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Mereo BioPharma Group plc (the “Company”) – Registration Statement on Form S-3 Exhibit 5.1

INTRODUCTION

Purpose

Defined terms and headings

capitalised terms used without definition in this letter or the schedules hereto have the meanings assigned to them in the Registration Statement unless a contrary indication appears;

“AstraZeneca Shares” means the 2,044,390 Ordinary Shares issued to AstraZeneca on 11 November 2024 pursuant to the AstraZeneca Subscription Agreement;

“AstraZeneca Subscription Agreement” means the subscription agreement dated 28 October 2017, as amended on 21 May 2021 and 8 November 2024, between the Company and AstraZeneca AB (“AstraZeneca”);

“Instruments” means the AstraZeneca Subscription Agreement, the SVB and Kreos Instruments, the Novartis Instruments, and the TAP Instrument;

“Novartis Shares” means up to 20,555,067 Ordinary Shares that may be issued to Novartis Pharma AG (“Novartis”) pursuant to (1) a convertible loan instrument issued by the Company and held by Novartis, dated 10 February 2020, as amended on 24 November 2020 and 10 February 2023, together with the form of Conversion Notice (as defined therein), and (2) a warrant instrument issued by the Company and held by Novartis dated 10 February 2020, as amended on 24 November 2020, together with the form of Notice of Subscription and Warrant Certificate (in each case as defined therein) (the “Novartis Instruments”);

“Shares” means the Underlying Shares and the AstraZeneca Shares;

“SVB and Kreos Shares” means up to 2,487,816 Ordinary Shares that may be issued to Silicon Valley Bank (“SVB”) and Kreos Capital V (UK) Limited (“Kreos”) pursuant to certain warrant instruments issued by the Company and held by SVB and Kreos dated 21 August 2017 and 1 October 2018, each as amended on 15 December 2020, together with the relevant form of Notice of Subscription and Warrant Certificate (in each case as defined therein) (the “SVB and Kreos Instruments”);

“TAP Shares” means up to 1,551,699 Ordinary Shares that may be issued to The Alpha-1 Project, Inc. (“TAP”) pursuant to a warrant instrument issued by the Company and held by TAP dated 2 November 2018, as amended on 29 March 2021 together with the form of Notice of Subscription and Warrant Certificate (in each case as defined therein) (the “TAP Instrument”);

“Underlying Shares” means the Novartis Shares, the SVB and Kreos Shares and the TAP Shares; and

headings are for ease of reference only and shall not affect interpretation.

Legal review

an online search at the UK Companies House in respect of the Company conducted on 25 November 2024;

an enquiry at the Central Registry of Winding Up Petitions, London on 25 November 2024 at 10.03 a.m. (London time) with respect to the Company ((a) and (b) together, the “Searches”);

a PDF executed copy of the minutes of a meeting of the board of directors of the Company dated 3 December 2020 approving the establishment of a financing and share allotment committee of the board of directors of the Company (the “Financing Committee”);

a PDF executed copy of the written resolutions of the board of directors of the Company dated: (i) 2 August 2021 approving the terms of reference of the Financing Committee; and (ii) 2 June 2023 adopting revised terms of reference of the Financing Committee, together with such terms of reference;

a PDF executed copy of the minutes of a meeting of the board of directors of the Company dated 25 October 2017, of the written resolutions of the Financing Committee dated 13 May 2021, and of the written resolutions of the board of directors of the Company dated 1 November 2024, approving the entry into the AstraZeneca Subscription Agreement;

a PDF executed copy of the written resolutions of the board of directors of the Company dated 3 November 2024 delegating authority to the Chief Executive Officer of the Company in connection with, and of the Chief Executive Officer of the Company dated 11 November 2024 authorising, the issue and allotment of the AstraZeneca Shares;

a PDF executed copy of the minutes of a meeting of the board of directors of the Company dated 8 February 2020, of the minutes of a meeting of a financing committee of the Company dated 9 February 2020, of the written resolutions of the board of directors of the Company dated 10 November 2020, and of the written resolutions of the board of directors of the Company dated 8 February 2023, approving the entry into the Novartis Instruments and the issue of the warrants and convertible loan notes by the Company thereunder;

