VRNA 20-F Report ended Dec. 31, 2019

☐	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 ensifentrine, including statements regarding the expected initiation, timing, progress and availability of data from our clinical trials and regulatory approval;

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

•	our ability to successfully commercialize ensifentrine, 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;

•	the duration of our patent portfolio; and

•	our ability to retain key personnel and recruit qualified personnel, as well as the successful transition of our chief executive officer and chief financial officer roles.

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•	conduct our ongoing and planned Phase 2 clinical trials and, subject to regulatory review, initiate and conduct Phase 3 clinical trials and other future clinical trials of ensifentrine for the treatment of chronic obstructive pulmonary disease, or COPD;

•	conduct any clinical trials of ensifentrine for the treatment of cystic fibrosis, or CF, asthma or other indications;

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

•	conduct pre-clinical studies to support ensifentrine and potentially other future product candidates;

•	develop the manufacturing processes and produce clinical and commercial supplies of the ensifentrine active pharmaceutical ingredient and formulated drug products derived from it;

•	seek regulatory approvals of ensifentrine;

•	potentially establish a sales, marketing and distribution infrastructure and scale-up manufacturing capabilities to commercialize ensifentrine, 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 costs, progress and results of our planned Phase 3 clinical trials for the maintenance treatment of COPD, subject to regulatory review;

•	the costs, timing and outcome of the regulatory review of ensifentrine, including any post-marketing studies that could be required by regulatory authorities, if regulatory approval is received;

•	the cost, progress and results of any other studies required to support the commercial positioning of ensifentrine for the treatment of COPD, if regulatory approval is received;

•	the cost, progress and results of any clinical trials for the treatment of CF or other indications;

•	the cost of manufacturing clinical and commercial supplies of the ensifentrine active ingredient and derived formulated drug products;

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

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

•	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 ensifentrine;

•	the sales price and availability of adequate third-party coverage and reimbursement for ensifentrine;

•	the effect of competing technological and market developments; and

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

•	we may not be able to demonstrate that ensifentrine 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, which would increase our costs and prolong our development;

•	the results of clinical trials of ensifentrine 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;

•	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 ensifentrine outweigh its safety risks or may disagree with our interpretation of data;

•	our ability to demonstrate a non-clinical safety profile that is acceptable to the applicable regulatory authorities;

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

•	unexpected manufacturing issues, product performance issues or stability issues may delay or otherwise adversely affect the progress of our clinical development program;

•	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;

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•	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 their approval policies or adopt new regulations;

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

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

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

•	if approved, acceptance of ensifentrine 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 withdrawal of the United Kingdom 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;

•	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, or public health emergencies, such as the novel coronavirus (COVID-19).

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•	delays in or failure to obtain regulatory agreement on appropriate Phase 3 trial design, including dose and frequency of administration;

•	delays in of 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;

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•	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 ensifentrine;

•	unexpected technical issues during manufacture of ensifentrine and the corresponding drug products;

•	variability in drug product performance and/or stability;

•	inability to manufacture sufficient quantities of ensifentrine for use in clinical trials;

•	third-party actions claiming infringement by ensifentrine in clinical trials 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 ensifentrine falling below acceptable standards for either safety or efficacy; and

•	discoveries that may reduce the commercial viability of ensifentrine .

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•	regulatory authorities may withdraw approvals of such products and require us to take ensifentrine 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 ensifentrine outweigh its risks;

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

•	we may be subject to limitations on how we may promote ensifentrine;

•	sales of ensifentrine may decrease significantly;

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

•	our reputation may suffer.

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•	decreased demand for ensifentrine;

•	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 ensifentrine .

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

•	we may be unable to demonstrate that ensifentrine'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 FDA, the EMA or comparable foreign regulatory authorities may find that the dose or doses evaluated in Phase 3 clinical trials or the way in which double blinding was effected to be unacceptable

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•	the data collected from clinical trials of ensifentrine 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; and

•	the FDA, the EMA or comparable foreign regulatory authorities may disagree with our proposed product specifications and performance characteristics.

