Zerlasiran

LONDON--( BUSINESS WIRE )--Silence Therapeutics plc, Nasdaq: SLN (“Silence” or “the Company”), a global clinical stage biotechnology company committed to transforming people’s lives by silencing diseases through precision engineered medicines, today reported its financial results for the third quarter ended September 30, 2024 and reviewed recent business highlights. “The Silence team is focused on continued execution across the business,” said Craig Tooman, President and Chief Executive Officer at Silence. “We look forward to presenting additional data from our wholly owned clinical programs at upcoming medical meetings and progressing our pipeline to bring innovative gene silencing medicines to patients around the world.” “We ended the quarter with more than $172 million and are well positioned to advance our lead clinical programs,” said Rhonda Hellums, Chief Financial Officer at Silence. “We are continuing to be prudent with cash and prioritizing investment in key areas where we believe we can deliver the highest value to our shareholders and patients.” Third Quarter 2024 & Recent Business Highlights R&D Highlights Results from the ALPACAR-360 Phase 2 study of zerlasiran in atherosclerotic cardiovascular disease (ASCVD) patients with high Lp(a) will be presented during the Late-Breaking Science Session of the American Heart Association (AHA) Annual Scientific Sessions in Chicago, Illinois, on Monday, November 18, 2024. Results from the Phase 1 portion of the SANRECO Phase 1/2 study of divesiran in polycythemia vera (PV) patients have been selected for oral presentation at the American Society of Hematology (ASH) Annual Meeting taking place December 7-10, 2024, in San Diego, California. The ASH abstract and viewing details are listed below. Presentation Title: Initial Results from a Phase 1/2 Study Evaluating Divesiran, a Novel Galnac Conjugated siRNA, in Patients with Polycythemia Vera (SANRECO) Abstract Number: 656 Presentation Date & Time: Sunday, Dec. 5, 4:45 p.m. PST Location: Manchester Grand Hyatt San Diego, Grand Hall D Presenter: Dr. Marina Kremyanskaya Additional Business Updates On June 30, 2024, the market value of our ordinary shares held by non-affiliates exceeded $700.0 million. Starting January 1, 2025, we will be classified as a “large accelerated filer” by U.S. Securities and Exchange Commission (SEC) and will follow periodic disclosure and reporting requirements applicable to U.S. domestic issuers. Financial Highlights for the Period Ended September 30,2024 Cash Position: Cash, cash equivalents and U.S. Treasury Bills of £129.0 million ($172.7 million) as of September 30, 2024, compared with £54.0 million ($68.8 million) as of December 31, 2023. Collaboration Revenue: Collaboration revenue for the three and nine months ended September 30, 2024, was £1.1 million (September 30, 2023: £2.7 million) and £14.0 million (September 30, 2023: £22.8 million), respectively. Revenue from the current year period primarily related to our AstraZeneca collaboration. R&D Expenses: Research and development (R&D) expenses for the three and nine months ended September 30, 2024, was £15.3 million (September 30, 2023: £8.9 million) and £35.5 million (September 30, 2023: £34.1 million), respectively. The increase compared to the prior year period primarily related to the timing of clinical studies and manufacturing activities. G&A Expenses: General and administrative (G&A) expenses for the three and nine months ended September 30, 2024, was £5.6 million (September 30, 2023: £5.0 million) and £16.1 million (September 30, 2023: £16.5 million), respectively. The £0.6 million increase compared to the prior three-month period was mainly due to increased professional services costs. The £0.5 million decrease from the prior nine-month period was mainly due to decreased payroll costs and equity-based compensation. Net Loss: Net loss for the three and nine months ended September 30, 2024, was £27.0 million, or 19.1 pence basic and diluted net loss per share, (September 30, 2023: £8.2 million or 7.4 pence) and £44.4 million, or 32.3 pence basic and diluted net loss per share (September 30, 2023: £28.9 million or 26.4 pence), respectively. Total ADSs outstanding were approximately 47,214,829, as of September 30, 2024. About Silence Therapeutics Silence Therapeutics is a global clinical stage biotechnology company committed to transforming people’s lives by silencing diseases through precision engineered medicines created with proprietary siRNA (short interfering RNA) technology. Silence leverages its mRNAi GOLD™ platform to create innovative siRNAs designed to precisely target and silence disease associated genes in the liver, which represents a substantial opportunity. Silence focuses on areas of high unmet medical need with programs advancing in cardiovascular disease, hematology and rare diseases. Silence also maintains research and development collaborations with AstraZeneca and Hansoh Pharma, 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, potential partnerships or collaborations under new and existing collaborations and the initiation, advancement or completion of the Company’s clinical trials. These forward-looking statements are not historical facts but rather are based on the Company's current assumptions, beliefs, expectations, estimates and projections about its industry. Words such as “anticipate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” 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 Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission on March 13, 2024. 