Company: NCNA
Filing Date: 2025-06-27
Form Type: 424B5
Source: 0001193125-25-151464
Chunk: 1

Company: NuCana plc
Filing Date: 2025-06-27
Form: 424B5
Chunk 1
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 OF WARRANTS                           |     | 35 |
| DESCRIPTION OF RIGHTS                             |     | 36 |
| DESCRIPTION OF UNITS                              |     | 38 |
| DESCRIPTION OF AMERICAN DEPOSITARY SHARES         |     | 40 |
| EXPENSES                                          |     | 51 |
| LEGAL MATTERS                                     |     | 52 |
| EXPERTS                                           |     | 52 |
| ENFORCEMENT OF JUDGMENTS                          |     | 52 |
| WHERE YOU CAN FIND MORE INFORMATION               |     | 53 |
| INCORPORATION OF DOCUMENTS BY REFERENCE           |     | 54 |

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ABOUT THIS PROSPECTUS SUPPLEMENT

This prospectus supplement is part of a registration statement that we filed with the SEC utilizing a “shelf” registration process.
Under this shelf registration process, we may from time to time sell ADSs representing our ordinary shares having an aggregate offering price of up to $100.0 million under this prospectus supplement at prices and on terms to be determined by
market conditions at the time of the offering.

Before buying any of the ADSs that we are offering, we urge you to carefully read this
prospectus supplement and all of the information incorporated by reference herein and therein, as well as the additional information described under the headings “Where You Can Find More Information” and “Incorporation of Documents by
Reference.” These documents contain important information that you should consider when making your investment decision.

We provide
information to you about this offering of our ADSs representing our ordinary shares in: (1) this prospectus supplement, which describes the specific details regarding this offering; and (2) the accompanying base prospectus, which provides
general information, some of which may not apply to this offering. Generally, when we refer to this “prospectus,” we are referring to both documents combined. If information in this prospectus supplement is inconsistent with the
accompanying base prospectus, you should rely on this prospectus supplement. To the extent there is a conflict between the information contained in this prospectus supplement, on the one hand, and the information contained in any document
incorporated by reference in this prospectus supplement, on the other hand, you should rely on the information in this prospectus supplement. If any statement in one of these documents is inconsistent with a statement in another document having a
later date—for example, a document incorporated by reference in this prospectus supplement— the statement in the document