NuCana : Annual Report - 2025
NCNA
Published on 05/06/2026 at 07:31 am EDT
A New Era in Oncology
ANNUAL REPORT
2025
For the year ended 31 December 2025
A New Era in Oncology
Directors Hugh Griffith Andrew Kay Martin Mellish Cyrille Leperlier Elliott Levy
Adam George (retired 21 March 2025)
Bali Muralidhar (retired 21 October 2025)
Secretary
Martin Quinn
Auditors
Ernst & Young LLP 144 Morrison Street Edinburgh
EH3 8EX U.K.
Registered Office
77-78 Cannon Street London
EC4N 6AF U.K.
Global Headquarters
Lochside House 3 Lochside Way Edinburgh EH12 9DT
U.K.
E: [email protected] https://www.nucana.com
Registered No. 03308778
Contents
Strategic report 2
Directors' report 16
Directors' remuneration report 19
Statement of directors' responsibilities 33
Independent auditor's report to the members of NuCana plc 35
Financial statements 43
Notes to the financial statements 50
Advisers 75
rsetproarttegic
introduction
NuCana was incorporated under the laws of England and Wales on 28 January 1997 under the name Biomed (UK) Limited and commenced operations in 2008. On 28 April 2008, we changed our name to NuCana BioMed Limited. On 29 August 2017, we re-registered as a public limited company and changed our name to NuCana plc. On 2 October 2017, we completed our initial public offering of American Depositary Shares, or ADSs, on the Nasdaq Global Select Market. On 9 November 2023 we transferred our listing to The Nasdaq Capital Market. Our ADSs are traded under the symbol "NCNA". NuCana plc on behalf of itself and its subsidiaries, NuCana, Inc., NuCana Limited (incorporated in Ireland) and NuCana Biomed Trustee Company Limited (which may be referred to as "the Group", "the Company", "we", "us" or "our"), is required to produce a strategic report complying with the requirements of the Companies Act 2006.
overview
We are a clinical-stage biopharmaceutical company focused on significantly improving treatment outcomes for patients with cancer by applying our ProTide™ technology to transform some of the most widely prescribed chemotherapy agents, nucleoside analogs, into more effective and safer medicines, while also enabling the therapeutic development of nucleosides that have historically failed due to resistance mechanisms and metabolic limitations. While these conventional agents remain part of the standard of care for the treatment of many solid and haematological tumours, they have significant shortcomings that limit their efficacy and they are often poorly tolerated. Utilising our proprietary technology, we are developing new anti-cancer medicines, ProTides, designed to overcome the key limitations of nucleoside analogs and generate much higher concentrations of anti-cancer metabolites in cancer cells. Our pipeline includes NUC-7738 and NUC-3373.
NUC-7738 is a novel anti-cancer agent that disrupts RNA polyadenylation, profoundly impacts gene expression in cancer cells, and targets multiple aspects of the tumour microenvironment (TME). NUC-7738 is being evaluated in a Phase 1/2 clinical study (NuTide:701). The Phase 1 part evaluated NUC-7738 as a monotherapy in patients with advanced solid tumours. The Phase 2 part is evaluating NUC-7738 in combination with pembrolizumab in patients with PD-1 inhibitor-resistant melanoma. This Phase 2 part consists of an initial dose-confirmation stage followed by an ongoing expansion stage and we expect to report data from this expansion study in 2026. We also anticipate seeking regulatory guidance from the U.S. Food and Drug Administration (FDA) in 2026 regarding the potential registrational pathway for NUC-7738 in melanoma.
NUC-3373 is a targeted Thymidylate Synthase (TS) inhibitor designed to overcome key pharmacologic limitations associated with other TS inhibitors. NUC-3373 is a novel chemical entity derived from the TS inhibitor and nucleoside analog 5-fluorouracil (5-FU), which remains one of the most widely used chemotherapeutic agents worldwide and is included on the World Health Organization's List of Essential Medicines. NUC-3373 has been designed to enhance TS inhibition, improve tolerability, and reduce certain administration burdens associated with other TS inhibitors including 5-FU. NUC-3373 has been evaluated in a Phase 1 clinical study for patients with advanced solid tumours; a Phase 1b/2 clinical study, in combination with other agents, for patients with metastatic colorectal cancer; a randomised Phase 2 clinical study of NUC-3373, in combination with other agents, for the second-line treatment of patients with advanced colorectal cancer; and a Phase 1b/2 modular clinical study of NUC-3373 in combination with the PD-1 inhibitor pembrolizumab for patients with advanced solid tumours and NUC-3373 in combination with docetaxel in patients with lung cancer. We are currently evaluating optimal combinations and indications for potential further clinical studies of NUC-3373.
The treatment of cancer can be divided into three principal modalities: surgery, radiotherapy and therapeutics. Therapeutics include chemotherapy, immunotherapy, cell-based therapies and targeted and hormonal agents. The backbone of treatment for patients with cancer consists of chemotherapeutics, which are expected to achieve global revenues of approximately $106 billion by 2030. Despite significant progress having been made in the development of new therapeutics, most patients continue to receive chemotherapy either in combination with other treatments or as single agents at some point in their treatment pathway. Thus, we believe that more effective and safer chemotherapeutic agents will have an important role to play in the treatment of patients with cancer for the foreseeable future. We are transforming an important class of chemotherapeutic agents, nucleoside analogs, by applying a well-validated medicinal chemistry approach to overcome their limitations.
strategic report/
01
Through harnessing the power of phosphoramidate chemistry, we convert nucleoside analogs into activated nucleotide analogs with the addition of a phosphate group, which is protected by specific combinations of aryl, ester and amino acid groupings. By adding and protecting this phosphate group, we design our ProTides to avoid or overcome the limitations associated with breakdown, uptake, activation and administration of nucleoside analogs. In the antiviral field, this phosphoramidate chemistry approach has resulted in the most successful drug launches in the history of medicine, Gilead's sofosbuvir, or Sovaldi® which is also a key component of Harvoni®, Vosevi® and Epclusa®; and tenofovir alafenamide fumarate (TAF), which is a key component of Biktarvy®, Genvoya®, Descovy®, Symtuza®, Vemlidy®, and Odefsey®. In addition, phosphoramidate chemistry is used in Gilead's remdesivir, or Veklury®, for the treatment of patients with COVID-19.
NUC-7738 is a phosphoramidate prodrug of 3'-deoxyadenosine (3'-dA), designed to generate higher intracellular concentrations of the active anti-cancer metabolite 3'-deoxyadenosine triphosphate (3'-dATP) compared with administration of 3'-dA. In preclinical studies, NUC-7738 increased intracellular 3'-dATP levels in human cancer cell lines, consistent with its design to address known limitations associated with the metabolism and activation of 3'-dA.
The principal mechanism of action of NUC-7738 is disruption of RNA polyadenylation, resulting in broad changes in gene expression affecting multiple cellular pathways relevant to tumour biology. These effects have been observed across a range of cancer cell lines and translational models, including patient-derived organoids (PDOs) and PDO-tumour-infiltrating lymphocyte (TIL) co-culture systems. Affected pathways include those associated with antigen presentation and T-cell activation, PD-L1 processing, cancer cell metabolism, and ribosomal biogenesis. Comparable changes were not observed in resting peripheral blood mononuclear cells, suggesting a selective effect in malignant cells. Based on these observations, we believe NUC-7738 has potential as a rational combination partner, given its ability to modulate both tumour-intrinsic pathways and pathways within the tumour microenvironment. While current clinical evaluation is focused on combination with immune checkpoint inhibitors, the observed multi-pathway effects provide a rationale for assessment in additional therapeutic combination strategies.
NUC-7738 is in the Phase 2 part of a Phase 1/2 clinical study (NuTide:701) which evaluated NUC-7738 as a monotherapy in patients with advanced solid tumours and is currently evaluating NUC-7738 in combination with pembrolizumab in patients with melanoma. In September 2021, we presented interim data from the first 29 patients treated in this study at the European Society of Medical Oncology (ESMO) Congress. These interim data indicated a favourable pharmacokinetic and safety profile for NUC-7738. Additionally, three case studies highlighted patients with encouraging tumour reductions who remained on NUC-7738 treatment for extended periods of time. In September 2022, we presented data from the Phase 1 dose-finding part of the NuTide:701 study in 38 patients at ESMO. NUC-7738 had a favourable safety profile with low rates of treatment-related AEs (TRAEs), very few Grade 3 TRAEs, and no patients experiencing Grade 4 or 5 TRAEs. The maximum tolerated dose was established at 1350 mg/m2. Encouraging signals of anti-tumour activity across a range of tumour types were observed with numerous patients staying on treatment for extended periods, including one patient with metastatic melanoma who became eligible for complete surgical resection following eleven months of treatment with NUC-7738. In April 2023, we presented data at the American Association of Cancer Research (AACR) Annual Meeting indicating that NUC-7738 reduces soluble PD-L1 and exosomal PD-L1
in melanoma cell lines and in patients. Soluble and exosomal expression of PD-L1 have been implicated in resistance to PD-L1 and PD-1 inhibitors and these data indicate that NUC-7738 has the potential to act as an immune sensitizer and as an effective combination partner for PD-L1 pathway inhibitors.
In October 2023, we presented interim data from the Phase 2 part of the NuTide:701 study at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2023. NUC-7738 was well tolerated both as a monotherapy and in combination with pembrolizumab. Encouraging signs of efficacy, including tumour volume reductions and prolonged time on treatment, were observed in both the monotherapy and combination cohorts. In the combination cohort of melanoma patients, who had all been previously treated with PD-1 inhibitor-based therapy, numerous patients achieved tumour volume reductions and prolonged time on treatment. One patient who was refractory to the anti-PD-1 plus anti-CTLA-4 therapy combination of nivolumab plus ipilimumab achieved a 50% reduction in tumour volume on NUC-7738 plus pembrolizumab. Seven of the eleven patients recruited remained on treatment at the time of the data cut-off for the presentation. Patient tumour biopsy data showed that, following treatment with NUC-7738 plus pembrolizumab, expression of PD-1 was reduced and CD8+ T-cells increased, indicating that NUC-7738 may have the ability to potentiate immunotherapy. This finding provides a rationale as to why NUC-7738 in combination with PD-1 inhibitor-based therapy, such as pembrolizumab, may be effective in patients who have progressed on prior immunotherapy.
In April 2024, we presented data from the NuTide:701 study at the AACR Annual Meeting. First, NUC-7738 was found to increase polyunsaturated fatty acids within the TME, which is indicative of a shift to a less aggressive cancer type, and to decrease monounsaturated fatty acids which are associated with malignant behaviour and chemotherapy resistance. In addition, NUC-7738 was shown to reduce lipids associated with protection against cancer cell death and to increase lipids associated with cancer cell death. Multi-modal imaging indicated that this lipid reprogramming is a result of the alteration in enzymes associated with lipid metabolism. Second, data from cancer cell lines, confirmed using paired biopsies from patients treated with NUC-7738, demonstrated that NUC-7738 caused PolyA tail shortening and significantly modulated the stability of RNAs that are important for translational control of protein synthesis. Furthermore, data also highlighted NUC-7738's potential to influence the regulation of genes critical for cancer cell growth and survival.
