Zerlasiran

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 second quarter ended June 30, 2024 and reviewed recent business highlights. “The first half of this year has been marked by strong execution across Silence, including outstanding clinical results in both our wholly owned clinical programs and advancing our first partnered program into the clinic under our AstraZeneca collaboration,” said Craig Tooman, President and Chief Executive Officer at Silence. “Silence’s siRNA technology is continuing to demonstrate itself in the clinic and we expect that positive momentum to continue into the second half of this year and beyond.” “With the $120 million equity raise and milestones from our collaborations, we are well positioned to execute on key clinical objectives for both our zerlasiran and divesiran programs,” said Rhonda Hellums, Chief Financial Officer at Silence. “We will continue to evaluate partnering opportunities for our proprietary mRNAi GOLD™ platform and zerlasiran program with the ultimate goal of delivering maximum value to Silence shareholders and patients.” Second Quarter 2024 & Recent Business Highlights Zerlasiran for cardiovascular disease Announced positive topline 48-week data from the ALPACAR-360 Phase 2 study of zerlasiran in patients with elevated lipoprotein(a) (Lp(a)). Zerlasiran produced highly significant and sustained reductions in Lp(a) to week 48 (end of treatment period) and was well tolerated. Data support advancing zerlasiran into Phase 3. Divesiran for hematological diseases Announced positive results from the ongoing SANRECO Phase 1 study of divesiran in polycythemia vera (PV) patients. Divesiran eliminated the need for phlebotomy in all well-controlled patients following infrequent dosing and was well tolerated. Data support advancing divesiran into Phase 2. Collaborations Achieved a $2.0 million research milestone payment under our collaboration with Hansoh Pharmaceutical Group Company Limited (Hansoh). Organizational updates Promoted Rhonda Hellums, Silence’s Chief Financial Officer, and Steven Romano, MD, Silence’s Chief R&D Officer, to Executive Vice President. Hired Gianine Esposito as Chief Human Resources Officer (CHRO). Gianine brings 25 years of Human Resources experience with over 15 years of pharmaceutical experience and joins Silence from Shionogi Inc. where she was the SVP and CHRO. In her time at Shionogi, Gianine assisted in building out its US-based clinical and commercial organizations through different stages of growth. Hired Marianna Anesti as Vice President, Head of Business Development. Marianna brings 18 years of diverse Biotech & Pharmaceutical experience and joins Silence from Siga Technologies where she was the VP, Business Development & Corporate Strategy. In her time at Siga, Marianna built a pipeline of M&A opportunities, strategic partnerships, and potential in-licensing deals. Prior to Siga, Marianna was Director, R&D Strategy & Consulting at Pfizer where she partnered with Senior R&D leaders across the business to help shape new BD strategies. Financial Highlights for the Period Ended June 30,2024 Cash Position: Cash, cash equivalents and U.S. Treasury Bills of £149.6 million ($189.2 million) as of June 30, 2024, compared with £50.2 million ($63.4 million) as of June 30, 2023. Collaboration Revenue: Collaboration revenue for the three and six months ended June 30, 2024 was £0.6 million (June 30,2023: £9.0 million) and £12.9 million (June 30, 2023: £20.2 million), respectively. Revenue from the current year period primarily related to our ongoing AstraZeneca and Hansoh collaborations and from our Mallinckrodt collaboration we completed in March 2024. R&D Expenses: Research and development (R&D) expenses for the three and six months ended June 30, 2024 was £11.0 million (June 30,2023: £12.6 million) and £20.2 million (June 30, 2023: £25.2 million), respectively. The decrease compared to the prior year period primarily related to the timing of clinical studies and manufacturing activities for our divesiran clinical program. G&A Expenses: General and administrative (G&A) expenses for the three and six months ended June 30, 2024 was £5.3 million (June 30,2023: £5.1 million) and £10.5 million (June 30, 2023: £11.6 million), respectively. The decrease from the prior year six-month period was mainly due to decreased payroll costs and equity-based compensation. Net Loss: Net loss for the three and six months ended June 30, 2024 was £15.6 million, or 11.1 pence basic and diluted net loss per share, (June 