Silence Therapeutics plc

Previous wording

We are a biotechnology company focused on discovering and developing novel molecules incorporating short interfering ribonucleic acid, or siRNA, to inhibit the expression of specific target genes thought to play a role in the pathology of diseases with significant unmet medical need. Our siRNA molecules are designed to harness the body’s natural mechanism of RNA interference, or RNAi, by specifically binding to and degrading messenger RNA, or mRNA, molecules that encode specific targeted disease-associated proteins in a cell. By degrading the message that encodes the disease-associated protein, the production of that protein is reduced and its level of activity is lowered. In the field of RNAi therapeutics, this reduction of disease-associated protein production and activity is referred to as “gene silencing.” Our proprietary mRNAi GOLD™ (GalNAc Oligonucleotide Discovery) platform consists of siRNA product candidates designed to precisely target and ‘silence’ specific disease-associated genes in the liver. Using our mRNAi GOLD platform, we have generated siRNA product candidates both for our internal development pipeline as well as for out-licensed programs with third-party collaborators. Our wholly owned pipeline is currently focused in three therapeutic areas of high unmet need: cardiovascular disease, hematology and rare diseases.

Current wording

We are a biotechnology company focused on discovering and developing novel molecules incorporating short interfering ribonucleic acid, or siRNA, to inhibit the expression of specific target genes thought to play a role in the pathology of diseases with significant unmet medical need. Our siRNA molecules are designed to harness the body’s natural mechanism of RNA interference, or RNAi, by specifically binding to and degrading messenger RNA, or mRNA, molecules that encode specific targeted disease-associated proteins in a cell. By degrading the message that encodes the disease-associated protein, the production of that protein is reduced, and its level of activity is lowered. In the field of RNAi therapeutics, this reduction of disease-associated protein production and activity is referred to as “gene silencing.” Our proprietary mRNAi GOLD™ (GalNAc Oligonucleotide Discovery) platform consists of siRNA product candidates designed to precisely target and ‘silence’ specific disease-associated genes in the liver. Using our mRNAi GOLD platform, we have generated siRNA product candidates both for our internal development pipeline as well as for out-licensed programs with third-party collaborators. Our wholly owned pipeline is currently focused on three therapeutic areas of high unmet need: cardiovascular disease, hematology and rare diseases.

Previous wording

Divesiran (SLN124) is our wholly owned siRNA product candidate designed to inhibit TMPRSS6 expression in the liver. TMPRSS6 is a negative regulator of hepcidin, the body's master regulator of iron metabolism, including its absorption, distribution and storage. Divesiran has shown preclinical potential in several hematological disorders and proof-of-mechanism in a Phase 1 healthy volunteer trial. Divesiran is currently being evaluated in the SANRECO Phase 2 clinical trial in polycythemia vera, or PV, patients. We believe divesiran has the potential to be the first-in-class siRNA in 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, or HCT, levels. 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. In December 2024, we presented positive interim results from the Phase 1 portion of the SANRECO clinical trial at the American Society of Hematology annual meeting. Interim results showed divesiran substantially reduced phlebotomy requirements and lowered HCT levels following infrequent dosing in a range of PV patients. Divesiran has been well tolerated to-date with no dose-limiting toxicities. In December 2024, we also announced the first subject has been dosed in the Phase 2 portion of the SANRECO clinical trial, which is currently underway. The U.S. Food and Drug Administration, or FDA, has granted divesiran Fast Track and orphan drug designations for PV. In December 2024, the European Commission, or EC, granted divesiran orphan drug designation for PV in Europe.

Current wording

Divesiran (SLN124) is our wholly owned siRNA product candidate that works by temporarily silencing TMPRSS6 expression in the liver. TMPRSS6 is a negative regulator of hepcidin, the body's master regulator of iron metabolism, including its absorption, distribution and storage. Divesiran has shown promising pre-clinical potential in several hematological disorders and is a potentially first-in-class siRNA in Phase 2 development for polycythemia vera, or 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, or HCT, levels. Elevated HCT, defined as 45% or higher, 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 pruritus. Longer term, PV may also progress to myelofibrosis and acute myeloid leukemia. The aim of PV treatment is to maintain HCT less than 45%, a level that is associated with a reduced incidence of thrombosis and cardiovascular-associated death. The current standard of care includes repeated phlebotomies to reduce HCT and/or cytoreductive agents to reduce red blood cell production. There are currently no approved therapies that specifically target red blood cells and HCT. By silencing TMPRSS6 in people living with PV, divesiran aims to increase hepcidin levels and redirect iron delivery away from the bone marrow, lowering red blood cell production and potentially reducing the high red blood cell count. In the SANRECO Phase 1 clinical trial of divesiran in PV patients, divesiran lowered and maintained durable control of HCT and essentially eliminated the need for phlebotomies in phlebotomy-dependent PV patients. Importantly, divesiran was well tolerated with no dose-limiting toxicities. The SANRECO Phase 2 clinical trial is ongoing and remains on track to complete enrollment by year-end 2025. The U.S. Food and Drug Administration, or FDA, has granted divesiran Fast Track and orphan drug designations for PV. In December 2024, the European Commission, or EC, granted divesiran orphan drug designation for PV in Europe.

