展覽1.1

ProQR Therapeutics N.V. 公司資料

一千八百萬普通股

承銷協議

日期：2024年10月22日

ProQR Therapeutics N.V. 公司資料

一千八百萬普通股

承銷協議

2024年10月22日

Evercore集團有限責任公司。

康坦菲茨傑和公司。

作爲各個承銷商的代表，

收件人：evercore集團有限責任公司

東52街55號

紐約紐約10055

寄自康拓菲茨傑拉德及公司

東59街110號，6樓
紐約，紐約10022

作爲幾家承銷商的代表

女士們，先生們：

ProQR Therapeutics N.V.，一家有限責任制的上市公司，確認與evercore集團LLC的協議naamloze vennootschap）根據荷蘭法律（即“公司確定與Evercore Group LLC的協議evercore確定與康泰菲茲爾和公司的協議Cantor”） 和其他在中被提名的承銷商中的每一個 附表A （以下統稱爲“承壓商，”該術語還應包括根據本合同第10條下文提供的進行替代的承銷商，Evercore 和 Cantor 作爲代表（“代表”），涉及（i）公司的出售以及承銷商的購買，各自而不是聯合，每個普通股票的名義價值爲 €0.04，公司的普通股數量（“普通股）在 附表A 公司向作爲獨立而非共同代表的包銷商授予前述2(b)節所述的購買全部或部分額外普通股權利。上述的18,000,000股普通股（“首次發行證券”）將由包銷商購買，以及2,700,000股普通股權利的全部或部分，即2(b)節中描述的選擇權（“超額證券”）在此稱爲「所有板塊」。證券.”

本協議中對公司出售的證券或從公司購買的證券（以及相關概念的使用）的引用，應理解爲指這些證券由公司發行或授予，並分別由公司認購。類似地，本協議中對證券交付的引用，應理解爲指這些證券由公司發行。

公司了解承銷商打算在執行本協議並根據下文定義的註冊聲明進行交付後儘快公開發行證券增發計劃代表人認爲適當後，根據註冊聲明（如下所定義）進行交付後，立即進行證券的公開發行。

公司已經準備並向證券交易委員會（「證交會」）提交了基於表格F-3（No. 333-282419）的牆外註冊聲明，包括一份擬用於與證券的公開發行和銷售相關的基本意向書（「擬用於發行的基本意向書」）。委員會:公司已經準備並向證券交易委員會（「證交會」）提交了基於表格F-3（No. 333-282419）的牆外註冊聲明，包括一份擬用於與證券的公開發行和銷售相關的基本意向書（「擬用於發行的基本意向書」）。基本展望書公司已經準備並向證券交易委員會（「證交會」）提交了基於表格F-3（No. 333-282419）的牆外註冊聲明，包括一份擬用於與證券的公開發行和銷售相關的基本意向書（「擬用於發行的基本意向書」）。這份註冊聲明包括基本報表、陳述、附表，以及根據1933年證券法（修訂後的「證券法」）及其下屬規則和法規生效的形式。1933法案公司已經準備並向證券交易委員會（「證交會」）提交了基於表格F-3（No. 333-282419）的牆外註冊聲明，包括一份擬用於與證券的公開發行和銷售相關的基本意向書（「擬用於發行的基本意向書」）。這份註冊聲明包括基本報表、陳述、附表，以及根據1933年證券法（修訂後的「證券法」）及其下屬規則和法規生效的形式。1933年法規於2024年10月10日由委員會發布的所有文件，包括引用或視爲引用的文件以及任何根據1933年法案第4300億條規定在生效時視爲其一部分的信息，被稱爲“蘋果公司CEO庫克大規模拋售股票，套現逾3億港元，資金已存入上市公司設立的專項帳戶(「信託帳戶」)，以公共股東(定義詳見下文)爲受益人的註冊聲明(FORM S-1)中所規定的一定金額及特定款項。信託帳戶中持有的基金類型(包括資金持有的利息)除支付公司稅費以外，一旦實現以下最早的情況之一即可支取: (i) 完成首次（業務）組合；(ii) 如果公司未能在2025年3月3日之前完成首次（業務）組合，則可以贖回100%的發行股份（如下所述）；或 (iii) 股東表決贖回發行股份。 若要批准修訂本Amended and Restated Certificate，必須就修訂對決定最早如下情形之一的公司的義務以在首次業務組合中允許贖回或未在終止日期之前完成首次業務組合即贖回100%的發行股份產生影響或涉及股東權益或首次業務組合前的活動（如第9.7節所述），對修訂進行表決。發售期(「發售期」)所出售單位的組成部分的Common Stock股份的持有人(「發售股份」)，不論這些發售股份是在發售期內還是在發售市場上的二級市場中購買，也不論這些持有人是公司的發起人，高管或董事，或上述任何關聯方的子公司，均在此被稱爲「公共股東」。。公司根據1933年法案第462(b)條規定提交的與證券的發行和銷售有關的任何註冊聲明被稱爲“第462(b)條註冊聲明”，自任何此類第462(b)條註冊聲明的提交日期和時間起，“蘋果公司CEO庫克大規模拋售股票，套現逾3億港元，資金已存入上市公司設立的專項帳戶(「信託帳戶」)，以公共股東(定義詳見下文)爲受益人的註冊聲明(FORM S-1)中所規定的一定金額及特定款項。信託帳戶中持有的基金類型(包括資金持有的利息)除支付公司稅費以外，一旦實現以下最早的情況之一即可支取: (i) 完成首次（業務）組合；(ii) 如果公司未能在2025年3月3日之前完成首次（業務）組合，則可以贖回100%的發行股份（如下所述）；或 (iii) 股東表決贖回發行股份。 若要批准修訂本Amended and Restated Certificate，必須就修訂對決定最早如下情形之一的公司的義務以在首次業務組合中允許贖回或未在終止日期之前完成首次業務組合即贖回100%的發行股份產生影響或涉及股東權益或首次業務組合前的活動（如第9.7節所述），對修訂進行表決。發售期(「發售期」)所出售單位的組成部分的Common Stock股份的持有人(「發售股份」)，不論這些發售股份是在發售期內還是在發售市場上的二級市場中購買，也不論這些持有人是公司的發起人，高管或董事，或上述任何關聯方的子公司，均在此被稱爲「公共股東」。”將包括第462(b)條註冊聲明。

2024年10月22日簽署的初步招股說明書補充資料，描述了證券及其發行，連同基本招股說明書，被稱爲“初步招股說明書，” 以及預備招股說明書和任何其他針對基本招股說明書的初步形式招股說明書補充資料，描述了證券及其發行，在提交招股說明書（如下所定義）之前使用，連同基本招股說明書，被稱爲“初步招股書.”

在本文件中，“招股書“應指基本招股說明書的最終招股補充資料，描述證券及其發售情況（“最終招股補充資料”），連同首次由承銷人用於確認證券銷售或首次由公司提供以滿足根據1933年法案第173條向承銷人提出要求的購買者規定的形式中的基本招股說明書。本文件中對初步招股說明書、任何初步招股說明書和招股說明書的引用應指該招股說明書的招股補充資料和基本招股說明書的各組成部分。對於本協議的目的，所有對基本招股說明書、註冊聲明、任何初步招股說明書、招股說明書或對前述任何文件的任何修訂或補充的引用應被視爲包括幷包含隨後根據下文定義的1934年法案（以下稱「1934年法案」）而提交、被視爲被自願引用或被視爲根據1933年法規的文件中的文件，以及包括根據其電子數據收集、分析和檢索系統或任何後繼系統向委員會提交的拷貝（“您可以在我們最近完成的財政年度的經審計的合併財務報表和管理層的討論和分析中找到有關Equinox Gold的財務信息。這些文件可以在我們的網站www.equinoxgold.com、在線備份文件系統Sedar（www.sedarplus.ca）以及EDGAR（www.sec.gov/edgar）上找到。”）。按照本協議的用法：

「1934法案」指修正後的1934年證券交易所法案。

「適用時間」指2024年10月22日晚上8:15，紐約時間，或公司與代表另行約定的其他時間。

「一般披露文件套餐」指在適用時間發佈的任何發行人一般使用的免費書面募集說明書，適用時間之前發佈給投資者的任何初步招股說明書，以及所包括的信息 附表b-1 所有板塊一起考慮。

「集團」指公司及公司的每一家子公司（根據本協議規定，在1933年法案規定的405條規定中定義爲“規則405”)).

「發行人自由寫作招股說明書」 是指 任何 「發行人自由寫作招股說明書」，如《1933年法案實施細則》第433條所定義（”規則 433”）， 包括但不限於任何與證券有關的 「免費書面招股說明書」（定義見規則405） (i) 必須由公司向委員會提交，(ii) 「書面信函路演」 根據第 433 (d) (8) (i) 條的定義，無論是否要求向委員會提交，或 (iii) 免於申報 根據第 433 (d) (5) (i) 條，向委員會提交信息，因爲其中包含對證券或發行的描述 不反映最終條款，在每種情況下都以向委員會提交或要求提交的表格中反映最終條款，如果沒有要求 按照《上市規則》第 433 (g) 條以保留在公司記錄中的形式提交。

“Issuer General Use Free Writing Prospectus” means any Issuer Free Writing Prospectus that is intended for general distribution to prospective investors (other than a “bona fide electronic road show,” as defined in Rule 433 (a “Bona Fide Electronic Road Show”)), as evidenced by its being specified in Schedule B-2 hereto.

“Issuer Limited Use Free Writing Prospectus” means any Issuer Free Writing Prospectus that is not an Issuer General Use Free Writing Prospectus.

“Rule 430B Information” means documents and information deemed to be a part of or included in the Registration Statement pursuant to Rule 430B of the 1933 Act Regulations.

SECTION 1.         Representations and Warranties

(a)            Representations and Warranties by the Company. The Company represents and warrants to each Underwriter as of the date hereof, the Applicable Time, the Closing Time (as defined below) and any Date of Delivery (as defined below), and agrees with each Underwriter, as follows:

(i)  Registration Statement and Prospectuses. Each of the Registration Statement and any amendment thereto has become effective under the 1933 Act. No stop order suspending the effectiveness of the Registration Statement or any post-effective amendment thereto has been issued under the 1933 Act, no order preventing or suspending the use of any preliminary prospectus or the Prospectus has been issued and no proceedings for any of those purposes have been instituted or are pending or, to the Company’s knowledge, threatened. The Company has complied in all material respects with each request (if any) from the Commission for additional information.

Each of the Registration Statement and any post-effective amendment thereto, at the time it became effective, complied in all material respects with the requirements of the 1933 Act and the 1933 Act Regulations. Each preliminary prospectus, the Prospectus and any amendment or supplement thereto, at the time each was filed with the Commission, complied in all material respects with the requirements of the 1933 Act and the 1933 Act Regulations. Each preliminary prospectus delivered to the Underwriters for use in connection with the Offering and the Prospectus was or will be identical to the electronically transmitted copies thereof filed with the Commission pursuant to EDGAR, except to the extent permitted by Regulation S-T.

公司符合《1933年法案》下使用F-3表格的適用要求。該公司是根據1933年法案405號規則的「外國私募發行人」。

在註冊聲明、任何初步招股意向書和招股說明書中併入或被視爲併入的文件，在其生效時或隨後在提交委員會時，均在所有實質方面符合並將符合1934法案的要求。

(ii)   每份初步意向書以及備案後的招股說明書在一切重大方面均符合1933年法案的規定，如果根據EDGAR進行電子傳輸備案，其與交由承銷商用於證券發行和銷售的複印件完全一致（除《1933年法案》下S-t規定允許的情況）。在有效時間、結算時間或任何交割日期，註冊聲明或任何事後的修訂內容，均不包含或將不包含任何不實陳述重大事實或遺漏或將遺漏必須在其中聲明的任何重要事實，或者有必要使其中的陳述不具有誤導性。在適用時間、結算時間和任何交割日期，無論是（A）一般披露文件還是（B）任何個別發行人有限使用的免費書面要約說明書，在與一般披露文件一起考慮時包含或將包含任何不實陳述重要事實或遺漏或將遺漏必要在其中聲明的任何重要事實，以使其中陳述不論在其製作時的情況下如何看待，都不會具有誤導性。招股說明書或其任何修訂內容（包括任何說明書封套）在其發行日期時，在根據427(b)條款向委員會提交任何文件時，在結算時間或任何交割日期時，都不包含或將不包含任何不實陳述重要事實或遺漏或將遺漏必要在其中聲明的任何重要事實，以使其中的陳述不論在其製作時的情況下如何看待，都不會具有誤導性。

本小節中的聲明和保證 不適用於註冊聲明（或其任何修正），普通披露文件 或招股說明書（或其任何修正或補充，包括任何招股說明書封套）是根據並符合代表通過書面信息向公司提供的任何承銷商爲在其中明確使用而作出的陳述或遺漏。根據本協議，僅向公司提供的唯一信息應爲有關「承銷」下第三段有關特讓和重新讓度 和有關「承銷」下第八段有關穩定的第一和第二句的信息，這些信息分別包含在招股說明書中（統稱爲“發行人免費書面招股說明。 沒有發行人免費書面招股說明與註冊聲明或招股書中包含的信息發生衝突或將會發生衝突，還包括在任何書面材料之前或其他預備材料當中的任何情況，未被取代或修改。公司必須遵照1933年法案和1933年法律法規的要求在提交文書給委員會時提交任何公司免費書面招股說明”).

