Part I [Key Information](index=6&type=section&id=Item%203.%20Key%20Information) The company faces significant risks including heavy reliance on RUCONEST®, intense market competition, regulatory hurdles, and material weaknesses in internal controls [Risk Factors](index=7&type=section&id=D.%20Risk%20Factors) Key risks include heavy dependence on RUCONEST®, intense market competition, material weaknesses in internal controls, customer concentration, and regulatory compliance - The company is heavily dependent on sales of **RUCONEST®** in the United States and Europe, with its development pipeline reliant on the C1INH franchise, and faces intense competition from other approved acute and prophylactic treatments for **Hereditary Angioedema (HAE)**[32](index=32&type=chunk)[33](index=33&type=chunk)[37](index=37&type=chunk) - Management has identified **material weaknesses** in its internal control over financial reporting across all five components of the **COSO framework**, potentially affecting accurate and timely financial reporting[167](index=167&type=chunk)[168](index=168&type=chunk) - The company faces significant customer concentration, with two U.S. specialty pharmacies accounting for **84% of revenues in 2022**, posing a material risk if volume from these customers is lost or reduced[93](index=93&type=chunk) - Commercial success depends on market acceptance by physicians and payors, and the ability to secure adequate coverage and reimbursement, facing pricing pressure from competitors and government cost-containment initiatives[38](index=38&type=chunk)[46](index=46&type=chunk) - The company is subject to complex laws and regulations regarding sales, marketing, data privacy (like **GDPR**), and anti-corruption (like **FCPA**), with non-compliance potentially leading to significant fines and reputational damage[125](index=125&type=chunk)[128](index=128&type=chunk)[131](index=131&type=chunk) [Information on the Company](index=43&type=section&id=Item%204.%20Information%20on%20the%20Company) Pharming is a global biopharmaceutical company focused on rare diseases, with commercial products like RUCONEST® and newly approved Joenja®, leveraging transgenic manufacturing and pipeline expansion [History and Development of the Company](index=43&type=section&id=A.%20History%20and%20Development%20of%20the%20Company) Pharming Group N.V. was incorporated in 1988, listed on Euronext and Nasdaq, with capital expenditures detailed from 2020-2022 - Pharming Group N.V. was incorporated in The Netherlands on **November 11, 1988**, with ordinary shares trading on **Euronext Amsterdam** and American Depositary Shares (ADSs) listed on the **Nasdaq Global Market** since **December 22, 2020**[211](index=211&type=chunk)[212](index=212&type=chunk) Capital Expenditures (2020-2022) | Year | Capital Expenditure (in millions USD) | | :--- | :--- | | 2022 | $1.4 | | 2021 | $10.7 | | 2020 | $4.7 | [Business Overview](index=43&type=section&id=B.%20Business%20Overview) The company's business overview highlights its product portfolio including RUCONEST® and Joenja®, strategic focus on rare diseases, proprietary transgenic manufacturing, and market competition Product Portfolio Overview | Product/Candidate | Indication | Status | | :--- | :--- | :--- | | **RUCONEST®** | Acute Hereditary Angioedema (HAE) attacks | Commercialized in US, EEA, UK | | **Joenja® (leniolisib)** | Activated PI3K delta syndrome (APDS) | FDA approved (Mar 2023); EMA review ongoing | | **OTL-105** | HAE (Gene Therapy) | Preclinical | | **Alpha-Glucosidase** | Pompe Disease (Enzyme Replacement) | Preclinical | - **Joenja® (leniolisib)** was approved by the **FDA** on **March 24, 2023**, for treating APDS, marking it as the **first and only approved treatment** for this rare primary immunodeficiency, with an EMA opinion anticipated in H2 2023[216](index=216&type=chunk)[223](index=223&type=chunk) - The company's strategy focuses on creating long-term value by leveraging its clinical development and commercialization strengths in rare diseases, expanding its pipeline through internal R&D and in-licensing/acquisitions beyond the rhC1INH platform[277](index=277&type=chunk)[278](index=278&type=chunk)[279](index=279&type=chunk) - The company utilizes a proprietary **transgenic manufacturing technology platform** for recombinant human proteins produced in transgenic animal milk, while relying on **Contract Manufacturing Organizations (CMOs)** for small molecules like leniolisib[273](index=273&type=chunk)[275](index=275&type=chunk) - The company faces significant competition in the **HAE** market from companies like BioCryst, CSL Behring, and Takeda, offering both acute and prophylactic treatments, while for leniolisib, there are currently no known ongoing development programs for **APDS**[288](index=288&type=chunk)[289](index=289&type=chunk) [Organizational Structure](index=74&type=section&id=C.