Silence Therapeutics plc

Previous wording

Divesiran (SLN124) is our potential first-in-class siRNA in Phase 2 development for polycythemia vera, or PV. PV is a rare myeloproliferative neoplasm characterized by the overproduction of red blood cells, or RBCs. Elevated hematocrit, or HCT, - an index of RBC mass - is a hallmark of the disease and HCT levels above 45% increase the risk of thrombotic and cardiovascular events. The current standard of care in all PV patients to control HCT is phlebotomy, daily low-dose aspirin therapy, sometimes in combination with cytoreductive therapies. PV patients have low levels of hepcidin the body’s master regulator of iron. Divesiran works by "silencing" the TMPRSS6 gene, lifting the natural brake on hepcidin - the body's master iron regulator. When TMPRSS6 is turned down in people living with PV, hepcidin levels rise, reducing iron availability to the bone marrow. With less iron available, the overproduction of RBCs seen in PV is reduced. This helps keep HCT levels in a safer range and can reduce or eliminate the need for phlebotomies. Additionally, siRNA therapies have a highly potent and durable effect - enabling less frequent and more convenient dosing. In the Phase 1 part of the SANRECO clinical trial evaluating divesiran treatment in 21 PV patients, divesiran produced durable HCT control and substantially reduced phlebotomy use following infrequent dosing (Q6W). Based on the strong durability observed in Phase 1, the ongoing Phase 2 part of the SANRECO trial is evaluating both a Q6W and Q12W dosing interval. The SANRECO Phase 2 trial is fully enrolled and topline results are anticipated in August 2026. The U.S. Food and Drug Administration, or FDA, has granted divesiran Fast Track and orphan drug designations for PV. Divesiran has also been granted orphan drug designation by the European Commission for PV in Europe. While our initial focus is on PV, divesiran has shown the potential in preclinical studies to address multiple hematological conditions through the unifying mechanism of elevating hepcidin in conditions with dysregulation of iron homeostasis.

Current wording

Divesiran (SLN124) is our potential first-in-class siRNA in Phase 2 development for polycythemia vera, or PV. PV is a rare myeloproliferative neoplasm characterized by the overproduction of red blood cells, or RBCs. Elevated hematocrit, or HCT, - an index of RBC mass - is a hallmark of the disease and HCT levels above 45% increase the risk of thrombotic and cardiovascular events. The current standard of care in all PV patients to control HCT is phlebotomy, daily low-dose aspirin therapy, sometimes in combination with cytoreductive therapies. PV patients have low levels of hepcidin the body’s master regulator of iron. Divesiran works by "silencing" the TMPRSS6 gene, lifting the natural brake on hepcidin - the body's master iron regulator. When TMPRSS6 is turned down in people living with PV, hepcidin levels rise, reducing iron availability to the bone marrow. With less iron available, the overproduction of RBCs seen in PV is reduced. This helps keep HCT levels in a safer range and can reduce or eliminate the need for phlebotomies. Additionally, siRNA therapies have a highly potent and durable effect - enabling less frequent and more convenient dosing. In the Phase 1 part of the SANRECO clinical trial evaluating divesiran treatment in 21 PV patients, divesiran produced durable HCT control and substantially reduced phlebotomy use following infrequent dosing (Q6W). Based on the strong durability observed in Phase 1, the ongoing Phase 2 part of the SANRECO trial is evaluating both a Q6W and Q12W dosing interval. The SANRECO Phase 2 trial completed patient dosing in June 2026 and topline results are anticipated in August 2026. The U.S. Food and Drug Administration, or FDA, has granted divesiran Fast Track and orphan drug designations for PV. Divesiran has also been granted orphan drug designation by the European Commission for PV in Europe. While our initial focus is on PV, divesiran has shown the potential in preclinical studies to address multiple hematological conditions through the unifying mechanism of elevating hepcidin in conditions with dysregulation of iron homeostasis.

Previous wording

SLN365 is our potential first-in-class siRNA product candidate that works by "silencing" GPR146, a novel mechanism of action for the management of cholesterol levels in patients, independent of LDLR function. Hypercholesterolemia is a highly prevalent indication with an estimated one in 300 individuals worldwide living with the familial form HeFH (heterozygous) and around one in 300,000 individuals suffering from the form HoFH (homozygous) globally. SLN365 has demonstrated promising preclinical results in non-human primates and we anticipate additional preclinical data in the second quarter of 2026.

