Good day, ladies and gentlemen, and welcome to Syncona's full year results for the 2021-2022 financial year. At this time, all participants are in listen-only mode. Later, we will conduct a question and answer session through the phone lines, and instructions will follow at the time. I would like to remind all participants that this call is being recorded. I will now hand over to the CEO of Syncona Ltd, Martin Murphy, to open the presentation. Martin, please go ahead. Good morning and welcome to Syncona's annual results. Before we step into the specifics of last year, I would like to just step back and look at what we've achieved over the last 10 years. Syncona was founded back in 2012. At that time, we set out with a very ambitious plan to transform the way in which innovative life science technology in the U.K. was commercialized through company creation and to thereby deliver economic returns and innovative new treatments for patients. Since 2012, we've built 18 companies. We've delivered over GBP 900 million with attractive returns. From a patient perspective, we've taken three products into pivotal trials, which is the last trials prior to approval. One of those products, Axumin, has been approved and commercialized in the United States. We're proud of what we've achieved toward those goals over the last 10 years. It's caused us to begin to think about what the next decade might look like in Syncona. That's something we'll look forward to coming back later in the presentation to discuss. Coming to last year's results, it was a strong performance in Syncona in what can only be described as exceptionally demanding conditions for biotech generally. The XBI index was down 60% from its February 2021 high. Set against that, Syncona closed our year with a NAV of GBP 1.3 billion, representing 194 pence per share, a positive return of 0.3%. At the level of unpicking that underlying return, it was really a game of two halves, with the private portfolio performing strongly, seeing good financings across Quell and Anaveon, and of course, an excellent return from the sale of Gyroscope to Novartis right at the end of last calendar year. Unfortunately, the gains from these private companies were almost perfectly offset by declines in the value of the listed holdings. What this demonstrates, I think, is the value of a diversified portfolio and our ability to manage across that portfolio to deliver balanced returns for shareholders. One thing I would really like to draw out is the strength of our financial position. We raised significant capital at the level of the portfolio, and that was really a decision that we took to put capital into these companies at a time when we felt market conditions may become more challenging. We raised over $700 million across the portfolio with Syncona investing $126 million in those financings. What that demonstrates, I think, is the prudence of our approach to be looking to put capital at the right time into our companies, but also our ability to effectively leverage our own capital to bring substantial amounts of external capital into those businesses at good valuations. Towards the end of the year, as I mentioned, we sold Gyroscope to Novartis. As a consequence of that, we end the year with a very strong balance sheet at the level of Syncona itself, closing the year with our capital pool at just under GBP 785 million. We are really at a point at which the markets are currently pivoting, certainly the public markets, but probably also the private biotech markets as well. Moving away from technology-led stories towards more defined product opportunities with clinical data that specify an opportunity in a defined patient setting, for efficacy, for safety, and for reimbursability. That's the transition that we're moving, I think, very aggressively into and what underlies a lot of what we're seeing at the level of the public markets. We feel we're well-positioned to take advantage of these conditions, both through the strategies that we're running within our own portfolio companies, where historically our companies have all been focused around a defined product opportunity. Also with the strength of our balance sheet, where our permanent capital base will allow us to take advantage of the opportunities that we expect to see over the coming years. I mentioned the sale of Gyroscope to Novartis. That really was a highlight during the year. It was an exceptional result. I would now like to pass to Chris Hollowood, the Chief Investment Officer at Syncona, to give you some more color on that transaction. Thank you, Martin. Clearly, one of the big events at Syncona this year was the sale of Gyroscope to Novartis. Gyroscope is a company that wouldn't have existed without Syncona, who were fundamental to generating the concept of the company, and actually one of the key inventions came from the Syncona team. The company addresses a disease called dry age-related macular degeneration, and really represents the beachhead of the next wave of our gene therapy strategy. First wave of Syncona companies in gene therapy address rare diseases, but this represents a chronic degenerative condition where there are millions of patients. Ultimately, it's these kind of conditions that I believe will be the place for gene therapy in the years to come, and very much where we're now focusing our strategy. It also demonstrates the repeatability of the model. When we came to you in 2016 to come public. We told about two of our great companies, Blue Earth and Nightstar, and clearly they were successes. At that point, Gyroscope