Antibiotic-resistant superbugs could become a greater threat than cancer. Bruno and Pedro at the startup Immunethep explain how they’re tackling the crisis with vaccines.

We discuss how Immunethep could challenge Pfizer’s $7bn+ Prevnar, and how one pharma company got on board after a representative said he doesn’t believe in vaccines!

For transparency, this episode has been sponsored by Immunethep. Learn more at https://bit.ly/flot-immunethep

⭐️ ABOUT THE SPEAKERS

Bruno is Immunethep’s co-founder and CEO, and co-founder of the startup creator Venture Catalysts. He also co-founded the tech startup Abyssal, which was acquired by marine robotics company Ocean Infinity in 2021.

Co-founder and CSO Pedro is a biomedical scientist previously serving as an Assistant Researcher at i3S. He has a PhD in Biomedical Sciences from the University of Porto and boasts over 30 peer-reviewed publications.

🔗 LINKS MENTIONED

• Immunethep website — https://www.immunethep.com/
• When Cancer is no longer the biggest threat: AMR’s growing shadow over oncology — https://www.incate.net/when-cancer-is-no-longer-the-biggest-threat-amrs-growing-shadow-over-oncology/
• Antimicrobial resistance WHO page — https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance
• Center for Global Development: The Economics of Antibiotic Resistance — https://www.cgdev.org/sites/default/files/economics-antibiotic-resistance.pdf
• GSK completes Affinivax acquisition — https://www.gsk.com/en-gb/media/press-releases/gsk-completes-acquisition-of-affinivax-inc/
• António Portela, BIAL 🇵🇹 | Parkinson’s, Family-Owned Biotech | E54 —
  https://flot.bio/episode/antonio-portela-bial-parkinsons-biopharma/

Transcript

[00:00:00] Intro

Philip Hemme: I’ve heard this crisis for I think over 10 years that it’s like really urgent to get it solved. 

Bruno Santos: Actually, not many people are aware of the problem that this is. So when we say even to our family that this could be greater than cancer, if you don’t do anything about it, even they think, okay, you probably overreacting.

We see that bacteria can interact with the immune system. It can block it. And so if we target this common wireless mechanism, we are stopping a lot of bacteria at the same time. 

Pedro Madureira: Sometimes when you hear a no, it’s not a no from the company. It’s a no from, that’s not the first person in one of the, this big pharma, the first guy that we first talk from that big pharma company.

It was the only thing that instead of, I don’t believe in vaccines, actually, it was big pharma company that help us the most.

Philip Hemme: We have new to a new episode. I’m your host Philip, and on the Flood Bio Show, I’m talking to the best Europeans in biotech to help you grow. Antimicrobial resistance or a MR is a growing crisis with several millions of deaths per year. The Portuguese biotech immune tip is working on a potential solution, the crisis, with a new form of vaccines.

So I talked to Bruno and Pedro while I was in Lisbon. I actually knew Bruno from 2018 when we had a coffee and a here in Lisbon. We talked about the Mable resistance crisis and why it’s still far from being solved. We also talked about biotech entrepreneurship and the biotech ecosystem in Portugal, and why you shouldn’t take no financial, especially from someone in the larger organization.

For transparency, this episode has been sponsored by Immune Tech. So please, my conversation is Bruno and Pedro, and please hit the like of follow button if you’re enjoying it.

All right. Welcome, Toho. 

Pedro Madureira: Thank you very much. 

Philip Hemme: And whatever owner, good to be here. Thanks for coming. Lisbon you’re, from from Porto. It’s good to have you. 

[00:02:10] The overlooked antimicrobial resistance crisis

Philip Hemme: I wanna start with the, general landscape of the antimicrobial resistance. A MRI think we’ll, use that word more. I’ve heard this crisis for I think, over 10 years that it’s like really urgent to get it solved.

I think there are some steps in the right direction, but I think we are far from having it solved. Like how, do you look at it 

Pedro Madureira: where we are today? 

Bruno Santos: Yeah. Actually, we’re. We speak a lot about that between, ourselves and we think that everyone knows about what’s happening. And as you say, like it seems like we’re speak about it by, 14 years.

Yeah. But actually not many people are aware of the problem that, that this is, so when we, say even to our family that no, this would be greater than cancer. If you don’t do anything about it, even they think, okay, you are probably overreacting but we’re not. Unfortunately we are seeing it more and more in our own hospitals, in our own families, or we know someone that for some reason went to the hospital lot related with infectious disease, and it, gets there and he has to take two, three antibiotics and luckily hope that they all survive.

But we are seeing that even more we about Portugal, Europe. Not, talking about the third world or the bean country, nothing like that. So it’s a real problem that is coming close to us. And actually we’re talking about that. Yes. Yes. 

Pedro Madureira: Yes, just that’s exactly that first, thank It’s very nice to be here very much though.

Yes. It’s our, not our own town, but our own countries. Yeah. It’s even more pleasure in, the, in being here but talking about this EMR problem I really think that one of the things that even when people are aware of it. I, think there is this in the back of their minds when you think when you, hear some news that’s someone in the hospital got an infection and there was no antibiotics to treat him.

I think that’s in the back of our heads. People used to think, oh, the hospital didn’t do it right. But it is not, we are reaching that point where we don’t have nothing to treat people that are infected with the, super strains that are resistant to antibiotic. A few weeks ago or a few months ago, we saw cases in, in cities just like Baan.

Yeah. They don’t have the antibiotic at the right time, but we are talking about Baan. It’s, yeah, the center. If they don’t have it, we will have it. And it’s not the hospital’s fault. We really need to sync on different things. Yeah. To, tackle on this to replace the antibiotics where they don’t work.

Philip Hemme: Yeah. 

Pedro Madureira: Yeah. 

Philip Hemme: And you’re, bringing we’ll talk, bringing some of the solution just on the, macro level, I feel like, is it the, I think the WHO classified am rs I think top 10 these, and even in the number of cases per year is like huge. Some of the countries, I dunno, do you have some stats on that?

Top 

Bruno Santos: three? 

Philip Hemme: Top three even. Wow. 

Bruno Santos: And so that, that’s where I say usually people don’t, realize how high it is on the Yeah on the list already. 

