6-K
Silence Therapeutics plc (SLN)
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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 6-K
REPORT OF FOREIGN PRIVATE ISSUER
PURSUANT TO RULE 13a-16 OR 15d-16
UNDER THE SECURITIES EXCHANGE ACT OF 1934
For the Month of May 2021
Commission File Number: 001-39487
Silence Therapeutics plc
(Exact Name of Registrant as Specified in Its Charter)
72 Hammersmith Road
London W14 8TH
United Kingdom
(Address of principal executive offices)
Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.
Form 20-F ☒ Form 40-F ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1): ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ☐
On May 19, 2021, Silence Therapeutics plc (the “Company”) issued a press release titled “Silence Therapeutics Announces Positive Data from GEMINI Phase 1 Study of SLN124 in Healthy Volunteers.” The press release is furnished as Exhibit 99.1 to this Report on Form 6-K.
On May 19, 2021, the Company posted an updated corporate investor presentation on its website (https://www.silence-therapeutics.com). A copy of the corporate investor presentation is furnished as Exhibit 99.2 to this Report on Form 6-K.
The information contained in Exhibits 99.1 and 99.2 shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, unless expressly set forth by specific reference in such a filing.
EXHIBIT INDEX
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| Silence Therapeutics plc | ||
|---|---|---|
| By: | /s/ Mark Rothera | |
| Name: | Mark Rothera | |
| Title: | President and Chief Executive Officer |
Date: May 19, 2021
sln-ex991_6.htm
Exhibit 99.1
Silence Therapeutics Announces Positive Data from GEMINI Phase 1 Study of SLN124 in Healthy Volunteers
| – | Data showed SLN124, an siRNA which targets TMPRSS6, was safe and effective in reducing plasma iron levels and had a long duration of action |
|---|---|
| – | Data support ongoing phase 1 study of SLN124 in patients with thalassemia and myelodysplastic syndrome (MDS) |
| --- | --- |
| – | First clinical data from Silence’s proprietary mRNAi GOLD™ platform – two more clinical data readouts anticipated this year |
| --- | --- |
19 May 2021
LONDON, Silence Therapeutics plc, AIM:SLN and Nasdaq: SLN (“Silence” or “the Company”), a leader in the discovery, development and delivery of novel short interfering ribonucleic acid (siRNA) therapeutics for the treatment of diseases with significant unmet medical need, today announced positive topline data from the GEMINI phase 1 study of its wholly owned product candidate, SLN124, in healthy volunteers. SLN124, an siRNA which targets TMPRSS6, is in development for the treatment of iron-loading anemia conditions, thalassemia and myelodysplastic syndrome (MDS).
The GEMINI phase 1, randomized, double-blind, placebo-controlled, single-ascending dose study evaluated the safety and tolerability of SLN124 (1.0, 3.0 and 4.5 mg/kg doses) in 24 healthy volunteers (18 active and 6 placebo). Pharmacokinetic parameters and pharmacodynamic biomarkers of iron metabolism were also measured to assess reduction in iron.
Initial data from the study showed all doses of SLN124 were generally well-tolerated with no serious or severe treatment emergent adverse events (TEAEs) or TEAEs leading to withdrawal. TEAEs did not appear to be dose dependent and the majority were mild, including transient injection site reactions which resolved without intervention.
Notably, up to an approximate four-fold increase in average hepcidin and 50% reduction in plasma iron levels were also observed after a single dose of SLN124. Effects on hepcidin and iron appear to be dose dependent and were still observed at the end of the 8-week study at all dose levels, indicating a sustained and long duration of action.
These clinical data support preclinical findings which demonstrated SLN124 effectively improved red blood cell production and reduced anemia by increasing levels of hepcidin – a key natural regulator of iron balance and distribution in the body. The Company expects to measure red blood cell production and effects on anemia in the ongoing GEMINI II phase 1 study of SLN124 in people with thalassemia and MDS, who unlike healthy volunteers have significantly elevated iron levels.
