for a great explainer. One that gets to the heart of where cancer vaccines sit within immunotherapy. Let's start at the start.

 Immunotherapies are a relatively new way to either turn up the volume on the immune system or clue it in to the fact that they tumour exists. It is possible because of several major breakthroughs in the last two decades. 

One is the discovery of how to turn off checkpoint inhibitors, such as the PD-1 receptor on T cells. These keep the immune system in check. If you remove the check, you ramp up immune activity. 

Monoclonal antibodies or lab made antibodies are one of the main therapies today. 

And then there is CAR-T cell therapy. It's been super successful for blood cancers. But not so useful yet for solid cancer tumours. And at up to half a million dollars per infusion in Australia, it is expensive. That's because it's autologous or uses a patient's own cells as opposed to an off-the-shelf or allergenic option. You could say it's my bespoke green smoothie hangover cure to your Panadol. 

Into this mix are vaccines. They get the immune system to remember the cancer. Oncolytic viruses do this too. But for Imugene and their pox virus, which uses DNA for the hard work, it's not the remembering, but the killing they're into. CEO Leslie Chong says this is the key point of difference. 

You don't have a vaccine, you have an oncolytic virus. So the virus itself does the killing.

Leslie Chong: 2:54

Absolutely. It ruptures the cancer cells because it replicates, fills the cavity of the cancer cells with these white blood cells and immunity. It bursts. And then in addition to that, it draws your immunity to the site so your immune system finally sees it because there's so much damage happening in that, in that environment.

 So for instance, with our bile tract cancer patient, he took the drug for a period of months, so our virus, and then now he's cancer free, but because his immune system is inactive. So his immune system is finally seeing the tumours and comes to rescue to the fight. So it's in this beautiful enabling your immune system to finally see the cancer by creating a situation where your cancer is bursting and infection happens and your immune system, you know, the policing of your body comes to see what's going on and they realize there's some bad things going on. So they clear it.

Rachel Williamson: 4:01

Just to give a, um, our listeners an explainer, you're using the CF33 virus. It's a pox virus, like smallpox or mpox, and it inhabits the cytoplasm of the cell, which is the jelly outer bit, rather than the nucleus in the middle, which is where viruses normally colonize, and then it does its thing. So tell me about this virus and what you're using it for.

Leslie Chong: 4:25

We're currently in a phase one study with the CF33, which stands for Dr. Chin. Dr. Fong and it was a 33rd virus that they saw that had the most cancer killing power. And so we knew that it was pretty powerful and we've already started seeing that. In the clinic we have one patient in particular, bile tract cancer patient who has had a complete remission, no tumour growth going on two years and it's in a cancer type that normally nothing has really penetrated. So we're gleefully happy about that. 

And we have an expansion off that. We're really focused on one indication so that we can get the most amount of data so that we can move into that highly coveted phase two area. So we know it only replicates in cancer cells. There's something in the cytoplasm that's missing in a malignant or tumour cells.

Rachel Williamson: 5:26

So that's the naked oncolytic virus, so to speak. What might happen if you mix it with something else? After all, that's what the experts say is where the power lies for immunotherapies, and vaccines in particular. 

Imugene is combining its virus with a CAR-T therapy, that's the breakout blood cancer treatment. They reckon the virus might be a way to get CAR-T to work for solid cancers. The idea is to cover a solid tumour and a protein only found in blood cancer, then whack it with the CAR-T. They will find out soon enough whether the theory works. Imugene started a phase one clinical trial in California in July. 

Oncolytic viruses aren't a vaccine at Imugene. But when Lezsie started with the company in 2015, its focus was protein-based cancer vaccines. Today, they're getting out of those. I asked Leslie what they're selling and why now? When the market appears to be heating up for cancer vaccines.

Leslie Chong: 6:33

Our leading pipeline roughly about five years ago was what we called a B cell peptide-based cancer vaccine. We had HER-vaxx, and that is still ongoing, but it's primarily, um, we're looking to out-license that. And along with that, our PD 1 vax, which is also a cancer vaccine, will likely fall into that category, B cell peptide vaccine, so therefore, when we're looking to out-license HER-vaxx, there's a lot of conversations about including PD 1 as well.

Rachel Williamson: 7:06

Why are you out licensing those now? Because you've been working on those for a very long time now.

