to this Report on Form 6-K. Our actual results may differ materially from those contained in or implied by the forward-looking statements contained in the following discussion and analysis. Overview Silence Therapeutics

Condensed consolidated income statement (unaudited)

Condensed consolidated statement of comprehensive income (unaudited)

Condensed consolidated balance sheet (unaudited)

Condensed consolidated statement of changes in equity (unaudited)

Condensed consolidated statement of cash flows (unaudited)

Notes to the Financial Statements

Three and six months ended June 30, 2024

1. General information

Silence Therapeutics plc and its subsidiaries (together, the Group ) are primarily involved in the discovery, delivery and development of RNA therapeutics. Silence Therapeutics plc (the Company ), a public company limited by shares registered in England and Wales, with company number 02992058, is the Group's ultimate parent company. The Company's registered office is 27 Eastcastle Street, London, W1W 8DH and the principal place of business is 72 Hammersmith Road, London, W14 8TH.

These unaudited condensed consolidated interim financial statements were approved for issue on August 15, 2024.

These unaudited condensed consolidated interim financial statements do not comprise statutory accounts within the meaning of section 434 of the Companies Act 2006. Statutory accounts for the year ended December 31, 2023 were approved by the board of directors on April 8, 2024 and delivered to the Registrar of Companies. The report of the auditors on those accounts was unqualified and did not contain any statement under section 498 of the Companies Act 2006.

The condensed consolidated interim financial statements have not been audited.

Basis of preparation and accounting policies

This unaudited condensed consolidated interim financial statements and this report for the three and six-month reporting periods ended June 30, 2024 have been prepared in accordance with International Accounting Standard 34, Interim Financial Reporting as issued by the International Accounting Standards Board ( IASB ).

The unaudited condensed consolidated financial statements have been prepared on the same basis as the audited annual consolidated financial statements as of and for the year ended December 31, 2023, and, in the opinion of management, reflect all adjustments, consisting of normal recurring adjustments, necessary for the fair presentation of the Company's consolidated balance sheet as of June 30, 2024, the consolidated results of its operations for the three and six months ended June 30, 2024 and 2023, its statements of shareholders' equity for the six months ended June 30, 2024 and 2023 and its consolidated cash flows for the six months ended June 30, 2024 and 2023.

The interim report does not include all of the notes of the type normally included in an annual financial report. Accordingly, these financial statements should be read in conjunction with the Company's audited consolidated financial statements and the accompanying notes for the year ended December 31, 2023 included in the Company's Annual Report for the year ended December 31, 2023 which was prepared in accordance with IFRS ( International Financial Reporting Standards ) as issued by the IASB and filed with the Securities and Exchange Commission on March 13, 2024.

The accounting policies adopted are consistent with those of the previous financial year and corresponding interim reporting periods.

The preparation of these unaudited condensed consolidated interim financial statements requires management to make judgments, estimates and assumptions that affect the application of accounting policies and the reported amounts of assets and liabilities, income and expense. Actual results might differ from these estimates.

The Company's significant accounting policies are disclosed in the audited consolidated financial statements for the year ended December 31, 2023 included in the Annual Report. There have been no changes to the Company's significant accounting policies since the date of the audited consolidated financial statements for the year ended December 31, 2023 included in the Annual Report.

New accounting standards issued by the IASB that are not yet effective and have not been early adopted by the Company

IFRS 18 Presentation and Disclosure in Financial Statements was issued by the International Accounting Standards Board in April 2024. IFRS 18 is effective on January 1, 2027, and is required to be applied retrospectively to comparative periods presented, with early adoption permitted. IFRS 18, upon adoption replaces IAS Standards 1 - Presentation of Financial Statements. IFRS 18 sets out new requirements focused on improving financial reporting by:

requiring additional defined structure to the statement of profit or loss (i.e. consolidated statement of income), to reduce diversity in the reporting, by requiring five categories (operating, investing, financing, income taxes and discontinued operations) and defined subtotals and totals (operating income, income before financing, income taxes and net income),

requiring disclosures in the notes to the financial statements about management-defined performance measures (i.e. non-IFRS measures), and

adding new principles for aggregation and disaggregation of information in the primary financial statements and notes.

