Executive Summary / Key Takeaways

• Proprietary ProTide Technology as Core Differentiator: NuCana plc is a clinical-stage biopharmaceutical company leveraging its proprietary ProTide technology to develop novel cancer treatments, aiming to enhance the efficacy and safety of existing chemotherapy agents and nucleoside analogs by generating higher concentrations of anti-cancer metabolites in cancer cells.
• Extended Cash Runway and De-risked Nasdaq Listing: A significant de-risking event occurred with NuCana regaining compliance with Nasdaq's listing rules in September 2025, coupled with management's guidance that existing cash resources are sufficient to fund planned operations into 2029, extending the company's financial lifeline through key value-driving milestones.
• Advancing Clinical Pipeline: The company continues to progress its pipeline candidates, NUC-3373 and NUC-7738, with ongoing Phase 1b/2 and Phase 2 studies for various advanced solid tumors and colorectal cancer, including a new expansion study for NUC-7738 in combination with Pembrolizumab for PD-1 inhibitor-resistant melanoma.
• High-Risk, High-Reward Profile: NuCana operates in an intensely competitive oncology market, facing significant financial challenges typical of clinical-stage biotechs, including consistent net losses and a reliance on capital raises, which positions it as a high-risk, high-reward investment.
• Competitive Niche and Challenges: While its ProTide technology offers a potential competitive moat, NuCana's smaller scale and developmental stage mean it lags significantly behind large pharmaceutical competitors in terms of financial performance, market presence, and operational execution.

The ProTide Promise: Reshaping Cancer Therapy

NuCana plc, established in 1997 as NuCana BioMed Limited before its 2017 rebranding, is a clinical-stage biopharmaceutical company dedicated to transforming cancer treatment through its innovative ProTide technology. The company's foundational strategy revolves around applying this proprietary platform to enhance the effectiveness and safety of existing chemotherapy agents and nucleoside analogs. This technology is designed to overcome the inherent limitations of traditional nucleoside analogs by facilitating the generation of higher concentrations of anti-cancer metabolites directly within cancer cells. This targeted approach aims to improve therapeutic outcomes and potentially reduce systemic toxicity, offering a qualitative advantage over conventional treatments.

The ProTide platform represents NuCana's core technological differentiator, a patented intellectual property that forms the bedrock of its competitive moat. While specific quantitative performance metrics for the technology's benefits, such as a precise percentage increase in drug delivery or reduction in side effects, are not publicly detailed, the strategic intent is clear: to create "more effective and safer medicines". This innovation is crucial in the intensely competitive oncology market, where differentiation is key to capturing value. NuCana's research and development efforts, supported by an assignment, license, and collaboration agreement with Cardiff ProTides Ltd, are continuously focused on discovering and screening new purine and pyrimidine-based nucleosides as potential drug candidates, underscoring a long-term commitment to technological advancement.

Within this competitive landscape, NuCana operates as a niche player, contrasting sharply with the broad commercial scale and diversified portfolios of pharmaceutical giants like Gilead Sciences (GILD), AstraZeneca (AZN), Merck (MRK), and Bristol-Myers Squibb (BMY). These larger entities leverage extensive resources, established market presence, and robust revenue streams from commercialized products. For instance, while NuCana reports zero revenue and consistent net losses, its larger competitors demonstrate strong profitability and positive price-to-earnings ratios, reflecting their mature commercial operations. NuCana's competitive advantage lies in its specialized technological innovation, aiming for superior efficacy in specific cancer types through its ProTide platform. However, its smaller scale and early-stage development mean it lags in financial performance, market share capture, and the speed of innovation compared to these well-resourced rivals.

Clinical Progress and Strategic Adjustments

NuCana's pipeline is spearheaded by two key ProTide candidates: NUC-3373 and NUC-7738. NUC-3373, a derivative of 5-fluorouracil, is currently undergoing a Phase 1b/2 study for metastatic colorectal cancer, a Phase 2 clinical trial for second-line treatment of advanced colorectal cancer, and a Phase 1 modular clinical trial for advanced solid tumors and lung cancer. Encouraging initial data from a Phase 1b/2 modular study of NUC-3373 in combination with pembrolizumab or docetaxel, announced in November 2024, showed disease stabilization in hard-to-treat patient populations.

