Initiation of Expansion Study of NUC-7738 in Combination with Pembrolizumab for Patients with PD-1 Inhibitor-Resistant Melanoma Initial Data from the Expansion Study of NUC-7738 Expected in Q4 2025 with Final Data in 2026 Additional Data from the Ongoing Phase 1b/2 Study of NUC-3373 in Combination with Pembrolizumab Remain on track for 2025 Anticipated Cash Runway Extended into Q4 2026 to Support Key Value-Driving Milestones and Complete the Expansion Study of NUC-7738 EDINBURGH, United Kingdom, June 02, 20 ...

Financial Performance - Research and development expenses for 2024 were £18,017 thousand, a decrease of 28% from £25,062 thousand in 2023[29]. - Administrative expenses decreased to £4,988 thousand in 2024 from £6,063 thousand in 2023, representing a reduction of 18%[29]. - The operating loss for 2024 was £22,809 thousand, down 30% from £32,784 thousand in 2023[29]. - The net loss for the year 2024 was £18,997 thousand, a 31% improvement compared to £27,632 thousand in 2023[29]. - The basic and diluted loss per ordinary share improved to £0.26 in 2024 from £0.53 in 2023[29]. - The company has an accumulated deficit totaling £224.3 million and cash flows used in operating activities of £19.1 million for the year ended December 31, 2024[67]. - The company has cumulative carry forward tax losses of £104.2 million as of December 31, 2024, which may be subject to restrictions limiting their utilization[77]. Cash and Assets - As of December 31, 2024, cash and cash equivalents were £6,749 thousand, a significant decrease from £17,225 thousand in 2023[30]. - Total assets decreased to £14,774 thousand in 2024 from £27,811 thousand in 2023, reflecting a decline of 47%[30]. - As of December 31, 2024, the company had cash and cash equivalents of £6.7 million, indicating a need for substantial additional funding to continue operations[67]. Future Financial Outlook - The company expects to continue incurring losses for the foreseeable future, indicating ongoing financial challenges[44]. - The company expects to incur significant expenses and operating losses for the foreseeable future, with net losses fluctuating significantly from quarter to quarter[45]. - The company may require additional capital to continue operations, which could dilute ownership interests[50]. - The company plans to commence an equity financing process to raise additional capital, but there is no assurance of success, and failure to raise funds could lead to operational wind down or bankruptcy[70]. - The company faces uncertainty regarding its ability to raise additional capital within the going concern period, which may negatively impact its trading price and relationships with third parties[68]. Product Development and Regulatory Challenges - The company is currently evaluating product candidates NUC-7738 and NUC-3373 in ongoing clinical trials, which are critical for future revenue generation[44]. - The company has invested substantially in the development of product candidates NUC-7738 and NUC-3373, with no revenues generated from product sales expected for at least the next several years[51]. - The company plans to seek regulatory approval for NUC-7738 and NUC-3373 in the United States and the European Union, facing varying regulatory requirements across jurisdictions[55]. - The company may face significant delays or inability to commercialize product candidates if it does not overcome various development and regulatory challenges[53]. - The company anticipates that expenses will increase substantially as it completes ongoing clinical trials and initiates additional trials for its product candidates[48]. - The company has not submitted any New Drug Applications (NDA) or Marketing Authorization Applications (MAA) for its product candidates and does not expect to do so in the foreseeable future[51]. - The company must obtain marketing approvals in multiple jurisdictions, which requires substantial investment and significant marketing efforts[103]. Clinical Trials and Market Risks - NUC-7738 is