Good day, ladies and gentlemen. And welcome to the Silence Therapeutics Full Year 2020 Conference Call and Webcast. At this time, all participants are in a listen-only mode. Later we will conduct a live question-and-answer session through the phone lines and instructions will follow at that time. Participants can also submit questions through the webinar platform, which will be answered by the company at a later date. As a reminder, listeners should join the call through either the webcast or phone lines for best viewing experience. I will now hand over to Gem Hopkins, Head of Investor Relations and Corporate Communications to open the webinar. Please go ahead, madam.

Good morning, and good afternoon, everyone. Thank you for joining us today for the Silence Therapeutics full year 2020 results call. During the call we will be walking through a slide presentation. If you haven’t already received the slide deck please be sure to visit the Investors section of our Corporate website at www.silence-therapeutics.com to download a copy or follow along on the webcast. Turning to slide two. I’d like to remind you that during the course of today’s call management will make projections or other forward-looking statements regarding anticipated future events or the future financial performance of the company, including clinical development objectives, the therapeutic potential of our product candidate, our operational plans and strategies, anticipated milestone payments, anticipated operating and capital expenditures, business prospects and projected cash runway. Actual results may differ materially from current expectations and projections, depending on a number of factors affecting the Silent’s business. These factors are detailed in the prospectus that we filed with the Securities and Exchange Commission on March 15, 2021, and may be updated by our periodic filings with the SEC from time-to-time. It’s important to note that such statements and events are forward looking and reflect our current perspective of the business trends and information as of today, Tuesday, March 30, 2021. Silence disclaims any intent or obligation to update these forward-looking statements except as expressly required by law. Joining me today on the call are Mark Rothera, our President and CEO, who will provide an update on the business. Craig Tooman, our Chief Financial Officer, will discuss our financial performance and then turn the call over to Dr. Giles Campion, our Head of R&D and Chief Medical Officer to give an update on our clinical programs. Mark will then provide some closing remarks before turning the call to the operator for Q&A. With that, I will turn the call over to Mark. Mark?

Thanks, Gem. Good afternoon, and good morning, everyone. Thank you for joining us today. So, moving to slide three. Looking back at 2020 and for the first period of 2021, Silence has made remarkable progress at both the scientific and corporate level. 2020 set the stage for 2021, which I believe is going to be a breakout year for Silence, as we looked to position ourselves as a leading global RNAi business. After 20 years of developing our science in the field of RNAi, we have entered 2021 as a clinical stage company with three Phase 1 data readouts anticipated this year. This is an important moment, as we look to demonstrate the potential and maximize the opportunity of our proprietary mRNAi GOLD Platform. To get to this point, we have achieved key regulatory milestones in 2020 and successfully advanced two wholly-owned programs into the clinic, SLN360 for cardiovascular disease due to high levels of lipoprotein(a) or LP(a) and SLN124 for rare iron loading anaemia conditions like thalassemia and myelodysplastic syndrome or MDS. Last month, we started dosing patients in the SLN360 APOLLO Phase 1 study in people with high levels of LP(a). We’re on track to readout data from the single ascending dose portion of the study in the second half of this year. Our plan is to rapidly advance SLN360 in the clinic, positioning ourselves to initiate Phase 2 studies in the second half of 2022, while creating more value for the asset and options for the future. For SLN124, we recently completed enrollment in the GEMINI I Phase 1 study in healthy volunteers and remain on track to report data in the first half of this year. This is an important milestone, not only for the SLN124 program, but it will also be the first inhuman data…