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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 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;

•	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; 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;

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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. federal government, claims for payment or approval that are false or fraudulent, knowingly making, using or causing to be made or used, a false record or statement material to a false or fraudulent claim, or from knowingly making a false statement to avoid, decrease or conceal an obligation to pay money to the U.S. federal government. In addition, the government may assert that a claim including items and services resulting from a violation of the U.S. federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act;

•	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

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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 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), certain health care professionals beginning in 2022, 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. For example, California recently enacted legislation, the California Consumer Privacy Act, or CCPA, which went into effect January 1, 2020. The CCPA, among other things, creates new data privacy obligations for covered companies and provides new privacy rights to California residents, including the right to opt out of certain disclosures of their information. The CCPA also creates a private right of action with statutory damages for certain data breaches, thereby potentially increasing risks associated with a data breach. Although the law includes limited exceptions, including for “protected health information” maintained by a covered entity or business associate, it may regulate or impact our processing of personal information depending on the context; and

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European and other foreign law equivalents of each of the laws, including reporting requirements detailing interactions with and payments to healthcare providers and laws governing the privacy and security of certain protected information, such as Regulation 2016/679, known as the General Data Protection Regulation, or GDPR, which imposes obligations and restrictions on the collection and use of personal data relating to individuals located in the EU (including health data).In addition, the United Kingdom leaving the EU could also lead to further legislative and regulatory changes. It remains unclear how the United Kingdom data protection laws or regulations will develop in the medium to longer term and how data transfer to the United Kingdom from the EU will be regulated, especially following the United Kingdom's departure from the EU on January 31, 2020 without a deal. However, the United Kingdom has transposed the GDPR into domestic law with the Data Protection Act 2018, which remains in force following the United Kingdom's departure from the EU.

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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 side 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 ensifentrine 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;

•	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 ensifentrine;

•	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 liabilities under our agreement with Ligand Pharmaceuticals, Inc., or Ligand, which acquired Vernalis Development Limited, or Vernalis, in October 2018.

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•	Others may be able to make compounds that are the same as or similar to our product candidates 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 our product candidates .

•	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 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.

•	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 product candidates 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, clinical trials of ensifentrine;

•	developments in our competitors’ businesses;

•	delays in entering into collaborations and strategic relationships with respect to development or commercialization of ensifentrine 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 ensifentrine;

•	financing or other corporate transactions;

•	publication of research reports or comments by securities or industry analysts or commentators;

•	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 or board members, and significant holders of our ADSs or ordinary shares; 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;

•	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 initially developing ensifentrine in a nebulized formulation for the maintenance treatment of COPD patients. While ensifentrine can be used as a standalone treatment in these patients, we are focusing on COPD patients who are symptomatic despite using currently available standard-of-care COPD treatments, because ensifentrine has shown improvements in lung function when administered as an add-on therapy to single and dual bronchodilators. We also are developing ensifentrine in both DPI and MDI formulations for the maintenance treatment of COPD. In addition, we may explore the development of ensifentrine in inhaled formulations for the treatment of CF, asthma and other respiratory diseases. Based on the favorable properties of ensifentrine that we have observed in our clinical trials, we believe ensifentrine 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 benefit and favorable tolerability as a single agent and as an add-on therapy in clinical trials. We have reported data from fifteen Phase 1 and 2 clinical trials for ensifentrine with over 1,300 subjects enrolled. 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 ensifentrine is added to several commonly used bronchodilators as compared to such

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Differentiated mechanism of action in a single compound. Ensifentrine is an investigational potential first-in-class, inhaled, dual inhibitor of PDE3 and PDE4 that is designed to act as both a bronchodilator and an anti-inflammatory agent in a single compound and stimulate 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, CF and asthma. In addition, through this dual mechanism, ensifentrine is also designed to stimulate the CFTR, which we believe is important in the treatment of CF and potentially COPD. We believe that ensifentrine, if successfully developed and approved, has the potential to be a more effective and better tolerated treatment for COPD than existing treatments, including roflumilast, the only currently approved PDE4 inhibitor. This dual mechanism of action also suggests that ensifentrine could be a useful treatment for patients with moderate to severe asthma that remain symptomatic despite being treated with standard-of-care.

