(State or other jurisdiction of

incorporation or organization)

(I.R.S. Employer

Identification Number)

108 Cannon Street

London EC4N 6EU

United Kingdom

Mitchell S. Bloom

Michael H. Bison
Goodwin Procter LLP
100 Northern Avenue
Boston, MA 02210
(617) 570-1000

Andrew Harrow
Goodwin Procter (UK) LLP

100 Cheapside

London EC2V 6DY

United Kingdom

+44 20 7447 4200

Title of Securities

to be Registered⁽¹⁾

Amount

to be

Registered⁽²⁾

Proposed

Maximum

Offering Price

per Share

Proposed

Maximum

Aggregate

Offering Price

Amount of

Registration Fee

Ordinary shares, nominal value £0.10 per share

— reserved for issuance pursuant to Registrant’s 2018 Share Option and Incentive Plan

— reserved for issuance pursuant to Registrant’s 2018 Employee Share Purchase Plan

Total

These shares may be represented by the American Depositary Shares (“ADSs”) of Orchard Therapeutics plc (the “Registrant”). Each ADS represents one Ordinary Share. ADSs issuable upon deposit of the Ordinary Shares registered hereby were registered pursuant to a separate Registration Statement on Form F-6 (File No. 333-227905).

Pursuant to Rule 416 under the Securities Act of 1933, as amended (the “Securities Act”), this Registration Statement shall also cover any additional Ordinary Shares of the Registrant which become issuable under the above-named plans by reason of any stock dividend, stock split, recapitalization or any other similar transaction effected without the receipt of consideration which results in an increase in the number of the Registrant’s outstanding Ordinary Shares.

Represents an automatic increase on January 1, 2019 to the number of shares available for issuance under the Registrant’s 2018 Stock Option and Incentive Plan (the “2018 Plan”), pursuant to the terms of the 2018 Plan. Shares available for issuance under the 2018 Plan were previously registered on Form S-8 filed with the Securities and Exchange Commission on October 31, 2018 (Registration No. 333-228067).

Represents an automatic increase on January 1, 2019 to the number of shares available for issuance under the Registrant’s 2018 Employee Stock Purchase Plan (the “2018 ESPP”), pursuant to the terms of the 2018 ESPP. Shares available for issuance under the 2018 ESPP were previously registered on Form S-8 filed with the Securities and Exchange Commission on October 31, 2018 (Registration No. 333-228067).

The price of $15.57 per share, which is the average of the high and low sale prices of the ADSs of the Registrant as quoted on the Nasdaq Global Select Market on March 15, 2019, is set forth solely for purposes of calculating the registration fee pursuant to Rules 457(c) and (h) of the Securities Act, and has been used as these shares are without a fixed price.

The price of $13.23 per share, which is 85% of the average of the high and low sale prices of the ADSs of the Registrant as quoted on the Nasdaq Global Select Market on March 15, 2019, is set forth solely for purposes of calculating the registration fee pursuant to Rules 457(c) and (h) of the Securities Act, and has been used as these shares are without a fixed price. Pursuant to the 2018 ESPP, the purchase price of the shares of Ordinary Shares reserved for issuance thereunder will be 85% of the fair market value of an Ordinary Share on the first trading day of the offering period or on the exercise date, whichever is less.

Exhibit No.

Description

Filed as Exhibit 1.1 to Registrant’s Annual Report on Form 20-F (File No. 001-38722), filed with the Securities and Exchange Commission on March 22, 2019, and incorporated herein by reference.

Filed as Exhibits 2.1 and 2.2 to Registrant’s Annual Report on Form 20-F (File No. 001-38722), filed with the Securities and Exchange Commission on March 22, 2019, and incorporated herein by reference.

Filed as Exhibit 4.3 to Registrant’s Annual Report on Form 20-F (File No. 001-38722), filed with the Securities and Exchange Commission on March 22, 2019, and incorporated herein by reference.

Filed as Exhibit 10.10 to Registrant’s Registration Statement on Form F-1/A (File No. 333-227698), filed with the Securities and Exchange Commission on October 23, 2018, and incorporated herein by reference.

Filed herewith.

/s/ Mark Rothera

/s/ Frank E. Thomas

/s/ James A. Geraghty

/s/ Joanne T. Beck

/s/ Marc Dunoyer

/s/ Jon Ellis

/s/ Bobby Gasper

/s/ Charles A. Rowland, Jr.

/s/ Alicia Secor

/s/ Hong Fang Song

      Title:   Assistant Secretary on

                  behalf of Cogency Global Inc.