(iii)  發行人免費書面招股書。 沒有發行人自由撰寫招股說明書與註冊聲明或招股說明書中包含的信息存在或將存在衝突， 任何未被取代或修改的初步或其他招股說明書被視爲其一部分。

(iv)  公司不屬於不合格的發行人在提交註冊聲明以及任何發帖生效修正後的最早時間之後，公司進行了最早的報盤， 真實 在1933年法規中第164(h)(2)條的含義下提供證券，以及在簽署和交付本協議的當時，公司既不是也不曾是「不合格發行人」

(v)  獨立會計師KPMG會計師事務所，證實年度基本報表和支持陳述的會計師（如有的話），並納入註冊聲明、一般披露文件和招股說明書，均符合1933年法案、1933年法案法規和上市公司會計監督委員會的要求，屬於獨立的上市會計師。

(vi)  財務報表。財務 註冊聲明、一般披露一攬子文件和招股說明書中包含的聲明以及相關附表 並公允地附註公司在指定日期的財務狀況以及運營報表、股東 股權（自己的功率）以及公司在指定期限內的現金流量；上述財務報表已經編制完畢 符合《國際財務報告準則》(”國際財務報告準則”）由《國際會計報》發佈 標準委員會 (”國際會計準則B”）在所涉期間始終如一地適用，未經審計的情況除外， 中期財務報表，但須進行正常的年終審計調整，不包括某些腳註。支持時間表， 如有，按照《國際財務報告準則》公正地提供其中所要求的信息。摘要財務數據包含在 註冊聲明、一般披露一攬子計劃和招股說明書公平地呈現了其中顯示的信息，而且一直是 在與其中所列經審計的財務報表相一致的基礎上編制.除其中包含的內容外，沒有歷史記錄 或預計的財務報表或輔助附表必須包括在登記中或以提及方式納入 聲明、一般披露一攬子計劃或1933年法案條例下的招股說明書。

(vii)  營業沒有重大不利變化除非在註冊聲明中另有說明，在註冊聲明、概要文件或招股說明書中給出信息的各自日期起至今，公司及其子公司的財務狀況或其他方面，以及收入、業務事務、財產或前景，作爲整體，沒有發生重大不利變化，無論是否是業務的正常過程中發生的（「 控件 」）Material Adverse Effect公司尚未進行除營業常規活動之外的交易，這些交易對公司具有重大意義（除了預期與本次證券發行同時發生的公司的定向增發給Eli Lilly and Company的發行和銷售，在註冊聲明、概要文件和招股說明書中有所描述），且公司尚未對其任何一類股本宣佈、支付或發放任何形式的股利或分配。

(viii)  公司的良好聲譽公司已經依法成立，並作爲一家有限責任的公司合法存在（naamloze vennootschap）根據荷蘭法律，公司具有擁有、租賃和經營其資產以及進行其業務的權力和權限，如註冊聲明、總披露文件和招股說明書所描述，並進入並履行本協議項下的義務；公司已經取得資格在每個要求的司法管轄區內開展業務並且處於良好的地位（若有此概念存在），無論是因爲擁有或租賃財產還是經營業務，除非未能取得資格或保持良好地位不會合理預期導致重大不利影響。

(ix)  資本化 公司授權並已發行的股本以及公司現有的股份如註冊聲明、通用披露文件和招股說明書中的「資本構成」欄下所載明（除非根據本協議進行的後續發行，根據註冊聲明、通用披露文件和招股說明書中提到的保留、協議或僱員福利計劃，或根據註冊聲明、通用披露文件和招股說明書中提到的可轉換證券或期權的行使進行的發行）。截至本協議日期，公司股本中所有已發行的普通股已獲得有效授權併合法發行，並已全額繳足。公司股本中的任何一股未違反公司的任何股東的優先購買權或其他類似權利而發行。

(x) 子公司公司的每個「子公司」（根據1933年法案第405條下的定義，在本協議中）均已合法組建並依法存在，且如適用，保持良好的法律地位，該等子公司具有擁有、租賃和經營其財產以及進行註冊聲明、概要披露文件和招股說明書描述的業務的權限和權力。公司的每個子公司均取得了適當的資格以從事業務，並在每個需要進行資格認證的司法管轄區保持良好法律地位（如有該概念的情況除外），無論因所有財產的擁有或租賃，還是經營業務。除非未能取得該資格或保持良好法律地位不會合理預期地對公司產生實質性不利影響，否則通過資本或其他權益發行的所有已發行和未發行的股份或所有權利益均已合法授權和有效發行，已足額支付且不可再評估（如存在該概念），由公司直接或通過子公司完全擁有，沒有任何安全利益、抵押、質押、留置權、擔保或不利索賠。公司既不直接也不間接擁有或控制任何除在註冊聲明中列出的或附表中的子公司以外的任何公司、協會或其他實體。

(xi)授權協議。本協議已得到公司的合法授權、簽署和交付。

(xii)  證券的授權和描述承銷商應從公司購買的證券已獲得授權，根據本協議發行並銷售給承銷商，在公司根據本協議發行交付證券並支付本協議規定的對價時，這些證券將被有效發行並全部支付；並且證券的發行不受任何優先購買權或其他類似權利的限制。普通股在所有重要方面符合註冊聲明、概要披露文件和招股說明書中包含的所有相關陳述；這些描述在所有重要方面符合定義同一的工具中規定的權利。除了必須全額支付所購買證券之外，任何證券持有人不會因爲成爲該持有人而承擔個人責任。

(xiii)  註冊權益沒有任何人擁有註冊權或其他類似權利，根據《登記聲明》或根據本協議，公司將其註冊供出售，也未註冊出售的證券，除了在《登記聲明》、《一般披露文件》和《招股說明書》中披露的那些權利。

(xiv)  違規、違約和衝突的缺失本集團未（A）違反其章程，（B）在履行或遵守任何義務、協議、契約或合同中的條件（其中包括但不限於任何合同、債券、抵押、信託契約、貸款或信貸協議、票據、租約或其他協議或文件，公司爲其中一方當事人或可能受其約束的或公司的任何資產所受制約的，統稱爲「 」），除非就（B）而言，出現的違約不會單獨或合計合理地預計導致重大不利影響，或（C）違反任何法律（包括就公司而言，特別是1934年法案的情況），法規，規章，判決，命令, 管轄該集團或其各自的財產，資產或運營而具有管轄權的仲裁員，法庭，政府機構，監管機構，行政機構或其他機構或機構（統稱爲「 」），除C類違法行爲不會單獨或合計合理地預計導致重大不利影響公司成立的章程、公司章程或類似組織文件未有違規情形1934年法案規定”，判決，命令，書寫或仲裁員，法院，政府機構，監管機構，行政機構或其他有管轄權的權威機構，以及集團或其任何財產，資產或運營的情況”，C類違法行爲不會單獨或合計合理地預期產生重大不利影響。本協議的簽訂，交付和執行以及本協議和註冊聲明，一般披露文件和招股說明書（包括證券的發行和銷售以及從銷售證券的收益中所述的用途，標題下的使用收益）以及公司在此項義務下的遵守已得到所有必要的公司行動的授權，不會，無論是否有通知或經過時間或兩者都有，與或構成衝突，構成違約或違約事件（依下文定義）或導致根據協議和文件進行任何財產或資產設定或抵押權的產生或施加公司的情況，約束（但不包括可能導致重大不利影響的衝突，違約，違約事項或違約事件或抵押或定罪或定罪）。這一行動不會導致違反公司章程或任何政府實體的法律，法規，規章，判決，命令，書寫或仲裁員; 除了可能不會，單獨或合計，導致重大不利影響的違法行爲所需的授權批准或文件申報除了所有基金類型以外，本公司完成交易所需其他全球國內和外國的任何國家、地區、聯邦、國家或地方法院、行政性或監管機構、委員會或其他政府當局或工具機構 (各稱爲"政府機構")，都是不必要的，只有這些授權批准和文件申報，如果沒有獲得、提出或給出，就不太可能對本公司完成交易產生實質上或合併後產生實質或合併性影響。在此使用，“還款事件是指任何事件或情況，使證券持有人（或其代表）有權要求公司或其子公司回購、贖回或償還全部或部分債務。「」表示任何可以使任何票據、債券或其他債務證明持有人（或代表此類持有人的人）有權要求公司贖回、彌補或償還全部或部分債務的事件或條件。

(xv)  勞資糾紛的缺席集團員工與公司之間無任何實質性勞資糾紛，據公司所知，目前也沒有即將發生的糾紛，公司也沒有意識到其主要供應商、製造商、客戶或承包商的員工存在或即將發生的任何重大勞資紛擾。

(xvi)  訴訟缺席沒有任何行動、訴訟、訴訟程序、調查或調查正在進行，或由任何政府實體提起，也沒有公司現在掛起，或據公司所知，威脅到集團的，合理地預期將導致重大不利影響的事項，或合理預期會嚴重和不利地影響其各自的財產或資產，或完成本協議中所預期的交易，或公司根據本協議的義務履行；以及集團是當事方或其財產或資產是主體的所有未決法律或政府程序的總和，包括與業務相關的普通日常訴訟，如果對集團作出不利決定，則不會合理地預期會導致重大不利影響。

(xvii)  陳列品的準確性沒有合同或文件需要在註冊聲明、一般披露文件或招股說明書中描述，也沒有需要作爲註冊聲明的附件提交的，這些合同或文件都已經按要求描述和提交。

(xviii)  無進一步要求公司在履行本協議項下的義務、與本協議有關的發行或銷售證券以及本協議所涉及的交易完成的過程中，不需要或無需獲得任何政府機構的備案、授權、批准、同意、許可、訂貨、註冊、資格或裁定，除非已經獲得或根據1933年法案、1933年法案規定、納斯達克股票市場有關規定、美國各州證券法律或金融業監管局規定可能需要。納斯達克資本市場FINRA”).

(xix)  持有執照和許可證。 集團擁有此類許可、執照、批准、同意和其他授權（統稱，”政府許可”) 由開展目前由其經營的業務所必需的適當政府實體簽發，包括但不限於所有 美國食品藥品監督管理局要求的此類許可證、執照、批准、同意和其他授權（ ”食品藥品管理局”）、歐洲藥品管理局（”艾瑪”)，或任何其他聯邦、州、地方或外國 從事臨床試驗、藥品、生物製劑或生物危害物質或材料監管的機構或團體， 除非不這樣擁有此類政府許可證，無論是單獨還是總體而言，都不會有合理的預期 造成重大不利影響。本集團遵守所有政府許可的條款和條件，但以下情況除外 不這樣做，無論是單獨還是總體而言，都不會合理地預期會造成重大不利影響。所有的 政府許可證有效且完全有效，除非此類政府許可證無效或失效 無論是單獨還是總體而言，都不能合理地預期此類政府許可證的全面生效和生效 造成重大不利影響。專家組尚未收到任何與實際撤銷或修改有關的書面訴訟通知 任何政府許可證，如果作出不利的決定、裁決或裁決，無論是單獨還是總體而言，都會 合理地預計會造成重大不利影響。在食品和藥物管理局適用法律法規要求的範圍內， 該小組已向美國食品和藥物管理局提交了每項臨床試驗的研究性新藥申請或其修正或補充 它曾在美國進行或贊助或正在進行或贊助；所有此類呈件（如果有）均符合實質性規定 提交時附有適用的法律和法規，而且食品和藥物管理局沒有斷言任何此類存在重大缺陷 提交。在歐盟國家適用法律和法規要求的範圍內，該集團已提交 向這些國家的國家醫療機構提交臨床試驗授權申請、修正或補充 它在這些國家進行或贊助或正在進行或贊助的每項臨床試驗；所有此類提交的文件（如果有）是 提交時基本符合適用的法律法規，國家沒有斷言存在重大缺陷 藥品機構對任何此類呈件的看法。

(xx)  財產所有權集團不擁有任何實物產權。集團擁有其所有的個人和其他財產的良好和可變轉讓的所有權（不包括本節(1)(a)(xxi)中定義的「知識產權」），在任何情況下，均不受任何抵押、質押、留置權、安全權益、索賠、限制或任何形式的負擔的約束，除非（A）在註冊聲明書、普通披露文件和招股說明書中有描述，或（B）不管是單獨還是總體上，均不會對該財產的價值產生重大影響，並且不會對集團對該財產的使用現在和擬定的方式產生重大幹擾；而且對於對集團業務重要的租賃和轉租，集團根據註冊聲明書、普通披露文件或招股說明書持有的屬性是有效的，並且集團沒有收到任何有關任何人對上述租賃或轉租中影響集團權利的任何權利爭議的重大主張的通知，或有關影響或質疑集團對出租或轉租物業的繼續佔有權利的通知。

(xxi)  Intellectual Property. The Group owns, or has obtained valid, binding and enforceable licenses for the right to use, patents, patent applications, inventions, copyrights, know how (including trade secrets and other unpatented and/or unpatentable proprietary or confidential information, systems or procedures), trademarks, service marks, trade names or other intellectual property (collectively, “Intellectual Property”) necessary to carry on the business of the Group as now conducted and as proposed to be conducted, insofar as such Intellectual Property is described in the Registration Statement, the General Disclosure Package and the Prospectus (collectively, the “Company Intellectual Property”), except where failure to own, license or have such rights would not, individually or in the aggregate, have a Material Adverse Effect; and to the knowledge of the Company, the patents, trademarks, and copyrights, if any, included within the Company Intellectual Property are valid, enforceable, and subsisting. Other than as disclosed in the Registration Statement, the General Disclosure Package and the Prospectus, (A) the Group is not obligated to pay a material royalty, grant a license, or provide other material consideration to any third party in connection with the Company Intellectual Property, (B) the Group has not received any notice of any claim of infringement, misappropriation or conflict with any Intellectual Property rights of others with respect to any of the Group’s product candidates or processes or the Company Intellectual Property, (C) to the knowledge of the Group, neither the manufacture nor the sale or use of any of the product candidates or processes of the Group referred to in the Registration Statement, the General Disclosure Package or the Prospectus do or will infringe, misappropriate or violate any existing, non-patent Intellectual Property right or any existing valid, granted patent claim of any third party, (D) to the knowledge of the Group, no third party has any ownership rights in or to any Intellectual Property that is owned by the Group and, to the knowledge of the Group, no third party has any ownership right in or to any Intellectual Property that is exclusively licensed to the Group in any field of use other than any licensor to the Group of such Intellectual Property, (E) there is no pending or, to the knowledge of the Group, threatened action, suit, proceeding or claim by others challenging the Group’s rights in or to any Company Intellectual Property, (F) to the Group’s knowledge, no employee of the Group is or has been in violation of any term of any employment contract, patent disclosure agreement, invention assignment agreement, non-competition agreement, non-solicitation agreement, nondisclosure agreement or any restrictive covenant to or with a former employer where the basis of such violation relates to such employee’s employment with the Group, and (G) to the knowledge of the Group, the Group has complied with the terms of each agreement pursuant to which Intellectual Property has been licensed to the Group, except where failure to comply would not, individually or in the aggregate, have a Material Adverse Effect, and, to the knowledge of the Group, all such agreements are in full force and effect. The statements relating to the Group’s intellectual property rights contained in the Registration Statement, the General Disclosure Package and the Prospectus are complete and accurate in all material respects. The Registration Statement, the General Disclosure Package, and the Prospectus did not and do not contain any untrue statement of a material fact or omit to state a material fact required to be stated therein or necessary to make the intellectual property statements, in light of the circumstance under which they were made, not misleading.

