☐	REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT

☒	ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

☐	TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

☐	SHELL COMPANY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

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•	the development of RPL554, including statements regarding the expected initiation, timing, progress and availability of data from our clinical trials;

•	the potential attributes and benefit of RPL554 and its competitive position;

•	our ability to successfully commercialize RPL554, if approved;

•	our estimates regarding expenses, future revenues, capital requirements and our need for additional financing;

•	our ability to acquire or in license new product candidates;

•	potential collaborations; and

•	the duration of our patent portfolio.

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▪	conduct our ongoing Phase 2 clinical trials and initiate and conduct our planned Phase 1 and 2 and PK clinical trials and any other future clinical trials of RPL554 for the treatment of COPD;

▪	develop RPL554 as DPI and pMDI formulations for maintenance treatment of COPD, asthma and other respiratory diseases;

▪	conduct our ongoing Phase 2a clinical trial and any future clinical trials of RPL554 for the treatment of CF;

▪	seek to discover and develop or in-license additional respiratory product candidates;

▪	conduct pre-clinical studies to support RPL554 and potentially other future products;

▪	develop the manufacturing process and produce clinical and commercial supplies of RPL554;

▪	seek regulatory approvals of RPL554;

▪	potentially establish a sales, marketing and distribution infrastructure and scale-up manufacturing capabilities to commercialize RPL554, if approved;

▪	maintain, expand and protect our intellectual property portfolio;

▪	secure, maintain or obtain freedom to operate for our in-licensed technologies and products;

▪	add clinical, scientific, operational, financial and management information systems and personnel, including personnel to support our product development and potential future commercialization efforts; and

▪	expand our operations in the United States, the United Kingdom and possibly elsewhere.

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▪	the cost, progress and results of our ongoing Phase 2 clinical trials and our planned Phase 1 and 2 and PK clinical trials and any other future clinical trials of RPL554 for the treatment of COPD and CF;

▪	the cost of manufacturing clinical and commercial supplies of RPL554;

▪	the scope, progress, results and costs of pre-clinical development, laboratory testing and clinical trials for RPL554 in other indications and for the development of DPI and pMDI formulations of RPL554 for maintenance treatment of COPD and potentially asthma and other respiratory diseases;

▪	the costs, timing and outcome of regulatory review of RPL554, including post-marketing studies that could be required by regulatory authorities;

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▪	the costs, timing and outcome of potential future commercialization activities, including manufacturing, marketing, sales and distribution, for RPL554;

▪	the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims, including any claims by third parties that we are infringing upon their intellectual property rights;

▪	the timing and amount of revenue, if any, received from commercial sales of RPL554;

▪	the sales price and availability of adequate third-party coverage and reimbursement for RPL554;

▪	the effect of competing technological and market developments; and

▪	the extent to which we acquire or invest in businesses, products and technologies, including entering into licensing or collaboration arrangements for RPL554, although we currently have no commitments or agreements to complete any such transactions.

▪	we may not be able to demonstrate that RPL554 is safe and effective as a treatment for our targeted indications to the satisfaction of the applicable regulatory authorities;

▪	the applicable regulatory authorities may require additional pre-clinical or clinical trials of RPL554 for the treatment of COPD, which would increase our costs and prolong our development;

▪	the results of clinical trials of RPL554 may not meet the level of statistical or clinical significance required by the applicable regulatory authorities for marketing approval;

▪	the applicable regulatory authorities may disagree with the number, design, size, conduct or implementation of our planned clinical trials;

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▪	the contract research organizations, or CROs, that we retain to conduct clinical trials may take actions outside of our control that materially adversely impact our clinical trials;

▪	the applicable regulatory authorities may not find the data from pre-clinical studies and clinical trials sufficient to demonstrate that the clinical and other benefits of RPL554 outweigh its safety risks;

▪	unexpected operational or clinical issues may prevent completion or interpretation of clinical study results;

▪	the applicable regulatory authorities may disagree with our interpretation of data from our pre-clinical studies and clinical trials or may require that we conduct additional studies;

▪	the applicable regulatory authorities may not accept data generated at our clinical trial sites;

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if we submit an NDA to the FDA, and it is reviewed by an advisory committee, the FDA may have difficulties scheduling an advisory committee meeting in a timely manner or the advisory committee may recommend against approval of our application or may recommend that the FDA require, as a condition of approval, additional pre-clinical studies or clinical trials, limitations on approved labeling or distribution and use restrictions;

▪	the applicable regulatory authorities may require development of a risk evaluation and mitigation strategy, or REMS, as a condition of approval;

▪	the applicable regulatory authorities may identify deficiencies in the manufacturing processes or facilities of our third-party manufacturers;

▪	the applicable regulatory authorities may change its approval policies or adopt new regulations;

▪	if we license RPL554 to others, the efforts of those parties in completing clinical trials of, receiving regulatory approval for and commercializing, RPL554;

▪	through our clinical trials, we may discover factors that limit the commercial viability of RPL554 or make the commercialization of RPL554 unfeasible;

▪	if we retain rights under a collaboration agreement for RPL554, our efforts in completing pre-clinical studies and clinical trials of, receiving marketing approvals for, establishing commercial manufacturing capabilities for and commercializing, RPL554; and

▪	if approved, acceptance of RPL554 by patients, the medical community and third-party payors, effectively competing with other therapies, a continued acceptable safety profile following approval and qualifying for, maintaining, enforcing and defending our intellectual property rights and claims.

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▪	economic weakness, including inflation, or political instability in particular non-U.S. economies and markets;

▪	differing regulatory requirements for drug approvals in non-U.S. countries;

▪	differing jurisdictions could present different issues for securing, maintaining or obtaining freedom to operate in such jurisdictions;

▪	potentially reduced protection for intellectual property rights;

▪	difficulties in compliance with non-U.S. laws and regulations;

▪	changes in non-U.S. regulations and customs, tariffs and trade barriers;

▪	changes in non-U.S. currency exchange rates of the euro and currency controls;

▪	changes in a specific country's or region's political or economic environment, including the implications of the recent decision of the eligible members of the U.K. electorate for the United Kingdom to withdraw from the EU;

▪	trade protection measures, import or export licensing requirements or other restrictive actions by U.S. or non-U.S. governments;

▪	differing reimbursement regimes and price controls in certain non-U.S. markets;

▪	negative consequences from changes in tax laws;

▪	compliance with tax, employment, immigration and labor laws for employees living or traveling abroad;

▪	workforce uncertainty in countries where labor unrest is more common than in the United States;

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▪	difficulties associated with staffing and managing international operations, including differing labor relations;

▪	production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and

▪	business interruptions resulting from geo-political actions, including war and terrorism, or natural disasters including earthquakes, typhoons, floods and fires.