Additionally, in September 2024, we presented promising data from the Phase 2 part of the NuTide:701 study at ESMO on NUC-7738 in combination with pembrolizumab for patients with metastatic melanoma who were refractory to or had relapsed on prior PD-1 inhibitor-based therapy. The data showed that 9 of the 12 patients achieved disease control when treated with NUC-7738 in combination with pembrolizumab. One of these patients, who had received two prior lines of PD-1 inhibitor-based therapy and had progressed on their latest treatment of ipilimumab plus nivolumab within two months, achieved a confirmed Partial Response with a 55% reduction in tumour volume. Another patient, who had progressed on three prior lines of PD-1 inhibitor-based therapy, achieved a Partial Response (unconfirmed) with a 32% reduction in tumour volume. These results showed encouraging median progression-free survival (PFS) of over five months for patients receiving NUC-7738 plus pembrolizumab, which is highly atypical in this patient population.
In June 2025, we initiated an expansion of the Phase 2 part of the NuTide:701 study evaluating NUC-7738 in combination with
pembrolizumab in patients with metastatic melanoma and expect to report final data from this expansion study in 2026. In October 2025, we presented data at ESMO describing a novel model system evaluating the synergistic effects of NUC-7738 and PD-1 inhibition in primary organoids derived from patients with renal cell carcinoma (RCC). Using PDOs from 10 patients with RCC and autologous TILs, co-culture experiments demonstrated enhanced tumour cell killing with the combination of NUC-7738 and PD-1 inhibitors compared to PD-1 inhibition alone. These findings support the potential of NUC-7738 in combination with PD-1 inhibitors, including in tumour types that have progressed following prior anti-PD-1 therapy, through modulation of tumour-intrinsic and tumour microenvironment pathways associated with disruption of RNA polyadenylation and downstream changes in gene expression. The data presented at ESMO are consistent with the proposed mechanism of action of NUC-7738 and with observations from the ongoing Phase 2 NuTide:701 clinical study. In December 2025, we presented further data from the Phase 2 part of the NuTide:701 study at the ESMO Immuno-Oncology Congress, including one patient whose disease converted to a complete metabolic response with no detectable active disease. The presentation also included preliminary results from 9 patients enrolled in the Phase 2 expansion cohort of the NuTide:701 study, with evidence of clinical activity and the combination continuing to be well-tolerated. We anticipate seeking regulatory guidance from the FDA in 2026 regarding the potential registrational pathway for NUC-7738 in melanoma.
In preclinical studies, NUC-3373 was shown to be a targeted TS inhibitor and overcame the key limitations associated with 5-FU, generating significantly higher intracellular levels of the active anti-cancer metabolite than 5-FU while not generating toxic metabolites commonly associated with 5-FU's side effects. NUC-3373 has been evaluated in a Phase 1 clinical study, known as the NuTide:301 study, in 59 patients with advanced solid tumours. The maximum tolerated dose and schedule for NUC-3373 monotherapy was established as 2500 mg/m2 weekly. NUC-3373 generated high levels of the active anti-cancer metabolite inside the patients' cells and demonstrated a favourable pharmacokinetic and safety profile. Evidence of durable anti-cancer activity was observed, with at least 10 patients remaining on treatment for more than four months and three of these patients achieving prolonged stable disease with PFS lasting more than nine months. The results of this study suggest that NUC-3373 has the potential to overcome the limitations associated with 5-FU and may be capable of achieving anti-cancer activity even in patients who have progressed on prior treatment with a fluoropyrimidine.
NUC-3373 was evaluated in a Phase 1b/2 study, known as the NuTide:302 study, in 107 patients with metastatic colorectal cancer in which NUC-3373 was combined with agents typically used with 5-FU, including leucovorin, irinotecan, oxaliplatin and bevacizumab. In October 2019, we presented interim data from this study at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. These interim data supported the previously reported favourable pharmacokinetic profile of NUC-3373. In April 2021, we presented further interim data from this study at the virtual AACR Annual Meeting. These interim data highlighted 38 patients who received NUC-3373 either as monotherapy or in combination with leucovorin. Eleven patient case studies showed NUC-3373's ability to stabilise disease in a heavily pre-treated population of patients with advanced colorectal cancer and achieve prolonged durations of PFS. Several patients achieved periods of PFS that were longer than those achieved on previous regimens and tumour size reductions were observed, including in a patient known to be refractory to all prior fluoropyrimidine-containing regimens. NUC-3373 was also shown to have a favourable safety
profile with no hand-foot syndrome observed, which is associated with the toxic metabolite, FBAL, and no neutropenia or Grade 3 or 4 mucositis or diarrhoea adverse events, which are associated with the toxic metabolite, FUTP. In September 2022, we presented data from this study at ESMO. These data demonstrated promising anti-tumour activity and a favourable safety and pharmacokinetic profile in combination with leucovorin and either irinotecan (NUFIRI) or oxaliplatin (NUFOX) in heavily pre-treated patients with metastatic colorectal cancer. In October 2023, we presented data from this clinical study at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2023. In this study, NUC-3373 demonstrated a favourable safety profile when combined with NUFIRI and bevacizumab (NUFIRI + bev) and with NUFOX and bevacizumab (NUFOX + bev). Additionally, both regimens demonstrated encouraging signs of efficacy, including tumour volume reductions in patients who were refractory to or had progressed on prior fluoropyrimidine treatment. Several patients achieved a longer PFS, on NUFIRI + bev and NUFOX + bev as compared to the PFS achieved in their first-line treatment with 5-FU-based therapy.
A randomised Phase 2 study, known as the NuTide:323 study, comparing NUC-3373 in combination with NUFIRI + bev, with 5-FU in combination with irinotecan, leucovorin, and bevacizumab (FOLFIRI + bev), for the second-line treatment of patients with advanced colorectal cancer was initiated in 2022. In October 2023, we presented data from the NuTide:323 study at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2023. The study recruited well, and no new safety signals were observed from the aggregated safety data from the first 40 patients enrolled. In August 2024, we announced the discontinuation of the NuTide:323 study following a pre-planned initial analysis and recommendation from the NuTide:323 study Steering Committee. While there were prognostic imbalances favouring the control arm, the Steering Committee believed that NUFIRI + bev was unlikely to achieve the study's primary objective of superior PFS compared to the control arm of FOLFIRI + bev in the final analysis. In all three arms, the treatment regimens were observed to have a favourable safety profile and to be generally well-tolerated, with only 12 of the 175 patients, four patients in each arm, discontinuing treatment due to adverse events.
In order to evaluate the therapeutic potential of NUC-3373 across other cancer indications and the significant global commercial opportunity for a targeted TS inhibitor, we initiated a Phase 1b/2 modular study, known as the NuTide:303 study. The NuTide:303 study evaluated NUC-3373 in combination with the PD-1 inhibitor pembrolizumab in patients with advanced solid tumours (Module 1) and in combination with docetaxel for patients with lung cancer (Module 2). In November 2024, we published data from the NuTide:303 study in medRxiv, an online preprint server for health sciences research. Module 1 included 12 patients who had exhausted all other treatment options, with the majority of patients having received prior PD-1 inhibitor-based therapy. Significant tumour volume reductions and prolonged PFS were observed, including a patient with urothelial bladder cancer who achieved 100% reduction in their target lesions and a patient with cutaneous melanoma who achieved an 81% reduction in tumour volume. These signals of anti-cancer activity indicate that NUC-3373, in addition to being a targeted TS inhibitor, may promote an anti-tumour immune response and potentiate the activity of immune checkpoint inhibitors. We are currently evaluating optimal combinations and indications for potential further clinical studies of NUC-3373.
Acelarin is a ProTide transformation of the nucleoside analog gemcitabine. In clinical studies, Acelarin was well tolerated and
showed anti-cancer activity in patients who were refractory to, or had progressed on, prior gemcitabine treatment. Disease control, as well as tumour shrinkages, including partial and complete responses, were observed in challenging indications, including ovarian and biliary tract cancers. In March 2022, we announced the discontinuation of the Phase 3 clinical study, also known as the NuTide:121 study, investigating Acelarin in combination with cisplatin versus the standard of care, gemcitabine plus cisplatin, in patients with previously untreated locally advanced or metastatic biliary tract cancer. This decision was made following a pre-planned futility analysis by the study's Independent Data Monitoring Committee. Although a higher objective response rate, as assessed by Blinded Independent Central Review, was observed in the Acelarin plus cisplatin arm, this did not translate into an overall survival benefit. We are assessing future development options for Acelarin in biliary tract cancer which may explore lower doses of Acelarin, alternative combination partners or specific sub-sets of biliary tract cancer patients. Indications other than biliary tract cancer are also being assessed as future development options for Acelarin.
Our proprietary ProTide technology was invented in the Cardiff University laboratory of our late Chief Scientific Officer, Professor Christopher McGuigan, who conceived of and filed the original composition of matter patents for our initial ProTides. The unique feature of his discovery was the specific combination of aryl, ester and amino acid groupings that protect the activated, or phosphorylated, nucleoside analog. This phosphoramidate chemistry approach is the key to the ProTide technology. Every ProTide grouping is distinct, and Professor McGuigan and his team synthesised and tested thousands of compounds in order to identify the optimal ProTide grouping for each underlying nucleoside analog.
We have licensed what we believe to be the foundational patent estate for the application of phosphoramidate chemistry in oncology. We own granted patents in key markets, including the United States, Europe, China and Japan, protecting the composition of matter of NUC-7738 and NUC-3373 and other of our product candidates. Professor McGuigan's work preceded and helped lead to the development of several FDA-approved anti-viral drugs containing ProTides, including: sofosbuvir, or Sovaldi®, which is also a key component of Harvoni®, Vosevi® and Epclusa®; and tenofovir alafenamide fumarate (TAF), which is a key component of Biktarvy®, Genvoya®, Descovy®, Symtuza®, Vemlidy®, and Odefsey®; and remdesivir, or Veklury®.
We are led by Hugh Griffith, our founder and Chief Executive Officer (CEO), who brings over 30 years of experience in the biopharmaceutical industry, including at Abbott Laboratories (now AbbVie Inc.) and Parke-Davis Warner Lambert (now Pfizer Inc.). Before founding NuCana, he was Chief Operating Officer at Bioenvision, Inc. from start-up through its acquisition by Genzyme Corporation. While at Bioenvision, he was instrumental in developing and commercialising clofarabine, a nucleoside analog for the treatment of paediatric acute leukaemia.
our strategy
"Our goal is to improve the survival outcomes and
the safety profile of treatment for patients with
cancer across a wide range of indications."
Our strategy includes the following key components:
Rapidly develop NUC-7738 as a treatment for patients with cancer.
In June 2025, we initiated an expansion of the Phase 2 part of the NuTide:701 study of NUC-7738 in combination with pembrolizumab in patients with metastatic melanoma and we expect to announce data from this NuTide:701 expansion study in 2026. We also anticipate obtaining regulatory guidance from the FDA on our registrational strategy for NUC-7738 in melanoma in 2026.
