Overview

We are a patient-focused, innovative, commercial-stage, global biopharmaceutical company with a substantial presence in both Greater China and the United States. We are discovering, developing and commercializing innovative products that target medical conditions with unmet needs affecting patients in Greater China and worldwide, particularly in the areas of oncology, autoimmune disorders, infectious diseases and neuroscience. As of May 5, 2022, we have four commercialized products that have received marketing approval in one or more territories in Greater China and twelve programs in late-stage product development.

Since our inception, we have incurred net losses and negative cash flows from our operations. Substantially all of our losses have resulted from funding our research and development programs and general and administrative costs associated with our operations. Developing high quality product candidates requires a significant investment related to our research and development activities over a prolonged period of time, and a core part of our strategy is to continue making sustained investments in this area. Our ability to generate profits and to generate positive cash flow from operations over the next several years depends upon our ability to successfully market our four commercial products - ZEJULA, Optune, QINLOCK and NUZYRA - and our other product candidates that we are able to successfully commercialize. We expect to continue to incur substantial expenses related to our research and development activities. In particular, our licensing and collaboration agreements require us to make upfront payments upon our entry into such agreements and milestone payments upon the achievement of certain development, regulatory and commercial milestones as well as tiered royalties based on the net sales of the licensed products. These upfront payments and milestone payments upon the achievement of certain development and regulatory milestones are recorded in research and development expense in our unaudited condensed consolidated financial statements. We did not accrue any such payments during the three months ended March 31, 2022. In addition, we expect to incur substantial costs related to the commercialization of our product candidates, in particular during the early launch phase.

Furthermore, as we pursue our strategy of growth and development, we anticipate that our financial results will fluctuate from quarter to quarter based upon the balance between the successful marketing of our commercial products and our significant research and development expenses. We cannot predict whether or when new products or new indications for marketed products will receive regulatory approval or, if any such approval is received, whether we will be able to successfully commercialize such product(s) and whether or when they may become profitable.



Recent Developments

Recent Business Developments

On January 6, 2022, we announced that the NMPA accepted the new drug application
(NDA) for margetuximab, an investigational,
Fc-engineered
monoclonal antibody that targets HER2. The margetuximab NDA is for the treatment
of adult patients with metastatic HER2-positive breast cancer who have received
two or more prior anti-HER2 regimens, at least one of which was for metastatic
disease, in combination with chemotherapy.

On January 12, 2022, we announced treatment of the first patient in Greater
China in the
PANOVA-3
trial, a Phase 3 pivotal trial of Tumor Treating Fields in patients with
pancreatic cancer.
PANOVA-3
is a global, open-label, randomized Phase III trial evaluating the efficacy of
TTFields administered concomitantly with gemcitabine and
nab-paclitaxel
as front-line treatment for patients with unresectable, locally advanced
pancreatic cancer. The primary endpoint is overall survival. Secondary endpoints
include progression-free survival, local progression-free survival, objective
response rate,
one-year
survival rate, quality of life, pain-free survival, resectability rate and
toxicity.

In February 2022, the Center for Drug Evaluation (CDE) of the NMPA granted
Breakthrough Therapy Designation for repotrectinib for the treatment of patients
with ROS1-positive metastatic NSCLC who have not been treated with a ROS1 TKI.
The breakthrough therapy designation was supported by the initial data from both
global and Chinese
TKI-naïve
ROS1-positive NSCLC patients enrolled in the Phase I/II
TRIDENT-1
study. We plan to participate in all cohorts of the global
TRIDENT-1
study.

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In March 2022, we presented positive results from the Phase 3 PRIME study of ZEJULA (niraparib) as maintenance therapy at the Society of Gynecologic Oncology (SGO) 2022 Annual Meeting. ZEJULA demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with a tolerable safety profile in Chinese patients with newly diagnosed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (collectively termed as ovarian cancer) following a response to platinum-based chemotherapy, regardless of biomarker status. In the PRIME study, median PFS was significantly longer for patients treated with niraparib compared to placebo: 24.8 months versus 8.3 months, hazard ratio (HR), 0.45; p<0.001.

We also continued to strengthen and expand our leadership team. On March 15, 2022, we announced the appointment of Joshua Smiley as our Chief Operating Officer, effective on August 1, 2022. Mr. Smiley brings over 26 years of experience working with the biopharmaceutical industry, including experience leading finance, corporate strategy, business development, venture capital and global business services operations at Eli Lilly and Company. In addition, in April 2022, Jonathan Wang became our Chief Business Officer, taking on increased responsibilities after the departure of Tao Fu, our former Chief Strategy Officer.