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▪	delays in or failure to obtain regulatory approval to commence a trial;

▪	delays in or failure to reach agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites;

▪	delays in or failure to obtain institutional review board, or IRB, approval at each site;

▪	delays in or failure to recruit suitable patients to participate in a trial;

▪	failure to have patients complete a trial or return for post-treatment follow-up;

▪	clinical sites deviating from trial protocol or dropping out of a trial or committing gross misconduct or fraud;

▪	adding new clinical trial sites;

▪	inability to achieve or maintain double blinding of RPL554;

▪	unexpected technical issues during manufacture of RPL554 and the corresponding drug product;

▪	inability to manufacture sufficient quantities of RPL554 for use in clinical trials;

▪	third-party actions claiming infringement by RPL554 in clinical trials inside or outside of the United States and obtaining injunctions interfering with our progress;

▪	business interruptions resulting from geo-political actions, including war and terrorism, or natural disasters including earthquakes, typhoons, floods and fires;

▪	safety or tolerability concerns causing us or our collaborators, as applicable, to suspend or terminate a trial if we or our collaborators find that the participants are being exposed to unacceptable health risks;

▪	changes in regulatory requirements, policies and guidelines;

▪	lower than anticipated retention rates of patients and volunteers in clinical trials;

▪	our third-party research contractors failing to comply with regulatory requirements or to meet their contractual obligations to us in a timely manner, or at all;

▪	delays in establishing the appropriate dosage levels or frequency of dosing or treatment in clinical trials;

▪	difficulty in certain countries in identifying the sub-populations that we are trying to treat in a particular trial, which may delay enrollment and reduce the power of a clinical trial to detect statistically significant results;

▪	the quality or stability of RPL554 falling below acceptable standards for either safety or efficacy; and

▪	discoveries that may reduce the commercial viability of RPL554.

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▪	regulatory authorities may withdraw approvals of such products and require us to take RPL554 off the market;

▪	regulatory authorities may require the addition of labeling statements, specific warnings, a contraindication or field alerts to physicians and pharmacies;

▪	regulatory authorities may require a medication guide outlining the risks of such side effects for distribution to patients, or that we implement a REMS plan to ensure that the benefits of RPL554 outweigh its risks;

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▪	we may be required to change the way RPL554 is administered, conduct additional clinical trials or change the labeling of RPL554;

▪	we may be subject to limitations on how we may promote RPL554;

▪	sales of RPL554 may decrease significantly;

▪	we may be subject to litigation or product liability claims; and

▪	our reputation may suffer.

▪	decreased demand for RPL554;

▪	injury to our reputation;

▪	withdrawal of clinical trial participants;

▪	costs to defend related litigation;

▪	diversion of management's time and our resources;

▪	substantial monetary awards to trial participants or patients;

▪	regulatory investigation, product recalls or withdrawals, or labeling, marketing or promotional restrictions;

▪	loss of revenue; and

▪	the inability to commercialize or promote RPL554.

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▪	we may be unable to demonstrate to the satisfaction of the FDA, the EMA or comparable foreign regulatory authorities that RPL554 is safe and effective, with the required level of statistical significance, for its proposed indication;

▪	we may be unable to demonstrate that RPL554's clinical and other benefits outweigh its safety risks;

▪	the FDA, the EMA or comparable foreign regulatory authorities may disagree with our interpretation of data from pre-clinical studies or clinical trials or may find the data to be unacceptable;

▪	the data collected from clinical trials of RPL554 may, for other reasons, not be sufficient to support the submission of an NDA in the United States, an MMA in the EU, or other comparable submission to obtain regulatory approval in other countries;

▪	the FDA, the EMA or comparable foreign regulatory authorities may fail to approve the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies;

▪	the approval policies or regulations of the FDA, the EMA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval; and

▪	the FDA, the EMA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials.

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▪	an annual, non-deductible fee payable by any entity that manufactures or imports certain branded prescription drugs and biologic agents, which is apportioned among these entities according to their market share in certain government healthcare programs;

▪	a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 50% point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer's outpatient drugs to be covered under Medicare Part D;

▪	new requirements to report certain financial arrangements with physicians and certain others, including reporting "transfers of value" made or distributed to prescribers and other healthcare providers and reporting investment interests held by physicians and their immediate family members;

▪	an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program to 23.1% and 13.0% of the average manufacturer price for branded and generic drugs, respectively;

▪	a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected;

▪	extension of a manufacturer's Medicaid rebate liability to covered drugs dispensed to individuals who are enrolled in Medicaid managed care organizations;

▪	expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to certain individuals with income at or below 133% of the federal poverty level, thereby potentially increasing a manufacturer's Medicaid rebate liability;

▪	a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research;

▪	creation of the Independent Payment Advisory Board, which, once empanelled, will have the authority to recommend certain changes to the Medicare program that could result in reduced payments for prescription drugs and those recommendations could have the effect of law unless overruled by a supermajority vote of Congress; and

▪	establishment of a Center for Medicare Innovation at the Centers for Medicare & Medicaid Services, or CMS, to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending.

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the U.S. federal Anti-Kickback Statute, which prohibits, among other things, persons or entities from knowingly and willfully soliciting, offering, receiving or providing any remuneration (including any kickback, bribe, or certain rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, lease, order or recommendation of, any good, facility, item or service, for which payment may be made, in whole or in part, under U.S. federal and state healthcare programs such as Medicare and Medicaid. A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation;

▪	the U.S. federal false claims and civil monetary penalties laws, including the civil False Claims Act, which, among other things, impose criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the U.S.

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the U.S. federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal and civil liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, or knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement, in connection with the delivery of, or payment for, healthcare benefits, items or services; similar to the U.S. federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation;

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HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and its implementing regulations, which also imposes certain obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information without appropriate authorization by covered entities subject to the rule, such as health plans, healthcare clearinghouses and healthcare providers as well as their business associates that perform certain services involving the use or disclosure of individually identifiable health information;

▪	the U.S. federal Food, Drug and Cosmetic Act, or FDCA, which prohibits, among other things, the adulteration or misbranding of drugs, biologics and medical devices;

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the U.S. federal legislation commonly referred to as Physician Payments Sunshine Act, enacted as part of the ACA, and its implementing regulations, which requires certain manufacturers of drugs, devices, biologics and medical supplies that are reimbursable under Medicare, Medicaid, or the Children's Health Insurance Program to report annually to the government information related to certain payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, as well as ownership and investment interests held by the physicians described above and their immediate family members;

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analogous state laws and regulations, including: state anti-kickback and false claims laws, which may apply to our business practices, including but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services reimbursed by any third-party payor, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry's voluntary compliance guidelines and the relevant compliance guidance promulgated by the U.S. federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws and regulations that require drug manufacturers to file reports relating to pricing and marketing information, which requires tracking gifts and other remuneration and items of value provided to healthcare professionals and entities; and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts; and

▪	European and other foreign law equivalents of each of the laws, including reporting requirements detailing interactions with and payments to healthcare providers.

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▪	have significantly greater name recognition, financial, manufacturing, marketing, drug development, technical and human resources than we do, and future mergers and acquisitions in the biopharmaceutical and pharmaceutical industries may result in even more resources being concentrated in our competitors;

▪	develop and commercialize products that are safer, more effective, less expensive, more convenient or easier to administer, or have fewer or less severe effects;

▪	obtain quicker regulatory approval;

▪	establish superior proprietary positions covering our products and technologies;

▪	implement more effective approaches to sales and marketing; or

▪	form more advantageous strategic alliances.

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▪	the timing of market introduction;

▪	the number and clinical profile of competing products;

▪	the clinical indications for which RPL554 is approved;

▪	our ability to provide acceptable evidence of safety and efficacy;

▪	the prevalence and severity of any side effects;

▪	relative convenience, frequency, and ease of administration;

▪	cost-effectiveness;

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▪	marketing and distribution support;

▪	availability of adequate coverage, reimbursement and adequate payment from health maintenance organizations and other insurers, both public and private; and

▪	other potential advantages over alternative treatment methods.