Philip Hemme: Yeah. And I feel one of your back car, I think he’s, they’re supporting quite a lot of project as well. Like how, do you see the, like the landscape in terms of like support, financing, progress, 

Bruno Santos: the, I think the good thing is that people are becoming more aware and so they are moving more to this. And we have great organizations like the, Gates Foundation that’s giving us some importance to it. Then the car back, the, this global fund that is focusing exactly on, on working on this and the place as well.

So we, we can see that there is a lot of people getting together to try to, really solve the problem. ’cause it’s real, it’s happening every day. But on the other hand, it’s seems like we are very few that are developing new things. And it’s like Pad is saying it, it, doesn’t seem that there is enough funding that to support all of the projects that need to be developed due to this problem that is growing and we are not.

Having weapons in us. Yeah. Being antibiotics, being vaccines, being forever to, help us deal with it. 

Philip Hemme: And, where I guess there’s several bottlenecks, but I feel like one bottlenecks was all, what I heard was like the reimbursement and antibiotics, it’s not necessary there. So I guess some big pharma don’t like shy away from it.

Is that still true? 

Bruno Santos: Yes. The, problem is the antibiotics that are the solution are also causing the problem. As you, you use more and more antibiotics because some of them are not working, you are creating more and more resistance and so we need more antibiotics or more solutions to overcome it.

Yeah. And that’s the, problem. It’s probably we’re only thinking about antibiotics and when you have one that works, oh, let’s save it because otherwise you, you’ll get resistance. And so we don’t use it, and so you don’t get enough money from it, 

Philip Hemme: okay. 

Bruno Santos: To vicious, circle. So it’s a vicious circle.

Okay. So we, are stuck on this, on that vicious circle. We’re trying to act in terms of the reimbursement strategies to try to overcome that. But the same is, valid in the, vaccine space as well. 

Pedro Madureira: Yes. I, really think of course this is that there are huge problems associated with that money and investment.

It’s always the basis of the problem because if you don’t have money to do it you will be stuck on that, on, on that problem. But one of the things I think it also get away some, investors is that we are for decades that we are trying to do the same thing and expecting different results.

I don’t think we should enter in that discussions. Vaccines are better than antibiotics. Antibiotics are better than vaccines. They are all needed. Antibiotics are incredibly important, incredibly useful for the bacteria they are able to, treat. Yeah, they are amazing.

There’s nothing like antibiotics. Traditional vaccines come on, traditional vaccines. They, help us eradicated. Infectious diseases is better than that, but neither antibiotics nor traditional vaccines are working for a specific type of bacteria that are now the top agents that, infect us. And it’s not for lack of trying that.

Antibiotics and traditional vaccines are not working. We really need to think on different ways to approach the problem. And now what we see is some, somehow investors getting away from this because they say, oh, no, vaccines don’t work. Antibiotics. Don’t get the enough reimbursement or revenue come on.

We need to think differently in order to have new products. That’s, again, would be very nice for people because they don’t have nothing to, treat or to prevent that. Yeah. And would be for sure be very nice to investors and for pharma company because come if you, come out one vaccine or one treatment that works for a single bacteria that is associated with hospital acquired infections, I don’t think that any investor wouldn’t want to be on that weight.

So we really need to think different in order to have different outcome as well. Yeah. 

[00:10:26] Immunethep: When Bruno Santos and Pedro Madureira teamed up

Philip Hemme: Yeah, and I, it’s a good segue into to Immune Tap and, also I saw that there are some recent deals announced that were pretty sizable as well. But let’s start with Immune Tap because I think you’re bringing quite a different solution to.

Game, I don’t think we can call it a game, but with a space. Can you I think you have found it basic a bit more than 10 years ago. Can you go into the, story of the foundation until, now, maybe for you? 

Bruno Santos: Yes. Actually the, beginning of the story, it’s more with Pieros, so as the, it comes from his PhD.

So I’ll, let him stack from there and then I can add something. 

Pedro Madureira: It’s a long time ago now. But when the, to cut a long story short yes. So when I, graduated in biochemistry, but then I started to work as a researcher in the academy, in university here at Portugal.

And so basically at that time, one of the things that were in fashion in immunology field was trying to understand how. Microbial molecules. 

Bruno Santos: Yeah. 

Pedro Madureira: Interfere with our immune system and in a general fashion. In a good way. In a bad way, yeah. So that but we were lucky enough to, observe that some bacteria could excrete molecules that were highly immunosuppressive.

So meaning that once those bacteria infect us, they start to excrete throughout our body, molecules that shut down our immune system. 

Philip Hemme: Okay. So they escape the immune system. 

Pedro Madureira: They escape the immune system. They, disable our immune system to work properly. 

Philip Hemme: Yeah. 

Pedro Madureira: And at that time I remember we were thinking, oh, this is, this could be very nice.

But I was, a researcher. I, do love to to, work on science, to research, and I never had that idea of let’s, turn this into a company or turn that into a product. For me, it was a really nice. Science. Yeah, I know I’m biased again, but I really liked what we were doing and that’s when I met Bruno and and his associates and venture catalysts.

And now I bless you. 

Bruno Santos: Now it’s the part of the story where I am. No, my, my background is on biological engineering. Yeah. But I was working in the different industries for 10 years until the point where I decided, oh, I want to go more on the management side. And I did an MBA and together with some colleagues there.

We did a program that was to make the transactional science and so help to get the science to, the market. And so we liked it a lot. That’s the, program we liked more at, the MBA at Port of Business School. And actually we decided to call, oh, let’s do this. This should be our, work.

We like to do this. And we started looking for things around in the universities what was being developed and could be interesting for for developing a company. So that’s when we met Pedro and we challenged him and say, okay, this looks good. We should take this and and take this to the market.

What do you think about it? And actually he said, okay, let’s try. I never thought about it. And he said, okay, there’s one thing that we need to make sure. You don’t need to come to the land, but I don’t wanna know about the, Excel sheets. And okay, so after that we’ve been working together for this 10 years.

And with, 

Pedro Madureira: but let me just add something because this is really important. I I at, that time, it was not that frequent in Portugal for this translation of science. It was the dark side of science to, to become to, found a company. And, but then again, there were some of my friends or some of researchers they, had that, entrepreneurial mindset.