In March 2022, our shareholders approved a Share Subdivision whereby the Company
subdivided each of its issued and unissued ordinary shares into ten ordinary
shares, effective March 30, 2022. The
one-to-ten
Share Subdivision increased the number of our ordinary shares in issue and
reduced the nominal value and trading price of each ordinary share. Our Board of
Directors believes that the Share Subdivision will increase the trading
liquidity of the ordinary shares, lower the investment barrier, and attract more
investors to trade in the ordinary shares. In connection with the Share
Subdivision, the Company also effected the ADS Ratio Change, whereby the
conversion ratio of our ADSs to ordinary shares changed from one ADS to one
ordinary share to a new ratio of one ADS representing ten ordinary shares. The
Share Subdivision and ADS Ratio Change did not result in any change to the
number of outstanding ADSs of the Company.

In March 2022, SEC staff conclusively identified us under the HFCAA as a
"Commission-Identified Issuer" because Deloitte Touche Tohmatsu Certified Public
Accountants LLP and Deloitte Touche Tohmatsu (together, "Deloitte"), our auditor
for the financial statements included in our 2021 Annual Report, is located in a
foreign jurisdiction and the PCAOB has determined that it is unable to inspect
or investigate the auditor completely because of a restriction imposed by a
non-U.S.
authority in the auditor's local jurisdiction. In April 2022, the Audit
Committee of our Board of Directors approved the engagement of KPMG, an auditor
located in the United States that is subject to PCAOB inspection, as our
independent registered public accounting firm for the fiscal year ending
December 31, 2022. KPMG will be engaged to audit our annual consolidated
financial statements filed with the SEC and our internal controls over financial
reporting in accordance with the Exchange Act. KPMG also will be engaged to
audit our consolidated financial statements submitted to The Hong Kong Stock
Exchange in accordance with the Rules Governing the Listing of Securities of the
Hong Kong Stock Exchange, subject to our receipt of the requisite approvals from
the Hong Kong Stock Exchange and the Financial Reporting Council of Hong Kong
("FRC"), which are expected to be administrative in nature. KPMG is in the
process of concluding its standard client evaluation procedures, including
obtaining approval from the Hong Kong Stock Exchange to be appointed as our
auditor. Upon completion of these standard procedures, KPMG will be in a
position to execute an engagement letter and formally commence the engagement.
For more information on the HFCAA and risks related to audits of companies with
significant operations in China, see "Item 1A. Risk Factors" in this Quarterly
Report on Form
10-Q.

In April 2022, we presented new data from its internal oncology discovery
portfolio at the American Association for Cancer Research (AACR) Annual Meeting
2022. Key early-stage discovery programs were featured in these presentations,
including first preview of preclinical data on
ZL-1218
(a novel anti-CCR8 antibody for solid tumors) in oral presentation, as well as
poster presentations featured
ZL-1201
(a CD47-targeting antibody for advanced hematologic malignancies and solid
tumors),
ZL-1211
(a
Claudin18.2-specific
antibody for gastric and pancreatic cancer) and
ZL-2201
(a highly selective small-molecule
DNA-PK
inhibitor for anti-cancer therapy).

In April 2022, we announced topline data for repotrectinib within the China
region from the previously disclosed Phase 1/2
TRIDENT-1
study dataset. We plan to discuss topline TKI-naïve data with Chinese health
authority in the fourth quarter of 2022.

     •    In TKI-naïve patients
          (EXP-1),
          in 71 total patients, there was a confirmed objective response rate
          (cORR) of 79% across the global trial. Ten of 11 patients responded
          within China for a cORR of 91% (95% CI: 59,100) and DOR ranged from 3.6+
          to 7.5+ months with a median duration of follow-up of 3.7 months.



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     •    In patients previously treated with 1 TKI and platinum-based chemotherapy
          (EXP-2),
          in 26 total patients, there was a cORR of 42% across the global trial.
          Two of 3 patients responded within China for a cORR of 67% (95% CI:9,99)
          and DOR ranged from 3.6+ to 3.7+ months with a median duration of
          follow-up of 3.7 months.



     •    In patients previously treated with two TKIs without prior chemotherapy
          (EXP-3), in 18 total patients, there was a cORR of 28% across the global
          trial. Two of 4 patients responded within China for a cORR of 50% (95%
          CI: 7,93) and DOR ranged from 1.9+ to 3.4+ months with a median duration
          of follow-up of 2.6 months.



     •    In patients previously treated with 1 TKI without prior chemotherapy
          (EXP-4), in 56 total patients, there was a cORR of 36% across the global
          trial. Four of 11 patients responded within China for a cORR of 36% (95%
          CI: 11,69) and DOR ranged from 2.0+ to 3.7+ months with a median duration
          of follow-up of 3.1 months.