a PDF executed copy of the minutes of a meeting of the board of directors of the Company dated 27 June 2017, of the minutes of a financing committee of the Company dated 4 August 2017, of the minutes of a meeting of the board of directors of the Company dated 26 September 2018, of the minutes of a meeting of a financing committee of the Company dated 26 September 2018, of the minutes of a meeting of the board of directors of the Company dated 3 December 2020, and of the written resolutions of the Financing Committee dated 12 December 2020, approving the entry into the SVB and Kreos Instruments and the issue of the warrants by the Company thereunder;

a PDF executed copy of the written resolutions of the Financing Committee dated 26 March 2021 approving the entry into the amendment to the TAP Instrument dated 29 March 2021;

a PDF executed copy of the minutes of the annual general meeting of shareholders of the Company held on 27 June 2017, 21 June 2018, 19 June 2019, 29 June 2020, 27 May 2021, 16 May 2022 and 22 May 2023 (the “General Meeting Minutes”);

a PDF copy of the certificate of incorporation of the Company dated 10 March 2015 and certificate of incorporation on re-registration of the Company dated 23 June 2016;

a PDF copy of the articles of association of the Company which were adopted by special resolution passed on 2 June 2016;

a PDF copy of the articles of association of the Company which were adopted by special resolution passed on 6 April 2018;

a PDF copy of the articles of association of the Company which were adopted by special resolution passed on 16 May 2022 and amended by a special resolution passed on 18 December 2023 (the “Articles of Association”);

PDF executed copies of each of the Instruments; and

a PDF copy of the Registration Statement filed with the SEC on 25 November 2024.

Applicable law

we have not investigated the laws of any country other than England and we assume that no foreign law, (including, for the avoidance of doubt, European Union law on and after 1 January 2021), affects the opinion stated below; and

we express no opinion in this letter on the laws of any jurisdiction other than England.

Assumptions and reservations

OPINION

the AstraZeneca Shares registered in the name of AstraZeneca in the register of members of the Company and delivered as described in the Registration Statement and pursuant to the AstraZeneca Subscription Agreement have been duly and validly authorised and issued, fully paid or credited as fully paid, and will not be subject to any call for payment of further capital; and

in addition, and subject further to the following:

the Registration Statement, as finally amended and supplemented, having become effective under the Securities Act and continuing to be so effective;

the directors of the Company at the time of any allotment and issue of Underlying Shares being duly authorised pursuant to the articles of association of the Company in force at the time of such allotment and issue, the Companies Act and any relevant authority given by the members of the Company to allot such Underlying Shares and any rights of pre-emption under such articles of association or the Companies Act in respect of such allotment having been validly disapplied;

the directors of the Company having validly resolved to allot the Underlying Shares;

the receipt in full by the Company of payment for the Underlying Shares in an amount of “cash consideration” (as defined in section 583(3) of the Companies Act) of not less than the aggregate nominal value for such Underlying Shares; and

valid entries having been made in relation to the allotment and issue of the Underlying Shares in the books and registers of the Company,

EXTENT OF OPINION

RELIANCE AND DISCLOSURE

the genuineness of all signatures, stamps and seals on all documents, the authenticity and completeness of all documents submitted to us as originals, and the conformity to authentic original documents of all documents submitted to us as copies;

that in the case of a document signed electronically, the person signing it intended to sign and be bound by the document;

that, where a document has been examined by us in draft or specimen form, it will be or has been duly executed in the form of that draft or specimen;

that the filing of the Registration Statement with the SEC has been authorised by all necessary actions under all applicable laws other than English law;

that the Articles of Association remain in full force and effect, and no alteration has been made or will be made to the Articles of Association, in each case prior to any date on which Underlying Shares are allotted or issued (each such date being an “Allotment Date”);

that a complete prospectus supplement will have been prepared and filed with the SEC describing the Underlying Shares offered before each Allotment Date;

that all documents, forms and notices which should have been delivered to the UK Companies House in respect of the Company have been or will be so delivered, that the results of the Searches are complete and accurate, and that the position has not changed since the times at which the Searches were made and that the results of the Searches will remain complete and accurate as at each Allotment Date;

that the Instruments (and the other documents referred to therein) remain accurate and complete and have not been amended, terminated, revoked or otherwise discharged as at the date of this letter;

that each of the persons executing and/or issuing (as applicable) the Instruments on behalf of the relevant parties thereto executed and/or issued (as applicable) an identical final version of such document, in each case in the form reviewed by us;