Current wording

SLN365 is our potential first-in-class siRNA product candidate that works by "silencing" GPR146, a novel mechanism of action for the management of cholesterol levels in patients, independent of LDLR function. Hypercholesterolemia is a highly prevalent indication with an estimated one in 300 individuals worldwide living with the familial form HeFH (heterozygous) and around one in 300,000 individuals suffering from the form HoFH (homozygous) globally. SLN365 has demonstrated promising preclinical results in non-human primates and the program is well positioned for a potential IND filing in 2027.

Previous wording

SLN098 is our siRNA product candidate that works by "silencing" INHBE, a novel target for obesity supported by human genetics, strong preclinical data and emerging third-party clinical data demonstrating early efficacy and safety. Despite recent advances in obesity treatment, limitations of current standards of care leave millions at risk of further complications. Around one billion patients worldwide are affected by obesity and associated co-morbidities. Current obesity treatments offer weight loss around 15-20% which plateaus after 12-24 months and are associated with up to 40% lean muscle mass loss. More than two thirds of weight loss is regained within the first year after discontinuation of treatment. There is also poor tolerability and compliance with up to 30% of patients discontinuing GLP/GIP agonists treatment. SLN098 has the opportunity to address unmet needs including increasing fat loss, preventing muscle mass loss and slowing weight regain. SLN098 has demonstrated deep and durable knockdown in nonhuman primates and we anticipate additional disease model data in the second quarter of 2026 to further validate the mechanism of action. We believe there is an opportunity to develop SLN098 either as a monotherapy or add-on to GLP/GIP agonists or as a weight maintenance treatment.

Current wording

SLN098 is our siRNA product candidate that works by "silencing" INHBE, a novel target for obesity supported by human genetics, strong preclinical data and emerging third-party clinical data demonstrating early efficacy and safety. Despite recent advances in obesity treatment, limitations of current standards of care leave millions at risk of further complications. Around one billion patients worldwide are affected by obesity and associated co-morbidities. Current obesity treatments offer weight loss around 15-20% which plateaus after 12-24 months and are associated with up to 40% lean muscle mass loss. More than two thirds of weight loss is regained within the first year after discontinuation of treatment. There is also poor tolerability and compliance with up to 30% of patients discontinuing GLP/GIP agonists treatment. SLN098 has the opportunity to address unmet needs including increasing fat loss, preventing muscle mass loss and slowing weight regain. SLN098 has demonstrated deep and durable knockdown in nonhuman primates and the program is well positioned for a potential IND filing in 2027. We believe there is an opportunity to develop SLN098 either as a monotherapy or add-on to GLP/GIP agonists or as a weight maintenance treatment.

Previous wording

First Quarter 2026 and Recent Business Developments

Current wording

Second Quarter 2026 and Recent Business Developments

Previous wording

SANRECO Phase 2 double-blind, placebo-controlled trial evaluating divesiran 6 mg (Q6W and Q12W dosing intervals) in 48 phlebotomy-dependent PV patients is ongoing with topline results on-track for the third quarter of 2026.

Current wording

Completed dosing in the Phase 2 SANRECO double-blind, placebo-controlled trial evaluating divesiran 6 mg (Q6W and Q12W dosing intervals) in 48 phlebotomy-dependent PV patients.

Previous wording

SLN312 (AZD1705): Phase 1 siRNA with a competitive profile for dyslipidemia

Current wording

SLN312 (AZD1705): Phase 1 siRNA silencing ANGPTL3 with a competitive profile for dyslipidemia

Previous wording

Phase 1 study abstract accepted for late-breaking oral presentation at the European Atherosclerosis Society (EAS) Congress taking place May 24-27, 2026.

Current wording

Phase 1 results generated under our AstraZeneca collaboration were presented by AstraZeneca during a late-breaking oral presentation at the European Atherosclerosis Society (EAS) Congress in May 2026. Results demonstrated a favorable safety profile and dose-dependent, durable reductions in ANGPTL3 protein levels as well as in atherogenic lipoproteins including LDL-C, Apo-B and non-HDL-C.