IFRS 18 will not impact the recognition or measurement of items in the financial statements, but it might change what an entity reports as its operating profit or loss', due to the classification of certain income and expense items between the five categories of the consolidated income statement. It might also change what an entity reports as operating activities, investing activities and financing activities within the statement of cash flows, due to the change in classification of certain cash flow items between these three categories of the cash flows statement. The Company is currently assessing the impact of adopting IFRS 18.

The Group has incurred recurring losses since inception, including net losses of 15.6 million for the three months ended June 30, 2024 and 17.4 million for the six months ended June 30, 2024. As of June 30, 2024, the Group had accumulated losses of 320.2 million.

The Group expects to incur operating losses for the foreseeable future as it continues its research and development efforts, seeks to obtain regulatory approval of its product candidates and pursues any future product candidates the Group may develop.

To date, the Group has funded its operations through upfront milestone payments from collaboration agreements, equity offerings and proceeds from private placements, as well as management of expenses and other financing options to support its continued operations. In 2023, the Group received a $10.0 million (approximately 7.9 million) milestone payment from the AstraZeneca collaboration and $4.0 million (approximately 3.2 million) in milestone payments from the collaboration with Hansoh Pharmaceutical Group Company Limited ( Hansoh ). In fiscal 2023, the Group also raised gross proceeds of approximately $32.2 million (approximately 25.5 million) pursuant to its at-the-market facility with Jefferies LLC, before deducting 1.0 million in placement agent fees and other expenses. In the first six months of 2024, the Group raised additional proceeds of 15.7 million ($20 million) pursuant to its at-the-market facility with Jefferies LLC, before deducting 0.5 million ($0.6 million) in placement agent fees and other expenses. On February 5, 2024, the Group announced a private placement of 5,714,286 of the American Depositary Shares ( ADSs ), each ADS representing three ordinary shares, at a price of US $21.00 per ADS, with new and existing institutional and accredited investors (the Private Placement ). The aggregate gross proceeds of the Private Placement was approximately 95.4 million ($120 million) before deducting approximately 6.1 million ($7.7 million) in placement agent fees and other expenses. In the second quarter of 2024, the Group received a $10.0 million (approximately 7.9 million) milestone payment from the AstraZeneca collaboration and achieved another $2 million (approximately 1.6 million) in milestone payments from the Hansoh collaboration. As of June 30, 2024, the Group had cash, cash equivalents and U.S. treasury bills of 149.6 million ($189.2 million).

The Group will need to raise additional funding to fund its operating expenses and capital expenditure requirements as it continues to pursue its ongoing clinical development activities. The Group may seek additional funding through public or private financings, debt financings, collaborations or similar arrangements. Specifically, the Group may receive future milestone payments from existing collaboration agreements which will extend the ability to fund

operations. Additional future milestone payments are dependent on achievement of certain development or regulatory objectives that may not occur. The inability to obtain future funding could impact; the Group's financial condition and ability to pursue its business strategies, including being required to delay, limit, reduce or eliminate some of its research and development or product development programs, or being unable to continue operations or unable to continue as a going concern.

Revenue from collaboration agreements for the three and six months ended June 30, 2024 predominately relates to collaboration revenue recognized pursuant to the research collaboration agreement the Company entered into with AstraZeneca in March 2020.

Revenue for the three months ended June 30, 2024 was compromised of 0.6 million of research collaboration income (June 30, 2023: 9.0 million) and no royalty income (June 30, 2023: 0.2 million).

Revenue for the six months ended June 30, 2024 was comprised of 12.9 million of research collaboration income (June 30, 2023: 20.2 million) and 0.1 million of royalty income (June 30, 2023: 0.3 million).

