VAXXED: And the winner is... with OneVentures and Ose Immunotherapeutics

Moderna and BioNTech are getting all of the attention with their phase 3 clinical trials for lung cancer and melanoma.  But someone else is already further ahead.
 
French company Ose Immunotherapeutics has already done a phase 3 study for non small cell lung cancer, and if the final run of work confirms that data it will have the first cancer vaccine on the market in 2028.

And it's results like those emerging from Ose that are inspiring investors to start getting set for a cancer vaxxed future. 

In our final episode of VAXXED we feature OneVentures partner Dr. Jeannie Joughin and Ose Immunotherapeutics CEO Nicolas Poirier. 

Chapters

• 1:50 OneVentures partner Dr Jeannie Joughin
• 13:47 Ose Therapeutics Nicolas Poirier

Transcript

Rachel Williamson: 0:00

The first biotech to market with a cancer vaccine is not likely to be who you think it will be.

I'm Rachel Williamson and this is Phase III.

Moderna and BioNTech are getting all of the attention with their phase 3 clinical trials for a form of lung cancer and melanoma. But someone else is already further ahead. French company Ose Immunotherapeutics has already done a phase 3 study and if the final run of work confirms that data, it will have the first cancer vaccine on the market in 2028. CEO Nicolas Poirier says the holy grail is rewiring the immune system, and especially for people for whom the shiny new tools of immunotherapy simply don't work. And it's results like those emerging from Ose that are inspiring investors to start getting set for a cancer vaxxed future.

But Nicholas comes in a little later in our final episode of Vaxxed. As first up we have Dr. Jeannie Joughin, a partner with venture investor OneVentures. She personally talent spotted ImmVirX, which we featured in Episode 2, and she has her eye on a couple of very, very early stage biotechs, but she wouldn't be drawn on revealing her hand just yet.

So instead I asked her about the vibe amongst investors for cancer vaccine biotechs today. After all, there are the exciting mRNA developments and those results from Ose. But as the Financial Times put it, there are also two decades of crushing disappointments.

Jeannie Joughin: 1:51

There have been so many advances in cancer research and I would say particularly since COVID as well, the whole advent of the mRNA technology has really reinvigorated the field and I think there's a lot of excitement. We have more understanding of neo-antigens and we have great understanding of some cancers and the absolutely phenomenal success of the preventative vaccines, so Gardasil and, and Cervarix and, and, you know, the HPV vaccines as well for for liver cancer prevention. The sales of the products are very good. The uptake with the market is very good and that propels the investor interest. And then there's a lot of government and foundation, um, interest in cancer and their funding through grants, a lot of You know, bench research that people are going in and well, effectively creating companies from.

Rachel Williamson: 2:56

Are you seeing excitement amongst investors in Australia? Or is it largely a global vibe, if you like.

Jeannie Joughin: 3:05

I think there's a global excitement on immuno oncology products. Um, and also because it's also driven by big pharma as well, because as they outsource their internal R and D, they look locally, they look globally as well. I would say there are a few companies that are developing products within Australia as well. I, I also believe that companies in the university's spin outs are quite well funded and are being better funded.

Rachel Williamson: 3:39

It's clear that for investors, cancer vaccines are back, again. But what I wanted to know was how big is the opportunity they're buying into? The preventative vaccines are worth about $US8 to 10 billion a year. But Jeannie thinks the analysts might be undercooking just how much bigger this market could become if therapy vaccines succeed.

Jeannie Joughin: 4:02

There's several, uh, reputable market research reports out there, and they've analysed the the products that are in development and where they think the growth will come from. And they're anticipating that within 10 years time, the market will be worth, say, $US30 to 40 billion. Now that's going to be because as a result of some of these products that are in development. Now on one side of the coin, let's take that with a grain of salt because they are predicting very, very, very high pricing for those products. And that's driven by the US market because the US market can demand and receive a high price. But on the other side, I think they have underestimated the number of products that might make it in the next 10 years because of the rapid evolution and the changing way that we're evaluating the efficacy of these vaccines and because of the advances we've made in the development of the melanoma vaccine, the colorectal cancer vaccine, other prostate cancer vaccines.