(xxii)  Patents and Patent Applications. All patents and patent applications owned by or licensed to the Group or under which the Group has rights have, to the knowledge of the Group, been duly and properly filed and maintained; except for routine ex parte patents prosecution activities before patent offices, there is no pending or, to the knowledge of the Company, threatened legal proceeding, including, but not limited to, any government or patent office proceeding, such as inter partes review, reexamination, opposition, or other patent office proceeding, in any jurisdiction challenging the validity, enforceability, or scope of any patents and/or pending patent applications owned by or licensed to the Group; to the knowledge of the Group, each individual associated with the filing and prosecution of such patents and applications has complied with their duty of candor and disclosure to the U.S. Patent and Trademark Office (the “USPTO”) in connection with such patents and applications; and the Group is not aware of any information required to be disclosed to the USPTO that was not disclosed to the USPTO in connection with the prosecution of the aforementioned patents and applications.

(xxiii)  Environmental Laws. Except as would not, singly or in the aggregate, reasonably be expected to result in a Material Adverse Effect, (A) the Group is not in violation of any applicable federal, state, local or foreign statute, law, rule, regulation, ordinance, code, policy or rule of common law or any judicial or administrative interpretation thereof, including any judicial or administrative order, consent, decree or judgment, relating to pollution or protection of human health, the environment (including, without limitation, ambient air, surface water, groundwater, land surface or subsurface strata) or wildlife, including, without limitation, laws and regulations relating to the release or threatened release of chemicals, pollutants, contaminants, wastes, toxic substances, hazardous substances, petroleum or petroleum products, asbestos-containing materials or mold (collectively, “Hazardous Materials”) or to the manufacture, processing, distribution, use, treatment, storage, disposal, transport or handling of Hazardous Materials (collectively, “Environmental Laws”), (B) the Group has all permits, authorizations and approvals required for its operations under any applicable Environmental Laws and is in compliance with its requirements, (C) there are no pending or, to the knowledge of the Company, threatened, administrative, regulatory or judicial actions, suits, demands, demand letters, claims, liens, notices of noncompliance or violation, investigation or proceedings relating to any Environmental Law against the Group and (D) to the knowledge of the Company, there are no events or circumstances that would reasonably be expected to form the basis of an order for clean-up or remediation, or an action, suit or proceeding by any private party or Governmental Entity, against or affecting the Group relating to Hazardous Materials or any Environmental Laws.

(xxiv)  Accounting Controls. The Company maintains an effective system of “internal control over financial reporting” (as defined under Rule 13-a15(f) and 15d-15(f) under the 1934 Act Regulations) that complies with the requirements of the 1934 Act and a system of internal accounting controls sufficient to provide reasonable assurances that (A) transactions are executed in accordance with management’s general or specific authorization; (B) transactions are recorded as necessary to permit preparation of financial statements in conformity with IFRS as issued by the IASB and to maintain accountability for assets; (C) access to assets is permitted only in accordance with management’s general or specific authorization; (D) the recorded accountability for assets is compared with the existing assets at reasonable intervals and appropriate action is taken with respect to any differences; and (E) the interactive data in XBRL included or incorporated by reference in the Registration Statement, the General Disclosure Package or the Prospectus is in compliance with the SEC’s published rules, regulations and guidelines applicable thereto. Since the end of the Company’s most recent audited fiscal year, there has been no material weakness in the Company’s internal control over financial reporting (whether or not remediated) and except as described in the Registration Statement, the General Disclosure Package and the Prospectus, there has been no change in the Company’s internal control over financial reporting that has materially adversely affected, or is reasonably likely to materially adversely affect, the Company’s internal control over financial reporting.

(xxv) Compliance with the Sarbanes-Oxley Act. The Company has taken all necessary actions to ensure that, upon the effectiveness of the Registration Statement, it will be in compliance with all provisions of the Sarbanes-Oxley Act of 2002 and all rules and regulations promulgated thereunder or implementing the provisions thereof (the “Sarbanes-Oxley Act”) that are then in effect and with which the Company is required to comply as of the effectiveness of the Registration Statement, and is actively taking steps to ensure that it will be in compliance with other provisions of the Sarbanes-Oxley Act not currently in effect, upon the effectiveness of such provisions, or which will become applicable to the Company at all times after the effectiveness of the Registration Statement.

(xxvi)  Disclosure Controls. The Company has established “disclosure controls and procedures” (as defined in Rules 13a-15(e) and 15d-15(e) of the 1934 Act Regulations) that complies with the requirements of the 1934 Act; the Company’s “disclosure controls and procedures” are reasonably designed to ensure that all information (both financial and non-financial) required to be disclosed by the Company in the reports that it files or submits under the 1934 Act is recorded, processed, summarized and reported within the time periods specified in the rules and regulations under the 1934 Act, and that all such information will be accumulated and communicated to the Company’s management as appropriate to allow timely decisions regarding required disclosure and to make the certifications of the Chief Executive Officer and Chief Financial Officer of the Company required under the 1934 Act with respect to such reports.

(xxvii)  Preclinical and Clinical Data and Regulatory Compliance. The preclinical tests and clinical trials that are described in, or the results of which are referred to in, the Registration Statement, the General Disclosure Package or the Prospectus (collectively, “Studies”) were and, if still pending, are being conducted in all material respects in accordance with the protocols, procedures and controls designed and approved for such Studies and with all applicable standard medical and scientific research procedures; each description of the results of such Studies is accurate and complete in all material respects and fairly presents the data derived from such Studies; and the Company has no knowledge of any other Studies the results of which are inconsistent with, or otherwise call into question, the results described or referred to in the Registration Statement, the General Disclosure Package or the Prospectus. Except as described in the Registration Statement, the General Disclosure Package and the Prospectus, the Group has not received any written notice of, or correspondence from, any Governmental Entity requiring the termination, suspension or material modification of any Studies. The Company has operated and currently is in compliance with the United States Federal Food, Drug, and Cosmetic Act (21 U.S.C. §301 et seq.) and all applicable regulations of the FDA (collectively, the “FDCA”), and all applicable regulations of the EMA and other federal, state, local and foreign governmental bodies exercising comparable authority, except where the failure to so operate or be in compliance would not have a Material Adverse Effect.

(xxviii) Compliance with Health Care Laws. The Group and its directors, officers, employees and, to the knowledge of the Company, the Group’s independent contractors and agents, are, and at all times have been, in material compliance with all applicable Health Care Laws. For purposes of this Agreement, “Health Care Laws” means: (i) the FDCA and the Public Health Service Act (42 U.S.C. § 201 et seq.); (ii) all applicable federal, state, local and all applicable foreign health care related fraud and abuse laws, including, without limitation, the federal Anti-Kickback Statute (42 U.S.C. § 1320a-7b(b)), the federal criminal false claims law (42 U.S.C. § 1320a-7b(a)), the federal civil monetary penalties law (42 U.S.C. § 1320a-7a), the federal Civil False Claims Act (31 U.S.C. § 3729 et seq.), the exclusions law (42 U.S.C. § 1320a-7), the Physician Payments Sunshine Act ( 42 U.S.C. § 1320a-7h), federal criminal laws relating to health care fraud and abuse, including but not limited to, 18 U.S.C. §§ 286, 287 and 1349, the health care fraud criminal provisions under the Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) (42 U.S.C. § 1320d et seq.), and the regulations promulgated pursuant to such statutes; (iii) HIPAA as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH Act”) (42 U.S.C. § 17921 et seq.), each as amended, and their implementing regulations; (iv) Medicare (Title XVIII of the Social Security Act) and Medicaid (Title XIX of the Social Security Act), and the regulations promulgated pursuant to such statutes; (v) the Patient Protection and Affordable Care Act of 2010 (Public Law 111-148), as amended by the Health Care and Education Reconciliation Act of 2010 (Public Law 111-152), and the regulations promulgated thereunder; and (vi) all other local, state, federal, national, supranational and foreign health care laws relating to the regulation of the Group. The Group: (a) has not received written notice of any claim, action, suit, proceeding, hearing, enforcement, investigation, arbitration or other action from any Governmental Entity or other party alleging that any operation or activity is in violation of any Health Care Laws (collectively, “Action”); (b) has no knowledge that any Action is threatened; and (c) has no knowledge of any event or condition that would reasonably be expected to result in an Action. The Group has filed, maintained and submitted all material reports, documents, forms, notices, applications, records, claims, submissions and supplements or amendments as required by any Health Care Laws, and all such reports, documents, forms, notices, applications, records, claims, submissions and supplements or amendments were complete and accurate on the date filed in all material respects (or were corrected or supplemented by a subsequent submission). Neither the Group nor any of their employees, officers, directors nor, to the knowledge of the Company, the Group’s independent contractors or agents is a party to any corporate integrity agreements, plans of correction, monitoring agreements, consent decrees, settlement orders, or similar agreements with or imposed by any Governmental Entity regarding any Health Care Laws. Additionally, neither the Group nor any of their employees, officers, directors nor, to the knowledge of the Company, the Group’s independent contractors or agents has been excluded, suspended or debarred from participation in any U.S. federal health care program or human clinical research or, to the knowledge of the Group, is subject to a governmental inquiry, investigation, proceeding, or other similar action that could reasonably be expected to result in debarment, suspension, or exclusion.

(xxix)  Payment of Taxes. The Group has filed all necessary Dutch and United States national, federal, state and foreign income and franchise tax returns that are required to have been filed by it pursuant to applicable national, federal, state, local, foreign or other law except insofar as the failure to file such returns would not reasonably be expected to result in a Material Adverse Effect, and has paid all taxes required to be paid by any of them pursuant to such returns or pursuant to any assessment received by the Group, except for such taxes, if any, as are being contested in good faith and as to which adequate reserves have been established by the Group or except insofar as the failure to pay such taxes would not reasonably be expected to result in a Material Adverse Effect. The charges, accruals and reserves on the books of the Company in respect of any income and corporation tax liability for any years not finally determined are adequate to meet any assessments or re-assessments for additional income and corporation tax for any years not finally determined, except to the extent of any inadequacy that would not reasonably be expected to result in a Material Adverse Effect. The Group is not involved in any current material dispute with any tax authority and the Group is currently not subject to any material investigation or audit from any tax authority. To the Company’s knowledge, except for any net (corporate) income taxes imposed on the Underwriters by the Netherlands or any political subdivision or taxing authority thereof or therein as a result of any present or former connection between the Underwriters and the Netherlands, no transaction, value added (“VAT”), stamp, capital or other issuance, registration, transaction, transfer or withholding tax or duty is payable in the Netherlands by or on behalf of the Underwriters to any taxing authority in connection with (i) the issuance, sale and delivery of the Securities by the Company in the manner contemplated herein; (ii) the purchase from the Company, and the initial sale and delivery by the Underwriters of the Securities to purchasers thereof as contemplated herein; or (iii) the execution and delivery of this Agreement or any other document to be furnished hereunder.

(xxx)  DAC6. No transaction contemplated by this Agreement forms part of an arrangement that meets any hallmark set out in Annex IV of the Council Directive of 25 May 2018 (2018/822/EU) amending Directive 2011/16/EU (“DAC6”).

(xxxi)  Insurance. The Group carries or is entitled to the benefits of insurance, with financially sound and reputable insurers, in such amounts and covering such risks as is customary and adequate for the conduct of its business, and all such insurance is in full force and effect. The Group has no reason to believe that it will not be able (A) to renew its existing insurance coverage as and when such policies expire or (B) to obtain comparable coverage from similar institutions as may be necessary or appropriate to conduct its business as now conducted and at a cost that would not reasonably be expected to result in a Material Adverse Effect. The Group has not been denied any insurance coverage which it has sought or for which it has applied.

(xxxii)  Investment Company Act. The Company is not required, and upon the issuance and sale of the Securities as herein contemplated and the application of the net proceeds therefrom as described in the Registration Statement, the General Disclosure Package and the Prospectus will not be required, to register as an “investment company” under the Investment Company Act of 1940, as amended (the “1940 Act”).

(xxxiii) Absence of Manipulation. Neither the Company nor, to the Company’s knowledge, any affiliate of the Company has taken, nor will the Company or any affiliate take, directly or indirectly any action which is designed, or would reasonably be expected, to cause or result in, or which constitutes, the stabilization or manipulation of the price of any security of the Company to facilitate the sale or resale of the Securities or to result in a violation of Regulation M under the 1934 Act.

(xxxiv)  FCPA. Neither the Company nor any of its subsidiaries nor, to the knowledge of the Company, any director, officer, agent, employee, affiliate or other person acting on behalf of the Company or any of its subsidiaries is aware of or has taken any action, directly or indirectly, that would result in a violation or a sanction for violation by such persons of the Foreign Corrupt Practices Act of 1977 or the U.K. Bribery Act 2010, each as may be amended, or similar law of any other relevant jurisdiction, or the rules or regulations thereunder; and Company and its subsidiaries and, to the knowledge of the Company, the Company’s affiliates have conducted their respective businesses in compliance with the FCPA or any other applicable anti-bribery or anti-corruption law and have instituted and maintain policies and procedures to ensure compliance therewith. No part of the proceeds of the offering will be used, directly or indirectly, in violation of the Foreign Corrupt Practices Act of 1977 or the U.K. Bribery Act 2010, each as may be amended, or similar law of any other relevant jurisdiction, or the rules or regulations thereunder.