Under the Company's collaboration agreement with Mallinckrodt (the Mallinckrodt Collaboration ), the Company received an upfront cash payment of 16.4 million ($20.0 million) in 2019 and was eligible to receive specified development, regulatory and commercial milestone payments. No milestone payments were achieved under the Mallinckrodt Collaboration during the six months ended June 30, 2024 (six months ended June 30, 2023: nil). In addition to the upfront and potential milestone payments, Mallinckrodt agreed to fund some of the Company's research personnel and preclinical development costs. The Company recognized the initial upfront payment received, milestone payments, payments for personnel costs and other research funding payments over time, in accordance with IFRS 15 para 35 c).

In March 2023, the Company reacquired exclusive worldwide rights to two preclinical siRNA assets under the Mallinckrodt Collaboration, which resulted in a modification of the underlying collaboration agreement. No additional performance obligations were identified as a result of the modification as there were no additional goods or services to be provided by the Company and the modification resulted in the partially satisfied performance obligations relating to the two reacquired targets becoming fully satisfied as the Company was no longer obligated to develop these targets. SLN501, the C3 targeting program, remained under the original terms of the Mallinckrodt Collaboration. The Company accounted for the modification of the collaboration agreement as if it were part of the existing contract as the remaining services to be delivered under the Mallinckrodt Collaboration form part of a single performance obligation that was partially satisfied at the date of contract modification. Therefore, the effect of the contract modification was that the consideration originally received for the two preclinical siRNA assets was reallocated to the SLN501 program. The Company recognized the effect of the contract modification on the measure of progress towards complete satisfaction of the SLN501 performance obligation, and recognized an adjustment to revenue at the date of the contract modification on a cumulative catch-up basis. The Company recognized 8.0 million on the contract modification date in the first quarter of 2023. In relation to the reacquired targets under the Mallinckrodt Collaboration, the two preclinical siRNA assets were recognized at fair value. The fair value of those assets has been determined to be nil. Under the modification, the Company agreed to pay future success-based milestones and low single digit royalties on net sales if the projects advance pursuant to the Mallinckrodt Collaboration. The Company will recognize these variable success-based milestones as an intangible asset at cost when triggered. Any royalties payable will be expensed in cost of sales.

In March 2024, Mallinckrodt notified the Company that it 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 Mallinckrodt Collaboration agreement. During the six months ended June 30, 2024, the Company recognized the remaining 0.5 million in revenue related to the Mallinckrodt Collaboration (six months ended June 30, 2023: 10.2 million).

Under the Company's collaboration agreement with AstraZeneca (the AstraZeneca Collaboration ), the Company received an upfront cash payment of 17.1 million ($20.0 million) in 2020 with a further amount of 30.8 million ($40.0 million) received in May 2021. The Company is also eligible to receive specified development and commercial milestone payments under the AstraZeneca Collaboration as well as tiered royalties on net sales, if any. The Company recognizes the upfront payment and milestone payments over time, in accordance with IFRS 15 para 35 c). During the six months ended June 30, 2024, the Company achieved a milestone payment of approximately 7.9 million ($10.0 million) (six months ended June 30, 2023: 7.9 million). In March 2024, the Company met the obligations for the second product candidate under the AstraZeneca Collaboration. As a result, the remaining revenue of 4.1 million associated with the target was recognized. During the six months ended June 30, 2024, the Company recognized a total of 11.9 million in revenue under the AstraZeneca Collaboration, mainly due to the factors mentioned above (six months ended June 30, 2023: 9.9 million).