currently in the Phase 2 part of a Phase 1/2 clinical trial (NuTide:701) for advanced solid tumors and melanoma, with favorable results from Phase 1 not guaranteed to replicate[100]. - NUC-3373 is being evaluated in a Phase 1b/2 modular clinical trial (NuTide:303) in combination with pembrolizumab and docetaxel for advanced solid tumors and lung cancer, respectively[100]. - The risk of failure in drug development is high, with significant delays or inability to complete clinical trials potentially harming business prospects[110]. - Delays in patient enrollment for clinical trials could significantly impact the development timeline and increase costs[109]. - The FDA may require additional studies or impose new requirements that could delay or prevent marketing approval for product candidates[112]. Compliance and Regulatory Environment - The company is subject to the GDPR and U.K. GDPR when conducting clinical trials involving U.K.- or E.E.A.-based data subjects, which imposes strict requirements for handling personal data[118]. - The GDPR allows for fines of up to €20 million or 4% of total worldwide annual turnover for non-compliance, with the potential for increased fines based on turnover[128]. - The company faces increasing complexity and costs due to various U.S. state privacy laws, such as California's CCPA and the recently enacted "My Health My Data" Act in Washington State[131][132]. - The company must navigate potential legal challenges and regulatory scrutiny related to data transfers between the E.E.A. and the U.S., which may affect service provision and financial results[120][123]. - The company is subject to healthcare laws and regulations that could expose it to criminal sanctions and civil penalties[155]. Market Competition and Commercialization - The company faces substantial competition from major pharmaceutical and biotechnology companies, which may hinder the commercialization of its product candidates[206]. - If product candidates receive marketing approval, their market acceptance will depend on factors such as efficacy, safety, pricing, and reimbursement availability[205]. - The company currently lacks marketing capability or a sales force, which may impede its ability to effectively sell or market approved product candidates[215]. - There is a risk that competitors may develop safer, more effective, or less expensive products, potentially reducing the company's market opportunity[209]. - The company may face delays in obtaining reimbursement for newly approved drugs, which could negatively impact revenue generation[214]. Cybersecurity and Operational Risks - Cybersecurity incidents pose a risk to the company's internal systems and could disrupt product development programs[217]. - The company has implemented cybersecurity measures to prevent and respond to incidents, but vulnerabilities remain, which could lead to significant operational disruptions and financial harm[219]. - Loss of clinical trial data could delay development and regulatory approval efforts, significantly increasing recovery costs and exposing the company to regulatory enforcement and reputational damage[219]. - Product liability lawsuits pose substantial risks, potentially leading to significant liabilities and limiting commercialization of developed products[220]. Intellectual Property and Collaboration - Intellectual property protection is crucial for the company's technology and products; failure to secure adequate patents could impair commercialization efforts[223]. - The company's patent portfolio includes both patents and applications covering novel product candidates, formulations, and manufacturing processes[224]. - The company is required to maintain compliance with various obligations under its collaboration agreement, failure of which could result in loss of rights to essential intellectual property[204]. - Collaborations with third parties for product development may not be successful, impacting the company's ability to generate additional product candidates[198].

