BeyondSpring(BYSI) - 2023 Q4 - Annual Report

PART I Item 3. Key Information The company faces significant risks across its financial position, clinical development, regulatory approval, and commercialization efforts Risks Related to Financial Position and Capital Needs The company has a history of net losses and requires additional financing to continue as a going concern Net Loss and Accumulated Deficit | Fiscal Year End | Net Loss (in millions) | Accumulated Deficit (in millions) | | :--- | :--- | :--- | | Dec 31, 2021 | $68.2 | - | | Dec 31, 2022 | $36.3 | $375.3 | | Dec 31, 2023 | $21.9 | $396.3 | - The company's independent registered accountants have issued an opinion expressing substantial doubt about its ability to continue as a going concern due to recurring operating losses and negative cash flows[36] Net Cash Used in Operating Activities | Fiscal Year End | Net Cash Used (in millions) | | :--- | :--- | | Dec 31, 2021 | $47.2 | | Dec 31, 2022 | $28.2 | | Dec 31, 2023 | $16.5 | Risks Related to Clinical Development The company's success is highly dependent on its lead product, Plinabulin, which faces significant clinical trial risks - In November 2021, the company received a Complete Response Letter (CRL) from the FDA for its Plinabulin NDA, requiring a second well-controlled trial for the CIN indication[52] - The company's entire clinical pipeline currently revolves around Plinabulin, and its failure would severely harm the business[54] - Patient enrollment in clinical trials has been affected by external factors, including the COVID-19 pandemic and geopolitical conflicts in Ukraine and Russia[57][59] Risks Related to Regulatory Approval The company faces a lengthy and unpredictable regulatory approval process, with risks related to data sufficiency and applicability - In March 2023, the company withdrew its NDA submission for Plinabulin for the CIN indication from the NMPA in China and plans to re-file[74] - The company's late-stage clinical trials included a majority of patients from China, which the FDA may not consider applicable to the U.S. population[76][77] - The FDA's CRL for the CIN indication stated that the single registrational trial was not sufficiently robust, highlighting the risk of insufficient clinical data[79][88] Risks Related to Commercialization The company faces significant hurdles in market acceptance, competition, and pricing for its product candidates, if approved - The company has an exclusive commercialization agreement with Hengrui in Greater China and plans to seek a partner for the U.S. and the rest of the world[132][133] - The company faces substantial competition from major pharmaceutical companies with greater financial resources and expertise[136][137] - Recent legislation, such as the Inflation Reduction Act of 2022, may negatively affect drug prices the company can obtain in the U.S[150] Risks Related to Intellectual Property The company's success depends on obtaining and maintaining patent protection, which is subject to uncertainty and potential challenges - As of April 10, 2024, the company owned 17 issued U.S. patents related to Plinabulin, with expiration dates ranging from 2025 to 2039[162] - The company has 17 families of pending patent applications for Plinabulin which, if issued, would expire between 2033 and 2042[162] - Protecting intellectual property rights globally is expensive and challenging, as laws in some non-U.S. countries offer less protection than U.S. law[166] Risks Related to Reliance on Third Parties The company depends on third-party CROs and manufacturers, with a key supply chain risk related to a sole supplier - The company depends on third-party CROs for clinical programs, and their failure to comply with Good Clinical Practices (GCPs) could render data unreliable[194][197] - The company relies on BASF SE as the sole supplier of Kolliphor HS15, a critical agent for Plinabulin, posing a significant supply risk[206] - The company's collaborations, such as with Eli Lilly and Hengrui, are subject to risks including partners not committing sufficient resources or terminating agreements[209][211] Risks Related to Industry, Business, and Operation The company faces operational risks including dependence on key personnel and two material weaknesses in internal controls - The company's subsidiary, Wanchunbulin, holds the IP rights to Plinabulin in China and has granted exclusive commercialization rights to Hengrui[218][219] - The company is highly dependent on its Founder, Chairperson, and CEO, Dr. Lan Huang, and her loss could impede objectives[220] - Two material weaknesses in internal control over financial reporting were identified related to inadequate review of reconciliations and journal entries[233][234] - An arbitration with partner Hengrui was resolved in the company's favor, and approximately $9.6 million of frozen assets were returned in February 2024[259] Risks Related to Doing Business in China The company's extensive operations in China expose it to political, economic, and complex regulatory risks - Changes in Chinese government policies or U.S.-China relations could materially affect the business[266] - The company's shares may be delisted under the HFCAA, but it does not expect to be identified as a Commission-Identified Issuer for FY2023 due to its U.S.