Rachel Williamson: 5:10

How many more vaccines you think might actually make it to market compared to what they've estimated?

Jeannie Joughin: 5:19

I think it's a little bit of a result of all of the big data that we have to analyze and the speed at which we can analyze that data. So we get the cancer from an individual patient. We sequence it and we can see all of the neoantigens. You know, in one of the vaccines that's being developed for melanoma, for example, there's 34 neoantigens in that vaccine. And they've identified them as the most immunogenic based on the analysis with the improved technology and AI. Now imagine them if that evolves, then they optimize the treatment. What about you get rid of the bulk of the cancer by resection, radiotherapy, chemotherapy, if you like, if it's possible and then you use the vaccine as the surveillance mechanism to go around and mop up all that residual malignancy. And that's the advances that will come and that's why there'll be many cancer vaccines because it is personalized therapy rather than off the shelf. Or you could decide to develop an off the shelf therapy, but you're going to have lower remission rates and you may not have a cure.

Rachel Williamson: 6:33

But personalised medicine is expensive and we're in an era of ever tightening budgets. And yet, this investor at least, thinks this option is now on the table for public and private health buyers. Jeannie holds a contrarian view about the prospects for cancer vaccines as personalised medicine.

Jeannie Joughin: 6:54

I think that the cost can come down considerably for these individualized vaccine therapies for patients because the cost of mRNA, you know, and the other thing about the mRNA, it speeds up the development of the vaccine. So what used to take six plus weeks with the cell based therapies is only taking less than three weeks. It's just quicker. It just goes in and it transcribes and it's just much quicker. So you've got three weeks worth of, uh, less of costs involved as well as, as, as well as the technology being cheaper itself too. So I think the cost will be able to come down considerably. And you will be able to have that personalized vaccine. And when it's something takes three weeks, that that's not an unacceptable methodology. It's not like someone's disease is going to get out of control in that time either.

Rachel Williamson: 7:48

Even ovarian and pancreatic cancer, which moves so fast, is still not going to kill you in just three weeks.

Jeannie Joughin: 7:56

And, you know, the other thing I think is in the future, If it bears out that maybe a cancer vaccine is better given to prevent relapse and prevent further disease we could have a whole change in the way products are reimbursed in the future too. Like why wouldn't the government say, okay, I'm going to reimburse X for the remission of this cancer. Now, no matter how you get there, this is what you're going to get. And then that would encourage companies with their different modalities to package the best treatment that will be most likely to create a cure in that patient. And they get the reimbursement so it's not drug by drug, and it would encourage combination therapy used optimally and to get the optimal results for the patient.

Rachel Williamson: 8:57

Reimbursement is a tricky one. As we've heard, even Jeannie, with her long experience of oncology, isn't quite sure where they might fit into the future mix of cancer therapies. There are other hurdles that must also be overcome to get a cancer vaccine to market. The biggest one is the limitations of working with biological substances. Cancer is stealthy. A therapy must be tailored to the right target on a tumor. Delivered to the right place and make sure the cancer can't mute the immune system. It has a lot to do. But what could be the big decider is what investors will fund, Jeannie says.

Jeannie Joughin: 9:37

Whether we do personalized vaccines or we go for an off the shelf version and accept that we're not going to get a hundred percent remission and we might go for stable disease. That's another hurdle I think, because that'll determine which activities we fund and which activities we don't fund.

Rachel Williamson: 9:56

Where will this modality be in 50 years time?

Jeannie Joughin: 10:00

I think it'll be commonplace. I think it'll only take 20 to 30 years, actually, because of the speed at which we're discovering factors that either stop the immune response from responding or the triggers that are causing the mutations. So I think in the next 20 to 30 years, there'll be many vaccines and because of the move to therapeutic vaccines and personalized medicines, there will be many because each individual will probably have their own. And in 50 years, it'll be commonplace. But as I said, I don't believe that cancer will go away. I think as long as we're living longer, And cells are going to continue to divide and mutate. We just might have the advent of new variations...

Rachel Williamson: 10:46

That is terrifying, new variations of cancer.