%20Organizational%20Structure) Pharming Group N.V. serves as the ultimate parent company, overseeing wholly-owned subsidiaries in the Netherlands and the United States - **Pharming Group N.V.** is the ultimate parent company, wholly owning several subsidiaries in The Netherlands (e.g., Pharming B.V.) and the United States (e.g., Pharming Healthcare, Inc.)[414](index=414&type=chunk) [Property, Plant and Equipment](index=74&type=section&id=D.%20Property,%20Plant%20and%20Equipment) The company maintains administrative, laboratory, and production facilities in the Netherlands, France, and the United States, with a notable investment in machinery and equipment in 2022 - The company's administrative offices, laboratories, and production facilities are primarily located in The Netherlands, with additional R&D facilities in France and commercial offices in the United States[415](index=415&type=chunk)[418](index=418&type=chunk)[419](index=419&type=chunk) - In 2022, the company invested **$1.4 million** in new machinery and laboratory equipment, a significant decrease from **$10.7 million** in 2021, and repurposed a newly constructed building in Oss for alternative uses instead of downstream production[420](index=420&type=chunk) [Operating and Financial Review and Prospects](index=75&type=section&id=Item%205.%20Operating%20and%20Financial%20Review%20and%20Prospects) For the fiscal year 2022, the company reported a 3.4% increase in revenues to $205.6 million, driven by higher RUCONEST® sales, but profit decreased to $13.7 million from $16.0 million in 2021, primarily due to a 44.3% increase in marketing and sales expenses related to the anticipated launch of leniolisib, while maintaining a strong liquidity position with $207.3 million in cash and cash equivalents [Operating Results](index=76&type=section&id=A.%20Operating%20Results) Operating results show a 3.4% revenue increase to $205.6 million in 2022, driven by RUCONEST® sales, alongside a 44.3% rise in marketing expenses and a 25.3% decrease in R&D, leading to a profit decline Consolidated Statement of Income (2020-2022) | Amounts in $'000 | 2022 | 2021 | 2020 | | :--- | :--- | :--- | :--- | | **Revenues** | **205,622** | **198,871** | **212,174** | | Costs of sales | (17,562) | (21,142) | (23,539) | | **Gross profit** | **188,060** | **177,729** | **188,635** | | Other income | 14,523 | 2,620 | 1,829 | | Research and development | (52,531) | (70,369) | (38,519) | | General and administrative | (46,016) | (36,974) | (24,085) | | Marketing and sales | (85,803) | (59,445) | (51,604) | | **Operating profit** | **18,233** | **13,561** | **76,256** | | Profit before tax | 14,987 | 23,078 | 44,094 | | Income tax expense | (1,313) | (7,082) | (6,348) | | **Profit for the year** | **13,674** | **15,996** | **37,746** | - Revenues increased by **3.4%** to **$205.6 million** in 2022 from **$198.9 million** in 2021, primarily due to higher sales of **RUCONEST®** in the U.S. market[441](index=441&type=chunk) - Marketing and sales costs increased significantly by **44.3%** to **$85.8 million** in 2022, up from **$59.4 million** in 2021, mainly due to the expansion of the commercial organization in preparation for the launch of **leniolisib**[457](index=457&type=chunk) - Research and development expenses decreased by **25.3%** to **$52.5 million** in 2022 from **$70.4 million** in 2021, primarily due to reduced share-based compensation and favorable currency effects, partially offset by increased spending on leniolisib[453](index=453&type=chunk) - Profit for the year decreased to **$13.7 million** in 2022 from **$16.0 million** in 2021, driven by higher operating costs, particularly in marketing and sales, which outpaced revenue and gross profit growth[440](index=440&type=chunk) [Liquidity and Capital Resources](index=86&type=section&id=B.