-based auditor[304][305] - China's evolving data protection laws impose strict requirements on the collection, use, and cross-border transfer of data, increasing compliance costs[314][318] - New CSRC regulations require PRC domestic companies seeking overseas listings to complete a filing, which will apply to the company for future refinancing activities[336][340] Risks Related to Ordinary Shares Shareholders face risks including share price volatility, potential dilution, and limited rights as a Cayman Islands company - The trading price of the company's ordinary shares is likely to be volatile due to clinical results, regulatory news, and market fluctuations[343][344] - The company does not expect to pay dividends in the foreseeable future, so investors must rely on share price appreciation for returns[350] - As of April 1, 2024, directors, officers, and principal shareholders beneficially owned approximately 40.90% of ordinary shares, giving them substantial influence[360] - The company may be classified as a Passive Foreign Investment Company (PFIC), which could result in adverse U.S. tax consequences for shareholders[372][374] Item 4. Information on the Company This section details the company's history, business strategy, clinical development of Plinabulin, and its TPD platform collaboration History and Development The company was incorporated in 2014, completed its IPO in 2017, and has funded operations through equity offerings and collaborations - The company completed its initial public offering (IPO) in March 2017, listing on the Nasdaq Capital Market under the symbol "BYSI"[381] - In November 2020, its subsidiary SEED entered a research collaboration with Eli Lilly, receiving a $10 million upfront payment and eligibility for up to $780 million in milestones[385] - In August 2021, its subsidiary Wanchunbulin entered an agreement with Hengrui for Plinabulin in Greater China, receiving an upfront payment of approximately $31 million[388] Business Overview The company is a clinical-stage biopharmaceutical firm focused on its lead asset Plinabulin and a TPD molecular glue platform - The lead asset, Plinabulin, is a first-in-class agent being developed for direct anti-cancer effects and prevention of CIN[389][396] - The global Phase 3 DUBLIN-3 study for NSCLC met its primary endpoint of overall survival, and the company plans to file an NDA in China[391][411] - For the CIN indication, the company received a CRL from the FDA in November 2021 and withdrew the China NDA in March 2023, with plans to re-file[394] - The subsidiary SEED is developing a Targeted Protein Degradation (TPD) 'molecular glue' platform and is collaborating with Eli Lilly[389][464] Organizational Structure The company is a Cayman Islands-based holding company with subsidiaries in the U.S., China, Hong Kong, and the BVI - The company is a holding company with subsidiaries including BeyondSpring Pharmaceuticals Inc. (U.S.), Dalian Wanchunbulin Pharmaceuticals Ltd. (China), and SEED Therapeutics Inc. (BVI)[660][980] Property, Plants and Equipment The company leases all its facilities, with principal executive offices in New Jersey and other locations in China and Pennsylvania - The company leases 9,727 sq. ft. of office space in New Jersey, with the lease expiring in February 2027[661] - Subsidiary SEED leases approximately 10,086 sq. ft. of office and lab space in Pennsylvania to support its R&D efforts[662] Operating and Financial Review and Prospects (MD&A) The company's net loss decreased in FY2023, but its ability to continue as a going concern depends on raising additional capital Operating Results The company's net loss decreased to $21.9 million in FY2023, driven by a significant reduction in R&D and G&A expenses Comparison of Operations (FY2023 vs. FY2022) | Metric | FY 2023 (in thousands) | FY 2022 (in thousands) | Change % | | :--- | :--- | :--- | :--- | | Revenue | $1,751 | $1,351 | 30% | | R&D Expenses | ($14,635) | ($25,582) | -43% | | G&A Expenses | ($10,230) | ($13,008) | -21% | | Net Loss | ($21,948) | ($36,280) | -40% | - The $11.0 million decrease in R&D expenses in 2023 was primarily due to lower clinical development expenses and reduced personnel costs[693][694] - In January 2022, the company initiated an organizational streamlining, including a 35% reduction in its U.S. workforce, to preserve cash[680] Liquidity and Capital Resources The company has a history of negative cash flows, and management has substantial doubt about its ability to continue as a going concern Cash Position | As of | Cash, Cash Equivalents & Restricted Cash (in millions) | Accumulated Deficit (in millions) | | :--- | :--- | :--- | | Dec 31, 2022 | $34.4 | $375.3 | | Dec 31, 2023 | $17.8 | $396.3 | - Net cash used in operating activities decreased to $16.5 million in 2023 from $28.2 million in 2022[717][721] - The company's ability to continue as a going concern is dependent on obtaining additional capital, and failure to do so would adversely affect the business[718] Critical Accounting Estimates Key accounting estimates involve significant judgment, particularly in accruing for research costs and valuing deferred tax assets - The company makes significant judgments in determining accrued balances for ongoing research costs by analyzing study progress and contracted costs[741] - A full valuation allowance is provided against deferred tax assets as it is more likely than not that they will not be realized[742] Item 6. Directors, Senior Management and Employees This section details the company's leadership, board composition, compensation structure, and reduced employee base of 36 as of year-end 2023 Directors and Senior Management The company is led by co-founder and CEO Dr. Lan Huang, with a board of directors consisting of six members - Dr. Lan Huang is the co-founder, Chairperson, and Chief Executive Officer[747] - The Board of Directors consists of 6 members, with 2 identifying as female and 4 as male[757] Compensation Aggregate cash compensation for directors and executives was $1.3 million in FY2023, supplemented by equity awards 2023 Executive and Director Compensation | Compensation Type | Aggregate Amount (in