Leslie Chong: 7:12

Yeah, so we actively had been developing HER-vaxx for roughly about four and a half years and to get a phase two positive phase two data on gastric in four and a half years is it's it's unheard of. However, the next level is that registrational phase three, and that is going to be at an enormous cost. And it's really, um, it's really a huge burden on a small size company like ours. So the idea was to out-license those and then look to develop our oncolytic virus as well as our own allogeneic CAR-T product that we call Azer-Cel.

Rachel Williamson: 7:58

You've been at Imugene since 2015.

Leslie Chong: 8:01

Yes.

Rachel Williamson: 8:02

How has the investment climate for these products, these assets changed in the time that you have been there?

Leslie Chong: 8:12

So I think the investor environment for biotech or tech has completely changed in the last few years. I have to be an optimist and think that it's coming back. But earlier on, you know, when we even had the, HER-vaxx, initial, uh, vaccine, it took years for people to finally understand what we're doing and then come in for the ride. So we had investments, um, largely retail at the, at that time. So this is roughly about nine years ago when I joined and it was a 5 million market cap when I joined and it kind of stagnated. It went up to 10, 30 for a number of years before it actually jumped to a hundred million is when we made the acquisition of the oncolytic virus that we started to, to establish more, uh, ourselves as a clinical developer in the cancer space.

Rachel Williamson: 9:10

Right now the arena for cancer vaccines is starting to get really, really exciting. Mostly because of mRNA though, not so much for DNA or peptide or protein, based vaccines that you guys are working with, HER-vxax and PD-vaxx. Does that make this a good time to be licensing out that asset that you've been testing for such a long time?

Leslie Chong: 9:36

I think with, uh, our B cell platform, our HER-vaxx and PD-1 vax, there are other products that those targets are so well served, uh, to the point where. If we wanted to get back into the market, it would have to be a phase three study at a significant cost. mRNa I think is, is still in its infancy. And so until a product gets approved, then everyone will move towards it. So, you know, I think it will excite people, to up to a point until it proves itself, but it may actually help us, um, out license our product because of that excitement. We need all various different kind of arsenals against cancer. And if that's one way to show or certain kind of cancer type is served, then I think I'm all for it. And the better results that we get for various different mechanism of actions for for cancer drug, the better the market will be, the more impressed investors will come in, you know, with that. So I'm all for. innovation. I'm all for, you know, moving ahead and looking at where the puck's going to be, as opposed to just following along with the me too.

Rachel Williamson: 10:55

Yeah. And you think it's oncolytic viruses now. It's in that space, at least.

Leslie Chong: 11:02

I definitely think that oncologic virus is having a, having a shine in the sun, um, currently with GC Therapeutics having some, you know, significant response rates in a bladder that I've seen recently. Um, I also think that the world needs an off the shelf allogeneic CAR-T product because autologous CAR-T will help you to a certain point, but I think we need something off the shelf so that we're not reliant on so much of the personal T cells to do the job.

Rachel Williamson: 11:35

That was Imugene CEO Leslie Chong. She says their virus kills the cancer and recruits the immune system, but isn't a vaccine. Over at ImmVirX, their virus is different. It's an RNA virus. After the break, we'll find out why they swing the other way, towards the vaccine definition.

Charis Palmer: 11:57

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: 12:36

ImmVirX may as well be the reincarnation of a company that was Australia's most successful biotech sale. 

Dr. Malcolm McCall was the boss of Viralytics when Merck bought it for 500 million Australian dollars in 2018. It was doing RNA oncolytic viruses with a focus on melanoma. But Merck dumped the main asset, Cavatak just four years after buying it. A casualty of being a little fish in a big pharma pipeline. 

And to be honest, oncolytic viruses have been stuck in early stage research for a very long time. Only three companies are listed as currently running phase three clinical trials and the US. There's oncolytic virus specialist, Genelux, whose share price has halved since it listed last year. It is testing a pox virus, just like Imugene. Chinese biotech Binhui and US biotech Replimune are separately using a souped up herpes virus for melanoma. And that's it. But Malcolm clearly believes in the concept. He got the old team back together to do a different RNA virus for some different brands of cancer.