Thank you, Mark. Let me just provide some context around the financials we reported today beginning on slide 10. For the period ending December 31, 2020, the company recorded £5.5 million in revenues versus £0.2 million in 2019, which is largely a reflection of the partnership programs with Mallinckrodt and Takeda. As you know, according to these programs, we record revenue based on percentage of contract completion. For direct reimbursements by our partners, there is a cost of sales that is attributed to the revenues. As additional programs progress, such as the SLN501 program did in 2020. Our revenue should build over time. This will include programs partnered with AstraZeneca as well. As expected, R&D costs rose in 2020 to £20.2 million versus £13.3 million in 2019. In addition to partnership program costs this includes our proprietary program costs for SLN360 and SLN124 in addition to headcount increases. As Giles will update you on next we are very enthused about our projects in development and continue to evaluate new opportunities in the area as well. General and administrative costs were approximately £14 million in 2020 versus £9.6 million in 2019. The increase was primarily driven by costs associated with the Nasdaq listing and additional needs required for being a public company trading in the U.S. The company’s net loss for the full year 2020 was £32.5 million versus £19.6 million in 2019. We talked about the two main areas of investment having an impact on the P&L, namely the R&D programs and the G&A spending. Turning to slide 11. The company’s cash, cash equivalents and deposits were £37.4 million at the end of December 2020. However, we successfully raised net proceeds of approximately £30.8 million in oversubscribed financing that closed in early February and we expect contractual proceeds of £39.3…

Thanks, Craig. Moving to slide 12, I’m pleased to be here today to talk in more detail about our proprietary clinical programs starting with SLN360 for cardiovascular disease due to high LP(a). Moving to slide 13, LP(a) has been shown to be an independent risk factor for cardiovascular disease. It can’t be modified by lifestyle or diet, but is rather genetically determined. High LP(a) is very common, up to 10% of individuals worldwide have levels above 90 milligrams per deciliter, which is considered to significantly increase cardiovascular event risk. Moving to slide 14, you can see the global prevalence figures on the right. 50 milligrams per deciliter is the threshold of which cardiovascular experts agree that we should look to treat patients and that is around 20% of the global population. 90 milligrams per deciliter holds an even higher risk and that is 10% of the population. The table on the left illustrates the associated risks with having 90 milligrams per deciliter. You can see that these individuals are 2 times to 3 times more likely to have a heart attack or aortic stenosis compared to people with normal LP(a) levels. They are also at greater risk for other cardiovascular events like heart failure and stroke. There’s clearly a high unmet need here. Moving to slide 15. We view the size and opportunity of the LP(a) market like the cholesterol-lowering market. Most of us are familiar with high LDL cholesterol, a massive market with multiple blockbuster drugs. On the bottom left of the slide, you can see we’re looking at a very similar medically-treated population. The estimated population with high LP(a) greater than 50 milligrams per deciliter is 132 million, compared to 136 million with high cholesterol requiring medical treatments. However, there’s an important difference between high cholesterol versus high…

Thank you, Giles. Moving to slide 23. This is a really important year for Silence. After 20 years of developing a science and expertise in the field of sRNA, our GOLD Platform is now in the clinic, with three Phase 1 day to readout anticipated this year from our wholly-owned programs. Strategically, we are looking to maximize our GOLD Platform, and over the next few years, we expect to deliver two to three INDs per year, both through developing our wholly-owned programs and through our partnerships. We are well capitalized through both non-dilutive funding and the recent $45 million financing. 2020 set the stage for 2021, which I believe is going to be a breakout year for Silence as we look to position ourselves as a leading global RNAi business. With that, I’d like to thank everyone for listening today and I’ll pass back over to the operator for questions. Operator?

Thank you. [Operator Instructions] Thank you. Your first question today comes from the line of Tom Shrader from BTIG.

Hi. This is Julian on for Tom. Congrats on all the recent progress and thank you for taking my question. Tissue distribution is becoming an emerging theme in the wake of recent events in the broader antigen space. So I guess, with that in mind, can you remind us what gives you confidence your sRNA’s can get to where they need to, and inadequate and mounts maybe in the context of your LP(a) and hepcidin programs?

Great. Tom, thank you very much for the question. And I think the best person to answer that is Giles, who is on the line in the U.K. So Giles, do you want to tackle that one?

Yeah. To answer the question, it’s a very important one, because I think it speaks to the great advantage that sRNA -- GalNAc conjugated sRNA offers over other modalities. You got targeting of the hepatocytes that is where the LP(a) gene is. And as I indicated during the talk, the important thing is that you get less than 1% of peak liver levels in other organs, so it means you get a very restricted distribution with the resulting reduction and likely off target effects.