Exhibit 99.1 NuCana Reports Fourth Quarter and Year-End 2024 Financial Results and Provides Business Update Remains on Track to Initiate an Expansion Study of NUC-7738 in Combination with Pembrolizumab for Patients with PD-1 Inhibitor-Resistant Melanoma in 2025 Data from the Expansion Study to Support Interaction with FDA and Define Regulatory Strategy for NUC-7738 Data from the Ongoing Phase 1b/2 Study of NUC-3373 in Combination with Pembrolizumab Anticipated Cash Runway Extended into Q3 2025 Edinburgh, Un ...

Core Insights - NuCana plc is advancing its clinical development programs for two lead anti-cancer medicines, NUC-7738 and NUC-3373, with significant data updates shared throughout 2024 [2][3] - The company plans to initiate an expansion study of NUC-7738 in combination with pembrolizumab for patients with PD-1 inhibitor-resistant melanoma in 2025, aiming to gather data to support regulatory strategy with the FDA [1][4] Clinical Development - NUC-7738 has shown promising results in the NuTide:701 study, with 75% of patients demonstrating disease control and notable tumor reductions [3] - NUC-3373 is being evaluated in a Phase 1b/2 study (NuTide:303) with two modules: one combining it with pembrolizumab for advanced solid tumors and another with docetaxel for lung cancer [3][9] - The company is encouraged by the significant tumor volume reductions observed in the NuTide:303 study, including a patient with 100% reduction in target lesions [3] Financial Performance - As of December 31, 2024, NuCana reported cash and cash equivalents of £6.7 million, down from £17.2 million a year prior, primarily due to cash used in operating activities [5][6] - The net loss for Q4 2024 was £0.7 million, a significant reduction from £7.7 million in Q4 2023, while the annual net loss decreased to £19.0 million from £27.6 million [6][11] - Basic and diluted loss per ordinary share for the year ended December 31, 2024, was £0.26, compared to £0.53 for the previous year [6][11] Future Outlook - The company anticipates key milestones in 2025, including the initiation of the expansion study for NUC-7738 and data announcements from the NuTide:303 study for NUC-3373 [4][9] - NuCana has strengthened its intellectual property portfolio with a new patent granted for NUC-7738's composition of matter [3]

Financial Performance - For the three months ended September 30, 2024, the operating loss was £5.3 million, a decrease of 35% compared to £8.3 million for the same period in 2023[3]. - The loss for the period attributable to equity holders of the Company for the nine months ended September 30, 2024, was £18.3 million, compared to £20.0 million in 2023, reflecting a 8.2% improvement[3]. - The Company reported a total comprehensive loss of £18.4 million for the nine months ended September 30, 2024, compared to £20.0 million in 2023[5]. - For the three months ended September 30, 2024, the company reported a loss of £4.5 million, compared to a loss of £6.7 million for the same period in 2023, indicating a 32.6% improvement[28]. - The basic and diluted loss per ordinary share for the nine months ended September 30, 2024, was £0.32, an improvement from £0.38 in 2023[3]. - The basic and diluted loss per share for the three months ended September 30, 2024, was £0.07, compared to £0.13 for the same period in 2023, reflecting a 46.2% reduction in loss per share[28]. Cash and Assets - Cash and cash equivalents at the end of the period were £11.4 million, down from £17.2 million at the end of 2023[7]. - Total assets decreased to £19.5 million as of September 30, 2024, from £27.8 million at December 31, 2023[7]. - The accumulated deficit increased to £223.7 million as of September 30, 2024, compared to £207.7 million at the end of 2023[7]. - Cash and cash equivalents decreased to £11.4 million as of September 30, 2024, from £17.2 million as of December 31, 2023, representing a decline of 33.8%[31]. Operating Activities - The Company has not generated any revenues from operations to date and does not expect to in the foreseeable future[22]. - The Company incurred cash flows used in operating activities of £11.7 million for the nine months ended September 30, 2024[22]. Going Concern - The company has a going concern period of 12 months, and current cash and cash equivalents are insufficient to fund anticipated operations during this period[23]. - There is substantial doubt about the company's ability to continue as a going concern, raising uncertainty regarding the realization of assets and discharge of liabilities[24]. Research and Development - Research and development expenses for the nine months ended September 30, 2024, were £17.3 million, down 5% from £18.2 million in 2023[3]. - The company intends to seek additional capital through equity or debt financing to fund ongoing research and development activities[23]. Share Capital - Share capital as of December 31, 2023, was £2,860,000, with a premium of £1,414,000[37]. - The number of issued shares is 98,630,052, with an ordinary share value of £0.004 each[37]. - Balance at September 30, 2024, was £9,630,303, with a share capital of £5,662,145[37]. - The exercise of share options resulted in an increase of £1,825,543 in share capital[37]. - The company reported a fully paid ordinary share balance of £5,286,602 as of December 31, 2023[37]. Tax Credits - The income tax credit recognized primarily represents U.K. research and development tax credits, with a total income tax credit of £740,000 for the three months ended September 30, 2024[26]. - The company has a current income tax receivable of £4.4 million as of September 30, 2024, down from £5.1 million as of December 31, 2023[27]. Share-Based Payments - The company recognized £0.4 million in share-based payment expense for the three months ended September 30, 2024, down from £0.9 million for the same period in 2023, a decrease of 55.6%[36]. Intangible Assets - The company acquired intangible assets related to patents at a cost of £0.2 million during the nine months ended September 30, 2024[30].