In April 2022, the Board of Directors of the Company authorized the Company's senior management to proceed with the relevant preparatory work and undertake necessary steps to pursue a voluntary conversion to dual-primary listing on the Hong Kong Stock Exchange. Following the voluntary conversion, the Company's ordinary shares and American Depositary Shares will continue to be traded on the Hong Kong Stock Exchange and the Nasdaq Global Market, respectively, and remain mutually fungible. Becoming a dual-primary listed company will enable the Company to be eligible for the Hong Kong Stock Exchange Stock Connect, a channel by which investors in mainland China can invest in stocks traded on the Hong Kong Stock Exchange.

Recent Legal and Regulatory Developments

Provisions on Strengthening Confidentiality and Archives Administration of Overseas Securities Offering and Listing by Domestic Companies (Draft for Comments)

On April 2, 2022, the CSRC published the revised Provisions on Strengthening Confidentiality and Archives Administration of Overseas Securities Offering and Listing by Domestic Companies (Draft for Comments) (the "Draft Archives Rules").

The Draft Archives Rules require that, in relation to the overseas securities offering and listing activities of Chinese domestic enterprises, such domestic enterprises, as well as securities companies and securities service institutions providing relevant securities services, are required to strictly comply with the relevant requirements on confidentiality and archives management, establish a sound confidentiality and archives system and take necessary measures to implement their confidentiality and archives management responsibilities.

According to the Draft Archives Rules, if during the course of an overseas offering and listing (whether listed directly or indirectly), if a Chinese domestic company needs to publicly disclose or provide, or publicly disclose or provide through its overseas listed entity, to relevant entities or individuals including securities companies, other securities service providers and overseas regulators, any documents and materials that contain relevant state secrets, government department work secrets or that have a sensitive impact (i.e., that are detrimental to national security or the public interest if divulged), the Chinese domestic company should complete the relevant approval/filing and other regulatory procedures stipulated by applicable national regulations.

In addition, the Draft Archives Rules explicitly include within the scope of its supervision overseas accounting firms that engage in auditing business related to overseas securities offering and listings of Chinese domestic enterprises. Overseas accounting firms that engage in auditing business related to overseas securities offering and listings of Chinese domestic enterprises are required to abide by corresponding procedures in accordance with relevant Chinese national regulations.

Amended China Civil Procedure Law

The Civil Procedure Law of the People's Republic of China, or the China Civil Procedure Law, which was adopted on April 9, 1991 and amended on October 28, 2007, August 31, 2012, June 27, 2017, and December 24, 2021, prescribes the conditions for instituting a civil action, the jurisdiction of the people's courts, the procedures for conducting a civil action and the procedures for enforcement of a civil judgment or ruling. The most recent amendments to the China Civil Procedure Law on December 24, 2021, which came into effect on January 1, 2022, include the following improvements to the civil procedure under China's current judicial system: (i) with the consent of the parties, civil litigation activities may be conducted online through the information network platform and such online litigation activities have the same legal effect as offline litigation activities; (ii) in addition to civil cases followed by summary procedure, civil cases followed by ordinary procedure and civil cases of second instance which meet certain criteria may also be tried by a single judge; (iii) the scope of the litigation documents which are allowed to be served by electronic means expands to include judgments, awards and mediation statements; (iv) the period of service which is effected by public announcement in cases where the location of the recipient of the service is unknown or the service cannot be served by other means specified in the China Civil Procedure Law is shortened from 60 days to 30 days; (v) with respect to small claims procedure, the amount of the subject matter applicable to small claims procedure is raised, the trial time for small claims procedure is limited to three months and certain types of cases, such as cases of personal relation, are excluded from application of small claims procedure; and (vi) the jurisdiction of judicial conformation of a mediation agreement is further clarified and the parties to a mediation agreement are given more options in terms of choosing the people's court for judicial conformation.



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Collecting and Using China-Sourced Human Genetic Resources and Derived Data

On March 4, 2022, the Ministry of Science and Technology (MOST) issued Answers to Frequently Asked Questions Regarding Human Genetic Resources (HGRs) Administration, or the Q&A Series I. The Q&A Series I provides short answers to 30 frequently asked questions relating to the collection, preservation, utilization and external provision of China-sourced HGRs. For example, the Q&A Series I clarifies that a notification filing with the Human Genetic Resources Administration Office of China, or HGRAC, is required for purpose of transferring China-sourced HGRs to regulatory authorities in other jurisdictions.

On March 22, 2022, the Ministry of Science and Technology (MOST) issued the Draft Implementing Rules of the Regulation on the Administration of Human Genetic Resources (Draft for Comment), or the Draft Implementing Rules, which closely scrutinizes all HGRs-related activity from upstream collection of HGR materials to downstream exploitation and external provision of the HGR materials and data derived therefrom ("HGR data"). The Draft Implementing Rules are intended to provide operational details and clarify questions that have emerged in the past few years after the Regulation on the Administration of Human Genetic Resources became effective. Under the Draft Implementing Rules, clinical studies conducted for purpose of obtaining marketing authorization for drugs and medical devices in China, if not involving the export of HGR materials, will be eligible for a notification filing (as opposed to the advance approval) if the HGR materials are collected by sites, and processed by sites or an onshore third-party lab specified in the clinical trial protocol. The Draft Implementing Rules provide clearer guidance on how to allocate the intellectual property derived from a Sino-foreign cooperative research utilizing China-Sourced HGRs. The Draft Implementing Rules enumerate situations where a security review is required for external provision or utilization in an open manner of HGR data, such as external provision or utilization in an open manner of HGR data about important genetic pedigrees, HGR data from specific regions, and exome sequencing and genome sequencing information of over 500 individuals.