%20Liquidity%20and%20Capital%20Resources) The company maintains a strong liquidity position with $207.3 million in cash, despite a decrease in operating cash flow, supported by €125 million in convertible bonds due 2025 - As of December 31, 2022, the company had cash and cash equivalents of **$207.3 million**, expected to fund operations for more than twelve months[512](index=512&type=chunk)[513](index=513&type=chunk) Cash Flow Summary (2020-2022) | Amounts in $'000 | 2022 | 2021 | 2020 | | :--- | :--- | :--- | :--- | | Net cash from operating activities | 22,458 | 37,842 | 83,626 | | Net cash from (used in) investing activities | 5,323 | (21,305) | (15,629) | | Net cash from (used in) financing activities | (4,982) | (27,947) | 60,686 | | **Net change in cash and cash equivalents** | **15,418** | **(13,235)** | **130,811** | - Net cash from operating activities decreased to **$22.5 million** in 2022 from **$37.8 million** in 2021, mainly due to lower profit before tax and changes in non-cash adjustments[518](index=518&type=chunk) - The company has **€125 million** in 3.00% convertible bonds due in **2025**, issued in January 2020, with proceeds used to redeem a previous loan and fund capital expenditures and potential acquisitions[524](index=524&type=chunk) [Directors, Senior Management and Employees](index=89&type=section&id=Item%206.%20Directors,%20Senior%20Management%20and%20Employees) The company operates under a one-tier board structure with one executive director (CEO Sijmen de Vries) and seven non-executive directors, with a remuneration policy combining fixed salary with performance-based short-term (cash bonus) and long-term (restricted shares) incentives, and the total number of full-time equivalent employees grew to 332 in 2022, up from 277 in 2021, reflecting business expansion [Directors and Senior Management](index=89&type=section&id=A.%20Directors%20and%20Senior%20Management) The company operates with a one-tier board structure, comprising one executive director and seven non-executive directors, chaired by Paul Sekhri - The company has a **one-tier board structure** with a single board of directors, consisting of **one executive director** (CEO Sijmen de Vries) and **seven non-executive directors**, chaired by Paul Sekhri, as of December 31, 2022[532](index=532&type=chunk)[534](index=534&type=chunk) [Compensation](index=92&type=section&id=B.%20Compensation) Executive compensation includes fixed salaries, short-term cash bonuses, and long-term performance-based restricted shares, while non-executive directors receive fixed retainers - The executive remuneration policy includes a fixed base salary, a short-term cash bonus (on-target **70% of salary for CEO**, **50% for others**), and a long-term incentive (LTI) program with performance-based restricted shares vesting over **three years**[556](index=556&type=chunk)[565](index=565&type=chunk)[566](index=566&type=chunk) CEO Remuneration (2022) | Amounts in $'000 | Fixed Remuneration | Short-term Bonus | Share-based Payments | Post Employment | Other | Total | | :--- | :--- | :--- | :--- | :--- | :--- | :--- | | Sijmen de Vries, CEO | 636 | 394 | 1,221 | 112 | 34 | 2,396 | - Non-executive directors receive a fixed annual retainer, paid partly in cash and partly in unrestricted shares, and do not participate in performance-based incentive plans to ensure their independence[573](index=573&type=chunk)[576](index=576&type=chunk) [Employees](index=100&type=section&id=D.%20Employees) The total number of full-time equivalent employees increased to 332 in 2022, reflecting growth across various regions and functions Average Full-Time Equivalent Employees (2020-2022) | Region/Function | 2022 | 2021 | 2020 | | :--- | :--- | :--- | :--- | | The Netherlands | 198 | 186 | 145 | | United States | 102 | 77 | 66 | | Other | 32 | 22 | 19 | | **Total** | **332** | **285** | **229** | [Major Shareholders and Related Party Transactions](index=101&type=section&id=Item%207.%20Major%20Shareholders%20and%20Related%20Party%20Transactions) As of March 31, 2023, no single shareholder was known to beneficially own more than 5% of the company's shares, while executive officers and directors as a group beneficially owned approximately 2.35% of outstanding shares, with key related party transactions including fill and finish services with BioConnection B.V., in which Pharming holds a 22.98% stake [Major Shareholders](index=101&type=section&id=A.