Previous wording

Under the AstraZeneca collaboration, we received an upfront cash payment of $20.0 million and an additional payment of $40.0 million in May 2021. We are also eligible to receive specified development and commercial milestone payments as well as tiered royalties on net sales, if any. We recognize the upfront payment and milestone payments over time. During the three months ended March 31, 2026, we recognized a total of $0.4 million in revenue under the AstraZeneca collaboration (three months ended March 31, 2025: $0.1 million).

Current wording

Under the AstraZeneca collaboration, we received an upfront cash payment of $20.0 million and an additional payment of $40.0 million in May 2021. We are also eligible to receive specified development and commercial milestone payments as well as tiered royalties on net sales, if any. We recognize the upfront payment and milestone payments over time. There was no revenue for the three months ended June 30, 2026 (three months ended June 30, 2025: $0.2 million). During the six months ended June 30, 2026, we recognized a total of $0.4 million in revenue under the AstraZeneca collaboration (six months ended June 30, 2025: $0.4 million).

Previous wording

Foreign exchange gains and losses primarily relate to cash and short-term investments held in foreign currencies (primarily USD and Euros).

Current wording

Foreign exchange gains and losses primarily relate to cash and short-term investments held in foreign currencies (primarily GBP and Euros).

Previous wording

Unsurrendered U.K. tax losses may be carried forward indefinitely to be offset against future taxable profits, subject to numerous utilization criteria and restrictions. The amount that can be offset each year is limited to $6.5 million (£5.0 million) plus an incremental 50% of U.K. taxable profits. After accounting for tax credits receivable, we had accumulated tax losses for carry forward in the United Kingdom of $237.0 million as of March 31, 2026 ($187.7 million as of March 31, 2025). However, in the event of a change in ownership of a U.K. company, certain provisions may apply to restrict the utilization of carried forward tax losses in future periods. These provisions apply where there is a major change in the nature or conduct of a trade in connection with the change in ownership. For the avoidance of doubt, we do not recognize a deferred tax asset in respect of the accumulated tax losses. In addition to our accumulated tax losses in the United Kingdom, we also had $50.5 million of accumulated tax losses as of March 31, 2026 ($48.7 million as of March 31, 2025), related to our operations in Germany for corporate income taxes. We also had $48.9 million of accumulated losses related to trade taxes in our German entity ($47.2 million as of March 31, 2025). We had a foreign tax expense in Germany of nil for the three months ended March 31, 2026 (three months ended March 31, 2025: nil). Tax losses in the United States were negligible.

Current wording

Unsurrendered U.K. tax losses may be carried forward indefinitely to be offset against future taxable profits, subject to numerous utilization criteria and restrictions. The amount that can be offset each year is limited to $6.5 million (£5.0 million) plus an incremental 50% of U.K. taxable profits. After accounting for tax credits receivable, we had accumulated tax losses for carry forward in the United Kingdom of $248.2 million as of June 30, 2026 ($214.7 million as of June 30, 2025). However, in the event of a change in ownership of a U.K. company, certain provisions may apply to restrict the utilization of carried forward tax losses in future periods. These provisions apply where there is a major change in the nature or conduct of a trade in connection with the change in ownership. For the avoidance of doubt, we do not recognize a deferred tax asset in respect of the accumulated tax losses. In addition to our accumulated tax losses in the United Kingdom, we also had $48.4 million of accumulated tax losses as of June 30, 2026 ($52.6 million as of June 30, 2025), related to our operations in Germany for corporate income taxes. We also had $47.3 million of accumulated losses related to trade taxes in our German entity ($50.9 million as of June 30, 2025). We had a foreign tax expense in Germany of nil for the six months ended June 30, 2026 (six months ended June 30, 2025: nil). Tax losses in the United States were negligible.

Previous wording

Comparison of the three months ended March 31, 2026, and 2025

Current wording

Comparison of the three and six months ended June 30, 2026, and 2025

Previous wording

The following table summarizes the results of our operations for the three months ended March 31, 2026, and 2025 (in thousands).

Current wording

The following table summarizes the results of our operations for the three months and six months ended June 30, 2026, and 2025 (in thousands).

Previous wording

Revenue for the three months ended March 31, 2026 was $0.4 million, reflecting an increase of $0.3 million as compared to the same period in 2025 due to activity associated with the AstraZeneca collaboration.