Previous wording

Zerlasiran (SLN360) is our wholly owned siRNA product candidate, which is designed to lower the body's production of apolipoprotein(a), a key component of lipoprotein(a), or Lp(a), that has been associated with an increased risk of cardiovascular events. Zerlasiran works by targeting messenger RNA required to translate the LPA gene into particles of Lp(a), effectively ‘silencing’ the gene to reduce Lp(a) production. High Lp(a), defined as 125nmol/L or higher, is a genetically determined cardiovascular risk factor affecting at least 20% of the world’s population and is associated with a high risk of heart attack, stroke and aortic stenosis. Unlike low-density lipoprotein, or LDL, Lp(a) levels are predominantly genetically determined, typically by age five, and unaffected by diet or lifestyle. There are currently no approved medicines that selectively lower Lp(a). Lp(a) levels can be measured by a simple blood test and while there is no generalized consensus on Lp(a) risk thresholds, growing evidence supports three main levels: Low or Normal (less than 75 nmol/L), Elevated (75 nmol/L to 124 nmol/L) and High (125 nmol/L or higher). A recent US based registry study in over 16,000 individuals showed that there is substantial risk of major cardiovascular events in individuals with elevated levels below the current accepted risk threshold of 125 nmol/L. Guidelines from the European Atherosclerosis Society, or EAS, and Canadian Cardiovascular Society, or CCS, suggest at least one test in an adult lifetime. The American College of Cardiology, or ACC, and American Heart Association, or AHA, recommend testing for those with a family history of premature atherosclerotic cardiovascular disease, or ASCVD, or personal history of ASCVD. In Phase 1 and Phase 2 clinical trials, zerlasiran was shown to substantially lower Lp(a) levels in ASCVD patients with persisting effects following infrequent dosing and was observed to be well tolerated with no major safety concerns. During the fourth quarter of 2024, we received positive regulatory feedback from the FDA and European Medicines Agency, or EMA, on the Phase 3 cardiovascular, or CV, outcomes study design for zerlasiran in patients with high Lp(a). We are engaged in global partnership discussions to seek a third-party partner for potential Phase 3 development of zerlasiran as well as potential future commercialization activities.

Current wording

based registry study in over 16,000 individuals showed that there is substantial risk of major cardiovascular events in individuals with elevated levels below the current accepted risk threshold of 125 nmol/L. Guidelines from the European Atherosclerosis Society and Canadian Cardiovascular Society suggest at least one test in an adult lifetime. The American College of Cardiology, or ACC, and American Heart Association, or AHA, recommend testing for those with a family history of premature atherosclerotic cardiovascular disease, or ASCVD, or personal history of ASCVD. In Phase 1 and Phase 2 clinical trials, zerlasiran substantially lowered Lp(a) levels in ASCVD patients with persisting effects following infrequent dosing. Importantly, zerlasiran was well tolerated with no major safety concerns. During the fourth quarter of 2024, we received positive regulatory feedback from the FDA and European Medicines Agency, or EMA, on the Phase 3 cardiovascular, or CV, outcomes study design for zerlasiran in patients with high Lp(a). We are engaged in global partnership discussions to seek a third-party partner for potential Phase 3 development of zerlasiran as well as potential future commercialization activities.

Previous wording

In addition to our wholly owned clinical pipeline, we have a third siRNA product candidate from our mRNAi GOLD platform in Phase 1 development in an undisclosed indication through our collaboration with AstraZeneca. We believe the potential for our mRNAi GOLD platform to address disease-associated genes in the liver is substantial and are progressing several undisclosed preclinical programs that have shown promising results. We are committed to maximizing our mRNAi GOLD platform by advancing a pipeline of both wholly owned and partnered programs.

