B&M: David, perhaps you can start by outlining the elevator pitch for Synpromics?
DV: So Synpromics is a synthetic biology company. We have IP and knowhow in the design of synthetic promoters – stretches of DNA just upstream of a gene which determine protein transcription/translation efficiency. By synthetic promoters, we mean they are promoters which don’t exist in nature. Our synthetic promoters are designed to enable the controlled expression of genes under specific conditions: in a specific place or environment, or in response to a specific biological condition.
We provide a huge game changer in promoter design compared to the natural promoters that have been used in the biotech industry to date. We develop these promoters and provide them as solutions to our customers, for them to use across multiple fields of use, such as in bio-therapeutic protein production. For example, we’ve developed a synthetic promoter specific for Chinese Hamster Ovarian (CHO) cell lines, which have expression levels of greater than five to ten fold higher than the typically used Cytomegalovirus Virus (CMV) promoter.
We’re also targeting the gene therapy and DNA vaccine areas. Here we’re focused in two areas. Firstly, we’re developing promoters that are cell line specific, as well as having high expression levels. So for example we have a contract with uniQure where we’re developing liver specific promoters of a small size that have high expression levels, for use in developing products or gene therapy vectors that are specifically expressed in the liver.
Secondly we are developing promoters which can drive higher yields of vector production from gene therapy bioprocessing.Our promoters can also be used in other areas like cell therapies, industrial biotechnology, plant science or as diagnostic or research tools. Our approach is to provide these promoters to our clients and for them to use in their applications and products. So we’re not a product developer ourselves, but we provide a tool and enabler in other people’s product development.
B&M: What are Synpromics’ technology aims? What do biotech companies turn to you for?
DV: There are a couple of challenges for any biotechs looking to produce a protein product. One is always about yield. How do you increase yield of production to lower cost of goods and manufacture? By having a more powerful promoter you can boost the yield of recombinant protein and bring cost of goods down.
But the other challenge, increasingly, is being able to manufacture proteins that are difficult to produce; proteins which might have an interesting or complex glycosylation pattern, or maybe a complex protein that is produced inefficiently by the cell, so hence you get a lot of misfolding or impurities as well as the active protein.
Our intent is to develop a panel of promoters so you can select the right promoter for the protein that is going to enable some of these difficult to produce proteins to be manufactured much more efficiently.
B&M: How does the process work? Does a client come up to you and say ‘we need to be able to produce this kind of protein in this kind of cell and our promoters don’t work, can you make us one that works better?’
DV: In terms of the process it’sprobably easier to use gene therapy as an example of the promoter technology and how it works. In the gene therapy context, companies who develop a product are looking for activity of the gene therapy vector within a specific cell line. People have been trying to do that by selecting different AAV (adeno associated virus) serotypes for example. But we’re able to circumvent that and do it at the promoter level.
This is the difference with our technology. We don’t start with existing promoters and tweak them. We start totally from scratch, looking at regulatory elements, transcriptional control elements within the cell and build libraries of elements. Using our knowhow and technology, we can custom design these promoters from those elements to achieve particular purposes.
And then having the gene only expressed in certain cell types means much more efficient and precise targeting of expression which then obviously has an improved safety profile because of that as well. The other issue is looking for strong expression over a long period of time so that the dose you deliver can be much lower. This obviously also has efficiencies when it comes to manufacturing scale.
B&M: So to change topic slightly, I wonder if you could tell us a little about your background personally and what attracted you to this company?
DV: I’ve got nearly twenty five years’ experience in the biotech industry now. I started off originally with my research and PHD in bioprocessing, initially with monochronal antibodies and then vaccines; so of my years of experience, about ten of those have been involved in bioprocessing and product development. I’ve worked with a number of different companies, taking two vaccines to market and having them licenced.
I’ve then spent about half my time, another ten years, working in the contract research and contract manufacturing business. In this area I did a lot of early work in process development for gene therapy vectors back in the mid to late 90’s.
And for the last two to three years I’ve been involved in supporting start-up companies with getting started, getting funding and going to IPO. The reason I was attracted to Synpromics was out of all the companies I’ve seen recently and have been evaluating, Synpromics really stood out as having novel and unique capabilities and technologies.
In the ‘90s, the initial interest in gene therapy subsided and companies went back to the drawing board to address some of the original safety and efficacy concerns. Now, seeing it come back again with renewed enthusiasm and renewed investment, what I was looking for was a technology that added something significantly new to that field. That’s what I found in Synpromics. They were taking a totally different approach, using synthetic biology principles to solve some of the issues that gene therapy was facing around specificity and expression levels. I just thought this was an exciting team, a great bunch of scientists and a great scientific founder in Michael Roberts, who had something truly unique with a very clear application not just in gene therapy, but also with broader applications in biotechnology.
So much of biotechnology is about expression of genes, and expression of genes is all about promoters.
Focusing on promoters opens up many fields of use, in bioprocessing and cell line development, industrial biotechnology and in crop research, and in diagnostics and research tools.
B&M: Certainly I’ve noticed that emphasis in biotechnology often concerns gene products rather than the mechanisms of transcription and translation. In light of this, do you think more companies like Synpromics are going to pop up in the future? Do you think there’s a gap needing to be filled?