Jeannie Joughin: 10:49

We have new viruses popping up all the time too, right? But we know how to treat them. Case in point, Covid. Well, we haven't eradicated Covid but we do know how to minimize its effects. So again, that's I believe that's how cancer will be as well because we just need to get that immune system switched on and not switched off by that enemy within and I think that's when we'll have a hope of being able to cure some forms of cancers in some people.

Rachel Williamson: 11:24

That was Dr. Jeannie Joughin, venture partner at biotech investor One Ventures. She thinks cancer vaccines will be bigger and cheaper than anyone expects, and she's leaning towards mRNA to do the heavy lifting. But our next guest, after this break, is in the peptide game.

Charis Palmer: 11:45

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: 12:23

Ose means to dare in French. For Ose Immunotherapeutics CEO Nicolas Poirier, It's a word that transforms into something else entirely in the context of what they're trying to achieve. To explore the frontiers of science and to dare for patients. 

He says the emergence of mRNA during the pandemic opened people's eyes to the way a vaccine could adapt to a virus and how it might be able to do the same for tumour antigens. But the French biotech's vaccine, Tedopi, is not mRNA. It uses protein fragments, called epitopes, to stimulate T cell production. It targets five antigens and is an off the shelf treatment rather than a personalised medicine. And it is leading the race to market in non small cell lung cancer, the same as what BioNTech and Moderna are leading with. And yet even after Jeannie's excitement and four episodes of investors, analysts, scientists, and executives saying this time, this time, it really is different, I can't shake the fact that different iterations of cancer vaccines have been this close before and failed. So I asked Nicholas, who is closest to touching the Holy Grail, is it really different this time? And if so, why?

Nicolas Poirier: 13:47

I think several things have changed this last year. Two elements, I think, will be key for the success of cancer vaccines. One is first it's a learning curve, and we have learned a lot. So now we know better why they failed in the past. We know better the immune system of the patients and the tumour antigens. So now we can select the same tumour antigens but engineer them in the lab having several round of iterations of engineering, testing, engineering, testing. And this is what we have done to have a cancer vaccine with different antigens that have been engineered to be very foreign for the immune system. So the immune system can be really activated against these tumour antigens.

Rachel Williamson: 14:29

And what's your second?

Nicolas Poirier: 14:31

The second one, which is really important, is now we know better the patients. In the past, we treat all the patients. Now, with the revolution of immunotherapy, we can select patients that previously benefit from immunotherapy so it means that these patients lose a battle, the first battle, the immune system works, attacks the tumours, but they lose their first battles. It doesn't mean they lose the war. We need to refresh a pool of soldiers and these vaccine can prime, and arm new soldiers, send new soldiers on the battlefields. And we can rewire, revitalise their immune response.

Rachel Williamson: 15:08

What about patients who don't respond to immunotherapy? What's, what's the option for them?

Nicolas Poirier: 15:13

So we can design better vaccines with RNA or peptides, quicker, cheaper, better antigens. And we can test, engineer in the lab, and select the patients that are most likely to, to, to respond to these innovations.

Rachel Williamson: 15:27

You just mentioned the pandemic and MRNA therapies. These have clearly supercharged interest, particularly from investors in cancer vaccines. All of these vaccine methods have their own advantages and disadvantages. So if you can speak ss an objective observer, leading a company that has an asset at the forefront of this, which category do you think is likely to dominate the cancer vaccine field if they can get up?

Nicolas Poirier: 15:59

Yeah, yeah, it's a very excellent question. So, for sure, right now, the RNA vaccines are under the spotlight after the pandemic. They have advantages, for sure, it's quite cheap in terms of manufacturing. It's really versatile. We can produce very rapidly. That's definitely a very good advantage. But...

Rachel Williamson: 16:16

And investors love them.

Nicolas Poirier: 16:18

Yeah, you know, there is some trend, fashions there is definitely advantage. There is also a weakness, which is today it's really poor productivity of the good antigens. When we look at the response against the vaccines is not so broad, not so strong, but definitively, it will provide probably, benefits in particular at the early stages of the disease after surgery. So it's a mix between preventing relapse or regrowth of the tumour. So that's I think that's really interesting for the personalised approach due to the versatility of the technology.
 