On April 15, 2022, MOST issued Answers to Frequently Asked Questions Regarding Human Genetic Resources Administration (Q&A Series II), or the Q&A Series II. The Q&A Series II provide formal written reply to 5 frequently asked questions relating to the collection, preservation, utilization and external provision of China-Sourced HGRs. The Q&A Series II specifies that collection, external provision or utilization in an open manner of the data related to clinical practices, patient demographics, lab tests, medical images, etc. that do not carry genetic attributes will not be regulated as collection, external provision or utilization in an open manner of HGR data. The Q&A Series II stipulates that no advance approval for Sino-foreign cooperative research is required for a research utilizing China-Sourced HGRs, if the foreign entity who provides funding support will not substantially participate in the research and have any access to or ownership of the research data and research results.

Auxiliary Rules for the Regulations on Supervision and Administration of Medical Devices



On March 18, 2021, the State Council published new Regulations on Supervision
and Administration of Medical Devices, or Order 739, which became effective on
June 1, 2021. This
top-level
medical device administrative regulation contains a number of important changes,
the practical effects of which will be implemented in corresponding auxiliary
regulations and rules. Recently, a series of regulations have been amended
accordingly to support the implementation of Order 739 in terms of the
production, distribution and clinical trials of medical devices.

• Measures for the Supervision and Administration of the Production of

Medical Devices

On May 1, 2022, a revised version of the Measures for the Supervision and Administration of the Production of Medical Devices, or Order 53, promulgated by the State Administration for Market Regulation, or SAMR, became effective. All medical device manufacturing activities within China should comply with Order 53. Order 53 clarifies the responsibilities and obligations of medical device registrants/ record-filing applicants and their entrusted manufacturers where applicable. Order 53 also establishes a medical device reporting system with an aim to improve administration of medical device production. The reporting system consists of several types of report, including annual self-inspection report, production product variety report, production conditions change report, re-production report and recall and disposal report. The medical device registrants/ record-filing applicants and/or the medical device manufacturers need to submit corresponding reports to the local relevant Medical Product Administrations in accordance with Order 53.

• Measures for the Supervision and Administration of the Distribution of

Medical Devices

On May 1, 2022, a revised version of the Measures for the Supervision and Administration of the Distribution of Medical Devices, or Order 54, promulgated by SAMR came into effect. All medical device distribution activities within China should comply with Order 54. Under Order 54, explicit regulatory requirements were introduced to distributors of medical devices. For example, Order 54 requires medical device distributors to establish quality management system and adopt quality control measures covering the total process of distribution and submit annual self-inspection reports to local relevant Medical Product Administrations.



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  •   Good Practices for Medical Device Clinical Trials

On May 1, 2022, a revised version of the Good Practices for Medical Device Clinical Trials, or 2022 Medical Device GCP, jointly released by the NMPA and the National Health Commission, came into effect. Going forward, all medical device clinical trials that haven't passed ethical review by May 1, 2022 should be conducted in compliance with the 2022 Medical Device GCP, if they are conducted for purpose of applying for medical device registration. The 2022 Medical Device GCP specifies responsibilities of each party participating in a medical device clinical trial, in particular the responsibilities of the sponsor. The 2022 Medical Device GCP no longer requires clinical trials of medical devices to be conducted in two or more clinical trial institutions. This will make it easier for medical device companies to conduct medical device registration studies.

Factors Affecting our Results of Operations

Research and Development Expenses

We believe our ability to successfully develop product candidates will be the primary factor affecting our long-term competitiveness, as well as our future growth and development. Developing high quality product candidates requires a significant investment of resources over a prolonged period of time, and a core part of our strategy is to continue making sustained investments in this area. As a result of this commitment, our pipeline of product candidates has been steadily advancing and expanding, with twelve late-stage clinical product candidates being investigated as of March 31, 2022.