Malcolm McColl: 13:54

So we're this time with we're tackling some of the most globally prevalent cancer types, including colorectal cancer. Last time with Viralytics we were targeting melanoma, which is sort of really far less common. So, yeah, it's sort of a similar broad approach but just a different virus. I think the fact we've moved so quickly just means that all the learnings from the previous company have been applied here. So I've been able to very rapidly take the program from just a whiteboard idea and now dosing patients, obviously. But this is genuinely just very straightforward to scale up and manufacture. And we've actually taken a lot of process steps here to make it even easier to transfer to big pharma, you know, at that time when we're acquired or licensed.

Rachel Williamson: 14:32

You are referring to this as a cancer vaccine.

Malcolm McColl: 14:36

Well, it has a, it has a vaccination effect, so it has sort of a, a dual mechanism of action, if you like, the oncolytic virus, uh, IVXO37 is our lead candidate, has a direct ability to infect and then replicate or multiply within those cancer cells and then burst them. But in that whole process it inflames the tumour. It's kind of a danger signal to the immune system. And when those cancer cells are sort of fractured, they release what's called neoantigens, which are very sort of unique to the cancer, unique in fact to that patient into that tumour within the patient, but they can then be seen as foreign. And so then you'd get an immune response against these neoantigens, which really enables the, the virus to not only just kill the cancer where it's injected, but also drive an immune response against cancers around the rest of the body. So we saw this very clearly with Viralytics. And I think we'll see the same, uh, uh, In fact, I think we are already seeing signals with IVXO37, so it's a dual activity. The cancer killing effect also drives an immune response to cancer neoantigens.

Rachel Williamson: 15:36

Yeah, I I ask you whether, how you're referring to it simply because Imugene is doing something very, very similar with oncolytic viruses, but they don't like calling it a vaccine. And I think it highlights some of the confusion around what a cancer vaccine, a therapeutic cancer vaccine is and what it can do, in what is still a very, very emerging field.

Malcolm McColl: 16:01

Yeah, I think it's really very clear if you sort of, I mean, take the independent view and independent approach. I mean, academics in the space very much think of this as, you know, as I say, the cancer killing effect from the oncolytic virus, but also driving this, um, broader immune response through exposure to the tumor neo antigens in this inflamed environment. As I said, that's what can, uh, oncolytic viruses do very, very well. So yeah, it's definitely a well described process.

Rachel Williamson: 16:25

What is the virus that you're using?

Malcolm McColl: 16:29

We haven't actually disclosed that yet. We're sort of, uh, as a private company, we're able to keep a fair bit up our sleeve it's different to the Viralytics Cavatak, but it's in the same broad family of small RNA viruses. The difference being that this small RNA virus targets the receptors that are over-expressed on colorectal, gastric, ovarian, hepatocellular carcinoma, whereas Cavatak really targeted the receptors that were overexpressed on melanoma. So that's why we had to move to a different virus targeting different receptors because not all cancers are the same in terms of the receptor expression.

Rachel Williamson: 17:01

So are you saying that you've got almost a, a multi cancer vaccine that you could roll out for these different...

Malcolm McColl: 17:10

Cancers that express that particular receptor are all great targets. Now, we've done pre clinical work across the indications that I've described, obviously we're in the clinic and showing some really nice single agent activity in colorectal cancer patients. Um, and our second asset that is now moving through preclinical development will target um, receptors that are overexpressed, for example, on lung cancer. So that'll, that'll be our second asset moving into the clinic middle of next year.

Rachel Williamson: 17:35

So as you've said, your technology is looking at a whole range of cancers from colorectal, liver, lung, ovarian, gastric...

Malcolm McColl: 17:43

Yes.

Rachel Williamson: 17:44

Give us your elevator pitch on where the clinical trials are now.

Malcolm McColl: 17:48

Yeah, look, so we are, we have completed first in patient in April, 2023. So three years from whiteboard idea to get into the clinic, which is about a world record and in terms of time, and also very low cost to do that, reflecting the qualities of the team. We've now completed, um, dose escalation, where you start at a low dose and gradually increase and increase the number of doses. So now we've just uh, about to dose patients in the phase 1B study, which is where you combine the oncolytic virus with one of these anti PD 1 inhibitors. So the checkpoints that are the most important drug in cancer therapy. And what we saw with Viralytics was really excellent additive effect between the oncolytic virus and the checkpoint. So, you know, we were kind of pretty optimistic about seeing that in this case, that the checkpoint, um, requires T cells to be in the tumour. And what the virus does is really inflame the tumour, drives those T cells in the checkpoint, takes the brakes off them, and therefore you do get this, um, really nice additive effect. So we're pretty optimistic actually. And I think we'll recruit the phase one B across colorectal gastric and ovarian in the first instance, actually quite quickly.