Mark Rothera, President and CEO of Silence Therapeutics, said: “These data represent the first clinical data from our mRNAi GOLD™ platform and underscore the promising potential for our technology to deliver precision medicines. We look forward to further data in patients anticipated from both of our wholly owned clinical programs later this year – the GEMINI II study of SLN124 for iron-loading anemia conditions and the APOLLO study of SLN360 for cardiovascular disease due to high lipoprotein(a).”
Giles Campion, M.D., EVP, Chief Medical Officer and Head of Research & Development of Silence Therapeutics, said: “Today’s results confirm the strong preclinical profile of SLN124 in humans – we observed excellent safety, robust gene knockdown expressed by up to an approximate four-fold increase in average hepcidin along with a 50% reduction in serum iron levels and a durable effect which lasted throughout the study. We are encouraged by these data in healthy volunteers and the opportunity for SLN124 to potentially address iron-loading anemia conditions such as thalassemia and MDS.”
John Porter, M.D., Professor and Consultant Haematologist, Red Cell Disorders Unit, University College London and University of College London Hospitals, commented: “Despite advances in our understanding of thalassemia and MDS, there are no existing treatments that specifically target the underlying mechanisms of these conditions as a way to improve the degree of anemia. There is a major unmet need for a therapy that can provide safe and continuous control of iron balance and distribution as a way to improve the efficiency of red cell production. I’m encouraged by data from the SLN124 study in healthy volunteers and look forward to further clinical testing.”
Silence expects to present full data from the GEMINI phase 1 study of SLN124 in healthy volunteers at an appropriate scientific meeting later this year. In addition, the Company plans to report data from the single-ascending dose portion of the ongoing GEMINI II phase 1 study of SLN124 in people with thalassemia and MDS in the second half of this year. SLN124 has Orphan Drug Designation for both conditions and rare pediatric disease designation for beta thalassemia.
Enquiries:
| Silence Therapeutics plc<br><br><br>Gem Hopkins, Head of IR and Corporate Communications<br><br><br>ir@silence-therapeutics.com | Tel: +1 (646) 637-3208 |
|---|---|
| Investec Bank plc (Nominated Adviser and Broker)<br><br><br>Daniel Adams/Gary Clarence | Tel: +44 (0) 20 7597 5970 |
| European PR<br><br><br>Consilium Strategic Communications<br><br><br>Mary-Jane Elliott/ Angela Gray / Chris Welsh<br><br><br>silencetherapeutics@consilium-comms.com | Tel: +44 (0) 20 3709 5700 |
About Thalassemia and Myelodysplastic Syndrome (MDS)
Thalassemia and MDS are both rare diseases that prevent a person from producing enough healthy red blood cells. Low levels of healthy red blood cells, known as anemia, result in less oxygen being delivered to different parts of the body. This can cause symptoms such as excessive tiredness and weakness. It can also lead to other serious health problems, such as heart disease. People living with thalassemia or MDS can also store too much iron in their bodies, leading to a phenomenon called ‘iron overload’, which damages organs such as the heart and liver.
Both conditions are typically treated with regular blood transfusions, which add to the problem of iron overload. Iron chelation therapy removes excess iron from the body using special medicines. While it helps reduce the amount of iron in the blood for people with thalassemia or MDS, it does not treat the underlying cause of the condition or stop it from progressing. There is, therefore, a need for therapies that directly address the biological drivers of disease.
About SLN124
SLN124 is a gene ‘silencing’ therapy – one that is designed to temporarily block a specific gene’s message that would otherwise trigger an unwanted effect. In this case, SLN124 aims to temporarily ‘silence’ TMPRSS6, a gene that prevents the liver from producing a particular hormone
that controls iron levels in the body – hepcidin. As hepcidin increases, it is hoped that iron levels in the blood will decrease, which could in turn allow more healthy red blood cells to be produced, thereby improving anemia. In preclinical studies, SLN124 has shown positive effects on improving levels of red blood cells and reducing harmful iron levels.
SLN124 is now being studied in the GEMINI clinical trial program. GEMINI II is a phase 1 study to investigate the effects of SLN124 in people with thalassemia or myelodysplastic syndrome (MDS), whose bodies produce fewer healthy red blood cells than normal and who can store too much iron in their bodies. For more information on the GEMINI II study, please click here.