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Established regulatory pathway and well-defined clinical endpoints. Our planned clinical trials for ensifentrine for the maintenance treatment of COPD will be designed to evaluate the compound's effect on FEV 1 , COPD symptoms, exacerbations and its duration of action. We will also monitor COPD-like symptoms as an improvement would be considered very important to these patients. 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 and especially in moderate to severe patients with limited further treatment alternatives. We believe the properties of ensifentrine, namely bronchodilation and the reduction of COPD-like symptoms, 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 ensifentrine 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

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Advance the development of nebulized ensifentrine for the maintenance treatment of COPD. We intend to initially develop nebulized ensifentrine for the maintenance treatment of COPD. We believe there is a large market opportunity for ensifentrine as a maintenance treatment as many of the moderate-to-severe COPD patients continue to be uncontrolled and symptomatic despite treatment with currently available medications. We believe that we have validated the dose and commercial positioning of ensifentrine in our comprehensive Phase 2 clinical trial program, and we plan to participate in an End of Phase 2 Meeting with the FDA to obtain guidance on our planned Phase 3 program, which we anticipate will include two large-scale pivotal studies. We expect to meet with the FDA for our End of Phase 2 Meeting in the first half of 2020, and initiate our Phase 3 clinical studies in the third quarter of 2020, subject to FDA feedback and to funding.

▪	We have shown that ensifentrine can provide additional bronchodilation as add-on to patients treated with maximum approved bronchodilator therapy (LAMA/LABA), as measured by FEV 1 and residual volume, over a 24-hour period and, in particular, following the evening dose. This data is very encouraging in a large but hard-to-treat population who have very limited alternative treatment options.

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Taking into account the data from all clinical trials conducted with ensifentrine to date, interactions with regulatory authorities and our commercial assessment of different development options for nebulized ensifentrine, we are focusing our development plans on proceeding rapidly towards Phase 3 clinical trials with nebulized ensifentrine for the maintenance treatment of COPD. Therefore our focus is currently on the COPD maintenance market as a priority in the short term over progressing our planned trials to evaluate nebulized ensifentrine as a treatment for acute exacerbations of COPD hospitalized patients and as a treatment for CF and asthma patients.

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Adapt the current nebulized formulation and presentation of ensifentrine. The ensifentrine suspension for nebulized administration has been presented in a glass vial with a flip, tear-up cap in clinical studies to date. 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 ensifentrine in plastic ampules, which is also more cost effective for manufacturing in larger volumes. A unit dose plastic ampule presentation format for the ensifentrine nebulizer suspension has been under development, and we are positioning this for use in Phase 3 clinical trials.

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Develop DPI and MDI formulations of ensifentrine. In addition to our nebulized formulation of ensifentrine, we are developing ensifentrine in both DPI and MDI formulations for the maintenance treatment of COPD. We believe the development of DPI and MDI formulations has the potential to substantially increase the market opportunity for ensifentrine, if approved, for the maintenance treatment of COPD. We have now developed DPI and MDI formulations of ensifentrine, and have obtained favorable Phase 2 clinical trial results for our DPI formulation. We expect complete results from our Phase 2 MDI trial in the third quarter of 2020, and we are seeking partnerships with larger commercial-stage pharmaceutical and biotechnology companies to advance these programs further, including potential opportunities to explore the development of ensifentrine in these formulations for the treatment of asthma and other respiratory diseases.