was very nascent. It was founded in May 2016, so it's less than a year old. What we've been able to do, because we became public and got a bigger capital platform, is build it with more ambition. That ambition has translated into a bigger exit number and a bigger reward for the Syncona shareholders. We received two point nine times the cost of our investment, and our investment cost was over GBP 100 million. We deployed substantial capital into this company, and we structured it in a way where our shareholders can stay exposed to the upside of this program as Novartis develop it and take it all the way to approval. If they achieve that, we can receive up to five point one times our original cost. The Gyroscope exit happened against an incredibly challenging macro backdrop in the biotech industry. When you look at the lower half of the NASDAQ Biotechnology Index, it's down over 40% across the year. Actually, if you look at those companies that are in the novel third wave modalities or in the clinical translation stage, it is much more profound than 40%. You recall that we pulled the Gyroscope IPO back in May last year at the beginning of this downturn. There was an IPO that Gyroscope could execute on, but we felt it was weak. We felt a high-quality company that did not deserve the consequence of how it might have traded subsequently. What we'd seen at the time was a fundamental decoupling from the capital market's view of biotech and this industry and pharma's view of fundamental value. Ultimately, pharmaceutical companies are the people that value a product on the basis of the impact for patients and what it can get reimbursed at, which is a fundamental way to value it. The capital markets get moved around by stories and technologies. The technologies are just enablers of products. They're not products themselves in the therapeutic setting. What Syncona represents is a fundamental investor. That's what we focused on across the year. You see that when we look at our NAV. Our NAV is roughly flat on the year, but in the private portfolio where we've been able to focus on the fundamentals, really drive the execution, drive financings in the Gyroscope drive and exit. We've seen substantial value appreciation against a market going the other way. Clearly, Gyroscope's a big driver of that, but also notable high-quality financing at uplifts across Quell and OMass. That's almost entirely offset by what's happened in the public markets. That public market trading is really driven by the macro conditions and not necessarily the underlying fundamental value of the programs in Syncona's listed holdings. What Syncona is able to do, given its balance sheet, its strategic view, and the strength of that overall balance sheet currently, is help those companies ensure that they are capitalized with clinical data, which should drive future value. I want to talk a little bit about that later. There's been quite a lot of discussion this year over cell and gene therapy and is it really all it's made out to be? I think we need to take a step back and remember why we got excited by cell and gene therapy. We got excited because for the first time we've come across a modality that could actually cure diseases. Previously in our industry, most therapeutic interventions help you manage a disease, so it does not impact long as a patient. The gene and cell therapy brought the promise that you could aspire to a cure. That is a fundamental step change. What I believe we're seeing right now is the natural course of that technology as it enters clinic and we find out what are the parameters of technology, what can it do, what can't it do, how should we develop it? That naturally leads to some delays, some extra investment. All of these problems appear solvable to me, and therefore the promise of further gene therapy products and cell therapy products remains intact. If you look at the specifics in cell therapy, manufacturing is a big issue. We take cells from a patient, we manipulate those cells, and we return those cells back to the patient. This is not a white pill that you get in a jar. That represents a level of manufacturing and logistical complexity the industry has not had to face today. Worth facing because if you get it right, the efficacy you can then deliver is profound. We have seen delays in some clinical trials as companies put this infrastructure in place. They've worked through that, are able to deliver the clinical data, and the clinical data does appear to be what we expect and the promise remains there. On the gene therapy side, there's been talk around the toxicity in gene therapy. I think we need to be very careful about applying that to all gene therapy. When you actually look where that data has come from, it's come from where companies have had to push dose incredibly high to get the efficacy signal they want, and they've pushed it too high. We strategically at Syncona have never advocated moving into those kind of therapies. We've very much taken the view that you should take gene therapy where gene therapy can have impact and not push the envelope for technology. In the eye, Gyroscope got bought, and so have been through a full due diligence, by Novartis, looking at all of their patient data, including all of the safety data. They're entirely satisfied with that. In the spine, in the kidney, and in the liver, it is reasonable to expect, because of the doses that we are, dosing at, and because of the clinical base that already exists in a number of those tissues, there are safe paths there. We are not in, muscle disorders