About Silence Therapeutics
Silence Therapeutics is developing a new generation of medicines by harnessing the body's natural mechanism of RNA interference, or RNAi, to inhibit the expression of specific target genes thought to play a role in the pathology of diseases with significant unmet need. Silence's proprietary mRNAi GOLD™ platform can be used to create siRNAs (short interfering RNAs) that precisely target and silence disease-associated genes in the liver, which represents a substantial opportunity. Silence's wholly owned product candidates include SLN360 designed to address the high and prevalent unmet medical need in reducing cardiovascular risk in people born with high levels of lipoprotein(a) and SLN124 designed to address iron-loading anemia conditions. Silence also maintains ongoing research and development collaborations with AstraZeneca, Mallinckrodt Pharmaceuticals, and Takeda, among others. For more information, please visit https://www.silence-therapeutics.com/.
Forward-Looking Statements
Certain statements made in this announcement are forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and other securities laws, including with respect to the Company’s clinical and commercial prospects and the anticipated timing of data reports from the Company’s clinical trials. These forward-looking statements are not historical facts but rather are based on the Company's current expectations, estimates, and projections about its industry; its beliefs; and assumptions. Words such as 'anticipates,' 'expects,' 'intends,' 'plans,' 'believes,' 'seeks,' 'estimates,' and similar expressions are intended to identify forward-looking statements. These statements are not guarantees of future performance and are subject to known and unknown risks, uncertainties, and other factors, some of which are beyond the Company's control, are difficult to predict, and could cause actual results to differ materially from those expressed or forecasted in the forward-looking statements, including those risks identified in the Company’s most recent Admission Document and its amended Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission on April 29, 2021. The Company cautions security holders and prospective security holders not to place undue reliance on these forward-looking statements, which reflect the view of the Company only as of the date of this announcement. The forward-looking statements made in this announcement relate only to events as of the date on which the statements are made. The Company will not undertake any obligation to release publicly any revisions or updates to these forward-looking statements to reflect events, circumstances, or unanticipated events occurring after the date of this announcement except as required by law or by any appropriate regulatory authority.
May 2021 Corporate Presentation Silence Therapeutics Exhibit 99.2
Forward-Looking Statements The information contained in this presentation is being supplied and communicated to you solely for your information and may not be reproduced, further distributed to any other person or published, in whole or in part, for any purpose. The distribution of this presentation in certain jurisdictions may be restricted by law, and persons into whose possession this presentation comes should inform themselves about, and observe, any such restrictions. Although reasonable care has been taken to ensure that the facts stated in this presentation are accurate and that the opinions expressed are fair and reasonable, the contents of this presentation have not been verified by Silence Therapeutics plc (the “Company”) or any other person. Accordingly no representation or warranty, express or implied, is made as to the fairness, accuracy, completeness or correctness of the information and opinions contained in this presentation and no reliance should be placed on such information or opinions. None of the Company, or any of its respective members, directors, officers or employees nor any other person accepts any liability whatsoever for any loss howsoever arising from any use of such information or opinions or otherwise arising in connection with this presentation. No part of this presentation, or the fact of its distribution, should form the basis of or be relied upon in connection with any contract or commitment or investment decision whatsoever. This presentation does not