Current wording

In addition to our wholly owned clinical pipeline, we have a third siRNA product candidate from our mRNAi GOLD platform in Phase 1 development in an undisclosed indication through our collaboration with AstraZeneca. We are committed to maximizing our mRNAi GOLD platform by advancing a pipeline of both wholly owned and partnered programs. Beyond the liver, we are focused on progressing our extra-hepatic programs based on initial clinical feedback.

Previous wording

We advanced enrollment into the Phase 2 portion of the SANRECO study of divesiran in PV patients and remain on-track to complete enrollment by year-end 2025.

Current wording

In June 2025, we exceeded 50% enrollment in the SANRECO Phase 2 trial of divesiran in PV patients and remain on track to complete enrollment of the trial by year-end 2025.

Previous wording

We advanced core Phase 3 readiness activities for our zerlasiran program, including manufacturing and supply scale-up, which remain on-track to complete by mid-2025. Partnering discussions for potential Phase 3 development are ongoing.

Current wording

We have completed core Phase 3 readiness activities for our zerlasiran program, including manufacturing and supply scale-up. We continue to be in dialogues with potential third-party partners for Phase 3 development of zerlasiran as well as potential future commercialization activities.

Previous wording

A Phase 1 study of SLN312 (licensed to AstraZeneca) is ongoing.

Current wording

A Phase 1 trial of our siRNA product candidate, SLN312, which is licensed to AstraZeneca, is ongoing.

Previous wording

In March 2020, we entered into a collaboration agreement with AstraZeneca to discover, develop and commercialize siRNA therapeutics for the treatment of cardiovascular, renal, metabolic and respiratory diseases. Under this agreement, AstraZeneca made an upfront cash payment to us of $20.0 million in May 2020. AstraZeneca made an additional unconditional cash payment to us of $40.0 million which was received in May 2021. In March 2020, an affiliate of AstraZeneca also subscribed for 4,276,580 new ordinary shares for an aggregate subscription price of $20.0 million.

Current wording

In March 2020, we entered into a collaboration agreement with AstraZeneca, or the AstraZeneca Collaboration, to discover, develop and commercialize siRNA therapeutics for the treatment of cardiovascular, renal, metabolic and respiratory diseases. Under the AstraZeneca Collaboration, AstraZeneca made an upfront cash payment to us of $20.0 million in May 2020. AstraZeneca made an additional unconditional cash payment to us of $40.0 million, which was received in May 2021. In March 2020, an affiliate of AstraZeneca also subscribed for 4,276,580 new ordinary shares for an aggregate subscription price of $20.0 million.

Previous wording

The collaboration covers five targets initially, with AstraZeneca having the option to extend the collaboration to a further five targets. AstraZeneca has agreed to pay us $10.0 million upon the exercise of each option to collaborate on an additional target. In May 2023, AstraZeneca nominated the first product candidate under our collaboration, triggering a $10 million option fee to us to advance development on an undisclosed program. In February 2024, AstraZeneca initiated a Phase 1 clinical trial for this undisclosed program which triggered another $10 million milestone payment to us. In March 2024, we completed our obligations for the second product candidate under the collaboration. For each target selected, we will be eligible to receive up to $140.0 million in potential milestone payments upon the achievement of milestones relating to the initiation of specified clinical trials, the acceptance of specified regulatory filings and the first commercial sale in specified jurisdictions. For each target selected, we will also be eligible to receive up to $250.0 million in potential commercial milestone payments, upon the achievement of specified annual net sales levels, as well as tiered royalties as a percentage of net sales ranging from the high single digits to the low double digits.

Current wording

The AstraZeneca Collaboration covers five targets initially, with AstraZeneca having the option to extend the collaboration to a further five targets. AstraZeneca has agreed to pay us $10.0 million upon the exercise of each option to collaborate on an additional target. In May 2023, AstraZeneca nominated the first product candidate under the AstraZeneca Collaboration, triggering a $10 million option fee to us to advance development on an undisclosed program. In February 2024, AstraZeneca initiated a Phase 1 clinical trial for this undisclosed program which triggered another $10 million milestone payment to us. In March 2024, we completed our obligations for the second product candidate under the AstraZeneca Collaboration. For each target selected, we will be eligible to receive up to $140.0 million in potential milestone payments upon the achievement of milestones relating to the initiation of specified clinical trials, the acceptance of specified regulatory filings and the first commercial sale in specified jurisdictions. For each target selected, we will also be eligible to receive up to $250.0 million in potential commercial milestone payments, upon the achievement of specified annual net sales levels, as well as tiered royalties as a percentage of net sales ranging from the high single digits to the low double digits.