Okay. Got it. That’s helpful. And then quickly on SLN360, I’m wondering if you have a sense now for the target dosing interval and when might that be better elucidated? And in terms of the sad portion, the Phase 1 expected to readout in the back half of this year? Are you framing any expectations for LP(a) knockdown?

Giles, do you want to take that?

Yes. I mean, obviously, that’s what the Phase 1 study that we’re -- the ongoing is designed to show. I think what’s encouraging is that, obviously, we’ve seen the results with interest around which targets TKS line [ph], which is now associated with a six monthly dosing. And again, one of the advantage of sRNA is the ability to have long intervals between dosing. From the data that we’ve seen from Amgen, we’re seeing a similar sort of dosage interval, the potential dosage in full. So we would imagine that we should see something similar, if not better.

Okay. Great. Thank you very much.

Thank you.

Thank you. Your next question today comes from the line of Patrick Trucchio from H.C. Wainwright.

Hi. Good morning and good afternoon. I have a few follow-up questions on SLN124. So, first, in the GEMINI Phase 1 study of SLN124 in healthy volunteers. Can you discuss the doses of 1 milligram kilo -- per kilogram and 3 milligrams per kilogram being evaluated and why the dose levels were chosen? And secondly, safety and tolerability is the primary outcome. So I’m wondering, first, what you’d be looking for in terms of change occurred in hepcidin and hemoglobin based on what you’ve seen generated pre-clinically? And to what extent the pharmacodynamics in the healthy volunteers could translate to MDS and thalassaemia patients?

Patrick, these are great questions. And of course, this is the first set of data that we’re anticipating this year in the first half of this year. So it’s an important question. Giles, do you want to tackle this question around dosing and what we can expect from the study?

Yeah. I think, we base our dosing both from what we’ve seen in terms of the models both in healthy rodents and also the beta thalassemia model, as well as what we’ve seen in terms of knockdown in primates. So there’s -- we do quite extensive modeling to make assumptions about our initial human dose, and of course, that has to be supported by safety. We, as Mark has indicated, we should be reporting -- we will be reporting our healthy volunteer data out very shortly in the first half of this year. So I don’t want to predict that too much. But we know what other compound in this area has achieved in terms of changes in hepcidin and iron levels and we feel confident that we should be in that range. I think in terms of the patient study, we anticipate getting good proof-of-concept in healthy volunteers, so we obviously can’t do want to go too high in healthy volunteers. I mean, what we would expect to see in patients is potentially a greater effect, since these patients are actually iron overloaded and also potentially a longer duration of action.

Can you discuss what changes in hepcidin serum iron hemoglobin would be considered clinically relevant or what changes would -- should we interpret that could translate to clinically meaningful outcomes in later stage trials?

Giles?

Yeah. I mean, I don’t want to elaborate too much on that at this moment in time. I mean, ultimately, of course, what we’re looking to do is to increase our -- is to have an effect on the anemia. So what we’ve seen in our preclinical studies in the mice was an increase of 2.5 grams per deciliter. And I think if we can see anything greater than a gram, which I think is the key point in terms of our longer term studies, then that would be as if with us feeling comfortable about the effect of the drug. In terms of hepcidin, we would expect us see at least a doubling, if not more of hepcidin and with -- associated with a reduction in serum iron in terms of our healthy volunteers study.

Got it. That’s helpful. I have another follow-up on, just on the GOLD Platform, if I may, just regarding the…

Yeah.

…potential novel targets in the liver. Can you discuss how Silence is going to decide to pursue novel targets? Specifically, what level of validation would you be looking for, is it genetic validation or how is the decision going to be made to pursue a novel target?

It’s a great question, because as you recall, we have set ourselves a goal of two to three INDs per year by 2023. And that will be a combination of both expanding our wholly-owned pipeline, which will include novel targets, but also pursuing targets on behalf of partners. So as you may recall, we have set up a translational genomics team under Giles and enhanced our machine learning capabilities. And this has been a really important strategic thrust, especially given the fact that we think there’s still substantial opportunity to build -- to find targets and deliver. Perhaps, Giles, do you want to add a little bit more color on this team and how they’re going to go about defining targets that are of interest to us.