In December 2025, we presented data from the NuTide:701 study at the annual ESMO Immuno-Oncology Congress on NUC-7738 in combination with pembrolizumab for patients with metastatic melanoma who were refractory to or had relapsed on prior PD-1 inhibitor-based therapy. The data from the Phase 2 initial dose-confirmation stage of the NuTide:701 study showed that 9 of the 12 patients achieved disease control when treated with NUC-7738 in combination with pembrolizumab. Two patients achieved Partial Responses, one confirmed with a 55% reduction in tumour volume and one unconfirmed with a 32% reduction in tumour volume. Seven patients achieved stable disease including one ongoing stable disease converting to a complete metabolic response with no detectable active disease. These results showed encouraging median PFS of over five months.
Identify optimal combinations and indications for development of NUC-3373.
In October 2025, we published data in medRxiv from the Phase 1b/2 modular NuTide:303 clinical study of NUC-3373 in combination with the PD-1 inhibitor pembrolizumab for patients with advanced solid tumours and in combination with docetaxel for patients with lung cancer. Significant tumour volume reductions and prolonged PFS were observed, including a patient with urothelial bladder cancer who achieved 100% reduction in their target lesions and remained on treatment for over 15 months; and a patient with metastatic melanoma that was resistant to prior pembrolizumab therapy who achieved an 81% reduction in tumour volume and remained progression-free at 23 months. These signals of anti-cancer activity indicate that NUC-3373, in addition to being a targeted TS inhibitor, may promote an anti-tumour immune response and potentiate the activity of immune checkpoint inhibitors.
We are currently evaluating optimal combinations and indications for potential further clinical studies of NUC-3373 and expect to announce our development plan in 2026.
Leverage our proprietary ProTide technology platform to develop additional product candidates.
We are pursuing the transformation of both widely used nucleoside analogs and novel nucleoside analogs, which we believe have the potential to address additional areas of unmet medical need in oncology.
Continue to protect and strengthen our intellectual property position.
We own or have exclusive rights to the core technologies underlying our ProTide technology platform. We have been granted patents in key markets, including the United States, Europe, China and Japan, protecting the composition of matter of NUC-7738, NUC-3373 and other of our product candidates. We intend to further expand and enhance our intellectual property position. We are actively evaluating new intellectual property opportunities as they arise, with the intention of further expanding our intellectual property position and defending our patents when necessary.
Build a focused commercial organisation.
We have worldwide rights to all product candidates that we are developing. We believe that the healthcare professionals who treat the majority of patients with the cancers we are initially targeting with our ProTides can be addressed by a relatively focused sales and marketing team. We currently plan to commercialise any product candidates for which we receive regulatory marketing approval using a specialised sales force, either independently or in partnership with a commercialisation partner, in the United States and Europe.
our pipeline
We take a scientifically driven approach to designing ProTides, which we believe have the potential to result in highly efficacious cancer therapies with improved tolerability. Our pipeline of product candidates in clinical development and their current development stage is summarised below.
NuCana is currently developing a portfolio of new medicines to address a broad range of cancers, but we do not have any approved products. As further described in "Our Strategy", our current intention is to build a sales and marketing capability in the United States and Europe to commercialise our ProTides. We may also consider partnerships, co-promotion agreements or other commercial arrangements, in certain geographic areas or otherwise, to most effectively address our market opportunities.
review of the business
Since our inception, we have incurred significant net losses and negative cash flows from operations. To date, we have financed our operations primarily through issuances of our equity securities.
DEVELOPMENT AND PERFORMANCE DURING THE PERIOD
Comparison of Year Ended 31 December 2024 and 2025
The following table summarises the results of our operations for the years ended 31 December 2024 and 2025.
Year ended 31 December
2025
2024
Research and development expenses
£ (12,737)
(in thousands)
£ (18,017)
Administrative expenses
(8,096)
(4,988)
Impairment of intangible assets
-
(33)
Other income
841
-
Net foreign exchange (losses) gains
(118)
229
Operating loss
(20,110)
(22,809)
Other income
1,851
-
Finance income
386
358
Finance expense
(12,648)
-
Loss before tax
(30,521)
(22,451)
Income tax credit
1,168
3,454
Loss for the year
(29,353)
(18,997)
Other comprehensive (expense) income:
Items that may be reclassified subsequently to profit or loss:
Exchange differences on translation of foreign operations
(61)
15
Total comprehensive loss for the year
£ (29,414)
£ (18,982)
Research and Development Expenses
Research and development expenses were £12.7 million for the year ended 31 December 2025 as compared to £18.0 million for the year ended 31 December 2024.
In the year ended 31 December 2025:
Clinical study expenses decreased by £11.1 million due to reduced expenditure across most clinical studies, predominantly NuTide:323, partially offset by increased expenditure on NuTide:701;
Share-based payment expenses increased by £5.9 million primarily due to the number of options granted in the second quarter of 2025 following the dilutive impact of the registered direct offering completed in May 2025; and
Other research and development costs decreased by £0.1 million principally due to lower personnel costs, offset by higher manufacturing costs.
The following table gives a breakdown of the research and development costs incurred by product for the years ended 31 December 2025 and 2024:
Year ended 31 December
2025
2024
NUC-7738
£ 8,676
(in thousands)
£ 2,630
NUC-3373
3,379
14,825
Acelarin
32
(467)
Other
650
1,029
£ 12,737
£ 18,017
Administrative Expenses
Administrative expenses were £8.1 million for the year ended 31 December 2025 as compared to £5.0 million for the year ended 31 December 2024. In the year ended 31 December 2025:
Share-based payment expenses increased by £2.5 million primarily due to the number of options granted in the second quarter of 2025 following the dilutive impact of the registered direct offering completed in May 2025;
Professional fees related to the issue of warrants were £1.4 million, with no corresponding cost in the year ended 31 December 2024; and
Other administrative expenses decreased by £0.8 million.
Other Income
Other income totalled £2.7 million for the year ended 31 December 2025 as compared to £nil for the year ended 31 December 2024. In the year ended 31 December 2025:
One-off insurance proceeds of £0.8 million were received; and
American Depositary Receipt (ADR) depositary contributions of £1.9 million were received from the ADR depositary in relation to the ADS ratio change completed in August 2025, with no corresponding income in the year ended 31 December 2024.
Net Foreign Exchange (Losses) Gains
For the year ended 31 December 2025, we reported a net foreign exchange loss of £0.1 million as compared to a net foreign exchange gain of £0.2 million for the year ended 31 December 2024. In 2025, the loss primarily reflected the depreciation of the U.S. dollar against the U.K. pound sterling. In contrast, in 2024, the gain arose from the appreciation of the U.S. dollar relative to the U.K. pound sterling.
Finance Income
Finance income represents bank interest and was £0.4 million for the year ended 31 December 2025 and £0.4 million for the year ended 31 December 2024.
Finance Expense
Finance expense relates to fair value revaluation losses from derivative financial instruments being remeasured at fair value through profit or loss and was £12.6 million for the year ended 31 December 2025, with no such expense for the year ended 31 December 2024.
Income Tax Credit
The income tax credit, which is largely comprised of research and development tax credits, amounted to £1.2 million for the year ended 31 December 2025 and £3.5 million for the year ended 31 December 2024. The decrease in the income tax credit was primarily attributable to a decrease in our eligible research and development expenses.
POSITION OF GROUP AT YEAR END
Liquidity and Capital Resources
Overview
Since our inception, we have incurred significant operating losses and negative operating cash flows. We anticipate that we will continue to incur losses for at least the next several years. As a result, we will need additional capital to fund our operations, which we may obtain from additional equity financings, debt financings, research funding, collaborations, contract and grant revenue or other sources.
As of 31 December 2025 and 31 December 2024, we had cash and cash equivalents of £24.3 million and £6.7 million, respectively. We do not currently have any approved products and have never generated any revenue from product sales. To date we have financed our operations primarily through the issuances of our equity securities. We expect that our existing cash and cash equivalents will be sufficient to meet our anticipated cash requirements into 2029. However, we may need to raise additional funds if we choose to expand our current development program.
In May 2025, we completed a registered direct offering, raising £9.6 million in gross proceeds, £5.2 million upfront and £4.4 million from the exercise of warrants.
In June 2025, we entered into an "at-the-market" (ATM) sales agreement with A.G.P./Alliance Global Partners, or A.G.P., and Laidlaw & Company (UK) Ltd., or Laidlaw, pursuant to which we may periodically sell ADSs having an aggregate offering price of up to $100.0 million through A.G.P. and Laidlaw acting as our agents. Sales of our ADSs pursuant to this ATM program are subject to certain conditions specified in the sales agreement. In connection with entering into the agreement with A.G.P. and Laidlaw, we terminated the ATM sales agreement from August 2021 between us and Jefferies LLC, or Jefferies. Sales under the ATM program are registered on a shelf registration statement on Form F-3 that we filed with the SEC in June 2025, and which permits the offering, issuance and sale by us of up to a maximum aggregate offering price of $150.0 million of our securities, inclusive of our ADSs sold under the ATM program. During the year ended 31 December 2025 we sold and issued 394,303 ADSs, representing 9,857,575 ordinary shares, under the ATM program with Jefferies, raising gross proceeds of £0.5 million, and we sold and issued 450,758,552 ADSs, representing 11,268,963,800 ordinary shares, under the ATM program with A.G.P. and Laidlaw, raising gross proceeds of £19.0 million.
Cash Flows
The following table summarises the results of our cash flows for the years ended 31 December 2025 and 2024.
Year ended 31 December 2025 2024
(in thousands)
Net cash used in operating activities
£ (7,467)
£ (19,118)
Net cash from investing activities
159
79
Net cash from financing activities
25,006
8,184
Net increase (decrease) in cash and cash equivalents
£ 17,698
£ (10,855)
Operating activities
Net cash used in operating activities was £7.5 million for the year ended 31 December 2025 as compared to £19.1 million for the year ended 31 December 2024, a net decrease in cash outflows of £11.6 million.
In the year ended 31 December 2025:
Operating loss cash outflows were lower by £13.1 million; and
Working capital outflows were £3.7 million as compared to £2.2 million in the year ended 31 December 2024.
Investing activities
Net cash from investing activities was £0.2 million for the year ended 31 December 2025 as compared to £0.1 million for the year ended 31 December 2024.
In the year ended 31 December 2025, cash used to acquire intangible assets was lower by £0.1 million.
Financing activities
Net cash from financing activities was £25.0 million for the year ended 31 December 2025 as compared to £8.2 million for the year ended 31 December 2024.