form part of any offer of securities, or constitute a solicitation of any offer to purchase or subscribe for securities or an inducement to enter into any investment activity. Recipients of this presentation are not to construe its contents, or any prior or subsequent communications from or with the Company or its representatives as investment, legal or tax advice. In addition, this presentation does not purport to be all-inclusive or to contain all of the information that may be required to make a full analysis of any transaction. Further, the information in this presentation is not complete and may be changed. Recipients of this presentation should each make their own independent evaluation of the information and of the relevance and adequacy of the information in this document and should make such other investigations as they deem necessary. This presentation may contain forward-looking statements that reflect the Company’s current views and expectations regarding future events. In particular certain statements with regard to management’s strategic vision, aims and objectives, the conduct of clinical trials, the filing dates for product license applications and the anticipated launch of specified products in various markets, the Company’s ability to find partners for the development and commercialisation of its products as well as the terms for such partnerships, anticipated levels of demand for the Company’s products (including in development), the effect of competition, anticipated efficiencies, trends in results of operations, margins, the market and exchange rates, are all forward looking in nature. Forward-looking statements involve risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward looking statements. Although not exhaustive, the following factors could cause actual results to differ materially from those the Company expects: difficulties inherent in the discovery and development of new products and the design and implementation of pre-clinical and clinical studies, trials and investigations, delays in and results from such studies, trials and investigations that are inconsistent with previous results and the Company’s expectations, the failure to obtain and maintain required regulatory approvals, product and pricing initiatives by the Company’s competitors, inability of the Company to market existing products effectively and the failure of the Company to agree beneficial terms with potential partners for any of its products or the failure of the Company’s existing partners to perform their obligations, the ability of the Company to obtain additional financing for its operations and the market conditions affecting the availability and terms of such financing, the successful integration of completed mergers and acquisitions and achievement of expected synergies from such transactions, and the ability of the Company to identify and consummate suitable strategic and business combination transactions and the risks described in our most recent Admission Document. By participating in this presentation and/or accepting any copies hereof you agree to be bound by the foregoing restrictions and the other terms of this disclaimer.
Poised for Transformation in 2021 Two decades of know-how combined with robust and growing IP estate Global footprint – R&D in Berlin, headquarters in London and NYC office Pioneers in RNAi Clinical data demonstrated safety, robust gene knockdown and long duration of action Anticipate 2-3 INDs per year starting in 2023 (wholly owned and partnered programs) Significant opportunity to address disease causing targets in the liver Major Clinical Data Readouts in Wholly Owned Programs Combined with Rapid Discovery Pipeline Growth Clinically Validated Positive topline healthy volunteer data in SLN124 program for iron-loading anemia conditions On-track to deliver patient data in two wholly owned programs this year SLN360 targeting high and prevalent unmet need in cardiovascular disease due to high lipoprotein(a) SLN124 targeting high unmet need in thalassemia and myelodysplastic syndrome Rapidly Advance Clinical Programs Cash runway beyond key data milestones for both SLN360 and SLN124 clinical programs AIM and Nasdaq listed (SLN) - market cap ~£535m /~$755m* Strong Financial Position * Market Capitalization as of May 18, 2021 Platform
