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Silence Therapeutics Plc (SLN) Q4 2020 Earnings Call Transcript

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SLN earnings call for the period ending December 31, 2020.

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Silence Therapeutics Plc  (SLN 1.27%)
Q4 2020 Earnings Call
Mar 30, 2021, 8:00 a.m. ET


  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:


Good day, ladies and gentlemen, and welcome to the Silence Therapeutics full-year 2020 conference call and webcast. [Operator instructions] I will now hand over to Gem Hopkins, head of investor relations and corporate communications to open the webinar. Please go ahead, madam.

Gem Hopkins -- Head of Investor Relations and Corporate Communications

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 make sure to visit the investors section of our corporate website at www.silence/ to download a copy or follow along on the webcast.

Turning to Slide 2. I would 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 candidates, 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 Silence 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?

Mark Rothera -- President and Chief Executive Officer

Thanks, Gem. Good afternoon, and good morning, everyone. Thank you for joining us today. So moving to Slide 3.

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 to 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 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 and for cardiovascular disease due to high levels of lipoprotein A, or Lp(a); and SLN124 for rare iron loading anemia conditions like thalassemia and myodisplastic 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 read out 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 1 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-in-human data from our GOLD platform. We also started enrollment last month in the GEMINI 2 patient study with SLN124 and expect to report interim data in the second half of this year. Giles will provide more detail on both programs later in the call.

Alongside advancing our wholly owned pipeline, developing high-value collaboration is a core part of our strategy. And we made great strides with this in 2020, including a landmark deal with AstraZeneca in March for up to 10 targets across cardiovascular, renal, metabolic and respiratory diseases. We received an upfront cash payment of $20 million and are due to receive another $40 million in the first half of this year. In January 2020, we also commenced the technology evaluation deal with Takeda to explore the potential of our platform against the novel target.

In addition, we also expanded our collaboration with Mallinckrodt for complement-mediated diseases. In 2020, Mallinckrodt exercised options on two additional targets, each triggering a $2 million research milestone payment to us. We've now initiated work on all three targets covered by our agreement with them. Collectively, these partnerships represent up to 14 programs and economics of up to $6 billion in potential milestones plus royalty.

From a financial perspective, we're in a strong position and have already started to see the benefits of our NASDAQ listing last September, with the completion of an oversubscribed $45 million financing last month. This financing, combined with the non-dilutive funding from our collaborations, gives us a pro forma cash position of GBP 97.5 million, which is sufficient capital to see us well beyond key clinical data readouts for both the SLN360 and and SLN124 programs. Craig will discuss our financials in more detail in a few minutes. Over the past 18 months, we've continued to strengthen our team with key appointments across clinical, regulatory, IT and finance.

This includes myself, Giles and Craig, who all bring over 30 years of experience in the industry. We also recently appointed Dr. Michael Davidson, a world-leading lipidology experts with tremendous experience in cardiovascular clinical trials to our board. I believe we have the right people in place to drive successful execution of our plan.

And we're committed to advancing our pipeline as fast and efficiently as we can. And our goal is to file two to three INDs per year from 2023, representing a combination of both wholly owned and partnership programs. Moving to Slide 4. We believe Silence has a clear path to value creation.

This chart illustrates our peer group in the RNAi field. You can see they all have multibillion-dollar market caps, while Silence today is under $1 billion, the way I see it, to build value we must expand our pipeline, have more wholly owned programs, and advance our pipeline in the clinic rapidly and effectively. All of this should create substantial value moving forward. We have developed a road map together.

In addition, as you'll see in a moment SLN360, our wholly owned lead program is a program with blockbuster potential that on a stand-alone basis can create tremendous value. Moving to Slide 5. Our approach is based on our GOLD platform that we've built and refined over the last two decades. Using our GOLD platform, we aim to optimize molecular design so as to maximize efficacy, minimize our target effects, improve stability and consequently, the duration of action and whenever possible, ensure ease of manufacturing.

We have a robust and growing IP estate, not only covering our platform but also each target that we are pursuing. Moving to Slide 6. We believe there is a tremendous potential and opportunity to leverage our GOLD platform. There are over 14,000 genes expressed in the liver.