because we believe in those disorders, we really do need to push the dose very, very high. We need to remember that, there are nine cell and gene therapy products approved already. This is not this technology failing in the clinic. This is this technology being worked out in the clinic and things still getting through to approval. Indeed, in the last two weeks, there were two positive Advisory Committees to the FDA. This is a committee convened by FDA to make a recommendation on an approval. FDA is not obliged to follow it, but both votes unanimous for approval. I would expect two more approvals in the coming months. For the 60 products that we expect to be approved by 2030, people say that trajectory remains there. Syncona remains heavily committed to it and the exposure and the upside that we then get from that. In the portfolio over the last year, we've seen 12 clinical data readouts. It's probably the richest set of data readouts we've had over a 12-month period at Syncona and really represents the growing maturity of the portfolio and the opportunity to drive growth because it's clinical data in our sector that really drives growth. We are in a very, very bad market from a macro level here, and luckily for Syncona companies, they sit on a well-funded strategic balance sheet. What we've worked on with the portfolio companies is to make sure they're being sensible about their business plans and their budget, and they're getting themselves capitalized so they can get to meaningful data. If they get to meaningful data, and that data proves that their product works, fundamental value will have been generated. We're also focused on the pre-clinical companies because this will be the driver of growth in the medium term. We've executed a couple of notable financings, particularly Quell and OMass that happened at an uplift. There's two companies that I'll draw to your attention. One is Resolution Therapeutics. This is a company that's looking at a new cell type called macrophages. We believe it is in the leading space in this field. It's actually based around an existing academic clinical study on a first-generation version, which means that we are getting real clinical data that de-risks the platform in that company and gives it a path forward. We expect to come and tell you more about this company and our ambition for it so we can maintain in the forefront of the field itself. The second one is Purespring. In Purespring, we think we've combined all of our gene therapy knowledge to put together a company as well as we've ever put together a gene therapy company. That company represents the first substantive gene therapy company looking at the kidney, which is an ideal organ for gene therapy. We can deliver locally to it, and the diseases there are driven by predominantly chronic cell death, which is exactly what gene therapy is good to treat. There are a number of diseases that are not well managed and are crying out for innovation. The team we've built around this company with Richard Francis coming in as CEO and Julian Hanak, who was head of manufacturing at Nightstar, returning to take that role, here at Purespring, is very exciting to have in place at such an early stage. As we enter this financial year, we have a number of companies already in the clinic and a number due to enter. I don't think in Syncona, we've ever had as many companies that will report on clinical data across a financial year. These companies are across a range of stages, whether that be clinical entry or in Autolus's case, a pivotal trial. A range of technologies, whether that be cell therapy, whether that be antibody, whether that be gene therapy, and a range of therapeutic areas, whether that be oncology or, rare diseases such as adrenomyeloneuropathy, in SwanBio. What that means is our shareholders can be exposed to the cutting edge of this industry while being appropriately risked across stage, therapeutic area, and modality. We're excited to see these companies progress across the next 12 months and the data that they will bring. As we look at the new company formation, we believe that the pipeline is very, very strong. We talked to you about Clade. This is our recent investment in allogeneic cells. Allogeneic cells represent a technology that may allow us to take one cell line and treat all patients. If we can get that technology to work, we can circumvent some of the challenges of autologous cell therapy. On the gene therapy side, we're increasingly focusing the strategy towards chronic genetic conditions. We think the technology is mature enough to allow us to address these kind of diseases, and we think these diseases are ideally addressed by gene therapy and represent substantive markets. Gyroscope very much being the spearhead of that strategy. This strategy may play out through the pipelines of already existing portfolio companies, or we may start new companies. Clearly we have had significant success, mostly Gyroscope and Nightstar in the gene therapy space, and we will look to repopulate the portfolio at some level. When we talk to the capital markets today, we made the point that we're not exclusively a cell and gene therapy company. What the genetics revolution brought is obviously new modalities like cell and gene therapy, but also a way to exquisitely understand the drivers of disease at the molecular level. What that means is that you can find ways to target diseases very impactfully, but then also choose your patients in your clinical trial so that they will be the high responding patient group, which then reduces the number of