The Company entered into a collaboration agreement with Hansoh (the Hansoh Collaboration ) on October 14, 2021. The Company received an upfront cash payment of approximately $16.0 million ( 10.7 million, net of taxes based on the exchange rate at the payment date) in December 2021. The Company is eligible to receive development, regulatory and commercial milestones under the Hansoh Collaboration as well as royalties on Hansoh net product sales, if any. During the six months ended June 30, 2024, the Company achieved a milestone payment of approximately 1.6 million ($2.0 million) (six months ended June 30, 2023: 3.2 million). The Company recognizes the upfront payment and milestone payments over time, in accordance with IFRS 15 para 35 c). During the six months ended June 30, 2024, the Company recognized a total of 0.5 million in revenue under the Hansoh Collaboration (six months ended June30, 2023: 0.1 million).

In December 2018, the Company entered into a settlement and license agreement with Alnylam Pharmaceuticals Inc. ( Alnylam ) pursuant to which the Company settled outstanding patent litigation with Alnylam related to its RNAi product ONPATTRO. As part of the settlement, the Company licenses specified patents to Alnylam, and Alnylam pays the Company a tiered royalty of up to one percent of net sales of ONPATTRO in the European Union. The Company was eligible to receive these royalties through December 2023. The Company invoiced Alnylam quarterly in arrears based on sales data for that quarter as reported to the Company by Alnylam. Royalty revenue is recognized based on the level of sales when the related sales occur. During the six months ended June 30, 2024, the Company recognized a total of 0.1 million in royalty income from Alnylam (six months ended June 30, 2023: 0.3 million).

4. Segment reporting

In 2024, the Group operated in the specific technology field of RNA therapeutics.

The Group has identified its Chief Executive Officer as the chief operating decision maker ( CODM ). For the three and six months ended June 30, 2024 and 2023, the CODM determined that the Group had one business segment, the development of RNAi-based therapeutics. This is consistent with reporting to senior management. The information used internally by the CODM is the same as that disclosed in the financial statements.

An analysis of the Group's assets and revenues by location is shown below:

5. Loss per ordinary share (basic and diluted)

The calculation of the loss per ordinary share is based on the loss for the three months ended June 30, 2024 and on the weighted average number of ordinary shares in issue during the three months ended June 30, 2024 of 140,208,929 (three months ended June 30, 2023: 108,487,501).

The calculation of the loss per ordinary share is based on the loss for the six months ended June 30, 2024 and on the weighted average number of ordinary shares in issue during the six months ended June 30, 2024 of 136,045,022 (six months ended June 30, 2023: 108,194,728).

The options outstanding at June 30, 2024 and 2023 are considered to be anti-dilutive as the Group is loss-making.

7. Contract liabilities

Contract liabilities comprise entirely deferred revenue in respect of the Mallinckrodt Collaboration, AstraZeneca Collaboration and Hansoh Collaborations. The current contract liabilities represent the amount of estimated revenue to be reported in the next twelve months related to amounts invoiced to the Company's partners. Current and non-current contract liabilities include future revenue from collaborations, recharged expenses, upfront payments, and milestones achieved through June 30, 2024.

An additional 2.1 million current tax asset was recognized in respect of research and development tax credits in the three months ended June 30, 2024 (three months ended June 30, 2023: 2.2 million). In addition to this credit, the Company has recognized 0.1 million of income from the R&D expenditure credit (RDEC) scheme from the UK government. This income is reflected in the income statement within research and development costs for the three months ended June 30, 2024 (three months ended June 30, 2023: 0.1 million). The Company had no foreign tax expense for the three months ended June 30, 2024 (three months ended June 30, 2023: 0.2 million). In the three months ended June 30, 2024, 0.2 million of tax expense was recognized on withholding tax (three months ended June 30, 2023: 0.4 million). Since the Group does not have an establishment or place of business in China, the Group is subject to withholding tax on gross income from dividends, interest, lease of property, royalties and other China-source passive income.