%20Major%20Shareholders) As of March 31, 2023, no single shareholder held over 5% beneficial ownership, while executive officers and directors collectively owned 2.35% of outstanding shares - As of March 31, 2023, there were no known beneficial owners of more than **5%** of the company's common shares[608](index=608&type=chunk) - Executive officers and directors as a group beneficially owned 15,452,443 ordinary shares, representing **2.35%** of the total, with CEO Sijmen de Vries being the largest individual holder at **1.66%** beneficial ownership[610](index=610&type=chunk)[611](index=611&type=chunk) [Related Party Transactions](index=102&type=section&id=B.%20Related%20Party%20Transactions) The company engages in related party transactions with BioConnection B.V. for fill and finish services, in which Pharming holds a 22.98% stake - The company engages in transactions with its fill and finish partner, BioConnection B.V., in which it holds a **22.98%** stake, paying BioConnection **$3.0 million** for these services in 2022[614](index=614&type=chunk) [Financial Information](index=103&type=section&id=Item%208.%20Financial%20Information) This section confirms that the consolidated financial statements are included at the end of the report, and the company states it is not currently a party to any material legal proceedings and has not declared or paid dividends, with no plans to do so in the foreseeable future - The company has never declared or paid dividends on its ordinary shares and does not anticipate paying any in the foreseeable future, intending to retain earnings for business use[624](index=624&type=chunk) - The company is not currently a party to any material legal or administrative proceedings[623](index=623&type=chunk) Part II [Controls and Procedures](index=117&type=section&id=Item%2015.%20Controls%20and%20Procedures) Management, including the CEO and CFO, concluded that the company's disclosure controls and procedures were not effective as of December 31, 2022, based on identified material weaknesses in internal control over financial reporting across all five components of the COSO framework, with the independent auditor also issuing an adverse opinion on the effectiveness of internal controls, and a remediation plan is underway to address these deficiencies - The CEO and CFO concluded that the company's disclosure controls and procedures were **not effective** as of **December 31, 2022**, due to **material weaknesses** in internal control over financial reporting[704](index=704&type=chunk) - **Material weaknesses** were identified across all **five components of the COSO framework**: Control Environment, Risk Assessment, Control Activities, Information & Communication, and Monitoring, indicating an ineffective control environment and insufficient controls to address risks of material misstatement[707](index=707&type=chunk)[722](index=722&type=chunk) - The independent registered public accounting firm, Deloitte, issued an **adverse opinion** on the company's internal control over financial reporting as of **December 31, 2022**, concurring with management's assessment of material weaknesses[715](index=715&type=chunk)[763](index=763&type=chunk) - A **remediation plan** is in process, including developing a formal risk assessment framework, implementing key controls based on the new **SAP ERP system**, and hiring a risk and control officer, with implementation proceeding in a phased approach[709](index=709&type=chunk)[710](index=710&type=chunk)[711](index=711&type=chunk) [Corporate Governance and Other Matters](index=120&type=section&id=Item%2016.