patients you need to recruit and speeds up the development of those programs, so you are able to generate rapid value. It will not be appropriate for all of these insights to be addressed as cell and gene therapy. Sometimes it'll be small molecules, sometimes it'll be antibodies, sometimes it'll be other third life modalities like RNA. In the pipeline, we're seeing great opportunity for antibodies and biologics to try and address some of the immunological conditions that currently are not well-served. On the small molecule side, we think that targeted small molecules have had a tremendous track record in cancer. For the first time, we think the platform exists and the clinical paths exist that allow us to think of sophisticated ways of combining those to really dial up the efficacy without impacting overall safety. We very much look forward to coming to tell you about these companies as we form them over the course of the next twelve months. Now I hand over to Rolf. Thank you, Chris. This balance sheet is a key strategic differentiator. It allows us to make the optimal financial decisions to support our investments and to drive shareholder return. This includes funding new and exciting science and building the infrastructure and capabilities around it to support the transition into successful businesses. It also gives us flexibility and negotiating strength on how, when, and who we syndicate our investments with. It gives us options on whether we hold assets privately for longer to maximize our returns. The dynamic nature of our portfolio means that when we do leverage our capital, we do so from a position of strength, typically through well-funded later-stage businesses, which are attractive to other investors, where we can bring in new additional capital, building on our own previous investment, such as in Orphanless or Gyroscope, or through syndication, where we bring in high-quality institutions alongside us. Across seven financings this year, we have leveraged our capital by a multiple of 5.6x, delivering $712 million into our portfolio companies. In the current challenging markets, we have positioned the existing portfolio to be well-financed and retain financial flexibility to drive continued portfolio growth going forward. We ended the year with a capital pool of GBP 785 million. We deployed GBP 123 million in new and exciting investments last year, and we're very excited by our pipeline opportunities and maturing existing portfolio and the opportunity to hold some of our companies privately for longer. Looking forward, we expect to invest between GBP 160 million and GBP 250 million in the current year. Our principal capital focus remains on liquidity. We aim to keep a minimum of a rolling 12-24 months in cash and treasuries, so we always have immediate access to capital. We've reviewed our expected U.S. dollar exposure and aim to hold a portion of our capital pool in U.S. dollars to match our future requirements. Currently, this is around 40%. We're introducing a small number of low-risk multi-asset funds to give some protection against inflation over time. Over to you, Martin. Thank you, Rolf. I mentioned that Syncona is now 10 years old, and we've made substantial progress in delivering the goals that we set out for ourselves when we founded the business back in 2012. We now have a significant business with substantial assets both at the people level, portfolio level, and the capital level. After 10 years, there really is a pause for reflection to begin to ask what the next 10 years holds for Syncona and how we should reset our ambitions in order to aggressively enter that next decade. At the heart of that, what we've done is go back to look at really the core things that have got us to where we are today. Which is really our skill and ability to identify raw science, identify where that science could be leveraged to create a novel medical product, and to build a company around that opportunity. We've demonstrated repeatedly now that we're able to build those businesses to a global standard, and critical to our ability to do that is our permanent evergreen capital base, which really represents a differentiated market proposition and allows us to repeatedly deliver this business model. One area where we think we can optimize going forward is in our ability to finance these companies. We've talked to shareholders about that in prior discussions. One thing we're really looking at is how we leverage our financial strength to hold a small number of our companies privately longer, holding them privately through to clinical proof of concept. There are other areas where we're working very hard as well, which is our ability to bring world-class people to our portfolio. I think something we're getting better at as we've grown over the last 10 years, but an area where we need to focus. Increasingly on operations. We're very good at starting these companies, but we think we can improve the way that we interact, manage these businesses really in the second, third, fourth, fifth year as the operational complexity of these businesses increases. That's an area where we're very focused. We're working hard on this area, and we would expect at the mid-year to come back to shareholders with a fuller update. We think that the next decade has the prospects to be similarly exciting for Syncona, and we look forward to talking that through with you when we meet in the mid-year. In summary, this has been a strong year for Syncona. There's no doubt that there's challenging market conditions out there, but I think our model and our