Core Insights - NuCana plc presented encouraging Phase 2 data for NUC-7738 in combination with pembrolizumab at the ESMO Congress 2024, showing a median progression-free survival of over five months in PD1 inhibitor-resistant melanoma patients [2][3] - The company also announced promising Phase 1b/2 data for NUC-3373, indicating significant tumor volume reductions and prolonged progression-free survival in patients with advanced solid tumors [2][5] - NuCana's cash position as of September 30, 2024, was £11.4 million, with expectations to fund operations into Q2 2025 [6][7] Clinical Development Updates - NUC-7738: The Phase 2 part of the NuTide:701 study demonstrated that 9 out of 12 patients achieved disease control, with one patient showing a 55% reduction in tumor volume [2] - NUC-3373: Initial data from the NuTide:303 study showed that NUC-3373 may enhance anti-tumor immune responses when combined with pembrolizumab or docetaxel, including a patient with urothelial bladder cancer achieving a 100% reduction in target lesions [2][5] Financial Performance - For Q3 2024, NuCana reported a net loss of £4.5 million, an improvement from a net loss of £6.7 million in Q3 2023, with a basic and diluted loss per share of £0.07 compared to £0.13 in the prior year [7][11] - The company had cash and cash equivalents of £11.4 million as of September 30, 2024, down from £17.2 million at the end of 2023, primarily due to cash used in operating activities [6][11] Future Milestones - For NUC-7738, the company plans to initiate an expansion of the Phase 1/2 study and announce data from this expansion in 2025 [3] - For NUC-3373, the company aims to expand the Phase 1b/2 study and announce data from this study in the upcoming year [5]

Core Insights - Baillie Gifford has acquired 917,600 shares of NuCana PLC at $3.66 per share, indicating a strategic investment in the biotechnology sector [1] - The firm is known for its long-term investment approach, focusing on companies with growth potential, particularly in technology and consumer cyclical sectors [2] Company Overview - Baillie Gifford, established over a century ago, manages assets for large professional investors and emphasizes fundamental analysis and proprietary research [2] - NuCana PLC specializes in developing cancer treatments using its ProTide technology, which aims to enhance the efficacy of nucleotide analogs [4] Financial Metrics - NuCana's current market capitalization is approximately $4.235 million, with a significant stock price decline of 48.57% since the acquisition [4] - The company has a Profitability Rank of 1/10 and an ROE of -181.32%, indicating struggles with profitability, although it maintains a strong balance sheet with a cash-to-debt ratio of 41.36 [5] Strategic Rationale - The acquisition aligns with Baillie Gifford's strategy of investing in innovative technologies with substantial growth potential, despite the immediate financial impact being minimal [6] - NuCana's focus on niche technology differentiates it from competitors, although it faces high R&D costs and regulatory challenges [7] Future Prospects - The success of NuCana's ProTide technology could redefine its market position or lead to further financial strain, making the investment a calculated risk for Baillie Gifford [8] - The long-term implications of this acquisition will depend on NuCana's ability to advance its technology and achieve commercial success [9]