And what they did was, so they, went and tried to learn management. They tried to learn accounting and ba and basically what I frequently saw is that you lost the guy that knows. Most about science to have a manage management guide that has very few experience on that. 

Philip Hemme: Yeah. Yeah. Okay.

Pedro Madureira: And actually the, this model of venture catalyst is really nice because I I, continue to do science that’s my job. And I we were almost assured that the accounting, financing management, daily management legal, yeah. Was supported by, by, by them. So I really think if, it wasn’t for, their model, for their, unique mindset this never happen.

[00:15:41] Taking down multiple superbugs with a single vaccine

Philip Hemme: And now you, so how the product, can you talk about the product? I think you’re in like free I and d which is already really good. Can you, and I think you have from my understanding, you have. Vaccine more therapeutics approach, the vaccine is the most advanced. Can you talk about, that part?

Yeah. 

Bruno Santos: So actually the, once we, we are this, nausea started to think, okay, this is great. So we see that bacteria can interact with immune system, it can block it, and multiple bacteria are using exactly the same viral mechanism. And so if we target this common viral mechanism, we are stopping a lot of bacteria at the same time.

So that in itself would be unique. And okay, let’s do it. Let’s reach for the stars. So that’s where we, started de developing a vaccine that would be able to block all all of the bacteria and actually that’s good. 

Philip Hemme: The target. G-A-P-G-V-D-H. 

Bruno Santos: Exactly. Yeah. And so as, it is a lot coming between these, different bacteria, we could target it at at the, same time.

Philip Hemme: Yeah. 

Bruno Santos: And so we started developing the, formulation got to good immunogenic formulation. Yeah. To to develop and a good practical package. And that’s when we started talking with ary entities and try to, understand what would be the, path to move forward. 

Pedro Madureira: Yeah. 

Bruno Santos: And that’s when we, hit the roadblock.

Because we saw Okay. Usually what to vaccines do they, show that they are immunogenic and they need to prove efficacy on the serotypes that they are targeting. Yeah. But we are targeting all serotypes. And more than one bacteria. If we need to prove that for each one, this would be a, gigantic clinical trial.

So we, it wouldn’t be possible. We tried to do it by focusing on the mechanism itself, on showing that we were targeting the different gats, but we, couldn’t approve a product based only on that. Yeah. And okay. We need to change our approach, although the results were good and probably there will be a time where that vaccine will be possible to, be on the market when we start getting it all together.

But for getting it an approval we, need to have a different strategy. When we started focusing on having a formulation dedicated to a family of bacteria. And at this point we have three different formulations. One of them that’s I would say our lead product for pneumococcal.

Yeah. So per pneumococcal species. So not only St. Pneumonia, that is the best. Let’s not only pneumonia that is, has already a vaccine on the market. Yeah. And several ones, 

Pedro Madureira: yes. 

Bruno Santos: But they cover some serotypes. And in our case, we would cover not only all the serotype for str NoMo, but other strep species as well.

Okay. We still have a very broad coverage in, terms of of our vaccine, but we won’t need to prove such a enormous as we did before. And for example, another program that we are developed with CarX for e coli, again, a dedicated formulation that will help us cover all the, 

Philip Hemme: whole eco, basically any Eli strain.

Bruno Santos: Yes. 

Philip Hemme: Okay. And then when you tap the whole strain, you don’t have any kind, not side effects slash I don’t know, e coli tapping the microbiome, for example. I don’t like, 

Pedro Madureira: that’s a very nice point. No, the answer is no. Okay. So if I may, let me go back a little bit just for you to understand or for everyone to understand this, mechanism.

Yeah. So one of one of the questions that that, we did to ourselves was, why isn’t our immune system able to control this infection? For, if we think on why antibiotics don’t work, why traditional vaccines don’t work, we came to the same conclusion. Our immune system is not, it is our immune system that is not working properly.

You have people having recurrent infections with the same bacteria. Even if we don’t understand anything about our immune system, we know that there are, we, if we survive infection, we should be protected for the rest of our lives. We, but why, are this happening with this bacteria? And that’s our, main, question at Immune Immunes.

And even before immune Sep was trying to understand why our immune system isn’t coping with this type of infection. And that’s when we found that all different bacteria, which is also very interesting in a biological perspective. Yeah. If different organisms evolve the same way to escape our immune.

It’s probably because it’s, it works. Yeah. It’s a good strategy for, them. Yeah. And again, targeting that we are not we are not directly killing the bacteria. We are not working as an antibiotic first. When you take an antibiotic, it’ll completely kill the bacteria that we have. But here, what we are doing is restoring the ability of our immune system to fight infection.

Okay. So we won’t need to, so o only when the, bacteria starts, the infectious process to start to invade us. Okay. That’s when our immune system needs to work. Needs to, okay. No, here you cannot, pass. And also, 

Philip Hemme: so it’s similar to even similar to a checkpoint ter immuno-oncology where you, activate the immune system.

Yeah. It’s okay. 

Pedro Madureira: You are, instructing your immune system to. Blood. Basically to neutralize Yeah. The thing that bacteria use to neutralize our immune system. Exactly. If they are in our gut, it is no problem. Yeah. Because they are there, they are not causing any infection. They are not Yeah.

Causing any harm. But if they invade, for instance, our bloodstream, they are able to get to, to to an organ, then our immune system should know that is a threat. Yeah. And, should control the infection. That’s what Naturalizing app DH is doing is restoring the ability of our immune system to recognize the threat and control the infection.

Philip Hemme: And what’s your data package, your preclinical data package? Is there like model how do you model that? What’s the pre efficacy like?

Pedro Madureira: So we there are for a vaccine. There, there are a lot of things that you need to do. One is to show. That once you inject the vaccine, when you treat the, animals with the vaccine it, induces a strong immune response. Yeah. It’s to say it is immunogenic. Yeah. It increases the amount of antibodies.

It’s against the, vaccine, the antigen per c that is the first thing. The other thing you need to show that in the mice model in the, nan model, in the laboratory model if you, vaccinate, we work with the mice. Yeah. If you vaccinate the mice and if you infect and afterwards the vaccinated one are protected from infection, that’s what we need to do.