team have been tested, and the returns that we've delivered over the last year really, I think, highlight both the strength of that team, the strength and the diversification of that portfolio. The market has turned. It's pivoted from a story phase, technology stories, through to a rigorous demand for defined products with clinical data. That's completely aligned with Syncona's strategy over the last 10 years, and we think our portfolio is well-positioned to thrive in that environment. Through the decisions we've taken, both at the level of portfolio-level financing and also our own balance sheet, it was amplified by the Gyroscope transaction. We have an exceptionally strong capital position, and never has capital been more strategic than it is in the current environment. I think that we're extremely well-positioned to do well for our portfolio companies and for our shareholders in the years to come. Our goals remain unchanged, which is to grow our portfolio aggressively. We're very active on that. As Chris has set out, the pipeline of opportunities looks good. We want to grow our portfolio to a steady state of 15-20 companies, and the ten-year rolling goal remains the same, which is to deliver three to five of those companies all the way through to approved product. If we do that, we think that we will be able to deliver exciting returns for our shareholders and also make meaningful impact for the patients that those therapies can treat. To close, I'd like to thank shareholders for their continued support throughout the year. We look forward to taking any questions. What we'll now do is turn over to a Q&A. We will now begin the question-and-answer session of the event. Everyone on the line, if you would like to ask a question, please press star then one on your telephone. Thank you. Thank you. Our first question is coming from the line of Miles Dixon from Peel Hunt. Please go ahead. Your line is open now. Good morning. Thank you. A few questions, if I could. Firstly, on the capital deployment, Martin, you mentioned that never has capital been more strategically important than it is now. Can you give me a broad brush understanding of the new guidance of GBP 175 million-GBP 250 million? I mean, you mentioned the potential for some multi-asset funds in there as well. Roughly what proportion of that is expected to back your existing portfolio opportunities? Then maybe if I could ask a question after that. Yeah. Morning, Myles. So first of all, the capital deployment that we set out is GBP 150-GBP 250, and that's deployment into the life science assets. Separately, we have decided, and Rolf can perhaps pick up on that, if you have further questions, that the capital pool, which is the non-life science capital pool that we hold, a portion of that will be invested into a number of multi-asset funds, really to protect that money in real terms. That's the goal of what we're looking to doing. The guidance that we provided on the life science side is GBP 150-GBP 250. The bulk of that will be into the existing portfolio. There will absolutely be a portion of it. We don't provide guidance, but it's a minority that will go into new investments. Right now, as Chris commented in the presentation, we have a pretty thick pipeline of opportunities, and we're excited about what we're seeing. Headline is the bulk of the GBP 150-GBP 250 will go into the existing portfolio. Miles, it's Rolf here. Maybe just to reemphasize Martin's point there on the capital pool. This is really about treasury management, and just, you know, in a high inflation environment, we're just looking to make sure that in a balanced and conservative way, we're just protecting some of the value of our capital pool. Just to clarify that point. Sure. Understood. Thank you. Then I don't think I can not ask a question on the backdrop. You talked about the incredibly challenging times for biotech on the market. Has it changed the kind of profile of the deal flow that you're seeing? Are you seeing many more earlier companies and later stage companies come to you now? Also, could you give me the take of your listed assets as well? How do they see the world view at the moment? What I'll do is I'll talk about the backdrop and then perhaps pass to Chris on the list of assets. In terms of the backdrop, first thing to say is we've been here before. The management team here, this is, I think, for me and Chris, it's our third time round the block in the cycle now. Don't want to make Rolf feel bad, but I think he may have even more cycles than that under his belt. We've been here before. We know what this looks like. Really the properties you need in a management team at that point are to be a real expert, fundamentals-driven asset picker. You need to have capital, and you need to have discipline, and you need to be brave. If you do those things, actually the returns in the vintages immediately following a downturn in a cycle have been very good historically. We actually think this is a rather exciting time for us. As a consequence of really the decisions that we took maybe getting, you know, somewhat defensive last year in advance of this sort of phase of the market, and the evidence for that is clearly, one, the decision to sell Gyroscope, but also the rounds that we undertook in the private companies, Quell, Anaveon, and Autolus, where we put capital into those businesses. What was noteworthy was that our level of participation in those rounds was rather modest by historical precedent. Rolf mentioned that we got about five and half-fold leverage for every $1 that we invested in