(xxxv)  AML. The operations of the Company and its subsidiaries are and have been conducted at all times in compliance with applicable financial recordkeeping and reporting requirements and the money laundering statutes and the rules and regulations thereunder and any related or similar rules, regulations or guidelines, issued, administered or enforced by any governmental agency (collectively, the “Money Laundering Laws”) and no action, suit or proceeding by or before any court or governmental agency, authority or body or any arbitrator involving the Company or any of its subsidiaries with respect to the Money Laundering Laws is pending or, to the best knowledge of the Company, threatened.

(xxxvi)  Sanctions. Neither the Company nor any of its subsidiaries nor, to the knowledge of the Company, any director, officer, agent, employee or affiliate of the Company or any of its subsidiaries (i) is, or is controlled or 50% or more owned in the aggregate by or is acting on behalf of, one or more individuals or entities that are currently the subject of any sanctions administered or enforced by the United States (including any administered or enforced by the Office of Foreign Assets Control of the U.S. Department of the Treasury, the U.S. Department of State or the Bureau of Industry and Security of the U.S. Department of Commerce), the United Nations Security Council, the European Union, a member state of the European Union (including sanctions administered or enforced by His Majesty’s Treasury of the United Kingdom) or other relevant sanctions authority (collectively, “Sanctions” and such persons, “Sanctioned Persons” and each such person, a “Sanctioned Person”), (ii) is located, organized or resident in a country or territory that is, or whose government is, the subject of Sanctions (currently, Crimea, Cuba, Iran, North Korea, Syria, and the so-called Donetsk People’s Republic and so-called Luhansk People’s Republic regions of Ukraine) that broadly prohibit dealings with that country or territory (collectively, “Sanctioned Countries” and each, a “Sanctioned Country”) or (iii) will, directly or indirectly, use the proceeds of this offering, or lend, contribute or otherwise make available such proceeds to any subsidiary, joint venture partner or other individual or entity in any manner that would result in a violation of any Sanctions by, or could result in the imposition of Sanctions against, any individual or entity (including any individual or entity participating in the offering, whether as underwriter, advisor, investor or otherwise). Neither the Company nor any of its subsidiaries has engaged in any dealings or transactions with or for the benefit of a Sanctioned Person, or with or in a Sanctioned Country, since April 24, 2019, nor does the Company or any of its subsidiaries have any plans to engage in dealings or transactions with or for the benefit of a Sanctioned Person, or with or in a Sanctioned Country.

(xxxvii)  Lending Relationships. The Group (i) does not have any material lending or other relationship with any banking or lending affiliate of any Underwriter and (ii) does not intend to use any of the proceeds from the sale of the Securities to repay any outstanding debt owed to any affiliate of any Underwriter.

(xxxviii)  Statistical and Market-Related Data. Any statistical and market-related data included in the Registration Statement, the General Disclosure Package or the Prospectus are based on or derived from sources that the Company believes, after reasonable inquiry, to be reliable and accurate and, to the extent required, the Company has obtained the written consent to the use of such data from such sources.

(xxxix)  Listing Approval. The Ordinary Shares are registered pursuant to Section 12(b) of the 1934 Act. The Company has filed a Notice of Listing of Additional Shares with the Nasdaq Capital Market, and the Company has taken no action designed to, or likely to have the effect of, terminating the registration of the Ordinary Shares under the 1934 Act or delisting the Securities from the Nasdaq Capital Market, nor has the Company received any written notification that the Commission or the Nasdaq Capital Market is contemplating terminating such registration or listing. The Company is in compliance with all applicable listing requirements of the Nasdaq Capital Market, except to the extent as would not reasonably be expected to result in a Material Adverse Effect.

(xl)  FINRA Matters. There are no affiliations or associations between any member of FINRA and any of the Company’s officers, directors or 5% or greater shareholders. There are no relationships, direct or indirect, or related-party transactions involving the Company or any other person required to be described in the Registration Statement and the Prospectus which have not been described in such documents and the General Disclosure Package as required.

(xli) Brokers. Except pursuant to this Agreement, there is no broker, finder or other party that is entitled to receive from the Company any brokerage or finder’s fee or other fee or commission as a result of any transactions contemplated by this Agreement.

(xlii) Submission to Jurisdiction. The Company has the power to submit, and pursuant to Section 16 of this Agreement, has legally, validly, effectively and irrevocably submitted, to the personal jurisdiction of each United States federal court and New York state court located in the City and County of New York, Borough of Manhattan, State of New York, U.S.A., and the Company has the power to designate and pursuant to Section 16 of this Agreement, has legally, validly, effectively and irrevocably designated the notice address provided in Section 11 of this Agreement for the effective service of process in any action arising out of or relating to this Agreement or the Securities in any of the above courts, and service of process effected on such address will be effective to confer valid personal jurisdiction over the Company as provided in Section 16 hereof.

(xliii) No Rights of Immunity. Except as provided by laws or statutes generally applicable to transactions of the type described in this Agreement, neither the Company nor any of its respective properties, assets or revenues has any right of immunity under the laws of the Netherlands, New York State law or United States federal law, from any legal action, suit or proceeding, from the giving of any relief in any such legal action, suit or proceeding, from set-off or counterclaim, from the jurisdiction of any Dutch, New York or United States federal court, from service of process, attachment upon or prior to judgment, or attachment in aid of execution of judgment, or from execution of a judgment, or other legal process or proceeding for the giving of any relief or for the enforcement of a judgment, in any such court, with respect to its obligations, liabilities or any other matter under or arising out of or in connection with this Agreement. To the extent that the Company or any of its respective properties, assets or revenues may have or may hereafter become entitled to any such right of immunity in any such court in which proceedings may at any time be commenced, the Company waives or will waive such right to the extent permitted by law and has consented to such relief and enforcement as provided in Section 14 through Section 16 of this Agreement.

(xliv) Forward-Looking Statements. Each financial or operational projection or other “forward-looking statement” (as defined by Section 27A of the 1933 Act or Section 21E of the 1934 Act, as applicable) contained in the Registration Statement, the General Disclosure Package or the Prospectus (i) was so included by the Company in good faith and with reasonable basis after due consideration by the Company of the underlying assumptions, estimates and other applicable facts and circumstances and (ii) is accompanied by meaningful cautionary statements identifying those factors that could cause actual results to differ materially from those in such forward-looking statement. No such statement was made with the knowledge of a director or senior manager of the Company that is was false or misleading.

(xlv) XBRL. The interactive data in the eXtensible Business Reporting Language (“XBRL”) included as an exhibit or incorporated by reference to the Registration Statement fairly presents the information called for in all material respects and has been prepared in accordance with the SEC’s rules and guidelines applicable thereto.

(xlvi) Data Privacy and Security Laws. The Company and its subsidiaries are, and at all prior times since January 1, 2021 were, in material compliance with all applicable data privacy and security laws and regulations (collectively, the “Privacy Laws”). To ensure material compliance with the Privacy Laws, the Company and its subsidiaries have in place, comply with, and take appropriate steps reasonably designed to ensure compliance in all material respects with their policies and procedures relating to data privacy and security and the collection, storage, use, disclosure, handling, and analysis of Personal Data (the “Policies”). The Company provides accurate notice of its Policies then in effect to data subjects in material compliance with Privacy Laws. Each of the Company Policies provides accurate and sufficient notice of the Company’s privacy practices relating to its subject matter and such Company Policies do not contain any material omissions of the Company’s privacy practices. “Personal Data” means (i) a natural person’s name, street address, telephone number, e-mail address, photograph, social security number or tax identification number, driver’s license number, passport number, credit card number, bank information, or customer or account number; (ii) any information which would qualify as “personally identifying information” or similar term under applicable Privacy Laws, or (iii) any other piece of information that allows the identification of such natural person, or his or her family, or permits the collection or analysis of any data related to an identified person’s health or sexual orientation. The execution, delivery and performance of this Agreement or any other agreement referred to in this Agreement will not result in a material breach of violation of any Privacy Laws or Policies. The Company further certifies that neither it nor any subsidiary: (i) has received notice of any actual or potential material liability under or relating to, or actual or potential violation of, any of the Privacy Laws; (ii) is currently conducting or paying for, in whole or in part, any investigation, remediation, or other corrective action pursuant to any Privacy Law; or (iii) is a party to any order, decree, or agreement that imposes any obligation or liability under any Privacy Law.

(xlvii) Cybersecurity; Data Protection. The Company and its subsidiaries’ information technology and computer systems and assets, networks, hardware, software, websites, applications, databases equipment or technology (collectively, “IT Systems”) are adequate for, and operate and perform in all material respects as required in connection with the operation of the business of the Company and its subsidiaries as currently conducted, free and clear of all material bugs, errors, defects, Trojan horses, time bombs, malware and other corruptants. The Company and its subsidiaries have implemented and maintained commercially reasonable controls, policies, procedures, and safeguards designed to maintain and protect the integrity, continuous operation, redundancy and security of all IT Systems and all Personal Data, sensitive, confidential, and/or regulated data (collectively, “Data”) used in connection with their businesses. (i) Except as may be included or incorporated by reference in the Registration Statement, the General Disclosure Package and the Prospectus, (x) to the Company’s knowledge, the Company has not had any material security breach, violations, outages or unauthorized uses of or accesses to same, or other material compromise of or relating to any of the Company’s or its subsidiaries’ IT Systems or Data, and (y) the Company and its subsidiaries have not been notified of, and have no knowledge of any event or condition that would reasonably be expected to result in, any material security breach or other material compromise to their IT Systems or Data; (ii) the Company and its subsidiaries are presently in compliance with all applicable laws or statutes and all judgments, orders, rules and regulations of any court or arbitrator or governmental or regulatory authority, internal policies and contractual obligations relating to the privacy and security of IT Systems or Data and to the protection of such IT Systems or Data from unauthorized use, access, misappropriation or modification, except as would not, in the case of this clause (ii), individually or in the aggregate, have a Material Adverse Effect; and (iii) the Company and its subsidiaries have implemented backup and disaster recovery technology consistent in material respects with applicable industry standards and practices.

(xlviii) Compliance with ERISA. The Company does not maintain any “employee benefit plan” subject to Title IV of the Employee Retirement Income Security Act of 1974, as amended (“ERISA”), or the regulations and published interpretations thereunder.

(b)           Certificates. Any certificate signed by any management board member of the Company delivered to the Representatives or to counsel for the Underwriters shall be deemed a representation and warranty by the Company to each Underwriter as to the matters covered thereby.

SECTION 2.         Sale and Delivery to Underwriters; Closing.

(a)            Initial Securities. On the basis of the representations and warranties herein contained and subject to the terms and conditions herein set forth, the Company agrees to sell to each Underwriter, severally and not jointly, and each Underwriter, severally and not jointly, agrees to purchase from the Company, at the price per share set forth in Schedule A, that number of Initial Securities set forth in Schedule A opposite the name of such Underwriter, plus any additional number of Initial Securities which such Underwriter may become obligated to purchase pursuant to the provisions of Section 10 hereof, subject, in each case, to such adjustments among the Underwriters as the Representatives in their sole discretion shall make to eliminate any sales or purchases of fractional shares.

(b)            Option Securities. In addition, on the basis of the representations and warranties herein contained and subject to the terms and conditions herein set forth, the Company hereby grants an option to the Underwriters, severally and not jointly, to purchase up to an additional 2,700,000 Ordinary Shares, at the price per share set forth in Schedule A, less an amount per share equal to any dividends or distributions declared by the Company and payable on the Initial Securities (on a per-share basis) but not payable on the Option Securities. The option hereby granted may be exercised for 30 days after the date hereof and may be exercised in whole or in part at any time from time to time upon notice by the Representatives to the Company setting forth the number of Option Securities as to which the several Underwriters are then exercising the option and the time and date of payment and delivery for such Option Securities. Any such time and date of delivery (a “Date of Delivery”) shall be determined by the Representatives, but any Date of Delivery occurring after the Closing Time shall not be later than seven full business days (i.e. a day on which banks are generally open for ordinary business in Amsterdam, the Netherlands, and New York, United States of America, a “Business Day”) nor earlier than one full Business Day after the exercise of said option (unless mutually agreed by the Representatives and the Company), nor in any event prior to the Closing Time. If the option is exercised as to all or any portion of the Option Securities, each of the Underwriters, acting severally and not jointly, will purchase that proportion of the total number of Option Securities then being purchased which the number of Initial Securities set forth in Schedule A opposite the name of such Underwriter bears to the total number of Initial Securities, subject, in each case, to such adjustments as the Representatives in their sole discretion shall make to eliminate any sales or purchases of fractional shares.

(c)            Payment. Payment of the purchase price for the Initial Securities shall be made at the offices of Cooley LLP, 55 Hudson Yards, New York, NY 10001 or at such other place as shall be agreed upon by the Representatives and the Company, at 9:00 A.M. (New York City time) on the first (second, if the pricing in connection with the Offering occurs after 4:30 P.M. (New York City time) on any given day) Business Day after the date hereof (unless postponed in accordance with the provisions of Section 10), or such other time not later than ten Business Days after such date as shall be agreed upon by the Representatives and the Company (such time and date of payment and delivery being herein called “Closing Time”). Delivery of the Initial Securities at the Closing Time shall be made through the facilities of The Depository Trust Company unless the Representatives shall otherwise instruct.

In addition, in the event that any or all of the Option Securities are purchased by the Underwriters, payment of the purchase price for such Option Securities shall be made at the above-mentioned offices, or at such other place as shall be agreed upon by the Representatives and the Company, on each Date of Delivery as specified in the notice from the Representatives to the Company. Delivery of the Option Securities on each such Date of Delivery shall be made through the facilities of The Depository Trust Company unless the Representatives shall otherwise instruct.