And another very important aspect is, the vaccine safe? Yeah. Again, we need to, show that there was no difference in the gut microbiome composition. There was no adverse effect associated with vaccination. Yeah. And basically this is the preclinical package that you need to show to the regulatory agencies.

To the regulatory entities. And also, I would say this is a, an important part of the preclinical package as well. Yeah. It’s how easy it is to produce your, vaccine. Yeah. How, easy it is to scale up if we want G gmp. Exactly. Because one of the things that, that it may have something that is amazing that can save a lot of people, but you cannot produce it.

That would be a problem even for the regulatory agencies as well. And actually one of the things that we are, we have been improving in this last year is that scalability of the vaccine working with with with 

Bruno Santos: car back specialists. Always. 

Pedro Madureira: Yes. With car back specialists. And try to be sure.

So we know now that our vaccine is safe. It’s very immunogenic. It protects against this, different bacteria. And we have been optimizing as well, the products that we are using, yeah. The process that we are using. And now I think we get to that point that we have a very scalable product and a very safe and efficient vaccine.

Philip Hemme: That’s good. Yeah. We’ll talk about the finance side afterwards. Okay. But to finish on the,

on the product now on the product itself, because my understanding is you are using magic is a peptides that are, present on, on the strains instead of, if I can say the package, them Suzanne injected as a, vaccine. Can you talk about this, I dunno how much you can disclose, but how do you, formulate it?

Like how do you isolate it? How do you manufacture it? There? 

Pedro Madureira: Yes. Do you want to start, or shall start? I dunno. 

Bruno Santos: Can give a general picture on. So in terms of the product, what we are doing is we are using parts of the, protein. Yeah. That we identified as the ones that are completely only present in, in bacteria, not present in human because humans also have capt.

And so that was a very important part and contributes to the safety of our vaccine. And we selected the, major regions that we are able to, target. And so that’s what we do. So we, have three different regions of the protein and the pep text that we use are representing those regions.

Okay. As I mentioned before we are targeting, depending on the, bacteria to which we are targeting, we make it like 100%. Similar to the e coli GA dh, for example. And so we have a dedicated vaccine for e coli, but if we are doing it to strepto for example, we will use the strepto ga d that is is somehow different.

But again, using the, those same areas that we know that are the ones that are immunogenic. And so what we have to do later, we, in terms of reducing the, number of drug substances that, we have we, fuse these peptides together and we put it together with a carrier protein in order to have the immunogenicity that we extend.

So in general terms, I would say this is what the product that we have. We are targeting different zones of the, protein, of the ga th protein specific for that strain bacteria together with a carrier protein that allow us to have very good immunogenicity and very good results.

Okay. 

Philip Hemme: Sounds good. 

[00:27:30] Preparing to challenge Pfizer’s $7bn+ Prevnar

Philip Hemme: Yeah. And and on the five side, I heard you. Raising a round at the moment. 

Bruno Santos: Yeah. 

Philip Hemme: How is that going? Yeah. 

Bruno Santos: Actually it’s, already going in a pretty advanced way. So we are looking for a 16 million round at this point. We already raised six, so we have 10 million to go.

So Eric, if you want to then Yes. And that’s something that we expect to, to close on the, next mass. So we are working to close the CSA for, the next almost 

Philip Hemme: and, soap and 16, just to give in perspective, because so far you have raised 14 something around there. 

Bruno Santos: Yes. Something around that.

Philip Hemme: Okay. 

Bruno Santos: Between venture capital and also non dilu, non-dilutive funding. 

Philip Hemme: Yeah. Okay. And what’s the core targets? I guess VCs, some agents, 

Bruno Santos: yes. In this case, we are looking for VCs, especially VCs in the, area of infectious disease and the biotech in general. Yeah. 

Philip Hemme: Okay. Okay. And also like some foundation, like whether been the Gates Foundation, 

Bruno Santos: Yeah, actually the number the amount of money is not that high because in the car back contribution, for example, that is a non-dilutive funding.

They are funding a big part of, the project, in this case the DLA vaccine. And so we just need to assure the remaining part that is not funded by them. And so that helps us also a lot. Okay. As not only the specialists that we have, but also a big part a significant part of the non-relative funding that we need to move to the 

Pedro Madureira: next stage.

Okay. Sounds good. And 

Philip Hemme: on the, market, on the competition, because I was surprised when I looked at it, but that, Pfizer, 

Pedro Madureira: basically the vaccine 

Philip Hemme: they have is like 

Bruno Santos: almost eight billion annual. Yeah. On the antibiotics. 

Pedro Madureira: Yeah. 

Bruno Santos: We are talking about a vaccine. 

Pedro Madureira: Vaccine. 

Philip Hemme: Yeah. 

Bruno Santos: Vaccine Pneumococcal vaccine.

And so Prevnar, it’s the, biggest in the market from from Pfizer. 

Philip Hemme: Oh yeah. 6.5. Okay. The, Merck one. That’s okay. Merck is one 

Bruno Santos: together, we are talking about around billion market a year. Wow. And the, what we see in the pipeline is, a lot of companies trying to make a, better product than the one that’s in the market by adding additional coverage.

So for example, Prevnar covers 20 serotypes from Primo Cox. And what we see is that to GSK, for example, just acquire a VAC that has 34 serotype coverage. It was 

Philip Hemme: a big deal. Is that two, 2 billion. So figure, 

Bruno Santos: and we are seeing the VAC sites that is developing as 31 serotype coverage vaccine as well.

Yes. And so we are seeing a lot of people that, players that are trying to add some additional coverage. With our approach by having only one target, because we are not targeting each serotype by itself. We can cover all the different invasive serotypes. And so 

Philip Hemme: how many others? 

Pedro Madureira: Around 90. 

Philip Hemme: 90, 

Bruno Santos: okay.

90. Okay. So if we go step by step, serotype by serotype, as we are saying, probably we’ll get there in 100 years when the technology allows us to do it, and with our approach we, can do it. So that’s, how different our approach is. 

Philip Hemme: Okay. And how is the vaccine? What’s, that’s the, how is the product?

How does it work? Just for example, Prevnar. How does it what’s the fa work? 

Pedro Madureira: So basically w the bacteria we, heard, a lot of viral variants, right? Because they have different structure at the surface. Yeah. Because what our immune system sees and is able to attack is the surface of 

Philip Hemme: the antigen on the surface.