Previous wording

In July 2019, we entered into a collaboration agreement with Mallinckrodt to develop and commercialize RNAi drug targets designed to silence the complement cascade in complement-mediated disorders. In connection with the execution of this agreement, Mallinckrodt made an upfront cash payment to us of $20.0 million. Under a separate subscription agreement, Cache Holdings Limited, a wholly owned subsidiary of Mallinckrodt, concurrently subscribed for 5,062,167 new ordinary shares for an aggregate subscription price of $5.0 million. Under the agreement, we granted Mallinckrodt an exclusive worldwide license to our C3 targeting program, SLN501, with options to license two additional undisclosed complement-mediated disease targets from us. In July 2020, Mallinckrodt exercised options on the two additional complement targets.

Current wording

In July 2019, we entered into a collaboration agreement with Mallinckrodt, or the Mallinckrodt Collaboration, to develop and commercialize RNAi drug targets designed to silence the complement cascade in complement-mediated disorders. In connection with the Mallinckrodt Collaboration, Mallinckrodt made an upfront cash payment to us of $20.0 million. Under a separate subscription agreement, Cache Holdings Limited, a wholly owned subsidiary of Mallinckrodt, concurrently subscribed for 5,062,167 new ordinary shares for an aggregate subscription price of $5.0 million. Under the Mallinckrodt Collaboration, we granted Mallinckrodt an exclusive worldwide license to our C3 targeting program, SLN501, with options to license two additional undisclosed complement-mediated disease targets from us. In July 2020, Mallinckrodt exercised options on the two additional complement targets.

Previous wording

In March 2023, we reacquired exclusive worldwide rights from Mallinckrodt to the two undisclosed preclinical complement targets. Under the terms of the modified agreement, we did not make any upfront payment to get the two assets back and will potentially pay future success-based milestones and low single digit royalties on net sales if the projects advance. SLN501, the C3 targeting program, remained under the original collaboration agreement. In March 2024, Mallinckrodt notified us that they will not pursue further development of SLN501 following the completion of the Phase 1 clinical trial. This completion also concludes all required development activities and commitments under the collaboration.

Current wording

In March 2023, we reacquired exclusive worldwide rights from Mallinckrodt to the two undisclosed preclinical complement targets. Under the terms of the modified agreement, we did not make any upfront payment to get the two assets back and will potentially pay future success-based milestones and low single digit royalties on net sales if the projects advance. SLN501, the C3 targeting program, remained under the original collaboration agreement. In March 2024, Mallinckrodt notified us that they will not pursue further development of SLN501 following the completion of the Phase 1 clinical trial. This completion also concludes all required development activities and commitments under the Mallinckrodt Collaboration.

Previous wording

In October 2021, we announced a collaboration agreement with Hansoh, one of the leading biopharmaceutical companies in China, to develop siRNAs for three undisclosed targets leveraging our proprietary mRNAi GOLD™ platform. Under the terms of the agreement, Hansoh had the exclusive option to license rights to the first two targets in Greater China, Hong Kong, Macau and Taiwan following the completion of Phase 1 trials. We retained exclusive rights for those two targets in all other territories. We were responsible for all activities up to option exercise and will retain responsibility for development outside the China region post Phase 1 trials. Hansoh also had the exclusive option to license global rights to a third target at the point of Investigational New Drug filing. Hansoh was responsible for all development activities post option exercise for the third target. Hansoh made a $16 million upfront payment to us in December 2021. We achieved our first $2 million research milestone payment in the Hansoh collaboration in April 2022. In 2023, we achieved two additional preclinical milestones and received $4 million from the collaboration. In 2024, we achieved an additional preclinical milestone of $2.0 million from the Hansoh collaboration. In December 2024, Hansoh notified us that it will not pursue further development under the Hansoh collaboration. This represented the conclusion of all required development activities and commitments under the terms of the Hansoh collaboration and we will retain exclusive rights globally for all three targets.