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▪	we may not be able to control the amount and timing of resources that the collaborator devotes to the development of RPL554;

▪	the collaborator may experience financial difficulties;

▪	we may be required to relinquish important rights such as marketing, distribution and intellectual property rights;

▪	a collaborator could move forward with a competing product developed either independently or in collaboration with third parties, including our competitors;

▪	business combinations or significant changes in a collaborator's business strategy may adversely affect our willingness to complete our obligations under any arrangement; or

▪	the collaboration may not provide sufficient funds to be profitable for us after we fulfill our payment obligations under our agreement with Vernalis Development Limited, or Vernalis.

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▪	Others may be able to make compounds that are the same as or similar to RPL554 but that are not covered by the claims of the patents that we own or have exclusively licensed.

▪	The patents of third parties may impair our ability to develop or commercialize RPL554.

▪	We or our licensors or any future strategic collaborators might not have been the first to conceive or reduce to practice the inventions covered by the issued patent or pending patent application that we own or have exclusively licensed.

▪	We or our licensors or any future strategic collaborators might not have been the first to file patent applications covering certain of our inventions.

▪	Others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights.

▪	It is possible that our pending patent applications will not lead to issued patents.

▪	Issued patents that we own or have exclusively licensed may not provide us with any competitive advantage, or may be held invalid or unenforceable, as a result of legal challenges by our competitors.

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▪	Our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets.

▪	Third parties performing manufacturing or testing for us using our products or technologies could use the intellectual property of others without obtaining a proper license.

▪	We may not develop additional technologies that are patentable.

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▪	positive or negative results from, or delays in, testing and clinical trials by us, collaborators or competitors;

▪	delays in entering into collaborations and strategic relationships with respect to development or commercialization of RPL554 or entry into collaborations and strategic relationships on terms that are not deemed to be favorable to us;

▪	technological innovations or commercial product introductions by us or competitors;

▪	changes in government regulations;

▪	developments concerning proprietary rights, including patents and litigation matters;

▪	public concern relating to the commercial value or safety of RPL554;

▪	financing or other corporate transactions;

▪	publication of research reports or comments by securities or industry analysts;

▪	general market conditions in the pharmaceutical industry or in the economy as a whole;

▪	the loss of any of our key scientific or senior management personnel;

▪	sales of our ADSs or ordinary shares by us, our senior management and board members, holders of our ADSs or our shareholders in the future; or

▪	other events and factors, many of which are beyond our control.

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▪	have a majority of the board of directors consist of independent directors;

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▪	require non-management directors to meet on a regular basis without management present;

▪	promptly disclose any waivers of its code of conduct for directors or executive officers;

▪	have an independent nominating committee and compensation committee;

▪	solicit proxies and provide proxy statements for all shareholder meetings; and

▪	seek shareholder approval for the implementation of certain equity compensation plans and issuances of ordinary shares.

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Potential for multiple targeted indications, formulations and add-on therapies.  We are developing RPL554 in a nebulized formulation for the maintenance treatment of COPD patients, as an add-on therapy to short-acting bronchodilators and other commonly used therapies for the treatment of hospitalized patients with acute exacerbations of COPD and the treatment of CF. We also are developing RPL554 in both DPI and pMDI formulations for the maintenance treatment of COPD. In addition, we may explore the development of RPL554 in these formulations for the treatment of asthma and other respiratory diseases. Based on the favorable properties of RPL554 that we have observed in our clinical trials, we believe RPL554 has broad potential applicability in the treatment of other respiratory diseases, either as a single agent or as an add-on therapy.

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Observed clinical benefit as a single agent and as an add-on therapy with a favorable safety profile.  We have completed enrollment of patients in twelve Phase 1 and 2 clinical trials for RPL554 with over 700 subjects enrolled; ten of these studies have been reported, one study is expected to report late in the first quarter of 2018 and one study is expected to report early in the second quarter of 2018. We have observed statistically significant improvements in lung function as compared to placebo, as well as clinically meaningful and statistically significant improvements in lung function when RPL554 is added to several commonly used bronchodilators as compared to such bronchodilators administered as a single agent. In addition, we observed a more rapid time of onset of bronchodilation when RPL554 was administered as an add-on therapy to these bronchodilators. RPL554 also has shown anti-inflammatory effects and been well tolerated in our clinical trials, and has not been observed to result in the gastrointestinal or other side

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Differentiated mechanism of action in a single compound.  RPL554 is a first-in-class, inhaled, dual inhibitor of PDE3 and PDE4 that acts as both a bronchodilator and an anti-inflammatory agent in a single compound and stimulates the CFTR. Dual inhibition of PDE3 and PDE4 has been shown to be more effective than inhibition of either PDE alone at relaxing airway smooth muscle cells and suppressing the activation and functions of pro-inflammatory cells residing in the lung, both of which are commonly understood to play a significant role in COPD and CF. In addition, through this dual mechanism, RPL554 also stimulates the CFTR, which is important in the treatment of CF and potentially COPD. We believe that RPL554 has the potential to be a more effective and better tolerated treatment of COPD than existing treatments for COPD, including the approved PDE4 inhibitor.

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Established regulatory pathway and well-defined clinical endpoints.  Our planned clinical trials for RPL554 for the maintenance treatment of COPD will be designed to evaluate the effect on FEV1 and duration of action of our product candidate. These clinical endpoints are commonly used in clinical trials for respiratory diseases and have been used by other companies in obtaining FDA approval of drugs addressing respiratory diseases.

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Addressing significant market opportunities.  Despite the availability of bronchodilators and anti-inflammatory corticosteroid or PDE4 inhibitor treatments for COPD, many patients continue to suffer from significant symptoms and may experience acute exacerbations leading to hospitalization. Furthermore, current therapies have not demonstrated an ability to change the progressive decline in lung function or reduce the mortality associated with COPD. We believe a large market opportunity with significant unmet medical need exists in COPD. We believe the properties of RPL554 make it attractive as an important and novel potential treatment of patients with COPD, as well as for patients with CF and asthma. We plan to seek orphan drug designation of RPL554 for the treatment of CF.

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Experienced management team.  Members of our management team and board of directors have extensive experience in large pharmaceutical and biotechnology companies in respiratory product development from drug discovery through commercialization and have played important roles in the development and commercialization of several approved respiratory treatments. We believe that the experience of our management team and our network of relationships within the industry and medical community provides us with insight into product development and identification of other opportunities in the respiratory field.

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Rapidly advance the development of nebulized RPL554 for the maintenance treatment of COPD.  We intend to develop RPL554 for the maintenance treatment of COPD. We are conducting an ongoing four‑week Phase 2b dose ranging clinical trial to evaluate RPL554 for the maintenance treatment of COPD. In this trial, we are comparing the use of RPL554 in a nebulized formulation to placebo in approximately 400 patients. This trial has completed patient enrollment and we expect to report top‑line data early in the second quarter of 2018.

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Depending on the data from all clinical trials conducted with RPL554 to date, future interactions with regulatory authorities and our commercial assessment of different development options for RPL554 we will consider any opportunity to focus and accelerate our development plans for RPL554, including proceeding more rapidly towards Phase 3 clinical trials, particularly with nebulized RPL554 for the maintenance treatment of COPD. This could possibly avoid or shorten the previously planned 12-week Phase 2b dose-ranging clinical trial. Earlier entry into Phase 3 clinical trials with nebulized RPL554 for the maintenance treatment of COPD could require us to focus our resources and funding initially on the maintenance market as a priority in the short term over progressing our planned trials to evaluate nebulized RPL554 as a treatment for acute exacerbations of COPD hospitalized patients and as a treatment for CF patients.