Current wording

Revenue for the six months ended June 30, 2026 was $0.4 million, reflecting a negligible increase as compared to the same period in 2025 due to activity associated with the AstraZeneca collaboration.

Previous wording

Cost of sales movement was negligible for the three months ended March 31, 2026, as compared to the same period in 2025. The change was due to activity associated with our collaboration agreements, which fluctuates based on the timing of activities and project progression.

Current wording

Cost of sales movement was negligible for the three and six months ended June 30, 2026, as compared to the same periods in 2025. Cost of sales is related to activity associated with our collaboration agreements, which fluctuates based on the timing of activities and project progression.

Previous wording

The following table summarizes our research and development costs for the three months ended March 31, 2026 and 2025, based on their classification (in thousands).

Current wording

The following table summarizes our research and development costs for the three and six months ended June 30, 2026 and 2025, based on their classification (in thousands).

Previous wording

Research and development costs for the three months ended March 31, 2026 decreased by $11.7 million to $9.1 million. This change was mainly due to a decrease in contracted development costs of $10.3 million associated with the Phase 3 readiness for zerlasiran in 2025 as well as a decrease in personnel costs of $1.4 million mainly due to reduced headcount.

Current wording

Research and development costs for the three months ended June 30, 2026 decreased by $8.5 million, as compared to the same period in 2025. This change was mainly due to a decrease in contracted development costs of $7.5 million associated with the Phase 3 readiness for zerlasiran in 2025, as well as a decrease in personnel costs of $0.8 million mainly due to reduced headcount.

Previous wording

Contracted development costs for the three months ended March 31, 2026 decreased by $10.3 million to $4.3 million. The decrease was largely due to a decrease in costs related to contract manufacturing activities related to our zerlasiran Phase 3 readiness completed in 2025.

Current wording

Contracted development costs for the three months ended June 30, 2026 decreased by $7.5 million and $17.8 million for the six months ended June 30, 2026, compared to the same periods in 2025. The decrease was largely due to a decrease in costs related to contract manufacturing activities related to our zerlasiran Phase 3 readiness completed in 2025. The remaining decrease is due to the timing of clinical manufacturing and clinical studies for divesiran.

Previous wording

General and administrative expenses decreased by $0.7 million for the three months ended March 31, 2026 compared to the same period in 2025. These decreases were mainly due to an effort to reduce administrative costs.

Current wording

General and administrative expenses decreased by $0.4 million for the three months ended June 30, 2026 and $1.1 million for the six months ended June 30, 2026, compared to the same periods in 2025. These decreases were mainly due to an effort to reduce administrative costs.

Previous wording

As of January 1, 2026, the functional currency of our U.K. entity changed to USD and as a result, foreign currency activity included in net income for the three months ended March 31, 2026 was a loss of $0.5 million. In the prior year, foreign exchange gains and losses included in net income resulted primarily from foreign currency (USD and EUR) denominated bank accounts. The foreign exchange losses for the three months ended March 31, 2025 were primarily due to remeasurement of U.S. treasury bills held in USD to the related functional currency.

Current wording

As of January 1, 2026, the functional currency of our U.K. entity changed to USD and as a result, foreign currency activity included in net gain of $0.2 million for the three months ended June 30, 2026 and a net loss of $0.3 million for the six months ended June 30, 2026. In the prior year, foreign exchange gains and losses included in net income resulted primarily from foreign currency (USD and EUR) denominated bank accounts. The foreign exchange losses for the three and six months ended June 30, 2025 were primarily due to remeasurement of U.S. treasury bills held in USD to the related functional currency.

Previous wording

As of March 31, 2026, we had cash, cash equivalents, and short-term investments of $70.1 million. We believe that our cash, cash equivalents, and short-term investments will be sufficient to fund our anticipated operating and capital expenditure requirements into 2028.

Current wording

As of June 30, 2026, we had cash and cash equivalents of $72.1 million. We believe that our cash and cash equivalents will be sufficient to fund our anticipated operating and capital expenditure requirements into 2028.