Current wording

In October 2021, we announced a collaboration agreement with Hansoh, or the Hansoh Collaboration, one of the leading biopharmaceutical companies in China, to develop siRNAs for three undisclosed targets leveraging our proprietary mRNAi GOLD™ platform. Under the terms of the Hansoh Collaboration, Hansoh had the exclusive option to license rights to the first two targets in Greater China, Hong Kong, Macau and Taiwan following the completion of Phase 1 trials. We retained exclusive rights for those two targets in all other territories. We were responsible for all activities up to option exercise and will retain responsibility for development outside the China region post Phase 1 trials. Hansoh also had the exclusive option to license global rights to a third target at the point of Investigational New Drug filing. Hansoh was responsible for all development activities post option exercise for the third target. Hansoh made a $16 million upfront payment to us in December 2021. We achieved our first $2 million research milestone payment in the Hansoh collaboration in April 2022. In 2023, we achieved two additional preclinical milestones and received $4 million from the Hansoh Collaboration. In 2024, we achieved an additional preclinical milestone of $2.0 million from the Hansoh Collaboration. In December 2024, Hansoh notified us that it will not pursue further development under the Hansoh Collaboration. This represented the conclusion of all required development activities and commitments under the terms of the Hansoh Collaboration and we will retain exclusive rights globally for all three targets.

Previous wording

In March 2024, Mallinckrodt notified us that they will not pursue further development of the SLN501 program following the completion of the Phase 1 clinical trial. The completion of the Phase 1 clinical trial also represented the conclusion of all required development activities and commitments under the terms of the Mallinckrodt Collaboration.

Current wording

In March 2024, Mallinckrodt notified us that they will not pursue further development of the SLN501 program following the completion of the Phase 1 clinical trial. The completion of the Phase 1 clinical trial also represented the conclusion of all required development activities and commitments under the terms of the Mallinckrodt Collaboration. During the six months ended June 30, 2025, we did not recognize revenue under the Mallinckrodt Collaboration (six months ended June 30, 2024: $0.7 million).

Previous wording

Under our collaboration agreement with AstraZeneca, 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, 2025, we recognized a total of $0.1 million in revenue under the AstraZeneca collaboration (three months ended March 31, 2024: $14.7 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. During the six months ended June 30, 2025, we recognized a total of $0.4 million in revenue under the AstraZeneca Collaboration (six months ended June 30, 2024: $15.0 million).

Previous wording

Under the Hansoh Collaboration, we received an upfront cash payment of approximately $16.0 million (net of taxes based on the exchange rate at the payment date) in December 2021. In December 2024, Hansoh notified us that it will not pursue further development under the Hansoh collaboration. This represented the conclusion of all required development activities and commitments under the terms of the Hansoh collaboration. During the three months ended March 31, 2025, we did not recognize revenue under the Hansoh collaboration (three months ended March 31, 2024: $0.2 million).

Current wording

Under the Hansoh Collaboration, we received an upfront cash payment of approximately $16.0 million (net of taxes based on the exchange rate at the payment date) in December 2021. In December 2024, Hansoh notified us that it will not pursue further development under the Hansoh Collaboration. This represented the conclusion of all required development activities and commitments under the terms of the Hansoh Collaboration. During the six months ended June 30, 2025, we did not recognize revenue under the Hansoh Collaboration (six months ended June 30, 2024: $0.6 million).

Previous wording

In December 2018, we entered into a settlement and license agreement with Alnylam Pharmaceuticals Inc., or Alnylam, pursuant to which we settled outstanding patent litigation with Alnylam related to its RNAi product ONPATTRO. As part of the settlement, we license specified patents to Alnylam, and Alnylam pays us a tiered royalty of up to one percent of net sales of ONPATTRO in the European Union. We were eligible to receive these royalties until December 2023. We invoice Alnylam quarterly in arrears based on sales data for that quarter as reported to us by Alnylam. Royalty revenue is recognized based on the level of sales when the related sales occur. During the three months ended March 31, 2024, we recognized a total of $0.1 million in royalty income from Alnylam.

Current wording

In December 2018, we entered into a settlement and license agreement with Alnylam Pharmaceuticals Inc., or Alnylam, pursuant to which we settled outstanding patent litigation with Alnylam related to its RNAi product ONPATTRO. As part of the settlement, we license specified patents to Alnylam, and Alnylam pays us a tiered royalty of up to one percent of net sales of ONPATTRO in the European Union. We were eligible to receive these royalties until December 2023. We invoice Alnylam quarterly in arrears based on sales data for that quarter as reported to us by Alnylam. Royalty revenue is recognized based on the level of sales when the related sales occur. During the six months ended June 30, 2025, we did not recognized any royalty income from Alnylam (six months ended June 30, 2024: $0.1 million).

