Zerlasiran

Study demonstrated highly significant and sustained reductions in Lp(a) to week 48 Data support advancing zerlasiran into phase 3 with 300 mg dose LONDON--(BUSINESS WIRE)-- Silence Therapeutics plc, Nasdaq: SLN (“Silence” or the “Company”), an experienced and innovative biotechnology company committed to transforming people’s lives by silencing diseases through precision engineered medicines, today announced positive topline 48-week data from the ALPACAR-360 phase 2 study of zerlasiran (SLN360) in 178 subjects with baseline lipoprotein(a), or Lp(a), levels at or over 125 nmol/L at high risk of atherosclerotic cardiovascular disease (ASCVD) events. Zerlasiran is a siRNA (short interfering RNA) designed to lower the body’s production of Lp(a), a key genetic risk factor for cardiovascular disease affecting up to 20% of the world’s population. In the double-blind placebo-controlled treatment period, zerlasiran was administered at 300 mg subcutaneously every 16 or 24 weeks and 450 mg every 24 weeks to patients with a median baseline Lp(a) of approximately 215 nmol/L. These data demonstrated a highly significant reduction from baseline in Lp(a) compared to placebo to 48 weeks (end of treatment and dosing period). Median maximum Lp(a) reduction of approximately 90% or greater was observed for both doses during the treatment period. Zerlasiran was well tolerated with no serious safety concerns. As previously announced, the study met its primary endpoint with a highly significant reduction from baseline in Lp(a) compared to placebo to 36 weeks. The study is ongoing, and patients will be followed through to week 60 (end of study). “We are encouraged by the strength of the phase 2 data and emerging competitive pro zerlasiran, which support an infrequent dosing regimen of at least quarterly with the 300 mg dose,” said Steven Romano, MD, Head of Research and Development at Silence. “We look forward to advancing zerlasiran to phase 3 as a potential treatment for this major unmet need in cardiovascular disease.” The Company plans to provide full results at a future scientific meeting or publication following completion of the study. 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 zerlasiran designed to address the high and prevalent unmet medical need in reducing cardiovascular risk in people born with elevated levels of lipoprotein(a) and divesiran designed to address rare hematological diseases, including polycythemia vera. Silence also maintains ongoing research and development collaborations with AstraZeneca and Hansoh Pharma, among others. For more information, please visit . Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements in this press release other than statements of historical facts are “forward-looking statements. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding: the Company’s clinical development plans of zerlasiran; the assessment of the data from the ALPACAR-360 study of zerlasiran; the efficacy and safety of zerlasiran; the estimated world’s [adult population] who have Lp(a), a key genetic risk factor for cardiovascular disease; the Company’s plans to advance zerlasiran into a Phase 3 registrational program in patients with baseline Lp(a); the potential clinical benefits of zerlasiran; and the Company’s plans to submit additional data from the ALPACAR-360 study for publication at a conference or in a peer-reviewed journal. These forward-looking statements are based on the Company’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause the Company’s clinical development programs, future results or performance to differ materially from those expressed or implied by the forward-looking statements. Many factors may cause differences between current expectations and actual results, including: the potential that success in preclinical testing and earlier clinical trials does not ensure that later clinical trials will generate the same results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidate; the impacts of macroeconomic conditions, including the conflict in Ukraine and the conflict between Israel and Hamas, heightened inflation and uncertain credit and financial markets, on the Company’s business, clinical trials and financial position; unexpected safety or efficacy data observed during preclinical studies or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; the Company’s ability to realize the benefits of its collaborations and license agreements; changes in expected or existing competition; changes in the regulatory environment; the uncertainties and timing of the regulatory approval process; and unexpected litigation or other disputes. Other factors that may cause the Company’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are identified in the section titled "Risk Factors" in the Company’s Annual Report on Form 20-F for the year ended December 31, 2023 filed with the U.S. Securities and Exchange Commission (the “SEC”) on March 13, 2024 as well as its other documents subsequently filed with or furnished to the SEC. The Company expressly disclaims any obligation to update any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise, except as otherwise required by law.