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Develop ensifentrine for the treatment of CF. We have completed a Phase 2a single‑dose trial in the United Kingdom of ensifentrine in ten CF patients to evaluate the PK and PD profile and tolerability of ensifentrine, as well as examine the effect on lung function. Ensifentrine demonstrated a statistically significant bronchodilator effect, a PK profile that is consistent with that observed in patients with COPD while being well tolerated.

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Pursue development of ensifentrine in other forms of respiratory disease. We believe that ensifentrine'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 ensifentrine to treat other forms of respiratory disease following development of ensifentrine for the treatment of COPD, CF and asthma.

▪	Seek strategic collaborative relationships. We may seek strategic collaborations with market-leading biopharmaceutical companies to develop and commercialize ensifentrine. We believe these

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▪	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 product candidates that we believe have the potential to become novel treatments for respiratory diseases with significant unmet medical needs.

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•	The first of these patent families relates to ensifentrine per se . As of February 6, 2020, 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.

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The second of these patent families relates to a crystalline polymorph of ensifentrine. As of February 6, 2020, this patent family included granted patents in Australia, Canada, China, Europe, Indonesia, Israel, Japan, South Korea, Malaysia, Mexico, the Philippines, Russia, the United States and Taiwan and patent applications in 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 ensifentrine with a beta‑adrenergic receptor agonist. As of February 6, 2020, this patent family included granted patents in 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 ensifentrine with a muscarinic receptor antagonist. As of February 6, 2020, this patent family included granted patents in Australia, Europe, Japan, Russia and the United States (two patents) and patent applications in Canada, China, India, South Korea, Mexico and Thailand. We expect patents in this family to expire in March 2034.

•	The fifth of these patent families relates to certain specific salts of ensifentrine. As of February 6, 2020, this patent family included a granted patent in the United States and patent applications in Australia, Canada, China, Europe, Israel, Japan, Mexico, New Zealand, the United States (continuation application) and South Africa. We expect patents in this family to expire in February 2036.

•

The sixth of these patent families relates to use of ensifentrine to treat certain diseases associated with the function of CFTR (including cystic fibrosis). As of February 6, 2020, this patent family included a granted patents in Europe (two patents) and Russia and patent applications in Australia, Canada, Israel, Mexico, 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 ensifentrine. As of February 6, 2020, this patent family included granted patents in Europe (two patents), Hong Kong (two patents), Israel, Russia, the United States, Singapore and South Africa and patent applications in Australia (parent and divisional applications), Brazil, Canada, China (parent and divisional applications), Europe (divisional application), Hong Kong (divisional application), Indonesia, India, Japan (parent and divisional applications), South Korea, Mexico, Malaysia, New Zealand, the Philippines, Thailand and the United States (continuation application).  We expect patents in this family to expire in September 2035.

•

The eighth of these patent families relates to a new intermediate for the manufacture of ensifentrine and to processes useful for the production of ensifentrine and related compounds. As of February 6, 2020, this patent family included a granted European patent and patent applications in China, Hong Kong, India, Japan, United States and Taiwan. We expect patents in this family to expire in July 2037.

•	The ninth of these patent families relates to a formulation comprising ensifentrine for a MDI.  As of February 6, 2020, this patent family included a pending, unpublished PCT patent application and a pending, unpublished patent application in the United Kingdom.  We expect patents in this family to expire in October 2039.

•	The tenth of these patent families relates to a formulation comprising ensifentrine for DPI. As of February 6, 2020, this patent family included a pending, unpublished patent application in the United Kingdom. We expect patents in this family to expire in August 2040.

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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;

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▪	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.