Yes. 

Pedro Madureira: The antigen had to surface. That’s it. But bacteria is the same. They can have different molecules. Usually sugars. Yeah. That may differ. Different variants have different molecular composition of their sugars at the surface. So what, the, those vaccines do is they pick a sugar from a serotype variant and they put it in the vaccine in the shot.

Philip Hemme: Okay. 

Pedro Madureira: But with 90 different serotypes, they need to put 90 different molecules in the same shot. 

Philip Hemme: I guess even for the serotype it changes. 

Pedro Madureira: Yes, It’s practically impossible with the technology that we have today. And and there’s another interesting thing because actually those vaccines, they work pretty well.

Yeah. For the serotypes that they cover those vaccines, they work pretty well. So because they work pretty well with those 20 serotypes, what we see is that the other serotypes that weren’t. That represented, started to be the ones that increase their business. 

Bruno Santos: Yeah. What we talked about with the psoriatic replacements Yeah.

As well in the vaccine 

Pedro Madureira: is now there’s even one adaptation that is really interesting. There are some streptococcal pneumonia vaccines that cannot be included in any serotype. They, are, what we call it encapsulated strains. They don’t have sugars on the surface. Okay. So none of those vaccines we were able in those unc encapsulated strains.

Yeah. And just for you to know, for instance, in Portugal here in Portugal, I’m not the, those unca unencapsulated strains represent already 9% of the infections caused by strep pneumonia. There’s no vaccine that can address those type of problem, 

Bruno Santos: at least with the, 

Pedro Madureira: so traditional fact, and again.

They all excrete gap, DH, they all use gap D. So again, we really need that. When I was mentioned, we need to sync a little bit different in order to get different products. Yeah. I think I was mentioning our, have that in my mind. So not only we need to sync on platforms or different technologies to increase the serotypes, the sugar mocos, but we really need to think in different ways of targeting this bacteria.

Yeah. That would be that have widely coverage. 

Philip Hemme: Yeah. 

Pedro Madureira: For the pin cocom, but for the others. 

Philip Hemme: Yeah, same. 

Pedro Madureira: Those, that strategy of targeting surface antigens don’t work at all. So we likely need to, not to change the surface antigen that we are targeting because that to be surface antigen, but really think on why our immune system is not coping.

Philip Hemme: Yeah. And at the end of the day it’s. As you said, all the approaches are complimentary. Of course, you need all of them to fix, or to solve the problem course. And, how, but, and you said that, they target the different antigens, so they, formulate what if they are at 20 or 30? They formulate the 30 together.

Pedro Madureira: Yes. 

Philip Hemme: Is it what, like inactivated back to how do they deliver it? What’s the actual package like? 

Pedro Madureira: Man, actually it’s, nowadays we can isolate or we can synthesize the molecule that we want. It’s not back on those past days the idea was let’s at ate the, pathogen. But 

Philip Hemme: even today, some for viruses at least you still in 

Bruno Santos: this case.

Pedro Madureira: Yeah. And it worked very nice, but one, one strategy that could be easier instead of attenuating the old pathogen, you can pick a few representative molecules of that pathogen. And put them in the shot and present that to our immune system. 

Philip Hemme: Okay. So they’re not encapsulated, it’s just 

Pedro Madureira: no, it’s just the sugar conjugated with a carrier protein.

Philip Hemme: Okay. Okay. Yeah. 

Pedro Madureira: And basically you need to put 20 sugars each conjugated with a carrier protein in the same shot. 

Philip Hemme: Okay. Yeah. 

Pedro Madureira: And that start to be practically impossible because it’s, 

Philip Hemme: and then you inject intramuscular, intravascular and okay. 

Pedro Madureira: So I, no, I don’t. One of the important aspects of the vaccine, so again, our immune system has this amazing ability, which is once he encounters an antigen, a new, let’s say a new pathogen, our immune system the first time our immune system needs some days to have a full activation of its immune response.

But an amazing thing is that on a second or on a posterior encounter, our immune system acts immediately. Some, it has this ability to create a memory to that specific pathogen. And the second, third time it can act almost immediately. What is the problem? Sometimes the first infection, because our immune system has still that memory, the first infection can, be fat on, can give you sequels.

So the vaccines, what the vaccines do they present to our immune system, the pathogen, without causing the disease. They are, saying, so the, thing that you need to attack, that’s the way of traditional vaccines. What we see for some of these bacteria is that presenting surface antigens is not working per say.

And why? Because if, our immune system is able to recognize the surface of bacteria, it’ll produce antibodies against it. Those antibodies will not kill the bacteria. Those antibodies will signal our immune system that should be activated and kill the bacteria. Yeah. So let’s imagine you have a bacteria, you have antibodies against bacteria, but that bacteria is ex exploiting the age, so those antibodies will never be able to activate immune system.

You need to neutralize the gat and then again, having antibodies would be good. Okay. Yeah. But what we are seeing not only with our data, but with all the data that we have from the vaccines that fail on clinical trials, we are seeing that antibodies against bacteria is not enough. 

Philip Hemme: Yeah. 

Pedro Madureira: We really need to, neutralize the immunosuppression that the bacteria is able to do.

Philip Hemme: And one side question, but the, how much is it connected? I, feel like quite a few of, anti-me infection happens for patients who are a bit. A bit later in life or where they, I guess the immune system is already a bit suppressed. I guess it’s the same as with, onco, with cancer or oncology, where checkpoint inhibitors work, I think only in 30% of patients, because if the immune system is too depressed or suppressed you, it cannot accurate.

In your case, it’s also you have a similar mechanism, or you expect, see similar mechanism or like 

Pedro Madureira: more or less made with a, with we think a slightly advantage. Okay. Because in cancer, then again I, think that’s a very nice analogy. Our immune system is perfectly able to recognize some cancer antigens.

If you put a in vitro, if you have a cancer cell and immune cells, we see that our immune cells are able to recognize cancer cells. They have new antigens. They have they are, but what we see in vi. Yeah. Is that somehow the cancer is suppressing our immune system to work the, of it. It causes some kind of environment, anti-inflammatory immunosuppressive environment that disables our immune system to work.