Yeah. I think one of the key criteria is unmet need. I mean, we obviously want to develop new medicines, where there’s a great need for them. I think if we can just go back to the compounds that are going into the clinic right now gives you a sense of what makes a really good target. So for example, SLN360, which is targeting LP(a), this gene is found exclusively in hepatocyte. So there is very little risk of off target effects or the level of off target effects is diminished. It also means you’re going to get a specific action. We know from human genetic data, that having low levels or zero levels is not associated with any untoward effect. So that means there’s a reduction in terms of concerns about potential super pharmacology. And actually, the gene is not expressed in logan. So it’s allowed us to go pretty quickly from sequence through to non-human primate to patient. So these are the sort of things that we bear in mind when we select a target. And that’s why genetic validation offers a big clue in terms of whether a target is likely to be relevant for human disease.

Got it.

I would just…

Thank you very much.

…say we have. Okay. I was going to say just we also pursued various data agreements, access to databases that will allow us also to mined databases for novel targets as part of this process.

Great. Okay. Thank you so much.

Thank you, Patrick.

Thank you. [Operator Instructions] Your next question comes from the line Miles Dixon from Peel Hunt.

Many thanks for the question. And I think, firstly, to me that, if I could get an update on AstraZeneca please, I previously understood that that was you talked about 10 targets. I previously understood that to be two, five target trances, with the second five extrahepatic. Is that still the case in terms of what you’re targeting and what’s the progress in that second five? Thank you.

Yeah. Thank you very much for the question, Miles. The collaboration with AstraZeneca is in really great shape. They are really good partner. We’re continuing to expand the scope of work with them in line with our expectations. And I would say that, one -- just over one year in we’re on track to have five targets underway within three years, which was the initial goal that we set for this collaboration. So at the rate things are going we’re looking like we’re very much on track for that.

Great. Thank you. And just one more leading to intellectual curiosity to Giles. He showed some interesting data on SLN360 on the highest 10% of the population of LP(a) expresses. I think it was 90 micrograms per deciliter and the chances of relative adverse event in cardiovascular disease being increased by two-fold to three-fold. How does that compare to the most sort of the highest expressed LDL cholesterol in the population with adverse events in cardiovascular disease? Thank you.

Well, it’s a little bit difficult to give you a straight answer for that, because the demographics are quite different and also individuals tend to have mixed pictures. So I think it’s difficult to give a straight answer to that.

Understood. Thank you.

Thank you. Your next question comes from the line of Myles Minter from William Blair.

Hi. Thanks for taking the questions. I feel like Giles is getting the majority. So probably stick with him. Just in the APOLLO study, obviously, a lot of doses that you’re potentially looking at in the sub portion here. I’m just wondering what dose ranges you would expect to be in the therapeutic levels, I think, Amgen showing in the higher dose levels for 90% that they’re getting 75% or greater knockdown of LP(a) and you have shown 90% pre-clinically. So what sort of dose ranges would you expect to replicate that in the clinic? And with the less than or equal to 900 milligram dose, does that come anywhere near close to the no adverse -- no observed adverse effect like what you saw in the non-human primates?

Yeah. Thanks for the question, Miles. Over to Giles.

Yeah. I have to deal with that last question, first. I mean, again, I think, that’s one of the advantages of the sRNA platform is that the preclinical safety profile looks pretty good. So in the presentation we made at the American Heart, we have a margin of 60-fold between the no effect level and the dosing starting match in terms of the clinical study. So we’re well within anticipated ranges for even the highest dose and that’s obviously part of the conversation we have with the regulatory authorities. You’re right in terms of what people are looking for knocking down LP(a) is around about 70% to 80%. I mean, if you can get above that, then potentially you can also deal with those individuals that have very high levels. And I was referring to 90 milligrams per deciliter has been associated with significantly increased cardiovascular risks, but there are people out there with 200 milligrams per deciliter, 300 milligrams per deciliter. So there are individuals with quite high levels, and obviously, the more you get them down to what’s considered acceptable ranges, the better your therapeutic is at.