30,2023: £10.4 million or 9.6 pence) and £17.4 million, or 12.8 pence basic and diluted net loss per share (June 30, 2023: £20.6 million or 19.0 pence), respectively. Total ADSs outstanding were approximately 46,797,823, as of June 30, 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 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 Six months ended Six months ended June 30, 2024 June 30, 2023 June 30, 2024 June 30, 2023 £000s (except per share information) £000s £000s £000s £000s Revenue 598 9,104 13,004 20,478 Cost of sales (2,638 ) (2,831 ) (4,851 ) (7,365 ) Gross profit (2,040 ) 6,273 8,153 13,113 Research and development costs (10,995 ) (12,615 ) (20,174 ) (25,154 ) General and administrative expenses (5,288 ) (5,115 ) (10,458 ) (11,565 ) Operating loss (18,323 ) (11,457 ) (22,479 ) (23,606 ) Finance and other expenses (183 ) (893 ) (25 ) (1,753 ) Finance and other income 1,065 340 1,698 676 Loss for the period before taxation (17,441 ) (12,010 ) (20,806 ) (24,683 ) Taxation 1,879 1,609 3,368 4,078 Loss for the period after taxation (15,562 ) (10,401 ) (17,438 ) (20,605 ) Loss per ordinary share (basic and diluted) (11.1) pence (9.6) pence (12.8) pence (19.0) pence Condensed consolidated balance sheet (unaudited) June 30, 2024 December 31, 2023 £000s £000s Non-current assets Property, plant and equipment 1,686 1,813 Goodwill 7,662 7,840 Other intangible assets 267 284 Other long term assets 2,361 2,580 Financial assets at amortized cost 284 284 12,260 12,801 Current assets Cash and cash equivalents 109,482 54,031 Financial assets at amortized cost 40,112 - R&D tax credit receivable 12,852 17,627 Other current assets 12,244 9,135 Trade receivables 1,686 228 176,376 81,021 Non-current liabilities Contract liabilities (58,187 ) (58,910 ) Lease liability - (93 ) (58,187 ) (59,003 ) Current liabilities Contract liabilities (2,766 ) (5,161 ) Trade and other payables (14,992 ) (12,429 ) Lease liability (184 ) (179 ) (17,942 ) (17,769 ) Net assets 112,507 17,050 Capital and reserves attributable to the owners of the parent Share capital 7,019 5,942 Capital reserves 423,831 313,769 Translation reserve 1,807 1,951 Accumulated losses (320,150 ) (304,612 ) Total shareholders' equity 112,507 17,050

Divesiran eliminated the need for phlebotomy in all well-controlled patients following infrequent dosing and was well tolerated Data support advancing divesiran into Phase 2 LONDON, UK I June 27, 2024 I Silence Therapeutics plc (“Silence” or the “Company”), (Nasdaq: SLN), an experienced and innovative biotechnology company committed to transforming people’s lives by silencing diseases through precision engineered medicines, today announced positive results from the ongoing SANRECO Phase 1 repeat dose study of divesiran (SLN124), a siRNA (short interfering RNA) targeting TMPRSS6 , in patients with polycythemia vera (PV). “With today’s very exciting PV data, Silence is continuing to emerge as a true platform company. Both of our lead proprietary programs are now generating excellent clinical results,” said Craig Tooman, President and CEO at Silence. “Divesiran is poised to be the first siRNA for PV, and we look forward to advancing development with a phase 2 start planned by year-end.” The 34-week, open-label Phase 1 study is evaluating divesiran (3 mg/kg, 6 mg/kg and 9 mg/kg) administered subcutaneously every 6 weeks for four doses, with a 16-week follow-up period following the date of the last administered dose in up to 24 PV patients. Key inclusion criteria include a PV diagnosis and a history of requiring at least three phlebotomies in the last six months or five in the last year prior to screening. Patients are allowed to be on stable doses of cytoreductive agents. Given the exploratory nature of this Phase 1 study, both well-controlled patients – defined as those with hematocrit (HCT) levels at 45% or less – as well as those with HCT levels greater than 45% at baseline on current standard of care treatment were enrolled. The data being presented today are based on a data cut-off date of March 29, 2024, and include analysis of 16 patients over a time range of approximately 4 to 34 weeks of study involvement. Of the 16 patients, 8 patients are considered well-controlled and 8 patients have HCT levels over 45% at baseline. To date, divesiran has been observed to be well tolerated with no major safety issues. None of the 8 patients entering the trial with well-controlled HCT levels required a phlebotomy during the divesiran treatment period, which was defined in the