•	We plan on studying RPL554 on top of two commonly used long acting bronchodilators in a dose ranging, three way cross-over trial involving up to 100 patients with moderate to severe COPD. We plan on starting this trial in the fourth quarter of 2018.

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Adapt the current nebulized formulation and presentation of RPL554. RPL554 for nebulized administration is currently presented in a glass vial with a flip, tear-up cap. This format is adequate for clinical trials but patient acceptance in a commercial setting is expected to be improved by a switch to presenting the suspension formulation of RPL554 in plastic ampules. We will investigate the feasibility to manufacture and supply RPL554 nebulized suspension formulation in plastic ampules. In addition to patient acceptance, switching to plastic ampules may also be more cost-effective for manufacturing in larger volumes. A decision on presentation form will be made before the start of Phase 3 clinical trials; during this evaluation process we will also review and optimize the nebulized suspension formulation as part of a quality by design program.

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Advance the development of nebulized RPL554 for the treatment of acute exacerbations of COPD. We also are developing RPL554 as an add‑on therapy to short‑acting bronchodilators and other commonly used therapies for the treatment of hospitalized patients with acute exacerbations of COPD. We plan to commence a Phase 2 clinical trial in the United States for RPL554 for this indication late in the second half of 2018. Depending on the data from all clinical trials conducted with RPL554 to date, future interactions with regulatory authorities and our commercial assessment of different development options for RPL554 we will consider any opportunity to focus and accelerate our development plans for RPL554, including proceeding more rapidly towards Phase 3 clinical trials, particularly with nebulized RPL554 for the maintenance treatment of COPD. Earlier entry into Phase 3 clinical trials with nebulized RPL554 for the maintenance treatment of COPD could require us to focus our resources and funding initially on the maintenance market as a priority in the short term over progressing our planned trials to evaluate nebulized RPL554 as a treatment for acute exacerbations of COPD in hospitalized patients and as a treatment for CF patients.

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Develop RPL554 for the treatment of CF. In March 2017, we commenced a Phase 2a single‑dose trial in the United Kingdom of RPL554 in up to ten CF patients to evaluate the PK and PD profile and tolerability of RPL554, as well as examine the effect on lung function. We expect to report top‑line data from this trial late in the first quarter of 2018. The results of this trial are expected to support dose selection for a proof‑of‑concept Phase 2b trial in Europe in approximately 100 patients with CF, which we plan to commence late in the second half of 2018.Depending on the data from all clinical trials conducted with RPL554 to date, future interactions with regulatory authorities and our commercial assessment of different development options for RPL554 we will consider any opportunity to focus and accelerate our development plans for RPL554, including proceeding more rapidly towards Phase 3 clinical trials, particularly with nebulized RPL554 for the maintenance treatment of COPD. Earlier entry into Phase 3 clinical trials with nebulized RPL554 for the maintenance treatment of COPD could require us to focus our resources and funding initially on the maintenance market as a priority in the short term over progressing our planned trials to evaluate nebulized RPL554 as a treatment for acute exacerbations of COPD in hospitalized patients and as a treatment for CF patients.

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Develop DPI and MDI formulations of RPL554.  In addition to our nebulized formulation of RPL554, we are developing RPL554 in both DPI and pMDI formulations for the maintenance treatment of COPD. We believe the development of DPI and pMDI formulations has the potential to significantly increase the market opportunity for RPL554, if approved, for the maintenance treatment of COPD. Following the progression of our DPI and pMDI formulation process, we plan to commence pre‑clinical studies for RPL554 in these formulations in 2018, to be followed by the first clinical trials in healthy subjects or patients with COPD. In addition, we may explore the development of RPL554 in these formulations for the treatment of asthma and other respiratory diseases.

▪	Pursue development of RPL554 in other forms of respiratory disease.  We believe that RPL554's properties as an inhaled, dual inhibitor of PDE3 and PDE4 give it broad potential applicability in the treatment of other respiratory diseases. We may explore development of RPL554 to treat other forms of respiratory disease following development of RPL554 for the treatment of COPD and CF.

▪	Seek strategic collaborative relationships.  We may seek strategic collaborations with market-leading biopharmaceutical companies to develop and commercialize RPL554. We believe these collaborations could provide significant funding to advance the development of RPL554 while allowing us to benefit from the development or commercialization expertise of our collaborators.

▪	Acquire or in-license product candidates for the treatment of respiratory diseases.  We plan to leverage our respiratory disease expertise to identify and in-license or acquire additional clinical-stage

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▪	relying on a chemical structure that is distinct from other PDE4 inhibitors and avoids gastrointestinal and other side effects typically associated with PDE4 inhibition;

▪	having high selectivity for PDE3 and PDE4 over other enzymes, including other PDE enzymes, and receptors to minimize off-target effects; and

▪	enabling delivery directly to the lung by inhalation, thereby maximizing pulmonary exposure to RPL554 while minimizing systemic distribution and related adverse events.

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Clinical benefit as an add-on therapy and as a single agent with a favorable safety profile. We have completed patient enrollment in twelve Phase 1 and 2 clinical trials for RPL554 with over 700 subjects enrolled; ten of these studies have been reported, one study is expected to report late in the first quarter of 2018 and one study is expected to report early in the second quarter of 2018. In these trials, RPL554 has been observed to result in statistically significant improvements in lung function as compared to placebo. Our clinical trials also have shown clinically meaningful and statistically significant improvements in lung

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Bronchodilator and anti-inflammatory effects in one compound.  RPL554 utilizes a novel mechanism of action that inhibits PDE3 and PDE4 to act as both a bronchodilator and an anti-inflammatory agent in a single compound. We are not aware of any therapy in a single compound in clinical development or approved by the FDA or the EMA, for the treatment of COPD that acts as both a bronchodilator and anti-inflammatory agent. Inhibition of PDE3 is largely responsible for the bronchodilatory effects of RPL554, while the inhibition of PDE4 is largely responsible for the anti-inflammatory effects. By simultaneously targeting PDE3 and PDE4, we believe that RPL554 results in a more profound effect that addresses both airway constriction and chronic inflammation, which are the hallmarks of COPD. As a result, we believe RPL554, if approved, has the potential to become an important and novel treatment and standard of care for patients with COPD.

▪

Inhaled administration. We are developing RPL554 as an inhaled therapy, which we believe is advantageous for the treatment of COPD patients because it delivers high concentrations of RPL554 directly to the patient’s airways, thereby potentially improving efficacy while minimizing some of the side effects resulting from the systemic exposure associated with orally administered bronchodilators and anti‑inflammatory drugs. For example, roflumilast, the only currently marketed PDE4 inhibitor approved for the treatment of COPD, is administered orally and has been associated with adverse side effects such as back pain, decreased appetite, diarrhea, dizziness, flu‑like symptoms, headache, weight loss, nausea and vomiting. In our clinical trials, RPL554 has been well tolerated and has not been associated with the typical adverse effects associated with roflumilast. In this inhaled form, we believe RPL554, if approved, would provide significant advantages over orally administered therapies and potentially lead to better and more effective treatment of COPD.