Goodwin Procter (UK) LLP

100 Cheapside
London EC2V 6DY

goodwinlaw.com

+44 (0) 20 7447 4200

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; and

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

Legal review

an online search at Companies House in respect of information available for inspection on the Company’s file conducted on 22 March 2019 at 10.30 a.m. (London time);

an enquiry of the Central Index of Winding Up Petitions, London on 22 March 2019 at 10.30 a.m. (London time) ((a) and (b) together, the “Searches”);

a PDF copy of the minutes of the meeting of the Board held on 25 September 2018 at which it was resolved, inter alia, to approve the Plans;

a PDF executed copy of the written resolutions passed by the shareholders of the Company on 25 October 2018 approving, inter alia, the Plans (together, the “Written Resolutions”);

PDF copies of the Plans;

a PDF copy of the current articles of association of the Company dated 2 November 2018 (the “Articles”), the certificate of incorporation of the Company dated 1 August 2018 and the certificate of incorporation on re-registration of the Company as a public limited company dated 29 October 2018; and

a draft copy of the Registration Statement as at 22 March 2019 and to be filed with the SEC on 22 March 2019.

Applicable law

we have not investigated the laws of any country other than England and we assume that no foreign law affects any of the opinions stated below;

we do not undertake or accept any obligation to update this letter and/or the opinions given in it to reflect subsequent changes in English law or factual matters; and

we express no opinion in this letter on the laws of any jurisdiction other than England. It is assumed that no foreign law which may apply to the matters contemplated by the Registration Statement, the Company, any document or any other matter contemplated by any document would or might affect this letter and/or the opinions given in it.

Assumptions and reservations

OPINION

the Registration Statement, as finally amended, having become effective under the Securities Act;

the shareholders of the Company having resolved: (i) as may be required, as an ordinary resolution, or within the Company’s articles of association, to authorise the board of directors of the Company pursuant to section 551 of the Companies Act 2006 (the “Companies Act”) to allot Shares, or to grant rights to subscribe for Shares, pursuant to the Plans; and (ii) as may be required, as a special resolution, or within the Company’s articles of association, to empower the directors of the Company pursuant to section 570 of the Companies Act to allot such Shares, and grant such rights (as applicable), free of the restrictions in section 561 of the Companies Act, and such resolutions and authorities remaining in full force and effect and not having expired, been rescinded or amended;

the delegation of authority to the compensation committee of the Board (the “Compensation Committee”) having been validly effected (inter alia, in accordance with the Articles, the Companies Act and the Plans);

the Board and the shareholders of the Company having validly approved the Plans;

the Board or the Compensation Committee having validly granted the awards in respect of the Shares under the Plans;

the receipt in full of payment for the 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 Shares, assuming in each case that the individual grants or awards under the relevant Plan are duly authorised by all necessary corporate action (as described in (e) above) and duly granted or awarded and exercised in accordance with the requirements of law, the Company’s articles of association and the relevant Plan (and the agreements and awards duly adopted thereunder and in accordance therewith); and

valid entries having been made in relation to the allotment and issue of the Shares in the books and registers of the Company, it is our opinion that, as at today’s date, the Shares, if and when allotted and issued, registered in the name of the recipient in the register of members of the Company and delivered in accordance with the terms and conditions referred to in the Plans and as described in the Registration Statement, will be duly and validly authorised and issued, fully paid (subject to the receipt of valid consideration by the Company for the issue thereof) or credited as fully paid and will not be subject to any call for payment of further capital.

EXTENT OF OPINIONS

DISCLOSURE AND RELIANCE

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 original documents of all documents submitted to us as copies;

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, and that each of the signed documents examined by us has been duly executed and, where applicable, delivered on behalf of the Company;

that the Articles remain in full force and effect, and no alteration has been made or will be made to such articles of association, in each case prior to the relevant date of allotment and issue of the Shares (the “Allotment Date”);

on the relevant Allotment Date the Company will comply with all applicable laws to allot and issue the Shares and the Company will receive such amounts as are necessary to fully pay the nominal value of the Shares and any applicable share premium;

that the Plans remain in full force and effect and no alteration has been made or will be made to the Plans prior to an Allotment Date;

that all documents, forms and notices which should have been delivered to the Registrar of Companies in respect of the Company have been so delivered, that information revealed by the Searches was complete and accurate in all respects and has not, since the time of the Searches, been altered and that the results of the Searches will remain complete and accurate as at the relevant Allotment Date;

that (i) the resolutions described in the written resolutions of the board of directors of the Company provided to us in connection with the giving of this opinion or otherwise contemplated in connection with the matters referred to herein were and/or will be duly passed as written resolutions of the board of directors of the Company, all constitutional, statutory and other formalities were and/or will be observed and such resolutions have not been, and will not be, revoked or varied and remain in full force and effect and will remain so at each Allotment Date; and (ii) the proceedings and resolutions described in the minutes of the meetings of the board of directors of the Company provided to us in connection with the giving of this opinion or otherwise contemplated in connection with the matters referred to herein were and/or will be duly conducted as so described, and that each of the meetings referred to therein was and/or will be duly constituted, convened and conducted and all constitutional, statutory and other formalities were and/or will be duly observed (including, if applicable, those relating to the declaration of directors’ interests or the power of interested directors to vote), a quorum was and/or will be present throughout, the requisite majority of directors voted and/or will vote in favour of approving the resolutions and the resolutions passed thereat were and/or will be duly adopted, 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;