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▪

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 human medicinal products, such as medicines derived from biotechnology processes, advanced therapy medicinal products (such as gene therapy, somatic cell therapy and tissue engineered products), orphan designated medicinal products, products that contain a new active substance indicated for the treatment of certain diseases such as HIV/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. Under the centralized procedure the maximum timeframe for the evaluation of a Marketing Authorization Application, or MAA, by the EMA is 210 days, excluding clock stops, when additional written or oral information is to be provided by the applicant in response to questions asked by the Committee for Medicinal Products for Human Use, or CHMP. Accelerated assessment might be granted by the CHMP in exceptional cases, when a medicinal product is expected to be of a major public health interest, particularly from the point of view of therapeutic innovation. The timeframe for the evaluation of an MAA under the accelerated assessment procedure is 150 days, excluding clock stops; 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 contract manufacturing organizations;

▪	fees and other costs paid to contract research organizations 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 ensifentrine.

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▪	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 ensifentrine or any other future product candidate, if approved.

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▪	initiate and conduct Phase 3 clinical trials for ensifentrine for the maintenance treatment of COPD;

▪	continue the clinical development of our DPI and pMDI formulations of ensifentrine and research and develop other formulations of ensifentrine;

▪	initiate and conduct further clinical trials for ensifentrine for the treatment of acute COPD, CF or any other indication;

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

▪	seek to discover and develop additional product candidates;

▪	seek regulatory approvals for any of our product candidates that successfully complete 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 continuing operations as a UK and U.S. public company; 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.

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

▪	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 ensifentrine 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 ensifentrine 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 ensifentrine or any future product candidates;

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

▪	selling and marketing activities undertaken in connection with the anticipated commercialization of ensifentrine 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 ensifentrine or any future product candidates, if approved.

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(1)	Amount shown reflect bonuses awarded for achievement of performance goals, including retention bonuses in 2019 .

(2)	Amount shown represents the aggregate grant date fair value of option and restricted share units awards granted in 2019 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 Annual Report.

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

(4)	Dr. Zaccardelli was appointed as our President and Chief Executive Officer, effective as of February 1, 2020.

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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 the 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;

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

•	monitoring our review and mitigation of corporate and operational risk.

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•	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 engagement 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.

•	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 the Board 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 (including ordinary shares in the form of our ADSs);

▪	each member of our board of directors and each of our 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 Schedule 13D filed with the SEC on April 2, 2019. 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 Shah, the Managing Director of Vivo Capital, is a member of our Board of Directors and disclaims beneficial ownership of these shares except to the extent of his pecuniary interest arising as a result of his employment by Vivo Capital. Beneficial ownership information is based on information known to us and Forms TR-1 provided to us on May 30, 2017. Vivo Capital's mailing address is 505 Hamilton Avenue, Suite 200, Palo Alto, CA 94301.

(3)

Consists of (a) 10,003,174 ordinary shares held directly by OrbiMed Private Investments VI, LP, or OPI VI, of which 10,003,168 are held in the form of ADSs and (b) warrants to purchase 1,867,938 ordinary shares are held directly by OPI VI. OrbiMed Capital GP VI LLC, or GP VI, is the general partner of OPI VI. OrbiMed Advisors LLC, or Advisors, pursuant to its authority as the sole managing member of GP VI, the sole general partner of OPI VI, may be deemed to indirectly beneficially own the ordinary shares held by OPI VI. GP VI, pursuant to its authority as general partner or OPI VI, may be deemed to indirectly beneficially own the ordinary shares held by OPI VI. As a result, Advisors and GP VI share the power to direct the vote and to direct the disposition of the ordinary shares held by OPI VI. Advisors exercises this investment and voting power through a management committee comprised of Carl L. Gordon, Sven H. Borho and Jonathan T. Silverstein, each of whom disclaims beneficial ownership of the ordinary shares held by OPI VI. Beneficial ownership information is based on information known to us and a Schedule 13D/A filed with the SEC on January 26, 2018. The mailing address of OPI VI, GP VI and Advisors is 601 Lexington Avenue, 54th Floor, New York, NY 10022.