▪

Rapid onset of action.  In our Phase 2a clinical trials for RPL554, we have observed a rapid onset of bronchodilation when RPL554 was administered as an add-on therapy to a range of currently marketed short-acting and long-acting bronchodilators: ipratropium, tiotropium and albuterol. The time of onset of action of ipratropium was 18.4 minutes, while the time of onset of action for RPL554 was approximately 14.6 minutes. When RPL554 was administered as an add-on therapy to ipratropium, the time of onset was reduced by 75% to 4.8 minutes as compared to ipratropium alone, which is similar to albuterol alone, albuterol being one of the fastest acting bronchodilators. The time of onset of action of tiotropium was approximately 37 minutes; when RPL554 was administered as an add-on therapy to tiotropium, the time of onset was reduced by 86% to approximately five minutes as compared to tiotropium alone, which again is similar to albuterol alone. When RPL554 was administered as an add-on therapy to albuterol, the time to onset was more rapid than with albuterol alone. We believe RPL554 has the potential to provide significant benefits as an add-on therapy to short- and long-acting bronchodilators in both the maintenance treatment, and the treatment of acute exacerbations, of COPD due to its effect on time of onset of action.

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Maintenance treatment of COPD. In July 2017 we announced the commencement of a Phase 2b dose-ranging study for RPL554 for the maintenance treatment in approximately 400 patients with COPD in Europe. The Phase 2b clinical trial is a four-week double-blind placebo-controlled parallel group trial. The primary endpoint is improvement in lung function, as measured by FEV1, after dosing with RPL554 or placebo. We expect to report top-line data from the Phase 2b trial early in the second quarter of 2018.

•

The study investigates the effect of 4 weeks of twice daily treatment of four different doses of RPL554 (0.75mg, 1.5mg, 3mg and 6mg) or placebo, each administered twice per day, in patients with moderate to severe COPD. Patients will be instructed to wash out any long-acting bronchodilators but can continue with an inhaled corticosteroid if maintained at the same dose throughout the study. Albuterol may be used as rescue medication.

•	The primary outcome measure is the effect of RPL554 or placebo on change from baseline in peak FEV1 over 4 weeks.

•	Secondary outcome measures include various additional measurements of lung function, COPD symptoms based on a range of different scales and methodologies, and tolerability.

•

Following completion of this ongoing 4-week Phase 2b clinical trial we will evaluate and possibly adjust the overall and near-term development plans for RPL554. Depending on the data from all clinical trials conducted with RPL554 to date, future interactions with regulatory authorities and our commercial assessment of different development options for RPL554 we will consider any opportunity to focus and accelerate our development plans for RPL554, including proceeding more rapidly towards Phase 3 clinical

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•

pMDI and DPI development for treatment of COPD patients. In addition to our nebulized formulation of RPL554, we are developing RPL554 in both DPI and pMDI formulations for the maintenance treatment of COPD. In addition, we may explore the development of RPL554 in these formulations for the treatment of asthma and other respiratory diseases. DPI and pMDI inhaler devices are the most common forms of drug delivery in non‑hospitalized patients with COPD and are well‑suited for the maintenance therapy of COPD patients. We believe the development of DPI and pMDI formulations has the potential to significantly increase the market opportunity for RPL554, if approved, for the maintenance treatment of COPD. Following the progression of our DPI and pMDI formulation process, we plan to commence pre‑clinical studies for RPL554 in these formulations in 2018, to be followed by the first clinical trials in healthy subjects or patients with COPD.

•

Treatment of hospitalized patients with acute exacerbations of COPD. We plan to commence a Phase 2 clinical trial in the United States for RPL554 for the treatment of acute COPD patients requiring hospitalization. We plan this Phase 2 clinical trial as a double‑blind, placebo‑controlled, parallel group trial starting during the patients’ hospitalization for COPD exacerbation and continuing for 30 days after discharge. RPL554 will be added to the standard‑of‑care treatment these patients receive. This trial will be designed to evaluate the efficacy and safety of RPL554 when administered for patients experiencing a COPD exacerbation requiring hospitalization. Depending on the data from all clinical trials conducted with RPL554 to date, future interactions with regulatory authorities and our commercial assessment of different development options for RPL554 we will consider any opportunity to focus and accelerate our development plans for RPL554, including proceeding more rapidly towards Phase 3 clinical trials, particularly with nebulized RPL554 for the maintenance treatment of COPD. Earlier entry into Phase 3 clinical trials with nebulized RPL554 for the maintenance treatment of COPD could require us to focus our resources and funding initially on the maintenance market as a priority in the short term over progressing our planned trials to evaluate nebulized RPL554 as a treatment for acute exacerbations of COPD in hospitalized patients and as a treatment for CF patients.

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▪	The first of these patent families relates to RPL554 per se. As of February 6, 2018, this patent family includes granted patents in Australia, Brazil, Canada, China, Europe, Japan, Mexico as well as four granted patents in the United States. We expect patents in this family to expire in March 2020.

▪

The second of these patent families relates to a crystalline polymorph of RPL554. As of February 6, 2018, this patent family included granted patents in Australia, Canada, China, Europe, Indonesia, Japan, Malaysia, Mexico, Philippines, Russia, the United States and Taiwan and patent applications in Israel, Japan, South Korea, Thailand and the Gulf Cooperation Council. We expect patents in this family to expire in August 2031.

▪	The third of these patent families relates to the combination of RPL554 with a beta-adrenergic receptor agonist. As of February 6, 2018, this patent family included granted patents Europe and the United States and a patent application in Canada. We expect patents in this family to expire in March 2034.

▪

The fourth of these patent families relates to the combination of RPL554 with a muscarinic receptor antagonist. As of February 6, 2018, this patent family included granted patents in Europe and the United States and patent applications in Australia, Canada, China, Israel, India, Japan, South Korea, Mexico, Russia, Thailand and the United States (continuation application). We expect patents in this family to expire in March 2034.

▪	The fifth of these patent families relates to certain specific salts of RPL554. As of February 6, 2018, this patent family included patent applications in Australia, Canada, China, Europe, Israel, Japan, Mexico, New Zealand, the United States and South Africa. We expect patents in this family to expire in February 2036.

▪	The sixth of these patent families relates to use of RPL554 to treat certain diseases associated with the function of CFTR (including CF). As of February 6, 2018, this patent family included patent applications in Australia, Canada, Europe (parent and divisional applications), Israel, Mexico, Russia, the United States and South Africa. We expect patents in this family to expire in May 2035.

▪

The seventh of these patent families relates to an inhalable formulation of RPL554. As of February 6, 2018, this patent family included patent applications in Australia, Brazil, Canada, China, Europe (parent and divisional applications), Indonesia, Israel, India, Japan, South Korea, Mexico, Malaysia, New Zealand, the Philippines, Singapore, South Africa, Thailand, and the United States. A notice of allowance issued on the United States application on January 11, 2018. A Communication under Rule 71(3) EPC (notice of allowance) issued on the European parent application on November 15, 2017. . We expect patents in this family to expire in September 2035.

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▪	The eighth of these patent families relates to a new compound related to RPL554 and to processes useful for the production of RPL554 and related compounds. As of February 6, 2018, this patent family included a PCT application and a patent application in Taiwan. We expect patents in this family to expire in July 2037.

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▪	completion of pre-clinical laboratory tests, animal studies and formulation studies in compliance with the FDA's good laboratory practice, or GLP, regulations;

▪	submission to the FDA of an investigational new drug application, or IND, which must become effective before human clinical trials may begin;

▪	approval by an independent institutional review board, or IRB, at each clinical site before each trial may be initiated;

▪	performance of adequate and well-controlled human clinical trials in accordance with good clinical practice, or GCP, requirements to establish the safety and efficacy of the proposed drug product for each indication;

▪	submission to the FDA of an NDA;

▪	satisfactory completion of an FDA advisory committee review, if applicable;

▪	satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product is produced to assess compliance with current good manufacturing practice, or cGMP, requirements and to assure that the facilities, methods and controls are adequate to preserve the drug's identity, strength, quality and purity; and

▪	FDA review and approval of the NDA.