LONDON--(BUSINESS WIRE)--Silence Therapeutics plc, Nasdaq: SLN (“Silence” or “the Company”), an experienced and innovative biotechnology company committed to transforming people’s lives by silencing diseases through precision engineered medicines, today reported its financial results for the first quarter ended March 31, 2024 and reviewed recent business highlights. “Silence’s first quarter performance reflects another period of solid execution with the continued advancement of both our wholly owned and partnered pipelines in the clinic,” said Craig Tooman, President and Chief Executive Officer at Silence. “Silence is well positioned heading into key data readouts in our zerlasiran and divesiran programs, and we remain excited about the potential for our mRNAi GOLD™ platform to address a wide range of genetic diseases.” First Quarter 2024 & Recent Business Highlights Zerlasiran for cardiovascular disease In March 2024, we announced positive topline 36-week data from the ongoing 60-week ALPACAR-360 phase 2 study of zerlasiran in patients with a median baseline Lp(a) of approximately 215 nmol/L. Study met primary endpoint and demonstrated highly significant reductions in Lp(a) to week 36 No new safety concerns were identified during this treatment period 48-week data (end of treatment period) expected in the second quarter of 2024 In April 2024, additional phase 1 data from the APOLLO single and multiple dose study of zerlasiran in subjects with baseline Lp(a) levels at or over 150 nmol/L were published in the Journal of the American Medical Association (JAMA), linked here. Divesiran for hematological diseases Advanced the SANRECO phase 1 study of divesiran in polycythemia vera (PV) patients. Emerging data from the open-label study continue to look promising On-track to report phase 1 data by the end of June 2024 Collaborations In February 2024, we achieved a $10 million milestone following the initiation of a phase 1 trial of the first product candidate under our AstraZeneca collaboration. First Quarter 2024 Financial Highlights Cash Position: Cash, cash equivalents and U.S. Treasury Bills of £152.8 million ($192.8 million) as of March 31, 2024, compared with £62.9 million ($77.8 million) as of March 31, 2023. Collaboration Revenue: Collaboration revenue was £12.4 million, an increase of £1.0 million compared with the first quarter of 2023. The increase was primarily driven by a £9.2 million milestone received from our AstraZeneca collaboration. This was offset by a decrease in revenue from our Mallinckrodt collaboration of £8.5 million as we reacquired exclusive worldwide rights to two preclinical siRNA assets under our modified Mallinckrodt collaboration in March 2023. R&D Expenses: Research and development (R&D) expenses were £9.2 million, a decrease of £3.4 million compared to the first quarter of 2023. The was primarily due to a decrease in contracted R&D expenses of £2.5 million resulting from the completion of the divesiran phase 1 study in thalassemia patients and timing of manufacturing activities for divesiran compared to the same period in 2023. G&A Expenses: General and administrative (G&A) expenses were £5.2 million, a decrease of £1.3 million compared to the first quarter of 2023. The decrease is primarily due to decreased payroll costs and equity-based compensation. Net Loss: Net loss was £1.9 million, or 1.4 pence basic and diluted net loss per share, compared to a net loss of £10.2 million, or 9.5 pence basic and diluted net loss per share for the first quarter of 2023. Total ADSs outstanding were approximately 46,575,984, as of March 31, 2024. 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 zerlasiran (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 divesiran (SLN124) designed to address rare hematological diseases including polycythemia vera. Silence also maintains ongoing research and development collaborations with AstraZeneca and Hansoh Pharma, among others. For more information, please visit . 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 cash runway and forecast operating cash flow, the Company’s clinical and commercial prospects, regulatory approvals of the Company’s product candidates, potential partnerships or collaborations or payments under new and existing collaborations, the initiation or completion of the Company’s clinical trials and the anticipated timing or outcomes 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 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 March 31, 2024 March 31, 2023 £000s (except per share information) '£000s '£000s Revenue 12,406 11,374 Cost of sales (2,213 ) (4,534 ) Gross profit 10,193 6,840 Research and development costs (9,179 ) (12,539 ) General and administrative expenses (5,170 ) (6,450 ) Operating loss (4,156 ) (12,149 ) Finance and other expenses (13 ) (860 ) Finance and other income 804 336 Loss for the period before taxation (3,365 ) (12,673 ) Taxation 1,489 2,469 Loss for the period after taxation (1,876 ) (10,204 ) Loss per ordinary equity share (basic and diluted) (1.4) pence (9.5) pence Condensed consolidated balance sheet (unaudited) March 31, 2024 December 31, 2023 £000s £000s Non-current assets Property, plant and equipment 1,791 1,813 Goodwill 7,731 7,840 Other intangible assets 275 284 Other long term assets 2,565 2,580 Financial assets at amortized cost 284 284 12,646 12,801 Current assets Cash and cash equivalents 113,056 54,031 Financial assets at amortized cost 39,698 - R&D tax credit receivable 10,690 17,627 Other current assets 10,149 9,135 Trade receivables 8,140 228 181,733 81,021 Non-current liabilities Contract liabilities (56,208 ) (58,910 ) Lease liability (93 ) (93 ) (56,301 ) (59,003 ) Current liabilities Contract liabilities (3,505 ) (5,161 ) Trade and other payables (10,487 ) (12,429 ) Lease liability (184 ) (179 ) (14,176 ) (17,769 ) Net assets 123,902 17,050 Capital and reserves attributable to the owners of the parent Share capital 6,986 5,942 Capital reserves 420,759 313,769 Translation reserve 1,861 1,951 Accumulated losses (305,704 ) (304,612 ) Total shareholders equity 123,902 17,050