the absence of fraud or mutual mistake of fact or law or any other arrangements, agreements, understandings or course of conduct or prior or subsequent dealings, amending, rescinding or modifying or suspending any of the terms of the Instruments or which would result in the inclusion of additional terms therein, and that the relevant parties have acted in accordance with the terms of the Instruments;

that all requirements and conditions precedent for the Instruments to be entered into and/or issued (as applicable) have been satisfied;

each of the Instruments has been or will be duly authorised, executed, delivered and issued (as applicable) by or on behalf of all relevant parties and are or will be legal, valid, binding and enforceable against all relevant parties in accordance with their terms under all relevant laws;

all preconditions to the obligations of the parties to the applicable Instruments, including to the obligation of the Company to issue and allot any Underlying Shares under any such Instrument, will have been satisfied or duly waived prior to the issue and allotment of any such Underlying Shares (as applicable), and there will be no breach of the terms of the applicable Instruments;

that: (i) the proceedings and resolutions described in the minutes of the meetings of the board of directors of the Company, of the Financing Committee, and of any other committee of the Company, were duly conducted as so described, and that the meetings referred to therein were duly constituted and convened and all constitutional, statutory and other formalities were duly observed (including, if applicable, those relating to the declaration of directors’ interests or the power of interested directors to vote), a quorum was present throughout, the requisite majority of directors voted in favour of approving the resolutions and such resolutions were duly adopted, and have not been and will not be revoked or varied and remain in full force and effect and will remain so as at each Allotment Date (as applicable), and (ii) the resolutions described in the written resolutions of the board of directors of the Company, of the Financing Committee, and of Chief Executive Officer of the Company, were duly passed as written resolutions of the board of directors of the Company, of the Financing Committee, or of the Chief Executive Officer of the Company (as applicable), and all constitutional, statutory and other formalities were duly observed (including, if applicable, those relating to the declaration of directors’ interests or the power of interested directors to vote) and such resolutions were duly adopted, and have not been and will not be revoked or varied and remain in full force and effect and will remain so as at each Allotment Date (as applicable);

that the proceedings and resolutions described in the General Meeting Minutes provided to us were duly conducted as so described and that the meetings referred to therein were duly constituted and convened and all constitutional, statutory and other formalities were duly observed, a quorum was present throughout, the requisite majority of shareholders voted in favour of approving the resolutions and the resolutions passed thereat were duly adopted, and have not been and will not be revoked or varied and remain in full force and effect;

that, as at the date of entry into each Instrument by the Company, the directors of the Company had sufficient authority and powers conferred upon them to grant rights to subscribe for, and/or to convert any security into, Underlying Shares under section 551 of the Companies Act and under section 570 or section 571 (as applicable) of the Companies Act as if section 561 of the Companies Act did not apply to such grant of rights to subscribe for and/or to convert any security into Underlying Shares;

that immediately prior to each Allotment Date, the directors of the Company shall have sufficient authority and powers conferred upon them to allot and issue such Underlying Shares under section 551 of the Companies Act and under section 570 or section 571 (as applicable) of the Companies Act as if section 561 of the Companies Act did not apply to such allotment and issue, and the directors of the Company shall not allot or issue (or purport to allot or issue) Underlying Shares in excess of such powers or in breach of any other limitation on their power to allot and issue Underlying Shares;

that at the time of each allotment and issue of any Underlying Shares, the Company has or shall have received “cash consideration” (as such term is defined in section 583(3) of the Companies Act) in full, equal to the subscription price payable for such Shares and has or shall have entered the holder or holders thereof in the register of members of the Company showing that all such Shares have been fully paid up as to their nominal value and any premium thereon or shall have been fully paid up as to their nominal value and any premium thereon as at each Allotment Date;

that no Underlying Shares shall be allotted or issued, or shall be committed to be allotted or issued, at a discount to their nominal value (whether in pounds sterling or equivalent in any other currency);

that any allotment and issue of Underlying Shares will be duly made in accordance with both the Articles of Association (as may be amended), the Companies Act and the applicable law, rules and regulations in force at the time of such allotment and issue, including without limitation, the rules of any stock exchange on which the Company’s securities may be traded;

that there is, at each Allotment Date, no matter affecting the authority of the directors to issue and allot the Underlying Shares which would have any adverse implications in relation to the opinion given above;