In the year ended 31 December 2025:
Net proceeds from the issue of share capital were higher by £10.4 million;
Net proceeds from the issue, exercise and cancellation of warrants were £6.2 million; and
Payments for lease liabilities were lower by £0.2 million.
main business trends and factors
NUC-7738 is in the Phase 2 part of a Phase 1/2 study which is evaluating NUC-7738 as a monotherapy in patients with advanced solid tumours and in combination with pembrolizumab in patients with melanoma. NUC-3373 has recently been evaluated in a Phase 1b/2 modular clinical study of NUC-3373 in combination with the PD-1 inhibitor pembrolizumab for patients with advanced solid tumours and in combination with docetaxel for patients with lung cancer, and we are currently evaluating optimal combinations and indications for further clinical studies of NUC-3373. We have retained worldwide rights to these lead product candidates as well as our preclinical product candidates, all of which we refer to as ProTides. The key business trends affecting our development and performance during and at the period ended 31 December 2025 are detailed above.
In addition to these internal trends that have impacted our financial results, we may also in the future face competition for our products if they are approved. The most common methods of treating patients with cancer are surgery, radiation and drug therapy, including chemotherapy, hormone therapy, immunotherapy and targeted drug therapy. There are a variety of available drug therapies marketed for cancer, including many which are administered in combination to enhance efficacy. We believe that our product candidates, if approved, will principally face competition from other chemotherapies, immunotherapy and targeted drug therapies. In the field of chemotherapy, our competitors include companies that manufacture off-patent chemotherapies, including 5-FU, as well as companies that have developed new or improved chemotherapies. In addition, our product candidates, if approved, may face competition from cancer therapies developed by other companies using phosphoramidate chemistry, as well as other approved drugs or drugs that may be approved in the future for indications for which we may develop our product candidates.
The availability of reimbursement from government and other third-party payors will also significantly affect the pricing and competitiveness of our products. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market. Many of the companies against which we may compete have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical studies, obtaining regulatory approvals and marketing approved products than we do.
Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical study sites and patient registration for clinical studies, as well as in acquiring technologies complementary to, or necessary for, our programs.
key performance indicators
As a measurement of liquidity, we review our total liquidity position (including cash and cash equivalents), as well as our operating cash flow. At 31 December 2025, the total liquidity position was £24.3 million (at 31 December 2024: £6.7 million). Net cash used in operating activities was £7.5 million for the year ended 31 December 2025 (year ended 31 December 2024: £19.1 million).
Total liquidity position Net cash used in operating activities
£24.3
million
(at 31 December 2025)
million
(at 31 December 2024)
£6.7
£7.5
million
(for the year ended 31 December 2025)
£19.1
million
(for the year ended 31 December 2024)
principal risks and uncertainties
In common with other pharmaceutical development companies NuCana faces a number of risks and uncertainties. Internal controls are in place to help identify, manage and mitigate these risks. Further details of risk factors considered by NuCana for the year ended 31 December 2025 are included on Form 20-F filed with the SEC on 19 March 2026.
Financial
We have incurred significant operating losses since our inception. We incurred net losses of £29.4 million for the year ended 31 December 2025 and £19.0 million for the year ended 31 December 2024. As of 31 December 2025, we had an accumulated deficit of £252.3 million. Our product candidate, NUC-7738, is currently in the Phase 2 part of a Phase 1/2 clinical study (NuTide:701) evaluating NUC-7738 as a monotherapy and in combination with pembrolizumab in patients with melanoma. Our product candidate, NUC-3373, has recently been evaluated in a Phase 1b/2 modular clinical study (NuTide:303) of NUC-3373 in combination with the PD-1 inhibitor pembrolizumab for patients with advanced solid tumours and in combination with docetaxel for patients with lung cancer, and we are currently evaluating optimal combinations and indications for further clinical studies of NUC-3373. It may be several years, if ever, before we have a product candidate ready for commercialisation. To date, we have financed our operations primarily through public and private placements of our equity securities. We expect to continue to incur significant expenses and operating losses for the foreseeable future. The net losses we incur may fluctuate significantly from quarter to quarter.
We anticipate that our expenses will increase substantially if and as we conduct larger-scale clinical studies of, and seek marketing approval for, our product candidates. In addition, if we obtain marketing approval for any of our product candidates, we expect to incur significant commercialisation expenses related to product sales, marketing, manufacturing and distribution. We may also need to raise additional funds sooner if we choose to pursue additional indications or geographies for our product candidates or otherwise expand more rapidly than we presently anticipate. Furthermore, we will continue to incur costs associated with operating as a public company. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations. If we fail to obtain additional financing, we may be unable to complete the development and commercialisation of our product candidates or continue our development programmes.
Dependence on Clinical Candidates
We do not currently generate any revenues from sales of any products, and we may never be able to develop or commercialise a marketable product. We have invested substantially all of our efforts and financial resources to date in the development of NUC-7738 and NUC-3373, as well as Acelarin, for which we discontinued the NuTide:121 clinical study in March 2022. Our ability to generate product revenues, which we do not expect will occur for at least the next several years, if ever, will depend heavily on the successful development and eventual commercialisation of these product candidates, if approved, which may never occur. Each of NUC-7738 and NUC-3373 will require additional clinical development, management of clinical, preclinical and manufacturing activities, regulatory approval in multiple jurisdictions, procurement of manufacturing supply, commercialisation, substantial additional investment and significant marketing efforts before we generate any revenues from product sales, if at all. We are not permitted to market or promote any product candidates in the United States, Europe or other countries before we receive regulatory approval from the FDA, the European Medicines Agency (EMA) or comparable foreign regulatory authorities, and we may never receive such regulatory approval for NUC-7738, NUC-3373 or any future product candidate. We have not submitted a New Drug Application to the FDA, a Marketing Authorisation Application to the EMA or comparable applications to other regulatory authorities for any of our product candidates and do not expect to be in a position to do so in the foreseeable future.
Going Concern
The development of pharmaceutical drugs is capital-intensive. We have incurred recurring losses from our operations, have an accumulated deficit totalling £252.3 million and cash flows used in operating activities of £7.5 million as of and for the year ended 31 December 2025. We had cash and cash equivalents of £24.3 million at 31 December 2025. We expect our expenses to increase in the medium to longterm with our ongoing activities, particularly if we conduct larger-scale clinical studies of, and seek marketing approval for, our product candidates. In addition, if we obtain marketing approval for any of our product candidates, we expect to incur significant commercialisation expenses related to product sales, marketing, manufacturing and distribution. Furthermore, we will continue to incur costs associated with operating as a public company. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations. In addition, we have based estimates of our cash runway on assumptions including, but not limited to, our expectations as to our future expenses and costs and our continued eligibility to receive tax relief or credits in connection with our research and development expenditure in the United Kingdom. There is no assurance that these assumptions will be correct and, as a result, we could use our available capital resources sooner than we currently expect and may identify conditions or events that may raise material uncertainty on our ability to continue as a going concern and we may be unable to realise our assets and discharge our liabilities in the normal course of business. If we are unable to obtain funding on a timely basis, we may be required to significantly curtail, delay or discontinue one or more of our research or development programs or the commercialisation of any product candidate or be unable to expand our operations or otherwise capitalise on our business opportunities. We may also need to raise additional funds if we choose to pursue additional indications or geographies for development and commercialisation of our product candidates or otherwise expand more rapidly than we presently anticipate.
If there is material uncertainty about our ability to continue as a going concern in the future, it may negatively impact the trading price of our securities, have an adverse impact on our relationship with third parties with whom we do business, including our customers, vendors and employees, and could make it challenging and difficult for us to raise additional equity or debt financing to the extent needed, all of which could have a material adverse impact on our business, results of operations, financial condition and prospects. In addition, in the future, we may commence an equity financing process in order to raise additional capital and if we do, there can be no assurance that we will be successful and if we are unable to raise additional capital, we could potentially be forced to complete a wind down of our operations and/or seek bankruptcy protection.
Economic and Political
As a company based in the United Kingdom, our business is subject to risks associated with conducting business internationally. Many of our suppliers and collaborative and clinical study relationships are located outside of the United Kingdom and United States. Accordingly, our future results or our ability to raise additional capital could be harmed by a variety of factors, including:
business interruptions resulting from geo-political actions, including war and terrorism, or natural disasters including earthquakes, typhoons, floods and fires; and
changes in financial markets or general economic conditions, including the effects of recession or slow economic growth, interest rates, tariffs, fuel prices, international currency fluctuations, corruption, political instability, acts of war, including the ongoing conflicts in Ukraine, the Middle East, and other countries and regions, and any potential spread of such conflicts into wider wars, acts of terrorism, and pandemics or other public health crises.
Manufacturing
We do not currently own or operate, nor do we have any plans to establish in the future, any manufacturing facilities. We rely, and expect to continue to rely, on third parties for the manufacture and shipment of our product candidates for preclinical studies and clinical studies, as well as for the commercial manufacture of our drugs if any of our product candidates receive marketing approval. This reliance on third parties increases the risk that we will not have sufficient quantities of our product candidates or drugs or such quantities at an acceptable cost or quality, which could delay, prevent or impair our development or commercialisation efforts.
Commercialisation
We currently have no marketing capability or sales force, but we intend to commercialise or participate in the commercialisation of our product candidates for which we receive regulatory approval in major markets, such as the United States and Europe. This may necessitate building a specialised sales force and other commercial capabilities in such markets. To achieve commercial success for any approved product candidate for which we retain sales and marketing responsibilities, we must build our sales, marketing, managerial and other non-technical capabilities or make arrangements with third parties to perform these services. There are risks involved with both establishing our own sales and marketing capabilities and entering into arrangements with third parties to perform these services. For example, recruiting and training a sales force is expensive and time consuming and could delay any drug launch. If the commercial launch of a product candidate for which we recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialisation expenses. This may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.
Regulation
Our product candidates and the activities associated with their development and commercialisation, including their design, testing, manufacture, safety, efficacy, recordkeeping, labelling, storage, approval, advertising, promotion, sale, distribution, import and export are subject to comprehensive regulation by the FDA and other regulatory agencies in the United States and by comparable authorities in other countries.
The process of obtaining marketing approvals, both in the United States and in other countries, is expensive and takes several years, if approval is obtained at all, and can vary substantially based upon a variety of factors, including the type, complexity and novelty of the product candidates involved. Failure to obtain marketing approval for a product candidate will prevent us from commercialising. We have not received approval to market any of our product candidates from regulatory authorities in any jurisdiction. We have limited experience in planning and conducting the clinical studies required for marketing approvals, and we expect to rely on third-party contract research organisations to assist us in this process. Obtaining marketing approval requires the submission of extensive preclinical and clinical data and supporting information to regulatory authorities for each therapeutic indication to establish the product candidate's safety and efficacy. Securing marketing approval also requires the submission of information about the product manufacturing process, and in many cases the inspection of manufacturing facilities by the regulatory authorities. Our product candidates may not be effective, may be only moderately effective or may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude our obtaining marketing approval or prevent or limit commercial use. Regulatory authorities have substantial discretion in the new drug approval process and may refuse to accept any application or may decide that our data are insufficient for approval and require additional preclinical studies or clinical studies. Our product candidates could be delayed in receiving, or fail to receive, marketing approval.