In the conferences, the majority of the talks and the new technologies are not based on RNA. There is still a huge interest on the DNA, on the peptide, on the cell and so on. And in particular for the, uh, peptides, they are off the shelf, ready to use. That's a big advantage, in particular for the metastatic disease patients. Uh, when the tumour is progressing, we have no time, we have no time to wait for weeks to manufacture the vaccines. We need something that is ready to use right now, and we need a vaccine that is really strong.

Rachel Williamson: 17:29

It sounds like you're saying it's the form that matters, not the technology. So off the shelf will be better for some cancers than personalised, and peptides will be better for some patients over mRNA, and so on. Does that sound correct?

Nicolas Poirier: 17:41

All technologies have their own advantage and there we need to explore and to play with all of these technologies for the benefit of patients and probably some technology will have more advantage in one settings, one clinical settings or one type of patients and will be different in other type of patients. So,

Rachel Williamson: 18:00

And then there are the um, the companies which are mixing the different therapies

Nicolas Poirier: 18:05

Sure,

Rachel Williamson: 18:06

Mutant cancer vaccines, if you like. Tell me about Tedopi, which is your cancer vaccine. I understand you could have it on the market as early as 2028, that would mean you'd be the first with a modern therapy cancer vaccine. So tell us about what the results are saying, what your expectations are for this phase three registrational global trial, and what could prevent you from getting there.

Nicolas Poirier: 18:37

Yeah. Thank you very much for this question. So, yeah, Tedopi is currently the most advanced, um, therapeutic cancer vaccine in developments while running a second pivotal phase three, uh, in Europe, North America, Canada, UK, and so on. We are targeting 2028. This is our ambitions to register Tedopi, but not only Tedopi, open the door for additional new cancer vaccine technologies. And, uh, this is today the only one vaccine that demonstrated its clinical efficacy in randomized trials.

Rachel Williamson: 19:10

I think your competitors might have something to say about that!

Nicolas Poirier: 19:12

The others are still demonstrating very promising results, but in phase 2 non randomised. What we have demonstrated in a randomised phase three that in nearly half of the patients, we have demonstrated that the vaccine alone in monotherapy extend significantly survival, versus the patient that receive only chemotherapy. The one year survival was 44% for therapy and 27% for chemo. So it's a big change in terms of survival. 

What I think is really important is threefold less toxicity adverse events. So the patients survive longer and better with less toxicity. And this translated in a very good quality of life. And this is better, of course, in advantage of the vaccines compared chemo. So just because we have a better tumour control, less toxicity at the end, the patients live better.

Rachel Williamson: 20:07

Longer and better is definitely a more hopeful outcome when you're living with a disease as nasty as some of these forms of cancer. You're in the final phase 3 leg with secondary resistance lung cancer. That's when one immunotherapy has been tried and the tumour becomes resistant to it. What does the timeline look like for this?

Nicolas Poirier: 20:26

We think that in the next three years, we will have the results by 2027, if everything goes well, and then a registration for 2028. So this is our target, uh, our ambitions, uh, in that.

Rachel Williamson: 20:38

And what could stop you getting there?

Nicolas Poirier: 20:40

What could stop? I think regulatory modifications. We rely on the rules, so we need to make sure that the rules are not changing during we are playing the games for sure. So regulatory stability is key for sure. We need to enrol patients. This is always a challenge, but now we have a, I think a really strong support for the medical community, both in US and Europe, that are really confident that the data we have generated, uh. And then what we could stop is if we don't confirm the results, of course it will prevent registrations, but it will mean that the technology is not working like we like we predict or like we we want so right now the things are on track.

Rachel Williamson: 21:23

Are you concerned at all about regulatory stability in the US?

Nicolas Poirier: 21:28

I don't know if we're really, we don't have any particular concerns right now. But we know that we are living in a in the world of [drug] development, that is long. We are speaking about decades to develop a drug. So if we are changing the rules every two years or every three years, we rely on the strategy. And then if the things are changing, that's not possible. So that's really important. This is a message that we are, we would like to report is uh, stability and regulatory is really important. Because at the end, it's not only about winning, uh, or being the first or winning more money is patients that have very high unmet needs and that needs innovation. So for that, we need to have really clear regulatory paths, uh, for the benefits of the patients at the end.