that the Instruments and all obligations thereunder have been entered into and/or issued (as applicable), and the Underlying Shares will be allotted and issued, in good faith and on bona fide commercial terms and on arms’ length terms and for the purpose of carrying on the business of the Company and that there will be, in respect of the Underlying Shares, reasonable grounds for believing that the entry into and/or issue of (as applicable) the relevant Instrument, and the allotment and issue of the relevant Underlying Shares will, promote the success of the Company for the benefit of its members as a whole;

that the AstraZeneca Shares were allotted and issued in good faith and on bona fide commercial terms and on arms’ length terms and for the purpose of carrying on the business of the Company and that there were reasonable grounds for believing that the entry into the Subscription Agreement and the allotment and issue of the AstraZeneca Shares would promote the success of the Company for the benefit of its members as a whole;

that in relation to the allotment and issue of the Shares, the directors of the Company have acted and will act in the manner required by section 172 of the Companies Act (Duty to promote the success of the Company), and there has not and will not be any bad faith, breach of duty, breach of trust, fraud, coercion, duress or undue influence on the part of any of the directors of the Company in relation to any allotment and issue of Shares;

that no Shares or rights to subscribe for Shares have been or shall be offered to the public in the United Kingdom in breach of the Financial Services and Markets Act 2000, as amended (“FSMA”) or of any other United Kingdom laws or regulations concerning offers of securities to the public, and no communication has been or shall be made in relation to the Shares in breach of section 21 of FSMA or any other United Kingdom laws or regulations relating to offers or invitations to subscribe for, or to acquire rights to subscribe for or otherwise acquire, Shares or other securities;

that, in issuing and allotting the AstraZeneca Shares the Company was not, and in issuing and allotting the Underlying Shares the Company is not, carrying on a regulated activity for the purposes of section 19 of FSMA;

that the Company has complied and will comply with all applicable anti-terrorism, anti-money laundering, sanctions and human rights laws and regulations and that each allotment and issue of Shares was and will be consistent with all such laws and regulations;

that except to the extent expressly set out in the opinion given in this letter no consents, approvals, authorisations, orders, licences, registrations, filings or similar formalities are or were required from any governmental or regulatory authority in connection with the execution, delivery and performance of the Registration Statement or the entrance into and/or issue of the Instruments (as applicable) by the Company, or if such consents, approvals, authorisations, orders, licences, registrations, filings or similar formalities are or were required, these have been made or will be made within the prescribed time limits; and

that the Company has not taken any corporate or other action nor have any steps been taken or legal proceedings been started against the Company for:

the liquidation, administration, winding up, dissolution, reorganisation, or bankruptcy or similar procedures in other relevant jurisdictions, of; or

the commencement of a moratorium in respect of; or

the appointment of a liquidator, receiver, trustee, administrator, administrative receiver, monitor or similar officer of,

the Searches are not capable of revealing conclusively whether or not a winding-up or administration petition, filing or order has been presented or made, a monitor or receiver appointed, a company voluntary arrangement proposed or approved or a moratorium or any other insolvency proceeding commenced. We have not made enquiries of any District Registry or County Court;

any limitations arising from applicable laws relating to insolvency, bankruptcy, administration, reorganisation, liquidation, moratoria, schemes, restructuring plans or analogous circumstances; and

an English court exercising its discretion under section 426 of the Insolvency Act 1986 (co-operation between courts exercising jurisdiction in relation to insolvency) to assist the courts having the corresponding jurisdiction in any part of the United Kingdom or any relevant country or territory;

we express no opinion as to matters of fact;

we express no opinion on the compliance of the allotment and issue of the Shares with the rules or regulations of the New York Stock Exchange or the rules or regulations of any other securities exchange that are applicable to the Company;

we express no opinion in relation to the legality, enforceability or validity of any of the Instruments;

it should be understood that we have not been responsible for investigating or verifying the accuracy of the facts, including statements of foreign law, or the reasonableness of any statements of opinion, contained in the Registration Statement, or that no material facts have been omitted from it; and

we have not undertaken any consideration, analysis or assessment of whether the National Security & Investment Act 2021 (“NS&IA”) may or will apply to any of the transactions contemplated herein for the purposes of the opinions in this letter. We express no opinion on the application or potential application of the NS&IA in relation to the Company or any transaction contemplated herein.