Of these, 99% are not currently being targeted by an existing or potential siRNA program as estimated across our peer group. Even if there were only another 1% of meaningful targets that we could address to treat diseases with unmet need, that's another 140 programs that we can look for. So we think there's a tremendous opportunity and mileage to be had in leveraging this platform. To this end, we've established a translational genomics team in-house that is working hard to identify and validate novel targets.

We're also open to developing best-in-class molecules against known targets. Moving to Slide 7. As mentioned earlier, what is particularly attractive about our GOLD platform and the GalNAc siRNA approach is it is a proven modality. In fact, the likelihood of successfully moving a GalNAc siRNA program through the clinic from Phase 1 to Phase 3 and then to approval is significantly higher compared to the industry average.

This means that the return on discovery investment in the GOLD platform has the potential to be much better than is typical for our industry. Moving to Slide 8. We are doing several things to capitalize on this opportunity and maximize the output of our GOLD platform. Firstly, as I mentioned, we have invested in a translational genomics group that we have been building over the past year and a half, and that group is focused on novel targets in the liver.

We're also looking to reduce attrition so that when we do go for a target, there is a higher likelihood of success. Finally, we continue to seek strategic partnerships to enhance our pipeline opportunities, in addition to growing our wholly owned strategy. As I mentioned earlier, we intend to file two to three INDs per year from 2023 through a combination of both our wholly owned and partnership programs. Moving to Slide 9.

Our strategy is based on a hybrid model. We're advancing our wholly owned pipeline, but also servicing our partners. And this pipeline chart highlights this, showing our lead wholly owned assets SLN360 and SLN124, along with the programs of our partners, Mallinckrodt and AstraZeneca below. So with that overview, I'll now hand over the call to Craig to discuss our financial performance in more detail.


Craig Tooman -- Chief Financial Officer

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 GBP 5.5 million of revenues versus GBP 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 GBP 20.2 million pounds versus GBP 13.3 million in 2019.

In addition to partnership program costs, this includes our proprietary program cost 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 GBP 14 million in 2020 versus GBP 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 GBP 32.5 million versus GBP 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 GBP 37.4 million at the end of December 2020.

However, we successfully raised net proceeds of approximately GBP 30.8 million in an oversubscribed financing that closed in early February. And we expect contractual proceeds of GBP 39.3 million from AstraZeneca in the first half of this year. In total, the pro forma cash using these balances is GBP 97.5 million, as Mark noted. We are showing it to you both ways for your information.

We are also depicting our share count on this slide at year-end 2020 and after our February financing. Obviously, for modeling purposes, going forward, you will want to use the post financing figure of 89.4 million shares. We believe we have a strong cash position at present. Importantly, this should allow us to comfortably fund the company through the data readouts on our key programs, SLN360 and SLN124 that we have been discussing today.

In 2021, as noted in today's press release, we anticipate investing in the continued growth of the company. We expect to incur higher R&D costs as our programs advance compared to prior periods. We will also spend on additional G&A to support a growing organization and to comply with greater regulatory requirements. We are not providing any specific guidance on this spending today, but we will be investing as prudent to support the success of our clinical programs.

With that, I'll turn the call over to Giles to provide an update on our wholly owned clinical programs, SLN360 and SLN124. Giles?

Giles Campion -- Head of R&D and Chief Medical Officer

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 a threshold at 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 two to three 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 loan market. Most of us are familiar with high LDL cholesterol, a massive market with multiple 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 treatment.

However, there's an important difference between high cholesterol versus high Lp(a). High cholesterol is a modifiable risk factor, not all patients require medical treatment, and lifestyle changes can have a positive impact. High Lp(a) is something you're born with. Most patients will require medical treatment, and lifestyle changes have no effect on Lp(a) levels.

Patient stories inform us that the first thing an effective person knows is experiencing a catastrophic event such as a heart attack, not uncommonly on the background of a healthy lifestyle. Right now, there are no approved treatments for high Lp(a) and only a handful of drugs in development, including SLN360. Moving to Slide 16. We believe SLN360 has the ideal therapeutic profile based on our nonhuman primate data.