Core Viewpoint - NuCana plc has received a new patent for NUC-7738, enhancing its intellectual property protection and supporting its ongoing clinical studies for this novel anti-cancer agent [1][2]. Group 1: Patent and Intellectual Property - The United States Patent and Trademark Office (USPTO) issued a new patent (US12,054,510) for NUC-7738's composition of matter, which is a significant addition to the company's existing portfolio of over 80 issued patents worldwide [1][2]. - The new patent strengthens the intellectual property protection for NUC-7738, which is crucial for the company's competitive positioning in the biopharmaceutical market [2]. Group 2: Clinical Development and Efficacy - NUC-7738 is currently in a Phase 2 clinical study in combination with pembrolizumab for patients with PD-1 inhibitor resistant melanoma, with encouraging data presented at the ESMO Congress 2024 [1][2]. - The majority of patients with PD-1 inhibitor resistant metastatic melanoma achieved a progression-free survival of more than 5 months when treated with NUC-7738 plus pembrolizumab, compared to a median progression-free survival of 2-3 months with the current standard of care [2]. - NUC-7738 targets multiple aspects of the tumor microenvironment, which may contribute to its ability to make previously resistant tumors sensitive to treatment [2]. Group 3: Company Overview and Technology - NuCana is a clinical-stage biopharmaceutical company focused on improving cancer treatment outcomes through its ProTide technology, which transforms conventional chemotherapy agents into more effective and safer medicines [3]. - The company's pipeline includes NUC-3373 and NUC-7738, with NUC-3373 currently being evaluated in multiple clinical studies for various cancer types [3].

Core Insights - NuCana plc's shares surged by 150.8% following positive final data from the mid-stage study of its candidate NUC-7738 in combination with Merck's Keytruda for treating metastatic melanoma [1] Study Results - In the phase II NuTide:701 study, 75% of the 12 patients treated with the NUC-7738/Keytruda combination achieved disease control, including two partial responses [2] - One patient, previously treated with two rounds of PD-1 inhibitors, showed a 55% reduction in tumor size, and seven patients had progression-free survival exceeding five months, compared to a median of 2-3 months with standard treatments [3] Safety Profile - The combination therapy of NUC-7738 and Keytruda exhibited a favorable safety profile [4] Mechanism of Action - NUC-7738 disrupts RNA polyadenylation, sensitizing PD-1-resistant tumors to PD-1 inhibitors, with data showing increases in genes related to antigen presentation and T-cell activation [5] Future Development Plans - NuCana believes NUC-7738's mechanism may extend beyond melanoma to other PD-1 inhibitor-resistant tumors, with further development plans to be announced soon [8] Other Pipeline Programs - NuCana is also developing NUC-3373, which is being evaluated in combination with other agents for colorectal cancer, lung cancer, and advanced solid tumors, with data readouts expected by the end of 2024 [9] Market Context - Merck's Keytruda, a leading anti-PD-1 therapy, accounted for 47% of the company's pharmaceutical sales in 2023 and continues to expand into new indications and markets [7]

Core Insights - NuCana plc presented final data from the Phase 2 NuTide:701 study at the ESMO Congress, focusing on NUC-7738 in combination with pembrolizumab for patients with metastatic melanoma who were refractory to or had relapsed on prior PD-1 inhibitor therapy [1][4] Efficacy Results - In a cohort of 12 patients, 75% (9 patients) achieved disease control, with two patients showing Partial Responses. One patient experienced a 55% reduction in tumor volume after progressing on previous treatments [2] - Seven out of the 12 patients had a progression-free survival time exceeding five months, which is significantly better than the typical 2-3 months seen with current standard care [4] Mechanism of Action - NUC-7738 is believed to sensitize PD-1 resistant tumors to PD-1 inhibitors by targeting multiple aspects of the tumor microenvironment through the disruption of RNA polyadenylation and subsequent changes in gene expression [3] - Data from tumor biopsies indicated increases in genes related to antigen presentation and T-cell activation following NUC-7738 treatment [3] Company Overview - NuCana is a clinical-stage biopharmaceutical company focused on improving cancer treatment outcomes through its ProTide technology, which transforms nucleoside analogs into more effective and safer medicines [5] - The company's pipeline includes NUC-3373 and NUC-7738, with NUC-3373 currently evaluated in two ongoing clinical studies for metastatic colorectal cancer and advanced solid tumors [5]