Previous wording

costs incurred under agreements with contract research organizations, or CROs, and investigative sites that conduct our preclinical studies and clinical trials;

Current wording

costs incurred under agreements with CROs and investigative sites that conduct our preclinical studies and clinical trials;

Previous wording

costs associated with obtaining and maintaining patents for intellectual property; and

Current wording

costs associated with establishing patent rights for intellectual property; and

Previous wording

Foreign exchange gains and losses relate to cash 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 USD 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 $187.7 million as of March 31, 2025 ($158.1 million as of March 31, 2024). 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 $48.7 million of accumulated tax losses as of March 31, 2025 ($52.3 million as of March 31, 2024), related to our operations in Germany for corporate income taxes. We also had $47.2 million of accumulated losses related to trade taxes in our German entity ($50.8 million as of March 31, 2024). We had a foreign tax expense in Germany of nil for the three months ended March 31, 2025 (three months ended March 31, 2024: $0.2 million). 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 $214.7 million as of June 30, 2025 ($203.6 million as of June 30, 2024). 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 $52.6 million of accumulated tax losses as of June 30, 2025 ($51.2 million as of June 30, 2024), related to our operations in Germany for corporate income taxes. We also had $50.9 million of accumulated losses related to trade taxes in our German entity ($49.7 million as of June 30, 2024). We had a foreign tax expense in Germany of nil for the six months ended June 30, 2025 (six months ended June 30, 2024: $0.3 million). Tax losses in the United States were negligible.

Previous wording

Comparison of the three months ended March 31, 2025, and 2024

Current wording

Comparison of the three months and six months ended June 30, 2025, and 2024

Previous wording

The following table summarizes the results of our operations for the three months ended March 31, 2025, and 2024 (in thousands).

Current wording

The following table summarizes the results of our operations for the three months and six months ended June 30, 2025, and 2024 (in thousands).

Previous wording

Revenue for the three-month period ended March 31, 2025, was $0.1 million, reflecting a decrease of $15.6 million from the same three-month period in 2024. This change was mainly due to revenue from our Collaboration with AstraZeneca which decreased by $14.5 million. This difference was mainly due to the fact that there were no similar milestones in 2025.

Current wording

Revenue for the six months ended June 30, 2025 was $0.4 million, reflecting a decrease of $16.1 million from the same period in 2024. This change was mainly due to an impact of the revenue from the AstraZeneca Collaboration, which decreased by $14.7 million as we did not achieve any milestones during the period under the terms of the AstraZeneca Collaboration. This difference was mainly due to the fact that there were no similar milestones in 2025.

Previous wording

Cost of sales decreased $2.7 million for the three months ended March 31, 2025, as compared to the same period in 2024. 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 decreased $3.2 million for the three months ended June 30, 2025, as compared to the same period in 2024. The change was due 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, 2025, and 2024, 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, 2025 and 2024, based on their classification (in thousands).

Previous wording

Research and development costs increased by $9.0 million for the three months ended March 31, 2025, as compared to the same period in 2024. This was largely due to advancement of our clinical trials and an increase in contract manufacturing activities for our proprietary programs.

Current wording

Research and development costs increased by $3.8 million for the three months ended June 30, 2025, and $12.8 million for the six months ended June 30, 2025, as compared to the same periods in 2024. This was largely due to advancement of our proprietary programs; primarily the Phase 2 clinical trial for diversiran and an increase in contract manufacturing activities related to our zerlasiran Phase 3 readiness.

Previous wording

Net foreign exchange gains and losses result primarily from foreign currency (USD and EUR) denominated bank accounts.

Current wording

Net foreign exchange gains and losses result primarily from foreign currency (USD and EUR) denominated bank accounts. The foreign exchange losses in the current year were primarily due to remeasurement of U.S. treasury bills held in USD to the related functional currency.

Previous wording

Taxation expense relates to foreign taxation.

Current wording

Taxation expense relates to foreign taxation expenses.

Previous wording

As of March 31, 2025, we had cash, cash equivalents, and short-term investments of $136.5 million. We believe that our cash, cash equivalents, and treasury instruments will be sufficient to fund our anticipated operating and capital expenditure requirements into 2028, which includes receipt of anticipated milestones from collaboration agreements of $20 million in the next three years.