As you can see here, we saw fast-acting robust knockdown of Lp(a) levels over 90%. That was sustained throughout the duration of the study. Importantly, in rodents, there was less than 1% of peak level drug levels outside the liver and kidney, with no detected off-target effects. Safety is always important, but particularly when you're looking to introduce a potential preventative medicine to such a large population that is otherwise healthy, aside from increased cardiovascular risk.

Moving to Slide 17. You can see the design of the APOLLO Phase 1 study that is now under way. The initial phase is in healthy volunteers with high Lp(a) levels, so we're looking for a knockdown of the Lp(a) levels in this population. While we're continuing to navigate the pandemic headwinds, we remain on track to read out data from the single ascending dose portion in the second half of this year.

Moving to Slide 18. Our second wholly owned program, SLN124, is in development for iron loading anemia conditions. Moving to Slide 19. We're initially targeting two rare disease populations, MDS and thalassemia.

Both of these conditions are associated with a lower quality of life and are poorly maintained by the therapies currently on the market. SLN124 has orphan drug designations for both indications, in addition to rare pediatric designation for thalassemia. Moving to Slide 20. SLN124 aims to normalized iron levels in the body by restoring hepcidin, a key naturally occurring regulator of iron balance.

It does this by knocking down or silencing a gene called TMPRSS6 in the liver. Here, we are looking at data from a mouse model for beta thalassemia. You can see we saw a reduction of TMPRSS6 in the liver which then increased hepcidin levels and iron levels were lowered to a more normal level. That then allows for improved red cell production.

And you will see in the chart on the right, the 2.5 gram per deciliter increase in red blood cell production. Moving to Slide 21. We have two ongoing studies for SLN124. The first is in healthy volunteers.

The study is looking at safety, as well as hepcidin and iron levels. The GEMINI study is fully enrolled, and we are on track to read out data in the first half of this year. As Mark mentioned, this is not only important for the SLN124 program, but it also represents the first-in-human data from our GOLD platform. Moving to Slide 22.

We're also enrolling through our GEMINI 2 study in adult thalassemia and MDS. Data is expected in the second half of this year. With that, I'll hand the call back to Mark.

Mark Rothera -- President and Chief Executive Officer

Thank you, Giles. Moving to Slide 23. This is a really important year for Silence. After 20 years of developing our science and expertise in the field of siRNA, our GOLD platform is now in the clinic, with three Phase 1 data readouts 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 would like to thank everyone for listening today, and I'll pass back over to the operator for questions.


Questions & Answers:


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

Julian Harrison -- BTIG -- Analyst

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 antisense space. So I guess, with that in mind, can you remind us what gives you confidence your siRNAs can get to where they need to and in adequate amounts maybe in the context of your Lp(a) and hepcidin programs?

Mark Rothera -- President and Chief Executive Officer

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 wanna tackle that one?

Giles Campion -- Head of R&D and Chief Medical Officer

Yeah, thanks for the question. It's a very important one because I think it speaks to the great advantage that siRNA -- GalNAc-conjugated sRNA offers over the modalities. You got targeting of the hepatocyte, and that is where the Opa 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 that you get a very restricted distribution with the resulting reduction in likely off-target effects.

Julian Harrison -- BTIG -- Analyst

OK, 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 of the Phase 1 expected to read out in the back half of this year, are you framing any expectations for Lp(a) knockdown?

Mark Rothera -- President and Chief Executive Officer

Giles, do you wanna take that?

Giles Campion -- Head of R&D and Chief Medical Officer

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 inclisiran, which targets TKS, which is now associated with the six monthly dosing. And again, one of the advantages 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 -- a potential dosage interval. So we would imagine that we should see something similar, if not better.

Julian Harrison -- BTIG -- Analyst

OK, great. Thank you very much.

Mark Rothera -- President and Chief Executive Officer

Thank you.


Thank you. Our next question today comes from the line of Patrick Trucchio from H.C. Wainright.