▪	Phase 1: The drug is initially introduced into healthy human subjects or patients with the target disease or condition and tested for safety, dosage tolerance, absorption, metabolism, distribution, excretion and, if possible, to gain an early indication of its effectiveness.

▪	Phase 2: The drug is administered to a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage.

▪	Phase 3: The drug is administered to an expanded patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product, and to provide adequate information for the labeling of the product.

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▪	public health concerns emerge that were unrecognized at the time of the protocol assessment:

▪	the director of the review division determines that a substantial scientific issue essential to determining safety or efficacy has been identified after testing has begun;

▪	a sponsor fails to follow a protocol that was agreed upon with the FDA; or

▪	the relevant data, assumptions, or information provided by the sponsor in a request for SPA change, are found to be false statements or misstatements, or are found to omit relevant facts.

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▪	restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;

▪	fines, warning letters or holds on post-approval clinical trials;

▪	refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product approvals;

▪	product seizure or detention, or refusal to permit the import or export of products; or

▪	injunctions or the imposition of civil or criminal penalties.

▪

the Community MA, which is issued by the European Commission through the Centralized Procedure, based on the opinion of the Committee for Medicinal Products for Human Use of the European Medicines Agency, or EMA, and which is valid throughout the entire territory of the EEA. The Centralized Procedure is mandatory for certain types of products, such as biotechnology medicinal products, orphan medicinal products and medicinal products indicated for the treatment of AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and viral diseases. The Centralized Procedure is optional for products containing a new active substance not yet authorized in the EEA, or for products that constitute a significant therapeutic, scientific or technical innovation or which are in the interest of public health in the EU; and

▪

National MAs, which are issued by the competent authorities of the Member States of the EEA and only cover their respective territory, are available for products not falling within the mandatory scope of the Centralized Procedure. Where a product has already been authorized for marketing in a Member State of the EEA, this National MA can be recognized in another Member State through the Mutual Recognition Procedure. If the product has not received a National MA in any Member State at the time of application, it can be approved simultaneously in various Member States through the Decentralized Procedure.

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▪	employee-related expenses, such as salaries, share-based compensation, benefits and travel expense, for our research and development personnel;

▪	costs for production of drug substance by CMOs;

▪	fees and other costs paid to CROs and consultants to conduct our clinical trials and pre-clinical and non-clinical studies;

▪	costs of related facilities, materials and equipment;

▪	costs associated with obtaining and maintaining patents and other intellectual property; and

▪	amortization and depreciation of intangible and tangible fixed assets used to develop RPL554.

▪	the scope, rate of progress and expense of our research and development activities;

▪	the progress and results of clinical trials and pre-clinical and non-clinical studies;

▪	the terms and timing of regulatory approvals;

▪	the expense of filing, prosecuting, defending and enforcing patent claims and other intellectual property rights; and

▪	the ability to market, commercialize and achieve market acceptance for RPL554 or any other future product candidate, if approved.

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▪	initiate and conduct our planned clinical trials for RPL554 for the maintenance treatment of COPD and as a treatment for acute COPD;

▪	initiate and conduct our planned clinical trials for RPL554 for the treatment of CF;

▪	continue the research and development of other formulations of RPL554, including developing our DPI andpMDI formulations of RPL554;

▪	initiate and progress pre-clinical studies relating to other potential indications of RPL554;

▪	seek to discover and develop additional product candidates;

▪	seek regulatory approvals for any of our product candidates that successfully completes clinical trials;

▪	potentially establish a sales, marketing and distribution infrastructure and scale-up manufacturing capabilities to commercialize any products for which we may obtain regulatory approval;

▪	maintain, expand and protect our intellectual property portfolio;

▪	add clinical, scientific, operational, financial and management information systems and personnel, including personnel to support our product development and potential future commercialization efforts and to support our operations as a U.S. public company listed on the Nasdaq; and

▪	experience any delays or encounter any issues from any of the above, including but not limited to failed studies, complex results, safety issues or other regulatory challenges.

▪	the progress, timing and completion of pre-clinical testing and clinical trials for RPL554 or any future product candidates and the potential that we may be required to conduct additional clinical trials for RPL554;

▪	the number of potential new product candidates we decide to in-license and develop;

▪	the costs involved in growing our organization to the size needed to allow for the research, development and potential commercialization of RPL554 or any future product candidates;

▪	the costs involved in filing patent applications and maintaining and enforcing patents or defending against claims or infringements raised by third parties;

▪	the time and costs involved in obtaining regulatory approvals for RPL554 or any future product candidate we develop and any delays we may encounter as a result of evolving regulatory requirements or adverse results with respect to RPL554 any future product candidates;

▪	any licensing or milestone fees we might have to pay during future development of RPL554 or any future product candidates;

▪	selling and marketing activities undertaken in connection with the anticipated commercialization of RPL554 or any future product candidates, if approved, and costs involved in the creation of an effective sales and marketing organization; and

▪	the amount of revenues, if any, we may derive either directly or in the form of royalty payments from future sales of RPL554 or any future product candidates, if approved.

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(1)	Amount shown reflects bonuses awarded for achievement of performance goals in 2017.

(2)	Amount shown represents the aggregate grant date fair value of option and restricted stock units awards granted in 2017 measured using the Black Scholes model. For a description of the assumptions used in valuing these awards, see note 16 to our Annual Consolidated Financial Statements included elsewhere in this prospectus.

(3)	Amount shown represents health benefits payments and pension contributions made by us.

(4)	Amount shown represents health benefits payments made by us.

(5)	Mrs Luthman began her employment with us on June 12, 2017.

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•	recommending the appointment of the independent auditor to the general meeting of shareholders;

•	the appointment, compensation, retention and oversight of the independent auditor;

•	pre-approving the audit services and non-audit services to be provided by our independent auditor before the auditor is engaged to render such services;

•	evaluating the independent auditor's qualifications, performance and independence, and presenting its conclusions to our Board on at least an annual basis;

•	reviewing and discussing with the executive officers, our Board and the independent auditor our financial statements and our financial reporting process; and

•	considering and recommending to our Board whether the audited financial statements be approved.

•	identifying, reviewing and proposing policies relevant to the compensation of the Company’s directors and executive officers;

•	evaluating each executive officer's performance in light of such policies and reporting to the Board;

•	analyzing the possible outcomes of the variable remuneration components and how they may affect the remuneration of the executive officers;

•	recommending any equity long-term incentive component of each executive officer's compensation in line with the remuneration policy and reviewing our executive officer compensation and benefits policies generally;

•	appointing and setting the terms of reference for any remuneration consultants who advise the Committee and obtain benchmarking data with respect to the directors' and executive officers’ compensation; and

•	reviewing and assessing risks arising from our compensation policies and practices.

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•	reviewing and evaluating the structure, size and composition of our Board and making recommendations with regard to any adjustments considered necessary;

•	drawing up selection criteria and appointment procedures for Board members;

•	identifying and nominating, for the approval of our Board, candidates to fill vacancies on theBoard and its corresponding committees;

•	keeping under review the leadership needs of the Company, both executive and non-executive, and planning the orderly succession of such appointments; and

•	assessing the functioning of our Board and individual members and reporting the results of such assessment to the Board.

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▪	each person, or group of affiliated persons, that beneficially owns 3% or more of our outstanding ordinary shares;

▪	each member of our board of directors and each of our other executive officers; and

▪	all board members and executive officers as a group.