Rachel Williamson: 18:56

Moving on to something a little bit different. You mentioned that big pharma has a problem and that a range of drugs are coming off patent from 2025. Why is this relevant to cancer vaccines and to ImmVirX in particular?

Malcolm McColl: 19:12

Well, I mean, it's just, I think the figure is something like, you know, they will lose about $US300 billion in annual sales over the sort of next five years. And they, you know, that's just unacceptable to their shareholders, to their board of directors, to their management, et cetera. So, big pharma has a lot of money in the bank and will certainly be very active in terms of M&A activity over this sort of coming five years. I'm sure there'll be a lot of activity so they can kind of restock their pipelines and not have you know, massive loss of revenue. 

I mean, Merck is a perfect example of that, have a wonderful drug called Keytruda with annual sales around $US30 billion that comes off patents. So they need to replace those revenues and they have the cash to make acquisitions. They'll be looking for companies that have assets that are meaningful in terms of revenues and certainly, you know an agent an oncolytic virus that tackles the cancer types we've talked about would very very definitely be in that in that basket.

Rachel Williamson: 20:05

This deal that you guys have done with a Chinese company, Innovent, they're a 9 billion U. S. dollar company. 75 billion hong Kong dollars. So I always wonder when someone like that does a deal with a startup, which is compared to them, what you guys are, what the story is, where did that come from and what's the end goal? Cause you guys the Viralytics team do have track record in doing like an exceptional deal in this space.

Malcolm McColl: 20:35

Yeah. So sure. I mean, uh, these guys are all always just looking for, I mean, it's a bit like Merck, it's a bit like any of these pharma companies that are always looking for new assets to put into their pipeline. And they're an exceptional company. They've got a really strong sort of oncology portfolio and a pipeline as well. But one of the things they don't have is an oncolytic virus. And, uh, we've kind of known, you know, the folks an Innovent in fact, the president and founder there for, you know, going back to prior to COVID and he'd always shown interest in us. Uh, Innovent don't have an oncolytic virus, they think ours has great prospects, so, you know, who knows how that ends up down the track. And so whether we might do a, carve out a Chinese territory, that's certainly possible in the future, as opposed to just doing a straight global deal, but these are important indications to Innovent, and also, they, uh, they like the technology.

Rachel Williamson: 21:21

Interesting to see an Australian company doing a deal with someone in Asia, because it's not a common occurrence. Most people look to, the US or to Europe, then very rarely look to those markets, Korea, Taiwan, China, Singapore, even.

Malcolm McColl: 21:39

Well, yeah, no, exactly. And look, we, we've got a bit of a track record here too, because just before the Merck acquisition, we did, uh, got investment from, from Lepiu who are a big player in China. They invested about $30 million in us. We didn't give them any rights, but they just liked the technology. So you've got to, uh, look at the Chinese, um, biopharma market and it's just some of the technology coming out of there is remarkable. And it's going to really enhance the way we treat cancer in the next 20 or 30 years. So we're very delighted to have a relationship with Innovent and, and I'm very happy to work with Chinese companies, both in Viralytics days and with ImmVirX. And, obviously it still leaves you open to do the big global deal in the future as well. But no, we've been very happy to work with Chinese companies.

Rachel Williamson: 22:20

That was ImmVirX CEO Dr. Malcolm McCall. The mRNA wave has created a new fervour around cancer vaccines. But it's not the only pathway out there. Oncolytic viruses that can act like vaccines are in the next two, depending on who you speak to and what their virus is. But this is where Australian companies are focusing or at least the ones that are ready to publicly claim this spot in the sector.

In our next episode, we ask two analysts for their take on these two companies. But also the wider cancer vaccine industry. Will it fizzle again? Or will mRNA provide the firepower it needs for investors to take another look.