Okay. Cool. And then on GEMINI, the healthy volunteers study, obviously, GEMINI II is ongoing at the same time as this. I’m wondering if you would be able to glean any information from the readout of the healthy volunteer’s study that might inform on any sort of potential changes in GEMINI II that you might want to make or potential expansion into indications like hereditary hemochromatosis or polycythemia rubra vera, like, what additional information you’re hoping to get out of that trial?

Well, I think, the trial -- the key thing, yeah, the key thing from the healthy volunteers study really is to show proof-of-principle. So, as we’ve discussed earlier on it, it’s all about showing that you’re able to increase hepcidin and you are reducing iron levels and then ultimately having an effect on red cell production. So -- and I think that there is increasing evidence that given that you’re dealing with a master regulator of iron flux and that the amount of iron actually available to return or the appearance of toxic iron, which is what happens with iron overload to rethrone [ph] is key in terms of determining that subsequent effects. So the hypothesis with toxic iron is that by reducing iron overload, you improve the ability to make new red cells in treating anemia in diseases such as polycythemia rubra vera were interesting results being shown with the hepcidin mimetic for example, there what you’re doing is you’re restricting iron levels by increasing hepcidin. So I think the fact that we’re dealing with a major mechanism that is so important for controlling the most important substrates for red cell production doesn’t mean that there are a number of other opportunities there. So I think if we see a good proof-of-principle it does open the opportunity to explore a number of different avenues.

Okay. Cool. And then last one, if I may, just wanted to the company in general, just under £100 million pro forma in the bank building to two to three INDs per year by 2023. How do we think about sort of balancing the capital needs for the company versus the non-dilutive capital that you’re bringing from those partnerships moving forward? And what are the strategies, maybe the probably thinking about to address the liquidity on the Nasdaq here?

Miles you spot on. Craig, do you want to take that one?

Yeah. I appreciate it very much. As we noted in the release, we’re not going to provide more specific guidance on cash, just as a reminder, but thank you for reiterating that £97.5 million, it’s nice on a pro forma basis. And just as again, as a reminder, we already have captured that $45 million from the pipe, which occurred and closed in February, which is £38 point -- £30.8 million net. So again, that’s £30.8 million net and £29.3 million is coming from that $40 million payment from AstraZeneca. So those two combined with the £37.4 million, which we had at year end get to that £97.5 million. So just you’d have all those. Look -- if you look back one year, our R&D programs were in earlier stages of spending and we weren’t listed on Nasdaq. So the company’s come quite away, but also has new needs, which you’re guessing. And importantly, even with these required investments that we’re talking about, we anticipate our cash position gets us to the next level, where we see the data that we’re highlighting to you today. And we understand how important that is to our investors. So going beyond that, we’ll look at the data. We’ll evaluate what that looks like and what our financing needs are, but we think we’re just in a great position sitting here in front of the data. It’s a…

[Inaudible]

It’s interesting, sorry, just in this phase where we’re getting the AstraZeneca proceeds and we’ve raised from the equity markets, that it really speaks to this hybrid approach, because we’re getting funds from both of those angles.

Okay. Thanks for the questions.

The -- at the end of -- in the second half of next year, we’re looking to initiate the Phase 2 trial for SLN360. So that’s the other thing just to bear in mind that, we’re heading in the direction of really moving that program forward and making sure that we do the right thing for what is a clearly a very important lead program.

Well, thanks for the questions, Miles.

Thank you. We have no further questions. So I would like to hand back to Mr. Mark Rothera for any closing comments.

Thank you, Operator. Well, I hope you’ve heard that 2020 really set the stage for 2021, which I believe is going to be a breakout year for Silence as we look to position ourselves as a leading global RNAi business. After 20 years of developing our science in the field of RNAi, we’ve entered 2021 as a clinical stage company and we have three Phase 1 data readouts this year. So it’s a very important moment, as we’re looking to demonstrate the potential of and maximize the opportunity of our proprietary GOLD Platform through advancing both our wholly-owned and our partner programs. Thank you for joining our earnings call and I’m looking forward to updating you over the coming months. Thank you very much.

Thank you. Ladies and gentlemen, that does conclude your call for today. Thank you all for participating and you may now disconnect. Speakers, please standby.