We have financed our activities primarily through private placements, our
initial public offering on Nasdaq in September 2017, multiple
follow-on
offerings and a secondary listing on the Hong Kong Stock Exchange in September
2020. Through March 31, 2022, we have raised approximately $164.6 million from
private equity financing and approximately $2,462.7 million in net proceeds
after deducting underwriting commissions and the offering expenses payable by us
from our initial public offering,
follow-on
offerings and secondary listing. Our operations have consumed substantial
amounts of cash since inception. The net cash used in our operating activities
was $87.1 million and $169.5 million, for the three months ended March 31, 2022
and 2021, respectively. We expect our expenditures to increase significantly in
connection with our ongoing activities, particularly as we advance the clinical
development of our twelve late-stage clinical product candidates, research and
develop our clinical- and
pre-clinical-stage
product candidates and initiate additional clinical trials of, and seek
regulatory approval for, these and other future product candidates. These
expenditures include:

     •    expenses incurred for contract research organizations (CROs), contract
          manufacture organizations (CMOs), investigators and clinical trial sites
          that conduct our clinical studies;



     •    employee compensation related expenses, including salaries, benefits and
          equity compensation expenses;



  •   expenses for licensors;



     •    the cost of acquiring, developing and manufacturing clinical study
          materials;



     •    facilities and other expenses, which include office leases and other
          overhead expenses;



  •   costs associated with
      pre-clinical
      activities and regulatory operations;



     •    expenses associated with the construction and maintenance of our
          manufacturing facilities; and



  •   costs associated with operating as a public company.

Selling, General and Administrative Expenses

Our selling, general and administrative expenses consist primarily of personnel compensation and related costs, including share-based compensation for commercial and administrative personnel. Other selling, general and administrative expenses include product distribution and promotion costs, professional service fees for legal, intellectual property, consulting, auditing and tax services as well as other direct and allocated expenses for rent and maintenance of facilities, insurance and other supplies used in selling, general and administrative activities. We anticipate that our selling, general and administrative expenses will increase in future periods to support increases in our commercial and research and development activities and as we continue to commercialize, develop and manufacture our products and assets. These increases will likely include increased headcount, increased share-based compensation charges, increased product distribution and promotion costs, expanded infrastructure and increased costs for insurance. We also anticipate to incur additional legal, compliance, accounting and investor and public relations expenses associated with being a public company.



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Our Ability to Commercialize Our Product Candidates



As of March 31, 2022, twelve of our product candidates are in late-stage
clinical development and various others are in clinical and
pre-clinical
development in Greater China and the United States. Our ability to generate
revenue from our product candidates is dependent on our receipt of regulatory
approvals for and successful commercialization of such products, which may never
occur. Certain of our product candidates may require additional
pre-clinical
and/or clinical development, regulatory approvals in multiple jurisdictions,
manufacturing supply, substantial investment and significant marketing efforts
before we generate any revenue from product sales.

Our License Arrangements

Our results of operations have been, and we expect them to continue to be, affected by our licensing, collaboration and development agreements. We are required to make upfront payments upon our entry into such agreements and milestone payments upon the achievement of certain development, regulatory and commercial milestones for the relevant products under these agreements as well as tiered royalties based on the net sales of the licensed products. These upfront payments and milestone payments upon the achievement of certain development and regulatory milestones are recorded in research and development expense in our unaudited condensed consolidated financial statements and totaled nil and $171.3 million for the three months ended March 31, 2022 and March 31, 2021, respectively.

Results of Operations

Three Months Ended March 31, 2022 Compared to Three Months Ended March 31, 2021

Revenues

Total revenues consist of the following:



                                Three months ended March 31,
(in thousands)            2022          %          2021          %

Revenues:

Product revenue, net $ 46,095 98.7 $ 20,103 100.0 Collaboration revenue 629 1.3

           -           -

Total                   $ 46,724       100.0     $ 20,103       100.0



Product Revenue, net

Our product revenue is primarily derived from the sales of ZEJULA, Optune, QINLOCK, and NUZYRA in mainland China and Hong Kong. The amount of revenue of ZEJULA for the three months ended March 31, 2022 and March 31, 2021, respectively, was adjusted by the normal process in mainland China to compensate distributors for products recently sold at prices prior to the NRDL implementation. The following table disaggregates net revenue by product for the three months ended March 31, 2022 and 2021, respectively:





                                     Three months ended March 31,
(in thousands)                 2022          %          2021          %
ZEJULA                       $ 29,597        64.2     $ 12,606        62.7
Optune                         12,797        27.8        7,130        35.5
QINLOCK                         2,959         6.4          367         1.8
NUZYRA                            742         1.6           -           -

Total product revenue, net   $ 46,095       100.0     $ 20,103       100.0




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Collaboration revenue

Collaboration revenue increased by $0.6 million to $0.6 million for the three months ended March 31, 2022 from nil for the three months ended March 31, 2021 from the collaborative arrangement with Huizheng (Shanghai) Pharmaceutical Technology Co., Ltd.

Cost of Sales

Cost of sales increased by $8.1 million to $15.6 million for the three months ended March 31, 2022 from $7.5 million for the three months ended March 31, 2021 primarily due to increasing sales volume, product costs and higher royalties during the three months ended March 31, 2022.