Patrick Trucchio -- H.C. Wainwright -- Analyst

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 per kilogram and 3 milligram 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 would be looking for in terms of change in ferritin, hepcidin and hemoglobin based on what you've seen generated preclinically? And to what extent the pharmacodynamics in the healthy volunteers could translate to MDS and thalassemia patients?

Mark Rothera -- President and Chief Executive Officer

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

Giles Campion -- Head of R&D and Chief Medical Officer

Yeah. I mean, we based 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 see in terms of knockdown in primate. 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 data out very shortly in the first half of this year. So I don't wanna predict that too much. But we know what other compounds in this area have 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 our healthy volunteer study. Obviously, you can't -- don't wanna go too high in the 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.

Patrick Trucchio -- H.C. Wainwright -- Analyst

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

Mark Rothera -- President and Chief Executive Officer


Giles Campion -- Head of R&D and Chief Medical Officer

Yeah. I mean, I don't wanna 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 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 with -- us feeling comfortable about the effect of the drug. In terms of hepcidin, we would expect to see at least a doubling, if not more, of hepcidin with -- associated with the reduction in serum iron in terms of our healthy volunteer study.

Patrick Trucchio -- H.C. Wainwright -- Analyst

Got it. That's helpful. I have another follow-up on just on the GOLD platform, if I may.

Mark Rothera -- President and Chief Executive Officer


Patrick Trucchio -- H.C. Wainwright -- Analyst

Just regarding the potential novel targets in the liver, can you discuss how Silence is gonna decide to pursue a novel target? Specifically, what level of validation would you be looking for? Is it genetic validation? Or how is the decision gonna be made to pursue a novel target?

Mark Rothera -- President and Chief Executive Officer

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 for us, especially given the fact that we think there's still substantial opportunity to find targets and deliver. Perhaps Giles, do you wanna add a little bit more color on this team and how they're gonna go about defining targets of interest to us?

Giles Campion -- Head of R&D and Chief Medical Officer

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? That gives you a sense of what makes a really good target.

So for example, 360, 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 we are gonna get a specific action. We know from human genetic data that having low levels or zero levels is not associated with untoward effect.

So that means there's a reduction in terms of concerns of our 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 nonhuman 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.

Patrick Trucchio -- H.C. Wainwright -- Analyst

Got it. Thank you very much.

Mark Rothera -- President and Chief Executive Officer

I would just add, we have -- OK. I was going to say just we have also pursued various data agreements, access to databases that will allow us also to mine databases for novel targets as part of this process.

Patrick Trucchio -- H.C. Wainwright -- Analyst

Great. OK, thank you so much.

Mark Rothera -- President and Chief Executive Officer

Thank you, Patrick.


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

Miles Dixon -- Peel Hunt -- Analyst

Many thanks for the question. And I think, firstly, to me, if I could get an update on AstraZeneca, please? I've previously understood that that was -- you talked about 10 targets. I previously understood that to be two, five target tranches 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 phase? Thank you.

Mark Rothera -- President and Chief Executive Officer

Yesah, thank you very much for the question, Miles. The collaboration with AstraZeneca is in really great shape. They're a 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 are on track to have five targets under way 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.

Miles Dixon -- Peel Hunt -- Analyst

Great. Thank you. And just one more maybe for intellectual curiosity to Giles. You showed some interesting data on SLN360 on the highest 10% of the population of Lp(a) expresses.

I think it was 90 micrograms a deciliter. And the chance of relative adverse event in cardiovascular disease being increased by two- to threefold. How does that compare the most -- sorry, the highest expressed LDL cholesterol in the population with adverse events in cardiovascular disease? Thank you.

Giles Campion -- Head of R&D and Chief Medical Officer

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.

Miles Dixon -- Peel Hunt -- Analyst

Understood. Thank you.


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

Myles Minter -- William Blair -- Analyst

Hi, thanks for taking the questions. Feels 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 SAD portion here. I'm just wondering what dose ranges you would expect to be in the therapeutic levels? I think Amgen has shown in the higher dose levels for 890 that they're getting 75% or greater knockdown of Lp(a) and you've shown 90% preclinically.