%20Corporate%20Governance%20and%20Other%20Matters) This section covers various governance and compliance topics, including the board's determination of an 'audit committee financial expert,' the adoption of a Code of Business Conduct & Ethics, fees paid to the principal accountant Deloitte totaling $1.4 million in 2022, and the company's reliance on home country governance practices as a foreign private issuer in lieu of certain Nasdaq requirements Principal Accountant Fees (Deloitte) | Amounts in $'000 | 2022 | 2021 | | :--- | :--- | :--- | | Audit Fees | (1,357) | (1,201) | | Audit Related Fees | — | (16) | | **Total** | **(1,357)** | **(1,217)** | - The company adopted a **Code of Business Conduct & Ethics** applicable to all directors, officers, and employees, which was updated in **August 2022**[727](index=727&type=chunk)[728](index=728&type=chunk) - As a **'foreign private issuer,'** the company complies with **Dutch home country governance requirements** and is exempt from certain Nasdaq corporate governance standards, such as the requirement for shareholder approval of all share option plans[741](index=741&type=chunk)[742](index=742&type=chunk) Part III [Financial Statements](index=124&type=section&id=Item%2018.%20Financial%20Statements) This section contains the audited consolidated financial statements for the years ended December 31, 2022, 2021, and 2020, prepared in accordance with IFRS, including the report of the independent registered public accounting firm, which provides an unqualified opinion on the financial statements but an adverse opinion on internal controls over financial reporting - The report includes audited consolidated financial statements for the fiscal years 2022, 2021, and 2020, prepared in conformity with **International Financial Reporting Standards (IFRS)** as issued by the **IASB**[750](index=750&type=chunk)[762](index=762&type=chunk) - The independent auditor, Deloitte, issued an **unqualified opinion** on the financial statements, stating they present fairly the financial position of the company, but also issued an **adverse opinion** on the company's internal control over financial reporting due to identified **material weaknesses**[762](index=762&type=chunk)[763](index=763&type=chunk)

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 6-K REPORT OF FOREIGN PRIVATE ISSUER PURSUANT TO RULE 13a-16 OR 15d-16 UNDER THE SECURITIES EXCHANGE ACT OF 1934 For the Month of April 2023 Commission File Number: 001-39822 Pharming Group N.V. (Exact Name of Registrant as Specified in Its Charter) Darwinweg 24 2333 CR Leiden The Netherlands (Address of principal executive offices) Indicate by check mark whether the registrant files or will file annual reports under cover of Form ...

Pharming Group N.V. (OTCPK:PHGUF) Q4 2022 Earnings Call Transcript March 16, 2023 8:30 AM ET Company Participants Sijmen de Vries - Executive Director & Chief Executive Officer Anurag Relan - Chief Medical Officer Jeroen Wakkerman - Chief Financial Officer Stephen Toor - Chief Commercial Officer & General Manager Americas Conference Call Participants Sushila Hernandez - Kempen Joe Pantginis - H.C. Wainwright Hartaj Singh - Oppenheimer Christian Glennie - Stifel Operator Hello, and welcome to today's Pharmin ...

www.pharming.com | investor@pharming.com Pharming Group N.V. Full Year 2022 Financial Results March 16, 2023 mm 2 �Pharming® MTT I Introduction One commercialized asset: RUCONEST® (rhC1INH) for the treatment of acute hereditary angioedema (HAE) | --- | --- | |-------|-----------------------------------------------------------------------------------------------------------| | | | | | Development of rare disease pipeline and leniolisib/ PI3Kδ for additional rare disease indications | EURONEXT Amsterdam: PHAR ...

Pharming Group N.V. (OTCPK:PHGUF) Q3 2022 Earnings Conference Call October 27, 2022 7:30 AM ET Company Participants Sijmen de Vries - Chief Executive Officer Anurag Relan - Chief Medical Officer Jeroen Wakkerman - Chief Financial Officer Conference Call Participants Hartaj Singh - Oppenheimer & Co. Joseph Pantginis - H.C. Wainwright Simon Scholes - First Berlin Operator Hello, and welcome to Pharming's Nine Months 2022 Results Call. My name is Lauren, and I will be coordinating your call today. [Operator In ...

Pharming Group N.V. (OTCPK:PHGUF) First Half 2022 Earnings Conference Call August 4, 2022 7:30 AM ET Company Participants Sijmen de Vries – Chief Executive Officer Anurag Relan – Chief Medical Officer Jeroen Wakkerman – Chief Financial Officer Conference Call Participants Joe Pantginis – H.C. Wainwright Hartaj Singh – Oppenheimer & Co. Simon Scholes – First Berlin Jacob Mekhael – Kempen Operator Hello, everybody, and welcome to the Pharming's First Half of 2022 Results Call. My name is Sam, and I'll be coor ...