Research and Development Expenses

The following table sets forth the components of our research and development expenses for the respective period indicated.



                                                    Three months ended March 31,
(in thousands)                               2022          %          2021           %

Research and development expenses: Personnel compensation and related costs $ 24,802 46.1 $ 12,697 6.2 Licensing fees

                                   -           -        171,282        84.0
CROs/CMOs/Investigators expenses             23,550        43.7        15,526         7.6
Other costs                                   5,502        10.2         4,347         2.2

Total                                      $ 53,854       100.0     $ 203,852       100.0


Research and development expenses decreased by $150.0 million to $53.9 million for the three months ended March 31, 2022 from $203.9 million for the three months ended March 31, 2021 primarily due to:




     •    a decrease of $171.3 million in licensing fees in connection with the
          upfront and milestone fee paid for licensing agreement due to no new
          licensing for the three months ended March 31, 2022; offset by



     •    an increase of $12.1 million in personnel compensation and related costs
          primarily attributable to increased employee compensation costs due to
          headcount growth during the three months ended March 31, 2022 and the
          grants of new share options and vesting of restricted shares to certain
          employees, and



     •    an increase of $8.0 million in CROs/CMOs/Investigators expenses in the
          three months ended March 31, 2022 as we advanced our drug candidate
          pipeline.

The following table summarizes our research and development expenses by program for the three months ended March 31, 2022 and 2021, respectively:



                                                             Three months ended March 31,
(in thousands)                                       2022           %           2021            %
Research and development expenses:
Clinical programs                                  $ 22,852         42.4      $ 186,256         91.4

Pre-clinical


programs                                              2,565          4.8          2,500          1.2

Unallocated research and development expenses 28,437 52.8 15,096 7.4



Total                                              $ 53,854        100.0      $ 203,852        100.0




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Research and development expenses attributable to clinical programs decreased by
$163.4 million from $186.3 million during the three months ended March 31, 2021
(which included the licensing fees of $171.3 million) to $22.9 million during
the three months ended March 31, 2022. Research and development expenses
attributable to
pre-clinical
programs remained relatively consistent during the three months ended March 31,
2022 compared to the three months ended March 31, 2021. Although we manage our
external research and development expenses by program, we do not allocate our
internal research and development expenses by program because our employees and
internal resources may be engaged in projects for multiple programs at any given
time.

Selling, General and Administrative Expenses

The following table sets forth the components of our selling, general and administrative expenses for the respective period indicated.



                                                        Three months ended March 31,
(in thousands)                                    2022          %          2021          %
Selling, General and Administrative Expenses:
Personnel compensation and related costs        $ 38,203        67.0     $ 23,412        65.3
Professional service fees                          7,433        13.0        3,583        10.0
Other costs                                       11,355        20.0        8,843        24.7

Total                                           $ 56,991       100.0     $ 35,838       100.0


Selling, general and administrative expenses increased by $21.2 million to $57.0 million for the three months ended March 31, 2022 from $35.8 million for the three months ended March 31, 2021 primarily due to:



     •    an increase of $14.8 million in personnel compensation and related costs
          which was primarily attributable to increased commercial and
          administrative personnel costs due to headcount growth during the three
          months ended March 31, 2022 and the grants and vesting of share options
          and restricted shares to certain employees;



     •    an increase of $3.9 million in professional service fees mainly
          attributable to our increased legal, compliance, accounting and investor
          and public relations expenses associated with being a public company and
          in connection with sales of ZEJULA, Optune, QINLOCK and NUZYRA in
          mainland China and Hong Kong after our commercial launch of these four
          commercialized products; and



     •    an increase of $2.5 million in other costs mainly including selling,
          rental, and administrative expenses primarily attributable to the
          commercial operation in mainland China, Hong Kong, and Taiwan.

Interest Income

Interest income were $0.2 million and $0.2 million for the three months ended March 31, 2022 and 2021, respectively.

Other Expenses, Net

Other expenses decreased by $3.6 million to $2.6 million for the three months ended March 31, 2022 from $6.2 million for the three months ended March 31, 2021, primarily as a result of an increase in foreign exchange gain and governmental subsidies net of equity investment loss in MacroGenics.



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Critical Accounting Policies and Significant Judgments and Estimates

We prepare our financial statements in conformity with U.S. GAAP, which requires us to make judgments, estimates and assumptions. We periodically evaluate these estimates and assumptions based on the most recently available information, our own historical experiences and various other assumptions that we believe to be reasonable under the circumstances. Since the use of estimates is an integral component of the financial reporting process, actual results could differ from our expectations as a result of changes in our estimates. Some of our accounting policies require a higher degree of judgment than others in their application and require us to make significant accounting estimates.