NUC-7738, a ProTide transformation of 3'-deoxyadenosine (cordycepin), is in the Phase 2 part of a Phase 1/2 clinical trial for patients with advanced solid tumors. Notably, an expansion study of NUC-7738 in combination with pembrolizumab has been initiated for patients with PD-1 inhibitor-resistant melanoma, following Phase 2 results that demonstrated significant disease control in 9 of 12 patients in this challenging population. This strategic move into combination therapies and resistant patient populations highlights NuCana's focus on addressing unmet medical needs. However, not all clinical paths have been smooth; the NuTide:323 study for NUC-3373 in metastatic colorectal cancer was discontinued after a pre-planned analysis indicated it was unlikely to achieve its primary objective of superior Progression Free Survival.

Financial Resilience and Nasdaq Compliance

As a clinical-stage biopharmaceutical company, NuCana has consistently reported negative net income, reflecting its significant investment in research and development and the absence of product revenue. The company's net loss improved from £27.6 million in 2023 to £19.0 million in 2024. However, cash and cash equivalents have seen a substantial decline, from £60.26 million in 2021 to £6.75 million by the end of 2024. This cash burn is typical for companies at this stage, necessitating strategic capital-raising efforts.

NuCana has actively managed its liquidity, evidenced by an increase in capital stock issuance, including £8.73 million in 2024. The company also successfully canceled all outstanding Series A Warrants in July 2025, having raised the necessary capital through an at-the-market (ATM) offering. Critically, management has provided guidance that its existing cash resources, including proceeds from the ATM offering, are anticipated to be sufficient to fund planned operations into 2029. This extended cash runway provides a crucial lifeline, allowing the company to pursue key value-driving milestones without immediate financing pressures.

A significant recent development that de-risked the investment profile was NuCana's successful resolution of its Nasdaq listing challenges. The company was notified in June and July 2025 of non-compliance with Nasdaq's minimum bid price requirement, which could have led to delisting. Following a hearing and the implementation of an American Depositary Share (ADS) ratio change (a 1-for-200 reverse ADS split effective August 11, 2025), NuCana received formal notification on September 4, 2025, confirming its compliance with all applicable Nasdaq continued listing criteria, including the $1.00 minimum bid price requirement. This resolution removes a significant overhang and provides stability for investors.

Outlook and Persistent Risks

The extended cash runway into 2029 provides NuCana with a critical window to advance its clinical programs and potentially reach significant value inflection points. Management's confidence in funding operations through "a number of key value-driving milestones" suggests a strategic roadmap focused on clinical progression. However, the inherent risks of clinical-stage biopharmaceutical development remain pronounced. Trial failures, such as the discontinuation of the NuTide:323 study, are a constant threat, impacting timelines and investor sentiment. Regulatory hurdles, intense competition from well-capitalized pharmaceutical companies, and the ongoing need for substantial R&D investment also pose significant challenges.

Despite the positive resolution of the Nasdaq listing and the extended cash runway, the company's financial profile, characterized by zero revenue and consistent operating losses, positions it as a speculative investment. An analyst projection suggests a substantial upside potential of over 5,000% from a recent trading price, with a one-year price target averaging $25.09, yet the consensus recommendation remains a "Hold." This dichotomy reflects the high-risk, high-reward nature of investing in clinical-stage biotech, where the promise of innovative technology must be weighed against the long and uncertain path to commercialization.

Conclusion

NuCana plc stands at a pivotal juncture, having successfully navigated the immediate threat of a Nasdaq delisting and secured an extended cash runway into 2029. This stability provides a crucial foundation for the company to continue advancing its proprietary ProTide technology, which represents a compelling attempt to overcome the limitations of conventional cancer therapies. The ongoing clinical progress of NUC-3373 and NUC-7738, particularly the expansion study for PD-1 inhibitor-resistant melanoma, underscores the potential of its differentiated platform.

However, the investment thesis for NuCana remains firmly rooted in its ability to translate technological innovation into clinical success and, eventually, commercial viability. The company operates in a fiercely competitive oncology market, where its smaller scale and developmental stage present significant challenges against established pharmaceutical giants. While the ProTide technology offers a potential competitive edge, investors must carefully weigh the substantial risks inherent in clinical development and the long path to profitability against the promising, yet unproven, potential of its pipeline. The coming years, marked by key clinical milestones, will be critical in determining whether NuCana can truly unlock the value embedded in its ProTide platform and deliver on its ambitious mission to redefine cancer treatment.