terms of external money. I think that sort of speaks to positioning, which was around having a strong capital base and then to leverage the properties of the team. Pass to Chris to comment on the listed companies. Yeah. Clearly, as we touched on in the presentation, the backdrop for listed biotech companies as a whole has been pretty dire since the beginning of the year and was falling through the second half of last year anyway. In our portfolio companies, you know, we believe in the programs, and we believe they have fundamental value. Those companies are trading at the valuation of the cash on their balance sheet or below currently. Across those three companies, we would expect some to report positive clinical data. If the markets return to valuing fundamental value, which they will over the medium term, then we'll get the credit for that. What we've done is we've made sure that those companies are capitalized to deliver meaningful data, and that's the strength of Syncona, because what the market's saying about the aggregate set of biotech companies is not all of them are gonna make it because the capital ain't there. That's not true for our companies. We're differentiated. Got it. Thank you. Just one last quick one, if I may. Chris, you alluded to the AdCom for bluebird bio's two assets. Now, do you think that this is the start of a potential change in risk appetite from the regulator, given that they're understanding some fundamental risks in some of the therapies that they're now looking to approve? Yeah, I think, you know, what you're seeing from the regulator is them looking at fundamental clinical data, and those two programs deliver dramatic efficacy, and in one case in a fatal disorder. I think that is clinicians saying, "We want these therapies." Where you've seen the regulators slow companies down, it's because those companies have not yet presented the convincing data. I personally think that the market has overreacted to that and read it as the regulators are not supportive of these therapies rather than regulators are, they just need more evidence. Clearly, there's isolated cases where people have pushed this technology into areas it shouldn't have gone, and that needs to stop, frankly. That's what you're seeing, but across some of the muscle disorders out there. That's not true of the bulk of where the gene therapy and cell therapy modalities are being used. Great. Thank you. The next one is coming from Simon Baker from Redburn. Please go ahead. Thank you for taking my questions. Morning, everyone. I'll be slightly cheeky and ask four, if I may. Firstly, a broader question, kind of going back to what Miles was asking about on the biotech landscape. There was an interesting piece out from Bloomberg yesterday saying that there was a record 111 biotechs trading below cash in the U.S., a third of whom will run out of cash within about 12 months. I was just wondering what opportunities, if any, that throws up for Syncona. A broader one on gene therapy. Just really to get your perspectives on the FDA draft industry guidance that came out earlier this year, on gene therapies and their development, if there were any surprises in there, positively or negatively. On the SwanBio Therapeutics funding round, you took a rather large percentage of that. I just wondered if you could give us some explanation for that. Was that a reflection of competing demand or your enthusiasm for the asset? Finally, a question I think I've asked probably about a year or so ago, just be good to get an update. What opportunities are you seeing early on in mRNA? Thanks so much. Thanks, Simon. What I'm gonna present is I'll take the first and the fourth of those, and Chris will pick up the middle two. On the landscape, look, there will be enormous opportunity in those companies. Again, you know, we've been through this cycle. A bunch of those companies will go out of business and probably deservedly so. There will undoubtedly be assets caught there which are short of capital and are still quality assets. There's a great opportunity to find creative ways to access those assets and make very good returns. Actually, in the history of Syncona, we've already done this once. I mean, that's what the Blue Earth transaction was about, where we picked up an unloved asset from an industrial partner who basically didn't want to fund it anymore, having spent five, six years funding it and spending tens of millions of dollars on it. We paid around $1 million to buy the asset, invested in it, and then sold it for $500 million five years later to Bracco. There's something intuitively very interesting about taking an unloved asset and essentially repricing some capital. That's the lens through which we will look at these companies. I think it's unlikely that we are gonna make, you know, small minority investments in listed businesses. I think the market conditions will be so extreme in this period that there will be the opportunity to access those assets, for example, potentially stripping them out or licensing them into private vehicles where, you know, you might have high levels of ownership and high levels of control and governance. That's really the lens of which we're looking through that. The real question, as we've sort of discussed in the whole field, is when the market gets in these conditions, it is about the product that you generate and clinical data, which is one of the eternal truths, is that where there are significant unmet needs, if you deliver a product that is shown to be effective and safe, addressing a significant niche, that will