Pharming Group N.V. H1 2022 Financial Results Analyst Call August 4, 2022 NASDAQ: PHAR | EURONEXT Amsterdam: PHARM 1177 Forward looking statements 2 This presentation may contain forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our development plans, our clinical results and other future condit ...

Pharming Group N.V. (OTCPK:PHGUF) Q1 2022 Earnings Conference Call May 12, 2022 7:30 AM ET Company Participants Sijmen de Vries - CEO Jeroen Wakkerman - CFO Anurag Relan - Chief Medical Officer Conference Call Participants Joe Pantginis - H.C. Wainright Hartaj Singh - Oppenheimer & Co. Christian Glennie - Stifel Simon Scholes - First Berlin Equity Operator Hello, everyone, and welcome to the Pharming's First Quarter Results Conference Call. My name is Victoria, and I'll be coordinating your call today. [Ope ...

[SEC Filing Information](index=1&type=section&id=SEC%20Filing%20Information) [Filing Details](index=1&type=section&id=Filing%20Details) This section identifies the filing as a Form 6-K for Pharming Group N.V. for April 2022, indicating its status as a foreign private issuer filing under Form 20-F - Pharming Group N.V. filed a **Form 6-K** for April 2022 as a foreign private issuer under Form 20-F[1](index=1&type=chunk)[2](index=2&type=chunk) [Exhibit Index](index=2&type=section&id=EXHIBIT%20INDEX) The exhibit index specifies that a press release announcing the filing of the 2021 Annual Report and Form 20-F, and the convening of the 2022 AGM, is filed as Exhibit 99.1 - **Exhibit 99.1** is a press release announcing the filing of the 2021 Annual Report, Form 20-F, and the 2022 AGM[4](index=4&type=chunk)[6](index=6&type=chunk) [Signature](index=2&type=section&id=SIGNATURE) The report is officially signed by Sijmen de Vries, CEO of Pharming Group N.V., on April 7, 2021 - The report was signed by **Sijmen de Vries**, CEO of Pharming Group N.V., on April 7, 2021[7](index=7&type=chunk)[9](index=9&type=chunk) [Company Announcement](index=3&type=section&id=Company%20Announcement) [Filing of 2021 Annual Report and Form 20-F](index=3&type=section&id=Pharming%20announces%20the%20filing%20of%20its%202021%20Annual%20Report%2C%20with%20Form%2020-F%20also%20filed%20with%20the%20U.S.%20Securities%20and%20Exchange%20Commission%20and%20convenes%20its%202022%20AGM) Pharming Group N.V. announced the filing of its Annual Report for the year ended December 31, 2021, and its Form 20-F with the U.S. SEC, making both documents available on the company's website - Pharming Group N.V. filed its **2021 Annual Report** and **Form 20-F** with the U.S. SEC for the period ended December 31, 2021[10](index=10&type=chunk) - The Annual Report and Form 20-F are available on the Company's website under Investors/Financial Documents and Investors/SEC filings, respectively[11](index=11&type=chunk) [Convening of 2022 Annual General Meeting (AGM)](index=3&type=section&id=2022%20AGM) The company announced its 2022 Annual General Meeting (AGM) will be held on Wednesday, May 18, 2022, at 2:00 pm (CEST), with all relevant meeting documents available on its website - The **2022 Annual General Meeting (AGM)** is scheduled for Wednesday, May 18, 2022, at 2:00 pm (CEST)[11](index=11&type=chunk) - Meeting documents, including the Notice to Convene, Explanatory Notes, and Form of Proxy, are available on the company's website[11](index=11&type=chunk) [About Pharming Group N.V.](index=3&type=section&id=About%20Pharming%20Group%20N.V.) [Company Overview](index=3&type=section&id=Company%20Overview) Pharming Group N.V. is a global, commercial-stage biopharmaceutical company dedicated to developing innovative protein replacement therapies and precision medicines for rare diseases and unmet medical needs - Pharming Group N.V. is a global, commercial-stage biopharmaceutical company[12](index=12&type=chunk) - The company focuses on developing innovative protein replacement therapies and precision medicines for rare diseases and unmet medical needs[12](index=12&type=chunk) [Product Portfolio and Pipeline](index=3&type=section&id=Product%20Portfolio%20and%20Pipeline) Pharming's