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(1)

Consists of (a) 12,389,985 ordinary shares held directly by Novo A/S, or Novo, and (b) warrants to purchase 1,769,626 ordinary shares. The board of directors of Novo A/S, or the Novo Board, has shared investment and voting control over the securities held by Novo and may exercise such control only with the support of a majority of the Novo Board. As such, no individual member of the Novo Board is deemed to hold any beneficial ownership or reportable pecuniary interest in the securities held by Novo. Beneficial ownership information is based on information known to us and a Form TR-1 provided to us on June 6, 2017. Novo's mailing address is Tuborg Havnevej 19, Hellerup, G7 2900, Denmark.

(2)

Consists of (a) 2,388,728 ordinary shares held directly by Vivo Ventures Fund VI, L.P., or Vivo VI, of which 1,126,760 are held in the form of ADSs, (b) warrants to purchase 370,871 ordinary shares held directly by Vivo VI, (c) warrants to purchase 2,717 ordinary shares held directly by Vivo Ventures VI Affiliates Fund, L.P., or Vivo Affiliates VI, (d) 9,554,917 ordinary shares held directly by Vivo Ventures Fund VII L.P., or Vivo VII, of which 4,507,040 are held in the form of ADSs, (e) warrants to purchase 1,462,477 ordinary shares held directly by Vivo VII, (f)  warrants to purchase 31,874 ordinary shares held directly by Vivo Ventures VII Affiliates Fund, L.P., or Vivo Affiliates VII. Vivo Ventures VI, LLC , or Vivo Ventures VI, is the sole general partner of Vivo VI and Vivo Affiliates VI. Vivo Ventures VII, LLC, or Vivo Ventures VII, is the sole general partner of Vivo VII and Vivo Affiliates VII. Vivo Ventures VI and Vivo Ventures VII disclaim beneficial ownership of all shares held by Vivo VI, Vivo Affiliates VI, Vivo VII and Vivo Affiliates VII except to the extent of any pecuniary interest therein. The managing members of Vivo Ventures VI are Drs. Albert Cha, Edgar Engleman and Frank Kung, each of whom may be deemed to have shared voting and dispositive power of the shares held by Vivo VI and Vivo Affiliates VI. The managing members of Vivo Ventures Vll are Drs. Albert Cha, Edgar Engleman, Frank Kung, Chen Yu and Mr. Shan Fu, each of whom may be deemed to have shared voting and dispositive power of the shares held by Vivo Vll and Vivo Affiliates Vll. Mahendra

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(3)

Consists of (a) 10,003,175 ordinary shares held directly by OrbiMed Private Investments VI, LP, or OrbiMed VI, of which 5,333,328 are held in the form of ADSs and (b) warrants to purchase 1,867,939 ordinary shares held directly by OrbiMed VI. OrbiMed Capital GP VI LLC, or GP VI, is the general partner of OrbiMed VI. OrbiMed Advisors LLC, or OrbiMed Advisors, is the managing member of GP VI. Samuel D. Isaly is the managing member of and owner of a controlling interest in OrbiMed Advisors. By virtue of such relationships, GP VI, OrbiMed Advisors and Mr. Isaly may be deemed to have voting and investment power with respect to the shares held by OrbiMed VI and as a result may be deemed to have beneficial ownership of such shares. Rishi Gupta, an employee of OrbiMed Advisors, is a member of our Board of Directors. Each of GP VI, OrbiMed Advisors, Mr. Isaly and Mr. Gupta disclaims beneficial ownership of the shares held by OrbiMed VI, except to the extent of its or his pecuniary interest therein, if any. Beneficial ownership information is based on information known to us and a Form TR-1 provided to us on May 25, 2017. OrbiMed Advisors' mailing address is 601 Lexington Avenue, 54th Floor, New York, NY 10022.

(4)

Consists of (a) 9,757,393 ordinary shares held directly by Growth Equity Opportunities Fund IV, LLC, or GEO, of which 5,333,328 are held in the form of ADSs, and (c) warrants to purchase 1,769,626 ordinary shares held directly by GEO. New Enterprise Associates 15, L.P., or NEA 15, is the sole member of GEO. NEA Partners 15, L.P., NEA Partners 15, is the sole general partner of NEA 15. NEA 15 GP, LLC, or NEA 15 LLC, is the sole general partner of NEA Partners 15. Peter J. Barris, Forest Baskett, Anthony Florence, Jr., Krishnu Kolluri, David M. Mott, Scott D. Sandell, Peter Sonsini, Jon Sakoda, Ravia Viswanthan and Henry Weller are the managers of NEA 15 LLC. NEA 15, NEA Partners 15, NEA 15 LLC and the managers of NEA 15 LLC share voting and dispositive power with regard to the securities held by GEO. Each of NEA 15, NEA Partners 15 and NEA 15 LLC as well as each of the managers of NEA 15 LLC disclaims beneficial ownership of all shares held by GEO except to the extent of their actual pecuniary interest therein. Beneficial ownership information is based on information known to us and a Form TR-1 provided to us on May 8, 2017. GEO's mailing address is 1954 Greenspring Drive, Suite 600, Timonium, MD 21093-4135.

(5)

Consists of (a) 7,215,553 ordinary shares held directly by Abingworth Bioventures VI, LP, or Abingworth VI, of which 3,705,000 are held in the form of ADSs, and (b) warrants to purchase 1,404,221 ordinary shares held directly by Abingworth VI. Abingworth Bioventures VI GP LP, or Abingworth GP VI, serves as general partner of Abingworth VI. Abingworth General Partner VI LLP, or Abingworth General Partner VI, serves as general partner of Abingworth GP VI. Abingworth General Partner VI has delegated to Abingworth LLP, all investment and dispositive power over the securities held by Abingworth VI. An Abingworth LLP investment committee comprised of Stephen Bunting, Timothy Haines, Kurt von Emster and Genghis Lloyd-Harris approves investment and voting decisions of Abingworth VI by a majority vote, and no individual member has the sole control or voting power over the securities held by Abingworth VI. Abingworth GP VI, Abingworth General Partner VI, Abingworth LLP and each of Stephen Bunting, Timothy Haines, Kurt von Emster and Genghis Lloyd-Harris disclaim beneficial ownership of securities held by Abingworth VI, except to the extent, if any of their pecuniary interest therein. Beneficial ownership information is based on information known to us and a Form TR-1 provided to us on May 9, 2017. Abingworth VI's mailing address is 38 Jermyn Street, London SW1Y 6DN, United Kingdom.

(6)	Consists of 7,000,000 ordinary shares held in the form of ADSs by VenBio Select Advisor. This information is based on information known to us. The mailing address for VenBio Select Advisor is 120 W 45th St #2802, New York, NY 10036

(7)

Consists of (a) 5,767,585 ordinary shares held in the form of ADSs by Biodiscovery 4 FCPI, or Biodiscovery, and (b) warrants to purchase 884,813 ordinary shares held directly by Biodiscovery. Beneficial ownership information is based on information known to us and a Form TR-1 provided to us on May 5, 2017. The mailing address for Biodiscovery is 47 rue du Faubourg Saint-Honoré75401 Cedex 08 Paris France

(8)	Consists of 5,000,000 ordinary shares held in the form of ADSs by Foresight Capital Management. This information is based on information known to us. The mailing address for Foresight Capital Management is [600 Montgomery Street, Suite 4500, San Francisco, CA 94111

(9)

Consists of (a) 4,412,031 ordinary shares held directly by Tekla World Healthcare Fund, or Tekla World, of which  2,200,000 are held in the form of ADSs, (b) warrants to 513,192 purchase ordinary shares held directly by Tekla World, and (c) warrants to purchase 371,622 ordinary shares held directly by Tekla Life. Tekla Capital Management LLC, or Tekla Capital, is an investment adviser registered pursuant to Section 203 of the Investment Advisers Act of 1940 and is the investment adviser of Tekla World and Tekla Life, each of which is a registered investment company pursuant to Section 8 of the Investment Company Act of 1940. Each of Tekla Capital and Daniel R. Omstead, through his control of Tekla Capital, has sole power to dispose of the shares beneficially owned by Tekla World and Tekla Life. Neither Tekla Capital nor Daniel R. Omstead has the sole power to vote or direct the vote of the shares beneficially owned by Tekla World and Tekla Life, which power resides in each fund's Board of Trustees. Tekla Capital carries out the voting of the shares under written guidelines established by each fund's Board of Trustees. Beneficial ownership information is based on information known to us and a Schedule 13G filed with the Securities and Exchange Commission on February 13, 2017. Tekla Capital's mailing address is 100 Federal Street, 19th Floor, Boston, MA 02110.