So what sort of dose ranges would you expect to replicate that in the clinic and would the less than or equal to 900-milligram dose? Does that come anywhere near close to the no observed adverse effect level you saw in the nonhuman primates?

Mark Rothera -- President and Chief Executive Officer

Yeah, thanks for the question, Myles. Over to Giles.

Giles Campion -- Head of R&D and Chief Medical Officer

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 American Heart, we have a margin of 60-fold between the no effect levels. And the dosing that starting at 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 as referring to 90 milligrams per deciliter being associated with significantly increased cardiovascular risk but there are people out there with 200, 300 milligrams per deciliter. So their individuals with quite high levels. And obviously, the more you get them down to what's considered acceptable ranges, the better your therapeutic effect.

Myles Minter -- William Blair -- Analyst

OK, cool. And then, on GEMINI, the healthy volunteer study, obviously, GEMINI 2 is ongoing at the same time as this. I'm wondering if you would be able to glean any information from the readout of a healthy volunteer study that might inform on any sort of potential changes in GEMINI 2 that you might wanna make or potential expansion into indications like hereditary hemochromatosis or polycythemia vera? Like what additional information are you hoping to get out of that trial?

Giles Campion -- Head of R&D and Chief Medical Officer

Well, I think the -- yes, the key thing from the healthy volunteer study really is to show proof of principle. So as we've discussed earlier on, it's all about showing that your able to increase hepcidin or 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 influx and the amount of iron actually available to return or the appearance of toxic iron, which is what happens with iron overload to reenthrone is key in terms of determining the subsequent effects. So the hypothesis with toxic iron is that by reducing iron overload you improve the ability to make new red cells, so in treating anemia, in disease such as polycythemia vera where interesting results have been shown with the hepcidin in hermetic, for example, there, what you're doing is you're restricting iron levels by increasing hepcidin.

So I think the fact that we are dealing with a major mechanism that is so important for controlling the most important substrate for red cell production does 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.

Myles Minter -- William Blair -- Analyst

OK, cool. And then, last one, if I may. Just one for the company in general. Just under GBP 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 these partnerships moving forward? And what are the strategies maybe that Craig is thinking about to address the liquidity on the NASDAQ here?

Mark Rothera -- President and Chief Executive Officer

Myles, you spot on. Craig, do you wanna take that one?

Craig Tooman -- Chief Financial Officer

Yeah, I appreciate it very much. As we noted in the release, we're not gonna provide more specific guidance on cash, just as a reminder. But thank you for reiterating that GBP 97.5 million. It's GBP 97 million 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 GBP 30.8 million net. So again, that's GBP 30.8 million net, and GBP 29.3 million is coming from that $40 million payment from AstraZeneca. So those two combined with a GBP 37.4 million which we had at year-end, get to that GBP 97.5 million, so just you have all of 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 has come quite a way 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 are just in a great position sitting here in front of the data. It's interesting, sorry, just in this phase where we're getting the AstraZeneca proceeds and we've raised from the equity markets that really speaks to this hybrid approach because we're getting funds from both of those angles.

Mark Rothera -- President and Chief Executive Officer

OK, thanks for the questions.

Craig Tooman -- Chief Financial Officer

The -- at the end of -- in the second half of next year, we are 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 clearly a very important lead program.

Mark Rothera -- President and Chief Executive Officer

So thanks for the questions, Myles.


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

Mark Rothera -- President and Chief Executive Officer

Thank you, operator. Well, I hope you've heard that 2020 really set the stage for 2021, which I believe is gonna 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 partnered programs.

Thank you for joining our earnings call, and I'm looking forward to updating you over the coming months. Thank you very much.


[Operator signoff]

Duration: 48 minutes

Call participants:

Gem Hopkins -- Head of Investor Relations and Corporate Communications

Mark Rothera -- President and Chief Executive Officer

Craig Tooman -- Chief Financial Officer

Giles Campion -- Head of R&D and Chief Medical Officer

Julian Harrison -- BTIG -- Analyst

Patrick Trucchio -- H.C. Wainwright -- Analyst

Miles Dixon -- Peel Hunt -- Analyst

Myles Minter -- William Blair -- Analyst

All earnings call transcripts

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