portfolio is anchored by its recombinant human C1 esterase inhibitor (rhC1INH) franchise, including RUCONEST®, and a pipeline featuring leniolisib for APDS, a strategic collaboration for OTL-105, and preclinical development for Pompe disease [RUCONEST® (rhC1INH) Franchise](index=3&type=section&id=RUCONEST%C2%AE) RUCONEST® is a plasma-free recombinant human C1 esterase inhibitor approved for acute hereditary angioedema attacks, with ongoing investigations for additional indications - **RUCONEST®** is the first and only plasma-free recombinant human C1 esterase inhibitor (rhC1INH) protein replacement therapy[13](index=13&type=chunk) - It is approved for the treatment of acute hereditary angioedema (HAE) attacks and commercialized in the US, EU, UK, and other regions[13](index=13&type=chunk) - Pharming is investigating rhC1INH for additional indications, including pre-eclampsia, acute kidney injury, and severe pneumonia from COVID-19[14](index=14&type=chunk) [Leniolisib (PI3K delta inhibitor)](index=3&type=section&id=Leniolisib) Leniolisib, an oral PI3K delta inhibitor, is under study for activated PI3K delta syndrome (APDS), having met primary endpoints in a Phase 2/3 study, with global regulatory filings targeted from Q2 2022 - **Leniolisib**, an oral phosphoinositide 3-kinase delta (PI3K delta) inhibitor, is being studied for activated PI3K delta syndrome (APDS)[15](index=15&type=chunk) - Leniolisib met both primary endpoints in a registration-enabling Phase 2/3 study in the US and Europe[15](index=15&type=chunk) - Global regulatory filings for leniolisib are targeted from **Q2 2022** onwards[15](index=15&type=chunk) [Strategic Collaborations and Next-Generation Therapies](index=3&type=section&id=Strategic%20Collaborations%20and%20Next-Generation%20Therapies) Pharming collaborates with Orchard Therapeutics on OTL-105 for HAE and develops next-generation protein replacement therapies, including a preclinical program for Pompe disease - Pharming collaborates with Orchard Therapeutics on OTL-105, an ex-vivo autologous hematopoietic stem cell (HSC) gene therapy for HAE[16](index=16&type=chunk) - The company is developing next-generation protein replacement therapies using its transgenic manufacturing technology, including a preclinical program for Pompe disease[17](index=17&type=chunk) [Disclaimers and Contact Information](index=4&type=section&id=Disclaimers%20and%20Contact%20Information) [Forward-looking Statements](index=4&type=section&id=Forward-looking%20Statements) This section outlines standard disclaimers regarding forward-looking statements, covering risks and uncertainties related to clinical trials, commercial prospects, COVID-19, and financial resources - The press release contains forward-looking statements regarding clinical trials, commercial prospects, COVID-19 impact, and financial requirements[18](index=18&type=chunk) - These statements are subject to risks and uncertainties described in Pharming's 2021 Annual Report and Form 20-F[18](index=18&type=chunk) [Inside Information and Contacts](index=4&type=section&id=Inside%20Information) This section notes the press release may contain inside information under EU Market Abuse Regulation and provides contact details for company executives and external PR consultants - The press release may contain inside information as per Article 7(1) of the EU Market Abuse Regulation[19](index=19&type=chunk) - Contact information is provided for Pharming Group's CEO, Investor Relations Manager, and FTI Consulting (London/USA) and LifeSpring Life Sciences Communication (Amsterdam) for public inquiries[19](index=19&type=chunk)

