Company: NCNA
Filing Date: 2025-06-27
Form Type: 424B5
Source: 0001193125-25-151464
Chunk: 5

Company: NuCana plc
Filing Date: 2025-06-27
Form: 424B5
Chunk 5
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 as additional information about us. The information contained on, or that can be accessed through, our website is not a part of this prospectus supplement. We have included our website address in this prospectus supplement solely as an inactive textual reference.

We use our registered trademarks, NuCana and Acelarin, and our trademark, ProTides, in this prospectus supplement. This prospectus supplement also includes trademarks, tradenames and service
marks that are the property of other organizations. Solely for convenience, trademarks and tradenames referred to in this prospectus supplement appear without the and symbols, but those references are not intended to indicate, in any way, that we will not assert, to the fullest extent under applicable law, our rights or that the applicable owner will not assert
its rights, to these trademarks and tradenames.

S-4

THE OFFERING

| ADSs offered by us | ADSs having an aggregate offering price of up to $100.0 million. |

| Manner of offering | “At the market offering” that may be made from time to time through our Sales Agents, A.G.P. and Laidlaw. See “Plan of Distribution” on page S-14 of this prospectus supplement. |

| The ADSs | Each ADS represents 25 ordinary shares, nominal value £0.0004 per share. The offered ADSs may be evidenced by American Depositary Receipts, or ADRs. |

| Depositary | Citibank, N.A. |

| Use of proceeds | We currently intend to use the net proceeds of this offering to fund activities relating to the advancement of our drug discovery and development programs, and for other general corporate purposes, including, but not limited to, working capital, 
 capital expenditures, investments, acquisitions, should we choose to pursue any, and collaborations. See the section titled “Use of Proceeds” on page S-11 of this prospectus supplement.                                                             |

| Risk factors | See “Risk Factors” beginning on page S-6 of this prospectus supplement and the other information included in, or incorporated by reference into, this prospectus supplement for a discussion of 
 certain factors you should carefully consider before deciding to invest in our ADSs.                                                                                                            |

| Ordinary shares outstanding prior to this offering | 9,540,891,147 ordinary shares outstanding as of June 20, 2025. The number of shares outstanding excludes (i) 3,480,390,631 ordinary shares issuable upon exercise of outstanding options