millions) | | :--- | :--- | | Cash Compensation | $1.3 | | Equity Compensation | $0.12 | - Non-employee directors receive a $40,000 annual cash retainer, committee fees, and annual stock option grants[760] - As of April 1, 2024, 2,126,762 shares remained available for grant under the 2017 Omnibus Incentive Plan[779] Board Practices The board has six members, four of whom are independent, and has established three standing committees - The board has determined that four of its six members are independent directors under Nasdaq rules[800] - The board has three standing committees: Audit, Compensation, and Nominating and Corporate Governance[801] - As a foreign private issuer, the company is not required to hold annual shareholder meetings and did not hold one in 2023[927] Employees The company significantly reduced its workforce, ending 2023 with 36 full-time employees, down from 103 in 2021 Employee Headcount by Year | Year End | R&D and Lab | G&A | Total | | :--- | :--- | :--- | :--- | | 2021 | 58 | 45 | 103 | | 2022 | 44 | 29 | 73 | | 2023 | 20 | 16 | 36 | Item 7. Major Shareholders and Related Party Transactions CEO Dr. Lan Huang and Decheng Capital are the principal shareholders, with insiders controlling a significant portion of shares Major Shareholders (as of April 1, 2024) | Shareholder | Beneficial Ownership % | | :--- | :--- | | Dr. Lan Huang (CEO) | 27.30% | | Entities affiliated with Decheng Capital | 12.70% | | All Directors & Executive Officers (as a group) | 28.20% | - As of April 1, 2024, approximately 29.7 million ordinary shares were held by 54 record holders in the U.S.[822] Item 8. Financial Information The company has never paid dividends and does not intend to, planning to reinvest earnings into the business - The company has never declared or paid cash dividends and does not intend to in the foreseeable future[829] - The company was party to an arbitration with Hengrui, which concluded on January 10, 2024, with the tribunal denying all of Hengrui's claims[659] Item 10. Additional Information This section details the company's corporate governance, material contracts with partners, and key tax considerations - The company is a Cayman Islands exempted company and is not required to hold annual general meetings[851][854] - Material contracts include collaboration agreements with Eli Lilly and Hengrui[859][863] - The company discusses the risk that it could be classified as a Passive Foreign Investment Company (PFIC), which would have adverse tax consequences for U.S. shareholders[888] Item 11. Qualitative and Quantitative Disclosures About Market Risk The company's primary market risks are foreign currency exchange risk, particularly with the Chinese Renminbi, and minimal interest rate risk - The company is exposed to foreign exchange risk as a portion of its transactions and assets are denominated in currencies like the RMB[905] - Interest rate risk is related to interest income on cash and investments but is not anticipated to be material[903] PART II Item 15. Controls and Procedures Management concluded that disclosure controls were not effective as of year-end 2023 due to two material weaknesses in internal control - Management concluded that disclosure controls and procedures were not effective as of December 31, 2023[910] - The ineffectiveness was due to two material weaknesses: lack of adequate review of reconciliations and consolidations, and lack of adequate review of journal entries[912] Item 16. Corporate Governance and Other Disclosures This section covers governance topics, including a change in auditor, home country practices, and a new cybersecurity risk management strategy - The company dismissed Ernst & Young and appointed Marcum LLP as its independent auditor for the fiscal year ended December 31, 2023[923] - As a foreign private issuer, the company follows its home country practice and did not hold an annual meeting in 2023[927] - The company's cybersecurity risk management relies on a third-party service provider with oversight from the Board of Directors[931][934] PART III Item 18. Financial Statements This section contains the audited consolidated financial statements, with the auditor's report highlighting substantial doubt about the company's ability to continue as a going concern Consolidated Balance Sheet Highlights (as of Dec 31) | Account (in thousands) | 2023 | 2022 | | :--- | :--- | :--- | | Cash, Cash Equivalents & Restricted Cash | $17,750 | $34,396 | | Total Assets | $24,808 | $46,222 | | Total Liabilities | $48,269 | $49,229 | | Total Shareholders' Deficit | ($35,335) | ($14,081) | Consolidated Statement of Comprehensive Loss Highlights (Year Ended Dec 31) | Account (in thousands) | 2023 | 2022 | 2021 | | :--- | :--- | :--- | :--- | | Revenue | $1,751 | $1,351 | $1,351 | | R&D Expense | ($14,635) | ($25,582) | ($36,888) | | G&A Expense | ($10,230) | ($13,008) | ($30,703) | | Net Loss | ($21,948) | ($36,280) | ($68,208) | - The independent auditor's report for 2023 includes an explanatory paragraph stating substantial doubt about its ability to continue as a going concern[948] Notes to Consolidated Financial Statements The notes detail accounting policies, collaboration revenue, segment reporting, and reiterate the going concern uncertainty - Note 2 reiterates that substantial doubt exists about the company's ability to continue as a going concern and its dependence on obtaining additional financing[983][986] - Note 4 details that the Eli Lilly agreement generated $1.8 million in revenue in 2023, while the $31.0 million upfront payment from Hengrui is deferred[1053][1062] - Note 18 provides a breakdown by the two reportable segments, with the Plinabulin pipeline segment incurring a $15.3 million operating loss in 2023[1151]