be a valuable asset. The lens through which any investment, either existing or new, needs to be made, which is, can you fund it to data? That's how we're looking at that space. That's how I think it may play out. We're focused on it, but it's really through that lens, I think, of trying to access these assets creatively rather than making, you know, small trading investments in a listed biotech portfolio. Chris, across to you for the FDA guidance. Yeah. The boring answer on the FDA guidance is it was pretty much in line. Clearly during the last calendar year, lots of questions were raised about various gene therapy parameters. The regulators had a meeting in September last year where they got a lot of the experts in, got all the data, and had the discussion. I think what came out of it is, you know, develop gene therapy as per the disease context. In some of these diseases, you know, the patients are going to die. Therefore it is entirely justifiable to risk some adverse events in order to save them. In other disorders, it is more chronic long-term diseases, and clearly that justification doesn't exist there. That was a clear steer from the FDA. There are aspects around manufacturing of these compounds and the quality of manufacturing. I do think that is a theme in gene therapy over the next decade or so, because when you look back at antibodies and what the regulators did on antibodies, is the first wave of antibodies the way they were made would not be acceptable now. As the technology's improved on manufacturing, the regulators tightened the quality specifications. I think you'll see that here, and I think that's all to the good, and that all sits on Syncona's strategy because we've invested heavily in manufacturing, in the analytics, and in the quality aspects because we believe that over the long term, that is the direction of travel. Swan. On Swan, look, this is a company that very much on strategy for us. You know, they're targeting a single disease compartment in the spine, lead indications in monogenic recessive disorder, thousands of patients. Technical risk on the target is low. The commercial opportunity is high. The team that we've built around that have executed brilliantly. You know, they got that IND approved in January, they also got Orphan Drug Designation. That was exactly on plan. The data that they've shared publicly has shown that every piece of data we've got has de-risked the program. It has performed in the models as we would expect. We're excited by it. Unfortunately, they arrived with our IND in a market that was basically plummeting. We had to take a view as to whether that was the right time to finance that company externally. Given the quality of the execution, we felt that we should finance it 'cause that gets it through to clinical data. We're guiding that it'll be in the clinic in the second half of this year. We'll get initial data, we'll get safety data, and hopefully in 12 months' time, we'll emerge in a better market as well. Simon, can I just add, you know, this is exactly what we mean by a strategic capital base. Which is we think there is an anomaly in the market right now. Some of it is rational, some of it is non-rational. When you have an asset that you like, by having a strategic capital base, you earn the right to take advantage of that anomaly and manage through. That's exactly what we've earned the right to do by building the capital base. We think there'll be plenty of opportunity to leverage that going forward. Coming to your last question, which is about mRNA. Obviously, I think you've picked up on the sort of, the hint about nucleic acids that's been printed in the, in the RNS. Actually, I think mRNA is quite challenging, frankly. You know, there are a couple of, you know, relatively successful mRNA businesses around now. I don't think there are opportunities in mRNA in the vaccine space. You know, people are looking in the oncology space, cancer vaccine space. I think we have some skepticism around that, frankly. Certainly the data is not compelling in that space, and so we would need to see more data there. In the nucleic acid space, of course, there's many different flavors of nucleic acid, whether that's the siRNA, antisense, microRNA, circular RNA. I mean, you know, pick your flavor really. We think it's more in those other areas rather than mRNA that we're more interested. We think there are gonna be opportunities there, particularly in the delivery space where, you know, we now know it's possible to deliver meaningfully for the liver. That's not really through targeting, it's just 'cause if you stick it into somebody's arm, that's where it goes. But actually the real opportunity is to be delivering nucleic acids to different tissues. We think that is coming, and we think that's an exciting space. We don't have something sort of really in the grooves at the moment ready to go, but we're looking pretty hard. Perfect. Thank you very much. The next question is coming from Stefan Hamill from Numis. Please go ahead. Hi, folks. Congrats on the year and the recent strong Gyroscope exit. I've got three left, after all that discussion. Just sort of digging into the public market seems a bit more. You know, you can look at the reverse argument to investing in PIPEs in terms of your public companies looking vulnerable. Can you just remind us of the extent of your control over those? With Freeline and Autolus, second question, you've sort of been quite focused in, you know, improving the focus of those businesses, limiting their cash burn. Are you doing the same with your