Yeah. Which is very similar to what we see bacteria. But in cancer, the checkpoint inhibitors that we are using in cancer, they are targeting, they are basically accelerating the activation of our leukocytes, of our immune cells. What we are doing in bacteria is not only that we are neutralizing what bacteria is producing.

So the actually the, real comparison or the more realistic comparison would be if in cancer we would be able to suppress, to neutralize what cancer cells are producing that is able, our immune system toward that could be, I think. You could have answer there. A universal vaccine for cancer.

Yes. And I think that this mechanism of targeting bacterial mechanism, so we know bacteria messes up with our immune system, how it masses with gt, so not loss that package. And then everything works properly and we don’t have any sequence and we are not even messing with our immune system. Yeah. We are just balancing the, sales 

Philip Hemme: response.

I like this. Back to the if, the sales are so, high, it means there is a market as in 

Bruno Santos: Yeah. 

Philip Hemme: As a reimbursement. There’s a market. Like how, does that when you talk to investors, I guess that’s like a, you show that there’s a there, I mean there’s a market, there’s potential returns.

How is the reaction 

Bruno Santos: that, that’s a clear market for strep pneumonia? Yeah. The market is there, it exists. So that’s clear. But for example, for the e coli vaccine, a lot of attempts were done and they didn’t reach okay. The market. So we don’t have, it’s a clearly un met medical need.

The same with the ef we are not being able by the traditional approaches to to, get the product to the market. And 

Philip Hemme: okay, so there is nothing on the market 

Bruno Santos: Exactly. So we see a clear marketing we wanna in, in our lead product, but in the other two, for e coli and for we are opening, we are able to open markets that will be probably not as huge as but like 5 billion or something like that.

And we are talking about three huge markets that we will be able to address. Okay. 

Philip Hemme: And are you already are you already talking with the big, like Pfizer? GSK is a 

Bruno Santos: big, pharma? Yes. We’re in contact with the, with big pharma, so not many pharma companies are vaccine we all know each other.

So it’s, easy to, bump into each other. For example, we’ll be at the World Vaccine Congress. Everyone is there. It’s easy to fight each other. But of course they, the, they know our approach. But usually pharma, companie are more interested in products that are inter clinical. But they are following a closely, and we already had collaborations with two big pharma companies during our development process.

Philip Hemme: Okay. Yeah. Okay. So they’re waiting for Yeah. A more clinical package. Yes, okay. 

[00:42:11] The Portuguese biotech ecosystem

Philip Hemme: I wanna talk maybe on a bit, expand a bit on, on Portugal since we are here in Portugal as well. So I think you are in the biggest ballpark of Portugal, from my understanding. 

Bruno Santos: Yeah. Based in can that’s yeah. In the center of Portugal.

Yeah, it’s close to Queen brother. 

Philip Hemme: Okay. Okay. Okay, but you live in, 

Solving Antimicrobial Resistance, Vaccines _ IMMUNETHEP 🇵🇹 _ E55 [Sponsored]: port. 

Philip Hemme: You live in Port. Okay. And how, do you look at the Portuguese ecosystem? Yeah. Biotech, ecosystem. How do you look at it? 

Bruno Santos: Actually we are growing with the Portuguese ecosystem. It’s interesting to see that when when we started, so 10 years ago not many people were, working on, this area.

Although we have a lot of of research and in terms of research, we start to have a lot of patent, a lot of publications on, on on the, biotech space. But there were not many companies in. Born from that. Yeah. So we are probably one of the, first lines of companies that Yeah.

Started to do that. Not much funding was available at, the time. Not a, real ecosystem. We went to that biotechnology park. Yeah. In can but there weren’t many options where we could we could create the company. And that’s not so true right now and thankful for the, new guys that starts and girls that started the, new companies because now they have much more spaces where to have the companies.

It’s much, there are much more money available to, help in these earlier stages and also the ecosystem in terms of knowledge on what to do even from the universities, it’s completely different. Yeah. So we are seeing that, that growth in terms of of the country on waste to support. Companies like like ourselves, probably we didn’t have the same support that they are able to have now.

And luckily for them that’s the, 

Philip Hemme: Yeah that’s, the game as how who, do you, what are your peers who have raised some good rounds? Like in the likes? 

Bruno Santos: That’s the point. So they are in earlier stages than there we are. But for example, we have a recent case from cell Max developing a, cancer therapy that was able to, sell it to BioEnTech with a, very nice, 

Philip Hemme: I heard about, I heard Ricardo from who invested in Yeah.

Bruno Santos: Okay. 

Philip Hemme: And that as a really good success story. 

Bruno Santos: And when, you have investors in Portugal that start having exits and start having success, they will have more money available for the next ones. And so yeah. Know it helps. We are all growing with that and taking advantage of 

Philip Hemme: that. Yeah. That’s good.

Yeah. And this morning recorded was, I told you from bi 

Bruno Santos: Yeah. Different story, but. 

Philip Hemme: Different story though, but are also 

Bruno Santos: very entrepreneurial 

Philip Hemme: entrepreneurial, a good one. Lot of, biopharma innovation. And I know you, you know him as well. Yes. You work at ya. So it’s a small world. But I think it’s really important and also more pharma partner.

Pedro Madureira: Yes, for sure. 

Philip Hemme: Because at the end of the day, it’s pharma development. 

Pedro Madureira: They know the markets. They better than anyone. Yeah, for sure. 

Philip Hemme: How do you, like, how do you see them? How do you collaborate with them? Or like indirectly I guess More than they’re not in the best 

Bruno Santos: accurate space.

That’s, the point. As we are not so many at this point. And in some cases we are in different areas. So days of that automation, they are on the neurological space. We are more on the infectious disease space. Not many connections there, but there are connections on other things and we talk with each other and help each other on on the developments.

Where it makes sense, of course, but unfortunately not in the same in same development space. Yeah. 

[00:46:10] Bruno Santos’ cross-disciplinary experience

Philip Hemme: And on a bit more on the on the personal background, I think you were also more in the tech space before biotech is correct. More tech, areas. Yes. How was that how, does that experience help you today?

Like what? 

Bruno Santos: Yeah, actually, my, my background is a little bit strange, although my background, I, it was in biological engineering. 

Philip Hemme: Yeah. 

Bruno Santos: I started working on the metal working industry. 