Previous wording

On February 2, 2024, we entered into a securities purchase agreement, or the Purchase Agreement, with the purchasers named therein, or the Investors. Pursuant to the Purchase Agreement, we agreed to sell an aggregate of 5,714,286 of our ADSs to the Investors, at a purchase price equal to $21.00 per ADS, or the Private Placement. The

Current wording

On February 2, 2024, we entered into a securities purchase agreement, or the Purchase Agreement, with the purchasers named therein, or the Investors. Pursuant to the Purchase Agreement, we agreed to sell an aggregate of 5,714,286 of our ADSs to the Investors, at a purchase price equal to $21.00 per ADS, or the Private Placement. The Purchase Agreement contained customary representations and warranties from us and the investors and customary closing conditions. The closing of the Private Placement occurred on February 7, 2024, and we received aggregate gross proceeds from the Private Placement of approximately $120.0 million before deducting $7.7 million in placement agent fees and other expenses.

Previous wording

On October 15, 2021, we entered into an Open Market Sale Agreement, or the Sales Agreement, with Jefferies LLC, or Jefferies, pursuant to which we may offer and sell, from time to time, our ADSs through Jefferies. In 2024, we raised proceeds of $27.7 million before deducting $0.9 million in placement agent fees and other expenses, from sales of ADSs under the Sales Agreement.

Current wording

In March 2026, we entered into an Open Market Sale Agreement, or the Sales Agreement, with Jefferies LLC, or Jefferies, as sales agent, pursuant to which we may offer and sell, from time to time through Jefferies, at our option, our ordinary shares. We agreed to pay Jefferies a commission of up to 3.0% of the aggregate gross proceeds for the ordinary shares sold through the Sales Agreement. During the three months ended June 30, 2026, no sales were made under the Sales Agreement.

Previous wording

The following table summarizes the results of our cash flows for the three months ended March 31, 2026 and 2025.

Current wording

The following table summarizes the results of our cash flows for the six months ended June 30, 2026 and 2025.

Previous wording

Net cash outflow from operating activities increased by $3.3 million for the three months ended March 31, 2026, as compared with the same period in 2025. This increase was mainly due to the receipt of $11.0 million related to the 2023 R&D benefit in the three months ended March 31, 2025, while no related claim was received in 2026. This was offset by a reduction in research and development spend in 2026.

Current wording

Net cash outflow from operating activities decreased by $20.0 million for the six months ended June 30, 2026, as compared with the same period in 2025. This decrease was mainly due to reduction in our research and development spend in 2026.

Previous wording

Net cash inflow from investing activities relates to redemptions of U.S. treasury bills, offset by purchases for the three months ended March 31, 2026. The same period in 2025 reflected $70.1 million in purchases of U.S. treasury bills offset by $25.7 million in redemptions.

Current wording

Net cash inflow from investing activities relates to $139.4 million redemptions of U.S. treasury bills, offset by $64.4 million in purchases for the six months ended June 30, 2026. The same period in 2025 reflected $72.4 million in purchases of U.S. treasury bills offset by $26.6 million in redemptions.

Previous wording

During the three months ended March 31, 2026 and 2025, our revenue from collaboration agreements was derived from the AstraZeneca collaboration.

Current wording

During the six months ended June 30, 2026 and 2025, our revenue from collaboration agreements was derived from the AstraZeneca collaboration.

Previous wording

For the three months ended March 31, 2026 and 2025, we determined actual costs and forecast costs for the remainder of the contract. We calculated total contract costs across the contract term, including costs that will be reimbursed to us, and costs incurred to date as a percentage of total contract costs. We multiplied this percentage by the consideration deemed highly probable of not having a significant reversal, calculating the cumulative revenue to be recognized. When variable consideration increases due to a further milestone becoming highly probable that a significant reversal of revenue will not occur, a catch-up in revenue is recorded to reflect efforts already expended by us up to that point. In the three months ended March 31, 2026, the estimated forecasted cost for partnered programs was not material and the related judgment was not significant.

Current wording

For the six months ended June 30, 2026 and 2025, we determined actual costs and forecast costs for the remainder of the contract. We calculated total contract costs across the contract term, including costs that will be reimbursed to us, and costs incurred to date as a percentage of total contract costs. We multiplied this percentage by the consideration deemed highly probable of not having a significant reversal, calculating the cumulative revenue to be recognized. When variable consideration increases due to a further milestone becoming highly probable that a significant reversal of revenue will not occur, a catch-up in revenue is recorded to reflect efforts already expended by us up to that point. In the six months ended June 30, 2026, the estimated forecasted cost for partnered programs was not material and the related judgment was not significant.