Little Pharma: Off the beaten track

There are hundreds of small, and medium-sized enterprises exploring drug and antibiotic discovery. Chris Smith spoke to Heather Fairhead is a Founder and the CEO of Cambridge startup Phico Therapeutics, about the drugs they are trying to develop.

Heather - We’re trying to develop a new approach to antibiotics, and particularly focussed on infections which are serious and occur in hospital patients, so we have a two pronged approach to this. The first component of our technology are bacterial viruses, so in the way that humans get viral infections, colds or flu, bacteria have their own viruses that can attack them. What viruses are designed to do is to latch onto their target cell, so in the nose it would be a nose cell for example. They inject their DNA and their function really is to make more copies of themselves and burst out of that cell and infect other cells and just escalate an infection.

We take these bacterial viruses and we strip out the genes in there that we don’t want, and we insert a gene which encodes our antibacterial protein. The beauty of our protein is that it’s a naturally occurring protein, so it’s evolved over millions of years to do what it does. It actually targets the DNA inside the bacteria and it changes the conformation or the shape of the DNA and it completely inactivates it.

Chris - This is in the bacteria you target, so it’s almost like you’re doing gene therapy on a bacterium?

Heather - Inside the bacteria themselves.

Chris - So you’re using a virus to deliver a genetic message that then distorts the DNA of the bacterial cell?

Heather - It’s a sort of anti-gene therapy if you like because gene therapy, of course, is used for good purposes, but they’re actually killing the bacteria. Or I should say really, the bacteria are actually killing themselves because they are making this protein which disables their DNA but they’re programmed to do that. The beauty of this really is that it doesn’t matter even if the bacterium mutate, which is how most antibiotic resistance arises, our protein will stick to and inactivate that DNA. So, for the antibacterial components, it’s very difficult to see how resistance would arise although, of course, in nature you can never say never.

Chris - When you say these are serious infections, what class of infection are you going for - what bugs is this targeting?

Heather - Our lead product is targeting a bacterium called pseudomonas aeruginosa, and that is really a problem in patients in hospitals. It can commonly cause hospital acquired pneumonia. But it’s really a major problem in patients on ventilators, so in ICU, and that can be a whole range of people, not just people that have gone into hospital because they’re already sick. But it could be young people who have had an accident or whatever and they end up on a ventilator and these infections are really difficult to treat, and pseudomonas is a really tough bug. It has a quite a high mortality rate so that’s our lead focus.

Chris - How would this be administered? Would it be squirted into someone’s lung or onto the skin infection, whatever the target is where the bug is growing, or would it be given via the bloodstream?

Heather - We can deliver this drug in a whole range of ways. We’ve developed a topical antibiotic for decolonising MRSA in the nose. That’s on hold at the moment while we focus on this higher clinical need area of pseudomonas aeruginosa. We are developing an IV drug, but initially we’re going for, as you say, direct delivery into the lung. This would be inhaled because people on ventilators obviously already have delivery into the lungs. We find that we can dose a lot lower amounts if we’re delivering directly into the lung and, of course, that plays into how much the drug eventually costs.

Chris - When you say that it’s very difficult for you to get resistance to this drug, because antibiotic resistance is a major, major problem. At the same time the bugs could, nonetheless, mutate so that the phage, the virus you’re delivering the chemical with can’t bind to them any more, couldn’t they?

Heather - Absolutely they can, and no technology is perfect. The fact is that, if you like, in our technology, which is called SASPject, the phage could be seen as the weak part of the technology. However, people understand bacteriophages; they’ve worked on them for many, many years. So we understand all of the weaknesses of the phage going into developing our product which means that we can actually influence its behaviour before we go forward into the clinic. That means that we suffer less losses later on because we can address those upfront during the development process.

Chris - Considering the business side of this, what’s your game plan? Is the idea that you will get this to a stage when a very big company that has the capacity to do the really big trials you need to do, and do the marketing that you need to do, and take the drug to market that you need to do will do that, or is the intention that you will get it all the way to market yourself?

Heather - No, we won’t take drugs to market. That’s incredibly expensive and very time consuming as your earlier guest said. We will take the drugs through the early clinical stages and then expect to licence that product to a bigger pharmaceutical company.

Chris - How far away are we?

Heather - From having a drug on the market? Several years.

Chris - Okay, but that still sounds optimistic. So you’ve got something that’s working?

Heather - Absolutely, and that’s the point, isn’t it? That we know the bacterial viruses can target bacterials so we don’t have the risk there later on that it won’t work. We know that our protein is designed to disable DNA so we know that works, and we’re just bringing together those two components. And, hopefully, in the end will have a drug that saves lives and that’s what keeps us all focused really.