An additional 3.7 million current tax asset was recognized in respect of research and development tax credits in the six months ended June 30, 2024 (six months ended June 30, 2023: 4.8 million). In addition to this credit, the Company has recognized 0.4 million of income from the RDEC scheme from the UK government. This income is reflected in the income statement within research and development costs for the six months ended June 30, 2024 (six months ended June 30, 2023: 0.1 million). The Company had a foreign tax expense of 0.2 million for the six months ended June 30, 2024 (six months ended June 30, 2023: 0.4 million). In the six months ended June 30, 2024, 0.2 million of tax expense was recognized on withholding tax (six months ended June 30, 2023: 0.4 million). Since the Group does not have an establishment or place of business in China, the Group is subject to withholding tax on gross income from dividends, interest, lease of property, royalties and other China-source passive income.

The current tax asset at June 30, 2024 was 12.9 million, which was comprised of 3.7 million in respect of research and development activities and 0.4 million from the RDEC scheme for the six months ended June 30, 2024 and 8.7 million in respect of the year ended December 31, 2023 compromising 7.8 million in respect of research and development activities and 0.9 million from the RDEC scheme.

The Group has only one class of shares. All ordinary shares have equal voting rights and rank pari passu for the distribution of dividends.

On October 15, 2021, the Company entered into an Open Market Sale AgreementSM (the Sales Agreement ), with Jefferies LLC ( Jefferies ), under which Jefferies, as the Company's exclusive agent, at its discretion and at such times that the Company may offer and sell up to a maximum of $100.0 million of ADSs from time to time. Under the terms of the Sales Agreement, Jefferies may sell the ADSs at market prices by any method that is deemed to be an at the market offering as defined in Rule 415 under the Securities Act of 1933, as amended. The ADSs offered under the

Sales Agreement are being offered pursuant to a registration statement on Form F-3 that became effective on October 22, 2021. During the year ended December 31, 2023, the Company sold 3.4 million ADSs for net proceeds of approximately $32.2 million (approximately 25.5 million), before deducting 1.0 million in placement agent fees and other expenses. During the six months ended June 30, 2024, the Company sold 1.1 million ADSs for net proceeds of approximately 15.7 million ($20 million), before deducting 0.5 million ($0.6 million) in placement agent fees and other expenses. As of June 30, 2024, approximately $47 million of ADSs remained available under the Sales Agreement.

On February 5, 2024, the Group announced a private placement of 5,714,286 of the Company's ADSs, each representing three ordinary shares, at a price of US $21.00 per ADS, with new and existing institutional and accredited investors (the Private Placement ). The aggregate gross proceeds of the Private Placement was approximately 95.4 million ($120 million) before deducting approximately 6.1 million ($7.7 million) in placement agent fees and other expenses.

Details of the ordinary shares (including ordinary shares in the form of ADSs) issued by the Company during the six months ended June 30, 2024 are as follows:

10. Related party transactions

There were no related party transactions between the Company and its directors, executive officers, or holders of more than 10% of its outstanding share capital and their affiliates, in the six months ended June 30, 2024.

11. Subsequent events

MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

You should read the following discussion and analysis of financial condition and operating results together with our unaudited financial statements as of and for the three and six months ended June 30, 2024 and the related notes to those unaudited condensed consolidated financial statements included as Exhibit 99.1 to this Report on Form 6-K, as well as our audited consolidated financial statements and related notes as disclosed in our Annual Report on Form 20-F for the year ended December 31, 2023 filed with the Securities and Exchange Commission, or the SEC, on March 13, 2024.

The statements in this discussion with respect to our plans and strategy for our business, including expectations regarding our future liquidity and capital resources and other non-historical statements, are forward-looking statements. These forward-looking statements are subject to numerous risks and uncertainties, including the risks and uncertainties described in Exhibit 99.1 to this Report on Form 6-K. Our actual results may differ materially from those contained in or implied by the forward-looking statements contained in the following discussion and analysis.

Silence Therapeutics plc ( we , us , our , the Company or Silence ) is 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 precision engineered product candidates designed to accurately 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.