Rachel Williamson: 22:20

Just touching on that idea of being the first, non small cell lung cancer is a really competitive market for cancer vaccines. It seems like this is on everyone's radar for clinical trials. So how much pressure are you feeling to be the first one to get that market share, to get it on the market? 

Nicolas Poirier: 22:40

It's a lot of pressure for sure. Uh, as a CEO of a small biotech in a very big world, facing big companies with big investments, uh, and big competitions is of course, a lot of pressure, uh, but yeah, this is what we have to do. Uh, we, we have built a company for that and, uh, and, and, and we will do it. So I think we are, we have advantage. We are really agile and flexible. Um, so far, unfortunately for the patients, all the competitors in terms of demonstrating, uh, better survival for the patients so far there is nothing registered and all the molecules except our vaccine for the moments felt in the extending survival for the patient, so it gave us a lot of energy and, uh, and duty to push you for, for the patients that need to have access to these innovations. And, and it's, it's not a surprise that there is so much competition, non small cell lung cancer, lung cancer is maybe one of the second cancer type in terms of incidents. It's the first one, unfortunately, in terms of mortality. And this is where the cancer vaccine can play a big, big role in the future.

Rachel Williamson: 23:54

Yeah, and if something like Tedopi is getting 50 percent of the patients, then perhaps one of the other methods, you know, dendritic cells, DNA, mRNA, maybe could even get that other 50%. Now, if Ose can be the first to commercialise a cancer with Tedopi, what do you think that will do for the broader cancer market?

Nicolas Poirier: 24:18

I think it, it will be a big change because it's a, it's a holy grail from decades that in theory, our immune system has been built to recognize viruses, infected cells, cancer cells. And so we are sure that to tomorrow, but this was also the case in the past. We will. cure patients with our immune system. So it's a big opp. And if our vaccine or another one succeeds it will definitively demonstrate this was the right path to move forward. It will open a new avenue, clearly open a new door in a new world where we can also envisage chemotherapy free regimen for patients. I think that's a big change for the patients. No more chemotherapy and replaced by more efficient modalities.

Rachel Williamson: 25:11

Where will cancer vaccine therapy be in 50 years time? Do you think? 

Nicolas Poirier: 25:16

50, you said? Wow.

Rachel Williamson: 25:19

Let your imagination go.

Nicolas Poirier: 25:21

Yeah, no, I have my own view on the holy grail. I think first, maybe in 10, 15 years, I'm quite pretty sure, quite confident that we will have this cancer vaccines, therapeutic cancer vaccines, so let's say in the 10, 20 years, chemotherapy, free regimens. 50 years. Uh, we have all, uh, hope, you know, prevent cancers. Uh, we know with Gardasil, we can prevent cervix cancers. If we have good technologies, good platform, very well tolerated, we know now very well the shared tumour antigens or tomorrow the shared neoantigens. We will have the possibility to vaccinate preventively the patients with high risk of disease, high risk of developing cancers. Let's speak about the smokers. The smokers, uh, in lung cancers. We can vaccinate preventively in the future. We will...

Rachel Williamson: 26:16

People living in heavily polluted cities.

Nicolas Poirier: 26:19

Yeah, exactly. And that's key because today, uh, it's the cure against metastatic disease is difficult because we are treating too late. If we can vaccinate preventively, eliminate the tumor cells at assumptions from the beginning, it will open not only a chemotherapy free world, Hopefully, uh, a cancer-free world

Rachel Williamson: 26:43

That was Ose Immunotherapeutics CEO Nicholas Poirier. 

The cancer vaccine boom times began with Gardasil. Sure there were vaccines that came before, but it really began with that preventative breakthrough. 

Today, two decades on since efforts began in earnest, biotechs are still trying. And this time they might finally come up with an answer researchers have been looking for for so long: a vaccine that can help a patient's own body find and hunt down tumour cells, and then inoculate them against a return of the cancer for years afterwards.