Great. Thanks everyone for joining. Maybe before I jump in, I'll give our research disclaimer. For important disclosures, please see the Morgan Stanley research disclosure website at morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. Craig, thanks for joining. Thank you for having us. My name's Jason Russell. I'm a managing director in the healthcare banking franchise here with Craig Tooman, President and CEO of Silence. Craig, jump in here to start. Silence has been a company that's been around for quite a while, but I think has really elevated your profile recently. Why don't we start with a little bit of background. Help us understand who Silence is what is the evolution of the company, and then we'll go from there. Excellent. Thank you. Yeah, Silence has two decades of experience, a UK-based company, London headquarters, a PLC. By virtue of that and some of the predecessor companies that turned into Silence, it was a little bit on the quiet front in Europe. Most recently, we've made a move both toward Nasdaq, and we're exclusively listed on Nasdaq, and we delisted on AIM, as Jason. We really moved toward trying to be better understood by the typical biotech investor, the funds, if you will. We have some just incredible investors, I will say, in the UK that own about half of the company, high-net-worth individuals. What we've made a concentrated effort to really appeal and be better understood by the healthcare fund. That is one thing that we did last year and have borne a lot of fruit. We've done a PIPE now with U.S. investors. Most recently, we did another financing here in August, again, very focused on the U.S. investors. We're growing that shareholder base out and aiming to enhance liquidity. The company did originally direct listing on Nasdaq, so it wasn't an IPO, if you will. We're now patching in those investors to better understand us and grow that out. The other thing that's really been outstanding for the company is the move into the clinical data, and you know that speaks for itself. We recently had a Phase I trial readout on SLN360, which is a very large potential market for us. Phase I readout with 98% knockdown, which in my 30 years of pharmaceuticals, I've never seen or envisioned an efficacy readout like that. 98% knockdown, but 96% at half of that dose, so even at a mid dose. A lot of people took notice. That ended up getting an incredible amount of publicity. Steve Nissen presented that at ACC in a late-breaking session here in April and with the JAMA publication as well, simultaneous. The combination of the gene silencing work that we're working on, the clinicals, and the move toward this investor base in the U.S. I think has all culminated in a lot more attention for the company. Great. Well, I definitely want to get into that a little bit more, particularly the recent data. Before we go there, just some general comments around RNAi as a modality. I think generally our audience will be familiar with the modality. What I'd like to understand are your perspectives around why is RNAi or gene silencing a good tool? Where is it going to work well? Where is it not going to work so well? Help me understand how you're thinking about that with your indication selection. We are specifically targeting right now genes in the liver, Lp(a), of course, and then we'll talk a little bit about SLN124 and TMPRSS6, two genes that are GalNAc focused. This is double-stranded, not single-stranded like the ASOs. It really is kind of a move in the technology forward. Practitioners that have used this have found it to be very durable, very safe, and they really believe that this is kind of a next generation, if you will, of technology. Some key opinion leaders refer to it as revolutionary, not evolutionary technology. Again, if you come to the 98% efficacy in silencing a gene, it's pretty profound. The other thing that we just really love about this is it's completely reversible. It's durable, but it also is reversible, so we're not permanently altering the genome. We think that's particularly a strong suit. Okay, great. Maybe switching gears to Lp(a). SLN360 lead program focused on Lp(a). Your program, I believe there's one other siRNA in the clinic, one other ASO. Let's start with Lp(a). What is it? Why does it matter? What are we trying to do? Lp(a), again, it's genetic based. You're actually born with the gene and the disorder. It's cardiovascular and associated with a higher cardiovascular issue long term, two to three times higher heart attack risk, for example, for those patients that have higher Lp(a). We target that Lp(a) specifically and are very effective at knocking it down. If you look at that cardiovascular space, you can imagine it appeals to the larger companies because it has very large potential. Lp(a) itself has epidemiology that's very similar to the statin market. Large companies are pursuing this and I think will continue to pursue this. We are the second, as you mentioned, in this particular technology, behind in timing, to Amgen and, we've just completed a Phase I, they've just completed a Phase II. We feel very good about our freedom to operate and our differentiation in that field. That is again, in that revolutionary field, if you will, of the siRNA. Novartis actually has the ASO, which is, a different technology, and my understanding is their first readout in their cardiovascular, trial, Phase III, will be in 2025. Really what you have is, and completely there's no treatment available for Lp(a), undertreated, if you will, or untreated. Also the awareness and the familiarity with this is very low. For example, if you go in for a test, very few people are getting tests for this 'cause there is no treatment, and so the awareness is very low. We're looking forward to the companies ahead of us educating that market for us with profound data, if replicated, to then enter as well, potentially with a partner. What is the general prevalence of Lp(a) in the population? That's what's really amazing because it's up to 10%-20% of the world population, depending on how you define that starting point. 