Payment shall be made to the Company by wire transfer of immediately available funds to a bank account designated by the Company against delivery to the Representatives for the respective accounts of the Underwriters of the Securities to be purchased by them. It is understood that each Underwriter has authorized the Representatives, for its account, to accept delivery of and receipt for, and to make payment of the purchase price for, the Initial Securities and the Option Securities, if any, which it has agreed to purchase. The Representatives (not as representatives of the Underwriters) may (but shall not be obligated to) make payment of the purchase price for the Initial Securities or the Option Securities, if any, to be purchased by any Underwriter whose funds have not been received by the Closing Time or the relevant Date of Delivery, as the case may be, but such payment shall not relieve such Underwriter from its obligations hereunder.

For purposes hereof, the difference between the public offering price per share for the Securities and the purchase price per share for the Securities to be paid by the several Underwriters, each set forth on Schedule A, is the fee paid by the Company to the several Underwriters in consideration of the services rendered by the Underwriters to the Company hereunder.

SECTION 3.         Covenants of the Company. The Company covenants with each Underwriter as follows:

(a)            Certain Notifications and Required Actions. The Company will notify the Representatives promptly and confirm the notice in writing, (i) when any post-effective amendment to the Registration Statement shall become effective or any amendment or supplement to the Prospectus shall have been filed, (ii) of the receipt of any comments from the Commission, (iii) of any request by the Commission for any amendment to the Registration Statement or any amendment or supplement to the Prospectus or for additional information, (iv) of the issuance by the Commission of any stop order suspending the effectiveness of the Registration Statement or any post-effective amendment or of any order preventing or suspending the use of any preliminary prospectus or the Prospectus, or of the suspension of the qualification of the Securities from any securities exchange upon which they are listed for trading or included or designated for quotation, or of threatening or initiation of any proceedings for any such purposes. The Company agrees that it will comply with all applicable provisions of Rule 424(b), Rule 433 and Rule 430B of the 1933 Act Regulations and will use its reasonable efforts to confirm that any filings made by the Company under Rule 424(b) or Rule 433 were received by the Commission through EDGAR. The Company will make every reasonable effort to prevent the issuance of any stop order, prevention or suspension and, if any such order is issued, to obtain the lifting thereof at the earliest possible moment.

(b)            Continued Compliance with Securities Laws. The Company will comply with the 1933 Act, the 1933 Act Regulations, the 1934 Act, the 1934 Act Regulations and the rules of Nasdaq so as to permit the completion of the distribution of the Securities as contemplated in this Agreement and in the Registration Statement, the General Disclosure Package and the Prospectus. If at any time when a prospectus relating to the Securities is (or, but for the exception afforded by Rule 172 of the 1933 Act Regulations (“Rule 172”), would be) required by the 1933 Act to be delivered in connection with sales of the Securities, any event shall occur or condition shall exist as a result of which it is necessary, in the reasonable opinion of counsel for the Underwriters or for the Company, to (i) amend the Registration Statement in order that the Registration Statement will not include an untrue statement of a material fact or omit to state a material fact required to be stated therein or necessary to make the statements therein not misleading, (ii) amend or supplement the General Disclosure Package or the Prospectus in order that the General Disclosure Package or the Prospectus, as the case may be, will not include any untrue statement of a material fact or omit to state a material fact necessary in order to make the statements therein not misleading in the light of the circumstances existing at the time it is delivered to a purchaser or (iii) amend the Registration Statement or amend or supplement the General Disclosure Package or the Prospectus, as the case may be, in order to comply with the requirements of the 1933 Act or the 1933 Act Regulations, the Company will promptly (A) give the Representatives notice of such event, (B) prepare any amendment or supplement as may be necessary to correct such statement or omission or to make the Registration Statement, the General Disclosure Package or the Prospectus comply with such requirements and, a reasonable amount of time prior to any proposed filing or use, furnish the Representatives with copies of any such amendment or supplement and (C) file with the Commission any such amendment or supplement; provided that the Company shall not file or use any such amendment or supplement to which the Representatives or counsel for the Underwriters shall reasonably object. The Company will furnish to the Underwriters such number of copies of such amendment or supplement as the Underwriters may reasonably request. Without limiting the generality of the foregoing, the Company will, during the period when a prospectus relating to the Securities is required by the 1933 Act to be delivered (whether physically or through compliance with Rule 172 under the 1933 Act or any similar rule), file on a timely basis with the Commission and Nasdaq all reports and documents required to be filed under the 1934 Act.

(c)            Delivery of Registration Statements. The Company has furnished or will deliver to the Representatives and counsel for the Underwriters, without charge, signed copies of the Registration Statement as originally filed and each amendment thereto (including exhibits filed therewith) and signed copies of all consents and certificates of experts, and will also deliver to the Representatives, without charge, a conformed copy of the Registration Statement as originally filed and each amendment thereto (without exhibits) for each of the Underwriters. The copies of the Registration Statement and each amendment thereto furnished to the Underwriters will be identical to the electronically transmitted copies thereof filed with the Commission pursuant to EDGAR, except to the extent permitted by Regulation S-T.

(d)            Delivery of Prospectuses. The Company has delivered to each Underwriter, without charge, as many copies of each preliminary prospectus as such Underwriter reasonably requested, and the Company hereby consents to the use of such copies for purposes permitted by the 1933 Act. The Company will furnish to each Underwriter, without charge, during the period when a prospectus relating to the Securities is (or, but for the exception afforded by Rule 172, would be) required to be delivered under the 1933 Act, such number of copies of the Prospectus (as amended or supplemented) as such Underwriter may reasonably request. The Prospectus and any amendments or supplements thereto furnished to the Underwriters will be identical to the electronically transmitted copies thereof filed with the Commission pursuant to EDGAR, except to the extent permitted by Regulation S-T.

(e)            Blue Sky Qualifications. The Company will cooperate with the Underwriters and counsel for the Underwriters to qualify the Securities for offering and sale under the applicable securities laws of such states and other jurisdictions (domestic or foreign) as the Representatives may designate and to maintain such qualifications in effect so long as required to complete the distribution of the Securities; provided, however, that the Company shall not be obligated to file any general consent to service of process or to qualify as a foreign corporation or as a dealer in securities in any jurisdiction in which it is not so qualified or to subject itself to taxation in respect of doing business in any jurisdiction in which it is not otherwise so subject.

(f)            Rule 158. The Company will timely file such reports pursuant to the 1934 Act as are necessary in order to make generally available to its security holders as soon as practicable an earnings statement for the purposes of, and to provide to the Underwriters the benefits contemplated by, the last paragraph of Section 11(a) of the 1933 Act.

(g)            Use of Proceeds. The Company will use the net proceeds received by it from the sale of the Securities in the manner specified in the Registration Statement, the General Disclosure Package and the Prospectus under “Use of Proceeds.”

(h)            Listing. The Company will use its best efforts to effect the listing of the Securities on the Nasdaq Capital Market, subject to notice of issuance.

(i)            Restriction on Sale of Securities. During a period of 60 days from the date of the Prospectus, the Company will not, without the prior written consent of Evercore and Cantor, directly or indirectly, (i) offer, pledge, sell, contract to sell (including any short sale), sell any option or contract to purchase, purchase any option or contract to sell, grant any option, right or warrant to purchase or otherwise transfer or dispose of any Ordinary Shares or any securities convertible into or exercisable or exchangeable for Ordinary Shares, including depository receipts of the Company (collectively, the “Lock-Up Securities”) or file or confidentially submit any registration statement under the 1933 Act with respect to any of the foregoing, (ii) enter into any swap or any other agreement or any transaction that transfers, in whole or in part, directly or indirectly, the economic consequence of ownership of the Ordinary Shares, whether any such swap or transaction described in clause (i) or (ii) above is to be settled by delivery of Ordinary Shares or such other securities, in cash or otherwise, or (iii) publicly disclose the intention to do any of the foregoing described in clauses (i) and (ii) above. The foregoing sentence shall not apply to (a) the Securities to be sold hereunder, (b) the grant of options or other equity-based awards pursuant to the terms of a plan disclosed in the Registration Statement, or the issuance of any Ordinary Shares upon the exercise of such options or other equity-based awards, provided that the recipient of such options or other equity-based awards (to the extent that such options or other equity-based awards shall vest within the period ending 60 days after the date of the Prospectus) or such Ordinary Shares shall execute and deliver a lock up agreement substantially in the form of Exhibit A hereto prior to receiving such options, equity-based awards or Ordinary Shares unless such recipient has previously executed such agreement, (c) the filing by the Company of a registration statement on Form S-8 or a successor form thereto solely with respect to the Company’s benefit plans disclosed in the Registration Statement, the General Disclosure Package and the Prospectus, a “universal shelf” registration on Form F-3 or a successor form thereto in replacement of the Registration Statement pursuant to which the Securities herein are being sold, (d) the establishment of a trading plan pursuant to Rule 10b5-1 under the 1934 Act, for the repurchase of Ordinary Shares, provided that such plan does not provide for the repurchase of Ordinary Shares during the 60-day restricted period and no public announcement or filing under the 1934 Act regarding the establishment of such plan shall be required of or voluntarily made by or on behalf of the Company or any other person, (e) the issuance of preferred shares pursuant to the exercise of the protective call option that was granted to Stichting Continuity ProQR Therapeutics on September 23, 2014 in accordance with its terms, (f) offer, issue and sell Ordinary Shares, or any securities convertible into or exercisable or exchangeable for Ordinary Shares, on an arm’s-length basis in connection with any joint venture, collaboration, partnership or other strategic alliance, provided, that (x) the aggregate number of Ordinary Shares issued or issuable in accordance with this clause (f) of this paragraph does not exceed 15% of the number of Ordinary Shares outstanding immediately after the issuance and sale of the Securities pursuant hereto and (y) each recipient of any such Ordinary Shares or other securities agrees to restrictions on the resale of securities that are consistent with the provisions set forth in the Lock-Up Agreement (as defined in Section 5(m)) for the remainder of the 60-day restricted period, (g) the issuance by the Company of Ordinary Shares in connection with sales under an “at-the-market” equity offering program pursuant to an Controlled Equity Offering^SM Sales Agreement (the “Sale Agreement”) between the Company and Cantor dated as of November 4, 2021, provided no sales shall be made under the Sale Agreement until the earlier of (x) the exercise in full by the Underwriters of their option to purchase the Option Securities or (y) the thirtieth day following the date of the Prospectus, or (h) the issuance and sale by the Company in a private placement concurrently with the Offering of the Securities contemplated hereby to Eli Lilly and Company at the same price as the public offering price as the Securities.

(j)             Issuer Free Writing Prospectuses. The Company agrees that, unless it obtains the prior written consent of the Representatives, it will not make any offer relating to the Securities that would constitute an Issuer Free Writing Prospectus or that would otherwise constitute a “free writing prospectus,” or a portion thereof, required to be filed by the Company with the Commission or retained by the Company under Rule 433; provided that the Representatives will be deemed to have consented to the Issuer Free Writing Prospectuses listed on Schedule B-2 hereto and any “road show that is a written communication” within the meaning of Rule 433(d)(8)(i) that has been reviewed by the Representatives. The Company represents that it has treated or agrees that it will treat each such free writing prospectus consented to, or deemed consented to, by the Representatives as an “issuer free writing prospectus,” as defined in Rule 433, and that it has complied and will comply with the applicable requirements of Rule 433 with respect thereto, including timely filing with the Commission where required, legending and record keeping. If at any time following issuance of an Issuer Free Writing Prospectus there occurred or occurs an event or development as a result of which such Issuer Free Writing Prospectus conflicted or would conflict with the information contained in the Registration Statement, any preliminary prospectus or the Prospectus or included or would include an untrue statement of a material fact or omitted or would omit to state a material fact necessary in order to make the statements therein, in the light of the circumstances existing at that subsequent time, not misleading, the Company will promptly notify the Representatives and will promptly amend or supplement, at its own expense, such Issuer Free Writing Prospectus to eliminate or correct such conflict, untrue statement or omission.

(k)            Investment Limitation. The Company shall not invest or otherwise use the proceeds received by the Company from its sale of the Securities in such a manner as would require the Company or any of its subsidiaries to register as an investment company under the 1940 Act.

(l)            No Stabilization or Manipulation; Compliance with Regulation M. The Company will not take, and will use commercially reasonable efforts to ensure that no affiliate of the Company will take, directly or indirectly, any action designed to or that might reasonably be expected to cause or result in stabilization or manipulation of the price of the Securities or any reference security with respect to the Securities, whether to facilitate the sale or resale of the Securities or otherwise, and the Company will, and shall use commercially reasonable efforts to cause each of its affiliates to, comply with all applicable provisions of Regulation M.

(m)            Tax Indemnity. The Company will indemnify and hold harmless the Underwriters against any VAT, documentary, stamp or similar issue tax, including any interest and penalties, on the creation, issue and sale of the Securities and on the execution and delivery of this Agreement.

(n)            Withholding taxes. All sums payable by the Group to the Underwriters under this Agreement shall be paid free and clear of all deductions or withholdings imposed by the Netherlands or by any other jurisdiction through which the Group chooses to make a payment, unless the deduction or withholding is required by law, in which event the Group shall pay such additional amount as shall be required to ensure that the net amount received by the relevant Underwriter will equal the full amount which would have been received by such Underwriter had no deduction or withholding been made.

(o)            VAT. All sums payable by the Group to the Underwriters under this Agreement shall be considered exclusive of any VAT or other similar taxes levied by reference to added value or sales. If the transactions described in this Agreement are subject to any VAT, the sums payable by the Group to the relevant Underwriter under this Agreement shall be increased with such VAT, provided that the relevant Underwriter shall provide the Group with a valid invoice that complies with all relevant tax regulations and that specifically states the applicable amount of VAT.

SECTION 4.         Payment of Expenses.