Philip Hemme: Yeah. 

Bruno Santos: Then to, make it closer I, went to the electronics industry. Yeah. And so, really high takes. Yeah.

Yeah. And but the, for example, the electronic had a lot, I was working more on quality control and that part I think it’s very similar to, what we have on the, pharmaceutical side, 

Philip Hemme: especially from a GP 

Bruno Santos: point of view. And so that is quite similar. And so that’s industrial approach and that control of the process and of the product that’s stick with me from from early on.

Philip Hemme: Okay. And, where is this entrepreneurial part coming from? Yeah. And you, answer partly 

Bruno Santos: no in, in this case after working with the different industries and seeing there’s so many cases. I say I, I wanted to do this, but I was like, maybe I shouldn’t do it. Maybe I should know more on how to do this.

And that’s where when I decided to do the An MBA Yeah. And after that, I felt more confident and with some partners that want, were willing to do it with, me. 

Pedro Madureira: Yeah. 

Bruno Santos: To, give this pass to this additional step that, yeah. That I, wanted. So something that was there and grew during the MBA and after that I, couldn’t look back and that was what I wanted to do.

Philip Hemme: Yeah. 

Bruno Santos: And luckily it was with Piero, but look at me. 

[00:48:09] Not taking ‘no’ for an answer from big pharma

Philip Hemme: And I guess it’s also opportunity, opportunistic way of, but you need the opportunity as well to get started. 

Pedro Madureira: Yeah, exactly. For when you said opportunistic, you pointed at me. 

Philip Hemme: No, because I’m not saying opportun, 

Bruno Santos: I’m joking. Come on. 

Philip Hemme: I, was not meaning opportunistic in a, personal way.

I’m meaning probably you bought the opportunity. 

Bruno Santos: Yes. That’s it. 

Philip Hemme: In that way. Yes, course. 

Bruno Santos: Actually, it was interesting because the first contact we had with the group where Pedro was at Yeah. Was with the, lead scientist for the group wa was a professor, but is Pedro’s professor as well.

And we, saw the publications, what they were doing. We find it very interesting. And we went to, to speak with her and they said, oh, we are interested in seeing if we could take this to, to the market. Would you be willing to, join or will you be interested on this? And I said, I want nothing to do with with companies.

And we said, oh, 

Philip Hemme: let’s stop. Let’s stop. 

Bruno Santos: Yeah. We, say, okay, this it’s a, project that we will we’ll d die in the, end, because that happened a lot with us when we are looking for, opportunities, as you were saying. But after that she said, may I have someone in my team that might be interested in on doing that?

I will present to you in the next meeting. And in the next meeting, pk. And he said, okay, would you be interested? I said, yes, I am. And then everything started from there. That’s, but the first approach was, I don’t have anything to do with it. 

Philip Hemme: You take no for an answers. Yes. Especially in entrepreneurship.

Pedro Madureira: Actually, that’s a good point. Sometimes when you, hear a no it’s, a, it’s not a no from the company, from the it’s a no from, that’s the 40 person. Yeah, and you should always, okay, that’s no for this guy, but what about this other one? The, I don’t know if I’m supposed to say that, but I will say that there in one of the, this big pharma, the one that we were actually have the best collaboration with the first guy, that we first talk from that big pharma company we we, spoke with him and the first thing we presented the project, oh, this is not, and the actually it was not the first, it was the only thing that he said, I don’t believe in vaccines.

Philip Hemme: Wow. 

Pedro Madureira: Okay. 

Philip Hemme: So discussion. 

Pedro Madureira: Let’s forget discussion. Let’s forget the, but no, actually it was the, comp the big pharma company. That’s. Help us the most. It was really recent interactions we were able to have with the we still have. Yeah. Yeah. And 

Bruno Santos: but actually that person was not the clearly the contact that we, 

Philip Hemme: I think it’s a good lesson for the conference as well, for people listening in partnering.

Pedro Madureira: Yeah. 

Bruno Santos: If, we 

Philip Hemme: decide taking in no, and then focusing on the people. I, heard that several times, but 

Pedro Madureira: it depends, 

Philip Hemme: especially in a big organization where you’re like hundreds of people doing partnering, 

Pedro Madureira: hundreds of people, a lot of turnover on the guys that worked there. Actually we, still have conversations.

We still had operation and it does not work there anymore. So it’s about, that’s real life. It’s not that weren’t a fit, it wasn’t a fit to the 

Bruno Santos: organization. 

Philip Hemme: I can, yeah, I would another story on that as well as maybe 

[00:51:44] Immunethep’s IP and tech transfer achievements

Philip Hemme: your last, a last question then I want to finish more like a quick fire, quick question.

Quick answer it. One thing I didn’t ask is about ip, but when I hear about talking to PIs University, I hearing tech transfer in the background as well. 

Bruno Santos: Exactly. 

Philip Hemme: How was that tech transfer process first and then more about the IP situation, or how was that like? 

Bruno Santos: Yeah, actually it was quite smooth because when we reached out to, the, research group and they, had some publication, but it was not fully developed.

And we were working like one and a half year with, Pedro on, what should be the, type of experiments that we needed to do to have a good intellectual property. So a 

Philip Hemme: pattern, there was no pattern, 

Bruno Santos: basically. Yeah. Okay. And so we were working from that time together with the group to, to do those first experiments.

We got good results and we, wrote the patent together with the patent office and the, university. And and I would say probably it’s a record in terms of University of Porto. Two weeks after the, patent submission, we were licensing it to tech to start the, product because we have done it all in parallel together with with them.

Okay. That helps. And licensing. And licensing, exactly. 

Philip Hemme: Okay. Because I, what I hear sometimes for universities who don’t have experience with licensing that they’re. Things are slow, the terms are not right. So in your case, I guess as 

Pedro Madureira: I was saying, the okay, actually the back when, back in those days, 10, 10 years ago, or we are not around that.

It wasn’t so the, patent office the, tech transfer offices at universities wouldn’t have in Portugal. Didn’t have that, that much experience on this process. Yeah. But, and actually the, tech transfer office at University of Corto was really willing to, change that process, to try to put that more, I would say swift, more, more practical, more and, actually I, I think go back a little bit again.