(10)

Consists of (a) 3,548,768 ordinary shares held directly by Aisling Capital IV, LP, or Aisling, of which 2,074,080 are held in the form of ADSs, and (b) warrants to purchase 589,875 ordinary shares held directly by Aisling. This information is based on information known to us and a TR-1 provided to us on June 6, 2017. The mailing address of Aisling is Aisling Capital, 888 Seventh Avenue, 12th Floor, New York, NY 10106

(11)

Consists of (a) 1,290,352 ordinary shares held directly by Arix Bioscience Holdings Ltd, or Arix, (b) warrants to purchase 516,141 ordinary shares held directly by Arix and (c) 2,110,000 ordinary shares held directly by Wales Life Sciences Investment Fund, or WLSIF. Arthurian Life Sciences Ltd, or Arthurian, is the general partner of WLSIF and a wholly owned subsidiary of Arix. Beneficial ownership information is based on information known to us and a Form TR-1 provided to us on August 3, 2016 and January 3, 2017. Arix's mailing address is 20 Berkeley Square, London W1J 6EQ, United Kingdom.

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(12)

Canaccord Genuity Group Inc. is the beneficial owner of an aggregate of 3,255,792 ordinary shares held directly by (a) Hargreave Hale which holds 2,941,250 ordinary shares and (b) Canaccord Genuity Wealth Management which holds 314,542 ordinary shares. This information is based on information known to us. The mailing address for Canaccord Genuity Group Inc. is 88 Wood Street, London, UK, EC2V 7QR.

(13)	Consists of (a) 89,150 ordinary shares and (b) 659,992 options to purchase ordinary shares that are or will be immediately exercisable within 60 days of February 1, 2018.

(14)	Consists of 100,000 options to purchase ordinary shares that are or will be immediately exercisable within 60 days of February 1, 2018.

(15)	Consists of 356,665 options to purchase ordinary shares that are or will be immediately exercisable within 60 days of February 1, 2018.

(16)	Consists of (a) 95,000 ordinary shares and (b) 141,663 options to purchase ordinary shares that are or will be immediately exercisable within 60 days of February 1, 2018.

(17)	Consists of (a) 13,000 ordinary shares and (b) 126,663 options to purchase ordinary shares that are or will be immediately exercisable within 60 days of February 1, 2018.

(18)	Consists of (a) 135,787 ordinary shares, and (b) warrants to purchase 4,916 ordinary shares.

(19)	Dr. Sinclair is a Partner and Portfolio Manager at Abingworth LLP. Dr. Sinclair does not have voting or dispositive power over any of the shares directly held by Abingworth Vl referenced in footnote (6) above. Dr. Sinclair's business address is 38 Jermyn Street, London SW1Y 6DN, United Kingdom.

(20)	Consists of 22,222 options to purchase ordinary shares that are or will be immediately exercisable within 60 days of February 1, 2018.

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▪	banks, insurance companies, and certain other financial institutions;

▪	U.S. expatriates and certain former citizens or long-term residents of the United States;

▪	dealers or traders in securities who use a mark-to-market method of tax accounting;

▪	persons holding ordinary shares or ADSs as part of a hedging transaction, "straddle," wash sale, conversion transaction or integrated transaction or persons entering into a constructive sale with respect to ordinary shares or ADSs;

▪	persons whose "functional currency" for U.S. federal income tax purposes is not the U.S. dollar;

▪	brokers, dealers or traders in securities, commodities or currencies;

▪	tax-exempt entities or government organizations;

▪	S corporations, partnerships, or other entities or arrangements classified as partnerships for U.S. federal income tax purposes;

▪	regulated investment companies or real estate investment trusts;

▪	persons who acquired our ordinary shares or ADSs pursuant to the exercise of any employee stock option or otherwise as compensation;

•	persons subject to special tax accounting rules as a result of any item of gross income with respect to ordinary shares or ADSs being taken into account in an applicable financial statement;

▪	persons holding our ordinary shares or ADSs in connection with a trade or business, permanent establishment, or fixed base outside the United States.

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(2)	a corporation, or other entity taxable as a corporation, created or organized in or under the laws of the United States, any state therein or the District of Columbia; or

▪	at least 75% of its gross income is passive income (such as interest income); or

▪	at least 50% of its gross assets (determined on the basis of a quarterly average) is attributable to assets that produce passive income or are held for the production of passive income.

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▪	the excess distribution or gain will be allocated ratably over your holding period for the ordinary shares or ADSs;

▪	the amount allocated to the current taxable year, and any taxable year prior to the first taxable year in which we became a PFIC, will be treated as ordinary income; and

▪	the amount allocated to each other year will be subject to the highest tax rate in effect for that year and the interest charge generally applicable to underpayments of tax will be imposed on the resulting tax attributable to each such year.

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*	Filed herewith.

**	Furnished herewith.

#	Indicates management contract or compensatory plan.

†	Confidential treatment granted as to portions of the exhibit. Confidential materials omitted and filed separately with the Securities and Exchange Commission.

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(a)	Goodwill

(b)	Patents

(c)	Computer software

(d)	In-process research & development ("IPR&D")

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(a)	Pension

(b)	Bonus plans

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(a)	Financial assets, initial recognition and measurement and subsequent measurement

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(b)	Financial liabilities, initial recognition and measurement and subsequent measurement

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▪	IFRS 9 "Financial instruments" (effective for annual periods beginning on or after January 1, 2018)

▪	IFRS 15 "Revenue from contracts with customers" (effective for annual periods beginning on or after January 1, 2018

▪	IFRS 16 "Leases" (effective for annual periods beginning on or after January 1, 2019)

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(1)	This table includes the undiscounted amount of the assumed contingent obligation. See note 18.

(1)	This table includes the undiscounted amount of the assumed contingent obligation. See note 18.

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▪	Quoted prices (unadjusted) in active markets for identical assets or liabilities (level 1);

▪	Inputs other than quoted prices included within level 1 that are observable for the asset or liability, either directly or indirectly (level 2); and

▪	Inputs for the asset or liability that are not based on observable market data (level 3).

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▪	development, regulatory and marketing risks associated with progressing the product to market approval in key target territories;

▪	market size and product acceptance by clinicians, patients and reimbursement bodies;

▪	gross and net selling price;

▪	costs of manufacturing, product distribution and marketing support;

▪	launch of competitive products; and

▪	discount rate and time to crystallization of contingent consideration.

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*	Options granted under the EMI Scheme.

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