(a)            Expenses. The Company will pay or cause to be paid all expenses (together with any irrecoverable VAT payable in respect of such expenses) incident to the performance of its obligations under this Agreement, including (i) the preparation, printing and filing of the Registration Statement (including financial statements and exhibits) as originally filed and each amendment thereto, (ii) the preparation, printing and delivery to the Underwriters of copies of each preliminary prospectus, each Issuer Free Writing Prospectus and the Prospectus and any amendments or supplements thereto and any costs associated with electronic delivery of any of the foregoing by the Underwriters to investors, (iii) the preparation, issuance and delivery of the Securities to the Underwriters, including any stock or other transfer taxes and any stamp or other duties payable upon the sale, issuance or delivery of the Securities to the Underwriters, (iv) the fees and disbursements of the Company’s counsel, accountants and other advisors, (v) the qualification of the Securities under securities laws in accordance with the provisions of Section 3(e) hereof, including filing fees and the reasonable fees and disbursements of counsel for the Underwriters in connection therewith and in connection with the preparation of a “Blue Sky Survey” and any supplement thereto, in an amount not to exceed $5,000, (vi) the fees and expenses of any transfer agent or registrar for the Securities, (vii) the costs and expenses of the Company relating to investor presentations on any “road show” undertaken in connection with the marketing of the Securities, including without limitation, expenses associated with the production of road show slides and graphics, fees and expenses of any consultants engaged by the Company in connection with the road show presentations, travel and lodging expenses of the Company’s officers and employees and any such consultants (provided that the travel, lodging and any car travel expenses of the representatives of the Underwriters shall be paid by the Underwriters), and 50% of the cost of any aircraft and other transportation chartered in connection with the road show, (viii) the reasonable fees and disbursements of counsel to the Underwriters in connection with the Offering, in an amount not to exceed $100,000, and the reasonable fees and disbursements of counsel to the Underwriters in connection with the review by FINRA of the terms of the sale of the Securities, in an amount not to exceed $20,000 (ix) the fees and expenses incurred in connection with the listing of the Securities on the Nasdaq Capital Market and (x) the costs and expenses (including, without limitation, any damages or other amounts payable in connection with legal or contractual liability) associated with the reforming of any contracts for sale of the Securities made by the Underwriters caused by a breach of the representation contained in the third sentence of Section 1(a)(ii). Notwithstanding the above, except as provided in this Section 4(a), Section 4(b) below, Section 6 (Indemnification) and Section 7 (Contribution), the Underwriters will pay all of their costs and expenses, including fees and expenses of their counsel.

(b)            Termination of Agreement. If this Agreement is terminated by the Representatives in accordance with the provisions of Section 5, Section 9(a)(i) or Section 9(a)(iii) hereof, the Company shall reimburse the Underwriters for all of their reasonably documented out-of-pocket expenses, including the reasonable fees and disbursements of counsel for the Underwriters.

SECTION 5.         Conditions of Underwriters’ Obligations. The obligations of the several Underwriters hereunder are subject to the accuracy of the representations and warranties of the Company contained herein or in certificates of any member of the management board of the Company delivered pursuant to the provisions hereof, to the performance by the Company of its covenants and other obligations hereunder, and to the following further conditions:

(a)            Effectiveness of Registration Statement; Rule 430B Information. The Registration Statement, including any Rule 462(b) Registration Statement, has become effective and, at the Closing Time, no stop order suspending the effectiveness of the Registration Statement or any post-effective amendment thereto has been issued under the 1933 Act or the 1934 Act, no order preventing or suspending the use of any preliminary prospectus or the Prospectus has been issued and no proceedings for any of those purposes have been instituted or are pending or, to the Company’s knowledge, contemplated; and the Company has complied in all material respects with each request (if any) from the Commission for additional information. A prospectus containing the Rule 430B Information shall have been filed with the Commission in the manner and within the time frame required by Rule 424(b) without reliance on Rule 424(b)(8) or a post-effective amendment providing such information shall have been filed with, and declared effective by, the Commission in accordance with the requirements of Rule 430B.

(b)            Opinion of United States Counsel for Company. At the Closing Time, the Representatives shall have received the opinion of Goodwin Procter LLP, United States counsel for the Company, dated the Closing Time, including with respect to regulatory matters, in form and substance satisfactory to counsel for the Underwriters and agreed upon between the parties, together with signed or reproduced copies of such letter for each of the other Underwriters.

(c)            Negative Assurance Letter of United States Counsel for the Company. At the Closing Time, the Representatives shall have received the negative assurance letter of Goodwin Procter LLP, United States counsel for the Company, dated the Closing Time, in form and substance satisfactory to counsel for the Underwriters and agreed upon between the parties, together with signed or reproduced copies of such letter for each of the other Underwriters.

(d)            Opinion of Dutch Counsel for the Company. At the Closing Time, the Representatives shall have received the opinion of A&O Shearman LLP, Dutch counsel for the Company, dated the Closing Time, including with respect to certain regulatory and Dutch tax matters, in the form and substance satisfactory to counsel of the Underwriters and agreed upon between the parties, together with signed or reproduced copies of such letter for each of the other Underwriters.

(e)            Opinions of Intellectual Property Counsels for the Company. At the Closing Time, the Representatives shall have received the opinions of Sterne, Kessler, Goldstein & Fox PLLC and Greaves Brewster LLP, intellectual property counsels for the Company, dated the Closing Time, in form and substance satisfactory to counsel for the Underwriters and agreed upon between the parties, together with signed or reproduced copies of such letter for each of the other Underwriters.

(f)            Opinion of United States Counsel for Underwriters. At the Closing Time, the Representatives shall have received the opinion of Cooley LLP, United States counsel for the Underwriters, dated the Closing Time, together with signed or reproduced copies of such letter for each of the other Underwriters with respect to such matters as the Representatives may reasonably request. In giving such opinion such counsel may rely, as to all matters governed by the laws of jurisdictions other than the law of the State of New York, the General Corporation Law of the State of Delaware and the federal securities laws of the United States, upon the opinions of counsel satisfactory to the Representatives. Such counsel may also state that, insofar as such opinion involves factual matters, they have relied, to the extent they deem proper, upon certificates of officers and other representatives of the Company and certificates of public officials.

(g)            Opinion of Dutch Counsel for the Underwriters. At the Closing Time, the Representatives shall have received the opinion of Stibbe N.V., Dutch counsel for the Underwriters in connection with the offer and sale of the Securities, dated the Closing Time, in form and substance satisfactory to the Underwriters.

(h)            Certificate. At the Closing Time, there shall not have been, since the date hereof or since the respective dates as of which information is given in the Registration Statement, the General Disclosure Package or the Prospectus, any material adverse change in the condition, financial or otherwise, or in the earnings, business affairs, properties or prospects of the Company and its subsidiaries, taken as a whole, whether or not arising in the ordinary course of business, and the Representatives shall have received a certificate of a management board member, dated the Closing Time, to the effect that (i) from the date of this Agreement through the Closing Time, there has been no Material Adverse Effect, (ii) the representations and warranties of the Company in this Agreement are true and correct with the same force and effect as though expressly made at and as of the Closing Time, (iii) the Company has complied in all material respects with all agreements and satisfied all conditions on its part to be performed or satisfied at or prior to the Closing Time, and (iv) no stop order suspending the effectiveness of the Registration Statement under the 1933 Act has been issued and remains outstanding, no order preventing or suspending the use of any preliminary prospectus or the Prospectus has been issued and remains outstanding and no proceedings for any of those purposes have been instituted or are pending or, to their knowledge, contemplated.

(i)             Accountant’s Comfort Letter. At the time of the execution of this Agreement, the Representatives shall have received from KPMG Accountants N.V. a letter, dated such date, in form and substance satisfactory to the Representatives, together with signed or reproduced copies of such letter for each of the other Underwriters containing statements and information of the type ordinarily included in accountants’ “comfort letters” to underwriters with respect to the financial statements and certain financial information contained in the Registration Statement, the General Disclosure Package and the Prospectus.

(j)             Bring-down Comfort Letter. At the Closing Time, the Representatives shall have received from KPMG Accountants N.V a letter, dated as of the Closing Time, to the effect that they reaffirm the statements made in the letter furnished pursuant to subsection (h) of this Section, except that the specified date referred to shall be a date not more than two Business Days prior to the Closing Time.

(k)            CFO Certificate. The Representatives shall have received a certificate of the Chief Financial Officer of the Company, dated as of the Closing Time in form and substance satisfactory to the Representatives.

(l)             Approval of Listing. At the Closing Time, the Securities shall have been approved for listing on the Nasdaq Capital Market, subject only to official notice of issuance.

(m)            [Reserved].

(n)            Lock-up Agreements. At the date of this Agreement, the Representatives shall have received an agreement substantially in the form of Exhibit A hereto signed by the persons and entities listed on Schedule C hereto.

(o)            Conditions to Purchase of Option Securities. In the event that the Underwriters exercise their option provided in Section 2(b) hereof to purchase all or any portion of the Option Securities, the representations and warranties of the Company contained herein and the statements in any certificates furnished by the Company hereunder shall be true and correct as of each Date of Delivery and, at the relevant Date of Delivery, the Representatives shall have received:

(i) CFO Certificate. The Representatives shall have received a certificate of the Chief Financial Officer of the Company, dated as of such Date of Delivery and otherwise to the same effect as the certificate required by Section 5(k) hereof.

(ii)  Opinion of United States Counsel for Company. If requested by the Representatives, the opinion of Goodwin Procter LLP, U.S. counsel for the Company, including with respect to regulatory matters, in form and substance satisfactory to counsel for the Underwriters and agreed upon between the parties, dated such Date of Delivery, relating to the Option Securities to be purchased on such Date of Delivery and otherwise to the same effect as the opinion required by Section 5(b) hereof.

(iii)  Negative Assurance Letter of United States Counsel for the Company. If requested by the Representatives, the negative assurance letter of Goodwin Procter LLP, U.S. counsel for the Company, in form and substance satisfactory to counsel for the Underwriters and agreed upon between the parties, dated such Date of Delivery, relating to the Option Securities to be purchased on such Date of Delivery and otherwise to the same effect as the negative assurance letter required by Section 5(c) hereof.

(iv)  Opinion of Dutch Counsel for the Company. If requested by the Representatives, the opinion of A&O Shearman LLP, Dutch counsel for the Company, including with respect to certain regulatory and Dutch tax matters, in the form and substance satisfactory to counsel of the Underwriters and agreed upon between the parties, dated such Date of Delivery, relating to the Option Securities to be purchased on such Date of Delivery and otherwise to the same effect as the opinion required by Section 5(d) hereof.

(v)  Opinions of Intellectual Property Counsels for the Company. If requested by the Representatives, the opinions of Sterne, Kessler, Goldstein & Fox PLLC and Greaves Brewster LLP, intellectual property counsels for the Company, including with respect to intellectual property and regulatory matters, in form and substance satisfactory to counsel for the Underwriters and agreed upon between the parties, dated such Date of Delivery, relating to the Option Securities to be purchased on such Date of Delivery and otherwise to the same effect as the opinion required by Section 5(e) hereof.

(vi) Opinion of United States Counsel for Underwriters. If requested by the Representatives, the opinion of Cooley LLP, United States counsel for the Underwriters, dated such Date of Delivery, relating to the Option Securities to be purchased on such Date of Delivery and otherwise to the same effect as the opinion required by Section 5(f) hereof.

(vii)  Opinion of Dutch Counsel for the Underwriters. If requested by the Representatives, the opinion of Stibbe N.V., Dutch counsel for the Underwriters in connection with the offer and sale of the Securities, dated such Date of Delivery and otherwise to the same effect as the opinion required by Section 5(g) hereof.

(viii)  Bring-down Comfort Letter. If requested by the Representatives, a letter from KPMG Accountants N.V., in form and substance satisfactory to the Representatives and dated such Date of Delivery, substantially in the same form and substance as the letter furnished to the Representatives pursuant to Section 5(h) hereof, except that the “specified date” in the letter furnished pursuant to this paragraph shall be a date not more than three Business Days prior to such Date of Delivery.

(p)            Additional Documents. At the Closing Time and at each Date of Delivery (if any) counsel for the Underwriters shall have been furnished with such documents and opinions as they may reasonably require for the purpose of enabling them to pass upon the issuance and sale of the Securities as herein contemplated, or in order to evidence the accuracy of any of the representations or warranties, or the fulfillment of any of the conditions, herein contained; and all proceedings taken by the Company in connection with the issuance and sale of the Securities as herein contemplated shall be reasonably satisfactory in form and substance to the Representatives and counsel for the Underwriters.

(q)            Termination of Agreement. If any condition specified in this Section shall not have been fulfilled when and as required to be fulfilled, this Agreement, or, in the case of any condition to the purchase of Option Securities on a Date of Delivery which is after the Closing Time, the obligations of the several Underwriters to purchase the relevant Option Securities, may be terminated by the Representatives by notice to the Company at any time at or prior to Closing Time or such Date of Delivery, as the case may be, and such termination shall be without liability of any party to any other party except as provided in Section 4 and except that Sections 1, 6, 7, 8, 14, 15 and 16 shall survive any such termination and remain in full force and effect.

SECTION 6.         Indemnification.