Intellectual Property
If we are unable to obtain and maintain intellectual property protection for our technology and products, or if the scope of the intellectual property protection obtained is not sufficiently broad, our competitors could commercialise technology and products similar or identical to ours, and our ability to successfully commercialise our technology and products may be impaired. In addition, if we infringe the valid patent rights of others, we may be prevented from making, using or selling our products or may be subject to damages or penalties. Even if our patent applications issue as patents, they may not issue in a form that will provide us with any meaningful protection, prevent competitors from competing with us or otherwise provide us with any competitive advantage. Our competitors may be able to circumvent our owned or licensed patents by developing similar or alternative technologies or products in a non-infringing manner. We may become involved in administrative adversarial proceedings in the United States Patent and Trademark Office or in the patent offices of other countries brought by a third party to attempt to cancel or invalidate our patent rights, which could be expensive, time consuming and cause a loss of patent rights. We may have to file one or more lawsuits in court to prevent a third party from selling a product or using a product in a manner that infringes our patent, which could be expensive, time consuming and unsuccessful, and ultimately result in the loss of our proprietary market. Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could hurt our business. We may not be able to effectively enforce our intellectual property rights throughout the world. Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements. Our intellectual property licenses with third parties may be subject to disagreements over contract interpretation, which could narrow the scope of our rights to the relevant intellectual property or technology or increase our financial or other obligations to our licensors. We may be subject to claims by third parties asserting that our employees or we have misappropriated their
intellectual property, or claiming ownership of what we regard as our own intellectual property. If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed. Our proprietary information, or that of our suppliers and any future collaborators, may be lost or we may suffer security breaches. Intellectual property rights do not necessarily address all potential threats to our competitive advantage.
We may not have sufficient financial or other resources to adequately conduct litigation or proceedings relating to intellectual property claims. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources and more mature and developed intellectual property portfolios. Accordingly, despite our efforts, we may not be able to prevent third parties from infringing upon, misappropriating or successfully challenging our intellectual property rights.
Conduct of Clinical Studies
We rely on, and expect to continue to rely on, third parties to conduct our clinical studies for our product candidates. If these third parties do not successfully carry out their contractual duties, comply with regulatory requirements or meet expected deadlines, we may not be able to obtain marketing approval for or commercialise our product candidates, and our business could be substantially harmed. We do not have the ability to independently conduct clinical studies. Nevertheless, we will be responsible for ensuring that each of our clinical studies are conducted in accordance with the applicable protocol, legal and regulatory requirements and scientific standards.
Employees
We currently have a limited number of employees, and our future success depends on our ability to retain key executives and to attract, retain and motivate qualified personnel. We are a clinical development-stage group, and, as of 31 December 2025, had 12 employees, including four executive officers. We are highly dependent on the research and development, clinical and business development expertise of Hugh Griffith, our founder and CEO, as well as the other principal members of our management team and our collaborators' scientific and clinical teams. Recruiting and retaining qualified scientific, clinical, manufacturing, finance, sales and marketing personnel will also be critical to our success. The loss of the services of our executive officers or other key employees could impede the achievement of our research, development and commercialisation objectives and seriously harm our ability to successfully implement our business strategy.
environmental matters
We currently outsource our research, development and manufacturing activities.
Our leased offices in the United Kingdom drive the majority of our carbon emissions. The building currently has a current Energy Performance Certificate, with a Building Energy Performance Rating of "A" (between 0 to 15 kgCO2 per m2 per year). The certificate has been produced under the Energy Performance of Buildings (Scotland) Regulations 2008 from data lodged to the Scottish EPC register. The building energy performance rating is a measure of the effect of a building on the environment in terms of carbon dioxide CO2 emission, with ratings ranging between "A+" (net zero carbon) to "G" (very poor). The better the rating, the less impact on the environment. The current rating is based upon an assessor's survey of the building, using EPCgen, V6.1.e.0.
Our report on greenhouse gas emissions is included in our Directors' Report on page 18 of this Annual Report.
employees
The number of employees by function and geographic location at 31 December 2025 and 2024 was as follows:
2025
2024
By Function:
Research and development
8
16
Management and administrative
4
6
Total
12
22
By Geography:
United Kingdom
11
20
United States of America
1
2
Total
12
22
As of 31 December 2025, we had 10 full-time employees and 2 part-time employees. We have never had a work stoppage and none of our employees are covered by collective bargaining agreements or represented by a labour union. We believe our employee relations are good.
Diversity
We make appointments based on merit according to the balance of skills and experience offered by prospective candidates. Whilst acknowledging the benefits of diversity, individual appointments are made irrespective of personal characteristics such as sex, race, disability, gender, sexual orientation, religion or age.
A breakdown of the statistics as at 31 December 2025 is as follows:
Position
Male
Female
Total
Company Director
5
-
5
Senior Manager
4
3
7
Other Employees
3
1
4
Total Employees(1)
8
4
12
Total Employees includes one Executive Director, the CEO.
employee consultation and human rights
We place considerable value on the involvement of our employees. Meetings are held with employees to discuss the operations and progress of the business and employees are encouraged to become involved in the success of the Group through share option schemes (see note 15 to the financial statements). We endeavour to impact positively on the communities in which we operate. We do not, at present, have a specific policy on human rights. However, we have several policies that promote the principles of human rights, including our Anti-Slavery and Human Trafficking Policy, which governs our zero-tolerance approach to modern slavery and our commitment to acting ethically and with integrity in all our business dealings; and an Anti-Corruption and Bribery Policy in order to reflect our policy to conduct our business in an honest and ethical manner. Our Health & Safety policy sets out our commitment to provision of a safe working environment for our employees. Furthermore, our Equal Opportunities Policy promotes the right of every employee to be treated with dignity and respect and not to be harassed or bullied on any grounds. Accordingly, we have a policy framework in place to ensure that we will respect the human rights of all our employees, including: provision of a safe, clean working environment; ensuring employees are free from discrimination and coercion; not using child or forced labour and respecting the rights of privacy and protecting access and use of employee personal information. This report does not contain information relating to social or community matters as such information is not relevant in understanding our development, performance, or position.
section 172(1) statement
Section 172 of the Companies Act 2006 requires each of directors to act in the way they consider, in good faith, would be most likely to promote the success of the company for the benefit of its members as a whole, and in doing so, have regard (amongst other matters) to:
the likely consequences of any decision in the long term;
the interests of the company's employees;
the need to foster the company's business relationships with suppliers, customers and others;
the impact of the company's operations on the community and the environment;
the desirability of the company maintaining a reputation for high standards of business conduct; and
the need to act fairly between members of the company.
The directors continue to have regard to the interests of our key stakeholders, including our shareholders, holders of ADSs, and employees. The Board recognises its responsibility to take into consideration the needs and concerns of all our stakeholders as part of our discussion and decision-making processes.
Details of our interactions and engagement with shareholders, ADS holders and analysts are summarised below.
Interests - issues and factors which are most important to shareholders, ADS holders and analysts
Engagement - examples of engagement in 2025
Outcomes - any actions which resulted
Successful research and development of our pipeline
Sufficient cash and cash equivalents on hand to fund our anticipated operations
Annual General Meeting in June 2025
Directors and senior management meet investors and analysts
Quarterly financial results and regular press
Investor outreach programme, including investor conferences and events
Helped to inform the objectives and strategy of the business, as outlined in the Our Strategy section of this Strategic Report on page 6
Attracted new investors in the Group
Our engagement and consultation with employees are outlined in the Employee Consultation and Human Rights section of this Strategic Report on page 14.
The consideration and impact of our operations on the environment are contained in the Environmental Matters section of this Strategic Report on page 13.
The Strategic Report was approved by the Board on 30 April 2026.
On behalf of the Board
Hugh S. Griffith
Chief Executive Officer
rdeiproertctors'
directors' report
Company registration
NuCana plc is registered in England and Wales with the registered number 03308778.
Results and dividends
directors' report/ 02
The loss for the year after taxation amounted to £29.4 million (2024: £19.0 million). The directors do not recommend a final dividend (2024: £nil).
Principal activities
NuCana is a clinical-stage biopharmaceutical Group developing a portfolio of new medicines (ProTides) to treat patients with cancer. The unique feature of ProTides is their ability to overcome the key limitations associated with many widely used anti-cancer medicines and have the potential to be more effective and safer treatments for patients with cancer.
Future developments
The future developments have been set out in the Strategic Report on page 2.
Research and development activities
NuCana's research and development strategy and activities have been set out in the Strategic Report on pages 2 to 15.
Directors
The directors who served the Company during the year and up to the date of this report were as follows:
Hugh Griffith Elliott Levy
Andrew Kay Adam George (retired 21 March 2025)
Martin Mellish Bali Muralidhar (retired 21 October 2025) Cyrille Leperlier
Going concern
The Group's financial statements have been presented on the basis that it is a going concern. The Group has not generated any revenues from operations to date and does not expect to in the foreseeable future. As such, the Group has incurred recurring net losses, has an accumulated deficit totalling £252.3 million and cash flows used in operating activities of £7.5 million for the year ended 31 December 2025. The Group had
£24.3 million of cash and cash equivalents at 31 December 2025.
The Group's board of directors have reviewed the operating budgets and development plans for the 18-month period to 30 June 2027 (the "going concern assessment period"). The base case forecast prepared for the going concern assessment period includes assumptions regarding, among other things, research and development expenses, administrative expenses, staff costs and R&D tax credits. The base case forecast has been reviewed and approved by the board of directors in accordance with the Group's normal budgeting and forecasting processes.
Based on the base case forecast, the Group believes that its cash and cash equivalents of £24.3 million at 31 December 2025 will be sufficient to fund the Group's anticipated operations for the entirety of the going concern assessment period.
In stress testing these forecasts and assumptions, severe but plausible downside scenarios have been modelled, which include inflationary increases to clinical study budgets, increased insurance costs and a less favourable U.S. dollar to pound sterling exchange rate. Furthermore, a reverse stress test has been modelled to consider what combination of downside scenarios could result in liquidity being exhausted during the going concern assessment period.
To the extent any of the severe but plausible scenarios materialised, the directors believe the Group would have sufficient controllable mitigating actions to reduce expenditure through the going concern assessment period, including management of third-party, such as phasing of clinical study costs, and internal resource costs. The directors do not consider that a situation where the Group would run out of cash over the going concern assessment period is plausible given the likelihood of such downside scenarios and the Group's ability to implement controllable mitigations.
However, as the Group continues to incur losses, the transition to profitability is dependent upon the successful development, approval and commercialisation of its product candidates and achieving a level of revenues adequate to support its cost structure. The Group may never achieve profitability, and unless and until it does, it will continue to need additional capital beyond the going concern assessment period. The Group may also need to raise additional funds if it chooses to expand its current development program. There can be no assurances, however, that additional funding will be available on acceptable terms.
Financial instruments
Details of financial instruments are set out in note 19 to the financial statements on page 71.
Charitable and political contributions
No charitable contributions were paid during the 2025 financial year (2024: £nil).
No donations were made during the 2025 financial year to political organisations (2024: £nil).
Structure of Group's capital
Details of the structure of the Group's capital are set out in note 15 to the financial statements on page 65.