study as the period up to 6 weeks after the last dose. All patients in the well-controlled group maintained adequate control of HCT levels as per treatment guidelines. Of the 8 patients entering the trial with HCT levels above 45%, 2 patients each required one phlebotomy. The baseline HCTs of these 2 patients were 56% and 53%. None of the 6 other patients in this group required a phlebotomy. Notably, none of the 13 patients entering the trial with HCT levels of 50% or below – 8 well-controlled patients and 5 patients with HCT levels of 46-50% – have required a phlebotomy to date. In all dose groups, there was a sustained reduction in hematocrit during the treatment period and favorable effects on indices of iron metabolism. Hepcidin levels increased and were sustained within physiological levels in all dose groups, demonstrating target engagement. “Divesiran treatment in PV patients results in sustained increases in hepcidin, reflecting crucial target engagement,” said Professor Tomas Ganz, MD, PhD, Distinguished Professor of Medicine and Pathology Department of Medicine, UCLA. “Divesiran exerts a beneficial effect on hematological parameters and significantly reduces phlebotomies. These exciting data suggest that divesiran has the potential to produce clinically meaningful outcomes in this patient population.” “Based on these early results, divesiran appears to meaningfully impact key hematological parameters in this rare myeloproliferative neoplasm,” said Steven Romano, MD, Silence’s Head of Research and Development. “We are particularly encouraged by the safety profile and the potential for divesiran to be administered infrequently to PV patients requiring pharmacological intervention to manage their disease.” As of today, Silence has enrolled 21 patients in the SANRECO study and the Company anticipates closing enrollment at the end of this month. Full results are expected to be presented at a scientific meeting later this year. Divesiran has received FDA Fast Track designation and FDA Orphan Drug Designation for PV. Conference Call and Webcast Details Management will host a conference call and webcast today, June 27, 2024, at 8:30 am ET to discuss results from the ongoing SANRECO phase 1 study. To access the call, please register online at https://register.vevent.com/register/BI33ea9b075fa841ea9597cc915562e79c . Participants are requested to register at a minimum of 15 minutes before the start of the call. A replay of the call will be available two hours after the call and archived on the same web page for six months. A live webcast will also be available on the Investors section of the Company’s website at www.silence-therapeutics.com . An archived webcast will be available on the Company’s website approximately two hours after the event. About PV PV is a rare, myeloproliferative neoplasm – a type of blood cancer – characterized by the excessive production of red blood cells, often resulting in elevated hematocrit levels. Elevated hematocrit above 45-percent is associated with a four-times higher rate of death from cardiovascular or thrombotic events. PV is associated with a range of burdensome symptoms including fatigue, cognitive disturbance and pruritis and additionally, longer term can transform to myelofibrosis and Acute Myeloid Leukemia. The aim of treatment is to maintain hematocrit less than 45%, a level that is associated with a reduced incidence of thrombosis and CV-associated death. The current standard of care includes repeated phlebotomies to reduce hematocrit and/or cytoreductive agents to reduce red blood cell production. There are currently no approved therapies that specifically target red blood cells and hematocrit. About Divesiran Divesiran is Silence’s wholly owned siRNA developed from its proprietary mRNAi GOLD™ platform that “silences” TMPRSS6 expressed almost exclusively in the liver. TMPRSS6 is a negative regulator of hepcidin, the body’s master regulator of iron metabolism including its absorption, distribution, and storage. By silencing TMPRSS6 in PV patients, divesiran aims to increase hepcidin production and release by liver hepatocytes, leading to the restriction of iron to the bone marrow and, thus, reducing the excessive production of red blood cells, a process dependent on availability of iron. 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 high levels of lipoprotein(a) and divesiran designed to address 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 https://www.silence-therapeutics.com/ . SOURCE: Silence Therapeutics