(a)            Indemnification of Underwriters. The Company agrees to indemnify and hold harmless each Underwriter, its directors and officers, its affiliates (as such term is defined in Rule 501(b) of the 1933 Act Regulations (each, an “Affiliate”)), its selling agents and each person, if any, who controls any Underwriter within the meaning of Section 15 of the 1933 Act or Section 20 of the 1934 Act as follows:

(i)  against any and all loss, liability, claim, damage and expense whatsoever, as incurred, arising out of any untrue statement or alleged untrue statement of a material fact contained in the Registration Statement (or any amendment thereto), including the Rule 430B Information, or the omission or alleged omission therefrom of a material fact required to be stated therein or necessary to make the statements therein not misleading or arising out of any untrue statement or alleged untrue statement of a material fact included (A) in any preliminary prospectus, any Issuer Free Writing Prospectus, the General Disclosure Package or the Prospectus (or any amendment or supplement thereto), or (B) in any materials or information provided to investors by, or with the approval of, the Company in connection with the marketing of the Offering of the Securities, including any roadshow or investor presentations made to investors by the Company (whether in person or electronically) (“Marketing Materials”), or the omission or alleged omission in any preliminary prospectus, Issuer Free Writing Prospectus, Prospectus or in any Marketing Materials of a material fact necessary in order to make the statements therein, in the light of the circumstances under which they were made, not misleading;

(ii)  against any and all loss, liability, claim, damage and expense whatsoever, as incurred, to the extent of the aggregate amount paid in settlement of any litigation, or any investigation or proceeding by any governmental agency or body, commenced or threatened, or of any claim whatsoever based upon any such untrue statement or omission, or any such alleged untrue statement or omission; provided that (subject to Section 6(d) below) any such settlement is effected with the written consent of the Company; and

(iii)  against any and all expense whatsoever, as incurred (including the reasonable fees and disbursements of counsel chosen by the Representatives), reasonably incurred in investigating, preparing or defending against any litigation, or any investigation or proceeding by any governmental agency or body, commenced or threatened, or any claim whatsoever based upon any such untrue statement or omission, or any such alleged untrue statement or omission, to the extent that any such expense is not paid under (i) or (ii) above;

provided, however, that this indemnity agreement shall not apply to any loss, liability, claim, damage or expense to the extent arising out of any untrue statement or omission or alleged untrue statement or omission made in the Registration Statement (or any amendment thereto), including the Rule 430B Information, the General Disclosure Package or the Prospectus (or any amendment or supplement thereto) in reliance upon and in conformity with the Underwriter Information.

(b)            Indemnification of Company, Directors and Senior Management. Each Underwriter severally and not jointly agrees to indemnify and hold harmless the Company, its directors, and each of its senior managers who signed the Registration Statement, and each person, if any, who controls the Company within the meaning of Section 15 of the 1933 Act or Section 20 of the 1934 Act, against any and all loss, liability, claim, damage and expense described in the indemnity contained in subsection (a) of this Section, as incurred, but only with respect to untrue statements or omissions, or alleged untrue statements or omissions, made in the Registration Statement (or any amendment thereto), including the Rule 430B Information, the General Disclosure Package or the Prospectus (or any amendment or supplement thereto) in reliance upon and in conformity with the Underwriter Information.

(c)            Actions against Parties; Notification. Each indemnified party shall give notice as promptly as reasonably practicable to each indemnifying party of any action commenced against it in respect of which indemnity may be sought hereunder, but failure to so notify an indemnifying party shall not relieve such indemnifying party from any liability hereunder to the extent it is not materially prejudiced as a result thereof and in any event shall not relieve it from any liability which it may have otherwise than on account of this indemnity agreement. In the case of parties indemnified pursuant to Section 6(a) above, counsel to the indemnified parties shall be selected by the Representatives, and, in the case of parties indemnified pursuant to Section 6 (b) above, counsel to the indemnified parties shall be selected by the Company. An indemnifying party may participate at its own expense in the defense of any such action; provided, however, that counsel to the indemnifying party shall not (except with the consent of the indemnified party) also be counsel to the indemnified party. In no event shall the indemnifying parties be liable for the reasonable fees and expenses of more than one counsel (in addition to any local counsel) separate from their own counsel for all indemnified parties in connection with any one action or separate but similar or related actions in the same jurisdiction arising out of the same general allegations or circumstances. No indemnifying party shall, without the prior written consent of the indemnified parties, settle or compromise or consent to the entry of any judgment with respect to any litigation, or any investigation or proceeding by any governmental agency or body, commenced or threatened, or any claim whatsoever in respect of which indemnification or contribution could be sought under this Section 6 or Section 7 hereof (whether or not the indemnified parties are actual or potential parties thereto), unless such settlement, compromise or consent (i) includes an unconditional release of each indemnified party from all liability arising out of such litigation, investigation, proceeding or claim and (ii) does not include a statement as to or an admission of fault, culpability or a failure to act by or on behalf of any indemnified party.

(d)            Settlement without Consent if Failure to Reimburse. If at any time an indemnified party shall have requested an indemnifying party to reimburse the indemnified party for reasonable fees and expenses of counsel, such indemnifying party agrees that it shall be liable for any settlement of the nature contemplated by Section 6(a)(ii) or settlement of any claim in connection with any violation referred to in Section 6(e) effected without its written consent if (i) such settlement is entered into more than 60 days after receipt by such indemnifying party of the aforesaid request, (ii) such indemnifying party shall have received notice of the terms of such settlement at least 30 days prior to such settlement being entered into and (iii) such indemnifying party shall not have reimbursed such indemnified party in accordance with such request prior to the date of such settlement.

(e)            The indemnity and contribution agreements contained in Section 6 and Section 7 and the representations and warranties of the Company set forth in this Agreement shall remain operative and in full force and effect, regardless of (i) any investigation made by or on behalf of any Underwriter, its directors or officers or any person controlling any Underwriter, the Company, its directors or officers or any persons controlling the Company, (ii) acceptance of any Securities and payment therefor hereunder, and (iii) any termination of this Agreement. A successor to any Underwriter, its directors or officers or any person controlling any Underwriter, or to the Company, its directors or officers, or any person controlling the Company, shall be entitled to the benefits of the indemnity, contribution and reimbursement agreements contained in Section 6 and Section 7.

SECTION 7.         Contribution. If the indemnification provided for in Section 6 hereof is for any reason unavailable to or insufficient to hold harmless an indemnified party in respect of any losses, liabilities, claims, damages or expenses referred to therein, then each indemnifying party shall contribute to the aggregate amount of such losses, liabilities, claims, damages and expenses incurred by such indemnified party, as incurred, (i) in such proportion as is appropriate to reflect the relative benefits received by the Company, on the one hand, and the Underwriters, on the other hand, from the Offering of the Securities pursuant to this Agreement or (ii) if the allocation provided by clause (i) is not permitted by applicable law, in such proportion as is appropriate to reflect not only the relative benefits referred to in clause (i) above but also the relative fault of the Company, on the one hand, and of the Underwriters, on the other hand, in connection with the statements or omissions, or in connection with any violation of the nature referred to in Section 6(e) hereof, which resulted in such losses, liabilities, claims, damages or expenses, as well as any other relevant equitable considerations.

The relative benefits received by the Company, on the one hand, and the Underwriters, on the other hand, in connection with the Offering of the Securities pursuant to this Agreement shall be deemed to be in the same respective proportions as the total net proceeds from the Offering of the Securities pursuant to this Agreement (before deducting expenses) received by the Company, on the one hand, and the total underwriting discount received by the Underwriters, on the other hand, in each case as set forth on the cover of the Prospectus, bear to the aggregate public offering price of the Securities as set forth on the cover of the Prospectus.

The relative fault of the Company, on the one hand, and the Underwriters, on the other hand, shall be determined by reference to, among other things, whether any such untrue or alleged untrue statement of a material fact or omission or alleged omission to state a material fact relates to information supplied by the Company or by the Underwriters and the parties’ relative intent, knowledge, access to information and opportunity to correct or prevent such statement or omission or any violation of the nature referred to in Section 6(e) hereof.

The Company and the Underwriters agree that it would not be just and equitable if contribution pursuant to this Section 7 were determined by pro rata allocation (even if the Underwriters were treated as one entity for such purpose) or by any other method of allocation which does not take account of the equitable considerations referred to in this Section 7. The aggregate amount of losses, liabilities, claims, damages and expenses incurred by an indemnified party and referred to in this Section 7 shall be deemed to include any legal or other expenses reasonably incurred by such indemnified party in investigating, preparing or defending against any litigation, or any investigation or proceeding by any governmental agency or body, commenced or threatened, or any claim whatsoever based upon any such untrue or alleged untrue statement or omission or alleged omission.

Notwithstanding the provisions of this Section 7, no Underwriter shall be required to contribute any amount in excess of the underwriting commissions received by such Underwriter in connection with the Securities underwritten by it and distributed to the public.

No person guilty of fraudulent misrepresentation (within the meaning of Section 11(f) of the 1933 Act) shall be entitled to contribution from any person who was not guilty of such fraudulent misrepresentation.

For purposes of this Section 7, each person, if any, who controls an Underwriter within the meaning of Section 15 of the 1933 Act or Section 20 of the 1934 Act and each Underwriter’s Affiliates and selling agents shall have the same rights to contribution as such Underwriter, and each director of the Company, each officer of the Company who signed the Registration Statement, and each person, if any, who controls the Company within the meaning of Section 15 of the 1933 Act or Section 20 of the 1934 Act shall have the same rights to contribution as the Company. The Underwriters’ respective obligations to contribute pursuant to this Section 7 are several in proportion to the number of Initial Securities set forth opposite their respective names in Schedule A hereto and not joint.

SECTION 8.         Representations, Warranties and Agreements to Survive. All representations, warranties and agreements contained in this Agreement or in certificates of the Company submitted pursuant hereto, shall remain operative and in full force and effect regardless of (i) any investigation made by or on behalf of any Underwriter or its Affiliates or selling agents, any person controlling any Underwriter, its officers or directors or any person controlling the Company and (ii) delivery of and payment for the Securities.

SECTION 9.         Termination of Agreement.

(a)            Termination. The Representatives may terminate this Agreement in the absolute discretion of the Representatives, by notice to the Company, at any time at or prior to the Closing Time (i) if there has been, in the sole judgment of the Representatives, since the time of execution of this Agreement or since the respective dates as of which information is given in the Registration Statement, the General Disclosure Package or the Prospectus, any material adverse change in the condition, financial or otherwise, or in the earnings, business affairs, properties or prospects of the Company and its subsidiaries, taken as a whole, whether or not arising in the ordinary course of business, or (ii) if there has occurred any material adverse change in the financial markets in the United States or the international financial markets, any outbreak of hostilities or escalation thereof or other calamity or crisis or any change or development involving a prospective change in national or international political, financial or economic conditions, in each case the effect of which is such as to make it, in the sole judgment of the Representatives, impracticable or inadvisable to proceed with the completion of the Offering or to enforce contracts for the sale of the Securities, or (iii) if trading in any securities of the Company has been suspended or materially limited by the Commission or the Nasdaq Capital Market, or (iv) if trading generally on the NYSE MKT or the New York Stock Exchange or in the Nasdaq Capital Market has been suspended or materially limited, or minimum or maximum prices for trading have been fixed, or maximum ranges for prices have been required by, any of said exchanges or by order of the Commission, FINRA or any other governmental authority, or (v) a material disruption has occurred in commercial banking or securities settlement or clearance services in the United States or with respect to Clearstream or Euroclear systems in Europe, or (vi) if a banking moratorium has been declared by either Federal or New York authorities.

(b)            Liabilities. If this Agreement is terminated pursuant to this Section 9, such termination shall be without liability of any party to any other party except as provided in Section 4 hereof, and provided further that Sections 1, 6, 7, 8, 14, 15 and 16 shall survive such termination and remain in full force and effect.

SECTION 10.         Default by One or More of the Underwriters. If one or more of the Underwriters shall fail at the Closing Time or a Date of Delivery to purchase the Securities which it or they are obligated to purchase under this Agreement (the “Defaulted Securities”), the Representatives shall have the right, within 24 hours thereafter, to make arrangements for one or more of the non-defaulting Underwriters, or any other underwriters, to purchase all, but not less than all, of the Defaulted Securities in such amounts as may be agreed upon and upon the terms herein set forth; if, however, the Representatives shall not have completed such arrangements within such 24-hour period, then:

(i)  if the number of Defaulted Securities does not exceed 10% of the number of Securities to be purchased on such date, each of the non-defaulting Underwriters shall be obligated, severally and not jointly, to purchase the full amount thereof in the proportions that their respective underwriting obligations hereunder bear to the underwriting obligations of all non-defaulting Underwriters, or

(ii)  if the number of Defaulted Securities exceeds 10% of the number of Securities to be purchased on such date, this Agreement or, with respect to any Date of Delivery which occurs after the Closing Time, the obligation of the Underwriters to purchase, and the Company to sell, the Option Securities to be purchased and sold on such Date of Delivery shall terminate without liability on the part of any non-defaulting Underwriter.

No action taken pursuant to this Section 10 shall relieve any defaulting Underwriter from liability in respect of its default.

In the event of any such default which does not result in a termination of this Agreement or, in the case of a Date of Delivery which is after the Closing Time, which does not result in a termination of the obligation of the Underwriters to purchase and the Company to sell the relevant Option Securities, as the case may be, either the (i) Representatives or (ii) the Company shall have the right to postpone the Closing Time or the relevant Date of Delivery, as the case may be, for a period not exceeding seven days in order to effect any required changes in the Registration Statement, the General Disclosure Package or the Prospectus or in any other documents or arrangements. As used herein, the term “Underwriter” includes any person substituted for an Underwriter under this Section 10.

SECTION 11.        Notices. All notices and other communications hereunder shall be in writing and shall be deemed to have been duly given if mailed or transmitted by any standard form of telecommunication. Notices to the Underwriters shall be directed to Evercore Group L.L.C., 55 East 52nd Street, 36th Floor New York, New York 10055, Attention: ECM General Counsel (fax: (212) 857-3101)) and Cantor Fitzgerald & Co., 110 East 59th Street, New York, New York 10022 (fax: (212) 307-3730)), Attention: Capital Markets; notices to the Company shall be directed to it at ProQR Therapeutics N.V., Zernikedreef 9, 2333 CK Leiden, the Netherlands, attention of the Chief Executive Officer (telephone: + 31 88 166 7000).