Our Product Candidate, Zerlasiran (SLN360)

Zerlasiran (SLN360) is our wholly owned siRNA product candidate 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. Elevated Lp(a) is a genetically determined cardiovascular risk factor affecting up to 20% of the world's population and is associated with a high risk of heart attack, stroke and aortic stenosis. There are currently no approved medicines that selectively lower Lp(a). In February 2022, we reported positive results from the single-ascending dose portion of the APOLLO Phase 1 program evaluating zerlasiran in 32 healthy adults with Lp(a) levels at or over 150 nmol/L. In the single dose trial, participants in the top two zerlasiran single dose groups (300 mg and 600 mg) were observed to have experienced up to a 96% and 98% median reduction in Lp(a) levels, respectively, and median reductions of up to 71% and 81% from baseline persisted at 150 days. Further analysis showed median time-averaged Lp(a) reductions over 150 days exceeded 80% in the zerlasiran 300 mg and 600 mg dose groups. At day 365, some participants still exhibited substantial knockdown of Lp(a) to approximately 50% of baseline. Zerlasiran was well tolerated with no serious safety concerns reported. In November 2023, we reported positive top-line results from the multiple dose portion of the APOLLO program in 36 adults with baseline Lp(a) levels at or over 150 nmol/L and stable atherosclerotic cardiovascular disease, or ASCVD. In the multiple dose trial, zerlasiran (200 mg, 300 mg and 450 mg) was administered twice subcutaneously at two different dosing intervals. Data demonstrated a significant reduction from baseline in Lp(a) of up to 99% at 90 days following injection of repeated doses. Lp(a) levels remained approximately 90% lower than baseline at 201 days (end of treatment period) at the two highest doses. A dose dependent reduction in low-density lipoprotein cholesterol, or LDL cholesterol, and apolipoprotein B, or ApoB, was also observed. Zerlasiran was well tolerated; no clinically important safety concerns were identified. Zerlasiran is currently being evaluated in the ALPACAR-360 Phase 2 clinical trial in patients with Lp(a) levels at or over 125 nmol/L at high risk of ASCVD events. In March 2024, we announced the trial met its primary endpoint and demonstrated statistically significant reductions in Lp(a) to week 36. In June 2024, we announced the study also demonstrated highly significant and sustained reductions in Lp(a) to week 48 (end of treatment period). Zerlasiran was well tolerated with no serious safety issues observed during the treatment period. We are continuing to prepare and finalize development plans for the zerlasiran Phase 3 program, which is expected to start in the first half of 2025 dependent on feedback from regulatory agencies such as the U.S. Food and Drug Administration, or the FDA. In addition, we are engaged in global partnership discussions for Phase 3 development and potential future commercialization.

Our Product Candidate, Divesiran (SLN124)

Divesiran (SLN124) is our wholly owned siRNA 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, including 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 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 myelpofibrosis and Acute Myeloid Leukemia. The aim of treatment is to maintain HCT 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 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 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 May 2021, we observed proof-of-mechanism with divesiran in the GEMINI Phase 1 clinical trial in healthy volunteers. In the GEMINI trial, divesiran was observed to increase average hepcidin approximately four-fold and reduce serum iron by approximately 50% after a single dose with effects persisting for at least two months. Data were presented at the American Society of Hematology, or ASH, 2021 Annual Meeting and published in the American Journal of Hematology in July 2023. Divesiran is being studied in the SANRECO Phase 1/2 clinical trial in PV patients. In June 2024, we reported positive results from the ongoing Phase 1 portion of the SANRECO trial. The 34-week, open-label Phase 1 clinical trial 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. The interim data included 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 (defined as entering the study with baseline HCT levels at 45% or less) and 8 patients have HCT levels over 45% at baseline. The interim data showed divesiran eliminated the need for phlebotomy in all well-controlled patients following infrequent dosing and was well tolerated with no major safety issues. Based on these results, we plan to advance divesiran into Phase 2 development by the end of 2024. Divesiran has received FDA Fast Track and orphan disease designations for PV.