Current wording

As of June 30, 2025, we had cash, cash equivalents, and short-term investments of $114.2 million. We believe that our cash, cash equivalents, and treasury instruments will be sufficient to fund our anticipated operating and capital expenditure requirements into 2028, which includes receipt of anticipated milestones from collaboration agreements in the aggregate amount of $20 million in the next three years.

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, the Group raised additional proceeds of $27.7 million before deducting $0.9 million in placement agent fees and other expenses, from sales of ADSs under its Sales Agreement.

Current 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 additional 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.

Previous wording

The following table summarizes the results of our cash flows for the three months ended March 31, 2025, and 2024.

Current wording

The following table summarizes the results of our cash flows for the six months ended June 30, 2025 and 2024.

Previous wording

Net cash outflow from operating activities increased by $3.2 million for the three months ended March 31, 2025, compared with the prior period, mainly due to an increase in expenditures related to contracted development costs.

Current wording

Net cash outflow from operating activities increased by $19.5 million for the six months ended June 30, 2025, compared with the prior period, mainly due to a reduction in milestones from our collaboration agreements. In the six months ended June 30, 2024, we received a $10 million milestone payment pursuant to the terms of the AstraZeneca Collaboration. This remainder was due to an increase in expenditures related to contracted development costs associated with our clinical studies.

Previous wording

Net cash outflow from investing activities relates to purchases of U.S. treasury bills offset by redemptions for the three months ended March 31, 2025. The same period in 2024 reflected only a purchase of a U.S. treasury bill.

Current wording

Net cash outflow from investing activities relates to purchases of U.S. treasury bills offset by redemptions for the six months ended June 30, 2025.

Previous wording

In 2024, we raised aggregate gross proceeds from the Private Placement (as defined below) of $120 million before deducting $7.7 million in placement agent fees and other expenses. The remainder of the inflow was due to

Current wording

In 2024, we raised aggregate gross proceeds from the Private Placement of $120 million before deducting $7.7 million in placement agent fees and other expenses. The remainder of the inflow was due to

Previous wording

proceeds from sales under our at-the-market facility. There was no related financing activities in 2025.

Current wording

proceeds from sales under our at-the-market facility. There were no related financing activities in 2025.

Previous wording

The lease liability recognized on the balance sheet comprises our London office. There are two short-term leases in Berlin, Germany and a lease in New Jersey, United States, not included in the "lease liability" line of the table above. Both leases in Berlin are on a rolling contract basis with either party being able to end the lease with a cancellation notice period of 11.5 months, while the leases in the United States are on a rolling contract basis with a notice period of three months, thus allowing exemption using the practical expedient.

Current wording

The lease liability recognized on the balance sheet comprises our London office. Our balance sheet also reflects two short-term leases in Berlin, Germany and a lease in New Jersey, United States, neither of which is included in the "lease liability" line of the table above. Both leases in Berlin are on a rolling contract basis with either party being able to end the lease with a cancellation notice period of 11.5 months, while the leases in the United States are on a rolling contract basis with a notice period of three months, thus allowing exemption using the practical expedient.

Previous wording

At March 31, 2025, we had a gross commitment on our office rental in Berlin, Germany and in the United States equal to an aggregate of $0.5 million in the next year. No amounts are payable after more than one year.

Current wording

At June 30, 2025, we had a gross commitment on our office rental in Berlin, Germany and in the United States equal to an aggregate of $0.6 million in the next year. No amounts are payable after more than one year.

Previous wording

During the three months ended March 31, 2025, a significant portion of our revenue from collaboration agreements was derived from our agreement with AstraZeneca (three months ended March 31, 2024, revenue was from our collaborations with Mallinckrodt, AstraZeneca, and Hansoh).

Current wording

During the six months ended June 30, 2025, a significant portion of our revenue from collaboration agreements was derived from the AstraZeneca Collaboration (six months ended June 30, 2024, revenue was from our collaborations with Mallinckrodt, AstraZeneca, and Hansoh).