that the resolutions of the shareholders of the Company provided to us in connection with the giving of this opinion and as referred to at paragraph 1.3(d) of this letter or otherwise contemplated in connection with the matters referred to herein were and/or will be duly passed, all constitutional, statutory and other formalities were and/or will be observed in relation to such resolutions and such resolutions have not been and/or will not be revoked or varied and will not be revoked or varied prior to each Allotment Date and remain in full force and effect and will remain in full force and effect as at each Allotment Date;

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

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 been and will not be any bad faith, 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 any Shares by the Company pursuant to the Plans, that the recipient will have become entitled to such Shares under the terms of the relevant Plan such Shares or rights over Shares will, where applicable, be fully vested each in accordance with the terms of the relevant Plan and such recipient has or will have complied with all other requirements of the relevant Plan in connection with the allotment and issue of such Shares;

that all awards have been made under the terms of the relevant Plan, that the terms of all awards have not materially deviated from the terms set out in the relevant Plan and that any Shares will be allotted and issued in accordance with the terms set out in the relevant Plan and in accordance with the Articles;

that the Plans have been validly adopted and no alteration has been or shall be made to the Plans since the date of their respective adoption except to the extent expressly set out in this letter;

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

that in relation to the allotment and issuance of Shares pursuant to the Plans or otherwise to an employee benefit trust, that such Shares will be allotted and issued in accordance with the terms of the relevant Plan, the Company’s articles of association and the requirements of all applicable laws;

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

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 (“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 the 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 and granting rights to acquire Shares and administering the Plans, the Company is not carrying on a regulated activity for the purposes of section 19 of FSMA; 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, winding up, dissolution, reorganisation or bankruptcy of, or for the appointment of a liquidator, receiver, trustee, administrator, administrative receiver or similar officer of, the Company or all or any of its assets (or any analogous proceedings in any jurisdiction) and the Company is not unable to pay its debts as they fall due within the meaning of section 123 of the Insolvency Act 1986 and will not become unable to pay its debts within the meaning of that section as a result of any of the transactions contemplated herein, is not insolvent and has not been dissolved or declared bankrupt (although the Searches gave no indication that any winding-up, dissolution or administration order or appointment of a receiver, administrator, administrative receiver or similar officer has been made with respect to the Company).

the Searches are not capable of revealing conclusively whether or not a winding-up or administration petition or order has been presented or made, a receiver appointed, a company voluntary arrangement proposed or approved or any other insolvency proceeding commenced, and the available records may not be complete or up-to-date. In particular, the Central Registry of Winding-Up Petitions in England may not contain details of administration applications filed, or appointments recorded in or orders made by, district registries and county courts outside London. Searches at Companies House and at the Central Registry of Winding Up Petitions in England are not capable of revealing whether or not a winding up petition or a petition for the making of an administration order has been presented and, further, notice of a winding up order or resolution, notice of an administration order and notice of the appointment of a receiver may not be filed at Companies House immediately and there may be a delay in the relevant notice appearing on the file of the company concerned. Further, not all security interests are registrable, such security interests have not in fact been registered or such security interests have been created by an individual or an entity which is not registered in England. We have not made enquiries of any District Registry or County Court in England;

the opinions set out in this letter are subject to: (i) any limitations arising from applicable laws relating to insolvency, bankruptcy, administration, reorganisation, liquidation, moratoria, schemes or analogous circumstances; and (ii) 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 have made no enquiries of any individual connected with the Company;

we express no opinion on the compliance of the Plans, or the compliance of any award made under the Plans, with the rules or regulations of the NASDAQ Stock Market LLC 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 the Plans or any award agreement entered into pursuant to such Plans. In particular, but without prejudice to the generality of the foregoing, we have assumed that the Shares to be allotted under the Plans or any such award agreement will be paid up in full (as to their nominal value and any premium) in cash (within the meaning of section 583(1) of the Companies Act) and we express no opinion as to whether any consideration other than “cash consideration” (as such term is defined in section 583(3) of the Companies Act) which might be paid, or purport to be paid, for the Shares would result in such Shares being validly issued, fully paid and not subject to any call for payment of further capital;

a certificate, documentation, notification, opinion or the like might be held by the English courts not to be conclusive if it can be shown to have an unreasonable or arbitrary basis or in the event of a manifest error; and

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.