The selection of critical accounting policies, the judgments and other uncertainties affecting application of those policies and the sensitivity of reported results to changes in conditions and assumptions are factors that should be considered when reviewing our financial statements. We believe the following accounting policies involve the most significant judgments and estimates used in the preparation of our financial statements.

Revenue recognition

Description

In mainland China, we sell our products to distributors, who ultimately sell the products to healthcare providers. Based on the nature of the arrangements, the performance obligations are satisfied upon the product's delivery to distributors.

Judgments and Uncertainties

Rebates are offered to distributors, consistent with pharmaceutical industry practices. The estimated amount of unpaid or unbilled rebates, if any, is recorded as a reduction of revenue. Estimated rebates are determined based on contracted rates, sales volumes and level of distributor inventories. We regularly review the information related to these estimates and adjust the amount accordingly.

Sensitivity of Estimate to Change

Actual amounts of rebates ultimately paid or billed may differ from our estimates. We will reassess estimates for rebates periodically. If actual results in the future vary from our estimates, we will adjust these estimates, which would affect net product revenue and earnings in the period such variances become known.

Research and Development Expenses

Description

Research and development expenses are charged to expense as incurred when these expenditures relate to our research and development services and have no alternative future uses.

Preclinical and clinical trial costs are a significant component of our research and development expenses. We have a history of contracting with third parties that perform various preclinical and clinical trial activities on behalf of us in the ongoing development of our product candidates. Expenses related to preclinical and clinical trials are accrued based on our estimates of the actual services performed by the third parties for the respective period.

Judgments and Uncertainties



The process of estimating our research and development expenses involves
reviewing open contracts and purchase orders, communicating with our personnel
to identify services that have been performed on our behalf and estimating the
level of service performed and the associated costs incurred for the services
when we have not yet been invoiced or otherwise notified of the actual costs.
The majority of our service providers invoice us in arrears for services
performed, on a
pre-determined
schedule or when contractual milestones are met; however, some require advanced
payments. We make estimates of our expenses as of each balance sheet date in our
financial statements based on facts and circumstances known to us at that time.

Sensitivity of Estimate to Change

Although we do not expect our estimates to be materially different from amounts actually incurred, our understanding of the status and timing of services performed relative to the actual status and timing of services performed may vary and may result in us reporting expenses that are too high or too low in any particular period. To date, we have not made any material adjustments to our prior estimates of research and development expenses.



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Share-Based Compensation

Description

Employees' share-based awards are measured at the grant date fair value of the awards and recognized as expenses (1) immediately at grant date if no vesting conditions are required; or (2) using graded vesting method over the requisite service period, which is the vesting period.

To the extent the required vesting conditions are not met resulting in the forfeiture of the share-based awards, previously recognized compensation expenses relating to those awards are reversed.

Judgments and Uncertainties

We determine the fair value of the stock options granted to employees using the Black-Scholes option valuation model. Using this model, fair value is calculated based on assumptions with respect to (i) expected volatility of our ADS price, (ii) the periods of time over which grantees are expected to hold their options prior to exercise (expected lives), (iii) expected dividend yield on our ADS, and (iv) risk-free interest rates, which are based on quoted U.S. Treasury rates for securities with maturities approximating the options' expected lives. Expected volatility has been estimated based on actual movements in some comparable companies' stock prices over the most recent historical periods equivalent to the options' expected lives. Expected lives are principally based on our historical exercise experience with previous option grants. The expected dividend yield is zero as we have never paid dividends and do not currently anticipate paying any in the foreseeable future.

Sensitivity of Estimate to Change

The assumptions used in this method to determine fair value of ordinary shares consider historical trends, macroeconomic conditions, and projections consistent with the Company's operating strategy. Changes in these estimates can have a significant impact on the determination of fair value of the stock options. If factors change or different assumptions are used, the share-based compensation expenses could be materially different for any period.

Income Taxes

Description

In accordance with the provisions of ASC 740, Income Taxes, we recognize in our financial statements the benefit of a tax position if the tax position is "more likely than not" to prevail based on the facts and technical merits of the position. Tax positions that meet the "more likely than not" recognition threshold are measured at the largest amount of tax benefit that has a greater than fifty percent likelihood of being realized upon settlement. We estimate our liability for unrecognized tax benefits which are periodically assessed and may be affected by changing interpretations of laws, rulings by tax authorities, changes and/or developments with respect to tax audits, and expiration of the statute of limitations. The ultimate outcome for a particular tax position may not be determined with certainty prior to the conclusion of a tax audit and, in some cases, appeal or litigation process.

Judgments and Uncertainties

We consider positive and negative evidence when determining whether some portion or all of our deferred tax assets will not be realized. This assessment considers, among other matters, the nature, frequency and severity of current and cumulative losses, forecasts of future profitability, the duration of statutory carry-forward periods, our historical results of operations and our tax planning strategies. The ultimate realization of deferred tax assets is dependent upon the generation of future taxable income during the periods in which those temporary differences become deductible. Based upon the level of our historical taxable income and projections for future taxable income over the periods in which the deferred tax assets are deductible, we believe it is more likely than not that we will not realize the deferred tax assets resulted from the tax loss carried forward in the future periods.