Market Capitalization as of May 18, 2021 Pipeline programs = company disclosed partnered and wholly owned programs discovery phase – marketed We believe the Path to Value Creation is Clear $Billion Highest phase: Commercial 31+ pipeline programs, 4 in registration/commercial, 7 in the clinic, 9+ wholly owned Highest phase: Ph2 13 pipeline programs, 8 in the clinic, 7 wholly owned Highest phase: Ph3 20 pipeline programs, 3 in the clinic, 2 wholly owned Highest phase: Ph1 6+ pipeline programs, 2 in the clinic, 3+ wholly owned Market capitalization of established RNAi companies
Executive Leadership Team with Deep Sector Experience Mark Rothera President and CEO 30+ years of experience in the biopharmaceutical industry Former President & CEO of Orchard Therapeutics and CCO of PTC Therapeutics Drove the transition of multiple emerging biotech companies from R&D stage to commercialization EVP, Head of R&D and CMO Giles Campion 30+ years of experience in the biopharmaceutical industry Former CMO and SVP R&D at Prosensa, playing a major role in their Nasdaq IPO and subsequent sale to Biomarin for $680m Most recently CMO at Albumedix and held senior R&D roles at GE Healthcare, Novartis and SmithKline Beecham prior Medical degree and doctorate from Bristol University Chief Financial Officer Craig Tooman 30+ years of experience in the biopharmaceutical industry Over a decade of experience as public company CFO Proven track record raising capital and leading M&A deals SVP, Head of Manufacturing Jorgen Wittendorff 25+ years experience in pharmaceutical development Extensive experience in complex manufacturing and regulatory compliance (FDA, EMA, and PMDA) SVP, Molecular Design Dr. Marie Wikström Lindholm 13+ years’ experience with oligonucleotide therapeutics Former Expert Scientist in Discovery Technology and Head of Targeted Delivery at Santaris Pharma / Roche Authored 60+ patent applications and peer-reviewed scientific publications Dr. Barbara Ruskin SVP, General Counsel and CPO 25+ years of global experience in life science IP and corporate law Former Partner at Ropes and Gray, associate at Fish & Neave, and SVP GC / CPO at biopharma companies Managed general legal and IP matters related to financing and regulatory, BD, licensing and patent portfolio management
siRNA Can Inhibit Expression of Disease-Associated Genes HEALTHY DISEASE nucleus cytoplasm DNA Genes encode messages for all features in the body In certain diseases the DNA is mutated or abnormally expressed mRNA is then made into proteins. Proteins are responsible for most functions in the body The information in DNA is transcribed into messenger RNA (mRNA) Abnormal DNA message is carried into resulting mRNA In some cases mutations instruct the cell to produce too much protein or the protein made does not work mRNA protein
siRNA Can Precisely Target and Silence Disease-Associated Genes Mutated DNA mRNA is degraded and gene is “silenced” Reduction in disease- causing protein Target-specific short interfering RNA (siRNA) binds to the mRNA mRNA Natural Harnesses natural cellular mechanisms present in every cell in the human body
Durable Long-lasting gene knockdown possible for > 2 months following a single injection
Precise siRNA designed to bind only to target sequence
Our Toolbox Considers all Elements of siRNA and Ligand Design siRNA molecule GalNAc Ligand (delivery tool) siRNA matched to target gene Silence has developed chemical modifications patterns that enhance stability and improve activity Silence has developed proprietary linkers, enabling the attachment of targeting ligands to the siRNA molecule GalNAc ligand delivers molecule to specific liver tissues/cells Highly targeted to liver Linker Continuous Fine-Tuning to Further Improve Performance
Platform Approach: Precision-Engineered Therapies High-quality discovery programs Improves molecular design Maximizes efficacy Minimizes off-target effects Stabilizes molecules Ensures ease of manufacturing Robust and growing IP estate GalNAc OLigonucleotide Discovery Platform
We Believe the Opportunity for our Platform is Substantial Only ~1% of genes expressed in the liver have been targeted by publicly known siRNAs Source: Human Protein Atlas, GlobalData Opportunity to identify new siRNAs targeting many of the remaining 99% (~14,000) of liver-expressed genes Existing RNAi programs have only scratched the surface of the liver target space
Our Pipeline Targets