10%-20% just tells you it is a very large, again, statin size market. Mm-hmm. What's different from the statins is that, you really can't influence this with diet or exercise. This is a genetic disorder. It is something you're born with. It's something that you'll need to treat if in fact you have it and you're not able to alter yourself. Okay. Excellent. Let's go back to the spring. You mentioned it in the opening remarks, but you provided some pretty groundbreaking data at ACC. Let's just dive into the details there. What did you report? What was really exciting about that data? That was our Phase I trial. Again, very atypical that you see a JAMA publication simultaneously reporting all of that data with ACC session. 98% efficacy we saw at the highest dose, 600 mg. It Craig, define efficacy for us. What do you mean in that case? That's 60 mgs per deciliter. It's a determination of your level of Lp(a). Okay. From there, the knockdown. There is kind of a linear relationship in terms of that. That gets into the definition of the magnitude of the market. Companies are continually exploring what is the right level to measure. But we measured it at that level and saw incredible efficacy between 96%-98% at the two highest doses. What we will do next, as you can imagine, is we will move to start a Phase II, do some further exploring on dose, safety and efficacy, and move that forward as quickly as we can. Okay. You referenced this, and maybe this is not a fair question on how different companies are measuring knockdown different ways. But any tidbits you can help provide us comparing what we've seen so far with our program versus the Novartis program, the ASO and the Amgen/Arrowhead program. Yeah. All I can say is the companies, as they enter, I think are looking at this growing field and growing interest and what the experts are saying about the right measurement. There does seem to be a continuum here in that dialogue. Increasingly you're getting awareness from the bodies, if you will, external validation that Lp(a) is real and Lp(a) should be targeted and should be treated. Whether that definition is different by 10 mgs per deciliter or not, I don't think is going to be the important point. It really is going to be the knockdown that you demonstrate and the patient type. Okay. Is there any basis to compare the data that people have seen, yourselves included, or too early for me to kind of try and draw that? Of course, I'm trained initially in big pharma, where you never- I tried the first time. Yeah, non-comparable studies. Just been trained that way. I think what you see, at least in the technology, the siRNA technology, with our program and Amgen, is you see a consistent kind of 90% effect. You saw the readout initially on their Phase II. That was in the 90% ±. Again, I've referenced our 96%-98%, so that definitely is in a better category. Fair enough. You referenced going to Phase II. Do we have a trial design plan yet? Is that subject to FDA feedback? What are the next steps here for 360? Great question. We're moving as quickly as we can to try and initiate that by year-end. As you can imagine for that, you have the dialogue with the FDA, and we have a plan that we think we will work toward. Because of our great efficacy, actually, we think we can accomplish this study with fewer patients. But we continue to look at ways we can differentiate that Phase II program and leading into what will likely be a CVOT for us too. A larger Phase III program. I know we'll probably talk about that later, but that's the point where it probably makes sense to be considering a partner for assistance in that larger resource requirement. Okay. Just for our audience, CVOT, cardiovascular outcomes trial. Any drug trying to knock down Lp(a), the consensus is or that you're going to have to have that type of large Phase III. Demonstrate the cardiovascular outcomes. That's right. Okay. Novartis will have that first, most likely, readout 2025. That will most likely be followed by Amgen. Wonderful. Okay. I guess we'll stay tuned for updates on 360. Do you plan to communicate to investors trial initiation or study design kind of when you've come to that place or stay tuned? Yeah, I think we do. We try to do a very good job of communicating. I think we discuss things in more detail than most companies. We really like to bring people with us. As we have in the Phase I, although that was very unique with the JAMA article, we will continue to provide data on the initiation and most likely the trial design as we move forward. We have been more clear about what our goals are and what we're trying to achieve, I think, as a company, just to bring the investors with us. Again, we're moving into the U.S. to have new investors understand us a little bit better. That's all part of the same idea. Yeah. Okay, great. Switch gears. Second clinical stage asset, SLN124. Let's start with what is the design of this candidate, and what is the goal? Because it is a little bit unique in what you're trying to do with 124. It's part of the same platform, of course, which we're very intrigued by. This one actually targets the TMPRSS6 gene, again, liver, which regulates hepcidin. Hepcidin, when you're influencing hepcidin, really deals with iron disorders. We're really talking about a cluster, if you will. Not just one large market like Lp(a), but a series of smaller markets. They're all very unique and quite interesting. That can be thalassemia, for example. We're very excited to be kicking off the PV study by the end of the year as well, polycythemia vera. That's one we think has larger market potential, but is also part of this overall iron regulation. Okay. 124 has already been in patients? Yes. We will demonstrate some data in a single ascending dose trial in the next couple weeks. Okay. Next few weeks. We're also doing a multiple dose trial, so that will be next year when the readout comes on the multiple dose trial. Okay. Targeting what population, Craig? That's for thalassemia. Okay. Yeah. Beyond that, we'll start the PV trial. There will probably be others beyond that, just to give you the notion that we think it works in a variety of areas. Okay, wonderful. Polycythemia