Silence Therapeutics Announces Positive Results from Ongoing SANRECO Phase 1 Study of Divesiran in Polycythemia Vera Patients Divesiran eliminated the need for phlebotomy in all well-controlled patients following infrequ

Silence Therapeutics Announces Positive Results from Ongoing SANRECO Phase 1 Study of Divesiran in

Polycythemia Vera Patients

Divesiran eliminated the need for phlebotomy in all well-controlled patients following infrequent dosing and

Data support advancing divesiran into Phase 2

Company to host conference call today at 8:30am Eastern Time

LONDON, 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.

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.

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/.

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 activities and timelines for divesiran including the expected timing for reporting further data from the SANRECO trial; the timing and future occurrence of other clinical and clinical activities

including proposed clinical trial enrollment and the Company s plans and timing to advance divesiran into Phase 2; expected clinical benefits of divesiran and the potential to produce clinically meaningful outcomes in PV patients; and the

Company s plans to submit additional data from the SANRECO trial for publication at a future conference. 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: preliminary or topline results are based on a preliminary analysis of key efficacy and

safety data; 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.