Maximizing Output through the Silence Platform High-quality target identification using translational genomics Lower attrition rates in discovery enabled by machine learning GalNAc strategic partnerships to enhance pipeline opportunities (e.g. target selection)
Early-stage GalNAc-conjugated RNAi Programs Have a Much Greater Likelihood of Approval vs. Industry Average Phase success is defined as the movement of the program to the next phase, not an evaluation of whether endpoints were met. GalNAc-conjugated RNAi includes both GalNAc-conjugated siRNA and GalNAc-conjugated ASO GalNAc-conjugated RNAi Pharma industry average (excluding GalNAc-conjugated RNAi) Likelihood of Approval from Current Phase: GalNAc RNAi vs. others Source: Pharmapremia, Informa Pharma Custom Intelligence analysis
SLN360 for Cardiovascular Disease Due to High Lp(a)
Targeting Lp(a) with SLN360 has the potential to address major unmet needs in cardiovascular disease SLN360 Targets Lipoprotein(a) or Lp(a): an Independent Risk Factor for Cardiovascular Disease 1 Varvel et al. Arterioscler Thromb Vasc Biol. 2016;36:2239, Tsimikas et al. Atherosclerosis. 2020;300:1 2 Kamstrup et al. Circulation. 2008;117:176, Kamstrup et al. JAMA. 2009;301(22):2331
Cardiovascular Event Risk Significantly Increases with High Lp(a) Heart Attack1 2 - 3x Aortic Stenosis2 2 - 3x Heart Failure3 1.6 - 1.8x Ischemic Stroke4 1.2 - 1.6x Mortality5 (all cause/CV) 1.2 - 1.7x Increased Risk Event Substantial Risk of CV Event at Lp(a) ~90 mg/dL 780 Million Worldwide with >90 mg/dL Lp(a) 1 Kamstrup et al. Circulation. 2008;117:176, Kamstrup et al. JAMA. 2009;301(22):2331, 2 Kamstrup et al. J Am Coll Cardiol. 2014;63(5):470, 3 Kamstrup et al. JACC Heart Fail. 2016;4(1):78, 4 Langsted et al. J Am Coll Cardiol. 2019;74(1):54, 5 Langsted et al. Eur Heart J. 2019;40(33):2760, Arsenault et al. JAMA Netw Open. 2020;3(2):e200129, 6 Varvel et al Arterioscler Thromb Vasc Biol. 2016;36:2239, Tsimikas et al. Atherosclerosis. 2020;300:1, Nordestgaard et al. Eur Heart J. 2010;31:2844 Populations: USA 328.2 million, EU 513.5 million (incl. UK), Global 7,800 million
Lp(a)-lowering Drugs Present a Similar Opportunity to Cholesterol-lowering Drugs, Which Had Sales of >$30B at Peak Blockbuster Potential Similar Medically Treated Population Patients with High Total Cholesterol vs. High Lp(a) US + EU5 Markets High Lp(a)2 ≥ 50 mg/dL (no indicated treatments) High Total Cholesterol1 US ≥ 200 mg/dL EU5 ≥ 190 mg/dL Lipitor® (atorvastatin) $12.9B peak sales Crestor® (rosuvastatin) $7.0B peak sales Zocor® (simvastatin) $5.2B peak sales Sales of Cholesterol-Lowering Drugs Peaked at >$30B3,4 High Cholesterol vs High Lp(a) in Cardiovascular Disease High Cholesterol is a Modifiable Risk Factor Most patients will require Lp(a) lowering treatment: Lifestyle changes have no effect on Lp(a) levels High Lp(a) is a Genetic Risk Factor Some patients require cholesterol lowering treatment: Lifestyle changes can have a positive impact 1 Datamonitor Healthcare | Informa 2018, 2 Varvel et al Arterioscler Thromb Vasc Biol. 2016;36:2239, Tsimikas et al. Atherosclerosis 2020;300:1, Nordestgaard et al. Eur Heart J. 2010;31:2844, 3 Biomedtracker, Internal Analysis; 4 Kidd, J., Nat Rev Drug Discov. 2006;5(10):813
SLN360 demonstrated ideal profile in NHP model Efficacy: Robust Lp(a) knockdown observed after first dose (>90%) Durability: Sustained reduction of Lp(a) serum levels (>90%) for duration of study Safety: <1% exposure outside liver with no detected off target effects Serum Lp(a) reduction SLN360 Demonstrated Sustained and Deep Lp(a) Knockdown in Non-Human Primate Model
SLN360 Phase 1 Program Overview PD: Pharmacodynamics; PK: Pharmacokinetics
Now enrolling – Data from single- ascending dose portion expected in H2 2021
SLN124 for Iron-Loading Anemia Conditions