DV: Yes, I think people are realising that there’s much more to gene therapy than getting the correct version of the gene into the cell. It’s getting the right vector. It’s getting the right expression cassette. And now what we’ve done is provided a new tool in the armoury by saying ‘let’s get the right promoter too’.
Up until now people had very limited options in terms of what promoters they could use. People had to live with the inefficiencies of the CMV systems and other naturally occurring viral promoters that were used. We’ve come up with something that has totally novel capability and makes gene therapy much more effective.
B&M: Just to provide some background for our readers, what do you think were the main setbacks that caused gene therapy to sink back into the shadows twenty years ago?
DV: There was a number of things. In the early days there was a lot of focus on adeno-viruses, the original virus of choice. There were issues in immune responses. There were pre-existing antibodies against adeno-viruses in the population, or a very rapidly developing immune response against the virus, which obviously knocked down the efficacy.
There was a particular incident where in a clinical trial a subject enrolled in the trial unfortunately died during that trial so that raised a number of concerns and questions around safety that knocked the industry back and required people going back to the drawing board.
It was a number of different issues that really scared investors away and chilled some of the initial enthusiasm.
B&M: Obviously that has changed a lot now, the Cell Therapy Catapult having received so much from the government. What do you think has been the recent game changer? Why has the interest come back into the area?
DV: I think we’re starting to see some great clinical data. There’s now a wider range of virus types that can be used: different serotypes in AAV for example that address some of the original concerns. We’ve also seen a number of companies, particularly in the US, able to go out and raise significant amounts of money to support their clinical programmes and clinical development.
There’s some exciting clinical data coming out showing the use of gene therapy to restore sight and functionality in the eye for certain genetic diseases as well as gene therapy based haemophilia treatments and CAR-T therapies are using gene therapy or viral vectors to genetically modify the T-cells ex vivo before introducing them back to the patient. Gene therapy is experiencing a resurgence on the back of those things. That, and the general excitement that the industry has matured a lot.
B&M: That’s great. How attractive would you say your technology is to investors?
DV: We’ve certainly gone out during our fundraising and spoken to a lot of people. We got very positive responses towards the technology because it was so unique and game changing. People could see the value of what we were bringing and could see the clear value in both the business model and that we were not taking the risk of developing products ourselves, but making our platform available to other companies instead. In that sense it’s a de-risked approach, and investors like that. They also recognised that, as we continue to develop the platform and develop applications of the platform, it would give us optionality further down the road to take the company in some interesting new directions. There’s future potential over and above the scope of the initial offering.
B&M: And moving on from that, do you think it was similar factors that made you such an attractive target for the enterprise investment scheme?
DV: Yes. We were an early stage company that had shown it had a lot of room for quite significant growth: the company was essentially formed and funded from friends and family investment, and also from grant funding we were able to secure. So this was the first time we’d gone out to get a fund to invest in us.
They saw that they were coming in at a very early stage in the company’s evolution, but also a stage where the technology had already got some very good data validating its utility, and understood that with more funds behind us we could advance the platform further. That was very attractive from the EIS perspective.
B&M: Obviously you’ve already told us what kind of applications your technology has. Can you tell us any more about what projects you’re going to be working on over the next few years?
DV: Yes, so as I said, the platform can be applied to many areas within the biotech world: for us it was a matter of looking at all opportunities and picking the areas where we felt we could have the biggest impact and acquire the most value.
We’ve looked at the technology from the perspective of research tools, bio-assay development and industrial biotechnology, and these are all areas we can operate in. But we feel the area we can provide greatest value is in gene medicine, where the promoter is an integral part of the product and a key enabler of the efficacy of the product. So you’ll see us increasingly focus on creating diversity within the gene medicine field; in gene therapy, cell therapy, DNA vaccines and genetic medicines.
B&M: A slight aside. In your eyes what do you think the future holds for the UK life sciences scene?
DV: In my view, it’s currently a very exciting time for life sciences in the UK. We’re hopefully coming out of a period where funding was hard to come by, and innovation was being starved of opportunity. It’s meant that the strong science and the good product opportunities have survived.
I think there are some really good, investable opportunities out there at the moment. There are encouraging signs that money is starting to flow and investment is starting to come in. I think good science, good technology and good products are attracting funding. So on that basis we are looking at a robust and optimistic future.
B&M: Would you say that the last few years of science austerity if you will, where only the best science has survived, has acted like a filter?
DV: That’s my view, yes. But I’m sure that whilst some of the not so good may have been weeded out, we may also have lost some of the good. But what has survived has survived for good reason. And that’s because it’s based on good, strong science.
B&M: What do you think are the biggest challenges that Synpromics will face in the coming 12 to 18 months?
DV: One of the biggest challenges is that there are so many fields of use that we could be active in. We need to stay disciplined to maintain focus and not get distracted. We’re being approached by a huge number of companies with great ideas of how our technology could be developed and adapted to their particular purpose, and for a small company just starting out and building up critical mass and infrastructure, if we respond to too many of these opportunities too quickly then we will have growth pains. It’s a matter of getting the balance right between growing the company at as quick a pace as we can to make the most of the opportunities that are available without over-reaching.