vera start that Q4. Yes. I mean, maybe just to pause on PV for a second. Why PV? Why is that an attractive indication? Certainly, unmet need. Certainly one with a larger market potential than the more typical, orphan-only, diseases. We think, again, with a pretty profound, cause and effect on hepcidin that we're going to have an opportunity here. Okay. Maybe shift gears a little bit, Craig, and some of this will relate to the history of the company. Historically, silence you're relatively new in the seat. Silence has a history of having done quite a number of collaborations. Maybe first focusing on the two clinical assets first. Kind of what's your strategy? Are you taking these all the way to the end yourself, or is there a plan? Would love to hear your thoughts there. Yeah, great question. If you look at the portfolio, if you will, of the company Lp(a), SLN360 is really an outsized asset for a company our size. Huge market potential. I don't say that lightly. We think based on what we've seen, it just has incredible market potential. In that regard, we would likely involve a partner to assist us both in the later stage development and commercialization, because we do have big partners that are very interested and who we will likely be competing with as well. SLN124, as I mentioned, is a cluster of, we think, potential projects. We feel like we could do that, take that all the way to the market ourselves. In terms of the portfolio, that's how we look at that. Now we also have a hybrid model. What's very unique in biotech and in my experience as well, we have our own projects that we've just discussed, and then we are also working with partners currently to help them develop projects and targets. For example, AstraZeneca, Mallinckrodt, and Hansoh from China. These are 10 target deals in the case of AstraZeneca and three target deals for the other two companies, that if all the financials work out, we would actually earn $7.5 billion, if you can imagine the milestones and royalties over the life of those programs. It's a great non-dilutive source of income in addition to the equity financing that the typical biotechs do. Very enthused, very innovative company. We have our own projects, and then we work with other companies to help them develop their projects, so. There will probably more of those to come if you look at that hybrid model. Okay. Any of those three partners that you referenced, any particular one that you'd like to call out? Any upcoming milestones for one of those partners to the extent you can comment? They're all different, they're all confidential, but I have to say they're all advancing very nicely. As they do, we tend to see $5 million milestones and over time, $10 million milestones. Those really become meaningful for a company our size. Those are built into our model. We have a high assumption rate for those actually being successful in this next Phase. As I mentioned, we look beyond that, when we need to finance the company, and we're very happy that we just financed the company now, until mid-2024. Really happy to have done that in August. Okay. That's a perfect segue. Cash runway into mid-2024, obviously biotech cash runway is king. Are you providing specific waypoints and milestones of what we're going to accomplish as a company over that period of time? or will we see an interim readout of the Phase II, for instance, or something from one to four? How should we think about this next period? Well, very happy with this raise to have in excess of $100 million. That really ensures our plan as we had envisioned it. As I mentioned, we really want to file or initiate the Phase II trial for SLN360. That's a key priority for us. And on SLN124, the PV trial. Those are really our initiatives. Once we get into that, we'll talk a little bit about timing and how long it'll get to complete those trials, but until you start, it's really hard to know exactly when you'll complete, as you know. Very enthused about those, and very happy to have the capital today to do those. We really wanted to take control of the Phase II trial financially. With this financing, we've done that, Jason. Okay. Perfect. Maybe we've got a couple more minutes, Craig. Just thinking about the platform technology, the underpinning capabilities of Silence, and there's a few parties with siRNA expertise. Silence been around a very long time. What are the tools in the toolkit or however you want to describe it, that make silence apart from the clinical stage assets and what really makes the engine run? I have to tell you, we get a lot of inbound interest, by companies big and small, who want us to assist them in searching for the things that they would like for their companies, and I'm a bit flattered by that. I know our science team is. They're very skilled at what they do. It's a combination, as you can imagine, the chemistry, the sequencing, the linkers. It's a secret sauce of all of those in creating the IP, and we have just an incredible internal IP team as well that's been doing this for a long period of time. We feel like we've got what we need to take it to the next level, and we realize that other companies that have come in and tried to see what we can do for them are also very impressed. I mean, you can imagine that a great company like AstraZeneca is going to do their homework before we're a research arm of AstraZeneca. We're very pleased that they've selected us to help them. Okay. Wonderful. Few more minutes. Anything else you'd like to cover or share with our audience today? I think you've covered all of the major points, Jason. Honestly, as I mentioned, we're really trying to become better known, better understood in the kind of commercial and investor world. I think our science team, for years, has been very well respected, and I think now that we've moved to being a public company and being better understood in the US, that side is growing as well. It really is a great little global company with a lot of perspective. Excellent. Craig, thank you. Congratulations on all the progress. Appreciate you joining here. Thank you. Thank you very much for having us. Thank you.