The potential of our mRNAi GOLD platform has been validated through ongoing research and development collaborations with leading pharmaceutical companies, such as AstraZeneca plc, or AstraZeneca and Hansoh Pharmaceutical Group Company Limited, or Hansoh. These collaborations collectively represent over a dozen potential pipeline programs and approximately $5 billion in potential milestones plus royalties.

We believe the potential for our mRNAi GOLD platform to address disease-associated genes in the liver is substantial. Only around one percent of the approximately 14,000 liver expressed genes have been targeted by publicly known siRNAs. Once in the clinic, early-stage GalNAC-conjugated RNAi programs have shown a much greater likelihood of advancement from the current phase of development compared to the pharmaceutical industry average. We aim to maximize our mRNAi GOLD platform by advancing both our proprietary and partnered pipelines.

Second Quarter 2024 and Recent Business Highlights

Zerlasiran (cardiovascular disease)

-In June 2024, we announced positive topline 48-week data from the ALPACAR-360 Phase 2 clinical trial in patients with elevated Lp(a).

oZerlasiran produced highly significant and sustained reductions in Lp(a) to week 48 (end of treatment period) and was observed to be well tolerated. Based on this data, we are planning to advance the program into Phase 3 development, dependent on feedback from the FDA.

-In April 2024, additional results from the APOLLO Phase 1 clinical trial of zerlasiran in subjects with elevated Lp(a) were published in the Journal of the American Medical Association (JAMA). Published findings demonstrated zerlasiran was well-tolerated and significantly reduced Lp(a) after single and multiple dosing. Results from the single ascending dose portion of the trial were previously published in the April 2022 issue of JAMA.

Divesiran (hematological disorders)

-In June 2024, we announced positive results from the ongoing SANRECO Phase 1 clinical trial of divesiran in PV patients.

oDivesiran eliminated the need for phlebotomy in all well-controlled patients following infrequent dosing and was well tolerated. Based on this data, we are planning to advance divesiran into Phase 2 development.

mRNAi GOLD Partnered Program Updates

-In June 2024, we achieved a $2.0 million research milestone payment under our collaboration with Hansoh.

AstraZeneca Collaboration

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, or the AstraZeneca Collaboration. 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.

The collaboration covered 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 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 under the collaboration, 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.

Mallinckrodt Collaboration

In July 2019, we entered into a collaboration agreement with Mallinckrodt plc, or Mallinckrodt, to develop and commercialize RNAi drug targets designed to silence the complement cascade in complement-mediated disorders, or the Mallinckrodt Collaboration. In connection with the entry into the collaboration, Mallinckrodt made an upfront cash payment to us of $20.0 million (equivalent to 16.4 million as of the payment date). 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 (equivalent to 4.0 million as of the payment date). Under the 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.

In March 2023, we reacquired exclusive worldwide rights from Mallinckrodt to the two undisclosed preclinical complement targets. Under the terms of the modified collaboration, 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 terms of the collaboration. 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.

Hansoh Collaboration

On October 15, 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, or the Hansoh Collaboration. Under the terms of the Hansoh Collaboration, we retain exclusive rights to the first two targets in all territories except the China Region (Greater China, Hong Kong, Macau and Taiwan). Hansoh has the exclusive option to license rights to those two targets in the China Region following the completion of Phase 1 clinical trials. We will be responsible for all activities up to option exercise and will retain responsibility for development outside the China region post Phase 1 clinical trials. Hansoh will also have the exclusive option to license global rights to a third target at the point of the filing of an Investigational New Drug, or IND, application. Hansoh will be responsible for all development activities post option exercise for the third target. Hansoh made a $16 million upfront payment to us in December 2021. Under the Hansoh Collaboration, 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 $4.0 million from the collaboration. In 2024, we achieved an additional preclinical milestone of $2.0 million from the Hansoh Collaboration. We are eligible to receive up to $1.3 billion in additional development, regulatory and commercial milestones. We will also receive royalties tiered from low double-digit to mid-teens on Hansoh net product sales.