Directors' insurance and indemnities
The directors have the benefit of the indemnity provisions contained in the Company's Articles of Association, and the Company has maintained throughout the year directors' and officers' liability insurance for the benefit of the Company, the directors and its officers. The Company has entered into qualifying third-party indemnity arrangements for the benefit of all its directors in a form and scope which comply with the requirements of the Companies Act 2006 and which were in force throughout the year and remain in force.
Overseas branches
The Company has no overseas branches.
Environmental matters
The Group measures and reports its greenhouse gas emissions.
directors' report/ 02
As 2020 was the first year of reporting, it is reported as the baseline year against which future performance is measured.
Quantification and reporting methodology
This report was compiled by management. The 2019 U.K. Government Environmental Reporting Guidelines and the GHG Protocol Corporate Accounting and Reporting Standard (revised edition) were followed to ensure the Streamlined Energy and Carbon Reporting requirements were met.
The energy data was collated using existing reporting mechanisms for the Group's leased office in the United Kingdom, where the majority of the Group's employees are based. These methodologies provided a continuous record of electricity use.
The energy data was converted to carbon emissions using the 2025 U.K. Government GHG Conversion Factors for Company Reporting. The associated emissions are divided into the combustion of fuels and the operation of facilities (scope 1), purchased electricity, heating and cooling (scope 2) and indirect emissions that occur as a consequence of company activities (scope 3). During the year the Group only had emissions relating to scope 2.
Estimations
The electricity use was compiled from invoices and meter readings.
2025
2024
2023
2022
2021
2020
Energy used by the company (in KWH)
13,656
75,576
77,495
111,631
128,699
164,026
Emissions associated with the reported energy use (tCO2e)
2
16
16
22
27
38
Intensity Ratio
2025
2024
2023
2022
2021
2020
0.16
0.65
0.59
0.72
1.01
1.37
The chosen primary intensity ratio is total gross emissions in metric tonnes CO2e (mandatory emissions) per employee.
Tonnes of CO2e per employee
Energy efficiency action during current financial year
The Group will continue to monitor its carbon emissions and look for cost-effective improvements of energy performance.
Energy consumption is expected to be broadly stable this year as the Group continues to adopt a blended approach to working, with a mix of remote and office working.
Climate change
The Group relies on third parties to manufacture and ship its product candidates for preclinical studies and clinical studies, as well as conducting the associated preclinical and clinical studies. As a result, the Group's direct operational footprint is such that it does not expect any material impact on its operations and financial position as a result of climate change.
The Audit Committee makes recommendations to the Board on the principal risks of relevance to the business. Climate-related issues are considered in terms of potential for contribution to these principal risks. The issues considered include both the risk of physical disruption to the business from climate change, and the risks and opportunities as the global economy transitions to significantly lower carbon emissions. In the current period, the Audit Committee concluded that climate-related risks did not rise to the level of a principal risk.
Events after the reporting period
Details of important events affecting the Group, which have occurred since 31 December 2025, are set out in note 21 to the financial statements on page 74.
Disclosure of information to the auditors
So far as each person who was a director at the date of approving this report is aware, there is no relevant audit information, being information needed by the auditor in connection with preparing its report, of which the auditor is unaware. Having made enquiries of fellow directors and the Group's auditor, each director has taken all the steps that they are obliged to take as directors in order to make themselves aware of any relevant audit information and to establish that the auditor is aware of that information.
Auditors
Resolutions to re-appoint Ernst & Young LLP as auditor of the Company and to authorise the Board to set its remuneration will be proposed at the Company's forthcoming annual general meeting.
The Directors' Report was approved by the Board on 30 April 2026. On behalf of the Board
Hugh S. Griffith Director
remuneration
directors' remuneration report/ 03
committee chair's annual statement
The information provided in this part of the Directors' Remuneration Report is not subject to audit.
On behalf of the Board of Directors of NuCana, I am pleased to present the Directors' Remuneration Report for the year ended 31 December 2025.
Voting at our 2025 AGM was conducted on a poll. At the 2025 AGM, the resolution to approve the 2024 Directors' Remuneration Report was approved by a majority of the votes cast as follows:
9,473,261,451 votes for and 59,738,325 votes against which equates to over 99% of the proxy vote being in favour of the resolution. 6,125,750 votes were withheld.
Voting at our 2023 AGM was conducted on a show of hands by those shareholders (or their proxies, as applicable) in attendance at the 2023 AGM. The resolution to approve the existing Directors' Remuneration Policy was approved by a majority of the votes cast at the 2023 AGM on a show of hands. Had a poll been called the proxy vote directions given to the Chairman of the 2023 AGM (and other officers of the Company) would have been exercised as follows:
Resolution 8 regarding approval of our existing Directors' Remuneration Policy: 49,749,595 votes for and 1,069,642 votes against which equates to over 97% of the proxy vote in favour of the resolution. 118,152 votes were withheld.
A copy of the existing Directors' Remuneration Policy (which was effective from 15 June 2023 and throughout the financial year ending 31 December 2025) is available for inspection at the Global Headquarters of the Company at 3 Lochside Way, Edinburgh, EH12 9DT, United Kingdom, and is also available on pages 25 to 29 of our 2022 Annual Report, which is on our website at https://www.nucana.com.
As the shareholders must receive and approve our Directors' Remuneration Policy every three years the Remuneration Committee has undertaken a review of the existing policy to ensure it remains aligned with the Company's strategy and concluded it does. Accordingly, the proposed Directors' Remuneration Policy, set out in pages 27 to 31 of this annual report, is unchanged in any substantive way and this policy will be put to a shareholder vote at the 2026 AGM to be held on 8 June 2026. If approved, this proposed policy will take effect immediately following the 2026 AGM and is intended to apply for the next three years.
Remuneration Committee
The Remuneration Committee consists of two independent non-executive directors, Andrew Kay (Chair since 18 November 2025) and Elliott Levy (member since 6 May 2022). Given the current size of the Company and the Board, we believe it is appropriate and beneficial, for the time being, for the Chairman to chair the Remuneration Committee. Andrew Kay holds significant experience in executive remuneration and stakeholder engagement and consequently, the Board considers him best placed to lead the Remuneration Committee at this stage. The Board feels that adding another independent Non-Executive Director to take on this specific role is not currently cost-effective or necessary for the proper functioning of the Board or the Remuneration Committee. The Board keeps the composition of the Remuneration Committee under review and will reconsider the composition of the Remuneration Committee as the Company grows and as part of its succession planning.
The Remuneration Committee is responsible for reviewing and establishing our executive remuneration policy and philosophy, including reviewing the performance of the Officers and other senior executives and setting the scale and structure of their remuneration and the basis of their service agreements with due regard to the interests of the shareholders. It is the policy of the Remuneration Committee that no individual can participate in discussions or decisions concerning his or her own remuneration.
The Directors' Remuneration Report that follows is for the year from 1 January 2025 to 31 December 2025 except where otherwise stated. The Directors' Remuneration Policy is designed to:
Increase shareholder value;
Reward senior executive officers for their contribution to the Company's development and value creation;
Recognise individual initiative, leadership, achievement, and other contributions; and
Provide competitive compensation that will attract and retain qualified executives.
Activities and Major Decisions
During the year ended 31 December 2025, the Remuneration Committee undertook the following activities and major decisions:
Performed a review of Director, Officer and other senior executive compensation, which was undertaken to ensure that remuneration for our Directors, Officers and other senior executives remains competitive for the retention and engagement of key talent.
As a result of the review completed in 2025, the Officers and other senior executives received increased base salary awards at a level that is broadly aligned with historical peer group comparator data.
Awarded share options to employees in June 2025.
2026 Annual General Meeting
On behalf of the Board, I wish to thank our shareholders for their input and support during the year ended 31 December 2025. The Remuneration Committee and the Board of Directors welcome feedback from our shareholders on the Directors' Remuneration Report. We look forward to receiving the support of our shareholders for the Directors' Remuneration Report at our 2026 AGM to be held on 8 June 2026.
Andrew Kay
Chair of Remuneration Committee and Non-Executive Director 30 April 2026
report on remuneration
directors' remuneration report/ 03
The information provided in this part of the Directors' Remuneration Report is subject to audit.
The Remuneration Committee presents the Report on Remuneration for the year ended 31 December 2025, which will be put to shareholders for a non-binding vote at the 2026 AGM to be held on 8 June 2026.
Single Total Figure for Remuneration of each Director
The following table shows the remuneration received by the Directors for the years ended 31 December 2025 and 31 December 2024.
Name of Director
Salary & Fees(1)
£
Taxable Benefits(2)
£
Annual Bonus(3)
£
Share Options(4)
£
Pension Benefit(5)
£
Total
£
Total Fixed Remuneration(6)
£
Total Variable Remuneration(7)
£
Executive Directors(8)
Hugh Griffith
YE 31 Dec 2025
596,636
5,348
429,578
3,295,794
59,664
4,387,020
661,648
3,725,372
YE 31 Dec 2024
596,636
4,865
-
2,418
59,664
663,583
661,165
2,418
Non-Executive Directors
Andrew Kay
YE 31 Dec 2025
73,785
-
-
11,847
-
85,632
73,785
11,847
YE 31 Dec 2024
79,723
-
-
-
-
79,723
79,723
-
Martin Mellish
YE 31 Dec 2025
51,566
-
-
7,885
-
59,451
51,566
7,885
YE 31 Dec 2024
48,384
-
-
-
-
48,384
48,384
-
Cyrille Leperlier
YE 31 Dec 2025
46,171
-
-
7,346
-
53,517
46,171
7,346
YE 31 Dec 2024
65,898
-
-
-
-
65,898
65,898
-
Elliot Levy
YE 31 Dec 2025
38,944
-
-
5,329
-
44,273
38,944
5,329
YE 31 Dec 2024
54,914
-
-
-
-
54,914
54,914
-
Adam George(9)
YE 31 Dec 2025
17,091
-
-
-
-
17,091
17,091
-
YE 31 Dec 2024
57,184
-
-
-
-
57,184
57,184
-
Bali Muralidhar(10)
YE 31 Dec 2025
-
-
-
2,950
-
2,950
-
2,950
YE 31 Dec 2024
-
-
-
-
-
-
-
-
Total
YE 31 Dec 2025
824,193
5,348
429,578
3,331,151
59,664
4,649,934
889,205
3,760,729
YE 31 Dec 2024
902,739
4,865
-
2,418
59,664
969,686
967,268
2,418
The majority of the remuneration was set and paid in pounds sterling (£). For the purposes of this table, the fees paid in any other currency in which remuneration was paid have been converted into pounds sterling based on the currency/pounds sterling average exchange rate for the period the costs relate to. All of the figures in the table above are in pounds sterling.
The amount for taxable benefits represents the Company's contribution to medical insurance.
The annual bonus amounts shown for the year ended 31 December 2025 represent the total bonus payments that related to performance in 2025, which was paid in early 2026.
These options only have service conditions attached. There are no performance conditions. The values of these share option awards are therefore recorded in this table at the date of grant. Where the options have vested before the date of this report the value is based on the market value of the shares at the date of vesting, less the exercise price. Where the options have not vested the market value of the options at the date of vesting is not ascertainable. Therefore, the value included in this table is based on the average market value of the shares over the three months to 31 December 2025 and 31 December 2024 respectively, less the applicable exercise price.