Sensitivity of Estimate to Change

The actual benefits ultimately realized may differ from our estimates. As each audit is concluded, adjustments, if any, are recorded in our financial statements in the period in which the audit is concluded. Additionally, in future periods, changes in facts, circumstances and new information may require us to adjust the recognition and measurement estimates with regard to individual tax positions. Changes in recognition and measurement estimates are recognized in the period in which the changes occur. As of March 31, 2022 and 2021, we did not have any significant unrecognized uncertain tax positions.

B. Liquidity and Capital Resources



We have financed our activities primarily through private placements, our
September 2017 initial public offering on the Nasdaq stock exchange, various
follow-on
offerings and our September 2020 secondary listing on the Hong Kong Stock
Exchange of our ordinary shares and/or ADSs. Through March 31, 2022, we have
raised approximately $164.6 million from private equity financing and
approximately $2,462.7 million in net proceeds after deducting underwriting
commissions and the offering expenses payable by us from our initial public
offering, secondary listing and subsequent
follow-on
offerings.

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Our operations have consumed substantial amounts of cash since inception. The net cash used in our operating activities was $87.1 million and $169.5 million, for the three months ended March 31, 2022 and 2021, respectively. We have commitments for capital expenditure of $22.3 million as of March 31, 2022, mainly for the purpose of plant construction and installation. We currently are not aware of any events that are reasonably likely to cause a material change in the relationship between costs and revenues.

As of March 31, 2022, we had cash, cash equivalents, restricted cash and short-term investment of $1,313.0 million. Our expenditures are principally focused on research and development and are largely discretionary. As such, we believe that our current losses and cash used in operations do not present going concern issues. Based on our current operating plan, we expect that our cash, cash equivalents, restricted cash and short-term investments will enable us to fund our operating expenses and capital expenditures requirements for at least the next 12 months. However, in order to bring to fruition our research and development objectives, we will ultimately need additional funding sources and there can be no assurances that they will be made available.

The following table provides information regarding our cash flows for the three months ended March 31, 2022 and 2021:



                                                                Three months ended
                                                                     March 31,
(in thousands)                                                 2022             2021
Net cash used in operating activities                       $  (87,127 )     $ (169,500 )
Net cash (used in) provided by investing activities            (30,144 )        742,005
Net cash provided by (used in) financing activities                258             (271 )
Effect of foreign exchange rate changes                           (130 )           (930 )

Net (decreases) increases in cash, cash equivalents and restricted cash

$ (117,143 )     $  571,304

Net cash used in operating activities



During the three months ended March 31, 2022, our operating activities used
$87.1 million of cash, which resulted principally from our net loss of
$82.4 million, adjusted for
non-cash
charges of $23.0 million, and cash used in our operating assets and liabilities
of $27.7 million.

During the three months ended March 31, 2021, our operating activities used
$169.5 million of cash, which resulted principally from our net loss of
$232.9 million, adjusted
for non-cash charges
of $72.1 million, and cash used in our operating assets and liabilities of
$8.7 million. The decrease in cash used in operating activities was primarily
due to the decrease of license payments.

Net cash (used in) provided by investing activities

Net cash used in investing activities was $30.1 million for the three months ended March 31, 2022 compared to net cash provided by investing activities of $742.0 million for the three months ended March 31, 2021. The decrease in cash provided by investing activities was primarily due to the decrease of proceeds from maturity of short-term investments during the three months ended March 31, 2022 compared to the three months ended March 31, 2021.

Net cash provided by (used in) financing activities

Net cash provided by financing activities was $0.3 million for the three months ended March 31, 2022 compared to net cash used in financing activities of $0.3 million for the three months ended March 31, 2021. The increase in cash provided by financing activities was primarily due to the reduced payment of public offering costs during the three months ended March 31, 2022.

C. Research and Development Activities and Expenditures, Including Patents and Licenses

Full details of our research and development activities and expenditures are provided in the "Research and Development Expenses" and "Results of Operations" sections above.



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D. Trend Information

Other than as described elsewhere in this Quarterly Report on Form 10-Q, we are not aware of any trends, uncertainties, demands, commitments or events that are reasonably likely to have a material adverse effect on our revenue, income from continuing operations, profitability, liquidity or capital resources, or that would cause our reported financial information not necessarily to be indicative of future operation results or financial condition.

Recently Issued Accounting Standards

For more information regarding recently issued accounting standards, please see "Item 8. Financial Statements and Supplementary Data-Recent accounting pronouncements" in our 2021 Annual Report.

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