SLN124: Addressing a Major Unmet Need in Thalassemia and Myelodysplastic Syndrome (MDS) Group of rare malignant blood disorders that impact older patients Low quality of life and poor response to current therapies Burdens include severe anemia, transfusion dependence, toxic iron overload Progression to acute myeloid leukemia (30% of MDS patients) A rare genetic blood disorder that affects children and adults The majority are dependent on regular blood transfusions (TDT), while others are transfused less frequently (NTDT) Severe limitations and low quality of life with current treatments Opportunity to improve quality of life by reducing the frequency of blood transfusions Burdens include severe anemia, transfusion dependence, toxic iron overload MYELODYSPLASTIC SYNDROME (MDS) Prevalence1: ~160,000 pts (US+EU5) Onset: Later in life (60+) Orphan Drug Designation THALASSEMIA Prevalence2: ~35,000 pts (US+EU5) TDT and NTDT Onset: TDT: early childhood NTDT: teens or later Orphan Drug Designation Rare Pediatric Disease Designation 1 Internal analysis; 2 Kattamis et.al, Eur J Haematol. 2020;105:692; TDT: transfusion-dependent thalassemia; NTDT: non- transfusion-dependent thalassemia
SLN124 Aims to Reduce Anemia and the Need for Blood Transfusions and Iron Chelation Therapies SLN124 is Designed to Restore Endogenous Hepcidin and Normalize Iron Levels Study performed in a rodent model for beta thalassemia (Hbbth3/+); *** p≤0.001
SLN124 Phase 1 Healthy Volunteer Study Design PD: Pharmacodynamics; PK: Pharmacokinetics
Strong Positive Results from SLN124 Healthy Volunteer Study First clinical data from mRNAi GOLD™ platform Demonstrates proof of mechanism for SLN124 All 3 dose levels of SLN124 were safe and generally well-tolerated No serious or severe treatment emergent adverse events (TEAEs) or TEAEs leading to withdrawal Majority of TEAEs were mild, including transient injection site reactions which resolved without intervention SLN124 increased average hepcidin up to ~4-fold after a single dose with effect sustained for at least 2 months SLN124 reduced serum iron by ~50% after a single dose with effect sustained for at least 2 months
SLN124 Increased Average Hepcidin up to ~4-Fold After a Single Dose with Effect Sustained for ≥ 2 Months n=6 healthy volunteers in each treatment group
SLN124 Reduced Serum Iron by ~50% After a Single Dose with Effect Sustained for ≥ 2 Months n=6 healthy volunteers in each treatment group
SLN124 Phase 1 Study in Adult Thalassemia and MDS MDS: myelodysplastic syndrome; PD: Pharmacodynamics; PK: Pharmacokinetics; VL/LR-MDS: very low- and low-risk MDS Now enrolling - Data expected in H2 2021
Note: all programs are at potential risk of delay due to COVID-19 = data milestone Major Potential Value Creating Milestones in 2021 = positive data reported
Partnership Programs Further Expand Pipeline and Provide Up to $6 Billion in Potential Milestones Plus Royalties Signed major deal to discover, develop and commercialize siRNA therapeutics for cardiovascular, renal, metabolic and respiratory diseases in March 2020 Upfront cash payment of $60 million and an equity investment of $20 million1 Up to $4 billion in potential milestones plus tiered royalties for a total of 10 targets AZN to cover preclinical, CMC, clinical development and commercialization costs Commenced technology evaluation to explore the potential of using our platform to generate siRNA molecules against a novel, undisclosed target in January 2020 1 Of the $60m, $20m was paid in May 2020 and a further $40m is unconditionally payable in H1 2021.
Tap into the huge opportunity to silence genes outside of the liver FUTURE PRESENT Developing a New Extra-Hepatic siRNA Delivery Platform
Financial Highlights *includes £37.4m at 12/31/20, plus £30.8m capital raise in Feb’21 and £29.3m due from AstraZeneca in H1’21
Poised for Transformation in 2021 Two decades of know-how combined with robust and growing IP estate Global footprint – R&D in Berlin, headquarters in London and NYC office Pioneers in RNAi Clinical data demonstrated safety, robust gene knockdown and long duration of action Anticipate 2-3 INDs per year starting in 2023 (wholly owned and partnered programs) Significant opportunity to address disease causing targets in the liver Major Clinical Data Readouts in Wholly Owned Programs Combined with Rapid Discovery Pipeline Growth Clinically Validated Positive topline healthy volunteer data in SLN124 program for iron-loading anemia conditions On-track to deliver patient data in two wholly owned programs this year SLN360 targeting high and prevalent unmet need in cardiovascular disease due to high lipoprotein(a) SLN124 targeting high unmet need in thalassemia and myelodysplastic syndrome Rapidly Advance Clinical Programs Cash runway beyond key data milestones for both SLN360 and SLN124 clinical programs AIM and Nasdaq listed (SLN) - market cap ~£535m /~$755m* Strong Financial Position * Market Capitalization as of May 18, 2021 Platform