The amount for pension benefit represents the Company's contribution into a money purchase plan.
Total fixed remuneration includes salary and fees, taxable benefits and pension benefit.
Total variable remuneration includes annual bonus and share options.
Changes to the compensation for our Executive Directors take effect from 1 January in each year.
Adam George retired from the Board on 21 March 2025.
Bali Muralidhar retired from the Board on 21 October 2025.
Annual bonus
Our Executive Directors, Officers and other senior executives are eligible for an annual bonus at the discretion of the Remuneration Committee. Bonus awards are reviewed at the end of each calendar year and any such awards are determined by the performance of the individual and the Company as a whole, based upon the achievement of strategic objectives set at the beginning of the year. In determining Executive Director, Officer and other senior executive compensation for the year ended 31 December 2025, the Remuneration Committee considered achievement of specific performance measures which had been previously approved by the Remuneration Committee to be achieved by the executive team during 2025. These are considered to be commercially sensitive and will not be disclosed in detail, but are linked to our business strategies which include to:
Generate data from the Phase 1/2 study of NUC-7738;
Generate data from the Phase 1b/2 modular study of NUC-3373; and
Continue to protect and strengthen our intellectual property position
Share options awarded during the financial year
The table below shows, for each director, the total number of options awarded in the year ended 31 December 2025. The face value of the award is calculated as the share price per ordinary share at date of grant, in pounds sterling, multiplied by the number of options granted. The options granted have no performance conditions, only service conditions.
We periodically grant share options to employees, directors and consultants to enable them to share in our successes and to reinforce a corporate culture that aligns their interests with that of our shareholders.
Name of director
Type of plan
Number of options granted
Exercise price
£
Share price at date of grant
£
Value at date of grant
£
Performance period end
Date of expiry
Executive Directors
Hugh Griffith
2016 Share Option Scheme
62,499,995
0.004(1)
0.004
250,000
20-Jun-25
20-Jun-35
2020 Long-Term Incentive Plan
1,221,867,885
0.0004(2)
0.004
4,887,472
20-Jun-25
20-Jun-35
2020 Long-Term Incentive Plan
691,582,704
0.0004(2)
0.004
2,766,331
20-Jun-29
20-Jun-35
Non-Executive Directors
Andrew Kay
2020 Long-Term Incentive Plan
52,934,010
0.004(1)
0.004
211,736
20-Jun-25
20-Jun-35
2020 Long-Term Incentive Plan
52,934,010
0.0004(2)
0.004
211,736
20-Jun-26
20-Jun-35
Martin Mellish
2020 Long-Term Incentive Plan
35,231,753
0.004(1)
0.004
140,927
20-Jun-25
20-Jun-35
2020 Long-Term Incentive Plan
35,231,753
0.0004(2)
0.004
140,927
20-Jun-26
20-Jun-35
Cyrille Leperlier
2020 Long-Term Incentive Plan
32,823,199
0.004(1)
0.004
131,293
20-Jun-25
20-Jun-35
2020 Long-Term Incentive Plan
32,823,199
0.0004(2)
0.004
131,293
20-Jun-26
20-Jun-35
Elliott Levy
2020 Long-Term Incentive Plan
23,811,896
0.004(1)
0.004
95,248
20-Jun-25
20-Jun-35
2020 Long-Term Incentive Plan
23,811,896
0.0004(2)
0.004
95,248
20-Jun-26
20-Jun-35
Bali Muralidhar(3)
2020 Long-Term Incentive Plan
13,181,363
0.004(1)
0.004
52,725
20-Jun-25
20-Jun-35
2020 Long-Term Incentive Plan
13,181,363
0.0004(2)
0.004
52,725
20-Jun-26
20-Jun-35
The share options were granted on 20 June 2025.
The share options were granted on 20 June 2025. The exercise price of these share options is the nominal value of our ordinary shares of £0.0004 rather than at the share price at the date of grant of £0.004. The exercise price of the share options has not changed since the date of the grant.
Bali Muralidhar retired from the Board on 21 October 2025. All unvested options lapsed on the date of his retiral.
Statement of directors' shareholdings and share interests
The table below shows, for each director, the total number of ordinary shares owned, the total number of share options held and the number of share options vested as at 31 December 2025. The table only reflects ordinary shares held individually by each director and does not include ordinary shares held by any investment fund with which the director is affiliated.
Name of director
Shares owned
Share options Vested not yet exercised(1)
Share options Unvested with
performance conditions(1)
Share options Exercised during the year
Total (Shares and Share
Options)
Executive Directors
Hugh Griffith
1,265,026
1,284,367,880
691,582,704
-
1,977,215,610
Non-Executive Directors
Andrew Kay
-
52,934,010
52,934,010
-
105,868,020
Martin Mellish
36,117
35,231,753
35,231,753
2,887
70,499,623
Cyrille Leperlier
-
32,823,199
32,823,199
-
65,646,398
Elliott Levy
18,751
23,811,896
23,811,896
-
47,642,543
Adam George(2)
-
307,400
-
-
307,400
Bali Muralidhar(3)
540
13,181,363
-
-
13,181,903
All share options that were outstanding as at 31 December 2025 use time-based vesting and are not subject to performance targets other than continued service until the date of vesting.
Adam George retired from the Board on 21 March 2025. All unvested options lapsed on the date of his retiral.
Consists of 540 ordinary shares. Excludes 3,333,333 ordinary shares held by Abingworth Bioventures VII, LP ("Abingworth VII"). Abingworth VII (acting by its general partner Abingworth Bioventures VII GP LP, acting by its general partner Abingworth General Partner VII LLP) has delegated to Abingworth LLP ("Abingworth") all investment and dispositive power over the securities held by Abingworth VII. Abingworth holds the reported securities indirectly through Abingworth VII. Bali Muralidhar is a managing partner and investment committee member of Abingworth and disclaims beneficial ownership of the ADSs held by Abingworth VII. Bali Muralidhar retired from the Board on 21 October 2025. All unvested options lapsed on the date of his retiral.
Policy on shareholding requirements
We do not currently have a policy requiring our directors to hold a certain number or value of our shares.
Directors' equity-based awards held at 31 December 2025
The table below presents the interests of the directors in options to acquire our ordinary shares with a nominal value of £0.0004 per share as at 31 December 2025. A total of 2,291,915,026 options were granted to directors during the year ended 31 December 2025. One of our directors exercised options during the year ended 31 December 2025.
Name of director
Options held
Grant date
Start date for vesting
Earliest date of potential exercise of any options(1)
Date of expiry
Executive Directors
Hugh Griffith
1,284,367,880
20-Jun-2025
20-Jun-2025
20-Jun-2025
20-Jun-2035
691,582,704
20-Jun-2025
20-Jun-2025
20-Jun-2026
20-Jun-2035
Total
1,975,950,584
Non-Executive Directors
Andrew Kay
52,934,010
20-Jun-2025
20-Jun-2025
20-Jun-2025
20-Jun-2035
52,934,010
20-Jun-2025
20-Jun-2025
20-Jun-2026
20-Jun-2035
Total
105,868,020
Martin Mellish
35,231,753
20-Jun-2025
20-Jun-2025
20-Jun-2025
20-Jun-2035
35,231,753
20-Jun-2025
20-Jun-2025
20-Jun-2026
20-Jun-2035
Total
70,463,506
Cyrille Leperlier
32,823,199
20-Jun-2025
20-Jun-2025
20-Jun-2025
20-Jun-2035
32,823,199
20-Jun-2025
20-Jun-2025
20-Jun-2026
20-Jun-2035
Total
65,646,398
Elliott Levy
23,811,896
20-Jun-2025
20-Jun-2025
20-Jun-2025
20-Jun-2035
23,811,896
20-Jun-2025
20-Jun-2025
20-Jun-2026
20-Jun-2035
Total
47,623,792
Adam George(2)
21,000
8-May-2018
8-May-2018
8-May-2019
8-May-2028
25,000
15-May-2019
15-May-2019
15-May-2020
15-May-2029
47,832
10-Jun-2020
10-Jun-2020
10-Jun-2021
10-Jun-2030
9,567
9-Sep-2020
9-Sep-2020
9-Sep-2021
9-Sep-2030
34,650
10-Feb-2021
10-Feb-2021
10-Feb-2022
10-Feb-2031
33,413
15-Sep-2021
15-Sep-2021
15-Sep-2022
15-Sep-2031
28,125
9-Mar-2022
9-Mar-2022
9-Mar-2023
9-Mar-2032
9,375
12-Jul-2022
12-Jul-2022
12-Jul-2023
12-Jul-2032
9,375
16-Jun-2023
16-Jun-2023
16-Jun-2024
16-Jun-2033
18,750
12-Jul-2023
12-Jul-2023
12-Jul-2024
12-Jul-2033
70,313
13-Mar-2024
13-Mar-2024
13-Mar-2025
13-Mar-2034
Total
307,400
Bali Muralidhar(3)
13,181,363
20-Jun-2025
20-Jun-2025
20-Jun-2025
20-Jun-2035
Total
13,181,363
All share options awarded to directors that were outstanding as at 31 December 2025 use time-based vesting and are not subject to performance targets other than continued service until the date of vesting.
Adam George retired from the Board on 21 March 2025. All unvested options lapsed on the date of his retiral.
Bali Muralidhar retired from the Board on 21 October 2025. All unvested options lapsed on the date of his retiral.
The closing market price of our ADSs on 31 December 2025 was $3.60 or $0.001 per ordinary share. One ADS represents five thousand ordinary shares.
Payments made to past directors
During the year ended 31 December 2025, no payments were made to former directors of the Company.
Payments for loss of office
During the year ended 31 December 2025, no payments were made with respect to a director's loss of office.
Policy on payments for loss of office
Our approach to payments in the event of termination of an Executive Director is to take account of the individual circumstances including the reason for termination, individual performance, contractual obligations and the terms of the share option scheme in which the Executive Director participates.
Payment obligations would include base salary, target bonus and benefits. In addition, our option scheme rules allow some or all of the options held by our Executive Directors and Officers to vest in certain circumstances upon the event of a change of control.
There are no contractual provisions agreed prior to 27 June 2012 that could impact on the quantum of the payment.
We will comply with applicable disclosure and reporting requirements of the Securities and Exchange Commission with respect to remuneration arrangements with a departing Executive Director.
Illustration of total shareholder return
The information provided in this part of the Directors' Remuneration Report is not subject to audit.
The graph below shows the daily movements up to 31 December 2025, of $100 invested in NuCana plc ADS at our IPO price on 28 September 2017 compared with the value of $100 invested in the SPDR Series Trust SPDR S&P Biotech ETF (XBI). We believe this graph reflects our relative performance against a group of similarly situated comparator companies.