SECTION 12.       No Advisory or Fiduciary Relationship. The Company acknowledges and agrees that (a) the purchase and sale of the Securities pursuant to this Agreement, including the determination of the public offering price of the Securities and any related discounts and commissions, is an arm’s-length commercial transaction between the Company, on the one hand, and the several Underwriters, on the other hand, (b) in connection with the Offering of the Securities and the process leading thereto, each Underwriter is and has been acting solely as a principal and is not the agent or fiduciary of the Company or its shareholders, creditors, employees or any other party, (c) no Underwriter has assumed or will assume an advisory or fiduciary responsibility in favor of the Company with respect to the Offering of the Securities or the process leading thereto (irrespective of whether such Underwriter has advised or is currently advising the Company on other matters) and no Underwriter has any obligation to the Company with respect to the Offering of the Securities except the obligations expressly set forth in this Agreement, (d) the Underwriters and their respective affiliates may be engaged in a broad range of transactions that involve interests that differ from those of the Company and (e) the Underwriters have not provided any legal, accounting, regulatory or tax advice with respect to the Offering of the Securities and the Company has consulted its own respective legal, accounting, regulatory and tax advisors to the extent it deemed appropriate.

SECTION 13.       Parties. This Agreement shall each inure to the benefit of and be binding upon the Underwriters and the Company and their respective successors. Nothing expressed or mentioned in this Agreement is intended or shall be construed to give any person, firm or corporation, other than the Underwriters and the Company and their respective successors and the controlling persons and officers and directors referred to in Sections 6 and 7 and their heirs and legal representatives, any legal or equitable right, remedy or claim under or in respect of this Agreement or any provision herein contained. This Agreement and all conditions and provisions hereof are intended to be for the sole and exclusive benefit of the Underwriters and the Company and their respective successors, and said controlling persons and officers and directors and their heirs and legal representatives, and for the benefit of no other person, firm or corporation. No purchaser of Securities from any Underwriter shall be deemed to be a successor by reason merely of such purchase.

SECTION 14.       Trial by Jury. The Company (on its behalf and, to the extent permitted by applicable law, on behalf of its shareholders and affiliates) and each of the Underwriters hereby irrevocably waives, to the fullest extent permitted by applicable law, any and all right to trial by jury in any legal proceeding arising out of or relating to this Agreement or the transactions contemplated hereby.

SECTION 15.        GOVERNING LAW. THIS AGREEMENT AND ANY CLAIM, CONTROVERSY OR DISPUTE ARISING UNDER OR RELATED TO THIS AGREEMENT SHALL BE GOVERNED BY, AND CONSTRUED IN ACCORDANCE WITH THE LAWS OF, THE STATE OF NEW YORK WITHOUT REGARD TO ITS CHOICE OF LAW PROVISIONS.

SECTION 16.        Consent to Jurisdiction; Waiver of Immunity. Any legal suit, action or proceeding arising out of or based upon this Agreement or the transactions contemplated hereby shall be instituted in (i) the federal courts of the United States of America located in the City and County of New York, Borough of Manhattan or (ii) the courts of the State of New York located in the City and County of New York, Borough of Manhattan (collectively, the “Specified Courts”), and each party irrevocably submits to the exclusive jurisdiction (except for proceedings instituted in regard to the enforcement of a judgment of any such court, as to which such jurisdiction is non-exclusive) of such courts in any such suit, action or proceeding. Service of any process, summons, notice or document by mail to such party’s address set forth above shall be effective service of process for any suit, action or other proceeding brought in any such court. The parties irrevocably and unconditionally waive any objection to the laying of venue of any suit, action or other proceeding in the Specified Courts and irrevocably and unconditionally waive and agree not to plead or claim in any such court that any such suit, action or other proceeding brought in any such court has been brought in an inconvenient forum.

SECTION 17.        Recognition of the U.S. Special Resolution Regimes.

(a) In the event that any Underwriter that is a Covered Entity becomes subject to a proceeding under a U.S. Special Resolution Regime, the transfer from such Underwriter of this Agreement, and any interest and obligation in or under this Agreement, will be effective to the same extent as the transfer would be effective under the U.S. Special Resolution Regime if this Agreement, and any such interest and obligation, were governed by the laws of the United States or a state of the United States.

(b) In the event that any Underwriter that is a Covered Entity or a BHC Act Affiliate of such Underwriter becomes subject to a proceeding under a U.S. Special Resolution Regime, Default Rights under this Agreement that may be exercised against such Underwriter are permitted to be exercised to no greater extent than such Default Rights could be exercised under the U.S. Special Resolution Regime if this Agreement were governed by the laws of the United States or a state of the United States.

As used in this Section 17, “BHC Act Affiliate” has the meaning assigned to the term “affiliate” in, and shall be interpreted in accordance with, 12 U.S.C. § 1841(k); “Covered Entity” means any of the following: (i) a “covered entity” as that term is defined in, and interpreted in accordance with, 12 C.F.R. § 252.82(b), (ii) a “covered bank” as that term is defined in, and interpreted in accordance with, 12 C.F.R. § 47.3(b) or (iii) a “covered FSI” as that term is defined in, and interpreted in accordance with, 12 C.F.R. § 382.2(b); “Default Right” has the meaning assigned to that term in, and shall be interpreted in accordance with, 12 C.F.R. §§ 252.81, 47.2 or 382.1, as applicable; and “U.S. Special Resolution Regime” means each of (i) the Federal Deposit Insurance Act and the regulations promulgated thereunder and (ii) Title II of the Dodd-Frank Wall Street Reform and Consumer Protection Act and the regulations promulgated thereunder.

SECTION 18.       TIME. TIME SHALL BE OF THE ESSENCE OF THIS AGREEMENT. EXCEPT AS OTHERWISE SET FORTH HEREIN, SPECIFIED TIMES OF DAY REFER TO NEW YORK CITY TIME.

SECTION 19.       Counterparts. This Agreement may be executed in any number of counterparts, each of which shall be deemed to be an original, but all such counterparts shall together constitute one and the same agreement.

SECTION 20.       DAC6. Nothing in this Agreement shall prevent disclosure of any confidential information or other matter to the extent that preventing that disclosure would otherwise cause any transaction contemplated by this Agreement to become (part of) an arrangement described in Part II A 1 of Annex IV of DAC6.

SECTION 21.       Effect of Headings. The Section headings herein are for convenience only and shall not affect the construction hereof.

[Remainder of this page intentionally left blank.]

If the foregoing is in accordance with your understanding of our agreement, please sign and return to the Company a counterpart hereof, whereupon this instrument, along with all counterparts, will become a binding agreement among the Underwriters and the Company in accordance with its terms.

Signature Page to Underwriting Agreement

CONFIRMED AND ACCEPTED,

as of the date first above written:

EVERCORE GROUP L.L.C.

For themselves and as Representatives of the other Underwriters named in Schedule A hereto.

[Signature Page to Underwriting Agreement]

SCHEDULE A

The public offering price per share for the Securities shall be $3.50.

The purchase price per share for the Securities to be paid by the several Underwriters shall be: $3.29, subject to adjustment in accordance with Section 2(b) for dividends or distributions declared by the Company and payable on the Initial Securities but not payable on the Option Securities.

SCHEDULE B-1

Pricing Terms

SCHEDULE B-2

Free Writing Prospectuses

None.

SCHEDULE C

List of Persons and Entities Subject to Lock-up

Dinko Valerio

Alison Lawton

Theresa Heggie

Bart Filius

James Shannon

Daniel de Boer

Gerard Platenburg

Martin Maier

Sheila Sponselee

Jurriaan Dekkers

Begoña Carreño

René Beukema

Exhibit A

Form of Lock-Up Agreement

ProQR Therapeutics N.V.

October      , 2024

Evercore Group L.L.C.

Cantor Fitzgerald & Co.

c/o Evercore Group L.L.C.

55 East 52nd Street

New York, New York 10055

c/o Cantor Fitzgerald & Co.

110 East 59th Street, 6th Floor

New York, New York 10022

Ladies and Gentlemen:

The undersigned is a holder of ordinary shares, a member of the board of directors, and/or a member of senior management of ProQR Therapeutics N.V., a public company with limited liability (naamloze vennootschap) (the “Company”). The undersigned understands that Evercore Group L.L.C. and Cantor Fitzgerald & Co. (the “Representatives”) propose to enter into an Underwriting Agreement (the “Underwriting Agreement”) with the Company providing for a public offering (the “Public Offering”) of the ordinary shares of the Company (the “Ordinary Shares”). In recognition of the benefit that such an offering will confer upon the undersigned, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the undersigned agrees with each underwriter to be named in the Underwriting Agreement (collectively, the “Underwriters”) that, during the period beginning on the date hereof and ending on the date that is 60 days from the date of the Underwriting Agreement (the “Lock-Up Period”), the undersigned will not, without the prior written consent of the Representatives, directly or indirectly, (i) offer, pledge, sell, contract to sell, sell any option or contract to purchase, purchase any option or contract to sell, grant any option, right or warrant for the sale of, or otherwise dispose of or transfer any Ordinary Shares or any securities convertible into or exchangeable or exercisable for Ordinary Shares, including depository receipts of the Company, whether now owned or hereafter acquired by the undersigned or with respect to which the undersigned has or hereafter acquires the power of disposition (collectively, the “Lock-Up Securities”), or exercise any right with respect to the registration of any of the Lock-Up Securities, or file or cause to be filed any registration statement in connection therewith, under the Securities Act of 1933, as amended, or (ii) enter into any swap or any other agreement or any transaction that transfers, in whole or in part, directly or indirectly, the economic consequence of ownership of the Lock-Up Securities, whether any such swap or transaction is to be settled by delivery of Ordinary Shares or other securities, in cash or otherwise.

儘管有上述規定，但須遵守 在以下條件下，未經事先書面同意，下列簽署人可以在封鎖期內轉讓封鎖證券 的代表，前提是 (1) 就下文第 (i)、(ii)、(iii)、(iv)、(v) 和 (vi) 款而言，代表 視情況而定，收到每位受贈人、受託人、分銷人或受讓人簽署的關於鎖定期餘額的協議 應說明該人正在接收和持有封鎖證券，但須遵守本封鎖協議的規定，(2) 就第 (i)、(ii)、(iii)、(iii)、(iv)、(v) 和 (vi) 條而言，任何此類轉讓均不得涉及價值處置，(3) 就下文第 (i)、(ii)、(iii)、(vi) 和 (vii) 條而言，此類轉賬無需向美國證券申報 和交易委員會（”秒”）且不觸發任何申報或報告義務或要求任何公開公告 在任何其他適用法律規定的封鎖期內，以及 (4) 對於下文 (i)、(ii)、(iii)、(vi) 和 (vii) 條款， 在封鎖期內，下列簽署人不會以其他方式自願提交任何有關此類轉讓的公開申報或報告：

此外，在封鎖期內，下列簽署人 可以（a）在公開發行後在公開市場上出售下列簽署人購買的公司普通股，前提是 (i) 除證券交易所第13D-G條例的要求外，無需向美國證券交易委員會報告此類銷售情況 經修訂的 1934 年法案（”《交易法》”），並且不要觸發任何申報或報告義務或要求任何申報或申報義務 根據任何其他適用法律在封鎖期內公告，以及 (ii) 下列簽署人不是自願的 在封鎖期內發佈任何有關此類銷售的公開申報或報告，（b）制定合同、指示或計劃 (a”10b5-1 計劃”) 符合《交易法》第10b5-1 (c) (1) 條的要求 封鎖期內的時間，前提是 (i) 此類10b5-1計劃不規定在封鎖期內轉讓普通股 封鎖期和 (ii) 不得由交易所或代表自願發佈任何公告或根據《交易法》提交 下列簽署人或公司關於制定此類10b5-1計劃以及下列簽署人或公司所作的任何公開披露 關於制定《交易法》所要求的此類10b5-1計劃，應包括一份聲明，說明下列簽署人不是 允許在封鎖期內轉移、出售或以其他方式處置此類交易計劃下的證券，這違反了 本封鎖協議，或（c）根據本協議發佈之日生效的10b5-1計劃出售公司的普通股，前提是 根據《交易法》要求或自願提交的任何申報均應註明此類交易是根據預先確立的交易進行的 10b5-1 計劃。

簽署人還同意並同意向公司的股份過戶代理和登記處進行停止過戶指令，禁止過戶鎖定證券，除非符合上述限制。

簽署人承認並同意在公開發行，本封鎖協議或相關事項方面，承銷商既未提供任何建議或投資建議，也未要求籤署人採取任何行動，並已諮詢過自己的法律、會計、金融、監管和稅務顧問，如認爲適當。簽署人進一步承認並同意，儘管承銷商可能在公開發行過程中向簽署人提供某些有關監管最佳利益和CRS表披露或其他相關文檔，但承銷商並未作出並不作出建議，建議簽署人進入本封鎖協議，或轉讓、賣出或處置或停止轉讓、出售或處置任何普通股份，且所述披露或文檔中載明的任何內容均不意味着任何承銷商正在作出此類建議。

本鎖定協議應自動終止，並且簽署人在下文規定的最早發生之日期解除義務：（i）如果，在承銷協議執行前，代表承銷商或公司的代表書面告知對方，決定不繼續進行公開發行，（ii）公司申請撤回與公開發行相關的註冊聲明，（iii）如果承銷協議已經執行但在公開發行結束前終止（除延續終止的規定外），或（iv）2024年10月31日，如果到該日期爲止尚未執行承銷協議。

簽署人特此聲明並保證 簽署人擁有充分的權力、能力和權限進入此鎖定協議。本鎖定協議是不可撤銷的 並將對簽署人及簽署人的繼任者、遺產繼承人、個人代表和受讓人具有約束力。

簽署人特此同意以電子形式接收本限制協議，並理解並同意可以以電子形式簽署本限制協議。如果任何簽名通過電子郵件，或其他電子傳輸方式傳遞，證明意圖簽署本限制協議，該電子郵件或其他電子傳輸將產生與原始簽名相同的有效和約束力義務。通過電子郵件或其他電子傳輸執行和交付本限制協議，在法律上具有合法、有效和約束力，適用於所有目的。

此鎖定協議可通過傳真、電子郵件（包括pdf或符合2000年美國聯邦ESIGN法的任何電子簽名，例如www.docusign.com或www.echosign.com）或其他傳輸方式交付，已交付的任何副本應視爲已被妥善有效地交付，並對所有目的均有效。

本限售協議應受紐約州法律管轄，並按照其進行解釋。

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