Previous wording

We have out-licensed the rights to some of our intellectual property associated with our siRNA stabilization chemistry technology to AstraZeneca in the context of a Research Collaboration, Option and License Agreement dated March 24, 2020, under which we and AstraZeneca will collaborate to discover, develop and commercialize siRNA therapeutics for the treatment of cardiovascular, renal, metabolic and respiratory diseases. AstraZeneca made an upfront cash payment of $60 million, of which $20 million was paid in May 2020 and the remaining $40 million was paid in May 2021. The upfront payment has been allocated evenly between the ten targets on the basis of a benchmarking exercise that took into account the standalone selling price per target, of similar precedent transactions that had been publicly announced by comparable companies. Subsequent milestones are allocated to the target to which they are related. The upfront and milestone payments will be recognized as revenue as the services are provided. We anticipate initiating work on up to five targets in the early stages of the collaboration, with AstraZeneca having the option to extend the collaboration to a further five targets. Under the collaboration, utilizing our technology, we are responsible for designing siRNA molecules against gene targets selected by AstraZeneca, and for manufacturing of material to support GLP toxicology studies and phase 1 clinical trials. We and AstraZeneca will collaborate during the discovery phase, and AstraZeneca will lead clinical development and commercialization of molecules arising from the collaboration. For each target selected under the collaboration, we will be eligible to receive up to $140 million in milestone payments upon the achievement of milestones relating to initiation of specified clinical trials, the acceptance of specified regulatory filings and the first commercial sale in specified jurisdictions. AstraZeneca has the right to terminate the agreement in its entirety or on a target-by-target basis, for any reason upon specified prior written notice to us. We may terminate the agreement on a target-by-target basis in the event that AstraZeneca begins a legal or administrative proceeding challenging the patentability, validity, ownership or enforceability of our patents. Either party may terminate the agreement on a target-by-target basis upon a material breach by the other party that is not cured within a specified period after receiving written notice, or in its entirety upon giving written notice following the other party’s bankruptcy, insolvency or similar instance. The license of the intellectual property and the R&D services are not distinct, as AstraZeneca cannot benefit from the intellectual property absent the R&D services, as those R&D services are used to discover and develop a drug candidate and to enhance the value in the underlying intellectual property, which could not be performed by another party, indicating that the two are high…

Excerpt shortened here; the source contains the full paragraph.

Current wording

We have out-licensed the rights to some of our intellectual property associated with our siRNA stabilization chemistry technology to AstraZeneca in the context of a Research Collaboration, Option and License Agreement dated March 24, 2020, under which we and AstraZeneca will collaborate to discover, develop and commercialize siRNA therapeutics for the treatment of cardiovascular, renal, metabolic and respiratory diseases. AstraZeneca made an upfront cash payment of $60 million, of which $20 million was paid in May 2020 and the remaining $40 million was paid in May 2021. The upfront payment has been allocated evenly between the ten targets on the basis of a benchmarking exercise that took into account the standalone selling price per target, of similar precedent transactions that had been publicly announced by comparable companies. Subsequent milestones are allocated to the target to which they are related. The upfront and milestone payments will be recognized as revenue as the services are provided. We anticipate initiating work on up to five targets in the early stages of the collaboration, with AstraZeneca having the option to extend the collaboration to a further five targets. Under the collaboration, utilizing our technology, we are responsible for designing siRNA molecules against gene targets selected by AstraZeneca, and for manufacturing of material to support GLP toxicology studies and phase 1 clinical trials. We and AstraZeneca will collaborate during the discovery phase, and AstraZeneca will lead clinical development and commercialization of molecules arising from the collaboration. For each target selected under the collaboration, we will be eligible to receive up to $140 million in milestone payments upon the achievement of milestones relating to the initiation of specified clinical trials, the acceptance of specified regulatory filings and the first commercial sale in specified jurisdictions. AstraZeneca has the right to terminate the agreement in its entirety or on a target-by-target basis, for any reason upon specified prior written notice to us. We may terminate the agreement on a target-by-target basis in the event that AstraZeneca begins a legal or administrative proceeding challenging the patentability, validity, ownership or enforceability of our patents. Either party may terminate the agreement on a target-by-target basis upon a material breach by the other party that is not cured within a specified period after receiving written notice, or in its entirety upon giving written notice following the other party’s bankruptcy, insolvency or similar instance. The license of the intellectual property and the R&D services are not distinct, as AstraZeneca cannot benefit from the intellectual property absent the R&D services, as those R&D services are used to discover and develop a drug candidate and to enhance the value in the underlying intellectual property, which could not be performed by another party, indicating that the two are …

Excerpt shortened here; the source contains the full paragraph.

Previous wording

For the three months ended March 31, 2025 and 2024, 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.

Current wording

For the six months ended June 30, 2025 and 2024, 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.