200.0
180.0
160.0
140.0
120.0
100.0
Sept-17Dec-17 Mar-18 Jun-18 Sep-18Dec-18Mar-19 Jun-19 Sep-19 Dec-19Mar-20 Jun-20 Sep-20Dec-20Mar-21 Jun-21 Sep-21Dec-21Mar-22 Jun-22 Sep-22 Dec-22Mar-23Jun-23 Sep-23Dec-23 Mar-24Jun-24 Sep-24Dec-24 Mar-25Jun-25 Sep-25Dec-25
NuCana plc ADS
XBI
220.0
80.0
60.0
40.0
20.0
Chief Executive Officer historical remuneration
The table below sets out total remuneration delivered to the CEO over the last ten years valued using the methodology applied to the single total figure of remuneration. The Remuneration Committee does not believe that the remuneration payable in its earlier years as a private company bears any comparative value to that paid in its later years and therefore the Remuneration Committee has chosen to disclose remuneration only for the ten most recent financial years.
Period
Single total figure of remuneration
£
Annual bonus payout against maximum opportunity
Long term incentive vesting rates against maximum opportunity
Year ended 31 December 2025(1)
4,387,020
72%
100%
Year ended 31 December 2024(1)
663,583
0%
100%
Year ended 31 December 2023(1)
1,073,184
59%
100%
Year ended 31 December 2022(1)
1,292,730
78%
100%
Year ended 31 December 2021(1)
2,158,116
60%
100%
Year ended 31 December 2020(1)
1,709,183
60%
100%
Year ended 31 December 2019
827,586
57%
100%
Year ended 31 December 2018
786,311
58%
n/a
Year ended 31 December 2017(1)
11,033,025
82%
100%
Year ended 31 December 2016
407,533
35%
100%
(1) The years ended 31 December 2025, 31 December 2024, 31 December 2023, 31 December 2022, 31 December 2021, 31 December 2020 and 31 December 2017 include unrealised gains on share options, which have not been exercised.
Change in director remuneration compared to other employees
The following table below shows the percentage change in the remuneration of directors and the average change per employee from 2020 onwards.
Percentage change in remuneration
Salary & Fees
%
Taxable Benefits
%
Annual Bonus
%
Executive Directors
Hugh Griffith
2024 to 2025
-
9.9
100.0
2023 to 2024
4.0
28.3
(100.0)
2022 to 2023
4.0
11.4
(18.0)
2021 to 2022
3.8
(2.9)
30.0
2020 to 2021
(3.7)
17.6
3.0
Non-Executive Directors(1)
Andrew Kay
2024 to 2025
(7.4)
-
-
2023 to 2024
1.2
-
-
2022 to 2023
9.3
-
-
2021 to 2022
22.4
-
-
2020 to 2021
3,219.8
-
-
Martin Mellish
2024 to 2025
6.6
-
-
2023 to 2024
1.1
-
-
2022 to 2023
7.5
-
-
2021 to 2022
16.3
-
-
2020 to 2021
(3.5)
-
-
Cyrille Leperlier
2024 to 2025
(29.9)
-
-
2023 to 2024
1.3
-
-
2022 to 2023
7.7
-
-
2021 to 2022
57.8
-
-
2020 to 2021
10.5
-
-
Elliott Levy
2024 to 2025
(29.1)
-
-
2023 to 2024
1.3
-
-
2022 to 2023
12.3
-
-
2021 to 2022
656.3
-
-
2020 to 2021
-
-
-
Adam George(2)
2024 to 2025
(70.1)
-
-
2023 to 2024
1.1
-
-
2022 to 2023
7.4
-
-
2021 to 2022
15.6
-
-
2020 to 2021
(3.9)
-
-
Bali Muralidhar(3)
2024 to 2025
-
-
-
2023 to 2024
-
-
-
2022 to 2023
(100.0)
-
-
2021 to 2022
(31.7)
-
-
2020 to 2021
378.2
-
-
Employees(4)
2024 to 2025
0.1
(4.0)
100.0
2023 to 2024
13.3
53.1
(100.0)
2022 to 2023
7.9
97.7
(2.3)
2021 to 2022
(1.4)
18.3
25.3
2020 to 2021
8.9
(1.3)
14.3
Fees for non-executive directors are set in US dollars and converted to pounds sterling (£) at the average rate for each year. Fees paid also reflect membership of various sub-committees, such as the Audit, Remuneration or Nominations Committee, in each respective year.
Adam George retired from the Board on 21 March 2025.
Bali Muralidhar retired from the Board on 21 October 2025.
The employee group comprises employees of the Company. The percentage change compares the average annualised costs for all employees employed by the Company in a specific year.
Relative importance of spend on pay
The following table sets forth the total amounts spent by the Group on remuneration for the year ended 31 December 2025 and the year ended 31 December 2024. The comparator chosen to reflect the relative importance of the Group's spend on pay is the Group's research and development expenses as shown in its consolidated income statement on page 44 of its Annual Report and Financial Statements for the year ended 31 December 2025. Dividend distribution and share buyback comparators have not been included as the Group has no history of such transactions.
Period:
Year ended 31 December 2025
Year ended 31 December 2024
£
(in thousands)
£
(in thousands)
Total spend on remuneration(1)
15,056
7,025
Research and development expenses
12,737
18,017
(1) The total spend on remuneration includes the value of equity-based awards as recognised in the financial statements in accordance with International Financial Reporting Standard 2 "Share-Based Payments".
directors' remuneration policy
The information in this part of the Directors' Remuneration Report is not subject to audit.
The Remuneration Committee presents the Directors' remuneration policy, which will be presented for approval at the Annual General Meeting held on 8 June 2026 to be adopted, if approved, with effect from that date. This policy is effective for a maximum of three years, or until a revised policy is approved by shareholders.
There will continue to be an advisory vote on the Directors' Remuneration Report presented at the Annual General Meeting on an annual basis.
For the avoidance of doubt, in approving the Directors' remuneration policy, authority is given to the Group to honour any commitments entered into with current or former Directors (such as the payment of a pension or the vesting/exercise of past share option awards). Details of any payments to former Directors will be set out in the Annual Report on Remuneration as they arise.
Future policy tables
The policy tables set out below describe the Group's proposed remuneration policy for Directors and seek to explain how each element of the Directors' remuneration packages will operate.
Summary of remuneration policy: Executive Directors & Officers
As NuCana plc is a U.K. incorporated company listed on The Nasdaq Stock Market LLC in the U.S., the Remuneration Committee considers it appropriate to examine and be informed by compensation practices in both the U.K. and U.S., particularly in the matter of equity-based incentives. The Remuneration Committee considers that the following proposed Directors' Remuneration Policy is appropriate and fit for purpose, but the Remuneration Committee is committed to reviewing the remuneration policy on an ongoing basis in order to ensure that it remains effective and competitive.
The following proposed Directors' Remuneration Policy will be used to determine the remuneration for our Executive Directors, Officers, and other senior executives, current and future. The Remuneration Committee is committed to reviewing the remuneration policy on an ongoing basis in order to ensure that it continues to be effective and competitive.
The following table presents the various elements of remuneration for the Executive Directors and Officers. The principles described below are also used for determining the remuneration of the senior executives.
Element of Remuneration
Purpose and link to strategy
Operation
Maximum
Performance Targets
Base salary
Rewards skills and experience and provides the basis for a competitive remuneration package.
Salaries are reviewed annually by reference to market data.
Salaries are benchmarked against comparable roles at relevant companies.
We typically expect to align salaries with the 75th percentile of peer companies.
The Remuneration Committee may also decide to approve future increases in base salaries following changes to job responsibilities or to reflect experience within the role.
Salaries will not generally exceed the 90th percentile of selected peer companies.
The Remuneration Committee retains discretion to adjust the Executive Directors' and Officers' base salaries to ensure that
we can attract and retain the necessary talent to compete in the global marketplace.
Not applicable.
cont
Element of Remuneration
Purpose and link to strategy
Operation
Maximum
Performance Targets
Pension
Enables Executive Directors and Officers to build long-term retirement savings.
Company contribution to a personal pension scheme or salary supplement. Levels are reviewed annually.
Will not generally exceed 10% of basic salary.
Not applicable.
Benefits
Protects against risks and provides other benefits in line with market practice.
Benefits currently include a supplemental health care plan, death-in-service life assurance, family private medical cover, ill-health income protection and car allowance for selected directors. The Remuneration Committee reviews benefits offered from time to time and retains the discretion to add or substitute benefits to ensure they remain market competitive.
In the event that the Group requires an Executive Director or Officer to relocate, we would offer appropriate relocation assistance..
Not applicable.
Not applicable.
Annual bonus
Rewards achievement of the business objectives set at the start of each calendar year.
Objectives are set at the start of each calendar year.
The choice of annual performance objectives will reflect the Remuneration Committee's assessment of the key milestones/metrics required to be achieved within the calendar year in order to make progress towards achieving our strategic goals.
The target annual cash bonus for our Executive Directors and Officers will be established as a percentage of base salary.
The annual bonus is payable in cash after it is awarded.
When business opportunities or challenges change substantially during the course of the year, the Remuneration Committee may adjust objectives to meet the changed circumstances and correspondingly realign potential rewards.
Awards will normally be limited to a maximum of 100% of basic salary.
In exceptional periods, considered to be those years in which achievements lead to a transformational effect on the future prospects or the valuation of the business, the annual maximum may increase up to 200% of basic salary.
Judgement as to whether achievements in a calendar year are considered to be exceptional is at the discretion of the Remuneration Committee.
The Remuneration Committee retains the responsibility of setting performance objectives annually.
These objectives can be company-based and/or individual, financial and/or non-financial, and are likely to include achievements linked to successful execution of our strategy.
A number of these objectives are considered to be commercially sensitive and are therefore not disclosed here in detail.
Long-term equity incentives
Motivates and rewards multi-year performance, encouraging achievement of strategy over the medium to long term.
Aligns the interests of our Executive Directors and Officers with those of our shareholders.
Encourages retention as entitlement to full benefits arising from equity-based awards only accrues over a period of years.
Enables us to compete with equity-based remuneration offered by a set of comparable companies with which we may compete for executive talent.
Under our share option schemes, the Remuneration Committee generally grants equity-based remuneration to Executive Directors and Officers at the time they commence employment and from time to time thereafter based on performance.
The Remuneration Committee is able to grant share options, conditional share awards (sometimes called restricted stock units), RSU style options and/or joint ownership shares, which permit phased vesting over the period.
Conditional share awards are rights to receive shares for free automatically to the extent the award vests.
There is no fixed annual maximum limit to the size or value of equity-based
compensation awards made in a year to Executive Directors and Officers, or in the aggregate over a period of years.
The Remuneration Committee will always work within benchmarking guidelines provided by our compensation consultants. Additionally, there is a maximum limit on the grant of options to all employees based on the number of authorised shares available for option grants.
Generally we grant equity-based remuneration awards that
vest over time without specific performance targets other than continued service.(1)
When making awards, the Remuneration Committee considers: the size and value of past awards; the performance of the Executive Director or Officer; and competitive data on awards made to executives at comparable companies.
cont
Disclaimer
NuCana plc published this content on May 06, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 06, 2026 at 11:26 UTC.