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. Condensed consolidated income statement (unaudited) Three months ended Three months ended Nine months ended Nine months ended September 30, 2024 September 30, 2023 September 30, 2024 September 30, 2023 £000s (except per share information) £000s £000s £000s £000s Revenue 1,142 2,798 14,146 23,276 Cost of sales (2,774 ) (1,607 ) (7,625 ) (8,972 ) Gross profit (1,632 ) 1,191 6,521 14,304 Research and development costs (15,305 ) (8,934 ) (35,479 ) (34,088 ) General and administrative expenses (5,600 ) (4,956 ) (16,058 ) (16,521 ) Operating loss (22,537 ) (12,699 ) (45,016 ) (36,305 ) Finance and other expenses (8,602 ) (8 ) (8,627 ) (97 ) Finance and other income 981 2,046 2,679 1,058 Loss for the period before taxation (30,158 ) (10,661 ) (50,964 ) (35,344 ) Taxation 3,146 2,411 6,514 6,489 Loss for the period after taxation (27,012 ) (8,250 ) (44,450 ) (28,855 ) Loss per ordinary share (basic and diluted) (19.1) pence (7.4) pence (32.3) pence (26.4) pence Condensed consolidated balance sheet (unaudited) September 30, 2024 December 31, 2023 £000s £000s Non-current assets Property, plant and equipment 1,647 1,813 Goodwill 7,538 7,840 Other intangible assets 258 284 Other long term assets 2,144 2,580 Financial assets at amortized cost 284 284 11,871 12,801 Current assets Cash and cash equivalents 61,953 54,031 Financial assets at amortized cost 67,037 - R&D tax credit receivable 16,271 17,627 Other current assets 11,963 9,135 Trade receivables 288 228 157,512 81,021 Non-current liabilities Contract liabilities (57,955 ) (58,910 ) Lease liability - (93 ) (57,955 ) (59,003 ) Current liabilities Contract liabilities (2,503 ) (5,161 ) Trade and other payables (14,271 ) (12,429 ) Lease liability (139 ) (179 ) (16,913 ) (17,769 ) Net assets 94,515 17,050 Capital and reserves attributable to the owners of the parent Share capital 7,082 5,942 Capital reserves 432,367 313,769 Translation reserve 1,714 1,951 Accumulated losses (346,648 ) (304,612 ) Total shareholders' equity 94,515 17,050

While drugs are available that reduce levels of a lipoprotein (a), a protein associated with cardiovascular disease, no currently available therapies target this protein directly. Several companies are in various stages of clinical development with drugs that could tackle this protein, and AstraZeneca is paying $100 million to license a preclinical drug gives it a contender in the chase. AstraZeneca’s new cardiovascular asset comes from Hong Kong-based CSPC Pharmaceutical Group. Beyond the upfront payment, the pharmaceutical giant could pay out up to $1.92 billion if the drug achieves development and commercialization milestones, according to deal terms announced Monday. CSPC will also receive royalties from sales of a commercialized product. The CSPC drug, named YS2302018, is in development for dyslipidemia, which is abnormally high levels of cholesterol in the blood. One biological indicator of this condition is high levels of lipoprotein (a), or Lp(a), a type of protein that transports cholesterol through the blood. High Lp(a) levels increase the likelihood of cholesterol buildup in the walls of blood vessels and they are a known risk factor for cardiovascular disease, including coronary artery disease and stroke. presented by Sponsored Post The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani - mHUB Lp(a) levels can already be reduced by therapies addressing PCSK9, a liver protein that regulates cholesterol. Studies of the approved PCSK9 inhibitors Repatha from Amgen, and Praluent from Regeneron Pharmaceuticals, showed reductions in Lp(a) levels. Novartis’s approved small interfering RNA (siRNA) therapy Leqvio takes a different approach by silencing the gene that produces PCSK9. That drug also reduces Lp(a). But these therapies do not address Lp(a) directly and they are all administered as injections. AstraZeneca describes CSPC’s YS2302018 as an oral Lp(a) disruptor. Compared to the available injectable therapies addressing PCSK9, the CSPC drug offers the convenience of once-daily oral dosing. That formulation gives AstraZeneca a way to catch up to and potentially compete with Eli Lilly in the treatment of dyslipidemia. Lilly’s muvalaplin is an oral small molecule disrupter of Lp(a) currently in Phase 2 testing. Lilly is also part of a group of companies developing siRNA therapies that reduce Lp(a) levels. The Indianapolis-based pharma giant’s lepodisiran earlier this year began a Phase 3 clinical trial in atherosclerotic cardiovascular disease. Amgen’s olpasiran is in Phase 3 testing in the same indication while Silence Therapeutics’ is preparing to enter pivotal testing with its Lp(a)-reducing drug candidate, zerlasiran. Pelacarsen, an Ionis Pharmaceuticals antisense oligonucleotide intended to reduce Lp(a) production, is in Phase 3 testing under a partnership with Novartis. AstraZeneca’s cardiovascular, renal, and metabolism drug lineup is anchored by the blockbuster products Farxiga (approved for type 2 diabetes, heart failure, and chronic kidney disease) and Brilinta (approved for coronary acute syndromes). The company says the CSPC drug has potential uses in a range of cardiovascular disease indications as a standalone treatment or in combination with other therapies. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum One potential combination could pair the CSPC drug with AstraZeneca’s own PCSK9 inhibitor, AZD0780. In May, the pharma giant reported Phase 1 results showing once-daily oral doses of AZD0780 on top of statin therapy led to a statistically significant 52% reduction in levels of LDL cholesterol. The drug was well tolerated and no serious adverse events were reported. AstraZeneca is currently testing the pill in a Phase 2 clinical trial with a targeted enrollment of 428 participants. “Given the scale of unmet need, with cardiovascular disease being a leading cause of death globally, advancing novel therapies that can be used alone or in combination to effectively address known risk factors and advance patient care is particularly important and a key part of our strategy,” Sharon Barr, AstraZeneca executive vice president and head of biopharmaceuticals R&D, said in a prepared statement.