private holdings? We seem to be seeing that with Swan, for instance. Just, can you give comment on your overall conviction in Autolus over the next 12 months as it looks for that pivotal data? Thanks. Okay. Stefan, could you elaborate on the first question? I'm not sure I really understood the first question. I mean, you could argue that in this kind of environment, you know, there will be PIPE opportunities for you guys, but also your public holdings are pretty vulnerable. I just, you know, could you just remind us of your control over those? Basically, do acquirers need to come to you to take those businesses out? No, I mean, you know, we're shareholders, and of course, they're public companies, so we have to be, you know, fully compliant with the way public companies run. You don't get the rights of control that you have other than your right to vote as a shareholder through in a public company rather than to a private company. That said, of course, you know, we are particularly in two of those companies, Autolus and Freeline, represented on the board, one as chairman. Chris is chairman of Freeline, and I think it's fair to say I'm a very active director on the board of Autolus. I think we have the ability to be close to events and have a significant influence on them. Clearly, we don't have the protective rights that you would have inside a private company. I think the second question on Freeline and on Autolus was around cost control and whether that's being reflected into the private companies. I think the answer is yes. You know, I think in this environment, the cost of capital has gone up. We're in a very fortunate place in that we have capital, largely as a consequence of the decisions that we've taken over the last few years. In this environment, it is moving, as we've said, I think, you know, a couple of times already from a position where the broader capital market would buy stories, i.e., I have a technology, here's what it can do downstream, to a market where it says, "I'm not interested in stories. Show me the data." The flexibility that you have in a private company to believe you might be able to sell a story to raise capital, I think we have lower confidence in that. What we're saying to our companies, make sure you are funded to deliver the data because the road to redemption here is through delivery of data. I think we're very focused on that. It's important not to overdo it. The point of having capital is that you can invest it to deliver that data. It's about finding a prudent balance, and I think we're doing that sort of pretty well across the portfolio, but we're active on it. The third point in Autolus is, you know, that study will read out significantly this year. I believe it's highly likely to have a positive outcome. I don't know that, of course, and there is risk in clinical studies. I think the data that we've seen historically in that program is very encouraging. If it were to be replicated in a phase III, I think would be a meaningful product. As I say, you know, we can't predict the outcome, and there is risk in these studies, as you know. On the basis of what we've seen historically, I'm excited about it. Thanks. Just one follow-up for Chris on Freeline. You know, the recent release that those guys made seemed to suggest that they found a dose level in that trial, you know, which is a much lower dose than peers. Just can you give us your thoughts and comments on that and how that potentially reads through to Fabry and Gaucher’s? Yes. As you know, Stefan, we had a bit of a hiatus in that program because of COVID. We felt for a long time we know the dose that we think will give patients, you know, a functional cure. So their factor nine activity levels between 50 and 150, and we have a lead-in study to a pivotal trial. The company's announced that it's dosed the first three, and then most recently it started to dose the second three of those. I think from that you can infer that that study is on track. There will be some data coming out from Freeline. Also what we're studying in that, in those patients, whether the immune regimen, the new immune regimen works. There's actually data out there that showed at least in one patient, it's worked very well because it's the same regimen we used in the Fabry study in patient two. So I think, you know, there's data there that you can read across as to whether we're honing in on a good immune management regimen. Look, the technology I think is relatively convincing that it gives incredibly high protein-level expression from the liver relative to other technologies. In a world where everyone's getting very sensitized to high doses of gene therapy, having a very efficient capture that allows you to dose an order of magnitude lower than everyone else is kinda meaningful. Where that means we dose in Fabry and Gaucher is to be seen because we've got to dose escalate those studies. I think you can conclude that, when we dose escalate and we find a dose, it's gonna be substantially lower than any other competitor. Thanks, Chris. Thanks, folks. There are no further questions in the queue. Ladies and gentlemen, that concludes today's question and answer. I will now hand back to Martin Murphy for his concluding remarks. Well, thanks very much everybody for listening in. We'll be seeing many of you on the road in the next week or so. We look forward to that and thanks for taking part today. Thank you so much, ladies and gentlemen. That concludes your conference call for today. You may now disconnect. Thank you for joining, and enjoy the rest of your day.