That, that contribution of venture catalysts on that process was really nice because actually. Yeah, they were able to we were able to find an environment where all of us wanted that thing to work, 

Philip Hemme: Erica. 

Pedro Madureira: And I think that was also, obviously we have that issues of going back forward trying to, have the, superior opinion and approval.

Obviously we have that, we have some discussions, but I think that overall, yeah. It’s, we will all, all of us wanted that a thing that’s really worked. 

Philip Hemme: Yeah. 

Pedro Madureira: For all of us. So I, guess that’s. 

Philip Hemme: And what’s the IP situation now? What’s your IP package? 

Bruno Santos: So we have this initial package that was licensed for the University of Portal.

That works like an umbrella patent. So covers That’s 

Philip Hemme: 10 years old, 

Bruno Santos: basically. Exactly. And now for this specific formulations, we have a, new patent that is like formulation patent that directed to the products in itself. And so that’s part of our strategy, this umbrella patent that allowed us to make the developments and now the specific product patents to start the, countdown later on.

Philip Hemme: And that’s enough that’s enough to then cover potentially the whole clinical trial? Yes. Cy. Okay. 

Bruno Santos: That’s it. 

Philip Hemme: Okay, cool. 

[00:55:44] Quick-fire questions

Philip Hemme: Let’s finish with more like quick questions, quick answer, I guess you can, we can do one of you start the answer and then the other person, 

Pedro Madureira: thanks. 

Philip Hemme: One question is did, COVID help did COVID help to to bring more awareness to antimicrobial in general?

The pandemic? Yeah. Yes or no 

Bruno Santos: No. Actually, it people got more get to know what vaccines are, what different strains of a virus are and so on. And so it was interesting by, that. But then it was so much information that in the end people knew that thought they knew everything about that.

And when you’re talking about the, infection space, everyone was a specialist. And 

Pedro Madureira: kicking in a short answer the goods for I don’t think COVID out anything for a MR space. Yes, no, for sure. 

Bruno Santos: Okay. That’s the, 

Pedro Madureira: if that is the question. No. Is the, obviously we have in real time in the news people discussion, discuss, discussing about connect the kinetics of an infection and of the kinetics of a vaccination.

Yeah. Yeah. That was, a good global awareness for the importance of vaccines. That’s for sure. For a MR space 

Philip Hemme: one mistake you made in the past 12 months. One mistake each. 

Pedro Madureira: Only one 

Philip Hemme: if it’s not the same mistake. 

Pedro Madureira: We never do mistakes now. We have a lot we were, it’s me. It’s not you. No.

You can 

Bruno Santos: start 

Pedro Madureira: I think one mistake, and we were discussing this very recently, I think one of the mistakes that we did is not to be, is not to push enough to this message. What this message that we really need different things. We really need to innovate to, in innovate, to innovate on different things.

This is a space where where there is a space for everyone, but we really need to start doing different things if we want to have different, outcomes. And I really think that we didn’t push this enough. We didn’t press, we didn’t highlight this enough to our investors to once, perhaps the public in general, but if I, had to, choose a mistake, obviously we, in the lab, we did a lot of mistakes on a daily basis.

But the one that keeps coming in the back of man, and we really need to push this. In a more intense way. We, don’t need, I think there is no time anymore to be polite on this. We will, this is the problem. The problem is there. We need new solutions. 

Bruno Santos: Yeah. I, think I, agree. I think the, urgency of the, problem we are probably not passing it enough.

Maybe we should be much more strict on 

Pedro Madureira: bringing people to this. 

Philip Hemme: I think now you were quite quite pushy. At least quite clear. 

Pedro Madureira: Okay. Tough. 

Philip Hemme: What’s the most common mis misconception that the industry leaders have about the A MR crisis? 

Pedro Madureira: No, I think it’s this, I think it’s that developing, 

Philip Hemme: but it’s not two crisis are not big enough.

Pedro Madureira: Yes. The, sorry, two crisis? 

Philip Hemme: No. Yeah. What what the misconception? 

Bruno Santos: No, I think the it is clear that it’s a crisis. I think the misconception is. We should do more of the same to overcome it. Yeah. And that’s not working. And it’s not working in antibiotics. It’s not working in vaccines. And what we are saying is we should be doing different things.

Yeah. We are bringing different things because this is something we need to act on and need to bring different strategies to, to it. And we believe, of course, that our strategy is a, different approach, that it deserves its space and will show that new, approaches will help solve the problem.

Yeah. And that’s what I believe the industry needs is that someone with a new approach shows that there are results and probably some new approaches will pop up and help us solve these problems. 

Philip Hemme: I like it. Two more or second. Last one. One of your biotech heroes or mentors?

Pedro Madureira: I don’t know. I, there are some because I’m, coming from a. The research, more research field or research area. Some of my mentors are more on the academic side. Yeah. Yeah. Actually I’ve been, actually, I never said this so, this is the first in public at least.

I think that, and I’m saying this as honestly as I can say, one of my heroes in this industry is part of our advisory report as Don Jersen is a guy that worked in vaccines for many decades. He developed so many vaccines. He was important in so many ways in this vaccine field, and I think that we are really lucky and to, bring to, bring him to, to our board is now part of the company actually.

Is a r is around here and yeah, Don Jaren. I, would pick this guy as my biotech hero. Open 

Bruno Santos: very choice cycle name at anything else? 

Philip Hemme: Last one, one advice to you when you are starting the companies, 

Bruno Santos: start now and be pushy. We follow your intuition. 

Philip Hemme: Good one. 

Bruno Santos: Thanks guys. Thank 

Pedro Madureira: you. Yeah. Thank you very much.

Thank you very much. 

Philip Hemme: Cool. It’s good talk. Yeah. Thank you guys.

I am impressed by how Bruno and Pedro are one of the pioneers in building biotech companies out of Portugal. I’m also impressed by their determination to bring a solution to the antimicrobial resistance crisis. If you’ve enjoyed this episode, please hit the follow a review button, any of these action help many more people.

Discover the podcast. If you wanna find similar videos, you can check out our channel where we have many more. I would also be curious to hear what you think. So if you could drop a comment wherever you are, or shoot me an email@philipatflo.bio. That’s P-H-I-L-I-P at Ft Bio. Alright, thanks for staying to the end and see you in the next episode.