Revenue Performance - Revenues from the sale of RUCONEST® for the treatment of acute HAE attacks were US$198.9 million in 2021, a decrease of 6.3% from US$212.2 million in 2020[420][441] - The U.S. market accounted for US$193.4 million of RUCONEST® sales in 2021, down from US$202.7 million in 2020, primarily due to the impact of the COVID-19 pandemic[441][444] - Revenue in Europe decreased to US$4.9 million in 2021 from US$8.2 million in 2020, attributed to phasing of ordering[442] - Two U.S. customers represented 79% of total revenues in 2021, highlighting reliance on a limited customer base[443] Operating Profit and Costs - Operating profit for 2021 was US$13.6 million, a significant decrease from US$76.3 million in 2020[440] - Cost of sales decreased by US$2.4 million, or 10.2%, from US$23.5 million in 2020 to US$21.1 million in 2021, with product sales costs at US$19.1 million[445] - Gross profit decreased by US$10.9 million, or 5.8%, from US$188.6 million in 2020 to US$177.7 million in 2021, primarily due to reduced sales in the U.S. and EU[448] Research and Development - The company is developing rhC1INH for additional indications, including pre-eclampsia and AKI, which may require significant investment and regulatory approval[422] - The leniolisib Phase 2/3 clinical trial has been completed, and the company plans to submit a New Drug Application (NDA) to the FDA in mid-2022[423] - The company incurred research and development costs of US$70.4 million in 2021, up from US$38.5 million in 2020, reflecting increased investment in product development[440] - Research and development expenses increased by US$31.9 million, or 82.7%, from US$38.5 million in 2020 to US$70.4 million in 2021, mainly due to investments in clinical studies[452] Administrative and Marketing Costs - General and administrative costs increased by US$12.9 million, or 53.5%, from US$24.1 million in 2020 to US$37.0 million in 2021, largely due to impairment losses and additional administrative resources[454] - Marketing and sales costs increased by US$7.8 million, or 15.2%, from US$51.6 million in 2020 to US$59.4 million in 2021, driven by expansion in the U.S. and Europe[455] Financial Performance and Cash Flow - Other income related to grants increased by US$0.8 million, or 43.2%, from US$1.8 million in 2020 to US$2.6 million in 2021[451] - Other finance income surged by US$14.2 million, or 1983.1%, from US$0.7 million in 2020 to US$14.9 million in 2021, primarily due to favorable currency effects[460] - Other finance expenses decreased by US$27.1 million, or 81.4%, from US$33.3 million in 2020 to US$6.2 million in 2021, attributed to currency exchange rate changes and absence of settlement fees[463] - Income tax expense increased by US$0.7 million, or 11.6%, from US$6.3 million in 2020 to US$7.1 million in 2021, despite lower profit before tax[467] - Net cash flows generated from operating activities were US$37.8 million in 2021, down from US$83.6 million in 2020[515] - The company anticipates that sales of RUCONEST® will continue to cover operating costs and finance costs in 2022[513] Capital Expenditures and Financing - Net cash flows used in investing activities increased to US$21.3 million for the year ended December 31, 2021, compared to US$15.6 million in 2020, primarily due to capital expenditures of US$10.7 million[519] - The company experienced a net cash outflow of US$27.9 million from financing activities for the year ended December 31, 2021, a significant change from a net cash inflow of US$60.7 million in 2020, mainly due to the absence of proceeds from convertible bonds[521] - The company issued €125 million of 3.00% convertible bonds due 2025 on January 21, 2020, with net proceeds used to redeem US$51 million of a loan and support capital expenditures[523] - Capital expenditures in 2021 were primarily related to investments in new production facilities and machinery, totaling US$10.7 million[519] Future Outlook and Risks - The company expects an increase in research and development and administrative costs due to ongoing clinical trials and product development[509] - The company may consider raising capital through equity or debt to support acquisitions or in-licensing of additional assets if favorable terms are available[514] - The company expects to continue facing uncertainties due to the ongoing COVID-19 pandemic, which may impact future sales growth[424] - The company’s financial risks include liquidity, market risk, and credit risk, with the Board responsible for risk management policies[692]