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(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) 7,215,544 ordinary shares held directly by Abingworth Bioventures VI, LP, or Abingworth VI, all of which 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. Andrew Sinclair is a Partner and Portfolio Manager at Abingworth LLP and a member of our board of directors. Dr. Sinclair does not have voting or dispositive power over any of the securities held by Abingworth Vl. 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 5,300,000 ordinary shares of which (a) 4,500,000 ordinary shares are held directly by Polar Biotechnology Fund, or PBF, (b) 800,000 are held by PBF in the form of ADSs, and (c) warrants to purchase 68,819 ordinary shares held directly by PBF. PBF and PCGH are managed by Polar Capital Holdings plc, or PCH. Beneficial ownership information is based on a TR-1 provided to us on September 9, 2019 and information known to us.

(8)

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 purchase 513,192 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 SEC on February 12, 2019. Tekla Capital's mailing address is 100 Federal Street, 19th Floor, Boston, MA 02110.

(9)

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.

(10)	Consists of (a) 147,009 ordinary shares, (b) 238,420 ordinary shares issuable from restricted stock units that will vest within 60 days of December 31, 2019 and (c) 1,326,933 options to purchase ordinary shares that are, or will be within 60 days of December 31, 2019, immediately exercisable.

(11)	Consists of (a) 130,575 ordinary shares and (b) 668,566 options to purchase ordinary shares that are, or will be within 60 days of December 31, 2019, immediately exercisable.

(12)	Consists of (a) 395,387 ordinary shares and (b) warrants to purchase 4,916 ordinary shares.

(13)	Consists of (a) 22,222 ordinary shares and (b) options to purchase 80,256 ordinary shares that are or will be immediately exercisable withint 60 days of December 31, 2019.

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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 our 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;

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•	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.

(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 such holder's holding period for our 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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▪	taxes (including applicable interest and penalties) and other governmental charges;

▪	the registration fees as may from time to time be in effect for the registration of ordinary shares on the share register and applicable to transfers of ordinary shares to or from the name of the custodian, the depositary or any nominees upon the making of deposits and withdrawals, respectively;

▪	certain cable, telex and facsimile transmission and delivery expenses;

▪	the expenses and charges incurred by the depositary in the conversion of foreign currency;

▪	the fees and expenses incurred by the depositary in connection with compliance with exchange control regulations and other regulatory requirements applicable to ordinary shares, ADSs and American Depositary Receipts; and

▪	the fees and expenses incurred by the depositary, the custodian, or any nominee in connection with the servicing or delivery of deposited property.

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•	We do not follow Nasdaq Rule 5620(c) regarding quorum requirements applicable to meetings of shareholders. Such quorum requirements are not required under English law. In accordance with generally accepted business practice, our articles of association provide alternative quorum requirements that are generally applicable to meetings of shareholders.

•	We do not follow Nasdaq Rule 5605(b)(2), which requires that independent directors regularly meet in executive session, where only independent directors are present. Our independent directors may choose to meet in executive session at their discretion.

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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 SEC.

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(a)	Goodwill

(b)	Patents

(c)	Computer software

(d)	In-process research & development ("IP R&D")

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

•	gross and net selling price;

•	costs of manufacturing, product distribution and marketing support;

•	costs of the Company's overhead;

•	size and make up of a sales force;

•	probabilities of success; and

•	discount rate.

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

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

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•	the use of a single discount rate of 8% to a portfolio of leases with reasonably similar characteristics;

•	accounting for leases with a remaining lease term of less than 12 months as at January 1, 2019, as short-term leases; and

•	the use of hindsight in determining the lease term where the contract contains options to extend or terminate the lease.

▪	IFRS 16 "Leases"

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•	This table includes the undiscounted amount of the assumed contingent liability. See note 20.

(1)	This table includes the undiscounted amount of the assumed contingent liability. See note 20.

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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;

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▪	launch of competitive products;

▪	probabilities of success; and

▪	time to crystallization of contingent consideration.

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*	Options granted under the EMI Scheme.

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